\n\n \n\nThe project work was funded by the European Commission (EC) 7th Framework Programme (FP7), under the 9th Call for projects on Information and Communication Technologies. The publishing of this book was funded by the EC FP7 Post-Grant Open Access Pilot programme. 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',editors:null,equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1278",title:"Industrial Robot",slug:"cognitive-robotics-industrial-robot"}],chapters:[{id:"56412",title:"Foreword: The Impact of RoCKIn on Robotics",doi:"10.5772/intechopen.70307",slug:"foreword-the-impact-of-rockin-on-robotics",totalDownloads:1179,totalCrossrefCites:1,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Alessandro Saffiotti and Tijn van der Zant",downloadPdfUrl:"/chapter/pdf-download/56412",previewPdfUrl:"/chapter/pdf-preview/56412",authors:[{id:"152268",title:"Dr.",name:"Alessandro",surname:"Saffiotti",slug:"alessandro-saffiotti",fullName:"Alessandro Saffiotti"}],corrections:null},{id:"56203",title:"The RoCKIn Project",doi:"10.5772/intechopen.70011",slug:"the-rockin-project",totalDownloads:1236,totalCrossrefCites:1,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The goal of the project “Robot Competitions Kick Innovation in Cognitive Systems and Robotics” (RoCKIn), funded by the European Commission under its 7th Framework Program, has been to speed up the progress toward smarter robots through scientific competitions. Two challenges have been selected for the competitions due to their high relevance and impact on Europe’s societal and industrial needs: domestic service robots (RoCKIn@Home) and innovative robot applications in industry (RoCKIn@Work). The RoCKIn project has taken an approach to boosting scientific robot competitions in Europe by (i) specifying and designing open domain test beds for competitions targeting the two challenges; (ii) developing methods for scoring and benchmarking that allow to assess both particular subsystems as well as the integrated system; and (iii) organizing camps to build up a community of new teams, interested to participate in robot competitions. A significant number of dissemination activities on the relevance of robot competitions were carried out to promote research and education in robotics, as to researchers and lay citizens. The lessons learned during RoCKIn paved the way for a step forward in the organization and research impact of robot competitions, contributing for Europe to become a world leader in robotics research, education, and technology transfer.",signatures:"Pedro U. Lima",downloadPdfUrl:"/chapter/pdf-download/56203",previewPdfUrl:"/chapter/pdf-preview/56203",authors:[{id:"78836",title:"Dr.",name:"Pedro U.",surname:"Lima",slug:"pedro-u.-lima",fullName:"Pedro U. Lima"}],corrections:null},{id:"56373",title:"RoCKIn@Home: Domestic Robots Challenge",doi:"10.5772/intechopen.70015",slug:"rockin-home-domestic-robots-challenge",totalDownloads:1391,totalCrossrefCites:2,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Service robots performing complex tasks involving people in houses or public environments are becoming more and more common, and there is a huge interest from both the research and the industrial point of view. 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Strict guidelines on data logging were imposed on participating teams to ensure gathered data could be automatically evaluated. This also had the positive effect that teams were made aware of the importance of data logging, not only during a competition but also during research as useful utility in their own laboratory. Tasks and functionality benchmarks are explained in detail, starting with their use case in industry, further detailing their execution and providing information on scoring and ranking mechanisms for the specific benchmark.",signatures:"Rainer Bischoff, Tim Friedrich, Gerhard K. 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\r\n\tOn-road and off-road vehicles constitute an important part of the land transportation sector. Even the economic and chip crises cannot completely stop the production of vehicles in a product range that varies according to customer demand. The use of automobiles in the world is increasing day by day, and vehicle users demand from the sector smarter, more environmentally friendly, and safer vehicles. Vehicle dynamics is one of the most important aspects that all vehicle manufacturers and related researchers should compute and pay attention to before the production of vehicles. Modeling and simulation of dynamic elements of vehicle parts such as tires, steering, brakes, the integrated driver helped systems, etc., is a crucial step before prototyping.
\r\n
\r\n\tIn this book, the dynamics of vehicles will be deeply illustrated, from fundamental to futuristic approaches. The primary aim is to convey to the readers how important the dynamic analysis of vehicles is and how it affects their production, from simple to detailed.
\r\n
\r\n\tFinally, the effects of intelligent systems to be used in autonomous vehicles with developing technologies on vehicle dynamics and future perspectives will be analyzed.
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1. Introduction
The clinical benefit of cardiac pacemakers has been long proven through numerous studies. Millions of pacemakers have been implanted worldwide and, as a result the quality of life for these patients has been drastically improved, not forgetting the reduced morbidity and mortality. The first stimulations through transthoracic electrodes were pioneered by Zoll in the early fifties (Zoll, 1952)), then came percutaneous endocardial pacing in 1959 (Furman & Schwedel. (1959).. A “permanent” pacemaker using epicardial electrodes was first described in 1960 (Chardack, 1960). Pacemakers and implantation techniques have progressed rapidly since the then; Generators are more reliable, more compact, filled with micro-electronic components, can be controlled automatically and remotely and thus providing more options for programmation and monitoring and a longer pacemaker life span (Kusomoto & Goldschlager, 1996; Trohman, et al, 2004). Leads are thinner and more resistant to damage and thus equally longer-lasting.
The latest European guidelines published in 2007 confirmed the classic indications; symptomatic bradyarrhythmias including sinus node dysfunction and atrioventricular or intraventricular conduction disturbances (Vardas et al., 2007). The guidelines also recommended cardiac pacing for specific conditions (vasovagal syncope, hypertrophic cardiomyopathy, heart failure with prolonged QRS duration, etc). Since over 10 years, left ventricular resynchronisation therapy has proved to be beneficial to patients presenting heart failure with complete left bundle block in association with optimal medical treatment; the European guidelines were updated for this indication in 2010 (Dickstein,2010)
The correct implantation of a pacemaker is capital for optimal function. A recent trend shows pacemaker implantation can be performed as successfully in the electrophysiology study environment as in the operating room (Garcia-Bolao & Alegria, 1999). This requires a centre with a qualified team of cardiologists as well as experienced nursing and technical staff. Continued education for the team and follow-up of complications is essential. The cardiologists’ or surgeons’ experience, and the volume of pacemakers implanted in the centre, plays a role in reducing post-implantation complications; thus, guidelines discourage this procedure in centres with a low volume of implantation.
Despite these precautions, some early complications, occurring within the first 6 weeks after implantation, may be observed. Their incidence is probably underestimated (approximately 7%), as is their severity (Kiviniemi et al., 1999; Klug et al., 2003). Less than 5% have to incur reintervention. Per-procedure mortality is extremely rare; only one case was observed in the cohort of 650 patients implanted at Columbia-Presbyterian Medical Centre. The dutch database FLOOWPACE PM has indexed/listed six variables associated with at least one complication prior to hospital discharge; a low body mass index, history of heart failure (one of the principal indications for implantation), a subclavian venous access, an active fixation auricular pacing lead, and double lead implantation. These patients should be considered at risk for complications (van Eck et al., 2007).
2. Clinical cases
Early complications of pacemaker implantation are not uncommon, even in an experienced team of cardiologists or surgeons. Before discharge, careful evaluation of the pacing system is required. Diagnosis of malfunction is not always evident. Most of the patients needed an invasive procedure or medical intervention to prevent further morbidity.
Through practical clinical examples, we aim to elaborate the principal complications of electronic implanted cardiac devices, as well as discuss situations in which the presence of such a device needs to be kept in mind for the work-up of disorders that may or may not seem pacemaker-related.
2.1. Case 1 - Latrogenic pneumothorax resulting from subclavian puncture
A 61 year old man presents to his general practitioner with right thoracic pain and dyspnoea, progressively worsening since three days. He was discharged from cardiology a week before, for implantation of a double chamber pacemaker for sick sinus syndrome with symptomatic atrial fibrillation and bradycardia. Clinical examination revealed good cicatrisation of the implantation site, normal cardiac sounds with no murmur, but abolished respiratory sounds in the right lung. Twelve-lead electrocardiogram (EKG) showed a sinus rhythm with paced ventricular response (typical left bundle block pattern). Chest X-ray confirmed the presence of a complete right pneumothorax (Figure 1). The patient was therefore treated with a chest tube and his recovery was uneventful. The additional hospital stay was three days.
Figure 1.
Chest X-ray showing complete right pneumothorax, which was treated with a chest tube.
Comments: Iatrogenic pneumothorax after subclavian venous access is a rare complication whose incidence varies from 1-5% depending on the series, on the realisation of routine post-procedural chest X-ray and on the exact definition of this complication (consideration of both complete and partial pneumothorax, the need for chest tube insertion, hemothorax or gas embolism) (Res et al., 2004). It is usually an immediate complication and is rarely witnessed after discharge. To avoid this complication, access through a central cephalic vein is possible. However, this technique is subject to failure in approximately 20%. The operator’s anatomical knowledge and experience reduce this risk. Pneumothorax is usually asymptomatic and resolves spontaneously in most cases. It is to be suspected in all patients presenting with dyspnoea, unexplainably low blood pressure and variable or elevated stimulation thresholds. Chest tube placement with aspiration is necessary if pneumothorax exceeds 10% of lung volume, if tension pneumothorax or hemothorax are diagnosed.
2.2. Case 2 - Skin necrosis, suture line failure, and lead erosion due to a large pocket hematoma
An 80 year old male needed pacing for complete atrioventricular block is re-admitted three months after implantation. Despite daily wound care by a home-based nurse, the suture line at the site of implantation would not cicatrize. Patient history included myocardial infarction for which percutaneous cardiac intervention (PCI) with a bare metal stent was performed, as well as receiving classical medical treatment that included clopidogrel and aspirin on a daily basis. After implantation, a large hematoma formed in the generator pocket. A conservative treatment was initially proposed. On re-admission, the hematoma had almost completely disappeared, but severe skin necrosis was impeding site closure to the extent that the leads were visible with the naked eye. The absence of infection, as proved by numerous negative swab cultures, allowed for the pacemaker generator to be re-implanted under the pectoralis muscle.
Figure 2.
Hematoma. Lack of suture line healing, pacemaker leads visible.
Comments: Pocket hematoma is the most frequent complication (5% of cases) and can lead to prolonged hospital stay and in the latter case, re-implantation (1-2%) (Kiviniemi et al., 1999 ; Wiegand et al., 2004). Risk factors include use of high doses of low molecular weight heparin, of the association aspirin-clopidogrel, and inexperienced operator. Aspirin alone or an oral anticoagulant like warfarin, to take international normalized ratio (INR) of < 2.0, does not increase the risk of hematoma. Electrocautery or a second look to the pocket is useful to minimize bleeding and the risk of large hematoma. Selective use of topical thrombin is reserved for high risk patients; in Reynolds’s series, the incidence of significant hematoma dropped from 20.8% to 8%. Sometimes drain placement may be necessary and sufficient. Evacuation of hematoma is realised in less than 0.5% with a major risk of infection; potential reasons include persistent bleeding, pain refractory to analgesics, failed healing and skin necrosis.
2.3. Case 3 - Recurrent syncope due to lead displacement
A 60 year old female patient with no medical history and under no current treatment was admitted for complete atrioventricular block causing shortness of breath and dizziness. Implantation of a double chamber pacemaker was performed with ease. P/R sensings were measured at 3.1 mV and 7.8 mV respectively, and both thresholds for stimulation are 0.5 volt/0.4 msec. The next day, the patient represented with dizziness and faints. Lead displacement was suspected. EKG no longer showed physiological stimulation and chest X-ray confirmed lead displacement (Figure 3). Lead repositioning and active fixation was performed successfully.
Figure 3.
Chest X-ray showing migration of both atrial and ventricular leads.
• Failure to OUTPUT: no pacemaker activity. NO SPIKE • battery failure or EOL (end of life), battery trauma lead problems : lead fracture, lead dislodgement, fractured lead insulation, poor lead connection • oversensing causes (myopotentials, electromagnetic interference, cross-talk phenomenon) • "cross-talk” phenomenon • extreme electromagnetic interference • pseudo-malfonction : hystérésis, normal algorithmes (AV conduction)
• Failure to CAPTURE: no depolarisation of the cavity. SPIKE without P/QRS complexes • normal situation : Functional non-capture—output delivered during refractory period • inappropriate programming of the pacemaker (too low safe margin) • lead problems : lead fracture, lead dislodgement, fractured lead insulation, poor lead connection • myocardial perforation • elevated pacing threshold : ○ myocardial infarction (necrosis) at the lead tip ○ drugs (eg, flecainide) ○ dyskaliemia ○ metabolic abnormalities (eg, acidosis, alkalosis)
• Oversensing (Oversensing occurs when a pacemaker incorrectly senses cardiac/noncardiac electrical activity and is inhibited from pacing): • Myopotentials or muscular activity (particularly the diaphragm or pectoralis muscles) • cross-talk phenomenon • electromagnetic interference (eg, Magnetic Resonance Imaging (MRI) • lead fracture and fractured lead insulation
• Undersensing (Undersensing occurs when a pacemaker incorrectly misses intrinsic depolarization and paces despite intrinsic activity) • Normal device function—misinterpretation : triggered mode, fusion and pseudo-fusion beats, functional undersensing (long refractory periods, blanking period, safety pacing, oversensing) • poor lead positioning (poor intrinsic signal amplitude), lead dislodgment, lead fibrosis or thrombosis • magnet application • battery depletion • drugs (eg, flecainide, amiodarone) • metabolic abnormalities (eg, acidosis, alkalosis) • dyskaliemia (eg, hyperkaliemia) • hypothyroidism • ischemia and myocardial infarction • or electrical shock (transient)
Table 1.
Pacemaker Troubleshooting and early complications of pacemaker insertions
Comments: Lead displacement can be found in 2-10% of cases depending on the series (Kiviniemi et al., 1999 ; van Eck et al., 2007). Atrial leads migrate more often than ventricular leads. Active fixation reduces the risk, especially in patients having undergone cardiac surgery. Manifestations include undersensing, failure to capture and increase in pacing thresholds. Repositioning of leads is primordial. Causes of undersensing include lead displacement, fibrosis at the site of fixation of the lead, myocardial ischemia and necrosis, some antiarrhythmic agents (flecainide), dyskaliemia, or transient undersensing following an electric shock (Table I) (de Meester, 2008). When lead displacement is induced by the patient, following a repetitive rotational movement (twisting of the box) and leading to winding of the leads around the generator, we talk of Twiddler’s syndrome; this is observed in certain psychiatric cases, or when the pocket is too big for the pacemaker generator.
2.4. Case 4 - Minor right ventricular perforation
A 77 year-old patient had a physiological pacemaker implanted for symptomatic sinus bradycardia, with sinus arrest. A few days after the intervention, she presented with continuous chest pain. Upon clinical examination, blood pressure was 130/80 mmHg, heart sounds were regular but a pericardial friction rub was audible. EKG showed a sinus rhythm with ventricular capture. Chest X-ray revealed a ventricular lead projecting further than the apex (Figure 4). Cardiac ultrasounds confirmed myocardial perforation by the lead and a minimal pericardial effusion. We decided to abstain from removing the lead, which would have been to some extent invasive in this elderly patient. Treatment by anti-inflammatory drug was installed and was sufficient for pain relief.
Figure 4.
Chest X-ray showing atrial and ventricular leads, with the ventricular lead clearly beyond the cardiac shadow
Comments: Cardiac perforation is a serious complication, with risk of tamponnade and death. It occurs in less than 2% of cases (Ellenbogen et al., 2002). Clinical symptoms are variable, including chest pain, shortness of breath and more rarely hypotension and shock. Advanced age, use of active fixation leads and operator inexperience are contributing factors (Mahapatra et al., 2005). Furthermore, atrial leads seem to perforate more frequently (Hirschl et al., 2007). The new Magnetic Resonance Imaging (MRI)-compatible leads are more rigid, but increased frequency of perforation does not seem to be induced by the use of these leads. Treatment is not standardised, but removal (and replacement) of these leads is crucial in the case of tamponnade and shock. Pericarditis without perforation has been observed in 5% of cases and must lead to close follow-up. Figure 5 illustrates a case of tamponnade. The patient remained stable after drainage.
Figure 5.
Chest scan showing significant pericardial effusion, responsible for pre-tamponnade and shock.
2.5. Case 5 - Skin erosion and exterisation of the generator
An 85 year old female patient is admitted for malaise and confusion. Medical history is positive for asthma treated regularly by corticoids and B2 mimetic aerosols. EKG shows a complete atrioventricular block and, after excluding all reversible causes, a physiological pacemaker is implanted. No complications are noted during her hospital stay. Having regained her autonomy and the confusional episode resolved, the patient returns to her old age home with instructions for routine care for the following weeks. A follow-up is programmed at six weeks and the cardiologist is confronted with a case of skin erosion and exteriorisation of the pacemaker generator (Figure 6). Due to the high risk of infection in this case, the device is removed and a new device is implanted on the contra-lateral side after six weeks of antibiotherapy and with negative hemocultures.
Figure 6.
Erosion and exteriorisation of pacemaker generator in our elderly patient.
Comments: Skin erosion is caused by the pacemaker generator, and is usually a result of pocket infection. Other precipitating factors can be present, for example, the extremely fragile skin of elderly patients, a pocket that is too small, precarious subcutaneous fat, chronic use of corticoids, and use of abrasive disinfectants (Kiviniemi et al., 1999). Exteriorisation of a generator, and/or a lead, is always associated with bacterial contamination, making removal of the material an obligation, accompanied by antibiotherapy and eventually re-implantation on the contra-lateral side. Skin erosion is hence to be sort for and detected before exteriorisation. This is rarely an early complication, and incidence is estimated to be 1%.
2.6. Case 6 - Ventricular lead malposition and right bundle branch block morphology on EKG
A 55 year old patient with history of hypertension, obesity, diabetes, anterior myocardial infarction and severe left ventricular dysfunction has a defibrillator implanted in primary prevention of sudden death. The follow-up is satisfactory with acceptable sensing, impedance and threshold stimulation values on the device programmer. EKG shoes a sinus rhythm with evident old anterior infarction. Chest X-ray, performed in a recumbent position and under non-optimal condition seems satisfactory and the patient is discharged. Upon follow-up one month later, the parameters of the defibrillator are still satisfactory, but the ventricular stimulation shows atypical right bundle block. Chest X-ray confirms the suspected left ventricular stimulation, via a permeable foramen ovale (Figure 7). Lead replacement is indicated seeing the high risk of thrombo-embolic complications in this young patient.
Figure 7.
Chest X-ray showing a ventricular lead that is located higher than usual; this lead is in the left ventricle, having gone through a patent foramen ovale.
Comments: an erroneous lead placement is extremely rare. It remains possible in patients with a patent foramen ovale or an atrial septal defect. Less than twenty cases are reported in the literature (Allie et al, 2000; Blommaert et al., 2000 ; Van Gelder al, 2000; Le Dolley et al, 2009). An EKG during stimulation and chest X-ray in an upright position (antero-posterior and lateral takes) are recommended. The risk of thrombo-embolism, including stroke, of mitral insufficiency should be evaluated. Repositioning of the lead or long term anticoagulation should be considered. When right bundle branch block pacing morphology appears in a patient with a permanent or temporary transvenous right ventricular pacemaker, myocardial perforation or malposition of the pacing lead must be ruled out, even though the patient may be asymptomatic. The overall causes of right bundle branch block morphology include:
erroneous left ventricular lead placement in patient with an atrial septal defect
biventricular stimulation or cardiac resynchronisation therapy (CRT) (Figure 8)
epicardial lead placement.
some cases of “normal” right ventricular apical stimulation
Figure 8.
Chest X-ray showing implantation of 3 leads including a left ventricular lead placed in a branch of the coronary sinus (cardiac resynchronisation therapy).
2.7. Case 7 - Twiddler syndrome in a psychiatric patient
A 68 year old patient, with a history of chronic obstructive pulmonary disease and psychosis, underwent pacemaker implantation for repeated loss of consciousness due to sinus hypersensitivity. Carotid sinus massage resulted in 10 second pauses. The pacemaker was set in double chamber mode and after satisfactory programmation control (P-R sensing 2.5 mV and 12.5 mV, impedance at 564 ohms and 496 ohms respectively, stimulation thresholds at 0.5 volts/0.4 msec), the patient was discharged to his psychiatric institution. At one month follow-up, the patient has no complaints, though anamnesis is laborious. Check-up of the stimulator shows absence of detection of both P and R waves, and absence of atrioventricular capture despite maximal stimulation. Displaced leads are suspected and confirmed by chest x-ray (Figure 9). The patient later admits to having manipulated the pace generator by repeatedly twisting it around. Correct repositioning and fixation of the leads were conducted.
Comments: Twiddler\'s syndrome is describes as the migration of cardiac stimulator leads due to repetitive rotatory movements of the generator in its pocket, secondary to manipulation by the patient himself, which may be intentional or non-intentional (for example, sportsmen). In certain cases, the stimulation of displaced leads can cause pectoral muscle contraction, or life-threatening symptoms in the case of pacemaker dependency (Nicholson et al, 2003; Castillo & Cavusoglu, 2006; Essoh et al., 2010) (Figure 10).
Figure 9.
Chest X-ray showing displaced lead (ventricular lead tip indicated by the star).
Figure 10.
Chest X-ray showing dual-coil ventricular lead displacement, causing pectoral permanent stimulation, in a case previously reported by our team (Essoh et al, 2010). Repositioning the lead was required and successfully reported.
Risk factors include obesity (adipose tissue being less firm in these patients), female sex, elderly patients, patients known as having stigmata for character disorders (obsessive compulsive tendencies, dementia). Treatment consists of repositioning the leads, and changing them in the event of fracture. Several surgical techniques have been proposed to avoid recurrence; implanting the pacemaker generator under the aponevrosis, active lead fixation (almost always the case with implantable cardioverter-defibrillators), Parsonet\'s dacron pouches. Patient education, and psychiatric treatment if indicated, should be proposed.
2.8. Case 8 - Early venous thrombosis after defibrillator with resynchronisation (CRT-D) placement
A 73 year old male has a defibrillator with resynchronisation implanted for ischemic cardiomyopathy after an anterior infarction left him with a left ventricular ejection fraction of 25%. He had presented an episode of ventricular tachycardia with syncope. Implantation of the device was by the subclavian route. There were no immediate post-operative complications and good parameters were recorded for all three leads. Three weeks later, the patient complains of discomfort in the left arm, followed by oedema of the whole arm, forearm and hand (Figure 11); ultrasound and vascular tomodensitometry confirmed complete thrombosis of the left subclavian vein, of the axillary vein, leading up until the convergence of the jugular vein. Anticoagulation therapy was commenced and evolution was slow but favourable in the following weeks.
Figure 11.
Oedema of the left arm, forearm and hand caused by massive thrombosis of the subclavian vein after defibrillator with Cardiac Resynchronisation Therapy (CRT-D).
Comments: Subclavian vein thrombosis is not uncommon. It can occur in about 30% of cases, but usually remains asymptomatic due to the rapid development of collateral circulation (Oginosawa et al., 2002). Less than 5% of patients are symptomatic, presenting mainly with pain or oedema of the arm closest to the implantation site. Risk is higher in cases where three leads are implanted (Cardiac Resynchronisation Therapy (CRT), when the patient is under hormonal therapy, when personal history of thrombo-embolic event is present, with temporary ipsilatérale transvenous lead, during upgrade of a simple pacemaker to a pacemaker with resynchronisation, dual coil leads, and when the ejection fraction is less than or equal to 40% (Da Costa et al., 2003 ; Rozmus et al., 2005). The risk of thrombosis does not differ for pacemakers and implantable cardioverter-defibrillators. Preventive measures may be necessary (platelet aggregation inhibiting drugs or anticoagulation therapy).
2.9. Case 9 - Unusual tachycardia after implantation of a double-chamber pacemaker
A 75 year old male is admitted for repeated fainting caused by major sinus dysfunction as shown by a 24 hour Holter monitor which revealed pauses of up to 8 seconds and paroxystic atrial fibrillation. Medical history was negative and patient was on no current treatment. EKG at rest showed a sinus rhythm with a frequency of 68 bpm and normal repolarisation. A physiological pacemaker is implanted in the operating room. After the intervention, the patient feels palpitations and an EKG recording shows probable pacemaker-mediated tachycardia (Figure 12). Programmation control shows a P-R sensing of 15.8 mV and 1.2 mV respectively, and threshold values for stimulation both inferior to 0.5 volts for 0.4 msec; a connection error is confirmed during threshold verification. Programming in AAI mode would result in VVI pacing, and programming in VVI mode would result in AAI pacing. Re-intervention allowed the correction of this connection error.
Figure 12.
Tachycardia due to an error in the connection of the atrial and ventricular leads. We note the same QRS configuration as with VVI pacing from the apex.
Comments: Atrial and ventricular lead connection errors are rare at implantation, but have already been documented (Barold et al, 2010). Programmation verification allows rapid detection of the switch (“green wire on the green button and red wire on the red button”). A control of the programmation of a stimulator is mandatory before patient discharge. It allows detection and correction of such an error, as well as early detection of a lead displacement. Different types of tachycardia are to be excluded:
Classical "endless loop" or pacemaker mediated tachycardia is rare with the double chamber generators of today.
it is usually initiated by an extra-systole with a retrograde p wave which is easily detected and sustains the circuit. Pacemaker mediated tachycardia can also be provoked by ventricular extra-systoles, by atrial over-detection (myopotentials, interferences) or underdetection and failure to capture
long post-ventricular atrial refractory period (PVARP), excluding retrograde P wave and retrograde conduction, may prevent pacemaker mediated tachycardia
Runaway Pacemaker is due to a malfunction of the pacemaker generator resulting in life-threatening rapid tachycardia (up to 200 bpm).
the generator may malfunction for various causes, including battery failure or external damage.
the use of a magnet can reduce the rate of the rhythm induced by the defiant pacemaker. Generator replacement is necessary.
Atrioventricular nodal reentrant tachycardia. In this case, the stimulator does not intervene in the circuit.
figure 13 shows the initiation of the common type (slow-fast) of atrioventricular nodal reentrant tachycardia ; this is a typical example where the arrhythmia is triggered by an atrial extrasystole which blocks the rapid pathway of the atrioventricular node and allows flow through the slow pathway and thus initiation of the supraventricular tachycardia circuit
radiofrequency ablation is the treatment of choice.
Other reentrant tachycardia includes
atrial flutter
orthodromic circus movement tachycardia using an accessory pathway in the retrograde direction and the AV node in the anterograde direction (concealed or not, in the Wolff-Parkinson-White syndrome)
atrial tachycardia (paroxysmal and nonparoxysmal)
Figure 13.
Baseline rhythm strip showing atrial, ventricular and shock intracardiac electrogram leads, and marker atrial and ventricular channels. This is an example of initiation of common atrioventricular node reentrant tachycardia; see text.
2.10. Case 10 - Recurrent malaise after pacemaker implantation
A man aged 65 with history positive for high blood pressure, diabetes and renal failure actually undergoing haemodialysis receives a pacemaker for complete atrioventricular block with syncope. His treatment includes ramipril, aspirin and insulin. No immediate post-operative complications occur. Just before a haemodialysis session a few days later, the patient complains of feeling faint. An EKG shows evident signs of hyperkaliemia (very wide QRS complexes with tall peaked T waves and obliteration of the ST segment, as well as a long PR interval) and of double chamber stimulation without atrial or ventricular captures (Figure 14). Blood work-up confirms severe hyperkaliemia (potassium 7.8 mEq/L). The atrioventricular underdetection and the absence of capture are caused by the high level of potassium and corrected as soon as kaliemia is normalised by haemodialysis.
Figure 14.
Twelve-lead EKG showing signs of hyperkaliemia and defiant AV detection and stimulation.
Comments: Causes of atrioventricular underdetection and failure to capture are shown in table I. Hypokaliemia is another cause of life-threatening undersensing (de Meester et al, 1996). Correction of the cause is essential for adequate pacemaker function. The risk of triggering ventricular fibrillation, due to a ventricular stimulation during the vulnerable T wave period (R-on-T phenomenon), is present, as is present in asynchronous VOO stimulation or the use of a magnet (Oupadia et al., 1998).
2.11. Case 11 - Important dyspnoea and malaise at follow-up
A 68 year old patient was admitted for class III dyspnoea according to the New York Heart Association (NYHA) score and repeated episodes of malaise since implantation of a single chamber pacemaker in another centre. Her personal history is positive for hypertension and sick sinus syndrome with atrial fibrillation associated with a slow ventricular rhythm and pauses of more than 8 seconds, hence the indication for cardiac pacing. Her treatment is comprised of ramipril, amlodipin and an oral anticoagulant, (acenocoumarol). Clinical examination is unremarkable. Blood pressure was 130/80 mmHg. Twelve-lead EKG shows regular ventricular stimulation at 70 beats per minute, and a basal sinus rhythm. Dissociated P waves are seen (Figure 15). Pacemaker syndrome is suspected, and confirmed. The pacemaker was reprogrammed to VVI 30 bpm to avoid deleterious ventricular stimulation in this patient.
Figure 15.
Twelve-lead EKG showing a dissociated sinus rhythm with right ventricular stimulation.
/Comments:/ This is not a veritable implantation complication but the erroneous choice of a single chamber pacemaker whereas a physiological (or double chamber) stimulator would have avoided the problem. Pacemaker syndrome is described as a combination of symptoms evoking cardiac failure and hypotension in a patient with a cardiac stimulator (Chalvidan et al., 2000). It is caused by the loss of atrioventricular synchronism leading to a drop in cardiac output, elevated atrial pressure and hypotension. The Mode Selection Trial (MOST) investigators defined pacemaker syndrome as occurring if either one of two different criteria occurred (Link et al., 2004). The first criterion was new or worsened dyspnea, orthopnea, elevated jugular venous pressure, rales, and oedema with ventricular (VA) conduction during ventricular pacing. The second criterion was symptoms of dizziness, weakness, presyncope, or syncope, and a >20 mmHg reduction of systolic blood pressure when the patient had VVIR pacing compared with atrial pacing or sinus rhythm. Its incidence is 7-20% of stimulators in VVI mode with a sinus rhythm. Pacemaker syndrome can also be seen in AAIR mode and in double chamber modes (VDD, DDI, DDD) if the stimulator if programmation is sub-optimal or the stimulation mode is incorrectly selected. Dyspnoea should, besides pacemaker syndrome, evoke:
chronotrope insufficiency, especially during exertion, requiring programmation in rate-responsive mode.
Wenckeback functioning in DDD mode
intermittent dysfunction (sensing and pacing)
2.12. Case 12 - Acute infection of the pocket and the cardiac device
A 45 year old female patient suffering from idiopathic congestive cardiomyopathy with a left ventricular ejection fraction of 35%, class III dyspnoea on the New York Heart Association (NYHA) scale, left bundle branch block morphology, with a QRS duration of 175 msec, on EKG and under optimal medical treatment for over three months receives a pacemaker with left ventricular resynchronisation. Implantation was complicated immediately by left ventricular lead displacement. A Starfix Attain OTW 4194 (Medtronic Inc., Minneapolis, MN, USA) was necessary for stability (The Attain Starfix’s design includes three soft, polyurethane lobes near the lead tip that, when expanded, enable stable lead placement in the target location) (de Meester, 2010). After one month, the implantation site becomes suppurative (Figure 16). Local wound care and 10 day antibiotherapy did not help. Bacteriological studies revealed the presence of pseudomonas aeruginosa. Treatment required complete ablation of the material and prolonged antibiotherapy. Re-implantation on the counter-lateral side in this case was performed two months after the end of the antibiotic course.
Figure 16.
Photograph showing suppurative wound with visible pacemaker leads. Ablation of all material was necessary.
Comments: Suture or pocket infection is not a rarity during the first month and incidence is estimated to be 1% (del Rio et al., 2003 ; Klug et al., 2007). Principal risk factors are re-intervention, diabetes, old age, corticoids, operator inexperience, and renal failure. Antibiotic prophylaxis prior to pacemaker implantation has a protective effect. In the case of very early infection, a per-operatory contamination by cutaneous flora (staphylococcus aureus) is the principal source of infection (Kearney et al., 1994 ; Da Costa et al., 1998). Successful treatment of an infected device requires removal of the entire system and administration of antimicrobials. Infection after one month usually originates from the lead (and not the pocket). Sepsis is uncommon and diagnosis includes positive blood cultures (80% of cases) and transesophageal echography showing lead anomalies. Skin erosion at pocket site and other local signs of infection are common. Staphylococcus epidermidis or other gram negative bacteria are most commonly found.
3. Conclusions
Early complications after pacemaker and other cardiac device implantation are not uncommon. Hematoma, skin erosion and pocket infection, as well as lead displacement are the most common of these complications and should be looked for and recognised during routine follow-up, as well as during work-up of any patient presenting a new symptom in the first couple of weeks after implantation. Operator inexperience and implantation in a low-volume centre increases the risk of these complications. Adhesion to good practice and recommended guidelines is indispensable.
\n',keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/19403.pdf",chapterXML:"https://mts.intechopen.com/source/xml/19403.xml",downloadPdfUrl:"/chapter/pdf-download/19403",previewPdfUrl:"/chapter/pdf-preview/19403",totalDownloads:22061,totalViews:1553,totalCrossrefCites:0,totalDimensionsCites:1,totalAltmetricsMentions:6,impactScore:1,impactScorePercentile:62,impactScoreQuartile:3,hasAltmetrics:1,dateSubmitted:"November 6th 2010",dateReviewed:"April 24th 2011",datePrePublished:null,datePublished:"September 6th 2011",dateFinished:null,readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/19403",risUrl:"/chapter/ris/19403",book:{id:"290",slug:"cardiac-pacemakers-biological-aspects-clinical-applications-and-possible-complications"},signatures:"Kabayadondo Maidei Gugu and de Meester Antoine",authors:[{id:"37387",title:"Dr.",name:"Antoine",middleName:null,surname:"de Meester",fullName:"Antoine de Meester",slug:"antoine-de-meester",email:"antoine.demeester@skynet.be",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"53501",title:"Dr.",name:"Gugu",middleName:null,surname:"Kabayadondo",fullName:"Gugu Kabayadondo",slug:"gugu-kabayadondo",email:"mgkabayadondo@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Clinical cases",level:"1"},{id:"sec_2_2",title:"2.1. Case 1 - Latrogenic pneumothorax resulting from subclavian puncture ",level:"2"},{id:"sec_3_2",title:"2.2. Case 2 - Skin necrosis, suture line failure, and lead erosion due to a large pocket hematoma ",level:"2"},{id:"sec_4_2",title:"2.3. Case 3 - Recurrent syncope due to lead displacement ",level:"2"},{id:"sec_5_2",title:"2.4. Case 4 - Minor right ventricular perforation ",level:"2"},{id:"sec_6_2",title:"2.5. Case 5 - Skin erosion and exterisation of the generator",level:"2"},{id:"sec_7_2",title:"2.6. Case 6 - Ventricular lead malposition and right bundle branch block morphology on EKG",level:"2"},{id:"sec_8_2",title:"2.7. Case 7 - Twiddler syndrome in a psychiatric patient",level:"2"},{id:"sec_9_2",title:"2.8. Case 8 - Early venous thrombosis after defibrillator with resynchronisation (CRT-D) placement",level:"2"},{id:"sec_10_2",title:"2.9. Case 9 - Unusual tachycardia after implantation of a double-chamber pacemaker",level:"2"},{id:"sec_11_2",title:"2.10. Case 10 - Recurrent malaise after pacemaker implantation",level:"2"},{id:"sec_12_2",title:"2.11. Case 11 - Important dyspnoea and malaise at follow-up",level:"2"},{id:"sec_13_2",title:"2.12. Case 12 - Acute infection of the pocket and the cardiac device",level:"2"},{id:"sec_15",title:"3. Conclusions",level:"1"}],chapterReferences:[{id:"B1",body:'AllieD. E.LirtzmanM. D.WyattC. H.VitrellaD. A.WalkerC. M.2000 Septic paradoxal embolus through a patent ovale after pacemaker implantation. Ann Thorac Surg,\n\t\t\t\t\t699468'},{id:"B2",body:'BaroldS. S.StroobandtR. X.SinnaeveA. F.2010\n\t\t\t\t\tCardiac Pacemakers and Resynchronization Step by Step: An Illustrated Guide,Wiley-Blackwell editors.\n\t\t\t'},{id:"B3",body:'BlommaertD.MucumbitsiJ.De RoyL.2000 Images in cardiology. Ventricular pacing and right bundle branch block morphology: diagnosis and management. 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M.et al.2004\n\t\t\t\t\tHigh incidence of pacemaker syndrome in patients with sinus node dysfunction treated with ventricular-based pacing in the Mode Selection Trial (MOST).J Am Coll Cardiol, 43206671\n\t\t\t'},{id:"B26",body:'MahapatraS.BybeeK. A.BunchT. J.EspinosaR. E.SinakL. J.Mc GoonM. D.HayesD. L.2005\n\t\t\t\t\tIncidence and predictors of cardiac perforation after permanent pacemaker placement.Heart Rhythm, 290711\n\t\t\t'},{id:"B27",body:'NicholsonW. J. .TuohyK. A. .TilkemeierP.2003 Twiddler’s syndrome. N Eng J Med, 3417267'},{id:"B28",body:'OginosawaY.AbeH.NakashimaY.2002\n\t\t\t\t\tThe incidence and risk factors for venous obstruction after implantation of transvenous pacing leads.Pacing Clin Electrophysiol, 25160511'},{id:"B29",body:'OupadiaP.RamasswamyK.1998 R-on-T phenomenon” Images in Cardiology. N Engl J Med, 338: 1812 EOF'},{id:"B30",body:'ResJ. C. J.de PriesterJ. A.AAvan Liervan EngelenC. L. J. M.BronzwaerP. N. A.Tan-HP.VisserM.2004\n\t\t\t\t\tPneumothorax resulting from subclavian puncture: a complication of permanent pacemaker lead implantationNeth Heart,\n\t\t\t\t\t121015'},{id:"B31",body:'RozsmusG.DaubertJ. P.HuangD. T.RoseroS.HallB.FrançisC.2005 Venous thrombosis and stenosis after implantation of pacemakers and defibrillators. Pacing Clin Electrophysiol, 13919'},{id:"B32",body:'SohailM. R.UslanD. Z.KhanA. H.et al.2007\n\t\t\t\t\tManagement and outcome of permanent pacemaker and implantable cardioverter-defibrillator infectionsJ Am Coll Cardiol,\n\t\t\t\t\t4918519'},{id:"B33",body:'TrohmanR. G.KimM. H.PinskiS. L.2004\n\t\t\t\t\tCardiac pacing: the state of the art.Lancet364170119'},{id:"B34",body:'van EckJ. W. M.van HemelN. M.ZuithofP.et al.2007\n\t\t\t\t\tIncidence and predictors of in-hospital events after first implantation of pacemakersEuropace98849'},{id:"B35",body:'BMVan GelderBrackeF. A.OtoA.YildirirA.HaasP. C.SegerJ. J.et al.2000\n\t\t\t\t\tDiagnosis and management of inadvertently placed pacing and ICD leads in the left ventricle: a multicenter experience and review of the literature.Pacing Clin Electrophysiol, 2387783\n\t\t\t'},{id:"B36",body:'VardasP. E.AuricchioA.BlancJ. J.et al.2007 for the Task Force Members. Guidelines for cardiac pacing and cardiac resynchronisation therapy. (2007). Europace, 995998'},{id:"B37",body:'WiegandU. K.Le JeuneD.BoguschewskiF.BonnemeierH.EberhardtF.SchunkertH.BodeF.2004\n\t\t\t\t\tPocket hematoma after pacemaker or implantable cardioverter defibrillator surgery: influence of patient morbidity, operation strategy, and perioperative antiplatelet/anticoagulation therapy.Chest126117786\n\t\t\t'},{id:"B38",body:'ZollP. M.1952\n\t\t\t\t\tResuscitation of the heart in ventricular standstill by external electric stimulationN Engl J Med, 247: 768.\n\t\t\t'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Gugu Kabayadondo Maidei",address:null,affiliation:'
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1. Introduction: from bioethanol to biorefineries
The progenitor of the modern biorefinery concept was bioethanol production. In the 1970s, Brazil and the United States started mass production of bioethanol grown from sugarcane and corn respectively. The most common usage of bioethanol is to power automobiles by mixing it with petrol. The sugar yield from these feedstocks is very high and the biomass processing is rather simple, thus fueling the transportation this way was economically viable, especially in the countries with scarce fossil fuel resources, like Brasil.
Bioethanol is generally CO2 neutral because the released during the burning of ethanol is compensated by the absorption of the CO2 by growing the feedstock biomass. This however does not consider the CO2 generated by the logistics of the biomass production and processing. Besides, blending bioethanol with gasoline helps to reduce greenhouse gases (GHG) emissions by oxygenating the fuel mixture which makes it burn more completely. Thus bioethanol was considered to be an environmentally friendly alternative to petrol.
In the future, with improved efficiency, utilization of non-agricultural feedstocks and use of renewable energy, the respective life cycle GHG emissions could be cut by up to 86 percent relative to gasoline as reported in EPA’s Emission Facts [EPA (2007) Emission Facts; Greenhouse Gas Impacts of Expanded Renewable and Alternative Fuels Use. Emission Facts Report (EPA420-F-07-035). Office of Transportation and Air Quality, EPA, US].
Thus the agenda of bioethanol production was shifted to the products derived from lignocellulosic biomass to avoid competition with food and limit the use of agricultural land.
In the brink of the 21st century a considerable public and private effort to implement the so-called second-generation bioethanol industry based on lignocellulosic, non-edible feedstock was undertaken, and eventually faded away due to economic inefficiency. The frustrating experience of lignocellulosic bioethanol hype of the past years triggered the formation of a broader view of the biorefinery concept. It grew with the understanding that if only a part of the biomass, namely the cellulose, is used to make a product, moreover, not a high-value product such as bioethanol, the economics of such an undertaking does not work [1].
This notion coincided with the growing understanding that biomass is not merely a quick fix for a deficit of fossil resources in some countries, but a fundamental raw material for bioeconomy. Consequently, a biorefinery concept was forming with the term borrowed from the petroleum oil refinery, which goes beyond the exhaustion of biomass into a spectrum of products. Biorefineries are based on four principles [2], namely principles of sustainability, cascading, non-conflict with food, and neutral carbon footprint.
Thus to implement the biorefineries as fundamental units of bioeconomy, all biomass components cellulose, hemicellulose, and lignin need to be utilized. Moreover, the general approach should be similar to the oil refinery concept - the raw material needs to be fractionated to result in a range of intermediates leading to a variety of products from high to low-value. Ideally, there has to be in-built flexibility allowing to change the product portfolio according to the current market demands.
One of the fundamental differences of biorefineries from oil refineries is the repertoire of tools that can be used, where enzymes - the natural catalysts play an important role.
Nature is using biocatalysts – the protein molecules called enzymes - for performing virtually all biochemical reactions happening inside organisms, and often outside as well.
It is logical to assume that a bio-based economy would be largely relying on bio-catalysis. Extremely high specificity and selectivity as well eco-friendliness make enzymes potentially very attractive in many industrial applications.
2. Biorefinery as an industry sector
Following the concept of Biorefineries, the society has to make a leap from biofuel factories using local agricultural feedstocks to produce bioethanol for fulfilling local demand for automobile fuel to the biorefineries providing raw materials for various industries from energy to chemicals and materials producers. From this perspective, wood seems to be the most likely feedstock to be able to fulfill the industry demand.
It has to be noted that biomass alone, wood or other types, is unlikely to fulfill the energy demand of modern society from the volume point of view. Other energy-providing technologies, like solar and wind energy need to fill in the gap. However, biomass is suited to assume other roles in a circular economy, related to materials and chemicals. This notion provides only more motivation for diversifying the biorefineries’ product range.
Wood is one of the most abundant, sustainable raw materials on Earth, which is available around the year. It requires no roof for storage and has a high density, which is favorable for logistics and handling. Furthermore, it requires no additional field space and has no agricultural or nutritional use.
If wood is the most likely feedstock of the rising bioeconomy, then the pulp and paper industry is the most likely first block in the value chains of the biobased products. This industry has many years of experience in maintaining and working forests, as well as harvesting, transporting, and processing wood. It is also noteworthy that in the Nordic countries, the volume of sustainably harvested forests is growing faster than the current consumption: regulation and standardized systems are in place to allow forests to be harvested sustainably to meet significant industrial demand.
The drawback of this industry being at the foundation of the biobased economy is that this industry has highly refined processes focusing on cellulose fibers only, the industry is highly conservative due to low-margin economic positioning and besides this industry in its current state is used to offering a very narrow product portfolio which is marketed through distributors.
Diversifying the product offering of the pulp and paper industry may require changes in the processes or the addition of parallel process lines and more intimate interaction with various markets. This in turn requires investments and a change in attitude.
Biorefineries can be positioned on the interface of pulp and paper/forestry industry and chemicals and materials industry. And it has to be admitted that this interface is yet to be created. For example, it can be implemented with a third party operating a biorefinery with the over-the-fence supply of raw materials (feedstocks) and possibly even utilities from a pulp and paper mill. These feedstocks may comprise lignin, zero fibers (short fibers disposed of with the wastewater), pulp products depending on the demand of both markets. This could be set up as a joint venture so that both organizations can benefit from this model. Alternatively, a joint venture with the end-user of the biorefinery products can be envisaged as well.
Enzymes as an important part of the economics and the technology of the biorefineries can also be considered as part of the production process. On-site manufacturing of enzymes allows saving costs on concentration, formulation, storage, and shipping of the enzymes. Some companies embracing biorefineries, develop their own enzymatic solutions to be implemented in their biorefineries, and can set up on-site manufacturing at their will. Whereas other types of biorefinery owners, like pulp and paper companies, usually rely on an external enzyme supplier. Usually, enzyme suppliers are not open to providing their production strains to third parties for on-site manufacturing. In this respect, MetGen has a more flexible business model towards supplying enzymatic solutions for biorefineries, including a possibility of on-site manufacturing.
3. Enzymes—ultimate tools for biobased industries
Many if not most industrial chemical processes are dependent on catalysts - substances that accelerate chemical reactions without themselves being consumed in the catalyzed reaction and can continue to act repeatedly. Because of this, only very small amounts of catalyst are required to have a dramatic effect on the reaction rate. The development of affordable durable and efficient catalysts was vital for the establishment and economic viability of fossil-based chemistry and material science.
It is equally important for the biobased economy to adapt and further develop nature’s catalytic tools.
The historic concern about enzymes is that they are vulnerable to industrial conditions and often could not be applied to existing industrial processes. Modern molecular biology and bioengineering pave the way to much wider use of enzymes in the industry by making it possible to adapt enzymes to performing in unnatural harsh conditions. The development time for new enzymes was further reduced with the development of bioinformatics tools and genome editing.
Especially as new bio-based processes are being developed it is a good time to consider making them more enzyme-adaptable by assuming somewhat longer retention times while transitioning to lower temperatures and pressures, as compared to currently common conditions.
Enzymatic processes are truly similar to chemical catalysis. They can be run as homogeneous catalysis with a soluble enzyme added and disposed of with every production batch, or as heterogeneous catalysis, where the enzyme is used in the immobilized form and reused from batch to batch or used in a continuous process with a column set up.
Importantly, the enzymes present also a third option not applicable with the chemical catalysts - a continuous membrane bioreactor. Sometimes this technology is called “enzymes immobilized by perfusion”. This setup exploits the best of the previous two - affordability of the soluble enzyme and reusability of the immobilized one. In this setup, the enzyme is trapped in a bioreactor connected to a tangential flow micro-filtration membrane unit allowing the low-molecular-weight product to penetrate through the membrane but retaining the enzyme inside.
This setup allows not only an efficient use of the enzyme but can also provide product fractionation and more complex designs with parallel processes. Ultra and nano-filtration is also a very useful and economical water removal tool. We will further discuss this setup in the section dedicated to lignin valorization.
3.1 Bioconversion—enzyme or whole cell?
One important aspect of enzyme-dependent catalysis is the necessity of a cofactor for some enzymes. Cofactors are important accessories to biochemical processes. They are small organic compounds or metal ions empowering enzymes to function at maximal catalytic effectiveness or endurance. Cofactors may aid in substrate binding, catalysis, stabilizing the transition state, or contributing to the overall stability of the enzyme’s structure. In some cases cofactors are modified during the reaction, for example, providing or accepting an electron in reduction–oxidation reactions, or providing energy through a high energy bond braking. In this case, in order to be reused, cofactors need to be regenerated during the reaction - oxidized/reduced/phosphorylated respectively. Regeneration requires another enzyme and a co-substrate to be oxidized or reduced. With the cofactor regeneration in place, the reaction can proceed continuously with only a small amount of the cofactor present. The chemistry of cofactor regeneration is well known nowadays [3]. The challenge is mostly regarding how to achieve the regeneration with immobilized enzyme systems which are preferred for industrial processes to facilitate the recovery and continuous use of the catalysts. This has become a great hurdle for the industrialization of many promising enzymatic processes. Once again, recent advances in membrane technologies led to the development of sustainable methods based on membrane entrapment [4].
Nevertheless, the necessity of a cofactor complicates the enzymatic process and increases the cost. Thus most of the bio-transformations involving cofactors have been traditionally performed in the industry with living cells often referred to as microbial cell factories [5].
Whole-cell biotransformation has advantages and disadvantages as compared to the enzymatic process. As mentioned before it solves the problem with the cofactors as they are widely used in cell metabolism and regeneration routes are in place. The balance of cellular metabolic fluxes can be further genetically adjusted for the increased level of the components necessary for the product synthesis. Another advantage of the microbial cell factories is that multistep reactions can be carried out, and it is often possible to use simple and affordable raw materials such as glucose because the cell has a metabolic pathway in place to convert it to a large variety of precursor and eventually to the final product. Among the shortcomings of the cell factories, one should mention a very narrow operational space due to microorganisms viability constraints. While some individual enzymes can tolerate high temperatures close to water boiling point and a wide range of pH, industrial microorganisms are usually performing only in ambient conditions. Besides, there are often multiple pathways in the cell to convert the starting material, which leads to the formation of side products. In more detail, the cons and pros of enzymatic and whole-cell bioconversions are listed in Table 1. In conclusion, as opposed to whole microorganism bio-conversions, more common in the past, enzymes provide faster and safer processes with a broader operational range.
Enzymatic process
Whole call process
Temperature, pH range
Wide
Narrow
Substrate/product load
High
Low
Tolerance to solvents
Moderate
Low
External cofactors/cofactor regeneration system
Needed
Not needed
Multistep processes
Difficult
Natural
Control over the reaction speed
By increasing the enzyme concentration
Only by increasing the size of the vessel
Side products
No
Yes
Table 1.
Enzymatic process vs. whole-cell bioconversion.
Enzymes are also attractive in industrial use from the safety point of view: enzymes are not living organisms and they cannot breed (as opposed to the whole-cell factories) and can be considered environmentally safe. Additionally, being proteins, enzymes do not create toxic waste and decompose naturally over time. It should be noted that enzymes – as is the case with all proteins – may cause allergenic irritation. Therefore, the use of highly concentrated industrial enzymes should always be done according to handling instructions and material safety documentation.
Thus, with all the pros and cons in mind, the preferred type of bioconversion needs to be identified for each particular process.
Respective sectors of molecular biology dealing with enzymatic processes and whole-cell bioconversions are Enzyme engineering [6] and Metabolic engineering [7] respectively. Where enzyme engineering provides tools for optimizing protein structure for better performance; and metabolic engineering provides tools for optimizing the microbial genome to redistribute metabolic pathways in favor of the desired product formation. It has to be noticed that industrial process engineering is extremely important to go hand in hand with molecular engineering.
3.2 Enzyme resources of nature
Enzymes are extremely abundant in nature and exist in all living organisms from bacteria to humans. All industrial enzymes have their origin and prototypes in nature, where wood is decomposed by rot microorganisms, the most efficient of which are fungi. It is thus natural that most enzymes used in industry for wood and other biomass applications are of fungal origin. Robust industrial strains and processes for fungal enzyme production have been developed through decades of optimization.
One of the major problems of fungal enzymes is that fungi are not known to live in extreme environments, such as elevated temperatures and extreme pHs, and their enzymes are usually not tolerant to harsh industrial conditions, which is sometimes limiting their application. In contrast, bacteria populate such environments as hot springs, salt lakes, and ocean depths. Some bacteria also possess individual enzymes with relevant catalytic activities for industrial biomass applications. Recent advances in molecular biology, genome sequencing, and genetic engineering made bacterial enzymes an attractive alternative to their fungal counterparts. Bacteria offer more diverse natural prototypes, and there are better-developed tools for genetic engineering in bacteria, allowing further optimization of the enzymes to required conditions.
Some unique industrial enzymes of bacterial origin have been developed in the past years breaking the boundaries of industrial enzyme applications. Nevertheless, when multiple enzymes are required in one process, such as cellulases, fungal production is usually a preferred option.
4. Biomass hydrolysis
4.1 Biomass pretreatment
The biorefinery platform requires pretreatment of lignocellulosic materials, which can be very recalcitrant, to improve further processing through enzymatic hydrolysis, and for other downstream unit operations.
Pretreatment employs a combination of chemical and physical elements such as temperature, pressure, and acid or alkali. This partially separates biomass components such as cellulose, hemicellulose, and lignin from each other resulting in a paste-like rather than a solid substance. This level of destruction allows access of enzymes to all the biomass components and further separation and hydrolysis.
Many pretreatment methods and unit operations were inherited from the bioethanol-oriented processes, where the target product was a fermentable sugar mix, and the ultimate goal to reduce the cost of the process. Now, when the focus of the biorefinery concept has shifted from the design of more or less energy-driven biorefineries to much more versatile facilities where chemicals and other raw materials can be produced apart from energy carriers, the view to the pretreatment has been transforming as well. In some cases, a pretreatment with a higher cost, but also better separation of the biomass components and higher quality streams are preferred. For example, organosol or chemical treatment employing ionic liquids and deep eutectic solvents. In the end, the choice of pretreatment must be based on a thorough techno-economic evaluation considering the proposed applications and the source of the biomass. This topic is reviewed in detail elsewhere [8, 9].
4.2 Cellulases for biomass hydrolysis
It is well known that wood is efficiently decomposed in nature by filamentous fungi. In their natural habitat, these microorganisms live on a solid substrate like wood and secrete a number of hydrolytic enzymes degrading all wood components down to low molecular weight substances that can be used as nutrients. In industry, the enzyme preparations were traditionally obtained by the propagation of the fungal strains in a liquid medium, and such production method resulted in a cocktail of different enzymatic activities, often generally referred to as cellulase [10]. Fungal metabolism has a complex regulation in order to be able to produce the set of enzymes relevant to the available type of biomass [11]. Thus, for example, cellulase production by the fungal cells is induced by certain compounds generated in wood hydrolysis. The enzymatic cocktail produced by a fungus depends on the fungal strain properties and is not always optimal for a particular industrial application.
The most noticeable hurdle for the industrial application of natural fungal cellulase cocktails is the mechanism preventing glucose accumulation in the environment of the fungal cell. Such accumulation could provide a favorable environment for competing microbes such as bacteria, which cannot degrade wood themselves. To achieve this regulation, all of the enzymes of the cellulase cocktail are inhibited by their reaction products [12]. As seen in Figure 1, cellulose is initially attacked by a number of enzymes most prominent one - exoglucanase (also known as cellobiohydrolase or CBH) comprising more than 50% of total protein in the cocktail, which is assisted by accessory enzymes endoglucanase, oxidative cellulase lytic polysaccharide monooxygenase (LPMO), and indirectly by other enzymes. The concerted action of these enzymes results in the formation of glucose dimer, cellobiose. This is followed by the last step of the cellulose hydrolysis, splitting cellobiose to two glucose, performed by beta-glucosidase. Glucose is further absorbed by the cell and metabolized. If the hydrolysis proceeds faster than glucose is consumed causing glucose accumulation, beta-glucosidase is inhibited by glucose and slows down, this, in turn, results in cellobiose accumulation slowing down exoglucanase, and thus the entire chain of the reactions is regulated by the feedback response from the last step (as shown with red arrows in Figure 1). However, in industrial biomass hydrolysis, glucose accumulation is the ultimate goal. Thus, this feedback loop needs to be overruled. This is usually done by artificially increasing the amount of beta-glucosidase in the cocktail. This can be done by inserting additional genes for beta-glucosidase into the fungal strain. Besides, some beta-glucosidases are less inhibited by glucose (or more glucose-tolerant) than others, and this can also be exploited in composing industrial cellulase cocktails. It has to be noted that glucose tolerance of beta-glucosidases is poorly understood and occurs more often in bacterial enzymes than in fungal ones. Elucidating the molecular mechanisms of glucose tolerance is a very important aspect of cellulose biotechnology research of glucose tolerance [13].
Figure 1.
Natural regulation of cellulose hydrolysis.
Apart from providing a feedback regulation of hydrolysis speed, beta-glucosidase has another important function - generating the inducers of cellulase gene expression and ultimately the cellulase production. Those inducers are unusual glucose dimers of which sophorose, a glucose dimer with β-1,2 bond, is the most efficient one. In nature, these compounds appear in small amounts in the presence of cellobiose as a result of a side-activity of some beta-glucosidases. This activity is referred to as trans-glycosylation [14]. The molecular mechanism underlying the ability of the beta-glucosidase to perform trans-glycosylation is obscure. There are several different glucosidases in the fungal cell, extracellular as well as intracellular. Most probably it is the intra-cellular beta-glucosidases that are responsible for the inducer generation in nature [15].
In the industrial hydrolysis process, the inducer sugar is produced artificially from glucose either using random chemical dimerization catalyzed by phosphoric acid under elevated temperature and pressure or using beta-glucosidase with transglucosylase activity.
Thus in cellulose hydrolysis, CBH is the most prominent enzyme comprising more than a half of the total protein content of the cocktail, however, beta-glucanase is the most important enzymatic tool to providing cellulase efficiency in industrial hydrolysis applications.
Biochemists and molecular biologists have been studying the components of fungal cellulases and identified specific proteins responsible for the degradation of various plant polymers such as cellulose, other glucans, pectin, xylan, mannan, lignin, etc.
The native cocktails were improved after discovering that certain additional activities could enhance the conversion rates of specific biomass feedstock types [16, 17, 18, 19]. For example, feedstocks could comprise different plants, pretreatments, or combinations of both. These augmented cellulases were produced by blending different secretomes containing the desired activities. More recently, some required activities have been genetically engineered into production strains.
Despite the considerable improvements in general-purpose cellulases available from the main enzyme-producing companies, a “one-size-fits-all” cellulase does not effectively address the wide range of biomass type-pretreatment chemistry combinations. However, customization of the cellulase cocktail is not commonly offered by enzyme producers. On the contrary, MetGen offers customization of the hydrolysis solution MetZyme® SUNO™ to the client’s specific substrate/pretreatment as well as an option for on-site enzyme manufacturing.
4.3 Special enzymes for biomass degradation and valorization
Biomass is mostly comprised of polymers. The main structural components of plant biomass are polysaccharides (cellulose, hemicellulose, starch, pectin, and other plant polymers), and polyphenols (lignin). All these polymers apart from cellulose are branched and diverse in structure. In the plant cell, they are interlaced to form a complex and often recalcitrant structure.
Natural fungal cocktails are instrumental in the full hydrolysis of the biomass to monomers or low molecular weight compounds. This was the mainstream strategy of non-food biomass processing in the biofuel era. When we think of wider and wiser use of the biomass in a range of industrial applications it may appear sensible to preserve the polymeric structure of certain components. This can be partly achieved by choosing the right pretreatment method and other chemical and physical methods of processing the streams. Further, the process of biomass fractionation can be tuned by enzymes.
Generally speaking, the same enzyme toolbox is applicable both in the biorefinery industry and in Pulp and Paper sector. Notably, however, while in the P and P industry enzymes are minor and optional components of the process, in the biorefinery concept, enzymatic processes play a major role and represent a major cost, thus also opening a major market.
Let us consider how various product streams from biomass can be tuned by specific enzymes. An overview of the individual enzyme activities used in enzymatic solutions provided by MetGen is given in Table 2.
4.3.1 Lignin valorization
In the earlier biorefinery concepts, lignin was often mostly regarded as a recalcitrance factor, fermentation inhibitor, sugar stream contaminant, etc. A broader view of the biorefinery, however, considers the valorization of lignin as a vital component of the economics of the entire concept. This is why it is one of the fastest-growing research and development areas in the biomass valorization field [20, 21, 22, 23].
The main hurdles of lignin valorization are its diverse structure and poor solubility. Liquefaction of lignin would allow its use as fuel, as it is reached in high-energy chemical structures. More precise depolymerization or fragmentation of lignin may enable higher-value products for various industries from construction to high-performance materials. Even though lignin-based replacement products have already been reported [20, 24, 25, 26] to be useful as binders, coatings, and fillers, and others, these applications are not yet widely industrially implemented. The main challenges for the full valorization of lignin are the economical production of suitable lignin and maintaining consistent quality throughout different batches. In order to achieve desirable properties for the industrial application, lignin usually needs to be fragmented and refined to a lower molecular weight and often chemically modified as well.
Enzymatic degradation of lignin, which occurs in nature, was speculated for a long time to be applicable in the industry [27]. This approach seems attractive because the catalysis takes place in water and under mild conditions avoiding high pressure, temperatures, and hazardous and expensive chemical catalysts, thus saving CAPEX and lowering environmental impact.
Research efforts for enzymatic lignin depolymerization were especially focusing on laccases (copper oxidases), as these enzymes require no cofactors, or co-substrates (such as hydrogen peroxide), they use oxygen as an electron acceptor and produce water as the only by-product. Prospective and challenges of laccase application in biotechnology were recently reviewed [28, 29]. The vast majority of industrially available laccases are fungal enzymes. These enzymes, however efficient, work in acidic-to-neutral pH [30], at which lignin is hardly soluble in water. This prevents their industrialization in this area.
Recently METGEN has developed and brought to the market a proprietary lignin refining technology METNIN™. This technology is based on combining enzyme-catalyzed lignin oxidation and cascading membrane fractionation. The enzymatic element of this technology is a proprietary artificially evolved enzyme MetZyme® METNIN™ laccase able to function under extremely alkaline conditions (typical process pH 10.5) [31, 32]. METNIN™ process is outlined in Figure 2. Membrane-based separation of lignin by molecular size provides useful fractions of various molecular weights.
Figure 2.
METNIN™ process, schematic representation.
Lignin preparations of different molecular weights can be further valorized and utilized in various industrial applications [20, 25] as long as chemical/physical properties are matching the requirements [33]. Thus, the target of lignin refining is to create lignin fractions that are bioequivalent, for example, to oil-based compounds used as resins, adhesives, composites and foams (Table 3).
MetGen’s product families and respective enzymatic activities.
Lignin type
Application areas examples
Bio-equivalent of
Indicative price of the oil-based chemical
Crude Lignin
Fuel
Oil/Electricity
50–100 €/ton
METNIN™ MACRO
Bitumen, Fillers (Market established products, agro)
SBS Polymer, Inorganic fillers
400–600 €/ton
METNIN™ MICRO
Coatings & Surface treatment (Sizing value chain, Carbon fibers, agro)
Phenol resins, AKD, ASA, Wax, Latex
1000–2000 €/ton
METNIN™ ULTRA
Composites (Toy value chain)
Polyols
1500–3000 €/ton
METNIN™ NANO
Carbon Fibers (re-polymerized version), new materials
Specialty Chemicals, aromatics & phenols
> 4000 €/ton
Table 3.
METNIN™ products.
Importantly, the absence of organic solvents in the reaction mixture allows for utilization of polymer-based ultrafiltration membranes widely used in the food industry, making this technology scalable and economically feasible. Ultrafiltration membranes of different cut-off are available and widely used in industry. The choice of membranes can be customized and adds flexibility to the technology. By adjusting process parameters, outcoming lignin properties and mass distribution between the fractions can be changed.
Demethylation is a desirable process in lignin upgrade, as it increases the number of hydroxyls and thus results in activation of lignin. Demethylation can be monitored by measuring MeOH in the reaction mixture after depolymerization using Purpald-method [34]. This is a fast and convenient method to monitor the oxidation process, however, it does not give the full picture of the chemical modification of the lignin, as some of the resulting hydroxyls can end up in new ester bonds or be further oxidized. For further characterization, titration methods and NMR need to be used. Using these methods, we observed an increased number of hydroxyls and sometimes carboxylic groups per gram of dry matter, especially towards lower Mw fractions.
METNIN™ process allows tuning the resulting fractions in several ways: by choosing membranes with different cut-offs according to the desired molecular weight, by adjusting the extent of oxidation to tune other properties such as the content of OH-groups (phenolic aliphatic and carboxylic), and controlled polymerization, which affects reactivity and solubility of the resulting fractions. Thus variance in the starting material can be compensated by the process adjustment and the refining process results in more homogeneous fractions with a less batch-to-batch variation. Post-fractionation processing of the fractions can further tune the properties – purity and solubility in water or solvents.
Refining of lignin in METNIN™ process is accompanied by chemical activation via demethylation and benzylic oxidation as well as increased solubility in neutral and acidic pH and altered colloidal behavior. The process parameters largely depend on the starting lignin itself. In practice, each new lignin needs to be investigated to understand its behavior in the process.
One of the biggest challenges of lignin valorization is that lignin’s structure is highly dependent not only on the species of wood but also on the treatment and extraction method. Therefore, the process parameters of lignin oxidation and fractionation need to be optimized experimentally. MetGen not only provides the licensing of the technology but also offers customer-specific projects for demonstration of the impact of METNIN™ process on customer’s lignin.
METNIN™ process has been demonstrated and is routinely run at a pilot-scale (400 Liters reactor vessel). In addition, technology transfer to a ton (1000 kg) scale batch production has been completed and an engineering package for the industrial scale is developed and available for licensing from MetGen. Lignin fractions were tested in various applications.
Oligomeric fraction METNIN™ ULTRA was used as lignopolyol to completely replace a commercial polyol in polyurethane rigid foam formulations [35]. The specifications of the obtained foams such as closed cell count, water uptake, and compression characteristics, were all within industry standards for rigid foam applications.
METNIN™ MICRO showed excellent potential in paper coating application and the respective product is being developed together with the pulp and paper industry. Other applications are being tested with industry partners.
4.3.2 Cellulose fibers modification
Cellulose is the most traditional product from non-food biomass. Cellulose fibers further turned into paper were produced for centuries by the pulp and paper industry. However, if the printing and writing paper used to be the main product of this industry, the recent changes in the consumer market and the digitalization of the information market shifted the focus of the pulp and paper industry to hygiene and packaging products, which are much more diverse in terms of the required properties of the fibers (strength, softness, odor, water absorption/resistance etc). Changing the fiber properties can be achieved by adjusting the wood refining and chemical treatment, however, it can also be enhanced by enzymatic treatment [36]. For this purpose, individual enzymes or a set of enzymes are needed rather than a natural hydrolytic cocktail.
The main component of fiber strength improvement cocktail is endoglucanase, an enzyme that introduces individual brakes in a cellulose strand [37]. It attacks amorphous regions of cellulose fiber, where the crystalline structure was distorted by refining. These brakes make fibers more “hairy” and improve fibrillation (incorporation of the fibers into paper webbing), which eventually translates into improved strength properties of the paper [38, 39]. This enzymatic activity can also be used to even further cleave the amorphous region and help to create nano-cellulose [40], which is widely used in various applications from packaging to electronics and health. The conventional mechanical process of obtaining nanocellulose is highly energy demanding and enzymes can considerably reduce the required refining energy. Another cellulose base product with growing demand is the so-called dissolving pulp, which is used for viscose production. The process of liquefying the pulp by separating the fibrils (the strands of cellulose) is also highly energy demanding and chemically polluting. Viscose production can be more eco-friendly and economic by using enzymes, specifically xylanases and cellulases to selectively remove hemicelluloses and improve pulp reactivity, respectively [41].
These cellulose products are usually not considered to be in the scope of biorefineries but rather pulp and paper industry, however, some fiber-based products could be introduced into the biorefineries offering. The MetZyme®BRILA™ product family of MetGen’s portfolio is dedicated to fiber modification solutions (see Table 2).
4.3.3 Glucose conversion
The main outcome of cellulose processing in the biorefineries is currently glucose. Glucose is the central nutrient in the microbial world. Almost all microorganisms can be cultivated on glucose with some supplement of nitrogen-containing compounds and microelements. Thus the demand for glucose will grow as the bioeconomy develops. And glucose can be a starting material for bioconversion to practically any natural compound by a whole-cell microbial factory.
Apart from being a central nutrient for microbial production glucose can also serve as a starting material for platform chemicals [42]. By acid catalysis, sugar molecules can be converted to platform chemicals such as hydroxy-methyl furfural (HMF), furfuryl alcohol (FAL), and levulinic acid (LA) which can be further used for polymer synthesis [43].
HMF is an important emerging platform chemical that can be further converted to 2,5-furan dicarboxylic acid (FDCA) by chemical [44] or enzymatic [45] oxidation. In turn, FDCA is a precursor for a new to the world polymer polyethylene 2,5-furandicarboxylate (PEF) which provides an alternative to the oil-based plastics polyethylene terephthalates (PET) used for the majority of disposable plastic bottles. Remarkably, PEF represents not only a biobased alternative to PET but also provides a technical advantage in gas retention, which is extremely important for carbonated drinks’ shelf life. Apart from PEF, other polyesters and various polyamides and polyurethanes containing FDCA have been described in the literature [46].
HMF can be obtained by dehydration of carbohydrates. The preferred substrate for dehydration is fructose, which can be obtained by the chemical or enzymatic isomerization of glucose (Figure 3).
Figure 3.
Bioconversion of glucose using MetZymes® and related processes.
The respective enzyme is called glucose isomerase, although biochemically speaking it is xylose isomerase with a side activity of glucose isomerization [47]. These enzymes are widely available: they are one of the largest in volume in the industrial enzyme market for their production of widely-used High Fructose Syrups (HFS) for food applications. Isomerization is a reversible reaction; enzymes bring the mixture of glucose and fructose to the equilibrium ratio of about 1:1 and the reaction stops. Fructose provides sweetness for food and beverages, but can also be used as an intermediate for bioplastics.
The currently available commercial enzymes are highly sensitive to substrate sugar impurities. This is acceptable for food industry applications, where sugar has to be pure anyway. Typically, even sugar produced from starch requires activated carbon filtration, ion-exchange chromatography, and degasification before it can proceed to isomerization reaction as described by the technology providers, see, for example https://www.myandegroup.com/starch-syrup-process-technology.html. Sugars produced from 2nd generation biorefinery (especially from wood) have much more impurities than starch-derived sugar, including lignin, extractives, etc. It would need a lot of purification to enable utilization of currently available glucose isomerase, and the required level of purity is not justified for the technical sugar. MetGen has developed a proprietary industrially relevant recombinant bacterial glucose isomerase with high tolerance to substrate impurities. The enzyme can work directly in biomass hydrolysate. Lower requirements for purification lead to reduced process costs. This enzyme was further engineered to be much less sensitive to the presence of xylose - a preferred substrate of all of the natural glucose isomerases, and thus a potent competitive inhibitor in the reaction with glucose.
Proposed enzymatic solutions for biorefinery and especially for sugars-to-biochemicals pathways are numerous, however, they are still mostly in the research and development stage [48], and the takeoff of the bio-based economy largely depends on the success of this effort. MetZyme® PURECO™ product family – to which previously mentioned glucose isomerase also belongs – is dedicated to next-generation enzymes allowing specific conversions towards high value-addition renewable chemicals, which are beyond sugars. One of these enzymes MetZyme® PURECO™Pyranose oxidase opens an economical route to previously commercially unavailable above a gram scale compound glucosone (2-Keto-D-glucose). While until now the use of d-glucosone has been limited due to its high price and limited availability, it has been envisaged for a long time to provide an alternative route to fructose [49]. As opposed to isomerization reaction, oxidation of glucose to glucosone can be driven to completion, and glucoson’s aldehyde group can be further reduced with high specificity to a hydroxyl leading to fructose (Figure 3). The second step can be performed either by chemical hydrogenation [50] or enzymatically by an aldose reductase [49]. Recently, more applications of glucosone started to be developed, for example, it has been shown, that certain fine chemicals such as kojic acid could potentially be produced from this source (Figure 3) [51].
MetZyme®PURECO™ Pyranose oxidase and glucose isomerase are commercially available proprietary enzymes developed by MetGen in the course of the Horizon 2020 research and innovation program, funded by the European Union’s Bio-Based Industries Joint Undertaking.
5. Concluding remarks
MetGens philosophy in serving biobased industries is to provide a full solution rather than on-shelf enzymes to the customers, and where possible an engineering package. Therefore, MetGen embraces all stages of enzyme technology development from enzyme discovery and molecular biology to application testing, streamlined efficient production, and integration into an industrial process. We call this ENZYNE platform.
Another vastly important principle for us is to take an active part in open innovation to combine forces with industry players to build the new value chains in the bioeconomy.
Building consumer awareness is also key for the expansion of the bioeconomy. Society needs to gain a common understanding of the importance of bio-based solutions and their impact on sustainability and circularity.
Acknowledgments
This research recieved funding from the Bio Based Industries Joint Undertaking under the European Union’s Horizon 2020 research and innovation program under grant agreement No: 792061 SWEETWOODS is acknowledged.
\n',keywords:"enzyme, lignocellulosic biomass, lignin, cellulose, hemicellulose, laccase",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/78299.pdf",chapterXML:"https://mts.intechopen.com/source/xml/78299.xml",downloadPdfUrl:"/chapter/pdf-download/78299",previewPdfUrl:"/chapter/pdf-preview/78299",totalDownloads:176,totalViews:0,totalCrossrefCites:0,dateSubmitted:"June 25th 2021",dateReviewed:"July 12th 2021",datePrePublished:"August 27th 2021",datePublished:"April 28th 2022",dateFinished:"August 27th 2021",readingETA:"0",abstract:"The biorefinery concept in its modern meaning has emerged after it has become apparent that biofuel production from non-food biomass is struggling for economic viability. Lignocellulosic biomass is more recalcitrant and more complex than the starch-based feedstocks used for food. The former, therefore, calls for a more complex approach to its utilization. This chapter reflects MetGen’s vision of the future development of biorefineries. We will discuss the zero-waste approach to lignocellulosic biomass utilization and various ways to valorize the resulting streams to boost the economic viability of the biorefinery. We will mostly explore the relevant enzyme-based approaches and will make a special focus on lignin valorization. Enzymatic and cell-based approaches to sugar valorization will be discussed as well.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/78299",risUrl:"/chapter/ris/78299",signatures:"Klara Birikh, Alex Michine, Matti Heikkilä and Petri Ihalainen",book:{id:"10684",type:"book",title:"Biorefineries",subtitle:"Selected Processes",fullTitle:"Biorefineries - Selected Processes",slug:"biorefineries-selected-processes",publishedDate:"April 28th 2022",bookSignature:"Krzysztof Biernat",coverURL:"https://cdn.intechopen.com/books/images_new/10684.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83969-735-7",printIsbn:"978-1-83969-734-0",pdfIsbn:"978-1-83969-736-4",isAvailableForWebshopOrdering:!0,editors:[{id:"155009",title:"Prof.",name:"Krzysztof",middleName:null,surname:"Biernat",slug:"krzysztof-biernat",fullName:"Krzysztof Biernat"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"414863",title:"Ph.D.",name:"Klara",middleName:null,surname:"Birikh",fullName:"Klara Birikh",slug:"klara-birikh",email:"klara@metgen.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"424401",title:"Mr.",name:"Matti",middleName:null,surname:"Heikkilä",fullName:"Matti Heikkilä",slug:"matti-heikkila",email:"matti@metgen.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"424402",title:"Mr.",name:"Alex",middleName:null,surname:"Michine",fullName:"Alex Michine",slug:"alex-michine",email:"alex@metgen.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"424404",title:"Dr.",name:"Petri",middleName:null,surname:"Ihalainen",fullName:"Petri Ihalainen",slug:"petri-ihalainen",email:"petri.ihalainen@metgen.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction: from bioethanol to biorefineries",level:"1"},{id:"sec_2",title:"2. Biorefinery as an industry sector",level:"1"},{id:"sec_3",title:"3. Enzymes—ultimate tools for biobased industries",level:"1"},{id:"sec_3_2",title:"3.1 Bioconversion—enzyme or whole cell?",level:"2"},{id:"sec_4_2",title:"3.2 Enzyme resources of nature",level:"2"},{id:"sec_6",title:"4. Biomass hydrolysis",level:"1"},{id:"sec_6_2",title:"4.1 Biomass pretreatment",level:"2"},{id:"sec_7_2",title:"4.2 Cellulases for biomass hydrolysis",level:"2"},{id:"sec_8_2",title:"4.3 Special enzymes for biomass degradation and valorization",level:"2"},{id:"sec_8_3",title:"Table 2.",level:"3"},{id:"sec_9_3",title:"4.3.2 Cellulose fibers modification",level:"3"},{id:"sec_10_3",title:"4.3.3 Glucose conversion",level:"3"},{id:"sec_13",title:"5. Concluding remarks",level:"1"},{id:"sec_14",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'Huang K, Fasahati P, Maravelias CT. 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The Cetus process revisited: A novel enzymatic alternative for the production of aldose-free D-fructose. Biocatalysis and Biotransformation. Harwood Academic Publishers GmbH; 1998. p. 365-382. Available from: https://www.tandfonline.com/doi/abs/10.3109/10242429809003629'},{id:"B50",body:'Lassfolk R, Aho A, Murzin DY, Leino R. Hydrogenation of crude and purified d-glucosone generated by enzymatic oxidation of d-glucose. RSC Adv. 2020 Aug 18;10(51):30476-30480. Available from: https://pubs.rsc.org/en/content/articlehtml/2020/ra/d0ra05512c'},{id:"B51",body:'Lassfolk R, Suonpaä A, Birikh K, Leino R. Chemo-enzymatic three-step conversion of glucose to kojic acid. Chem Commun. 2019 Dec 5;55(98):14737-14740. Available from: https://pubs.rsc.org/en/content/articlehtml/2019/cc/c9cc07405h'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Klara Birikh",address:"klara@metgen.com",affiliation:'
'}],corrections:null},book:{id:"10684",type:"book",title:"Biorefineries",subtitle:"Selected Processes",fullTitle:"Biorefineries - Selected Processes",slug:"biorefineries-selected-processes",publishedDate:"April 28th 2022",bookSignature:"Krzysztof Biernat",coverURL:"https://cdn.intechopen.com/books/images_new/10684.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83969-735-7",printIsbn:"978-1-83969-734-0",pdfIsbn:"978-1-83969-736-4",isAvailableForWebshopOrdering:!0,editors:[{id:"155009",title:"Prof.",name:"Krzysztof",middleName:null,surname:"Biernat",slug:"krzysztof-biernat",fullName:"Krzysztof Biernat"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},profile:{item:{id:"346933",title:"M.Sc.",name:"Fengmin",middleName:null,surname:"Luo",email:"lfm359541965@126.com",fullName:"Fengmin Luo",slug:"fengmin-luo",position:null,biography:null,institutionString:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",totalCites:0,totalChapterViews:"0",outsideEditionCount:0,totalAuthoredChapters:"1",totalEditedBooks:"0",personalWebsiteURL:null,twitterURL:null,linkedinURL:null,institution:null},booksEdited:[],chaptersAuthored:[{id:"77278",title:"Ecological Effects of Oasis Shelterbelts in Ulan Buh Desert",slug:"ecological-effects-of-oasis-shelterbelts-in-ulan-buh-desert",abstract:"In arid region, shelterbelt is the ecological barrier for oasis. Understanding its ecological effects can provide theoretical supports for its long-term management and sustainable development. Two standard meteorological stations were used to monitor climatic factors continuously for 7 years, and two 50 m dust monitoring towers were used to continuously monitor sandstorm for 10 times, which were located inside and outside oasis shelterbelts in the northeastern edge of Ulan Buh Desert. The microclimate differences were analyzed, as well as the ecological effects of oasis shelterbelts was clarified inside and outside oasis. In the present study, under the influence of a large-scale shelterbelts, air temperature, land ground temperature and evaporation respectively decreased 5.13% ~ 24.74%, 2.38% ~ 20.09% and 7.06% ~ 17.68%, whereas the relative humidity and precipitation respectively increased 6.93% ~ 25.53% and 4.30% ~ 50.15%. During the occurrence of sandstorms, the wind speed inside and outside shelterbelt showed an increasing trend with the increase in height. The relationship between wind speed and height was expressed as a power function. The wind direction was mainly W, WNW and NE, but the proportion of each direction was different inside and outside shelterbelt. When the sandstorm passed through oasis shelterbelts, the wind speed was significantly weakened, with an average reduction of 30.68%. The horizontal aeolian sediment flux decreased 414.44 g·m−2 and the aeolian deposition flux decreased 0.81 g·m−2. The results revealed that the microclimate was improved by oasis shelterbelts, especially in the growing season. Therefore, oasis shelterbelts help to maintain the sustainable development of oasis.",signatures:"Fengmin Luo, Zhiming Xin, Junliang Gao, Yuan Ma, Xing Li and Huaiyuan Liu",authors:[{id:"346933",title:"M.Sc.",name:"Fengmin",surname:"Luo",fullName:"Fengmin Luo",slug:"fengmin-luo",email:"lfm359541965@126.com"},{id:"347020",title:"MSc.",name:"Zhiming",surname:"Xin",fullName:"Zhiming Xin",slug:"zhiming-xin",email:"xzmlkn@163.com"},{id:"347023",title:"Dr.",name:"Junliang",surname:"Gao",fullName:"Junliang Gao",slug:"junliang-gao",email:"gaojunliang1985@163.com"},{id:"347072",title:"MSc.",name:"Yuan",surname:"Ma",fullName:"Yuan Ma",slug:"yuan-ma",email:"453239598@qq.com"},{id:"347075",title:"MSc.",name:"Xing",surname:"Li",fullName:"Xing Li",slug:"xing-li",email:"1220742449@qq.com"},{id:"347077",title:"Mr.",name:"Huaiyuan",surname:"Liu",fullName:"Huaiyuan Liu",slug:"huaiyuan-liu",email:"1350084482@qq.com"}],book:{id:"8969",title:"Deserts and Desertification",slug:"deserts-and-desertification",productType:{id:"1",title:"Edited Volume"}}}],collaborators:[{id:"347020",title:"MSc.",name:"Zhiming",surname:"Xin",slug:"zhiming-xin",fullName:"Zhiming Xin",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"347023",title:"Dr.",name:"Junliang",surname:"Gao",slug:"junliang-gao",fullName:"Junliang Gao",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"347072",title:"MSc.",name:"Yuan",surname:"Ma",slug:"yuan-ma",fullName:"Yuan Ma",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"347075",title:"MSc.",name:"Xing",surname:"Li",slug:"xing-li",fullName:"Xing Li",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"347077",title:"Mr.",name:"Huaiyuan",surname:"Liu",slug:"huaiyuan-liu",fullName:"Huaiyuan Liu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"348247",title:"Dr.",name:"Peter",surname:"Hyde",slug:"peter-hyde",fullName:"Peter Hyde",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"348338",title:"Prof.",name:"Guoqi",surname:"Li",slug:"guoqi-li",fullName:"Guoqi Li",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"419631",title:"Dr.",name:"Alex",surname:"Mahalov",slug:"alex-mahalov",fullName:"Alex Mahalov",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"422528",title:"Dr.",name:"Shujun",surname:"Li",slug:"shujun-li",fullName:"Shujun Li",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"422529",title:"Dr.",name:"Wenshan",surname:"Shao",slug:"wenshan-shao",fullName:"Wenshan Shao",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null}]},generic:{page:{slug:"OA-publishing-fees",title:"Open Access Publishing Fees",intro:"
The Open Access model is applied to all of our publications and is designed to eliminate subscriptions and pay-per-view fees. This approach ensures free, immediate access to full text versions of your research.
As a gold Open Access publisher, an Open Access Publishing Fee is payable on acceptance following peer review of the manuscript. In return, we provide high quality publishing services and exclusive benefits for all contributors. IntechOpen is the trusted publishing partner of over 140,000 international scientists and researchers.
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1,400 GBP Chapter - Edited Volume
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10,000 GBP Monograph - Long Form
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4,000 GBP Compacts Monograph - Short Form
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850 GBP Journal Article (Across Portfolio)
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During the launching phase journals do not charge an APC, rather they will be funded by IntechOpen.
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*These prices do not include Value-Added Tax (VAT). Residents of European Union countries need to add VAT based on the specific rate in their country of residence. Institutions and companies registered as VAT taxable entities in their own EU member state will not pay VAT as long as provision of the VAT registration number is made during the application process. This is made possible by the EU reverse charge method.
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Services included are:
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English language copyediting and proofreading, including the correction of grammatical, spelling, and other common errors
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XML Typesetting and pagination - web (PDF, HTML) and print files preparation
\\n\\t
Discoverability - electronic citation and linking via DOI
\\n\\t
Permanent and unrestricted online access to your work
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\\n\\n
What isn't covered by the Open Access Publishing Fee?
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If your manuscript:
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\\n\\t
Exceeds the number of pages defined by the publishing guidelines, an additional fee per page may be required
\\n\\t
If a manuscript requires Heavy Editing or Language Polishing, this will incur additional fees.
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Your Author Service Manager will inform you of any items not covered by the OAPF and provide exact information regarding those additional costs before proceeding.
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Open Access Funding
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To explore funding opportunities and learn more about how you can finance your IntechOpen publication, go to our Open Access Funding page. IntechOpen offers expert assistance to all of its Authors. We can support you in approaching funding bodies and institutions in relation to publishing fees by providing information about compliance with the Open Access policies of your funder or institution. We can also assist with communicating the benefits of Open Access in order to support and strengthen your funding request and provide personal guidance through your application process. You can contact us at funders@intechopen.com for further details or assistance.
\\n\\n
For Authors who are still unable to obtain funding from their institutions or research funding bodies for individual projects, IntechOpen does offer the possibility of applying for a Waiver to offset some or all processing feed. Details regarding our Waiver Policy can be found here.
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Added Value of Publishing with IntechOpen
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Choosing to publish with IntechOpen ensures the following benefits:
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Indexing and listing across major repositories, see details ...
\\n\\t
Long-term archiving
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Visibility on the world's strongest OA platform
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Live Performance Metrics to track readership and the impact of your chapter
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Dissemination and Promotion
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Benefits of Publishing with IntechOpen
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Proven world leader in Open Access book publishing with over 10 years experience
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+5,700 OA books published
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Most competitive prices in the market
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+184,650 citations in Web of Science databases
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As a gold Open Access publisher, an Open Access Publishing Fee is payable on acceptance following peer review of the manuscript. In return, we provide high quality publishing services and exclusive benefits for all contributors. IntechOpen is the trusted publishing partner of over 140,000 international scientists and researchers.
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The Open Access Publishing Fee (OAPF) is payable only after your book chapter, monograph or journal article is accepted for publication.
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OAPF Publishing Options
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1,400 GBP Chapter - Edited Volume
\n\t
850 GBP Chapter - Book Series Topic (Annual Volume)
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10,000 GBP Monograph - Long Form
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4,000 GBP Compacts Monograph - Short Form
\n\t
850 GBP Journal Article (Across Portfolio)
\n
\n\n
During the launching phase journals do not charge an APC, rather they will be funded by IntechOpen.
\n\n
*These prices do not include Value-Added Tax (VAT). Residents of European Union countries need to add VAT based on the specific rate in their country of residence. Institutions and companies registered as VAT taxable entities in their own EU member state will not pay VAT as long as provision of the VAT registration number is made during the application process. This is made possible by the EU reverse charge method.
\n\n
Services included are:
\n\n
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An online manuscript tracking system to facilitate your work
\n\t
Personal contact and support throughout the publishing process from your dedicated Author Service Manager
\n\t
Assurance that your manuscript meets the highest publishing standards
\n\t
English language copyediting and proofreading, including the correction of grammatical, spelling, and other common errors
\n\t
XML Typesetting and pagination - web (PDF, HTML) and print files preparation
\n\t
Discoverability - electronic citation and linking via DOI
\n\t
Permanent and unrestricted online access to your work
\n
\n\n
What isn't covered by the Open Access Publishing Fee?
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If your manuscript:
\n\n
\n\t
Exceeds the number of pages defined by the publishing guidelines, an additional fee per page may be required
\n\t
If a manuscript requires Heavy Editing or Language Polishing, this will incur additional fees.
\n
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Your Author Service Manager will inform you of any items not covered by the OAPF and provide exact information regarding those additional costs before proceeding.
\n\n
Open Access Funding
\n\n
To explore funding opportunities and learn more about how you can finance your IntechOpen publication, go to our Open Access Funding page. IntechOpen offers expert assistance to all of its Authors. We can support you in approaching funding bodies and institutions in relation to publishing fees by providing information about compliance with the Open Access policies of your funder or institution. We can also assist with communicating the benefits of Open Access in order to support and strengthen your funding request and provide personal guidance through your application process. You can contact us at funders@intechopen.com for further details or assistance.
\n\n
For Authors who are still unable to obtain funding from their institutions or research funding bodies for individual projects, IntechOpen does offer the possibility of applying for a Waiver to offset some or all processing feed. Details regarding our Waiver Policy can be found here.
\n\n
Added Value of Publishing with IntechOpen
\n\n
Choosing to publish with IntechOpen ensures the following benefits:
\n\n
\n\t
Indexing and listing across major repositories, see details ...
\n\t
Long-term archiving
\n\t
Visibility on the world's strongest OA platform
\n\t
Live Performance Metrics to track readership and the impact of your chapter
\n\t
Dissemination and Promotion
\n
\n\n
Benefits of Publishing with IntechOpen
\n\n
\n\t
Proven world leader in Open Access book publishing with over 10 years experience
\n\t
+5,700 OA books published
\n\t
Most competitive prices in the market
\n\t
Fully compliant with OA funding requirements
\n\t
Optimized processes that assure your research is made available to the scientific community without delay
\n\t
Personal support during every step of the publication process
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+184,650 citations in Web of Science databases
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Currently strongest OA platform with over 175 million downloads
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\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{},profiles:[{id:"6700",title:"Dr.",name:"Abbass A.",middleName:null,surname:"Hashim",slug:"abbass-a.-hashim",fullName:"Abbass A. Hashim",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/6700/images/1864_n.jpg",biography:"Currently I am carrying out research in several areas of interest, mainly covering work on chemical and bio-sensors, semiconductor thin film device fabrication and characterisation.\nAt the moment I have very strong interest in radiation environmental pollution and bacteriology treatment. The teams of researchers are working very hard to bring novel results in this field. I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. I have served as the editor for many books, been a member of the editorial board in science journals, have published many papers and hold many patents.",institutionString:null,institution:{name:"Sheffield Hallam University",country:{name:"United Kingdom"}}},{id:"54525",title:"Prof.",name:"Abdul Latif",middleName:null,surname:"Ahmad",slug:"abdul-latif-ahmad",fullName:"Abdul Latif Ahmad",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"20567",title:"Prof.",name:"Ado",middleName:null,surname:"Jorio",slug:"ado-jorio",fullName:"Ado Jorio",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidade Federal de Minas Gerais",country:{name:"Brazil"}}},{id:"47940",title:"Dr.",name:"Alberto",middleName:null,surname:"Mantovani",slug:"alberto-mantovani",fullName:"Alberto Mantovani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"12392",title:"Mr.",name:"Alex",middleName:null,surname:"Lazinica",slug:"alex-lazinica",fullName:"Alex Lazinica",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12392/images/7282_n.png",biography:"Alex Lazinica is the founder and CEO of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his PhD studies in Robotics at the Vienna University of Technology. Here he worked as a robotic researcher with the university's Intelligent Manufacturing Systems Group as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and most importantly he co-founded and built the International Journal of Advanced Robotic Systems- world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career, since it was a pathway to founding IntechOpen - Open Access publisher focused on addressing academic researchers needs. Alex is a personification of IntechOpen key values being trusted, open and entrepreneurial. Today his focus is on defining the growth and development strategy for the company.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"19816",title:"Prof.",name:"Alexander",middleName:null,surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/19816/images/1607_n.jpg",biography:"Alexander I. Kokorin: born: 1947, Moscow; DSc., PhD; Principal Research Fellow (Research Professor) of Department of Kinetics and Catalysis, N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow.\r\nArea of research interests: physical chemistry of complex-organized molecular and nanosized systems, including polymer-metal complexes; the surface of doped oxide semiconductors. He is an expert in structural, absorptive, catalytic and photocatalytic properties, in structural organization and dynamic features of ionic liquids, in magnetic interactions between paramagnetic centers. The author or co-author of 3 books, over 200 articles and reviews in scientific journals and books. He is an actual member of the International EPR/ESR Society, European Society on Quantum Solar Energy Conversion, Moscow House of Scientists, of the Board of Moscow Physical Society.",institutionString:null,institution:{name:"Semenov Institute of Chemical Physics",country:{name:"Russia"}}},{id:"62389",title:"PhD.",name:"Ali Demir",middleName:null,surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62389/images/3413_n.jpg",biography:"Dr. Ali Demir Sezer has a Ph.D. from Pharmaceutical Biotechnology at the Faculty of Pharmacy, University of Marmara (Turkey). He is the member of many Pharmaceutical Associations and acts as a reviewer of scientific journals and European projects under different research areas such as: drug delivery systems, nanotechnology and pharmaceutical biotechnology. Dr. Sezer is the author of many scientific publications in peer-reviewed journals and poster communications. Focus of his research activity is drug delivery, physico-chemical characterization and biological evaluation of biopolymers micro and nanoparticles as modified drug delivery system, and colloidal drug carriers (liposomes, nanoparticles etc.).",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"61051",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"100762",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"St David's Medical Center",country:{name:"United States of America"}}},{id:"107416",title:"Dr.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Texas Cardiac Arrhythmia",country:{name:"United States of America"}}},{id:"64434",title:"Dr.",name:"Angkoon",middleName:null,surname:"Phinyomark",slug:"angkoon-phinyomark",fullName:"Angkoon Phinyomark",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/64434/images/2619_n.jpg",biography:"My name is Angkoon Phinyomark. I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. I had been a visiting research student at Faculty of Computer Science, University of Murcia, Murcia, Spain for three months.\n\nI have published over 40 papers during 5 years in refereed journals, books, and conference proceedings in the areas of electro-physiological signals processing and classification, notably EMG and EOG signals, fractal analysis, wavelet analysis, texture analysis, feature extraction and machine learning algorithms, and assistive and rehabilitative devices. I have several computer programming language certificates, i.e. Sun Certified Programmer for the Java 2 Platform 1.4 (SCJP), Microsoft Certified Professional Developer, Web Developer (MCPD), Microsoft Certified Technology Specialist, .NET Framework 2.0 Web (MCTS). 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In general, the pyrolysis types are classified base on heating rate mainly either fast or slow pyrolysis. The characteristic and properties of wood vinegar are primarily influenced by the type of carbonaceous feedstocks as well as the production techniques. Wood vinegar is a complex mixture of polar and non-polar chemicals with various molecular weights and compositions. Its major constituent is water (80–90%). Some physical properties; such as pH, specific gravity, dissolved tar content are, respectively, within the range of 2–4, 1.005–1.016 g/mL, 0.23–0.89% wt, and color, odor and transparency have been reported. In addition, the degree of oBrix was ranged between 1.7 and 6.6. Besides water, the chemical compositions of wood vinegars consisted of acetic acid with the largest component (30.45–70.60 mg.mL−1). A high number of phenol derivatives have been found and those in higher concentrations were 4-propyl-2-methoxyphenol (5–11 mg.mL−1) followed by 2-methylphenol (2–4 mg.mL−1). Wood vinegar has been regarded as a natural product, which claimed to be capable in several fields of application. In agriculture, wood vinegar has been used in vegetable cropping in order to combat disease, pest control, improve growth and fruit quality, seed germination accelerator as well as herbicide. In pharmaceutical and medical applications, it is used for the preparation of detoxification pad while in veterinary and animal production, incorporation of the wood vinegar in feed could promote acidity in large intestine to inhibit growth of enteropathogenic microbes. In food processing, wood vinegar has a characteristic smoke flavor, and also exhibits microbial growth inhibition. In addition, several investigators reported that bio-oil and wood vinegar obtained from fast pyrolysis and carbonization showed a high potential on organic wood preservative. In summary, the wood vinegar prepared from the tropical wood and/or biomass waste is widely beneficial. 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Sustainable forest management practices, alternatives for shifting cultivation, promotion of plantation outside the forest and the usage of certified forest products, etc. are some of the measures that can be adopted to curb the rate of deforestation.",book:{id:"7629",slug:"forest-degradation-around-the-world",title:"Forest Degradation Around the World",fullTitle:"Forest Degradation Around the World"},signatures:"Rima Kumari, Ayan Banerjee, Rahul Kumar, Amit Kumar, Purabi Saikia and Mohammed Latif Khan",authors:[{id:"276688",title:"Prof.",name:"Mohammed Latif",middleName:null,surname:"Khan",slug:"mohammed-latif-khan",fullName:"Mohammed Latif Khan"},{id:"279797",title:"Dr.",name:"Purabi",middleName:null,surname:"Saikia",slug:"purabi-saikia",fullName:"Purabi Saikia"},{id:"279806",title:"MSc.",name:"Rima",middleName:null,surname:"Kumari",slug:"rima-kumari",fullName:"Rima Kumari"},{id:"279807",title:"BSc.",name:"Ayan",middleName:null,surname:"Banerjee",slug:"ayan-banerjee",fullName:"Ayan Banerjee"},{id:"285660",title:"Dr.",name:"Amit",middleName:null,surname:"Kumar",slug:"amit-kumar",fullName:"Amit Kumar"},{id:"285661",title:"MSc.",name:"Rahul",middleName:null,surname:"Kumar",slug:"rahul-kumar",fullName:"Rahul Kumar"}]},{id:"45219",doi:"10.5772/56279",title:"Potential Future Ranges of Tree Species in the Alps",slug:"potential-future-ranges-of-tree-species-in-the-alps",totalDownloads:4893,totalCrossrefCites:2,totalDimensionsCites:15,abstract:null,book:{id:"3403",slug:"management-strategies-to-adapt-alpine-space-forests-to-climate-change-risks",title:"Management Strategies to Adapt Alpine Space Forests to Climate Change Risks",fullTitle:"Management Strategies to Adapt Alpine Space Forests to Climate Change Risks"},signatures:"Niklaus E. Zimmermann, Robert Jandl, Marc Hanewinkel, Georges\nKunstler, Christian Kölling, Patrizia Gasparini, Andrej Breznikar,\nEliane S. Meier, Signe Normand, Ulrich Ulmer, Thomas\nGschwandtner, Holger Veit, Maria Naumann, Wolfgang Falk, Karl\nMellert, Maria Rizzo, Mitja Skudnik and Achilleas Psomas",authors:[{id:"165202",title:"Prof.",name:"Niklaus",middleName:"E.",surname:"Zimmermann",slug:"niklaus-zimmermann",fullName:"Niklaus Zimmermann"}]}],mostDownloadedChaptersLast30Days:[{id:"31959",title:"Structure, Diversity, Threats and Conservation of Tropical Forests",slug:"structure-diversity-threats-and-conservation-of-tropical-forests",totalDownloads:8024,totalCrossrefCites:2,totalDimensionsCites:5,abstract:null,book:{id:"902",slug:"tropical-forests",title:"Tropical Forests",fullTitle:"Tropical Forests"},signatures:"Madhugiri Nageswara-Rao, Jaya R. Soneji and Padmini Sudarshana",authors:[{id:"79318",title:"Dr.",name:"Padmini",middleName:null,surname:"Sudarshana",slug:"padmini-sudarshana",fullName:"Padmini Sudarshana"},{id:"120847",title:"Dr.",name:"Madhugiri",middleName:null,surname:"Nageswara-Rao",slug:"madhugiri-nageswara-rao",fullName:"Madhugiri Nageswara-Rao"},{id:"120848",title:"Dr.",name:"Jaya",middleName:null,surname:"Soneji",slug:"jaya-soneji",fullName:"Jaya Soneji"}]},{id:"66710",title:"Deforestation in India: Consequences and Sustainable Solutions",slug:"deforestation-in-india-consequences-and-sustainable-solutions",totalDownloads:2012,totalCrossrefCites:12,totalDimensionsCites:16,abstract:"Deforestation is one of the most pressing environmental issues that the world is facing currently. It is the conversion of forested land to non-forested land by humans. Deforestation occurs when a land dominated by naturally occurring trees is converted to provide certain services in response to the human demand. The indiscriminate felling of trees has resulted in a reduction of 3.16% in the global forest cover from 1990 to 2015. Although India has seen an increment in the total forest cover of ca. 1%, still there are certain regions in the country that have sought a decrease in the forest cover. The main reasons attributed to the reduction in forest cover are shifting cultivation, rotational felling, other biotic pressures, diversion of forest lands for developmental activities, etc. Continuous illicit cutting of trees has impacted the microclimatic conditions, hydrological cycle, soil quality, biodiversity, etc. of the country, thereby making the country more vulnerable for any uneventful happening. Sustainable forest management practices, alternatives for shifting cultivation, promotion of plantation outside the forest and the usage of certified forest products, etc. are some of the measures that can be adopted to curb the rate of deforestation.",book:{id:"7629",slug:"forest-degradation-around-the-world",title:"Forest Degradation Around the World",fullTitle:"Forest Degradation Around the World"},signatures:"Rima Kumari, Ayan Banerjee, Rahul Kumar, Amit Kumar, Purabi Saikia and Mohammed Latif Khan",authors:[{id:"276688",title:"Prof.",name:"Mohammed Latif",middleName:null,surname:"Khan",slug:"mohammed-latif-khan",fullName:"Mohammed Latif Khan"},{id:"279797",title:"Dr.",name:"Purabi",middleName:null,surname:"Saikia",slug:"purabi-saikia",fullName:"Purabi Saikia"},{id:"279806",title:"MSc.",name:"Rima",middleName:null,surname:"Kumari",slug:"rima-kumari",fullName:"Rima Kumari"},{id:"279807",title:"BSc.",name:"Ayan",middleName:null,surname:"Banerjee",slug:"ayan-banerjee",fullName:"Ayan Banerjee"},{id:"285660",title:"Dr.",name:"Amit",middleName:null,surname:"Kumar",slug:"amit-kumar",fullName:"Amit Kumar"},{id:"285661",title:"MSc.",name:"Rahul",middleName:null,surname:"Kumar",slug:"rahul-kumar",fullName:"Rahul Kumar"}]},{id:"68528",title:"Forest Biodiversity and Deforestation in Bangladesh: The Latest Update",slug:"forest-biodiversity-and-deforestation-in-bangladesh-the-latest-update",totalDownloads:1507,totalCrossrefCites:3,totalDimensionsCites:11,abstract:"Located in the Indo-Burma biodiversity hotspot, Bangladesh is a tropical country in Southeast Asia and a transitional point for flora and fauna between the Indo-Himalayan and Indo-Chinese subregions. About 11% land area (1,429,000 hectares) of the country is covered with four major forest types: mixed-evergreen forests, deciduous forests, mangrove forests, and freshwater swamp forests. Though Bangladesh is a small and densely populated country, it is the home of 1952 species of invertebrates, 653 fish, 50 amphibians, 147 reptiles, 566 birds, and 127 mammalian species of which many of them are globally threatened. We have discussed the latest status of all the major vertebrate groups in this chapter. Thirty-one species of vertebrates have gone extinct from Bangladesh over the last century. Many of the species are facing continuous threat of extinction due to deforestation and degradation of habitat caused by various anthropogenic activities. In this chapter, we are going to discuss about the current management and conservation practices and issues related to the forests and wildlife of Bangladesh.",book:{id:"7629",slug:"forest-degradation-around-the-world",title:"Forest Degradation Around the World",fullTitle:"Forest Degradation Around the World"},signatures:"Ahm Ali Reza and Md. Kamrul Hasan",authors:[{id:"281012",title:"Dr.",name:"Md. Kamrul",middleName:null,surname:"Hasan",slug:"md.-kamrul-hasan",fullName:"Md. Kamrul Hasan"},{id:"302258",title:"Dr.",name:"AHM Ali",middleName:null,surname:"Reza",slug:"ahm-ali-reza",fullName:"AHM Ali Reza"}]},{id:"61747",title:"Physicochemistry and Utilization of Wood Vinegar from Carbonization of Tropical Biomass Waste",slug:"physicochemistry-and-utilization-of-wood-vinegar-from-carbonization-of-tropical-biomass-waste",totalDownloads:2156,totalCrossrefCites:9,totalDimensionsCites:18,abstract:"Pyroligneous acid also called wood vinegar is an aqueous liquid produced from pyrolysis of lignocellulose waste and biomass. In general, the pyrolysis types are classified base on heating rate mainly either fast or slow pyrolysis. The characteristic and properties of wood vinegar are primarily influenced by the type of carbonaceous feedstocks as well as the production techniques. Wood vinegar is a complex mixture of polar and non-polar chemicals with various molecular weights and compositions. Its major constituent is water (80–90%). Some physical properties; such as pH, specific gravity, dissolved tar content are, respectively, within the range of 2–4, 1.005–1.016 g/mL, 0.23–0.89% wt, and color, odor and transparency have been reported. In addition, the degree of oBrix was ranged between 1.7 and 6.6. Besides water, the chemical compositions of wood vinegars consisted of acetic acid with the largest component (30.45–70.60 mg.mL−1). A high number of phenol derivatives have been found and those in higher concentrations were 4-propyl-2-methoxyphenol (5–11 mg.mL−1) followed by 2-methylphenol (2–4 mg.mL−1). Wood vinegar has been regarded as a natural product, which claimed to be capable in several fields of application. In agriculture, wood vinegar has been used in vegetable cropping in order to combat disease, pest control, improve growth and fruit quality, seed germination accelerator as well as herbicide. In pharmaceutical and medical applications, it is used for the preparation of detoxification pad while in veterinary and animal production, incorporation of the wood vinegar in feed could promote acidity in large intestine to inhibit growth of enteropathogenic microbes. In food processing, wood vinegar has a characteristic smoke flavor, and also exhibits microbial growth inhibition. In addition, several investigators reported that bio-oil and wood vinegar obtained from fast pyrolysis and carbonization showed a high potential on organic wood preservative. In summary, the wood vinegar prepared from the tropical wood and/or biomass waste is widely beneficial. The chapter attempts to provide essential knowledge relevant to physicochemical characteristics of wood vinegar and its applications.",book:{id:"6370",slug:"tropical-forests-new-edition",title:"Tropical Forests",fullTitle:"Tropical Forests - New Edition"},signatures:"Yongyuth Theapparat, Ausa Chandumpai and Damrongsak\nFaroongsarng",authors:[{id:"219997",title:"Dr.",name:"Yongyuth",middleName:null,surname:"Theapparat",slug:"yongyuth-theapparat",fullName:"Yongyuth Theapparat"},{id:"226821",title:"Dr.",name:"Ausa",middleName:null,surname:"Chandumpai",slug:"ausa-chandumpai",fullName:"Ausa Chandumpai"},{id:"398427",title:"Dr.",name:"Damrongsak",middleName:null,surname:"Faroongsarng",slug:"damrongsak-faroongsarng",fullName:"Damrongsak Faroongsarng"}]},{id:"54603",title:"Methodological Considerations in the Study of Earthworms in Forest Ecosystems",slug:"methodological-considerations-in-the-study-of-earthworms-in-forest-ecosystems",totalDownloads:1792,totalCrossrefCites:0,totalDimensionsCites:5,abstract:"Decades of studies have shown that soil macrofauna, especially earthworms, play dominant engineering roles in soils, affecting physical, chemical, and biological components of ecosystems. Quantifying these effects would allow crucial improvement in biogeochemical budgets and modeling, predicting response of land use and disturbance, and could be applied to bioremediation efforts. Effective methods of manipulating earthworm communities in the field are needed to accompany laboratory microcosm studies to calculate their net function in natural systems and to isolate specific mechanisms. This chapter reviews laboratory and field methods for enumerating and manipulating earthworm populations, as well as approaches toward quantifying their influences on soil processes and biogeochemical cycling.",book:{id:"5539",slug:"forest-ecology-and-conservation",title:"Forest Ecology and Conservation",fullTitle:"Forest Ecology and Conservation"},signatures:"Dylan Rhea-Fournier and Grizelle González",authors:[{id:"82355",title:"Dr.",name:"Grizelle",middleName:null,surname:"Gonzalez",slug:"grizelle-gonzalez",fullName:"Grizelle Gonzalez"},{id:"194800",title:"M.Sc.",name:"Dylan",middleName:null,surname:"Rhea-Fournier",slug:"dylan-rhea-fournier",fullName:"Dylan Rhea-Fournier"}]}],onlineFirstChaptersFilter:{topicId:"138",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[],lsSeriesList:[],hsSeriesList:[],sshSeriesList:[],testimonialsList:[]},series:{item:{id:"10",title:"Physiology",doi:"10.5772/intechopen.72796",issn:"2631-8261",scope:"Modern physiology requires a comprehensive understanding of the integration of tissues and organs throughout the mammalian body, including the cooperation between structure and function at the cellular and molecular levels governed by gene and protein expression. While a daunting task, learning is facilitated by identifying common and effective signaling pathways mediated by a variety of factors employed by nature to preserve and sustain homeostatic life. \r\nAs a leading example, the cellular interaction between intracellular concentration of Ca+2 increases, and changes in plasma membrane potential is integral for coordinating blood flow, governing the exocytosis of neurotransmitters, and modulating gene expression and cell effector secretory functions. Furthermore, in this manner, understanding the systemic interaction between the cardiovascular and nervous systems has become more important than ever as human populations' life prolongation, aging and mechanisms of cellular oxidative signaling are utilised for sustaining life. \r\nAltogether, physiological research enables our identification of distinct and precise points of transition from health to the development of multimorbidity throughout the inevitable aging disorders (e.g., diabetes, hypertension, chronic kidney disease, heart failure, peptic ulcer, inflammatory bowel disease, age-related macular degeneration, cancer). With consideration of all organ systems (e.g., brain, heart, lung, gut, skeletal and smooth muscle, liver, pancreas, kidney, eye) and the interactions thereof, this Physiology Series will address the goals of resolving (1) Aging physiology and chronic disease progression (2) Examination of key cellular pathways as they relate to calcium, oxidative stress, and electrical signaling, and (3) how changes in plasma membrane produced by lipid peroxidation products can affect aging physiology, covering new research in the area of cell, human, plant and animal physiology.",coverUrl:"https://cdn.intechopen.com/series/covers/10.jpg",latestPublicationDate:"May 14th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:11,editor:{id:"35854",title:"Prof.",name:"Tomasz",middleName:null,surname:"Brzozowski",slug:"tomasz-brzozowski",fullName:"Tomasz Brzozowski",profilePictureURL:"https://mts.intechopen.com/storage/users/35854/images/system/35854.jpg",biography:"Prof. Dr. Thomas Brzozowski works as a professor of Human Physiology and is currently Chairman at the Department of Physiology and is V-Dean of the Medical Faculty at Jagiellonian University Medical College, Cracow, Poland. His primary area of interest is physiology and pathophysiology of the gastrointestinal (GI) tract, with the major focus on the mechanism of GI mucosal defense, protection, and ulcer healing. He was a postdoctoral NIH fellow at the University of California and the Gastroenterology VA Medical Center, Irvine, Long Beach, CA, USA, and at the Gastroenterology Clinics Erlangen-Nuremberg and Munster in Germany. He has published 290 original articles in some of the most prestigious scientific journals and seven book chapters on the pathophysiology of the GI tract, gastroprotection, ulcer healing, drug therapy of peptic ulcers, hormonal regulation of the gut, and inflammatory bowel disease.",institutionString:null,institution:{name:"Jagiellonian University",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"10",title:"Animal Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/10.jpg",isOpenForSubmission:!0,editor:{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. Dr. Rutland has also written popular science books for the public. https://orcid.org/0000-0002-2009-4898. www.nottingham.ac.uk/vet/people/catrin.rutland",institutionString:null,institution:{name:"University of Nottingham",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null},{id:"11",title:"Cell Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/11.jpg",isOpenForSubmission:!0,editor:{id:"133493",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",profilePictureURL:"https://mts.intechopen.com/storage/users/133493/images/3091_n.jpg",biography:"Prof. Dr. Angel Catalá \r\nShort Biography Angel Catalá was born in Rodeo (San Juan, Argentina). He studied \r\nchemistry at the Universidad Nacional de La Plata, Argentina, where received aPh.D. degree in chemistry (Biological Branch) in 1965. From\r\n1964 to 1974, he worked as Assistant in Biochemistry at the School of MedicineUniversidad Nacional de La Plata, Argentina. From 1974 to 1976, he was a Fellowof the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor oBiochemistry at the Universidad Nacional de La Plata, Argentina. He is Member ofthe National Research Council (CONICET), Argentina, and Argentine Society foBiochemistry and Molecular Biology (SAIB). His laboratory has been interested for manyears in the lipid peroxidation of biological membranes from various tissues and different species. Professor Catalá has directed twelve doctoral theses, publishedover 100 papers in peer reviewed journals, several chapters in books andtwelve edited books. Angel Catalá received awards at the 40th InternationaConference Biochemistry of Lipids 1999: Dijon (France). W inner of the Bimbo PanAmerican Nutrition, Food Science and Technology Award 2006 and 2012, South AmericaHuman Nutrition, Professional Category. 2006 award in pharmacology, Bernardo\r\nHoussay, in recognition of his meritorious works of research. Angel Catalá belongto the Editorial Board of Journal of lipids, International Review of Biophysical ChemistryFrontiers in Membrane Physiology and Biophysics, World Journal oExperimental Medicine and Biochemistry Research International, W orld Journal oBiological Chemistry, Oxidative Medicine and Cellular Longevity, Diabetes and thePancreas, International Journal of Chronic Diseases & Therapy, International Journal oNutrition, Co-Editor of The Open Biology Journal.",institutionString:null,institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}},editorTwo:null,editorThree:null},{id:"12",title:"Human Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/12.jpg",isOpenForSubmission:!0,editor:{id:"195829",title:"Prof.",name:"Kunihiro",middleName:null,surname:"Sakuma",slug:"kunihiro-sakuma",fullName:"Kunihiro Sakuma",profilePictureURL:"https://mts.intechopen.com/storage/users/195829/images/system/195829.jpg",biography:"Professor Kunihiro Sakuma, Ph.D., currently works in the Institute for Liberal Arts at the Tokyo Institute of Technology. He is a physiologist working in the field of skeletal muscle. He was awarded his sports science diploma in 1995 by the University of Tsukuba and began his scientific work at the Department of Physiology, Aichi Human Service Center, focusing on the molecular mechanism of congenital muscular dystrophy and normal muscle regeneration. His interest later turned to the molecular mechanism and attenuating strategy of sarcopenia (age-related muscle atrophy). His opinion is to attenuate sarcopenia by improving autophagic defects using nutrient- and pharmaceutical-based treatments.",institutionString:null,institution:{name:"Tokyo Institute of Technology",institutionURL:null,country:{name:"Japan"}}},editorTwo:null,editorThree:{id:"331519",title:"Dr.",name:"Kotomi",middleName:null,surname:"Sakai",slug:"kotomi-sakai",fullName:"Kotomi Sakai",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000031QtFXQA0/Profile_Picture_1637053227318",biography:"Senior researcher Kotomi Sakai, Ph.D., MPH, works at the Research Organization of Science and Technology in Ritsumeikan University. She is a researcher in the geriatric rehabilitation and public health field. She received Ph.D. from Nihon University and MPH from St.Luke’s International University. Her main research interest is sarcopenia in older adults, especially its association with nutritional status. Additionally, to understand how to maintain and improve physical function in older adults, to conduct studies about the mechanism of sarcopenia and determine when possible interventions are needed.",institutionString:null,institution:{name:"Ritsumeikan University",institutionURL:null,country:{name:"Japan"}}}},{id:"13",title:"Plant Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/13.jpg",isOpenForSubmission:!0,editor:{id:"332229",title:"Prof.",name:"Jen-Tsung",middleName:null,surname:"Chen",slug:"jen-tsung-chen",fullName:"Jen-Tsung Chen",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000031RJmlQAG/Profile_Picture_1600760167494",biography:"Dr. Jen-Tsung Chen is currently a professor at the National University of Kaohsiung in Taiwan. He teaches cell biology, genomics, proteomics, medicinal plant biotechnology, and plant tissue culture in college. Dr. Chen's research interests are bioactive compounds, chromatography techniques, in vitro culture, medicinal plants, phytochemicals, and plant biotechnology. He has published over 60 research papers, reviewed over 260 manuscripts, and edited at least 150 papers in international peer-review journals.",institutionString:null,institution:{name:"National University of Kaohsiung",institutionURL:null,country:{name:"Taiwan"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:43,paginationItems:[{id:"81796",title:"Apoptosis-Related Diseases and Peroxisomes",doi:"10.5772/intechopen.105052",signatures:"Meimei Wang, Yakun Liu, Ni Chen, Juan Wang and Ye Zhao",slug:"apoptosis-related-diseases-and-peroxisomes",totalDownloads:2,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"The Metabolic Role of Peroxisome in Health and Disease",coverURL:"https://cdn.intechopen.com/books/images_new/10837.jpg",subseries:{id:"11",title:"Cell Physiology"}}},{id:"81723",title:"Peroxisomal Modulation as Therapeutic Alternative for Tackling Multiple Cancers",doi:"10.5772/intechopen.104873",signatures:"Shazia Usmani, Shadma Wahab, Abdul Hafeez, Shabana Khatoon and Syed Misbahul Hasan",slug:"peroxisomal-modulation-as-therapeutic-alternative-for-tackling-multiple-cancers",totalDownloads:3,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"The Metabolic Role of Peroxisome in Health and Disease",coverURL:"https://cdn.intechopen.com/books/images_new/10837.jpg",subseries:{id:"11",title:"Cell Physiology"}}},{id:"81638",title:"Aging and Neuropsychiatric Disease: A General Overview of Prevalence and Trends",doi:"10.5772/intechopen.103102",signatures:"Jelena Milić",slug:"aging-and-neuropsychiatric-disease-a-general-overview-of-prevalence-and-trends",totalDownloads:14,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Senescence",coverURL:"https://cdn.intechopen.com/books/images_new/10935.jpg",subseries:{id:"11",title:"Cell Physiology"}}},{id:"81566",title:"New and Emerging Technologies for Integrative Ambulatory Autonomic Assessment and Intervention as a Catalyst in the Synergy of Remote Geocoded Biosensing, Algorithmic Networked Cloud Computing, Deep Learning, and Regenerative/Biomic Medicine: Further Real",doi:"10.5772/intechopen.104092",signatures:"Robert L. Drury",slug:"new-and-emerging-technologies-for-integrative-ambulatory-autonomic-assessment-and-intervention-as-a-",totalDownloads:9,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Autonomic Nervous System - Special Interest Topics",coverURL:"https://cdn.intechopen.com/books/images_new/10835.jpg",subseries:{id:"12",title:"Human Physiology"}}}]},overviewPagePublishedBooks:{paginationCount:11,paginationItems:[{type:"book",id:"7264",title:"Calcium and Signal Transduction",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7264.jpg",slug:"calcium-and-signal-transduction",publishedDate:"October 24th 2018",editedByType:"Edited by",bookSignature:"John N. Buchholz and Erik J. Behringer",hash:"e373a3d1123dbd45fddf75d90e3e7c38",volumeInSeries:1,fullTitle:"Calcium and Signal Transduction",editors:[{id:"89438",title:"Dr.",name:"John N.",middleName:null,surname:"Buchholz",slug:"john-n.-buchholz",fullName:"John N. Buchholz",profilePictureURL:"https://mts.intechopen.com/storage/users/89438/images/6463_n.jpg",biography:"Full Professor and Vice Chair, Division of Pharmacology, Loma Linda University, School of Medicine. He received his B.S. Degree in Biology at La Sierra University, Riverside California (1980) and a PhD in Pharmacology from Loma Linda University School of Medicine (1988). Post-Doctoral Fellow at University of California, Irvine, College of Medicine 1989-1992 with a focus on autonomic nerve function in blood vessels and the impact of aging on the function of these nerves and overall blood vessel function. Twenty years of research funding and served on NIH R01 review panels, Editor-In-Chief of Edorium Journal of Aging Research. Serves as a peer reviewer for biomedical journals. Military Reserve Officer serving with the 100 Support Command, 100 Troop Command, 40 Infantry Division, CA National Guard.",institutionString:null,institution:{name:"Loma Linda University",institutionURL:null,country:{name:"United States of America"}}}]},{type:"book",id:"6925",title:"Endoplasmic Reticulum",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6925.jpg",slug:"endoplasmic-reticulum",publishedDate:"April 17th 2019",editedByType:"Edited by",bookSignature:"Angel Català",hash:"a9e90d2dbdbc46128dfe7dac9f87c6b4",volumeInSeries:2,fullTitle:"Endoplasmic Reticulum",editors:[{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",profilePictureURL:"https://mts.intechopen.com/storage/users/196544/images/system/196544.jpg",biography:"Angel Catalá studied chemistry at Universidad Nacional de La Plata, Argentina, where he received a Ph.D. in Chemistry (Biological Branch) in 1965. From 1964 to 1974, he worked as an Assistant in Biochemistry at the School of Medicine at the same university. From 1974 to 1976, he was a fellow of the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor of Biochemistry at the Universidad Nacional de La Plata. He is a member of the National Research Council (CONICET), Argentina, and the Argentine Society for Biochemistry and Molecular Biology (SAIB). His laboratory has been interested for many years in the lipid peroxidation of biological membranes from various tissues and different species. Dr. Catalá has directed twelve doctoral theses, published more than 100 papers in peer-reviewed journals, several chapters in books, and edited twelve books. He received awards at the 40th International Conference Biochemistry of Lipids 1999 in Dijon, France. 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