Reported prevalence of subclinical endometritis in some studies that used different sampling methods, postpartum diagnosis periods, and PMN% cutoff values.
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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
\n\n\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"1912",leadTitle:null,fullTitle:"Protein Structure",title:"Protein Structure",subtitle:null,reviewType:"peer-reviewed",abstract:"Since the dawn of recorded history, and probably even before, men and women have been grasping at the mechanisms by which they themselves exist. Only relatively recently, did this grasp yield anything of substance, and only within the last several decades did the proteins play a pivotal role in this existence. In this expose on the topic of protein structure some of the current issues in this scientific field are discussed. The aim is that a non-expert can gain some appreciation for the intricacies involved, and in the current state of affairs. 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The son of a chemist and a history teacher he was absorbed in critical thought from a young age. At the age of 21 he entered the joint math and physics program at the Hebrew University completing his studies with accolades and salutations. Upon graduation he started for a physics doctorate degree with the University of Texas at Austin, and wrote a marvellous dissertation on various questions associated with two-dimensional ferromagnetism under the supervision of Linda Reichl. He has worked on a multitude of scientific areas including discrete time, cell division and laser-flesh interactions. 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An intelligence inkjet printhead includes a number of heater and nozzle devices formed on a silicon substrate. For reliable operation of the jet heater in a practical thermal ink-jet printhead chip [1–10], external sources of noise become an extremely important concern. It is desirable that the jet heater be disposed on the chip at a location as close as possible to the channels themselves for a most accurate reading of the actual temperature of the liquid ink just before a given ejector is fired. At the same time, the location of the jet heater must be rigorous designed because an additional requirement of a experiential bubble jet printhead is that the chip be as small as physically possible, yet still contain all the circuits required for valid operation [11–16].
\nInkjet printer heads system and multi-channel printhead jets.
The DNA droplet ejection of our addressing N bits jets elements switch multiplexer circuit system printhead has been measured of ejected DNA droplet behavior. There is up to 1024 and even a larger number of elements for a variety of printhead nozzle examinations. The jets interference and the power consumption for such a high-density system, however, make it difficult to achieve a high printing speed, low cost, economic, high-performance, and high-resolution device. In order to alleviate the low noise interference and low-power requirement of jets, a high-voltage driver and logic multiplexer are nowadays employed to match each nozzle of the printhead jet elements and therefore improves the printhead’s overall power dissipation. Figure 1 shows inkjet printer heads system and multi-channel printhead jets using novel encoding algorithm system. Addressing N bits jets elements switch circuit system is using in inkjet chip. Logic functions integrated, enabling TIJ-based products have become increasingly high-end market [17–23]. Inkjet printers can put small number of DNA droplets (usually only a few picoliters, 10–12 l) accurately sprayed on to DNA glasses media. Integrated circuit of the TIJ described transducer array to provide the 1024 ejection jets, includes a data interface, an DNA ink-jet treatment, short-pulse generation, and bidirectional method operation. The chip system also has an output function to manage of multi-chip electronic components into larger arrays. TIJ spray hole array chip design architecture allows less than 10 input lines op addressing 1024 nozzles. Figure 2 shows printed DNA droplets “AGCT” arrangement and detection.
\nPrinted DNA droplets “AGCT” arrangement and detection.
Human birth, old age, sickness and death process, and cellular changes are related to changes in the cell and turn machine in the DNA have been around for a round to be free from the disease, prevent aging dream, universally invested considerable manpower material, and finally solved the mystery of the human DNA code. However, the cause of the test, the correct dosage, and even tailored drugs are dependent on fast, accurate, simple, and inexpensive test technology.
\nTraditional testing methods, slow and time-consuming, difficult to control the accuracy and cost is very high, limiting the rapid development of biomedical science. Use Biomedical MEMS and microfluidic system technology developed in the biomedical wafer, for DNA sequencing, testing, screening, and development of new drugs, quantitative release of the drug, as well as food, environmental testing and other diseases, to provide a fast, accurate, large, and automation platform. I believe will be able to promote the development of the next stage of biotechnology, provide a degree of contribution.
\nBiomedical wafer has to do trace detection, quantitative precision, automation, and fast parallel processing, and many other advantages, compared with the traditional biomedical detection, have tremendous advantages, and so far, it has also been a lot of breakthrough technological developments. But it must be said, biomedical wafer also faces many technical challenges, by scientists in different fields need to be overcome. The use of high-density microfluidic device similar to a color inkjet printer’s thermal bubble inkjet and other key technologies, each has independent probe of the trace liquid tank, pipeline microfluidics, liquid discharge hole. Trace each liquid tank filling oligonucleotide, after large pieces of DNA probe solution or sugars, can be more than one million droplets ejection.
\nWe use liquid jetting method in addressing the DNA on the slide; it is a precise and rapid deployment of quantitative methods. Generating and physical aspects of the process model simulation of heat dissipated in the growing bubble. It is used thermal bubble nucleation theory (bubble nucleation theory) to simulate the physical mechanism of heat generated by the bubble. It is to discuss ejection chamber (firing chamber) and cavity geometry shapes to reach backfill mechanism of DNA as shown in Figure 3. Calculation procedure thermal bubble jet pump decline is a fluid field problem free surface, while the shape of the free surface of the flow field will change with those changes, so to understand the characteristics of injection, must respect the free surface Discussion of issues to be studied.
\nNumerical simulation of a need to calculate immiscible dominated by the surface tension of the free liquid surface control (free surface). This free surface on both sides and the physical properties of the fluid pressure has discontinuous nature of change; computer simulation program is the key to success lies in tracking the exact location of this discontinuous liquid level.
\nEjection chamber (firing chamber) and cavity geometry shapes.
Computer simulation is the traditional type of single channel for supplying a fluid ejection chamber (firing chamber) simulation. Injection cavity geometry is shown in Figure 4. Orifice diameter of 60 μm, the thickness of the orifice sheet is 50 μm, dry film thickness of 60 μm, the bottom area of the injection chamber is 120 μm × 120 μm, the area of the heater was 105 μm × 105 μm. Figure 5 calculated result is for the injected fluid which is water to 5 kHz operating frequency, and the three-dimensional side view of a two-dimensional cross-sectional view in the XZ 10, 20, 30, 40, and 200 μs injection case.
\nComputer simulation is still the traditional type in a single passage of the fluid supplied to the injector chamber to simulate. Figure 6 calculated result is for the injected fluid which is changed to DNA. It is 5 kHz operating frequency, three-dimensional, and three-dimensional side view view at 10, 20, 30, 40, and 200 μs injection scenario. Single-channel injection cavity is not for Z-axis direction completely symmetrical design. It is a droplet drag tail vulnerable asymmetrical flow field forces. It makes the deflection direction of flight. On a three-dimensional view, it can be seen clearly. The fluid is water or gasoline, because both the geometry of the cavity injection asymmetry makes the tail dragging flight direction deflection. Figure 7 for the two-dimensional calculation results X–Z sectional view. X–Z sectional view of the results in 200 μs moment, we can see that the liquid level of the fluid, although not yet fully reached the nozzle exit, but DNA is still almost complete backfill. The results also show the geometry of this injection cavity design, operating at a frequency of 5 kHz for, in terms of the DNA is the upper limit of the operating frequency. To further increase, the operating frequency may be less than the ink supply phenomenon. Figure 8 is compared with two-dimensional flow field inside the internal cavity of the injection X–Y sectional view of the results. It is the internal flow field vector and water, as shown in below. It is not much difference, showing backfill speed slower than the water.
\nComputer simulation created by (a) calculation of regional, (b) three-dimensional map of the microfluidic single channel.
Computer simulation of water in the nozzle diameter 60 μm and 50 μm thickness of a single channel injection cavity, an operating frequency of 5 kHz, in (a) a three-dimensional side view (b) XZ sectional view of a two-dimensional, 10, 20, 30, 40 and 200 μs injection scenario.
Numerical simulation of DNA in the nozzle diameter 60 μm and 50 μm thickness single-channel injection cavity to 5 kHz operating frequency, to (a) a three-dimensional side view (b) on a three-dimensional view, 10, 20, 30, 40 and 200 μs of injection scenario.
DNA computer simulation in the nozzle diameter 60 μm and 50 μm thickness of a single channel injection cavity to 5 kHz operating frequency, in the two-dimensional X–Z sectional view, at 10, 20, 30, 40 and 200 μs injection scenario.
Numerical simulation of DNA in the nozzle diameter 60 μm and 50 μm thickness of the single-aisle jet cavity to 5 kHz operating frequency, the X–Y two-dimensional cross-sectional view, in 10, 20, 30, 40 and 200 μs injection scenario.
It is at the same voltage, the heating time, and other conditions. Because different working fluids (water and DNA), and for the same single injection but may result in different maximum flow. The cause of this problem, there are two possible reasons, the first is due to the poor design of single microfluidic channel, resulting in the flow of work done when the thermal bubble jet DNA monomer heater inlet to the push-back is greater than the flow path to the nozzle holes the launch of the top jet fuel. Thus, causing loss affects a large number of heater acting DNA spray flow. At the same time, due to differences in the physical properties of DNA and water, so that the DNA greater than water leakage, resulting in a smaller flow nozzle exit. Narrowing the channel inlet cross-sectional area is a method you can try, but this method also simultaneously increase the time required for DNA backfilling injection chamber, the monomer jet ejection frequency may therefore need to fall. In addition, since the monomer jet DNA to reduce the cooling effect is reduced, so cause DNA monomer generates heat accumulation effect and affect the efficiency of DNA spray, spray a vicious cycle that causes DNA not been apparent efficiency. Another possibility is due to the thermodynamic properties of water and DNA in the table. Temperature, the vertex (critical point) of the magnitude of the pressure is not the same. Even under the same operating conditions of voltage and time of heating, the heat generated bubble internal pressure is not the same size, that is, have different sizes of thrust. Thermal bubble pressure and water produced large thrust, the jet and the flow rate is also larger. In the same function and the same thrust geometric shape of micro-channel design, the simulation by calculation, preliminary verification can launch jet monomer droplets, the difference volume flow (volume flux) of. Release of DNA volumetric flow rate is relatively low, due to the different physical properties of DNA inference with water, causing DNA to the channel inlet neck (neck channel entrance) the loss is greater than the flow rate of water flow loss. Figure 9 is the volumetric flow rate of the working fluid through the top of the water and the DNA cross-sectional area of the calculated change with time in figure. This showed that both the volumetric flow rate is not much difference with the total volume of traffic resulting time integration. The inference from the above calculation results under the same operating conditions, hot water bubble pressure, and thrust generated by comparing DNA large, resulting in the ejection of the flow is also larger.
\nVolumetric flow rate of water through the top and DNA computing sectional area of change with time of the case.
A method for increasing the injection flow rate, in addition to increasing the frequency of injection outside, increasing the ejection orifice diameter of the cavity is also a method to try. But may have other negative effects such as fluid leakage orifice is easy to form puddles (puddling), the need for evaluation by computer simulation verification, in order to determine the negative impact is not the whole jetting performance. Figure 10 evaluates to the orifice diameters ranging from 60 μm increased to 80 μm, when the injected fluid remains gasoline to 5 kHz ejection frequency, three-dimensional and three-dimensional side view at 10, 20, 30, 40, and 200 μs in the case of injection. With the results shown in Figure 10, comparison can be learned in the same circumstances thrust function, because the spray hole diameter increases, so the ejected droplet volume increases. In 40 μs results instantly show droplet flying speed quite significantly reduced. It is produced a relatively large volume of satellites and flying very slowly. Figure 11 for the two-dimensional calculation results XZ section; at the moment of 40 μs results showed, as exports slow so that the droplet is not out of the nozzle holes with respect to the results in Figure 10 for spray when the hole is 60 μm, in an instant 40 μs, the droplet tail is already out of the nozzle holes. Figure 12 is the result of the calculation of the X–Y two-dimensional section, due to the increase in the spray orifice diameter, relatively large volumes of a spray of droplets. In the cross-sectional area of the flow path, inlet same circumstances take longer to completely fill the internal cavity of the injection orifice until the surface, while the inner flow field to stabilize. Internal flow velocity vector field is still supplying single-channel direction of the fluid toward the discharge chamber in the direction of the moment of 200 μs.
\nNumerical simulation of DNA in the nozzle diameter 80 μm and 50 μm thickness single-channel injection cavity to 5 kHz operating frequency, to (a) a three-dimensional side view (b) on a three-dimensional view, 10, 20, 30, 40 and 200 μs of injection scenario.
DNA computer simulation in the nozzle diameter 80 μm and 50 μm thickness of a single channel injection cavity to 5 kHz operating frequency, in the two-dimensional X–Z sectional view, at 10, 20, 30, 40 and 200 μs injection scenario.
Numerical simulation of DNA in the nozzle diameter 80 μm and 50 μm thickness of the single-aisle jet cavity to 5 kHz operating frequency, the X–Y two-dimensional cross-sectional view, in 10, 20, 30, 40 and 200 μs injection scenario.
Increase the injection flow rate of the other direction of thinking in order to increase the volume inside the cavity injection, in order to that the injected volume of the droplet can be increased, so the study also hope that through computer simulation to verify its feasibility. Figure 13 for the calculation of simulated gasoline nozzle diameter and 60 μm thickness of 50 μm, dry film (dry film layer) increases the height by 60 μm to 90 μm single-aisle jet chamber, which internal cavity volume 150% increases in operating frequency of 5 kHz, XZ dimensional, three-dimensional side view, and sectional view, in 10, 20, 30, 40, and 200 μs in the case of injection. The result of the calculation shows that the droplet flying speed and directivity of Figures 3–12 dry film 60 μm when the height of the result is not much difference, but when 40 μs has been out of the spray droplets hole; but 200 μs instantaneous results show that the fluid has reached the finish filling orifice surface, while the overflow orifice phenomenon is easy to form puddles phenomenon. Therefore, increasing the height of the dry film that is to increase the volume inside the cavity injection, although you can increase the flow rate of backfill raise, it is still possible because the backfill too fast, and out of the orifice puddles formed on the surface of the phenomenon, probably because last fluid left in the orifice surface, so that subsequent ejection of a droplet directionality poor is to increase the dry film thickness may be required to pay attention to the negative effects derived.
\nDNA computer simulation in the nozzle diameter 60 μm and a thickness of 50 μm, a height of 90 μm dry film of the single-channel injection cavity, an operating frequency of 5 kHz, in (a) a three-dimensional side view (b) XZ sectional view of a two-dimensional, in 10, 20, 30, 40 and 200 μs injection scenario.
It is an injection operation in various applications nozzle (ink jet head). It is a special microfluidic flow channel structure. Backfill fluid injection and two complementary action this period, to be injected fluid within the microfluidic flow path ilk field direction opposite directions. This phenomenon will seriously affect the speed of the fluid backfill supplement and seriously affect the operation frequency of jets. From the simulation result, the system is to solve the problem of liquid flow. It is a dual-type injection cavity design having a fluid passage. At the same time, the fluid has a single-flow direction. It is to reduce the resistance of the fluid, shortening the filling time of the fluid. It is possible to increase the operating frequency of the monomer injection, thereby increasing the maximum injection flow rate.
\nIn this study, it is the geometry and design by microfluidic flow channel. It is a single-direction flow velocity field compared to the entire cycle of backfill fluid flow direction. Therefore, it is to enhance its complement backfill fluid velocity. When the nozzle operating frequency increases, the fluid flow to replenish backfill required for stabilization of fluid ejection chamber fluid level backfill added time will dominate the operating frequency of the jets. Therefore, reducing the time to replenish the fluid needed for backfill will greatly enhance the operating frequency of the jets. Since the droplet ejection but also take away a lot of heat generated by the water heater, a considerable cooling effect reduces the internal temperature of the wafer. So there is also always a considerable improvement in the service life of the wafer. To achieve the above purpose, it is designed to spray a tapered cavity structure of dual-channel microfluidic. Figure 14 is the three-dimensional microfluidic tapered dual-channel region of a perspective view of the computing range. This type of gradual reduction for dual-channel microfluidic injection chamber numerical simulation conducted to assess the effectiveness of its injection. Figure 15 for DNA to orifice diameter 30 μm and 50 μm thickness tapered dual-channel injection chamber to 10 kHz operating frequency, three-dimensional side view of 10, 20, 30, 40, 100 110, 120, 130, 140, and 200 μs injection scenario. 110, 120, 130, 140, and 200 μs belong to second injection stage. Figure 16 is compared to the two-dimensional X–Y sectional view, in the case of injection 10, 20, 30, 40, 100, 110, 120, 130, 140, and 200 μs.
\nComputer simulation created by (a) calculation of regional scope, (b) a tapered three-dimensional map of the dual-channel microfluidic.
Numerical simulation of DNA in the nozzle diameter 30 μm and 50 μm thickness tapered dual channel injection chamber to 10 kHz operating frequency, three-dimensional side view, in 10, 20, 30, 40, 100, 110, 120, 130, injection of the case 140 and 200 μs.
Numerical simulation of DNA in the nozzle diameter 30 μm and 50 μm thickness tapered dual channel injection chamber to 10 kHz operating frequency, the XY two-dimensional cross-sectional view, in 10, 20, 30, 40, 100, 110, 120, injection case 130, and 140 of 200 μs.
The XY two-dimensional cross-sectional view shows that the internal flow field this injection cavity does not have the speed of the flow field in a single direction, so it becomes counter-flow injection of small, but the volume of the second droplet ejection seems to be more for the first time the injection volume is slightly larger. The reason may be due to the tapered microfluidic injection chamber at the start of the two-channel state under stationary conditions. When the first injection, the injection inside the cavity and cannot be achieved immediately single-flow velocity flow field. It requires a certain number of jet action, or the need to increase the flow path style tapered angle, have a chance to achieve a single direction of flow velocity field.
\nFigure 17 is the result of the calculation of the initial conditions set for the injection inside the cavity has a single-class field direction of situations. DNA double-tapered channel in the injection chamber to 5 kHz operating frequency, three-dimensional and three-dimensional side view on view at 10, 20, 30, 40 and 50 μs injection scenario. From the results shown that the results of the droplet ejection volume comparing Figure 16. There is an increasing convergence of big. Results indicate if the ejection velocity flow field inside the cavity having a single direction of the flow field. It is the ejection of flow convergence increase, while reducing the time required for the fluid filling the cavity of the injection, but also to simultaneously increase the ejection frequency. Figure 18 is compared with the two-dimensional X–Y sectional view at 10, 20, 30, 40 and 50 μs injection scenario.
\nNumerical simulation of DNA in the nozzle diameter 30 μm thickness and tapered dual channel injection cavity 50 μm to 5 kHz operating frequency, to (a) a three-dimensional side view (b) on a three-dimensional view, 10, 20, 30, 40 and 50 μs injection case.
Because of the time course of planning this program, yet there is enough time for this can be tapered dual channel injection chamber, do computer simulation analyzes of various design parameters such as the angle of the tapered flow channel type, respectively to be few degrees preferred design. Application of the heater to produce instant hot bubble of high pressure jet thrust derived monomer. While allowing fluid flow velocity has a single field. Ejection frequency can be increased, and thus get the most traffic. It is currently unable to give details of the desired design dimensions apply to this program the best dual-channel injection tapered cavity to obtain maximum injection efficiency. Continue to be the future of the current simulation analysis to identify micro-injection monomer flow path design can operate at high operating frequencies.
\nNumerical simulation of DNA in the nozzle diameter 30 μm thickness and tapered dual channel injection cavity 50 μm to 5 kHz operating frequency, the X-Y two-dimensional cross-sectional view, in 10, 20, 30, 40 and 50 μs injection case.
Printing method is the change comes from an inkjet printer, with the heated bubble manner nucleic acid probe is placed on a glass slide using a gene chip production to 30,000 points as shown in Figure 19.
\nDNA droplets profile.
Situ synthesis (in situ synthesised), the nucleotide sequence of molecules by using different methodologies to control chemical reactions forming a jieshangqu a nucleic acid sequence, the rapid production of precision (accurate positioning and orientation uniform), ultra-high density (1 million–200 million points) wafer. Synthesis There are two kinds, one is the use of liquid jet technology, such as nucleotide-like ink injected into a specific location subjected to solid phase synthesis (solid phase phosphoramidite chemistry). The whole chip layout is show in Figure 20.
\n(a) The whole chip layout. (b) The detail circuit(DFF) diagram of chip.
System is to determine a DNA liquid printed head with two hundred orifices, each orifice to orifice distance is another 2000 μm. It is to select the drive mode, respectively, following several ways. The first is the direct voltage direct drive via Pad on the wafer, the drawback is the number of multi-Pad. The second drive element is a driving thin-film resistance element. It is the driving element has a variety of points. It is the n-type metal-oxide half effect transistor factory.
\nDNA droplet chip and module.
Multiplexer DNA solution jet part.
It is the use of an n-type metal-oxide plant halftime effect transistor to drive a thermal film. It is the thermal resistance of the film due to the long drive driving the heat bubble reagent sprayed onto glass slides. Taking into account the upper and lower symmetrical design of the wafer, so we must first decide with each other and each of the driving elements thin-film resistance elements are arranged. It is the liquid discharge head of the wafer area is very large. We design each wafer map 384 orifices as shown in Figure 20a. Our first idea is to spray the wafer to contact aligner way DNA production. The entire wafer is DFF(D-Flip-Flop) data staging operation and high-voltage driver circuit as shown in Figure 20b. This circuit can be applied to one or more of the control input signal to change the state, and there will be one or two outputs. Flip-flop is the basic logic unit is configured to sequence logic circuit and a variety of complex digital systems. Flip-flops and latches are essential components used in computer, communications and many other types of systems in the digital electronic systems.
\nIntegrated spray liquid infusion tube sheet and the card brake package as shown in Figures 21 and 22. It is the result of a special liquid jet architecture DNA cloth into the slide.
\nSince microarray dataset wafer has a very large number of the number of genes. It is based on grouping method to automatically discover biological modules (biological modules) is an important theme of the microarray chip analysis. It is a functional grouping (functional Clustering). It is a common occurrence frequency by corresponding functional gene annotations (functional annotation) between (co-occurrences) measurements for clustering. So it can make related genes and annotations easy reach of digital analysis to facilitate the subsequent establishment of the assumptions and experimental design.
\nThe core principles behind the array hybridization between two strands of DNA, the complementary nature of the nucleic acid sequences specifically complementary pair hydrogen bonding between pairs of nucleotide bases to each other through the formation.
\nWithin the liquid jet module integrated HV-ESD Clamp prospective multi-bit output integrated circuit, as shown in Figure 22, the DNA gene sequence of printing cards poured into 384 gates, such as nucleotide-like ink injected into specific the position of solid phase synthesis (solid phase phosphoramidite chemistry).
\nTwo sets of data are by the AIP (PIN29) and BIP (PIN30).
The system will be open print dot DNA. It is the use of multi-circuit will print out the orifice of addressing DNA shown in Figure 23. There are two sets of data are by the AIP (PIN29) and BIP (PIN30) simultaneously into two 16 bits Register. With instructions sent switch control signal, each generating 384 thermal outputs. CK1 transfer instructions simultaneously send data, CK2 execute instructions simultaneously sending data to the thermal output.
\nESD clamp circuit between the power (Power-Rail ESD Clamp Circuit) and inner circuit, when the electrostatic discharge protection device is used in the power supply ESD clamp device, under normal working operation, ESD protection essential element is closed. And the occurrence of electrostatic discharge when the electrostatic discharge protection device must be able to quickly turn on to ground the electrostatic discharge current, in order to protect the internal circuit purposes as shown in Figure 24.
\nDNA droplets arrangement and detection are observation by high speed cameras. It is by the power supply, light source, liquid discharge frequency and synchronization signals to observe droplet trajectory as shown in Figure 25. It is modulated the observation flat-top building to a suitable position, to approve from droplet observation to catch droplet orbit phenomenon. The measurement system could calculate the droplet area、blob length、droplet injection position. Figure 26 is shown in 5 kHz operating frequency at 30, 40 μs injection.
\nFigure 27 is printed chip module photo. 50 μm thickness of a single channel injection cavity to 5 kHz operating frequency at 10, 20, 30, 40 μs injection is shown in Figure 28.
\nThermal inkjet(TIJ) printhead with multi-level output voltage ESD protection system.
DNA droplets observation platform.
5 kHz operating frequency at 30, 40 μs injection.
Printed chip module.
5 kHz operating frequency at 10, 20, 30, 40 μs injection.
The heated bubble manner nucleic acid probe is placed on a glass slide using a gene chip production to 30,000 points as shown in Figure 29. The special printing architecture method is used in system. Among them DNA time interleaving scanning sequence droplets ejection with “even group” jets, DNA droplets ejection with an addressing of two elements on the same time period driving, and DNA droplets ejection with an addressing of three elements on the same time period driving were shown in Figure 30. The time interleaving scanning sequence is controlled spatially on the jet elements to avoid the strong interference with DNA droplets caused by the excitation of the neighbor driven elements.
\nNucleic acid probe placed on a glass slide.
The special printing architecture method.
The authors acknowledge financial supports of MOST 104-2220-E-151-001.
\nOne of the main factors affecting reproductive performance of dairy cattle is postpartum uterine disease. Metritis and endometritis have been associated with delays in restarting ovarian activity postpartum, prolonged intervals from calving to first service, increased number of days open, decreased conception rates, and increased culling rates [1, 2, 3, 4, 5]. Affected animals are easily identified when they show clinical signs indicative of uterine disease. Though symptoms of systemic illness are often absent, a purulent or mucopurulent vaginal discharge warrants further investigation, and therefore, clinical metritis and endometritis rarely remain undiagnosed.
\nFourteen years ago, Kasimanickam et al. [6] found that many clinically normal postpartum cows had subclinical endometritis (SE). Those authors evaluated endometrial cytologies collected from 228 healthy cows at 21–33 days postpartum and related the cytological findings with the subsequent reproductive performance of cows. They used a receiver/response operating characteristic (ROC) curve to determine a threshold percentage of polymorphonuclear leukocytes (PMN%) in the cytological smears above which fertility was significantly reduced, and therefore, subclinical endometritis was diagnosed based on PMN% threshold. Since that pioneer work, many other studies have investigated the etiology, prevalence, and impact on reproduction of SE in dairy cows.
\nSubclinical endometritis is the inflammation of the endometrium without clinical signs and often without evidence of infection [7, 8, 9]. Alteration of the inflammatory response postpartum could be at the origin of this condition.
\nThere is no doubt that uterine pathogens may negatively affect reproduction both by causing direct endometrial damage and by producing toxins [10, 11]. Bacterial endotoxins are known to have numerous effects on reproduction: (a) they may affect estradiol and progesterone secretion and alter follicular growth and the normal development of the corpus luteum [10, 11, 12], (b) may interfere with LH production and cause ovulation failure [13, 14], (c) may increase PGE2 secretion and prolong the life span of corpus luteum [15], and (d) may induce embryo mortality [16].
\nIn cows with metritis and clinical endometritis, recognized pathogens such as
In several studies, cows with clinical and subclinical endometritis were shown to have increased endometrial mRNA expression and elevated serum concentrations of pro-inflammatory mediators as compared with healthy cows [20, 21, 22, 23, 24]. Situations of prolonged inflammation after elimination of bacterial contamination may occur when an exacerbated production of eicosanoids concurs with a low production of anti-inflammatory substances, originating a delayed restoration of homeostasis in the affected tissues [25]. It has also been suggested that an unbalanced production of pro-inflammatory/anti-inflammatory cytokines during the first week postpartum could play a determinant role in the subsequent development of SE. A high ratio of pro-inflammatory/anti-inflammatory cytokines during the first week postpartum could lead to an excessive inflammatory response [26], whereas a low ratio of pro-inflammatory/anti-inflammatory cytokines might impair activation of inflammation and clearance of bacteria and lead to development of endometritis [22, 27].
\nOn the other hand, diet fat levels and the type of fatty acids present in diet may affect cellular immune function [28]. Linoleic acid-enriched diets fed to dairy cows during the transition period [29] induced a pro-inflammatory status during the first week postpartum. Several studies have demonstrated that excess of adipose tissue and high serum concentrations of non-esterified fatty acids constitute risk factors for postpartum pro-inflammatory diseases in dairy cows, such as metritis or mastitis [30, 31, 32]. Innate immune response is activated when an aggressor agent is recognized by toll-like receptors (TLR). Different aggressor agents are recognized by specific TLR, which might also be activated by certain molecules in the absence of aggressor agents. For instance, lipopolysaccharides present in the cell wall of gram-negative bacteria are recognized by TLR4, which may also be activated by some fatty acids (lauric, palmitic, and oleic) [33]. Thus, an inflammatory response might be induced without the existence of infection.
\nIn addition, the oxidative stress may contribute to an abnormal inflammatory response during postpartum [33, 34]. Increase of oxygen metabolism during postpartum would increase ROS production rate [33, 35]. Studies carried out in bovine endothelial cells evidenced that oxidative stress increased lipid hydroperoxide formation which enhanced a pro-inflammatory phenotype of these cells [36, 37, 38].
\nIndependently of the cause of inflammation, the inflammatory status of the endometrium may have a major impact on reproduction. A direct negative effect of SE on embryo quality and survival has already been described [39, 40], which would affect conception rates. In addition, results from various studies suggest that SE may be associated to altered patterns of prostaglandin E2 and F2α synthesis [41, 42] which could compromise luteal function and pregnancy.
\nOn the other hand, certain cytokines are known to play essential roles on the physiological regulation of ovarian function [43]. Cytokines are involved in regulation of follicular growth, ovulation, luteal formation, and regression [44, 45]. Inflammatory mediators, such as cytokines released in SE, may perturb this regulatory function.
\nCows with subclinical endometritis, by definition, do not show any clinical sign of endometritis, and therefore, the diagnosis of this condition requires the use of endometrial cytology, biopsy, or any other method able to evidence the presence of endometrial inflammation.
\nUltrasonography has been used as a method to diagnose SE based on the presence of intrauterine fluid and on the evaluation of uterine diameter. A small amount of fluid in the uterine lumen and/or thickened uterine walls can be considered signs of endometrial inflammation. However, in various studies ultrasound was found to be less sensitive than endometrial cytology [6, 46, 47] for SE diagnosis. Presence of intrauterine fluid and a thick uterine mucosa may be normal findings in physiological situations such as estrus or early postpartum [48], and perhaps the evaluation of fluid characteristics could improve the sensitivity of ultrasound diagnosis [49]. Mariño et al. [9] found a significant relationship between presence of abnormal intrauterine fluid and SE diagnosed by biopsy but not by cytology.
\nDoppler ultrasonography might be useful for the diagnosis of endometritis in cattle, but it is still an unexplored tool. Debertolis et al. [50] found significantly increased blood flow in uterine arteries of cows to which acute endometritis had been experimentally induced. Whether patterns of vascular flow may differ between healthy uterus and those with SE still has to be investigated.
\nEndometrial cytology is considered the most reliable method for the diagnosis of SE [46], and therefore, it is the one most frequently used. Samples for cytology can be obtained by two main techniques, cytobrush and uterine lavage.
\nThe cytobrush technique consists of connecting a cytobrush to the plunger of an insemination catheter [6] and, protected by the catheter, introducing it into the uterus as for doing artificial insemination. Inside the uterus, the cytobrush is pushed out of the catheter, gently rotated against the uterine wall, guarded back inside the catheter, and removed from the uterus. The brush is rolled onto a microscopic slide and stained. Cytology samples can be obtained from the uterine body or from one of the uterine horns. Mariño et al. [9] compared cytology and biopsy findings between the two horns of 100 bovine uteri collected postmortem and observed that samples collected from the left horn were more representative of both uterine horns than those collected from the right one.
\nThe uterine lavage technique consists of infusing sterile saline solution into the uterus with a catheter, gently massaging the uterus to allow fluid distribution within the lumen, and recovering some of the fluid by aspiration using the same catheter. The collected fluid is centrifuged, the supernatant discarded, and the sediment smeared onto a microscopic slide. Regardless of the collection technique, cytological smears are fixed and stained using conventional stains (e.g., Diff-Quick).
\nKasimanickam et al. [51] did a comparative study of the two sampling techniques and concluded that cytobrush had some advantages over uterine lavage: it was less time-consuming, was easier to perform independently of the uterine size, did not produce endometrial irritation, and induced lower degree of cell structure distortion and lower presence of erythrocytes. One disadvantage of cytobrush is that the sample is collected from a specific area of the endometrium, whereas uterine lavage provides cells from the whole endometrial surface.
\nRecently, Pascottini [52] described a new method for sample collection that consisted of using a paper tape rolled around the top of an insemination catheter. With this method the author observed less contamination with erythrocytes and a better preserved structure of epithelial cells than when using cytobrush. Moreover, this system would allow taking a sample for cytology at the same time of doing insemination.
\nConcerning the threshold used in different studies for the diagnosis of SE, the cutoff PMN% reported by the different authors has varied between 4 and 25% (Table 1) depending on the postpartum period at which the diagnosis was done.
\nSampling method | \nPostpartum diagnosis period | \n\n | ||
---|---|---|---|---|
Cytobrush | \nWeek 3–5 | \nWeek 5–7 | \n≥7 week | \nPMN% | \n
Lopdell et al. [53] | \n35.0% | \n\n | \n | >18.0% | \n
Kasimanickam et al. [6] | \n35.1% | \n\n | \n | >18.0% | \n
Heidarpour et al. [54] | \n13.5% | \n\n | \n | >18.0% | \n
Kaufmann et al. [55] | \n12.4% | \n\n | \n | >18.0% | \n
Barrio et al. [56] | \n17.6% | \n\n | \n | >18.0% | \n
Madoz et al. [57] | \n21.5% | \n\n | \n | >8.0% | \n
Dubuc et al. [58] | \n19.3% | \n\n | \n | >6.0% | \n
Plöntzke et al. [59] | \n38.0% | \n\n | \n | >5.0% | \n
Lopdell et al. [53] | \n\n | 7.0% | \n\n | >18.0% | \n
Kasimanickam et al. [6] | \n\n | 34.0% | \n\n | >10.0% | \n
Barlund et al. [46] | \n\n | 11.8% | \n\n | >8.0% | \n
Madoz et al. [57] | \n\n | 16.0% | \n\n | >6.0% | \n
Plöntzke et al. [59] | \n\n | 19.0% | \n\n | >5.0% | \n
Barrio et al. [60] | \n\n | 14.9% | \n\n | >5.0% | \n
Madoz et al. [57] | \n\n | \n | 16.0% | \n>4.0% | \n
Dubuc et al. [58] | \n\n | \n | 11.1% | \n>4.0% | \n
Uterine lavage | \n\n | \n | \n | \n |
Hammon et al. [61] | \n51.8% | \n\n | \n | >25.0% | \n
Barlund et al. [46] | \n15.8% | \n\n | \n | >8.0% | \n
Gilbert et al. [62] | \n\n | 53.0% | \n\n | >5.0% | \n
Cheong et al. [63] | \n\n | 25.9% | \n\n | >10.0% | \n
Cytotape | \n\n | \n | \n | \n |
Pascottini [52] (at AI, cows) | \n\n | \n | 27.8% | \n≥1% | \n
Pascottini [52] (at AI, heifers) | \n\n | \n | 7.86% | \n≥1% | \n
Reported prevalence of subclinical endometritis in some studies that used different sampling methods, postpartum diagnosis periods, and PMN% cutoff values.
Uterine contamination at parturition or in the following days is unavoidable and normal, with 80–100% of animals having bacteria in the uterine lumen in the first 2 weeks postpartum [17]. Uterine contamination elicits neutrophil migration from peripheral blood to the uterine lumen and the subsequent phagocytosis of contaminating organisms by neutrophils. Prunner et al. [18] observed that uterine bacterial growth density increased from calving to 15 days postpartum and decreased from day 21 onwards and the PMN% in cytological samples decreased from calving to day 9, then increased around days 15–21, and decreased thereafter, but at each sampling period, the proportion of PMN strongly depended on bacterial counts.
\nKasimanickam et al. [6] used ROC analysis to identify the PMN% above which fertility was significantly reduced, and this percentage was 18% for samples taken 20–33 days postpartum and 10% for those taken 34–47 days postpartum. Other authors also established the cutoff PMN% for diagnosing SE based on detrimental effects on subsequent reproductive performance [46, 57, 58, 64], and some [59, 61, 62] used arbitrary values. In general, most authors used PMN% thresholds of 15–18% for SE diagnosis at 21–30 days postpartum and values of 4–10% for diagnosis at later periods. Prunner et al. [18] categorized clinically normal cows at 21 days postpartum as having SE when PMN% ≥5% and found that SE-positive cytological samples had an average of 30% PMN; however, on day 28, cows previously categorized as having healthy uteri (i.e., <5% PMN on day 21) had a similar PMN% as those categorized as having SE, and for both groups, it averaged 15%. During the first month postpartum, healthy cows may show relatively high percentages of PMN in cytological samples, and therefore, diagnosis of SE during this period will be less accurate than a later diagnosis.
\nIt has been suggested that the stage of the estrous cycle might have an effect on the proportion of PMN present in the cytology and, therefore, on the diagnosis of SE. During the follicular phase of the estrous cycle, there is an increased infiltration of PMN in the endometrium elicited under estrogenic influence [65]. Several studies [9, 52, 57] have found that the PMN% in cytological samples taken with cytobrush was not affected by the stage of the estrous cycle. However, when the SE diagnosis was done by biopsy, a higher degree of inflammatory infiltration could be observed in the follicular phase of the cycle [9]. This was because cytology only detects PMN infiltration in the superficial epithelium, whereas biopsy allows identifying inflammatory cells in deeper layers of the endometrium.
\nAnother possibility to evidence the existence of endometrial inflammation is the use of urinary test stripes, which detect the presence of leukocytes in urine [66, 67, 68]. The diagnosis of endometritis can be done using uterine lavage fluids, or an endometrial cytobrush can be immersed in saline solution during 30 sec and then the strip introduced in the solution for 2 sec. It is a qualitative colorimetric test that showed a variable correlation with cytology. Santos et al. [66] reported a sensitivity of 96% and specificity of 98%. However, Cheong et al. [67] observed 77% sensitivity and 52% specificity. This test is rarely used in commercial dairy farms probably because it is not specifically designed for the diagnosis of endometritis.
\nUterine biopsy is commonly used in human medicine as it is considered the gold standard for evaluating the human endometrium [69]. In domestic animals, uterine biopsy has been used since the 1960s to investigate causes of infertility in mares [70], and it is a routine diagnosis method today [71]. However, in dairy cattle uterine biopsy is rarely performed by practitioners, and it is almost exclusively used for research purposes. The limited use of biopsy in clinical practice may be related with inconveniences associated to sampling time, requirement for laboratory skills, laboratory costs, and time to report [71] and also to the risk of inducing endometritis and the subsequent negative effects on fertility [72].
\nThere are few studies using uterine biopsy for the diagnosis of SE in dairy cattle [73], and when biopsy and cytology findings were compared, the two diagnosis methods showed poor agreement [8, 9, 47]. The histopathological examination of biopsy samples gives detailed information about the degree of inflammation, distribution of the inflammatory infiltrate, or the lesions that may exist, whereas cytology only assesses the superficial layer of the endometrium [47]. Thus, it is not surprising that direct comparison between biopsy and cytology results showed low agreement. Evaluation criteria for SE diagnosis on biopsy samples, as for cytology, should be established based on detrimental effect on subsequent reproductive performance rather than on the presence of an arbitrary number of inflammatory cells [47].
\nThe reported prevalence of SE in postpartum dairy cows has varied between 7 and 53% (Table 1). Such disparity among studies in SE prevalence may be due to differences in (i) postpartum period in which the diagnosis was made, (ii) PMN% established as threshold above which an endometrial cytology was considered positive for SE, and (iii) the method used to take the cytological sample, i.e., cytobrush, uterine flushing, or cytotape. In general, SE prevalence tended to be higher when the sample was collected by uterine lavage, the diagnosis was made before 30 days postpartum, and the cutoff PMN% applied was >5%.
\nThere are some discrepancies among authors concerning the effects of SE on reproductive performance of dairy cows. Whereas some authors [59, 74, 75] did not find significant effects on reproduction, many other studies described a variety of negative effects on fertility (Table 2). The disparity of results may not only be due to the different diagnosis criteria (e.g., postpartum period for SE diagnosis, threshold of PMN applied, etc.) used in the different studies but also to the numerous confounding factors that may have a negative effect on reproduction (e.g., poor heat detection, inadequate nutrition, insufficient cow comfort, old cows, poor semen quality, other diseases, etc.).
\nReference | \nCharacteristics of the study | \nReproductive impact | \nAffected parameters | \n
---|---|---|---|
Kasimanickam et al. [6] | \nn = 228; farms = 2; no cows with PVD; cytobrush; 20–33 DIM: >18% PMN; 34–47 DIM: >10%PMN | \nAdverse | \nDays open. Pregnancy rate | \n
Gilbert et al. [62] | \nn = 141; farms = 5; no cows with PVD; uterine lavage; 40–60 DIM: ≈5%PMN | \nAdverse | \nPostpartum anestrus. First-service pregnancy rate. Services per conception. Days open. Pregnancy rate | \n
Barlund et al. [46] | \nn = 221; farms = 8; no cows with PVD; cytobrush; 28–41 DIM: >8%PMN | \nAdverse | \nFirst-service pregnancy rate. Services per conception. Days open. Pregnancy rate | \n
Dubuc et al. [58] | \nn = 1044; farms = 6; some cows with PVD; cytobrush; 35 ± 3 DIM: >6% PMN; 56 ± 3 DIM: >4% PMN | \nAdverse | \nPregnancy rate | \n
Plöntzke et al. [59] | \nn = 201; farms = 3; no cows with PVD; cytobrush; 18–38 DIM: >5%PMN; 32–52 DIM: >5%PMN | \nWithout effect | \nDays to first service. Services per conception. Days open. Pregnancy rate | \n
Burke et al. [76] | \nn = 78; farms = 1; no cows with PVD; cytobrush; 42 DIM: >6%PMN | \nAdverse | \nPostpartum anestrus | \n
Green et al. [77] | \nn = 169; farms = 1; no cows with PVD; cytobrush; 21 ± 3 DIM: >18%PMN; 42 ± 3 DIM: >18%PMN | \nAdverse | \nPostpartum anestrus | \n
McDougall et al. [64] | \nn = 303; farms = 1; some cows with PVD; cytobrush; 29 ± 2.4 DIM: >9%PMN; 43 ± 2.3 DIM: >7%PMN | \nAdverse | \nPostpartum anestrus. First-service pregnancy rate. Days open | \n
Drillich et al. [39] | \nn = 48; farms = 1; no cows with PVD; cytobrush; IA: 0% PMN; embryo collection: 0% PMN | \nAdverse | \nTransferable embryo recovery rate | \n
Fernandez-Sanchez et al. [40] | \nn = 41; farms = 1; no cows with PVD; cytobrush; no PMN% cutoff; donor cows in embryo transfer programs | \nAdverse | \nTransferable embryo recovery rate | \n
Prunner et al. [74] | \nn = 383; farms = 10; no cows with PVD; cytobrush; 20–30 DIM: >5%PMN | \nWithout effect | \nDays to first service. Services per conception. Days open. Pregnancy rate. Culling rate | \n
Barrio et al. [56] | \nn = 467; farms = 1; no cows with PVD; cytobrush; 30 ± 2 DIM: >18%PMN | \nAdverse | \nFirst-service pregnancy rate | \n
Barrio et al. [60] | \nn = 65; farms = 25; no cows with PVD; cytobrush; 30–45 DIM: >5%PMN | \nAdverse | \nDays open | \n
Gobikrushanth et al. [75] | \nn = 126; farms = 1; no cows with PVD; cytobrush; 25 ± 1 DIM: >8%PMN | \nWithout effect | \nFollicular development and ovulation. First-service pregnancy rate. Cows pregnant at 150 and 250 days postpartum | \n
Reported effects of subclinical endometritis on reproduction.
n, number of animals; PVD, purulent vaginal discharge; DIM, days in milk.
Subclinical endometritis has been related with the repeat breeder cow syndrome with controversial results. Whereas in some studies [78, 79] the prevalence of SE in repeat breeder cows was reported to be close to 50%, in another study [80] the observed prevalence was lower than 15%. The PMN% thresholds used in those studies differed from 3% [78] and 5% [80] to 10% [79].
\nIn addition to the potential effects on reproduction, endometritis may negatively affect milk production [81]. Clinical and subclinical endometritis have been related with a decrease in milk production of 0.6–1.03 kg/cow/day, reduction of milk fat and protein, and with increased somatic cell counts in milk [64, 76, 82]. Nevertheless, some authors [83] question these effects.
\nAntibiotics and prostaglandins F2α, combined or individually, have constituted the most common treatment for clinical endometritis postpartum. Haimerl et al. [84] and Lefebvre and Stock [85] did a critical evaluation of the scientific literature that in the last 20 years reported the use of PGF2α alone or combined with antibiotics for the treatment of clinical endometritis in postpartum dairy cows. Both groups of researchers concluded that there was not enough clinical evidence that using PGF2α in endometritis postpartum had a beneficial effect. And the only antibiotic that seemed to be effective for clinical endometritis was cephapirin (a first-generation cephalosporin).
\nIn the case of SE, the treatment with PGF2α and/or antibiotics was tested only in a few studies that cannot be easily compared as included different hormonal protocols for synchronization of estrus or ovulation, animals in different postpartum periods, and different diagnosis criteria for SE. In the studies of Kasimanickam et al. [51], Galvão et al. [86], and Denis-Robichaud and Dubuc [87], intrauterine infusion of cephalosporins was tested as treatment of SE, and Kasimanickam et al. [51], Galvão et al. [88], and Lima et al. [89] tested the use of prostaglandins. Kasimanickam et al. [51] and Denis-Robichaud and Dubuc [87] obtained higher pregnancy rates at first insemination in cows treated with intrauterine cephapirin than in control cows, whereas Galvão et al. [86] did not observe any positive effect on reproduction when cows diagnosed with SE were treated with intrauterine ceftiofur infusion. Concerning the use of PGF2α in cows with SE, Kasimanickam et al. [51] and Galvão et al. [88] observed positive effects on reproductive performance, whereas Lima et al. [89] did not find any effect. It should be pointed out that the magnitude of the positive effects observed in some of the cited studies was dependent on other factors such as existence of ovarian activity at the time of treatment [87] or body condition [88]. The scarce number of studies done so far and the different results obtained do not allow us to draw a conclusion about the efficacy of using PGF2α and/or cephalosporins for the treatment of SE.
\nBecause in many cases of SE there is no uterine content or positive bacterial culture, treatment with antibiotics or prostaglandins should be expected to be unsuccessful. However, there is an inflammatory response that very likely is the cause of the negative effects of SE, and therefore, the use of nonsteroidal anti-inflammatory drugs (NSAID) would be fully warranted. Priest [5] tested the use of the NSAID carprofen, three doses administered at 3-day intervals between 21 and 31 days postpartum, in cows diagnosed with SE when the cytology showed >14% PMN at 14 days postpartum. The treatment did not reduce the incidence of SE at day 42, but increased pregnancy rate as compared with untreated control cows. However, in a subsequent study [90], cows were treated with carprofen at 1 or at 3 weeks after calving, and the treatment did not improve milk production, indicators of health or reproductive performance.
\nUterine lavage with sterile saline solution is a common treatment for endometrial inflammation in mares. Uterine lavage favors the elimination of inflammatory products, such as nonfunctional PMN, and induces uterine contractions that facilitate the evacuation of any content. In addition, elimination of nonfunctional PMN favors migration of new functional PMN that is able to counter the infection [91]. In bovine, potential usefulness of uterine lavage has been described in connection with treatment of repeat breeder cows, either as the only treatment or combined with prostaglandins and/or antibiotics, assuming that many repeat breeder cows may suffer chronic endometritis [92]. In cases of SE postpartum, uterine lavage with physiological saline at day 30 postpartum was associated with a reduction of the PMN% in cytological samples obtained at day 40, but its effect on reproduction was not evaluated [93].
\nOther protocols that have been used for the treatment of metritis or clinical endometritis, such as intrauterine infusion of dextrose [94], ozone [95], or N-acetylcysteine combined with amoxicillin and clavulanic [96], have not been tested in cows with subclinical endometritis. Nevertheless, the effect of those substances is mainly antibacterial or mucolytic, whereas in SE there is no mucopurulent secretion and, in most cases, no pathogen bacteria.
\nSubclinical endometritis is a uterine inflammation probably originated by the alteration of the inflammation regulatory mechanisms. The inflammatory status may abnormally persist after elimination of postpartum bacterial contamination, which may be associated with an unbalanced production of anti- and pro-inflammatory factors. Prevalence of subclinical endometritis in dairy farms may reflect the immune status of cows, which in turn would be indicative of the metabolic status of cows in transition and, eventually, of the nutritional management of farms.
\nThe study was supported by Xunta de Galicia (Programa Sectorial de Medio Rural, Proyecto Ref. PGIDIT07MRU002E) and FEFRIGA, Santiago de Compostela, Spain.
\n"Open access contributes to scientific excellence and integrity. It opens up research results to wider analysis. It allows research results to be reused for new discoveries. And it enables the multi-disciplinary research that is needed to solve global 21st century problems. Open access connects science with society. It allows the public to engage with research. To go behind the headlines. And look at the scientific evidence. And it enables policy makers to draw on innovative solutions to societal challenges".
\n\nCarlos Moedas, the European Commissioner for Research Science and Innovation at the STM Annual Frankfurt Conference, October 2016.
",metaTitle:"About Open Access",metaDescription:"Open access contributes to scientific excellence and integrity. It opens up research results to wider analysis. It allows research results to be reused for new discoveries. And it enables the multi-disciplinary research that is needed to solve global 21st century problems. Open access connects science with society. It allows the public to engage with research. To go behind the headlines. And look at the scientific evidence. And it enables policy makers to draw on innovative solutions to societal challenges.\n\nCarlos Moedas, the European Commissioner for Research Science and Innovation at the STM Annual Frankfurt Conference, October 2016.",metaKeywords:null,canonicalURL:"about-open-access",contentRaw:'[{"type":"htmlEditorComponent","content":"The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
\\n\\nIntechOpen’s co-founders, both scientists themselves, created the company while undertaking research in robotics at Vienna University. Their goal was to spread research freely “for scientists, by scientists’ to the rest of the world via the Open Access publishing model. The company soon became a signatory of the Budapest Initiative, which currently has more than 1000 supporting organizations worldwide, ranging from universities to funders.
\\n\\nAt IntechOpen today, we are still as committed to working with organizations and people who care about scientific discovery, to putting the academic needs of the scientific community first, and to providing an Open Access environment where scientists can maximize their contribution to scientific advancement. By opening up access to the world’s scientific research articles and book chapters, we aim to facilitate greater opportunity for collaboration, scientific discovery and progress. We subscribe wholeheartedly to the Open Access definition:
\\n\\n“By “open access” to [peer-reviewed research literature], we mean its free availability on the public internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, crawl them for indexing, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than those inseparable from gaining access to the internet itself. The only constraint on reproduction and distribution, and the only role for copyright in this domain, should be to give authors control over the integrity of their work and the right to be properly acknowledged and cited” (reference: http://www.budapestopenaccessinitiative.org)
\\n\\nOAI-PMH
\\n\\nAs a firm believer in the wider dissemination of knowledge, IntechOpen supports the Open Access Initiative Protocol for Metadata Harvesting (OAI-PMH Version 2.0). Read more
\\n\\nLicense
\\n\\nBook chapters published in edited volumes are distributed under the Creative Commons Attribution 3.0 Unported License (CC BY 3.0). IntechOpen upholds a very flexible Copyright Policy. There is no copyright transfer to the publisher and Authors retain exclusive copyright to their work. All Monographs/Compacts are distributed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). Read more
\\n\\nPeer Review Policies
\\n\\nAll scientific works are Peer Reviewed prior to publishing. Read more
\\n\\nOA Publishing Fees
\\n\\nThe Open Access publishing model employed by IntechOpen eliminates subscription charges and pay-per-view fees, enabling readers to access research at no cost. In order to sustain operations and keep our publications freely accessible we levy an Open Access Publishing Fee for manuscripts, which helps us cover the costs of editorial work and the production of books. Read more
\\n\\nDigital Archiving Policy
\\n\\nIntechOpen is committed to ensuring the long-term preservation and the availability of all scholarly research we publish. We employ a variety of means to enable us to deliver on our commitments to the scientific community. Apart from preservation by the Croatian National Library (for publications prior to April 18, 2018) and the British Library (for publications after April 18, 2018), our entire catalogue is preserved in the CLOCKSS archive.
\\n\\nOpen Science is transparent and accessible knowledge that is shared and developed through collaborative networks.
\\n\\nOpen Science is about increased rigour, accountability, and reproducibility for research. It is based on the principles of inclusion, fairness, equity, and sharing, and ultimately seeks to change the way research is done, who is involved and how it is valued. It aims to make research more open to participation, review/refutation, improvement and (re)use for the world to benefit.
\\n\\nOpen Science refers to doing traditional science with more transparency involved at various stages, for example by openly sharing code and data. It implies a growing set of practices - within different disciplines - aiming at:
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\\n\\n\\n"}]'},components:[{type:"htmlEditorComponent",content:'
The Open Access publishing movement started in the early 2000s when academic leaders from around the world participated in the formation of the Budapest Initiative. They developed recommendations for an Open Access publishing process, “which has worked for the past decade to provide the public with unrestricted, free access to scholarly research—much of which is publicly funded. Making the research publicly available to everyone—free of charge and without most copyright and licensing restrictions—will accelerate scientific research efforts and allow authors to reach a larger number of readers” (reference: http://www.budapestopenaccessinitiative.org)
\n\nIntechOpen’s co-founders, both scientists themselves, created the company while undertaking research in robotics at Vienna University. Their goal was to spread research freely “for scientists, by scientists’ to the rest of the world via the Open Access publishing model. The company soon became a signatory of the Budapest Initiative, which currently has more than 1000 supporting organizations worldwide, ranging from universities to funders.
\n\nAt IntechOpen today, we are still as committed to working with organizations and people who care about scientific discovery, to putting the academic needs of the scientific community first, and to providing an Open Access environment where scientists can maximize their contribution to scientific advancement. By opening up access to the world’s scientific research articles and book chapters, we aim to facilitate greater opportunity for collaboration, scientific discovery and progress. We subscribe wholeheartedly to the Open Access definition:
\n\n“By “open access” to [peer-reviewed research literature], we mean its free availability on the public internet, permitting any users to read, download, copy, distribute, print, search, or link to the full texts of these articles, crawl them for indexing, pass them as data to software, or use them for any other lawful purpose, without financial, legal, or technical barriers other than those inseparable from gaining access to the internet itself. The only constraint on reproduction and distribution, and the only role for copyright in this domain, should be to give authors control over the integrity of their work and the right to be properly acknowledged and cited” (reference: http://www.budapestopenaccessinitiative.org)
\n\nOAI-PMH
\n\nAs a firm believer in the wider dissemination of knowledge, IntechOpen supports the Open Access Initiative Protocol for Metadata Harvesting (OAI-PMH Version 2.0). Read more
\n\nLicense
\n\nBook chapters published in edited volumes are distributed under the Creative Commons Attribution 3.0 Unported License (CC BY 3.0). IntechOpen upholds a very flexible Copyright Policy. There is no copyright transfer to the publisher and Authors retain exclusive copyright to their work. All Monographs/Compacts are distributed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). Read more
\n\nPeer Review Policies
\n\nAll scientific works are Peer Reviewed prior to publishing. Read more
\n\nOA Publishing Fees
\n\nThe Open Access publishing model employed by IntechOpen eliminates subscription charges and pay-per-view fees, enabling readers to access research at no cost. In order to sustain operations and keep our publications freely accessible we levy an Open Access Publishing Fee for manuscripts, which helps us cover the costs of editorial work and the production of books. Read more
\n\nDigital Archiving Policy
\n\nIntechOpen is committed to ensuring the long-term preservation and the availability of all scholarly research we publish. We employ a variety of means to enable us to deliver on our commitments to the scientific community. Apart from preservation by the Croatian National Library (for publications prior to April 18, 2018) and the British Library (for publications after April 18, 2018), our entire catalogue is preserved in the CLOCKSS archive.
\n\nOpen Science is transparent and accessible knowledge that is shared and developed through collaborative networks.
\n\nOpen Science is about increased rigour, accountability, and reproducibility for research. It is based on the principles of inclusion, fairness, equity, and sharing, and ultimately seeks to change the way research is done, who is involved and how it is valued. It aims to make research more open to participation, review/refutation, improvement and (re)use for the world to benefit.
\n\nOpen Science refers to doing traditional science with more transparency involved at various stages, for example by openly sharing code and data. It implies a growing set of practices - within different disciplines - aiming at:
\n\nWe aim at improving the quality and availability of scholarly communication by promoting and practicing:
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr.",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Rheinmetall (Germany)",country:{name:"Germany"}}},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. He has contributed in stochastic estimation of control area especially, in the Multiple Target Tracking and Interactive Multiple Model (IMM) research, Ball & Beam Control Problem, Robotics, Levitation Control. He has contributed in developing Algorithms for Fingerprint Matching, Computer Vision and Face Recognition. He has been supervising Pattern Recognition, Formal Languages and Distributed Processing projects for several years. He has reviewed many books on Management, Computer Science. Currently, he is an active and permanent reviewer for many international conferences and symposia and the program committee member for many international conferences.\nIn teaching he has taught the core computer science subjects like, Digital Design, Real Time Embedded System Programming, Operating Systems, Software Engineering, Data Structures, Databases, Compiler Construction. 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Ortega-Villaizan and Veronica Chico",coverURL:"https://cdn.intechopen.com/books/images_new/9848.jpg",editedByType:"Edited by",editors:[{id:"254101",title:"Dr.",name:"Maria Del Mar",middleName:null,surname:"Ortega-Villaizan",slug:"maria-del-mar-ortega-villaizan",fullName:"Maria Del Mar Ortega-Villaizan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8959",title:"Innate Immunity in Health and Disease",subtitle:null,isOpenForSubmission:!1,hash:"cea4f56328f9d1ee0c6f1486a12afa23",slug:"innate-immunity-in-health-and-disease",bookSignature:"Shailendra K. Saxena and Hridayesh Prakash",coverURL:"https://cdn.intechopen.com/books/images_new/8959.jpg",editedByType:"Edited by",editors:[{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena"}],equalEditorOne:{id:"287184",title:"Prof.",name:"Hridayesh",middleName:null,surname:"Prakash",slug:"hridayesh-prakash",fullName:"Hridayesh Prakash",profilePictureURL:"https://mts.intechopen.com/storage/users/287184/images/system/287184.jpg",biography:"Dr. Hridayesh Prakash is a fellow of the Royal Society of Biology, London. Currently, he is an associate professor at the Institute of Virology and Immunology, Amity University, NOIDA. He has expertise in innate immunity with a special interest in macrophage immunobiology, tumor immunology/immunotherapy, cell-based immunotherapies, pulmonary infection biology, and radiation biology. \n\nDr. Prakash conducts research to exploit various immunotherapeutics for managing persistent bacterial and viral Infections and gastric cancer. He is unraveling the therapeutic potential of M1 effector macrophages against solid tumors. He is also studying various mechanisms that certain pathogens like Helicobacter pylori, Chlamydia, and Mycobacteria are exploiting for polarizing M1 effector macrophages towards the M2 phenotype during chronic and persistent infections. Under this major objective, he is now validating the therapeutic impact of M1 effector macrophages for the control of persistent infection-driven cancer (adenocarcinoma) progression. \n\nDr. Prakash is also exploring the palliative potential of macrophages against autoimmunity and chronic inflammatory disorders like IBD, radio-pneumonitis, pulmonary fibrosis, and radiation syndrome.",institutionString:"Amity University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Maharishi Markandeshwar University, Mullana",institutionURL:null,country:{name:"India"}}},equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8798",title:"Cells of the Immune System",subtitle:null,isOpenForSubmission:!1,hash:"4e8acf20a4e80bc7c97cb34d1672e53d",slug:"cells-of-the-immune-system",bookSignature:"Ota Fuchs and Seyyed Shamsadin Athari",coverURL:"https://cdn.intechopen.com/books/images_new/8798.jpg",editedByType:"Edited by",editors:[{id:"36468",title:"Dr.",name:"Ota",middleName:null,surname:"Fuchs",slug:"ota-fuchs",fullName:"Ota Fuchs"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3396",title:"Current Trends in Atherogenesis",subtitle:null,isOpenForSubmission:!1,hash:"914c59b8518185a41a0931cc0637c0bf",slug:"current-trends-in-atherogenesis",bookSignature:"Rita Rezzani",coverURL:"https://cdn.intechopen.com/books/images_new/3396.jpg",editedByType:"Edited by",editors:[{id:"63457",title:"Prof.",name:"Rita",middleName:null,surname:"Rezzani",slug:"rita-rezzani",fullName:"Rita Rezzani"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:4,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"67756",doi:"10.5772/intechopen.86600",title:"Neutrophil Function Impairment Is a Host Susceptibility Factor to Bacterial Infection in Diabetes",slug:"neutrophil-function-impairment-is-a-host-susceptibility-factor-to-bacterial-infection-in-diabetes",totalDownloads:1047,totalCrossrefCites:5,totalDimensionsCites:11,abstract:"Diabetes mellitus is a highly prevalent noncommunicable disease globally. One of the main complications of diabetes is the increased susceptibility to bacterial infection. Neutrophils play a crucial role in inflammatory response against bacterial infections, once they are the first cells recruited to the sites of injury. In diabetes, there is a failure in the neutrophil functions, including migration, ROS production, phagocytosis, and bacterial killing, which are associated with the high incidence of bacterial infections. Herein, we point out pieces of evidence revealing the primary molecular mechanisms involved with impairment of neutrophil functions in diabetes, with relationship with high susceptibility to bacterial infections.",book:{id:"8798",slug:"cells-of-the-immune-system",title:"Cells of the Immune System",fullTitle:"Cells of the Immune System"},signatures:"Daniella Insuela, Diego Coutinho, Marco Martins, Maximiliano Ferrero and Vinicius Carvalho",authors:[{id:"296748",title:"Dr.",name:"Vinicius",middleName:null,surname:"Carvalho",slug:"vinicius-carvalho",fullName:"Vinicius Carvalho"},{id:"303254",title:"Dr.",name:"Daniella",middleName:null,surname:"Insuela",slug:"daniella-insuela",fullName:"Daniella Insuela"},{id:"303255",title:"Dr.",name:"Diego",middleName:null,surname:"Coutinho",slug:"diego-coutinho",fullName:"Diego Coutinho"},{id:"303256",title:"Dr.",name:"Maximiliano",middleName:null,surname:"Ferrero",slug:"maximiliano-ferrero",fullName:"Maximiliano Ferrero"},{id:"303257",title:"Dr.",name:"Marco Aurelio",middleName:null,surname:"Martins",slug:"marco-aurelio-martins",fullName:"Marco Aurelio Martins"}]},{id:"42857",doi:"10.5772/53035",title:"Atherosclerosis and Current Anti-Oxidant Strategies for Atheroprotection",slug:"atherosclerosis-and-current-anti-oxidant-strategies-for-atheroprotection",totalDownloads:3122,totalCrossrefCites:4,totalDimensionsCites:7,abstract:null,book:{id:"3396",slug:"current-trends-in-atherogenesis",title:"Current Trends in Atherogenesis",fullTitle:"Current Trends in Atherogenesis"},signatures:"Luigi Fabrizio Rodella and Gaia Favero",authors:[{id:"118762",title:"Prof.",name:"Luigi Fabrizio",middleName:null,surname:"Rodella",slug:"luigi-fabrizio-rodella",fullName:"Luigi Fabrizio Rodella"},{id:"160911",title:"Dr.",name:"Gaia",middleName:null,surname:"Favero",slug:"gaia-favero",fullName:"Gaia Favero"}]},{id:"42907",doi:"10.5772/54636",title:"MicroRNAome of Vascular Smooth Muscle Cells: Potential for MicroRNA-Based Vascular Therapies",slug:"micrornaome-of-vascular-smooth-muscle-cells-potential-for-microrna-based-vascular-therapies",totalDownloads:1824,totalCrossrefCites:2,totalDimensionsCites:4,abstract:null,book:{id:"3396",slug:"current-trends-in-atherogenesis",title:"Current Trends in Atherogenesis",fullTitle:"Current Trends in Atherogenesis"},signatures:"Kasturi Ranganna, Omana P. Mathew, Shirlette G. Milton and Barbara E. Hayes",authors:[{id:"63103",title:"Dr.",name:"Katsuri",middleName:null,surname:"Ranganna",slug:"katsuri-ranganna",fullName:"Katsuri Ranganna"}]},{id:"71468",doi:"10.5772/intechopen.91730",title:"Multiplex Technology for Biomarker Immunoassays",slug:"multiplex-technology-for-biomarker-immunoassays",totalDownloads:672,totalCrossrefCites:4,totalDimensionsCites:4,abstract:"The simultaneous measurement of different substances from a single sample is an emerging area for achieving efficient and high-throughput detection in several applications. Although immunoanalytical techniques are established and advantageous over alternative screening analytical platforms, one of the challenges for immunoassays is multiplexing. While ELISA is still commonly used to characterise a single analyte, laboratories and organisations are moving towards multiplex immunoassays. The validation of novel biomarkers and their amalgamation into multiplex immunoassays confers the prospects of simultaneous measurement of multiple analytes in a single sample, thereby minimising cost, time and sample. Therefore, the technological advancement in clinical sciences is helpful in the identification of analytes or biomarkers in test samples. However, the analytical bioanalysers are expensive and capable of detecting only a small amount or type of analytes. The simultaneous measurement of different substances from a single sample called multiplexing has become increasingly important for the quantification of pathological or toxicological samples. Although multiplex assays have many advantages over conventional assays, there are also problems that may cause apprehension among clinicians and researchers. Hence, many challenges still remain for these multiplexing systems which are at early stages of development.",book:{id:"8959",slug:"innate-immunity-in-health-and-disease",title:"Innate Immunity in Health and Disease",fullTitle:"Innate Immunity in Health and Disease"},signatures:"Haseeb Ahsan and Rizwan Ahmad",authors:[{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad"},{id:"412254",title:"Dr.",name:"Haseeb",middleName:null,surname:"Ahsan",slug:"haseeb-ahsan",fullName:"Haseeb Ahsan"}]},{id:"41447",doi:"10.5772/54726",title:"The Role of Cyclic 3’-5’ Adenosine Monophosphate (cAMP) in Differentiated and Trans-Differentiated Vascular Smooth Muscle Cells",slug:"the-role-of-cyclic-3-5-adenosine-monophosphate-camp-in-differentiated-and-trans-differentiated-vascu",totalDownloads:2272,totalCrossrefCites:1,totalDimensionsCites:4,abstract:null,book:{id:"3396",slug:"current-trends-in-atherogenesis",title:"Current Trends in Atherogenesis",fullTitle:"Current Trends in Atherogenesis"},signatures:"Martine Glorian and Isabelle Limon",authors:[{id:"161259",title:"Dr.",name:"Martine",middleName:null,surname:"Glorian",slug:"martine-glorian",fullName:"Martine Glorian"}]}],mostDownloadedChaptersLast30Days:[{id:"70362",title:"Resident Memory T Cells",slug:"resident-memory-t-cells",totalDownloads:964,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Until recently, T cells were thought to remain in circulation until recruitment of the inflammation and only a small number of T cells remained in the peripheral tissues without inflammation. However, studies have found that a group of T cells settled in the tissues and remained there for a long time. Those cells are named as tissue-resident memory T cells (TRM). TRM cells are transcriptionally, phenotypically, and functionally distinct from other T cells, which recirculate between blood, secondary lymphoid organs, and non-lymphoid tissues. They undergo a distinct proliferation that discriminates them from circulating T cells and their main cell surface markers are CD69, CD103, and CD49a. Upon exposure to the same or similar diseases, TRM cells provide a first line of adaptive cellular defense against infection in peripheral non-lymphoid tissues, such as skin, lungs, digestive, and urogenital tracts. This approach forms the basis of a novel vaccination strategy called “prime and pull”, which ensures long-term local immunity. On the other hand, abnormal activated and malignant TRM may contribute to numerous human inflammatory diseases such as psoriasis and vitiligo. Here in this chapter, we aimed to emphasize TRM cell location, migration, phenotypic structure, maintenance, and diseases associated with TRM cells.",book:{id:"8798",slug:"cells-of-the-immune-system",title:"Cells of the Immune System",fullTitle:"Cells of the Immune System"},signatures:"Hasan Akbaba",authors:[{id:"260489",title:"Dr.",name:"Hasan",middleName:null,surname:"Akbaba",slug:"hasan-akbaba",fullName:"Hasan Akbaba"}]},{id:"71769",title:"Immune Dysfunction during Enteric Protozoal Infection: The Current Trends",slug:"immune-dysfunction-during-enteric-protozoal-infection-the-current-trends",totalDownloads:792,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Enteric protozoa usually cause severe morbidity and mortality in humans. Protozoal infections contribute to the high burden of infectious diseases. Despite recent advances in the epidemiology, diagnostic tool, molecular biology, and treatment of protozoan illnesses, gaps in knowledge still exist; hence, protozoal infections require further research. We are describing here some important enteric protozoal infections along with the immune dysfunction produced by them. Genus- 1. Entamoeba; 2. Giardia; 3. Cryptosporidium; 4. Cyclospora; 5. Cystoisospora; 6. Dientamoeba; 7. Blastocystis; 8. Balantidium.",book:{id:"8959",slug:"innate-immunity-in-health-and-disease",title:"Innate Immunity in Health and Disease",fullTitle:"Innate Immunity in Health and Disease"},signatures:"Renu Kumari Yadav, Shalini Malhotra and Nandini Duggal",authors:[{id:"176430",title:"Dr.",name:"Shalini",middleName:null,surname:"Malhotra",slug:"shalini-malhotra",fullName:"Shalini Malhotra"},{id:"315666",title:"Dr.",name:"Renu",middleName:null,surname:"Kumari Yadav",slug:"renu-kumari-yadav",fullName:"Renu Kumari Yadav"}]},{id:"69233",title:"Innate Immune Defense in the Male Reproductive System and Male Fertility",slug:"innate-immune-defense-in-the-male-reproductive-system-and-male-fertility",totalDownloads:824,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"To protect the male germ cells from adverse immune reaction, the male reproductive system adopts special immune environment such as immunoprivileged status. The male genital organs can be infected by various microorganisms via hematogenous dissemination and ascending genitourinary tracts. To overcome the immunoprivileged status, the male genital organs also adopt their own innate defense against microbial infection. The tissue-specific cells in the male reproductive system are well equipped with innate immune machineries, including pattern recognition receptors (PRRs) and their negatively regulatory system. PRR-initiated immune responses must be tightly regulated by the negative regulatory system for the maintenance of immune homeostasis. The immune homeostasis can be disrupted by unrestrictive innate immune response, which may lead to inflammatory conditions in the male genital tracts, an important etiological factor contributing to male infertility. This chapter describes the current understanding of the innate immune responses in the male reproductive system and their effects on male fertility.",book:{id:"8959",slug:"innate-immunity-in-health-and-disease",title:"Innate Immunity in Health and Disease",fullTitle:"Innate Immunity in Health and Disease"},signatures:"Fei Wang, Ran Chen and Daishu Han",authors:[{id:"295978",title:"Dr.",name:"Daishu",middleName:null,surname:"Han",slug:"daishu-han",fullName:"Daishu Han"},{id:"303373",title:"Dr.",name:"Fei",middleName:null,surname:"Wang",slug:"fei-wang",fullName:"Fei Wang"},{id:"309874",title:"Dr.",name:"Ran",middleName:null,surname:"Chen",slug:"ran-chen",fullName:"Ran Chen"}]},{id:"71781",title:"Innate Immunity and Autoimmune Diseases",slug:"innate-immunity-and-autoimmune-diseases",totalDownloads:819,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The innate immune response is responsible for the initial defense against invading pathogens and signs of damage; in turn, it activates the adaptive immune response to result in highly specific and lasting immunity, mediated by the clonal expansion of antigen-specific B and T lymphocytes. Inflammation is the acute response to infection and tissue damage to limit aggression to the body. It is a complex reaction of vascularized tissues to infection, toxin exposure or cell injury that includes extravasation of plasma proteins and leukocytes. Paradoxically, uncontrolled and prolonged inflammation can result in secondary damage and the development of immune pathology in the host. The components of the innate immune system have recently been studied as responsible mechanisms in various chronic diseases such as diabetes mellitus, atherosclerosis, asthma and allergies, among others. Autoimmune disease is an attack on auto tissues by the adaptation of the immune system. In general, such diseases are characterized by autoantibodies and/or autoreactive lymphocytes directed at antigens against themselves. The innate immune system is often considered an effector of self-reactive lymphocytes, but also provides protection. Studies in mice with specific gene-directed mutations show that defects in innate immune system proteins may predispose to the development of a systemic lupus erythematosus-like syndrome (lupus) characterized by autoantibodies against double-stranded DNA (ds DNA) or nuclear components. This seems to be due to a failure in the removal of apoptotic cells or nuclear waste. These observations imply that the innate immune system has a general protective role against autoimmune disease. For example, in systemic diseases such as lupus, innate immunity is important in the elimination of nuclear antigens and, therefore, in the improvement of tolerance to B lymphocytes. Alternatively, in specific organ disorders such as type diabetes 1 o Crohn’s disease, the innate immune system can be protective by eliminating pathogens that trigger or exacerbate the disease or regulate the presentation of antigens for T lymphocytes. Discuss various disease models in which the innate immune system could provide a protective role, deficiencies in the regulation of B lymphocyte signaling through the antigen/receptor or in the clearance of lupus antigens, (dsDNA and nuclear proteins), can lead to a disease similar to lupus. The repertoire of B cells seems to be very biased toward self-activity, as, possibly, that of the T-cell. This tendency toward self-activity is not surprising because B and T cells are positively selected against highly conserved autoantigens.",book:{id:"8959",slug:"innate-immunity-in-health-and-disease",title:"Innate Immunity in Health and Disease",fullTitle:"Innate Immunity in Health and Disease"},signatures:"Marcela Catalina Fandiño Vargas",authors:[{id:"312253",title:"M.D.",name:"Marcela Catalina",middleName:null,surname:"Fandiño Vargas",slug:"marcela-catalina-fandino-vargas",fullName:"Marcela Catalina Fandiño Vargas"}]},{id:"69097",title:"Assessment of Immune Reconstitution Following Hematopoietic Stem Cell Transplantation",slug:"assessment-of-immune-reconstitution-following-hematopoietic-stem-cell-transplantation",totalDownloads:1019,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potential curative treatment for both congenital and hematological malignancies. Immune reconstitution after allogeneic hematopoietic stem cell transplantation is implicated in successful transplant outcomes such as overall survival and relapse-free survival. The reconstitution of immune cell subsets after HSCT occurs in different phases at different time points encompassing pre-engraftment, engraftment, and post-engraftment. The recovery of innate cellular immunity with the appearance of monocytes, dendritic cells, and natural killer cells in peripheral blood correlates with initiation of cellular engraftment. The cellular adaptive immunity is characterized by both thymic-independent expansion of T cells infused with graft and thymus-dependent expansion of naïve T cells derived from donor stem cells. The humoral immunity consists of B-cell reconstitution, which consists primarily of transitional and naïve subsets with the recovery of memory B cells that occur much later. In this review, we highlight the factors affecting immune reconstitution, the reconstitution of innate and adaptive immunity, techniques to assess immune reconstitution, and ways to enhance it.",book:{id:"8798",slug:"cells-of-the-immune-system",title:"Cells of the Immune System",fullTitle:"Cells of the Immune System"},signatures:"Meenakshi Singh, Selma Z. D’Silva and Abhishweta Saxena",authors:[{id:"217471",title:"Dr.",name:"Selma",middleName:null,surname:"D\\'Silva",slug:"selma-d'silva",fullName:"Selma D\\'Silva"},{id:"267032",title:"Dr.",name:"Meenakshi",middleName:null,surname:"Singh",slug:"meenakshi-singh",fullName:"Meenakshi Singh"},{id:"310438",title:"Dr.",name:"Abhishweta",middleName:null,surname:"Saxena",slug:"abhishweta-saxena",fullName:"Abhishweta Saxena"}]}],onlineFirstChaptersFilter:{topicId:"1034",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:18,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:139,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:122,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:21,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"24",title:"Sustainable Development",doi:"10.5772/intechopen.100361",issn:"2753-6580",scope:"
\r\n\tThis book series will offer a comprehensive overview of recent research trends as well as clinical applications within different specialties of dentistry. Topics will include overviews of the health of the oral cavity, from prevention and care to different treatments for the rehabilitation of problems that may affect the organs and/or tissues present. The different areas of dentistry will be explored, with the aim of disseminating knowledge and providing readers with new tools for the comprehensive treatment of their patients with greater safety and with current techniques. Ongoing issues, recent advances, and future diagnostic approaches and therapeutic strategies will also be discussed. This series of books will focus on various aspects of the properties and results obtained by the various treatments available, whether preventive or curative.
",coverUrl:"https://cdn.intechopen.com/series/covers/3.jpg",latestPublicationDate:"August 4th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:2,numberOfPublishedChapters:139,numberOfPublishedBooks:9,editor:{id:"419588",title:"Ph.D.",name:"Sergio",middleName:"Alexandre",surname:"Gehrke",fullName:"Sergio Gehrke",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038WgMKQA0/Profile_Picture_2022-06-02T11:44:20.jpg",biography:"Dr. Sergio Alexandre Gehrke is a doctorate holder in two fields. The first is a Ph.D. in Cellular and Molecular Biology from the Pontificia Catholic University, Porto Alegre, Brazil, in 2010 and the other is an International Ph.D. in Bioengineering from the Universidad Miguel Hernandez, Elche/Alicante, Spain, obtained in 2020. In 2018, he completed a postdoctoral fellowship in Materials Engineering in the NUCLEMAT of the Pontificia Catholic University, Porto Alegre, Brazil. He is currently the Director of the Postgraduate Program in Implantology of the Bioface/UCAM/PgO (Montevideo, Uruguay), Director of the Cathedra of Biotechnology of the Catholic University of Murcia (Murcia, Spain), an Extraordinary Full Professor of the Catholic University of Murcia (Murcia, Spain) as well as the Director of the private center of research Biotecnos – Technology and Science (Montevideo, Uruguay). Applied biomaterials, cellular and molecular biology, and dental implants are among his research interests. He has published several original papers in renowned journals. In addition, he is also a Collaborating Professor in several Postgraduate programs at different universities all over the world.",institutionString:null,institution:{name:"Universidad Católica San Antonio de Murcia",institutionURL:null,country:{name:"Spain"}}},subseries:[{id:"1",title:"Oral Health",keywords:"Oral Health, Dental Care, Diagnosis, Diagnostic Imaging, Early Diagnosis, Oral Cancer, Conservative Treatment, Epidemiology, Comprehensive Dental Care, Complementary Therapies, Holistic Health",scope:"\r\n\tThis topic aims to provide a comprehensive overview of the latest trends in Oral Health based on recent scientific evidence. Subjects will include an overview of oral diseases and infections, systemic diseases affecting the oral cavity, prevention, diagnosis, treatment, epidemiology, as well as current clinical recommendations for the management of oral, dental, and periodontal diseases.
",annualVolume:11397,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/1.jpg",editor:{id:"173955",title:"Prof.",name:"Sandra",middleName:null,surname:"Marinho",fullName:"Sandra Marinho",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRGYMQA4/Profile_Picture_2022-06-01T13:22:41.png",institutionString:null,institution:{name:"State University of Paraíba",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"267724",title:"Prof.",name:"Febronia",middleName:null,surname:"Kahabuka",fullName:"Febronia Kahabuka",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRZpJQAW/Profile_Picture_2022-06-27T12:00:42.JPG",institutionString:"Muhimbili University of Health and Allied Sciences, Tanzania",institution:{name:"Muhimbili University of Health and Allied Sciences",institutionURL:null,country:{name:"Tanzania"}}},{id:"70530",title:"Dr.",name:"Márcio",middleName:"Campos",surname:"Oliveira",fullName:"Márcio Oliveira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRm0AQAS/Profile_Picture_2022-08-01T12:34:46.jpg",institutionString:null,institution:{name:"State University of Feira de Santana",institutionURL:null,country:{name:"Brazil"}}}]},{id:"2",title:"Prosthodontics and Implant Dentistry",keywords:"Osseointegration, Hard Tissue, Peri-implant Soft Tissue, Restorative Materials, Prosthesis Design, Prosthesis, Patient Satisfaction, Rehabilitation",scope:"