\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 179 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 252 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
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These are directly linked with agricultural mechanization, automation and robotics, high-efficiency irrigation systems, farm energy systems, post-harvest handling and processing, wastewater management, and the associated sustainable bio environment. Such agricultural, biological, and environmental engineering studies are the need of the 21st century, particularly from the viewpoint of the agricultural water–energy–food security nexus. Moreover, the wide range and interdisciplinary nature of research for agricultural engineering and technologies and system as well as the proliferation and technological advancement in agricultural engineering technologies will be the focus of this book. 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\r\n\t
In recent years, there has been a dramatic increase in the importance given to the theory that the tissue microenvironment participates in determining the “bone niche” in the progression of bone tumours and in establishing resistance processes to conventional therapies. Originally, the concept of tumour niche has emerged based on the “seed and soil theory” proposed by Stephan Paget at the end of the nineteenth century [1, 2]. This tumour niche is defined as a specific microenvironment promoting the emergence of cancer initiating cells and providing all the factors required for their quiescence, proliferation and migration. Therefore, the tumour microenvironment is composed of a complex, interconnected network of protagonists, including soluble factors such as cytokines, extracellular matrix components, interacting with fibroblasts, endothelial cells, immune cells and various specific cell types depending on the location of the cancer cells (e.g. osteoblasts, osteoclasts in the bone tissue or pulmonary epithelium in case of lung metastasis). This cellular diversity defines three main “niches” depending on their functional implication: an immune niche involved in local immune tolerance, a vascular niche associated with tumour cell extravasation/migration and a metastatic niche (e.g. bone, lung and liver) hosting the metastatic tumour cells [3, 4].
\nThe concept of “bone niche” was initially described in the context of haematological malignancies, such as leukaemia [5] or multiple myeloma [6], and then extended to bone metastases, such as breast or prostate cancers [7]. As all tumours, the pathogenesis of osteosarcoma (OS) is closely related to the microenvironment in which the tumour grows. Even though the aetiology of OS has not been clearly established, its development has the special feature of being strongly associated with the “soil” described by Paget. In physiological and pathological bone tissue, the various cells communicate together by direct contacts involving adhesion molecules or channels, but also in an autocrine/paracrine/endocrine manner involving cytokines and growth factors [8]. Among these glycoproteins, the triad osteoprotegerin (OPG)/Receptor Activator of NF-κB (RANK)/RANK Ligand (RANKL) plays a pivotal role in OS development [9]. In case of OS, there is effectively a dysregulation in this balance between OPG/RANK/RANKL, provoking exacerbated local bone remodelling (Figure 1). As a result, numerous factors initially trapped in this matrix are released, which in turn stimulate sarcoma cell proliferation, leading to the establishment of a vicious cycle between bone and tumour cells [10]. These events are associated with early and late events in the metastatic process by promoting the neoangiogenesis and extravasation of tumour cells [11, 12]. But until today, the characterisation of the microenvironment of OS has not been fully documented [13, 14]. The immune niche, with its huge cell diversity including more specifically tumour infiltrating lymphocytes (TILs) and tumour-associated macrophages (TAMs), regulates the OS microenvironment [15, 16]. TAMs exert different effects on tumour development because of their polarisation. In oncology, M1-polarised macrophages are considered to be anti-tumour effectors, and M2-polarised macrophages are defined as pro-tumour modulators as they increase the neoangiogenic process [17–19]. The density of TAMs is correlated with tumour cell proliferation, invasion, metastasis and poor prognosis in various epithelial and haematological cancers and in bone metastases [20].
Osteosarcoma and its niches. In osteosarcoma, the microenvironment plays a pivotal role in the pathogenesis of tumour cells. It facilitates the transport of gas and nutriments to cancer cells and extravasation to their metastatic location (vascular niche), induces a tolerant environment (immune niche) and dysregulates bone remodelling (bone niche), in which the molecular OPG/RANKL/RANK triad plays a key role in regulation. OPG and RANKL are produced by osteoblasts and/or stromal cells, whereas RANK is expressed at the surface of osteoclasts and their precursors. The immune niche is one of the source of therapeutic targets against osteosarcoma.
Osteoimmunology is a recent term proposed for describing the complex immune environment controlling the bone remodelling and related diseases [21]. Several reports have underlined the therapeutic interest to use immunotherapies or immunomodulatory-based therapies for OS. In this context, the number of new drugs activating the immune system has exploded in the last 10 years, and numerous phase I and II clinical trials are in progress in OS. The present chapter will describe the main roles of the immune system in the pathogenesis of OS and the most recent therapeutic development based on its regulation.
As said above, the niche of OS is composed of a complex network of diverse cells, which interact together by direct contacts, or in an autocrine/paracrine/endocrine manner involving cytokines and growth factors. This chapter will focus specifically on the main cellular protagonists: lymphocytes, macrophages and the principal associated cytokines.
\nHeterogeneity of tumour cells with various osteosarcoma sub-entities further complicates identification of robust biomarkers with broad clinical application [22]. Analysis of the tumour microenvironment in patients with a variety of haematological pathologies and solid tumours such as bone metastases and soft tissue sarcomas has revealed that a major subset of tumours shows evidence of a T cell–infiltrated phenotype [23, 24]. Selected T lymphocytes migrate from secondary lymphoid organs to the tumour sites and invade the tumour tissues. They are composed of various T lymphocyte subpopulations, which exhibit highly specific immunological reactivity compared to circulating and non-infiltrating lymphocytes [25]. The final immune response resulting from the activation of T lymphocytes is complex and depends on the nature of these T cells (e.g. Treg, CD4+) and the presence of the other immune protagonists such as macrophages.
\nAs other immune cells, lymphocytes seem to play an essential role in osteosarcoma growth and prognosis, but publications reporting this population in OS remain rare [16, 22, 26]. The presence of T lymphocytes in human OS tissues was previously studied by Trieb et al. by immunohistochemical techniques [26]. Phenotypic analyses have revealed that the infiltrating lymphocytes into OS were 95% CD3+ and 68% CD8+. At this time, human CD4+ Treg was unknown and not included in the study, which did not detect any correlation of TILs with OS outcome. A few years later, Theoleyre et al. supported the presence of specific T subpopulations in OS: TILs isolated from OS samples exhibited lytic activity in vitro, which were apparently no efficient in patients [16]. The study of the microenvironment has a strong impact on targeted patient treatment for which little progress has been achieved since introduction of neo-adjuvant chemotherapy 30 years ago. Prognostic biomarkers for risk stratification at the time of diagnosis are missing and are a major drawback in clinical testing of novel therapeutic agents. Alternatively, analysis of the tumour microenvironment for osteosarcoma outcome-related biomarkers might be less dependent from the osteosarcoma subtype. Recently, Fritzsching et al. have reported for the first time CD8+/FOXP3+ ratio as strong prognostic factor at time of OS diagnosis, pointing out the functional key role of Treg in OS pathogenesis. Multivariate analysis showed that this novel parameter was independent from tumour metastasis and response to neoadjuvant chemotherapy and could be validated in an independent patient cohort with current state of diagnosis and treatment of OS [22]. It has been suggested in other solid tumours (e.g. colon cancers) that intensity of tumour microenvironment infiltration with T-cells, especially cytotoxic tumour infiltrating CD8+T-cells (CD8+ TILs) allows more powerful prognostic staging than traditional staging. The characterisation of this simple immune system-based biomarker has been termed the “immunoscore”, and this is currently tested for some tumours in a multicenter study [27, 28].
\nLymphocytes are immune cells regulated by diverse cytokines, in particular the triad OPG/RANK/RANKL, which represents a setting up a fertile soil for cancer cells as well [9]. Bone remodelling results from a balance between two opposite cellular activities: (i) osteoblasts in charge of the synthesis of new organic extracellular matrix, which will become progressively mineralized and (ii) osteoclasts specialised in the degradation of the mineralised extracellular matrix, process named bone resorption. Osteoclastogenesis and osteoclast activities are regulated by a master cytokine called NF-κB Ligand (RANKL), member of the tumour necrosis factor (TNF) superfamily (official TNF nomenclature: TNFSF11) [9]. RANKL is a soluble and/or membrane cytokine expressed by osteoblasts and stromal cells, binds to RANK a membrane receptor expressed at the surface of mature osteoclasts and their precursors. RANKL binding to RANK induces specific NF-κB–dependent signal transduction pathways and stimulates osteoclast differentiation, survival and resorption activity. RANKL binds to a soluble receptor named osteoprotegerin (OPG), which is a ubiquitous protein and acts as a decoy blocking RANKL binding to RANK [29]. OPG is then considered as a strong inhibitor of osteoclastogenesis and bone resorption. LGR4 is the last receptor of RANK recently identified. LGR4 expressed at the osteoclast/osteoclast precursor membrane is a negative regulator of RANKL-RANK activation (see review in Ref. [9]). It is widely accepted that the multiple components of the bone niche (e.g. soluble factors, extracellular matrix) strongly contribute to the bone tumour initiation and the metastatic process [30, 31]. RANKL influences the microenvironment of cancer cells by acting on the local immunity. Indeed, the major role of RANKL in the immune system has been initially identified in RANKL-knockout mice in which the development of secondary lymphoid organs was impaired especially the lymph nodes [32] but also at the “central” level where the maturation of thymic epithelial cells necessary for T cell development was affected [33]. RANKL is also involved in the modulation of the immune response by inducing T cell proliferation [34] and dendritic cells survival [29]. Indeed, activated T cells through RANKL expression stimulate dendritic cells, expressing RANK, to enhance their survival and thereby increase the T cell memory response [34]. More recently, Khan et al. demonstrated that RANKL blockade can rescue melanoma-specific T cells from thymic deletion and increases anti-tumour immune response as shown in melanoma [35]. In 2007, Mori et al. reported for the first time functional RANK expression in human OS cells strengthening the involvement of the RANK/RANKL/OPG axis in OS [36, 37]. Moreover, in animal OS models, OPG gene transfer prevents the formation of osteolytic lesions associated with OS development, in reducing the tumour incidence and the local tumour growth, leading to a fourfold increase in mice survival 28 days post-implantation [38]. This opened a new door of novel therapeutic approaches for OS.
The mononuclear phagocyte system is composed by heterogeneous populations participating in the body’s first line of defence against pathogens and parasites [39]. This system includes cells circulating cells into the body fluids such as monocytes, and integrates resident cells such as macrophages, dendritic cells (DC) and their precursors located in the bone marrow [40]. Their production and activities are controlled by numerous cytokines and growth factors but are more specifically regulated by the two ligands of macrophage-colony stimulating factor (M-CFR, cFMS or CD115): M-CSF (or CSF-1) and interleukin (IL)-34 [41, 42].
\nTAMs are the predominant leukocytes infiltrating solid tumours and can represent up to 50% of the tumour mass. These cells play a pivotal role in tumour behaviour illustrated by the significant link between TAM number and density and the prognosis [18, 43, 44]. Whereas TAMs can exert anti-tumour activities, the ambiguous role of macrophages in tumour progression is reflected in the finding that TAMs can also actively contribute to each stage of cancer development and progression [45]. Macrophage subtypes are conventionally classified in M1 considered as the classical population and M2 identified as an alternative subpopulation in link to their differentiation/activation state. However, if the parallel between M1 and M2 can be drawn with the Th1 and Th2 T lymphocyte classification, Th1/Th2 cells do not regulate macrophage polarisation. On the contrary, macrophage subtypes are versatile, are non-permanent cell populations, initiate and influence T lymphocyte polarisation resulting in differential immune response (e.g. Th1 response against virus and bacteria, Th2 response against parasites) [46]. Indeed, M1 and M2 macrophages are characterised by specific profiles of cytokine secretion. M1 macrophages are characterised by the secretion of IL-12, IL-1, IL-6, TNF or ROS, considered as pro-inflammatory mediators and directly involved in the control of infections and anti-tumour activities. On the opposite, M2 macrophages constitute a heterogeneous population (M2a, b and c) inducing a Th2 immune response and secreting IL-4, IL-10 and IL-13. M2 macrophages are pro-angiogenic, pro-fibrotic and pro-tumorigenic.
\nThe exact role of macrophages in OS is still unclear and controversial. Some studies have defined TAMs as anti-tumour effectors. Buddingh et al. thus demonstrated that higher TAM infiltration was associated with better overall survival in high-grade osteosarcoma. However, the authors did not observe any differences between metastatic and non-metastatic osteosarcomas, and TAMs exhibited both M1 and M2 characteristics [47]. On the contrary, the impact of macrophages in tumour development has been also suspected. Lewis and Pollard distinguished the anti-tumour M1-macrophages from M2-macrophages leading to tumour growth and invasion, angiogenesis, metastasis and immune-suppression [18]. OS development may thus be accompanied by a switch in the phenotype of infiltrating TAMs, from anti-metastatic M1-macrophages to pro-metastatic M2-macrophages. This hypothesis is in agreement with the in vivo work described by Xiao et al. who showed a switch in macrophage subpopulations in a mouse model of human osteosarcoma from M1-macrophages during the first week of tumour growth, to M2-macrophages after 2–3 weeks [48]. In addition, Pahl et al. demonstrated that human M1-like macrophages can be induced to exert direct anti-tumour activity against osteosarcoma cells, mediated by TNF-α and IL-1β [49]. In the same manner, Ségaliny et al. demonstrated that osteosarcoma cells expressed IL-34, increasing the recruitment of M2-polarised macrophages into the tumour tissue, which correlates with tumour vascularization and the metastatic process [50]. TAMs accumulate in tumour microenvironment and according to their M2 or M1 phenotype contribute to tumour growth, angiogenesis and metastasis [51]. RANK is present at the cell membrane of monocytes/macrophages and RANKL acts as chemoattractant factor for these cells [52]. M2 subtype is strongly associated with the angiogenic process and interestingly RANK is mainly expressed by M2 macrophage subtype [53]. RANK/RANKL signalling in M2 subtype modulates the production of chemokines promoting the proliferation of Treg lymphocytes in favour of an immunosuppressive environment [54]. In breast carcinoma, RANKL is mainly produced by CD4+CD25+ T lymphocytes expressing Foxp3 and corresponding to Treg lymphocytes. In this context, a vicious cycle is established between TAMs, Treg and tumour cells resulting in the tumour growth, the spreading of cancer cells and the amplification of the metastatic process [55].
The therapeutic protocol currently used for osteosarcoma was established by Rosen et al. at the end of the 1970s [56]. It comprises preoperative (neoadjuvant) chemotherapy associating mainly four drugs (doxorubicin, cisplatin, methotrexate and ifosfamide) [57], and followed by surgical removal of all detectable disease (including metastases), and postoperative (adjuvant) chemotherapy, preferably within the setting of clinical trials [58]. OS is considered resistant to applicable doses of radiation [59, 60]. Supplemental therapeutic approaches such as chemoembolisation or angioembolisation, thermal ablation, radiofrequency ablation and cryotherapy are experimental or palliative [59]. Unfortunately, patients, who are diagnosed with metastatic disease or who relapse post-therapy have an extremely poor prognosis, with little to no improvements in survival seen over the past 30 years [61]. Several reports have underlined the therapeutic value of using immunotherapies or immunomodulatory-based therapies for osteosarcoma [15, 62–64]. In this context, the number of new drugs activating the immune system has exploded in the last 10 years and numerous phase I and II clinical trials are in progress in osteosarcoma (Figure 1). In this chapter, the most recent therapeutic developments targeting the regulation of T lymphocytes and macrophages will be exposed.
\nDetection of specific T lymphocyte populations in the tumour microenvironment and in human tumour tissues defines an immunoscore and leads to patient stratification based on this immunophenotyping. These analyses have identified new predictive biomarkers and new therapeutic targets, which have stimulated the development of immunotherapies [65].
\nMonoclonal antibodies targeted against cell surface antigens specific to tumour cells have been proven to be effective in patients with breast cancer, lymphoma and neuroblastoma [66–68]. Usually these bispecific antibodies are engineered antibodies linking a tumour antigen recognition domain to a second domain that activates a receptor on immune effector cells, typically T cells. The expression of the glycosphingolipid GD2 is restricted to the central and peripheral nervous system, skin (melanocyte) and mesenchymal cells located in the stroma [69–71]. In addition to the healthy tissues, GD2 was detected in neuroblastomas, melanomas, sarcomas, lung and central nervous system tumours, in which a variable number of cancer cells express this antigen [72–75]. Based on this relative restricted distribution, GD2-targeting appeared very quickly as an interesting immunotherapy, especially for high-risk neuroblastomas, for which anti-GD2 antibodies improved significantly patient survival [68, 76]. In patients with stage IV neuroblastoma, anti-GD2 antibody ch14.18 has been shown to improve EFS effectively when given in the setting of minimal residual disease. The rationale for using this antibody in patients with OS lies in that 95% of osteosarcoma express GD2 [77]. Consequently, given the success of anti-GD2 mAb therapy in neuroblastoma, studies exploring the use of these mAbs in OS are underway [78]. Current trials include the GD2mAbs humanized3F8 (NCT01419834 and NCT01662804) and hu14.18K322A (NCT00743496) [61].
Nivolumab is an immunomodulator, which acts by blocking the activation of the programmed cell death-1 (PD-1) receptor, induced by one of its two ligands (PD-L1) on activated T cells [79]. Numerous preclinical investigations have demonstrated that inhibition of the interaction between PD-1 and PD-L1 enhances the T-cell response, resulting in increased anti-tumour activity. PD-L1 or PD-1 blockade with monoclonal antibodies results in strong and often rapid anti-tumour effects in several mouse models. A high PD-L1 expression has been identified in OS cell lines [80], and PD-1 expression on CD4 and CD8 T-cells was found higher in OS patients than in healthy controls and in patients with metastasis at diagnosis, high tumour stage or bone fracture [81]. A phase I/II trial will be conclude in 2016 on refractory solid tumours and sarcomas including osteosarcoma. A total of 242 patients will be enrolled and treated with Nivolumab IV over 60 minutes twice a month. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Dendritic cells have the specific ability to initiate and modulate adaptive immune responses [82]. This specificity, associated with their role in antigen presentation, has led to their use in vaccine approaches in cancer. Matured autologous dendritic cells loaded with tumour lysates derived from tumour tissue were used as the vaccine product. In a pre-clinical model of osteosarcoma, it has been demonstrated that killer dendritic cells were able to induce an adaptive anti-tumour immune response with a decrease in tumour development after cross-presentation of the tumour cell-derived antigen [83]. A phase I clinical trial demonstrated the feasibility and good tolerance of dendritic cells pulsed with MAGE-A1, MAGE-A3 and NYESO-1 full length peptides in combination with decitabine. Anti-tumour activity was observed in some patients [84]. In 2012, 12 osteosarcoma patients were vaccinated with tumour lysate pulsed dendritic cells, but evidence of a clinical benefit was observed in only two of these patients [85]. These authors concluded that osteosarcoma patients may be relatively insensitive to DC-based vaccine treatments. A new clinical trial was initiated, enrolling 56 patients (>1 year) with confirmed sarcoma, either relapsed or without known curative therapies, and treated with autologous dendritic cells pulsed with tumour lysate. NCT02409576 is a pilot trial (“Pilot Study of Expanded, Activated Haploidentical Natural Killer Cell Infusions for Sarcomas (NKEXPSARC)”) analysing the effect of donor NK cells on clinical response determined by imaging. About 20 patients (aged 6 months–80 years) will be included between 2015 and 2016. The patients will receive lymphodepleting chemotherapy with cyclophosphamide (1 day) followed by fludarabine (5 days) and each patient will receive IL-2 1 day before infusion of the NK cell (total six doses).
As it has been discussed above, the density of TAM is linked to a poor diagnosis. In osteosarcoma, Buddingh et al. showed that macrophages exhibit M1 and M2 phenotypes and demonstrated a link between M2 macrophages and angiogenesis. Similarly, in preclinical models of osteosarcoma, the recruitment of the M2 subtype is correlated with tumour angiogenesis and lung metastasis [47, 50].
\nL-MTP-PE is a synthetic analogue of muramyl dipeptide of the bacterial cell walls, which was identified as a powerful activator or monocyte/macrophage lineage. Indeed, L-MTP-PE induces the expression of pro-inflammatory mediators such TNF-α, IL-1, IL-6, lymphocyte function-associated antigen 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM1) leading to an M1 macrophage response. The therapeutic interest of L-MTP-PE was widely studied in osteosarcoma [86, 87]. The largest clinical experience with combination chemotherapy and L-MTP derives from the Intergroup 0133 osteosarcoma study. No difference in survival was found for patients who received ifosfamide in addition to the standard three-drug chemotherapy (doxorubicin, cisplatin and methotrexate). But this study did suggest that L-MTP had a beneficial impact on survival, improving the 5-year overall survival rate from 70 to 78% (p = 0.03) [88]. However, no significant difference in survival was observed between the two groups of treatment concerning the patients with metastatic disease (40% without L-MTP versus 53% with L-MTP, p = 0.27). Based on these results, the European Medicines Agency granted L-MTP an indication for the treatment of non-metastatic osteosarcoma in 2009; the American Food and Drug Administration (FDA) did not. L-MTP is also approved for use in Turkey, Mexico and Israel. Recently, Biteau et al. have proved the efficacy of association of zoledronate and L-mifamurtide combination in osteosarcoma. This association induced an additional and in some cases synergistic inhibition of primary tumour progression [89].
GM-CSF is one of the master regulators of myeloid cell lineage by controlling their differentiation, proliferation and activities. Indeed, this growth factor exerts immunomodulatory and immunostimulatory activities by stimulating the functional activities of neutrophil granulocytes but also of macrophages and DC. More specifically, GM-CSF promotes the recruitment and cytotoxic functions of macrophages, stimulates natural killer and dendritic cells, and consequently, upmodulates the number of CD4 T lymphocytes [90]. Arndt et al. have recently performed a phase I clinical trial using inhaled GM-CSF in patients with first isolated pulmonary recurrence of OS. Unfortunately, even though the clinical studies demonstrated the safety of administered GM-CSF (e.g. aerosolized delivery), no biological benefit (e.g. local immunomodulation in lung metastases) or improved clinical outcome was demonstrated. A future larger prospective randomised trial may demonstrate improved outcomes in OS patients probably [91, 92].
The therapies focused on the immune niche partially represent the potential therapeutic targets available for OS nowadays. Blood vessels, bone cells and tumour cells are targeted as well in the current clinical trials. However, in the future, the key to success will lie in better understanding and characterisation of the disease, leading to better patient stratification and, consequently, to personalised medicine.
This work was supported by the Bone Cancer Research Trust (UK, research project number 144681).
One of the most intriguing variables in science must be time. Without time, there would be no physical substances, no space, and no life. In other words, time and substance have to coexist. In the chapter, I will start with Einstein’s relativity theory to show his famous energy equation, derived from in which we will show that energy and mass can be traded. Since mass is equivalent to energy and energy is equivalent to mass, we see that mass can be treated as an energy reservoir. We will show any physical space cannot be embedded in an absolute empty space and it cannot have any absolute empty subspace in it and empty space is a timeless (i.e., t = 0) space. We will show that every physical space has to be fully packed with substances (i.e., energy and mass), and we will show that our universe is a subspace within a more complex space. We see that our universe could have been one of the many universes outside our universal boundary. We will also show that it takes time to create a subspace, and it cannot bring back the time that has been used for the creation. Since all physical substances exist with time, all subspaces are created by time and substances (i.e., energy and mass). This means that our cosmos was created by time with a gigantic energy explosion, for which every subspace coexists with time. This means that without time the creation of substances would not have happened. We see that our universe is in a temporal (i.e., t > 0) space, and it is still expanding based on current observation. This shows that our universe has not reached its half-life yet, as we have accepted the big bang creation. We are not alone with almost absolute certainty. Someday, we may find a planet that once upon a time had harbored a civilization for a period of light-years. In short, the burden of a scientific postulation is to prove a solution exists within our temporal universe; otherwise it is not real or virtual as mathematics is.
Professor Hawking was a world renowned astrophysicist, a respected cosmic scientist, and a genius who passed away last year on March 14, 2018. As you will see, our creation of universe was started with the same root of the big bang explosion, but it is not a sub-universe of Hawking’s. You may see from this chapter that the creation of temporal universe is somewhat different from Hawking’s creation.
The essence of Einstein’s special theory of relativity [1] is that time is a relative quantity with respect to velocity as given by
where
We see that the time window
Equivalently, Einstein’s relativity equation can be shown in terms of relative mass as given by
where m is the effective mass (or mass in motion) of a particle, mo is the rest mass of the particle, v is the velocity of the moving particle, and c is the speed of light. In other words, the effective mass (or mass in motion) of a particle increases at the same amount with respect to when the relative time window increases.
With reference to the binomial expansion, Eq. (2) can be written as
By multiplying the preceding equation with the velocity of light c2 and noting that the terms with the orders of v4/c2 are negligibly small, the above equation can be approximated by
which can be written as
The significance of the preceding equation is that m − mo represents an increase in mass due to motion, which is the kinetic energy of the rest mass mo. And (m − mo)c2 is the extra energy gain due to motion.
What Einstein postulated, as I remembered, is that there must be energy associated with the mass even at rest. And this was exactly what he had proposed:
where ε represents the total energy of the mass and
the energy of the mass at rest, where v = 0 and m ≈ mo.
We see that Eq. (6) or equivalently Eq. (7) is the well-known Einstein energy equation.
One of the most enigmatic variables in the laws of science must be “time.” So what is time? Time is a variable and not a substance. It has no mass, no weight, no coordinate, and no origin, and it cannot be detected or even be seen. Yet time is an everlasting existing variable within our known universe. Without time there would be no physical matter, no physical space, and no life. The fact is that every physical matter is associated with time which includes our universe. Therefore, when one is dealing with science, time is one of the most enigmatic variables that are ever present and cannot be simply ignored. Strictly speaking, all the laws of science as well every physical substance cannot exist without the existence of time.
On the other hand, energy is a physical quantity that governs every existence of substance which includes the entire universe. In other words without the existence of energy, there would be no substance and no universe! Nonetheless based on our current laws of science, all the substances were created by energy, and every substance can also be converted back to energy. Thus energy and substance are exchangeable, but it requires some physical conditions (e.g., nuclei and chemical interactions and others) to make the conversion start. Since energy can be derived from mass, mass is equivalent to energy. Hence every mass can be treated as an energy reservoir. The fact is that our universe is compactly filled with mass and energy. Without the existence of time, the trading (or conversion) between mass and energy could not have happened.
Let us now start with Einstein’s energy equation which was derived by his special theory of relativity [1] as given by
where m is the rest mass and c is the velocity of light.
Since all the laws in science are approximations, for which we have intentionally used an approximated sign. Strictly speaking the energy equation should be more appropriately presented with an inequality sign as described by
This means that in practice, the total energy should be smaller or at most approaching to the rest mass m times square of light speed (i.e.,
In view of Einstein’s energy equation of Eq. (8), we see that it is a singularity-point approximation and timeless equation (i.e., t = 0). In other words, the equation needs to convert into a temporal (i.e., t > 0) representation or time-dependent equation for the conversion to take place from mass into energy. We see that, without the inclusion of time variable, the conversion would not have taken place. Nonetheless, Einstein’s energy equation represents the total amount of energy that can be converted from a rest mass m. Every mass can be viewed as an energy reservoir. Thus by incorporating with the time variable, the Einstein’s energy equation can be represented by a partial differential equation as given by [2]
where
One of the important aspects in Eq. (10) must be that energy and mass can be traded, for which the rate of energy conversion from a mass can be written in terms of electromagnetic (EM) radiation or Radian Energy as given by [4]
where
Similarly the conversion from energy to mass can also be presented as
The major difference of this equation, as compared with Eq. (11), must be the energy convergent operator −∇·S(v), where we see that the rate of energy as in the form of EM radiation converges into a small volume for the mass creation, instead of diverging from the mass. Since mass creation is inversely proportional to
Incidentally, black hole [5, 6] can be considered as one of the energy convergent operators. Instead the convergent force is relied more on the black hole’s intense gravitational field. The black hole still remains an intriguing physical substance to be known. Its gravitational field is so intense even light cannot be escaped.
By the constraints of the current laws of science, the observation is limited by the speed of light. If light is totally absorbed by the black hole, it is by no means that the black hole is an infinite energy sink [6]. Nonetheless, every black hole can actually be treated as an energy convergent operator, which is responsible for the eventuality in part of energy to mass conversion, where an answer remained to be found.
In our physical world, every matter is a substance which includes all the elemental particles; electric, magnetic, and gravitation fields; and energy. The reason is that they were all created by means of energy or mass. Our physical space (e.g., our universe) is fully compacted with substances (i.e., mass and energy) and left no absolute empty subspace within it. As a matter of fact, all physical substances exist with time, and no physical substance can exist forever or without time, which includes our universe. Thus, without time there would be no substance and no universe. Since every physical substance described itself as a physical space and it is constantly changing with respect to time. The fact is that every physical substance is itself a temporal space (or a physical subspace), as will be discussed in the subsequent sections.
In view of physical reality, every physical substance cannot exist without time; thus if there is no time, all the substances which include all the building blocks in our universe and the universe itself cannot exist. On the other hand, time cannot exist without the existence of substance or substances. Therefore, time and substance must mutually coexist or inclusively exist. In other words, substance and time have to be simultaneously existing (i.e., one cannot exist without the other). Nonetheless, if our universe has to exist with time, then our universe will eventually get old and die. So the aspects of time would not be as simple as we have known. For example, for the species living in a far distant galaxy moving closer to the speed of light, their time goes somewhat slower relatively to ours [1]. Thus, we see that the relativistic aspects of time may not be the same at different subspaces in our universe (e.g., at the edge of our universe).
Since substances (i.e., mass) were created by energy, energy and time have to simultaneously exist. As we know every conversion, either from mass to energy or from energy to mass, cannot get started without the inclusion of time. Therefore, time and substance (i.e., energy and mass) have to simultaneously exist. Thus we see that all the physical substances, including our universe and us, are coexisting with time (or function of time).
Let us define various subspaces in the following, as they will be used in the subsequence sections:
An absolute empty space has no time, no substance, and no coordinate and is not event bounded or unbounded. It is a virtual space and timeless space (i.e., t = 0), and it does not exist in practice.
A physical space is a space described by dimensional coordinates, which existed in practice, compactly filled with substances, supported by the current laws of science and the rule of time (i.e., time can only move forward and cannot move backward; t > 0). Physical space and absolute empty space are mutually exclusive. In other words, a physical space cannot be embedded in an absolute empty space, and it cannot have absolute empty subspace in it. In other words, physical space is a temporal space in which time is a forward variable (i.e., t > 0), while absolute empty space is a timeless space (i.e., t = 0) in which nothing is in it.
A temporal space is a time-variable physical space supported by the laws of science and rule of time (i.e., t > 0). In fact, all physical spaces are temporal spaces (i.e., t > 0).
A spatial space is a space described by dimensional coordinates and may not be supported by the laws of science and the rule of time (e.g., a mathematical virtual space).
A virtual space is an imaginary space, and it is generally not supported by the laws of science and the rule of time. Only mathematicians can make it happen.
As we have noted, absolutely empty space cannot exist in physical reality. Since every physical space needs to be completely filled with substances and left no absolutely empty subspace within it, every physical space is created by substances. For example, our universe is a gigantic physical space created by mass and energy (i.e., substances) and has no empty subspaces in it. Yet, in physical reality all the masses (and energy) existed with time. Without the existence of time, then there would be no mass, no energy, and no universe. Thus, we see that every physical substance coexists with time. As a matter of fact, every physical subspace is a temporal subspace (i.e., t > 0), which includes us and our universe.
Since a physical space cannot be embedded within an absolute empty space and it cannot have any absolute empty subspace in it [7], our universe must be embedded in a more complex physical space. If we accepted our universe is embedded in a more complex space, then our universe must be a bounded subspace.
How about time? Since our universe is embedded in a more complex space, the complex space may share the same rule of time (i.e., t > 0). However, the complex space that embeds our universe may not have the same laws of science as ours but may have the same rule of time (i.e., t > 0); otherwise our universe would not be bounded. Nevertheless, whether our universe is bounded or not bounded is not the major issue of our current interest, since it takes a deeper understanding of our current universe before we can move on to the next level of complex space revelation. It is however our aim, abiding within our current laws of science, to investigate the essence of time as the enigma origin of our universe.
One of the most intriguing questions in our life must be the existence of time. So far, we know that time comes from nowhere, and it can only move forward, not backward, not even stand still (i.e., t = 0). Although time may somewhat relatively slow down, based on Einstein’s special theory of relativity [1], so far time cannot move backward and cannot even stand still. As a matter of fact, time is moving at a constant rate within our subspace, and it cannot move faster or slower. We stress that time moves at the same rate within any subspace within the universe even closer the boundary of our universe, but the difference is the relativistic time. Since time is ever existing, then how do we know there is a physical space? One answer is that there is a profound connection between time and physical space. In other words, if there is no time, then there would be no physical space. A physical space is in fact a temporal (i.e., t > 0) space, in contrast to a virtual space. Temporal space can be described by time, while virtual space is an imaginary space without the constraint of time. Temporal space is supported by the laws of science, while virtual space is not.
A television video image is a typical example of trading time for space. For instance, each TV displayed an image of (dx, dy) which takes an amount of time to be displayed. Since time is a forward-moving variable, it cannot be traded back at the expense of a displayed image (dx, dy). In other words, it is time that determines the physical space, and it is not the physical space that can bring back the time that has been expended. And it is the size (or dimension) of space that determines the amount of time required to create the space (dx, dy). Time is distance and distance is time within a temporal space. Based on our current constraints of science, the speed of light is the limit. Since every physical space is created by substances, a physical space must be described by the speed of light. In other words, the dimension of a physical space is determined by the velocity of light, where the space is filled with substances (i.e., mass and energy). And this is also the reason that speed of time (e.g., 1 s, 2 s, etc.) is determined by the speed of light.
Another issue is why the speed of light is limited. It is limited because our universe is a gigantic physical space that is filled with substances that cause a time delay on an EM wave’s propagation. Nevertheless, if there were physical substances that travel beyond the speed of light (which remains to be found), their velocities would also be limited, since our physical space is fully compacted with physical substances and it is a temporal (i.e., t > 0) space. Let me further note that a substance can travel in space without a time delay if and only if the space is absolutely empty (i.e., timeless; t = 0), since distance is time (i.e., d = ct, t = 0). However, absolute empty space cannot exist in practice, since every physical space (including our universe) has to be fully filled with substances (i.e., energy and mass), with no empty subspace left within it. Since every physical subspace is temporal (i.e., t > 0), in which we see that timeless and temporal spaces are mutually exclusive.
Strictly speaking, all our laws of physics are evolved within the regime of EM science. Besides, all physical substances are part of EM-based science, and all the living species on Earth are primarily dependent on the source of energy provided by the sun. About 78% of the sunlight that reaches the surface of our planet is well concentrated within a narrow band of visible spectrum. In response to our species’ existence, which includes all living species on Earth, a pair of visible eyes (i.e., antennas) evolved in us humans, which help us for our survival. And this narrow band of visible light led us to the discovery of an even wider band of EM spectral distribution in nature. It is also the major impetus allowing us to discover all the physical substances that are part of EM-based physics. In principle, all physical substances can be observed or detected with EM interaction, and the speed of light is the current limit.
Then there is question to be asked, why is the speed of light limited? A simple answer is that our universe is filled with substances that limit the speed of light. The energy velocity of an electromagnetic wave is given by [3]
where (μ, ε) are the permeability and the permittivity of the medium. We see that the velocity of light is shown by
where (μ0,ε0) are the permeability and the permittivity of the space.
In view of Eq. (13), it is apparent that the velocity of electromagnetic wave (i.e., speed of light) within an empty subspace (i.e., timeless space) is instant (or infinitely large) since distance is time (i.e., d = ct, t = 0).
A picture that is worth more than a thousand words [8] is a trivial example to show that EM observation is one of the most efficient aspects in information transmission. Yet, the ultimate physical limitation is also imposed by limitation of the EM regime, unless new laws of science emerge. The essence of Einstein’s energy equation shows that mass and energy are exchangeable. It shows that energy and mass are equivalent and energy is a form of EM radiation in view of Einstein’s equation. We further note that all physical substances within our universe were created from energy and mass, which include the dark energies [9] and dark matter [10]. Although the dark substances may not be observed directly using EM interaction, we may indirectly detect their existence, since they are basically energy-based substances (i.e., EM-based science). It may be interesting to note that our current universe is composed of 72% dark energy, 23% dark matter, and 5% other physical substances. Although dark matter contributes about 23% of our universe, it represents a total of 23% of gravitational fields. With reference to Einstein’s energy equation (Eq. (8)), dark energy and dark matter dominate the entire universal energy reservation, well over 95%. Furthermore, if we accept the big bang theory for our universe creation [11], then creation could have been started with Einstein’s time-dependent energy formula of Eq. (11) as given by
where [∇·S(v)] represents a divergent energy operation. In this equation, we see that a broad spectral band intense radian energy diverges (i.e., explodes) at the speed of light from a compacted matter M, where M represents a gigantic mass of energy reservoir. It is apparent that the creation is ignited by time and the exploded debris (i.e., matter and energy) starts to spread out in all directions, similar to an expanding air balloon. The boundary (i.e., radius of the sphere) of the universe expands at the speed of light, as the created debris is disbursed. It took about 15 billion chaotic light-years [12, 13, 14] to come up with the present state of constellation, in which the boundary is still expanding at the speed of light beyond the current observation. With reference to a recent report using the Hubble Space Telescope, we can see galaxies about 15 billion light-years away from us. This means that the creation process is not stopping yet and at the same time the universe might have started to de-create itself, since the big bang started, due to intense convergent gravitational forces from all the newly created debris of matter (e.g., galaxies and dark matter). To wrap up this section, we would stress that one of the viable aspects of Eq. (15) is the transformation from a spatially dimensionless equation to a space-time function (i.e., ∇·S); it describes how our universe was created with a huge explosion. Furthermore, the essence of Eq. (15) is not just a piece of mathematical formula; it is a symbolic representation, a description, a language, a picture, or even a video as may be seen from its presentation. We can visualize how our universe was created, from the theory of relativity to Einstein’s energy equation and then to temporal space creation.
Let us now take one of the simplest connections between physical subspace and time [15]:
where d is the distance, v is the velocity, and t is the time variable. Notice that this equation may be one of the most profound connections between time and physical space (or temporal space). Therefore, a three-dimensional (Euclidean) physical (or temporal) subspace can be described by
where (vx, vy, vz) are the velocities’ vectors and t is the time variable. Under the current laws of science, the speed of light is the limit. Then, by replacing the velocity vectors equal to the speed of light c, a temporal space can be written as
Thus, we see that time can be traded for space and space cannot be traded for time, since time is a forward variable (i.e., t > 0). In other words, once a section of time Δt is expended, we cannot get it back. Needless to say, a spherical temporal space can be described by
where radius r increases at the speed of light. Thus, we see that the boundary (i.e., edge) of our universe is determined by radius r, which is limited by the light speed, as illustrated in a composite temporal space diagram of Figure 1. In view of this figure, we see that our universe is expanding at the speed of light well beyond the current observable galaxies. Figure 2 shows a discrete temporal space diagram, in which we see that the size of our universe is continuously expanding as time moves forward (i.e., t > 0). Assuming that we have already accepted the big bang creation, sometime in the future (i.e., billions of light-years later), our universe will eventually stop expanding and then start to shrink back, preparing for the next cycle of the big bang explosion. The forces for the collapsing universe are mainly due to the intense gravitational field, mostly from giant black holes and matter that were derived from merging (or swallowing) with smaller black holes and other debris (i.e., physical substances). Since a black hole’s gravitational field is so intense, even light cannot escape; however, a black hole is by no means an infinite energy reservoir. Eventually, the storage capacity of a black hole will reach a limit for explosion, as started for the mass to energy and debris creation.
Composite temporal space universe diagram. r = ct, r is the radius of our universe, t is time, c is the velocity of light, and ε0 and μ0 are the permittivity and permeability of the space.
Discrete temporal universe diagrams; t is time.
In other words, there will be one dominant giant black hole within the shrinking universe, to initiate the next cycle of universe creation. Therefore, every black hole can be treated as a convergent energy sink, which relies on its intense gravitation field to collect all the debris of matter and energies. Referring to the big bang creation, a gigantic energy explosion was the major reason for the universe’s creation. In fact, it can be easily discerned that the creating process has never slowed down since the birth of our universe, as we see that our universe is still continuingly expanding even today. This is by no means an indication that all the debris created came from the big bang’s energy (e.g., mc2); there might have been some leftover debris from a preceding universe. Therefore, the overall energy within our universe cannot be restricted to just the amount that came from the big bang creation. In fact, the conversion processes between mass and energy have never been totally absent since the birth of our universe, but they are on a much smaller scale. In fact, right after birth, our universe started to slow down the divergent process due to the gravitational forces produced by the created matter. In other words, the universe will eventually reach a point when overall divergent forces will be weaker than the convergent forces, which are mostly due to gravitational fields coming from the newly created matter, including black holes. As we had mentioned earlier, our universe currently has about 23% dark matter, which represents about 23% of the gravitational fields within the current universe. The intense localized gravitational field could have been produced from a group or a giant black hole, derived from merging with (or swallowing up) some smaller black holes, nearby dark matter, and debris. Since a giant black hole is not an infinite energy sink, eventually it will explode for the next cycle of universal creation. And it is almost certain that the next big bang creation will not occur at the same center of our present universe. One can easily discern that our universe will never shrink to a few inches in size, as commonly speculated. It will, however, shrink to a smaller size until one of the giant black holes (e.g., swallowed-up sufficient physical debris) reaches the big bang explosive condition to release its gigantic energy for the next cycle of universal creation. The speculation of a possible collapsing universe remains to be observed. Nonetheless, we have found that our universe is still expanding, as observed by the Doppler shifts of the distant galaxies at the edge of our universe, about 15 billion light-years away [12, 13, 14]. This tells us that our universe has not reached its half-life yet. In fact, the expansion has never stopped since the birth of our universe, and our universe has also been started to de-create since the big bang started, which is primarily due to convergent gravitational forces from the newly created debris (e.g., galaxies, black holes, and dark matter).
Relativistic time at a different subspace within a vast universal space may not be the same as that based on Einstein’s special theory of relativity [1]. Let us start with the relativistic time dilation as given by
where Δt′ is the relativistic time window, compared with a standstill subspace, Δt is the time window of a standstill subspace, v is the velocity of a moving subspace, and c is the velocity of light. We see that time dilation Δt′ of the moving subspace, relative to the time window of the standstill subspace Δt, appears to be wider as velocity increases. For example, a 1-s time window Δt is equivalent to the 10-s relative time window Δt’. This means that a 1-s time expenditure within the moving subspace is relative to about a 10-s time expenditure within the standstill subspace. Therefore, for the species living in an environment that travels closer to the speed of light (e.g., at the edge of the universe), their time appears to be slower than ours, as illustrated in Figure 3. In this figure, we see an old man traveling at a speed closer to the velocity of light; his relative observation time window appears to be wider as he is looking at us, and the laws of science within his subspace may not be the same as ours.
Effects on relativistic time.
Two of the most important pillars in modern physics must be Einstein’s relativity theory and Schrödinger’s quantum mechanics [15]. One is dealing with very large objects (e.g., universe), and the other is dealing with very small particles (e. g., atoms). Yet, there exists a profound connection between them, by means of the Heisenberg’s uncertainty principle [16]. In view of the uncertainty relation, we see that every temporal subspace takes a section of time Δt and an amount of energy ΔE to create. Since we cannot create something from nothing, everything needs an amount of energy ΔE and a section of time Δt to make it happen. By referring to the Heisenberg uncertainty relation as given by
where h is the Planck’s constant. We see that every subspace is limited by ΔE and Δt. In other words, it is the h region, but not the shape, that determines the boundary condition. For example, the shape can be either elongated or compressed, as long as it is larger than the h region.
Incidentally, the uncertainty relationship of Eq. (21) is also the limit of reliable bit information transmission as pointed out by Gabor in [17]. Nonetheless, the connection with the special theory of relativity is that the creation of a subspace near the edge of our universe will take a short relative time with respect to our planet earth, since Δt’ > Δt. The “relativistic” uncertainty relationship within the moving subspace, as with respect to a standstill subspace, can be shown as
where we see ΔE energy is conserved. Thus a narrower time-width can be achieved as with respect to standstill subspace. It is precisely possible that one can exploit for time-domain digital communication, as from ground station to satellite information transmission.
On the other hand, as from satellite to ground station information transmission, we might want to use digital bandwidth (i.e., Δv) instead. This is a frequency-domain information transmission strategy, as in contrast with time domain, which has not been exploited yet. The “relativistic” uncertainty relationship within the standstill subspace as with respect to the moving subspace can be written as
Or equivalently we have
in which we see that a narrower bandwidth Δv can be in principle use for frequency-domain communication.
Every physical (or temporal) subspace is created by substances (i.e., energy and mass), and substances coexist with time. In this context, we see that our universe was essentially created by time and energy and the universe is continuously evolving (i.e., changing) with time. Although relativistic time may not be the same at the different subspaces within our universe, the rule of time may remain the same. As for the species living closer to the speed of light, relativistic time may not be noticeable to them, but their laws of science within their subspace may be different from ours. Nonetheless, our universe was simultaneously created by time with a gigantic energy explosion. Since our universe cannot be embedded in an empty space, it must be embedded in a more complex space that remains to be found. From an inclusive point of view, mass is energy or energy is mass, which was discovered by Einstein almost a century ago [1]. And it is this basic fundamental law of physics that we have used for investigating the origin of time. Together with a huge energy explosion (i.e., big bang theory [11]), time is the igniter for the creation of our universe. As we know, without the existence of time, the creation of our universe would not have happened. As we have shown, time can be traded for space, but space cannot be traded for time. Our universe is in fact a temporal physical subspace, and it is continuously evolving or changing with time (i.e., t > 0). Although every temporal subspace is created by time (and substances), it is not possible for us to trade any temporal subspace for time. Since every physical substance has a life, our universe (a gigantic substance) cannot be excluded. With reference to the report from a recent Hubble Space Telescope observation [12, 13, 14], we are capable of viewing galaxies about 15 billion light-years away and have also learned that our universe is still by no means slowing down in expansion. In other words, our universe has still not reached its half-life, based on our estimation. As we have shown, time ignited the creation of our universe, yet the created physical substances presented to us the existence of time.
In view of the preceding discussion, we see that our universe is a time-invariant system (i.e., from system theory stand point); as in contrast with an empty space, it is a not a time-invariant system and it is a timeless or no-time space. We see that timeless solution cannot be directly implemented within our universe. Since science is a law of approximation and mathematics is an axiom of absolute certainty, using exact math to evaluate inexact science cannot guarantee its solution to exist within our temporal (i.e., t > 0) universe. One important aspect of temporal universe is that one cannot get something from nothing: There is always a price to pay; every piece of temporal subspace (or every bit of information [7]) takes an amount of energy (i.e., ΔE) and a section of time (i.e., Δt) to create. And the subspace [i.e., f(x, y, z; t), t > 0] is a forward time-variable function. In other words, time and subspace coexist or are mutually inclusive. This is the boundary condition and constrain of our temporal universe [i.e., f(x, y, z; t), t > 0], in which every existence within our universe has to comply with this condition. Otherwise it is not existing within our universe, unless new law emerges since laws are made to be broken. Thus we see that any emerging science has to be proven to exist within our temporal universe [i.e., f(x, y, z; t), t > 0]. Otherwise it is a fictitious science, unless it can be validated by repeated experiments.
In mathematics, we see that the burden of a postulation is first to prove if there exists a solution and then search for a solution. Although we hardly have had, there is an existent burden in science. Yet, we need to prove that a scientific postulation is existing within our temporal universe [i.e., f(x, y, z; t), t > 0]; otherwise it is not real or virtual as mathematics is. For example such as the superposition principle in quantum mechanics, in which we have proven [18] it is not existed within our temporal universe (i.e., t > 0), since Schrödinger’s quantum mechanics is timeless as mathematics is.
There is however an additional constrain as imposed by our temporal universe which is the affordability. As we have shown that everything (e.g., any physical subspace) existed within our universe has a price tag, in terms of an amount of energy ΔE and a section of time Δt (i.e., ΔE, Δt). To be precise, the price tag also includes an amount of “intelligent” information ΔI or an equivalent amount of entropy ΔS (i.e., ΔE, Δt, ΔI) [7]. For example, creation of a piece of simple facial tissue will take a huge amount of energy ΔE, a section of time Δt, and an amount of information ΔI (i.e., equivalent amount of entropy ΔS). We note that on this planet Earth, only humans can make it happen. Thus we see that every physical subspace (or equivalently substance) within our universe has a price tag (i.e., ΔE, Δt, ΔS), and the question is that can we afford it?
Within our universe, we can easily estimate there were billions and billions of civilizations that had emerged and faded away in the past 15 billion light-years. Our civilization is one of the billions and billions of current consequences within our universe, and it will eventually disappear. We are here, and will be here, for just a very short moment. Hopefully, we will be able to discover substances that travel well beyond the limit of light before the end of our existence, so that a better observational instrument can be built. If we point the new instrument at the right place, we may see the edge of our universe beyond the limit of light. We are not alone with almost absolute certainty. By using the new observational equipment, we may find a planet that once upon a time had harbored a civilization for a period of twinkle thousands of (Earth) years.
We have shown that time is one of the most intriguing variables in the universe. Without time, there would be no physical substances, no space, and no life. With reference to Einstein’s energy equation, we have shown that energy and mass can be traded. In other words, mass is equivalent to energy, and energy is equivalent to mass, for which all mass can be treated as an energy reservoir. We have also shown that a physical space cannot be embedded in an absolute empty space or a timeless (i.e., t = 0) space, and it cannot even have any absolute empty subspace in it. In reality, every physical space has to be fully packed with physical substances (i.e., energy and mass). Since no physical space can be embedded in an absolute empty space, it is reasonable to assume that our universe is a subspace within a more complex space, which remains to be found. In other words, our universe could have been one of the many universes outside our universal boundary, which comes and goes like bubbles. We have also shown that it takes time to create a physical space and the time that has been used for the creation cannot be brought back. Since all physical substances exist with time, all physical spaces are created by time and substances (i.e., energy and mass). This means that our cosmos was created by time and a gigantic energy explosion, in which we see that every substance coexists with time. That is, without time, the creation of physical substances would not have happened. We have further noted that our universe is in a temporal space and it is still expanding based on current observation. This shows that our universe has not reached its half-life yet, as we have accepted the big bang creation. And it is noted that we are not alone with almost absolute certainty. Someday, we may find a planet that once upon a time had harbored a civilization for a period of light-years. We have further shown that the burden of a scientific postulation is to prove it exists within our temporal universe [i.e., f(x, y, z; t), t > 0]; otherwise it is not real or virtual as mathematics is.
Finally, I would like to take this opportunity to say a few words on behalf of Professor Stephen Hawking, who passed away last year on March 14, 2018. Professor Hawking was a world-renowned astrophysicist, a respected cosmic scientist, and a genius. Although the creation of temporal universe started with the same root of the big bang explosion, it is not a subspace of Professor Hawking’s universe. You may see from the preceding presentation that the creation of temporal universe is somewhat different from Hawking’s creation. One of the major differences may be at the origin of big bang creation. My temporal universe was started with a big bang creation within a “non-empty” space, instead within of an empty space which was normally assumed.
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