Arthropod-borne flaviviruses represent human pathogens of global medical importance, against which no effective small molecule-based antiviral therapy is currently available. Arbidol (umifenovir) is a broad spectrum antiviral compound approved in Russia and China for prophylaxis and treatment of influenza. This compound showed activity against numerous DNA and RNA viruses. Its mode of action is based predominantly on the impairment of critical steps of virus-cell interaction. Here we demonstrate that arbidol possesses a micromolar inhibition activity (EC50 values ranging from 10.57 ± 0.74 to 19.16 ± 0.29 µM) in Vero cells infected with Zika virus, West Nile virus, and tick-borne encephalitis virus, three medically important representatives of arthropod-borne flaviviruses. Interestingly, no antiviral effect of arbidol is observed in porcine stable kidney cells (PS), human neuroblastoma cells (UKF-NB-6), human hepatoma cells (Huh-7 cells) indicating that the antiviral effect of arbidol is strongly cell-type dependent. Arbidol presents a significant increasing in cytotoxicity profiles when tested in various cell lines in the order: Huh-7 < HBCA < PS < UKF-NB-6 < Vero with CC50 values ranging from 18.69 ± 0.1 to 89.72 ± 0.19 µM. Antiviral activity and acceptable cytotoxicity profiles suggest that arbidol could be a promising candidate for further investigation as a potential therapeutic agent in treating flaviviral infections.

Polyhydroxyalkanoates (PHA) are microbial biopolyesters utilized as “green plastics”. Their production under controlled conditions resorts to bioreactors operated in different modes. Because PHA biosynthesis constitutes a multiphase process, both feeding strategy and bioreactor operation mode need smart adaptation. Traditional PHA production setups based on batch, repeated batch, fed-batch or cyclic fed-batch processes are often limited in productivity, or display insufficient controllability of polyester composition. For highly diluted substrate streams like it is the case for (agro)industrial waste streams, fed-batch enhanced by cell recycling were recently reported as a viable tool to increase volumetric productivity. As emerging trend, continuous fermentation processes in single-, two-, and multi-stage setups are reported, which bring the kinetics of both microbial growth and PHA accumulation into agreement with process engineering, and allow tailoring PHA´s molecular structure. Moreover, we currently witness an increasing number of CO2-based PHA production processes using cyanobacteria; these light-driven processes resort to photobioreactors similar to those used for microalgae cultivation, and can be operated both discontinuously and continuously. This development goes in parallel to the emerging use of methane and syngas as an abundantly available gaseous substrates, which also calls for bioreactor systems with optimized gas transfer. The review sheds light on the challenges of diverse PHA production processes in different bioreactor types and operational regimes using miscellaneous microbial production strains such as extremophilic Archaea, chemoheterotrophic eubacteria and phototrophic cyanobacteria. Particular emphasize is dedicated to the limitations and promises of different bioreactor-strain combinations, and to efforts devoted to upscaling these processes to industrially relevant scales.

Single cell proteins are the dead dried cells of microorganisms or purified protein isolated from microorganism’s cell culture, used as a food supplement to humans’ food and animals feed. World suffer from malnutrition particularly developing countries, due to rapid increase in population, increased the demand for protein and nutrients requirement. Bacteria is potential microorganism for SCP production due to high protein content, fast generation time, bio-active secondary metabolites production and can grow on various substrates. Actinobacteria species and strain have capability to produce biological active compounds, produced about two-thirds of antibiotics available in the market, actively used as antibiotics, antiprotozoal, antifungal, antiviral, anticancer, anticholesterol, antihelminth and immunosuppressant. Actinomycetes can be used as probiotic as well as single cell protein that will deal with antibiotic as well as protein source.

Coccidioidomycosis (Valley Fever) is a disease caused by inhalation of Coccidioides spp. This neglected tropical disease of the Americas has substantial public health impact despite its geographic restriction to desert areas of the southwestern U.S., Mexico, Central and South America. The incidence of this infection in California and Arizona has been increasing over the past fifteen years. The burden of disease in outside the U.S. remains poorly understood. Several large cities are within the endemic region in the U.S. Coccidioidomycosis accounts for 25,000 hospital admissions per year in California. While most cases of coccidioidomycosis resolve spontaneously, up to 40% are severe enough to require anti-fungal treatment, and a significant number disseminate beyond the lungs. Disseminated infection, especially involving the meninges, is fatal without appropriate treatment. Infection with Coccidioides spp. is protective against a second infection, so vaccination seems biologically plausible. This review of efforts to develop a vaccine against coccidioidomycosis focuses on vaccine approaches and the difficulties in identifying protein antigen/adjuvant combinations that protect in experimental mouse models. Although the quest for a vaccine has not yet resulted in a clinically useful product, scientific efforts of vaccine development pave the way for future success.

Tumor microenvironment including cancer-associated fibroblasts (CAF) has developed as an important target for understanding tumor progression, clinical prognosis and treatment responses of cancer. Cancer cells appear to transform normal fibroblasts (NF) into CAFs involving direct cell-cell communication and epigenetic regulations. This review summarizes the current understanding on miR involvement in cancer cell – tumor environment/stroma communication, transformation of NFs into CAFs, their involved targets and signaling pathways in these interactions; and clinical relevance of CAF-related miR expression profiles. There is evidence that miRs have very similar roles in activating hepatic (HSC) and pancreatic stellate cells (PSC) as part of precancerous fibrotic diseases. In summary, deregulated miRs affect various intracellular functional complexes, such as transcriptional factors, extracellular matrix, cytoskeleton, EMT/MET regulation, soluble factors, tyrosine kinase and G-protein signaling, apoptosis and cell cycle & differentiation, but also formation and composition of the extracellular microenvironment. These processes result in the clinical appearance of desmoplasia involving CAFs and fibrosis characterized by deregulated stellate cells. In addition, modulated release of soluble factors can act as (auto)activating feedback loop for transition of NFs into their pathological counterparts. Furthermore, epigenetic communication between CAFs and cancer cells may confer to cancer specific functional readouts and transition of NF into their pathological counterparts. MiR related epigenetic regulation with many similarities should be considered as key factor in development of cancer and fibrosis specific environment.

Aims: In late December 2019, early reports predicted the onset of a potential Coronavirus outbreak in china, given the estimate of a reproduction number for the 2019 Novel Coronavirus (COVID-19). Because of high ability of transmission and widespread prevalence, the mortality of COVID-19 infection is growing fast worldwide. Absent of an anti-COVID-19 has put scientists on the urge to repurpose already approved therapeutics or to find new active compounds against coronavirus. Here in this study, a set of computational approaches were performed in order to repurpose antivirals for dual inhibition of the frontier proteases involved in virus replication, papain-like protease (PLpro; corresponding to nsp3) and a main protease (Mpro), 3C‑like protease (3CLpro; corresponding to nsp5). Materials and Methods: In this regard, a rational virtual screening procedure including exhaustive docking techniques was performed for a database of 160 antiviral agents over 3CLpro and PLpro active sites of SARS-CoV-2. The compounds binding energies and interaction modes over 3CLpro and PLpro active sites were analyzed and ranked with the aid of free Gibbs binding energy. The most potent compounds, based on our filtering process, are then proposed as dual inhibitors of SARSC-CoV-2 proteases. Key findings: Accordingly, seven antiviral agents including two FDA approved (Nelfinavir, Valaganciclovir) and five investigational compounds (Merimepodib, Inarigivir, Remdesivir, Taribavirine and TAS106-106) are proposed as potential dual inhibitors of the enzymes necessary for RNA replication in which Remdesivir as well as Inagrivir have the highest binding affinity for both of the active sites. Significance: The mentioned drug proposed to inhibit both PLpro and 3CLpro enzymes with the aim of finding dual inhibitors of SARSC-CoV-2 proteases.

Passiflora cincinnata Mast is a plant popularly used in traditional medicine in northeastern Brazil. The present study aimed to evaluate the anti-lipoperoxidative and anti-α-amylase properties, and cytotoxicity of an extract and fraction of passion fruit leaves (P. cincinnata Mast), as well as the antihyperglecemiant activity of the fraction rich in glycosylated flavonoids and showing low cytotoxicity in rats with a postprandial hyperglycaemia condition. The ethyl acetate fraction (F.ACT) of the P. cincinnata leaves presented the best anti-lipoperoxide properties with TBARs 81.49%, 95.48% and 75.62% lower than AAPH, FeSO₄ and H₂O₂ induced controls, respectively, at 200 μg.mL-1. In addition, it presented an anti-α-amylase potential, with a better ability to inhibit the α-amylase enzyme in comparison to the acarbose control (IC₅₀ 6.49 ± 0.11 and 12.01 ± 0.4 μg.mL-1, respectively). The hydroalcoholic extract of P. cincinnata (ExEt) presented high content of total tannins, flavonoids and flavonols. However, F.ACT had the highest concentration of flavonoids among the fractions studied. HPLC analysis of this fraction revealed the presence of the flavonoids isovitexin, orientin and isoorientin. F.ACT showed low to no cytotoxicity below 150 μg.mL-1. Regarding the post-prandial antihyperglycaemic activity of F.ACT, it was observed at 50 and 100 mg.kg-1.

: Nanotechnology options to road surface maintenance offers several advantages compared to traditionally used materials. The small particle sizer of hydrophobic Nano-Silane modified Nano-Polymers (NSNP) enables these nanotechnology products to deeply penetrate existing road surfaces, sealing micro-cracks and render surfacings to be water-resistant for extended periods of time. In comparison, traditionally used products contain minimum partial sizes of about 1 – 5 microns, that provide a superficial protection that wears off in a relatively short period of time. These traditional products are often associated with vehicle contamination while drying and requires the re-instatement of road markings. None of these disadvantages are associated with applicable NSNP technologies that are quick drying, with no vehicle contamination risks and is equivalent to a “clear-seal” requiring no reinstatement of road markings. In a similar vein, pot-hole repairs can be done using applicable, easy to use, pre-packed and treated pot-hole repair kits that are water-repellent and quick-drying at a fraction of the costs of conventional cold-mix products. Resurfacing using NME binder slurries can be done labour-intensively on a pre-treated NSNP surfacing, restoring cracked surfacing and providing a water-resistant long-lasting protective layer without the removal of existing cracked areas. The implementation of nanotechnology solutions for road surface maintenance operations is directly associated with ease of use, labour-intensive operations, prevention of considerable deterioration in riding quality due to removal and manual re-instatement of cracked surfaces, time and cost savings and a reduction in the risk of water damage to the sub-structure. TRANSLATE with x English ArabicHebrewPolish BulgarianHindiPortuguese CatalanHmong DawRomanian Chinese SimplifiedHungarianRussian Chinese TraditionalIndonesianSlovak CzechItalianSlovenian DanishJapaneseSpanish DutchKlingonSwedish EnglishKoreanThai EstonianLatvianTurkish FinnishLithuanianUkrainian FrenchMalayUrdu GermanMalteseVietnamese GreekNorwegianWelsh Haitian CreolePersian TRANSLATE with COPY THE URL BELOW Back EMBED THE SNIPPET BELOW IN YOUR SITE Enable collaborative features and customize widget: Bing Webmaster Portal Back TRANSLATE with x English ArabicHebrewPolish BulgarianHindiPortuguese CatalanHmong DawRomanian Chinese SimplifiedHungarianRussian Chinese TraditionalIndonesianSlovak CzechItalianSlovenian DanishJapaneseSpanish DutchKlingonSwedish EnglishKoreanThai EstonianLatvianTurkish FinnishLithuanianUkrainian FrenchMalayUrdu GermanMalteseVietnamese GreekNorwegianWelsh Haitian CreolePersian TRANSLATE with COPY THE URL BELOW Back EMBED THE SNIPPET BELOW IN YOUR SITE Enable collaborative features and customize widget: Bing Webmaster Portal Back

Non-melanoma skin cancers (NMSCs) are the leading cause of skin cancer-related morbidity and mortality. Effective strategies are needed to control NMSC occurrence and progression. Non-toxic, plant-derived extracts have been shown to exert multiple anti-cancer effects. Graviola (Annona muricata), a tropical fruit-bearing plant, has been used in traditional medicine against multiple human diseases including cancer. The current study investigated the effects of graviola leaf and stem extract (GLSE) and its solvent-extracted fractions on two human NMSC cell lines, UW-BCC1 and A431. GLSE was found to: i) dose-dependently suppress UW-BCC1 and A431 cell growth, motility, wound closure, and clonogenicity; ii) induce G₀/G₁ cell cycle arrest by downregulating cyclin/cdk factors while upregulating cdk inhibitors, and (iv) induce apoptosis as evidenced by cleavage of caspases-3, -8 and PARP. Further, GLSE suppressed levels of activated hedgehog (Hh) pathway components Smo, Gli 1/2, and Shh while inducing SuFu. GLSE also decreased the expression of pro-apoptotic protein Bax while decreasing the expression of the anti-apoptotic protein Bcl-2. We determined that these activities were concentrated in an acetogenin/alkaloid-rich dichloromethane subfraction of GLSE. Our data identify graviola extracts and their constituents as promising sources for new chemopreventive and therapeutic agent(s) to be further developed for the control of NMSCs

Vimentin is an intermediate filament protein that plays key roles in integration of cytoskeletal functions, and therefore in basic cellular processes such as cell division and migration. Consequently, vimentin has complex implications in pathophysiology. Vimentin is required for a proper immune response, but it can also act as an autoantigen in autoimmune diseases or as a damage signal. Although vimentin is a predominantly cytoplasmic protein, it can also appear at extracellular locations, either in a secreted form or at the surface of numerous cell types, often in relation to cell activation, inflammation, injury or senescence. Cell surface targeting of vimentin appears to associate with the occurrence of certain posttranslational modifications, such as phosphorylation and/or oxidative damage. At the cell surface, vimentin can act as a receptor for bacterial and viral pathogens. Indeed, vimentin has been shown to play important roles in virus attachment and entry of severe acute respiratory syndrome-related coronavirus (SARS-CoV), dengue and encephalitis viruses, among others. Moreover, the presence of vimentin in specific virus-targeted cells and its induction by proinflammatory cytokines and tissue damage contribute to its implication in viral infection. Here, we recapitulate some of the pathophysiological implications of vimentin, including the involvement of cell surface vimentin in interaction with pathogens, with a special focus on its role as a cellular receptor or co-receptor for viruses. In addition, we provide a perspective on approaches to target vimentin, including antibodies or chemical agents that could modulate these interactions to potentially interfere with viral pathogenesis, which could be useful when multi-target antiviral strategies are needed .

Metalloproteinases are zinc-dependent endopeptidases that function as primary effectors of tissue remodelling, cell-signalling, and many other roles. Their regulation is ferociously complex, and is exquisitely sensitive to their molecular milieu, making in vivo studies challenging. Phenanthroline (PhN) is an inexpensive, broad-spectrum inhibitor of metalloproteinases that functions by chelating the catalytic zinc ion, however its use in vivo has been limited due to suspected off-target effects. PhN is very similar in structure to phenanthrene (Phe), a well-studied poly aromatic hydrocarbon (PAH) known to cause toxicity in aquatic animals by activating the aryl hydrocarbon receptor (AhR). We show that zebrafish are more sensitive to PhN than Phe, and that PhN causes a superset of the effects caused by Phe. Morpholino knock-down of the AhR rescues the effects of PhN that are shared with Phe, suggesting these are due to PAH toxicity. The effects of PhN that are not shared with Phe (specifically disruption of neural crest development and angiogenesis) involve processes known to depend on metalloproteinase activity. Furthermore these PhN-specific effects are not rescued by AhR knock-down, suggesting that these are bona fide effects of metalloproteinase inhibition, and that PhN can be used as a broad spectrum metalloproteinase inhibitor for studies with zebrafish in vivo.

Warren Weaver, writing about the function that science should have in mankind’s developing future, ideas and ideals, proposed to classify scientific problems into ‘problems of simplicity’, ‘problems of disorganised complexity’, and ‘problems of organised complexity’ — the huge complementary class to which all biological, human, and social problems belong. Problems of simplicity have few components and variables and have been extensively addressed in the last 400 years. Problems of disorganised complexity have a huge number of individually erratic components and variables, but possess collective regularities that can be analysed by resourcing to stochastic methods. Yet, problems of organised complexity do not yield easily to classical or statistical treatment since interrelations among phenomenon elements change during its evolution alongside commonly used state variables, affecting behaviour and outcome. Moreover, organisation, the focal point in this complementary class, is still an elusive concept despite the gigantic efforts undertaken since a century ago to tame it. This paper addresses the description, representation and study of phenomena in the ‘problems of organised complexity’ class. Grounded on relational mathematical constructs, a theoretical framework providing operational definitions and schemes for formally modelling organisations and interaction of organisations is introduced. This framework extends the general systems’ concept and provides a novel perspective for addressing organised complexity phenomena as a collection of interacting organisations.

Cancer is a leading cause of death worldwide. It is theorized that underlying genetic and epigenetic changes enable cells to proliferate out of control by escaping regulatory mechanisms. The progression of cancer is associated with increased cell proliferation, metabolic modifications, resistance to apoptosis, genetic instability, induction of angiogenesis and augmented migratory capability. Recent developments in DNA and RNA analysis have made it possible to study these genetic changes systematically. These advances have enabled us to possess a deeper knowledge of the signaling pathways and involved processes. In-depth studies of the pathways involved in carcinogenesis have led to the identification of pathways that may be targeted for therapeutic purposes. In this review, we provide an overview of the relevant mechanisms and pathways involved in the development and progression of cancer.

Biohydrogen is a versatile energy carrier for the generation of electric energy from renewable sources. Hydrogenases can be used in enzymatic fuel cells to oxidize dihydrogen. The rate of electron transfer (ET) at the anodic side between the [NiFe]-hydrogenase enzyme distal iron-sulfur cluster and the electrode surface can be described by the Marcus equation. All parameters for the Marcus equation are accessible from DFT calculations. The distal cubane FeS-cluster has a three cysteine and one histidine coordination [Fe₄S₄](His)(Cys)₃ first ligation sphere. The reorganization energy (inner- and outer-sphere) is almost unchanged upon a histidine-to-cysteine substitution. Differences in rates of electron transfer between the wild-type enzyme and the all-cysteine mutant can be rationalized by a diminished electronic coupling between the donor and acceptor molecules in the [Fe₄S₄](Cys)₄ case. The fast and efficient electron transfer from the distal iron-sulfur cluster is realized by a fine-tuned protein environment which facilitates the flow of electrons. This study enables the design and control of electron transfer rates and pathways by protein engineering.

We evaluated the mono- and combination-therapy effects of valproic acid (VPA) and doxorubicin (DOX) in hepatocellular carcinoma (HCC) and identified a specific and efficient, synergistic anti-proliferative effect of the VPA and DOX combination in HCC cells, especially HepG2 cells; this effect was not apparent in MIHA cells, a normal hepatocyte cell line. The calculation of the coefficient of drug interaction confirmed the significant synergistic effect of the combination treatment. Concurrently, the synergistic apoptotic cell death caused by the VPA and DOX combination treatment was confirmed by Hoechst nuclear staining and western blot analysis of caspase-3 and poly (ADP-ribose) polymerase (PARP) activation. Co-treatment with VPA and DOX enhanced reactive oxygen species (ROS) generation and autophagy, which were clearly attenuated by ROS and autophagy inhibitors, respectively. Furthermore, as an indication of the mechanism underlying the synergistic effect, we observed that DOX internalization, which was induced in the VPA and DOX combination-treated group, occurred via by the caveolae-mediated endocytosis pathway. Taken together, our study uncovered the potential effect of the VPA and DOX combination treatment with regard to cell death, including induction of cellular ROS, autophagy, and the caveolae-mediated endocytosis pathway. Therefore, these results present novel implications in drug delivery research for the treatment of HCC.

Solid tumors display complex biology and most therapies including chemotherapy cannot prevent therapy resistance and relapse. Most therapeutics target cancer cells, but recent data suggest the presence of cancer stem cells as cells with self-renewal and tumorigenic abilities. Cancer stem cell markers have been suggested to have prognostic value and can be targeted during cancer treatment and in resistant disease. CSCs have been postulated to play significant contextual roles in tumor initiation, progression, therapy resistance and metastasis. CSCs have thus been targeted by new generation cancer drugs. The transcriptional expression of several CSC markers in different cancers was evaluated by searching publicly available The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases. We report here new findings on expression and prognostic significance of CSC markers in several cancers by examining the expression of CSCs markers in tumor tissues versus the adjacent normal tissues. We found that CSC markers were mostly highly expressed various tumors such as colon, lung, pancreatic and esophageal cancers. No CSC marker is expressed in the same pattern in all cancers and individual CSC marker expression was not linked to patient survival. This analysis calls for continued research on CSCs and clinical evaluation of the CSC markers in relation to prognosis of cancers in large population samples. Novel cancer drugs ought to target CSCs, cancer cells and tumor microenvironment variations.

Separation and interpretation of rebellious Circulating Tumor Cells (CTCs) originating from the primary tumor or cancer tissue plays a significant role in diagnostics, cancer progression analyses, suitable medicine exploration, and treatment proficiency examination. Cancer metastasis occurs when CTCs spread throughout the body and invade healthy tissues, leading to new tumors in that area. Although a dramatic rate of deaths begins from spreading CTCs around the body, valuable measures have been made to control their development. However, the first step is separating these harmful cells from the bloodstream and investigating their features. Having examined the characteristics of CTCs as cancer’s main strength, researchers can introduce complementary treatments that can affect cancerous cells without damaging the healthy cells. Therefore, according to their unique characteristics, numerous techniques have been established for continuous and fast separation and sorting of CTCs. Nevertheless, few separators enjoy the efficient performance and appropriate accuracy and can be produced in mass numbers due to the available fabrication equipment. Microfabrication advancements enable separators to combine the advantages of active and passive methods in a small-scale platform for probing individual cells and separation purposes. Reduction in reagents, sample volume, analysis time, and less harmfulness to patients are some of the motivations that encourage researchers to employ microfluidic instruments for CTCs separation from other blood cells over the last two decades. However, microfabrication limitations mean effective separators, and the diagnostic option they provide, are not readily available. Addressing these limitations requires optimizing the design and fabrication of separators such that they are reduced in their size and fabrication cost, while also maintaining high-throughput separating capability. The emergence of the Lab-On-a-Chip (LOC) and then Lab-On-a-CD (LOCD) technologies, having more inherent benefits than conventional microfluidic devices, has created new opportunities and become increasingly widespread in recent years. Evidence suggests that employing single methodologies or integrating approaches without sufficient understanding of potential outcomes is unlikely to result in successful diagnostic results. This paper contributes an extensive review of several separation systems, including fundamental theories and experimental details, and describes detailed operating principles and device performance.

Autophagy is a highly conserved catabolic mechanism that mediates the degradation of damaged cellular components by inducing their fusion with lysosomes. This process provides cells with an alternative source of energy for the synthesis of new proteins and the maintenance of metabolic homeostasis in stressful environments. Numerous studies have demonstrated beneficial roles for the induction as well as the suppression of autophagy in cancer cells. Autophagy may induce either survival or death depending on the cell/tissue type. Radiation therapy is widely used therapeutic option to treat cancer, and it induces autophagy in human cancer cell line. Also, melatonin seems to affect cancer cell death via regulation of programmed cell death. In this review, we summarize the current understanding of autophagy and its regulation in cancer.

In this study, a high energy conversion efficient dye-sensitized solar cells (DSSC) was successfully fabricated by attaching a double anti-reflection (AR) layer which is composed of a subwavelength moth-eye structured polymethyl methacrylate (PMMA) film and a polydimethylsiloxane (PDMS) film. The efficiency is up to 6.79%. The moth-eye structured PMMA film was fabricated by using anodic aluminum oxide (AAO) template which is simple, low-cost and scalable. The nano-pattern of AAO template has been precisely reproduced onto PMMA film. The photoanode is composed of Titanium dioxide (TiO₂) nanoparticles (NPs) with diameter of 25 nm deposited on the fluorine-doped tin oxide (FTO) glass substrate and the sensitizer N3. The double AR layer can effectively improve the short-circuit current density (JSC) and conversion efficiency from 14.77 to 15.79 mA/cm² and from 6.26% to 6.79%, respectively.

In the last decade, unprecedented progress in the development of neural networks influenced dozens of different industries, among which are signal processing for the electroencephalography process (EEG). Electroencephalography, even though it appeared in the first half of the 20th century, to this day didn’t change the physical principles of operation. But the signal processing technique due to the use of neural networks progressed significantly in this area. Evidence for this can serve that for the past 5 years more than 1000 publications on the topic of using machine learning have been published in popular libraries. Many different models of neural networks complicate the process of understanding the real situation in this area. In this manuscript, we provided the most comprehensive overview of research where were used neural networks for EEG signal processing.

Panel data of our interest consist of a moderate number of panels, while the panels contain a small number of observations. An estimator of common breaks in panel means without a boundary issue for this kind of scenario is proposed. In particular, the novel estimator is able to detect a common break point even when the change happens immediately after the first time point or just before the last observation period. Another advantage of the elaborated change point estimator is that it results in the last observation in situations with no structural breaks. The consistency of the change point estimator in panel data is established. The results are illustrated through a simulation study. As a by-product of the developed estimation technique, a theoretical utilization for correlation structure estimation, hypothesis testing, and bootstrapping in panel data is demonstrated. A practical application to non-life insurance is presented as well.

Cropland area per capita and pressure index on cropland is the important parameters measuring the social vulnerability and sustainability in the perspective of food security in a certain region in China during the historical periods. This study reconstructs the spatial distribution change of cropland area per labor/household and pressure index on cropland during the 17th-20th century by the methods of historical documents, regression analysis, pressure index model and GIS. Then it analyzed the impacting process of climate change and sustainability of cropland use during the different periods. It draws conclusions: (i) the spatial difference of labor/household density was obvious which had the same pattern as cropland distribution during the same periods, which is higher density in three agricultural areas. (ii) Cropland area per capita was relatively higher during the 17th-18th century, which were above 0.4 ha/person in majority counties and distributed homogenously. Till the 19th century and the beginning of 20th century, cropland area per capita in large amount of regions decreased below 0.2 ha/person embodying the increase of social vulnerability and unsustainability at that time. (iii) Pressure index on cropland also showed the similar spatial pattern as cropland area per capita which presented lower threshold than nowadays. During the 17th-18th century there was no pressure on cropland. While, in the 19th century and at the beginning of 20th century, two high value centers of pressure index on cropland appeared in Middle Shandong and the Jiaodong region, pressure on sustainable cropland use increased obviously and a food crisis is probably created. (iv) Higher sustainable extent of cropland use corresponds to cold period, and lower sustainable extent of cropland use corresponds to warm period in Shandong over the past 300 years. The turning point of 1680s from dry to wet attributes to the decrease of sustainable extent of cropland use in Shandong not very distinctively. More and more pressure on sustainability of cropland use finally since the beginning of 20th century would intensify the social conflict and increase the probability of social revolts.

Cellular response to mechanical stimuli is an integral part of cell homeostasis. The interaction of the extracellular matrix with the mechanical stress plays an important role in cytoskeleton organisation and cell alignment. Insights from the response can be utilised to develop cell culture methods that achieve predefined cell patterns, which are critical for tissue remodelling and cell therapy. We report the working principle, design, simulation and characterisation of a novel electromagnetic cell stretching platform based on the double-sided axial stretching approach. The device is capable of introducing a cyclic and static strain pattern on a cell culture. The platform was tested with fibroblasts. The experimental results are consistent with the previously reported cytoskeleton reorganisation and cell reorientation induced by strain. The orientation of the cells is highly influenced by external mechanical cues. Cells reorganise their cytoskeleton to avoid external strain and to maintain intact extracellular matrix arrangements.

Energy is a fundamental ingredient in economic development and energy consumption is an index of prosperity and the standard of living. The consumption of energy has increased significantly in the last number of decades, as the standard of living has improved. Renewable energy is a sustainable and clean source of energy derived from nature. Renewable energy technology is one of the solutions, which produces energy by transforming natural resources into useful energy forms. When you do something for the first time in the world, you never attain a perfect product or solution from the start. In Central Greece Lamia city, we are the first to design and implement an off-grid energy system using hydrogen energy storage technology and phase change materials for a house residence. The action plan for energy efficiency, a series of directives and incentive mechanisms, mandatory energy certification of buildings, indicate the urgent need to reduce energy consumption in buildings, which results in a more comfortable living, long service life of buildings, which in turn preserves the environment.

Microbial symbioses exhibit astounding adaptations, yet all symbionts face the problem of how to reliably associate with host offspring every generation. A common strategy is vertical transmission, in which symbionts are directly transmitted from the female to her offspring. The diversity of symbionts and vertical transmission mechanisms is as expansive as the diversity of eukaryotic host taxa that house them. However, there are several common themes among these mechanisms based on the degree to which symbionts associate with the host germline during transmission. In this review, we detail three distinct vertical transmission strategies, starting with associations that are transmitted from host somatic cells to offspring somatic cells, either due to lacking a germline or avoiding it. A second strategy involves somatically-localized symbionts that migrate into the germline during host development. The third strategy we discuss is one in which the symbiont maintains continuous association with the germline throughout development. Unexpectedly, the vast majority of documented vertically inherited symbionts rely on the second strategy: soma-to-germline migration. Given that not all eukaryotes contain a sequestered germline and instead produce offspring from somatic stem cell lineages, this soma-to-germline migration is discussed in the context of multicellular evolution. Lastly, as recent genomics data have revealed an abundance of horizontal gene transfer events from symbiotic and non-symbiotic bacteria to host genomes, we discuss their impact on eukaryotic host evolution.

This review focuses on the regulation and modulation of human DNA polymerase δ (Pol δ). The emphasis is on mechanisms that regulate the activity and properties of Pol δ in DNA repair and replication. The areas covered are the degradation of the p12 subunit of Pol δ, which converts it from a heterotetramer (Pol δ4) to a heterotrimer (Pol δ3), in response to DNA damage and also during the cell cycle. The biochemical mechanisms that lead to degradation of p12 are reviewed, as well as the properties of Pol δ4 and Pol δ3 that provide insights into their functions in DNA replication and repair. The second focus of the review involves the functions of two Pol δ binding proteins, PDIP46 and PDIP38, both of which are multi-functional proteins. PDIP46 is a novel activator of Pol δ4, and the impact of this function is discussed in relation to its potential roles in DNA replication. Several new models for the roles of Pol δ3 and Pol δ4 in leading and lagging strand DNA synthesis that integrate a role for PDIP46 are presented. PDIP38 has multiple cellular localizations including the mitochondria, the splicesosomes and the nucleus. It has been implicated in a number of cellular functions, including the regulation of specialized DNA polymerases, mitosis, the DNA damage response, Mdm2 alternative splicing and the regulation of the Nox4 NADPH oxidase.

Recent evidence indicates that the risk of being diagnosed with cancer in a tissue is strongly correlated (0.80) with the number of stem cell divisions accumulated by the tissue. Since cell division can generate random mutations during DNA replication, this correlation has been used to propose that cancer is largely caused by the accumulation of unavoidable mutations in driver genes. However, no correlation between the number of gene mutations and cancer risk across tissues has been reported. Because many somatic mutations in cancers originate prior to tumor initiation and the number of cell divisions occurring during tumor growth is similar among tissues, here I use whole genome sequencing information from 22,086 cancer samples and incidence data from the largest cancer registry in each continent to study the relationship between the number of gene mutations and the risk of cancer across 33 tissue types. Results show a weak positive correlation (mean = 0.14) between these two parameters in each of the five cancer registries. The correlation became stronger (mean = 0.50) when gender-related cancers were excluded. Results also show that 1,003 samples from 29 cancer types have zero mutations in genes. These data suggest that cancer etiology can be better explained by the accumulation of stem cell divisions than by the accumulation of gene mutations. Possible mechanisms by which the accumulation of cell divisions in stem cells increases the risk of cancer are discussed.

1) Background: Studies indicate that caffeic acid (CA), caffeic acid phenethyl ester (CAPE) are compounds with potent chemopreventive effects. Breast cancer is a common cancer among women worldwide. The study shows comparison of caffeic acid and its ester activity in the cells of breast cancer line MDA-MB-231; 2) Methods: The cells of MDA-MB-231 were treated by CA and CAPE with doses from 10 to 100 µM in time 24 h and 48 h. Cytotoxicity MTT test, apoptosis by Annexin V and cell cycle with Dead Cell Assay were performed; 3) Results: The cytotoxic activity was greater for CAPE comparing to CA, in both incubation time (same dosage). IC50 values for CAPE were 27.84 (24h) and 15.83 (48h) and >10000 (24h) and >1000 (48h) for CA. Polyphenols induced apoptosis, higher apoptotic effect observed for CAPE (dose dependent). CAPE induced cell cycle arrest in S phase (time and dose dependent). Dose dependent decline G0/G1 phase (48h) and elimination of phase G2/M (100 µM of CAPE). For CA, only after 48 hours, small effect of cell cycle at phase S (however dose dependent), and slight decline of phase G0/G1 and G2/M only for highest doses (50 and 100 µM); 4) Conclusions: Comparing CA and CAPE activity, on the MDA-MB-231, we clearly see better activity of CAPE, with the same dosage and experiment time.

Almond is worldwide consumed and renowned as a valuable healthy food. In spite of this, it is also a potent source of allergenic proteins able to trigger several mild to life-threatening immunoreactions. Food processing proved to alter biochemical characteristics of proteins, thus affecting the respective allergenicity. In this paper we investigated the effect of autoclaving, preceded or not by a hydration step, on the biochemical and immunological properties of almond proteins. Any variation in the stability and immunoreactivity of almond proteins extracted from the treated materials, were evaluated by total protein quantification, ELISA assay and protein profiling by electrophoresis-based separation (SDS-PAGE). The autoclaving alone was found to weakly affect almond proteins stability, despite what observed for the combination of hydration and autoclaving, which resulted in a loss of approximately 70% of total protein content compared to untreated sample, and in a final negligible immunoreactivity, as well. The final SDS-PAGE protein pattern recorded for almonds hydrated and autoclaved disclosed significant changes. In addition, the same samples were further submitted to in vitro simulated gastro-duodenal (GI) digestion to evaluate potential changes induced by these processing on allergens digestibility. Digestion products were identified by HPLC-HRMS/MS analysis followed by software-based data mining, and complementary information were provided by analyzing the proteolytic fragments lower that 6 kDa in size. The autoclave based treatment was found not to alter the allergens digestibility, whereas an increased susceptibility to proteolytic action of digestive enzymes was observed in almonds subjected to the combination of prehydration and autoclaving. Finally, the residual immunoreactivity of the GI resistant peptides was investigated in-silico by bioinformatic tools, confirming that by following both approaches, no epitopes survived the almond digestion, thus demonstrating the potential effectiveness of these treatments to reduce almond allergenicity.

Hybrid inorganic-polymer nanocomposites can be employed in diverse applications due to the potential combination of desired properties from both the organic and inorganic components. The use of novel bottom-up in situ synthesis methods for the fabrication of these nanocomposites is advantageous compared to top-down ex situ mixing methods, as it offers increased control over the structure and properties of the material. In this review, the focus will be on the application of the sol-gel process for the synthesis of inorganic oxide nanoparticles in epoxy and polysiloxane matrices. The effect of the synthesis conditions and the reactants used on the inorganic structures formed, the interactions between the polymer chains and the inorganic nanoparticles, and the resulting properties of the nanocomposites are appraised from several studies over the last two decades. Lastly, alternative in situ techniques and the applications of various polymer-inorganic oxide nanocomposites are briefly discussed.

Metabolic enzymes are often targeted for drug development programs of metabolic diseases such as diabetes and its complications. Many secondary metabolites isolated from natural products have shown therapeutic action against these enzymes. However, some commercially available synthetic drugs have shown unfriendly impacts with various side effects. Thus, this research has focused on a comprehensive study of secondary metabolites showing better inhibitory activities towards metabolic enzymes such as α-amylase, α-glucosidase, aldose reductase, and lipase. Further receptor-based virtual screening was performed against the various secondary metabolites database designed in-silico. Using Gold combined with subsequent post-docking analyses, the score was obtained as methyl xestospongic ester (Gold score 65.83), 2,″4″-O-diacetylquercitrin (Gold score 65.15), kaempferol-3-O-neohesperidoside (Gold score 53.37) and isosalvianolic acid C methyl ester (Gold score 53.44) for lipase, aldol reductase, α-amylase, and α-glucosidase, respectively. Besides, vitexin and isovitexin for α-amylase; N-trans-Caffeoyl-tyramin for α-glucosidase; purpurolide F and schaftoside for lipase; acteoside and orientin for aldose reductase could be potential drugs for respective enzymes based on in-silico analyses, supported by experimental IC₅₀ values reported. They could bind to the competitive sites of the various targets of metabolic enzymes, and finally, toxicity analysis using ProTox-II was also performed.

With the increasing of copper consumption, the in-use stock of copper tends to increase. This paper used the “average use life method” to quantify the amount of copper in-use stock, and calculated the average age of in-use stock. It was indicated that the total in-use stock had an overall smooth trends, and reached its peak in 2007 was about 68.9 Mt (million tons), in addition, in-use stock per capita reached its peak ,234 kg/capita in 2001. The results demonstrated that during the period 1992-2002, the average age of copper in-use stock was continually decreased, but gradually increased since the year 2003. The fixed assets depreciation method used in this paper is applied to analyze depreciated copper in-use stock, and to analyze the relationship with economic indicator (GDP). It is demonstrated that it was inconsistent with the theory of Environmental Kuznets Curve (EKC) before 2000, this might be the demand for copper in the service sector is greater than the reduced strength of alternatives. Finally, scenario analysis of future copper in-use stock and depreciated copper in-use stock per capita in the U.S. were presented. The corresponding average age of the in-use stock will have a slight rise in the next decade.

Infection by the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) results in the novel coronavirus disease COVID-19, which has posed a serious threat globally. Infection of SARS-CoV-2 during pregnancy is associated with complications like preterm labor and premature rupture of membranes; a proportion of neonates born to the infected mothers are also positive for the virus. During pregnancy, the placental barrier protects the fetus from pathogens and ensures healthy development. However, whether or not SARS-CoV-2 can infect the placenta is unknown. Herein, utilizing single-cell RNA-seq data, we report that the SARS-CoV-2 binding receptor ACE2 and the S protein priming protease TMPRSS2 are co-expressed by a subset of syncytiotrophoblasts (STB) in the first trimester and extra villous trophoblasts (EVT) in the second trimester human placenta. The ACE2- and TMPRSS2-positive (ACE2+TMPRSS2+) placental subsets express mRNA for proteins involved in viral budding and replication. These cells also express mRNA for proteins that interact with SARS-CoV-2 structural and non-structural proteins in the host cells. We also discovered unique signatures of genes in ACE2+TMPRSS2+ STBs and EVTs. The ACE2+TMPRSS2+ STBs are highly differentiated cells and express genes involved mitochondrial metabolism and glucose transport. The second trimester ACE2+TMPRSS2+ EVTs are enriched for markers of endovascular trophoblasts. Further, both these subtypes abundantly expressed genes in Toll like receptor pathway, the second trimester EVTs (but not first trimester STBs) are also enriched for component of the JAK-STAT pathway that drive inflammation. To conclude, herein we uncovered the cellular targets for SARS-CoV-2 entry and show that these cells can potentially drive viremia in the developing human placenta. Our results provide a basic framework towards understanding the paraphernalia involved in SARS-CoV-2 infections in pregnancy.

White and three types of black garlic (13, 32 and 45 days of fermentation, named 0C1, 1C2 and 2C1 respectively) were selected in order to check possible differences in their nutraceutic potential. For this purpose, garlic were physico-chemically characterised, and both in vivo and in vitro assays were carried out. Black garlic showed higher polyphenol content and antioxidant capacity than white garlic. The biological studies have shown that only white garlic was not safe showing toxicity effect. Furthermore, none garlic exert protective effects against H₂O₂, except the 0C1 black garlic. Moreover, garlic was non-genotoxic with the exception of the highest concentration of white garlic. On the other hand, 0C1 was the most antigenotoxic substance. The in vivo longevity assays yielded significant extension of lifespan results in some concentrations of white and 0C1and 1C2 black garlic. The in vitro experiments showed that all studied garlic induced a decrease in leukaemia cells growth. However, none type of garlic was able to induce proapoptotic internucleosomal DNA fragmentation. Taking into account the physicochemical and biological data, black garlic could be considered as a potential functional food and used in preventive treatment of age-related diseases. In addition, our findings could be relevant for the black garlic processing agrifood companies as the economical and timing costs are significantly reduced to 13 days aging.

Automated controlling the harvesting systems can significantly increase the efficiency of the agricultural practices and prevent food wastes. Modeling and improvement of the combine harvester can increase the overall performance. Machine learning methods provide the opportunity of advanced modeling for accurate prediction of the highest performance of the machine. In this study, the modeling of combine harvesting id performed using radial basis function (RBF) and the hybrid machine learning method of adaptive neuro-fuzzy inference system (ANFIS) to predict various variables of the combine harvester for the optimal performance. Response surface methodology (RSM) is also used to optimize the models. The comparative study shows that the ANFIS method outperforms the RBF method.

The nucleation and dynamics of Josephson and Abrikosov vortices determine the critical currents of layered high-T_c superconducting (HTS) thin films, grain boundaries, and coated conductors, so understanding their mechanisms is of crucial importance. Here we treat pair creation of Josephson and Abrikosov vortices in layered superconductors as a secondary Josephson effect, in which each full vortex is viewed as a composite fluid of micro-vortices, such as pancake vortices, which tunnel coherently via a tunneling matrix element. We introduce a two-terminal magnetic (Weber) blockade effect that blocks tunneling below a threshold current, and simulate time-correlated vortex tunneling above threshold. The model shows nearly precise agreement with voltage-current (V-I) characteristics of HTS cuprate grain boundary junctions, which becomes more concave rounded as temperature decreases, and also explains the piecewise linear V-I behavior observed in iron-pnictide bicrystal junctions and other HTS devices. When applied to either Abrikosov or Josephson pair creation, the model explains a plateau seen in plots of critical current vs. thickness of HTS coated conductors. The observed correlation between theory and experiment strongly supports the proposed quantum picture of vortex nucleation and dynamics in layered superconductors.

This paper proposes the impact of plug-in electric vehicles integrated into power distribution system based on voltage dependent control. The plug-in electric vehicles was modeled as the static load model in power distribution systems under balanced load condition. The power flow analysis is determined by using the basic parameters of the electrical network. The main point of this study are compare with voltage magnitude profiles, load voltage deviation, and total power losses of the electrical power system. There are investigating the affected from constant power load, constant current load, constant impedance load and plug-in electric vehicles load, respectively. The IEEE 33 bus test system is used to test the proposed method by assigning each load type to a balanced load in steady state and applied the solving methodology based on the bus injection to branch injection matric, branch current to bus voltage matrix, and current injection matrix to solve the power flow problem. The simulation results showed that the plug-in electric vehicles load had the lowest impact compared to other loads. The lowest plug-in values for the electric vehicle loads were 0.062, 119.67 kW and 79.31 kVar for the load voltage deviation, total active power loss and total reactive power loss, respectively. Therefore, this study can be verified that the plug-in electric vehicles load were affected to the lowest of the electrical power system in condition to same sizing and position. So that, in condition to the plug-in electric vehicles load added into the electrical power system with the conventional load type or complex load type could be considered that the affected from the plug-in electric vehicles load in next study.

Signal-to-noise ratio (SNR) is an important index to evaluate radiation performance and image quality of optical imaging systems under low illumination background. Under the nighttime lighting condition, the illumination of remote sensing objects is low and varies greatly, usually ranging from several lux to tens of thousands of lux. Nighttime light remote sensing imaging requires high sensitivity and large dynamic range of detectors. Luojia 1-01 is the first professional nighttime light remote sensing satellite in the world. In this paper, we took the nighttime light remote sensing camera carried on the satellite as research object, proposed an in-orbit SNR test method based on time series images to overcome the problem of low spatial resolution. We first analyzed the process of luminous flux transmission between objects and satellite and established a radiative transfer model. By combining the parameters of large relative aperture optical system and high sensitivity CMOS device, we established SNR model and specially analyzed the effect of exposure time and quantization bits on SNR. Finally we used the proposed in-orbit test method to calculate SNR of lighting images acquired by satellite. And the measured result is in good agreement with the model predicted data. Under the condition of 10lx illumination, the SNR of typical objects can reach 27.02dB, which is much better than the requirement of 20dB for engineering application.

Aflatoxins, which have been classified as a group-1 carcinogen are the well-known mycotoxins produced by Aspergillus flavus. Aflatoxins have been linked to liver diseases, acute hepatic necrosis, resulting in cirrhosis or hepatocellular carcinomas due to which it incurs a loss of value in international trade for peanuts contaminated with it. The four main aflatoxins are B1, B2, G1, and G2 of which B1 is predominant. In plants, the cell wall is the primary barrier against pathogen invasion. Cell wall fortifications such as deposition of callose, cellulose, lignin, phenolic compounds and structural proteins help to prevent the pathogen infection. Further, the host cell’s ability to rapidly repair and reinforce its cell walls will result in a reduction of the penetration efficiency of the pathogen. Peanut seed coat acts as a physical and biochemical cell wall barrier against both pre and post-harvest pathogen infection. The structure of seed coat and the presence of polyphenol compounds have been reported to inhibit the growth of A. flavus, however, not successfully employed to develop A. flavus resistance in peanut. A comprehensive understanding of peanut seed coat development and biochemistry will provide information to design efficient strategies for the seed coat mediated A. flavus resistance and Aflatoxin contamination.

This paper presents a methodology for determining the sensitivity of the main air flow directions in ventilation subnetworks to changes of aerodynamic resistance and of air density in mine workings. Formulae for determination of the sensitivity of the main subnetwork air flows by establishing the degree of dependency of the air volume stream in a given working on the variations in resistance or air density of other workings of the network have been developed. They have been implemented in the VentGraph mine ventilation network simulator. This software, widely used in Polish collieries provides an extended possibility to predict the process of ventilation, air distribution and, in the case of underground fire, also the spread of combustion gasses. The new method facilitates assessment by mine ventilation services of the stability of ventilation systems in exploitation areas and determine of the sensitivity of the main subnetwork air flow directions to changes of aerodynamic resistance and air density. Recently in some Polish collieries new longwalls are developed in seams located deeper then the bottom of the intake shaft. Such solution is called “exploitation below the level of access” or “sublevel”. The new approach may be applied to such developments to assess the potential of changes of direction and air flow rates. In addition, interpretation of the developed sensitivity indicator is presented. While analyzing air distributions for sublevel exploitation, application of current numerical models for calculations of the distribution results in tangible benefits, such as the evaluation of the safety or risk levels for such exploitation. Application of the VentGraph computer program, and particularly the module POŻAR (fire) with the newly developed options, enables an additional approach to the sensitivity indicator in evaluating air flow safety levels for the risks present during exploitation below the level of the intake shaft. The analyses performed and examples presented enabled useful conclusions in mining practice to be drawn.

Non-melanomatous skin cancers (NMSCs), which include basal and squamous cell carcinoma (BCC and SCC respectively), represent a significant burden on the population as well as an economic load to the health care system, yet treatments of these preventable cancers remain ineffective. Although primary prevention is possible through minimising sunlight exposure, the World Health Organisation estimates that between 2 and 3 million new cases of NMSCs are diagnosed each year, accounting for 1 in 3 of all newly diagnosed cancers. Furthermore, studies have estimated there has been a 2-fold increase in the incidence of NMSCs between 1960s and 1980s. The increase in cases of NMSCs as well as the lack of effective treatments makes the need for novel therapeutic approaches all the more necessary. To rationally develop more targeted treatments for NMSCs, a better understanding of the cell of origin, in addition to the underlying pathophysiological mechanisms that govern the development of these cancers, is urgent. NMSCs are generally thought to arise from specific types of stem cells that become the source of clonal expansion of tumourigenic cells. Previous research on SCC has alluded to these stem cells being localised in the basal compartment of the skin, which ordinarily houses the progenitor cells that contribute towards wound healing and normal cell turnover of overlying epidermal skin layers. More recent research has suggested that commitment to differentiation, which requires exiting the basal, progenitor-cell compartment, is a reversible mechanism. Genetic modifications engage differentiated cells into dedifferentiation, converting them into cancer-initiating cells (CICs) and thereby promoting a tumourigenic environment. Here we explore the most recent developments in the understanding of skin SCC cell of origin, and discuss a case study illustrating the loss of the Grainy-head like 3 (GRHL3) transcription factor in suprabasal layers, which confers a tendency towards tumour development and thereby challenging the “stem cell” theory of tumourigenesis.

Cyanobacteria are prokaryotes whose taxonomy follows the same rules of a code (the International Botanical Nomenclature Code, IBNC) built for eukaryotic photosynthetic organisms. Hence, names of cyanobacteria follow the same rules and are assigned to biological entities (species) that should correspond to eukaryotic species. The main difficulty in the current situation is that the species concept in eukaryotes is based theoretically mainly on the biological species concept, that is centered on genetic exchange through sexual reproduction or lack of them. However, as shown, this difference is important from a theoretical point of view, but also in eukaryotes, the boundaries between different species are very rarely checked experimentally by direct observation of sexual barriers and hybridization events. The main concept for species delimitation is hence that related to morphology and, more recently and always in relation to morphology, DNA sequences. The introduction of distances obtained from matrixes of aligned sequences in the framework of a barcoding project provides a quantitative interpretation of species delimitation in relation to genetic distance that can be used both in eukaryotes and prokaryotes. However, the introduction of quantitative criteria needs the definition of distance thresholds to identify the boundaries between different species and, for doing that, it is necessary to test the distance thresholds in models of traditionally defined and recognized species. An alternative approach may be the comparison of the molecular distance (quantitative approach) to data about the capability of strains/species to exchange genetic information. Unfortunately data about this last question is still scarce. The adoption of molecular criteria to check species boundaries based on morphological characters has proved particularly challenging in cyanobacteria: a known example is provided. In conclusion, the only possible approach appears to be the association of molecular data to the increase of available data about the cell structure and the variation thereof in different physiological situations, particularly at the ultrastructural level. A further necessity is the check of the typus for a large number of cyanobacteria species, often based on old basionyms. In many of these cases the typus is often a drawing and more rarely a herbarium specimen or a microscope slide. In many cases an epitypification or a neotypification appears to be necessary.

The introduction of the Internet of Things (IoT), i.e. the interconnection of embedded devices over the Internet, has changed the world we live in from the way we measure, make calls, print information and even the way we get energy in our offices or homes. The convenience of IoT products, like CCTV cameras, IP phones, and oscilloscopes, is overwhelming for end-users. In parallel, however, security issues have emerged and it is essential for infrastructure providers to assess the associated security risks. In this paper, we propose a novel method to detect IoT devices and identify the manufacturer, device model, and the firmware version currently running on the device using the page source from the web user interface. We performed automatic scans of the large-scale network at the European Organization for Nuclear Research (CERN) to evaluate our approach. Our tools identified 233 IoT devices that fell into eleven distinct device categories and included 49 device models manufactured by 26 vendors from across the world.

The value of QuantiFERON in the diagnosis of tuberculosis and in the monitoring of the response to anti-tuberculosis treatment is unclear. The aims of this study were to evaluate the accuracy of the QuantiFERON-TB Gold In-Tube (QFT-GIT) test in the diagnosis of tuberculosis and in the monitoring of the response to anti-tuberculosis treatment in patients with active pulmonary tuberculosis (PTB). Between January 2013 and December 2015, 128 cases with active PTB and 128 controls with no mycobacterial infection, matched by age (within 3 years) and by the week that they visited Tainan Chest Hospital, were enrolled in the study. Serial testing by QFT-GIT at baseline and after 2 and 6 months of treatment was performed. At these time points, a comparison of the performance of QFT-GIT with that of sputum culture status among study subjects was conducted. Compared to baseline, 116 (87.2%) cases showed a decreased response, whereas 17 (12.8%) showed persistent or stronger interferon-gamma (IFN-γ) responses at 2 months. Their IFN-γ responses declined significantly from baseline to 2 months (median, 6.32 vs. 4.12; P < 0.005). The sensitivity values of the QFT-GIT test for the detection of pulmonary tuberculosis at cut-off points of 0.35 IU/ml, 0.20 IU/ml, and 0.10 IU/ml were 74.4%, 78.2%, and 80.5%, respectively. The specificity values at cut-off points of 0.35 IU/ml, 0.20 IU/ml, and 0.10 IU/ml were 66.2%, 63.9%, and 57.1%, respectively. Our results support the QFT-GIT assay as a potential tool for diagnosing tuberculosis and for monitoring the efficacy of anti-tuberculosis treatment.

Pathogenic Salmonella strains have a set of virulence factors allowing them to generate systemic infections and damage in a variety of hosts. Among these factors, bacterial proteins secreted by specialized systems are used to penetrate the host’s intestinal mucosa, through the invasion and destruction of specialized epithelial M cells in the intestine. On the other hand, numerous studies have demonstrated that humans, as well as experimental animal hosts, respond to Salmonella infection by activating both innate and adaptive immune responses. Here, through live cell imaging of S. Typhimurium infection of zebrafish larvae, we showed that besides the intestinal colonization, a deformed cloacae region and a concomitant accumulation of S. Typhimurium cells was observed upon bacterial infection. The swelling led to a persistent inflammation of infected larvae, although the infection was non-lethal. The in vivo inflammation process was confirmed by the co-localization of GFP-tagged S. Typhimurium with mCherry-tagged neutrophils at 72 hours post exposition. Our live-cell analyses suggest that Salmonella Typhimurium induce cloacitis-like symptoms in zebrafish larvae. Typhimurium induce cloacitis-like symptoms in zebrafish larvae.

The understanding of various health-oriented vital sign data generated from body sensor networks (BSN) and discovery of the association between the generated parameters is an important task that may assist and promote important decision making in healthcare. For example, in a smart home scenario where the occupants’ health status is continuously monitored remotely, it is essential to provide required assistance when an unusual or critical situation is detected in their vital sign data. In this paper, we present an efficient approach to mine the incomplete (partial) periodic patterns obtained from BSN data. In addition, we employ a correlation test on the generated patterns and introduce the productive-associated partial periodic frequent patterns as the set of correlated partial periodical frequent items. The combination of these measures has the advantage of empowering healthcare providers and patients for quality of diagnosis, and also for better treatment and smart care, especially for the elderly people at smart home. We developed an efficient algorithm named PPFP-Growth (Productive Periodic Frequent Pattern growth) to discover all productive associated partial periodic patterns using these measures. PPFP-Growth is efficient, and the productiveness measure removes uncorrelated periodic items. An experimental evaluation on synthetic and real datasets shows the efficiency of the proposed PPFP-Growth algorithm, and can filter a huge number of partial periodic patterns to reveal only the correlated ones.

Abstract: DNA fragmentation factors 40 and 45 (DFF40 and DFF45) and B-cell lymphoma 2 (Bcl-2) expression were evaluated in the normal human endometrium and myometrium. DFF40, DFF45, and Bcl-2 expression was assessed via immunohistochemistry in the proliferative, secretory, and atrophic endometrium and myometrium collected postmenopausally and premenopausally during the proliferative and secretory phases of the menstrual cycle. The endometrium showed significantly higher DFF40 and DFF45 expression than that in the uterine myometrium; compared to the stroma, endometrial glands showed the highest expression in pre- and postmenopausal specimens. Glandular expression of DFF45 was dependent on the menstrual cycle, reaching its highest level in the secretory endometrium. The glandular expression of DFF40 and DFF45 was significantly lower in postmenopausal specimens than that in premenopausal tissue. No cycle-dependent changes were reported for stromal or myometrial DFF40 or DFF45 expression. Compared to the endometrial stroma and myometrium, Bcl-2 showed the highest expression in the glandular proliferative endometrium and the lowest expression in the stromal secretory endometrium and myometrium during the secretory phase of the cycle. DFF45 and Bcl-2 showed menstrual cycle-dependent expression, which was limited to the glandular layer of the endometrium.

This paper proposes a novel model for a PV cell with parameters variance dependency on temperature and irradiance included. The model relies on commercial available data, calculates the cell parameters for standard conditions and then extrapolates them for the whole operating range. An up-to-date review of the PV modeling is also included with series and parallel parasitic resistance values and dependencies discussed. The parameters variance is analyzed and included in the proposed PV model, where the self-heating phenomenon is also considered. Each parameter variance is compared to the results from different authors. The model includes only standard components and can be run on any SPICE-based simulator. Unlike other approaches that consider the internal temperature as a parameter, our proposal relies on air temperature as an input and computes the actual internal temperature accordingly. Finally, the model is validated via experiments and comparisons to similar approaches are provided.

A series of novel asymmetrical mono-carbonyl analogs of curcumin (AMACs) were synthesized and evaluated for cytotoxic activity using the brine shrimp lethality test (BSLT) and the methyl thiazolyl tetrazolium assay against Vero, HeLa, and MCF7 cell lines. The structures of the synthesized compounds were confirmed by Fourier transform infrared spectrophotometry (FTIR), ¹H-nuclear magnetic resonance (NMR), ¹³C-NMR, and mass spectral data. The results of the cytotoxicity evaluation showed that the synthesized compounds exhibited moderate to very high toxic activity in BSLT, requiring a concentration of 13.06–714.49 µg/mL to kill half the population. Most of the compound exhibited cytotoxic activity against HeLa cell lines, comparable to the activity of cisplatin with a concentration of the synthesized compounds required to inhibit 50% of the growth of the cell lines (IC₅₀) value of 40.65–95.55 µM, and most of the compounds tested against MCF7 cell lines exhibited moderate to very high cytotoxic activity (IC₅₀ value 7.86–35.88 µM). However, the selectivity index of the compounds was low, less than 1–1.96. Among the synthesized compounds, compound 1b showed the highest cytotoxicity and selectivity against MCF7 cell lines. Compound 1b could be considered for further development to obtain more active and selective chemotherapeutic agents against breast cancer.

The epidermis is the outermost layer of skin and provides a protective barrier against environmental insults. It is a rapidly renewing tissue undergoing constant regeneration, maintained by several types of stem cells. Hedgehog (HH) ligands activate one of the fundamental signaling pathways that contribute to epidermal development, homeostasis and repair. The HH pathway interacts with other signal transduction pathways such as those activated by Wnt and bone morphogenetic protein. Furthermore, aberrant activation of HH signaling is associated with various tumors, including basal cell carcinoma. Therefore, an understanding of the regulatory mechanisms of the HH signaling pathway is important to elucidate fundamental mechanisms underlying both organogenesis and carcinogenesis. In this review, we discuss the role of the HH signaling pathway in skin development, homeostasis and basal cell carcinoma formation, providing an update of current knowledge in this field.

Metastasis is the leading cause of cancer-related death and drives patient morbidity as well as healthcare costs. For several cancers, breast and prostate in particular, bone is the primary site of metastasis. Efforts to treat bone metastases have been stymied by a lack of models to study the progression and cellular players and signaling pathways driving bone metastasis. In this review, we examine the newly described and classic models of bone metastasis. Through the use of current in vivo, microfluidic and in silico computational models bone metastasis models we may eventually understand how cells escape the primary tumor and how these circulating tumor cells then home to and colonize the bone marrow. Further, future models may uncover how cell enter and escape dormancy to develop into overt metastases. Recreating the metastatic process will lead to the discovery of therapeutic targets for disrupting and treating bone metastasis.

Migraine is a common condition that affects children as they develop into adults. Transition of care from pediatric to adult care has becoming an increasingly popular topic in the medical literature. It has been suggested that discussions between patients, their families and providers should be initiated as early as age 13. Patients who are un or underprepared have poorer outcomes due to increased morbidity and worsening of their medical condition. Many children continue to have migraine into adulthood and if efforts are taken to ensure patients receive appropriate transfer of care, the results can significantly decrease the economic burden of this disease.

The formation of solid solution series Cs_1-xM_xGaQ₂-mC64 (M = K, Rb; Q = S, Se; x = 0–1) was studied by X-ray diffraction and spectroscopic methods, revealing a complete miscibility of CsGaQ₂-mC64 with RbGaQ₂ and KGaSe₂, and a large miscibility gap with KGaS₂. All solid solution members exhibit similar Raman spectra, indicating the covalent Ga-Q bonding character. The similar optical band gaps likewise further contribute to this conclusion. Up to a degree of substitution, these solid solutions undergo a phase transition similar to CsGaQ₂-mC64. The influence of the substitution parameter x on phase transition process was investigated in situ using high-temperature X-ray powder diffraction experiments. Phase-pure solid solutions of the high-temperature polymorphs Cs_1-xM_xGaQ₂-mC16 were obtained up to x_max(K) = 0.1 and x_max(Rb) = 0.3. The crystal structures of these new CsGaQ₂-mC16 analogous high-temperature phases were refined from synchrotron diffraction data by Rietveld-refinement.

Metal and alloy toughening was the core and long-term research direction in materials filed. As grain size had bimodal distribution, micro/nano-structured alloys presented excellent comprehensive mechanical properties, and this had become one of the research hotspots and developing trends in the field of nanotechnology. In-situ tensile test was a direct and effective method to study the deformation mechanism of materials, which revealed the multiple mechanisms responding to feature grain sizes and provided reliable experimental means and research technique. Research on development of in-situ technique and its applications in mechanical properties was reviewed in this paper according to the recent advances on the modern mechanical properties for high strength and high plasticity alloy at home and abroad. The disadvantages of the present study of preparation methods and investigation techniques for high-performance alloy had been concluded. Finally, the development prospects of high strength and high plasticity alloy materials were analyzed.

Solar cell layers technology has achieved global standing in the solar cell layers deposition process, and it covers the innovative methods and techniques in significant applications. Recent solar cell layers technology has an advanced interest in a refined approach to enhance performance and highlights the importance of recent proficient procedures for manufacturing. For example, the application is used to search for novel materials for solar cells' layers to clarify the current energy crisis. The technological process and various types of solar cells depend on climate change. Among them, layers of solar cells and silicon wafer solar cells are very encouraging. Solar cell layers technology has led to solar cells being a more reasonable active option in design and production. The productivities facilitated by new solar cells still need to be enhanced for the various processes involved in the additional enhancement from Copper Indium Gallium Selenide (CIGS) microfilms to solar cell crystal structure dye-sensitized solar cells. The hydrophobic coating works as an anti-dust coating, enhancing efficiency and decreasing the cost of cleaning solar cells. In Saudi Arabia Majmaah City, most solar projects are in dry regions, where the dusty weather reduces solar cell efficiency. Therefore, combining these two properties and applying an anti-reflective and superhydrophobic coating will increase solar cell efficiency by 20%. Solar cells' crystal structure results are substituted with layers or new materials to balance environmental impact and toxic nature.

Lp16-PSP from Lentinula edodes strain C91-3 has been reported previously in our laboratory to have selective cytotoxic activity against a panel of human cell lines. Herein, we have used several parameters in order to characterize the Lp16-PSP-induced cell death using HL-60 as model cancer. The results of phase contrast microscopy, nuclear examination, DNA fragmentation detection and flow cytometry revealed that high doses of Lp16-PSP resulted in the induction of apoptosis in HL-60 cells. The colorimetric assay showed the activation of caspase-8, -9 and -3 cascade highlighting the involvement of Fas/FasL-related pathway. Whereas, western blot revealed the cleavage of caspase-3, increased expression of Bax, the release of cytochrome c and decreased expression of Bcl-2 in a dose-dependent manner, suggesting the intrinsic pathway might be involved in Lp16-PSP-induced apoptosis either. Low doses of Lp16-PSP resulted in the anchorage-independent growth inhibition, induction of G1 phase arrest accompanied by the increased expression of p21WAF1/CIP1 along with the decreased expression of cyclin D, E, and cdk6. Our findings suggest that induction of apoptosis and p21WAF1/CIP1 mediated G1 arrest might be one of the mechanisms of the action of Lp16-PSP, however, further investigations on multiple leukemia cell lines and in vivo models are of ultimate need.

The aim of this work is to introduce new ways to model the I-V characteristic of a PV cell or PV module using straight lines and Bézier curves. This is a complete novel approach, Bézier curves being previously used mainly for computer graphics. The I-V characteristic is divided in three sections, modeled with lines and a quadratic Bézier curve in the first case and with three cubic Bézier curves in the second case. The result proves to be accurate and relies on the fundamental points usually present in the PV cell datasheets: Voc (the open circuit voltage), Isc (the short circuit current), Vmp (the maximum power corresponding voltage) and Imp (the maximum power corresponding current) and the parasitic resistances Rsh0 (shunt resistance at Isc) and Rs0 (series resistance at Voc). The proposed algorithm completely defines all the implied control points and the error is analyzed. The temperature and irradiance influence is also analyzed. The model is also compared using the least squares fitting method. The final validation shows how to use Bézier cubic curves to accurately represent the I-V curves of an extensive range of PV cells and arrays.

Background: Metabolic flux analysis (MFA) is an indispensable tool in metabolic engineering. The simplest variant of MFA relies on an overdetermined stoichiometric model of the cell’s metabolism under the pseudo-steady state assumption, to evaluate the intracellular flux distribution. Despite its long history, the issue of model error in the overdetermined MFA, particularly misspecifications of the stoichiometric matrix, has not received much attention. Method: We evaluated the performance of statistical tests from linear least square regressions, namely Ramsey RESET test, F-test and Lagrange multiplier test, in detecting model misspecifications in the overdetermined MFA, particularly missing reactions. We further proposed an iterative procedure using the F-test to correct such an issue. Result: Using Chinese hamster ovary and random metabolic networks, we demonstrated that: (1) a statistically significant regression does not guarantee high accuracy of the flux estimates, (2) the removal of a reaction with a low flux magnitude can cause disproportionately large biases in the flux estimates, (3) the F-test could efficiently detect missing reactions, and (4) the proposed iterative procedure could robustly resolve the omission of reactions. Conclusion: Our work demonstrated that statistical analysis and tests could be used to systematically assess, detect and resolve model misspecifications in the overdetermined MFA.

Blueberry (Vaccinium spp.) has been recognized worldwide as a valuable source of health-promoting compounds, becoming a crop with some of the fastest rising consumer demand trends. Fruit firmness is a key target for blueberry breeding as it directly affects fruit quality, consumer preference, transportability, shelf life, and the ability of cultivars to be machine harvested. Fruit softening naturally occurs during berry development, maturation, and postharvest ripening. However, some genotypes are better at retaining firmness than others, and some are crispy, which is a putatively extra-firmness phenotype that provides a distinct eating experience. In this review, we summarized important studies addressing the firmness trait in blueberry, focusing on physiological and molecular changes affecting this trait at the onset of ripening and also the genetic basis of firmness variation across individuals. New insights into these topics were also achieved by using previously available data and historical records from the blueberry breeding program at the University of Florida. The complex quantitative nature of firmness in an autopolyploid species such as blueberry imposes additional challenges for the implementation of molecular techniques in breeding. However, we highlighted some recent genomics-based studies and the potential of a QTL mapping analysis and genome editing protocols such as CRISPR to further assist and accelerate the breeding process for this important trait.

It is proposed that the primary living cells (“probionts”) cannot emerge of organic substance simply by continuous chemical complication of prebiotic macromolecules and microsystems. The complication must be accompanied by the radical thermodynamic transformation (“jump”) of prebiotic microsystems that resulted in the acquired ability to extract free energy from the environment and export entropy. This transformation is called “the thermodynamic inversion” The inversion may occur by means of the efficient (intensified) response of the microsystems on the oscillations of physic-chemical parameters in hydrothermal environment. In this case the surplus available free energy within a microsystem, when combined with the informational modality, facilitates its conversion into a new microsystem—a living probiont. It is shown the schematic representation of an oscillating prebiotic microsystem that is transforming into a living probiont. A new kind of laboratory and computational experiments on prebiotic chemistry under oscillating conditions is offered to verify the inversion concept.

Sickle cell disease is characterized by stiff, “sickled” red blood cells that have difficulty moving through the bloodstream and do not efficiently carry oxygen. It is an inherited disease with severely limited treatment options, and is caused by a point mutation. Its prevalence in black and brown communities makes the already limited treatment options even less accessible. Base editing and prime editing are two relatively recent discoveries in the field of genome editing and were developed after the groundbreaking discovery of the CRISPR Cas9 system. While not fully tested, they hold a lot of promise in providing alternative treatment options for sickle cell disease. Both editing systems are able to install individual point mutations in the beta globin gene, which is where the sickle cell mutation occurs, and can thus cure sickle cell disease (in theory). In this paper we outline the mechanisms of CRISPR-Cas9 systems and base and prime editing, and provide insight into how to apply them to treat SCD. Further investigation should be done on specific editing systems and designs to use to ensure optimal treatment of SCD.

A copula is a useful tool for constructing bivariate and/or multivariate distributions. In this article, we consider a new modified class of (Farlie-Gumbel-Morgenstern) FGM bivariate copula for constructing several dierent bivariate Kumaraswamy type copulas and discuss their structural properties, including dependence structures. It is established that construction of bivariate distributions by this method allows for greater flexibility in the values of Spearman's correlation coefficient rho,  and Kendall's tau . For illustrative purposes, one representative data set is utilized to exhibit the applicability of these proposed bivariate copula models.

The first part of this paper contains a brief description of the beginnings of modern cosmology, which, the author will argue, was most likely born in the Year 1912. Some of the pieces of evidence presented here have emerged from recent research in the history of science, and are not usually shared with the general audiences in popular science books. In special, the issue of the correct formulation of the original Big Bang concept, according to the precise words of Fred Hoyle, is discussed. Too often, this point is very deficiently explained (when not just misleadingly) in most of the available generalist literature. Other frequent uses of the same words, Big Bang, as to name the initial singularity of the cosmos, and also whole cosmological models, are then addressed, as evolutions of its original meaning. Quantum and inflationary additions to the celebrated singularity theorems by Penrose, Geroch, Hawking and others led to subsequent results by Borde, Guth and Vilenkin. And corresponding corrections to the Einstein field equations have originated, in particular, R², f(R), and scalar-tensor gravities, giving rise to a plethora of new singularities. For completeness, an updated table with a classification of the same is given.

Omega-3 polyunsaturated fatty acids (ω3-PUFAs), including docosahexaenoic acid (DHA), have been shown to exert anticancer effects by inducing apoptotic cell death. However, the mechanism for DHA-induced cell death in lung cancer is not fully understood. Here, we show that DHA induces apoptosis in two human EGFR mutant non-small cell lung cancer (NSCLC) cell lines, and that DHA-induced cell death is accompanied by SIRT6 activation and attenuated Hedgehog (Hh) signaling. Knockdown of SIRT6 using siRNAs inhibited DHA-induced apoptosis, whereas SIRT6 overexpression increased apoptotic cell death. DHA-induced SIRT6 activation was associated with downregulation of Hh signaling, and knockdown of SIRT6 resulted in augmentation of Hh signaling. Pretreatment of NSCLC cells with a Smoothened agonist prevented DHA-induced decreases in the levels of Hh signaling proteins and increases in cleaved PARP levels. Moreover, endogenous production of ω3-PUFAs in PC9 cells via fat-1 expression resulted in elevated SIRT6 levels and reduced levels of Hh signaling molecules, including Gli, following DHA treatment. Overall, these results implicate that ω3-PUFAs induce apoptosis by downregulating Hh signaling via SIRT6 activation in human EGFR mutant NSCLC cells. These findings suggest that ω3-PUFAs potentially represent an effective therapy for the chemoprevention and treatment of NSCLC.

A programmable DC power supply with Real-time Digital Simulator (RTDS)-based photovoltaic (PV) Power Hardware-In-the-Loop (PHIL) simulators have been used to improve the control algorithm and reliability of PV Inverter. This paper proposes a supervisory control algorithm for PV PHIL simulator with non-RTDS device that is an alternative solution of high cost PHIL simulator. However, when such a simulator with conventional algorithm which is used in RTDS is connected to a PV inverter, the output is in the transient state and it makes it impossible to evaluate the performance of the PV Inverter. Therefore proposed algorithm controls the voltage and current target values according to the constant voltage (CV) and constant current (CC) modes to overcome the limitation of the Computing Unit, DC power supply and also uses a multi-rate system to account for the characteristics of each component of simulator. A mathematical models of a PV system, programmable DC power supply, isolated DC measurement device and Computing Unit are integrated to form a real-time processing simulator. Performance tests using a PV PHIL simulator which is applied proposed algorithm connected a PV inverter are carried out and proved superiority and utility of this method against conventional methods.

This paper deals with bistatic subsurface probing of a horizontally layered dielectric half-space by means of ultra-wideband electromagnetic pulses. A receiver collects reflections from the air-ground interface and from the gradients of dielectric permittivity in the half-space. This scenario is of interest for ground penetrating radar (GPR) applications. For the analytical description of the received signal, we developed and implemented a novel time-domain version of the coupled-wave Wentzel–Kramers–Brillouin approximation. Our solution is in very good agreement with finite-difference time-domain results, radically accelerates calculations, and effectively accounts for the protracted return signals observed in the lower part of the GPR spectrum. The paper includes results showing the application of the proposed technique to two case studies: in particular, the method was employed for the post-processing of experimental radargrams collected on Lake Chebarkul, in Russia, and to simulate GPR probing of the Moon surface, to detect smooth gradients of the dielectric permittivity in lunar regolith.

Different organisms, cell types, and even similar cell lines can dramatically differ in resistance to genotoxic stress. This testifies to the wide opportunities for genetic and epigenetic regulation of stress resistance. These opportunities could be used to increas the effectiveness of cancer therapy, develop new varieties of plants and animals, and search for new pharmacological targets to enhance human radioresistance, for example, for -manned deep space expeditions. Based on the comparison of transcriptomic studies in cancer cells, in this review we propose that there is a high diversity of genetic mechanisms of development of genotoxic stress resistance. This review focused onpossibilities and limitations of the proposed regulation of the resistance of normal cells whole organisms to genotoxic and oxidative stress by overexpressing of stress-response genes. Moreover, the existing experimental data on the effect of such overexpression on the resistance of cells and organisms to various genotoxic agents has been analyzed and systematized. We suggest that the recent advances in the development of multiplex and highly customizable gene overexpression technology that utilizes the mutant Cas9 protein and the wealth of available data on gene functions and their signal networks open new opportunities for research in this field.

Demand response flexible loads can provide fast regulation and ancillary services as reserve capacity in power systems. This paper proposes a joint optimization dispatch control strategy for source-load system with stochastic renewable power injection and flexible thermostatically controlled loads (TCLs) and plug-in electric vehicles (PEVs). Specifically, the optimization model is characterized by a chance constraint look-ahead programming to maximal the social welfare of both units and load agents. By solving the chance constraint optimization with sample average approximation (SAA) method, the optimal power scheduling for units and TCL/PEV agents can be obtained. Secondly, two demand response control algorithms for TCLs and PEVs are proposed respectively based on the aggregate control models of the load agents. The TCLs are controlled by its temperature setpoints and PEVs are controlled by its charging power such that the DR control objective can be fulfilled. The effectiveness of the proposed dispatch and control algorithm has been demonstrated by the simulation studies on a modified IEEE 39 bus system with a wind farm, a photovoltaic power station, two TCL agents and two PEV agents.

The past two decades have seen a revolution in multiple myeloma (MM) therapy with the introduction of several small molecules, mostly orally effective, whose mechanisms are based on proteasome inhibition, histone deacetylase (HDAC) blockade, and immunomodulation. Immunotherapeutic approaches to MM treatment using monoclonal antibodies (mAbs), while long in development, began to reap success with the identification of CD38 and SLAMF7 as suitable targets for development, culminating in the 2015 FDA approval of daratumumab and elotuzumab, respectively. This review highlights additional mAbs now in the developmental pipeline. Isatuximab, another anti-CD38 mAb, currently is under study in four phase III trials and may offer certain advantages over daratumumab. Several antibody-drug conjugates (ADCs) in the early stages of development are described, including JNJ-63723283, which has attained FDA breakthrough status for MM. Other mAbs described in this review include denosumab, recently approved for myeloma-associated bone loss, and checkpoint inhibitors, although the future status of the latter combined with immunomodulators has been clouded by unacceptably high death rates that caused the FDA to issue clinical holds on several of these trials. Also highlighted are therapies based on the B Cell Maturation Antigen (BCMA), another very promising target for anti-myeloma development.

A crewed mission to and from Mars may include an exciting array of enabling biotechnologies that leverage inherent mass, power, and volume advantages over traditional abiotic approaches. In this perspective, we articulate the scientific and engineering goals and constraints, along with example systems, that guide the design of a surface biomanufactory. Extending past arguments for exploiting stand-alone elements of biology, we argue for an integrated biomanufacturing plant replete with modules for microbial \textit{in situ} resource utilization, production, and recycling of food, pharmaceuticals, and biomaterials required for sustaining future intrepid astronauts. We also discuss aspirational technology trends in each of these target areas in the context of human and robotic exploration missions in the coming century.

This paper discussed the concept of quality assurance (QA) in higher education and its implications to higher education institutions (HEIs) and the possible challenges. The study evaluated literature concerning QA in Zambia and elsewhere. The findings of the study show that QA is implemented through external and internal mechanisms such as accreditation, registration, institutional auditing, and the use of external examiners, self-evaluation, and peer reviews. The QA implications to HEIs in Zambia are that there is a need for accreditation of academic programmes with the Higher Education Authority (HEA) by HEIs. Further, HEIs should establish QA units to spearhead quality issues, reactive, and introduce the use of external examiners to ensure quality. The challenges identified in the implementation of QA in HEIs include inadequate funding, infrastructure, shortage of qualified academic staff, and lack of standalone QA units in some HEIs. In this regard, it has been recommended among other things, government improve funding in public HEIs, construct infrastructure, HEIs establish QA units, and recruit and retain qualified academic staff to ensure the quality of education.

Intermediate filaments constitute the third component of the cellular skeleton. Unlike actin and microtubule cytoskeletons, the intermediate filaments are composed of wide variety of structurally related proteins showing distinct expression patterns in tissues and cell types. Changes in expression patterns of intermediate filaments are often associated with cancer progression, in particular with phenotypes leading to increased cellular migration and invasion. In this review we will describe the role of vimentin intermediate filaments in cancer cell migration, cell adhesion structures, and metastasis formation. The potential for targeting vimentin in cancer treatment and the development of drugs targeting vimentin will be reviewed.

A cursory look at Indian prime time news tells us much about the tone and tenor of the people associated with it. Exaggerations, hyperbole, and tempers run wild and news anchors flail in theatrical rage. News channels and news editors display their ideological affiliations subliminally. These affiliations — a factor of personal political stance, funding bodies, and investors — lead to partisan bias in the framing of news and, in some cases, can easily translate into racial prejudice. In this paper, I examine news coverage related to Muslims in India. I study the coverage of two issues specifically– love jihad and triple talaq –in prime time English news of two channels – Times Now and Republic TV. My analysis of the content, tone, and tenor of their coverage shows that these channels propagate associations between Islam and backwardness, ignorance and violence through consistent employment of the following tropes – ‘Muslim women need to be saved from Muslim men’, ‘Hindu women need to be saved from Muslim men’, and ‘Muslims are not fully Indian – they are anti-national’. I place this study of news media within the current political climate in India and briefly touch on the conversations it guides and provokes. This is also a call for further analysis on this subject to examine and evaluate how discourse manipulates public conversations and policy decisions.

As a mediator variable, self-confidence is one of the most effective elements of the decision-making process of consumer behaviour. This research has studied the effects of different aspects of consuming fashion on the self-confidence and behaviour of consumers in Tehran’s clothing market. This study has considered the acceptance of new products, interest in mode and fashion, utilitarianism, and personal taste in its analysis. This research aims to understand the fashion buying behaviour amongst Iranian consumers in consideration of their attitude towards self-confidence and aspects of fashion consumption. The statistic sample is 400 consumers from Tehran’s clothing market who have been chosen based on the random availability procedure. The primary tool in this research was a questionary used to testify the assumptions and a model fit created by using structural equations and factor analysis. This research showed that the interest in mode and fashion, personal taste, utilitarianism, and new products positively impact self-confidence. In addition, the positive impact of self-confidence on fashion buying behaviour was confirmed.

Keeping in mind the increasing trend and need for serious games in science education, we have done a systematic literature review. These papers show the trends and patterns of research carried out in this field from the year 2011 to 2020. Specifically, we investigated country-wise concentration and the most common evaluation methods. Literature is reviewed from IEEEexplore, Springer, and Scopus. Moreover, we discussed the role of Augmented Reality(AR) games in teaching physics. Lastly, we have discussed the positive and negative aspects of serious games in science education in particular, and the trend of using serious games in the past decade in education in general.

This study aimed to enhance a micro hydroelectric generator system driven by free-flow vortex and to compare efficiency of Propeller and Crossflow turbines. Series of turbines in each type were designed and tested at water-flowrate of 0.02 m3/s. The turbine housing has 1 meter in diameter and 0.5-meter height with 2 meters outlet drain at the bottom. The best efficiency extracted from Crossflow turbines with the same height (0.3 meter) but different in diameter (0.4, 0.5, 0.6, and 0.7 meter) and numbers of blade (12, 18, 24, 30, and 23) was from an 18 blades turbine at 23.01% of efficiency. The best efficiency extracted from Propeller turbines with 5 blades was from a 0.4-meter-high turbine with a diameter of 0.7 meter at 13.92% of efficiency. There were 12 Propeller turbines designed in this study. They were different in height (0.2, 0.3, and 0.4 meter) and, in each height, 0.4, 0.5, 0.6, and 0.7 of diameter was applied. The result revealed that Cross Flow turbine had more efficiency to the system than Propeller turbine (9.09%) at the water-flowrate of 0.02 m3/s

The demand of high data rate and ubiquitous coverage in heterogeneous cellular (HetNets) is increasing progressively. In order to meet this demand, sophisticated model having applied interference reduction scheme and cell association technique is needed. The small base station (sBS)are deployed inside the broadcasting area of macro base station (mBS), in heterogeneous cellular networks (HetNets). Since mBS has high transmission power therefore a large number of users get connected with mBS. This causes disproportion of load distribution across the HetNets. For load balancing users from high power mBS are migrated to low power sBS to increase network capacity and to decrease the load from mBS. This results in interference in the communication signal because of strong mBS Interference. Hence, we need interference management technique to mitigate interference and user association and to efficiently use sBSs’ resources. Inter-cell interference (ICI) limit the HetNets’ performance. Additionally, there exist deliberate jamming interference which depends on jammers transmission power and its proximity with the target, which notably degrades the network performance. In this paper, we employ reverse frequency allocation scheme (RFA) to reduce inter cell interference, deliberate jamming interference and to accomplish load balancing. The proposed setup is analyzed inquisitively and with the help of simulations. The result shows reduction in interferences as well as balance of load distribution in the network achieved by employing RFA scheme together with cell association.

Background: While mankind is still dealing with the COVID-19 pandemic, on May 7, 2022, a case of monkeypox virus (MPXV) has been reported to the WHO. Monkeypox is a viral zoonotic disease with characteristics comparable to those seen in smallpox cases in the past. It has been a public health threat, particularly in Africa, but recently have been circulating the world, consequently, may become a global public health threat in a very short period. Thus, the current work was planned and then constructed a multi-epitope vaccine that can evoke an immunological response against MPXV utilizing cell surface-binding protein as a target in order to develop a novel vaccine that is both safe and almost free of side effects. Results: The proposed vaccine composed of 304 amino acids and was shown to be antigenic in Vaxijen server (0. 5311) and nonallergenic in AllerTop server. The 3D structure of the designed vaccine is predicted, refined and validated by various in silico tools to assess the stability of the vaccine. Moreover, solubility of the vaccine construct was found greater than the average solubility provided by protein-Sol server indicating the solubility of the vaccine construct. Moreover, the most promising epitopes bound to MHC I and MHC II alleles were found having good binding affinities with low energies ranging between ₋7.0 - ₋8.1kcal/mol. Conclusion: We conclude from our research that the cell surface-binding protein is one of the primary proteins involved in MPXV pathogenesis. The most promising epitopes were selected using a rigorous procedure and used for vaccine design. As a result, our study will aid in the development of appropriate therapeutics and prompt the development of future vaccines against MPXV, which could serve as an important milestone in the production of an antiviral vaccine against MPXV.

Lemon balm extracts by dry plant material of Melissa officinalis were tested against their efficacy against for different fungal species Alternaria alternata, Fusarium oxysporum, Aspergillus flavus and Beauveria bassiana. The aqueous phase of the extract was evaluated for antioxidant, antifungal and also anti-aflatoxigenic activity. A synergism evaluation was also performed concerning, the small quantity of lemon balm polar essential oil compounds extracted into the infusion and the water soluble compounds in the extract. The experiments were conducted in solid cultures and the growth inhibition was demonstrated by measuring mycelial diameter. Additionally, the effect on conidia production was also demonstrated. Lemon balm was also used for in situ test on Pistachia vera seed against Aspergillus flavus growth and aflatoxin production. Results revealed enhancement of fungal growth by lemon balm extracts however total inhibition of aflatoxins production on Pistachia vera seeds was observed, and both actions were tried to attributed to volatile and water soluble compounds identified based on GC/MS, HPLC/DAD and LC/MS, and the observed antioxidant activity. Volatile and water - soluble compounds found to be in absolute synergism in mycelium growth enhancement and the observed anti-aflatoxigenic activity addressed to the high antioxidant activity observed and synergistic action between the other water soluble phenolic compounds identified in the extract. The findings of this study underline the high biological active potential of lemon balm extracts under various screening test since for the first time full phytochemical analysis of lemon balm extracts.

The feasibility of using full ion kinetics, instead of gyrokinetics, in simulating low-frequency Ion-Temperature-Gradient (ITG) instabilities in tokamaks has recently been demonstrated by Sturdevant et al. [Physics of Plasmas 24, 081207 (2017)]. In that work, a variational integrator was developed to integrate the full orbits of ions in toroidal geometry, which proved to be accurate in capturing both the short-time scale cyclotron motion and long time scale drift motion. The present work extends that work in three aspects. First, we implement a relatively simple full orbit integrator, the Boris integrator, and demonstrate that the accuracy of this integrator is also sufficient for simulation of ITG instabilities. Second, the equilibrium magnetic configuration is extended to general toroidal configuration specified numerically, enabling simulation of realistic equilibria reconstructed from tokamak experiments. Third, we extend that work to the nonlinear regime and investigate the nonlinear saturation of ITG instabilities. To verify the new numerical implementation of the orbit integrator and magnetic configuration, the linear electrostatic ITG frequency and growth rate are compared with those given in Sturdevant's work and good agreement is found.

In interepidemic periods, a sapronoses typically employs a variety of mechanisms for maintaining viability of its causative agent in terrestrial parasitic systems, associated with different adaptive strategies utilized by its populations to survive. Unlike spore-forming bacteria, causative agents of sapronoses use resistant cell forms, which is a viable but nonculturable (VBNC) state, and persistence. Implementation of these strategies is conditioned by effects of various stress factors of the habitat and is characterized by decreased metabolism, alteration of the morphology and physiology of bacterial cell, and cessation of its replication. It is important that the resistant forms of cells retain virulence and, as favorable conditions come, turn back into the active vegetative form again. The discovery of the genetic modules of bacterial toxin–antitoxin systems in recent years has made it possible to identify a number of complicated regulatory molecular mechanisms responsible for maintaining the pathogenic potential of resistant forms of causative agents of natural-focus sapronoses in interepidemic periods.

Multiferroics, showing both ferroelectric and magnetic order, are promising candidates for future electronic devices. Especially, the fundamental understanding of ferroelectric switching is of key relevance for further improvements, which however is rarely reported in literature. On a prime example for a spin-driven multiferroic, LiCuVO₄, we present an extensive study of the ferroelectric order and the switching behavior as function of external electric and magnetic fields. From frequency-dependent polarization switching and using the Ishibashi-Orihara theory, we deduce the existence of ferroelectric domains and domain-walls. These have to be related to counterclockwise and clockwise spin-spirals leading to the formation of multiferroic domains. A novel measurement – multiferroic hysteresis loop – is established to analyze the electrical polarization simultaneously as a function of electrical and magnetic fields. This technique allows characterizing the complex coupling between ferroelectric and magnetic order in multiferroic LiCuVO₄.

The “stem cells” discipline represents one of the most dynamic areas in biomedicine. While adult marine/aquatic invertebrate stem cell (MISC) biology is of prime research and medical interest, studies on stem cells from organisms outside the classical vertebrate (e.g., human, mouse, zebrafish) and invertebrate (e.g., Drosophila, Caenorhabditis) models have not been pursued vigorously. Marine/aquatic invertebrates constitute the largest biodiversity and the widest phylogenetic radiation on Earth, from morphologically simple organisms (e.g. sponges, cnidarians), to the more complex mollusks, crustaceans, echinoderms and protochordates. These organisms illustrate a kaleidoscope of MISC-types that participate in the production of a large number of novel bioactive-molecules, many of which are of significant potential interest for human health. MISCs further participate in aging and regeneration phenomena, including whole-body regeneration. For years, the European MISC-community has been highly fragmented and scarce ties were established with biomedical industries in attempts to harness MISCs for human welfare. Thus, it is important to: i) consolidate the fragmented European community working on MISCs; ii) promote and coordinate European research on MISC biology; iii) stimulate young researchers to embark on research in MISC-biology; iv) develop, validate, and network novel MISC tools and methodologies; v) establish the MISC discipline as a forefront interest of biomedical disciplines, including nanobiomedicine; vi) establish collaborations with industries to exploit MISCs as sources of bioactive molecules. In order to fill the recognised gaps, the EC-COST Action 16203 “MARISTEM”, has recently been launched. At its initial stage the consortium unites 26 scientists from EC countries, Cooperating countries and Near Neighbor Countries.

The application of electrode-based microfluidic devices in biological entity often imposes a problem due to joule heating. The strong applied potentials or micro channels having narrow cross sections generate undesirable temperature inside the microfluidic channels leading to strong thermal distribution inside the micro channel. When intrinsic distribution of temperature, if not fix with threshold value, causes device damage or cell loss. In this work, we investigate the effects of temperature generated due to joules heating effects and we attempt to address the design constraints for minimizing the joule heating effects in the microfluidic device for developing effective microfluidic device. The device reliability was analyzed under different parametric constraints for various types of substrate materials (PDMS, PMMA, Polyimide and glass). We also attempt to investigate the effects of cell reliability due to strong temperature gradients generated through different applied potentials on different cell types. Furthermore, the response of the device performance due to different electrode configuration and different conductivity of the medium was also studied. Our investigation will eventually provide guidelines for microfluidic researchers to fabricate efficient electrode based microfluidic device which will ultimately help to choose a critical channel dimensions, threshold potentials, and conductivity of solutions in order to avoid device damage and cell loss.

Engineering of drug nanocarriers combining fine-tuned mucoadhesive/mucopenetrating properties is currently being investigated to ensure more efficient mucosal drug delivery. Aiming to improve the transmucosal delivery of hydrophobic drugs, we designed a novel kind nanogel produced by the self-assembly of amphiphilic chitosan graft copolymers ionotropically crosslinked with sodium tripolyphosphate. In this work, we synthesized for the first time chitosan-g-poly(methyl methacrylate) nanoparticles thiolated by the conjugation of N-acetyl cysteine. First, we confirmed that both non-crosslinked and crosslinked nanoparticles in the 0.05-0.1% w/v concentration range display very good cell compatibility in two cell lines that are relevant to oral delivery, Caco2 cells that mimic the intestinal epithelium and HT29-MTX cells that produce mucin. Then, we evaluated the effect of crosslinking, nanoparticle concentration and thiolation on the permeability in vitro utilizing monolayers of (i) Caco2 and (ii) Caco2:HT29-MTX cells (9:1 cell number ratio). Results confirmed that the ability of the nanoparticles to cross Caco2 monolayer was affected by the crosslinking. In addition, thiolated nanoparticles interact more strongly with mucin, resulting in a decrease of the apparent permeability coefficient (Papp) compared to the pristine nanoparticles. Moreover, for all the nanoparticles, higher concentration resulted in lower Papp suggesting indicating that the transport pathways could undergo saturation.

Morphogenesis remains a riddle, wrapped in a mystery, inside an enigma. It remains a formidable problem viewed from many different perspectives of morphology, genetics, and computational modelling. We propose a biochemical reductionist approach that shows how both internal and external physical forces contribute to plant morphogenesis via mechanical stress-strain transduction from the primary cell wall tethered to the plasma membrane by a specific arabinogalactan protein (AGP). The resulting stress vector with direction defined by Hechtian adhesion sites, has a magnitude of a few picoNewtons amplified by a hypothetical Hechtian growth oscillator. This paradigm shift involves stress activated plasma membrane Ca2+channels and auxin-activated H+-ATPase. The proton pump dissociates periplasmic AGP-glycomodules that bind Ca2+. Thus, as the immediate source of cytosolic Ca2+ an AGP-Ca2+ capacitor directs vectorial exocytosis of cell wall precursors and auxin efflux (PIN) proteins. In toto these components comprise the Hechtian Oscillator and also the gravisensor. Thus interdependent auxin and Ca2+ morphogen gradients account for the predominance of AGPs. The size and location of a cell surface AGP-Ca2+ capacitor is essential to differentiation and explains AGP correlation with all stages of morphogenetic patterning from embryogenesis to root and shoot. Finally, evolutionary origins of the Hechtian Oscillator in the unicellular Chlorophycean algae reflect the ubiquitous role of chemiosmotic proton pumps that preceded DNA at the dawn of life.

The sustainable development of our world has gain particular attention of a wide range of decisional factors, civil society, business sector, and scientific community, seeing that the prosperity of people and society is possible with the aid of sustained and inclusive economic growth of all countries and regions. Educational environment has a decisive impact on changes in the way that societies are coping with national, regional, and global challenges and opportunities brought by sustainable development. Looking at the implications of HE on the progress of society, the paper addressed the lack of HE institutional capacity to integrate the principles and practices of sustainable development into all aspects of education and learning. The scope of research problem was bounded on the capability of HEI as organization and school to act as entrepreneurial university by combining the scope of its responsibility within the value chain through a practical and effective mechanism needed to align the strategy with sustainable development goals (SDGs). Embarking on the path of SDGs requires HEI to design, launch, implement, and customize specific processes architectures to govern the advance of sustainability approach. The authors applied the process scoping diagram to capture and conceptualize the educational model needed to guide the HEI through the process of change to embrace sustainability into organizational culture and daily operations. It has been used the SIPOC method (Supplier, Input, Process, Output, Customer) with Visio software tool to articulate processes relationships embedded in the educational model of HEI. The benefits relied on the organized view of the work processes needed to be performed to incorporate SDGs into the strategy of any entrepreneurial HEI. Finally, the authors shared their views on the scalability of the model which may be customized and harmonized in accordance with different HE circumstances and priorities. Implementing the proposed educational model requires long-term institutional commitment, transparency, continuous performance improvement, and communicating the strategy for SDGs and its achievements to wider stakeholders.

The wide range of applications of nanoparticles (NPs) has increased the probability of environmental and occupational exposure. In a previous comparative study on cell line A549, we observed that oxidative stress caused by Co₃O₄ NPs affects the energetic homeostasis and the detoxification capacity, preventing autophagy induced by TiO₂ NPs. In this study, we have investigated the effects of NPs on the cell cycle.Cytofluorimetric analysis showed a slow-down of the cell cycle progression for both NPs, with increases in the percentage of resting cells in the G0/G1. These observations were confirmed by a reduced expression of all cyclins, especially of CCNE1 and CDK2, involved in the late stages of the G1 phase, coupled with a significant increase in the expression of p21 only for Co₃O₄ NP exposure. On the contrary, the effects of TiO₂ NPs were modest. Cell cycle related miRNA-34a, miRNA-126 and miRNA-1290 resulted increased at different early time-points (4-8h) but were down-expressed at 24h-48h only after TiO₂ NP exposure. Our results show that NPs have an antiproliferative effect and deregulate cell cycle on A549 cells. These effects should not be underestimated because regulation of cycle progression is crucial for cell survival and repair of genetic damage.

The highest efficiency solar cell won in the efficiency race does not always give the most excellent annual energy yield in the real world solar condition that the spectrum is ever-changing. The study of the radiative coupling of the concentrator solar cells implied that the efficiency could increase by the recycle of the radiative recombination generated by the surplus current in upper junction. Such configuration is called by a super-multi-junction cell. We expanded the model in the concentrator solar cell to non-concentrating installation. It was shown that this super-multi-junction cell configuration was found robust and can keep the maximum potential efficiency (50 % in realistic spectrum fluctuation) up to 10 junctions. The super-multi-junction cell is also robust in the bandgap engineering of each junction. Therefore, the future multi-junction may not be needed to tune the bandgap for matching the standard solar spectrum, as well as relying upon artificial technologies like ELO (Epitaxial lift-off), wafer-bonding, mechanical-stacking, and reverse-growth, but merely uses up-right and lattice-matching growth technologies. We have two challenging techniques; one is the optical cap layer that may be the directional photon coupling layer in the application of the photonics technologies, and another is the high-quality epitaxial growth with almost 100 % of the radiative efficiency.

During the past two decades there has been a major shift in the choice of agents to treat multiple myeloma, whether newly diagnosed or in the relapsed/refractory stage. The introduction of new drug classes, such as proteasome inhibitors, immunomodulators, and anti-CD38 and anti-SLAMF7 monoclonal antibodies, coupled with autologous stem cell transplantation, have approximately doubled the disease’s five-year survival rate. However, this positive news is tempered by the realization that these measures are not curative and patients eventually relapse and/or become resistant to the drug’s effects. Thus, there is a need to discover newer myeloma-driving molecular markers and develop innovative drugs designed to precisely regulate the actions of such putative targets. B cell maturation antigen (BCMA), which is found almost exclusively on the surfaces of malignant plasma cells to the exclusion of other cell types, including their normal counterparts, has emerged as a specific target of interest in this regard. Immunotherapeutic agents have been at the forefront of research designed to block BCMA activity. These agents encompass monoclonal antibodies, such as the drug conjugate belantamab mafodotin; bispecific T-cell engager strategies exemplified by AMG 420; and chimeric antigen receptor (CAR) T-cell therapeutics that include idecabtagene vicleucel (bb2121) and JNJ-68284528.

Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2) is the virus that caused COVID-19 around the world. The disease starts off as a flu-like symptom and then eventually spreads in the human body.Infections are easily transmitted from human to human which makes it more severe among individuals. SARS-CoV-2 virus is in the same family of viruses SARS and MERS.As of today, there is no approved vaccine that can cure COVID-19. However, potential treatments showing promising improvement results among affected COVID-19 patients. In this review, the effectiveness of the current treatments for COVID-19 has been explored.

The growth and dynamics of multicellular tissues involve tightly regulated and coordinated morphogenetic cell behaviours, such as shape changes, movement, and division, which are governed by subcellular machinery and involve coupling through short- and long-range signals. A key challenge in the fields of developmental biology, tissue engineering and regeneration is to understand how relationships between scales produce emergent tissue-scale behaviours. Recent advances in molecular biology, live-imaging and ex vivo techniques have revolutionised our ability to study these processes experimentally. To fully leverage these techniques and obtain a more comprehensive understanding of the causal relationships underlying tissue dynamics, computational modelling approaches are increasingly spanning multiple spatial and temporal scales, and are coupling cell shape, growth, mechanics and signalling. Yet such models remain technically challenging: modelling at each scale requires different areas of technical skills, while integration across scales necessitates the solution to novel mathematical and computational problems. This review aims to summarise recent progress in multiscale modelling of multicellular tissues and to highlight ongoing challenges associated with the construction, implementation, interrogation and validation of such models.

The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was isolated in 2012 and is well known to cause the respiratory syndrome. The orf1ab gene is known to mediate MERS-CoV replication. In this study, we have discussed the in silico prediction of potential siRNAs targeting MERS-CoV-orf1ab gene for antiviral therapeutics. To identify the potential siRNAs, various factors were considered. We have excluded the siRNAs with off-target effects and potential binding with human mRNAs. By using available softwares, total twenty-one functional, off-target reduced potential siRNA were selected from four hundred and sixty-two siRNAs based on greater potency and specificity. We have tested only seven siRNAs initially to evaluate their performance by reverse transfection approach by lipofectamine mediated delivery in Vero cells. The evaluation results showed no cytotoxicity at various concentrations of siRNAs used. The results obtained in this study provided preliminary information about the cytotoxicity which will help us to further evaluate siRNAs in other cell cultures to find out the replication inhibition efficiency of MERS-CoV. Finally, it is concluded that the in silico prediction and designing resulted in filtration and selection of potential siRNAs with high accuracy, efficiency, and strength which can be further utilized for the development of oligonucleotide-based therapeutics.

Patient-derived xenograft (PDX) models are created by engraftment of patients’ tumor tissues into immunocompetent mice. Since PDX model keep the characteristics of primary patient’s tumor such as gene expression profiles and drug sensitivity, it now becomes most reliable in vivo human cancer model. The engraftment rate are increased with the introduction of NOD/Scid based immunocompromised mice, especially, NK cell defective NOD strains such as NOD/Scid/IL2Rγnu (NOG/ NSG) mice and NOD/Scid/Jak3null (NOJ) mice. Success ratio differs from the origin of tumor: Gastrointestinal tumors tend to higher success rate and breast cancer is lower. Subcutaneous transplantation is most popular method to establish PDX, but some tumor needs orthotropic or renal capsule transplantation, and human hormone treatment is needed to establish hormone dependent cancers such as prostate and breast cancer. PDX library with patient’s clinical data, gene-expression patterns, mutational status, drug responsiveness and tumor architecture will be the powerful tool for developing specific biomarker and novel individualized therapy and establishing precision cancer medicine.

Bioelectrochemical systems (BES) encompass a group of biobased technologies capable of directly converting organic matter into electricity. In these systems, which are derived from conventional electrochemical systems, the ion exchange membrane represents a key element because of its influence on the economic feasibility and on the performance of BES. This study examines the impact of long-term operation of a BES on the mechanical, chemical and electrochemical properties of five different kind of cation exchange membranes (Nafion-117, CMI-7001, Zirfon UTP 500, FKE and FKB) through several techniques: (i) scanning electron microscopy (SEM) and atomic force microscopy (AFM) to assess the changes on the membranes surface, (ii) thermogravimetric analysis (TGA) to evaluate the structural stability of the membranes, and (iii) ion exchange capacity (IEC) to monitor any change in their electrochemical properties. Results confirmed that there is not an ideal membrane for BES. While Nafion and CMI-7000 exhibited the strongest chemical structure, they also underwent the highest fouling as revealed by a fast increase in surface roughness.

Microscale surgery on single cells and small organisms have enabled major advances in fundamental biology and in engineering biological systems. Examples of applications range from wound healing and regeneration studies to the generation of hybridoma to produce monoclonal antibodies. Even today, these surgical operations are often performed manually, but they are labor-intensive and lack reproducibility. Microfluidics has emerged as a powerful technology to control and manipulate cells and multicellular systems at the micro- and nanoscale with high precision. Here, we review the physical and chemical mechanisms of microscale surgery, and the corresponding design principles, applications, and implementations in microfluidic systems. We consider four types of surgical operations: 1) Sectioning, which splits a biological entity into multiple parts, 2) ablation, which destroys part of an entity, 3) biopsy, which extracts materials from within a living cell, and 4) fusion, which joins multiple entities into one. For each type of surgery, we summarize the motivating applications and the microfluidic devices developed. Throughout the review, we highlight existing challenges and opportunities. We hope that this review will inspire scientists and engineers to continue to explore and improve microfluidic surgical methods.

Poor survival of human pluripotent stem cells (hPSCs) following freezing, thawing, or passaging hinders maintenance and differentiation in stem cell research. Rho-associated kinases (ROCKs) play a crucial role in hPSC survival. To date, a typical ROCK inhibitor, Y-27632, has been the primary agent used in hPSC research. Here, we report that another ROCK inhibitor, fasudil, can be used as an alternative. Fasudil increased hPSC growth due to survival rather than proliferation following thawing and passaging, similar to Y-27632. It did not affect pluripotency and genetic integrity including mitochondrial genome (mtDNA). Notably, the genes related to metabolism, mTORC1, and TP53 have mainly displayed a faster recovery pattern with ROCK inhibitors than control. Furthermore, fasudil was confirmed as useful for the single dissociation of hPSCs and for aggregation. It also increased retinal pigment epithelium (RPE) differentiation and the survival of neural crest cells during differentiation. These findings suggest that fasudil can replace Y-27632 for use in stem cell research.

This paper presents findings of a study on continuous feed-in management and continuous synthetic inertia contribution with wind turbines. A realistic case study, based on real measurements, is outlined. A wind turbine feeds into a weak feeder, such that its power has to be adapted to the permissible loading of this feeder. At the same time the wind turbine is to provide inertia to the grid by applying the previously published variable inertia constant controller. It is discussed that optimal grid utilisation and simultaneous inertia contribution are mandatory for the frequency control in power systems that are heavily penetrated with renewable energies. The study shows that continuous feed-in management can be combined well with continuous inertia provision. There are hardly any negative consequences for the wind turbine. The benefits for the grid are convincing, both in terms of increased system utilisation and in terms of provided inertia. It is concluded that wind turbines can enhance angular stability in a power system to a larger extent than conventional power plants.

The protection of electronics against environmental influences and mechanical loads is important for integration of conventional electronics in textile conductive tapes. For this purpose, the sensors on the tapes are molded with plastic locally. This process step is recognized in the injection molding process. The molding compound is then later selected depending on: The field of application, the parameters of the manufacturing process and the textile tape properties. We have designed a mould for liquid silicone (LSR) as well as for the textile and electronic insertions. The cavities are sealed by a local compression of the textile and the two inserts are positioned with position pins representing the main aspect of the mould design. The sampling tool and the process parameter optimization are mainly based on the material properties of the silicone and the mechanical sensitivity of the inserts. To reduce the deformation of the circuit boards by the melt front and ensuring the functionality of the electronics a low-pressure process is used.

Enamel matrix derivative (EMD) is used for periodontal tissue regeneration therapy, and can induce mineralization in dental pulp cells (DPCs). We designed a synthetic peptide (SP) derived from the response of cells to EMD, and investigated the effect of the SP on potentiating osteogenesis in DPCs, which have a critical role of dental pulp homeostasis. DPCs were treated with 0, 10, 100, or 1000 ng/mL SP to determine its effect on cell proliferation, cell migration, cell differentiation, and mineralization. We then examined the molecular effects of the SP, focusing on changes in the mitogen-activated protein kinases (MAPK) signaling pathway in these cells. The SP significantly promoted DPC proliferation and migration. Cultures treated with the SP also showed an enhanced expression of markers of osteogenic differentiation and mineralization. The SP also induced the activation of MAPK signaling pathway components. These results suggest that our SP could promote the dental pulp tissue repair by hard tissue formation and the mineralization through activating MAPK signaling pathway. This study provides the first evidence that SP might be a new material for dental pulp tissue treatment.