The current spreading novel coronavirus SARS-CoV-2 is highly infectious and pathogenic and has attracted global attention. Recent studies have found that SARS-CoV-2 and SARS-CoV share around 80% of homology and use the same cell entry receptor, ACE2. These inspired us to study other receptors of SARS-CoV, which may be used for SARS-CoV-2 binding as well. In this study, we screened the gene expression of three receptors (ACE2, DC-SIGN and L-SIGN) in four datasets of normal lung tissue from lung adenocarcinoma patients and two single-cell RNA sequencing datasets from normal lung and bronchial epithelial cells separately. No significant difference in gene expression of these three receptors were found between gender groups (male vs female). We found higher gene expression of DC-SIGN in elder with age>60 and higher gene expression of L-SIGN in Caucasian than Asian. Similar to ACE2, we observed significantly higher DC-SIGN gene expression in the lungs of smokers, especially former smokers. However, smokers upregulate ACE2 and DC-SIGN gene expression in different cell types. In the whole lung, ACE2 is actively expressed in remodeled Alveolar Type II cells of former smokers, while DC-SIGN is largely expressed in monocytes of former smokers and dendritic cells of current smokers. In bronchial epithelium, no obvious gene expression of DC-SIGN and L-SIGN was observed while ACE2 was found to be actively expressed in goblet cells of current smokers and club cells of non-smokers. In conclusion, our findings may indicate that smokers, especially former smokers, and people over 60 have higher risk and are more susceptible to SARS-CoV-2 infection. Also, this study provides hints on possible SARS-CoV-2 pathogenicity mechanisms in lung infection.

The recurrent coronavirus outbreaks in China (SARS-CoV and its relative, SARS-CoV-2) have raised speculations that perhaps Asians are somehow more susceptible to these coronaviruses. Here, we test this possibility based on an analysis of the lung-specific expression of ACE2, which encodes the known cell-entry receptor of both SARS-CoV and SARS-CoV-2. We show that ACE2 expression is not affected during tumorigenesis, supporting that the abundant transcriptomes in cancer genomic studies can be informatively used to study ACE2 expression among diverse individuals without cancer. We find that ACE2 expression in the lung increases with age, but is not associated with sex. Further, Asians do not differ from other populations for ACE2 expression and do not harbor unique genetic polymorphisms in the ACE2 locus. Thus, beyond illustrating an innovative method for assessing the potential impacts of demographic factors for non-cancer diseases from large-scale cancer sample datasets, our statistically robust findings emphasize that individuals of all races require the same level of personal protection against SARS-CoV-2.

Epidemiological data indicate that 5.8% of cancer deaths world-wide are attributable to alcohol consumption. The risk of cancer is higher in tissues in closest contact on ingestion of alcohol, such as the oral cavity, pharynx and esophagus. The risk of these cancers is increased even in people who have only one alcoholic drink per day. However, since ethanol is not mutagenic and the carcinogenic metabolite of ethanol (acetaldehyde) is mostly produced in the liver, it is not clear why alcohol use preferentially exerts a local carcinogenic effect. It is well known that ethanol causes cell death at the concentrations present in alcoholic beverages; however, this effect has been overlooked probably because dead cells cannot give rise to cancer. Here I discuss that the cytotoxic effect of ethanol on the cells lining the oral cavity, pharynx and esophagus activates the division of the stem cells located in deeper layers of the mucosa to replace the dead cells. Every time stem cells divide, they become exposed to unavoidable errors associated with cell division (e.g., mutations arising during DNA replication and chromosomal alterations occurring during mitosis) and also become highly vulnerable to the genotoxic activity of endogenous and exogenous DNA-damaging agents (e.g., reactive oxygen species, acetaldehyde and tobacco carcinogens). Alcohol consumption probably increases the risk of developing cancer of the oral cavity, pharynx and esophagus by promoting the accumulation of cell divisions in the stem cells that maintain these tissues in homeostasis. Because the cytotoxic activity of ethanol is concentration-dependent, the risk of these cancers will not only increase with increasing amounts of ethanol, but also with increasing concentrations; an ounce of whisky is probably more carcinogenic when taken undiluted than when taken mixed with non-alcoholic beverages. The local cytotoxic effect of ethanol can also explain the known synergistic effect of alcohol and tobacco use on the risk of these cancers. Understanding the mechanisms of carcinogenicity of alcohol is important to reinforce the epidemiological evidence and to raise public awareness of the strong link between alcohol consumption and cancer.

In current severe global emergency situation of 2019-nCov outbreak, it is imperative to identify vulnerable and susceptible groups for effective protection and care. Recently, studies found that 2019-nCov and SARS-nCov share the same receptor, ACE2. In this study, we analyzed five large-scale bulk transcriptomic datasets of normal lung tissue and two single-cell transcriptomic datasets to investigate the disparities related to race, age, gender and smoking status in ACE2 gene expression and its distribution among cell types. We didn’t find significant disparities in ACE2 gene expression between racial groups (Asian vs Caucasian), age groups (>60 vs <60) or gender groups (male vs female). However, we observed significantly higher ACE2 gene expression in former smoker’s lung compared to non-smoker’s lung. Also, we found higher ACE2 gene expression in Asian current smokers compared to non-smokers but not in Caucasian current smokers, which may indicate an existence of gene-smoking interaction. In addition, we found that ACE2 gene is expressed in specific cell types related to smoking history and location. In bronchial epithelium, ACE2 is actively expressed in goblet cells of current smokers and club cells of non-smokers. In alveoli, ACE2 is actively expressed in remodelled AT2 cells of former smokers. Together, this study indicates that smokers especially former smokers may be more susceptible to 2019-nCov and have infection paths different with non-smokers. Thus, smoking history may provide valuable information in identifying susceptible population and standardizing treatment regimen.

Almost 6% of cancers worldwide are attributable to alcohol consumption. Approximately half of them occur in tissues highly exposed to ethanol, such as the oral cavity, pharynx, upper larynx and esophagus. However, since ethanol is not mutagenic and the carcinogenic metabolite of ethanol (acetaldehyde) is mainly produced in the liver, it is unclear why alcohol consumption preferentially causes a local carcinogenic effect. We recently hypothesized that the cytotoxic activity of ethanol could explain the high risk of these cancers in alcohol users. Here we report that short-term exposures (2-3 seconds) to ethanol concentrations between 10% and 15% start to cause a marked cytotoxic effect on human epithelial keratinocytes in a concentration-dependent manner. After discussing new evidence that cancer is the end-result of the accumulation of cell divisions in stem cells, we explain why regular alcohol consumption imposes a high risk of cancer on these tissues. Briefly, the cytotoxicity of ethanol reduces the lifespan of the cells lining these tissues. The stem cells located in deeper layers need to divide more often than usual to renew the damaged epithelia. The accumulation of cell divisions in stem cells leads to the accumulation of cancer-promoting errors (e.g., mutations arising during DNA replication) that increase their risk of malignant transformation. Cell division also exposes the DNA of the stem cells to the genotoxic activity of acetaldehyde and tobacco carcinogens. We propose that choosing alcoholic beverages containing non-cytotoxic concentrations of ethanol, or diluting ethanol to non-cytotoxic concentrations, is a simple way to reduce the risk of cancer of the oral cavity, pharynx, larynx and esophagus in alcohol users. This preventive strategy may also abolish the known synergistic effect of alcohol drinking and tobacco smoking on the risk of these cancers.

Exploring the biological significance of mutations in SARS-CoV-2 coronavirus, causing the COVID–19 pandemic, has recently become an area of paramount interest for many researchers, who are pouring their tremendous efforts, in cracking the COVID–19 pandemic code. One of many such mutations that have occurred in the viral genome is V483A mutation, which is a part of the receptor-binding motif (RBM), present in the S1 domain of the spike protein. V483A mutant virus is becoming popular in North America with 36 cases so far, due to its frequent occurrences in recent days. In this review, we have assembled all information, currently available on V483A mutation, and have made a critical analysis based on the perspectives of many researchers all around the world. Comparison is made between the wild type and the V483A mutants to analyze certain factors like the type of interaction between the virus and host cell interface, binding affinity, stability, partition energy, hydrophobicity, occurrence rate, and transmissibility. Insilico dynamic analysis shows minimal alteration in the receptor-binding domain (RBD) of V483A mutant protein in free-state and no significant change of mutant tertiary structure of RBM upon binding to the ACE2 receptor. Comprehensive details about infectivity and evasion of the immune system by the virus are discussed. This information can in turn be of monumental importance in the field of vaccine and drug development because the mutants are becoming resistant to the vaccines and monoclonal antibodies.

The current COVID-19 pandemic is one of the most devastating events in recent history. The virus causes relatively minor damage to young, healthy populations, imposing life-threatening danger to the elderly and people with diseases of chronic inflammation. Therefore, if we could reduce the risk for vulnerable populations, it would make the COVID-19 pandemic more similar to other typical outbreaks. Children don’t suffer from COVID-19 as much as their grandparents and have a much higher melatonin level. Bats are nocturnal animals possessing high levels of melatonin, which may contribute to their high anti-viral resistance. Viruses induce an explosion of inflammatory cytokines and reactive oxygen species, and melatonin is the best natural antioxidant that is lost with age. The programmed cell death coronaviruses cause, which can result in significant lung damage, is also inhibited by melatonin. Coronavirus causes inflammation in the lungs which requires inflammasome activity. Melatonin blocks these inflammasomes. General immunity is impaired by anxiety and sleep deprivation. Melatonin improves sleep habits, reduces anxiety and stimulates immunity. Fibrosis may be the most dangerous complication after COVID-19. Melatonin is known to prevent fibrosis. Mechanical ventilation may be necessary but yet imposes risks due to oxidative stress, which can be reduced by melatonin. Thus, by using the safe over-the-counter drug melatonin, we may be immediately able to prevent the development of severe disease symptoms in coronavirus patients, reduce the severity of their symptoms, and/or reduce the immuno-pathology of coronavirus infection on patients’ health after the active phase of the infection is over.

Artificial Intelligence based on Deep Learning is opening new horizons in Biomedical research and promises to revolutionize the Microscopy field. Slowly, it now transitions from the hands of experts in Computer Sciences to researchers in Cell Biology. Here, we introduce recent developments in Deep Learning applied to Microscopy, in a manner accessible to non-experts. We overview its concepts, capabilities and limitations, presenting applications in image segmentation, classification and restoration. We discuss how Deep Learning shows an outstanding potential to push the limits of Microscopy, enhancing resolution, signal and information content in acquired data. Its pitfalls are carefully discussed, as well as the future directions expected in this field.

An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred in China towards the end of 2019, and has spread rapidly ever since. Previous studies showed that some virus could affect the reproductive system and cause long-term complications. Recent studies exploring the source of SARS-CoV-2 using genomic sequencing have revealed that SARS-CoV-2 enters the host cells via the angiotensin-converting enzyme II (ACE2), the receptor that recognizes SARS-CoV. To investigate the expression of ACE2 and to explore the potential risk of infection in the reproductive system, we performed a thorough bioinformatic analysis on data from public databases involving RNA expression, protein expression, and single-cell RNA expression studies. The analyzed data showed high levels of ACE2 mRNA and protein expression in the testis and spermatids and equal levels of ACE2 expression in the uterus and lung. Comprehensive single-cell analysis identified ACE2 expression in the lung, testis, spermatids, and uterus. In conclusion, this study revealed the potential risk associated with the SARS-CoV-2 infection in the reproductive system and predicted that long-term complications might have a significant impact on the prevention and management of COVID-19, the disease caused upon infection with SARS-CoV-2.

Background: CD169 has been found overexpressed in the blood of COVID-19 patients and identified as a biomarker in the early disease. We have analysed CD169 in blood cells of COVID-19 patients to assess its role as predictive marker of the disease. Methods : The ratio of the CD169 Median median Fluorescence fluorescence Intensity intensity of CD169 between monocytes and lymphocytes (CD169 RMFI ) was analysed by flow cytometry in blood samples of COVID-19 patients (COV) and healthy donors (HD ) and correlated with immunophenotyping, inflammatory markers, cytokines mRNA expression, pulmonary involvement and disease progression. Results: CD169 RMFI increased in COV but not in HD. CD169 RMFI correlated with T-cell differentiation and exhaustion markers as well as with B cells maturation and differentiation. In vitro stimulation of PBMCs of HD with SARS-CoV-2 Spike spike protein induced CD169 RMFI together with IL-6 and IL-10 gene expression. Likewise, CD169 RMFI correlated with blood cytokine mRNA levels, inflammatory markers, and pneumonia severity in patients which that had not received any treatment at sampling. Notably, in untreated patients, CD169 RMFI reflected the respiratory outcome during hospitalization. Conclusion : Considering the immunological role of CD169 and its involvement during the infection and the progression of COVID-19, it could be considered as an early biomarker to evaluate disease progression and clinical outcome.

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.

Recent work on heavy metal pollution in Manila Bay suggests elevated concentration in the surface sediments. It is critical to identify the sources of these heavy metals to effectively rehabilitate the bay. Our study investigated the sources of the heavy metal pollution that ended up in Manila Bay and the risks associated with these toxic metals based on a recent survey conducted. Surface sediment samples with higher heavy metal concentrations were found in the upper to middle parts of the bay while lower concentrations were in the southeast areas. Multivariate analyses such as hierarchical cluster analysis (HCA), principal component analysis (PCA), and Pearson correlation analysis were used to identify the sources of the heavy metals. The heavy metal pollution in Manila Bay is attributed to several rivers draining northeast of Manila Bay, particularly the Marilao-Meycauayan-Obando River System (MMORS) which is cited as one of the 30 dirtiest river systems in the world. The ecological risks associated with heavy metals in the sediments found higher incidences of toxicity in north and middle parts of Manila Bay. Cu and Cr posed the highest risks of toxicities than any other heavy metals. Based on our analysis, the counterclockwise water gyre of the bay can explain the distribution and ecological risks associated with the heavy metals as supported by the findings of the PCA. Given the high priority by the Philippine government to rehabilitate the bay, our study strongly shows that efforts to restore the ecological status of Manila Bay will only succeed if the pollution from major rivers draining to it will be properly addressed.

Prothrombotic thrombocytopathy mimicking heparin-induced thrombocytopenia has been observed in patients with severe COVID-19 and after immunisation with the Vaxzevria vaccine. Herein, we discuss the possible pathogenesis of this disorder focusing on the possible involvement of anti-platelet factor 4 (PFA) autoantibodies.

Many of the wide-ranging symptoms of COVID-19 have not been associated previously with a respiratory illness. A similarity between these atypical symptoms and the symptoms of malnutrition was observed. To investigate, a comparison of COVID-19 symptomatology with recognised states of malnutrition showed a significant relationship that was further explored in a review of the literature. This hypothesis links the atypical symptoms to the effects of increasing protein malnutrition. The rapid appearance of malnutrition symptoms at the beginning of the COVID-19 infection is concurrent with the rapid cell proliferation of the immune system. Although previous work has, in general, assumed that the body is capable of providing for the needs of the immune system during infection, heightened immune activity from the commencement of COVID-19 could require an early increase in energy yielding sources. Should insufficient availability of protein resources occur, this could quickly lead to malnutrition. Any continuing insufficiency, during the active phase of the virus, might result in widespread depletions in the tissues and the consequential malfunctioning of many organs. A new appraisal of the immune system requirements needed to counteract the impact of the novel virus, COVID-19, could show the potential benefit for earlier protein intervention in the disease process. This hypothesis could also have relevance for other life situations where a rapid cell proliferation might occur.

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.

Cellular agriculture is defined as the production of agricultural products from cell cultures rather than from whole plants or animals. With growing interest in cellular agriculture as a means to address the public health, environmental, and animal welfare challenges of animal agriculture, the concept of producing seafood from fish cell- and tissue-cultures is emerging as a means to address similar challenges with industrial aquaculture systems and marine capture. Cell-based seafood - as opposed to animal-based seafood - can combine developments in biomedical engineering with modern aquaculture techniques. Biomedical engineering developments such as closed-system bioreactor production of land animal cells create a basis for large scale production of marine animal cells. Aquaculture techniques such as genetic modification and closed system aquaculture have achieved marked gains in production that can pave the way for innovations in cell-based seafood production. Here, we present the current state of innovation relevant to the development of cell-based seafood across multiple species as well as specific opportunities and challenges that exist for advancing this science. The authors find that the physiological properties of fish cell- and tissue- culture may be uniquely suited to cultivation in vitro. These physiological properties, including hypoxia tolerance, high buffering capacity, and low-temperature growth conditions, make marine cell culture an attractive opportunity for scale production of cell-based seafood; perhaps even more so than mammalian and avian cell cultures for cell-based meats. This, coupled with the unique capabilities of crustacean tissue-friendly scaffolding such as chitosan, a common seafood waste product and mushroom derivative, presents great promise for cell-based seafood production via bioreactor cultivation. To become fully realized, cell-based seafood research will require more understanding of fish muscle culture and cultivation; more investigation into serum-free media formulations optimized for fish cell culture; and bioreactor designs tuned to the needs of fish cells for large scale production.

Abstract The COVID-19 pandemic is thought to began in Wuhan, China in December 2019. Mobility analysis identified East-Asia and Oceania countries to be highly-exposed to COVID-19 spread, consistent with the earliest spread occurring in these regions. However, here we show that while a strong positive correlation between case-numbers and exposure level could be seen early-on as expected, at later times the infection-level is found to be negatively correlated with exposure-level. Moreover, the infection level is positively correlated with the population size, which is puzzling since it has not reached the level necessary for population-size to affect infection-level through herd immunity. These issues are resolved if a low-virulence Corona-strain (LVS) began spreading earlier in China outside of Wuhan, and later globally, providing immunity from the later appearing high-virulence strain (HVS). Following its spread into Wuhan, cumulative mutations gave rise to the emergence of an HVS, known as SARS-CoV-2, starting the COVID-19 pandemic. We model the co-infection by an LVS and an HVS, and show that it can explain the evolution of the COVID-19 pandemic and the non-trivial dependence on the exposure level to China and the population-size in each country. We find that the LVS began its spread a few months before the onset of the HVS, and that its spread doubling-time is $\sim 1.59\pm 0.17$ times slower than the HVS. Although more slowly spreading, its earlier onset allowed the LVS to spread globally before the emergence of the HVS. In particular, in countries exposed earlier to the LVS and/or having smaller population-size, the LVS could achieve herd-immunity earlier, and quench the later-spread HVS at earlier stages. We find our two-parameter (the spread-rate and the initial onset time of the LVS) can accurately explain the current infection levels (R^2$\mathrm{=0.74}$; correlation p-value (p) of 5x10^-13$$). Furthermore, countries exposed early should have already achieved herd-immunity. We predict that in those countries cumulative infection levels could rise by no more than 2-3 times the current level through local-outbreaks, even in the absence of any containment measures. We suggest several tests and predictions to further verify the double-strain co-infection model and discuss the implications of identifying the LVS.

Animals, with their complex and obligate multicellularity, evolved from microbial eukaryotes that were likely obligately or facultatively unicellular. The nature of the unicellular progenitors of animals has intrigued biologists since the late 19^th century, coinciding with the parallel spread of the cell theory and the theory of evolution. However, views on the ancestry of animals have been extremely varied. The huge diversity of single-celled organisms, the tremendous plasticity of animal cellular phenotypes, and the difficulties of organizing both into clear phylogenies in the pre-molecular era allowed a wide range of hypotheses to flourish, with nearly every major single-celled lineage, at one time or another, having been proposed as the precursor of animals. Most of these hypotheses never gained followers beyond their originator (such as the ideas that animals evolved directly from either bacteria, Volvox or fungi) and will not be discussed here. Three concepts, however, have been enduring and influential: (1) the amoeboid theory; (2) the flagellate theory; and the (3) the ciliate theory – to which a fourth category can now be added: (4) a mixed model, in which the ancestor was phenotypically plastic. We will discuss their origin, history, and current relevance.

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.

Efficiently targeted cancer therapy without causing detrimental side effects is necessary for alleviating patient care and improving survival rates. This paper presents observations of morphological changes in H1299 human lung cancer cells following W-band MMW irradiation (75 – 105 GHz) at a non-thermal power density of 0.2 mW/cm², investigated over 14 days of subsequent physiological incubation following exposure. Microscopic analyses of physical parameters measured indicate MMW irradiation induces significant morphological changes characteristic of apoptosis and senescence. The Immediate short-term responses translate into long-term effects, retained over the duration of the experiment(s); reminiscent of the phenomenon of Accelerated Cellular Senescence (ACS) achieving terminal tumorigenic cell growth. Further, results were observed to be treatment-specific in energy (dose) dependent manner and were achieved without the use of chemotherapeutic agents, ionizing radiation or thermal ablation employed in conventional methods; thereby overcoming associated side effects. Adaptation of the experimental parameters of this study for clinical oncology concomitant with current developmental trends of non-invasive medical endoscopy alleviates MMW therapy as an effective treatment procedure for human non-small cell lung cancer (NSCLC).

Food pathogens contaminate food products that allow their growth on the shelf and also under refrigerated conditions. Therefore, it is of utmost importance to lower the limit of detection (LOD) of the method used and to obtain the results within hours to few days. Biosensor methods exploit the available technologies to individuate and provide an approximate quantification of the bacteria present in a sample. The main bottleneck of these methods depend on the aspecific binding to the surfaces and on a change in sensitivity when bacteria are in a complex food matrix in respect to bacteria in a liquid food sample. In this review we introduce Surface Plasmon Resonance (SPR), new advancements in SPR techniques, and Electrochemical Impedance Spectroscopy (EIS), as label-free biosensing technologies for the detection of L. monocytogenes in foods. The application of the two methods has made possible the detection of L. monocytogenes with LOD of 1 log CFU/mL. Further advancement are envisaged through the combination of biosensor methods with immunoseparation of bacteria from larger volumes.

After UV excitation, gas phase thymine returns to ground state in 5 to 7 ps, showing multiple time constants. There is no consensus on the assignment of these processes, with a dispute between models claiming that thymine is trapped either in the first (S1) or in the second (S2) excited states. In the present study, nonadiabatic dynamics simulation of thymine is performed on the basis of ADC(2) surfaces, to understand the role of dynamic electron correlation on the deactivation pathways. The results show that trapping in S2 is strongly reduced in comparison to previous simulations considering only non-dynamic electron correlation on CASSCF surfaces. The reason for the difference is traced back to the energetic cost for formation of a CO p bond in S2.

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.

Following legalization, cannabis has quickly become an important horticultural crop in Canada and increasingly so in other parts of the world. However, due to previous legal restrictions on cannabis research there are limited scientific data on the relationship between nitrogen (N), phosphorus (P), and potassium (K) supply (collectively: NPK) and the crop yield and quality. This study examined the response of a high delta-9-tetrahydrocannabinol (THC) Cannabis sativa cultivar grown in deep-water culture with different nutrient solution treatments varying in their concentrations (mg L^-1) of N (70, 120, 180, 250, 290), P (20, 40, 60, 80, 100) and K (60, 120, 200, 280, 340) according to a central composite design. Results demonstrated that inflorescence yield responded quadratically to N and P, with the optimal concentrations predicted to be 194 and 59 mg L^-1, respectively. Inflorescence yield did not respond to K in the tested range. These results can provide guidance to cultivators when formulating nutrient solutions for soilless cannabis production and demonstrates the utility of surface response design for efficient multi-nutrient optimization.

Mass transfer restrictions of scaffolds are currently hindering the development of three-dimensional (3D), clinically viable, and tissue engineered constructs. For this situation, a 3D poly(lactide-co-glycolide)/hydroxyapatite porous scaffold, which was much favorable for transfer of nutrients to and waste products from the cells in the pores, was developed in this study. The 3D scaffold had an innovative structure, including macropores with diameters of 300−450 μm for cell ingrowth and microchannels with diameters of 2−4 μm for nutrition and waste exchange. The mechanical strength in wet state was strong enough to offer the structural support. The typical structure was more beneficial for the attachment, proliferation, and differentiation of rabbit bone marrow mesenchymal stem cells (rBMSCs). The alkaline phosphatase (ALP) activity and calcium (Ca) deposition were evaluated on the differentiation of rBMSCs, and the results indicated that the microchannel structure was very favorable for differentiating rBMSCs into maturing osteoblasts. For repairing rabbit radius defects in vivo, there was rapid healing in the defects treated with the 3D porous scaffold with microchannels, where the bridging by a large bony callus was observed at 12 weeks post-surgery. Based on the results, the 3D porous scaffold with microchannels was a promising candidate for bone defect repair.

Water quality assessment in pastoral of Tibetan Plateau, which is water sources for about 40% of world's population and the runoff-yield area of Yellow rivers, is very important. In this paper, Xiahe county which belongs to Tibetan Plateau pastoral was investigated. Six parameters(via, chloride, COD, ammonia nitrogen, nitrate, fluoride, sulfate) were selected to assess the water quality and health degree by using fuzzy comprehensive evaluation methods. The hydrochemical type in surface water was of HCO3--Mg2+-Ca2+ type. The cations and anions in surface water were mainly from weathering and dissolution of carbonate rock. Results showed that the water quality in all 69 sampling sites was all of class Ⅰ. The integrated health degree reached more than 0.85 and the health rate were 100%. Although ammonia nitrogen was regarded as the main contamination factor, but it had a little effect on the entire body of water. Overall, the surface water qualities of most samples in Xiahe County was good condition.

We evaluated oleanolic acid (OA)-induced anti-cancer activity, apoptotic mechanism, cell cycle status, and MAPK kinase signaling in DU145 (prostate cancer), MCF-7 (breast cancer), and U87 (human glioblastoma) cells. The IC50 values for OA-induced cytotoxicity were 112.57 in DU145, 132.29 in MCF-7, and 163.60 in U87 cells, respectively. OA (at 100 µg/mL) increased the number of apoptotic cells to 27.0% in DU145, 27.0% in MCF-7, and 15.7% in U87 cells, when compared to control cells. This enhanced apoptosis was due to increases in p53, cytochrome c, and Bax expression. OA-treated DU145 cells were arrested in G2 because of the activation of p-ERK and p21, and the decrease in cyclin B1 and cyclin E expression. Furthermore, OA-treated MCF-7 cells were arrested in G1 owing to the activation of p-JNK, p-ERK, p21, and p27, and the decrease in p-AKT, cyclin E, and CDK2. U87 cells also exhibited G1 phase arrest caused by the increase in p-ERK, p-JNK, p21, and p27, and the decrease in CDK2. Thus, OA arrests the cell cycle in different phases, and increases apoptosis in cancer cells. These results suggest that OA may alter the expression of cell cycle regulatory proteins in a cancer type-dependent manner.

In the study of relativistic jets one of the key open questions is their interaction with the environment on the microscopic level. Here, we study the initial evolution of both electron–proton (e^- - p⁺) and electron–positron (e^±) relativistic jets containing helical magnetic fields, focusing on their interaction with an ambient plasma. We have performed simulations of "global" jets containing helical magnetic fields in order to examine how helical magnetic fields affect kinetic instabilities such as the Weibel instability, the kinetic Kelvin-Helmholtz instability (kKHI) and the Mushroom instability (MI). In our initial simulation study these kinetic instabilities are suppressed and new types of instabilities can grow. In the e^- - p⁺ jet simulation recollimation-like instability occurs and jet electrons are strongly perturbed. In the e^± jet simulation a recollimation-like instability occurs at early times followed by a kinetic instability and the general structure is similar to a simulation without helical magnetic field. Simulations using much larger systems are required in order to thoroughly follow the evolution of global jets containing helical magnetic fields.

In urban area, one of the great problem is the rise of temperature, which leads to form the urban heat island effect. This paper refers to the trend of the urban surface temperature extracted from the Landsat images from which to consider changes in the formation of surface urban heat island for the north of Ho Chi Minh city in period 1995-2015. Research has identified land surface temperature from thermal infrared band, according to the ability of the surface emission based on characteristics of normalized difference vegetation index NDVI. The results showed that temperature fluctuated over the city with a growing trend and the gradual expansion of the area of the high-temperature zone towards the suburbs. Within 20 years, the trend of the formation of surface urban heat island with two typical locations showed a clear difference between the surface temperature of urban areas and rural areas with space expansion of heat island in 4 times in 2015 compared to 1995. An extreme heat island located in the inner city has an area of approximately 18% compared to the total area of the region. Since then, the solution to reduce the impact of urban heat island has been proposed, in order to protect the urban environment and the lives of residents in Ho Chi Minh City becoming better

The cell case temperature versus time profiles of a multistage fast charging technique (4C-1C-CV)/fast discharge (4C) in a 2.3 Ah cylindrical lithium-ion cell are analyzed using a 1D thermal model. Heat generation is dominated by the irreversible component associated to cell overpotential, although evidences of the reversible component are also observed, associated to the heat related to entropy from the electrode reactions. The final charging stages (i.e., 1C-CV) significantly reduce heat generation and cell temperature during charge, resulting in a thermally safe charging protocol. Cell heat capacity was determined from cell specific heats and cell materials thickness. The 1D model adjustment of the experimental data during the 2 min. resting period between discharge and charge allowed us to calculate both the time constant of the relaxation process and the cell thermal resistance. The obtained values of these thermal parameters used in the proposed model are almost equal to those found in the literature for the same cell model, which suggests that the proposed model is suitable for its implementation in thermal management systems.

This study was designed for the first time to improve phenolic yield and antioxidant activity of ultrasonic-assisted extraction from Acer truncatum leaves (ATL) using response surface methodology, and phenolic composition in ATL extracted under the optimized condition were characterized by UPLC-QTOF-MS/MS. Solvent and extraction time were selected based on preliminary experiments, and a four-factors-three-levels central composite design was conducted to optimize solvent concentration (X₁), material-to-liquid ratio (X₂), ultrasonic temperature (X₃) and power (X₄) for an optimal total phenol yield (Y₁) and DPPH• antioxidant activity (Y₂). The results showed that the optimal combination was ethanol: water (v:v) 66.21%, material-to-liquid ratio 1:15.31 g/mL, ultrasonic temperature 60 °C, power 267.30 W, and time 30 min with three extractions, giving a maximal total phenol yield of 7593.62 mg gallic acid equivalent /100 g d.w. and a maximal DPPH• antioxidant activity of 74241.61 μmol Trolox equivalent/100 g d.w.. Furthermore, 22 phenolics were first identified in ATL extract obtained under the optimized conditions, indicating that gallates, gallotannins, quercetin, myricetin and chlorogenic acid derivatives were the main phenolic composition in ATL. What’s more, a gallotannins pathway existing in ATL from gallic acid to penta-O-galloyl-glucoside was interpreted. All these results provided practical information aiming at full utilization of phenolics in ATL, together with fundamental knowledge for further research.

It is known that knockdown of the mitochondrial 18 kDa translocator protein (TSPO) as well as TSPO ligands modulate various functions, including functions related to cancer. To study the ability of TSPO to regulate gene expression regarding such functions, we applied microarray analysis of gene expression to U118MG glioblastoma cells. Within 15 minutes, the classical TSPO ligand PK 11195 induced changes in expression of immediate early genes and transcription factors. These changes also included gene products that are part of the canonical pathway serving to modulate general gene expression. These changes are in accord with reverse transcriptase (RT) real-time -PCR. At the time points of 15, 30, 45, and 60 minutes, as well as 3 and 24 hours of PK 11195 exposure, the functions associated with the changes in gene expression in these glioblastoma cells covered well known TSPO functions. These functions included cell viability, proliferation, differentiation, adhesion, migration, tumorigenesis, and angiogenesis. This was corroborated microscopically for cell migration, cell accumulation, adhesion, and neuronal differentiation. Changes in gene expression at 24 hours of PK 11195 exposure were related to downregulation of tumorigenesis and upregulation of programmed cell death. In the vehicle treated as well as PK 11195 exposed cell cultures, our triple labeling showed intense TSPO labeling in the mitochondria but no TSPO signal in the cell nuclei. Thus, mitochondrial TSPO appears to be part of the mitochondria-to-nucleus signaling pathway for modulation of nuclear gene expression. The novel TSPO ligand 2-Cl-MGV-1 appeared to be very specific regarding modulation of gene expression of immediate early genes and transcription factors.

ACE2, the putative receptor for the novel coronavirus (2019-nCoV), played an important role in cell entry of 2019-nCoV. However, it is not yet clear what cell types within the human body express ACE2. Here, a systematic analysis was undertaken using published single cell datasets. In total, our study analyzed 229652 cells, from five different organs, derived from 88 donors. The top ACE2 expressing cells include proximal tubule cells in the kidney and enterocytes in the intestine. Other major ACE2 expressing cells in the kidney include podocytes, intercalated cells and endothelial cells. Our results offer a comprehensive atlas of ACE2 expression at the single cell level and unravel the enormous potential targets of 2019-nCoVinfection beyond the lung.

Deformation of the surface of diamagnetic liquid by magnetic field is called the “Moses Effect”. Physics and applications of the direct and inverse Moses effects are reviewed. Experimental techniques enabling visualization of the effects are surveyed. Impact of magnetic field on micro- and macroscopic properties of liquids is addressed. Influence of the surface tension on the shape of the near-surface dip formed in a diamagnetic liquid by magnetic field is reported. Floating of diamagnetic bodies driven by the Moses effect is treated. The effect of the “magnetic memory of water” in its relation to the Moses Effect is discussed. The dynamics of self-healing of near-surface dips due to the Moses Effect is considered.

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.

Structure from Motion with Multi-View Stereo photogrammetry (SfM) is increasingly utilised in geoscience investigations as a cost-effective method of acquiring high resolution (sub-meter) topographic data, but has not been thoroughly tested in gullied savanna systems. The aim of this study was to test the accuracy of topographic models derived from aerial (via an Unmanned Aerial Vehicle, ‘UAV’) and ground-based (via a handheld digital camera, ‘Ground’) SfM in modelling a hillslope gully system in dry-tropical savanna, and to assess the strengths and limitations of the approach at different scales. A UAV survey covered an entire hillslope gully system (0.715 km²), whereas a Ground survey covered a single gully within the broader system (650 m²). SfM topographic models, including Digital Surface Models (DSM) and dense point clouds, were compared against RTK-GPS point data and a pre-existing airborne LiDAR Digital Elevation Model (DEM). Results indicate UAV SfM can deliver topographic models with a resolution and accuracy suitable to define gully systems at a hillslope scale (e.g., 0.1 m resolution with ~ 0.5 – 1.3 m elevation error), while ground-based SfM is more capable of quantifying gully morphology (e.g., 0.01 m resolution with ~ 0.1 m elevation error). Key strengths of SfM for these applications include: the production of high resolution 3D topographic models and ortho-photo mosaics, low survey instrument costs (< $AUD 3,000); and rapid survey time (4 and 2 hours for UAV and Ground survey respectively). Current limitations of SfM include: difficulties in reconstructing vegetated surfaces; uncertainty as to optimal survey and processing designs; and high computational demands. Overall, this study has demonstrated great potential for SfM to be used as a cost-effective tool to aid in the mapping, modelling and management of hillslope gully systems at different scales, in tropical savanna landscapes and elsewhere.

Nanocellulose is cellulose in the form of nanostructures, i.e. features not exceeding 100 nm at least in one dimension. These nanostructures include nanofibrils, e.g. in bacterial cellulose; nanofibers, e.g. in electrospun matrices; nanowhiskers and nanocrystals. These structures can be further assembled into bigger 2D and 3D nano-, micro- and macro-structures, such as nanoplatelets, membranes, films, microparticles and porous macroscopic matrices. There are four main sources of nanocellulose: bacteria (Gluonacetobacter), plants (trees, shrubs, herbs), algae (Cladophora) and animals (Tunicata). Nanocellulose has emerged for a wide range of industrial, technology and biomedical applications, e.g. for adsorption, ultrafiltration, packaging, conservation of historical artifacts, thermal insulation and fire retardation, energy extraction and storage, acoustics, sensorics, controlled drug delivery, and particularly for tissue engineering. Nanocellulose is promising for use in scaffolds for engineering of blood vessels, neural tissue, bone, cartilage, liver, adipose tissue, urethra and dura mater, for repairing connective tissue and congenital heart defects, and for constructing contact lenses and protective barriers. This review is focused on applications of nanocellulose in skin tissue engineering and wound healing as a scaffold for cell growth, for delivering cells into wounds, and as a material for advanced wound dressings coupled with drug delivery, transparency and sensorics. Potential cytotoxicity and immunogenicity of nanocellulose are also discussed.

Fossil fuels and carbon origin resources are affecting our environment. Therefore, alternative energy sources have to be established to co-produce energy along with fossil fuels and carbon origin resources until it is the right time to replace them. Microbial Fuel Cell (MFC) is a promising technology in the field of energy production. Compared to the conventional power sources it is more efficient and not controlled by the Carnot cycle. Its high efficiencies, low noise, and less pollutant output could make it revolutionize in the power generation industry with a shift from centrally located generating stations and long-distance transmission lines to dispersed power generation at load sites. In this review, several characteristics of the MFC technology will be highlighted. First, a brief history of abiotic to biological fuel cells and subsequently, microbial fuel cells is presented. Second, the focus is then shifted to elements responsible for the making MFC working with efficiency. Setup of the MFC system for every element and their assembly is then introduced, followed by an explanation of the working machinery principle. Finally, microbial fuel cell designs and types of main configurations used are presented along with scalability of the technology for the proper application.

Cell-penetrating peptides (CPPs), a group of small peptides capable of promoting the transport of molecular cargo across the plasma membrane, have become important tools in promoting the cellular uptake of exogenously delivered macromolecules. GV1001, a peptide derived from a reverse-transcriptase subunit of telomerase (hTERT) and developed as a vaccine against various cancers, reportedly has unexpected CPP properties. Unlike typical CPPs, such as the HIV-1 TAT peptide, GV1001 enabled the cytosolic delivery of macromolecules such as proteins, DNA and siRNA via extracellular heat shock protein 90 (eHSP90) and 70 (eHSP70) complexes. The eHSP-GV1001 interaction may have biological effects in addition to its cytosolic delivery function. GV1001 was originally designed as a MHC class II-binding cancer epitope, but its CPP properties may contribute to its strong anti-cancer immune response relative to other telomerase peptide-based vaccines. Cell signaling via eHSP-GV1001 binding may lead to unexpected biological effects, such as direct anticancer or antiviral effects. In this review, we focus on the CPP effects of GV1001 bound to eHSP90 and ehsp70.

Surface initiated atom transfer radical polymerization (SI-ATRP) is one of the most versatile technique to modify the surface properties of material. Recent developed metal free SI-ATRP makes such technique more widely applicable. Herein photo-induced metal-free SI-ATRP of methacrylates, such as methyl methacrylate, N-isopropanyl acrylamide, and N,N- dimethylaminoethyl methacrylate, on the surface of SBA-15 was reported to fabricate organic-inorganic hybrid materials. SBA-15 based polymeric composite with adjustable graft ratio was obtained. The structure evolution during the SI-ATRP modification of SBA-15 was monitored and verified by FT-IR, XPS, TGA, BET, and TEM. The obtained polymeric composite showed enhanced adsorption ability for the model compound toluene in aqueous. This procedure provides a low cost, ready availability, and facile modification way to synthesize the polymeric composites without the contamination of metal.

Extremely low-frequency electromagnetic fields (ELF-EMFs) are non-ionizing radiations typically emitted by power lines, electrical wiring and electrical appliances. Epidemiological studies have repeatedly shown a positive association between ELF-EMFs and childhood leukemia. Exposures greater than 0.3-0.4 µT increase the risk by approximately 1.5-2 fold, and estimates indicate that up to 2% of childhood leukemia cases in Europe may be attributable to ELF-EMFs. However, it is considered unlikely that ELF-EMFs can cause cancer, because carcinogenesis requires the accumulation of DNA alterations and ELF-EMFs do not have enough energy to damage the DNA. Lack of biological plausibility is a barrier to accept the evidence of carcinogenicity in human studies and to take measures to protect pregnant women and children from ELF-EMFs. Recent evidence indicates that non-mutagenic agents can cause DNA alterations and increase the risk of cancer by promoting the accumulation of cell divisions in stem cells. Cell division generates DNA alterations (e.g., mutations arising during DNA replication), which occur even in the absence of DNA-damaging agents. Importantly, ELF-EMFs can trigger the division of stem cells; this effect is under development in the field of regenerative medicine. A possible mechanism by which ELF-EMFs induce the malignant transformation of hematopoietic stem cells is discussed.

The present study aims to develop an efficient numerical method for computing the diffraction and radiation of water waves with horizontal long cylindrical structures, such as floating breakwaters. A higher-order scheme is used to discretize geometry of the structure as well as the relevant physical quantities. As the kernel of this method, Wehausen’s free-surface Green function is calculated by a newly-developed Gauss-Kronrod adaptive quadrature algorithm after elimination of its Cauchy-type singularities. To improve computational efficiency, a Chebyshev approximation approach is applied to a fast calculation of the Green function that needs evaluation thousands of times. In addition, OpenMP parallel technique is used to the formation of influence coefficient matrix, which significantly reduces CPU time. Finally, computations are performed on wave exciting forces and hydrodynamic coefficients for the long cylindrical structures, either floating or submerged. Comparison with other numerical and analytical methods demonstrates good performance of the present method.

An adequate representation of the water infiltration process in the soil allows improving the efficiency in application and the uniformity in surface irrigation. The Green and Ampt model has shown a good representation of the process, and researchers from the United States Department of Agriculture (USDA) determined the values of their parameters for soils of that country, which are shown in tables or through functional relationships and this information is used as reference in several parts of the world, although there is no certainty that they are representative of the soils in Mexico. In this study, the parameters of the Green & Ampt equation were determined and evaluated in some soils of agricultural importance in Mexico. The parameters were obtained in four ways: one of them applied a methodology adapted from Brooks and Corey to quantify the wetting front capillary pressure head and used an permeameter under constant hydraulic head to determine the saturated hydraulic conductivity, and the other three consisted in taking them from three studies reported by the USDA. The values of the parameters suggested in Mexico drastically underestimated the results with relative errors (RE) in a range of -49.0 to -94.0% and the most representative were those obtained with the methodology proposed in this research with RE of -15.0 to 6.0%.

The outbreak of the 2019 Novel Coronavirus (2019-nCoV) has rapidly spread from Wuhan, China to multiple countries, causing staggering number of infections and deaths. A systematic profiling of the immune vulnerability landscape of 2019-nCoV is lacking, which can bring critical insights into the immune clearance mechanism, peptide vaccine development, and antiviral antibody development. In this study, we predicted the potential of all the 2019-nCoV viral proteins to induce class I and II MHC presentation and form linear antibody epitopes. We showed that the enrichment for T cell and B cell epitopes is not uniform on the viral genome, with several focused regions that generate abundant epitopes and may be more targetable. We showed that genetic variations in 2019-nCoV, though fewer for the moment, already follow the pattern of mutations in related coronaviruses, and could alter the immune vulnerability landscape of this virus, which should be considered in the development of therapies. We create an online database to broadly share our research outcome. Overall, we present an immunological resource for 2019-nCoV that could significantly promote both therapeutic development and mechanistic research.

Electric vehicles (EV) are getting more commonplace in the transportation sector in recent times. As the present trend suggests, this mode of transport is likely to replace the internal combustion engine (ICE) vehicles in near future. Each of the main EV components has a number of technologies that are currently in use or can become prominent in the future. EVs can cause significant impacts on the environment, power system, and other related sectors. The present power system can face huge instabilities with enough EV penetration; but with proper management and coordination, EVs can be turned into a major contributor to the successful implementation of smart grid. There are possibilities of immense environmental benefits as well, as the EVs can extensively reduce the greenhouse gas emission from the transportation sector. However, there are some major obstacles for EVs to overcome before replacing the ICE vehicles totally. This paper is focused on reviewing all the useful data available on EV configurations, energy sources, motors, charging techniques, optimization techniques, impacts, trends, and possible directions of future developments. Its objective is to provide an overall picture of the current EV technology and ways of future development to assist in future researches in this sector.

In this work commercial 18650 lithium-ion cells with LiMn₂O₄, LiFePO₄ and Li(Ni_0.33Mn_0.33Co_0.33)O₂ cathodes were exposed to external heating in an Accelerating Rate Calorimeter (es-ARC, THT Company) to investigate the thermal behavior under abuse conditions. New procedures for measuring external and internal pressure change of cells were developed. The external pressure was measured utilizing a gas-tight cylinder inside the calorimeter chamber in order to detect venting of the cells. For internal pressure measurements, a pressure line connected to a pressure transducer was directly inserted into the cell. During the thermal runaway experiments, three stages (low rate, medium rate and high rate reaction) have been observed. Both pressure and temperature change indicated different stages of exothermic reactions, which produced gases or/and heat. The onset temperature of thermal runaway was estimated according to temperature and pressure changes. Moreover, the different activation energies for the exothermic reactions could be derived from Arrhenius plots.

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.

Ovarian cancer (OC) is the most lethal gynecologic malignancy. Cannabis sativa is being used to treat different medical conditions. We sought to examine the effectiveness of combinations of cannabis compounds against OC. Cytotoxic activity was determined by XTT assay on HTB75 and HTB161 cell lines. Apoptosis and cell cycle were determined by fluorescence-activated cell sorting (FACS). Gene expression was determined by quantitative PCR. The two most active fractions, F5 and F7, from a high Δ9–tetrahydrocannabinol (THC) cannabis strain extract and their standard mix (SM) showed cytotoxic activity against OC cells. The most effective phytocannabinoid combination was THC+cannabichromene (CBC)+cannabigerol (CBG). F5, F7 and SM affected cell cycle, led to cell apoptosis and to a marked reduction in cell migration. Moreover, these fractions act in synergy with niraparib, and were ~50 fold more cytotoxic to OC cells than to normal keratenocytes. Niraparib+F7 treatment was effective on OC patient's cells. F7 and the niraparin+fraction (F5 and F7) treatments reduced Mitogen-Activated Protein Kinase 4 (MAPK4) gene expression; this reduction may act in synergy with the niraparib inhibition of Poly (ADP-ribose) polymerase 1 (PARP1) activity. Combinations of cannabis compounds and niraparib should be examined for efficacy in pre-clinical studies and clinical trials.

Lamin A, B and C, the nuclear intermediate-filament proteins, play a role in epigenetic regulation. While Lamin B is expressed in all nucleated cells studied, Lamin A/C are transcribed in most somatic cell types except mature B lymphocytes. Since Epstein-Barr virus (EBV), a human gammaherpesvirus, is associated with tumorigenic processes and is known to alter the epigenotype of its host cells, we studied the expression of the LMNA gene and its epigenetic marks in EBV-carrying human lymphoid cell lines. We observed a high lamin A/C mRNA and protein expression in EBV-immortalized lymphoblastoid cell lines (LCLs) and in group III Burkitt lymphoma (BL) lines where hypomethylated first exons were observed with activating histone marks. In most cell lines with low promoter activity a highly methylated first exon could be detected. Our data showed that methylation of the first exon of LMNA was associated with the downregulation of LMNA expression whereas euchromatic histone marks were enriched at active LMNA promoters in EBV-immortalized LCLs. These data suggest a role for viral latency products to activate LMNAp in EBV-infected latency type III B cells in vitro. Expression of lamin A/C may contribute to the establishment of activated B cell phenotype that needs further explorations.

Here, we present a staged approach for an innovative repurposing of a portable infant humidicrib into a live cell growth, observation, and imaging system. Furthmore, humidicrib can support different variations of “umbilical” bioreactors, and can be used to conduct electrophysiology experiments and in situ immunohistochemistry. Modifications incorporate a closed loop carbon dioxide (CO₂) concentration control system with umbilical CO₂ and heating support for tailored bioreactors. The repurposing cost is inexpensive and allows for the continued observation and imaging of cells. This prototype unit has been used to continuously observe and image live primary neurons for up to 21 days. This demonstrates the repurposed units’ suitability for use in tissue culture based research, particularly where modifications to microscopes are required or where sensitive manipulation outside of a standard incubator is needed.

Low temperature cofired ceramics (LTCC) have conquered a niche segment in biological microelectromechanical systems (BioMEMS) during the last two decades. Since 3-dimensional assembly and rapid prototyping capability are outstanding features of the technology, bioreactors with complex geometry can easily be produced. Particularly needed functions are working electrodes, e.g. for impedance measurements and reference electrodes consisting in platinum or silver-silver chloride. Although the distinct grainy surface of thick film materials influences the double layer properties, data describing the bioelectronic interface and biocompatibility of common thick film materials are rarely published up to now. This works aims to fill this gap by studying the surface properties, composition, electrochemical properties and biocompatibility of commercially available thick film materials. It was found that thick film gold is suitable as electrode material in direct cell contact since an appropriate proliferation of the cell culture was observed. Poly(3,4-ethylenedioxythiophene) coating decreases the absolute value of the zeta potential of thick film gold from 16.55 V to 11.78 mV without any change in vitality of the cells. Thick film platinum layers have a porous structure entailing an enlargement of the effective surface by a factor of 21.6 and can be used as reference instead of silver/silver chloride, which was identified to be incompatible with cell culture. The investigations show that some commercially available cost-effective thick film materials are compatible with cell culture and the here presented data give an orientation for the use of the same in LTCC bioreactors.

Blood has certain significant physical properties, which the authors investigated. This paper provides values of surface tension and viscosity of blood at 37 °C, as well as relationship between them plotted on a cross-plot. By applying Hagen- Poiseuille equation and Jurin's law to the experimentally obtained data, the authors calculated with great accuracy viscosity and surface tension of blood. Evaluating both of the properties using described methods required from the authors to know the density of investigated liquid, which was found to be on average $\rho=1063,56 \frac{kg}{m^3}$. The authors took blood samples from 30 healthy subjects and determined aforementioned physical properties. There has been made a distinction in regard of a sex of the blood donor. Results indicate that both surface tension and viscosity are independent from sex of a subject, as well as indicate that there is no correlation between viscosity and surface tension of blood at 37\degree C. Average values of surface tension and viscosity were found to be $\sigma=5,241\pm 0,262 \cdot 10^{-2}\frac{J}{m^2}$ and $\eta=3,352\pm0,360 \cdot 10^{-3} Pa \cdot s$, respectively.

Nowadays, the study of preparing silica/rubber composites, which can be used in “green tire”, in energy saving method is fast-growing. In our work, silica modified by using alcohol polyoxyethylene ether (AEO) and 3-Mercaptopropyltriethoxysilane (K-MEPTS) together were investigated. Thermal gravimetric analyzer (TGA) result indicated that both AEO and K-MEPTS could be grafted on the silica surface. Raman spectroscopy confirmed that the AEO could generate a certain steric hindrance for the mercaptopropyl group on K-MEPTS. Silica modified by using AEO and K-MEPTS together can be completely co-coagulated with the rubber in preparing silica/natural rubber (NR) composites by latex compounding method. AEO can form a physical interface between silica and rubber; meanwhile, K-MEPTS can form a chemical interface between silica and rubber. The effects of chemical and physical interface between silica and rubber on dynamic and mechanical performances of silica/NR composites were also given in this research. A proper combination of physical and chemical interface between silica and NR can improve performances of silica/NR composites.

Pseudopterosin, produced by the sea whip of the genus Antillogorgia, possesses a variety of promising biological activities including potent anti-inflammatory effects. However, few studies examined pseudopterosin in the treatment of cancer cells and, to our knowledge, the ability to inhibit triple negative breast cancer (TNBC) proliferation or invasion has not been explored. Thus, we evaluated the as yet unknown mechanism of action of pseudopterosin: Pseudopterosin was able to inhibit proliferation of TNBC. Interestingly, analyzing breast cancer cell proliferation after knocking down glucocorticoid receptor α (GRα) revealed that anti-proliferative effects of pseudopterosin were significantly inhibited when GRα expression was reduced. Furthermore, pseudopterosin inhibited invasion of MDA-MB-231 3D tumor spheroids embedded in an extracellular-like matrix. Remarkably, the knockdown of GRα in 3D tumor spheroids revealed increased ability of cells to invade the surrounding matrix. In a co-culture, encompassing peripheral blood mononuclear cells (PBMC) and MDA-MB-231 cells, production of interleukin 6 (IL-6) and interleukin 8 (IL-8) significantly increased compared to monoculture. Notably, pseudopterosin proved to block cytokine elevation, representing key players in tumor progression, in the co-culture. Thus, our results reveal pseudopterosin treatment as a potential novel approach in TNBC therapy.

The stromal vascular cell fraction (SVF) of visceral and subcutaneous adipose tissue (VAT and SAT) has increasingly come into focus in stem cell research, since these compartments represent a rich source of multipotent adipose-derived stem cells (ASCs). ASCs exhibit a self- renewal potential and differentiation capacity. Our aim was to study the different expression of embryonic stem cell markers NANOG, SOX2 and OCT3/4 and to evaluate if there exists a hierarchal role in this network in ASCs derived from both SAT and VAT. ASCs were isolated from SAT and VAT biopsies of 72 consenting patients (23 men, 47 women; age 45 ± 10; BMI between 25 and 30 range) undergoing elective open-abdominal surgery. Sphere-forming capability was evaluated by plating cells in low adhesion plastic. Stem cell markers CD90 and CD105 were analyzed by flow cytometry and stem cell transcription factors NANOG, SOX2 and OCT3/4 were detected by immunoblotting and Real-Time PCR. NANOG, SOX2 and OCT3/4 interplay was explored by gene silencing. ASCs from VAT and SAT confirmed their mesenchymal stem cell (MSC) phenotype expressing the specific MSC markers CD90, CD105, NANOG, SOX2 and OCT3/4. NANOG silencing induced a significant OCT 3/4 (70% ± 0.05) and SOX2 (75% ± 0.03) down-regulation whereas SOX2 silencing did not affect NANOG gene expression. Adipose tissue is an important source of MSC, and siRNA experiments endorse a hierarchical role of NANOG in the complex transcription network that regulates pluripotency and plasticity.

The main objective of this study was to compare the removal efficiency of nutrients using Lactuca sativa, Medicago sativa and Phragmites australis in subsurface flow constructed wetlands with horizontal flow. In order to test water quality, fabricated reactors designed and the plants cultivated in the soil while their root were inside the wastewater. A long time study carried out from spring till end of autumn (9 months) in order to evaluate the difference in removal rate based on the seasonal changes. The highest removal rate was during summer which followed by spring and autumn. Thus, the effect of plants on the removal efficiency of organic matter (COD, BOD), TSS and nutrient (P and TN) appeared to be dependent on the seasonal growth. Phragmites australis the most sensitive species in order the removal of nutrient from wastewater.

Polylactic Acid (PLA) is an organic polymer commonly used in fused deposition (FDM) printing and biomedical scaffolding that is biocompatible and immunologically inert. However, variations in source material quality and chemistry make it necessary to characterize the filament and determine potential changes in chemistry occurring as a result of the FDM process. We used several spectroscopic techniques, including laser confocal microscopy, Fourier-Transform Infrared (FTIR) spectroscopy and photoacousitc FTIR spectroscopy, Raman spectroscopy, and X-ray photoelectron Spectroscopy (XPS) in order to characterize both the bulk and surface chemistry of the source material and printed samples. Scanning Electron Microscopy (SEM) and Differential Scanning Calorimetry (DSC) were used to characterize morphology, crystallinity, and the glass transition temperature following printing. Analysis revealed calcium carbonate-based additives which were reacted with organic ligands and potentially trace metal impurities, both before and following printing. These additives became concentrated in voids in the printed structure. This finding is important for biomedical applications as carbonate will impact subsequent cell growth on printed tissue scaffolds. Results of chemical analysis also provided evidence of the hygroscopic nature of the source material and oxidation of the printed surface, and SEM imaging revealed micro and sub-micron scale roughness that will also impact potential applications.

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.

When swine flu vaccines and circulating influenza A virus (IAV) strains are poorly matched, vaccine-induced antibodies may not protect from infection. Highly conserved T cell epitopes may, however, have a disease-mitigating effect. The degree of T cell epitope conservation among circulating strains and vaccine strains can vary, which may also explain differences in vaccine efficacy. Here, we evaluate a previously developed conserved T cell epitope-based vaccine and determine the persistence of T cell epitope conservation over time. We used a pair-wise homology score to define conservation between the vaccine’s swine leukocyte antigen (SLA) class I and II-restricted epitopes and T cell epitopes found in 1,272 swine IAV strains sequenced between 2013 and 2017. Twenty-four of the 48 total T cell epitopes included in the epitope-based vaccine were highly conserved and found in >1,000 circulating swine IAV strains over the five-year period. In contrast, commercial swine IAV vaccines developed in 2013 exhibited declining conservation with the circulating IAV strains over the same five-year period. Conserved T cell epitope vaccines may be useful adjunct for commercial swine flu vaccines and to improve protection against influenza when antibodies are not cross-reactive.

This article develops algorithms for the characterization and the visualization of micro-scale features by using a small number of sample points, and with a goal to mitigate for the measurement shortcomings which are often destructive or time consuming. We implement the algorithms to rapidly examine the microscopic features of a Microelectromechanical System (MEMS) surface. Such images are highly dense; therefore, traditional image processing techniques might be computationally expensive. The contribution of this research include first, we develop local and global algorithm based on modified Thin Plate Spline (TPS) model to reconstruct high resolution images of the micro-surface’s topography, and its derivatives by using low resolution images. Second, we obtain a bending energy algorithm from our modified TPS model, and use it to filter out image defects. Finally, we develop a computationally efficient Windowing technique, which combines TPS and Linear Sequential Estimation (LSE), to enhance the visualization of images. The Windowing technique allows rapid image reconstruction based on the reduction of inverse problem.

In this research paper a novel Ultra Violet Photo Catalyst Oxidation (UVPCO) sensor for air and surface sanitization using Common Source (CS) amplifier is presented. The ultra violet photo catalysis is the process in which the highly reactive radicals like H+, OH-and peroxides ions are produced from air in the presence of the ultra violet radiation and photo catalyst. In this process, the free radicals outbreaks the bio aerosols like bacteria, fungus and volatile organic compounds (VOCs) and destroy them. The proposed system is relies on the fast operation of PCS which operates under sub-threshold conditions and reduced computation time. The properties of common source amplifier like very high voltage gain and input output resistance increased the sensitivity as well as stability of the circuit. The system is more user friendly and the outcomes of simulation are fairly in agreement with the theoretical estimation. Keywords: bio aerosol, Photo Catalytic Oxidation (PCO), hydroxyl, hydrogen peroxide, SPICE, surface sanitizer.

Polyhydroxyalcanoates (PHAs) are biodegradable polymers synthesized in cytoplasmic granules in bacteria, such as Cupriavidus necator (Ralstonia eutropha), Alcaligenes latus, Pseudomonas spp., Comamonas spp. and other species. PHAs accumulation occurs in response to stress conditions, i.e. under high carbon and low nitrogen (24:1 ratio). PHA can be synthesized using recombinant microorganisms (provided with the operon phbA/phbB/phbC), escaping the constrains of nutrient request, except addition of high amount of sugar (glucose, lactose, fructose). In this study; E. coli was genetically modified for PHB production in biofermentors. The production of PHA at industrial scale requires a continuous supplementation of fermentable sugars to support the availability of nutrients and to assess the level of the exponential growth phase; since sugars are required either for bacterial growth either for PHA synthesis and energy storage. The biofermentors need to be run in automated system. Sensors are used at many points in fermentators; in the evaluation of parameters: consumption of sugars; cell density; quantification of PHB synthesis. The need of operational control during the fermentation has prompted us to application of three measurements; one unit linked to a Nanodrop to evaluate OD; one linked to a reaction chamber to measure sugars consumed by enzyme based fluorescence detection; and one for bacteria Nile Blue staining and fluorescence intensity reads. The growth of bacteria on three different plant by-products was monitored and PHB production in four days using a banana by-product feed was optimised. These detectors will make possible to exploit the full potential of bioreactors optimizing the time of use and maximizing the number of bacteria synthesizing PHA.

Fluid flow in human body is generally known to influence a variety of cellular behaviors. Different nanoparticle properties as well as cell type, interaction with other cells and cellular environments also show significant effect on nanoparticle uptake and drug efficacy. The aim of this study was to evaluate the effect of shear stress on cellular behaviors of biocompatible and biodegradable nanoparticles to cancer cells (A549 cell lines) in a biomimetic microfluidic system. We prepared a gelatin-oleic conjugate (GOC) as an amphiphilic biomaterial to prepare self-assembled gelatin-oleic nanoparticles (GON). Coumarin-6 and paclitaxel were used as the fluorescence marker and model drug, respectively, and were loaded into GONs by incubation (C-GONs; PTX-GONs). Additionally, we evaluated the cellular uptake of fluorescence labeled C-GONs and the drug efficacy of PTX-GONs. The cellular uptake of C-GONs by A549 cells in the absence of shear stress revealed that the mean fluorescence intensity was slightly decreased compared to that in the presence of shear stress. The results also indicated that negatively charged PTX-GONs had a lower cancer killing effect under dynamic conditions than that under static conditions. It also suggested that fluidic shear stress did not significantly affect drug uptake and efficiency in case of PTX-GONs. The cellular interactions between nanoparticles and cells in drug delivery should be carefully examined according to the physicochemical properties of nanoparticles such as the type of materials, size and mainly surface charge in a biomimetic microfluidic condition.

This paper introduces a new destriping algorithm for remote sensing data. The method is based on combined Haar Stationary Wavelet transform and Fourier filtering. State-of-the-Art methods based on the discrete wavelet transform (DWT) may not always be effective and may cause different artifacts. Our contribution is three-fold: i) we propose to use the Undecimated Wavelet transform (UWT) to avoid as much as possible shortcomings of the classical DWT; ii) we combine a spectral filtering and UWT using the simplest possible wavelet, the Haar basis, for a computational efficiency; iii) we handle 2D fields with missing data, as commonly observed in ocean remote sensing data due to atmospheric conditions (e.g., cloud contamination). The performances of the proposed filter are tested and validated on the suppression of horizontal strip artifacts in cloudy L2 Sea Surface Temperature (SST) and ocean color snapshots.

The variation of aerosols, especially dust aerosol, in time and space plays an important role in climate forcing studies. Aerosols can effectively reduce land surface longwave emission and re-emit energy at a colder temperature, making estimation of downwelling surface longwave radiation (DSLR) with satellite data difficult. Using the latest atmospheric radiative transfer code (MODTRAN 5.0), we simulate the outgoing longwave radiation (OLR) and DSLR under different land surface and atmospheric profile conditions. The results show that dust aerosol has an obvious “warming” effect to longwave radiation compared with other aerosols, that aerosol longwave radiative forcing (ALRF) increased with increasing aerosol optical depth (AOD), and that the atmospheric water vapor content (WVC) is critical to the understanding of ALRF. A method is proposed to improve the accuracy of DSLR estimation from satellite data for the skies under heavy dust aerosols. The AOD and atmospheric WVC under cloud-free conditions with a relatively simple satellite-based radiation model that yields the high accurate DSLR under heavy dust aerosol are used explicitly as model input to reduce the effects of dust aerosol on the estimation of DSLR. Validations of the proposed model with satellites data and field measurements show that it estimates the DSLR accurately under heavy dust aerosol skies. The root mean square errors (RMSEs) are 20.4 W/M² and 24.2 W/M² for Terra and Aqua satellites, respectively, at the Yingke site, and the biases are 2.7 W/M² and 9.6 W/M², respectively. For the Arvaikheer site, the RMSEs are 23.2 W/M² and 19.8 W/M² for Terra and Aqua, respectively, and the biases are 7.8 W/M² and 10.5 W/M², respectively. The proposed method is especially applicable to acquire relatively high accurate DSLR under heavy dust aerosol using MODIS data with available WVC and AOD data.

It has been declared repeatedly that cancer is a result of molecular genetic abnormalities. However, there has been no working model describing the specific functional consequences of the deranged genomic processes that result in the initiation and propagation of the cancer process during carcinogenesis. We no longer need to question whether or not cancer arises as a result of a molecular genetic defect within the cancer cell. The legitimate questions are: how and why? This article reviews the preeminent data on cancer molecular genetics and subsequently proposes that the sentinel event in cancer initiation is the aberrant production of fused transcription activators with new molecular properties within normal tissue stem cells. This results in the production of vital oncogenes with dysfunctional gene activation transcription properties, which leads to dysfunctional gene regulation, the aberrant activation of transduction pathways, chromosomal breakage, activation of driver oncogenes, reactivation of stem cell transduction pathways and the activation of genes that result in the hallmarks of cancer. Furthermore, a novel holistic molecular genetic model of cancer initiation and progression is presented along with a new paradigm for the approach to personalized targeted cancer therapy, clinical monitoring and cancer diagnosis.

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 .

Background: Studies employing next-generation sequencing (NGS) show that the oral fungal community (mycobiome) is far more complex than hitherto thought. However, the role of the oral mycobiome in health and disease, including oral carcinogenesis, has not been explored. Objective: To characterize the mycobiome associated with oral squamous cell carcinoma (OSCC). Methods: Tissue biopsies [cases: 25 OSCC; controls: 27 intra-oral fibro-epithelial polyp (FEP)] were collected from oral and maxillofacial units in Sri Lanka. Total DNA was extracted and subjected to sequencing of the fungal ITS2 region using Illumina’s 2x300 bp chemistry. High quality, non-chimeric merged reads were classified to species level using a BLASTN-algorithm with UNITE’s named species sequences as reference. Downstream analyses were performed using QIIME and LEfSe. Results: 364 species representing 160 genera and 2 phyla (Ascomycota and Basidiomycota) were identified, with Candida and Malassezia making up 48% and 11% of the average mycobiome, respectively. However, only 5 species and 4 genera were detected in ≥50% of the samples. The species richness and diversity were significantly lower in OSCC. At the genus level, Candida, Hannaella and Gibberella were overrepresented in OSCC while Alternaria and Trametes were more abundant in FEP. Species-wise, C. albicans, C. etchellsii and Hannaella luteola-like species were enriched in OSCC while Malassezia restricta, Aspergillus tamarii, Alternaria alternate, Cladosporium halotolerans, and Hanseniaspora uvarum-like species were the most significantly abundant in FEP. Conclusions: A dysbiotic mycobiome dominated by C. albicans was found in association with OSCC. Whether this dysbiosis plays a role in oral carcinogenesis warrants further investigation.

Even though the current classic aerospace propulsion methods are greatly improved, some of the most modern methods have already been introduced, among which the propulsion with electric motors. Energy can be obtained from hydrogen burners, honeycomb burners to protect the burning of hydrogen that burns 10 times faster than conventional oil fuels or alcohols. Hydrogen storage is also done in honeycomb cell reservoirs. Getting solar photovoltaic power even during flight is not yet profitable or efficient, but it can be proposed in the future for lighter and/or spacecraft. A great desire is to dismantle water in hydrogen and oxygen directly on the aircraft, so the stored fuel is actually water and the one actually used is the hydrogen removed from the water. In this case, there is no need for hydrogen storage. And other modern methods of propulsion and energy acquisition are briefly presented in the paper.

Land Surface Temperature (LST) is routinely retrieved from remote sensing instruments using semi-empirical relationships between top of atmosphere (TOA) radiances and LST, using ancillary data such as total column water vapor or emissivity. These algorithms are calibrated using a set of forward radiative transfer simulations that return the TOA radiances given the LST and the thermodynamic profiles. The simulations are done in order to cover a wide range of surface and atmospheric conditions and viewing geometries. This work analyses calibration strategies, considering some of the most critical factors that need to be taken into account when building a calibration dataset, covering the full dynamic range of relevant variables. A sensitivity analysis of split-windows and single channel algorithms revealed that selecting a set of atmospheric profiles that spans the full range of surface temperatures and total column water vapor combinations that are physically possible seems beneficial for the quality of the regression model. However, the calibration is extremely sensitive to the low-level structure of the atmosphere indicating that the presence of atmospheric boundary layer features such as temperature inversions or strong vertical gradients of thermodynamic properties may affect LST retrievals in a non-trivial way. This article describes the criteria established in the EUMETSAT Land Surface Analysis – Satellite Application Facility to calibrate its LST algorithms applied both for current and forthcoming sensors.

Surface acoustic wave (SAW) is effective for the manipulation of fluids and particles in microscale. The current approach of integrating interdigitated transducers (IDTs) for SAW generation into microfluidic channels involves complex and laborious microfabrication steps. These steps often require the full access to clean room facilities and hours to align the transducers to the precise location. This work presents an affordable and innovative method for fabricating SAW-based microfluidic devices without the need of clean room facilities and alignment. The IDTs and microfluidic channels are fabricated in the same process and thus precisely self-aligned in accordance with the device design. With the use of the developed fabrication approach, a few types of different SAW-based microfluidic devices have been fabricated and demonstrated for particle separation and active droplet generation.

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.

Intracellular aggregates of the alpha-synuclein protein result in cell loss and dysfunction in Parkinson’s disease and atypical parkinsonism, such as multiple system atrophy and dementia with Lewy bodies. Each of these neurodegenerative conditions, known collectively as alpha-synucleinopathies, may be characterized by a different suite of molecular triggers that initiate pathogenesis. The mechanisms whereby alpha-synuclein aggregates in turn mediate cytotoxicity also remain to be fully elucidated. However, recent studies have implicated the cell-to-cell spread of alpha-synuclein as the major mode of disease propagation between brain regions during disease progression. Here, we review the current evidence for different modes of alpha-synuclein cellular release, movement and uptake, including exocytosis, exosomes, tunnelling nanotubes, glymphatic flow and endocytosis. A more detailed understanding of the major modes by which alpha-synuclein pathology spreads throughout the brain may provide new targets for therapies that halt the progression of disease.

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

Motivated by diffraction experiments on the $\left(2\sqrt{3}\times \sqrt{3}\right)\mathrm{R}{30}^{\circ }$ reconstructed Si(111) due to deposition of rare earth elements (Dy, Tb) and silicide formation we analyse the splitting and non-splitting of superstructure spots. For this purpose, we model diffraction patterns for one dimensional structures generated by the binary surface technique and use supercell models to keep the analysis simple. Diffraction pattern are calculated in the framework of the kinematical diffraction theory and they are analyzed as a function of the domains and domain boundaries. Basic properties of the diffraction pattern are analyzed for model systems of a two-fold and a three-fold periodicity. The rules derived from these calculations are applied to the "real-world" system of Si(111)-($\left(2\sqrt{3}\times \sqrt{3}\right)\mathrm{R}{30}^{\circ }$)-RESi$2_{}$ (RE = Dy or Tb). Depending on the combination of domains and domain boundaries of different types a plethora of different features are observed in the diffraction patterns. These are analyzed to determine the sizes of both domain boundaries and domains from experimentally observed splitting of specific superstructure spots.

Studies on the possible association between bacteria and oral squamous cell carcinoma (OSCC) remain inconclusive, largely due to methodological variations/limitations. The objective of this study was to characterize the species composition as well as functional attributes of the bacteriome associated with OSCC. DNA obtained from 20 fresh OSCC biopsies (cases) and 20 deep-epithelium swabs (matched control subjects) were sequenced for the V1-V3 region using Illumina’s 2x300 bp chemistry. High quality, non-chimeric merged reads were classified to species level using a prioritized BLASTN-algorithm. Downstream analyses were performed using QIIME, PICRUSt, and LEfSe. Fusobacterium nucleatum subsp. polymorphum was the most significantly overrepresented species in the tumors followed by Pseudomonas aeruginosa and Campylobacter sp. Oral taxon 44, while Streptococcus mitis, Rothia mucilaginosa and Haemophilus parainfluenzae were the most significantly abundant in the controls. Functionally, genes involved in bacterial mobility, flagellar assembly, bacterial chemotaxis and LPS synthesis were enriched in the tumors while those responsible for DNA repair and combination, purine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, ribosome biogenesis and glycolysis/gluconeogenesis were significantly associated with the controls. This is the first epidemiological evidence for association of F. nucleatum and P. aeruginosa with OSCC. Functionally, an “inflammatory bacteriome” is enriched in OSSC.

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.

Abstract: The SARS-CoV-2 pandemic has significantly impacted world health and economic status. In response, much work has been undertaken to provide effective, safe vaccines, antibodies and antiviral drugs with which to address this pandemic. Treatment of a pandemic population presents multiple challenges in addition to the primary issue of drug efficacy and safety, such as large scale drug manufacture and distribution, drug stability, oral dosing and pharmacoeconomic considerations. Ideally, these factors must be addressed if new candidate drugs are to be advanced for treatment of large (pandemic) populations. Subsequently, new antivirals have reached the market but choices are few. According to the NIH Covid Treatment Guidelines, only three small molecule antiviral drugs are available to treat COVID-19 disease. As such, a significant part of the research towards discovery of new antiviral drugs has focused on screening and evaluation of ‘repurposed drugs’ or previously approved or clinical stage drugs. Yet, in spite of this increased research activity, one promising clinical stage candidate drug has received little attention regarding its potential as a monotherapy or component of combination therapy for treatment of COVID-19 disease. Tucaresol, with documented human safety and pharmacokinetic data, is an orally active, stable, small molecule amenable to large scale manufacture by a proprietary two-step synthesis developed by us. Tucaresol functions as a host-targeted antiviral by selective protection/reconstitution of CD4+ T helper cells as demonstrated in HIV patients and SIV macaques. In view of similarities between HIV and SARS-CoV-2, especially with respect to host CD4+ T helper cells, and the suitability of Tucaresol for facile treatment of pandemic populations, Tucaresol is presented herein for treatment of mild-to-moderate COVID-19 patients but may also be useful for treatment of advanced disease accompanied by lymphopenia.

Statement of problem: Henna has been added to polymethylmethacrylate (PMMA) as a new type of antifungal agent; however, its effect on the latter’s physical properties has not been investigated. Purpose: This study aimed to evaluate the effect of the addition of various henna concentrations on the surface roughness and hardness of PMMA denture base material. Materials and Methods: A total of 99 specimens of rectangular-shaped (10×20×3 mm3) acrylic specimens were prepared from heat-cured acrylic resin. Specimens were divided into one control group without the addition of henna and five test groups, which were prepared by adding Yamani henna powder to acrylic powder at concentrations of 1wt%, 2.5wt%, 5wt%, 7.5wt%, and 10wt%. The polymer was added to the monomer before being mixed, packed, and processed using the conventional water bath method. After processing, specimens were finished and polished, then kept in distilled water for 48+2 h. A profilometer and Vickers hardness tester were used to measure surface roughness and hardness respectively. Statistical data analysis was conducted via SPSS version 20.0 (IBM, USA). Results: The addition of henna at varying concentrations significantly increased surface roughness values (P ≤ 0.01) while decreasing hardness (P ≤ 0.0001). The most favorable addition value was 1% henna between all henna groups. Conclusion: The addition of henna to the acrylic resin may negatively affect the surface properties of PMMA acrylic denture base.

The urbanization effects on land surface phenology (LSP) have been investigated by many studies, but few studies focused on the temporal variations of urbanization effects on LSP. In this study, we used the MODIS EVI, MODIS LST data and China’s Land Use/Cover Datasets (CLUDs) to investigate the temporal variations of urban heat island intensity and urbanization effects on LSP in Northeast China during 2001–2015. Land surface temperature (LST) and phenology differences between urban and rural areas represented the urban heat island intensity and urbanization effects on LSP, respectively. Mann-kendall nonparametric test and Sen's slope were used to evaluating the trends of urbanization effects on LSP and urban heat island intensity. The results indicated that the average land surface phenology (LSP) during 2001–2015 was characterized by high spatial heterogeneity. The start of the growing season (SOS) in old urban area had become earlier and earlier than rural area and the differences of SOS between urbanized area and the rural area changed greatly during 2001–2015 (−0.79 days/year, p < 0.01). Meanwhile, the length of the growing season (LOS) in urban and adjacent areas had become increasingly longer than rural area especially in urbanized area (0.92 days/year, p < 0.01), but the differences of the end of the growing season (EOS) between urban and adjacent areas did not change significantly. Next, the UHII increased in spring and autumn during the whole study period. Moreover, the correlation analysis indicated that the increasing urban heat island intensity in spring contributed greatly to the increases of urbanization effects on SOS, but the increasing urban heat island intensity in autumn did not lead to the increases of urbanization effects on EOS in Northeast China.

Lactoperoxidase (LP), which is a high-value minor whey protein, has recently drawn extensive attention from research scientists and industry due to its multi-function and potential therapeutic applications. In this study, the separation and optimization of two similar-sized proteins, LP and lactoferrin (LF) were investigated using strong cation exchange column chromatography. Optimization was started with central composite design based experiments to characterize the importance of different decision variables. The three variables used in the optimization were flow rate, length of gradient and final salt concentration in the linear elution gradient step. The obtained empiric functional model represented the effect of the significant factors on the yield as the objective function. Afterwards, the calibrated mechanistic model was employed to predict accurate optimal set of variables. The optimal operating points were found and the results were compared with validation experiments. Predictions respecting yield confirmed a very good agreement with experimental results while keeping purity, a product quality characteristic, equal or above to a predefined value.

High pressure crystallization technique has been successfully used to prepare an elusive form II of a non-steroidal anti-inflammatory drug, Mefenamic acid. Single crystal of form II was grown at 0.3 GPa from an 4:1 methanol/ ethanol mixture as a solvent using Diamond Anvil Cell. Comparison of crystal structures show that the efficient packing of MA molecules in Form II results from the structural flexibility of MA acid molecules. Compression studies performed on the single crystal of form I resulted in 14 % decrease of unit cell volume up to 2.5 GPa. No phase transition was observed up to this pressure. A reconstructive phase transition is required to induce conformational changes in the structure, which is confirmed by crystallization at high pressure results.

Sickle cell disease (SCD) is an inherited disorder of major health challenge in Nigeria. Micronutrients deficiencies often associated with the disorder may cause inflammation and abnormal metabolisms in the body. The copper-to-zinc ratio is a more important assessment than the concentrations of either of the metals in clinical practice. This study seeks to evaluate serum levels of c-reactive protein (CRP), copper, zinc and copper-to-zinc ratio and to correlate copper-to-zinc ratio with CRP in adult subjects with SCD. Serum copper, zinc, CRP and plasma fibrinogen were assayed in 100 confirmed SCD patients in steady clinical state and 100 age and sex matched subjects with normal haemoglobin. Serum copper and zinc were assayed by colorimetric method using reagents supplied by Centronic, Germany while CRP and fibrinogen were assayed using reagents supplied by Sigma (St. Louis, MO, USA) and Anogen (Ontario, Canada), respectively. The copper to zinc ratio was calculated from serum levels of copper and zinc. The measured parameters were compared between the groups using Students t-test and Pearson correlation coefficient was used to relate CRP with the other parameters. Serum copper, CRP, fibrinogen and copper-to-zinc ratio were significantly higher (p < 0.001) while zinc level was lower in SCD patients than controls. Serum CRP concentration correlated with copper (r = 0.10; p < 0.02), zinc (r = −0.199; p < 0.05) and Copper-to-zinc ratio (r = 0.312; p < 0.002) but the correlation between CRP and fibrinogen was not significant. Inflammatory condition may modulate copper and zinc homeostasis and copper-to-zinc ratio may be used as marker of nutritional deficiency and inflammation in SCD patients.

We report magnetic silver nanoshells (M AgNSs) that have both magnetic and SERS properties for SERS-based detection. The M AgNSs are composed of hundreds of Fe3O4 nanoparticles for rapid accumulation and bumpy silver shell for sensitive SERS detection by near-infrared laser excitation. The intensity of the SERS signal from the M AgNSs was strong enough to provide single particle-level detection. We obtained much stronger SERS signal intensity from the aggregated M AgNSs than from the non-aggregated AgNSs. 4-Fluorothiophenol was detected at concentrations as low as 1 nM, which corresponds to 0.16 ppb. The limit of detection for tetramethylthiuram disulfide was 10 μM, which corresponds to 3 ppm. The M AgNSs can be used to detect trace amounts of organic molecules using a portable Raman system.

Electrostatic endothelial cell seeding has evolved as an exceptional technique to improve the efficiency of cell seeding in terms of frequency of attached cells and the amount of cell adhesion for the treatment of vascular diseases. In the recent times, both untreated and superhydrophilic thin film nitinol (TFN) have exhibited strong prospect as substrates for creation of small-diameter endovascular grafts due to their hallmark properties of superelasticity, ultra low-profile character, grown hemocompatible oxide layer with the presence of a uniform endothelial layer on the surface. The purpose of the current study is to understand the effects of endothelial cell seeding parameters (i.e., applied voltage, incubation time, substrate chemistry and cell suspension solution) to investigate the cell seeding phenomenon and to improve the cell adhesion and growth on the TFN surface under electrostatic transplantation. Both parallel plate and cylindrical capacitor models were used along with the Taguchi Design of Experiment (DOE) methods to design in vitro test parameters. A novel in vitro system for cylindrical capacitor model was created using a micro flow pump, micro incubation system, and silicone tubings. The augmented endothelialization on thin film nitinol was developed to determine the effect of cell seeding and deployed in a 6 Fr intravascular catheter setup. Cell viability along with morphology and proliferation of adhered cells were evaluated using fluorescent and scanning electron microscopy. Our results demonstrated that the maximum number of cells attached on STFN in the catheter was observed in 5V with the 2 hr exposure of in the cell culture medium (CCM) solution. The condition showed 5V voltage with 0.68×10-6 µC electrostatic charge and 5.11 V·mm-1 electric field. Our findings have first demonstrated that the electrostatic endothelialization on the superhydrophilic thin film nitinol endograft within the catheter prior to the endovascular procedure could enhance the biocompatibility for low-profile endovascular applications.

Abstract: High step-up voltage gain nonisolated DC-DC converter have attracted much attention in photovoltaic, fuel cells and other renewable energy system applications. In this paper, by combining input current ripple-free boost cell with coupled-inductor voltage-doubler cell, an input current ripple-free high voltage gain nonisolated converter is proposed. In addition, passive lossless clamp circuit is adopted to recycle the leakage inductor energy and to reduce the voltage spike across the power switch. By utilizing voltage-doubler cell consisting of diode and capacitor, the voltage stress of switch is further reduced and the resonance between the leakage inductor and the stray capacitor of the output diode is eliminated. A low switch-on-resistance low-voltage-rated MOSFET can therefore be employed to reduce the conduction loss and cost. The reverse recovery loss of output diode is reduced, and the efficiency of converter can be improved. Furthermore, the proposed converter can achieve nearly zero input current-ripple and make the design of electromagnetic interference (EMI) filter easy. Steady state analysis and operation mode of the converter is performed. Finally, experimental results are presented to verify the analysis results of the proposed converter.

We apply principles of Gibbs phase plane chemistry to and across the entire ocean-atmospheric interface. Surface tension increments support a two dimensional, tangential pressure well known to determine rates of bulk gas, bubble, salt, spray and momentum transfer plus both sensible and latent heat fluxes. Hence it is worth asking whether tension mapping follows from current understanding of two dimensional composition. A history is provided dating back centuries and demonstrating that detrital organic macromolecules are central; subtle surfactant functional variation creates a microforcing field which dissipates turbulent energy at the sub-meter scale. Since we have just distributed major biopolymeric classes emitted as primary organic aerosol, further climate links can be established by considering full planar thermochemistry. Organic microlayer behaviors are reviewed with attention to confined, analog phase transitions among two dimensional “solid, liquid, (and) gaseous” states serving as elasticity indicators. We also discuss surfactant properties of general marine dissolved organic carbon, demonstrating that only proteins and lipids are capable of occupying significant local micro-area. The literature often suggests albumin and stearic acid as best proxies, and so we distribute their concentrations through multilevel global ecodynamic simulations. Consensus distributions are obtained in order to control adsorptive equilibria. Working from conservation of planar free energy, a parametric equation of state is devised relating excess coverage to the surface pressure-modulus. Constant settings for the proxy pair are drawn from laboratory study, and they successfully reproduce frequencies for surfactant solid-to-gas occurrence in ambient compression experiments. Functionally resolved organic measurements are rare and so we group them into super-ecological province tables showing that our bulk concentration estimates are reasonable. Outputs are then fed into a coverage-tension-elasticity code. Resulting contours traverse the critical range for piston velocity, bubble-spray and damping effects on either a regional or seasonal basis. There is also a possibility for widespread microlayer crystallization in polar seas. The concepts are a direct extension of our organic aerosol work, and the two approaches could be inserted into Earth System Models in tandem. Uncertainties in the logic are enumerated and include kinetic and thermochemical factors at multiple scales. But the problems are reducible through molecular modeling coupled to renewed laboratory and field study. Connections to marine colloids-gels, microlayer iron chelation, and linings of the ice channel network are discussed additionally.

TTF1-NP(5,2′,4′-trihydroxy-6,7,5′-trimethoxyflavone nanoparticles), derived from the traditional Changbai Mountain medicinal plant Sorbaria sorbifolia (SS), has been showedits anti-cancer effect in various liver cancer cell types and tissues. The present study was designed to evaluate the antitumor mechanism of the TTF1-NP against HepG2 hepatoma cells and HepG2 cells-induced hepatocarcinoma (HCC) in nude mouse model. Here we demonstrated that TTF1-NP inhibits tube formation of HUVECs and HepG2 cell migration and invasion, and inhibits tumor growth in nude mice implanted with HepG2 cells through the downregulation of STAT3 protein and activation, along with VEGF, KDR, bFGF, MMP2 and MMP9 levels. We further revealed that TTF1-NP decreased the DNA-binding capacity of STAT3. Together our results provide a mechanism by which TTF1-NP suppresses cancer cell migration, invasion and angiogenesis through the action of STAT3 and suggests TTF1-NP as a potential therapy for hepatocellular cancer treatment.

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.

In this study, the efficiency of an anaerobic treatment system for wastewater from a South African poultry slaughterhouse was evaluated using a lab-scale static granular bed reactor (SGBR). The down-flow SGBR (2 L) was operated continuously for 138 days under mesophilic conditions (35-37 ˚C), at hydraulic retention times (HRTs) ranging from 24 to 96 h and average organic loading rates (OLRs) of 0.78 to 5.74 g COD/L.day. The SGBR achieved an average chemical oxygen demand (COD) removal efficiency of 80% and the maximum COD removal achieved was 95%, at an HRT of 24 h and average OLR of 5.74 g COD/L.day. The optimization of the SGBR, with regard to a suitable HRT and OLR, was determined using response surface methodology (RSM). The optimal SGBR performance with regard to the maximum COD removal efficiency was predicted for an OLR of 12.49 g COD/L.day and a HRT of 24 h, resulting in a 95.5% COD removal efficiency. The model R2 of 0.9638 indicated that the model is a good fit and is suitable to predict the COD removal efficiency for the SGBR.

Daily maximum surface air temperature (Tamax) is a crucial factor for understanding complex land surface processes under rapid climate change. Remote detection of Tamax has widely relied on the empirical relationship between air temperature and land surface temperature (LST), a product derived from remote sensing. However, little is known about how such a relationship is affected by the high heterogeneity in landscapes and dynamics in seasonality. This study aims to advance our understanding of the roles of land cover and seasonal variation in the estimation of Tamax using the MODIS (Moderate Resolution Imaging Spectroradiometer) LST product. We developed statistical models to link Tamax and LST in the middle and lower reaches of the Yangtze River in China for five major land-cover types (i.e., forest, shrub, water, impervious surface, cropland, and grassland) and two seasons (i.e., growing season and non-growing season). Results show that the performance of modeling the Tamax-LST relationship was highly dependent on land cover and seasonal variation. Estimating Tamax over grasslands and water bodies achieved superior performance; while uncertainties were high over forested lands that contained extensive heterogeneity in species types, plant structure, and topography. We further found that all the land-cover specific models developed for the plant non-growing season outperformed the corresponding models developed for the growing season. Discrepancies in model performance mainly occurred in the vegetated areas (forest, cropland, and shrub), suggesting an important role of plant phenology in defining the statistical relationship between Tamax and LST. For impervious surfaces, the challenge of capturing the high spatial heterogeneity in urban settings using the low-resolution MODIS data made Tamax estimation a difficult task, which was especially true in the growing season.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by the lack of estrogen receptors (ER), progesterone receptors, and HER-2 receptors. Thus, TNBC tumours do not benefit from the current therapies targeting ER or HER-2. Therefore, there is an urgent need to develop novel treatment for this subtype of breast cancer. Marijuana is a common name given to Cannabis plants, a group of plants in the Cannabis genus of the Cannabaceae family. Cannabis plants are among the oldest cultivated crops, traced back at least 12,000 years and are well known for their multi-purpose usage, including medicinal purposes. The main active compounds extracted from Cannabis plants are 21-carbon-containing terpenophenolics, which are referred to as phytocannabinoids. Of these, the tetrahydrocannabinol (THC) group contains highly potent cannabinoids, including delta-9-tetrahydrocannabinol (∆9-THC) and delta-8-tetrahydrocannabinol (∆8-THC), which are the most abundant THCs and are largely responsible for psychological and physiological effects of marijuana. The use of Cannabis plants for medicinal purposes was first recorded in 2337 BC in China, where Cannabis plants were used to treat pains, rheumatism, and gout. Recently, several cannabinoids have been approved for a number of treatments, one of which is the treatment of nausea and vomiting caused by chemotherapy in cancer patients. Furthermore, increasing evidence shows that cannabinoids not only attenuate side effects due to cancer treatment, but might also potentially possess direct antitumor effects in several cancer types, including breast cancer. However, anti-tumour activity of marijuana has been variable in different studies and even promoted tumour growth in some cases. In addition, the mechanisms of cannabinoid action in cancer remain unclear. This review summarizes evidence about the mixed actions of cannabinoids in cancer in general and triple-negative breast cancer in particular.

Coronavirus disease (COVID-19) is a new discovered strain where WHO officially declares the disease as COVID-19 while the virus responsible for it called Severe Acute Respiratory Syndrome Coronavirus 2 or SARS-CoV-2. The incubation period of this disease is between 14 days. Ordinary clinical symptoms that reported around the world include fever, cough, fatigue, diarrhoea and vomiting as well as asymptomatic for certain people. Infection is spread mainly through broad droplets. In early March 2020, WHO again has announced that COVID-19 is a pandemic with currently no specific treatment. The potential use of SARS-COV-2 proteome as a vaccine candidate by analysing through B-cell and T-cell antigenicity by using a immunoinformatics approach as a vaccine development early stage. In this study, we used consensus sequence for SARS-COV-2 proteome that was retrieved from NCBI database. VaxiJen 2.0 was mainly used to identify the antigenic property of SARS-COV-2 proteins. IEDB then used to analyse the B-cell epitope, the presence of T cell immunogenic epitope in SARS-COV-2 proteins was obtained by using compromise method of MHC class I and II tools that accessible respectively using ProPred-1 server and MHC II Binding Prediction in IEDB database. The best epitopes of B and T-cell epitopes were predicted with high antigencity and the information is disseminated through web-based database resource (https://covid-19.omicstutorials.com/epitopes/). This study will be useful to find a new epitope-based candidate for SARS-COV-2. However, further study needs to be done for the next stages of vaccine development.

While texturing of workpiece surfaces to promote lubrication in metal forming has been applied for several decades tool surface texturing is rather new. In the present paper tool texturing is studied as a method to prevent galling. Adopting a strip reduction test longitudinal pocket geometries oriented perpendicular to the sliding direction, with shallow pocket depth, small pocket angle to the workpiece surface and varying distance between pockets are investigated. The experiments reveal that the distance between pockets should be larger than the pocket width thereby creating a topography similar to flat table mountains to avoid mechanical interlocking in the valleys; otherwise an increase in drawing load and pick-up on the tools is observed. The textured tool surface lowers friction and improves lubrication performance provided that the distance between pockets is 2-4 times larger than the pocket width. Larger drawing speed facilitates escape of the entrapped lubricant in the pockets. Testing with low to medium viscosity oils leads to a low sheet roughness on the plateaus but also local workpiece material pick-up on the tool plateaus. Large lubricant viscosity results in higher sheet plateau roughness but also prevents pick-up and galling.

Solar energy is derived from photons of light coming from the sun in a form called radiation. Solar energy finds extensive application in air and water heating, solar cooking, as well as electrical power generation, depending on the way of capturing, converting and distribution. To enable such application, it is necessary to analyze the horizontal tilt angle of horizontal surfaces – in order that when the solar energy reaches the earth surface to be completely absorbed. This paper tends to describe the availability of solar radiation for south-facing flat surfaces. The optimal monthly, seasonal, and annual tilt angles have been estimated for Pristina. The solar radiation received by the incident plane is estimated based on isotropic sky analysis models, namely Liu and Jordan model. The annual optimum tilt angle for Pristina was found to be 34.7°. The determination of annual solar energy gains is done by applying the optimal monthly, seasonal and annual tilt angles for an inclined surface compared to a horizontal surface. Monthly, seasonal and annual percentages of solar energy gains have been estimated to be 21.35%, 19.98%, and 14.43%. Losses of solar energy were estimated by 1.13 % when a surface was fixed at a seasonal optimum tilt angle, and when it was fixed at an annual optimum tilt angle, those losses were 5.7%.

The Sentinel Application Platform (SNAP) architecture facilitates Earth Observation data processing (http://step.esa.int/main/toolboxes/snap/). In this work we present results from a new Snow Processor for SNAP. We also describe physical principles behind the developed snow property retrieval technique based on the analysis of Ocean and Land Colour Instrument (OLCI) onboard Sentinel-3A/B measurements over clean and polluted snow fields. Using OLCI spectral reflectance measurements in the range 400-1020nm, we derive important snow properties such as spectral and broadband albedo, snow specific surface area, snow extent and grain size on the spatial grid of 300m. The algorithm also incorporates cloud screening and atmospheric correction procedures over snow surfaces. We present validation results using ground measurements from Antarctica, the Greenland ice sheet and the French Alps. We find the spectral albedo retrieved with accuracy of better than 3% on average, making our retrievals sufficient for a variety of applications. Broadband albedo is retrieved with the average accuracy of about 5% over snow. Therefore, the uncertainties of satellite retrievals are close to experimental errors of ground measurements. The retrieved surface grain size shows good agreement with ground observations. Snow specific surface area observations are also consistent with our OLCI retrievals. We present snow albedo and grain size mapping over the inland ice sheet of Greenland for areas including dry snow, melted/melting snow and impurity rich bare ice. The algorithm can be applied to OLCI Sentinel-3 measurements providing an opportunity for creation of long – term snow property records essential for climate monitoring and data assimilation studies - especially in the Arctic region, where we face rapid environmental changes including reduction of snow/ice extent and, therefore, planetary albedo.

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.

All cancer registries constantly show striking differences in cancer incidence by age and among tissues. For example, lung cancer is diagnosed hundreds of times more often at age 70 than at age 20, and this cancer in nonsmokers occurs thousands of times more frequently than heart cancer in smokers. An analysis of these differences using basic concepts in cell biology indicates that cancer is the end-result of the accumulation of cell divisions in stem cells. In other words, the main determinant of carcinogenesis is the number of cell divisions that the DNA of a stem cell has accumulated in any type of cell from the zygote. Cell division, process by which a cell copies and separates its cellular components to finally split into two cells, is necessary to produce the large number of cells required for living. However, cell division can lead to a variety of cancer-promoting errors, such as mutations occurring during DNA replication, chromosome aberrations arising during mitosis, errors in the distribution of cell-fate determinants between the daughter cells, and failures to restore physical interactions with other tissue components. Some of these errors are spontaneous, others are promoted by endogenous DNA damage occurring during quiescence, and others are influenced by pathological and environmental factors. The cell divisions required for carcinogenesis are primarily caused by multiple local and systemic physiological signals rather than by errors in the DNA of the cells. As carcinogenesis progresses, the accumulation of DNA errors promotes cell division and eventually triggers cell division under permissive extracellular environments. The accumulation of cell divisions in stem cells drives not only the accumulation of the DNA alterations required for carcinogenesis, but also the formation and growth of the abnormal cell populations that characterize the disease. This model of carcinogenesis provides a new framework for understanding the disease and has important implications for cancer prevention and therapy.

Acquisition of real-time hydraulic data is an essential component for flood forecasting. However, we frequently face difficulties in obtaining discharge data using classical contact methods during high magnitude floods and for systems experiencing rapid hydro-geomorphological adjustment. Therefore, we developed low-cost, non-contact sensors and platforms that are designed to overcome these difficulties. These advances enable flood flow properties to be monitored at multiple locations across a river catchment, at low-cost, and communicated in near real-time by using an image velocimetry method. This is an optics-based approach for stream flow measurement using commercially available near-infrared digital cameras to acquire video footage in full HD (30fps). Video footage is then subjected to optical flow tracking techniques based on cross-correlation, and feature-based tracking, enabling the displacement rates of detected features (for example natural foam, seeds, woody debris, and turbulent structures) to be computed. This manual provides step by step guidance to install an image-based gauging station. It contains the list of necessary components, the calibration process of a new camera and the assembly procedure of the system.

Particulate matter (PM) contains heavy metals that affect various cellular functions and gene expression associated with an array of acute and chronic diseases, in humans. However, their specific effects on the stem cells remain unclear. Here, we report the effects of PM collected from Jeddah city on bone marrow mesenchymal stem cells (BM-MSCs) on proliferation, cell death, related gene expression and systems biological analysis aiming to understand the underlying mechanisms. Two different sizes (PM_2.5-₁₀) were tested in vitro at various concentrations (15 to 300 µg/ml) and durations (24 to 72 h). PMs induced cellular stress including membrane damage, shrinkage and death. Lower concentrations of PM_2.5 increased BM-MSCs proliferation, while higher concentrations decreased it. PM₁₀ decreased BM-MSCs proliferation in a concentration-dependant manner. The X-Ray Fluorescence spectrometric analysis showed that PM contains high levels of heavy metals. Ingenuity Pathway Analysis (IPA) and hierarchical clustering analyses showed that heavy metals were associated with signalling pathways involving cell stress/death, cancer and chronic diseases. qRT-PCR results showed differential regulation of the apoptosis genes (BCL2, BAX); upregulation of inflammation associated genes (TNF-a and IL-6) and downregulation of cell cycle regulation gene (P53). We conclude that PM could affect different cellular functions and predispose to debilitating diseases.