Background: This study aimed to assess the dementia literacy (DL) level of community-dwelling adults in the four cities (Hong Kong, Guangzhou, Macau and Zhuhai) of the Greater Bay Area of China and to determine the preferred mass media for receiving dementia information. Methods: A multi-city cross-sectional study with 788 community-dwelling adults completed the survey. Dementia literacy was indirectly measured by two validated scales, 30-item Alzhiemer’s Disease Knowledge Scale (ADKS) and 20-item Dementia Attitudes Scale (DAS). When the ADKS total score was <15 and DAS total score was <70, it was considered as ‘inadequate dementia literacy’. Participants were also asked to indicate whether they would like to receive dementia information via digital media or traditional media. Chi-square tests and logistic regressions were undertaken. Results: About one-third of the participants had inadequate dementia literacy. Those with young age or secondary education preferred to get dementia information from social media. But people living in public housing would like to get information from government or hospital websites. Middle-aged participants inclined to learn dementia from television or radio. Conclusion: It is worthy to conduct territory-wide public education in dementia and develop strategies according to their preferences in the types of mass media.

This work explores the use of Kuhn verdazyl radicals as building blocks in multifunctional molecular materials in an exemplary study, focusing on the magnetic and the electron transfer (ET) characteristics, but also addressing the question whether chemical modification by cross-coupling is possible. The ET in solution is studied spectroscopically whereas solid state measurements afford information about the magnetic susceptibility or the conductivity of the given samples. The observed results are rationalized based on the chemical structures of the molecules, which have been obtained by X-ray crystallography. The crystallographically observed molecular structures as well as the interpretation based on the spectroscopic and physical measurements are backed up by DFT calculations. The measurements indicate that only weak, antiferromagnetic coupling is observed in Kuhn verdazyls owed to the low tendency to form face-to-face stacks, but also that steric reasons alone are not sufficient to explain this behavior. Furthermore, it is also demonstrated that ET reactions proceed rapidly in verdazyls/verdazylium redox couples and that Kuhn verdazyls are suited as donor molecules in ET reactions.

The aim of the present cross-sectional study was to analyze the differential impact of the first COVID-19 lockdown (3rd April 2020) on stress, health practices, and self-care activities across different Hispanic countries, age range and gender groups. 1082 participants from Spain, Chile, Colombia, and Ecuador took part in this study. Irrespective of the country, and controlling for income level, young people, especially females, suffered a greater level of stress, perceived the situation as more severe, showed less adherence to health guidelines and reported lower levels of health consciousness, in comparison to their male peers and older groups. However, in the case of self-care, it seems that older and female groups are generally more involved in self-care activities and adopt more healthy daily routines. These results are mostly similar between Colombia, Ecuador, and Spain. However, Chile showed some different tendencies, as males reported higher levels of healthy daily routines and better adherence to health guidelines compared to females and people over the age of 60. Differences between countries, genders and age ranges should be considered in order to improve health recommendations and adherence to guidelines. It would also be crucial to identify vulnerable groups to promote the adoption of health behaviors that may help in the development of effective public health strategies. Future studies should be addressed to explore the possible causations of such differences in more cultural-distant samples and at later stages of the current outbreak.

Mass crises are disruptive to people's mental health. The study aimed to explore mental distress during COVID-19 quarantine in a sample of university workers in Brazil. The survey included sets of questions about demographics, health, and support, an open question about major concerns, and the Clinical Outcome Routine Evaluation (CORE-OM), a measure of mental distress. 407 professionals participated in the study: mean age of 40 years (SD = 11.2), mostly female (67.8%), married (64.8%) and fulfilling social distancing to avoid COVID-19 infection (99%). Using the Consensual Qualitative Research for simple qualitative data (CQR-M) the main areas of concern were grouped into six domains, as follows: Work, Health, Isolation, Personal life and routine, Social environment, and Future. Many responses were multiple. They form categories indicating specific concerns within these domains. Quantitative data were analyzed by identifying the simple effects of potential predictors of mental distress. The results indicated medium effects of help with household chores, psychiatric treatment, age and physical exercise. Having someone available to listen was the only variable with a large effect in reducing mental suffering. The hybrid approach showed that the psychological experience during the pandemic is quite multifaceted and complex pointing new clues for public mental health.

Optical coherence tomography (OCT) is one of the most promising, innovative and rapidly emerging intraoperative imaging modalities for neurosurgical guidance in brain tissue imaging, "optical biopsy", brain cerebral vascular detection, nerve fibers and white matter tracts detection. In this article, we provide a short survey of cross-polarization OCT and different types of OCT probes that can be used in routine neurosurgical practice. Through different types of probes there are multiple applications where OCT can play a highly complementary role in offering the real-time microscopic assessment and imaging of normal and pathological brain tissues. The biopsy-needle based probe for CP OCT was shown to be an effective instrument for brain tissue mapping and express estimation of tissue status as well as for detecting large blood vessels to prevent causing bleeding during biopsy sampling. The folded CP OCT probe for intraoperative use for brain tissue examination was shown as a potentially efficient sensor head for CP OCT. The probe demonstrated high lateral resolution in diffractive limited probing beam quality. The length of dismountable probe tip allows using the probe under operating microscope. Due to the designed family of specialized probes CP OCT fills in the niche of devices for express brain tissue examination in situ.

This article analyzes the emergence of partnerships between corporations and nongovernmental organizations (NGOs) through voluntary product labeling schemes. The economics, management, and business literatures are reviewed to highlight cross-checking, consistencies, and complementarities among these disciplines. The objective is to identify and analyze the motives, risks, and joint benefits of partnering via voluntary product labeling, using examples from the agri-food sector. This study is an attempt to offer a framework of corporate-NGO partnerships by showing that the drivers and risks of each partner merge because each takes a step into the sphere of the other. The main risks – namely, a loss of profitability, credibility and legitimacy – are related to the financial and existential dependency and the asymmetric information between the partners in favor of corporations, inducing an ``NGO-capture'' risk.

Zika virus (ZIKV) is a flavivirus that originated in Africa but emerged in Latin America in 2015. In this region, other flaviviruses such as Dengue (DENV), West Nile, and Yellow Fever Virus (YFV) also circulate, allowing for possible antigenic cross-reactivity to impact viral infections and immune responses. Studies have found antibody mediated enhancement between DENV and ZIKV, but the impact of YFV antibodies on ZIKV infection has not been fully explored. ZIKV infections cause congenital syndromes, such as microcephaly, necessitating further research into ZIKV vertical transmission through the placental barrier. Recent advancements in biomedical engineering have generated co-culture methods that allow for in vitro recapitulation of the maternal: fetal interface. This study utilized a transwell assay, which is a co-culture model utilizing human placental syncytiotrophoblasts, fetal umbilical cells, and a differentiating embryoid body to replicate the maternal: fetal axis. To determine if cross reactive YFV vaccine antibodies impact the pathogenesis of ZIKV across the maternal fetal axis, maternal syncytiotrophoblasts were inoculated with ZIKV or ZIKV incubated with YFV vaccine anti-sera, and viral load was measured 72 hours post inoculation. Here we report that BeWo and HUVEC cells are permissive to ZIKV and that the impact of YFV post-vaccination antibodies on ZIKV replication is cell line dependent. Embryoid bodies are also permissive to ZIKV and the presence of YFV antibodies collected 1 to 6 months post vaccination enhances ZIKV infection. Our data show that each of the cell lines and EBs have a unique response to ZIKV complexed with post-vaccination serum suggesting there may be cell-specific mechanisms that impact congenital ZIKV infections. Since ZIKV infections can cause severe congenital syndromes, it is crucial to understand any potential enhancement or protection offered from cross-reactive, post-vaccination antibodies.

Since 2007, highly pathogenic clade 2.3.2 H5N1 avian influenza A [A(H5N1)] viruses have evolved to clade 2.3.2.1a, b and c, and currently only 2.3.2.1c A(H5N1) viruses circulate in wild birds and poultry. During antigenic evolution, clade 2.3.2.1a and c A(H5N1) viruses acquired both S144N and V223I mutations around the receptor binding site of hemagglutinin (HA), with S144N generating an N-glycosylation sequon. We introduced single or combined reverse mutations, N144S and/or I223V, into the HA gene of clade 2.3.2.1c A(H5N1) virus and generated PR8-derived, 2 + 6 recombinant A(H5N1) viruses. When we compared replication efficiency in embryonated chicken eggs, mammalian cells and mice, the recombinant virus containing both N144S and I223V mutations showed increased replication efficiency in avian and mammalian hosts and pathogenicity in mice. The N144S mutation significantly decreased avian receptor affinity and egg white inhibition, but not all mutations increased mammalian receptor affinity. Interestingly, the combined reverse mutations dramatically increased the thermostability of HA. Therefore, the adaptive mutations possibly acquired to evade avian immunity may decrease viral thermostability as well as mammalian pathogenicity.

This is a theoretical and empirical article. In the first part, an original definition of the cross-border market for cultural services has been developed, based on classic market definitions. The structure and conditions of functioning for this market have also been presented. The next part of the article discusses the supply side of the cross-border market of cultural services for the two twin towns: Cieszyn (Poland) and Český Těšín (Czech Republic). Next, based on the surveys conducted, the participation of residents of both towns in the most important cultural events organised by cultural institutions on both sides of the border was examined.

Suppressors of cytokine signaling (SOCS) influence cytokine and growth factor signaling by negatively regulating the JAK-STAT pathway. This maintains homeostasis during host immune response. However, functional characterization of SOCS family members in invertebrates is limited. In this study, we discovered the Type-I subfamily of the SOCS genes in the mealworm beetle, T. molitor. The full-length ORFs of TmSOCS5, TmSOCS6, and TmSOCS7 consisted of 1,389, 897 and 1,458 nucleotides, encoding polypeptides of 462, 297 and 485 amino acids, respectively, The C-terminal region of TmSOCS was highly conserved in the SH2 and SOCS box domains. Phylogenetic analysis revealed that the three SOCS genes clustered within the same sub-family and the highest amino acid identity was with the Tribolium castaneum SOCS genes (TcSOCS). While the expression of TmSOCS5 and TmSOCS6 was low in larval, pupal, and adult stages of the insect, TmSOCS7 showed higher expression. The expression of TmSOCS5 and TmSOCS6 was higher in larval hemocytes and adult ovary. The microbes expressed the three TmSOCS genes to varying degrees. C. albicans elicited the strongest response in the host with highest 15-fold expression in TmSOCS7 3 h post-inoculation. Collectively, these data suggest that the Type I TmSOCS could play a role in eliciting host immunity.

The formability and failure behavior of TRIP steel blanks were investigated through various stress states. The forming limit diagram (FLD) at fracture is constructed both experimentally and numerically. Numerical studies are performed to evaluate the applicability of different damage criteria in predicting the FLD as well as complex cross-die deep drawing process. The fracture surface and numerical results revealed that the material failed in a different mode for different strain path. Therefore, Tresca model which is based on shear stress accurately predicted the conditions where shear had the profound effect on the damage initiation, whereas Situ localized necking criterion was able to calculate the conditions which localization was dominant.

Since the Sustainable Development Goals (SDGs) came into effect, both UNESCO and other international organisations recommend empowering youth to implement the SDGs in universities. Getting started with the SDGs at university level is of special relevance in pre-service teacher training since future teachers are powerful agents of change in the lives of young people. Future teachers need to acquire competencies in sustainability to be able to promote meaningful changes in sustainable behaviour. To that end, holistic approaches to facilitate their acquirement need to be developed. The aim of this study is to explore which teaching methodologies are suitable for the development of competencies in sustainability in Higher Education (HE) and how to empower students to take a leading role in implementing the SDGs in universities. The participants in the study are a group of 23 students in pre-service teacher training. The experimental educational model used for the development of sustainable competencies consists of a methodological sequence of Project-Oriented Learning (POL) and a Cross-disciplinary Workshop on Sustainable Food. This study provides evidence that a holistic approach is appropriate for developing sustainable competencies and contributes to empowering students to implement SDG 12 at their university.

Water stress (WS) and heat stress (HS) have a negative effect on soybean plant growth and crop productivity. During WS, soybean plants opt for survival through ion homeostasis and the conformations of proteins are disconcerted as plant cells lose water while HS leads to difficulties in flowering and fruiting. Some of these changes include oxidative stress leading to the destruction of photosynthetic apparatus, macromolecules within cells and the onset of complex signaling cascades. Changes in the physiological characteristics, proteome, and certain metabolites investigated on molecular and cellular functions were studied in two soybean cultivars exposed to different heat and water stress conditions independently and in combination. Leaf protein composition was studied using 2-DE and complemented with MALDI TOF mass spectrometry. While two cultivars displayed genetic variation in response to water and heat stress, thirty-nine proteins were significantly altered in their relative abundance in response to WS, HS and combined WS+HS in both cultivars; a majority of them involved in metabolism, response to heat and photosynthesis showing significant cross-tolerance mechanisms. Functional analysis revealing a majority of heat responsive-proteins were more abundant during HS and combined stress (WS+HS) whereas these proteins were low to WS in cultivar PI 471938 and heat shock proteins were in low abundance to water, heat and combined stresses in cultivar R95-1705. Most protein abundances were not correlated with their expression at mRNA levels in PI cultivar, however, in cultivar R 95, the expression levels of transcript follow their relative abundance in proteins. Our systems bioinformatics analyses revealed that MED37C, a probable mediator of RNA polymerase transcription II protein showed potential interacting partners in Arabidopsis and our studies signifies the marked impact of this protein in PI cultivar. Elevated activities in antioxidant enzymes indicate that the PI-371938 cultivar has the ability to restore the oxidation levels and sustain the plant during the stress. Our study hypothesizes the plant’s development of cross-stress tolerance which will help foster the ongoing ventures in genetic modifications in stress tolerance.

The pandemic associated with SARS-CoV-2 is a worldwide public health challenge. The WHO has proposed to achieve 70% COVID-19 vaccination coverage in all countries by mid-2022. Nevertheless, the prevention strategy based on COVID-19 vaccination and other applied prevention measures have not been sufficient to prevent SARS-CoV-2 epidemic waves. The study assessed the vaccination coverage that would be required to establish herd immunity against SARS-CoV-2 by taking into account virus transmissibility (Ro values from 1.1 to 10) and Covid-19 vaccination effectiveness. The study found that Covid-19 vaccination programs could establish herd immunity against SARS-CoV-2 with Ro &lt; 3 with levels of Covid-19 vaccination effectiveness of 10−100% and against viruses with Ro values ranging from 3 to 10 with levels of Covid-19 vaccination effectiveness of 70−100%. Factors reducing Covid-19 vaccination effectiveness (emergent variants, reinfections, high risk individuals) and factors increasing SARS-CoV-2 transmissibility (close settings) increased percentages of vaccination coverage that would be required to establish herd immunity. The vaccination coverage objective of 70% could be adequate against SARS-CoV-2 with Ro values of 1.1−2.5, while percentages of vaccination coverage of 80% and 90% could be more adequate against viruses with Ro values of 2.5−3.5 and &gt;3.5, respectively. On February 2022, the vaccination coverage for complete vaccination was lower than 70% in 73.2% of the countries of the world. Percentages of Covid-19 vaccination coverage must be increased in most countries of the world to increase individual and herd immunity levels in the population.

Dendritic cells (DCs) are the professional antigen-presenting cells that recognize and present antigens to naïve T cells to induce antigen-specific adaptive immunity. Among the T-cell subsets, T helper type 2 (Th2) cells produce the humoral immune responses required for protection against helminthic disease by activating B cells. DCs induce a Th2 immune response at a certain immune environment. Basophil, eosinophil, mast cells, and type 2 innate lymphoid cells also induce Th2 immunity. However, in the case of DCs, controversy remains regarding which subsets of DCs induce Th2 immunity, which genes in DCs are directly or indirectly involved in inducing Th2 immunity, and the detailed mechanisms underlying induction, regulation, or maintenance of the DC-mediated Th2 immunity against allergic environments and parasite infection. A recent study has shown that a genetic defect in DCs causes an enhanced Th2 immunity leading to a severe atopic dermatitis. We summarize the Th2 immune-inducing DC subsets, the genetic and environmental factors which involved in DC-mediated Th2 immunity, and current therapeutic approaches for Th2-mediated immune disorders. This review is to provide an improved understanding of DC-mediated Th2 immunity and Th1/Th2 immune balancing, leading to control over their adverse consequences.

This research was conducted to manufacture thermally expandable microspheres (TEMs) for vehicles’ underbody coating and to apply them on an industrial scale. TEMs heat resistance was studied depending on the ratios of a cross-linking agent and an initiator. This research focused on the content of a cross-linking agent and how it affected the results. The TEMs’ outer shell was thickened to solve the problem of the foam expansion ratio’s reduction that occurred due to the shrinkage after the maximum expansion (Tmax) was reached. After foaming, the cross-sectional thickness and surface of the sample with thickened outer shell were observed. The TEMs with the thickened shell showed the least shrinkage, which indicated excellent shrinkage stability, even after prolonged exposure to heat.

Zika virus (ZIKV) is a flavivirus that originated in Africa but emerged in Latin America in 2015. In this region, other flaviviruses such as Dengue (DENV), West Nile, and Yellow Fever Virus (YFV) also circulate, allowing for possible antigenic cross-reactivity to impact viral infections and immune responses. Studies have found antibody mediated enhancement between DENV and ZIKV, but the impact of YFV antibodies on ZIKV infection has not been fully explored. ZIKV infections cause congenital syndromes, such as microcephaly, necessitating further research into ZIKV vertical transmission through the placental barrier. Recent advancements in biomedical engineering have generated co-culture methods that allow for in vitro recapitulation of the maternal: fetal interface. This study utilized a transwell assay, which is a co-culture model utilizing human placental syncytiotrophoblasts, fetal umbilical cells, and a differentiating embryoid body to replicate the maternal: fetal axis. To determine if cross reactive YFV vaccine antibodies impact the pathogenesis of ZIKV across the maternal fetal axis, maternal syncytiotrophoblasts were inoculated with ZIKV or ZIKV incubated with YFV vaccine anti-sera, and viral load was measured 72 hours post inoculation. The data show that the impact of YFV on ZIKV replication is cell line dependent. In differentiating embryoids, the presence of YFV antibodies enhanced ZIKV infection. Since viral pathogenesis, and the impact of antigenic cross-reactive antibodies, is cell line specific at the maternal-fetal axis, this suggests there may be discreet mechanisms that impact congenital ZIKV infections.

Multi-task Gaussian processes (MTGPs) are a powerful approach for modeling structured dependencies among multiple tasks. Researchers on MTGPs have contributed to enhance this approach in various ways. Current MTGP methods, however, cannot model nonlinear task correlations in a general way. In this paper we address this problem. We focus on spectral mixture (SM) based kernels and propose an enhancement of this type of kernels, called multi-task generalized convolution spectral mixture (MT-GCSM) kernel. The MT-GCSM kernel can model nonlinear task correlations and mixtures dependency, including time and phase delay, not only between different tasks but also within a task at the spectral mixture level. Each task in MT-GCSM has its own generalized convolution spectral mixture kernel (GCSM) with a different number of convolution structures and all spectral mixtures from different tasks are dependent. Furthermore, the proposed kernel uses inner and outer full cross convolution between base spectral mixtures, so that the base spectral mixtures in the tasks are not necessarily aligned. Extensive experiments on synthetic and real-life datasets illustrate the difference between MT-GCSM and other kernels as well as the practical effectiveness of MT-GCSM.

Introduction: The top priority of active immunoprophylaxis of pertussis is immunisation of infants as they can develop severe multiple-organ complications or even die from this disease. Objectives: The aim of the work is the identification of factors negatively affecting vaccine immunity to pertussis in preschool children prior to the administration of the first booster. Patients and Methods: The research was conducted on 352 children from 4.5 to 5.9 years of age who were hospitalised in the University Children’s Hospital in Lublin (Poland) from 1 January 2012 to 31 December 2015. The children taking part in the study had been administered all the mandatory vaccines from their birth to the age of 2 or 2.5 years old according to the Polish Immunisation Program 2008-2009. The immunoenzymatic method ELISA was applied to assess vaccine immunity to tetanus, diphtheria, pertussis, Haemophilus influenzae type b (Hib), poliomyelitis (IPV), mumps, rubella and measles. The level of vaccine antibodies to hepatitis type B was determined chemilumiscently. Results: The protective antibody titer was not found in 41 (11.65%) children before the administration of the booster. To verify the collective impact of parameters analised on antibody titer to pertussis, the Generalized Linear Model (GLZ) was used. Gender, type of vaccine, asthma, Hib and mumps antibody titers have been shown to be predicators of vaccine immunity to pertussis. Conclusions: Immunomodulation considered on the example of titer of IgG antibody to pertussis can serve as a useful model of the assessment of development of acquired immunity after mandatory vaccinations.

Recently deep cross-modal hashing networks have received increasing interests due to its superior query efficiency and low storage cost. However, most of existing methods concentrate less on hash representations learning part, which means the semantic information of data cannot be fully used. Furthermore, they may neglect the high-ranking relevance and consistency of hash codes. To solve these problems, we propose a Self-Attention and Adversary Guided Hashing Network (SAAGHN). Specifically, it employs self-attention mechanism in hash representations learning part to extract rich semantic relevance information. Meanwhile, in order to keep invariability of hash codes, adversarial learning is adopted in the hash codes learning part. In addition, to generate higher-ranking hash codes and avoid local minima early, a new batch semi-hard cosine triplet loss and a cosine quantization loss are proposed. Extensive experiments on two benchmark datasets have shown that SAAGHN outperforms other baselines and achieves the state-of-the-art performance.

Façade elements are a building component that satisfies multiple performance parameters. Among other things, “advanced façades” take advantage of hybrid solutions, such as assembling laminated materials. In addition to the enhanced mechanical properties that are typical of optimally composed hybrid structural components, these systems are energy-efficient, durable, and offer lighting comfort and optimal thermal performance, an example of which is the structural solution developed in collaboration with the University of Zagreb and the University of Ljubljana within the Croatian Science Foundation VETROLIGNUM project. The design concept involves the mechanical interaction of timber and glass load-bearing members without sealing or bonding the glass-to-timber surfaces. Following earlier research efforts devoted to the structural analysis and optimization of thus-assembled hybrid Cross-Laminated Timber (CLT)-glass façade elements, in this paper, special focus is given to a thermal and energy performance investigation under ordinary operational conditions. A simplified numerical model representative of a full-size building is first presented by taking advantage of continuous ambient records from a Live-Lab mock-up facility in Zagreb. Afterwards, a more detailed Finite Element (FE) numerical analysis is carried out at the component level to further explore the potential of CLT–glass façade elements. The collected numerical results show that CLT–glass composite panels can offer stable and promising thermal performance for façades similar to national and European standard requirements.

Free volume is an extremely important intrinsic defect in polymers. Structurally, the free volume is the randomly distributed holes in the polymer molecular chain segments. From the perspective of molecular movement, it is also the space needed for the movement of molecular segments. In proton exchange membrane fuel cells, the free volume is also the space needed for the directional conduction of protons. Irradiation grafting sulfonated polyvinylidene fluoride (PVDF) is one of the methods to produce proton exchange membrane with good proton channel rate. Using the LYS-1 program, based on the linear absorption coefficient and backscatter coefficient models, the percentage of annihilated positrons in PVDF in the two-layer model and the three-layer model was studied, and comparing the two fitting results it is determined that the model closest to the positron annihilation percentage required by the PALS experiment is the two-layer model, which allows the percentage of positrons that are annihilated in PVDF films with a thickness of 100 μm to reach 46% using the high energy positron source ⁴⁴Ti without using the positron moderator. Using positron annihilation lifetime spectrum (PALS) analysis methods, based on Eldrup's classical model of free volume, the influence of absorbed doses of α particles on the free volume and crystallinity of PVDF was investigated, respectively. Based on the two test results the model of cross-linking and degradation of polyvinylidene fluoride irradiated by α particles was determined. Afterwards, X-ray diffraction (XRD) methods was used to study the change of PVDF crystal area before and after irradiation. The XRD results are consistent with the results measured by PALS.

As a universal pathogen leading to neonatal defects and transplant failure, Human cytomegalovirus (HCMV) has strict species specificity that the inability to using this virus in animals has hampered its pathogenesis study. However, the mechanism of cross-species barrier remains elusive that no non-human cell model has been established to fill this knowledge gap. We observed that primary dermis fibroblasts (TSDF) isolated from the Chinese tree shrew (Tupaia belangeri chinensis), a small laboratory animal with close affinity to primates, were permissive to HCMV replication. In TSDF infected with GFP-expressing HCMV, the green fluorescence and cytopathic effect were observed and the expression of 3 kinetic genes and replication of viral genome were detected. The cell-free viruses produced in TSDF reached 103 pfu/mL at 96 hpi, which were 10-fold lower than in primary human foreskin fibroblasts. Our results demonstrated that TSDF supported low level of lytic replication of HCMV. The TSDF model provides a useful platform for the mechanism study of species barrier of HCMV.

The role of innate immunity in neutralization of viral infections (including COVID-19) and forming long-lasting and specific immune memory is considered. It is assumed that antiviral protection is generated by the mechanism of RNA interference (RNAi) and is based on the presence of specific viral patterns in the DNA library of the host cells.

The limited information available on the structure of complexes involving transcription factors and cognate DNA response elements represents a major obstacle in the quest to understand their mechanism of action at the molecular level. We implemented a concerted structural proteomics approach, which combined hydrogen-deuterium exchange (HDX), quantitative protein-protein and protein-nucleic acid cross-linking (XL), and homology analysis, to model the structure of the complex between the full-length DNA binding domain (DBD) of FOXO4 and its DNA binding element (DBE). The results confirmed that FOXO4-DBD assumes the characteristic forkhead topology shared by these types of transcription factors, but its binding mode differs significantly from those of other members of the family. The results showed that the binding interaction stabilized regions that were rather flexible and disordered in the unbound form. Surprisingly, the conformational effects were not limited only to the interface between bound components but extended also to distal regions that may be essential to recruiting additional factors to the transcription machinery. In addition to providing valuable new insights into the binding mechanism, this project provided an excellent evaluation of the merits of structural proteomics approaches in the investigation of systems that arematerial not directly amenable to traditional high-resolution techniques.

Predator-prey interactions present heightened opportunities for pathogen spillover, as predators are exposed to novel parasites through consumption of prey harboring potentially infectious agents. Epizootics with high morbidity and mortality have been recorded following prey-to-predator spillover events with significant conservation implications, particularly for sensitive species. However, relatively few virulent infections following prey consumption are reported, given the very large number of exposures that presumably occur. Further, many transmitted agents are infectious but clinically silent and thus go unrecognized. Mechanisms that determine outcome of predator exposure to prey-based pathogens therefore represent an important, understudied component of disease dynamics that should be considered in modeling approaches and empirical research to better understand disease risk and emergence, particularly in vulnerable or threatened species.

This paper focuses on the impact of defects density and carrier capture cross-section area in the electron transport material (ETM), hole transport material (HTM), and absorber layers on the performance of perovskite solar cells and quantum efficiency (QE). Furthermore, the impact of defects density at the interface between ETM/absorber and absorber/HTM is also studied. SCAPS-1D software is used in the current study in determining solar cell performance. The proposed perovskite solar cell structure is a planar FTO/TiO2/ CH3NH3PbI3/ Cu2O. The results indicated that increasing the defect density in the absorber layer significantly affects cell performance, while in ETM and HTM layers, the cell parameters remain unaffected. It is also found that the defect capture cross-section has a similar behavior to the defect density in the main layers (ETM, absorber, and HTM). In addition, it is observed that by increasing the defects density in the ETM/absorber and absorber/HTM interfaces layer, the cell parameters FF, Jsc, and PCE have been slightly decreased, with no effect on Voc. Moreover, it is also noted that the quantum efficiency QE is sharply reduced. Finally, this paper introduced the correlation between the defect density and the capture cross-section, which is the first attempt to find such a relationship in perovskite solar cells to the knowledge of the authors.

A parallel between defense powers of sovereign nations and effective immunity that guards health is relevant to demonstrate vulnerability of immune system under external forces (vaccines, drugs). History demonstrated that sovereignty (power within) of small nations often threatened or destroyed by military might of powerful nations (power without) who use false-flags and propaganda for motives that are financial-control-driven. Similarly, we propose that body’s complex immune neuroplasticity (power within, adaptive, horizontal) is stretched-thin and weakened by the external forces, particularly by vaccination of the unborn/newborn or immune-compromised individuals. Validity of genomics (innate, perpendicular) as origins of ‘hereditary’ diseases (eg, allergies, diabetes, cancers) that for a century dominated research and treatment is also challenged. In conclusion, we propose that the pressure/power from within creates life with potential to sustain health, while the pressure/power from without, weaken and destroy life.

In humans, coronaviruses can cause infections of the respiratory system, with damage of varying severity depending on the virus examined: ranging from mild or moderate upper respiratory tract diseases, such as the common cold, to pneumonia, severe acute respiratory syndrome, kidney failure and even death. Human coronaviruses known to date, common throughout the world, are seven. The most common - and least harmful - ones were discovered in the 1960s and cause a common cold. Others, more dangerous, were identified in the early 2000s and cause more severe respiratory tract infections. Among these the SARS-CoV, isolated in 2003 and responsible for the Severe Acute Respiratory Syndrome (the so-called SARS), which appeared in China in November 2002, the Coronavirus 2012 (2012-nCoV) cause of the Middle Eastern Respiratory Syndrome from Coronavirus (MERS), which exploded in June 2012 in Saudi Arabia, and actually SARS-CoV-2. On December 31, 2019, a new Coronavirus strain was reported in Wuhan, China, identified as a new Coronavirus beta strain ß-CoV from Group 2B, with a genetic similarity of approximately 70% to SARS-CoV, the virus responsible. of SARS. In the first half of February, the International Committee on Taxonomy of Viruses (ICTV), in charge of the designation and naming of the viruses (i.e., species, genus, family, etc.), thus definitively named the new coronavirus as SARS-CoV-2. This article highlights the main knowledge we have about the biomolecular and pathophysiologic mechanisms of SARS-CoV-2.

The concept of sustainable management in culture has been recognised in global strategic documents on sustainable development for more than a decade. It is also increasingly reflected in the cultural polices of particular states, and – very importantly –cultural managers responsible for shaping the cultural offer in cities are becoming more interested in this concept. Despite the increasing attention being paid to this topic among both practitioners and theoreticians of management, in none of these documents or other works can we find any content directly related to the possibility of applying this concept in a town which, due to political turmoil, has been divided by a national border. Hence, this gap was the direct impulse for taking up research in this field. In the article, by using different notions of the market, our own definition of a cross-border market for cultural services was developed, and the conditions for the functioning of this market were presented based on the example town of Cieszyn (Poland) and Český Těšín (Czech Republic). In the opinion of the authors of the article, the development and functioning of a cross-border market for cultural services is essential for the application of the concept of sustainable management of the cultural offer in a town divided by a border. For the purpose of the article, a survey and individual interviews with experts shaping the cultural offer in Cieszyn and Český Těšín were conducted. The results of the research prove that despite numerous cross-border Czech-Polish projects carried out by cultural institutions, there are still many barriers in the town which make it difficult for the residents to benefit from the cultural offer available on the other side of the border. These barriers limit the full implementation and application of the concept of sustainable management of the cultural offer.

There is a global rise in the emergence of infectious diseases and the enigmatic coronavirus disease 2019 (COVID-19) being the most recent one. It is ravaging the world with little understanding of its etiology and factors affecting its transmission dynamics. Meanwhile, seasonal variations in weather are major factors impacting infectious disease transmission patterns. Developing countries are likely to be most affected by weather changes, largely because of challenges such as inadequate drainage and sewage management systems, healthcare facilities, education, and funding to efficiently mitigate infectious diseases. In Nigeria, weather conditions alternate between rainy and dry seasons. Conditions such as rainfall, flood, and humidity have been reported to influence infectious disease transmission. Thus, understanding the impact of weather changes in transmission dynamics and immune response to COVID 19 will help in preventive measures and policy making to curtail its spread most especially in Nigeria as the rainy season fully sets in.

Brain Tumor is one of the severe diseases and occurrence of this disease threats human life. Detection of brain tumor in advance can secure patient’s life from unwanted loss. Well-timed and swift disease detection and treatment strategy can lead to improved quality of life in these patients. This paper attempts to use Machine Learning based ensemble approaches for recognising patients with brain tumor. Ensemble technique based AdaBoost classifier and 10-fold stratified cross-validation method are assembled in single platform is proposed in this paper for prediction of brain tumor. This prediction is compared against three baseline classifiers such as Gradient Boost, Random Forest and Extra Trees classifier. Experimental result implies the superiority of this model with an accuracy of 98.97%, f1-score of 0.99, kappa statistics score of 0.95 and MSE of 0.0103.

Original and improved version of the Hardy Cross iterative method with related modifications are today widely used for calculation of fluid flow through conduits in loops-like distribution networks of pipes with known node fluid consumptions. Fluid in these networks is usually natural gas for distribution in the municipalities, water in waterworks or hot water in district heating system, air in the case of ventilation systems in buildings or mines, etc. Since, the resistances in these networks depend of flow, problem is not linear like in electrical circuits, and iterative procedure must be used. In both version of the Hardy Cross method, in original and in the improved one, initial results of calculation in iteration procedure is not flow, but rather the correction of flow. Unfortunately, these corrections should be added to or subtracted from a flow calculated in previous iteration according to complicate algebraic rules. After the here presented node-loop method, final results in each of the iterations is flow directly rather than flow correction. In that way complex algebraic scheme for sign of flow correction is avoided, while the final results still remain unchanged. Numbers of required iterations for the same results are comparable with the improved Hardy Cross method.

The genus Flavivirus contains pathogenic vertebrate-infecting flaviviruses (VIFs) and in-sect-specific flaviviruses (ISF). ISF transmission to vertebrates is inhibited at multiple stages of the cellular infection cycle, via yet to be elucidated specific antiviral responses. The Zinc-finger an-tiviral protein (ZAP) in vertebrate cells can bind CpG dinucleotides in viral RNA, limiting virus replication. Interestingly, the genomes of ISFs contain more CpG dinucleotides compared to VIFs. In this study, we investigated whether ZAP prevents two recently discovered lineage II ISFs, Binjari (BinJV) and Hidden Valley viruses (HVV) from replicating in vertebrate cells. BinJV protein and dsRNA replication intermediates were readily observed in human ZAP knockout cells when cultured at 34 ˚C. In ZAP expressing cells, inhibition of the interferon response via interferon response factors 3/7 did not improve BinJV protein expression, whereas treatment with kinase inhibitor C16, known to reduce ZAP’s antiviral function, did. Importantly, at 34 ˚C both BinJV and HVV successfully completed the infection cycle in human ZAP knockout cells evident from infectious progeny virus in the cell culture supernatant. Therefore, we identify vertebrate ZAP as an important barrier that protects vertebrate cells from ISF infection This provides new insights into flavivirus evolution and the mechanisms associated with host switching.

With the advent of COVID19, the attitude of health authorities around the world, led mainly by the West, demanded a level of proof as evidence for cheap, non-patented remedies while promoting expensive, patented, and untested remedies by using emergency use authorization and special provisions afforded to the status of a pandemic emergency. Western science has neither a tested nor a valid historical basis of a logical system that informs to authenticate scientific practices. Here we use a logical heuristic derived from ancient Buddhist logic, which is consistent with the conduct of modern science. We applied the heuristic to show that enough evidence was available for using cost-effective early therapies such as vitamin D supplementation as a public health measure during the first half of 2020. Strong supporting evidence has since accumulated. Apart from political and financial decisions incompatible with science and other conflicts of interest, a critical barrier to evaluating and approving early therapies appears to be the fallacy that the randomized controlled trial (RCT) is the superior proof method in medical hypotheses, including those for nutrients. Logically, no reason exists why properly designed retrospective, ecological, and naturalistic studies with adequate sample sizes and applied appropriate statistical methods would not be as valid as RCTs, especially when elucidating a causative factor instead of treatment. That assertion is particularly true for nutrient deficiencies, interventions, and other cost-effective therapies. Leading health authorities’ failure or refusal to consider other study types (because of either poor logic or vested interest) probably contributed to the spread of misinformation, symptomatic disease, complications, and deaths from COVID19. Partial immunity derived from vaccines and the later development of more contagious variants—and thus a sense of acceptance that SARS-CoV-2 had progressed from a pandemic to an endemic—shows the hollowness of the initial promotions and mandates of vaccines as a cure. Adequate knowledge was available in 2020 to advise that SARS-CoV-2 will continue to mutate, with variants emerging a few times per year, making the vaccine less effective. Emerging evidence confirms that natural immunity better protects against new variants than vaccination against the spike protein. Had vitamin D been adopted as part of the public health measure through a broader supplementation program in 2020 or even today (through sun exposure or as a prophylactic or adjunct therapy early on), the viral spread and symptomatic disease may have been suppressed, with minimal lockdowns and quarantine, and economic harm. The pandemic could have been halted with a significantly reduced need for hospitalization, complications, and deaths, potentially saving millions of lives.

Sea urchins are long-living invertebrates with a complex immune system which includes extended families of immune receptors. A central immune gene family in the sea urchins encodes for the Transformer (Trf) proteins. The Trf family was so far studied mainly in the purple sea urchin Strongylocentrotus purpuratus. In this study, we explored this protein family in the Mediterranean Sea urchin Paracentrotus lividus. The PlTrf genes and predicted proteins were found to be highly diverse and showed a typical Trf size range and structure. We found that P. lividus coelomocytes and hemolymph contain different PlTrf protein repertoires with a shared subset which specifically bind E. coli bacteria. Using FACS, we identified five different P. lividus coelomocyte sub-populations with cell surface Trf protein expression. The relative abundance of the Trf-positive cells sharply increased following immune challenge with E. coli bacteria, but not following challenge with LPS or sea urchin pathogen V. penaeicida. Finally, we demonstrated that the phagocytosis of E. coli bacteria by P. lividus phagocytes is mediated through the hemolymph and is inhibited by blocking Trf activity with anti-Trf antibodies. Together, our results suggest collaboration between cellular and humoral Trf-mediated effector arms in the P. lividus specific immune response to pathogens.

Limited observational studies have described the relationship between sleep duration and overall diet. The present study investigated the association between sleep duration at weekdays and empirically derived dietary patterns in a nationally representative sample of UK adults, aged 19-64 years old, participating in the 2008-2012 UK National Diet and Nutrition Survey Rolling Programme. Survey members completed between three to four days of dietary records. Sleep duration at weekdays was categorised into tertiles to reflect short, normal and long sleep duration. Social jetlag was calculated as the difference between sleep duration at weekends and weekdays. The association between sleep duration/ social jetlag and dietary patterns, derived by principal components analysis, was assessed regressing diet on sleep whilst accounting for the complex survey design and adjusting for relevant confounders. Survey members in the highest tertile of sleep duration had on average 0.45 (95% CI -0.78, -0.12) lower healthy dietary pattern score compared to middle tertile (p =0.007). There was an inverted u-shaped association between social jetlag and a healthy dietary pattern, such that when sleep at weekends exceeded weekday sleep by 1h 45min, scores for indicating a healthy dietary pattern declined (p =0.005). In conclusion, long sleep duration at weekdays and an increased social jetlag are associated with a lower healthy dietary pattern score. Further research is required to address factors influencing dietary patterns in long sleepers.

The human antibody response to influenza virus infection or vaccination is as complicated as it is essential for protection against flu. The constant antigenic changes of the virus to escape human herd immunity hinder the yearly selection of vaccine strains since it is hard to predict which virus strains will circulate for the coming flu season. A "universal" influenza vaccine that could induce broad cross-influenza subtype protection would help to alleviate this burden. However, the human antibody response is intricate and often obscure, with factors like antigenic seniority or original antigenic sin "OAS", and back-boosting ensuring that each person mounts a unique immune response to infection or vaccination with any new influenza virus strain. Notably, the effects of existing antibodies on cross-protective immunity after repeated vaccinations are unclear. More research is needed to characterize the mechanisms at play, but traditional assays such as hemagglutinin inhibition (HAI) and microneutralization (MN) are excessively limited in scope and too resource-intensive to effectively meet this challenge. In the past ten years, new multiple dimensional assays (MDAs) have been developed to help overcome these problems by simultaneously measuring antibodies against a large panel of influenza hemagglutinin (HA) proteins with a minimal amount of sample in a high throughput way. MDAs will likely be a powerful tool for accelerating the study of the humoral immune response to influenza vaccination and the development of a universal influenza vaccine.

Wheat (Triticum aestivum L.) breeding programs can take over a decade to release a new variety. However, new methods of selection such as genomic selection (GS) must be integrated to decrease the time it takes to release new varieties to meet the demand of a growing population. The implementation of GS into breeding programs is still being explored, with many studies showing its potential to change wheat breeding through achieving higher genetic gain. In this review, we explore the integration of GS for a wheat breeding program by redesigning the traditional breeding pipeline to implement GS. We propose implementing a two-part breeding strategy by differentiating between population improvement and product development. The implementation of GS in the product development pipeline can be integrated into most stages and can predict within and across breeding cycles. Additionally, we explore optimizing the population improvement strategy through GS recurrent selection schemes to reduce crossing cycle time and significantly increase genetic gain. The recurrent selection schemes can be optimized for parental selection, maintenance of genetic variation, and optimal cross-prediction. Overall, we outline the ability to increase the genetic gain of a breeding program by implementing GS and a two-part breeding strategy.

Molecular methods have revolutionised virtually every area of biology, and metazoan phylogenetics is no exception: molecular phylogenies, molecular clocks, comparative phylogenomics, and developmental genetics have collectively transformed our understanding of the evolutionary history of animals. Moreover, the diversity of methods and models within molecular phylogenetics has resulted in significant disagreement among molecular phylogenies as well as between these and traditional phylogenies. Here, I argue that tackling this multifaceted problem lies in integrating evidence to infer the best evolutionary scenario. I begin with an overview of recent developments in early metazoan phylogenetics, followed by a discussion of key conceptual issues in phylogenetics revolving around phylogenetic evidence and theory. I then argue that integration of different kinds of evidence is necessary for arriving at the best evolutionary scenario rather than the best-fitting cladogram. Finally, I discuss the prospects of this view in stimulating interdisciplinary cross-talk in early metazoan research and beyond.

We present a general approach to define reproduction ratios or numbers to monitor the outbreak of epidemics that are modeled by mathematical evolution equations. This provides a solution to an important topic that has not been completely settled in the literature, especially in the case of complex epidemiological models. We illustrate our procedure with a full implementation of a standard deterministic SEIR model that is applied to examine the Covid-19 outbreaks and the effects of intervention measures in several countries in America (Argentina, Brazil, Mexico, USA) and Europe (France, Italy, Spain and UK) in 2020. Our code is also used to investigate herd immunity levels for Covid-19, indicating values between 85% and 90%.

Finding new ways for the preparation of cross-linked structures is a significant problem in terms of materials for biomedical application, lithium batteries electrolytes, and etc. Within this work we have studied the possibility to utilize hydrosilylation and Piers-Rubinsztajn reactions to obtain cross-linked model phosphazene compounds, containing eugenoxy and guaiacoxy groups. It was shown that Piers-Rubinsztajn reaction cannot be efficiently used to prepare tailored polymer-matrix, due to the catalyst deactivation by nitrogen atoms of phosphazene units. A number of cross-linked phosphazene-based materials was obtained with the use of hydrosilylation reaction and their properties were studied by NMR spectroscopy, FTIR, DSC, and TGA. This work showed a perspective for the use of eugenoxy functional groups for the preparation of three-dimensional hybrid phosphazene/siloxane-based materials for various applications.

Influenza virus infection causes severe respiratory illness in people worldwide, disproportionately affecting infants. The immature respiratory tract coupled with the developing immune system is thought to synergistically play a role in the increased disease severity in younger age groups. Although vaccines remain the best solution for protecting this vulnerable population, no vaccines are available for those under 6 months, and for infants aged 6 months to 2 years, the vaccine elicits a dampened immune response. Dampened immune responses may be due to unique features of the infant immune system and a lack of pre-existing immunity. Unlike older children and adults, the infant immune system is Th2 skewed and has less antigen presenting cells and soluble immune factors. Paradoxically, we know that a person’s first infection with the influenza virus during infancy or childhood leads to the establishment of life-long immunity toward that particular virus strain. This is called influenza imprinting. To provide better protection against influenza virus infection and disease in infants, more research must be conducted to understand the imprinting event. We contend that by understanding influenza imprinting in the context of the infant immune system and the infant’s immature respiratory tract, we will be able to design more effective influenza vaccines for both infants and adults. Working through the lens of imprinting, using infant influenza animal models such as mice and ferrets, which have proven useful for infant immunity studies, we will gain a better understanding of imprinting and its implications regarding vaccine design. This review examines literature regarding infant immune development, current vaccine strategies, respiratory development, and the importance of researching the imprinting event in infant animal models to develop more effective and protective vaccines for young children.

Background: Public misconception and demand for the indication of antibiotics could lead to inappropriate prescribing and consumption. Successful treatment can only be achieved when the public and industrial users have knowledge on antibiotic use and resistance. This survey is aimed to assess antibiotic usage and knowledge regarding antibiotics and antimicrobial resistance (AMR) among undergraduate students of Universiti Brunei Darussalam (UBD), public university located in Brunei Darussalam. Methods: A cross-sectional study was performed using a self-administered questionnaire. The questionnaire was adapted from the World Health Organization (WHO) Antibiotic Resistance, Multi-country public awareness survey distributed online. Students at UBD were invited to participate in the online survey through internal email. The questionnaire consisted of 5 sections: demographic information, antibiotic usage, knowledge on antibiotics, antibiotic resistance (AMR) and use of antibiotics in agriculture. Data were analyzed descriptively and appropriate inferential statistics was used accordingly. Cronbach’s alpha was also done to determine the internal consistency. The section on antibiotic use and knowledge showed good internal consistency of Cronbach’s alpha 0.66 and 0.86 respectively. Research ethics approval was obtained from the PAPRSB Institute of Health Sciences, Universiti Brunei Darussalam (UBD). Results: A total of 145 students returned the complete questionnaire. The result of the study found that 50% of the students had good level of knowledge of antibiotic and antimicrobial resistance with a mean total knowledge score of 11.4 out of 14. Respondents reported the use of antibiotic in the past (69%). Many of the students could identify the use of antibiotics for the treatment of bacterial infection. However, there were also students who incorrectly thought that antibiotics can be used for cold and flu (43%) and fever (41%). Moreover, 76% of the respondents mistakenly believed that antibiotic resistance is the result of the body becoming resistant to antibiotics. Only 12% of the respondents were found to have poor knowledge in the study. Conclusions: Misconceptions in regards to the use of antibiotics for conditions related to viral illnesses was noticed among the respondents in our study. Thus, improving knowledge on antibiotics is crucial to address those beliefs.

Visualization is an essential tool for analysis of data and communication of findings in the sciences, and the Earth System Science (ESS) are no exception. However, within ESS specialized visualization requirements and data models --- particularly for those data arising from numerical models --- often make general-purpose visualization packages difficult, if not impossible, to effectively use. This paper presents VAPOR: a domain-specific visualization package that targets the specialized needs of ESS modelers, particularly those working in research settings where highly interactive exploratory visualization is beneficial. We specifically describe VAPOR’s ability to handle ESS simulation data from a wide variety of numerical models, as well as a multi-resolution representation that enables interactive visualization on very large data while using only commodity computing resources. We also describe VAPOR’s visualization capabilities, paying particular attention to features for geo-referenced data and advanced rendering algorithms suitable for time-varying, 3D data. Finally, we illustrate VAPOR's utility in the study of a numerically simulated tornado. Our results demonstrate both ease-of-use and the rich capabilities of VAPOR in such a use case.

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.

Over recent years globalisation has occasioned a dramatic rise in cross-cultural interactions – until this was disrupted by the COVID-19 pandemic (OECD 2018, Nelson &amp; Luetz 2021). The ability to competently engage in a multicultural world is often considered the “literacy of the future” (UNESCO 2013, OECD 2018). Global interconnectedness has brought studies into intercultural competence to centre stage (UNDP 2004, Bissessar 2018, Nelson et al. 2019). This has increased the demand for cross-cultural education experiences that facilitate such learning. However, there is a dearth of empirical research into the issues and effects surrounding short-term cross-cultural educational experiences for adolescents. This mixed methods study extends previous research by looking specifically into what impact short-term cross-cultural experiences may have on the formation of intercultural competence and emotional intelligence of Australian high school students. This study used two instruments for measuring intercultural competence and emotional intelligence in a pre- and posttest quasi-experimental design (n=14), the GENE Scale and TEQ. Moreover, it conducted in-depth post experience qualitative interviews (n=7) that broadly followed a phenomenological paradigm of inquiry. The findings suggest that fully embodied cross-cultural immersive experiences offer benefits in areas of intercultural competence and emotional intelligence and can offer meaningful application in areas of current affairs. A greater understanding of the linkages between immersive cross-cultural experiences and intercultural competence offers prospects for policy makers, educators, pastoral carers, and other relevant stakeholders who might employ such experiential learning to foster more interculturally and interracially harmonious human relations.

The combination of chemical cross-linking and mass spectrometry is currently a progressive technology for deriving structural information of proteins and protein complexes. In addition, chemical cross-linking is a powerful tool for stabilizing macromolecular complexes for single particle cryo-electron microscopy. Broad pallets of cross-linking chemistry, currently available for the majority of cross-linking experiments, still rely on the amine-reactive N-hydroxysuccinimide esters targeting mainly N-termini and lysine side chains. These cross-linkers are divided into two groups: water soluble and water insoluble; and research teams prefer one or another speculating on the benefits of their choice. However, the effect of cross-linker polarity on the outcome of cross-linking reaction has never been studied. Herein, we use both polar (bis(sulfosuccinimidyl) glutarate) and non-polar (disuccinimidyl glutarate) cross-linkers and systematically investigated the impact of cross-linker hydrophobicity on resulting distance constraints, using bovine serum albumin as a model protein.

Immunotherapy has gained great momentum with chimeric antigen receptor T cell (CAR-T) therapy, in which patient’s T lymphocytes are genetically manipulated to recognize tumor-specific antigens increasing tumor elimination efficiency. In the last years, CAR-T cell immunotherapy for hematological malignancies achieved a great response rate on patients and is a very promising therapy for several other malignancies. Each new CAR design requires a preclinical proof-of-concept experiment using immunodeficient mouse models. The absence of a functional immune system in these mice makes them simple and suitable to be mathematically modeled. In this work, we developed a three population mathematical model to describe tumor response to CAR-T cell immunotherapy in immunodeficient mouse models, encompassing interactions between a non-solid tumor and CAR-T cells (effector and long-term memory). We account for several phenomena, such as tumor-induced immunosuppression, memory pool formation, and conversion of memory into effector CAR-T cells in the presence of new tumor cells. Individual donor and tumor specificities were considered as uncertainties in the model parameters. Our model is able to reproduce several CAR-T cell immunotherapy scenarios, with different CAR receptors and tumor targets reported in the literature. We found that therapy effectiveness mostly depends on some specific parameters such as the differentiation of effector to memory CAR-T cells, CAR-T cytotoxic capacity, tumor growth rate, and tumor-induced immunosuppression. In summary, our model can contribute to reduce and optimize the number of in vivo experiments with in silico tests to select specific scenarios that could be tested in experimental research. Such in silico laboratory was made available in a Shiny R-based platform called CARTmath. It is an open-source, easy to run simulator, available at github.com/tmglncc/CARTmath or directly on the webpage cartmath.lncc.br, containing this manuscript results as examples and documentation. The developed model, together with the CARTmath platform, provides potential use for assessing different CAR-T cell immunotherapy protocols and associated efficacy, becoming an accessory towards in silico trials.

The purpose of this study was to see how dietary supplementation with phenylpyruvate affected broiler chicken growth, slaughter performance, gut health microbiota, and immunity. A total of 288 day old broiler chickens were randomly assigned to one of four groups (6 replicates each with 12 chicken). NC (basal diet), PC (basal diet plus antibiotic virginiamycin 15ppm), LCP and HCP (basal diet plus phenylpyruvate 1kg/t and 2kg/t, respectively). Results showed that PC had higher ADFI during the first 21 days, and better FCR than the NC, the LCP and HCP also improved broilers’ FCR 0.001 and 0.037% in relation to NC respectively. HCP has a higher all-eviscerated ratio than NC and less abdominal fat than LCP. HCP has increased villus length and crypt depth in the ileum compared to the NC. Bursa was lower in HCP and thymus was lower in LCP and PC. In contrast HCP have lower pro-inflammatory cytokine IL-1, as well as lower TLR4. The phenylpyruvate improved family Selenomonadaceae, genus Megamonas Bacteroides species that are known for beneficial effects like for maintenance of the cell surface structure, regulating aromatic amino acids and C. jejuni-suppressive treatment respectively. Finally, phenylpyruvate feed supplement can be utilized to improve growth performance and positively modulate gut microbiota, however this is less efficient than antibiotics in improving growth performance, although more efficient in improving productive performance and gut morphology. Moreover, high dose of phenylpyruvate is more effective than low dose

Zika virus (ZIKV) co-circulates with several closely related flaviviruses which exhibit similar clinical manifestations thus, clinicians rely on molecular and serological techniques for diagnosis. Cross-reactivity of patient specimens to flaviviruses is a significant impediment to serological diagnosis in areas where multiple flaviviruses co-circulate. Furthermore, patient exposure history to any of these viruses could complicate serological response patterns which could result in over and/or underdiagnosis of ZIKV infection. Three strains of ZIKV, dengue serotypes 1-4, West Nile virus, Japanese Encephalitis virus, and Yellow Fever virus were evaluated for neutralizing properties against 3 monoclonal antibodies, 4 ZIKV-naïve patients with flavivirus exposure history, 5 patients with verified ZIKV exposure and unknown flavivirus exposure history, and 5 flavivirus-naive patients with ZIKV-only exposure. Patients naïve for ZIKV exposure effectively neutralized multiple strains of ZIKV. Overall, the prototype ZIKV isolate MR-766 did not behave like the other ZIKV isolated used in this study. MR-766 was neutralized more completely by polyclonal patient serum than recent ZIKV isolates. MR-766 was neutralized better than dengue virus in ZIKV-naïve patients with prior dengue exposure. MR-766 was neutralized significantly less than recent ZIKV isolates when treated with monoclonal antibodies. The data herein show that without RT-PCR, serological diagnosis may not be possible in areas where multiple flaviviruses are endemic.

We report on the successful preparation of wet dressings hydrogels based on Chitosan-Poly(N-Vinyl-Pyrrolidone)-Poly(ethylene glycol)-Poly(acrylic acid) and Poly(ethylene oxide) by e-beam cross-linking in weakly acidic media, to be used for rapid healing and pain release of infected skin wounds. The structure and compositions of hydrogels investigated according to sol-gel and swelling studies, network parameters, as well as FTIR and XPS analyses showed the efficient interaction of the hydrogel components upon irradiation, maintaining the bonding environment while the cross-linking degree increasing with the irradiation dose and the formation of a structure with the mesh size in the range 11-67 nm. Hydrogels with gel fraction above 85% and the best-swelling properties in different pH solutions were obtained for hydrogels produced with 15 kGy. The hydrogels are stable in the simulated physiological condition of an infected wound and show appropriate moisture retention capability and the water vapor transmission rate up to 272.67 g m-2 day-1, to ensure fast healing. The hydrogels proved to have a significant loading capacity of ibuprofen (IBU), being able to incorporate a therapeutic dose for the treatment of severe pains. Simultaneously, IBU was released up to 25% in the first 2h, having a release maximum after 8h.

Hepatitis C virus (HCV) represents a challenging global health threat in ~200 million infected individuals. Clinical data suggests that only ~10-15% of acutely HCV-infected individuals will achieve spontaneous viral clearance despite exuberant virus-specific immune responses, which is largely attributed to difficulties in recognizing the pathognomonic symptoms during the initial stages of exposure to the virus. Given the paucity of a suitable small animal model, it is also equally challenging to study the early phases of viral establishment. Further, the host factors contributing to HCV chronicity in a vast majority of acutely HCV-infected individuals largely remain unexplored. The last few years have witnessed a surge in studies showing that HCV adopts a myriad mechanisms to disconcert virus-specific immune responses in the host to establish persistence that includes, but not limited to viral escape mutations, viral growth at privileged sites, and antagonism. Here, we discussed a few hitherto poorly explained mechanisms employed by HCV that are believed to lead to chronicity in infected individuals. A better understanding of these mechanisms would aid the design of improved therapeutic targets against viral establishment in susceptible individuals.

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system (CNS) characterized by varying degrees of demyelination of uncertain etiology, and is associated with specific environmental and genetic factors. Upon recognition of CNS antigens, the immune cells initiate an inflammatory process which leads to destruction and deterioration of the neurons. Innate immune cells such as macrophages, dendritic cells and natural killer cells are known to play critical roles in the pathogenesis of MS. Also, the activation of peripheral CD4+ T cells by CNS antigens leads to their extravasation into the CNS causing damages that exacerbates the disease. This could be accompanied by dysregulation of T regulatory cells and other cell types functions. Experimental autoimmune encephalomyelitis (EAE) is a mouse model used to study the pathophysiology of MS disease. In this review, we highlight the roles of innate and adaptive immune players in the pathogenesis of MS and EAE.

We present a model of infection dynamics that might explain slower approaching the herd immunity during the covid-19 epidemy in Sweden than it was predicted by a variety of other models; see graphs Fig. \ref{GROWTH2}. The new model takes into account the hierarchic structure of social clusters in the human society. We apply the well developed theory of random walk on the energy landscapes represented mathematically with ultrametric spaces. This theory was created for applications to spin glasses and protein dynamics. To move from one social cluster (valley) to another, the virus should cross a social barrier between them. The magnitude of a barrier depends on the number of social hierarchy's levels composing this barrier. As the most appropriate for the recent situation in Sweden, we consider linearly increasing (with respect to hierarchy's levels) barriers. This structure of barriers matches with a rather soft regulations imposed in Sweden in March 2020. In this model, the infection spreads rather easily inside a social cluster (say working collective), but jumps to other clusters are constrained by social barriers. This model's feature matches with the real situation during the covid-19 epidemy, with its cluster spreading structure. Clusters need not be determined solely geographically, they are based on a number of hierarchically ordered social coordinates. The model differs crucially from the standard models of spread of disease, such as the SIR-model. Our model describes such a specialty of spread of covid-19 virus as the presence of ``super-infectors'' who by performing a kind of random walk on a hierarchic landscape of social clusters spreads infection. In future, this model will be completed by adding the SIR-type counterpart. But, the latter is not a specialty of covid-19 spreading.

For enhancing the maximized profit from bank as well as customer perspective, term deposit can accelerate finance fields. This paper focuses on likelihood of term deposit subscription taken by the customers. Bank campaign efforts and customer details are influential while considering possibilities of taking term deposit subscription. An automated system is provided in this paper that approaches towards prediction of term deposit investment possibilities in advance. Neural network(NN) along with stratified 10-fold cross-validation methodology is proposed as predictive model which is later compared with other benchmark classifiers such as k-Nearest Neighbor (k-NN), Decision tree classifier (DT), and Multi-layer perceptron classifier (MLP). Experimental study concluded that proposed model provides significant prediction results over other baseline models with an accuracy of 88.32% and Mean Squared Error (MSE) of 0.1168.

Platelets have long been associated with sustaining the balance between hemostasis and thrombosis. Platelets, however, are also involved in a wide range of biological activities, including inflammation, immunology, wound healing, cancer biology, and angiogenesis. Platelets' diverse roles are mediated by the expression of various adhesive and immune receptors and the secretion of a diverse array of bioactive proteins, ions stored in granules, and several lipid mediators. Platelets also release pro-inflammatory and anti-inflammatory, and angiogenic factors and shed microparticles into the bloodstream. The challenge for therapeutic intervention in non-hemostatic disease is identifying the factors that primarily inhibit specific targets implicated in platelets' complicated contribution to inflammation or tumor growth while leaving their hemostatic function intact. In addition, blood platelets are involved in infection and innate and adaptive immunity by mediating complicated vascular homeostasis via specialized receptors and granule release, RNA transfer, and mitochondrial secretion. Anti-platelet drugs/bioactive compounds are developed based on their platelet anti-aggregatory properties; however, very little information is available on their effects on non-hemostatic function. Therefore, a better understanding of the impact of the anti-platelet bioactive on the platelets' diverse roles and mechanisms may help develop new strategies and prevent CVD and other diseases. In this review, a comprehensive overview of platelet multifunctional roles in CVD and other diseases and dietary factors' modulatory effects are described.

This paper examined the multifractal properties of six acknowledged agro-meteorological parameters, such as reference evapotranspiration (ET0), wind speed (U), incoming solar radiation (SR), air temperature (T), air pressure (P), and relative air humidity (RH) of five stations in California, USA. The investigation of multifractality of datasets from stations with differing terrain conditions: Dagget, Bakersfield, Santa Maria, Los Angeles and San Diego using the Multifractal Detrended Fluctuation Analysis showed the existence of a long term persistence and multifractality irrespective of the location. The scaling exponents of SR and ET0 time series are found to be higher for stations with higher altitudes. Subsequently, this study proposed using the novel multifractal cross correlation (MFCCA) method to examine the multiscale-multifractal correlations properties between ET0 and other investigated variables. MFCCA could successfully capture the scale dependent association of different variables and the dynamics in the nature of their associations from seasonal to multi-annual time scale. The multifractal exponents of pressure and relative air humidity are consistently lower than the exponents of ET0, irrespective of station location. This study found that joint scaling exponent was nearly the average of scaling exponents of individual series in different pairs of variables. Additionally, the α-values of joint multifractal spectrum were lower than the α values of both of the individual spectra, validating two universal properties in the mutifractal cross correlation studies for agro-meteorological time series. The temporal evolution of cross-correlation showed similar pattern for all pair-wise associations involving ET0, except for the RH-ET0 link.

A portable urea sensor for use in the fast flow condition was fabricated using porous polytetrafluoroethylene (PTFE) membranes coated with amine-functionalized parylene, parylene-A, by vapor deposition. To generate a specific electrochemical sensor signal from urea, the urea-hydrolyzing enzyme urease was immobilized on the parylene-A-coated PTFE membranes via chemical crosslinking using glutaraldehyde. The urease-immobilized membranes were assembled in a polydimethylsiloxane (PDMS) fluidic chamber, and a screen-printed carbon three-electrode system was used for electrochemical measurements. The success of urease immobilization was confirmed using fluorescence microscopy, scanning electron microscopy, and Fourier-transform infrared spectroscopy. The optimum concentration of urease for immobilization on the parylene-A-coated PTFE membranes was determined to be 48 mg/mL, and the optimum number of membranes in the PDMS chamber was found to be 8. Using these optimized conditions, we fabricated the urea biosensor and monitored urea samples under various flow rates ranging from 0.5 to 10 mL/min in the flow condition using chronoamperometry. To test the applicability of the sensor for physiological samples, we used it for monitoring urea concentration in the waste peritoneal dialysate of a patient with chronic renal failure, at a flow rate of 0.5 mL/min.

The recognition of (1→3)-β-D-glucans (BGs) by β-1,3-D-glucan recognition protein (BGRP) found in invertebrates plays a significant role in the activation of toll pathway and pro-phenol oxidase system in insect host defense against fungal invasion. To examine the structural diversity of BGs in BGRP interaction, the binding specificity of BGRPs cloned from four different insectswas characterized using ELISA. Recombinant BGRPs expressed as Fc-fusion proteins of human IgG1 bound to solid phase BGs. Because of the binding specificities, the BGRPs were categorized into two different ultrastructure- binding characters. The BGRPs from Silkworm and Indian meal moth bound to BGs containing triple-helical structure. Other BGRPs from red flour beetle and yellow mealworm beetle showed no binding to triple-helical BGs, but to alkaline-treated BGs, which have partially opened helical conformation. These evidences suggest that the innate immune system distinguishes different BG conformations and it is equipped for the diversity of BG structures.

ABSTRACT: The idea of a Common Mucosal Immune system (CMS) is 50 years old. Its relevance to immune protection at mucosal sites and its potential to modulate the impact of vaccination-induced protection against infection of the airway, has been poorly understood. The consequent failure of current SARS-CoV-2 vaccination to satisfy expectations with respect to prevention of infection, viral transmission, duration of protection and pattern of clinical protection, led to public health and medical decisions now under review. This review summarises knowledge of the CMS in man, including the powerful role it plays in immune protection and lessons with respect to what can and can not be achieved by systemic and mucosal vaccination for prevention of airway infection. The powerful impact in both health and disease of optimising delivery of immune protection using selected isolates from the respiratory microbiome, is demonstrated through review of randomised controlled trials (RCT’s) in subjects with chronic airway disease, and in otherwise healthy individuals with risk factors, in whom the idea of mucosal immune resilience is introduced.

Historically, macrophages have been long implicated in the control of the severity of infectious diseases. This has been based on the observations of a higher risk of severe disease and death upon rechallenge with viral variants due to antibody dependent enhance-ment (ADE) of infection into macrophages. The question remains as to what can account for this potent heterologous protection in macrophages? Here it is argued that the elusive defense mechanism of M1-like pro-inflammatory macrophages may pertain to a novel virus anti-virus response. This system initiates with high replication of human endogenous retrovirus K102 (HERV-K102), a non-pathogenic, protector foamy retrovirus of humans which generates M1-like pro-inflammatory foamy macrophages, glycolysis, and epigenetic changes, all characteristic of trained immunity. This virus-anti-virus system kills virally infected cells by several mechanisms, amplifies the innate interferon response via ‘viral mimicry’, has many unique components that interfere with exoge-nous virus replication, and may be especially adept at neutralizing enveloped exogenous pandemic viruses, such as SARS-CoV-2 and HIV-1. The goal of this treatise is to introduce the multifaceted HERV-K102 protector system, to illustrate how SARS-CoV-2 may target the HERV-K102 protector system by ADE, and to explore how this innate defense system may be exploited for pandemic preparedness.

Using a randomized, crossover approach, cyclists (N = 20, overnight fasted) engaged in three 75-km time trials while ingesting water (WAT) or carbohydrate (0.2 g/kg every 15 minutes) from bananas (BAN) or a 6% sugar beverage (SUG). Blood samples were collected pre-exercise and 0 h-, 1.5 h-, and 21 h-post-exercise, and analyzed for NK cytotoxicity activity (NKCA) using pure NK cell populations. The two carbohydrate trials (BAN, SUG) compared to WAT were associated with higher post-exercise glucose, and lower cortisol, total blood leukocyte, neutrophil, and NK cell counts (interaction effects, P < 0.001). The immediate post-exercise increase in NK cell counts was higher in WAT (78%) compared to BAN (32%) and SUG (15%) trials (P ≤ 0.017). The 1.5 h post-exercise decrease in NK cell counts did not differ after WAT (−46%), BAN (−46%), and SUG (−51%) trials. The pattern of change in post-exercise NKCA differed between trials (P < 0.001). The 1.5 h post-exercise decreases in NKCA were 23%, 29%, and 33% in the WAT, BAN, and SUG trials, respectively, but trial contrasts did not differ significantly. Carbohydrate ingestion from BAN or SUG attenuated immediate-post-exercise increases in leukocyte, neutrophil, and NK cell counts, but did not counter the 1.5-h decreases in NK cell counts and NKCA.

In spite of numerous predictions, the natural herd immunity for covid-19 visru had not been approahed anywhere in the world. Thus, the traditional mathematical models of disease spread demonstrated their inability to describe adequately the covid-19 pandemic. In author's works, the novel model of the disease spread was developed. This model reflects the basic features of the covid-19 pandemic: a) the social clustering character of virus spread, b) . Social clustering is mathematically modelled with ultrametric spaces having the treelike geometry encoding hierarchy of the regulation constraints. The virus spread is described by ultrametric diffusion or random walk on the hierarchic energy landscape. In contrast to the standard models which are characterized by the exponential decrease of the probability to become infected - at the stage of approaching of the herd immunity, the ultrametric model is characterized by the power law. Moreover, the model gives the possibility to quantify the influence of restriction measures up to the lockdown. Our main result is that the play with restrictions, including lockdowns, is counterproductive and leads to the essential slowdown of approaching the herd immunity or even makes this impossible.

Spatial planning holds a key role in preventing or mitigating the impacts of climate change on both cities and rural areas, taking a forward-thinking and holistic approach to urban and regional development. As such, spatial planning deals with challenges occurring at different scales and across sectors. The international literature points out the need for horizontal and vertical cooperation to tackle climate change impacts. While there is abundant knowledge regarding the challenges related to climate change at different spatial levels, procedural integration into planning frameworks and practice is currently under-researched. This paper presents a novel theoretical framework that integrates various steps towards a holistic, integrative and adaptive climate proofing process. An iterative process was used for conceptual development, based on literature review followed by external feedback meetings and two workshops with the core team of planning experts responsible for exchange across federal states. By specifically addressing the challenges relating to cross-regional and cross-sectoral planning, this novel framework attempts to (i) facilitate a hierarchy of measures, (ii) maximise co-benefits for various adaptation purposes and climate change mitigation and (iii) foster the long-term institutionalisation of integrative processes across sectors, planning areas and policy levels.

Significant recent advances in cancer immunotherapeutics include the vaccination of cancer patients with tumor antigen-associated peptide-pulsed dendritic cells (DCs). DC vaccines with homogeneous, mature, and functional activities are required to achieve effective acquired immunity; however, the yield of autologous monocyte-derived DCs varies in each patient. Priming with a low dose of recombinant human granulocyte colony-stimulating factor (rhG-CSF) 16–18 h prior to apheresis resulted in 50% more harvested monocytes, with a significant increase in the ratio of CD11c+CD80+ DCs/apheresed monocytes. The detection of antigen-specific cytotoxic T lymphocytes after Wilms’ tumor 1-pulsed DC vaccination was higher in patients treated with rhG-CSF than those who were not, based on immune monitoring using tetramer analysis. Our study is the first to report that DC vaccines for cancer immunotherapy primed with low-dose rhG-CSF are expected to achieve higher acquired immunogenicity.

Tropical corals construct the three-dimensional framework for one of the most diverse ecosystems on the planet, providing habitat to a plethora of species across taxa. However, these ecosystem engineers are facing unprecedented challenges, such as increasing disease prevalence and marine heatwaves associated with anthropogenic global change. As a result, major declines in coral cover and health are being observed across the world's oceans, often due to the breakdown of coral-associated symbioses. Here, we review the interactions between the major symbiotic partners of the coral holobiont – the cnidarian host, algae in the family Symbiodiniaceae, and the microbiome – that influence trait variation, including the molecular mechanisms that underlie symbiosis and the resulting physiological benefits of different microbial partnerships. In doing so, we highlight the current framework for the formation and maintenance of cnidarian-Symbiodiniaceae symbiosis, and the role that immunity pathways play in this relationship. We emphasize that understanding these complex interactions is challenging when you consider the vast genetic variation of the cnidarian host and algal symbiont, as well as their highly diverse microbiome, which is also an important player in coral holobiont health. Given the complex interactions between and among symbiotic partners, we propose several research directions and approaches focused on symbiosis model systems and emerging technologies that will broaden our understanding of how these partner interactions may facilitate the prediction of coral holobiont phenotype, especially under rapid environmental change.

Lipid nanoparticles (LNPs) have attracted extensive attention in tumor immunotherapy in recent years. The strategy of targeting immune cells in cancer therapy has become a research area of great interest. mRNA vaccines are a potential choice for tumor immunotherapy due to their ability to directly encode antigen proteins and stimulate a strong immune response. However, the mode of delivery and lack of stability of mRNA are key issues limiting its application. LNPs are an excellent mRNA delivery vector, and their structural stability and biocompatibility make them an effective means to deliver mRNA to specific targets. This study summarizes the research progress in LNP delivery vector-assisted targeted controlled release mRNA vaccines in tumor immunity. The role of LNPs in improving mRNA stability, immunogenicity and targeting is discussed. In addition, combined with the cutting-edge research results, the potential mechanisms and application prospects of LNP-mRNA vaccines in tumor immunotherapy were further analyzed. This review aims to systematically summarize the latest research progress in LNP delivery carrier-assisted targeted controlled-release mRNA vaccines in tumor immunity to provide new ideas and strategies for tumor immunotherapy and provide more effective treatment plans for patients.

Abstract Optimal targeting of nanoparticles (NP) to dendritic cells (DCs) receptors to deliver cancer-specific antigens is key to an efficient induction of anti-tumor immune responses. Poly (lactic-co-glycolic acid) (PLGA) nanoparticles containing tètanus toxoid and gp100 melanoma-associated antigen, toll-like receptor adjuvants were targeted to the DC-SIGN receptor in DCs by specific humanized antibodies or by ICAM3-Fc fusion proteins mimicking natural ligand. Despite higher binding and uptake efficacy of anti-DC-SIGN antibody-targeted NP vaccines than ICAM3-Fc ligand, no difference were observed in DC activation markers CD80, CD83, CD86 and CCR7 induced. DCs loaded with NP coated with ICAM3-Fc appeared more potent in activating T cells via cross-presentation than antibody-coated NP vaccines. This fact could be very crucial in the design of new cancer vaccines.

We analyze the Covid-19 mortality scenario in India and compare it with those in other large-population regions such as Asia-excluding-China, Africa, European Union, South America, and USA. We compare existing fatality data and offer an interpretation for low fatality based on immunity due to endemic malaria and TB. We identify the hot climate in the past summer as a possible cause for low death count in southern-hemisphere countries without endemic malaria and TB. We also make India-specific observations for easing the lockdown and estimations for the time required to attain herd immunity. Whatever optimism we present should be viewed as a guarded optimism. There should not be room for complacency.

The crystal nucleation and overall crystallization kinetics of cross-linked poly(ε-caprolactone) was studied experimentally by fast scanning calorimetry in a wide temperature range. With an increasing degree of cross-linking, both the nucleation and crystallization half-times increase. Concurrently, the glass transition range shifts to higher temperatures. In contrast, the temperatures of the maximum nucleation and the overall crystallization rates remain the same independent of the degree of cross-linking. The cold crystallization peak temperature generally increases as a function of heating rate, reaching an asymptotic value near the temperature of the maximum growth rate. A theoretical interpretation of these results is given in terms of classical nucleation theory. In addition, it is shown that the average distance between the nearest cross-links is smaller than the estimated lamellae thickness, which indicates the inclusion of cross-links in the crystalline phase of the polymer.

In this review, special emphasis will be placed on red grape polyphenols for their anti-oxidant and anti-inflammatory activities. Therefore, their capacity to inhibit major pathways responsible for activation of oxidative systems and expression and release of pro-inflammatory cytokines and chemokines will be discussed. Furthermore, regulation of immune cells by polyphenols will be illustrated with special reference to the activation of T regulatory cells which support a tolerogenic pathway at intestinal level. Furthermore, the effects of red grape polyphenols will be analyzed in obesity, as a low grade systemic inflammation. Also, possible modifications of inflammatory bowel disease biomarkers and clinical course have been studied upon polyphenol administration, either in animal models or in clinical trials. Moreover, the ability of polyphenols to cross the blood-brain barrier has been exploited to investigate their neuroprotective properties. In cancer, polyphenols seem to exert several beneficial effects, even if conflicting data are reported about their influence on T regulatory cells. Finally, the effects of polyphenols have been evaluated in experimental models of allergy and autoimmune diseases. Conclusively, red grape polyphenols are endowed with a great anti-oxidant and anti-inflammatory potential but some issues, such as polyphenol bioavailability, activity of metabolites and interaction with microbiota, deserve deeper studies.

Facade elements are known to represent a building component with multiple performance parameters to satisfy. Among others, “advanced facades” take advantage of hybrid solutions, like the assemblage of laminated materials. In addition to enhanced mechanical properties that are typical of optimally composed hybrid structural components, these systems are energy-efficient, durable, and offer lightening comfort and optimal thermal performance. This is the case of the structural solution developed in joint research efforts of the University of Zagreb and the University of Ljubljana, within the Croatian Science Foundation VETROLIGNUM project. The design concept involves the mechanical interaction of timber and glass load-bearing members, without sealing or bonded glass-to-timber surfaces. Laminated glass infilled timber frames are recognized as a new generation of structural members with relevant load-carrying capacity (and especially the enhancement of earthquake resistance of framed systems), but also energy-efficient and cost-effective solutions.

The uptake of buildings employing cross-laminated timber (CLT) assemblies and designed to Passivhaus standard has accelerated internationally over the past two decades due to several factors including design responses to the climate crisis by decarbonising the building stock. Structural CLT technology and the voluntary Passivhaus certification both show measurable benefits in reducing energy consumption, while contributing to durability and indoor comfort. However, there is a general lack of evidence to support a fast uptake of these technologies in Australia. This paper responds to the compelling need of providing quantitative data and adoption strategies, it explores their combined application as a potential pathway for climate-appropriate design of energy-efficient and durable mass timber envelope solutions for subtropical and tropical Australian climates. Hygrothermal risk assessments of interstitial condensation and mould growth of CLT wall assemblies inform best-practice design of mass timber buildings in hot and humid climates. This research found that the durability of mass timber buildings located in hot and humid climates may benefit from implementing the Passivhaus standard to manage interior conditions. The findings also suggested that climate-specific design of the wall assembly is critical for mass timber buildings, in conjunction with excellent stormwater management practices during construction and corrosion protection for metallic fasteners.

Maternal-derived immunity is a critical component for survival and success of offspring in pigs to protect from circulating pathogens like Type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV-2). The purpose of this study was to investigate the transfer of anti-PRRSV immunity to piglets from gilts that received modified-live virus (MLV) alone (TRT 0), or in combination with one of two autogenous inactivated vaccines (AIVs, TRT 1+2). Piglets from these gilts were challenged with the autogenous PRRSV-2 strain at two weeks of age and their adaptive immune response (IR) was evaluated until 4 weeks post inoculation (wpi). The systemic humoral and cellular IR was analyzed in the pre-farrow gilts, and in piglets, pre-inoculation, and at 2- and 4-wpi. Both AIVs partially protected the piglets with reduced lung pathology and increased weight gain; TRT 1 also lowered piglet viremia best explained by the AIV-induced production of neutralizing antibodies in gilts and their transfer to the piglets. In piglets, pre-inoculation, the main systemic IFN-γ producers were CD21α+ B cells. From 0 to 4 wpi, the role of these B cells declined and CD4 T cells became the primary systemic IFN-γ producers. In lungs, CD8 T cells were the primary and CD4 T cells the secondary IFN-γ producers including a novel subset of porcine CD8α-CCR7- CD4 T cells, potentially terminally differentiated CD4 TEMRA cells. In summary, this study demonstrates that maternal AIV vaccination can improve protection of pre-weaning piglets against PRRSV-2; it shows the importance of transferring neutralizing antibodies to piglets; and it introduces two novel immune cell subsets in pigs – IFN-γ producing CD21α+ B cells and CD8α-CCR7- CD4 T cells.

The 22q11.2 deletion syndrome is a multisystemic disorder characterized by a marked variability of phenotypic features making the diagnosis challenging for clinicians. The wide spectrum of clinical manifestations includes congenital heart defects, most frequently conotruncal cardiac anomalies, thymic hypoplasia and predominating cellular immune deficiency, laryngeal developmental defects, midline anomalies with cleft palate and velar insufficiency, structural airway defects, facial dysmorphism, parathyroid and thyroid gland hormonal dysfunctions, speech delay, developmental delay, neurocognitive and psychiatric disorders. Significant progress has been made in understanding the complex molecular genetic etiology of the 22q11.2 deletion syndrome underpinning the heterogeneity of clinical manifestations. The deletion is caused by chromosomal rearrangements in meiosis and is mediated by non-allelic homologous recombination events between low copy repeats or segmental duplications in the 22q11.2 region. A range of genetic modifiers, environmental factors as well as the impact of hemizygosity on the remaining allele contribute to the intricate genotype-phenotype relationships. This comprehensive review has been aimed at highlighting the molecular genetic background of 22q11.2 deletion syndrome in correlation with a clinical multidisciplinary approach.

The structure of synthetic mRNAs as used in vaccination against cancer and infectious diseases contain specifically designed caps followed by sequences of the 5’ untranslated repeats of β-globin gene. The strategy for successful design of synthetic mRNAs by chemically modifying their caps aims to increase resistance to the enzymatic deccapping complex, offer a higher affinity for binding to the eukaryotic translation initiation factor 4E (elF4E) protein and enforce increased translation of their encoded proteins. However, the cellular homeostasis is finely balanced and obeys to specific laws of thermodynamics conferring balance between complexity and growth rate in evolution. An overwhelming and forced translation even under alarming conditions of the cell during a concurrent viral infection, or when molecular pathways are trying to circumvent precursor events that lead to autoimmunity and cancer, may cause the recipient cells to ignore their differential sensitivities which are essential for keeping normal conditions. The elF4E which is a powerful RNA regulon and a potent oncogene governing cell cycle progression and proliferation at a post-transcriptional level, may then be a great contributor to disease development. The mechanistic target of rapamycin (mTOR) axis manly inhibits the elF4E to proceed with mRNA translation but disturbance in fine balances between mTOR and elF4E action may provide a premature step towards oncogenesis, ignite pre-causal mechanisms of immune deregulation and cause maturation (aging) defects.

This article presents the results of a cross-disciplinary applied study exploring investors’ protections in the context of distributed ledger technology (DLT) smart contracts. Fusing legal, business, and technical perspectives, we developed a framework for protection from non-commercial risks for stablecoins, taking advantage of DLT and AI. A key concept we propose is the monitoring of disinformation and fake news to prevent malicious parties from abusing our solution. Based on the similarities between central bank digital currencies (CBDCs) and stablecoins, we propose scaling up our results to all future internet investments performed without face-to-face contact between the investor and the company.

Coccidiosis remains a major disease and economic challenge for the global poultry industry. Coccidiosis in chickens is caused by seven Eimeria species that target specific regions of the gastrointestinal tract and cause malabsorptive or haemorrhagic disease. These Eimeria species infect segment-specific epithelial cells and thus need to navigate the host’s indigenous microbiome and intestinal defences to establish an infection and cause disease. Good husbandry practices, prophylactic use of anticoccidial drugs and/or live parasite vaccination have been the primary control measures employed but there are challenges with vaccination and growing constraints on anticoccidial drug use. This review, therefore, considers available information on the key steps of the infection process, notable microbiome- or host-related changes occurring, and the (potential) influence of dietary ‘alternatives’ to anticoccidial drugs. There is good available evidence to indicate that some phytogenics, prebiotics, probiotics, betaine, n-3 fatty acids, as well as carbohydrase enzymes and anti-IL-10 antibodies, can (beneficially) modulate at least some of these features in coccidiosis-specific challenge studies. As a minimum, these anticoccidial drug ‘alternatives’ could support the establishment of a desirable host microbiome and optimum immune system development. It is important to better understand the potential of these ‘alternatives’ in commercial production and how they can complement, or reduce, the use of anticoccidial drugs.

Hepatitis E virus (HEV) is responsible for large waterborne epidemics of hepatitis in endemic countries and is an emerging zoonotic pathogen worldwide. In endemic regions, HEV-1 or HEV-2 genotypes are frequently associated with fulminant hepatitis in pregnant women, while with zoonotic HEV (HEV-3 and HEV-4), chronic cases of hepatitis and severe neurological disorders are reported. Hence, it is important to characterize the interactions between HEV and its host. Here, we investigated the ability of the non-structural polyprotein encoded by the first open reading frame (ORF1) of HEV to modulate the host early antiviral response and in particular the type I interferon (IFN-I) system. We found that the amino-terminal region of HEV-3 ORF1 (MetPCP), containing a putative methyltransferase (Met) and a papain-like cysteine protease (PCP) functional domain, inhibited IFN-stimulated response element (ISRE) promoter activation and the expression of several IFN-stimulated genes (ISGs) in response to IFN-I. We showed that the MetPCP domain interfered with the Janus kinase (JAK)/signal transducer and activator of transcription protein (STAT) signalling pathway by inhibiting STAT1 nuclear translocation and phosphorylation after IFN-I treatment. By contrast, MetPCP had no effect on STAT2 phosphorylation and a limited impact on the activation of the JAK/STAT pathway after IFN-II stimulation. This inhibitory function seemed to be genotype-dependent as MetPCP from HEV-1 had no significant effect on the JAK/STAT pathway. Overall, this study provides evidence that the predicted MetPCP domain of HEV ORF1 antagonises STAT1 activation to modulate the IFN response.

For better export marketing strategies (EMS), companies mobilize their internal resources, which are managerial commitment, firm experience, and product uniqueness. However, Small businesses with constrained resources cannot be well explained with this view. So, more research on how small business come up with EMS have been called for. To explain how resource-restricted firms which rely heavely on entrepreneur, this study adopted the concept of dynamic managerial capabilities (DMCs) and resource versatility to better explain small business exports. We analyzed small businesses in Mongolia with qualitative research methods, including interviews with entrepreneurs and support organizations, site visits, and group discussions. We suggest international dynamic marketing capabilities (IDMCs), which are entrepreneurial orientation, networking capability, and versatile dynamic capability for small business. Theoretical and managerial implications are discussed.

This paper introduces the spatial component in cross-section econometric estimations and specifically, the spatial dependence effect inherent in some of the variables involved in the modelling process. First, the spatial structure of the data from thematic maps is observed and Moran's spatial autocorrelation indicators are presented. Subsequently, the spatial weights matrix is built under different specifications. Finally, several modelling specification strategies are shown and the interpretation of the estimated coefficients. The theoretical concepts are illustrated with examples and their corresponding R software codes. This code and databases are available in a freely accessible repository in the BE2SHARE-EUDAT platform so that they can be easily reproduced.

Nighttime lights (NTL) are a popular type of data for evaluating economic performance of regions and economic impacts of various shocks and interventions. Several validation studies use traditional statistics on economic activity like national or regional Gross Domestic Product (GDP) as a benchmark to evaluate the usefulness of NTL data. Many of these studies rely on dated and imprecise Defence Meteorological Satellite Program (DMSP) data and use aggregated units such as nation-states or the first sub-national level. Yet applied researchers who draw support from validation studies to justify their use of NTL data as a proxy for economic activity increasingly focus on smaller and lower level spatial units. This study uses a 2001-19 time-series of GDP for over 3100 US counties as a benchmark to examine the usefulness of the recently released version 2 VIIRS nighttime lights (V.2 VNL) products as proxies for local economic activity. Contrasts are made between cross-sectional predictions for GDP differences between areas and time-series predictions of GDP changes within areas. Disaggregated GDP data for various industries are used to examine what types of economic activity are best proxied by NTL data and comparisons are also made with the predictive performance of earlier NTL data products.

A major task in Functional Time Series Analysis is measuring the dependence within and between processes, for which lagged covariance and cross-covariance operators have proven to be a practical tool in well-established spaces. This article deduces estimators and asymptotic upper bounds of the estimation errors for lagged covariance and cross-covariance operators of processes in Cartesian products of abstract Hilbert spaces for fixed and increasing lag and Cartesian powers. We allow the processes to be non-centered, and to have values in different spaces when investigating the dependence between processes. Also, we discuss features of estimators for the principle components of our covariance operators.

used traditional microbial starters revealed that effective fermentation requires three microbial strains with complementary metabolic activities: filamentous fungi (Rhizopus oryzae), yeast (Saccharomyces cerevisiae), and lactic acid bacteria (Lactobacillus plantarum). Relative to natural communities, modulation of the ratio of these three microorganisms led to significant differences not only in terms of ethanol and organic acid production, but also with the profile of volatile compounds. However, inoculation of an equal ratio of spores/cells of the three aforementioned microbial strains led to a flavor profile and ethanol yield similar to that obtained with natural communities. Compartmentalization of metabolic tasks through the use of a biofilm cultivation device allowed further improvement of the entire fermentation process, notably by increasing the amount of key components of the aroma profile of the fermented beverage (i.e., mainly phenylethyl alcohol, isobutyl alcohol, isoamyl alcohol, and 2-methyl-butanol) and reducing the amount of off-flavor compound. This study represents an initial step toward understanding interkingdom microbial interactions with a strong potential for application in the food biotechnology.

COVID-19 has been a global healthcare concern impacting multiple aspects of individual and community wellness. As one moves forward with different methods to reduce the infection and mortality rates, it is critical to continue to study the impact that national and local ‘social distancing’ policies have on the daily lives of individuals. The aim of this study was to examine loneliness in relation to risk assessment, measures taken against risks, concerns, and social media use, while adjusting for sociodemographic variables. The cross-sectional study collected data from 3469 individuals from USA, UK, Norway, and Australia. Loneliness was measured with the de Jong Gierveld Loneliness Scale. Multiple linear regression was used in the analysis of associations between variables. The results showed that concerns about finances were more strongly associated with social loneliness, while concerns about the future was more strongly associated with emotional loneliness. Longer daily time spent on social media was associated with higher emotional loneliness. In conclusion, pandemic-related concerns seem to affect their perceptions of loneliness. While social media can be used productively to maintain relationships, and thereby prevent loneliness, excessive use may be counterproductive.

Since the COVID-19 caused by SARS-CoV-2 break out in Wuhan China from Dec. 2019, it has spread to hundreds of countries up to now. Scientists from all over the world have paid tremendous efforts to research and try to control the disease. Previous studies suggested that some of the wild animals could be intermediate hosts between humans and origination of SARS-CoV-2, and some companion animals of humans can be infected by SARS-CoV-2, which raised our curiosity about cross-infection of SARS-CoV-2 between animals and humans. Thus, we select some kinds of animals that might have contact with humans to estimate the susceptibility to SARS-CoV-2 in different animals by evolutionary analysis of their receptors for SARS-CoV-2. The results show that some companion animals of the Felidae family like the cat has a higher infection possibility while the species of the Rodent family like the rat and mouse having close contact with humans show an opposite result, which consist with recent animal experiments and researches. These should raise concerns about cross-infection between human and companion animals or animals having close contact with humans which might turn animals into depositaries of the coronavirus even after control of SARS-CoV-2 spreading and cause second or more waves of infections after social reopening. Another side of our results stands by the opinion that bioinformatic analysis can be consistent with experiments in some respects so that we can prevent unnecessary sacrifice of laboratory animals in future experiments.

G protein-coupled receptor 15 (GPR15, also known as BOB) is an extensively studied orphan GPCR involving HIV infection, colonic inflammation and smoking-related diseases. Recently, GPR15 was deorphanized and its corresponding natural ligand demonstrated an ability of inhibiting cancer cell growth. However, no study reported the potential role of GPR15 in a pan-cancer manner. Using large-scale publicly available data from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases, we found that GPR15 expression is significantly lower in colon adenocarcinoma (COAD) than in normal tissues. And among 33 cancer types, GPR15 expression is significantly correlated with the prognoses of COAD, neck squamous carcinoma (HNSC), lung adenocarcinoma (LUAD) positively and stomach adenocarcinoma (STAD) negatively. This study also revealed that commonly upregulated gene set in the high GPR15 expression group (stratified via median) of COAD, HNSC, LUAD and STAD are enriched in immune systems, indicating that GPR15 might be considered as a potential target for cancer immunotherapy. Furthermore, we modelled the 3D structure of GPR15 and conducted the structure-based virtual screening. The top 8 hits compounds were screened and then subjected to molecular dynamics (MD) simulation for stability analysis. Our study provided novel insights into the role of GPR15 in a pan-cancer manner and discovered a potential hit compound for GPR15 antagonists.

Patterns of age and growth of a sedentary damsel fish Acanthochromis polyacanthus were tested over a latitudinal range of approximately 10 degrees (1,200 km) on the Great Barrier Reef, Australia. Within latitudes these patterns were also compared on reefs across a continental shelf that ranged in width from 52 to 128 km. Although variation in length-max, growth, age-max and the von-Bertalanffy metrics of L, and K were found within and among latitudes, greatest variation in some demographic characteristics were found across the shelf regardless of latitude. Fish were always smaller at inner shelf reefs and grew more slowly when compared to mid and outer shelf reefs. The oldest fish collected was 11 years old and, there were no consistent variation in age-max among distances from shore. On outer reefs, there was a linear relationship with age-max and latitude. This ‘tropical gradient’ of age only explained 34% of the variation, further this was not found when the oldest 10% of fish were considered. Fish only reached an age-max of 6 years on the southern-most reefs. There was a trend for a smaller L with latitude but, it was not significant and L did not vary predictably with water temperature. The sampling of MPAs did not confound the resultant patterns. Instantaneous mortality rates were 0.245-0.685, highest at inner reefs and showed no consistent MPA-related patterns. Our study suggested that the mid and outer shelf waters of the GBR appeared best suited for growth of A. polyacanthus. In conclusion, position on continental shelves and related local environmental conditions needs to be considered in spatial models of growth.

Mast cells are long-lived, granular, myeloid-derived leukocytes that have significant protective and repair functions in tissues. Mast cells sense disruptions in the local microenvironment and are first responders to physical, chemical and biological insults. When activated, mast cells release growth factors, proteases, chemotactic proteins and cytokines thereby mobilizing and amplifying the innate and adaptive immune system. Mast cells are therefore significant regulators of homeostatic functions and may be essential in microenvironmental changes during pathogen invasion and disease. During infection by helminths, bacteria and viruses, mast cells release antimicrobial factors to facilitate pathogen expulsion and eradication. Mast cell-derived proteases and growth factors protect tissues from insect/snake bites and exposure to ultraviolet radiation. Finally, mast cells release mediators that promote wound healing in the inflammatory, proliferative and remodeling stages. Since mast cells have such a powerful repertoire of functions, targeting mast cells may be an effective new strategy for immunotherapy of disease and design of novel vaccine adjuvants. In this review, we will examine how certain strategies that specifically target and activate mast cells can be used to treat and resolve infections, augment vaccines and heal wounds. Although these strategies may be protective in certain circumstances, mast cells activation may be deleterious if not carefully controlled and any therapeutic strategy using mast cell activators must be carefully explored.

Microglial cells, the resident macrophages of the CNS, exist in a process-bearing, ramified/surveying phenotype under resting conditions. Upon activation by cell damaging factors they get transformed to an amoeboid phenotype releasing various cell products including pro-inflammatory cytokines, chemokines, proteases, reactive oxygen/nitrogen species and the excytotoxic ATP and glutamate. In addition, they engulf pathogenic bacteria or cell debris and phagocytose them. However, already resting/surveying microglia has a number of important physiological functions in the CNS; they e.g. shield small disruptions of the blood-brain barrier by their processes, dynamically interact with synaptic structures and clear surplus synapses during development. In neurodegenerative illnesses they aggravate the original disease by a microglia-based compulsory neuroinflammatory reaction. Therefore, the blockade of this reaction improves the outcome of Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, etc. The function of microglia is regulated by a whole array of purinergic receptors classified as P2Y12, P2Y6, P2Y4, P2X4, P2X7, A2A, A3, and being targets for endogenous ATP, ADP, or adenosine. ATP is sequentially degraded by the ecto-nucleotidases and 5’-nucleotidase enzymes to the weak adenosine agonist inosine as an end-product. The appropriate selective agonists/antagonists for purinergic receptors as well as the respective enzyme inhibitors may profoundly interfere with microglial functions and reconstitute the homeostasis of the CNS disturbed by neuroinflammation.

The article discusses the issue of the sustainable development of the cross-border market for cultural services in a city divided by the state border. The article uses the example of Cieszyn and Český Těšín, a city divided following the decision of the Council of Ambassadors in 1920. The research carried out so far indicates the main constraints in the harmonious functioning of the cross-border market for cultural services in this city, such as: different cultural policies implemented on both sides of the city, language barriers as well as legal and administrative differences. Therefore, the authors undertook research aimed at recognising the role of Euroregional structures in stimulating the sustainable development of this region. On the basis of the analysis of the Cieszyn Silesia Euroregion's documentation and the results of qualitative and quantitative research, the article describes the role of the Euroregion in building a cross-border market for cultural services. Recommendations were also prepared that could constitute the principles of a common cultural policy not only for Cieszyn and Český Těšín, but also for other European cities in the Schengen Area, which, like Cieszyn and Český Těšín, have been divided by a state border.

Diffusion bonding is often used on pre-machined parts to generate internal cavities, e.g. for cooling injection molding tools close to the mold cavity. Only then, the workpieces are finished to their final dimensions. In the case of micro-process devices, however, it is essential to precisely control the deformation, as otherwise uncontrollable pressure losses will occur with channel cross-sections in the sub-millimeter range. Post-processing is not possible. The most important process parameters for diffusion bonding are temperature, dwell time and contact pressure, with the bonding temperature and contact pressure acting in opposite directions and showing a strong non-linear dependence on deformation. In addition, the deformation is influenced by a number of other factors such as the absolute size of the cross-section and the aspect ratio of the parts, the dimensions and distribution of the internal cross sections and the overall percentage of the cross-section to be bonded. In micro process engineering, small material cross-sections in the range of the materials microstructure can facilitate additional deformation mechanisms such as grain boundary sliding, which are not relevant at all for larger structures. For parts consisting of multiple layers, tolerances in thickness and roughness of multiple surfaces must be levelled, contributing to the percentaged deformation. This makes it difficult, especially in micro process engineering and in single or small series production, to determine suitable joining parameters in advance, which on the one hand do not cause unforeseen large deformations, but on the other hand reliably produce highly vacuum-tight components. Hence, a definition of a fixed percentaged deformation does not work for all kinds of components. This makes it difficult to specify parameters for surely obtain high-vacuum tight parts. For successful diffusion bonding, atoms must diffuse over the bonding planes, forming a monolithic part in which the original layers are no longer visible. Only then, mechanical properties identical to those of the base material, which has been subjected to identical heat treatment, can be achieved. In this paper, the impacts of different material cross section widths as well as of the aspect ratio on deformation were investigated. By accident, it was found that also accuracy of the temperature measurement may have a serious impact in terms of deformation.

Nowadays, the human population is facing the third and may be the worst pandemic caused by human coronaviruses (CoVs). The virus was first reported in Wuhan, China on 31 December 2019 and spread within short time to almost all countries of the world. Genome analysis of the early virus isolates has revealed high similarity with SARS-CoV and hence the new virus was officially named SARS-CoV-2. Since CoVs have the largest genome among all RNA viruses, they can adapt many point mutation and recombination events; particularly in spike gene, that enable these viruses to rapidly change and evolve in nature. CoVs are known to cross the species boundaries by using different cellular receptors. SARS-CoV-2 is believed to originate in bats and transmitted to human being through an ill-defined intermediate host. In the current review, different aspects of SARS-CoV-2 biology and pathogenicity are discussed including virus genetics and evolution, spike protein and its role in evolution and adaptation to novel hosts, and virus transmission and persistence in nature. In addition, the immune response developed during SARS-CoV-2 infection is demonstrated with special reference to the interplay between immune cells and their role in disease progression. We believe that SARS-CoV-2 outbreak will not be the last and spillover of CoVs from bats will continue. Therefore, establishing intervention approaches to reduce the likelihood of future CoVs spillover from the natural reservoirs is a priority.

Toll-like receptors (TLRs) are a class of pattern recognition receptors (PRRs) family that identify pathogen-associated molecular patterns derived from microbes and activate immune cell response. Following TLRs ligation, different adaptor and transcription molecules such as myeloid differentiation primary response gene 88 (MyD88) and nuclear factor kappa B (NF-kB) are recruited that initiate inflammatory signaling pathways. The human Toll-like receptor 10 (hTLR10) is a novel member of the PRRs family with a regulatory function of immune responses because of unique cytoplasmic domains which lead to induction of both inflammatory and anti-inflammatory properties. Recent studies have reported the association of TLR10 polymorphisms with many inflammatory diseases and human cancer. Engagement of TLR10 on the surface of the epithelium and macrophages leads to the production of proinflammatory cytokines and chemokines, while other studies have proven an anti-inflammatory role of TLR10. Accordingly, TLR10 suppresses proinflammatory cytokine production via negative regulation of MyD88 and the Akt (protein kinase B) and MAPK (mitogen-activated protein kinase) signaling pathways. This review aimed to provide answers for these conflicting findings (Inflammatory and anti-inflammatory properties of TLR10) to further identify distinct biological functions of TLR10.

The prevalence of back pain (BP) among children and adolescents has increased over recent years. Some authors advocate promoting back-health education in the school setting. It is therefore important to adopt a uniform suite of assessment instruments to measure the various constructs. The present study aimed to perform a cultural adaptation of a validated measurement instrument (BackPEI), beginning with a translation and cultural adaptation phase, followed by a second phase to test reliability using a test-retest design. The translation and cross-cultural adaptation were performed based on the guidelines. Reliability was tested by applying the questionnaire to 224 secondary school students, at two different times with a 7-day interval between the tests. In general, the Spanish version presented adequate agreement for questions 1–20, with only question 9 achieving a low Kappa range of .312 [-.152- .189]. The question about pain intensity did not show differences between the averages for the test (4.72 ± 2.33) and re-test (4.58 ± 2.37) (p = .333), and the responses for these two tests were highly correlated (ICC= .951 [.928- .966]; p= .0001). Psychometric testing indicated that the Spanish version of the BackPEI is well-adapted and reliable, based on the test-retest design, providing similar results to the original Brazilian version.

The molecular evolution of medulloblastoma is more complex than was previously imagined as emerging evidence suggests that multiples interactions between the tumor cells and components of the tumor microenvironment (TME) are important for tumor promotion and progression. The identification of several molecular networks within the TME, which interact with tumoral cells, has provided new clues to understand the tumorigenic roles of many TME components as well as potential therapeutic targets. In this review, we discuss the most recent studies regarding the roles of astrocytes in supporting the sonic hedgehog (SHH)–activated medulloblastoma molecular subgroup, and provide an overview of medulloblastoma progression through SHH expression and signal transduction mechanisms into the complex tumor microenvironment. In addition, we highlight the associations between tumor and stromal cells as possible prognostic markers and new therapeutic strategies.

Despite significant advances in metallurgy and the potential to create high and very high-strength steel, all international specifications for steel design provided little information about the limits of slenderness for high-strength steel sections (HSSs) and didn’t give anything about the design of very high-strength steel sections (VHSSs). The American structural steel design specification covers circular hollow sections (CHS) of steel grades up to S690, while it isn't in ANSI/AISC 360-16 and ASTM A514/A514M. Euro code EN 1993-1-1 can be applicable only to steel grades up to S460. EN 1993-1-3 and EN 1993-1-12 contain supplementary rules for cold-formed members and HSS (S460- S700), respectively. Though ductility requirements for (HSS) are specifically established in EN 1993-1-12, it is largely a continuation of the normal-strength-steel design procedures standardized in EN 1993-1-1, where (HSSs) are largely treated as normal-strength steels in these rules, and the same design approaches are used. The behavior of high and very high-strength steel circular hollow sections under axial compression load is studied in this research. A total of 16 nonlinear finite-element (FE) models were generated to replicate stub column tests that were experimentally tested by others in previous research. Hence, a parametric study is conducted using forty FE models developed to investigate the local buckling behavior under various slenderness ratios comprehensively. The developed models cover slenderness ratios ranging from 20 to 1226 and steel grades S460 and S1100 with yield stress equal 460 MPa and 1152 MPa, respectively. The FE results were combined with 105 previously collected experimental results to assess the applicability of existing codified design methodologies in the Euro code and the North American codes of cold-formed CHS. Based on the results of this study, new cross-sectional slenderness limits and new design equations for more efficient simple designs were presented for high and very-high strength steel circular hollow sections and Compared with the results of experimental tests and FE models.

This letter aims to show the connection between the sinc approximation for high-energy absorption cross section and the shadow radius of the spherically symmetric black hole. This connection can give a physical interpretation of the absorption cross section in the eikonal limit parameters. Moreover, the use of this alternative way, one can extract its shadow radius from the absorption cross section in high energy limits to gain more information about the black hole spacetime. Our results indicate that the increasing the value of the shadow radius of the black hole, exponentially increase the the absorption cross section of the black hole in high-energy limits which can be captured by the Event Horizon Telescope (EHT) collaboration.

In cross-country skiing the time difference between a race winner and the person coming second is typically very small. Since much of the energy is spent on overcoming resistive forces, a relatively small reduction of these can have a significant impact on the results. The resistive forces come partly from the friction in the tribological interface, between the ski and the snow, and as with many tribological applications the characterisation of its origin, plays an important role in determining the frictional properties. Also in cross-country ski friction, there are several scales impacting the frictional performance, with the major contributors being the ski-camber profile and ski-base structure. Macro-scale measurements of the ski's camber profile under load, are often used to determine how adequate the ski is for a specific condition. The characteristic properties usually obtained are, the force required to collapse the ski to a certain camber height, the topography of the kick-wax zone, and by simple means a determined lengths of the frictional interface, i.e., the apparent contact length. To this date, there are some mathematical models, but there is no robust way of determining the macro-scale contact properties between a cross-country ski and a counter surface using simulations. In the present paper an Artificial neural networks (ANN) is trained to predict the ski-camber profile for various loads placed at different positions, and a well established deterministic approach is used to simulate the contact between the ANN-predicted ski-camber profile and a linearly elastic body with a flat surface, representing the snow. The results suggest that this method is feasible for the determination of the apparent contact characteristics of different skis. Moreover, we show that the apparent contact area does not linearly depend on the load, and that the elastic properties of the counter surface also has a large impact on the apparent contact area and the average apparent contact pressure.