The resistance of cancer cell subpopulations, including cancer stem cell (CSC) populations, to apoptosis-inducing chemotherapeutic agents is a key barrier to improved outcomes for cancer patients. The cationic amphiphilic drug hexamethylene amiloride (HMA) has been previously demonstrated to efficiently kill bulk breast cancer cells independent of tumor subtype or species, but acts poorly toward non-transformed cells derived from multiple tissues. Here we demonstrate that HMA is similarly cytotoxic toward breast CSC-related subpopulations that are resistant to conventional chemotherapeutic agents, but poorly cytotoxic toward normal mammary stem cells. HMA inhibits the sphere-forming capacity of FACS-sorted human and mouse mammary CSC-related cells in vitro, specifically kills tumor but not normal mammary organoids ex vivo, and inhibits metastatic outgrowth in vivo, consistent with CSC suppression. Moreover, HMA inhibits viability and sphere formation by lung, colon, pancreatic, brain, liver, prostate and bladder tumor cell lines, suggesting that its effects may be applicable to multiple malignancies. Mechanistically, HMA elicits the permeabilization of the limiting lysosomal membrane, a hallmark feature of the lysosome-dependent cell death pathway. Our observations expose a key vulnerability intrinsic to cancer stem cells, and point to novel strategies for the exploitation of cationic amphiphilic drugs in cancer treatment.

RNA silencing serves key roles in a multitude of cellular processes, including development, stress responses, metabolism, and maintenance of genome integrity. Dicer, Argonaute (AGO), double-stranded RNA binding (DRB), RNA-dependent RNA polymerase (RDR) and DNA-dependent RNA polymerases known as Pol IV and Pol V form core components to trigger RNA silencing. Common bean (Phaseolus vulgaris) is an important staple crop worldwide. In this study, we aimed to unravel the components of the RNA-guided silencing pathway in this non-model plant taking advantage of the availability of two genome assemblies of Andean and Meso-American origin. We identified six PvDCLs, thirteen PvAGOs, 10 PvDRB, 5 PvRDR, in both genotypes, suggesting no recent gene amplification or deletion after the gene pool separation. In addition, we identified one PvNRPD1 and one PvNRPE1 encoding the largest subunits of Pol IV and Pol V, respectively. These genes were categorized into subgroups based on phylogenetic analyses. Comprehensive analyses of gene structure, genomic localization and similarity among these genes were performed. Their expression patterns were investigated by means of expression models in different organs using online data and quantitative RT-PCR after pathogen infection. Several of the candidate genes were up-regulated after infection with the fungus Colletotrichum lindemuthianum.

Historical legacy of Eastern European and Balkans’ health systems was mutually interdependent and shaped by local socioeconomic circumstances. Three distinctive systems of risk sharing and health financing to develop since the late XIX century were the Bismarck, Beveridge, and Semashko systems. Modern day healthcare systems in these countries are challenged by population ageing, accelerated innovation in medical technology, growing purchasing power and rising demand for healthcare services. Supply side changes contribute to demand side efficiency bottlenecks in financing, driving the costs of the already expensive medical care up. All of the nations have a large share of citizens experiencing difficulty with affordability and access to medical care, particularly in rural and remote areas. Network of Health technology assessment agencies have mushroomed over the past three decades. Principles of health economics theory and cost-effective resource allocation are slowly gaining ground in governing authorities’ mindset and decision-making process. For many years to come, pharmaceuticals and medical services will remain dependent on out-of-pocket spending. Currently accelerating and spreading 4.0 Industrial Revolution, together with the Belt and Road Initiative, are likely to substantially impact the further economic development of this vast region. Post-Pandemic ‘Green’ Recovery strategies adopted by many of the Eastern European governments shall also make this transition towards sustainable development more difficult and challenging given the large dependency of all these economies upon traditional carbon fuels.

A new type of ordinary differential equation is introduced and discussed, namely, the time-dependent order ordinary differential equations. These equations can be solved via fractional calculus and are mapped into Volterra integral equations of second kind with singular integrable kernel. The solutions of the time-dependent order differential equations smoothly deforms solutions of the classical integer order ordinary differential equations into one-another, and can generate or remove singularities. An interesting symmetry of the solution in relation to the Riemann zeta function and Harmonic numbers was also proved.

Since life on earth developed, parasitic microbes have thrived. Increases in host numbers, or the conquest of a new species, provides an opportunity for such a pathogen to enjoy, before host defense systems kick in, a similar upsurge in reproduction. Outbreaks ‒ caused by ‘endemic’ pathogens ‒ and epidemics ‒ caused by ‘novel’ pathogens ‒ have thus been creating chaos and destruction since prehistorical times. To study such (pre)historic epidemics, recent advances in the ancient DNA field, applied to both archeological and historical remains, have helped tremendously to elucidate the evolutionary trajectory of pathogens. These studies offered new and unexpected insights in the evolution of, for instance, smallpox virus, hepatitis B virus and the plague-causing bacterium Yersinia pestis. Furthermore, burial patterns and historical publications can help in tracking down ancient pathogens. Another source of information is our genome, where selective sweeps in immune-related genes relate to past pathogen attacks, while multiple viruses have left their genomes behind for us to study.

Calandrinia compressa Schrad. ex DC (Prodr. 3: 359. 1828) is the name currently widely applied to a polymorphic annual species of Calandrinia sect. Calandrinia endemic to the Chilean Floristic Region. A total of ten validly published heterotypic names plus six horticultural designations (and orthographic variants thereof) have been considered at some point as taxonomically the same as C. compressa. Two additional heterotypic taxa and their synonyms and two other designations possibly refer to this species. Two other taxa sometimes referred to this species are excluded. I treat here a total of 77 distinct nomenclaturally valid names and invalid designations and variants thereof. The type of one of the valid and legitimate names, Calandrinia pilosiuscula DC (Rev. Portulac. 9. 1827), is judged here to be taxonomically the same as the type of C. compressa. Because of its chronological priority, Calandrinia pilosiuscula DC must be accepted as the correct name for Calandrinia compressa Schrad. ex DC when the two are considered taxonomic synonyms. Here, the taxonomic history of this taxon is articulated and, where possible, types are identified and/or designated. The natural and anthropogenic history of the species is summarized critically in a theoretical context.

ccJE+Advax is an inactivated cell culture Japanese encephalitis (JE) vaccine formulated with Advax™, a novel polysaccharide adjuvant based on delta inulin. This vaccine has previously shown promise in murine and equine studies and the current study sought to better understand its mechanism of action and assess the feasibility of single dose vaccine protection. Mice immunised with ccJE-Advax had higher serum neutralisation titres than those immunised with ccJE alone or with alum adjuvant. ccJE+Advax induced extraordinarily broad cross-neutralising antibodies against multiple flaviviruses including West Nile virus (WNV), Murray Valley Encephalitis Virus (MVEV), St Louis Encephalitis virus (SLE) and Dengue-1 and -2 viruses. Notably, the DENV-2 cross-neutralising antibodies from ccJE+Advax immunised mice uniquely had no DENV-2 antibody dependent enhancement (ADE) activity, by contrast to high ADE activity seen with DENV-1 cross-reactive antibodies induced by mbJE or ccJE alone or with alum adjuvant. JEV-stimulated splenocytes from ccJE+Advax immunised mice showed increased IL-17 and IFN-γ production, consistent with a mixed Th1 and Th17 response, whereas ccJE-alum was associated with production of mainly Th2 cytokines. There is an ongoing lack of human vaccines against particular flaviviruses, including WNV, SLE and MVEV. Given its ability to provide single-dose JEV protection as well as to induce broadly neutralising antibodies free of ADE activity, ccJE+Advax vaccine could be highly useful in all situations where rapid protection is desirable but ADE needs to be avoided, e.g. during a local outbreak or for use in travellers or the military requiring rapid travel to JEV endemic regions.

In this paper, we address the energy eigenvalues of two-dimensional Dirac oscillator perturbed by dynamical noncommutative space. We derived the relativistic Hamiltonian of Dirac oscillator in dynamical noncommutative space ($\tau$-space), in which the space-space Heisenberg–like commutation relations and noncommutative parameter are position-dependent. Then used this Hamiltonian to calculate the first-order correction to the eigenvalues and eigenvectors, based on the second quantization and using the perturbation theory. It is shown that the energy shift depends on the dynamical noncommutative parameter $\tau$. Knowing that with a set of two-dimensional Bopp-shift transformation, we mapped the noncommutative problem to the standard commutative one.

Ebola virus (EBOV) is a negative-sense RNA virus that can infect humans and nonhuman primates with severe health consequences. Development of countermeasures requires a thorough understanding of the interaction between host and pathogen, and the course of disease. The goal of this study was to further characterize EBOV disease in a uniformly lethal rhesus macaque model, in order to support development of a well-characterized model following rigorous quality standards. Rhesus macaques were intramuscularly exposed to EBOV and one group was euthanized at predetermined time points to characterize progression of disease. A second group was not scheduled for euthanasia in order to analyze survival, changes in physiology, clinical pathology, terminal pathology, and telemetry kinetics. On day 3, sporadic viremia was observed and pathological evidence was noted in lymph nodes. By day 5, viremia was detected in all EBOV exposed animals and pathological evidence was noted in the liver, spleen, and gastrointestinal tissues. These data support the notion that EBOV infection in rhesus macaques is a rapid systemic disease similar to infection in humans, under a compressed time scale. Biomarkers that correlated with disease progression at the earliest stages of infection were observed thereby identifying potential “trigger--to-treat” for use in therapeutic studies.

Real-time evolution of the electron densities under excitations in La₂CuO₄ was calculated by the time-dependent density functional theory (TDDFT). The author found, for the first time, under excitations, the electron cloud of Cu²⁺ changes obviously and the characteristic frequencies are 83 meV and 36 meV, respectively, for two different modes. The results are unexpected and close to that of lattice vibrations. The results show that the electron cloud of Cu²⁺ (just like the lattice) can be the electron-pairing medium in high temperature copper oxide superconductors.

Introduction: Body size is correlated with many aspects of an animal species' natural history, such as life span, abundance, dispersal capacity and diet breadth. However, contrasting trends have been reported for the relationship between body size and these ecological traits. Methods: Butterfly species from fruit-feeding guilds were used to investigate whether body size correlates with species abundances, dispersal, permanence, and diet breadth in a Neotropical savanna in Brazil (Cerrado). We used Blomberg’s K and Phylogenetic Generalized Least Squares models (PGLS) to measure phylogenetic signal strength in species traits, and to estimate size-dispersal-diet breadth associations while taking shared ancestry into account. Results: 539 individuals from 27 species were captured, and 190 individuals were recaptured, representing a 35% recapture rate. We found that body size negatively influenced butterfly abundance. In contrast, body size was positively associated with dispersal levels, distance traveled, number of traps visited, individual permanence, and diet breadth. These results indicate that larger butterflies have a greater proportion of dispersing individuals over longer distances, as they permanence were detected over longer periods than their smaller relatives. Moreover, larger butterflies are more generalized, based on the number of host plant families and genera they consume. Smaller butterflies demand fewer resources, which is reflected in their higher survival in small patches, and may explain their lower dispersal ability, and higher diet specialization. Nevertheless, lower dispersal ability, if not compensated by large population sizes, may threaten small-bodied species inhabiting environments with intense deforestation rates, such as the Cerrado. Conclusions: Body size positively influences dispersal and diet breadth in the fruit-feeding butterflies collected in this study.

Vitamin E is a group of eight compounds divided into two subgroups: four tocopherols (α-, β-, γ-, and δ-) and four tocotrienols (α-, β-, γ-, and δ-). α-Tocopherol is considered the most biologically active form. This review paper summarizes the current knowledge and historical progression of vitamin E research, with particular emphasis on its role in animal nutrition. Early studies in the 1920s identified vitamin E’s role in preventing neonatal mortality in rats. Over the following decades, scientists discovered the compound’s chemical structure and its importance for the immune system, skin health, anti-inflammatory properties, hormonal balance, and other bodily functions. Production of vitamin E products has evolved, starting with isolating the vitamin from natural sources and advancing to synthesizing it with greater efficiency and standardized potency units. Early animal studies focused on reproductive health and growth disorders, but further research demonstrated the importance of vitamin E in preventing encephalomalacia in domestic fowl and muscular dystrophy in rabbits and other animals. Today, vitamin E is commonly used as a feed additive to meet animals’ requirements and assure immune function and overall health. Despite much knowledge on vitamin E’s role in animal nutrition, many questions remain unanswered, and current research aims to determine optimal supplementation levels, interactions with other nutrients, impacts on gene expression, cell signaling and communication, and effects of supranutritional dosages in livestock. Vitamin E has a long and fascinating history in scientific research, with significant advancements in understanding its chemical structure and biological activity. In animal nutrition, vitamin E continues to play an important role in improving animal health, and ongoing research will continue to expand our understanding of its benefits and mechanisms of action.

Converting natural language into machine language that can be recognized by distributed systems is the core challenge of intelligent interactive interfaces and human-machine dialogue systems. The human-machine interface interaction of large distributed SCADA measurement and control system is tedious and the operation and maintenance cost is high, so it is significant to design an intelligent natural language interaction interface for distributed measurement and control system. In this paper, we design the intermediate language format of SCADA system, i.e., Key-value logic form, and then formulate the Text2SCADA framework and propose the TICS algorithm and SDPA algorithm, the former adopts the keyword extraction and cosine similarity optimization algorithm to complete the structured extraction of natural language for basic natural language instructions, and the latter adopts the keyword extraction and cosine similarity optimization algorithm to complete the structured extraction of natural language for relatively The latter one adopts the algorithm of dependent syntactic analysis for the structured representation of natural language instructions with relatively complex natural language instructions. Based on the above algorithms, a lightweight information extraction model based on DGCNN and probabilistic graph ideas is constructed, aiming to enhance the scientific generalization ability of the framework on unknown instruction sets. The experimental results show that the proposed intelligent natural language interface can better solve the human-machine interface interaction problem of distributed SCADA measurement and control system. The average accuracy, recall and F-value of instruction parsing reach 89.27\%, 89.28\% and 89.27\%, respectively. The average response time is 1.593 s. Especially, it provides a more convenient means of interaction for industrial and agricultural information control.

Loess provides a valuable terrestrial record of past environmental conditions, including the dynamics of air mass circulation responsible for dust transport. Here we explore variations in the luminescence characteristics of sedimentary quartz and feldspar – dominant minerals in loess-palaeosol sequences (LPS) - as possible tools for identifying changes in source. We investigate luminescence sensitivity, a rapidly measurable index which is the product of interplay between source lithology and the history of the mineral in question. Variations in sensitivity down profile may therefore reflect, among other factors such as pedogenesis and reworking, changes in sediment provenance. We undertake an empirical investigation of the luminescence sensitivity of quartz and feldspar from different grain-size fractions from the climatically sensitive Schwalbenberg LPS in the German Rhine valley, comparing samples from a 30 m core spanning the last full glacial cycle with samples of oxygen isotope stage (OIS) 3-2 age exposed within a c. 6 m profile downslope. The temporal overlap enables comparison of luminescence characteristics with respect to possible provenance change during that timeframe. We find an overall inverse relationship between quartz and feldspar sensitivity, as well as variability in sensitivity between different quartz grain sizes. There is some indication that feldspar sensitivity increases during periods of soil formation down the core. In particular, measurements of IR50 sensitivity on unprocessed sediments show correlation with down-profile trends in more established indicators of provenance. This suggests it may be used to provide a reliable, rapid scan of sensitivity changes, and may suggest source variability over millennial timescales.

Results are presented concerning the influence on the water splitting process of enantiopure tartaric acid present in bulk solution. Stainless steel and electrodeposited nickel are used as working electrode (WE) surface. The latter is obtained by electrodeposition on the two poles of a magnet. The influence and role played by the chiral compound in solution has been assessed by comparing the current values, in cyclic voltammetry (CV) experiments, recorded in the potential range at which oxygen evolution reaction (OER) occurs. In the case of tartaric acid and nickel WE a spin polarization of about 4 % is found. The use of the chiral environment (bulk solution) and ferromagnetic chiral Ni electrode allows for observing the OER at a more favourable potential: about 50 mV (i.e. a cathodic, less positive, shift of the potential at which the oxygen evolution is observed).

FeIFeI Fe2(S2C3H6)(CO)6(µ-CO) (1a-CO) and its FeIFeII cationic species (2a+-CO) are the simplest model of the CO-inhibited [FeFe] hydrogenase active site, which is known to undergo CO photolysis within a temperature- dependent process whose products and mechanism are still a matter of debate. Using Density Functional Theory (DFT) and Time-Dependent Density Functional Theory (TDDFT) computations, the ground state and low-lying excited state potential energy surfaces (PESs) of 1a-CO and 2a+-CO have been explored aimed at elucidating the dynamics of the CO photolysis yielding Fe2(S2C3H6)(CO)6 (1a) and Fe2(S2C3H6)(CO)6+ (2a+), two simple models of the catalytic site of the enzyme. Two main results came out from these investigations. First, a-CO and 2a+-CO are both bound with respect to any CO dissociation with lowest free energy barriers around 10 kcal mol-1, suggesting that at least 2a+-CO might be synthetized. Second, focusing on the cationic form, we found at least two clear excited state channels along the PESs of 2a+-CO that are unbound with respect to equatorial CO dissociation.

Neurological complications of infection by the mosquito-borne Zika virus (ZIKV) include Guillain-Barré syndrome (GBS), an acute inflammatory demyelinating polyneuritis. GBS was first associated with recent ZIKV epidemics caused by the emergence of ZIKV Asian lineage in South Pacific. Here, we hypothesize that ZIKV-associated GBS relates to a molecular mimicry between viral envelope E (E) protein and neural proteins involved in GBS. Analysis of ZIKV epidemic strains showed that glycan loop (GL) region of the E protein includes an IVNDT motif which is conserved in voltage-dependent L-type calcium channel subunit alpha-1C (Cav1.2) and Heat Shock 70 kDa protein 12A (HSP70 12A). Both VSCC-alpha 1C and HSP70 12A belong to protein families which have been associated with neurological autoimmune diseases in central nervous system. The purpose of our in silico analysis is to point out that IVNDT motif of ZIKV E-GL region should be taken in consideration for the development of safe and effective anti-Zika vaccines by precluding the possibility of adverse neurologic events including autoimmune diseases such as GBS.

A close analysis of the text of Gen. 2:8-15, pertaining to the garden of Eden, shows the structural differences between said text and others from ancient mythologies that mention or describe a paradise. Likewise, that analysis suggests that the data provided by the Bible to locate paradise is merely a narrative device meant to dissipate all doubts as to the existence of the garden where God put human beings. Similarly to other spaces that appear in the Bible, the garden of Eden is but an impossible place. Throughout the centuries, however, recurring proposals have been made that aim to find paradise. As time went by, those proposals were progressively modified by the intellectual ideas dominant at any given era, thus leading the representations of the location of Paradise further and further away from the information provided by the biblical text.

A non-relativistic theory of inertia based on Mach's principle is presented as has been envisaged but not achieved by Ernst Mach in 1872. Central feature is a space-dependent, anisotropic, symmetric inert mass tensor. The contribution of a mass element $dm$ to the inertia of a particle $m_0$ experiencing an acceleration from rest is proportional to $\cos^2\alpha$, where $\alpha$ is the angle between the line connecting $m_0$ and $dm$ and the direction of the acceleration. Apsidal precession for planets circling around a central star is not a consequence of this theory, thereby avoiding the prediction of an apsidal precession with wrong sign as is done by Mach-like theories with isotropic inert mass.

Potential dependent special relativity and Gauss's law for the electric field have been used for gravity by assuming vacuum energy to be generated when the energy is a minimum useful expression for vacuum energy has been found. This expression shows that elementary particles are generated by gravity vacuum filling their hollow balls; using Schrödinger equation for spherically symmetric particles vacuum energy is quantized. Treating mass as vibrating spheres thus solving Schrödinger, coordinate harmonic oscillator energy relation has been found.

Based on historical facts, revisited from a present-day perspective, and on the documented opinions of the scientists involved in the discovery themselves, strong arguments are given in favor of a proposal to include prominent astronomer Vesto Slipher to the suggested addition of Georges Lemaître's name to Hubble's law on the expansion of the Universe, and thus eventually call it Hubble-Lemaître-Slipher's (HLS) law.

Viruses continue to provide vital insights into the field of control of gene expression. Viral transactivators, in concert with other viral and cellular proteins, regulate expression of self, other viruses, and host genes with profound effects on infected cells, underlying inflammation, control of immune responses, and pathogenesis. The multifunctional Tat proteins of lentiviruses (HIV-1, HIV-2, and SIV) transactivate gene expression by recruiting host proteins and binding to trans-acting responsive regions (TARs) in viral and host RNAs. SARS-CoV-2 nucleocapsid participates in early viral transcription, recruits similar cellular proteins, and shares intracellular, surface, and extracellular distribution with Tat. SARS-CoV-2 nucleocapsid interacting with the Replication-Transcription complex might, therefore, transactivate viral and cellular RNAs in transcription and reactivation of self and other viruses, acute and chronic pathogenesis, immune evasion, and viral evolution, constituting a potential pan-coronaviral therapeutic target. Here, we show by using primary and secondary structural comparisons that the leaders of SARS-CoV-2 and other coronaviruses contain TAR-like sequences in stem-loops 2 and 3, the coronaviral nucleocapsid C-terminal domains (N-CTDs) harbor a region of similarity to TAR-binding regions of lentiviral Tat proteins, and the coronaviral nonstructural protein 12 has a cysteine-rich metal binding, dimerization domain similar to that in lentiviral Tat proteins.

Exercise affects various organs. However, its effects on nutrient digestion and absorption in the intestinal tract are not well understood. A few studies have reported that exercise training in-creases the expression of carbohydrate digestion and absorption molecules. Exercise was also shown to increase the concentration of blood glucagon like peptide-2(GLP-2), which regulates carbohydrate digestion and absorption in small intestinal epithelium. Therefore, we investigated the effects of exercise on intestinal digestion and absorption molecules and the levels of GLP-2. 6-wk-old of male mice were divided into 2 groups; sedentary (SED) and low-intensity exercise (LEx). LEx mice were required to run on a treadmill (12.5 m/min, 60 min), whereas SED mice rested. All mice were euthanized 1 h after exercise or rest and plasma, jejunum, ileum, and colon were sampled. Samples were analyzed using EIA and immunoblotting. The levels of plasma GLP-2 and the expression of the GLP-2 receptor, sucrase-isomaltase (SI), and glucose transporter (GLUT2) in the jejunum were increased in LEx group. We showed that acute low-intensity exer-cise affects the intestinal carbohydrate digestion and absorption molecules via GLP-2. Our results suggest that exercise might provide new benefits to the small intestine for people with intestinal frailty.

A review is here provided on the thermal effects on the optical chirality. To this goal, chiral objects dispersed in an embedding fluid are examined for their magnetoelectric coupling. Archetypal twisted-Omega particles are examined with respect to electron transport, phonon dynamics, and temperature effects. Continuum-mechanical aspect of thermo-elasticity is reviewed along with transverse deformations. A transition temperature delineating a sign flip in the chirality parameter is identified as well.

The discovery of microRNAs (miRNAs) has fundamentally transformed our understanding of gene regulation. The competing endogenous RNA (ceRNA) hypothesis postulates that not only messenger RNAs but also other RNA transcripts, such as long non-coding RNAs and pseudogenes, can act as natural miRNA sponges. These RNAs influence each other’s expression levels by competing for the same pool of miRNAs through miRNA response elements on their target transcripts, thereby modulating gene expression and protein activity. In recent years, these ceRNA regulatory networks have gained considerable attention in cancer research. Several studies have identified cancer-specific ceRNA networks. Nevertheless, prior bioinformatic analyses have focused on long non-coding RNAs-associated ceRNA networks. Here, we identify an extended-ceRNA network (including both long non-coding RNAs and pseudogenes) shared across a group of four hormone-dependent (HD) cancers, i.e., prostate, breast, colorectal, and endometrial cancers, using data from The Cancer Genome Atlas (TCGA). We performed a functional enrichment analysis for differentially expressed genes in the shared ceRNA network of HD cancers, followed by a survival analysis to determine their prognostic ability. We identified two long non-coding RNAs, nine genes, and seventy-four miRNAs in the shared ceRNA network across four HD cancers. Among them, two genes and forty-one miRNAs were associated with at least one HD cancer survival. This study is the first to investigate pseudogene associated ceRNAs across a group of related cancers and highlights the value of this approach to understanding shared molecular pathogenesis in a group of related diseases.

The recent advances in Human-Computer Interaction and Artificial Intelligence have significantly increased the importance of identifying human emotions from different sensory cues. Hence, understanding the underlying relationships between emotions and sensory cues have become a subject of study in many fields including Acoustics, Psychology, Psychiatry, Neuroscience and Biochemistry. This work is a preliminary step towards investigating cues for human emotion on a fundamental level by aiming to establish relationships between tonal frequencies of sound and emotions. For that, an online perception test is conducted, in which participants are asked to rate the perceived emotions corresponding to each tone. The results show that a crossover point for four primary emotions lies in the frequency range of 417–440 Hz, thus consolidating the hypothesis that the frequency range of 432–440 Hz is neutral from human emotion perspective. It is also observed that the frequency dependant relationships between emotion pairs Happy—Sad, and Anger—Calm are approximately mirrored symmetric in nature.

The study of co-fusion was one of the essential topics in the history of metallurgy in China. Simulation experiments had been an essential concept in the study of the co-fusion steelmaking process. This paper mainly studied the simulation experiments of co-fusion from two aspects: the replication of co-fusion swords by three different methods, and the micro-analysis of the co-fusion samples. The experimental results indicated that several co-fusion swords could be made by different processes, but the carbon content and surface hardness were quite different. During repeated forging welded, the microstructure of the samples transformed from laminated to homogenized, finally the steel with a uniform carbon content was obtained. It was challenging to find the characteristics of co-fusion from the homogenized samples. The results prompted people to rethink the microstructure characteristics of ancient co-fusion artifacts.

Human metapneumovirus is one of major causes of common cold among children, especially infants. Its key enzyme is RNA-dependent RNA-polymerase, which performs both replication and transcription, including capping and cap methylation. The goal of the work is to find possible inhibitors of RNA-dependent RNA-polymerase across the active compounds of Rosaceae plants. The candidates were selected by molecular docking to cap-transferring domain of RNA-polymerase (PDB ID: 4UCZ) in Autodock VINA. Among all the substances tested by docking, ellagic acid derivatives showed the most promising results (affinity values below -10 kcal/mol). Hence, they could be treated as possible candidate drugs against metapneumoviral infection after experimental examination. The main advantage of using these substances should be their low toxicity, which is quite uncommon for selective RNA polymerase inhibitors used in clinical practice. Occurrence of ellagic acid derivatives among the plants from Rosaceae family like raspberry could explain their effect during common cold.

Mexico shows a high birth prevalence of congenital hypothyroidism (CH) due to thyroid dysgenesis (TD). PAX8 defects underlie only 1% of these cases and NKX2-1 does not seem to be involved. Here, we analyzed other TD-related genes in 128 non-related Mexican patients (females 77.3%; 6 months to 16.6 years) with non-syndromic CH-TD diagnosis established by clinical evaluation, thyroid hormone serum profiling, and scintigraphy (74%) or ultrasonography (26%). We performed Sanger sequencing of FOXE1, NKX2-5, and TSHR and evaluated copy number variations (CNVs) in TSHR, FOXE1, PAX8, and NKX2-1 by multiplex ligation-dependent probe amplification. Odds ratios for TD risk were explored for FOXE1 polyalanine stretches [polyAla-rs71369530] in cases and controls (N=116). Five rare missense changes cataloged as benign (NKX2-5:p.(Ala119Ser)-rs137852684), of unknown significance (FOXE1:p.(Ala335Gly)-rs543372757; TSHR:p.(Asp118Asn)-rs1414102266), and likely pathogenic (FOXE1:p.(Gly124Arg)-rs774035532; TSHR:p.(Trp422Arg)-rs746029360) accounted for 1.5% (N=2/128) of clinically relevant genotypes (supported in part by protein modeling) in CH-TD. No CNVs were identified, nor did polyAla >14 alanines in FOXE1 significantly protect against TD. The present and previously published data collectively show that small clinically relevant germline variants in PAX8, FOXE1, and TSHR are found in only a very small proportion (2.5%) of isolated CH-TD Mexican patients.

Epithelial–mesenchymal transition (EMT) is defined as a cellular process during which epithelial cells acquire mesenchymal phenotypes and behavior following the downregulation of epithelial features. EMT and its reversed process, the mesenchymal-epithelial transition (MET), and the special form of EMT, the endothelial-mesenchymal transition (EndMT), have been extensively investigated in developmental biology and pathology. More than a half-century of EMT study has made it a large research field and a mainstream concept. However, discrepancies and disputes over EMT and EMT research have also grown over time. Particularly, neither the epithelial and mesenchymal states/properties nor their regulatory networks nor specific markers have been defined, rendering the EMT, MET and EndMT concepts groundless. EMT and MET effects represented by the change in cell shapes or adhesiveness or symbolized by EMT factors are biased interpretation of the overall change in cellular property and regulatory networks during developmental process and cancer progression. The true meaning of EMT effects in some developmental and pathological processes, such as fibrosis, needs re-evaluation. But the core EMT factors are actually a few components of the regulatory networks of neural stemness, which determines tumorigenicity and pluripotency. The EMT effects in cancer progression and neural crest formation are wrong attribution of the role of neural stemness during cancer progression and the cell-intrinsic property of neural crest cells to the unknown mesenchymal state. It is time to reassess the significance of EMT and its related concepts in scientific research.

Since its initial development in the 1970’s by Phil Burke and his collaborators, the R-matrix theory and associated computer codes have become the de facto approach for the calculation of accurate data for general electron-atom/ion/molecule collision and photoionization processes. The use of a non-orthonormal set of orbitals based on B-splines, now called the B-spline R-matrix (BSR) approach, was pioneered by Zatsarinny. It has considerably extended the flexibility of the approach and improved particularly the treatment of complex many-electron atomic and ionic targets, for which accurate data are needed in many modelling applications for processes involving low-temperature plasmas. Both the original R-matrix approach and the BSR method have been extended to the interaction of short, intense electromagnetic (EM) radiation with atoms and molecules. Here we provide an overview of the theoretical tools that were required to facilitate the extension of the theory to the time domain. As an example of a practical application, we show results for two-photon ionization of argon by intense short-pulse extreme ultraviolet radiation

Replication stress (RS) is a characteristic state of cancer cells as they tend to exchange precision of replication for fast proliferation and increased genomic instability. To overcome the consequences of improper replication control malignant cells frequently inactivate parts of their DNA damage response (DDR) pathways (the ATM-CHK2-p53 pathway), while relying on other pathways which help to maintain replication fork stability (ATR-CHK1). This creates a dependency on the remaining DDR pathways, vulnerability to further destabilization of replication and synthetic lethality of DDR inhibitors with common oncogenic alterations such as mutations of TP53, RB1, ATM, amplifications of MYC, CCNE1 and others. The response to RS is normally limited by coordination of cell cycle, transcription and replication. Inhibition of WEE1 and PKMYT1 kinases, which prevent unscheduled mitosis entry, leads to fragility of under-replicated sites. Recent evi-dence also shows that inhibition of Cyclin-dependent kinases (CDKs), such as CDK4/6, CDK2, CDK8/19 and CDK12/13 can contribute to RS through disruption of DNA repair and replication control. Here, we review the main causes of RS in cancers as well as main therapeutic targets – ATR, CHK1, PARP and their inhibitors.

Organic light-emitting diodes (OLEDs) are energy-efficient; however, the coordinating ligand can affect their stability. Sky-blue phosphorescent Pt(II) complexes with a C^N chelate, fluorinated-dbi (dbi = [1-(2,4-diisopropyldibenzo[b,d]furan-3-yl)-2-phenyl-1H-imidazole]), and acetylactonate (acac)(1)/picolinate (pic)(2) ancillary ligands were synthesized. The molecular structures were characterized using various spectroscopic methods. The Pt(II) coordination sphere in 2 exhibited a distorted square-planar geometry, with several intra- and inter-molecular interactions involving Cπ⋯H/Cπ⋯Cπ stacking. Complex 1 emitted bright sky-blue light (λmax = 485 nm) with a moderate photoluminescent quantum efficiency of 0.37 and short decay time (6.1 µs) compared to those of 2. Time-dependent density functional theory calculations suggested that the electronic transition of 1 arose from ligand(C^N)-centered π–π* transitions combined with metal-to-ligand charge transfer transitions (MLCT), whereas that of 2 arose from MLCT and ligand(C^N)-to-ligand(pic) charge transfer (LLCT), with minimal contribution from the C^N chelate to the lowest unoccupied molecular orbital. Multi-layered phosphorescent OLEDs using 1 as a dopant and a mixed host, 3,3-di(9H-carbazol-9-yl)-1,1-biphenyl:3-di(9H-carbazol-9-yl)-1,1-biphenyl (mCBP)/9-(3’-carbazol-9-yl-5-cyano-biphenyl-3-yl)-9H-carbazole-3-carbonitrile (CNmCBPCN) were successfully fabricated. At a 10% doping of 1, a current efficiency of 13.6 cd A−1 and external quantum efficiency of 8.4 % at 100 cd m−2 were achieved. These results show that the ancillary ligand in phosphorescent Pt(II) complexes must be considered.

The lateral pressure generated by liquefied soil on pile is a critical parameter in the analysis of soil-pile interaction in liquefaction-susceptible sites. Previous studies have shown that liquefied sand behaves like a non-Newton fluid, and its effect on piles has rate-dependent properties. In this study, a simplified pseudo-static method for liquefiable soil-pile interaction analysis is proposed by treating the liquefied soil as a thixotropic fluid, which considers the rate-dependent behavior. The viscous shear force generated by the relative movement between the viscous fluid (whose viscosity coefficient varies with excess pore pressure and shear strain rate) and the pile was assumed to be the lateral load on the pile. The results from the simplified analysis show that the distribution of bending moment is in good agreement with experiments data. Besides, the effects of various parameters, including relative density, thickness ratio of non-liquefiable layer to liquefiable layer, and frequency of input ground motion, on the pile-soil rate-dependent interaction were discussed in detail.

Influenza viruses cause acute respiratory infections responsible for significant mortality and morbidity around the world. Various factors, such as antigenic drift, allow influenza strains to avoid being fully suppressed by seasonal vaccines. This has led to the increased scrutiny of antivirals as treatment and prophylaxis options for seasonal outbreaks and potential pandemics. Unfortunately, many influenza antivirals suffer from a lack of adequate clinical trials, as well as a lack of toxicity data. This is especially true of umifenovir (arbidol), a drug popularly used for the prevention and treatment of influenza strains in China and Russia. Neuraminidase inhibitors, though widely prescribed, display a potential for future resistance. Adamantanes, while proven to be effective in treating influenza A, are already encountering rapid and widespread cross-resistance and are effectively obsolete. Baloxavir marboxil, a newer antiviral, shows promise in treating acute uncomplicated influenza and may avoid the development of resistance when co-administered with other antiviral drugs. Indeed, the low genetic barrier to resistance associated with influenza antivirals could potentially be overcome by co-administration with other antivirals. This review explores the most widely prescribed antivirals for influenza treatment, their mechanisms of action, and the data currently available about their susceptibility to resistance and efficacy.

There is a rich history of cancer treatments which provides a number of important lessons for present and future cancer therapies. We outline this history by looking in the past, reviewing the current landscape of cancer treatments, and by glancing at the potential future cancer therapies.

The first reports of the acute and often fatal illness known as the “English Sweat” are from 1485 and its last known outbreak was in 1551. During this period, the Sweat produced only five epidemic waves. Except for one outbreak which spread to the northern part of the continent of Europe in 1529, the Sweat was confined almost exclusively to England, with only anecdotal reports of isolated infections in other parts of the British Isles. The Sweat was thus only a minor component in the panorama of infectious disease affecting mediaeval and early modern Europe. Nevertheless, it continues to fascinate both medical historians and modern infectious disease biologists – the latter group now often engaged in competing exercises in retrospective diagnosis. This paper seeks to explore the reasons for such enduring interest, using the Early English Books Online (EEBO) text corpus to analyse the various contexts in which the Sweat was discussed up to 1700. EEBO shows that references to the Sweat occur repeatedly in astrological and religious discourses, especially from the mid-17^th century onwards. Four salient examples are examined in detail. It is proposed that the cultural memory of the Sweat, in the 150 years following its disappearance, was kept disproportionately alive not so much by accounts of its alarming symptoms but more due to its metaphorical and illustrative utility in non-medical discourse.

Regression models are mostly used in all fields of sciences for modelling the relationship between a dependent variable and independent variable(s). The least square method is often used to estimate the parameters in a linear model because it is the best linear unbiased estimator. These estimates can only be reliable if the assumption of normality is satisfied. In some cases the dependent variable might be bimodal and shows a non-linear relationship with the independent variable(s). In this case, a non-linear model should be used. In non-linear model, the standard errors are often obtained by linearizing the nonlinear function around the parameter, assuming central limit theorem. After the linearization, the least square parameter estimates are obtained. It should be noted that the error of the non-linear model is different from that of the transformed linear model. Thus, there is a need to transform back to the original non-linear model. In this note, a novel non-linear function was developed into a non-linear regression model, called Normal-Power model. The least square method was used to estimate the parameter of the transformed model. Its usefulness in regression model was demonstrated using real data of Nigeria Economy-Tourism model.

Cholest-4-en-3-one Δ1-dehydrogenase (AcmB) from Sterolibacterium denitrificans is successfully immobilized on 3-aminopropyltrimethoysilane functionalized MCF and SBA-15 silica supports using adsorption or covalently with glutaraldehyde or divinyl sulfone linkers. The best catalyst, AcmB on MCF linked covalently with glutaraldehyde, retains the specific activity of the homogenous enzyme while exhibiting a substantial increase of the operational stability. The immobilized enzyme was used continuously in the fed-batch reactor for 27 days, catalyzing 1,2-dehydrogenation of androst-4-en-3-one to androst-1,4-dien-3-one with a final yield of 29.9 mM (8.56 g/L) and 99% conversion. The possibility of reuse of the immobilized catalyst was also demonstrated and resulted with a doubling of the product amount compared to that in the reference homogenous reactor. Finally, it was shown that molecular oxygen from the air can efficiently be used as an electron acceptor either reoxidizing directly the enzyme or the reduced DCPIPH2. Keywords: 3-ketosteroid D1-dehydrogenase; KSTD; KSDH; AcmB; 1,2-dehydrogenation; cholest-4-en-3-one Δ1-dehydrogenase; enzyme immobilization, FAD-dependent enzymes; enzyme immobilization;

The epithelial cell adhesion molecule (EpCAM) is a stem cell and carcinoma antigen, which mediates cellular adhesion and proliferative signaling by the proteolytic cleavage. In contrast to low expression in normal epithelium, EpCAM is frequently overexpressed in various carcinomas, which correlates with poor prognosis. Therefore, EpCAM has been considered as a promising target for tumor diagnosis and therapy. Using the Cell-Based Immunization and Screening (CBIS) method, we previously established an anti‐EpCAM monoclonal antibody (EpMab-37; mouse IgG1, kappa). In this study, we investigated the antibody‐dependent cellular cytotoxicity (ADCC), complement‐dependent cytotoxicity (CDC), and an antitumor activity by a defucosylated mouse IgG2a-type of EpMab-37 (EpMab-37-mG2a-f) against an EpCAM‐expressing breast cancer cell line (BT-474). EpMab-37-mG2a-f recognized BT-474 cells with a moderate binding-affinity [a dissociation constant (KD): 2.9x10-8 M] by flow cytometry. EpMab-37-mG2a-f exhibited ADCC and CDC for BT-474 cells by murine splenocytes and complements, respectively. Furthermore, administration of EpMab-37-mG2a-f significantly suppressed the BT-474 xenograft tumor development compared with the control mouse IgG. These results indicated that EpMab-37-mG2a-f exerts antitumor activities against the BT-474 xenograft, and could provide valuable therapeutic regimen for the breast cancers.

Animal trypanosomiasis (AT) is a complex of veterinary diseases known under various names such as nagana, surra, dourine and mal de caderas, depending on the country, the infecting trypanosome species and the host. AT is caused by parasites of the genus Trypanosoma, and the main species infecting domesticated animals are T. brucei brucei, T. b. rhodesiense, T. congolense, T. vivax, T. evansi and T. equiperdum. AT transmission, again depending on species, is through tsetse flies or common Stomoxys and tabanid flies or through copulation. Therefore, the geographical spread of all forms of AT together is not restricted to the habitat of a single vector like the tsetse fly and currently includes almost all of Africa, and most of South America and Asia. The disease is a threat to millions of companion and farm animals in these regions, creating a financial burden in the billions of dollars to developing economies as well as serious impacts on livestock rearing and food production. Despite the scale of these impacts, control of AT is neglected and under-resourced, with diagnosis and treatments being woefully inadequate and not improving for decades. As a result, neither the incidence of the disease, nor the effectiveness of treatment is documented in most endemic countries, although it is clear that there are serious issues of resistance to the few old drugs that are available. In this review we particularly look at the drugs, their application to the various forms of AT, and their mechanisms of action and resistance. We also discuss the spread of veterinary trypanocide resistance and its drivers, and highlight current and future strategies to combat it.

The world’s human population is reaching record longevities. Consequently, our societies are experiencing the impacts of prolonged longevity, such as increased retirement age. A major hypothesised influence on ageing patterns is resource limitation, formalised under calorie restriction theory. This theory predicts extended organismal longevity due to reduced calorie intake without malnutrition. However, several challenges face current calorie restriction (CR) research and, although several attempts have been made to overcome these challenges, there is still a lack of holistic understanding of how CR shapes organismal vitality. Here, we conduct a literature review of 222 CR peer-reviewed publications to summarise the state-of-the-art in the field. We use this summary to highlight challenges of CR research in our understanding of its impacts on longevity. Our review demonstrates that experimental research in this field is biased towards short-lived species (98.2% of studies examine species with <5 years of mean life expectancy) and lacks realism in key areas, such as stochastic environments or interactions with other environmental drivers such as temperature. We argue that only by considering a range of short- and long-lived species and by taking more realistic approaches can the impacts of CR on longevity be examined and validated in natural settings. We conclude by proposing experimental designs and study species that will allow the discipline to gain a much-needed understanding of how restricting caloric intake affects long-lived species in realistic settings. Through incorporating more experimental realism, we anticipate crucial insights that will ultimately shape the myriad of socio-bio-economic impacts of senescence in humans and other species across the Tree of Life.

RNA interference is a highly conserved process in which non-coding small RNAs (sRNA) modulate gene expression at the post-transcriptional level influencing plant growth and development. Dicer-like (DCL), Argonaute (AGO) and RNA-dependent RNA polymerase (RDR) are the core elements involved in gene silencing and their gene families have been explored in many plants. However, these genes and their response to abiotic stresses have not yet been well in wheat. In this study, 82 AGO, 31 DCL, and 31 RDR genes were identified and phylogenetic analysis of these proteins showed that clustered into ten, four and four clades respectively. RNA-seq analysis revealed constitutive expression of AGO1, AGO9, and DCL2 family expression analysis in tissues under normal and stress conditions, whereas RDR1 which is known to engage in siRNA biogenesis showed higher expression levels in wheat leaf tissues. Our findings build the foundation for comparative genomics analyses of RNA silencing elements in cereal crops, as well as new insights into the functional complexity of RNA silencing in wheat stress responses, which is critical for understanding the processes underlying wheat stress responses.

The integrated stress response is a signaling network comprised of four branches, each of which senses different cellular stressors, converging on the phosphorylation of eIF2α to depress global translation and initiate recovery. One of these branches is composed of GCN2, which senses cellular amino acid insufficiency and participates in the maintenance of amino acid homeostasis. Previous studies have shown that GCN2 is a viable cancer target when amino acid stress is provoked by inhibiting an additional target. In this light, we screened a combination of drugs to identify biologically active compounds which synergize with the GCN2 inhibitor TAP20. First, a panel of 25 compounds was assayed in six cancer cell lines for drug sensitivity. Each compound was then combined with TAP20 at concentrations below their IC50, and the impact on cell growth was assessed. Selected strongly synergistic combinations were further characterised using synergy analyses and matrix-dependent invasion assays. Inhibitors of proteostasis, of the MEK-ERK pathway and pan-CDK inhibitors flavopiridol and seliciclib were found to potently synergize with TAP20 in two of the tested cell lines. Among their common CDK targets is CDK7, which was selectively targeted with THZ-1 and found to synergize with TAP20. Finally, these combinations were found to be partially synergistic when assessed using matrix-dependent invasion assays. However, we found that TAP20 alone was sufficient to restrict invasion at concentrations well below its growth-inhibitory IC50. We conclude that GCN2 can be targeted for treating cancers by polytherapy or even monotherapy.

If a subject learns about the properties of an alternative under a high state of food deprivation, it will prefer this alternative over a similar one in a later choice test, although the subject is currently under a relative state of satiety. In this experiment, we probe this effect in a delay-discounting task, where the reward of the experienced alternative is progressively delayed. Eight male Wistar rats were trained to respond to an alternative under a high state of deprivation and eight rats under a relative state of satiety. After 20 sessions, their weight was recalibrated to a state of relative satiety. Then, they were exposed to a delay-discounting task where the long-larger alternative was the one used during training. The group that experienced the alternative under a higher level of food deprivation preferred more this alternative, and its preference stayed across time. On the contrary, the group that experienced the alternative under a lower level of food deprivation systematically preferred the small-shorter alternative. Our results support that the reinforcement value may be sensitive to the organism's state at the moment an alternative is experienced for the first time.

In Secondary Education, the focus of History teaching must be on the development of global citizenship. The present research was a study contextualized in the Fiesta de la Historia Youth Congress in Seville (Spain). A documentary analysis with a descriptive and interpretive design was made of 63 projects of inquiry that pupils carried out. The main objectives were to assess the incidence of the proposal in terms of participation, and to determine whether the pupils' projects followed a logic of inquiry about socially relevant problems which favours the construction of global citizenship. The results point to a low incidence of schools participating in this initiative. The projects of inquiry analysed present for the most part themes related to the historical and social heritage of the locality. The proposals are approached as problems of a specific discipline, and are worked on through a method based on a pseudoscientific research process. The findings indicate the need to continue implementing initiatives based on school inquiry that allow the teaching of History to be articulated around relevant social problems, with the objective being to develop citizenship skills.

This paper analyzes the collection of George Viau (1855-1939) from a computational perspective. Indeed, this dental surgeon, close to the Impressionists, collected several hundred works of art in the first half of the 20th century: the auctions of his collection, in 1907, 1930 and after his death, in 1942, 1943 and 1948, accounted for 642 artworks and, during the Occupation, the 1942 sale produced a total of more than 46 million francs. Thanks to statistics, econometrics, network analysis and cartography, it is possible to understand the salient features of the collection and its place in the world of Parisian auctions.

Chimeric Antigen Receptor (CAR)-T cell immunotherapy revolutionized cancer treatment and consists of the genetic modification of T lymphocytes with a CAR gene, aiming to increase their ability to recognize and kill antigen-specific tumor cells. The dynamics of CAR-T cell responses in patients presents a multiphasic kinetics with distribution, expansion, contraction, and persistence phases. The characteristics and duration of each phase depend on the tumor type, the infused product, and on patient-specific characteristics. We present a mathematical model which describes the multiphasic CAR-T cell dynamics resulting from the interplay between CAR-T and tumor cells, considering patient and product heterogeneities. The CAR-T cell population is divided into functional (distributed and effector), memory, and exhausted CAR-T cell phenotypes. The model is able to describe the diversity of CAR-T cell dynamic behaviors in different patients and hematological cancers as well as their therapy outcomes. Our results indicate that the joint assessment of the area under the concentration-time curve in the first 28 days and the corresponding fraction of non-exhausted CAR-T cells may be considered as potential markers to classify therapy responses. Overall, the analysis of different CAR-T cell phenotypes can be a key aspect for a better understanding of the whole CAR-T cell dynamics.

A few empirical examples document fixed alternative male mating strategies in animals. Here we focus on the polymorphism of male mating strategies in the ruff (Calidris pugnax, Aves Charadriiformes). In ruffs, three fixed alternative male mating strategies coexist and are signaled by extreme plumage polymorphism. We first present relevant data on the biology of the species. Then we review the available knowledge of the behavioral ecology of ruffs during the breeding season and we detail the characteristics of each of the three known fixed male mating strategies. We next turn to the exceptional quality results accumulated on both the structural and functional genomics of the ruff over the past few years. We show how much these genomic data can shed a new, mechanistic light on the evolution and maintenance of the three fixed alternative male mating strategies. We then look if there are sufficient indication to support frequency-dependent selection as key mechanism in maintaining these three strategies. Specifically, we search for evidences of equal fitness among individuals using each of the three strategies. Finally, we propose three lines of research avenues that will help to understand the eco-evolutionary dynamics of phenotypic differences within natural populations of this iconic model species.

Dynamic variables in the non-equilibrium systems of life are determined by catalytic activities. These relate to the expression of the genome. The extent to which such a variable depends on the catalytic activity defined by a gene has become more and more important in view of the possibilities to modulate gene expression or intervene with enzyme function through the use of medicinal drugs. With all the complexity of cellular systems biology, there are still some very simple principles that guide the control of variables such as fluxes, concentrations, and half-times. Using time-unit invariance we here derive a multitude of laws governing the sums of the control coefficients that quantify the control of multiple variables by all the catalytic activities. We show that the sum of the control coefficients of any dynamic variable over all catalytic activities is determined by the control of the same property by time. When the variable is at a maximum, minimum or steady, this limits the sums to simple integers like 0, -1, 1, and -2, depending on the variable under consideration. Some of the implications for biological control are discussed as is the dependence of these results on the precise definition of control.

Antibody-dependent cell-mediated cytotoxicity (ADCC) by natural killer (NK) lymphocytes eliminates cells infected with viruses. Antiviral ADCC requires three components: 1) antibody; 2) effector lymphocytes with the Fc-IgG receptor CD16A; and 3) viral proteins in infected cell membranes. Fc-afucosylated antibodies bind with greater affinity to CD16A than fucosylated antibodies; individuals’ variation in afucosylation contributes to differences in ADCC. Current assays for afucosylated antibodies involve expensive methods. We report an improved bioassay for antibodies that support ADCC which encompasses afucosylation. This assay utilizes externalization of CD107a by NK-92-CD16A cells after antibody recognition. We used anti-CD20 monoclonal antibodies, GA101 WT or glycoengineered (GE), 10% or ~50% afucosylated, and CD20-positive Raji target cells. CD107a increased detection 7-fold compared to flow cytometry to detect Raji-bound antibodies. WT and GE antibody effective concentrations (EC50s) for CD107a externalization differed by 20-fold, with afucosylated GA101-GE more detectable. The EC50s for CD107a-externalization vs. 51Cr cell death were similar for NK-92 CD16A and blood NK cells. Notably, the %CD107a-positive cells negatively correlated with dead Raji cells and was nearly undetectable at high NK:Raji ratios required for cytotoxicity. This bioassay is very sensitive and adaptable to assess anti-viral antibodies but unsuitable as a surrogate assay to monitor cell death after ADCC.

In this article, we delve into the intricate behavior of electronic mechanisms underlying NMR magnetic shieldings, σ, in molecules containing heavy atoms such as cadmium, platinum, and mercury. Specifically, we explore PtXn^{−2} (X = F, Cl, Br, I; n = 4, 6) and XCl2 Te2 Y2 H6 (X = Cd, Hg; Y = N, P) molecular systems. It is known that the leading electronic mechanisms responsible for the relativistic effects on σ are well characterized by the linear response with elimination of small components model (LRESC). In this study, we present results obtained from the innovative LRESC-Loc model, which offers the same outcomes as the LRESC model but employs localized molecular orbitals (LMOs) instead of canonical MOs. These LMOs provide a chemist’s representation of atomic core, lone pairs, and bonds. The whole set of electronic mechanisms responsible of the relativistic effects can be expressed in terms of both non-ligand-dependent and ligand-dependent contributions. We elucidate the electronic origins of trends and behaviors exhibited by these di- verse mechanisms in the aforementioned molecular systems. In PtX4^{−2} molecules, the predominant relativistic mechanism is the well-established one-body spin-orbit (σ^SO(1) ) mechanism, while the paramagnetic mass-velocity (σ^Mv ) and Darwin (σ^Dw ) contributing mechanisms also demand con- sideration. However, in PtX6−2 molecules, the σ Mv+ Dw contribution surpasses that of the SO(1) mechanism, thus influencing the overall ligand-dependent contributions. As for complexes con- taining Cd and Hg, the ligand-dependent contributions exhibit similar magnitudes when nitrogen is substituted with phosphorus. The only discrepancy arises from the σ^SO(1) contribution, which changes sign between the two molecules due to the contribution of bond orbitals between the metal and tellurium atoms.

Calcium/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) regulates bone remodeling through its effects on osteoblasts and osteoclasts. However, its role in osteocytes, the most abundant bone cell type, and the master regulator of bone remodeling, remains unknown. Here we report that the conditional deletion of CaMKK2 from osteocytes using Dentine matrix protein 1 (Dmp1)-8kb-Cre mice led to enhanced bone mass only in female mice owing to a suppression of osteoclasts. Conditioned media isolated from female CaMKK2-deficient osteocytes inhibited osteoclast formation and function in in vitro assays, indicating a role for osteocyte-secreted factors. Proteomics analysis revealed significantly higher levels of extracellular calpastatin, a specific inhibitor of calcium-dependent cysteine proteases calpains, in female CaMKK2 null osteocyte conditioned media, compared to media from female control osteocytes. Further, exogenously added non-cell permeable recombinant calpastatin domain I elicited a marked, dose-dependent inhibition of female wild-type osteoclasts and depletion of calpastatin from female CaMKK2-deficient osteocyte conditioned media reversed the inhibition of matrix resorption by osteoclasts. Our findings reveal a novel role for extracellular calpastatin in regulating female osteoclast function and unravel a novel CaMKK2-mediated paracrine mechanism of osteoclast regulation by female osteocytes.

The evolutionary transition from single-celled to multicellular individuality requires organismal fitness to shift from the cell-level to the cell group. This reorganization of fitness occurs by allocating the two components of fitness, survival and reproduction, between two specialized cell types in the multicellular group – soma and germ, respectively. How does the genetic basis for such fitness reorganization evolve? One possible mechanism is the co-option of life-history genes present in the unicellular ancestors of a multicellular lineage. Single-celled organisms must regulate their investment in survival and reproduction in response to environmental changes, particularly decreasing reproduction to ensure survival when stressed. Such stress response life-history genes can provide the foundation for the genetic basis for cellular differentiation in multicellular lineages. The regA gene family in volvocine green algae provides a model system to study how this co-option occurs. We discuss the origin and evolution of the volvocine regA gene family, including regA – the gene that controls somatic cell development in the model organism Volvox carteri. We hypothesize that the co-option of life history trade-off genes is a general mechanism involved in the transition to multicellular individuality, making volvocine algae and the regA family a useful template for similar investigations in other lineages.

Flavin-dependent monooxygenases (FMOs) have made substantial influence as catalysts for monooxygenation reactions, impacting diverse field such as drug metabolism, environmental studies, and natural product synthesis. Their application in biocatalysis boasts several advantages over conventional chemical catalysis, such as heightened selectivity, safety, sustainability, and eco-friendliness. In the realm of biomedicine, FMOs are pivotal in antibiotic research, modulating natural products, antimicrobial agents, and pathways involved in drug synthesis. They're also underscored as potential pharmaceutical targets, pivotal in disease progression and viable for therapeutic intervention. Additionally, FMOs play a substantial role in environmental science, especially in pesticide processing and plant vitality. Their involvement in biosynthesizing compounds like polyethers, tropolones, and ω-hydroxy fatty acids, with remarkable regio- and stereoselectivity, renders them indispensable in drug discovery and development. As our comprehension of FMOs' catalytic mechanisms and structures advances, coupled with cutting-edge biotechnologies like computational design and directed evolution, FMOs are poised to occupy an increasingly significant role in both scientific exploration and industrial applications.

Durability of concrete requires a dense microstructure which can be achieved by using self-compacting concrete (SCC). Both calcined clay (CC) and rice husk ash (RHA) are promising supplementary cementitious materials (SCMs) that can partially replace cement, but their use in SCC is critical due to their higher water demand and specific surface area (SSA) compared to cement. Empirical method of SCC design was adopted considering the physical properties of both CC and RHA. The influence of partially substituting cement at 20 vol-% with binary and ternary blends of CC and RHA were investigated. The fresh properties of SCC were investigated using a variety of tests. The time dependent workability was monitored by plunger method and flow resistance determined based on the rheological measurements of SCC. The evolution of the hydrate phases of the binder in SCC was determined by thermogravimetric analysis, while the durability was evaluated by rapid chloride migration test. Cement partial replacement with 20 vol-% CC has no significant effect on SCC fresh, time dependent, compressive strength and durability properties. 20 vol-% RHA on the other hand requires higher dosage of SP to achieve self-compactability and increased the viscosity of SCC. Its workability retention is only up to 30 min after mixing and exhibited higher flow resistance. It consumes more CH and improves compressive strength and chloride resistance of SCC. The ternary blending with CC and RHA yielded better fresh SCC properties compared to the binary blend with RHA, while an improved chloride penetration resistance could be achieved compared to binary CC blend.

River valley bottoms have hydrological, geomorphological, and ecological importance and are buffers for protecting the river from upland nutrient loading coming from agriculture and other sources. They are relatively flat, low-lying areas of the terrain that are adjacent to the river and bound by increasing slopes at the transition to the uplands. These areas have under natural conditions, a groundwater table close to the soil surface. The objective of this paper is to present a stepwise GIS approach for the delineation of river valley bottom within drainage basins and use it to perform a national delineation. We developed a tool that applies a concept called cost distance accumulation with spatial data inputs consisting a river network and slope derived from a digital elevation model. We then used wetlands adjacent to rivers as a guide finding the river valley bottom boundary from the cost distance accumulation. We present results from our tool for the whole country of Denmark carrying out a validation within three selected areas. The results reveal that the tool visually performs well and delineates both confined and unconfined river valleys within the same drainage basin. We use the most common forms of wetlands (meadow and marsh) in Denmark's river valleys known as Groundwater Dependent Ecosystems (GDE) to validate our river valley bottom delineated areas. Our delineation picks about half to two-thirds of these GDE. However, we expected this since farmers have reclaimed Denmark's low-lying areas during the last 200 years before the first map of GDE was created. Our tool can be used as a management tool, since it can delineate an area that has been the focus of management actions to protect waterways from upland nutrient pollution.

This paper focuses on the so-called proportional intensity-based software reliability models (PI-SRMs), which are extensions of the common non homogeneous Poisson process (NHPP)-based SRMs, and describe the probabilistic behavior of software fault-detection process by incorporating the time-dependent software metrics data observed in the development process. Especially we generalize the seminal PI-SRM in Rinsaka, Shibata and Dohi (2006) by introducing eleven well-known fault-detection time distributions, and investigate their goodness-of-fit and predictive performances. In numerical illustrations with four data sets collected in real software development projects, we utilize the maximum likelihood estimation to estimate model parameters with three time-dependent covariates; test execution time, failure identification work and computer time-failure identification, and examine the performances of our PI SRMs in comparison with the existing NHPP-based SRMs without covariates. It is shown that our PI-STMs could give better goodness-of-fit and predictive performances in many cases.

The significance of Kashmir conflict as one of the world’s longest running conflicts has frequently drawn the attention of both communication and international relations’ scholars which makes it an important issue from the perspective of interdisciplinary approach. The researchers have attempted to assemble a brief history of the Indian held Jammu and Kashmir Conflict from the time of partition in 1947 to the developments which took place till 2019 in the light of the available literature. The paper provides substantial historical context of the important events like instrument of accession, UN resolutions on Kashmir conflict, Simla Accord, Gawkadal Massacre , Lahore Declaration, Kargil War, killing of Burhan Wani, Uri attack and Article 370’s abrogation .

Drought stress imposes substantial constraints on the growth and production of wheat (Triticum aestivum L.), a globally important cereal crop that is essential for food security. To mitigate these adverse effects, researchers are intensifying their efforts to comprehend how different genotypes respond to drought stress, aiding in the development of sustainable breeding and management strategies. This review summarized past and recent research on genotype-dependent responses of wheat to drought stress, encompassing morphological, physiological, biochemical, molecular, genetic, and epigenetic reactions in plants. Screening of drought-affected features at early developmental stages can provide valuable insights into the adult growth stages that are closely linked to plant productivity. The review underscores the importance of identifying key traits associated with drought resistance, and the potential of leveraging wheat diversity to select cultivars with desirable agronomic characteristics. It also highlights recent advancements in investigating Bulgarian wheat genotypes with varying levels of drought tolerance, specifically in detecting essential features contributing to drought tolerance. Cultivating drought-resistant wheat genotypes and understanding stress stability determinants could markedly contribute to enhancing wheat production and ensuring stable yields under changing climate conditions.

With reference to our recently proposed Planck Scale White Hole Cosmology (PS-WHC) or Flat Space Cosmology (PS-FSC), we make an attempt to quantify galactic dark matter and flat rotation speeds in terms of galactic visible matter and cosmic mass. Considering recently observed dwarf galaxies having very little dark matter and assuming a time dependent reference mass unit of $M_X\cong \left(\mbox{3.0 to 4.0}\right)\times 10^{38}$ kg, we suggest an empirical relation for galactic dark matter $M_d$ via galactic visible mass $M_v$ as,$M_d \cong \frac{M_v^{3/2}}{M_X^{1/2}}$. This relation helps in fitting flat rotation speeds starting from 8 km/sec (for Segue 2) to 500 km/sec (for UGC12591). Modifying MOND's galactic flat rotation speed relation with Hubble mass $M_0\cong \left(\frac{c^3}{2GH_0}\right)$ of the universe, ratio of galactic flat rotation speed $V_G$ to speed of light $c$ can be shown to be approximately $\frac{V_G}{c} \cong 0.5 \left(\frac{M_v}{M_0}\right)^{1/4}$. Considering the sum of galactic dark matter and visible matter, ratio of galactic flat rotation speed to speed of light can be shown to be approximately $\frac{V_G}{c}\cong 0.25 \left(\frac{M_v+M_d}{M_0}\right)^{1/4}$. With further study, dark matter's nature, effect and distribution can be understood in terms of visible matter's extended gravity and extended theories of gravity can be understood with 'distance cosmic mass' rather than the empirical 'minimum acceleration'.

Oxygen extraction fraction (OEF), the fraction of oxygen that tissue extracts from blood, is an es-sential biomarker for directly assessing tissue viability and function in neurologic disorders. For quantitative mapping of OEF, an integrative model of quantitative susceptibility mapping and quantitative blood oxygen level-dependent magnitude (QSM+qBOLD or QQ) was recently pro-posed. However, QQ assumes Gaussian noise in both susceptibility and multi-echo gradient echo (mGRE) magnitude signals for OEF estimation. This assumption is unreliable in low sig-nal-to-noise ratio (SNR) regions like disease-related lesions, risking inaccurate OEF estimation and potentially impacting clinical decisions. Addressing this, our study presents a novel multi-echo complex QQ (mcQQ) that models realistic noise in mGRE complex signals. The proposed mcQQ was implemented using a deep learning framework (mcQQ-NET) and compared with the existing deep learning-based QQ (QQ-NET) in simulations, ischemic stroke patients, and healthy subjects. Both mcQQ-NET and QQ-NET used identical training and testing datasets and schemes for a fair comparison. In simulations, mcQQ-NET provided more accurate OEF than QQ-NET. In the sub-acute stroke patients, mcQQ-NET showed a lower average OEF ratio in lesions relative to unaf-fected contralateral normal tissue than QQ-NET. In the healthy subjects, mcQQ-NET provided uniform OEF maps, similar to QQ-NET, but without unrealistically high OEF outliers in areas of low SNR. Therefore, mcQQ-NET improves OEF accuracy by better reflecting realistic data noise characteristics.

Metallo-β-lactamases (MBLs) are a group of Zn(II)-dependent enzymes that pose a major threat to global health. They are linked to an increasing number of multi-drug resistant bacterial pathogens, but no clinically useful inhibitor is yet available. Since β-lactam antibiotics, which are inactivated by MBLs, constitute ~65% of all antibiotics used to treat infections, the search for clinically relevant MBL inhibitors is urgent. Here, derivatives of a 2-amino-1-benzyl-4,5-diphenyl-1H-pyrrole-3-carbonitrile (1a) were synthesised and their inhibitory effects assessed against representatives of each of the three subgroups of MBLs (B1, B2, B3). Several compounds are potent inhibitors of each MBL tested, making them excellent candidates for the development of broad-spectrum drug leads. In particular, compound 5f is highly potent across the MBL subfamilies, with Ki values in the low µM range. Furthermore, this compound also dis-plays synergy in combination with antibiotics such as penicillin G, cefuroxime or meropenem. This molecule thus represents one of the most promising compounds developed yet to combat MBLs.

Clofazimine and Arbidol have both been reported to be effective in vitro SARS-CoV-2 fusion inhibitors. Both are promising drugs repurposed for treatment of COVID-19 and have been used in several previous and ongoing clinical trials. Small-molecule binding to expressed constructs of the trimeric S2 segment of Spike and the full-length SARS-CoV-2 spike protein were measured using a Surface Plasmon Resonance (SPR) binding assay. We demonstrate that Clofazimine, Toremifene, Arbidol and other Arbidol derivatives bind to the S2 segment of the Spike protein. Clofazimine provided the most reliable and highest quality SPR binding data to S2 over the conditions explored. A molecular docking approach was used to identify the most favorable binding sites on the S2 segment in the prefusion conformation, highlighting two possible small-molecule binding sites for fusion inhibitors. Results from molecular docking and modeling the structure-activity-relationship (SAR) of a newly reported series of Clofazimine derivatives supports the proposed Clofazimine binding site on the S2 segment. When the proposed Clofazimine binding site is superimposed with other experimentally determined coronavirus structures in structure-sequence alignments, the changes in sequence and structure may rationalize the broad-spectrum antiviral activity of Clofazimine in closely related coronavirus such as (SARS-CoV, MERS, hCoV-229E, hCoV-OC43).

In this study, we investigated, for the first time, the effects of the spatially varying effective mass, asymmetry parameter, and well width on the electronic and optical properties of the quantum well which has an improved Rosen-Morse potential. Calculations are made within the framework of the effective mass and parabolic band approximations. We have used the diagonalization method by choosing a wave function based on the trigonometric orthonormal functions to find eigenvalues and eigenfunctions of the electron confined within the improved Rosen-Morse potential. Our results show that the position-dependence mass, asymmetry, and confinement parameters cause significant changes in the electronic and optical properties of the structure we focus on since these effects create a significant increase in electron energies and a blue shift in the absorption spectrum. The increase in energy levels enables the development of optoelectronic devices that can operate at wider wavelengths and absorb higher energy photons. This offers potential advancements in fields such as optical communication, imaging technology, and solar cells.

Before the emergence of SARS-CoV-1, MERS-CoV, and most recently SARS-CoV-2, al-ready four other coronaviruses have been circulating in the human population. The alpha coronaviruses NL63 and 229E and the beta coronaviruses OC34 and HKU1. These circulating coronaviruses all cause mild respiratory illness during the winter seasons and most people are already infected in early life. Could antibodies and/or T cells, es-pecially against the beta coronaviruses have offered some form of protection against SARS-CoV-2? Related is the question whether survivors of SARS-CoV-1 or MERS-CoV would be relatively protected against SARS-CoV-2. More importantly, would humoral and cellular immunological memory, generated during the SARS-CoV-2 pandemic, ei-ther by infection or vaccination offer protection against future coronaviruses? Or rather than protection, could antibody dependent enhancement have taken place, a mecha-nism by which circulating corona antibodies enhance the severity of COVID-19? An-other related phenomenon, the original antigen sin, would also predict that the effec-tivity of the immune response to future coronaviruses would be impaired because of reactivation of memory against irrelevant epitopes. Current available evidence indicates that latter scenarios are highly unlikely and that especially cytotoxic memory T cells directed against conserved epitopes of human coronaviruses could at least offer partial protection against future coronaviruses.

Glioblastoma multiforme (GBM) is one of the deadliest cancers. Temozolomide (TMZ) is the most common chemotherapy used for GBM patients. Recently, combination chemotherapy strategies have more effective antitumor effects and focus on slowing down the development of chemotherapy resistance. A combination of TMZ and cholesterol lowering medications (statins) is currently under investigation in in vivo and clinical trials. In our current investigation, we have used a triple combination therapy of TMZ, Simvastatin (Simva), and Acetylshikonin (ASH) and investigated its apoptotic mechanism in GBM cell lines (U87 and U251). We used viability, apoptosis, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), caspase-3/-7, acridine orange (AO) and immunoblotting autophagy assays. Our results showed that TMZ/Simva/ASH combination therapy significantly induced more apoptosis compared to TMZ, Simva, ASH, and TMZ/Simva treatments in GBM cells. Apoptosis via TMZ/Simva/ASH treatment induced mitochondrial damage (increase of ROS, decrease of MMP) and induced caspase-3/7 activation in both GBM cell lines. Compared to all single treatments and the TMZ/Simva treatment, TMZ/Simva/ASH significantly increased positive acidic vacuole organelles. We further confirmed that the increase of AVOs during the TMZ/Simva/ASH treatment was due to partial inhibition of autophagy flux (accumulation of LC3β-II and decrease in p62 degradation) in GBM cells. Our investigation also showed that TMZ/Simva/ASH-induced cell death was depended on autophagy flux as further inhibition of autophagy flux increased TMZ/Simva/ASH-induced cell death in GBM cells. Finally, our results showed that TMZ/Simva/ASH treatment potentially depends on an increase of Bax expression in GBM cells. Our current investigation might open new avenues for more effective treatment of GBM but further investigations are required for better identification of the mechanisms.

Steel construction is used more often these days as an alternative to the R.C.C. when light weight, high strength, large-span structures with a faster erection are required. Extensive studies have been done by researchers to study the seismic performance of reinforced concrete and steel structures, both in terms of elastic and inelastic behavior. Composite construction is also a recent advancement in the building industry with similar advantages. However, no emphasis has been given to the comparison between the inelastic behavior of steel and composite structures when subjected to lateral loads. This study compares the inelastic behavior of steel and a composite frame designed to have the same plastic moment capacity for structural members. The responses, such as the formation of hinges, story drifts, story displacements, lateral stiffness, ductility, maximum strength, energy dissipated, joint accelerations, and performance points, are compared with the aid of the building analysis and design software ETABS-18. For this, response spectrum analysis, pushover analysis and nonlinear direct integration time history analysis have been performed on both frames. For design and analysis, international codes such as IS 800-2007, IS 875 (Part I, II, IV), IS 1893-2002, AISC 360 (16 &amp; 10) and FEMA 440 have been used. Part of this study also aims at comparing the response of these frames when subjected to near field and far field earthquakes. It can be concluded from the results that the post yield performance of the composite frame is superior to that of the steel frame when seismically excited.

Background: Dengue is the most common arthropod-borne sickness worldwide, impacting at least 50 million people each year. The dengue virus has four primary serotypes. Infection with one serotype confers homotypic immunity but not heterologous immunity, and secondary infections may be more severe. Although blood transfusions and organ donations have also been observed, the Aedes aegypti mosquito is the primary vector for the transmission of dengue. Infection causes a continuum of clinical illness, from asymptomatic infection to dengue fever, DHF, and dengue shock syndrome (DSS).Aim: To assess the presence of anti DENV IgG and anti DENV IgM antibodies specific to the four dengue serotypes in blood donor service donors and the importance of pre-donation screening in routine blood collection procedures.Method: 3 mL of peripheral venous blood from 507 blood donors was collected in tubes with BD vacutainer gel tube for serum separation after epidemiological records were reviewed. After that, serum was separated and tests were performed by SD Bioline Dengue Duo. Participants in the study completed a social and epidemiological questionnaire that contained information such as age, gender, and dengue diagnosis.Result: Out of the 507 blood samples that were taken, 473 (93.3%) came from male blood donors, while the remaining 34 (6.7%) belonged to female blood donors. The ratio of males to females is 13.91 to 1. The age range is 18–60 years, and the mean and standard deviation are both 27.7 and 6.5. 183 of the 507 samples produced anti DENV IgG positivity, while 324 did not. The ratio of positive to negative was 1.25:2.Conclusion: According to the findings of this study, quantitative methods for determining the presence of anti-dengue antibodies or detecting the dengue virus in blood donors in endemic areas should be devised in order to ensure the quality of blood transfusions.

This paper aims to establish a current relationship between pharmaceutical sciences and the development of perfumes and fragrances, which bring significant economic benefits and whose added value is among other professionals, the one made by professionals in Pharmacy. For this purpose, historical data are used as a starting point and galenic, chemical and botanical aspects are discussed in a transversal way. In this sense, it must be taken into account that in the case of Spanish pharmacy, it is closely linked to the knowledge and use of plants. Sources such as Web of Science (WOS) and databases such as Scopus, monographs and various web pages (where scientific-technical documents appear) have been used. The results and discussion are based on the selection of the 50 plant species most commonly used in high quality fragrances. Therefore, this publication should be considered as an approach to this subject based on an analysis of a representative sample of data. Some characteristics of perfumes (classification according to the concentration of essential oils and combination of plant extracts) are presented beforehand. They also briefly compile the traditional and modern ways in the treatment of these extracts. The main focus of this work is the botanical and chemical analysis of these described plants, pointing out their common name, correct botanical name, geographical place of origin, used part of the plant and main molecules. The 50 botanical species belong to 27 families of angiosperms and are represented in a large part of the phylogenetic tree of botanical systematics. The most significant families are aromatic: Rutaceae (16.7%), Lamiaceae (16.7%) and Apiaceae (6.5%). The most represented genus is Citrus (with seven species or hybrids). However, it should be noted that natural extracts of good quality natural fragrances may be supplemented with chemically synthesized molecules. Of the 50 botanical species selected, 84% of the extracts have their origin in Tropical Asia, the Middle East and the Mediterranean region. This figure generally coincides with the percentage of medicinal plants (or their extracts) admitted by the European Pharmacopoeia. All parts of a plant (depending on which one it is) can be a source of molecules for the elaboration of these products. The most commonly used parts to obtain extracts are flowers (34%) and leaves (30%), a biological circumstance that is explained in this work. On the opposite side are the resins (10%), rhizomes and roots (8%). In this work, 110 molecules have been found that are part of the essences of perfumes and fragrances, the most frequent are: linalool, limonene, 1,8-cineole, eugenol and derivatives, geraniol, vanillin and derivatives, β-cariophyllene, p-cmene and farnesene and derivatives (3.64%). However, in order to elaborate a quality perfume, many other molecules must be taken into account, according to the creative experience of the perfumer, which is subject to confidentiality and chemical analysis according to current legislation, which would avoid fraud, allergy and dermatitis problems.

The dynamic response of a Bell-and-Bloom magnetometer to a parallel (to the bias field) time-dependent field is modelled beyond the commonly assumed quasi-static regime. The results unveil features that are related to the parametric nature of the considered system. It is shown that a for low-amplitude time-dependent field different operating conditions are possible and that, beside the commonly reported low-pass-filter behaviour, a band-pass response emerges. Moreover, we numerically show that for larger field amplitude the system, due to its parametric nature, has a kind of ``non-linear'' response.

Typhulaceae Jülich is one of the cold-adapted fungal families in basidiomycetes. Typhula (Pers.) Fr. and Pistillaria Fr. representing the family are distinguished from the morphology of a stipe to a hymenium (Fries 1821). The hymenium of Typhula is distinguishable from the stipe, but indistinguishable and consecutive in the genus Pistillaria. This taxonomic criterion is ambiguous, and consequently the opinion of Karsten (1882) has been widely accepted; I the genus Typhula, basidiomata develop from sclerotia, while basidiomata develop directly from substrata in the genus Pistillaris. But, Corner (1970) observed basidiomata of Pistillaria petasitis S. Imai in Hokkaido, Japan, from sclerotia. We collected irregular sclerotia of Typhula hyperborea H. Ekstr. from Upernavik, West Greenland. This specimen had a stipe-like structure on a Poaceae plant, and sclerotia developed on its tip. In August, P. petasitis in Hokkaido, Japan, formed basidiomata directly from substrates on the ground. Similar phenomena were found from other Typhula spp. in Japan. All of these fungi had the potential to produce sclerotia in culture, and as well as the capacity of mycelial growth at ambient air temperatures in each locality when samples were collected. These findings suggest that Typhula spp. developed basidiomata not only from the sclerotia dispersed by the basidiospores but also mycelia generated by the spore germination formed basidiomata multiple times depending on their growth environments.

Aymaraism, as a socio-cultural phenomenon, has given rise to components and elements of representativeness in the population of the Andes. However, the dialectic component of the Aymara as a nation is annulled by fundamental historiographical elements that underlie this process of identification. The empirical analysis of the historical data leads us to conclude that the Aymara language and culture contain ambiguous elements that cannot be defined according to the dialectical interpretation and the current narrative. Thus, the analysis of the cultural, linguistic and social elements of this population from the Early Horizon period to the present confirms the historical distortion towards a narrative component of origin and presence in the territory of the Qullasuyu, in the current geographical area of the Collao. In order to understand this phenomenon, this work promotes the complementarity of the analysis through the use of ethnoarchaeological and documentary elements in order to clarify the origin, synthesis and development of the Aymara from a historical perspective, leaving aside the dialectical component of the present.

Architectural Education (AE), as a multidisciplinary field of knowledge, has been through various learning forms, and several learning theories have been adapted to respond to progressive change in the learning environment context and increasing demand for a sustainable built environment. However, it is noticeable that there needs to be more research collaboration efforts among architecture schools and more focus on practice sessions in AE. Therefore, this systematic literature review intends to synthesize the most dominant challenges and examine trends in AE during the early decades of the twenty-first century. This study used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) as the review protocol. The keywords have been identified and searched in Scopus and Web of Science (WoS) databases. The authors analyzed ninety-six articles between 2000 and 2023 based on the inclusion and exclusion criteria. The analysis of the relevant articles provided valuable insights into research intention. The review reveals the four main themes in AE, namely (1) learning approaches, (2)technology innovation, (3) sustainability, and (4) history. Furthermore, the researchers discuss experiential learning, blended learning, e-learning, and online learning as the most used learning methods in architecture schools. More research on art, social context, and the physical built environment seems crucial for enhancing AE. This study comprehensively reviews the state of the art on AE by interpreting the most dominant architectural issues and learning challenges. The outcome is valuable for improving the learning environment in architecture schools.

Natural gas hydrate has gained significant attention in recent years. To safely and sustainably exploit the natural gas from gas hydrate-bearing sediments, it is crucial to understand the long-term mechanical characteristics of the hydrate reservoir. In this study, the influence of hydrate and fine particles on the strain rate dependence of hydrate-bearing sediments under plane strain conditions has been studied. The experimental results show that the strain rate dependency of the mechanical properties of hydrate-bearing sediments is positively correlated with hydrate saturation instead of the morphology of hydrate in sediments. The residual strength of hydrate-bearing sediments is primarily controlled by the hydrate saturation and is independent of the strain rate. Changes in hydrate saturation, and fines content, can affect the relationship between the strain rate and shear band angle. Finally, the local volumetric expansion effect of hydrate-bearing sediments without fines content is more significant and shows a strong strain rate dependence characteristic. Overall, this study provides valuable insights into the long-term mechanical characteristics of hydrate reservoirs. These insights can contribute to the development of a constitutive model of hydrate-bearing sediments with time-dependence in the future, and which is meaningful to the exploitation of natural gas hydrate.

Historical and Endowment Properties are different from Heritage and cultural Properties, as Historical and Endowment properties are governed by a unique set of laws that Waqf recipients must abide by. Property that is entrusted is usually in the form of buildings, land or valuables which in preservation is not limited to time as long as the property can be utilized. Reliable information technology is needed to ensure data security both digitally and physically, while the rapid development of information technology demands information openness and this will be a challenge in itself. The objectives of this study include examining the collection of historical databases and endowments, the relationship between digital data and physical data and management organizations. The method of how to design a query model to display data is then analyzed whether the data conforms to the rules in waqf management. The results are expected to bring up accurate data between digital data and physical data and if there are differences into findings for the next analysis.

Fish tissue samples from 203 adult individuals were collected in the main ports and markets of the Pacific coast of Panama. Molecular identification based on cytochrome oxidase I gene segment of all species was verified GENBANK reference sequences. 34 species from 14 families (Ariidae, Lutjanidae, Caranjidae, Scianidae, Centropomidae, Serranidae, Scombridae, Sphyraenidae, Haemulidae, Gerreidae, Stromotidae, Lobotidae, Malacanthidae, Mugilidae) were identified at species molecular level from 164 sequences. Also, three Caribbean species were molecularly identified among the analyzed samples (Mycteroperca xenarcha, Paralonchurus brasilensis and Lobotes surinamensis). Species diversity was slightly higher in the Gulf of Panama than in the Gulf of Chiriquí. For species with 5 or more individual sequences, genetic diversity and genetic connectivity parameters such as: total number of haplotypes (H), haplotype diversity (Hd), and nucleotide diversity (π) were calculated. Overall, pelagic-migratory species showed higher values of genetic diversity than coastal and estuarine species with some exceptions. Connectivity between Gulf areas was compared using values of genetic distances and genetic differentiation (Fst). High level of connectivity observed between Gulf of Chiriqui and Gulf of Montijo indicates the existence of a single stock in that area for the following species: Scomberomorus sierra, Caranx caninus and Lutjanus guttatus. Demographic history of the most common species was examined using Tajima’s D values suggesting population expansion for two snapper species, L. peru and L. argentiventris, having significant and higher values. Another important contribution from this research was the production of primers and dual labeled probes for environmental DNA detection using qPCR for the five most abundant species (spotted rose snapper, yellow snapper, green jack, Pacific crevalle jack and the Pacific sierra fish). These markers represent a new set of tools for environmental DNA (eDNA) detection and molecular traceability of three commercially important fish species along the supply chain including landing sites and markets of the main fishery areas.

To further understand the role of phosphorylation in ISGF3- and STAT2/IRF9-mediated constitutive and long-term IFN-I-stimulated transcriptional responses, we performed RNA-Seq and ChIP-Seq, in combination with phosphorylation inhibition and anti-viral experiments. First, we identified a group of ISRE-containing ISGs that were commonly regulated in IFNα treated WT and STAT1-KO cells. Thus, in 2fTGH and Huh7.5 WT cells IFNα-inducible transcription and anti-viral activity relied on the recruitment of the ISGF3 components STAT1, STAT2 and IRF9 in a phosphorylation- and time-dependent manner. Likewise, in ST2-U3C and Huh-STAT1KO cells lacking STAT1, ISG expression correlated with DNA-binding of phosphorylated STAT2/IRF9. This pointed to a dominant role of classical ISGF3 and STAT2/IRF9, and not U-ISGF3 or U-STAT2/IRF9, in the regulation of early and prolonged ISG expression and viral protection, in WT and STAT1-KO cells. In addition, comparative experiments in U3C (STAT1-KO) cells overexpressing all ISGF3 components (ST1-ST2-IRF9-U3C), revealed a threshold-dependent role of U-ISFG3, and potentially U-STAT2/IRF9, in the regulation of constitutive and possibly long-term IFNα-treated ISG expression and anti-viral activity.

Chromium poisoning strongly influences the performance of solid oxide fuel cell (SOFC) stacks. A three-dimensional, time-dependent, computational fluid dynamics model of a single channel of a F10 SOFC stack in Forschungszentrum Jülich GmbH is developed to investigate chromium poisoning for different stack designs, temperatures and absolute air humidities. The model takes into account both chemical and electrochemical mechanisms of chromium poisoning and is able to predict the spatial distribution of SrCrO4 and Cr2O3. The voltage degradation over 100 kh can be simulated quantitatively. According to the simulation results, chromium poisoning is almost eliminated by the application of the protective coating fabricated by the atmospheric plasma-spraying (APS) technology. Besides, with the help of the APS protective coating, operating a SOFC stack with less dehumidified air at 650 oC is possible according to the simulation.

Chronoamperometric curves of the oxidation of a ferrocenyl derivative by the potential step showed diffusion controlled-like currents less than the Cottrell's equation at a platinum wire electrode. The lower deviation cannot be explained by the Butler-Volmer heterogeneous kinetics, but was ascribed to the negatively capacitive current associated with the redox reaction. The deviation at the fully oxidized potential corresponds to the non-zero concentration at the electrode surface, which cannot be predicted from the Nernst equation. The Nernst equation expresses the relationship of the potential with the activity at the electrode surface rather than the concentration. The diffusion equation provides the relation of the current with the surface concentration rather than the activity. The negative capacitance or the non-zero concentration may arise from structure formation on the electrode owing to the dipole-dipole interaction, which is similar to the generation of the double layer capacitance including frequency dispersion. On this concept, we derive here expressions for the lowered diffusion-controlled current and the time-dependent surface concentration. The negatively capacitive current shows the time-dependence of t-0.9, which is similar to the decay of the double layer capacitive currents. The surface concentration decays with the t-0.4-dependence.

Many studies on magnetorheological fluid (MRF) have been carried out over last three decades several salient advantages such as fast phase change, easy control of the yield stress and so forth. Especially, several review articles of MRF technology have been reported for last two decades summarizing the development of MRFs and their applications. As specific examples, the review articles including the optimization of the particles and carrier liquid to achieve minimum off-state viscosity and maximum yield stress at on-state, the formulation of many constitutive models in-cluding Casson model and Herschel-Bulkley (H-B) model, the sedimentation enhancement using additives and nanosized particles, many types of dampers for automotive suspension and civil structures, medical and rehabilitation devices, MRF polishing technology, the methods of mag-netic circuit design, and the synthesis of various controllers have been published. More recently, the effect of the temperature and thermal conductivity on the properties of MRFs and application systems are actively being investigated by several works. However, there is no review article on this issue so far despite of that the thermal problem is one of crucial factors to be seriously con-sidered for the development of advanced MRFs and commercial products of application systems. In this work, studies on the thermal conductivity and temperature in MRFs themselves and tem-perature-dependent application systems are reviewed, respectively, and principal results are summarized emphasizing on the followings: how to reduce the temperature effect on the field-dependent properties of MRFs and how to design application system to minimize the thermal effect. It is noted here that the review summary is organized in a chronological format using tables.

The focus of the current research indicates a new Bianchi type-V anisotropic, homogeneous astrophysical model with modified theory of f(R, T) gravity and Λ(t), time-dependent cosmological constant. The significant effect of the model is that the field equations solutions find using a time-dependent quadratic deceleration parameter. We observed anisotropy parameter remains constant both in the belated universe and early universe. The deportment of the equation of state (EOS) parameter, pressure, and energy density, cosmological constant and other parameters are also discussed. This cosmological model indicated the possibility of an accelerating universe with negative pressure, such as a universe dominated by dark energy. Om(z) diagnostic test suggested that the universe starts with quintessence nature and ends as a phantom model. Also, energy conditions of this model are represented here to ensure the model is physically reasonable and based on observations.

a Special Issue of Microorganisms devoted to ‘Microbial Biocatalysis and Biodegradation’ would be incomplete without some form of acknowledgement of the many important roles that dioxygen-dependent enzymes (principally mono- and dioxygenases) play in relevant aspects of biooxygenation. This is reflected by the multiple strategic roles that dioxygen -dependent microbial enzymes play both in generating valuable synthons for chemoenzymatic synthesis, and in facilitating key reactions that drive the global geochemical Carbon Cycle. A useful insight into this relationship can be gained by reviewing the evolution of the current status of 2,5-diketocamphane 1,2-monooxygenase (EC 1.14.14.108) from camphor-grown Pseudomonas putida ATCC 17453. Over the last sixty years, the perceived nature of this monooxygenase has transmogrified significantly. Commencing in the 1960s, extensive initial studies consistently reported that the enzyme was a monomeric true flavoprotein dependent on both FMNH₂ and nonheme iron as bound cofactors. However, over the last decade all those criteria have changed absolutely, and the enzyme is currently acknowledged to be a metal ion-independent homodimeric flavin-dependent two-component monooxygenase deploying FMNH₂ as a cosubstrate. That transition is a paradigm of the ever evolving nature of scientific knowledge.

From the first isolation of the cystovirus bacteriophage Φ6 from Pseudomonas syringae 50 years ago, we have progressed to a better understanding of the structure and transformations of the many parts of the virion. The three-layered virion encapsulating the tripartite double stranded RNA (dsRNA) genome, breaches the cell envelope on infection, generates its own transcripts, and coopts the bacterial machinery to produce its proteins. The generation of new virions starts with a procapsid with a contracted shape, followed by packaging single stranded RNA segments with concurrent expansion of the capsid, and finally replication to reconstitute the dsRNA genome. The outer two layers are then added, and the fully formed virions released by cell lysis. Most of the procapsid structure composed of the proteins P1, P2, P4 and P7 is now known, as well as its transformations to the mature, packaged nucleocapsid. The outer two layers are less well studied. One additional study investigated the binding of the host protein YajQ to the infecting nucleocapsid, where it enhances the transcription of the large RNA segment that codes for the capsid proteins. Finally, we relate the structural aspects of bacteriophage Φ6 top those of other dsRNA viruses, noting the similarities and differences.

The selection equation (replicator equation) has been independently discovered not only in various fields of biology (population genetics, ecology, prebiotic evolution, and sociobiology), but also in laser theory, where it accounts for the emergence of coherent light. Selection theory (replicator dynamics) is an ensemble theory, i. e., it describes the entire system rather than individual events, neglecting details in favor of a statistical view. However, the underlying processes at the individual level are well known in biology. For light quanta, this is not the case, because quantum theory says nothing about individual events. In the Copenhagen interpretation even the existence of causality on "quantum level" is denied. A large number of recent publications, however, makes this interpretation seem questionable.In the present paper, therefore, an attempt is made to describe the basic interactions between light and matter, as far as they are relevant for the emergence of coherent light in the laser (a photon pair interaction mediated by matter is postulated), and to apply replicator dynamics on this basis. Starting point are papers of A. Einstein about the interaction of light and matter as well as the photoelectric effect. Both theories are slightly modified. Furthermore, the double-slit experiment is investigated and finally the emergence of coherent light by density-dependent selection of photons of different phase in a laser-like model. The relationship between “mean fitness”, information content of the photon ensemble and the amplitude of the light is also analyzed.

The mathematical modelling of reverse logistics inventory systems ignores that returned items may arrive out of sequence, i.e. with different number of remanufacturing times. Moreover, such modelling assumes that the retuned items may retain the same quality upon recovery regardless of how many times they have been previously remanufactured. This paper develops a new mathematical expression of the percentage of retuned items that can be remanufactured a finite number of times. The proposed expression is modelled as a function of the expected number of times an item can be remanufactured on its life cycle and the number of times an item can be technologically (or optimally) remanufactured based on its quality upon recovery. The model developed in this paper considers joint production and remanufacturing options. The return rate is a varying demand dependent rate, which is a decision variable with demand, product deterioration, manufacturing and remanufacturing rates being arbitrary functions of time. The model considers the initial inventory of returned items in the mathematical formulation, which enables decision makers to adjust all functions and input parameters for subsequent cycles. Illustrative examples indicate that dependent purchasing price of recovery items and the incorporation of remanufacturing investment cost significantly impact on the optimal remanufacturing policy.

Due to the influence of bio-geographical and environmental factors, as well as anthropogenic landscape features, organism shows different reproductive strategies among different populations. There is lack of detailed information on the reproductive biology of Kentish plover Charadrius al-exandrinus in arid lands in Central Asia. In this study, we summarized the characteristics of the reproductive biology of three geographically distinct plover populations in Aibi Lake in the Northwestern Xinjiang, Taitema Lake in the Southern Xinjiang and artificial reservoirs around Urumqi City in Northern Xinjiang respectively, based on 440 eggs of 158 nests observed and ana-lyzed from April to July of 2019 and 2020. We find that there is no significant difference in clutch size among the three populations. However, the egg size of Taitema Lake population is signifi-cantly larger than those of the other two populations, whilst egg volume and clutch volume of ar-tificial reservoirs population are significantly larger than that of Aibi Lake. With the postpone-ment of laying date, the northern and northwestern populations respectively show the character-istics of small clutch size and relatively small egg size, and decrease of reproductive outputs. The heavier female plovers in Taitema Lake lays eggs earlier, and there was significantly positive cor-relation between the female body mass and the clutch size and egg size. The tarsometatarsus length of the female plovers was significantly positively correlated with the reproductive output in all three populations. The model selection results show that female body size and ambient tem-perature restrict the egg size and reproductive output of Kentish plovers, which is consistent with the upper limit hypothesis of the maternal condition and the maternal constraint. Our data sup-port that Kentish plover show distinct flexibility in breeding strategies to cope with the harsh nat-ural environment in arid lands of Xinjiang, China. The results of relatively high average clutch size and average egg size imply that saline wetlands in Western China are important breeding habitats for Kentish plover.

Since the beginning of the COVID-19 pandemic, extensive drug repurposing efforts sought to identify small molecule antivirals with various mechanisms of action. Here we aim to review research progress on small molecule viral entry and fusion inhibitors that directly bind to the SARS CoV-2 Spike protein. Early in the pandemic, numerous small molecules were identified in drug repurposing screens and reported to be effective in vitro SARS CoV-2 viral entry or fusion inhibitors. However, given minimal experimental information regarding the exact location of small molecule binding sites on Spike, it was unclear what the specific mechanism of action was, or where the exact binding sites were on Spike for some inhibitor candidates. The work of countless researchers has yielded great progress, with the identification of many viral entry inhibitors that target elements on the S1 receptor binding domain (RBD) or N-terminal domain (NTD) and disrupt S1 receptor binding function. In this review, we will also focus on highlighting fusion inhibitors that target inhibition of the S2 fusion function, either by disrupting the formation of the postfusion S2 conformation or alternatively by stabilizing structural elements of the prefusion S2 conformation to prevent conformational changes associated with S2 function. We highlight experimentally validated binding sites on the S1/S2 interface and on the S2 subunit. While most mutations to the Spike protein to date in variants of concern (VOCs) have been localized to the S1 subunit, the S2 subunit sequence is more conserved with only a few observed mutations in proximity to S2 binding sites. Several recent small molecules targeting S2 have been shown to have robust activity over numerous recent VOC mutant strains and/or greater broad spectrum antiviral activity for other more distantly related coronaviruses.

Thalassemia is a heterogeneous congenital hemoglobinopathy common in the Mediterranean region, Middle East, Indian subcontinent, and Southeast Asia with increasing incidence in Northern Europe and North America due to immigration. Iron overloading is one of the major long-term complications in patients with thalassemia and can lead to organ damage and carcin-ogenesis. Hepatocellular carcinoma (HCC) is one of the most common malignancies in both transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT). The incidence of HCC in patients with thalassemia has increased over time, as better chelation therapy confers a sufficiently long lifespan for the development of HCC. The mechanisms of iron overloading-associated HCC development include the increased　reactive oxygen species (ROS), inflammation cytokines, dysregulated hepcidin, and ferroportin metabolism. The treat-ment of HCC in patients with thalassemia was basically similar to those in general population. However, due to the younger age of HCC onset in thalassemia, regular surveillance for HCC development is mandatory in TDT and NTDT. Other supplemental therapy and experience of novel treatment for HCC in thalassemia population were also reviewed in this article.

The way humans use natural resources and especially freshwater, reflects their relationship with nature. It also influences the conceptual Water Resources Management (WRM) model. A historical review shows that the interplay between Humans and Nature is diachronically in constant change between two opposites: conflict and cooperation. Lessons from the past 20.000 years indicate that the WRM model is a function of two main parameters: (1) socio-economics, and (2) climate conditions. Three different Eras of the Humans-Nature relationship have been distinguished: (1) Naturalistic: Nature dominating Humans during the Last Glacial Period (100-10) kyr BC, (2) Dualistic: Nature-Humans cooperation and competition from 10 kyr BC to 1800 AD, and (3) Anthropocentric: Humans dominating Nature from 1800 AD to now. Since 2000, the Integrated WRM (IWRM) model is promoted as state-of-the-art and remains anthropocentric producing huge externalities. Its assessment during the last 20 years has given mixed results and needs to be reformulated. The new model we suggest is based on the dialectical tool for conflict resolution. It unifies Humans and Nature and enhances the social dimension of WRM. After identifying conflicts between stakeholders and the natural laws (eristic part), opposite objectives are unified to harmonize Humans with Nature (dialectical resolution). A case study of flood mitigation illustrates the eristic-dialectical methodology.

A monolayer of endothelial cells (ECs) lines the lumen of blood vessels and as such provides a semi-selective barrier between the blood and the interstitial space. Compromise of the lung EC barrier due to inflammatory or toxic events may results in pulmonary edema, which is a cardinal feature of acute lung injury (ALI) and its more severe form, the acute respiratory distress syndrome (ARDS). The EC functions are controlled, at least in part, via epigenetic mechanisms mediated by histone deacetylases (HDACs). Zinc-dependent HDACs represent the largest group of HDACs and are activated by Zn2+. Members of this HDAC group are involved in the epigenetic regulation primarily via modifying the structure of chromatin upon removal of acetyl groups from histones. In addition, they can deacetylate many non-histone histone proteins, including those located in extra nuclear compartments. Recently, the therapeutic potential of inhibiting zinc-dependent HDACs for EC barrier preservation has gained momentum. However, the role of specific HDAC subtypes in EC barrier regulation remains largely unknown. This review aims to provide an update on the role of zinc-dependent HDACs in endothelial dysfunction and its related diseases. We will broadly focus on biological contributions, signaling pathways and transcriptional roles of HDACs in endothelial pathobiology associated mainly with lung diseases and we will discuss the potential of their inhibitors for lung injury prevention.

Despite being a rare disease worldwide, rabies has the highest morbidity and mortality rates, with nearly all symptomatic cases leading to coma and death. Rabies represents an infectious disease caused by the Rabies virus (RABV), which is part of the Lyssavirus group and the Rhabdoviridae family, and it mainly spreads through the bite and scratch of an infected mammal, but particularly of wild animals, such as bats, foxes, wolves and racoons, and of domestic animals, such as dogs and cats, in rabies-prone areas of the world. Airborne transmission has been deemed as extremely rare, and no clinical case as such has been recorded worldwide yet, except in the enclosed environment, such as research laboratories and caves where infected bats are present. Domestic mammals, such as dogs and ferrets, represent other important reservoirs of disease transmission, and the human cases of Asia and Africa amount approximately 95% of all human cases worldwide. Infected animals most commonly start transmitting the virus once the first symptoms have occurred, and if they experience disease aggravation and death within 10 days, a case of rabies is registered, more easily if the incidence occurred in the urban area and then, any person or animal that had been potentially exposed are strongly recommended to receive the inoculation. It is rare for asymptomatic mammals to transmit the illness. Most First-World and several Second-World countries have recently been declared dog rabies-free by the World Health Organization. The disease can only be treated prophylactically, with three doses of a vaccine containing an inactivated form of RABV, or with five doses of the vaccine and two doses of anti-RABV immunoglobulins within 28 days if the patient is believed to have been exposed to the virus beforehand. It has been projected that, once the viral load reaches elements of the central nervous system, prophylactic approaches are no longer effective, even if symptoms have not begun yet, and this highlights the urgent trait of the medical condition, strongly recommending exposed people to receive the prophylactic doses immediately after the potential exposure to the virus. The pathogen first infects the bodily fluids, before reaching the peripheral nervous system, from where it will gradually move toward the spinal cord or the encephalon, at a speed of movement ranging from 1 to 40 cm per day. It was also found, in extremely rare circumstances, to infect the nasopharyngeal cavity and the lungs. The primary cause of a successful, gradual advance of the viral load toward the point of clinical no-return for the patient - the CNS - is a complex mechanism of induced innate immune evasion, with the interferon system being heavily targeted and silenced by RABV proteins. The ‘Milwaukee’ protocol is locally believed to decrease the mortality rate of the clinical illness to approximately 80%, although significantly more research is required in this sense. First-line immune evasion represents the central mechanism developed by viruses during their evolutionary process to gain control over human immunity, so it could be the development and adjustment of a counter-offensive to this evolutionary operating system that could address the core elements of the problem. Human recombinant Type I and Type III Interferons were found to be significant vaccine adjuvants and to considerably delay the clinical onset of the disease. Despite their central role in natural immunity-based prophylaxis, vaccine support and, in often cases, vaccination per se, a local administration of IFNs as such may not be enough to tackle the core problem of the endemic disease, and a specific and systemic treatment of potential host cells with IFN I and III, as well as IFN-stimulating proteins, may constitute a major research requirement in the coming years of disease investigation, as the inoculation efforts with the inactivated virus and immunoglobulin administration continue. The administration of a relatively low dosage of somatic Natural Killer cells, gamma-interferon and perhaps, of somatic helper CD4+ and somatic cytotoxic CD8+ T-lymphocytes treated with alpha-, beta- and lambda-interferon could be merged with the administration of a similar dosage of alpha-, beta- and lambda-interferon during the efforts to develop an effective and less costly prophylactic vaccine against rabies. A combination of a nasal substance containing a low dosage of IFN I and III with a reduced concentration of neutralized RABV copies, and/or with a low dose of anti-RABV IgA antibodies, could also be tested for humans for the purposes of pre- and post-exposure prophylaxis.

To resolve problems in the dietary life of university athletes, education is essential for enabling athletes to change their own dietary behavior. The purpose of this research, it was decided to verify the effectiveness of sports nutrition education based on self-determination theory (SDT). Methods, the subjects were thirty-six male university rowers. A stratified randomized comparison test was conducted by student year (SDT group and control group). Sports nutrition education was held three times, via an Internet conferencing system. Furthermore, group work over social media was used for the SDT group. Four evaluations were carried out based on anthropometric measurements, brief-type self-administered diet history questionnaire (BDHQ),sports nutrition knowledge (SNK), and treatment self-regulation questionnaire (TSRQ). Results, for the intra-group factor "Protein," a significant difference was evident in the self-determination theory group (50.0±28.5, 78.6±28.1, 81.0±21.5, p<0.000, units: %), and there were significant differences between after and before, and between three months after and before (p=0.002, p=0.002). For BDHQ, significant differences were evident for green/yellow vegetables, fruits, and dairy between after and before for the self-determination theory group (159.1±74.2-126.7±70.6, p=0.009, 306.0±196.2-195.2±146.1, p=0.020, 257.0±147.0-183.3±167.9, p=0.040, units: g). In conclusion, sports nutrition education based on SDT improved dietary knowledge and increased dietary intake.

E-commerce recommendation systems usually deal with massive customer sequential databases, such as historical purchase or click stream sequences. Recommendation systems’ accuracy can be improved if complex sequential patterns of user purchase behavior are learned by integrating sequential patterns of customer clicks and/or purchases into the user-item rating matrix input of collaborative filtering. This reviews focuses on algorithmic techniques of existing E-commerce recommendation systems that are sequential pattern based such as ChoRec05, ChenRec09, HuangRec09, LiuRec09, ChoiRec12, Hybrid Model RecSys16, Product RecSys16, SainiRec17, HPCRec18 and HSPCRec19. It provides a comprehensive and comparative performance analysis of these systems, exposing their methodologies, achievements, limitations, and potentials for solving more important problems in this domain. The review showed that integrating sequential pattern mining of historical purchase and/or click sequences into user-item matrix for collaborative filtering (i) improved recommendation accuracy (ii) reduced user-item rating data sparsity (iii) increased novelty rate of recommendations and (iv) improved scalability of the recommendation system.

Introduction: The first velvet worm (phylum Onychophora) was described nearly two centuries ago, by a British priest, in the tiny Caribbean island of Saint Vincent. He thought it was a new type of mollusk, a slug with tiny feet. Objective: Here I present a brief biographical account of the field of onychophorology, marking nearly two hundred years since the first scientific description of velvet worms. Method: I synthetize historical records, publications, personal experience and biographical sketches to construct an encompassing narrative of the field's development through the lives of researchers who have shaped it. Results: The narrative begins with Lansdown Guilding's initial discovery and extends to include pivotal figures like Jean Victor Audouin, Charles Émile Blanchard, Adolph Eduard Grube, Lorenzo Camerano, Eugène Louis Bouvier, Sidnie Milana Manton, Sylvia S. Campiglia, Roger Lavallard, Hilke Ruhberg, and Bernal Morera-Brenes. Contributions from Noel Tait, Robert Mesibov, Georg Mayer, Cristiano Sampaio, Ivo de Sena Oliveira, and José Pablo Barquero-González are also acknowledged. The article highlights their individual contributions to onychophorology, considering their scientific achievements and personal journeys, and presents portraits of nearly all of them. Conclusion: Our current knowledge of onychophorans is the results of hundreds of contributions from a large number of people who have lived varied, sometimes fascinating lives, but all united in their interest in velvet worms.

Background: Best Possible Medication History (BPMH) collected by clinical pharmacists is crucial for effective medication review but, in Italy, it is often left to the nursing staff. This study aims to compare the quality and accuracy of a clinical pharmacist-documented BPMH with the current standard practice of ward staff-collected BPMH at an Italian perioperative surgical setting. Methods: A 20-week prospective observational non-profit study was conducted in a major University hospital. The study comprised a feasibility, an observational, and an interventional phase. During the feasibility phase, 10 items for obtaining a correct BPMH were identified. The control group consisted of retrospectively analyzed BPMHs collected by the ward staff during the observational phase, while interventions included BPMHs collected by the clinical pharmacist during the third phase. Omissions between the two groups were compared. Results: 14 (2%) omissions were found in the intervention group, compared with 400 (57.4%) found in the controls (p<0.05); data collection was more complete when collected by pharmacists compared to the current modalities (98.0% versus 42.6%; p<0.05). Conclusions: The involvement of a pharmacist significantly reduced the number of omissions in perioperative surgical-collected BPMHs. This intervention holds the potential to decrease the risk of medication errors associated with inaccurate or incomplete BPMHs prior to surgical hospitalization.

The cyclin-dependent kinase (Cdk) 1–cyclin B (CycB) complex plays critical roles in cell cycle regulation. Before Drosophila male meiosis, CycB is exported from the nucleus to the cytoplasm via the nuclear porin 62kD (Nup62) subcomplex in the nuclear pore complex. When this is inhibited, Cdk1 is not activated, and meiosis does not initiate. We investigated the mechanism that controls cellular localization and activation of Cdk1. Cdk1–CycB continuously shuttled into and out of the nucleus in the prolonged G2 phase before meiosis. Overexpression of CycB, but not that with nuclear localization signal sequences, rescued reduced cytoplasmic CycB and inhibition of meiosis in Nup62-silenced cells. Full-scale Cdk1 activation occurred in the nucleus shortly after its rapid nuclear entry. Cdk1-dependent centrosome separation did not occur in Nup62-silenced cells, while Cdk1 interacted with Cdk-activating kinase and Twine/Cdc25C in the nucleus of Nup62-silenced cells, suggesting the involvement of another suppression mechanism. Silencing of roughex rescued Cdk1 inhibition and initiated meiosis. Nuclear exports of Cdk1 ensured its escape from inhibition by cyclin-dependent kinase inhibitor. The complex reentered the nucleus via importin β at the onset of meiosis. We propose a model regarding the dynamics and activation mechanism of Cdk1–CycB to initiate male meiosis.

A burgeoning body of scholarship identifies and discusses botanic gardens as increasingly important centres of biodiversity conservation and sustainability. Notwithstanding the high quality and richness of this literature, it encompasses relatively autonomous fields of expertise that are neither designed nor expected to promote cross-disciplinary, integrative, accounts of botanic gardens as institutions of conservation and sustainability. Bridging key aspects of the botanic garden literature, this article brings into conversation historical accounts with contemporary scholarship on the matter. In so doing, it unveils dilemmas and challenges faced by botanic gardens as they grapple with their historic legacies, but also renew their relevance in nurturing sustainable socio-environmental futures. The article proceeds by covering three focal points. First, it summarizes the scholarly literature on the history of botanic gardens. Second, it presents accounts of current scientific and biodiversity conservation endeavours as reflexive engagements with their historical legacies. Third, it addresses the recent emergence of socio-cultural missions at botanic gardens as a significant step beyond their historical focus on plants and plant ecosystems.

This article develops a multi-perspective view on motivations and methods for tobamovirus purification through the ages, and presents a novel efficient, easy-to-use approach that can be well-adapted to different species of native and functionalized virions. We survey the various driving forces prompting researchers to enrich tobamoviruses: from the search for the causative agents of mosaic diseases in plants to their increasing recognition as versatile nanocarriers in biomedical and engineering applications. Best practice and also rarely applied options for the serial processing steps required for successful isolation of tobamoviruses are then reviewed. Adaptations for distinct particle species, pitfalls and 'forgotten' or underrepresented technologies are considered as well. The article is topped off with our own development of a method for virion preparation, rooted in historical protocols. It combines selective re-solubilization of polyethylene glycol (PEG) virion raw precipitates with density step gradient centrifugation in biocompatible iodixanol formulations, yielding ready-to-use particle suspensions. This newly established protocol and some considerations for perhaps worthwile further developments could serve as putative stepping stones towards preparation procedures appropriate for routine practical uses of the multivalent soft-matter nanorods.

Thermally-assisted-occupation density functional theory (TAO-DFT) has been an efficient electronic structure method for studying the ground-state properties of large electronic systems with multi-reference character over the past few years. To explore the time-dependent (TD) properties of electronic systems (e.g., subject to an intense laser pulse), in this work, we propose a real-time (RT) extension of TAO-DFT, denoted as RT-TAO-DFT. Besides, we employ RT-TAO-DFT to study the high-order harmonic generation (HHG) spectra and related TD properties of molecular hydrogen H2 at the equilibrium and stretched geometries, aligned along the polarization of an intense linearly polarized laser pulse. The TD properties obtained with RT-TAO-DFT are compared with those obtained with the widely used time-dependent Kohn-Sham (TDKS) method. In addition, issues related to the possible spin-symmetry breaking effects in the TD properties are discussed.