The Asian world is home to a multitude of venomous and dangerous snakes, which are attributed to various medical effects used in the preparation of traditional snake tinctures and alcoholics, like the Japanese snake wine, named Habushu. The aim of this work was to perform the first quantitative proteomic analysis of the Protobothrops flavoviridis pit viper venom. Accordingly, the venom was analyzed by complimentary bottom-up and top-down mass spectrometry techniques. The mass spectrometry-based snake venomics approach revealed that more than half of the venom is composed of different phospholipases A2 (PLA2). The combination with an intact mass profiling led to the identification of the three main Habu PLA2s. Furthermore, nearly one-third of the total venom consists of snake venom metalloproteinases and disintegrins, and several minor represented toxins families were detected: CTL, CRISP, svSP, LAAO, PDE and 5’-nucleotidase. Finally, the venom of P. flavoviridis contains certain bradykinin-potentiating peptides and related peptides, like the svMP inhibitors pEKW, pEQW, pEEW and pENW. In preliminary MTT cytotoxicity assays the highest cancerous-cytotoxicity of the crude venom was measured against human neuroblastoma SH-SY5Y cells and shows in some fractions disintegrin-like effects.

In this review we extensively describe the main post-translational modifications that give rise to the multiple proteoforms characterized to date in the human salivary proteome and their potential role. Most of the data reported were obtained by our group in over twenty-five years of research carried out on human saliva mainly by applying a top-down strategy. At the beginning we describe the products generated by proteolytic cleavages, which can occur before and after secretion. In this section the most relevant families of salivary proteins are also described. Next, we report the current information concerning the human salivary phospho-proteome and the limited news available on sulfo-proteome. Three sections are dedicated to the description of the glycation and enzymatic glycosylation. Citrullination and N- and C- terminal PTMs and a miscellaneous of other modifications are described in the last two sections. Results highlighting the variation in the level of some proteoforms in local or systemic pathologies are also reviewed along the sections of manuscript to underline the impact and relevance of this information for the development of new diagnostic biomarkers useful in clinical practice.

Wildlife conservation is an important component of environmental sustainability and can be improved by reviewing the performance of its three major models – common pool, top-down regulatory, and private resource -- under varying environmental and socioeconomic conditions. Generally, the private resource model is the most sustainable because it provides the best incentives to balance the needs of humans and wildlife, to maintain general wildlife habitat, and to adapt quickly to changing environmental and/or socioeconomic conditions. Top-down or “command and control” regulation, however, can be employed as a model of last resort if the private resource model shows signs of failing to protect specific species from local extirpation or extinction, which it is most likely to do for migratory species, species with close commercial substitutes, and species with no direct commercial value. Top-down regulators may also be needed to enforce property rights arrangements like catch shares and to monitor resources that remain in the common pool in the event that socioeconomic or environmental conditions change sufficiently to trigger the tragedy of the commons.

Protein translational modifications (PTMs) generate an enormous, but as yet undetermined, expansion of the expressed proteoforms. In this Viewpoint, we firstly differentiate the concepts of proteoform and peptidoform by reviewing and discussing previous literature. We show that the current PTM biological investigation and annotation largely follow a PTM site-specific rather than proteoform-specific approach. We further illustrate a potentially useful matching strategy in which a particular “modified peptidoform” is matched to the corresponding “unmodified peptidoform” as a reference for the quantitative analysis between samples and conditions. We suggest this strategy could provide directly relevant information for learning the PTM site-specific biological functions. Accordingly, we advocate for the wider use of the nomenclature “peptidoform” in the future bottom-up proteomic studies.

Recent progress in the fabricating flexible electronics has been developed significantly due to the increased interest of the flexible electronics which can be applied to enormous fields not only to conventional electronic devices but to bio/eco electronic devices. Flexible electronics can be applied to wide range of fields such as flexible display, flexible power storage, flexible solar cells, wearable electronics and healthcare monitoring devices. Recently, flexible electronics are being attached on the skin and even implanted into human body to monitor the bio-signals and for treatment purpose. To improve the electrical characteristic and the mechanical properties of flexible electronics, nanoscale fabrications using novel nano-materials are required. Advanced in nanoscale fabrication methods allow construction of the active materials that can combine with the ultra-thin soft substrate to form flexible electronics with high performances and reliability. In this review, wide range of nanoscale fabrication methods for flexible electronics classified in either top-down or bottom-up approaches such as conventional photolithography, soft lithography, nanoimprint lithography, growth, assembly and chemical vapor deposition(CVD) will be reported with specific fabrication processes and results. Here, our aim is to introduce various fabrication methods that can be used to fabricate the flexible electronics.

T cell function is determined by transcriptional networks that are regulated by epigenetic programming via posttranslational modifications (PTMs) of histone proteins and DNA. Bottom-up mass spectrometry (MS) can identify histone PTMs, whereas intact protein analysis with high-field Fourier transform ion cyclotron resonance MS (FTICR-MS) can detect species missed by bottom-up approaches. We used high-resolution reversed-phase liquid chromatography (RPLC) FTICR-MS, alternating electron transfer dissociation (ETD) and collision-induced dissociation (CID) on precursor ions to maximize fragmentation of uniquely modified species. First online RPLC separation sorted histone families then weak cation exchange hydrophilic interaction liquid chromatography (WCX-HILIC) separated species heavily clad in PTMs. Tentative PTM identifications were assigned by matching peptide masses to predicted theoretical masses that were verified with tandem MS. We used this innovative approach for Histone-intact protein PTM mapping (HiPTMap) and to quantify PTMs on core histones purified from CD8+ T cells directly isolated ex vivo post-influenza infection. Activation significantly reduced PTMs in vivo following influenza infection, histone maps changed as T cells migrated to infections, and T cells responding to secondary heterologous infections had significantly more PTMs enhancing transcriptional activation. Thus, HiPTMap identifies and quantifies PTMs on CD8+ T cell histones and determines their combinations in T cell states.

Top-down models are defined by hardware architects to provide information on the utilization of the different hardware components. The target is to isolate the users from the complexity of the hardware architecture while giving them insight into how efficiently the code is using the resources. In this paper, we explore the applicability of 4 top-down models defined for different hardware architectures powering state-of-the-art HPC clusters (Intel Skylake, Fujitsu A64FX, IBM Power9, and Huawei Kunpeng 920) and propose a model for AMD Zen 2. We study a parallel CFD code used for scientific production to compare these 5 Top-Down models. We evaluate the level of insight achieved, the clarity of the information, the ease of use, and the conclusions that each one allows us to reach.

Down Syndrome (DS) is a chromosomal disorder due to the presence of an additional chromosome 21 that causes intellectual deficit and physical anomalies and predisposes patients to develop infections throughout their lives. Pneumonias are more serious in patients with DS, requiring hospitalization, and represent an important cause of mortality in this population. Cytomegalovirus (CMV) causes widespread and serious infections in immunocompromised individuals, affecting the respiratory tract and, causing interstitial pneumonia, is associated with a high mortality rate. However, CMV-induced pneumonia is not reported in DS patients. The prevalence and severity of CMV respiratory infections in subjects with DS is unknown. This case describes a 50-year-old female patient suffering from DS who developed extensive bilateral pneumonia with severe respiratory failure which required hospitalization in intensive care, intubation and mechanical ventilation after approximately 10 days of empiric antibiotic and anitimycotic therapy for fever, cough and dyspnea. The patient was diagnosed with CMV pneumonia and recovered after treatment with Ganciclovir. To the best of our knowledge, this is the first reported case of CMV pneumonia in a patient with DS. This case aims to highlight that CMV pneumonia in individuals with DS can be a life-threatening condition. It also clarifies the importance of early diagnosis of infections from opportunistic pathogens such as CMV to ensure timely and efficient treatment.

Sanitation, water supply and their governance remain major challenges in many Pacific Island Countries. National sustainable development strategies (NSDSs) are promoted throughout the Pacific as overarching improved governance instruments to identify priorities, plan solutions and fulfill commitments to sustainable development. Their relevance to local village-level development priorities is uncertain. The Kingdom of Tonga provides opportunities to compare both. Tonga’s Strategic Development Frameworks (TSDFI 2011-2014 and TSDFII 2015-2025) were developed to focus government and its agencies on national outcomes. From 2007 to 2016, 136 villages throughout Tonga’s five Island Divisions (IDs) formulated Community Development Plans (CDPs) involving separately 80% of women, youth and men in each village. Censuses in 2006 and 2016 show linked improvements in water supply and sanitation systems but reveal IDs with continuing challenges. Sanitation and water are prominent in TSDFI but absent from the current TSDFII. In contrast, CDPs show in one ID, 53% of villages ranked sanitation as a priority with marked differences between IDs and between women, youth and men. CDPs’ sanitation priorities in IDs mostly correspond to sanitation and water metrics in the Censuses, but some reflect impacts of natural disasters. Explanations for differences in sanitation priorities between national and local development plans, as well as suggestions for improving NSDS processes in island countries, are advanced.

At the LHC, the process of a Higgs boson decaying into bottom or charm quarks produced in association with a pair of top quarks, tt¯H, allows for an empirical exploration of the heavy-flavor quark Yukawa couplings to the Higgs boson. Accordingly, the cross sections for the tt¯ + heavy-flavor production without the appearance of the Higgs boson have been measured at the LHC in various phase spaces using data samples collected in pp collisions at s = 7, 8 and 13 TeV with the ATLAS and CMS experiments. Flavor ratios of cross sections of tt¯ + additional jets processes with different flavors are also measured. In this paper, the measured cross sections and ratios are reviewed and the prospects with more data are presented.

We study the propagation of a particular field that we call Gaussian-top-hat that presents self-focusing and maintains its shape for some propagation distances.

Research on microglia in Down syndrome (DS) has shown that microglial activation, increased inflammatory gene expression, and oxidative stress occur at different ages in DS brains. However, most studies resulted in simplistic definitions of microglia as quiescent or active, ignoring potential intermediate states. However, a recent work on microglial cells in young DS brains indicated that those evolve through different intermediate activation phenotypes before reaching a full activated state. Here we used single nucleus RNA sequencing, to examine how trisomy affects microglial states in the Ts65Dn mouse model of DS. Despite no substantial changes in the proportion of glial populations, differential expression analysis revealed cell type-specific gene expression changes, most notably in astroglia, microglia, and oligodendroglia. Focusing on microglia, we identified differential expression of genes associated with different microglial states, including disease-associated microglia (DAMs), activated response microglia (ARMs), and human Alzheimer’s disease microglia (HAMs), in trisomic microglia. Furthermore, pseudotime analysis reveals a unique reactivity profile in Ts65Dn microglia, with fewer in a homeostatic state and more in an intermediate aberrantly reactive state than in euploid microglia. This comprehensive understanding of microglial transcriptional dynamics sheds light on potential pathogenetic mechanisms but also possible avenues for therapy for neurodevelopmental disorders.

Abstract: Down Syndrome (DS) is a common genetic disorder characterized by an extra copy of chromosome 21, leading to dysregulation of various metabolic pathways. Oxidative stress in DS is associated with neurodevelopmental defects, neuronal dysfunction, and the onset of dementia re-sembling Alzheimer's disease. Additionally, chronic oxidative stress contributes to cardiovascular diseases and certain cancers prevalent in DS individuals. This study investigates the impact of ageing on oxidative stress and liver fibrosis using a DS murine model (Ts2Cje mice). The liver in DS mice shows increased oxidative stress and impaired antioxidant defenses, as evidenced by reduced glutathione levels and increased lipid peroxidation. Furthermore, DS liver exhibits an altered in-flammatory response as measured by the expression of cytokines and heat shock proteins. DS liver also displays dysregulated lipid metabolism, indicated by altered expression of peroxisome prolif-erator-activated receptors and fatty acid transport proteins. Consistently, these changes might contribute to non-alcoholic fatty liver disease development, a condition characterized by liver fat accumulation. Finally, histological analysis of DS liver reveals increased fibrosis and steatosis, in-dicative of potential progression to liver cirrhosis. This finding highlights the increased risk of liver pathologies in DS individuals, particularly when combined with the higher prevalence of obesity and metabolic dysfunctions in DS patients. These results shed light on the liver's role in DS-associated pathologies and suggest potential therapeutic strategies targeting oxidative stress and lipid metabolism to prevent or mitigate liver-related complications in DS individuals.

Monitoring the quality of stored bulk grain is generally done using temperature cables hung from silo roofs. Little investigation has been done into the effects of number of sensors and their placement in terms of reliability of the monitoring system with regard to making stored grain quality management decisions. A previously developed 3D finite element simulation model was verified and used to investigate these aspects. In the first study, a silo was loaded with about 228.6 Mg (9000 bushels) of maize and six temperature cables were placed in the grain mass. The maize was aerated continuously for a period of two weeks, and the cable sensor temperatures were compared to the predicted temperatures which were in close agreement with the observed readings. The standard error of prediction ranged from 2.0 to 3.7°C. In the second study, 15 and 30 sensors were placed at manufacturer recommended depths and horizontal locations in the grain mass of three silo sizes (i.e., 11x11, 14.6x14.6 and 14.6x18.3 m diameter by eave height). The average grain temperatures predicted by the 15 and 30 sensors over a one-year simulation period were compared to the average grain temperatures predicted for the entire grain mass (1968, 3052, and 3204 mesh nodes). The number of sensors needed to monitor stored grain temperatures reliably in the three silo sizes investigated heavily depended on whether the aeration control strategy achieved a sufficiently low temperature by the time the aeration fans were turned off and sealed ahead of the non-aerated storage period. Fifteen or 30 sensors were sufficient to monitor grain temperatures during the aeration cooling period but for the two larger silo sizes more than 30 sensors would be needed during the storage period. As silo size increased, and surface-to-volume ratio decreased, grain temperatures remained lower during the storage period. Results support the best management practice recommendation of leaving cooled grain cold and not warming it up in the spring ahead of storage into the summer.

People with Down syndrome present cognitive difficulties that affect their reading skills. In this study we present results about the use of gestural interaction with Kinect sensor to improve the reading skills of students with Down syndrome. Following a case of study method for small samples with disabilities, measuring different variables related to reading skills in an experimental group and in a control group. We found improvements in the visual association, visual comprehension, sequential memory, and visual integration after this stimulation in the experimental group compared to the control group. Also, we found that the number of error and delay time of interaction decrease between sessions in the experimental group.

We have revised the problem of the motion of a heavy symmetric top. When formulating equations of motion of the Lagrange top with the diagonal inertia tensor, the potential energy has more complicated form as compared with that assumed in the literature on dynamics of a rigid body. Using the Liouville's theorem, we solve the improved equations in quadratures and present the explicit expressions for the resulting elliptic integrals.

The issue of women’s participation in top management and boardroom positions has received increasing attention in the academic literature and the press. However, the pace of advancement for women managers and directors continues to be slow and uneven. The novel framework of this study organizes the factors at the individual, organizational and public policy level that affect both career persistence and the advancement of women in top management positions; namely, factors affecting 1) career persistence (staying at the organization) and 2) career advancement or mobility (getting promoted within the organization). In the study location, Chile, only 32 percent of women “persist”, or have a career without interruptions, mainly due to issues with work–family integration and organizational environments with opaque and challenging working conditions. Women who “advanced” in their professional careers represent 30 percent of high management positions in the public sector and 18 percent in the private sector. Only 3 percent of general managers in Chile are women. Women in Chile have limited access and are still not integrated into business power networks. Our findings will enlighten business leaders and public policy-makers interested in designing organizations that retain and promote talented women in top positions.

Richard Peto’s Paradox, first described in 1975 from an epidemiological perspective, established an inverse correlation between the probability of developing cancer in multicellular organisms and the number of cells. Larger animals exhibit fewer tumors compared to smaller ones, though exceptions exist. Mice are more susceptible to cancer than humans, while elephants and whales demonstrate significantly lower cancer prevalence rates than humans. How nature and evolution have addressed the issue of cancer in the animal kingdom remains largely unexplored. In the field of medicine, much attention has been devoted to cancer predisposing genes, as they offer avenues for intervention, including blocking, downregulating, early diagnosis, and targeted treatment. Predisposing genes also tend to manifest clinically earlier and more aggressively, making them easier to identify. However, despite significant strides in modern medicine, the role of protective genes lags behind. Identifying genes with a mild predisposing effect poses a significant challenge. Consequently, comprehending the protective function conferred by genes becomes even more elusive, and their very existence is subject to questioning. While the role of variable expressivity and penetrance defects of the same variant in a family is well-documented for many hereditary cancer syndromes, attempts to delineate the function of protective/modifier alleles have been restricted to a few instances. In this review, we endeavor to elucidate the role of protective genes observed in the animal kingdom and within certain genetic syndromes that appear to act as cancer-resistant/repressor alleles. The ultimate goal is to discern why individuals, like Winston Churchill, managed to live up to 91 years of age, despite engaging in minimal physical activity, consuming large quantities of alcohol daily, and not abstaining from smoking.

We have recently presented a unified quantum gravity theory [1]. Here we extend on that work and present an even simpler version of that theory. For about hundred years, modern physics has not been able to build a bridge between quantum mechanics and gravity. However, a solution may be found here; we present our quantum gravity theory, which is rooted in indivisible particles where matter and gravity are related to collisions and can be described by collision space-time. In this paper, we also show that we can formulate a quantum wave equation rooted in collision space-time, which is equivalent to mass and energy.The beauty of our theory is that most of the main equations that currently exist in physics are not changed (in terms of predictions), except at the Planck scale. The Planck scale is directly linked to gravity and gravity is, surprisingly, actually a Lorentz symmetry as well as a form of Heisenberg uncertainty break down at the Planck scale. Our theory gives a dramatic simplification of many physics formulas without altering the output predictions. The relativistic wave equation, the relativistic energy momentum relation, and Minkowski space can all be represented by simpler equations when we understand mass at a deeper level. This not attained at a cost, but rather a reflection of the benefit in having gravity and electromagnetism unified under the same theory.

Background: People with Down syndrome (DS) have a trisomy of chromosome 21 and marked deficits in verbal memory but relatively preserved visuospatial perception. Verbal memories are related to semantic knowledge. Little is known about the organization of semantic knowledge in people with DS, which was the aim of this study. Aims: The extent of false memory in people with DS was examined. Possible differences in the number of false memories induced by nominal and verbal themes were examined. Methods and Procedures: In the study phase, ten word lists with semantically related associates were presented. In the recognition phase, participants made judgments on whether each word had been represented previously as semantically related lures, old words, and semantically unrelated new words. Outcomes and Results: Differences in the processing of nominal and verbal theme-related lures were observed among people with DS. When processing nominal theme-related lures, people with DS showed delayed false positives. When processing verbal theme-related lures, people with DS showed no differences compared to controls. Similar patterns have been observed in people with DS when processing nominal theme-related associates and verbal theme-related associates. People with DS have delayed recognition of associates. When processing unrelated words, they showed significantly higher false positives than controls for both nominal and verbal eliciting themes. Further analyses of the themes revealed differences in false positives across syntactic categories among groups. Conclusions and Implications: People with DS showed a delayed recognition of associates and deviance in recognizing unrelated words in the nominal and verbal theme categories. People with DS were delayed in terms of nouns, but deviated with verbs in associated and unrelated words. Additionally, people with DS showed distinct patterns in processing five nominal lures and three verbal lures, suggesting that they formed false memories differently based on distinct syntactic categories. Thus, it was concluded that people with DS develop a deviant semantic structure. Category-based interventions for people with DS should be implemented in order to improve their semantic knowledge through lexical connections.

Down syndrome (DS) is a leading human genomic abnormality resulting from the trisomy of chromosome 21. The genomic base of the aneuploidy behind this disease is complex, and this complexity poses formidable challenges to understanding the underlying molecular basis. In the spectrum of the classic DS risk factor associations the role of nutrients, vitamins, and in general, the foodborne associated background as part of the events leading ultimately to chromosome nondisjunction has long been recognized as a well-established clinical association. The integrity of the microbiome is a basic condition in these events, and the dysbiosis may be associated with secondary health outcomes, the possible association of DS development with maternal gut microbiota should require more attention. We have hypothesized that different classes of antibiotics might promote or inhibit the proliferation of different microbial taxa and hence, we might find associations between the use of different classes of antibiotics and the prevalence of DS through the modification of the microbiome. As antibiotics are considered major disruptors of the microbiome, it could be hypothesized that the consumption/exposure of certain classes of antibiotics might be associated with the prevalence of DS in European countries (N=30). Utilizing three different statistical methods, comparisons have been made between the average yearly antibiotic consumption (1997-2020) and the prevalence of people living with DS estimated for 2019 as a percentage of the population in European countries. We have found strong statistical correlations between the consumption of tetracycline (J01A) and the narrow-spectrum, beta-lactamase-resistant penicillin (J01CF) and the prevalence of DS.

This study examines the unique circumstances surrounding state-owned equity participation in non-state-controlled enterprises in China. Specifically, this study examines the impact of state-owned equity participation on the environmental, social, and governance (ESG) performance of non-state-controlled enterprises. Focusing on A-share listed firms on the Shanghai and Shenzhen Stock Exchanges and using data from 2013 to 2021, empirical testing shows that state-owned equity participation can significantly improve the ESG performance of non-state-controlled enterprises, with this conclusion remaining reliable after a series of robustness tests. Top management incentives is a mediating mechanism for state-owned equity participation in enhancing ESG performance. This study also finds that when state-owned equity participates in large enterprises or companies with a high degree of digital transformation, the effect on ESG performance is greater than that of small to medium-sized enterprises (SMEs) or enterprises with a low level of digital transformation. The findings of this study add to the current body of the existing field of research on the factors influencing corporate ESG performance and the impact of state-owned equity on corporate non-financial performance.

This paper aims to explore the effect of humble leadership on project success by integrating the mediating role of employee creativity. Top management support moderates the direct relationship (humble leadership and project management effectiveness) and indirect relationships through employee creativity. Time-lagged data were obtained from 332 persons working in the matrix organization across the information technology. The results showed that humble leadership enhance project management effectiveness by mediating and moderating processes. This study provides a solution to an underlying research question that has gone unanswered in prior studies. What are the strategies proposed for humble leadership in fostering the effectiveness of the project?

A deep review of the existing literature on the culpeo ecology is carried out, using scientific articles, book chapters and web resources. For information published before 1988, the synthesis made by a previous report was used. For subsequent information, bibliographic searches were carried out through the main servers, considering all of the generic names used to define the species so far. From this update, new general patterns on ecology, behavior and conservation concerns about culpeos are described. Gaps in current knowledge have been identified and new lines of research are proposed.Most of the studies focused on diet, conflicts with the species in livestock areas, and on the use of space and habitat. We found an incomplete, poor justification for all of the proposed subspecies and their supposed geographical distribution, as well as a scarcity of studies on genetic issues, population dynamics and conservation concerns. It is remarkable that vast regions in South America holding culpeos lacked basic information on the species.Diet studies describe a marked trend towards resources selection at the local level, which supports the view of the culpeo as a facultative trophic specialist. In addition, it has been confirmed that in the high Andes the culpeo is also a top predator that may regulate carnivorous communities, as well as that in arid environments culpeos can act as important seed dispersers. The assessment of the conservation status of the species differs among regions, although there is no sufficient information to reach clear conclusions in most cases. Even so, in Ecuador and Colombia the species has been listed as ‘Vulnerable’. Direct persecution and habitat alteration are considered to be the most important threats that the species is facing in many countries, although other risk factors such as climate change could also have serious consequences for the canid at the global scale.

Citation frequencies represent the most significant contributions in any respective field. This bibliometric analysis aimed to identify and analyze the 100 most-cited publications in the field of antibiotics and to highlight the trends of research in this field. “All databases” of Clarivate Analytics' Web of Science was used to identify and analyze the 100 publications. The articles were then cross-matched with Scopus and Google Scholar. The frequency of citation ranged from 940 to 11051 for the Web of Science, 1053 to 10740 for Scopus, and 1162 to 20041 for Google Scholar. Five hundred thirteen authors made contributions to the ranked list, and Robert E.W. Hancock contributed in six articles, which made it to the ranked list. Sixty-six scientific contributions originated from the United States of America. In contrast, five publications were linked to the University of Manitoba, Canada, that was identified as the educational organization, which made the most contributions (n=5). According to the methodological design, 26 of the most cited works were review-type closely followed by 23 expert opinions/perspectives. Eight articles were published in Nature journal, making it the journal with the most scientific contribution in this field. Correlation analysis between the publication age and citation frequency was found statistically significant (P = .012).

This paper aims to determine the insecticidal activity of Panyawan (Tinospora rumphii) leaf extract against American cockroach (Periplaneta americana). A quantitative experimental research design was employed in the study. Cockroach strains were collected through trapping and hand catch methods. Panyawan leaf was collected and extracted to achieve seven different concentrations. The concentrations and controls were tested against the strains through the standard contact glass jar bioassay. Results revealed that the shortest knock-down time was achieved by the positive control at 1.08 minutes while the Extracts of Panyawan leaf reported a 1.42 to 20.25 minutes knock-down time. Probit Regression reported that the lethal concentration 50 of Panyawan leaf extract was 15.836%. One-Way ANOVA revealed that there is a significant difference in the knock-down times of cockroaches when exposed to different Panyawan leaf extract concentrations, negative and positive controls (p<0.01). Homogeneous subsets derived from Post Hoc Test using Tukey’s Honest Significant Difference reported that there is no significant difference between positive control and Extract 100% (p>0.01).

Failure of wind turbines is a multi-faceted problem and its monetary impact is often unpredicted. In this study, we present a novel application of survival analysis on wind turbine reliability performance that includes accounting of previous failures and history of scheduled maintenance. We investigate the operational, climatic and geographical factors which affect wind turbine failures and model the risk rate of wind turbine failures based on data from 109 turbines in Germany operating during a period of 19 years. Our analysis showed that adequately scheduled maintenance can increase the survivorship of wind turbine systems and electric subsystems up to 2.8 and 3.8 times, respectively compared to the ones without scheduled maintenance. Geared-drive wind turbines and their electrical systems were observed to have 1.2- and 1.4-times higher survivorship, respectively, compared to direct-drive turbines and their electrical systems. It is also found that survivorship of frequently-failed wind turbine components, such as switches, is worse in geared-drive than in direct-drive wind turbines. We show that survival analysis is a useful tool for guiding the reduction of operating and maintenance costs of wind turbines.

Trees, often referred to as the "lungs of the Earth," hold immense significance for both the natural world and human society. Their contributions span a multitude of ecological, environmental, economic, and social domains, making them essential components of a healthy and thriving planet. Phytoplasma association not only compromise tree aesthetics but also reduce photosynthetic capacity and overall vigour. Phytoplasma diseases also lead to increased tree mortality, altering ecosystem dynamics.This review article provides an in-depth exploration of phytoplasma diseases affecting trees worldwide, encompassing their epidemiology, symptomatology, impact and management strategies.

Background: Down Syndrome is the most well-studied aneuploidy condition in humans. It is associated with multiple disease phenotypes including cardiovascular, neurological, haemato-logical, and immunological disease processes. In this review paper we aim to discuss the research into gene expression studies performed at the fetal stage of development. Methods: A descriptive review was performed including all papers published on the PubMed database between Septem-ber 1960- September 2022. Results: In the amniotic fluid, genes such as COL6A1 and DSCR1 are affected, causing the phenotypical craniofacial changes. Other genes affected in amniotic fluid in-cluding: GSTT1, CLIC6, ITGB2, C21orf67, C21orf86 and RUNX1. In the placenta, MEST, SNF1LK and LOX were dysregulated, affecting nervous system development. In the brain DYRK1A, DNMT3L, DNMT3B, TBX1, olig2 and AQP4 were found to be dysregulated, affecting the nervous system and intellectual disability. In the cardiac tissues GART, EST2 and ERG found to be dysregulated causing secondary heart field abnormalities. XIST, RUNX1, SON, ERG and STAT1 dysregulated causing myeloproliferative disorders. Conclusions: Differential expression of genes provides clues to the genetic consequences of DS. A better understanding of these processes could eventually to lead to the development of genetic and pharmacological therapies.

People with Down syndrome have more visual problems than general population. They experience a premature aging, and it would be expected they will also have an acceleration in worsening visual function. A prospective observational study which includes visual acuity, refractive error, accommodation, binocular and colour vision was performed to young adults with (n=69) and without (n=65) Down syndrome and to a senior group (n=55) without Down syndrome. Results showed significant differences in visual acuity between groups (p&lt;0.001) and it can be improved with a new prescription in 40% of the participants with Down syndrome. Regarding to accommodative state, no significant differences were found between groups of young people. Concerning binocular vision, 64.7% of strabismus was observed in the group with Down syndrome (p&lt;0.001). Visual abnormalities are significant in young adults with Down syndrome and are different from those of older people without Down syndrome, some of which can be improved by providing the optimal prescription as well as regular eye examinations.

In this work, we compiled our research on lanthanide-based luminescent materials, prepared down-shifter layers, and studied their effect on photovoltaic (PV) mini-modules. The compounds we have prepared (C1-C17), with formulas [Eu2(phen)2(bz)6] (C1), [Eu2(bphen)2(bz)6] (C2), [Eu(tta)3bphen] (C3), [Eu(bta)3pyz-phen] (C4), [Eu(tta)3pyz-phen] (C5), [Eu(bta)3me-phen] (C6), [Er(bta)3me-phen] (C7), [Yb(bta)3me-phen] (C8), [Gd(bta)3me-phen] (C9), [Yb(bta)3pyz-phen] (C10), [Er(tta)3pyz-phen] (C11), [Eu2(bz)4(tta)2(phen)2] (C12), [Gd2(bz)4(tta)2(phen)2] (C13), [EuTb(bz)4(tta)2(phen)2] (C14), [EuGd(bz)4(tta)2(phen)2] (C15), [Eu1.2Gd0.8(bz)4(tta)2(phen)2] (C16) and [Eu1.6Gd0.4(bz)4(tta)2(phen)2] (C17), can be grouped into three families based on their composition: Series C1–6 were synthesized using Eu3+ ions and phenanthroline derivatives as the neutral ligands, and fluorinated β-diketonates as the anionic ligands. Complexes C7–11 were prepared with ligands similar to those of compounds C1–6 but were synthesized with Er3+, Yb3+, or Gd3+ ions. Series C12–17 exhibit the general formula [M1M2(bz)4(tta)2(phen)2], where M1 and M2 can be Eu3+, Gd3+, or Tb3+ ions, and the ligands are benzoate (bz–), 2-thenoyltrifluoroacetone (tta–) and 1,10–phenanthroline (phen). All compounds were characterized using X-ray techniques, and their photoluminescent properties were studied. We then examined their impact on the EQE (External Quantum Efficiency) of PV mini-modules and their durability in a climate chamber when embedded in PMMA and EVA films. This review emphasizes the methodology employed and the key findings, including enhanced mini-module efficiency. Additionally, we present promising results on the application of compound C6 in a bifacial solar cell.

Neurodevelopmental disorders arise from genetic and/or from environmental factors and are characterized by different degrees of intellectual disability. The mechanisms that govern important processes sustaining learning and memory, which are severely affected in intellectual disability, have classically been thought to be exclusively under neuronal control. However, this vision has recently evolved into a more integrative conception, in which astroglia, rather than just acting as metabolic supply and structural anchoring for neurons, interact at distinct levels modulating neuronal communication and possibly also cognitive processes. Recently, genetic tools have made it possible to specifically manipulate astrocyte activity unraveling novel functions that involve astrocytes in memory function in the healthy brain. However, astrocyte manipulation has also underscored potential mechanisms by which dysfunctional astrocytes could contribute to memory deficits in several neurodevelopmental disorders revealing new pathogenic mechanisms in intellectual disability. Here, we review the current knowledge about astrocyte dysfunction that might contribute to learning and memory impairment in neurodevelopmental disorders, with special focus on Fragile X syndrome and Down syndrome.

In the educational process, quality has long been considered a critical component. It may get impacted due to different factors especially when talking about the COVID19 pandemic. The purpose of this investigation is to explore the impact and relationship between COVID-19 and the quality of education using bibliometric analysis. As face-to-face learning shifts to online learning, this research investigates how the COVID-19 epidemic has affected education quality, concentrating on Programme Educational Outcomes (PEOs), Programme Learning Outcomes (PLOs), and Course Learning Outcomes (CLOs). The research covers pandemic online education, literature, and trends. There are two important steps in any bibliometric analysis selecting keywords and databases. The initial set of keywords was selected by the authors' experience and then an online survey study through Google Forms was conducted among experts in the research area. This was followed by a search of the selected keywords in the databases consisting of PubMed, Web of Science (WoS), and SCOPUS. Therefore, the final data was collected from the SCOPUS database on August 24, 2021. Hence, 182 documents were considered for the current study. The document's data were analysed by using the “visualization of similarities” (VOS) Viewer software and the R-Tool of the Bibliometrix-package that was specifically designed for quantitative Bibliometrics research. Based on the obtained data, the results showed the quality of education that may get impacted by the changing of the education delivery from face-to-face to online-based learning. In conclusion, this study showed the importance of studying the correlation and impact of COVID-19 on the quality of education.

Several recent epidemiological studies attempted to identify risk factors for Alzheimer's disease. Age, family history, genetic factors (APOE genotype, Down syndrome), physical activity, and a low level of schooling are significant risk factors. In this review, we summarize the known psychosocial risk factors for the development of Alzheimer's disease in Down syndrome patients and their association with neuroanatomical changes in the brains of people with Down syndrome. We completed a comprehensive review of the literature on PubMed, Google Scholar, and Web of Science about psychosocial risk factors for Alzheimer's disease, for Alzheimer's disease in Down syndrome, and Alzheimer's disease in Down syndrome and their association with neuroanatomical changes in the brains of people with Down syndrome. Alzheimer's disease causes early pathological changes in Down syndrome patients, especially in the hippocampus and corpus callosum. The field needs more data about the neuroanatomical changes during childhood, how they change with increasing age, and the presence or absence of psychosocial risk factors. Further neuroimaging and psychosocial assessment-focused research is needed to understand the mechanisms leading to Alzheimer's disease at an early age and create more sensitive and relevant clinical, memory, and reasoning assessments for people with Down syndrome.

CO2 has characteristic properties and reactions at converter smelting temperature, and the chemical reaction between CO2 and elements such as C and Si in the molten pool has bubble proliferation and cooling effects, which can effectively improve the kinetic and thermodynamic conditions of converter smelting. Here, an experimental study and industrial test on the application of CO2 in converter smelting were carried out. The smelting effects of Mode-1 and Mode-2 with total CO₂ injection amounts of 229 Nm³ and 196 Nm³, respectively, were compared, and the changes in molten steel and slag compositions, dust removal, and gas are analyzed. The test results show that converter top and bottom blowing CO₂ technology (COMI-B)technology had significant metallurgical advantages over the N-Mode; the dephosphorization rate increased by 4.2%, slag (FeO) content was reduced by 2.04%, end point nitrogen content of molten steel was reduced by 20%, gas recovery increased by 8.29 Nm³/t, and soot production reduced by 14.7%. The results of the study provide reference for the application of COMI-B technology in converters in the iron and steel industry and develop a new path for resource utilization of CO₂.

Abstract: The YF3: (Eu3+, Nd3+) nanoparticles (orthorhombic phase, D ~ 130 nm)) were synthesized via the co-precipitation method with subsequent hydrothermal treatment and annealing. The Eu3+ τdecay linearly descends with the increase of temperature in the 80 - 320 K range. The τdecay (T) slope values of the annealed YF3: Eu3+ (2.5 and 5.0 mol. %) nanoparticles were the highest (110·10-4 and 67·10-4, μs/K in the whole 80 – 320 K range, respectively. Thus, these samples were chosen for further doping with Nd3+. The maximum Sa and Sr values based on the LIR (IEu/INd) function were 0.67 K-1 (at 80 K) and 0.86 %·K-1 (at 154 K), respectively. As it was mentioned above, the sin-gle-doped YF3: Eu3+ (2.5. %) nanoparticles showed the linearly decreasing τdecay (T) function (5D0 – 7F1 emission). The main idea of Nd3+ co-doping was to increase this slope value (as well as the sensitivity) by increasing the rate of τdecay (T) descent via the addition of one more tempera-ture-dependent channel of 5D0 excited state depopulation. Indeed, we managed to increase the slope (Sa) up to 180·10-4 K-1 at 80 K. This result is one of the highest compared to the world analogs.

Field and numerical investigations at Happisburgh, East coast of England, UK, sought to characterize beach thickness and determine geologic framework controls on coastal change. After a major failure of coastal protection infrastructure, removal of about 1 km of coastal defense along the otherwise protected cliffed coastline of Happisburgh triggered a period of rapid erosion over 20 years of ca. 140 m. Previous sensitivity studies suggested that that beach thickness plays a major role in coastal recession. These studies were limited, however, by a lack of beach volume data. In this study, we have integrated the insights gained from our understanding of the Quaternary geology of the area, a novel non-intrusive passive seismic survey method, and a 3D novel representation of the subsurface source and transportable material into a coastal modelling environment to explore the role of beach thickness on the back wearing and down wearing of the cliffs and consolidated platform, respectively. Results show that beach thickness is non-homogeneous along the study site: we estimate that the contribution to nearshore sediment budget via platform down wearing is of a similar order of magnitude as sediment lost from the beach and therefore non-negligible. We have provided a range of evidence to support the idea that the Happisburgh beach is a relatively thin layer perched on a sediment rich platform of sand and gravel. This conceptualization differs from previous publications, which assumes that the platform was mostly till and fine material. This has direct implication on the regional sediment management of along this coastline. The present study contributes to our understanding of a poorly known aspect of coastal sediment budgeting and outlines a quantitative approach that allows for simple integration of geological understanding for coastline evolution assessments worldwide.

The effect of filling velocity on positive macrosegregations in large size steel ingots was studied. Macrosegregation and macro-/micro-structure were characterized on the hot-tops and a portion of the upper section of two ingots. The measurements revealed that segregation features in the two ingots varied as a function of the alloying elements, and that the severity of positive macrosegregation in the casting body was reduced when the filling rate was increased. It was also found that at the higher filling rate, grain morphologies in the first solidified zones of the ingot changed from columnar to equiaxe, and secondary dendrite arm spacing (SDAS) became slightly smaller in the intermediate and final solidified zones. The experimental findings were analyzed in the framework of diffusion and convection controlled solidification, as well as liquid metal flow theories. The solute dependence of segregation features was related to the difference in solid-liquid partition coefficient and diffusion capability of each element in the liquid iron. Calculation of Reynolds numbers (Re) during the filling process, for both ingots, showed that higher filling velocity caused more instable movement of the liquid metal in the initial solidification stage, resulting in the modification of grain morphology, as well as accelerated solidification rate.

Rapid draw-down in an earthfill dam has serious implications for dam safety regarding slope stability. The evaluation of reservoir draw-down impact on slope stability was carried out considering the case study of 8 hours of rapid draw-down of the Middle Marsyangdi Hydroelectric Power Project (MMHPP) rock-fill dam using the Limit Equilibrium Method (LEM) and stress-based Finite Element Method (FEM). The time-dependent factor of safety (FOS) was evaluated and found that the 8 hours of rapid draw-down undertaken in October 2012 for reservoir flushing was unsafe with a draw-down rate of 1.91m/h. The resulting FOS of 1.28 and 1.27 using LEM and FEM was classified as unsafe as per the US Army Corps of Engineers’ guideline, the minimum required factors of safety should be greater than 1.3. The minimum safe allowable draw-down rate of 0.76m/h for 20 hours was identified. Applying three layers of horizontal filter materials and increasing the upstream dam’s permeability provided adequate FOS results for all cases by increasing seepage discharge to reduce the destabilizing excess pore water pressure. Several gradual draw-down rates were also tested and found that FOS increases with decreased draw-down rates, as it reduces the excess pore water pressure controlled with stabilizing existing water load.

The absolute absorption cross section of the ethyl peroxy radical, C2H5O2, in the Ã←X ̃ electronic transition with the peak wavelength at 7596 cm-1, has been determined by the method of dual wavelengths time resolved continuous wave cavity ring down spectroscopy. C2H5O2 radicals were generated from pulsed 351 nm photolysis of C2H6/Cl2 mixture in presence of O2 and detected on one of the CRDS paths. Two methods have been applied for the determination of the C2H5O2 absorption cross section: (i) based on Cl-atoms being converted alternatively to either C2H5O2 by adding C2H6 or to hydro peroxy radicals, HO2, by adding CH3OH to the mixture, whereby HO2 was reliably quantified on the second CRDS path in the 21 vibrational overtone at 6638.2 cm-1 (ii) based on the reaction of C2H5O2 with HO2, measured under either excess HO2 or under excess C2H5O2 concentration. Both methods lead to the same peak absorption cross section of C2H5O2,7596 cm-1 = (1.0±0.2) × 10-20 cm2. The rate constant for the cross reaction between of C2H5O2 and HO2 has been measured to be (6.5±1.6) × 10-12 cm3 molecule-1 s-1.

Sustainable food systems imply the re-use of biowastes and water. In this paper we characterize 30 top soil improvers of anthropogenic, animal and green waste origin, and 11 irrigation waters from rivers, channels, and civil wastewater treatment plants (cWWTPs) for the presence of antimicrobials. Liquid chromatography coupled to hybrid High Resolution Mass Spectrometry (LC-HRMS/MS) was applied to determine 50 different drugs belonging to the classes of sulfonamides (11), tetracyclines (7), fluoroquinolones (10), macrolides (12), amphenicols (3), pleuromutilins (2), diaminopyrimidines (1), rifamycines (1) and lincosamides (1). Biowastes from cWWTPs and animal manure, slurry and litter revealed the highest loads for sulfonamides, tetracyclines, fluoroquinolones, and macrolides (80, 470, 885, and 4,487 ng/g wet weight, respectively) with nor- and cipro-floxacin as marker of anthropogenic sources. In composts and digestates antimicrobials were almost below the determination limits. Re-used waters for irrigation in open field lettuce production resulted contaminated in the range of 12-221 ng/L for sulfonamides, tetracyclines, and fluoroquinolones, against very few detects in channels and surface waters. Antimicrobials Hazard Index (HI) based on Predicted No Effect Concentration for Antimicrobial Resistance (PNEC_AMR) was largely >100 in contaminated top soil improvers from urban and animal sources. Accounting for worst-case inputs from top soil improvers and irrigation water and dilution factors of amended soil, fluoroquinolones only showed a HI around 1 in open fields for lettuce production. The origin of top soil improvers plays a pivotal role for safe and sustainable leafy vegetable productions, to abate the risk of AMR onset in food-borne diseases, as well the transfer of AMR elements to human gut flora.

Phenotypic plasticity is widely acknowledged as one of the most common solutions for coping with novel environmental conditions following climate change. However, it is less known wheth-er current amounts of trait plasticity, which is sufficient for matching with contemporary climate, will be adequate when global temperatures exceed historical levels. We addressed this issue by ex-ploring the responses of functional and structural leaf traits in Iris pumila clonal individuals to ex-perimentally increased temperature (~1.5°C), using an open top chamber (OTC) design. We de-termined phenotypic values of specific leaf area, leaf dry matter content, specific leaf water con-tent and leaf thickness in leaves sampled from the same clone inside and outside of the OTC de-ployed on it, over seasons and years within two natural populations. We analyzed the data by a repeated multivariate analysis of variance, which is primarily focused on profiles (reaction norms, RNs) of a variable gathered from the same individual at several different time points. We found that the mean RNs of all analyzed traits were parallel regardless of experienced temperatures, but differed in the level and the shape. The populations RNs were similar as well. Since the amount of plasticity in analyzed leaf trait was adequate for coping with elevated temperatures inside the OTCs, we predict that it will be also sufficient for responding to increased temperatures if they exceed the 1.5°C target.

In the extra-thick coal seams and multi-layered hard roofs, the longwall hydraulic support yielding, coal face spalling, strong deformations of goaf-side entry, and severe ground pressure dynamic events typically occur at the longwall top coal caving longwall faces. Based on the Key strata theory an overburden caving model is proposed here to predict the multilayered hard strata behaviour. The proposed model together with the measured stress changes in coal seam and underground observations in Tongxin coal mine provides a new idea to analyse stress changes in coal and help to minimise rock bursts in the multi-layered hard rock ground. Using the proposed primary Key and the sub-Key strata units the model predicts the formation and instability of the overlying strata that leads to abrupt dynamic changes to the surrounding rock stress. The data obtained from the vertical stress monitoring in the 38 m wide coal pillar located adjacent to the longwall face indicates that the Key strata layers have a significant influence on ground behaviour. Sudden dynamically driven unloading of strata was caused by the first caving of the sub-Key strata while reloading of the vertical stress occurred when the goaf overhang of the sub-Key strata failed. Based on this findings several measures were recommended to minimise the undesirable dynamic occurrences including pre-split of the hard Key strata by blasting and using the energy consumption yielding reinforcement to support the damage prone gate road areas. Use of the numerical modelling simulations was suggested to improve the key theory accuracy.

. The Tau protein is associated with microtubule function in the neuron and is crucial for normal axonal transport. In several different neurodegenerative disorders, Tau misfolding leads to hyper-phosphorylation (p-Tau) and intracellular p-Tau aggregates known as neurofibrillary tangles (NFTs). This is particularly evident in individuals with Down syndrome (DS), who develop Alzheimer’s disease-like (AD) neuropathology early in life with almost complete penetrance, associated with the development of dementia symptoms in their 40s or 50s. Our previous findings have shown that certain forms of p-Tau are present already in childhood in individuals with DS in neuron-derived exosomes, suggesting an early phosphorylation profile in this population that could influence the development of AD pathology. Misfolded p-Tau isoforms are known to be seeding competent and may be responsible for spreading AD pathology in different regions of the brain. This review is focused on the accumulation of p-Tau in the brain of individuals with DS and potential consequences for brain function.

AISI 1050 steel circular pocket milling under minimum quantity lubrication (MQL) surroundings including nozzle elevation angle, lubricant flow rate, air pressure and cutting speed was studied. The machined surface quality (Ra) was evaluated for Up-milling side and Down-milling side. In this study, to obtain an manifest explanation on the pivotal effective parameters of MQL surroundings and cutting speed on the machined surface quality (Ra) through analyzing Taguchi L9 (34-2) approach and ANOVA calculation to identify those parameters, by utilizing the experimental outcomes to interpret three-dimensional (3D) surface plots and the diagrams of Signal-to-Noise ratios and major impact plots of Mean. The obtained outcomes of optimal operating parameters indicated that the pivotal effective parameters of MQL surroundings are nozzle elevation angle and lubricant flow rate on the machined surface quality. Simultaneously, a quadratic mathematical paradigm generated by using response surface design (RSD) and desirableness function evaluation were utilized to forecast the optimal values of the machined surface quality compared to Taguchi method. The results unveiled that the optimal values of the machined surface quality are adjacent to experimental attained values. The machined surface quality has been significantly improved using MQL surroundings.

Dog Assisted Therapy is hypothesized to lower stress in children with Autism Spectrum Disorder (ASD) and children with Down Syndrome (DS), which may be visible on a physiological level. In this study, we measured Heart Rate Variability (HRV) and salivary cortisol of 20 children with DS or ASD at the beginning and end of 6 weekly sessions of Dog-Assisted Therapy. We found a decrease of cortisol levels during single sessions, but no overall effect after 6 sessions (6 weeks). The effect of Dog Assisted Therapy on the increase of HRV could not be confirmed. This study is one of the first to use physiological measurements to test the effects of DAT.

The distribution and variation of top-of-atmosphere longwave cloud radiative forcing (LCRFTOA) has drawn a significant amout of attention due to its importance in understanding the energy budget. Advancements in sensor and data processing technology, as well as a new generation of geostationary satellites, such as the FengYun-4A (FY-4A), allow for high spatial resolutions that are crucial for real-time radiation monitoring. Nevertheless, there is a distinct lack of official top-of-atmosphere outgoing longwave radiation products under clear-sky conditions (OLRclear). Consequently, this study addresses the challenge of constructing LCRFTOA data with high spatiotemporal resolution over the full disk region of FY-4A. After simulating the influence of atmospheric parameters on OLRclear based on SBDART radiation transfer model (RTM), we developed a model for estimating OLRclear using infrared channels from the advanced geosynchronous radiation imager (AGRI) onboard the FY-4A satellite. The OLRclear results showed an RMSE of 5.05 W/m2 and MBE of 1.59 W/m2 compared to ERA5. Besides, the calculated LCRFTOA results were validated against instantaneous, daily average, and monthly average ERA5 and CERES LCRFTOA products, supporting the validity of the algorithm proposed in this paper. Finally, the changes in LCRFTOA due to variaty cloud heights (high, medium, and low cloud) were analyzed. This study provides the basis for comprehensive studies on the characteristics of top-of atmosphere radiation.

In the post antimicrobial era, increasing attention is paid towards using bacteriophage (phage in short) therapy to control antibiotic-resistant bacteria. The first step in phage therapy applications is isolating highly efficient lytic phages or phage cocktails from various sources. When a double-layer- agar with around 0.7% agar in top agar is employed, it results in a low number of phage isolation with a poor resolution, and in many cases, you miss the phage. To address this problem, a low concentration of agar in top agar is examined for better phage isolation. Here, our results proved the efficiency of isolating phage upon formulating a double-layer agar with 0.3% agar in top agar. A sewage sample was collected then phages were isolated, purified, and spotted on a top layer agar with 0.3% agar. The results showed the possibility of isolating a higher number of phages on 0.3% top agar than 0.7%. The finding advocates using 0.3% top agar for the double-layer agar, as it will provide fast, better, and easy phage screening and isolation.

In the steeply inclined and extremely thick coal seams (SIETCS) mined using the horizontal sublevel top-coal caving (HSTCC) method, the uncertainty of gas emission is a safety threat to the mining operations. In order to reduce the occurrence of accidents, the determination of gas emission is crucial. In this paper, we first proposed a prediction model for workers at the floor coalbed to calculate gas emission on site. We then put forward a finite element numerical simulation for researchers to predict gas emission from the floor coalbed. At last, we measured gas emitted from the floor coalbed of SIETCS in Wudong Coal Mine in a specific mining period and used the data to verify the applicability and accuracy of these two gas-emission prediction methods. The results showed that the gas emission from Wudong Coal Mine was 1.08 m³/min calculated based on the prediction model and 1.07 m³/min obtained using the user-defined integration method. Both methods have their own advantages, disadvantages and applicable objects, and are important in predicting gas emission from SIETCS mined using HSTCC method.

Furthermore, the nasal congestion typical of rhinitis can contribute to upper airway obstruction and sleep-disordered breathing. A vicious circle is created between asthma and sleep-disordered breathing: uncontrolled asthma and sleep-disordered breathing can worsen each other. In children with genetic obesity, despite alterations in the immune system, fewer allergies are found compared to the general population. The causes of this reduced allergenicity are unclear but probably involve genetic, immunological, and environmental factors. Further studies are needed to understand the mechanisms. The study emphasizes the importance of jointly evaluating and managing allergies, obesity, and sleep-disordered breathing in children, considering their close interconnection.

The objective of parsing is to transform a natural language sentence it in to a standard order. and in a same way a sentence is tokenized with an appropriate format. There are certain English grammar evaluation rules and the parsing approach which is to be followed for the proper formation of a particular sentence syntactically and semantically using the parsing approach. A sentence in English language is the main element in the semantic parser, which creates a parse tree with the help of applying semantic dating technique to a number of phrases. A parser divides a token into smaller components by applying sets of guidelines that characterize and a series of the tokens to determine its structure of the language, which specified by grammar. The illustration provides easy records on grammatical connections, which can simply know and put into practice with those who have no prior knowledge of the language, such as those who need to obtain textual family members. The semantic family members represent the relationships of a number of the words in the sentence. We advocate utilizing our parser to acquire the tagged sets as well as a context-free layout grammatical representation for the source form. All pronouns, adverbs, singular, plural, nouns, verbs, people, adjectives, tenses and other words are kept in a database.

Device-mediated, non-invasive drug delivery across the blood-brain barrier (BBB) represents a significant advancement in treating neurological diseases. The BBB is a tightly packed layer of endothelial cells that shields the brain from harmful substances in the blood, allowing necessary nutrients to pass through. It is a highly selective barrier, which poses a challenge to delivering therapeutic agents into the brain. Several non-invasive techniques and devices have been proposed or investigated to enhance drug delivery across the BBB. This paper presents the current state of the art and case studies that address the pharmacology, technology, delivery systems, regulatory approval, ethical concerns, and future possibilities.

This work communicates cavity ring-down spectroscopy (CRDS) of methylidyne (CH) in a chemiluminescent plasma that is produced in a microwave cavity. Of interest are the rotational lines of the 0-0 vibrational transition for the A-X band and the 1-0 vibrational transition for the B-X band. The reported investigations originate from CH-radical research in 1996 that constituted the first case of applying CRDS to the CH radical. The report also includes recent analysis that shows excellent agreement of measured and computed data, and it communicates CH line strength data.

This paper develops mathematical models examining possible roles of oxytocin and oxytocin receptors in the development of autism. This is done by demonstrating that mathematical operations on normalized data from the Stanford study (K.J. Parker, 2016), which establishes a correspondence between severity of autism in children and their oxytocin blood levels, generates a graph that is the same as the graph of mathematical operations on a normalized theoretical model for the severity of autism. This procedure establishes the validity of the theoretical model and the significance of oxytocin receptors in autism. A steady-state model follows, explaining the constant baseline concentrations of oxytocin observed in the cerebral spinal fluid and blood in terms of the neuromodulation by oxytocin of oxytocin receptors on the magnocellular neurons that produce oxytocin in nuclei in the hypothalamus. The implications of these models for possible roles of oxytocin and oxytocin receptors in autism is considered for several unrelated conditions that may be associated with autism. These are: oxytocin receptor desensitization and down-regulation as factors during labor in offspring autism development; reductions in the oxytocin receptor numbers in the fixed oxytocin receptor expression that occurs before birth; MAST Immune System disease; and the excess number of dendritic spines from lack of pruning observed in brains of autistic people. Research into the feasibility of generating magnocellular neurons and other neurons from adult stem cells is suggested as a way of doing invitro studies of oxytocin and oxytocin receptors to assess the validity of theories presented in this paper.

To ensure the security of spatial-temporal Top-k query in two-tiered wireless sensor networks, many schemes have been proposed in the literature in the past decade. However, most of them only consider the scenario where sensor nodes are static, and cannot achieve the security goal for spatial-temporal Top-k query in mobile sensor networks, because the mobility of the sensor nodes will affect the spatial-temporal relationships of the sensory data items generated by the sensor nodes. Although we have proposed some schemes for two-tiered mobile wireless sensor networks (TMWSNs) in our previous work, there is still large room to improve their performances. In this paper, we proposed a novel scheme named STQ-TMWSN for secure fine-grained spatial-temporal Top-k query in TMWSNs based on the virtual-grid construction and the size-order encryption binding. Theoretic analysis shows that STQ-TMWSN can achieve low computation complexity and high security performance. Simulation results indicate that STQ-TMWSN brings much lower communication cost than the state-of-the-art schemes on securing Top-k query in TMWSNs.

The molecular basis of Down syndrome (DS) predisposition to leukemia is not fully understood but involves various factors such as chromosomal abnormalities, oncogenic mutations, epigenetic alterations, and changes in selection dynamics. Myeloid leukemia associated with DS (ML-DS) is preceded by a preleukemic phase called transient abnormal myelopoiesis driven by GATA1 gene mutations and progresses to ML-DS through additional mutations in cohesin genes, CTCF, RAS, or JAK/STAT pathway genes. DS-related ALL (ALL-DS) differs from non-DS ALL in terms of cytogenetic subgroups and genetic driver events and aberrant expression of CRLF2, JAK2 mutations, and RAS pathway activating mutations are frequent in ALL-DS. Recent advancements in single-cell multi-omics technologies have provided unprecedented insights into the cellular and molecular heterogeneity of DS-associated hematologic neoplasms. Single-cell RNA sequencing and digital spatial profiling enable the identification of rare cell subpopulations, characterization of clonal evolution dynamics, and exploration of the tumor microenvironment's role. These approaches may help identify new druggable targets and tailor therapeutic interventions based on distinct molecular profiles, ultimately improving patient outcomes with the potential to guide personalized medicine approaches and the development of targeted therapies.

As there exist no repulsive forces in strong interaction, in a hypothetical approach, strong interaction can be assumed to be equivalent to a large gravitational coupling. Based on this concept, strong coupling constant can be defined as a ratio of the electromagnetic force and the gravitational force associated with proton, neutron, up quark and down quark. With respect to the product of strong coupling constant and fine structure ratio, we review our recently proposed two semi empirical relations and coefficients 0.00189 and 0.00642 connected with nuclear stability and binding energy. We wish to emphasize that- by classifying nucleons as ‘free nucleons’ and ‘active nucleons’, nuclear binding energy can be fitted with a new class of ‘three term’ formula having one unique energy coefficient. Based on the geometry and quantum nature, currently believed harmonic oscillator and spin orbit magic numbers can be considered as the lower and upper “mass limits” of quark clusters.

Individuals residing in more deprived areas have a lower diet quality. While several studies have shown that individuals with a lower diet quality have a higher mortality risk, a low quality diet might also lead to poor health in highly deprived areas. We aimed to examine the association between deprivation within an area and all-cause mortality risk according to diet quality. Methods: We conducted a population-based prospective study on 27994 men and 33273 women aged 45–75 years. Neighborhood deprivation was assessed using the Japanese areal deprivation index (ADI). Dietary intakes were assessed using a validated 147-item food frequency questionnaire. Subsequently, Japanese Food Guide Spinning Top scores were calculated. Hazard ratios (HR) and 95% confidence intervals (CI) of mortality were calculated according to tertiles of ADI by diet quality score. Results: Individuals residing in the most deprived area had the lowest dietary scores. During the 16.7-year follow-up, compared to individuals with a high quality diet residing in the least deprived area, individuals with a low quality diet had a higher risk of mortality according to increment of ADI (P trend = 0.02); the multivariate adjusted HR (95% CI) was 1.07 (1.00-1.15), 1.15 (1.07-1.24), and 1.18 (1.08-1.29) in those residing in the lowest through the highest third of ADI, respectively. However, individuals with a high quality diet had no significant association between ADI and mortality (P trend =0.87). Conclusion: A well-balanced diet may prevent early death associated with neighborhood socioeconomic status among those residing in highly deprived areas.

Insufficient mixing in large-scale bioreactors, provokes gradient zones of substrate, dissolved oxygen, pH and other parameters. E. coli responds to a high glucose, low oxygen feeding zone with the accumulation of mixed acid fermentation products, especially formate, but also with the synthesis of non-canonical amino acids, such as norvaline, norleucine and -methyl-norleucine. These amino acids can be mis-incorporated into recombinant products, which causes a problem for pharmaceutical production whose solution is not trivial. While these effects can also be observed in scale down bioreactor systems, these are challenging to operate. Especially the high-throughput screening of clone libraries is not easy, as fed-batch cultivations would need to be controlled via repeated glucose pulses with simultaneous oxygen limitation, as has been demonstrated in well controlled robotic systems. Here we show that not only glucose pulses in combination with oxygen limitation can provoke the synthesis of these non-canonical branched-chain amino acids, but also that pyruvate pulses produce the same effect. Therefore we combined the enzyme based glucose delivery method Enbase® in a PALL24 mini-bioreactor system and combined repeated pyruvate pulses with simultaneous reduction of the aeration rate. These cultivation conditions, produced an increase in the non-canonical branched chain amino acids norvaline and norleucine in both the intracellular soluble protein and inclusion body fractions with mini-proinsulin as an example product, and this effect was verified in a 15 L stirred tank bioreactor. To our opinion this cultivation strategy is easy to apply for the screening of strain libraries under standard laboratory conditions if no complex robotic and well controlled parallel cultivation devices are available.

Apraxia of speech is a persistent speech motor disorder that affects speech intelligibility. Studies on speech motor disorders with transcranial Direct Current Stimulation (tDCS) have been mostly directed to post-stroke aphasia. Only a few tDCS studies have focused on apraxia of speech or childhood apraxia of speech (CAS), and no study has investigated individuals with CAS and people with trisomy 21 (T21, Down Syndrome). This study examined the effects of tDCS combined with a motor learning task in developmental apraxia of speech co-existing with T21 (ReBEC RBR-5435x9). The accuracy of speech sound production of nonsense words (NSWs) during Rapid Syllable Transition Training (ReST) under 10 sessions of anodal tDCS (1.5 mA, 25 cm) over the Broca’s area with cathode over the contralateral region was compared to 10 sessions of sham-tDCS and 4 control sessions in a 20-year-old male individual with T21 presenting moderate-severe childhood apraxia of speech (CAS). The accuracy for NSWs production progressively improved (gain 40%) under tDCS only (sham-tDCS and control sessions showed <20% gain). A decrease in speech severity from moderate-severe to mild-moderate indicated transfer effects in speech production. The speech accuracy under tDCS was correlated with Wernicke’s area activation (P3 current source density), which in turn, was correlated with the activation of the left supramarginal gyrus and the Sylvian Parietal Temporal Junction. Repetitive bihemispheric tDCS paired with ReST may have facilitated the speech sound acquisition in a young adult with T21 and CAS, possibly by recruiting brain regions required for the phonological working memory.

This work presents the mathematical framework of the Second-Order Comprehensive Adjoint Sensitivity Analysis Methodology for Response-Coupled Forward/Adjoint Linear Systems (abbreviated as “2nd-CASAM-L”), which enables the most efficient computation of exactly obtained mathematical expressions of first- and second-order sensitivities of a generic system response with respect to functions (“features”) of model parameters. Subsequently, the first- and second-order sensitivities with respect to the model’s uncertain parameters, boundaries, and internal interfaces are obtained analytically and exactly, without needing large-scale computations. Within the 2nd-FASAM-L methodology, the number of large-scale computations is proportional to the number of model features (defined as functions of model parameters), as opposed to being proportional to the number of model parameters, which are considerably more than the number of features, being incomparably more efficient and more accurate than any other methods (statistical, finite differences, etc.) for computing exact expressions of response sensitivities (of any order) with respect to the model’s features and/or primary uncertain parameters, boundaries, and internal interfaces. The application of the 2nd-CASAM-L methodology is illustrated using a simplified energy-dependent neutron transport model of fundamental significance in nuclear reactor physics.

Crosslinking of proteins for their irreversible immobilization on surfaces is a proven and popular method. However, many protocols lead to random orientation and the formation of undefined or even inactive by-products. Most concepts to obtain a more targeted conjugation or immobilization requires the recombinant modification of at least one binding partner, which is often impractical or prohibitively expensive. Here a novel method is presented, which is based on the chemical preactivation of Protein A or G with selected conventional crosslinkers. In a second step, the antibody is added, which is subsequently crosslinked in the Fc part. This leads to an oriented and covalent immobilization of the immunoglobulin with a very high yield. Protocols for Protein A and Protein G with murine and human IgG are presented. This method may be useful for the preparation of columns for affinity chromatography, immunoprecipitation, antibodies conjugated to magnetic particles, permanent and oriented immobilization of antibodies in biosensor systems, microarrays, microtitration plates or any other system, where the loss of antibodies needs to be avoided, and maximum binding capacity is desired. This method is directly applicable even to antibodies in crude cell culture supernatants, raw sera or protein-stabilized antibody preparations without any purification nor enrichment of the IgG. This new method delivered much higher signals as a traditional method and, hence, seems to be preferable in many applications.