Hematopoietic stem cell (HSC) transplantation (HSCT) is used to treat various hematologic disorders. Use of genetically modified mouse models of hematopoietic cell transplantation have been critical in our fundamental understanding of HSC biology and developing approaches for human patients. Pre-clinical studies in animal models provide insight into the journey of transplanted HSCs from infusion to engraftment in bone marrow (BM) niches. Various signaling molecules and growth factors secreted by HSCs and the niche microenvironment play critical roles in homing and engraftment of the transplanted cells. The sustained equilibrium of these chemical and biologic factors ensures that engrafted HSCs generate healthy and durable hematopoiesis. Transplanted healthy HSCs compete with residual host cells to repopulate stem cell niches in the marrow. Stem cell niches, in particular, can be altered by the effects of previous treatments, aging, and paracrine effects of leukemic cells that create inhospitable bone marrow niches that are unfavorable for healthy hematopoiesis. More work to understand how stem cell niches can be restored to favour normal hematopoieis may be key to reducing leukemic relapses following transplant.

The European heatwave of 2018 led to record-breaking temperatures and extremely dry conditions in many parts of the continent resulting in widespread decrease in agricultural yield, early tree-leaf senescence, and increase in forest fires in Northern Europe. Our study aims to capture the impact of the 2018 European heatwave on terrestrial ecosystem through the lens of a high-resolution solar-induced fluorescence (SIF) data acquired from the Orbiting Carbon Observatory (OCO-2) satellite. SIF is proposed to be a direct proxy for gross primary productivity (GPP) and thus can be used to draw inferences about changes in photosynthetic activity in vegetation due to extreme events. We explore spatial and temporal SIF variation and anomaly during spring and summer months across different vegetation types (agriculture, broadleaved forest, coniferous forest, and mixed forest) during the European heatwave of 2018 and compare it to non-drought conditions (most of Southern Europe). About one-third of Europe’s land area experienced a consecutive spring and summer drought in 2018. Comparing 2018 to mean (2015-2017) conditions, we found a change in intra-spring season SIF dynamics for all vegetation types, with lower SIF during the start of spring followed by an increase in fluorescence from mid-April. Summer, however, showed a significant decrease in SIF. Our results show that particularly agricultural areas were severely affected by the hotter drought of 2018. Furthermore, the intense heat wave in Central Europe showed about 31% decrease in SIF values during July and August as compared to the mean over three previous years. Furthermore, our MODIS and OCO-2 comparative results indicate that especially for forests, OCO-2 SIF has a quicker response and possible higher sensitivity to drought in comparison to MODIS’s fPAR and NDVI when considering shorter reference periods, which highlights the added value of remotely sensed solar-induced fluorescence for studying the impact of drought on vegetation.

Apple (Malus x domestica) fruit size is dependent on cell division and cell expansion, processes which are subsequently regulated by plant hormones such as auxins, gibberellins, and cytokinins. In this study, we investigated the role of cell division and cell expansion in apple growth and identified which of the two was more deterministic to final fruit size. Three cultivars of different sizes were selected, namely, ‘Twenty Ounce’ (large-sized), ‘Royal Gala’ (medium-sized), and ‘Crabapple’ (small-sized). Gene expression and cell size analyses were conducted over the course of two consecutive seasons. The expression patterns of three classes of genes were markedly similar across all cultivars. Two cell division markers, namely, MdCDKB2;2 and MdANT2, were discovered to be correlatively expressed as both displayed initially high expression levels, which gradually declined from the early to late stages of growth time course. For cell expansion markers, MdEXP3 was upregulated as the cells expanded, while MdARF106 was expressed in both the cell division and expansion stages. Meanwhile, the ripening related gene MdACO1 was expectedly expressed only during the ending stages associated with ripening. Interestingly, the cell measurements taken regularly from each cultivar throughout the same eperimental timespan showed that cell sizes were unaltered and remained constant from initial pollination at the zeroth Days After Pollination (DAP), to ripening at 120 Days After Full Bloom (DAFB).

Artificial Intelligence (AI) experienced significant advancements in recent years, and its impact is already recognized across various industries. Yet, the rise of AI has led to a growing concern about its impact on meeting the Sustainable Development Goals (SDGs). The aim of this paper was to evaluate contributions and the potential impact of AI to sustainable development in the society domain. Furthermore, the study analyzed GPT-3 responses, as one of the largest language models developed by OpenAI, descriptively. We conducted a set of queries on the SDGs to gather infor-mation on GPT-3`s perceptions of AI impact on sustainable development. Analysis of GPT-3’s contribution potential towards the SDGs showcased its broad range of capabilities for contributing to the SDGs in areas such as education, health, and communication. The study findings provide valuable insights into the contributions of AI to sustainable development in the society domain and highlight the importance of proper regulations to promote the responsible use of AI for sustainable development. We plan subsequent research for effects on ecologic and economic domains of SDGs. We highlighted the potential for improvement in neural language processing skills of GPT-3 by avoiding imitating weak human writing styles with more mistakes in longer texts.

The subject of study in the article is the method of industrial equipment vibration diagnostics using Allan variance. The goal is to increase the precision and accuracy of industrial equipment's vibration diagnostics processes by developing and implementing IoT-oriented solutions based on intelligent sensors and actuators per the IEEE 1451.0-2007 standard. Tasks: justify the feasibility of using platform-oriented technologies for vibration diagnostics of industrial equipment and choose a cloud service for the implementation of the platform; develop software and hardware solutions of the IoT platform for vibration diagnostics of industrial equipment; calibrate the vibration diagnostics system and check the measurement precision and accuracy. The methods used are the microservice approach, multilevel architecture, and assessing equipment state-based Allan variance. We obtained the following results. The architecture of the IoT system for vibration diagnostics of industrial equipment developed and presented in the article is three-level. The level of autonomous sensors provides readings of vibration acceleration indicators and transmits data to the Hub level, which is implemented based on a BeagleBone single-board microcomputer through the BLE digital wireless data transmission channel. BeagleBone computing power provides work with artificial intelligence algorithms. At the third level of the server platform, the tasks of diagnosing and predicting the condition of the equipment are solved, for which the Dictionary Learning algorithm implemented in the Python programming language is applied. Verifying the accelerometer calibration method for vibration diagnostics of industrial equipment was performed using a unique stand. Correct operation of the entire system is confirmed by the coincidence of expected and measured results. In the next step, we plan the development of additional microservices that will provide the possibility of using time series analysis methods and modern artificial intelligence technologies for complex diagnostics and forecasting of the equipment state.

3,4-dihydroxyphenylacetaldehyde (DOPAL) is the focus of the catecholaldehyde hypothesis for the pathogenesis of Parkinson disease and other Lewy body diseases. The catecholaldehyde is produced via oxidative deamination catalyzed by monoamine oxidase (MAO) acting on cytoplasmic dopamine. DOPAL is autotoxic, in that it can harm the same cells in which it is produced. Normally DOPAL is detoxified by aldehyde dehydrogenase (ALDH)-mediated conversion to 3,4-dihydroxyphenylacetic acid (DOPAC), which rapidly exits the neurons. Genetic, environmental, or drug-induced manipulations of ALDH that build up DOPAL promote catecholaminergic neurodegeneration. A concept derived from the catecholaldehyde hypothesis imputes deleterious interactions between DOPAL and the protein alpha-synuclein (S), a major component of Lewy bodies. DOPAL potently oligomerizes S, and S oligomers impede vesicular and mitochondrial functions, shifting the fate of cytoplasmic dopamine toward MAO-catalyzed formation of DOPAL—destabilizing vicious cycles. Direct and indirect effects of DOPAL and of DOPAL-induced misfolded proteins could “freeze” intra-neuronal reactions, plasticity of which is required for neuronal homeostasis. The extent to which DOPAL toxicity is mediated by interactions with S, and vice versa, are poorly understood. Because of numerous secondary effects such as augmented spontaneous oxidation of dopamine by MAO inhibition, there has been insufficient testing of the catecholaldehyde hypothesis in animal models. The clinical pathophysiological significance of genetics, emotional stress, environmental agents, and interactions with numerous proteins relevant to the catecholaldehyde hypothesis are matters for future research. The imposing complexity of intra-neuronal catecholamine metabolism seems to require a computational modeling approach to elucidate clinical pathogenetic mechanisms and devise pathophysiology-based, individualized treatments.

Respiratory Syncytial Virus (RSV) causes severe inflammation and airway pathology in children and the elderly by infecting the epithelial cells of the upper and lower respiratory tract. RSV replication is sensed by intracellular pattern recognition receptors upstream of the IRF and NF-B transcription factors. These proteins coordinate an innate inflammatory response via Bromodomain containing protein 4 (BRD4), a protein that functions as a scaffold for unknown transcriptional regulators. To better understand the pleiotropic regulatory function of BRD4, we examine the BRD4 interactome and identify how RSV infection dynamically alters it. To accomplish these goals, we leverage native immunoprecipitation and Parallel Accumulation – Serial Fragmentation (PASEF) mass spectrometry to examine BRD4 complexes isolated from human alveolar epithelial cells in the absence or presence of RSV infection. In addition, we explore the role of BRD4’s acetyl-lysine binding bromodomains in mediating these interactions by using a highly selective competitive bromodomain inhibitor. We identify 101 proteins that are significantly enriched in the BRD4 complex and are responsive to both RSV-infection and BRD4 inhibition. These proteins are highly enriched in transcription factors and transcriptional coactivators. Among them, we identify members of the AP1 transcription factor complex, a complex important in innate signaling and cell stress responses. We independently confirm the BRD4/AP1 interaction in primary human small airway epithelial cells. We conclude that BRD4 recruits multiple transcription factors during RSV infection in a manner dependent on acetyl-lysine binding domain interactions. This data suggests that BRD4 recruits transcription factors to target its RNA processing complex to regulate gene expression in innate immunity and inflammation.

Reducing under-five mortality is a key indicator of a country's overall development, yet in Angola, understanding the factors contributing to hospital deaths in this vulnerable demographic remains incomplete despite improvements in healthcare infrastructure and public health policies. With one of the highest under-five mortality rates in Sub-Saharan Africa, Angola grapples with significant challenges, including malaria, malnutrition, pneumonia, neonatal conditions, and intestinal infectious diseases, as leading causes of death among children. This study aimed to identify factors associated with these hospital deaths in children aged 28 days to five years admitted to DBPH in Luanda between May 2022 and June 2023. Utilizing a hospital-based case-control design, a total of 1020 children were studied, with 340 cases of hospital deaths. Notably, distal and intermediate determinants emerged as primary predictors of hospital mortality, revealing significant associations with maternal education status, maternal alcohol consumption during pregnancy, short hospital stays (≤24h), poor nutritional status, short interbirth intervals, maternal age ≤19 years, and maternal age ≥35 years. These findings underscore the preventable nature of most under-five hospital deaths and emphasize the urgent need to address social inequities and enhance the quality of primary healthcare services to effectively mitigate child mortality.

Micro-combs [1-4] - optical frequency combs generated by integrated micro-cavity resonators – offer the full potential of their bulk counterparts [5,6], but in an integrated footprint. The discovery of temporal soliton states (DKS – dissipative Kerr solitons) [4,7-11] as a means of mode-locking micro-combs has enabled breakthroughs in many fields including spectroscopy [12,13], microwave photonics [14], frequency synthesis [15], optical ranging [16,17], quantum sources [18,19], metrology [20,21] and more. One of their most promising applications has been optical fibre communications where they have enabled massively parallel ultrahigh capacity multiplexed data transmission [22,23]. Here, by using a new and powerful class of micro-comb called “soliton crystals” [11], we achieve unprecedented data transmission over standard optical fibre using a single integrated chip source. We demonstrate a line rate of 44.2 Terabits per second (Tb/s) using the telecommunications C-band at 1550nm with a spectral efficiency – a critically important performance metric - of 10.4 bits/s/Hz. Soliton crystals exhibit robust and stable generation and operation as well as a high intrinsic efficiency that, together with a low soliton micro-comb spacing of 48.9 GHz enable the use of a very high coherent data modulation format of 64 QAM (quadrature amplitude modulated). We demonstrate error free transmission over 75 km of standard optical fibre in the laboratory as well as in a field trial over an installed metropolitan optical fibre network. These experiments were greatly aided by the ability of the soliton crystals to operate without stabilization or feedback control. This work demonstrates the capability of optical soliton crystal micro-combs to perform in demanding and practical optical communications networks.

We report world record high data transmission over standard optical fiber from a single optical source. We achieve a line rate of 44.2 Terabits per second (Tb/s) employing only the C-band at 1550nm, resulting in a spectral efficiency of 10.4 bits/s/Hz. We use a new and powerful class of micro-comb called soliton crystals that exhibit robust operation and stable generation as well as a high intrinsic efficiency that, together with an extremely low spacing of 48.9 GHz enables a very high coherent data modulation format of 64 QAM. We achieve error free transmission across 75 km of standard optical fiber in the lab and over a field trial with a metropolitan optical fiber network. This work demonstrates the ability of optical micro-combs to exceed other approaches in performance for the most demanding practical optical communications applications.

Background: Hematopoietic cell transplantation (HCT) is an established therapy for hematologic malignancies and serious non-malignant blood disorders. Despite its curative potential, HCT is associated with substantial toxicity and health resource utilization. Effective delivery of HCT requires complex hospital-based care, which limits the number of HCT centers in Canada. In Canada, the quantity, indications, temporal trends, and outcomes of patients receiving HCT are not known. Methods: A retrospective cohort study of first transplants reported to the Cell Therapy Transplant Canada (CTTC) registry between 2000 and 2019. We determined overall survival (OS) and non-relapse mortality (NRM), categorizing the cohort into early (2000-2009) and later (2010-2019) eras to investigate temporal changes. Results: Of 18,046 transplants, 10,475 were allogeneic and 7,571 were autologous. Comparing the two eras, allogeneic transplants increased in number by 22.3%, with greater use of matched unrelated donors in the later era. Autologous transplants increased by 10.9%. Temporal improvements in NRM were observed in children and adults. OS improved in pediatric patients and in adults receiving autologous HCT. In adults receiving allogeneic HCT, OS was stable despite the substantially older age of patients in the later era. Interpretation: HCT is an increasingly frequent procedure in Canada which has expanded to serve older adults. Noted improvements in NRM and OS reflect progress in patient and donor selection, preparation for transplant, and post- transplant supportive care. In allogeneic HCT, unrelated donors have become the most frequent donor source, highlighting the importance of continued growth of volunteer donor registries. These results serve as a baseline measure for quality improvement and health services planning in Canada.

Abstract: Increasing physical activity (PA) and personal and social values are two of the greatest demands in the current educational system. This study examined the effect of a hybrid pro-gramme based on the Personal and Social Responsibility Model and Gamification. A total of 58 students (13.89 years old, SD = 1.14) in two groups (Experimental and Control) participated dur-ing a complete academic year. Motivation, physical activity and sedentary behaviour were as-sessed though questionnaires. Physical fitness was evaluated using previously validated field tests. The results showed significant differences over time between EG and CG in afterschool physical activity (APA) at the weekend (p = 0.003), sedentary time (p = 0.04) and speed-agility (p = 0.04). There were no significant differences in motivation. Regarding the intervention, speed-agility (p = 0.000), strength (p = 0.000), agility (p = 0.000), cardiorespiratory fitness (p = 0.001), APA-weekend (p = 0.000), APA-week (p= 0.000) and sedentary time (p = 0.000) increased signifi-cantly in the EG. Speed-agility (p = 0.000), APA-weekend (p = 0.03) and sedentary time (p = 0.008) increased in the CG. The use of this hybrid program can be useful to produced improvements in physical fitness, physical activity and sedentary hevaviours. The use of a hybrid program based on teaching personal and social responsibility and gamification strategies, produced improvements in physical fitness, physical activity and sedentary behavior, but not in motivation variables. Further research is demanded in order to contrast this relevant findings due to the potential drawbacks and diversity found in the scientific literature among model-based practice.

Candida glabrata has thoroughly adapted to successfully colonize human mucosal membranes and survive in vivo pressures prior to and during antifungal treatment. Out of all the medically relevant Candida species, C. glabrata has emerged as a leading cause of azole, echinocandin, and multidrug (MDR: azole + echinocandin) adaptive resistance. Neither mechanism of resistance is intrinsic to C. glabrata, since stable genetic resistance depends on mutation of drug target genes, FKS1 and FKS2 (echinocandin resistance), and a transcription factor, PDR1, which controls expression of major drug transporters, such as CDR1 (azole resistance). However, another hallmark of C. glabrata is the ability to withstand drug pressure both in vitro and in vivo prior to stable ‘genetic escape’. Additionally, these resistance events can arise within individual patients, which underscores the importance of understanding how this fungus is adapting to its environment and to drug exposure in vivo. Here, we explore the evolution of echinocandin resistance as a multistep model that includes general cell stress, drug adaptation (tolerance), and genetic escape. The extensive genetic diversity reported in C. glabrata will be highlighted.

Since the spread of the deadly virus SARS-CoV2 in late 2019, researchers have restlessly been seeking for unraveling how the virus factually enters the host cells. Some proteins on each side of the interaction between the virus and the host cells are involved as the major contributors to this process: 1- the nano-machine Spike protein on behalf of the virus, 2- angiotensin converting enzyme II, the mono-carboxypeptidase and the key component of renin angiotensin system on behalf of the host cell, 3- some host proteases and proteins exploited by SARS-CoV2, In this review, the complex process of SARS-CoV2 entrance into the host cells with the contribution of the involved host proteins as well as the sequential conformational changes in the Spike protein tending to increase the probability of complexification of the latter with angiotensin converting enzyme II, the receptor of the virus on the host cells, are discussed. Besides, the release of the catalytic ectodomain of angiotensin converting enzyme II as its soluble form in the extracellular space and its positive or negative impact on the infectivity of the virus are considered.

We present a method using contour integration to derive definite integrals and their associated infinite sums which can be expressed as a special function. We give a proof of the basic equation and some examples of the method. The advantage of using special functions is their analytic continuation which widens the range of the parameters of the definite integral over which the formula is valid. We give as examples definite integrals of logarithmic functions times a trigonometric function. In various cases these generalizations evaluate to known mathematical constants such as Catalan’s constant and π

For a long time, the transition to adulthood was seen as a troubled period where good development was synonymous with the absence of problems. Positive Youth Development (PYD) emerged as a holistic and strength-based perspective that focuses on the fact that young people may have the internal and external resources for healthy and successful development through five dimensions (5C’s) that empower them: Perceived Competence, Confidence, Character, Connection, and Caring. The aim of this study was to examine the relationship between the global PYD factor (and the 5C’s) and risk behaviors, in addition to analyzing gender differences. This study showed the results of a cross-sectional study of 1044 emerging adults from 11 Spanish universities in 2021. Data collection was performed by applying an online self-report measure. The results showed that the Character was protective against substance abuse, mainly in women, while the connection was related to the participation of betting money and online betting in men. Caring was protective against money bets in the men’s sample. However, controversial results were found regarding Perceived competence, which had a positive association with substance abuse, money bets, and drunk driving. It seems that high levels of Perceived competence, rather than objective competence, were associated with engagement in various risk behaviors, especially in the absence of other C´s. These results are discussed regarding the promotion of PYD to improve successful development and may suggest the need to foster healthy lifestyles and prevent risky behaviors in youth through the 5C's promotion programs within the university context.

Background: Mental health difficulties during teenage years e are common and are a risk factor for later mental and physical health problems. Rural young people are at greater risk for mental health difficulties and have less access to services than their urban counterparts. The purpose of this study was to explore young people and their carers’ experiences of mental health support provided by a rural mobile service, and to identify access enablers from the service users’ perspective. Methods: A qualitative descriptive approach was used to analyse twelve interviews with current service users and eight interviews with family members of young people who had accessed the service.Results: Three main themes were identified: (a) Access and flexibility, (b) Clinicians’ qualities and strategies, and (c) Experiences of change. The mobile service was perceived to be effective in producing positive change in mental health, relationships and attainment of life goals. Key enablers to access included the flexibility of the mobile service, the variety of service delivery modes and therapeutic methods offered, the ease of access facilitated by location in schools, and young people’s autonomy in how they chose to utilise the service. Conclusion: This study provides information about what is important to rural young people and their families in mental health service provision. The findings have implications for changing the way services are organized and operated. Healthcare policy and services could support user-led model design that incorporates the access and use enablers and removes the barriers to rural mental health support.

Cardiovascular diseases (CVDs) are the leading cause of death in the globally. Morbidity and disability related to non-fatal events are increasing exponentially. There are several symptoms that may arise after invasive therapeutic approaches such as coronary artery bypass graft (CABG), including chronic pain in anatomical areas connected to the mediastinum; these pains can be found not only initially after surgery, but also years later. We present a case where non-specific neck pain (NNP), in a patient undergoing CABG five years earlier, was approached with an osteopathic technique, working the pericardial area. To the knowledge of the Authors, it is the first case report where osteopathy is associated with a gentle treatment on the pericardial area to resolve a NNP.

The ability to self-direct a research program determines graduate degree completion. Yet, research on incompletion of graduate physics programs assume students’ present level of self-direction adequate and neglects to recognize a lack of self-directed learning as key. One theoretical mathematical physicist focused on changing this challenge of physics graduate education by promoting self-directed learning through the type research flow that has been found to bring the greatest satisfaction to researchers with respect to their insights. This he provided through his space, time, open mindedness and theoretical contributions with his students and in collaboration with his colleagues. A self-directed learner himself, David J. Rowe developed methods of mentoring for encouraging physics graduate students to recognize symmetry as valuable in identifying solutions to problems quickly—helping these students take the lead in finding insightful resolutions to complex, multidimensional, mathematical physics uncertainties. How Rowe set about supporting self-directed learning in his graduate physics education interactions will be examined with the use of narrative research to interpret the texts and conversations with the author he made available. His techniques will be presented and recommendations made regarding how Rowe’s work in this regard can be modeled to improve self-direction in STEM graduate education.

(S)-Atenolol ((S)-2-(4-(2-Hydroxy-3-(isopropylamino)propoxy)phenyl)acetamide) has been synthesized in >99% ee with use of Candida antarctica lipase B from Syncozymes (Shanghai, China), in a kinetic resolution of the corresponding racemic chlorohydrin. Deprotonation of the starting phenol building block was base catalyzed. The enantiopurity of the chlorohydrin building block remained unchanged upon subsequent amination. All four steps in the synthesis protocol have been optimized compared to previously reported methods, which makes this new protocol more sustainable and in accordance with green chemistry principles compared to previously reported protocols.

Aim: Streptococcus pneumoniae and influenza H1N1 virus are common organisms associated with human infections. These infections could play a significant role in immune regulation. The study was performed to analyse the genome sequences of these organisms with human genome and study its functional significance. Methods: The study was performed to analyse the overlapping of genome sequences in Streptococcus pneumoniae and Influenza (H1N1) virus against human genome sequences by BLASTn sequence analysis. The alignments are studied against the corresponding genes for their functional significance with DAVID and NDEx software.Results: Several hits or overlapping nucleotide segments were identified. Between streptococcus and homo sapiens 287 overlaps were identified, and among influenza and homo sapiens 124 hits were identified. A wide range of functional significance of these genes were identified, and the results are presented in this study. The results show insights into functional pathways and biological activities associated with the respective vaccinations or infections by these microorganisms. Conclusion: The common organisms like Streptococcus pneumoniae and Influenza H1N1 virus actively interact with the immune system and result in a wide range of immune regulations.

In this paper, we present a new concept of the generalized core orthogonality (called the C-S orthogonality) for two generalized core invertible matrices $A$ and $B$. $A$ is said to be C-S orthogonal to $B$ if $A^{\tiny\textcircled{S}}B=0$ and $BA^{\tiny\textcircled{S}}=0$, where $A^{\tiny\textcircled{S}}$ is the generalized core inverse of $A$. The characterizations of C-S orthogonal matries and the C-S additivity are also provided. And the connection between the C-S orthogonality and C-S partial order has been given using their canonical form. Moreover, the concept of the strongly C-S orthogonality is defined and characterized.

Skeletal muscle (SKM), despite comprising ~40% of body mass, is rare. This review explores the mechanisms that help to explain this rarity, including unique SKM architecture and function, which prohibits development of new cancer as well as negates potential metastasis to SKM. SKM also presents a unique immune environment that may magnify the anti-tumorigenic effect. Moreover, the SKM microenvironment manifests characteristics such as decreased extracellular matrix stiffness and altered lactic acid, pH, and oxygen levels that may interfere with tumor development. SKM also secretes anti-tumorigenic myokines and other molecules. Collectively, these mechanisms help account for the rarity of SKM cancer.

Optical artificial neural networks (ONNs) have significant potential for ultra-high computing speed and energy efficiency. We report a novel approach to ONNs that uses integrated Kerr optical micro-combs. This approach is programmable and scalable and is capable of reaching ultra-high speeds. We demonstrate the basic building block ONNs — a single neuron perceptron — by mapping synapses onto 49 wavelengths to achieve an operating speed of 11.9 x 10⁹ operations per second, or Giga-OPS, at 8 bits per operation, which equates to 95.2 gigabits/s (Gbps). We test the perceptron on handwritten-digit recognition and cancer-cell detection — achieving over 90% and 85% accuracy, respectively. By scaling the perceptron to a deep learning network using off-the-shelf telecom technology we can achieve high throughput operation for matrix multiplication for real-time massive data processing.

Vitamin D, unlike the micronutrients, vitamins A, E and K, is largely obtained, not from food, but by the action of solar UV light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Because no defined storage organ or tissue has been found for vitamin D, it has been assumed that adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D) which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into blood. This uptake and release of 25(OH)D by muscle, accounts for the very long half-life of this metabolite in the circulation. As 25(OH)D concentration in blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain adequate vitamin D status in winter.

Vitamin D, unlike the micronutrients, vitamins A, E and K, is largely obtained, not from food, but by the action of solar UV light on its precursor, 7-dehydrocholesterol, in skin. With the decline in UV light intensity in winter, most skin production of vitamin D occurs in summer. Because no defined storage organ or tissue has been found for vitamin D, it has been assumed that adequate vitamin D status in winter can only be maintained by oral supplementation. Skeletal muscle cells have now been shown to incorporate the vitamin D-binding protein (DBP) from blood into the cell cytoplasm where it binds to cytoplasmic actin. This intracellular DBP provides an array of specific binding sites for 25-hydroxyvitamin D (25(OH)D) which diffuses into the cell from the extracellular fluid. When intracellular DBP undergoes proteolytic breakdown, the bound 25(OH)D is then released and diffuses back into blood. This uptake and release of 25(OH)D by muscle, accounts for the very long half-life of this metabolite in the circulation. As 25(OH)D concentration in blood declines in winter, its cycling in and out of muscle cells appears to be upregulated. Parathyroid hormone is the most likely factor enhancing the repeated cycling of 25(OH)D between skeletal muscle and blood. This mechanism appears to have evolved to maintain adequate vitamin D status in winter.

Abstract: A simple protocol for preparation of O-acylated enol form - (R/S)-ethyl-2-acetoxy-4-phenyl-4H-chromene-3-carboxylate 5 was presented. The compound was characterized by 1H-, 13C-and DEPT135 NMR spectra, including {1H,1H} COSY, {1H,13C} HSQC, {1H,13C} HMBC and 2D-NOESY spectra. The preferred regioselectivity for O-acylation of 3,4-dihydrocoumarin 5 in the presence of substituent in 4-th position in the chroman ring and accounting the steric hindrance of the ester group in 3-th place was confirmed.

This paper shows the development of a numerical analysis model, which enables the calculation of the cargo transport capacity of a vehicle that circulates through a vacuum tube at high speed, whose effectiveness in transport is analyzed. The simulated transportation system is based on vehicles moving in vacuum tubes at high speed, a concept commonly known as Hyperloop, but assuming the vehicles for cargo containers. For the specific vehicle proposed, which does not include a compressor and levitates on magnets, the system formed by the vehicle and the vacuum tube has been conceptually developed, establishing the corresponding mathematical relationships that define its behavior. To properly model the performance of this transport system, it has been necessary to establish the relationships between the design variables and the associated constraints, such as the Kantrowitz limit, aerodynamics, transport, energy consumption, etc. Once the model was built and validated, it was used to analyze the effects of the variation of the number of containers, the operating speed and the tube length, considering the total and specific consumption of energy. Once the most efficient configuration was found regarding energy consumption and transport effectiveness, the complete system was calculated. The results obtained constitute a first approximation for the pre-design of this transport system and the built model allows different alternatives to be compared according to the design variables.

We study L_2-approximation problems in the weighted Hilbert spaces in the worst case setting. Three interesting weighted Hilbert spaces appear in this paper, whose weights are equipped with two positive parameters $\ga_j$ and $\az_j$ for $j=1,\,2,\dots,\,d$. We consider the worst case error of algorithms that use finitely many arbitrary continuous linear functionals. We discuss the exponential convergence-(t,s)-weak tractability (EC-(t,s)-WT) of these L_2-approximation problems under the absolute or normalized error criterion. In particular, we obtain the sufficient and necessary conditions for EC-(1,1)-WT and EC-(t,1)-WT with t

Open-pit uranium mining in the south Texas Gulf Coast region was active during the second half of the 20th century. Although some mines have extensive records documenting the locations and extents with descriptions of reclamation procedures and timelines, abandoned and reclaimed mines with minimal documentation concurrently exist where little is known about locations, mine waste volumes, and reclamation status. Advanced mapping of these mining operations is helpful for producing basic mine land inventories and assessments of mine waste; identifying potential undeveloped resources and environmental health issues; and for developing proper management, restoration, and reclamation strategies. We studied known reclaimed and unreclaimed mine sites to develop a spatiotemporal mapping approach utilizing multiple techniques in remote sensing as a proof of concept. A mapping classification system was developed to identify uranium mine waste-rock piles, mine pits (with and without waste water), the total area of land disturbance due to mining, and to differentiate abandoned and reclaimed mine features using lidar (Light Detection and Ranging) analysis and multispectral temporal analysis. Visual interpretation of Landsat imagery and time-series analysis revealed the temporal life-cycle of mining, historical areas of disturbance, and reclamation; however, mine features below vegetation canopies are not always visible in satellite imagery. Lidar laser scanning penetrates the vegetation canopy to measure the topographic elevation and exposes anthropogenic modifications to the landscape. Lidar analysis (bare earth elevation surface, slope, topographic contours, topographic textures, and overland-flow hydrography) revealed mine features, and expansive areas of mining disturbance. The spatiotemporal mapping approach proved to be useful for identifying and characterizing known mine features, areas of disturbance, and reclamation status. Historical pre-mining topographic data were available at only 4 of the mines for comparison where the cut-and-fill tool estimated 21% less waste-rock volume, indicating that information about pre-mining terrain topography and/or subsurface mine waste geometry is needed to improve accuracies for quantifying buried mine waste volume at reclaimed mine sites.

Lessons learned and risk-based outcomes from modernising the Australian Standard for post-mortem inspection and disposition judgement of beef, sheep, goat and pig carcases are described. Initial Risk Profiles identified priorities for quantitative assessments. The main difficulty encountered was the paucity of quantified performance of current inspection. Resolving this involved acquiring gross abnormality data representing regional production/proportional abattoir volumes, the range of gross abnormalities appearing nationally, proportional occurrence at carcase sites, and seasonality to enable comparisons. Evidence and discussion are provided for associated challenges experienced including preventing contamination, use of food chain information to support amendment, inspection as a part of industry Quality Assurance and opportunities to improve inspector training. Criteria considered by the Competent Authority for determination of equivalence of alternative post-mortem inspection techniques included comparisons of public health risk, non-detection rates for gross abnormalities, and microbial contamination resulting from inspection activities, as appropriate. Most gross abnormalities detected arose from animal health and welfare conditions affecting wholesomeness and did not present as food safety hazards. Non-detection rates between current and alternative inspection (observation) were negligible. A Quantitative Risk Assessment for Cysticercus bovis was conducted. Carcases with multiple gross abnormalities predominantly reflected historic infections (prior septicaemia) where trimming achieved wholesomeness unless cachexic.

Introduction: Given increasing adult use of amphetamine and methylphenidate and their high misuse potential, we examined suspected suicide attempts and other intentional misuse and medical outcomes and their associations with co-used other substances among amphetamine and methylphenidate exposure cases age 50+.Methods: Using the 2015-2021 U.S. National Poison Data System (N=7,701 amphetamine and/or methylphenidate cases), we fit two generalized linear models for a Poisson distribution with log link function, with suspected suicide attempt versus intentional misuse and major medical effect/death versus other outcomes as the dependent variables. Results: Of all amphetamine/methylphenidate exposure cases, suspected suicide attempts and intentional misuse were 28.4% and 13.2%, respectively. Benzodiazepine use was associated with a higher likelihood but any illicit drug use was associated with a lower likelihood of suspected suicide attempts compared to intentional misuse. Type of stimulant involved (amphetamine or methylphenidate) was not significant. Co-use of antidepressants (IRR=1.43, 95% CI=1.16-1.76), prescription opioids (IRR=1.48, 95% CI=1.21-1.81), drugs for cardiovascular disease (IRR=1.51 95% CI=1.20-1.90), antipsychotics (IRR=1.26, 95% CI=1.02-1.55), or illicit drugs (IRR=2.40, 95% CI=1.82-3.15) was associated with a higher likelihood of major effect/death.Conclusions: Suspected suicide attempts or intentional misuse accounted for more than 40% of amphetamine or methylphenidate exposure cases age 50+. The higher likelihood of major effect/death in cases involving antidepressants, antipsychotics, and cardiovascular disease drugs also suggests confounding effects of comorbid mental and physical health problems. Careful monitoring of those who were prescribed amphetamine or methylphenidate and use other substances are needed.

Background Nitrous Oxide (N₂O) is a dissociative anaesthetic that is sometimes used recreationally. The prevalence of N₂O use is difficult to quantify but appears to be increasing. Research on N₂O harms and application of harm reduction strategies are limited. The aim of this mixed method systematic review was to collate and synthesise the disparate body of research on recreational nitrous oxide use to inform harm reduction approaches tailored for young people. Methods To identify publications reporting recreational use of N₂O, a search of public health, psychology and social science databases was conducted. Databases included PubMed, CIHNAL, PsycINFO, Scopus and Web of Science. Gray literature and Google advanced search were also used. Due to limited published literature on the recreational use of N₂O, no limit was placed on publication date or study type. A thematic synthesis extracted descriptive and analytical themes from the selected studies. Quality appraisal was conducted using the CASP Tool for Qualitative studies and the Joanna Briggs Institute case report assessment tool Results The search retrieved 407 reports. Thirty-four were included in the final analysis including sixteen case reports. The included studies were primarily concerned with raising awareness of the apparently increasing use and subsequently increasing harms of recreational N₂O use. There was limited reference to policy or legislative responses in any published studies, no suggestions for harm reduction strategies or application of service level responses. In general, individuals lack awareness of N2O related harms. Conclusion The review found three key areas that deserve further consideration including: 1) policy, 2) service delivery, and 3) harm associated with N₂O use. We recommend a top-down (policy) and bottom-up (services delivery/services users) approach to harm reduction for N₂O use which also includes further consultation and research with both groups. Future research could explore young people’s experience of N₂O use including benefits and problems to inform contextually relevant harm reduction strategies.

The relative operating characteristic (ROC) curve is a popular diagnostic tool in forecast verification, with the area under the ROC curve (AUC) used as a verification metric measuring the discrimination ability of a forecast. Along with calibration, discrimination is deemed as a fundamental probabilistic forecast attribute. In particular, in ensemble forecast verification, AUC provides a basis for the comparison of potential predictive skill of competing forecasts. While this approach is straightforward when dealing with forecasts of common events (e.g. probability of precipitation), the AUC interpretation can turn out to be oversimplistic or misleading when focusing on rare events (e.g. precipitation exceeding some warning criterion). How should we interpret AUC of ensemble forecasts when focusing on rare events? How can changes in the way probability forecasts are derived from the ensemble forecast affect AUC results? How can we detect a genuine improvement in terms of predictive skill? Based on verification experiments, a critical eye is cast on the AUC interpretation to answer these questions. As well as the traditional trapezoidal approximation and the well-known bi-normal fitting model, we discuss a new approach which embraces the concept of imprecise probabilities and relies on the subdivision of the lowest ensemble probability category.

Topological indices have been used to modeling biological and chemical properties of molecules in quantitive structure property relationship studies and quantitive structure activity studies. All the degree based topological indices have been defined via classical degree concept. In this paper we define a novel degree concept for a vertex of a simple connected graph: S degree. And also we define S indices of a simple connected graph by using the S degree concept. We compute the S indices for well-known simple connected graphs such as paths, stars, complete graphs and cycles.

With the advancement of Additive Manufacturing and its applications in various industrial segments, it becomes increasingly important to investigate the processability parameters associated with nano-reinforcement. This study examines the influence of infill parameters, such as patterns (hexagonal, triangular and concentric), shape (solid and honeycomb) and concentrations by mass of Carbon Nanotubes (CNTs) at 1.0 wt% and 2.0 wt% on the mechanical compression properties of the 3D printed material. In this sense, nanocomposites based on Polylactic Acid (PLA) matrix nano-reinforced by CNTs were characterized using the Scanning Electron Microscopy -SEM, X-ray Diffraction, Raman Spectroscopy techniques and mechanical analysis. The mechanical properties of both the matrix and the nanocomposites were determined through mechanical compression tests, in accordance with [1]. SEM revealed compacted regions, voids, and detachment in the structures. XRD characterization indicated PLA predominantly amorphous nature, while CNTs exhibited characteristic diffractions of carbon nanotubes. Raman characterization showcased bands and characteristic vibrations of CNTs and PLA, nanocomposites' vibrational modes combine those of CNTs and PLA. Mechanical compression analysis indicates a direct influence of infill pattern, shape, and nano-reinforcement. The triangle pattern outperformed other patterns, exhibiting a 15.03% increase compared to concentric and 8.8% compared to hexagon infill. In nanocomposites, all showed higher compressive strength than the matrix. For PLA/1.0%CNTs, strength was 16.8%, and for PLA/2.0%CNTs, it reached 39.2%. In honeycomb shapes with infill variations, the triangular pattern excelled with a 0.97% increase over concentric and 6.12% over hexagon patterns. Honeycomb results indicate a 59.6% increase for (PLA/1.0%CNTs) and a 0.48% increase for (PLA/2.0%CNTs) compared to the matrix. This study highlights 3D printing parameters, emphasizing the effectiveness of the triangular pattern and the enhanced strength with the addition of CNTs, providing insights to enhance products manufactured through Additive Manufacturing.

Ship detection from synthetic aperture radar (SAR) imagery is crucial for various fields in real-world applications. Numerous deep learning-based detectors have been investigated for SAR ship detection, which require a substantial amount of labeled data for training. However, SAR data annotation is time-consuming and demands specialized expertise, resulting in that deep learning-based SAR ship detectors struggle due to a lack of annotations. With limited labeled data, semi-supervised learning is a popular approach for boosting detection performance by excavating valuable information from unlabeled data. In this paper, a semi-supervised SAR ship detection network is proposed, termed as Multi-Teacher Dempster-Shafer Evidence Fusion Net-work (MTDSEFN). The MTDSEFN is an enhanced framework based on the basic teacher-student skeleton frame, comprising two branches: the Teacher Group (TG) and the Agency Teacher (AT). The TG utilizes multiple teachers to generate pseudo-labels for different augmentation versions of unlabeled samples, which are then refined to obtain high-quality pseudo-labels by using Dempster-Shafer (D-S) fusion. The AT not only serves to deliver weights of its own teacher to the TG at the end of each epoch, but also updates its own weights after each iteration, enabling the model to effectively learn rich information from unlabeled data. The combination of TG and AT guarantees both reliable pseudo-label generation and learning comprehensive diversity information from numerous unlabeled samples. Extensive experiments were performed on two public SAR ship datasets, and the results demonstrated the effectiveness and superiority of the proposed approach.

Cardiovascular disease (CVD) is the leading cause of death worldwide. Cardiac rehabilitation (CR) has proven to be effective in reducing the rate of recurrence and disease as secondary prevention (evidence-based intervention) in patients who have suffered from myocardial infarction (MI). CR is a multidisciplinary path in which the patient is followed pharmacologically, from a psychological, nutritional, nursing and physiotherapy point of view. Post-MI patients present a reduction in the performance of the diaphragm muscle, the main inspiratory muscle, and this condition can become a risk factor for further relapses or for the onset of heart failure. Despite the solidity of the international guidelines for CR, the latter are lacking in specifically indicating an evaluation and training path regarding the inspiratory muscles in post-MI patients who have not undergone cardiac surgery. The article reviews the information on the adaptation of the diaphragm post-MI and highlights the need for clearer indications for a rehabilitation process that gives importance to the diaphragm.

A systematic study has been conducted on barbiturate complexes of all five alkali metals Li–Cs prepared from the metal carbonates or hydroxide in aqueous solution without other potential ligands present, varying the stoichiometric ratio of metal ion to barbituric acid (BAH). Eight polymeric compounds (two each for Na, K, and Rb and one each for Li and Cs) have been characterised by single-crystal X-ray diffraction. All contain some combination of barbiturate anion BA− (necessarily in a 1:1 ratio with the metal cation M+), barbituric acid, and water. All organic species and water molecules are coordinated to the metal centres via oxygen atoms as either terminal or bridging ligands. Coordination numbers range from 4 (for the Li complex) to 8 (for the Cs complex). Extensive hydrogen bonding plays a significant role in all the crystal structures, almost all of which include pairs of N–H…O hydrogen bonds linking BA− and/or BAH components into ribbons extending in one dimension. Factors influencing the structure adopted by each compound include cation size and reaction stoichiometry as well as hydrogen bonding.

Dissolved calcium (Ca2+) concentrations in freshwater ecosystems are of growing concern as increasing levels have been implicated in altering the environmental conditions and biodiversity. Elevated Ca2+ levels and sporadic re-emergence and disappearance of invasive zebra mussels in Kentucky Lake in recent years served as a motivation for this study. The objective of this study was to determine Ca2+ spatial and temporal patterns in Kentucky Lake, selected tributary streams, and the Ohio River during and following a zebra mussel invasion. Over 1000 water samples were collected and analysed for dissolved calcium during 2018-2022. Approved analytical methods were followed for sampling and measuring dissolved calcium levels. Results revealed significant spatial and temporal patterns. Kentucky Lake Ca2+ levels varied between 15-25 mg/L depending on the sampling location and month/year. Kentucky Lake channel sites exhibited comparably higher concentrations of Ca 2+ than did most embayment and/or stream sites, indicating that tributary streams did not serve as primary sources of calcium to the lake. Dissolved calcium levels at main lake sites exceeded the threshold for zebra mussel growth and reproduction in 2018 during the time when zebra mussels were present. Calcium in lake water samples collected from 2019 through 2022 was at or just below the threshold. Temporal trend data showed a gradual increase in Ca2+ in Kentucky Lake throughout the study period but remaining at or below the threshold level considered critical for the zebra mussels’ reproduction and development. Calcium levels in the Ohio River site at Paducah were similar to Kentucky Lake reflecting the predominance of Tennessee River water, while levels at the Brookport site were consistent with values known to support zebra mussel populations. The elevated calcium levels in Kentucky Lake waters during the late winter and early spring months may be due to natural sources (mineral weathering) as well as human activities in the Tennessee River basin. This study emphasizes the need for continued calcium monitoring in the watershed to determine the potential for future zebra mussel outbreaks and potential influences on the lake ecosystem and its functions.

Alzheimer’s Disease (AD) is a neurodegenerative condition that currently has no known cure. The principles of the expanding field of network medicine (NM) have recently been applied to AD research. The main principle of NM proposes that diseases are much more complicated than one mutation in one gene, and incorporate different genes, connections between genes, and pathways that may include multiple diseases to create full scale disease networks. AD research findings as a result of the application of NM principles have suggested that functional network connectivity, myelination, myeloid cells, and genes and pathways may play an integral role in AD progression, and may be integral to the search for a cure. Different aspects of the AD pathology could be potential targets for drug therapy to slow down or stop the disease from advancing, but more research is needed to reach definitive conclusions. Additionally, the holistic approaches of network pharmacology in traditional Chinese medicine (TCM) research may be viable options for the AD treatment, and may lead to an effective cure for AD in the future.

Despite well-documented health benefits of probiotics Saccharomyces, its application in oral health has not been comprehensively assessed. Dental caries is a transmissible disease initiated by acid production of cariogenic bacteria and yeast, such as Streptococcus mutans and Candida albicans, on tooth enamel and followed by subsequent enamel demineralization. Here, we investigated the effect of two Saccharomyces strains (Saccharomyces boulardii, Saccharomyces cerevisiae) on S. mutans-C. albicans cross-kingdom interactions using a cariogenic planktonic model. Viable cells, pH changes and gene expression were measured. S. cerevisiae and S. boulardii inhibited the growth of C. albicans either in dual-, or multi-species conditions. Saccharomyces also inhibited C. albicans hyphal formation. Furthermore, Saccharomyces reduced the acidity of the culture medium which usually plummeted below pH 5 when S. mutans and C. albicans were present in the model. The presence of Saccharomyces maintained the culture medium above 6 even after overnight incubation, demonstrating a protective potential against dental enamel demineralization. S. boulardii significantly downregulated S. mutans atpD and eno genes expression. Overall, our results shed light on a new promising candidate, Saccharomyces, for dental caries prevention due to its potential to create a less cariogenic environment marked by a neutral pH and reduced growth of C. albicans.

Prime numbers are the atoms of mathematics and mathematics is needed to make sense of the real world. Finding the Prime number structure and eventually being able to crack their code is the ultimate goal in what is called Number Theory. From the evolution of species to cryptography, Nature finds help in Prime numbers. One of the most important advances in the study of Prime numbers was the paper by Bernhard Riemann in November 1859 called “Ueber die Anzahl der Primzahlen unter einer gegebenen Grösse” (On the number of primes less than a given quantity). In that paper, Riemann gave a formula for the number of primes less than x in terms the integral of 1/log(x) and the roots (zeros) of the zeta function defined by: Where ζ(z) is a function of a complex variable z that analytically continues the Dirichlet series. Riemann also formulated a conjecture about the location of the zeros of RZF, which fall into two classes: the "trivial zeros" -2, -4, -6, etc., and those whose real part lies between 0 and 1. Riemann's conjecture Riemann hypothesis [RH] was formulated as this: [RH] The real part of every nontrivial zero z* of the RZF is 1/2. Proving the RH is, as of today, one of the most important problems in mathematics. In this paper we will provide a proof of the RH. The proof of the RH will be built following these five parts: PART 1: Description of the RZF PART 2: The C-transformation PART 3: Application of the C-transformation to in Re(z) 0 to obtain ζ(z)=X(z)-Y(z) PART 4: Analysis of the values of z such that X(z)=Y(z), and |X(z)|=|Y(z)|, that equates to ζ(z)=0 Proof that |X(z)|=|Y(z)| only if Re(z)=1/2 Conclude that ζ(z)=0 only if Re(z)=1/2 for Re(z) 0 PART 5: We will also prove that all non-trivial zeros of ζ(z) in the critical line of the form are not distributed randomly. There is a relationship between the values of those zeros and the Harmonic function that leads to an algebraic relationship between any two zeros.

Probiotics are living microbes that provide benefits to the host. The increasing data on health promotion following probiotics administration triggered growing interest among researchers and pharmaceutical companies looking for novel therapeutic or preventive tools. Infections of the lower genital tract in females are caused by a wide range of pathogens, they are widespread, and represent one of the main areas for the use of probiotics and postbiotics. Vulvovaginal candidiasis (VVC) affects 75% of women in their reproductive age at least once during their lifetime. Of these women 5-8% develop the recurrent form (RVVC). The disease onset is triggered by the overgrowth of Candida species on the vaginal mucosa. Here, we evaluated the beneficial properties of the Bacillus coagulans spore-producing LMG S-24828 against C. albicans and C. parapsilosis. Our results show that both alive B. coagulans and its Cell-Free-Supernatant (CFS) exerted antifungal activity against both fungi. Moreover, alive B. coagulans reduced hyphal formation, inhibited C. albicans adhesion to vaginal epithelial cells and showed co-aggregation capacity. Overall, B. coagulans LMG S-24828 exerted a protective effect on vaginal epithelial cells infected with C. albicans. These data suggest that B. coagulans LMG S-24828 may provide benefits in the context of Candida vaginal infections.

Modules composed of a resistance gene flanked by Xer site-specific recombination sites, the vast majority of which were found in Acinetobacter baumannii, are thought to behave as elements that facilitate horizontal dissemination. The A. baumannii xerC and xerD genes were cloned, and the recombinant clones used to complement the cognate Escherichia coli mutants. The complemented strains supported resolution of plasmid dimers, and, as is the case with E. coli and Klebsiella pneumoniae plasmids, the activity was enhanced when cells were growing in low osmolarity growth medium. Binding experiments showed that partially purified A. baumannii XerC and XerD proteins (XerC_Ab and XerD_Ab) bound synthetic Xer site-specific recombination sites, some of them with a nucleotide sequence deduced from existing A. baumannii plasmids. Incubation with suicide substrates resulted in covalent attachment of DNA to a recombinase, probably XerC_Ab, indicating that the first step in the recombination reaction took place. The results described show that XerC_Ab and XerD_Ab are functional proteins and support the hypothesis that they participate in horizontal dissemination of resistant genes among bacteria.

Diastolic dysfunction, a prevalent condition characterized by impaired relaxation and filling of the left ventricle, significantly contributes to heart failure with preserved ejection fraction (HFpEF). Galectin-3, a β-galactoside-binding lectin, has garnered attention as a potential biomarker and mediator of fibrosis and inflammation in cardiovascular diseases. This comprehensive review investigates the impact of galectin-3 on diastolic dysfunction. We explore its molecular mechanisms, including its involvement in cellular signaling pathways and interaction with components of the extracellular matrix. Evidence from both animal models and clinical studies elucidates galectin-3's role in cardiac remodeling, inflammation, and fibrosis, shedding light on the underlying pathophysiology of diastolic dysfunction. Additionally, we examine the diagnostic and therapeutic implications of galectin-3 in diastolic dysfunction, emphasizing its potential as both a biomarker and a therapeutic target. This review underscores the significance of comprehending galectin-3's role in diastolic dysfunction and its promise in enhancing diagnosis and treatment approaches for HFpEF patients.

Derelict asbestos mine sites in South Africa pose a considerable risk to human, environmental and socio-economic health. Comprehensive mineralogical and geochemical datasets for the existing hazardous geological materials still exposed in Southern African derelict asbestos mines remain largely non-existent, as very little published and up-to-date literature is available. In this study three representative types of asbestos mineral fibres from derelict asbestos mines in Southern Africa, namely chrysotile from Havelock mine, amosite from Penge mine and crocidolite from Prieska mine are characterized mineralogically and geochemically to critically evaluate real-life hazards in rural and asbestos-fibre contaminated regions. The samples were examined using polarising light microscopy, X-ray fluorescence (major and trace elemental analysis), X-ray diffraction (including Rietveld refinement), specific surface area analyses and bio-durability tests. Data are discussed in view of their potential toxicities on both human health and the environment in the context of developing countries. Finally, information on the mineralogical and geochemical status of asbestos mine waste and its importance as baseline data for rehabilitation considerations is also evaluated.

Euler’s product formula over the primes and Euler’s zeta function equate to enshrine the Fundamental Theorem of Arithmetic that every integer > 1 is the product of a unique set of primes. The product formula has no zero, and with a domain ≤1 Euler’s zeta diverges. Dirichlet’s eta function η(s), negates alternate terms of zeta, permitting convergence when s∈C and Re(s) < 1, and its non-trivial zeros {ρ}, have a deep relationship with the distribution of the primes. The Riemann Hypothesis is that all the non-trivial zeros have Re(ρ) = 1/2. This work examines the symmetries in a partial Euler’s zeta series with a complex domain equating it to the difference between two finite vector series whose matched terms have mirror-image arguments, but whose magnitudes differ when Re(s) ≠ 1/2. Analytical continuation generates a modified eta series η_l(s), in which every l^th term is multiplied by (1-l). If the integer l is appropriately determined by the Im(s), similar paired finite vector series have a difference that closely follows η_l (s) and their terminal vectors intersect in a unique way permitting zeros only when Re(s) = 1/2. Furthermore, those vectors tracking the derivatives of the series, have a special relationship permitting zeros of the differential only when Re(s) > 1/2.

Soils provide important regulating ecosystem services and have crucial implications for human well-being and environmental conservation. However, soil degradation and particularly soil erosion jeopardize the maintenance and existence of these services. This study explores the spatio-temporal relationships of soil erosion to understand the distribution patterns of sediment retention services in mainland Portugal. Based on Corine Land Cover maps from 1990 to 2018, the InVEST Sediment Delivery Ratio (SDR) model was used to evaluate the influence of sediment dynamics for soil and water conservation. Spatial differences in the sediment retention levels were observed within the NUTS III boundaries, showing which areas are more vulnerable to soil erosion processes. Results indicated that the Region of Leiria, Douro and the coastal regions have decreased importantly sediment retention capacity over the years. However, in most of the territory (77.52%) changes in sediment retention were little or not important (i.e., less than 5%). The statistical validation of the model proved the consistency of the results, highlighting the usefulness of this methodology to analyse the state of soil erosion in the country. These findings can be relevant to support strategies for more efficient land use planning regarding soil erosion mitigation practices.

In 2011, it was reviewed that there is a strong co-occurrence between major depression and chronic fatigue syndrome (CFS), with fatigue and physio-somatic symptoms being key symptoms of depression, and depressive symptoms appearing during the course of CFS. Moreover, the comorbidity between both conditions may in part be explained by activated immune-inflammatory pathways, including increased translocation of Gram-negative bacteria and increased levels of pro-inflammatory cytokines, such as interleukin (IL)-1. Nevertheless, the possible involvement of activated microglia in this comorbidity has remained unclear. This paper aims to review microglial disturbances in major depression, CFS and their comorbidity. A comprehensive literature search was conducted using the PubMed / MEDLINE database to identify studies that are relevant to this current review. Depressed patients present neuroinflammatory alterations, probably related to microglial activation, while animal models show that a microglial response to immune challenges including lipopolysaccharides is accompanied by depressive-like behaviors. Recent evidence from preclinical studies indicate that activated microglia have a key role in the onset of fatigue. In chronic inflammatory conditions, such as infections and senescence, microglia orchestrate an inflammatory microenvironment thereby causing fatigue. In conclusion, based on our review we may posit that shared immune-inflammatory pathways and activated microglia underpin comorbid depression and CFS and that activated microglia are the main orchestrators of this comorbidity. As such, microglial activation and neuro-inflammation may be promising targets to treat the overlapping manifestations of both depression and CFS.

. Protein cysteine S-glycosylation is a relatively rare and less well characterized post-translational modification (PTM). Creating reliable model proteins that carry this modification is challenging. The lack of available model or natural S-glycosylated proteins significantly hampers the development of MS-based methodologies for detecting protein cysteine S-glycosylation in real-world proteomic studies. There is also limited MS-sequencing data describing easier to create synthetic S-glycopeptides. Here, we present the results of an in-depth manual analysis of automatically annotated CID/HCD spectra for model S-glucopeptides. The CID spectra show a long series of y/b-fragment ions with retained S-glucosylation, regardless of the dominant m/z signals corresponding to neutral loss of 1,2-anhydroglucose from the precursor ions. In addition, the spectra show signals manifesting glucosyl transfer from the cysteine position onto Lys, Arg side chains, and a peptide N-terminus. Other spectral evidence indicates that the N-glucosylated initial products of transfer are converted into N-furanosylated (i.e., glycated) structures due to Amadori rearrangement. We discuss the peculiar transfer of the glucose oxocarbenium ion (Glc+) to positively charged guanidinium residue (ArgH+) and propose a mechanism for the gas-phase Amadori rearrangement involving a hydride ion shift.

Indirect effects of global change via changing species interactions have been largely ignored in studies predicting global change impacts on ecosystems. Antagonistic biotic interactions, however, can strongly affect ecosystems and are likely to be affected by global change drivers themselves. We synthesize current knowledge on the impact of invertebrate herbivores and pathogens on plant productivity, diversity and community composition, and outline theory and expectations on how important global change drivers – nitrogen enrichment, climate change and elevated CO², and plant and insect diversity loss, may affect enemy impact on plant communities. We illustrate that our ability to predict global change impact requires a holistic perspective, taking into account direct as well as indirect effects via the biotic component of ecosystems.

Bacillus Calmette-Guérin (BCG) vaccine is the only licensed vaccine against tuberculosis (TB) in humans and animals. It is most commonly administered parenterally but oral delivery is highly advantageous for immunisation of cattle and wildlife hosts of TB in particular. Since BCG is susceptible to inactivation in the gut, vaccine formulations were prepared from suspensions of Eudragit L100 copolymer powder and BCG in PBS, containing Tween 80, with and without the addition of mannitol or trehalose. Samples were frozen at -20oC, freeze-dried and the lyophilised powders were compressed to produce BCG-Eudragit matrices. Production of the dried powders resulted in a reduction in BCG viability. Substantial losses in viability occurred at the initial formulation stage and at the stage of powder compaction. Data indicated that the Eudragit matrix protected BCG against simulated gastric fluid (SGF). The matrices remained intact in SGF and dissolved completely in SIF within three hours. The inclusion of mannitol or trehalose in the matrix provided additional protection to BCG during freeze-drying. Control needs to be exercised over BCG aggregation, freeze-drying and powder compaction conditions to minimise physical damage of the bacterial cell wall and maximise the viability of oral BCG vaccines prepared by dry powder compaction.

Reuse of patterns is a self-evident approach for managing interoperability concerns. Although patterns for resolving interoperability barriers exist in the literature, no study exists on adoption of interoperability patterns by Geographic Information Systems (GIS) practitioners in industry. Thus there is limited understanding of pattern re-usability, yet the advantages offered by interoperability patterns provide a reasonably sound justification for their usage. This paper examines the adoption of proven interoperability best practices in the GIS industry. An empirical study that involved the use of semi-structured interviews was employed to gather data from GIS developers on domain interoperability best practices. Results indicated that industry and communities of practice have been converging on the technical level to ensure interoperability of GIS concerns. Semantic interoperability and related patterns are least understood, yet semantic barriers still exist. This is partly due to the complexity associated with the top-down approach used to develop semantic interoperability solutions. Therefore, this study proposes research into resolving barriers in the adoption of interoperability patterns that reduce complexity while solving semantic interoperability barriers.

Human-Computer Interaction, including technology-aided instruction, is beginning to focus on virtual reality (VR) technology due to its ability to support immersive learning, teaching through simulation, and gamification of learning. These systems can deliver high-level multisensory learning experiences that are important in the teaching of many subjects, especially those involving abstract concepts or requiring spatial skills, such as organic chemistry. Haptic experiences with VR, however, remain a challenge. In addition, development have focused on general entertainment/gaming; VR systems in chemistry implement simulations of the chemistry laboratory and other advanced systems whereas those that support safe, game-like, immersive and multisensory learning of organic chemistry with haptics at pre-university education levels are scarce. We developed the VR Multisensory Classroom (VRMC) as an immersive learning environment within a VR head-mounted display, where learners employ hand movements to build hydrocarbon molecules and experience haptic feedback through gloves with built-in sensors and hand-tracking with the Leap Motion system. We report here the evaluation of the first prototype by learners from diverse backgrounds who reported on the ability of the VRMC to support high engagement, motivation, interest and organic chemistry learning as well as diverse learning styles. The VRMC is a novel VR classroom that supports immersive learning in molecular organic chemistry with haptics for multisensory learning.

Fourteen (14) rack-mounted polycrystalline modules installed on the concrete roof of the solar energy applications laboratory at the Kwame Nkrumah University of Science and Technology (KNUST) in Ghana, a hot humid environment were assessed after 19 years of continuous outdoor expodure. The physical state of the modules was documented using a visual inspection checklist. They were further assessed by current-voltage (I-V) characterization and thermal imaging. The modules were found to be in good physical state, except some bubbles on front side and minor discolouration/corrosion at edge of the cells. Compared with reference values, the performance decline of the modules observed over the exposure period was: nominal power (P_nom), 21% to 35%; short circuit current (I_sc), 5.8% to 11.7%; open circuit voltage (V_oc) 3.6% to 5.6% and 11.9% to 25.7% for fill factor (FF). It is hoped that this study will provide some helpful information to project developers, manufacturers and the research community on the long-term performance of PV modules in Ghana.

The implementation of management systems has become a strategic advantage in achieving business goals, especially in industrial organizations, but the implementation of social responsibility requirements is especially ethical. Large multinational companies have long been developing and, in particular, implementing their own codes of conduct, which include their suppliers, to demonstrate their commitment to Corporate Social Responsibility (CSR). The compliance with CSR requirements from stakeholders is thus extended or intertwined with requirements in established management systems (MSs). The objectives of the study were to (1) analyze the different approaches to CSR in internationally recognized cross-industry and industry-specific standards and codes in different industries; (2) select the most appropriate framework for assessing the degree of applicability of CSR in the selected management systems and develop a methodology for its assessment; (3) apply the proposed methodology (referred to as SRIMS) in the selected areas: automotive industry, research organization, and metallurgical industry; (4) through ANOVA, validate its use for assessing the overall level of CSR applicability in an organization's established management systems. The application of the Bonferroni method confirmed the hypotheses that the developed SRIMS model is a sufficiently appropriate tool for assessing the overall level of applicability of CSR requirements to established MSs.

Products derived from Cannabis sativa have gained increased interest and popularity. As these products become common amongst the public, the heath and potential therapeutic values associated with hemp have become a premier focus of research. While the psychoactive and medicinal properties of Cannabis products have been extensively highlighted in literature, the antibacterial properties of CBD have not been explored in depth. This research serves to examine the antibacterial potential of CBD against Salmonella newington and Salmonella typhimurium. In this study we observed bacterial response to CBD exposure through biological assays, bacterial kinetics, and fluorescence microscopy. Additionally, comparative studies between CBD and ampicillin were conducted against Salmonella typhimurium and Salmonella newington to determine comparative efficacy. Furthermore, we observed potential resistance development of our Salmonella spp. against CBD treatment.

The severity and outcome of coronavirus disease 2019 (COVID-19) largely depends on a patient’s age. Over 80% of hospitalizations are of those over 65 years of age with a 23-fold greater risk of death. In the clinic, COVID-19 patients most commonly present with fever, cough and dyspnea. Particularly in those over 65, it can progress to pneumonia, lung consolidation, cytokine release syndrome, endotheliitis, coagulopathy, multiple organ failure and death. Comorbidities such as cardiovascular disease, diabetes, obesity and hypertension increase the chances of fatal disease, but they alone do not explain the variability in COVID-19 symptoms. Here, we present the molecular differences between the young, middle-aged and elderly that may determine whether COVID-19 is a mild or life-threatening illness. We also discuss several biological age clocks that could be used in conjunction with genetic tests to identify both the mechanisms of the disease and individuals most at risk. Finally, based on these mechanisms, we discuss treatments that could increase survival in the elderly, not simply by inhibiting the virus, but by restoring patients’ ability to clear the infection.

There is a large body of research on determining the impact of field variability of soil on crop yields. In contrast, site-specific information about crop responses to agronomic treatments is less frequent. On-Farm Precision Experimentation (OFPE) brings important information to understand the spatial variation of crop response to agronomic practices and thus to improve agronomic decisions. The objective of this work was to investigate the spatial variability of corn yield responses to nitrogen and seed rates using OFPE in four fields in the US Midwest. Geographically weighted regression was applied to generate local regression coefficients, which were used to delineate response zones in each field. The results showed the existence of great potential to adjust the rates of these inputs according to the response of each zone identified by the proposed method. The results of this study can be applied to reevaluate expectations on variable rate prescriptions guided largely by soil and variability.

Abstract: CRISPR/Cas systems are used for genome editing, both in basic science and in bio-technology. At the same time, CRISPR/Cas editors have several limitations, including insufficient specificity leading to "off-targets" and the dependence of activity on chromatin state. A number of highly specific Cas9 variants have been obtained now, but most of them are characterized by reduced activity on eukaryotic chromatin. We identified a spatial cluster of amino acid residues in the PAM-recognizing domain of Streptococcus pyogenes Cas9, whose mutations restore the activity of one of the highly specific forms of SpyCas9 without reducing its activity in Saccharomyces cere-visiae. In addition, one of these new mutations also increases the efficiency of SpyCas9-mediated editing of a site localized on the stable nucleosome. The improved Cas9 variants we obtained, which are capable of editing hard-to-reach regions of the yeast genome, may help in both basic research and yeast biotechnological applications.

We recently found that in human osteoblasts Homer1 complexes to CaSR and mediates AKT initiation via mTORC2 leading to beneficial effects in osteoblasts including -catenin stabilization and mTORC1 activation (doi: 10.1074/jbc.RA118.006587). Herein we further investigated the relationship between Homer1 and CaSR and demonstrate a link between the protein levels of CaSR and Homer1 in human osteoblasts in primary culture. Thus, when siRNA was used to suppress the CaSR, we observed upregulated Homer1 levels and when siRNA was used to suppress Homer1 we observed downregulated CaSR protein levels using immunofluorescence staining of cultured osteoblasts as well as western blot analyses of cell protein extracts. This finding was confirmed in vivo as the bone cells from osteoblast specific CaSR(-/-) mice showed increased Homer1 expression compared to wild-type. Furthermore, when the commonly used osteosarcoma cell lines MG63 and SAOS-2 were compared to primary osteoblasts, higher levels of Homer1 protein were associated with increased protein levels of the CaSR as well as mTOR and Rictor. CaSR and Homer1 protein were both expressed in osteocytes embedded in the long bones of wild-type mice, and immunofluorescent studies of these cells revealed that Homer1 protein sub-cellular localization was markedly altered in the osteocytes of CaSR(-/-) mice compared to wt. The study identifies additional roles for Homer1 in the control of the protein level and subcellular localization of CaSR in cells of the osteoblast lineage, in addition to its established role of mTORC2 activation downstream of the receptor.

This article reports new measurements of laser-induced plasma hypersonic expansion measurements of diatomic molecular cyanide (CN). Focused, high-peak power 1064-nm Q-switched radiation of the order of 1 TW/cm² generates optical breakdown plasma in a cell containing a 1:1 molar gas mixture of N₂ and CO₂ at a fixed pressure of 1.1 × 10⁵ Pascal and in a 100 ml/min flow of the mixture. Line-of-sight (LOS) analysis of recorded molecular spectra indicate the outgoing shockwave at expansion speeds well in excess of Mach number 5. Spectra of atomic carbon confirm an increased electron density near the shock wave, and equally, molecular CN spectra reveal higher excitation temperature near the shockwave. The results are consistent with corresponding high-speed shadow graphs obtained by visualization with an effective shutter speed of five n anosecond. In addition, LOS analysis and application of integral inversion techniques allow inferences about the spatio-temporal distribution of the plasma.

Poor therapeutic outcomes have been attributed to inter-individual and interethnic variability in cytochrome P450 (CYP450)-dependent metabolism and altered drug retention associated with P-glycoprotein (P-gp). An individualized pharmacotherapeutic approach would benefit the genetically diverse South African population. The study aim was to develop a validated, targeted, analytical method to quantify seven probe drugs and their metabolites in dried blood spots (DBS) using the Mitra™ volumetric absorptive micro-sampling device for blood collection. An Agilent liquid chromatography (LC) system coupled to a Sciex 4000 QTRAP tandem mass spectrometer (MS) was used for method optimization and validation. Targeted LC-MS/MS methods were validated according to ICH guidelines. The validated LC-MS/MS method met the required bioanalytical standards for specificity, sensitivity, linearity, accuracy, precision, carry-over, and stability. This study successfully validated the use of DBS, collected with the Mitra™ microsampling device, to measure expected probe drug and metabolite concentrations using the “Geneva phenotyping cocktail” for the purpose of simultaneous phenotyping of in vivo CYP450 metabolic activity of the CYP1A2, -2B6, -2C9, -2C19, -2D6, and -3A4 enzymes, and P-gp transport activity. However, statistical analysis using Bland-Altman plots showed that not all analytes exhibited linear distribution pharmacokinetics between DBS and plasma, which influenced the predicted vs real plasma concentrations based on measurements in a DBS matrix. These findings were attributed to the blood-to-plasma concentration ratio, the physicochemical properties and stability of the analytes, and the extraction efficiency of the Mitra™ sampler. More research is required before DBS sampling can be substituted for conventional plasma sampling

Quantum gravity theories rely on a minimal measurable length for their formulations, which clashes with the classical formulation of the uncertainty principle and with Lorentz invariance from general relativity. These incompatibilities led to the development of the generalized uncertainty principle (GUP) from string theories and its various modifications. GUP and covariant formulations of the uncertainty principle are discussed, together with implications for space-time quantization.

The present study examined music-induced dopamine release, as measured by a proxy measure of spontaneous eye blinks. Specifically, we explored the effects of uplifting and sombre tones in different sections of Vivaldi's Four Seasons to investigate the affective content of musical pieces within one composition. Seventeen participants listened to four concertos (Major modes: Spring, Autumn, Minor modes: Summer and Winter) and a silence condition while completing the 3-Stimulus Odd-ball attention task. Electrooculograms were recorded from electrodes placed above and under the left eye. Self-reported arousal and music preference measures were also gathered during the testing session. In addition, the P3a Event-Related Potential (ERP) component was analysed as another potential index of dopamine function. Results revealed significant differences in the blink rates during music listening and silence, with the largest effect observed for the sad, melancholic Winter concerto. However, no significant correlation was found between blink rate and music preference or arousal. Furthermore, no reliable association was found between blink rate and the P3a ERP component, suggesting that these measures tap into different aspects of dopamine function. These findings contribute to understanding the link between dopamine and blink rate, particularly in response to classical music. Crucially, the study's discovery that the Winter concerto, with its sorrowful tone, significantly increased the blink rate highlights the significance of sad music and perhaps the programmatic qualities of this concerto to induce a strong emotional response.

In this case series, we examine the impact of the Titan-iR Pro® deep spectrum biotherapeutic device on brain function in healthy individuals. Here we present 15 participants, aged 26-68 years, who enrolled in this open-label study, designed to assess the effect of a single 15-minute course of deep spectrum biotherapy on brain function. Although symptom-free upon enrollment, participants had diverse medical histories with some displaying early signs of cognitive decline. As part of the evaluation, all participants engaged in electroencephalogram (EEG) recording sessions that focused on assessing event-related potential (ERP) evaluations, including audio P300 amplitudes and latencies (speeds), neurocognitive testing, and physical reaction times. Following the Titan-iR Pro intervention an improvement in EEG-based cognitive markers was observed. These results underscore the importance of further investigation into the potential of advanced and deep spectrum photobiomodulation in the prevention and treatment of cognitive decline and other neurological disorders.

This paper shows the usage of a numerical analysis model which enables the calculation of the life of a railway wheels used for low-floor freight wagons as a function of its primary operating factors, which allows carrying out sensitivity analyses. Low-floor wagons are being increasingly used for combined transport applications and many types of bogies have been proposed in order to constitute the wagons. Due to the uniqueness of this type of wagons, the bogie configurations in terms of wheelbase and axle load have hardly been analyzed so far. The numerical analysis model used addresses the primary challenges that arise in the vehicle – track interaction and establish the relations among them. The main aspects of this model have been described in the paper, which has been later used to calculate the life of an ordinary-diameter wheel for several wheelbase and axle load values. This study has been replicated with reduced-diameter wheels, which are commonly used for low-floor wagons. In this way, it is possible to know the evolution of the life depending on the wheelbase and the axle load. The root causes underlying the observed behaviors can be explained by the entire understanding of the rolling phenomenon provided by the full analytical work.

The viewpoint and reaction of a country towards climate change are shaped by its political, cultural, and scientific backgrounds, in addition to the distinct characteristics of its evolving climate and the anticipated and actual consequences of the phenomenon in the times ahead. A region's climate has a significant impact on how water is managed and used, mostly in the primary sector (agroforestry systems, livestock, and agriculture), and both the distribution of ecosystem types and the amount and spreading of species on Earth. As a result, the environment and agricultural practices are affected by climate, so evaluating both distribution and evolution is extremely pertinent. Towards this aim, the climate distribution and evolution in the S. Francisco River basin (SFRB) is assessed in three periods (1970−2000, 1981−2022) in the past and 20412060 in the future from an ensemble of GCMs under two SSPs (Shared Socioeconomic Pathways), SSP2-4.5 and SSP5-8.5. The Köppen-Geiger (KG) climate classification system is analyzed, and climate change impacts are inferred for this watershed located in central-eastern Brazil, covering an area equivalent to 8% of the country. Results predict the disappearance of the hot-summer (Csa) and warm-summer (Csb) Mediterranean climates, and a reduction/increase in the tropical savanna with dry winter (Aw)/dry summer (As). A striking increase in the semi-arid hot (BSh-steppe) climate is predicted with a higher percentage (10%) under SSP5-8.5. The Source and the mouth of SFRB are projected to endure the major impacts of climate change that is followed by a predicted increase/decrease in temperature/precipitation. Future freshwater resource availability, and quality for human use will all be impacted. Consequences on ecosystems, agricultural and for the socioeconomic sectors within the SFRB might deepen the current contrasts between regions, urban and rural areas, and even between population groups, thus translating to a larger extent, the inequality that still characterizes Brazilian society. Maps depicting land use and cover changes in the São Francisco River basin from 1985 to 2022 highlight tendencies such as urbanization, agricultural expansion, deforestation, and changes in shrubland and water bodies. Urban areas fluctuated slightly, while cropland significantly increased from 33.57% to 45.45%, and forest areas decreased from 3.88% to 3.50%. Socioeconomic data reveals disparities among municipalities: 74.46% with medium Human Development Index (HDI), 0.59% with very high HDI, and 9.11% with low HDI. Most municipalities have a Gross Domestic Product (GDP) per capita below US$ 6,000. Population distribution maps show a predominance of small to medium-sized urban and rural communities, reflecting the basin's dispersed demographic and economic profile. To build routes towards a shared sustainable goal—namely, to adapt and reduce the expected climate change impacts in SFRB—it is imperative that integrated measures be conducted with the cooperation of stakeholders, local population, and decision-makers.

This article is about a framework for determining the degree of realism of any given 1 passenger ride motion discomfort measurement formula. After providing some context and reviewing 2 evidence of deficiency in currently popular ride motion discomfort measurement formulas, the article 3 outlines the research program that needs to be carried out in order to establish such a framework. 4 The research begins with gathering recordings of uncomfortable ride motion episodes encountered in 5 a chosen type of passenger transport service. It then has test subjects compare the episodes via a ride 6 motion simulator and adjust their amplitudes pair wise until they cause equal discomfort. It explains 7 how to take the pair wise amplitude adjustments and determine amplitude adjustments that bring all 8 of the motion episode recordings to a common level of discomfort so that they form a normalized set. 9 Then, the lower the scatter of the scores assigned by any given discomfort measurement formula to 10 the members of that set, the more realistic that formula will be for the chosen service.

We report on the role of synergistic polarization of Ba0.9Sr0.1TiO3 (BST) nanoparticles in sulfur cathodes to enhance the redox kinetics of polysulfides for high-capacity Li-S batteries. Ferroelectric nanoparticles are known to significantly improve the electrochemical performance of Li-S batteries due to their inherent self-polarization and high adsorption capacity towards polysulfides. X-ray diffraction spectra confirmed the tetragonal symmetry (c/a=1.0073), while Raman spectroscopic analysis validated the presence of tetragonal orientation Raman modes in BST-modified composites. Scanning electron microscope (SEM) images showed a homogeneous distribution of BST in the sulfur cathode system, with grain sizes ranging from 1 to 1.5 μm. Notably, the BST-coupled S50BST30CB10PVDF10 composite cathode achieved a capacity of approximately 820 mAh/g at 100 mA/g, maintaining stability over 100 cycles, demonstrating improved electrochemical performance. Two distinct plateaus between 2.3 V to 2.0 V and 2.0 V to 1.5 V further underscore the superior performance of BST ferroelectric nanoparticles in enhancing the redox kinetics of Li-S batteries. By leveraging the favourable affinity of polar substances towards polysulfides, we aimed to create a more stable reactive environment within the cathodic site, effectively trapping polysulfide intermediates through the synergistic polarization of BST nanoparticles. The synergistic polarization induced by the asymmetric crystal structure of ferroelectrics is anticipated to generate internal electric fields, enhancing chemisorption with heteropolar reactive. The observed high cyclic stability further validates the efficacy of these composite cathodes in mitigating the polysulfide shuttle effect, offering promising prospects for advancing Li-S battery technology.

Vertically aligned Fe, S, and Fe-S doped anatase TiO₂ nanotube arrays are prepared by electrochemical anodization process using an organic electrolyte in which lactic acid is added as an additive. In the electrolyte, nanotube layers of greater length (12 μm) and high order with inner diameter of approx. 90 nm and outer diameter of approx. 170 nm are achieved. Doping of Fe, S, and Fe-S via simple wet impregnation method substituted Ti and O sites with Fe and S, which leads to enhance the rate performance at high discharge current densities. Discharge capacities of TiO₂ tubes increased from 82 mAh g-1 (bare) to 165 mAh g-1 for Fe-S doped TiO₂ at high current densities of 0.3 mAcm-2 after 100 cycles with exceptional capacity retention of 85% after 100 cycles. Owing to the enhancement of thermodynamic and kinetic properties by doping of Fe-S, Li-diffusion increas2ed resulting in remarkable discharge capacities of 143 mAh g-1 and 89 mAh g-1 at a current density of 7.4 mA cm-2 and 19 mA cm-2, respectively.

Planning and implementation of construction projects are difficult processes and are burdened with many risk elements. The budget spread over time, which is developed on the basis of the schedule, presents the expected distribution of costs throughout the duration of the works, which during the implementation of the project is subject to constant changes resulting from time, cost and organizational factors. Managing construction contracts requires managers to be able to analyze on an ongoing basis the variances of production costs - from the values calculated in the offer cost estimate and assumed in the Budgeted Cost of Work Scheduled. The article attempts to analyze the emerging time and cost variances using proprietary C-S and S-C monitoring, based on simple indicators of the EVM method. An example of construction of a multi-family housing development was used to study the variances of planned and incurred costs.

This paper investigates the feasibility of a backend design for real-time, multiple-channel processing digital phased array system, particularly for high-performance embedded computing platforms constructed of using general purpose digital signal processors. Frist, we obtained the lab-scale backend performance benchmark from simulating beamforming, pulse compression, and Doppler filtering based on MicroTCA chassis using Serial RapidIO protocol in backplane communication. Next, a field-scale demonstrator of a multifunctional phased array radar is emulated by using the similar configuration. Interestingly, the performance of a barebone design is compared to that of emerging tools that systematically take advantage of parallelism and multicore capabilities, including Open Computing Language.

Novolac phenol-formaldehyde resins have gained extensive commercial utilization across diverse applications due to their exceptional mechanical, thermal, and chemical resistance properties. In this investigation, we successfully synthesized a traditional novolac, and a biobased novolac phenol-formaldehyde resin by partially substituting phenol with a bio-oil obtained from the organic phase resulting from the fast pyrolysis of pinewood biomass. Despite extensive investigations into the curing behavior of novolac resins crosslinked with hexamethylenetetramine (HMTA) through numerous model-fitting cure kinetic studies, a comprehensive model for predicting the crosslinking of bio-based phenol-formaldehyde resins in the presence of HMTA has not yet been studied. The primary objective of this research was to compare and apply several commonly used kinetic models to predict the degree of curing and cure rate of the synthesized resins, using DSC dynamic measurements. Our results demonstrated that the autocatalytic model exhibited excellent fitting for the traditional novolac resin and HMTA mixture, while the Kamal model showed better fitting with the experimental data obtained for the bio-based phenol-formaldehyde resin and HMTA system. In addition, the results evidenced a significant drop in the curing temperature by partially replacing phenol with bio-oil. Additionally, the results revealed a notable reduction in curing temperature when phenol was partially substituted with bio-oil. This substitution not only offers environmental benefits but also promotes energy efficiency and enhances production safety. The data collected in this study is pivotal for our subsequent research endeavors, which aim to develop environmentally sustainable materials optimized for use in 3D printing manufacturing processes.

In this systematic review, the PRISMA method was applied to examine publications from the last two decades that have investigated the noxious gaseous emissions from dairy barns. The aim was to analyse the outcomes from literature studies estimating the quantities of polluting gases produced in dairy barns, with specific focus on ammonia (NH₃) emissions. The review also explores proposed methods to reduce the associated effects through mitigation strategies. Estimation of NH₃ emissions is significantly influenced by the complex interactions among several factors, including animal management practices, such as controlling animal behavioral activities; manure management, like utilising practices for floor manure removal; the type of structure housing the animals, whether it is naturally or mechanically ventilated; and environmental conditions, such as the effects of temperature, wind speed, relative humidity, and ventilation rate on NH₃ release in the barn. These influential components have been considered by researchers, identifying targeted mitigation strategies. Despite growing attention to the issue, gaps in the scientific literature were identified and discussed, particularly regarding the analysis of mitigation strategies and their long-term impacts (i.e., environmental, economic and productivity-wise).

Protected areas have been used worldwide to conserve natural resources. Nevertheless, economic activities to provide income for communities living inside and surrounding conservation areas remain an issue. This study aimed to assess the sustainability of a Deuterodon iguape hatchery, placed inside an Atlantic Rainforest Park, to leverage this small native fish's grow-out farming, affording income and food security for local families. We have used a set of indicators of economic, social, and environmental sustainability. The initial investment is about US$ 40,000, which returned in ~2 years. The internal rate of return is close to 50%, including the externality costs, which is attractive for public and private investments. The hatchery generated few direct jobs, but the workforce can be recruited in the community, and hatchery can enable the establishment of several small grow-out farms, leveraging the development of indirect jobs and self-employments. The system had a low environmental impact, showing minor release of pollutants, low risk for biodiversity, and absorption of 18 g of CO2 equivalent per thousand post-larvae produced, contributing to the struggle against climate change. Therefore, D. iguape hatchery demonstrates the potential of combining biodiversity conservation and income generation, meeting the Sustainable Development Goals of Agenda 2030.

The objective of this work was to investigate the use of remotely sensed vegetation indices to improve the quality of yield maps. The method was applied to the yield data of twelve cornfields from the Data Intensive Farm Management project. The results revealed the need to time shift the yield values up to three seconds to better match the sensor readings with the geographic coordinates. The residuals of the yield prediction model were used to identify points with unlikely yield values for that location, as an alternative to traditional approaches using local spatial statistics, without any assumption of spatial dependence or stationarity. The temporal and spatial distribution of the standardized coefficients for each experimental unit highlighted the presence of trends in the data. At least five out of the twelve fields presented trends that could have been induced by data collection.

Bacterial nitroreductase enzymes that convert prodrugs to cytotoxins are valuable tools for creating transgenic targeted ablation models to study cellular function and cell-specific regeneration paradigms. We recently engineered a nitroreductase (“NTR 2.0”) for substantially enhanced reduction of the prodrug metronidazole, which permits faster cell ablation kinetics, cleaner interrogations of cell function, ablation of previously recalcitrant cell types, and extended ablation paradigms useful for modelling chronic diseases. To provide insight into the enhanced enzymatic mechanism of NTR 2.0, we have solved the X-ray crystal structure at 1.85 Angstroms resolution and compared it to the parental enzyme, NfsB from Vibrio vulnificus. We additionally present a survey of reductive activity with eight alternative nitroaromatic substrates, to provide access to alternative ablation prodrugs, and explore applications such as remediation of dinitrotoluene pollutants. The predicted binding modes of four key substrates were investigated using molecular modelling.

The COVID-19 pandemic over the past years has shown a great need for rapid, low-cost and on-site detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this paper, an aptamer-based colloidal gold nanoparticle lateral flow test strip was well developed to realize the visual detection of wild type SARS-CoV-2 spike protein (SP) and multiple variants. Under the optimal reaction conditions, a low detection limit of SARS-CoV-2 S protein of 0.68 nM was acquired, and the actual detection recovery was 83.3% to 108.8% for real world samples. This suggests a potential tool for the prompt detection of SARS-CoV-2 with good sensitivity and accuracy, and a new method for the development of alternative antibody test strips for the detection of other viral targets.

We report on the occurrence of natural Magnesium Alumina Silicate Hydrate (M-(A)-S-H) cement at Feragen and Leka in eastern and western Trøndelag Norway, respectively. Both occurrences are located in the sub-arctic climate zone and form in glacial till and moraine material deposited on ultramafic rock during the Weichselian glaciation. Weathering of serpentinized peridotite dissolve brucite and result in a relative high pH alkaline fluid that subsequently reacts with the felsic minerals of the till (quartz, plagioclase, K-feldspar) to form a cement consisting of an amorphous material or a mixture of nanocrystalline Mg-rich phyllosilicates, including illite. The presence of plagioclase in the till results in the enrichment of alumina in the cement, i.e., forms M-A-S-H instead of the M-S-H cement. Dissolution of quartz results in numerous etch-pits and negative quartz crystals filled with M-A-S-H cement. Where the quartz dissolution is faster that the cement precipitation, a honeycomb-like texture is formed. Compositionally the cemented till (tillite) contains more MgO and has a higher loss of ignition than the till, suggesting that the cement is formed by a MgO fluid that previously reacted with the peridotite. The M-(A)-S-H cemented till represent a new type of duricrust, coined magsilcrete. The study of natural Mg-cement provides information on peridotites as a Mg-source for Mg-cement and as a feedstock for CO2 sequestration.

There is increasing interest in identifying biological and imaging markers for the early detection of neurocognitive decline. In addition, non-pharmacological strategies including physical exercise and cognitive interventions may be beneficial for those developing cognitive impairment. The Feuerstein Instrumental Enrichment (FIE) Program is a cognitive intervention based on Structural Cognitive Modifiability and the Mediated Learning Experience (MLE) and aims to promote problem-solving strategies and metacognitive abilities. The FIE program uses a variety of instruments to enhance the cognitive capacity of the individual as a result of mediation. A specific version of the FIE program was developed for the cognitive enhancement of older adults, focusing on strengthening orientation skills, categorization skills, deductive reasoning and memory. We performed a prospective interventional pilot observational study on older subjects with MCI who participated in 30 mediated FIE sessions (two sessions weekly for 15 weeks). Of the 21 subjects who completed the study, there was a significant improvement in memory on the Neurotrax battery comparing pre- and post-intervention scores (pre: M=95.3, SD=12.2, post: M=101.2, SD=7.9, p<.05). Complete sets of anatomical MRI data for voxel-based morphometry, taken at the beginning and the end of the study, were obtained from 16 participants (mean age 83.5 years). Voxel-based morphometry showed an unexpected increase in grey matter (GM) in the anterolateral occipital border and the middle cingulate cortex. These initial findings of our pilot study support the design of randomized trials to evaluate the effect of cognitive training using the FIE Program on brain volumes and cognitive function.

This note first summarizes the history of the manuscript "On a Continuum Model for Avalanche Flow and Its Simplified Variants" by Grigorian and Ostroumov―published in the Special Issue on snow avalanche dynamics of Geosciences―since the early 1990s and explains the guiding principles in editing it for publication. The changes are then detailed and some explanatory notes given for the benefit of readers who are not familiar with the early Russian work on snow avalanche dynamics. Finally, the editor's personal views as to why he still considers this paper of relevance for avalanche dynamics research today are presented in brief essays on key aspects of the paper, namely the role of simple and complex models in avalanche research and mitigation work, the status and possible applications of Grigorian's stress-limited friction law, and non-monotonicity of the dynamics of the Grigorian–Ostroumov model in the friction coefficient. A comparison of the erosion model proposed by those authors with two other models suggests to enhance it with an additional equation for the balance of tangential momentum across the shock front. A preliminary analysis indicates that continuous scouring entrainment is possible only in a restricted parameter range and that there is a second erosion regime with delayed entrainment.

The present Feature Paper highlights the application of bacterial surface (S-) layer proteins as versatile components for the fabrication of biosensors. One technologically relevant feature of S‑layer proteins is their ability to self-assemble on many surfaces and interfaces to form a crystalline 2D protein lattice. The S-layer lattice on the surface of a biosensor becomes part of the interface architecture, linking the bioreceptor to the transducer interface, which may cause signal amplification. The S-layer lattice as ultrathin, highly porous structure with functional groups in a well-defined special distribution and orientation and an overall anti-fouling characteristics can significantly raise the limit in terms of variety and ease of bioreceptor immobilization, compactness of bioreceptor molecule arrangement, sensitivity, specificity, and detection limit for many types of biosensors. The present paper discusses and summarizes examples for the successful implementation of S-layer lattices on biosensor surfaces in order to give a comprehensive overview on the application potential of these bioinspired S-layer protein-based biosensors.

This study investigates the impact of vertical greenery systems (VGS) applied to heavyweight walls on indoor thermal conditions in a building module situated in the Mediterranean climate of Catania, Italy. Using dynamic simulations in TRNSYS, the research compares the thermal behavior of walls constructed from hollow clay blocks (Poroton) and lava stone blocks with a lightweight wall setup already in place at the University of Catania. The primary focus is on evaluating the VGS’s effect on reducing peak inner surface temperatures and moderating heat flux fluctuations entering the building. The findings indicate that adding a vertical greenery layer to heavyweight walls can decrease the peak inner surface temperature by up to 1.0°C compared to the same wall without vegetation. However, the greenery’s impact on mitigating heat flux fluctuations is less pronounced than in the case of the lightweight wall. This research underscores the potential of green facades in enhancing indoor thermal comfort in regions with climates similar to the Mediterranean, providing valuable insights for sustainable building design and urban planning.

Wastewater-Based Epidemiology (WBE) is currently used to monitor not only the spread of the pandemic virus SARS-CoV-2 but also for other viruses in endemic conditions, particularly in the absence of syndromic surveillance. Continuous monitoring of sewage requires high costs and significant time investment, highlighting the need for standardized methods and structured monitoring strategies. In this context, we conducted weekly wastewater monitoring in northwestern Italy, targeting Human Adenovirus (HAdV), Norovirus Genogroup II (NoVggII), Enterovirus (EV), and SARS-CoV-2. Samples collected at the entrance of treatment plants were concentrated using PEG/NaCl precipitation and viral nucleic acids were extracted and detected by real-time (RT-)qPCR. NoVggII resulted the most identified target (84.4%), followed by HAdV, SARS-CoV-2, and EV. Only HAdV and EV exhibited seasonal peaks in spring and summer. SARS-CoV-2 results compared with data previously collected in the same study area (February 2021 to September 2021) revealed a shift from an epidemic to a pandemic status, likely due to the evolution of variants. In conclusion, WBE, using standardized methods and an efficient monitoring strategy, proves valuable for virus surveillance in pandemic and epidemic scenarios, enabling the identification of temporal-local distribution patterns that are useful for making informed public health decision.

A land cover map of two arctic catchments, nearby the Abisko Scientific Research Station, was obtained from a classification of a Sentinel-2 satellite image and a ground survey performed in July 2022. The two contiguous catchments, Miellajokka and Stordalen, are covered by various ecotypes, from boreal forest to alpine tundra and peatland. The Random Forest algorithm correctly identified 83% of polygon pixels reserved for testing. The developed workflow relied solely on open source software and acquired ground observations. Space organization was directed by the altitude as shown by the intersection of the land cover with the topography. Comparison between this new land cover map and previous ones based on data acquired between 2008 and 2011 demonstrates some trends of vegetation cover evolution in response to climate change in the considered area. The potential applications in terms of permafrost modeling (hiperborea.omp.eu) are finally discussed.

Technological advances in the last decades have led to the realization of the concept of a smart environment. A significant part of this development is decentralized ledger technology and its variant, a blockchain. The blockchain database is immutable, open to all stakeholders, secure by architecture and robust. Applying a blockchain in water supply sanitary control creates opportunities for optimization, higher quality of service, cost reduction, better sanitary standards and public control. Physical, chemical, and biological water supply contamination is a great source of public health hazards. Implementation of a blockchain for water supply IoT, from the source point to the consumption point, enables effective response to changing environments, possible cross-contamination, stormwater management or disaster and emergency action. The chapter encompasses all fundamental elements and principles of water collection, distribution and consumption, with a focus on the health hazards and sanitary requirements for potable water. The chapter listed the main contaminants, methods of their registration and elimination, and requirements for drinking water in accordance with WHO, EU Drinking Water Directive and EPA standards. Blockchain technology solutions are described for smart water supply, including smart supply management, smart contracts, tokenization, smart compliance systems, and, most importantly, effective utilization of distributed ledger technologies for sanitary monitoring of water sources, water treatment, and water distribution systems.

Emerging pollutants pose significant threats to Uganda's ecosystems and public health amidst rapid urbanization, industrial growth, and intensified agriculture. This systematic review comprehensively assessed these pollutants by analyzing existing Ugandan literature and research studies, revealing various types in different environmental compartments. These pollutants, including pharmaceuticals, personal care products, pesticides, industrial chemicals, heavy metals, radionuclides, biotoxins, disinfection byproducts, hydrocarbons, and microplastics, originate from urban, industrial, and agricultural regions. Wastewater and improper waste disposal are major contributors. From an initial search of 794 articles across multiple databases such as PubMed, African Journal Online (AJOL), Web of Science, Science Direct, and Google Scholar, 138 were found relevant. The review underscores potential ecological and health impacts, including antibiotic resistance, endocrine disruption, and carcinogenicity. Existing monitoring and regulation efforts are discussed, alongside the need for specific regulations, improved data collection, and public awareness campaigns. Recommendations include advanced wastewater treatment, sustainable agriculture, and source control measures. Emphasis is placed on further research to address knowledge gaps and develop effective policies and interventions. Uganda can mitigate these risks by implementing comprehensive monitoring, robust regulations, and sustainable practices, safeguarding the environment and public health.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a devastating illness whose biomedical basis is now beginning to be elucidated. We reported previously that, after recovery from frozen storage, lymphocytes (peripheral blood monocytic cells, PBMCs) from ME/CFS patients die faster in culture medium than those from healthy controls. We also found that lymphoblastoid cell lines (lymphoblasts) derived from these PBMCs exhibit multiple abnormalities in mitochondrial respiratory function and signalling activity by the cellular stress-sensing kinase TORC1. These differences were correlated with disease severity, as measured by the Richardson and Lidbury Weighted Standing Test. The clarity of the differences between these cells derived from ME/CFS patient blood and those from healthy controls suggested that they may provide useful biomarkers for ME/CFS. Here we report a preliminary investigation into that possibility using a variety of analytical classification tools, including linear discriminant analysis, logistic regression and Receiver Operating Characteristic (ROC) curve analysis. We found that results from three different tests, lymphocyte death rate, mitochondrial respiratory function and TORC1 activity could each individually serve as biomarker with better than 90% sensitivity but only modest specificity vís a vís healthy controls. However, in combination they provided a cell-based biomarker with sensitivity and specificity approaching 100% in our sample. This level of sensitivity and specificity was almost equalled by a suggested protocol in which the frozen lymphocyte death rate was used as a highly sensitive test to triage positive samples to the more time consuming and expensive tests measuring lymphoblast respiratory function and TORC1 activity. This protocol provides a promising biomarker that could assist in more rapid and accurate diagnosis of ME/CFS.

The current disruptive innovation model has a limitation in incorporating customers’ demands while the customer can be a co-creator of value on performance, design, and price innovation. Thus, this research attempted to explore the disruptive innovation model which can include both the incumbent’s innovation trajectory and customer’s demand, and how incumbents behave to enable disruptive innovation in the smartphone market. Based on the Apple iPhone case study, this study verified that the current disruptive innovation model can incorporate customers’ demand by reflecting their demand in the direction of innovating the performance, design, or price of smartphones with the price-adjusted innovation trajectory. The secondary innovation trajectory which was found uniquely in this study is meaningful since it can be a creative solution for the innovator’s dilemma. Besides, Apple, as an incumbent, has behaved to innovate iPhone performance and design demands of customers creating significant papers and patents as outcomes of innovation activities. This study has practical implications for incumbents’ managers as well as customers to enable disruptive innovation in the smartphone market.

Nowadays, the identification and characterization of grapevine cultivars resilient to climate and water stress while preserving quality traits is crucial for the wine industry. Therefore, the objective of this work was to characterize according to their aromatic potential 9 white and 6 red minority cultivars recently recovered from Castilla-La Mancha region (Spain), subjected at two different water deficit regimes: rainfed, with subsistence irrigation, and irrigated. For this, the varietal aromatic potential index (IPAv) and the detailed aromatic composition were analyzed by HS-SBSE-GC/MS, in extracts of two different ph. For IPAv values, red varieties did not show a clear trend with respect to irrigation. However, in white minority varieties, higher values were obtained under irrigation conditions. Thus, a clear differentiation of the minority varieties in comparison to the references was observed, primarily attributed to the content of esters and acids, in both white and red varieties. A notable contrast was observed at different pH, indicating a greater extractability of certain compounds like linalool, under more acidic conditions. This suggests that some recovered minority cultivars could be promising for cultivation in semi-arid regions with limited water, contributing to the wine sector sustainability in the future.

Let R be a commutative graded ring with unity, S be a multiplicative subset of homogeneous elements of R and P be a graded ideal of R such that P\bigcap S=\emptyset In this article, we introduce several results concerning graded S-prime ideals. Then we introduce the concept of graded weakly S-prime ideals which is a generalization of graded weakly prime ideals. We say that P is a graded weakly S-prime ideal of R if there exists s\in S such that for all x, y\in h(R), if 0\neq xy\in P, then sx\in P or sy\in P. We show that graded weakly S-prime ideals have many acquaintance properties to these of graded weakly prime ideals.

This paper shows the development of a numerical analysis model which enables the calculation of the life of a reduced-diameter wheel used for freight wagons as a function of its operating factors. Reduced-diameter wheels are being increasingly used for combined transport applications and they can be arranged in a wide range of bogies and operated very differently. Due to the uniqueness of this type of wheels, their life has hardly been analyzed so far. To properly construct the numerical analysis model, it has been necessary to study the rolling phenomenon in-depth, tackle the main problems arising in the vehicle – track interaction and set the relations amongst them. Once the rail-wheel interaction model was built, it was used to calculate the life of an ordinary-diameter wheel, a medium-diameter wheel and a reduced-diameter wheels under the same conditions and compare them. In this way, it is possible to know how long the life of a reduced-diameter wheel is compared to that of an ordinary-diameter one and also the evolution of the life depending on the diameter. The root causes responsible for this evolution can be explained thanks to the comprehension of the rolling phenomenon provided by the full analytical work.

Neuromuscular adverse events following cancer treatment with anti-programmed cell death protein 1 (PD-1) monoclonal antibodies are relatively rare, yet potentially fatal. Using the PRISMA approach, we performed a systematic review to characterize the clinical presentation, diagnostic workup, and management of neuromuscular disorders (NMDs) in patients treated with nivolumab or pembrolizumab. Sixty-three publications on 85 patients (mean age 66,9 years (range 34–86); male/female 2.6:1; 59% metastatic melanoma) were identified from selected indexing databases until June 2018. Forty-eight patients had received nivolumab and 39 pembrolizumab. The mean number of PD-1 inhibitor treatment cycles prior to onset of symptoms was 3,6 (range 1–28). Symptoms included oculomotor (47%); respiratory (43%), bulbar (35%), and proximal weakness (35%); as well as muscle pain (28%). Diagnoses were categorized as myasthenia gravis (27%), neuropathy (23%), myopathy (34%) and a combination of these (16%). After critical review of the data, however, evidence did not support the stated NMD diagnosis in 13% of cases, while up to 14% of patients had signs of additional NMDs. PD-1 inhibitor associated myasthenia was associated with cardiac complications in almost 30% of patients and with a more rapid clinical progression compared with idiopathic myasthenia. Mortality was high despite adequate treatment strategies including corticosteroid, IV immunoglobulins and plasmapheresis. In conclusion, clinical presentation of NMDs associated with PD-1 inhibitors is often atypical, with significant overlap between myasthenia gravis and myopathy; and cardiac/respiratory complications are common, leading to more severe disease courses than idiopathic myasthenia.

Mallios and Zafiris emphasize that adjoint functors or adjunctions are not only "ubiquitous" in category theory but characterize the naturality of their approach to physical geometry. Hence in this paper, the history and theory of adjoint functors is investigated. Where do adjoint functors come from mathematically and how did the concepts develop historically?

Climate change has significant impacts on the distribution of orchids. The endemic and endan-gered orchids are more susceptible to climate change than widely distributed orchids. To date, lit-tle is known concerning the response of endangered Changnienia amoena, endemic to China, to different climate scenarios. Here, we chose RF, MaxEnt, and GBM to build an ensemble model af-ter using ten models from Biomod2 to project its potential distribution in China. The outcomes showed that the four key environmental factors influencing its distribution were mean diurnal temperature range, minimum temperature of the coldest month, temperature seasonality, and precipitation of the warmest quarter. This orchid was mainly distributed in western Hubei, the junction between Shaanxi and Sichuan, eastern Guizhou, northwestern Hunan, and the junction among Anhui, Henan, and Hubei provinces in the current. The total suitable area of C. amoena was 58.33 × 104 km2, only accounting for 6.08% of China's total territory, which is larger than known. However, only 4.48% of the suitable area is located within national nature reserves, and 3.33% within provincial nature reserves, respectively. During the Last Inter Glacial and mid-Holocene, its suitable areas were larger than the current. Under six future climate scenarios, its suitable areas may averagely decrease by 2.26% relative to the current, with severe habitat fragmentation. Col-lectively, the centroid of C. amoena is expected to migrate towards the southeast in the future. Therefore, our findings demonstrate that climate change takes an adverse effect on its potential distribution. We recommend expanding protected areas or establishing new conservation sites for C. amoena. Furthermore, our study can help to inform the development of conservation manage-ment strategies for other endangered orchids in China under climate change.

Testicular heat stress is a well described phenomenon that occurs in mammals that possess a scrotum. Different models to induce testicular hyperthermia, such as surgical cryptorchidism, hot water bath, scrotal insulation or increased environmental temperature have all shown that spermatocytes and spermatids are unambiguously affected by high temperature, resulting in poor sperm production weeks later. Furthermore, a body of evidence suggest the involvement of oxidative stress is either a major or contributory pathway, which gives rise to the potential to overcome this condition. Whilst experimental models conclusively show the deleterious effect of testicular heat on sperm quality, the physiological relevance of the work is still debated. Herein we summarise a cohort of studies that report the effect of “season” on sperm quality. The data show season can affect sperm production, motility and morphology depending on where the work was performed. In countries where temperatures drop below zero, there is evidence showing summer conditions tend to improve semen quality. However, in sub-tropical countries, some studies show a decrease in summer, whilst others show no change. Herein we offer a reasonable explanation for this apparent controversy and present a range of antioxidant supplements that may offer some protection against testicular hyperthermia.

There are limited proven therapies for the treatment of COVID-19. Vitamin C’s antioxidant, anti-inflammatory and immunomodulating effects, make it a potential therapeutic candidate, both for the prevention and amelioration of COVID-19 infection, and as an adjunctive therapy in the critical care of COVID-19, supporting anti-inflammatory treatment. This literature review focuses on vitamin C deficiency in respiratory infections including COVID-19; the mechanism of action in infectious disease and adrenal function supporting the anti-inflammatory actions of glucocorticosteroids: its role in preventing and treating colds and pneumonia and its role in treating sepsis and COVID-19. The evidence to date indicates that oral vitamin C (2-8g/d) may reduce incidence and duration of respiratory infections and intravenous vitamin C (2-24g/d) has been shown to reduce mortality, Intensive Care Unit and hospital stays, time on mechanical ventilation in severe respiratory infections. Further trials are urgently warranted. Given the favourable safety profile and low cost of vitamin C, and frequency of vitamin C deficiency in respiratory infections it may be worthwhile testing patients’ vitamin C status and treating accordingly with intravenous use within ICUs and orally with doses between 2 and 8g/day in hospitalised and infected persons.

SARS-CoV-2 is a novel betacoronavirus and the aetiological agent of the current COVID-19 outbreak that originated in Hubei Province, China. While polymerase chain reaction is the front-line tool for SARS-CoV-2 surveillance, application of amplification-free and culture-free methods for isolation of SARS-CoV-2 RNA, partnered with next-generation sequencing, would provide a useful tool for both surveillance and research of SARS-CoV-2. We here release into the public domain a set of bait capture hybridization probe sequences for enrichment of SARS-CoV-2 RNA from complex biological samples. These probe sequences have been designed using rigorous bioinformatics methods to provide sensitivity, accuracy, and minimal off-target hybridization. Probe design was based on existing, validated approaches for detecting antimicrobial resistance genes in complex samples and it is our hope that this SARS-CoV-2 bait capture platform, once validated by those with samples in hand, will be of aid in combating the current outbreak.