Small molecule kinase inhibitors (SMKIs) are one of the heightened concerns in the field of drug research and development. There are seventy-nine (up to July 2023) small molecule kinase inhibitors have been approved by FDA and hundreds kinase inhibitors candidates in clinical trials, which shed light on the treatment of some major diseases. As an important strategy of drug design, computer-aided drug design (CADD) plays an indispensable role in the discovery of SMKIs. CADD methods, such as docking, molecular dynamic, pharmacophore have been applied to the design and optimization of small molecule kinase inhibitors. In the review, we provide an overview of recent advances in CADD and SMKIs; and the application of CADD for discovery of SMKIs.

Appropriate use of perioperative antimicrobials can significantly reduce the risk of postoperative infections. However, inappropriate antimicrobial use can result in the creation of multidrug resistant bacteria, increased costs, host flora disruption, side effects, and increased risk of hospital-acquired infections This survey evaluated the current perioperative use of antimicrobials in small animals by Spanish veterinarians using a web-based questionnaire. Responses were represented using descriptive statistics and a statistical analysis of the association between demographic data and perioperative antimicrobial use was performed. Preoperative antimicrobials were administered in clean surgery by up to 68.3% of participants, 81.0% in clean-contaminated surgery and 71.3% in dirty surgery, while in the postoperative period, antimicrobials were administered by up to 86.3% of participants in clean surgery, 93.2% in clean-contaminated surgery and 87.5% in dirty surgery. Factors considered “very important” for antimicrobial selection were the degree of wound contamination, patient immunosuppression, and use of prosthesis. The most frequently used antimicrobial was beta-lactamase-resistant penicillin. Postoperative antimicrobial use was associated with participants without postgraduate training. This study highlights an overuse of antimicrobials in perioperative procedures in small animal surgery in Spain. Therefore, evidence-based guidelines and further education regarding the correct use of antimicrobial prophylaxis are recommended.

Traditional camera sensors rely on human eyes for observation. However, the human eye 1 is prone to fatigue when observing targets of different sizes for a long time in complex scenes, and 2 human cognition is limited, which often leads to judgment errors and greatly reduces the efficiency. 3 Target recognition technology is an important technology to judge the target category in camera 4 sensor. In order to solve this problem, a small size target detection algorithm for special scenarios was 5 proposed by this paper. Its advantage is that this algorithm not only has higher precision for small 6 size target detection, but also can ensure that the detection accuracy of each size is not lower than the 7 existing algorithm. In this paper, a new down-sampling method was proposed, which could better 8 preserve the context feature information. The feature fusion network was improved to effectively 9 combine shallow information and deep information. A new network structure was proposed to 10 effectively improve the detection accuracy of the model. In terms of accuracy, it is better than: YOLOX, 11 YOLOXR, YOLOv3, scaled YOLOv5, YOLOv7-Tiny and YOLOv8.Three authoritative public data sets 12 were used in this experiment: a) On Visdron data sets (small size targets), DC-YOLOv8 is 2.5% more 13 accurate than YOLOv8. b) On Tinyperson data sets (minimal size targets), DC-YOLOv8 is 1% more 14 accurate than YOLOv8. c) On PASCAL VOC2007 data sets (Normal size target), DC-YOLOv8 is 0.5% 15 more accurate than YOLOv8.

We develop the theory of Heyting small spaces and prove a new version of Esakia duality for such spaces. To do this, we notice that spectral spaces may be seen as sober small spaces with all smops compact and introduce the method of the standard spectralification. This helps to understand open continuous definable mappings between definable spaces over o-minimal structures.

The accumulation of process waste in the production line causes fluctuations, bottlenecks, and increased inventory in workstations disrupting process flow. In this paper, the aim is the use a simulated value stream mapping (SVSM) as a lean assessment tool for decision-making in the continuous improvement process to influence and provide consideration and consistency on productivity improvement in the production system. The proposed methodology applied discrete event simulation for production process operations improvement to eliminate non-value adding times and provides good quality products at the lowest cost and highest efficiency. The results are the analysis of the current state of the production system in a South African truck manufacturing industry small and medium enterprise (SMEs) as a potential solution for the production system future state. The identified non-value adding times in the 6 most critical workstations was eliminated by SVSM which resulted in a productivity improvement of 4%, most importantly bringing the productivity to 95% and total cycle time improvement to 451 for small units and 466 for large units. The results proposed combined VSM and Simulation techniques which enhance the LEAN application by DES to increase productivity and performance improvement to remain competitive in the global economy.

Although researchers have investigated widely the impact of IOD phases on human lives, only a few have examined such impacts on fisheries. In this study, we analyzed the influence of negative (positive) of IOD on a chlorophyll a (Chl-a) concentration as an indicator of phytoplankton biomass and small pelagic fish production in the eastern Indian Ocean (EIO) off Java. We also conducted field surveys in the EIO off Palabuhanratu Bay at the peak (October) and the end (December) of the 2019 positive IOD phase. Our findings show that the Chl-a concentration had a strong and robust association with the 2016 (2019) negative (positive) IOD phases. The negative (positive) anomalous Chl-a concentration in the EIO off Java associated with the negative (positive) IOD phase induced strong downwelling (upwelling), leading to the preponderant decrease (increasing) of small pelagic fish production in the EIO off Java.

Aminoacyl-tRNA synthetases (ARSs) are essential enzymes for translating amino acids for protein synthesis. Their function in pathogen-derived infectious diseases has been well established, which has led to development of small molecule therapeutics. The applicability of ARS inhibitors for other human diseases such as fibrosis has recently been explored in the clinical setting. There are active studies to find small molecule therapeutics for cancers. Studies on central nervous system (CNS) disorders are burgeoning as well. In this regard, we present a concise analysis of the recent development of ARS inhibitors based on small molecules from the discovery research stage to clinical studies as well as a recent patent analysis from the medicinal chemistry point of view.

We propose a new estimator for creating expansion factors for survey plots in the USDA Forest Inventory and Analysis program. This is a regularized version of the raking estimator widely used in sample surveys. The regularized raking method differs from other predictive modeling methods for integrating survey and ancillary data in that it produces a single set of expansion factors that can have general purpose use to produce small area estimates and wall-to-wall maps of any plot characteristic. This method also differs from other more widely used survey techniques, such of GREG estimation, in that it is guaranteed to produce positive expansion factors. We extend the previous method here to include cross-validation, and provide a comparison to expansion factors between the regularized raking and ridge GREG survey calibration.

Sustainable Development Goal (SDG) 6.2 sets an ambitious target of leaving no one without adequate sanitation by 2030. The key concern is the lack of local human and financial capital to fund the collection of reliable information to monitor progress towards the goal. As a result, national and local records may be telling a different story of the proportion of safely managed sanitation that counts towards achieving the SDGs. This paper unveils such inconsistency in sanitation data generated by urban authorities and proposes a simple approach for collecting reliable and verifiable information on access to safely managed sanitation. The paper is based on a study conducted in Babati Town Council in Tanzania. Using a smartphone-based survey tool, city health officers were trained to map 17,383 housing units in the town. A housing unit may comprise of two or more households. The findings show that 5% practice open defecation, while 82% of the housing units have some forms of sanitation. Despite the extensive coverage, only 31% of the faecal sludge generated is safely contained, while 64% is not. This study demonstrates the possibility of using simple survey tools to collect reliable data for monitoring progress towards safely managed sanitation in the towns of global south.

To address the challenges of climate change and food security, the establishment of smart farm complexes is necessary. While there have been numerous studies on the productivity and environmental control of individual greenhouses, research on greenhouse complexes is considerably limited. Conducting environmental studies during the design phase of these complexes poses financial constraints and practical limitations in terms of on-site experiments. To identify potential issues that may arise when developing large-scale greenhouse complexes, it is possible to utilize modeling techniques using Computational Fluid Dynamics (CFD) to assess environmental concerns and location issues before constructing the facilities. Consequently, simulating large-scale CFD models that incorporate multiple greenhouses and atmospheric conditions simultaneously presents significant numerical challenges. The objective of this study was to develop a guideline for verifying CFD models for a large-scale Venlo greenhouse, where acquiring field data before construction is not feasible for designing a greenhouse complex. The verification processes of the CFD models were conducted using 2D and 3D iterative simulations of a 2-hectare greenhouse model, using the improved Grid Independence Test (GIT) and wall Y+ approaches. Subsequently, the aerodynamic characteristics were analyzed in a 3D greenhouse model to access its performance when the wind direction was 90° in summer season. The findings revealed that a grid resolution of 0.8 meters and a first layer height of 0.04 meters were suitable for developing large-scale greenhouse models, resulting in a low Root Mean Square Error (RMSE) of 3.9% and a high coefficient of determination (R2) of 0.968. This process led to a significant reduction of 38% in the number of grid cells. These results will serve as design standards for large-scale greenhouses.

Lambertianic acid (LA) is a biologically active compound from the leaves of Pinus koraiensis. In the present study, apoptotic mechanisms of LA plus TNF-related apoptosis-inducing ligand (TRAIL) were elucidated in non-small cell lung cancer cells (NSCLCs). Cytotoxicity assay, flow cytometry, immunoprecipitation and Western blotting were performed. Here, combined treatment of LA and TRAIL increased cytotoxicity, sub-G1 population and cleaved poly (ADP-ribose) polymerase (PARP) and caspase3/8/9 in A549 and H1299 cells compared to LA or TRAIL alone. Furthermore, combined treatment of LA and TRAIL significantly decreased anti-apoptotic proteins such as B-cell lymphoma 2 (Bcl-2), Fas-like inhibitor protein (FLIP) and X-linked inhibitor of apoptosis protein (XIAP) and enhanced the activation of pro-apoptotic proteins Bid compared to LA or TRAIL alone. In addition, combined treatment of LA and TRAIL upregulated the expression of Death receptor 4 (DR4) and downregulated phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (p-NF-B), inhibitory protein of kB family (p-IB) and FLIP in A549 and H1299 cells along with disrupted binding of XIAP with caspase3 or NF-B. Overall, these findings suggest that lambertianic acid enhances TRAIL-induced apoptosis via inhibition of XIAP/NF-B in TRAIL resistant NSCLCs.

We describe the behavior of mixtures of stearic acid (SA) and its hydroxylated counterpart 12-hydroxystearic acid (12-HSA) in aqueous mixtures at room temperature, as function of the 12-HSA/(fatty acid) mole ratio R. The morphologies of the self-assembled aggregates are obtained by a multi-structural approach that combines confocal and cryo-TEM microscopies with Small-Angle Neutron Scattering (SANS) and Wide-Angle X-Rays Scattering (WAXS) measurements, coupled with rheology measurements. Fatty acids are solubilized by an excess of ethanolamine counterions, so that their heads are negatively charged. The behavior is driven by the competition between mixing entropy and enthalpic effects. A clear trend towards partitioning between the two types of fatty acids is observed, presumably driven by the favorable formation of a H-bond network between hydroxyl OH function on the 12th carbon. For all R, the self-assembled structures are locally lamellar, with bilayers composed of crystallized and strongly interdigitated fatty acids. At high R, multi-lamellar tubes are formed, similarly as for pure aqueous solutions of 12-HSA. The doping by a low amount of SA molecules only slightly modify the dimensions of the tubes (radius and length), and slightly decreases the bilayers rigidity. The solutions have a gel-like behavior originating from entanglements between tubes and show a yield stress. At intermediate R, a partial local partitioning occurs between the two types of fatty acids. The tubes coexist in solution with helical ribbons. The two structures possibly merge to form very long snaky objects with straight and curved parts. The rigidity of the bilayers and the rheological behavior of the solutions are very similar to those of the high R case. At low R, local partitioning also occurs, and the architecture of the self-assemblies associates the two morphologies of the pure fatty acids systems, respectively 2-D planar bilayers for SA and the tubes describe above for the 12-HSA molecules: they are facetted objects with planar domains enriched in SA molecules, capped with curved domains enriched in 12-HSA molecules. The rigidity of the bilayers is strongly increased, as well their storage modulus, compared to systems with larger R. The solutions remain however viscous fluids in this regime of low R.

Photoelectrochemical systems have the potential to contribute to de-carbonation of the energy system because solar energy can be directly converted to hydrogen which can be burnt without the release of greenhouse gases. However, meaningful deployment of photoelectrochemical (PEC) technology in the global energy system, even when highly efficient scaled up devices become available, shall only be a reality when their safe and reliable operation can be guaranteed over serveral years of service life. The first part of the review discusses the importance of hermetic sealing of up scaled PEC device provided by the casing and sealing joints from a reliability and risk perspective. The second part of the review presents a survey of fully functional devices and early demonstrators and uses this to establish the extent to which the state of the art in PEC device design address the issue of hermetic sealing. The survey revealed that current material choices and sealing techniques are still unsuitable for scale –up and commercialization. Accordingly, we examined possible synergies with related photovoltaic and electrochemical devices that have been commericalised and derived therefrom, recommendations for future research routes that could accelerate the development of hermetic sealings of PEC devices.

In recent times, a great interest has been motivated in plant-derived compounds known as phytochemicals. The pentacyclic oleanane-, ursane-, lupane-type triterpenes are phytochemicals that exert significant activities against diseases like cancer. Lung cancer is the leading cause of cancer-related death worldwide. Although chemotherapy is the treatment of choice for lung cancer, its effectiveness is hampered by the dose‐limiting toxic effects and chemoresistance. Herein, we investigated the structure-activity relationship of six pentacyclic triterpenes: oleanolic acid (OleA), ursolic acid (UrA), asiatic acid (AsA), betulinic acid (BeA), betulin (Betu), lupeol (Lupe), on NSCLC A549 cells. From our studies, we confirmed that all these triterpenes showed cytotoxicity in the mid µM range, where BeA showed the strongest effect. Then, we determined that most of these triterpenes induced S-phase and G2/M phase cycle arrest, reactive oxygen species, mitochondrial depolarization, and caspase 3 activation. For chemoresistance markers, we elucidated that most triterpenes downregulated STAT3 and PDL1 genes. In contrast, ursane-type UrA and AsA also induced DNA damage, reactive nitrogen species and autophagy. These results showed that even slight structural changes in these triterpenes can influence the cellular response and mechanistic pathways. This study opens promising perspectives for further research on the pharmaceutical role of phytochemical triterpenoids.

The contemporary landscape of education is witnessing a paradigm shift towards innovative instructional methods, with the flipped learning approach gaining considerable attention. The purpose of this research was to investigate the impact of the flipped learning approach on students' perception and acceptance throughout an entire semester in the 'Introduction to Programming with Java' course, using a research design with a quantitative approach, ultimately aiming to inform educational practice and advance our knowledge of innovative teaching methods in higher education. This study was conducted at a university with 174 students involved, divided into two groups, 87 students in the experimental group and 87 students in the control group. The data collected through the scales were analyzed by using descriptive and inferential statistical analysis techniques in statistical software. At the end of the measurements, the technology acceptance level and self-directed learning perceptions of engineering students who received education with flipped learning were high. The results suggest that educators should consider students' readiness for self-directed learning when implementing the flipped learning approach and focus on creating an environment that supports their autonomy and engagement. This research offers valuable guidance for instructors, curriculum designers, and educational policymakers seeking to enhance the effectiveness of flipped learning in higher education courses.

Background: The novel coronavirus (COVID-19) infection is primarily transmitted through respiratory droplets from an infected person and contact with tainted surfaces or items. Social distancing became the primary measure of preventing the spread of COVID-19, with the principal aim being to reduce the probability of contact with an already infected person. Social distancing can be distressing, as it is against the community's way of life. Saudi Arabia imposed a curfew and suspended all religious, entertainment, sporting, and mass congregations. The daily updates on COVID-19 infection and mortality are upsetting and further, aggravate depression and anxiety. With this background, this study was planned with the following objectives. To determine the sociodemographic profile of the study participants, to find the prevalence of psychological morbidity, and to measure the association between the sociodemographic details, COVID-19 associated factors, and psychological effects among Abha citizens during the COVID-19 pandemic. Methodology: A descriptive cross-sectional community-based study was conducted in the Abha city population from August 2021 to July 22. This study followed snowball sampling, the data was collected using an online Google form the link was shared in WhatsApp groups and through emails to contacts, asking friends to share it with their friends, until reaching the adequate sample size the responses were accepted. Results: A total of 530 participated, and their age ranged from 19 -70 years. Many of the participants (34.5%, n=183) belonged to 36-45 years old. Most of the responders were 69.8% married and Females (69.2%, n=367). Half of the participants had been quarantined (49.6%), and 51.5% were scared from fear of COVID-19. 64.8% of the participants had depression; 14.2%, 20.8%, 13.6%, and 16.2% had mild, moderate, severe, and extremely severe depression, respectively. Around 58.2% of participants suffered from anxiety; 5.8% experienced mild anxiety, 21.7% moderate anxiety, and 30.7% severe anxiety. The proportion of stress among the participants was 45.0%; 10.8% had mild stress, 9.4% had moderate stress, and 24.5% had severe to extremely severe stress. Conclusions: COVID-19 poses mental health problems among individuals and communities. There is a need to find the more susceptible individuals for mental health issues or other psychological disorders. Mental health and psychological problems can be resolved with health education, counseling, and appropriate interventions to curb the negative health impacts of COVID-19.

We reduplicate the Book “Dark Energy” by M. Li, X-D. Li, and Y. Wang, zero-point energy calculation with an unexpected “length’ added to the ‘width’ of a graviton wavefunction just prior to the entrance of ‘gravitons’ to a small region of space-time prior to a nonsingular start to the universe. We compare this to a solution worked out using Klauder Enhanced quantization, for the same given problem. The solution of the first Cosmological Constant problem relies upon the geometry of the multiverse generalization of CCC cosmology which is explained in this paper. The second solution, used involves Klauder enhanced quantization. We look at energy given by our methods and compare and contrast it with the negative energy of the Rosen model for a mini sub universe and estimate GW frequencies

When describing the tribological behaviour of technical surfaces, the need for full length scale microtopographic characterization often arises. The self-affine of surfaces and the characterization of self-affine by a fractal dimension and its implantation into tribological models are commonly used. The goal of our present work was to determine the frequency range of fractal behaviour of surfaces by analysing the microtopographic measurements of a brake plunger. We also wanted to know if the bifractal and multifractal behaviour can be detected in real machine parts. As a result, we developed a new methodology for determining the fractal range boundaries to separate the nano- and micro-roughness. In order to reach our goals, we used atomic force microscope (AFM) and stylus instrument to provide measurements in wide frequency range (19 nm - 3 mm). As a result of the power spectral density (PSD) based fractal evaluation, it was found that the examined surface could not be characterized by a single fractal dimension and that we developed a methodology for stopping the margin of validity of each fractal dimension, and we also developed a methodology for determining the limits of validity of certain fractal dimensions.

According to the standard cold dark matter (CDM) cosmology, the structure of dark halos including those of galaxy clusters reflects their mass accretion history. Older clusters tend to be more concentrated than younger clusters. Their structure, represented by the characteristic radius $r_s$ and mass $M_s$ of the Navarro-Frenk-White (NFW) density profile, is related to their formation time. In this study, we show that $r_s$, $M_s$, and the X-ray temperature of the intracluster medium (ICM), $T_X$, form a thin plane in the space of $(\log r_s, \log M_s, \log T_X)$. This tight correlation indicates that the ICM temperature is also determined by the formation time of individual clusters. Numerical simulations show that clusters move along the fundamental plane as they evolve. The plane and the cluster evolution within the plane can be explained by a similarity solution of structure formation of the universe. The angle of the plane shows that clusters have not achieved “virial equilibrium” in the sense that mass/size growth and pressure at the boundaries cannot be ignored. The distribution of clusters on the plane is related to the intrinsic scatter in the halo concentration--mass relation, which is originated from the variety of cluster ages. The well-known mass--temperature relation of clusters ($M_\Delta\propto T_X^{3/2}$) can be explained by the fundamental plane and the mass dependence of the halo concentration without the assumption of virial equilibrium. The fundamental plane can also be used for calibration of cluster masses.

Small rodents and insectivores are potential reservoirs of many pathogens transmissible to humans such as bacteria, parasites and viruses responsible for epidemics in sub-Saharan Africa, particularly in West Africa. Few studies on small mammal species in the Kolikoro and Sikasso regions are available, hence the interest in investigating the different species of small rodents and insectivores, and their role in the transmission of pathogens to humans. The study aims to identify commensal small mammal species circulating in Faladjè and Bougouni areas, and likely to represent major risks of epidemic disease emergence. Sessions of trapping were carried out in December 2016 in Faladjè and Bougouni with wire mesh traps type “Besançon tous services” (BTS) baited with peanut butter and/or onion. All animals captured were identified morphologically. Out of 123 small rodents and insectivores captured in 674 trap nights, 75 (60.97%) were from Faladjè and 48 (39.02%) from Bougouni, Of these, six species of small rodents belong to the family Muridae (Mastomys erythroleucus, Mastomys natalensis, Rattus rattus, Praomys daltoni, Gerbilliscus gambianus, Taterillus gracilis) and two species of insectivores associated with the genus Crocidura spp. belong to the family Soricidae and Erinaceidae (Crocidura cf olivieri and Atelerix cf albiventris) respectively. There is low specific diversity within these two stands, but the variation in relative abundance is significant (binomial test, p = 0.018 ˂ 0.05) between the Faladjè and Bougouni stands of small mammals. Mastomys erythroleucus was the most dominant species (57.33%, 43/75) in the Faladjè settlement and R. rattus dominated (37.5%,18/48) that of Bougouni. These two species of small mammals are potentially involved in the transmission of bacteria, parasites and pathogenic viruses to humans.

Neuroendocrine neoplasms (NENs) comprise a heterogeneous group of rare malignancies mainly originated from hormones secreting cells, which are widespread in human tissues. The identification of mutations in ATRX/DAXX genes in sporadic NENs, as well as the high burden of mutations scattered throughout MEN-1 gene in both sporadic and inherited syndromes, provided new insights into the molecular biology of tumour development. Other molecular mechanisms, such as the NOTCH signaling pathway, have shown to play an important role in the pathogenesis of NENs. NOTCH receptors are expressed on neuroendocrine cells and generally, act as tumour suppressor proteins, but in some contexts can function as oncogenes. The biological heterogeneity of NENs suggests that to fully understand the roles and the potential therapeutic implications of gene mutations and NOTCH signaling in NENs, a comprehensive analysis of genetic alterations, NOTCH expression patterns and their potential roles across all NEN subtypes is required.

Women's empowerment represents a process in which they are recognized as subjects of rights. Despite advances in women's rights, inequalities persist in various areas. This study aims to validate a psychometric scale of 31 items in seven factors: Participatory Empowerment, Temerity, External Influences, Independence, Social Satisfaction and Equality. The objective is to measure the empowerment of women in the university context. The research was carried out in a transversal and non-experimental manner, with the participants' voluntary collaboration, including the participation of 1,478 university students from four Higher Education Institutions in Zone 4 of Ecuador. The data was analyzed through inferential statistics, including exploratory and confirmatory factor analysis. The results indicated that the instrument for measuring empowerment can be made up of 24 items grouped into six factors, and this model showed a good fit.

The coastal zone, situated at the sensitive interface between land and sea, serves as a pivotal area of extensive human economic activities. As one of China's economic special zones, Xiamen exemplifies the comprehensive trajectory of coastal governance in China. This research adopts an interdisciplinary approach grounded in historical geography and political ecology, employing data collection methods encompassing historical literature, field surveys, and interviews. The research findings indicate that:(1) The year 1994 witnessed the pivotal role played by the United Nations Convention on the Law of the Sea (UNCLOS) in connecting Jimei Peninsula from a local context to the international arena, thus signifying a momentous turning point in the process of scale reconstruction. However, the subsequent implementation of the Coastal Exclusion Policy in 2002 had detrimental consequences, leading to the disintegration of the local scale, the erosion of maritime culture, and the disregard for the livelihood security of displaced coastal populations.(2)The Coastal Exclusion Policy serves as an instrumental tool for implementing scale politics, while its functional realignment has had profound implications for the coastal zone, encompassing economic transformation, ecological degradation, and the marginalization of the socio-cultural fabric that intertwines humans and the coastal environment.

The Principle of Indifference (“PI”: the simplest non-informative prior in Bayesian probability) has been shown to lead to paradoxes since Bertrand (1889). Von Mises (1928) introduced the “Wine/Water Paradox” as a resonant example of a “Bertrand paradox”, and which has been presented as demonstrating that the PI must be rejected. We now resolve these paradoxes by a Maximum Entropy (MaxEnt) treatment of the PI that also includes information provided by Benford’s “Law of Anomalous Numbers” (1938). We show that the PI should be understood to represent a family of informationally-identical MaxEnt solutions; each solution being identified with its own explicitly justified boundary condition. In particular, our solution of the Wine/Water Paradox exploits Benford’s Law to construct a non-uniform distribution representing the universal constraint of scale invariance, which is a physical consequence of the Second Law of Thermodynamics.

Land cover data are important basic data for earth system science and other fields. Multi-source remote sensing images have become the main data source for land cover classification. There are still many uncertainties in the scale effect of image spatial resolution on land cover classification. Since it is difficult to obtain multiple spatial resolution remote sensing images of the same area at the same time, the main current method to study the scale effect of land cover classification is to use the same image resampled to different resolutions, however errors in the resampling process lead to uncertainty in the accuracy of land cover classification. To study the land cover classification scale effect of different spatial resolutions of multi-source remote sensing data, we selected 1 m and 4 m of GF-2, 6 m of SPOT-6, 10 m of Sentinel-2 and 30 m of Landsat-8 multi-sensor data, and explored the scale effect of image spatial resolution on land cover classification from two aspects of mixed image element decomposition and spatial heterogeneity. For the study area, we compared the classification obtained from GF-2, SPOT-6, Sentinel-2, and Landsat-8 images at different spatial resolutions based on GBDT and RF. The results show that (1) GF-2 and SPOT-6 had the best classification results, and the optimal scale based on this classification accuracy was 4–6 m; (2) the optimal scale based on linear decomposition depended on the study area; (3) the optimal scale of land cover was related to spatial heterogeneity, i.e., the more fragmented and complex was the space, the smaller the scale needed; and (4) the resampled images were not sensitive to scale and increase the uncertainty of the classification. These findings have implications for land cover classification and optimal scale selection, scale effects and landscape ecology uncertainty studies.

The level of technological development of any civilization can be gaged in large part by the amount of energy they produce for their use, but also encompasses that civilization’s stewardship of their home world. Following the Kardashev definition, a Type I civilization is able to store and use all the energy available on its planet. In this study, we develop a model based on Carl Sagan’s K formula and use this model to analyze the consumption and energy supply of the three most important energy sources: fossil fuels (e.g., coal, oil, natural gas, crude, NGL and feedstocks), nuclear energy and renewable energy. We also consider environmental limitations suggested by United Nations Framework Convention on Climate Change, the International Energy Agency, and those specific to our calculations to predict when humanity will reach the level of a Kardashev scale Type I civilization.

Carton detection is an important technique in the automatic logistics system and can be applied to many applications such as the stacking and unstacking of cartons, the unloading of cartons in the containers. However, there is no public large-scale carton dataset for the research community to train and evaluate the carton detection models up to now, which hinders the development of carton detection. In this paper, we present a large-scale carton dataset named Stacked Carton Dataset (SCD) with the goal of advancing the state-of-the-art in carton detection. Images are collected from the Internet and several warehouses, and objects are labeled using per-instance segmentation for precise localization. There are total of 250,000 instance masks from 16,136 images. Naturelly, a suite of benchmarks are established with several popular detectors. In addition, we design a carton detector based on RetinaNet by embedding our proposed Offset Prediction between Classification and Localization module (OPCL) and Boundary Guided Supervision module (BGS). OPCL alleviates the imbalance problem between classification and localization quality which boosts AP by 3.1%∼4.7% on SCD at the model level while BGS guides the detector to pay more attention to boundary information of cartons and decouple repeated carton textures at the task level. To demonstrate the generalization of OPCL to other datasets, we conduct extensive experiments on MS COCO and PASCAL VOC. The improvements of AP on MS COCO and PASCAL VOC are 1.8%∼2.2% and 3.4%∼4.3% respectively. Source dataset is available here.

Friction is an important subject for sustainability due to problems associated with energy loss. Recent years, surface micro- and nanostructures have attracted much attention to reduce friction; however, suitable structures are still under consideration. Many functional surfaces are present in nature, such as the friction reduction surfaces of snake skins. In this study, we focused on firebrats, Thermobia domestica, living in narrow spaces such as under bark, so their surface frequently contacts with surrounding surfaces. We speculate that their body surface would be adapted to reduce friction. To investigate the firebrat surface functions, firebrat surfaces were observed by using a field-emission scanning electron microscope (FE-SEM) and a colloidal probe atomic force microscope (AFM), respectively. Results of surface observations by the FE-SEM revealed that firebrats are entirely covered with scales, whose surfaces have micro groove structures. Scale groove periods around the firebrat's head are almost uniform within a scale but vary between scales. AFM friction force measurements revealed that firebrat scale reduces friction by decreasing contact area between scales and a colloidal probe. The heterogeneity of groove periods of the scales suggest that it is difficult to fix the whole body in particular rough surfaces and that lead to be "fail-safe".

Size-based fungal growth studies have limitations. For example, the growth in size stops in closed systems once it reaches the borders and poorly describes the metabolic status, especially in the stationary phase. This might lead mycotoxin studies to unrealistic results. Color change could be a viable alternative as pigments are results of the mold’s metabolic activity. This study aimed to verify the possibility of using gray values and the RGB system to analyze the growth of Fusarium graminearum. It consisted color and area measurement using the ImageJ software for specimens grown in yeast extract agar (YEA). The results suggest the usability of color and gray values as reliable tools to analyze the growth of F. graminearum.

Higher-risk myelodysplastic syndrome (HR-MDS) has a poor prognosis in the absence of efficient therapy. The evaluation of new therapies in animal models of HR-MDS is hampered by the absence of accurate in vivo biomarkers of the disease. In this study we compared [18F]Fluoro-desoxyglucose Positron Emission Tomography (FDG-PET) and [18F]Fluoro-thymidine (FLT)-PET imaging for disease follow-up in a triple transgenic MMTVtTA/TetoBCL-2/MRP8NRASD12 mouse model of HR-MDS. Normal control FVB/N mice (G1,n=9) and HR-MDS mice (G2,n=12) underwent both FDG- and FLT-PET procedures at 2-day intervals, on a dedicated small animal device. Blood cell counting, BCL-2 and Mac-1hi/Gr-1lo expression measurements in blood were performed before each PET procedure. Visually, PET images of G2 mice demonstrated homogeneous FDG uptake in the whole skeleton similar to that observed in G1 mice, and abnormal FLT hot spots in bone marrow not observed in G1 mice. The intensity of FLT hot spots in bone marrow was higher in 3-months old G2 mice than in 2-months old G2 mice, concordant with a higher percentage of cells expressing Mac-1hi/Gr-1lo and lower platelets counts. We conclude that FLT-PET/CT imaging is a more valuable surrogate non-invasive quantitative marker of HR-MDS bone marrow involvement than FDG-PET/CT in our mouse model of HR-MDS.

After globalization, South Korea’s retail landscape has been saturated with large-scale, corporate type retails. However, recently new commercial districts composed of small retail units are returning and bringing about a change. This study sought to take note of this phenomenon and identify its features and meanings from the perspective of urban ecology. A density-distribution analysis was conducted to investigate how they were forms, and an analysis of traces on the Internet and an analysis on the types of businesses were done to identify sociocultural characteristics. Results showed that they had similar type of locations and growth patterns, that they harmoniously congregated in a form of smaller-individual stores, and that their use of similar names for their stores had an impact of branding their entire districts. It was also noted that a shared culture through social networking services served as a growth boost for their unfavorable location. The spontaneous formation of such commercial districts can be an outcome of an urban ecological process geared toward blank niches burgeoning in the current retail structure of Korea. The causes and conditions found in the cases reveal meaningful policy implications for cities facing the same urban crisis diversity.

Large-scale crowd phenomena are complex to model because the behaviour of pedestrians needs to be described at both strategic, tactical, and operational levels and is impacted by the density of the crowd. Microscopic models manage to mimic the dynamics at low densities, whereas mesoscopic models achieve better performances in dense situations. This paper proposes and evaluates a novel agent-based architecture to enable agents to dynamically change their operational model based on local density. The ability to combine microscopic and mesoscopic models for multi-scale simulation is studied through a use case of pedestrians at the Festival of Lights, Lyon, France. Pedestrian outflow data is extracted from video recordings of exiting crowds at the festival. The hybrid model is calibrated and validated using a genetic algorithm that optimizes the match between simulated and observed outflow data. Additionally, a local sensitivity analysis is then conducted to identify the most sensitive parameters in the model. Finally, the performance of the hybrid model is compared to different models in terms of density map and computation time. The results demonstrate that the hybrid model has the capacity to effectively simulate pedestrians across varied density scenarios while optimizing computational performance compared to other models.

Postprandial hyperlipidemia showing postprandial increase in serum triglyceride (TG) is atherogenic and associated with the development of coronary artery disease (CAD). To diagnose postprandial hyperlipidemia, the oral fat loading test (OFLT) should be performed, however, this test is very time-consuming and is difficult to perform. Ele-vated serum TG levels reflect an increase in TG-rich lipoproteins (TRL) such chylomi-crons (CM), very low-density lipoproteins (VLDL) and their remnants (CM remnant [CMR] and VLDL remnant [VLDLR]). Understanding of elevation in CMR and/or VLDLR can lead us to understand the existence of postprandial hyperlipidemia. The measurements of apo B48 which is a constituent of CM and CMR, non-fasting TG which includes TG content in all lipoproteins including CM and CMR, non-high-density lipoprotein-cholesterol (non-HDL-C) which includes TRL and low-density lipoprotein, and remnant cholesterol, are useful to suspect the existence of postprandial hyperlipidemia. Postprandial hyperlipidemia is observed in patients with familial type III hyperlipoproteinemia, familial combined hyperlipidemia, chronic kidney disease, metabolic syndrome and type 2 diabetes. Postprandial hyperlipidemia is closely related to postprandial hyperglycemia, and insulin resistance may be an in-ducing and enhancing factor for both postprandial hyperlipidemia and postprandial hyperglycemia. Remnant lipoproteins and metabolic disorders associated with post-prandial hyperlipidemia have various atherogenic properties such as induction of in-flammation and endothelial dysfunction. A healthy diet, calorie restriction, weight loss and exercise, positively impact postprandial hyperlipidemia. Anti-hyperlipidemic drugs such pemafibrate, bezafibrate, ezetimibe and eicosapentaenoic acid have shown to improve postprandial hyperlipidemia. Anti-diabetic drugs including metformin, alpha-glucosidase inhibitors, pioglitazone, dipeptidyl-peptidase-4 inhibitors and glu-cagon like peptide 1 analogues, have shown to ameliorate postprandial hyperlipidemia. Although sodium glucose cotransporter-2 inhibitors have not been proven to reduce postprandial hyperlipidemia, they reduced fasting apo B48 and remnant lipoprotein cholesterol. In conclusion, it is important to appropriately understand the existence of postprandial hyperlipidemia and to connect it to optimal treatments.

The increasing use of energy resources recovered from the subsurface environments and the resulting carbon imbalance in the environment has motivated the need to develop thermodynamically downhill pathways to convert and store CO₂ as water insoluble calcium or magnesium carbonates. While previous studies extensively explored aqueous routes to produce calcium and magnesium carbonates from CO₂, there has been a limited scientific understanding of the phase evolution and textural changes during the direct gas-solid conversion routes to produce calcium carbonate from calcium hydroxide, which is one of the abundant constituents of alkaline industrial residues. With increasing interest in developing integrated pathways for capturing, converting and storing CO₂ from dilute flue gases, understanding the compositions of the product phases as they evolve is essential for evaluating the efficacy of a given processing route. Therefore, in this study, we investigate the phase evolution and the corresponding textural changes as calcium hydroxide is converted to calcium carbonate under the continuous flow of CO₂ at an ambient pressure of 1 atm and on heating continuously from 30 °C to 500 °C using in-operando wide angle X-ray scattering (WAXS), small angle X-ray scattering (SAXS), and ultra-small angle X-ray scattering (USAXS) measurements.

When there are multiple key strata in the overburden of deep coal seam and the surface subsid-ence coefficient after mining is small, it indicates that the overlying key strata fail to break com-pletely after mining. On this occasion, the stress concentration on the working face occurs easily, which in turn leads to the occurrence of dynamic disasters such as rock burst. This study adopted a comprehensive analysis method of field monitoring and numerical simulation to explore the in-fluence of key stratum on the evolution law of mining-induced stress in the working face. Dis-tributed optical fiber sensor (DOFS) and surface subsidence GNSS monitoring system were re-spectively arranged inside and at the mouth of the ground observation borehole. According to the monitoring results of strain obtained from DOFS, the height of broken stratum inside the overlying strata was obtained; according to the monitoring results of surface subsidence, the sur-face subsidence coefficient was proved to be less than 0.1, indicating that the high key stratum does not break completely, but enters a state of bending subsidence instead. In order to reveal the influence of key stratum on the mining-induced stress of working face, two 3DEC numerical models with and without key stratum were established for comparative analysis. As the numeri-cal simulation results show, when there are multiple key strata in the overburden, the stress in-fluence range and stress concentration coefficient of coal seam after mining are relatively large. The study revealed the working mechanism of rock burst accidents after large-scale mining and predicted the potential area of rock burst risk after the mining of the working face, which has been verified by field investigation. The research results are of great guiding significance for the revelation of the working mechanism of rock burst in deep mining condition and its prevention and control.

The hypothesis posed was whether participation in LaLiga Genuine Santander (competitive football) influenced the quality of life (QL) of the people who participated in it, since their perception of themselves is enhanced by all the aformentioned factors (self-determination, social inclusion, emotional well-being, physical well-being, material well-being, rights, personal development, interpersonal relationships). The objective was to evaluate the QL of people with Down's Syndrome (DS) using their self-perception (n=39) and the perception of the informants (family members, teachers) (n=39). The KidsLife-Down Scale, with a few modifications was used. In general, differences of opinion between the subgroups of participants with DS and informants showed that results were higher in terms of perception for participants in the DS subgroup. Scores for all variables were higher for those participants with DS who said they did engage in practicing competitive football. Despite the perception of informants provides a great deal of information regarding the QL of participants with DS, the latter should be involved in the evaluation process and their self perceptions taken into account. Our research shows that participation in the league modifies the perceptions of the participants with Down's Syndrome regarding their quality of life. However, these perceptions are not shared by the informants.

Recent advances in understanding the Planck scale have led to a new, straightforward method for quantizing the general theory of relativity. This results in a theory of gravity that predicts the same outcomes as general relativity with greater fundamental comprehension connected directly to the Planck scale.

The papaya mealybug Paracoccus marginatus is an invasive, polyphagous pest and poses a quarantine threat to tropical and subtropical countries. Infested commodity internationally should be undergoing phytosanitary treatment, while irradiation is recommended to replace methyl bromide fumigation. Dose-response tests were conducted on the 2-, 4-, and 6-d-old eggs and gravid females of P. marginatus using the X-ray radiation doses of 15–105 Gy with an interval of 15 Gy, respectively. Radiotolerance was compared using fiducial overlapping and lethal dose ratio (LDR) test, resulting in insignificant difference except for LDR test at LD90 (leading 90% mortality at 95% confidence level (CL)); the estimated dose for 99.9968% mortality at 95% CL was 176.5–185.2 Gy, which was validated in the confirmatory tests using gamma irradiation because gammy and X-rays have equal biological effect on pests. Therefore, a total of estimating 60,386 gravid females of papaya mealybug irradiated with 146.8–185.0 Gy resulted in no F1 nymphs developing. Eggs can therefore be used as an alternative to gravid females for dose-response tests; the recommended minimum dose for phytosanitary treatment of P. marginatus on infested commodity is 185 Gy, with treatment efficacy ≥ 99.9950% at 95% CL.

Low charge density nanometric ions were recently shown to bind strongly to neutral hydrated matter in aqueous solution. This phenomenon, called (super-)chaotropic effect, arises from the partial dehydration of both, the nano-ion and the solute, leading to a high gain in enthalpy. Here, we investigate the chaotropic effect of the polyoxometalate α-PW12O403- on the triblock copolymer P84: (EO)19(PO)43(EO)19 with (EO)19 the polyethoxylated and (PO)43 the polypropoxylated chains. The combination of phase diagrams, spectroscopic (nuclear magnetic resonance) and scattering (small angle neutron/X-ray scattering) techniques reveals that (i) below the micellization temperature of P84, PW12O403- exclusively binds to the propylene oxide moiety of P84 unimers and (ii) above the micellization temperature, PW12O403- mostly adsorbs on the ethylene oxide micellar corona. The preferential binding of the PW12O403- to the PPO chain over the PEO chains suggests that the binding is driven by the chaotropic effect and reinforced by the hydrophobic effect. At higher temperatures, the copolymer micellization leads to the displacement of PW12O403- from the PPO chain to the PEO chains. This study deepens the understanding of the subtle interplay between the chaotropic and hydrophobic effects in complex salt-organic matter solutions.

Infrared dim and small target detection is a key technology of various detection tasks. However, due to the lack of shape, texture, and other information, it is a challenging task to detect dim and small targets. Recently, since many traditional algorithms ingore global information of infrared images, they generate some false alarms in complicated environments. To address this problem, in this paper, a coarse-to-fine deep learning-based method is proposed to detect dim and small targets. Firstly, a coarse-to-fine detection framework integrating deep learning and background prediction is applied for detecting targets. The framework contains of coarse detection module and fine detection module. In coarse detection stage, Region Proposal Network (RPN) is employed to generate masks in target candidate regions. Then, for further optimize the result, inpainting is utilized to predict the background by the global semnantic of images. In this paper, inpainting algorithm with a mask aware dynamic filtering module is incorporated into the fine detection stage to estimate background in candidate target areas. Finally, compared with existing algorithms, the experimental results indicate that the proposed framework have effective detection capability and robustness for complex surroundings.

We reduplicate the Book “Dark Energy” by M. Li, X-D. Li, and Y. Wang, given zero-point energy calculation with an unexpected “length’ added to the ‘width’ of a graviton wave just prior to specifying the creation of ‘gravitons’, while using Karen Freeze’s criteria as to the breakup of primordial black holes to give radiation era contributions to GW generation. The GW generation will be when there is sufficient early universe density so as to break apart Relic Black holes of the order of Planck mass (10^15 grams) which isabout when the mass of relic black holes is created, 10^-27 or so seconds after expansion starts. Need to state a key result will be in the initial potential V calculated, in terms of other input variables

Outcome of redo-mitral valve replacement in the small mitral annulus with the use of the chimney technology is not well documented. From 2019 to 2020, 77 consecutive patients underwent redo-mitral valve replacement with the use of the chimney technology because of a small mitral annulus. To evaluate heart structural integrity and clinical outcomes, postoperative clinical data and echocardiograms were examined. Mean age was 56.7 ± 15.98 years. All patients underwent mitral valve surgery of which 62 were mitral valve replacements, 7 mitral valve repairs, and 8 double valve replacements. Preoperative Mitral valve mean gradient was 18.07 ± 9.40 mmHg. Postoperative mitral prosthesis size 28.51 ± 1.22 mm. The median increment of mitral size enlargement was 4 (0, 6) valve sizes. Mean mitral gradient coming out of the operating room was 10.34 ± 2.12 mmHg and at follow-up echocardiogram performed at 3 years after the procedure was 10.36 ± 1.70 mmHg. One-year survival was 93.3%, while 4-year survival was 89.3% with no reoperation. Use of the chimney technology in small mitral valve re-mitral valve replacement results in larger valve sizes. Moreover, the mean gradients over the mitral valve are acceptable intraoperatively and over time.

Unmanned Aerial Vehicles (UAVs) image object detection has great application value in military and civilian fields. However, the objects in the captured images from UAVs have problems of large scale variation, complex backgrounds, and a large proportion of small objects. To resolve these problems, a multi-scale object detector based on coordinate and global information aggregation is proposed, named CGMDet. Firstly, a Coordinate and Global Information Aggregation Module (CGAM) is designed by aggregating local, coordinate, and global information, which can obtain features with richer context information. Secondly, a Multi-Feature Fusion Pyramid Network (MF-FPN) is proposed, which can better fuse features of different scales and obtain features containing more context information through repeated use of feature maps, to better detect multi-scale targets. Moreover, more location information of low-level feature maps is integrated to improve the detection results of small targets. Furthermore, we modified the bounding box regression loss of the model to make the model more accurately regress the bounding box and faster convergence. Finally, the proposed CGMDet was tested on VisDrone and UAVDT datasets and mAP0.5 of 50.9% and 48% was obtained, respectively. At the same time, our detector achieved the best results compared to other detectors.

Infrared small target detection (ISTD) plays a crucial role in both civilian and military applications. The detection of small targets against dense cluttered backgrounds remains a challenging task, requiring the collaboration of false alarm source elimination and target detection. Existing approaches primarily focus on modeling targets while often neglecting false alarm sources. To address this limitation, we propose a Target and False Alarm Collaborative Detection Network to leverage the information provided by false alarm sources and the background. Firstly, we introduce a False Alarm Source Estimation Block (FEB) that estimates potential interferences present in the background by extracting features on multiple scales and employing stepwise upsampling for feature fusion. Subsequently, we propose a framework that employs multiple FEBs to eliminate false alarm sources across multiple scales. Finally, a Target Segmentation Block (TSB) is introduced to accurately segment the targets to produce the final detection result. Experiments on public datasets demonstrate that, compared to other methods, our model achieves high accuracy in segmenting targets while being able to extract false alarm sources which can be used for further studies.

Ship detection in large-scene offshore synthetic aperture radar (SAR) images is crucial in civil and military fields, such as maritime management and wartime reconnaissance. However, the problems of low detection rates, high false alarm rates, and high missed detection rates of offshore ship targets in large-scene SAR images are due to the occlusion of objects or mutual occlusion among targets, especially for small ship targets. To solve this problem, this study proposes a target detection model (TAC_CSAC_Net) that incorporates a multi-attention mechanism for detecting marine vessels in large-scene SAR images. Experiments were conducted on two public datasets, the SAR-Ship-Dataset and high-resolution SAR image dataset (HRSID), with multi-scene and multi-size, and the results showed that the proposed TAC_CSAC_Net model achieves good performance for both small and occluded target detection. Experiments were conducted on a real large-scene dataset, LS-SSDD, to obtain the detection results of subgraphs of the same scene. Quantitative comparisons were made with classical and recently developed deep learning models, and the experiments demonstrated that the proposed model outperformed other models for large-scene SAR image target detection.

Entrepreneurial activities in economic and social domains are considered one of the conditional pillars for successful transformation of resource-rich countries to sustainable, knowledge-based and diversified economies. However, there is no, and cannot be, a single recipe for such a transformation as every country or region needs to develop its own strategy, policy toolbox and implementation plan depending on its historical and present socio-economic make up and trajectory. This paper advances the qualitative findings of a previously published work to delve deeper into the complexities of entrepreneurship within resource-based economies, with a particular focus on Qatar. Employing a mixed methodology that blends explanatory and quantitative analysis, this paper aims to validate and refine the entrepreneurship framework proposed previously, ensuring its relevance and adaptability to Qatar's unique economic and cultural context, and its extendibility to similar resource-rich country settings. It systematically focuses on discovering various social, economic, and environmental dimensions critical to fostering entrepreneurship in resource-rich countries. These include examining government policies, cultural and social factors, financial support mechanisms, innovation ecosystem, technology adaptation, and digitization. A primary component of this study is the methodological approach, which includes collecting and analyzing quantitative data through a survey developed based on previous findings on qualitative explorations. This approach allows for an objective assessment of the effectiveness of the proposed recommendations. The paper presents a set of detailed recommendations aimed at various stakeholders, including government bodies, supporting agencies, and entrepreneurs themselves. These recommendations encompass integrating entrepreneurship education into academic curricula, increasing easy access to business and market information, simplifying, unifying and streamlining policies and procedures, and adapting them into the legal system. Other important and unique recommendations include establishing a country-wide entrepreneurship free-zone (Ent-Q) and facilitating its operations though an online digital platform (Ryadah), allocating certain percentage of governmental ministries’, agencies’ as well as large corporations’ budgets into innovative small business development programs and preferred purchasing from small business. These initiatives are validated to become effective tools and avenues to create a conducive entrepreneurial environment, facilitating transformation into a diversified, knowledge-based and sustainable economy. The expected outcomes of implementing these recommendations include an increase in the efficiency of entrepreneurship-related policymaking, a rise in the number, quality and impact of entrepreneurs, and the sustained diversification of the economy into non-oil/gas sectors and actors. In conclusion, this paper provides a comprehensive set of strategies and recommendations expected to significantly contribute to the nurturing and growth of entrepreneurship in resource-based economies.

We investigated by Real-time PCR and end point PCR the presence of 10 potential zoonotic viruses in 91 small mammals sold as pets in pet shops of Southern Italy. The animals were analysed for: aichivirus, sapovirus, astrovirus, hepatitis A virus, noroviruses (GI and GII), rotavirus, circovirus, coronaviruses. Among the 9 species of small mammals analysed (golden hamsters, Java squirrels, mongolian gerbils, peruvian guinea pigs, pet mice, pet rats, dwarf rabbits, african hedgehogs and sugar gliders) 12 pet rats, 11 pet mice and 1 golden hamster tested positive to a PCR amplifying a conserved gene (RdRp) of coronavirus. However further characterizaton by sequencing gave not conclusive results. A pet rat resulted instead positive to aichivirus and its sequence showed similarity with a murine kobuvirus-1 strain identified in China. To our knowledge, this is the first study reporting the detection of aichivirus in rodents in Italy, the virus probably introduced through the importation of animals from Asia. Since living in close contact to humans, expecially with children, the continuous monitoring of the small mammals is very important to avoid the spread of new pathologies among animals and humans and further investigation is desirable in order to safeguard public health.

Arterial hypertension is a common condition worldwide and an important risk factor for cardio- and cerebrovascular events, renal diseases as well as microvascular eye diseases. Established hypertension leads to chronic vasoconstriction of small arteries as well as to decreased lumen diameter and thickening of the arterial media or wall with a consequent increased media-to-lumen ratio (MLR) or wall-to-lumen ratio (WLR). This process, defined as vascular remodeling, was first demonstrated in small resistance arteries isolated from subcutaneous biopsies and measured by micromyography, and this is still considered the gold-standard method for the assessment of structural alteration in small resistance arteries; however microvascular remodeling seems to represent a generalized phenomenon. An increased MLR may impair organ flow reserve, being relevant in the maintenance and, probably, also in the progressive worsening of hypertensive disease, as well as in the development of hypertension-mediated organ damage/cardiovascular events, possessing, therefore, a prognostic relevance. New, non-invasive techniques, such as Scanning Laser Doppler Flowmetry or Adaptive Optics, are presently under development, focusing mainly on the evaluation of WLR in retinal arterioles; recently, also retinal microvascular WLR was demonstrated to have a prognostic impact in term of cardio- and cerebrovascular events. A rarefaction of capillary network has also been reported in hypertension which may contribute to flow reduction and impairment in oxygen delivery to different tissues. These microvascular alterations seem to represent an early step in hypertension-mediated organ damage since they might concur to microvascular angina, stroke, and renal dysfunction. In addition, they could be a marker useful in monitoring the beneficial effect of antihypertensive treatment. Also conductance arteries may be affected by a remodeling process in hypertension, and a cross-talk may exist between structural changes in the small and large arteries. The review will address the possible relations between structural microvascular alterations and hypertension-mediated organ damage and their potential improvement with antihypertensive treatment.

The rampant misuse of drones poses a serious threat to national security and human life. Currently, the CNN method has been widely used in drone detection. However, there is a challenge that traditional CNN cannot cope with, which is small drone targets often have reduced amplitude or even lost features in infrared images. This paper proposes a Progressive Feature Fusion Network (PFFNet) that gradually increases the response amplitude of the target in the deep network. The Feature Selection Model (FSM) is designed to improve the utilisation of the output coding graph and enhance the feature representation of the target in the network. A lightweight segmentation head is also designed to achieve progressive feature fusion with multi-layer outputs. Experimental results show that the proposed algorithm can achieve low duration and high accuracy in drone target detection. On the public dataset, the IoU is improved by 2.53% and the detection time is reduced by 81.03%.

This manuscript critically reviews the design and delivery of spray-dried particles for the achievement of high total lung doses (TLD) with a portable dry powder inhaler. We introduce a new metric termed the product density, which is simply the TLD of a drug divided by the volume of the receptacle it is contained within. The product density is given by the product of three terms: the packing density (the mass of powder divided by the volume of the receptacle), the drug loading (the mass of drug divided by the mass of powder), and the aerosol performance (the TLD divided by the mass of drug). This manuscript discusses strategies for maximizing each of these terms. Spray drying at low drying rates with small amounts of a shell-forming excipient (low Peclet Number) leads to formation of higher density particles with high packing densities. This enables ultrahigh TLD (>100 mg of drug) to be achieved from a single receptacle. Emptying of powder from capsules is directly proportional to the mass of powder in the receptacle, requiring an inhaled volume of about 1 L for fill masses between 40 and 50 mg and up to 3.2 L for a fill mass of 150 mg.

Cancer cells utilize a number of mechanisms to increase their survival and progression as well as their resistance to anticancer therapy: deregulation of growth regulatory pathways by acquiring grow factor independence, immune system suppression, reducing the expression of antigens activating T lymphocyte cells (mimicry), induction of anti-apoptotic signals to counter the action of drugs, activation of several DNA repair mechanisms and driving the active efflux of drugs from the cell cytoplasm and epigenetic regulation by microRNAs (miRNAs). Due to the fact that it is commonly diagnosed late, lung cancer remains a major malignancy with a low five-year survival rate; when diagnosed, the cancer is often highly advanced and the cancer cells may have acquired drug resistance. This review summarizes the main mechanisms involved in cisplatin resistance and in interactions between cisplatin-resistant cancer cells and the tumor microenvironment. It also analyses changes in the gene expression profile of cisplatin sensitive vs. cisplatin resistant non–small cell lung cancer (NSCLC) cellular model using the GSE108214 Gene Expression Omnibus database. It describes a protein-protein interaction network that indicates highly-dysregulated TP53, MDM2 and CDKN1A genes as they encodes the top networking proteins that may be involved in cisplatin tolerance, these all being upregulated in cisplatin-resistant cells. Furthermore, it illustrates the multifactorial nature of cisplatin resistance by examining the diversity of dysregulated pathways present in cisplatin-resistant NSCLC cells based on KEGG pathway analysis.

Microbial contamination is now more common than chemical contamination in Tibet, and water-borne microbes can cause a number of diseases that threaten public health. Thus, in order to clarify the spatiotemporal distribution of bacteria in small watersheds for which there is no data in Tibet, we set up four sampling points along an upstream-downstream transect of the Xincang River Basin. We collected 239 water samples in 2014 and 2015, and evaluated their total constituent numbers of bacteria (TB) and coliforms (TC). The results of this study show that the microbial contamination of the Xincang River Basin is mild-to-moderate in terms of TB and TC contents, and that these concentrations vary significantly in different seasons. Results show that in summer TB and TC concentrations in the downstream section of this river were highest and that microbial contamination was most serious. Data also demonstrate that precipitation is the most important factor underlying increases in TB and TC concentrations during the summer months; both these variables are significantly correlated with precipitation, while animal husbandry and domestic sewage are the main sources of microbial contamination overall. The results of this study are likely to reflect the basic characteristics of small watersheds for which there is no data to some extent, and are thus of significant practical importance for protecting their ecological environments and promoting sustainable development.

The expansion of copper mining on the hyper-arid pacific slope of southern Peru has precipitated growing concern for scarce water resources in the region. Located in the headwaters of the Torata river, in the department of Moquegua, the Cuajone mine, owned by Southern Copper, provides a unique opportunity, in a little-studied region, to examine the relative impact of the landscape-scale mining on water resources in the region. Principal component analysis and cluster analysis of the water chemistry data from 16 sites, collected over three seasons during 2017 and 2018, show distinct statistical groupings indicating that, above the settlement of Torata, water geochemistry is a function of chemical weathering processes acting upon underlying geological units, and confirming that the Cuajone mine does not significantly affect water quality in the Torata river. Impact mitigation strategies that firstly divert channel flow around the mine and secondly divert mine waste to the Toquepala river and tailings dam at Quebrada Honda, below the Toquepala mine, in the department of Tacna, secure water quality in the Torata river for the foreseeable future. In the greater Moquegua river catchment, our results further suggest that water quality has been more significantly impacted by urban effluents and agricultural runoff than the Cuajone mine. The increase in total dissolved solids in the waters of the lower catchment reflects the cumulative addition of dissolved ions through chemical weathering of the underlying geological units, supplemented by rapid recharge of surface waters contaminated by residues associated with agricultural and urban runoff through the porous alluvial aquifer. Concentrations in some of the major ions exceeded internationally recommended maxima for agricultural use, especially in the coastal region. Occasionally, arsenic and manganese contamination also reached unsafe levels for domestic consumption. In the lower catchment, below the Cuajone mine, data and multivariate analyses point to urban effluents and agricultural run-off rather than weathering of exposed rock units, natural or otherwise, as the main cause of contamination.

Typhoons bring great damages to transmission line systems located in coastal areas. Strong wind and extreme precipitation are the main sources of damaging effects. Transmission lines suffered from wind-driven rain exhibit more susceptibility to damage due to the coupled effect of wind and rain water. This paper presents an integrated numerical simulation framework based on mesoscale WRF model, multiphase CFD model and FEM model to analyze the motions of a transmission line subjected to coupled wind and rain loads during typhoon events. A full-scale transmission line in Zhoushan island is employed to demonstrate the effectiveness of the proposed framework by simulating typhoon evolution in terms of wind fields and rainfall, solving the coupled wind and rain fields around the conductor and predicting the dynamic responses of the transmission line during Super Typhoon Lekima (2019). The results show that the horizontal displacements of the transmission line under the joint actions of wind and rain increases approximately 17%~18% compared to those of wind loads only. It is important to consider the coupled effects of wind-driven rain on conductors in the design of transmission lines under typhoon conditions.

Face verification for unrestricted faces in the wild is a challenging task. This paper proposes a method based on two deep convolutional neural networks(CNN) for face verification. In this work, we explore to use identification signal to supervise one CNN and the combination of semi-verification and identification to train the other one. In order to estimate semi-verification loss at a low computation cost, a circle, which is composed of all faces, is used for selecting face pairs from pairwise samples. In the process of face normalization, we propose to use different landmarks of faces to solve the problems caused by poses. And the final face representation is formed by the concatenating feature of each deep CNN after PCA reduction. What's more, each feature is a combination of multi-scale representations through making use of auxiliary classifiers. For the final verification, we only adopt the face representation of one region and one resolution of a face jointing Joint Bayesian classifier. Experiments show that our method can extract effective face representation with a small training dataset and our algorithm achieves 99.71% verification accuracy on LFW dataset.

Results from the phase III Keynote-024 clinical trial have established Pembrolizumab monotherapy as the first-line standard of care for patients with metastatic NSCLC who have PD-L1 expression ≥ 50%, EGFR and ALK wild-type. However, given the differences between patients treated in routine clinical practice and within a clinical trial, real-world data are needed to confirm the treatment benefit in standard practice. Given the lack of data on large cohorts of patients with long follow-up, we designed a retrospective observational study of patients with NSCLC who were treated with Pembrolizumab, starting from its reimbursement eligibility until December 2020. The primary endpoints were to assess PFS and OS using the Kaplan-Meier method, treatment response and safety. We followed 880 patients (median follow-up: 35.1 months) until February 2022. Median PFS and OS were 8.6 months (95% CI: 7.6-10.0) and 25.5 months (95% CI: 21.8-31.6), respectively. We also found that ECOG PS, PD-L1 expression and smoking habit were prognostic factors for PFS, while age, sex, ECOG PS, smoking habit and histology had an impact on OS. Multivariable analysis confirms prognostic role of PD-L1 for PFS and ECOG for both PFS and OS. 39.9% of patients reported an adverse event, but only 6.3% of patients discontinued therapy due to toxicity. Our results suggest a long-term benefit of Pembrolizumab in the first-line setting as well as a safety profile consistent with the results of Keynote-042. Many collected variables appear to influence clinical outcome, but results from these exploratory unadjusted analyses should be interpreted with caution.

: Molecular targeting strategies have been used for years to control cancer progression and are often based on targeting various enzymes involved in metabolic pathways. Keeping that in mind, it is essential to know the role of each enzyme in a particular metabolic pathway. In this review, we are providing in-depth knowledge of various enzymes such as ceramidase, sphingosine kinase, sphingomyelin synthase, dihydroceramide desaturase, and ceramide synthase, which are associated with multiple types of cancer that depend on ceramide metabolism. Focus has also been given to discussing physicochemical properties of well-studied inhibitors of natural products origin and their related structures for these enzymes. Targeting ceramide metabolism exhibited promise in mono and combination therapies at preclinical stages to prevent cancer progression and paved the way for the significance of sphingolipid metabolism in cancer treatments. Targeting ceramide metabolizing enzymes will help the medicinal chemist to design potent and selective small molecules for treating cancer progression at various levels.

A Friedmann-Lemaitre-Robertson-Walker space-time model with all curvatures k=0,±1 is explored in f(R,T) gravity. The solutions are obtained via the parametrization of the scale factor that leads to a model transiting from a decelerated universe to an accelerating one. The physical features of the model are discussed and analysed.

Metabolites are at the end of the gene-transcript-protein-metabolism cascade. As such, metabo-lomics is the omic approach that offers the most direct correlation with phenotype. This allows that, where genomics, transcriptomics and proteomics fail to explain a trait, metabolomics might give an answer. Complex phenotypes, which are determined by the influence of multiple small effect alleles, are an example of these situations. Consequently, the interest in metabolomics has increased ex-ponentially in the last years. As a newer discipline, the metabolomics bioinformatics analysis pipe-lines are not as standardized as in the other omic approaches. In this review we synthesized the different steps that need to be carried out to obtain biological insight from the annotated metabolite abundance raw data. These steps were grouped in three different modules: preprocessing, statistical analyses and metabolic pathway enrichment. We included within each one of them the different state-of-the art procedures and tools that can be used depending on the characteristics of the study, providing details about the characteristics of each method has, as well as the issues the reader might encounter. Finally, we introduce genome scale metabolic modeling as a tool for obtaining pseu-do-metabolomic data in situations where its acquisition is difficult, being possible to analyze the resulting data with the modules of the described workflow.

Vulnerabilities in smart contracts may trigger serious security events, and the detection of smart contract vulnerabilities has become a significant problem. In this paper, by using the multi-scale cascade encoder architecture as the backbone, we propose a novel Multi-scale Encoder Vulnerability Detection (MEVD) approach to detect well-known high-risk vulnerabilities in smart contracts. Firstly, we use the gating mechanism to design a unique Surface Feature Encoder (SFE) to enrich the semantic information of code features. Then, by combining a Base Transformer Encoder (BTE) and a Detail CNN Encoder (DCE), we introduce a dual-branch encoder to capture the global structure and local detail features of the smart contract code, respectively. Finally, to focus the model's attention on vulnerability-related characteristics, we employ the Deep Residual Shrinkage Network (DRSN). Experimental results on three types of high-risk vulnerability datasets demonstrate performance compared to state-of-the-art methods, and our method achieves an average detection accuracy of 90%.

We carry out in a thin heterogeneous porous layer, the multiscale analysis of Smoluchowski's discrete diffusion-coagulation equations describing the evolution density of diffusing particles that are subject to coagulate in pairs. Assuming that the thin heterogeneous layer is made of microstructures that are uniformly distributed inside, we obtain in the limit an upscaled model in lower space dimension. We also prove a corrector-type result very useful in numerical computations. In view of the thin structure of the domain, we appeal to a concept of two-scale convergence adapted to thin heterogeneous media to achieve our goal.

Interspecific competition between herbivorous insects is a major selection pressure affecting the distribution, abundance, and structure of their populations. Facilitator-mediated interactions, such as mutualism, can influence competition. Furthermore, the temporal dynamics of competitive relationships affect the interaction’s outcome. Here, we re-evaluated the data on the competition for space between two herbivorous insects commonly known as scales (Toumeyella martinezae and Opuntiaspis philococcus) in either the presence or absence of Liometopum apiculatum (a mutualistic species of T. martinezae) and its variations over time. We selected 27 Myrtillocactus geometrizans plants on which the studied insects were present; the plants were classified into one of five different conditions: either of the scale species were present on the plant, without its competitor; T. martinezae with neither its mutualistic species nor the competitor; and both scale species competing in either presence or absence of the mutualistic species. We kept a photographic record of each condition, measured the size of (as an indicator of the development stage) and area occupied by the individual scales, estimated the total coverage of each scale species, and assessed their relative occupation of space and their competitive intensity. We found temporal variations in competitive intensity. T. martinezae occupied more space during the first months, whereas O. philococcus did so towards the end of the study period. The population structure changed over time and between species, affecting the competitive interactions. In conclusion, the dynamics of competition change over time, and the mutualistic species has a positive effect on T. martinezae when the scales are in competition. However, temporal variations resulting from changes in the life cycle of the scales allow the two competitors to coexist in the same place at the same time.

Introduction: Lack of certainty or knowledge in health professions generates uncertainty, affecting clinical practice in decision-making (diagnostic or therapeutic), intervention design and therapeutic communication. In nursing, the lack of information to predict prognosis and outcome of interventions generates uncertainty: recognizing and managing it is essential for individualized, safe, and effective care. Objective: to assess uncertainty and the perception of a debriefing within the same shift ("intrathoracic pass") as a proposal for improvement. Method: ad-hoc survey of nursing professionals and Auxiliary Nursing Care Technicians (ANC). Variables: age, work experience, PRU scale (Physisicians' Reactions to Uncertainty) and additional question on intrathoracic pass. Results: Sample: 61 nurses and 10 TCAE (90.14 % female, 9.86 % male; mean age 35.18, standard deviation SD=13.04). Mean professional experience 11.74 years (SD=12.21); 56.33% had ≤4 years of experience. Origin: 49.30% Intensive Care Units (ICU), 11.27% Hospitalization, 7.04% Emergency, 1.41% Primary Care and 30.99% Other Services. The mean level of uncertainty was 27.99 points (max. possible 75; SD=7.50), with stress (mean=25.55, max. possible: 40; SD=5.24) and anxiety (mean=15.80, max. possible: 25; SD=3.05) as major manifestations. The association uncertainty-age (r=0.339; p=0.004) and uncertainty-experience (r=0.391; p=0.001) correlated negatively (the older and more experienced, the less uncertainty), with no significant differences between degrees or services. 91.55% stated that the intra-day pass was useful to reduce uncertainty during the working day. Conclusion: Uncertainty is frequent in nursing, and implementing the intrashift pass is perceived as a competent strategy.

The present paper is concerned with the study of the quality of life index. Such an index has become an important index for measuring the well-being of individuals. However, the quality of life index is always a subjective, intangible, and often hard to quantify with precision due to the lack of quantitative models dealing with. The main goal of the present paper is thus to propose a mathematical, quantitative model for the measurement of a quality of life index. The main novelty is firstly the construction of a wavelet dynamic multiscale model to quantify and investigate the effect of time scale on the quality of life index measuring. The proposed procedure is acted empirically on a sample corresponding to Saudi Arabia as a case of study during the period from 2003 to 2020 as part of the 2030-vision plan. Saudi Arabia has implemented the so-called 2030-vision plan where the quality of life improvement is one of the main goals to be attempted. The findings show that wavelets are capable to localize the time-wise behavior of the index contrarily to classical studies which estimate a global view of the index. Moreover, the study shows the link between the quality of life behavior and many other indices.

A robust hydrological assessment is challenging in regions where human interference, within all aspects of the hydrological system, significantly alters the flow regime of rivers. The challenge was to extend a large-scale water resources model, GWAVA, to better represent water resources without increasing the model complexity. A groundwater and a regulated reservoir routine were incorporated into GWAVA using modifications of the existing AMBHAS-1D and Hanasaki methodologies, respectively. The groundwater routine can be varied in complexity when sufficient input data is available but fundamentally is driven by three input parameters. The reservoir routine was extended to account for the presence of large, regulated reservoirs using two calibratable parameters. The additional groundwater processes and reservoir regulation was tested in two highly anthropogenically influenced basins in India: the Cauvery and Narmada. The inclusion of the revised groundwater routine improved the simulation of streamflow in the headwater catchments and was successful in improving the representation of the baseflow component. In addition, the model was able to produce a time series of daily groundwater levels, recharge to groundwater and groundwater abstraction. The regulated reservoir routine improved the simulation of streamflow in catchments downstream of major reservoirs, where the streamflow was largely reflective of reservoir releases, when calibrated using downstream observed streamflow records. The model was able to provide a more robust representation of the annual volume and daily outflow released from the major reservoirs and simulate the major reservoir storages adequately. The addition of one-dimensional groundwater processes and a regulated reservoir routine proved successful in improving the model performance and traceability of water balance components, without excessively increasing the model complexity and input data requirements.

The present paper investigates numerically the resistance at full-scale of a zero-emission, high-speed catamaran in both deep and shallow water, with the Froude number ranging from 0.2 to 0.8. The numerical methods are validated by two means: a) comparison with available model tests; b) a blind validation using two different flow solvers. The resistance, sinkage and trim of the catamaran, as well as the wave pattern, longitudinal wave cuts and cross-flow fields, are examined. The total resistance curve in deep water shows a continuous increase with the Froude number while in shallow water, a hump is witnessed near the critical speed. This difference is mainly caused by the pressure component of total resistance, which is significantly affected by the interaction between the wave systems created by the demihulls. The pressure resistance in deep water is maximised at a Froude number around 0.58, whereas the peak in shallow water is achieved near the critical speed (Froude number ≈ 0.3). Insight into the underlying physics is obtained by analysing the wave creation between the demihulls. Profoundly different wave patterns within the inner region are observed in deep and shallow water. Specifically, in deep water, both crests and troughs are generated and moved astern as the increase of the Froude number. The maximum pressure resistance is accomplished when the secondary trough is created at the stern, leading to the largest trim angle. In contrast, the catamaran generates a critical wave normal to the advance direction in shallow water, which significantly elevates the bow and creates the highest trim angle as well as pressure resistance. Moreover, significant wave elevations are observed between the demihulls at supercritical speeds in shallow water which may affect the decision for the location of the wet deck.

From physics to the social sciences, information is now seen as a fundamental component of reality. However, a form of information seems still underestimated, perhaps precisely because it is so pervasive that we take it for granted: the information encoded in the very environment we live in. We still do not fully understand how information takes the form of cities, and how our minds deal with it in order to learn about the world, make daily decisions, and take part in the complex system of interactions we create as we live together. This paper addresses three related problems that need to be solved if we are to understand the role of environmental information: (1) the physical problem: how can we preserve information in the built environment? (2) The semantic problem: how do we make environmental information meaningful? And (3) the pragmatic problem: how do we enact environmental information in our daily lives? Attempting to devise a solution to these problems, we introduce a three-layered model of information in cities, namely environmental information in physical space, environmental information in semantic space, and the information enacted by interacting agents. We propose forms of calculating entropy in these different layers, and apply these measures to archetypal urban cases and simulated scenarios. Our results suggest that ordered spatial structures and diverse land use patterns encode information, and that aspects of physical and semantic information affect coordination in interaction systems.

Abstract: Pericyte(s) (Pcs) and resident perivascular macrophages (rPVMΦs) are positioned perfectly in the neurovascular unit (NVU) and perivascular spaces to facilitate metainflammation that results in brain endothelial cell activation and dysfunction and neuroinflammation. Their positions within the NVU allow intimate contact with one another as follows: Brain endothelial cells (BECs) and the Pcs via their shared basement membrane and physical contact peg-socket junctions with N cadherins and gap junctions Cx43; Pcs and rPVMΦs intimate contacts. Additionally, rPVMΦs have intimate contact with the astrocyte endfeet (ACef) that form the outermost membrane of perivascular spaces. Importantly, ACef have intimate contact with BECs that have intimate physical contact with neuronal axons and dendrites to complete NVU coupling. The multiplicity of intimate contacts of NVU cells allow for continuous crosstalk communications to provide brain homeostasis. While each of the cells of the NVU play important roles in the development of enlarged perivascular spaces (EPVS), this review focuses on the Pcs and rPVMΦs and discusses each of the intimate contacts and their functional significance in detail with numerous illustrations and transition electron microscopic images to demonstrate their role in the development of EPVS. EPVS are known to be biomarkers for cerebral small vessel disease and impaired glymphatic system waste clearance. Additionally, EPVS associate with mixed dementias of vascular dementia, vascular contributions to cognitive impairment and dementia, and Alzheimer’s disease that results in high economic and psychosocial cost to the global community.

There is a growing consensus that to effectively adapt to climate change, cities need user-friendly tools and reliable high-resolution biophysical and socio-economic data for analysis, mapping, modeling, and visualization. This study examines availability of various types of information used in climate adaptation plans of 40 municipalities with population less than 300,000 people in the United and in France, probing into the choice and usage of relevant information by small municipalities. We argue that non-climatic spatial data, such as population demographic and socio-economic patterns, urban infrastructure, and environmental data must be integrated with climate tools and datasets to inform effective vulnerability assessment and equitable climate adaptation planning goals. Climate adaptation plans frequently fail to address the existing structural inequalities and environmental injustices in urban infrastructure and land use. Adaptation methodological approaches should be reassessed in the context of much needed societal transformation. Lessons learned from our studies offer valuable insights for potential development of the national and state-level climate adaptation information services for cities.

Digital Image Correlation (DIC) is an optical technique used to measure surface displacements and strains in materials and structures. This technique has demonstrated significant utility in structural examination and monitoring. This manuscript offers a comprehensive review of contemporary research and applications that have leveraged the DIC technique in laboratory-based structural tests. The reviewed works encompass a broad spectrum of structural components, such as concrete beams, columns, pillars, masonry walls, infills, composite materials, structural joints, steel beams, slabs, and other structural elements. These investigations have underscored the efficacy of DIC as a metrological instrument for precise quantification of surface deformation and strain in these structural components. Moreover, the constraints of the DIC technique have been highlighted, especially in scenarios involving extensive or complex test configurations. Notwithstanding these constraints, the DIC methodology has validated its effectiveness as a strain measurement instrument, offering numerous benefits such as non-invasive operation, full-field measurement capability, high precision, real-time surveillance, and compatibility with integration into other measurement instruments and methodologies.

The World Health Organization (WHO) recently added snakebite envenoming to the priority list of Neglected Tropical Diseases (NTD). It is thought that ~75% of mortality following snakebite occurs outside the hospital setting, making the temporal gap between a bite and antivenom administration a major therapeutic challenge. Small molecule therapeutics (SMTs) have been proposed as potential pre-referral treatments for snakebite to help address this gap. Herein, we discuss the characteristics, potential uses and development of SMTs as potential treatments for snakebite envenomation. We focus on SMTs that are secretory phospholipase A2 (sPLA2) inhibitors and metalloprotease (MP) inhibitors.

Phagosomal escape and intracellular survival, often accompanied by Small Colony Variants (SCVs) formation, are typical features of infections caused by S. aureus. The survival in macro-phages favours S. aureus dissemination and complicates treatment. RAW 264.7 murine macro-phages infected with S. aureus USA300 and treated with erythromycin and 20mM carnosine, alone and in combination, were used as experimental model. SCVs were isolated from all treat-ment conditions, but only those undergoing the pressure of combined erythromycin and carnosine for 48 hours were stable for at least six passages on blood agar. Nucleic acid extraction was car-ried out for S. aureus USA300 wild-type and stable SCVs. Whole Genome Sequencing (WGS) was performed using Illumina DNA Prep and Illumina MiSeq, and quantitative reverse transcription PCR was performed. WGS analysis did not yield mutations pointing to differences between S. au-reus USA300 and stable SCVs, therefore the focus was shifted to evaluating gene expression vari-ations. Genes such as zur, mntR, uhpt, fur, sdrE were shown to be significantly up-regulated in SCVs compared to S. aureus USA300 wild-type, suggesting a global change that allows adapta-tion to intracellular persistence, including protection from inflammatory response and evasion of the immune system.

UN 2030 Sustainable Development Goal 6 presents difficulties for small island developing states such as the Kingdom of Tonga, which relies on rainwater and groundwater lenses for freshwater supply. Planning and managing water resources to supply demands in dispersed small islands under variable climate and frequent extreme events is challenging. Tensions between water planning using top-down versus bottom-up processes have long been recognized. Tonga’s overarching national planning instrument is the Tonga Strategic Development Framework, 2015-2025 (TSDFII). This identifies desired national outcomes and is used to direct and resource Ministries and address international and regional commitments. Water supply was a low priority in the three-month consultations that led to TSDFII. Community Development Plans (CDPs), developed by rural villages throughout Tonga’s five Island Groups over nine years, involved participation from 80% of each village population who ranked local priorities. Analysis of priorities in 117 available village CDPs reveals improvements to village water supply was the highest overall priority in all five Island Groups and ranked within the top three priorities by 76% of all villages, with women, youth and men returning figures of 83%, 66% and 80% respectively. The mismatch between top-down and bottom-up priorities appears to result from an urban/rural divide.

This is the second of a two-paper series describing a multi-scale modeling approach developed to simulate crack sensing in polymer fibrous composites by exploiting interruption of electrically conductive carbon nanotube (CNT) networks. The approach is based on the finite element (FE) method. FE models at three different scales, namely the micro-scale, the meso-scale and the macro-scale, have been developed using the ANSYS PDL environment. In the present paper, the meso- and macro-scale analyses are described. In the meso-scale, a two-dimensional model of the CNT/polymer matrix reinforced by carbon fibers is used to develop a crack sensing methodology from a parametric study which relates the crack position and length with the reduction of current flow. In the meso-model, the effective electrical conductivity of the CNT/polymer computed from the micro-scale is used as input. In the macro-scale, the final implementation of the crack sensing methodology is performed on a CNT/polymer/carbon fiber composite volume using as input the electrical response of the cracked CNT/polymer derived at the micro-scale and the crack sensing methodology. Analyses have been performed for cracks of two different lengths. In both cases, the numerical model predicts with good accuracy both the length and position of the crack. These results highlight the prospect of conductive CNT networks to be used as a localized structural health monitoring technique.

As the global transition towards renewable energy accelerates, the integration of grid-scale energy storage systems has become increasingly critical for stabilizing energy supply and enhancing grid reliability. Among various storage technologies, lithium-ion batteries stand out for their high energy density, scalability, and relatively low environmental impact. This study investigates the performance and longevity of lithium-ion batteries in grid-scale applications, focusing on the impact of operational parameters such as cycling frequency, depth of discharge, temperature fluctuations, and charging/discharging rates. Employing a mixed-methods approach, we combined quantitative analysis of performance metrics (cycle life, capacity fade, efficiency) with qualitative assessments from case studies of existing grid-scale projects. Our findings reveal that while lithium-ion batteries exhibit robust performance in grid-scale storage, their longevity and efficiency are significantly influenced by operational conditions. Specifically, temperature management and optimized cycling strategies were identified as key factors in mitigating degradation and extending battery life. This research provides a comprehensive understanding of lithium-ion battery behavior in grid-scale environments, offering valuable insights for the design, optimization, and management of energy storage systems. By addressing the challenges of battery performance and longevity, our study contributes to the development of more sustainable and reliable grid storage solutions, facilitating the broader adoption of renewable energy sources.

Concatemeric viral DNA is packaged into Bacteriophage P22 procapsids via a headful packaging mechanism mediated by a molecular machine consisting of small (gp3) and large (gp2) terminase subunits. Although a negative stain reconstruction exists for the terminase holoenzyme, it is not clear how this complex binds dodecameric portal protein located at a 5-fold mismatch vertex. Herein, we describe new assemblies for the holoenzyme. Both native mass spectrometry and transmission electron microscopy reveal that the P22 terminase complex adopts three main assemblies, which include a nonameric S-terminase bound to two L-terminase 1(gp3)9:2(gp2), two nonameric S-terminase bound to five L-terminase 2(gp3)9:5(gp2), and three nonameric S-terminase bound to seven L-terminase 3(gp3)9:7(gp2). Native agarose gel electrophoresis shows that the terminase complex interacts with procapsid with mild crosslinking. These results herein illustrate the P22 terminase complex can adopt a variety of confirmations and assembly states.

Activating mutations in the Epidermal Growth Factor Receptor gene occur as early cancer-driving clonal events in a subset of patients with non-small cell lung cancer (NSCLC) and result in increased sensitivity to EGFR-tyrosine-kinase-inhibitors (EGFR-TKIs). Despite very frequent and often prolonged clinical response to EGFR-TKIs, virtually all advanced EGFR-mutated (EGFRM+) NSCLCs inevitably acquire resistance mechanisms and progress at some point during treatment. Additionally, 20-30% of patients do not respond or respond for a very short time (< 3 months) because of intrinsic resistance. While several mechanisms of acquired EGFR-TKI-resistance have been determined analyzing tumor specimens obtained at disease progression, the factors causing intrinsic TKI-resistance are less understood. However, recent comprehensive molecular-pathological profiling of advanced EGFRM+ NSCLC at baseline has illustrated the co-existence of multiple genetic, phenotypic, and functional mechanisms that may contribute to tumor progression and cause intrinsic TKI-resistance. Several of these mechanisms have been further corroborated by preclinical experiments. Intrinsic resistance can be caused by mechanisms inherent EGFR or by EGFR-independent processes, including genetic, phenotypic or functional tumor changes. This comprehensive review describes the identified mechanisms connected with intrinsic EGFR-TKI-resistance and differences and similarities with acquired resistance and among clinically implemented EGFR-TKIs of different generations. Additionally, the review highlights the need for extensive pre-treatment molecular profiling of advanced NSCLC for identifying inherently TKI-resistant cases and designing potential combinatorial targeted strategies to treat them.

Social customer relationship management (SCRM) is a new philosophy influencing the relationship between customer and organization, where the customer gets opportunity to control relationship through social media. The paper aims on (a) identification of current level of SCRM and also on (b) influence of basic organizational characteristics on SCRM level. The data were gathered through the questionnaire distributed in 362 organization headquartered in the Czech Republic. The questionnaire comprised 54 questions focusing on the significance of marketing and CRM practices, establishing a relationship with the customer, online communities, the use of social media in marketing, and acquiring and managing information. The majority of questions were scalable and used typical five-level Likert scale. Results showed that larger firms more often set up their own online communities and manage them strategically, moreover they are able to manage information better. Contrariwise, small sized organizations use social networks as a way to establish communication with the customer more than large sized entities. Use of social media for marketing purposes is significantly higher in organizations oriented on consumer markets than on business markets.

The two-scale method (TSM) is an effective approach to simulate electromagnetic (EM) scattering from rough sea surface, to interpret physical interaction of EM wave with rough sea surfaces. The sea surface roughness spectrum and the cutoff wavenumber are two key factors affecting the accuracy of TSM simulation. This paper takes the geophysical model functions (GMFs) of different band as reference, and quantitatively studies the two factors based on the numerical simulation of different polarization backscattering coefficients. The numerical simulation demonstrates that Apel spectrum is more suitable for the backscattering simulation in C/X/Ku-band, and the optimal cutoff wavenumbers are also derived for TSM simulation of EM scattering in C/X/Ku-band. Then an empirical model function of optimal cutoff wavenumbers with respect to frequency, incident angle and wind speed are obtained with regression method. Finally, the simulation results with the new model function of cutoff wavenumber are compared with the GMF and measured data in different bands and they are all consistent. Moreover, a physical explanation for the optimal cutoff wavenumber is also given.

This study investigated the removal characteristics of N-nitrosamines and their precursors at three pilot-scale water reclamation plants. These plants applies different integrated membrane systems: (1) microfiltration (MF) / nanofiltration (NF) / RO; (2) sand filtration/three-step RO; and (3) ultrafiltration (UF) / NF and UF / RO. Variable removal of N-nitrosodimethylamine (NDMA) by the RO membrane processes could be attributable to membrane fouling and feed water temperature. The effect of membrane fouling on N-nitrosamines removal was extensively evaluated at one of the plants by conducting one month of operation and chemical cleaning of the RO membrane element. Membrane fouling enhanced N-nitrosamines removal by the pilot-scale RO membrane process. This finding contributes to better understanding of variable removal of NDMA by RO membrane processes. This study also investigated the removal characteristics of N-nitrosamines precursors. The NF and RO membrane processes greatly reduced NDMA formation potential (FP), but the UF process had little effect. The contributions of MF, NF, and RO membrane processes for reducing FPs of NDMA, N-nitrosopyrrolidine (NPYR) and N-nitrosodiethylamine (NDEA) were different, suggesting different size distributions of their precursors.

Mathematical models of non-small cell lung cancer are powerful tools that use clinical and experimental data to describe various aspects of tumorigenesis. The developed algorithms capture phenotypic changes in the tumor and predict changes in tumor behavior, drug resistance, and clinical outcomes of anti-cancer therapy. The aim of this study was to propose a mathematical model that predicts the changes in the cellular composition of patient-derived tumor organoids over time with a perspective of translation of these results to the parental tumor, and therefore to possible clinical course and outcomes for the patient. Using the data on specific biomarkers of cancer cells (PD-L1), tumor-associated macrophages (CD206), natural killer cells (CD8), and fibroblasts (αSMA) as input, we proposed a model that accurately predicts the cellular composition of patient-derived tumor organoids at a desired time point. Combining the obtained results with “omics” approaches will improve our understanding of the nature of NSCLC. Moreover, their implementation into clinical practice will facilitate a decision-making process on treatment strategy and develop a new personalized approach in anti-cancer therapy.

In the vaginal ecosystem there is a symbiotic relationship between the microbiota and the host, particularly Candida spp., which are considered commensals of the vaginal mucosa. During pregnancy there is an increase in hormonal secretion that alters the vaginal microbiota and favors the development of Candida infection. Several studies have shown the increased prevalence of Candida during pregnancy, as well as its association with perinatal complications and current clinical practice guidelines recommend fluconazole as the treatment of choice during pregnancy in case of infection by Candida albicans and non-albicans Candida. However, in the Mexican population, this association has not been studied. So in this study, an intentional search for colonization by Candida spp. in pregnant women who attended the obstetric triage of the Hospital Regional de Alta Especialidad de Ixtapaluca during the period from May to October 2019, and they were followed up until the end of the pregnancy. Data on age, number of pregnancies, gestational age, body mass index, and perinatal outcomes were analyzed. Of 83 patients included in the study, yeasts corre-sponding to C. albicans (12) and C. glabrata (4) were isolated in 16. In the group of patients with Candida, the maternal age range was from 15 to 36 years old, of which 7 were adolescents and 2 with advanced maternal age, with an average of 2 gestations, the range of body mass index was from 19.3 to 42.4, of which 4 were overweight and 7 obese. Perinatal complications were observed in three patients, one presented chorioamnionitis and in two the neonates were small for gestational age. No association was found between colonization by Candida spp. and the number of preg-nancies, gestational age, body mass index or perinatal results. However, it was found that age (adolescence) may be a risk factor for the development of vulvovaginitis during pregnancy.

As gravitation and electromagnetism are closely analogous long-range interactions, and gravitation is formulated in terms of geometry in general relativity (GR), we expect the latter also to appear through the geometry. This unification has however remained an unfulfilled goal. The goal is achieved here in a new theory, which results from the principles of equivalence and Mach supplemented with a novel insight that the field tensors in a geometric theory of gravitation and electromagnetism must be traceless, since these long-range interactions are mediated by virtual exchange of massless particles whose mass is expected to be related to the trace of the field tensors. Hence the Riemann tensor, like the analogous electromagnetic field tensor, must be traceless. Thence emerges a scale- invariant, Machian theory of gravitation and electrodynamics unified, wherein the vanishing of the Ricci tensor appears as a boundary condition. While the field equations of the theory are given by the vanishing divergence of the respective field tensors and their duals, the matter and charge emerge from the spacetime. A quantitative formulation of the emergent fields embodied in ‘energymomentum super tensors’ follows from the respective Bianchi identities for the two fields. The resulting theory is valid at all scales and explains the observations without invoking the non-baryonic dark matter, dark energy or inflation. Moreover, it answers the questions that the GR-based standard paradigm could not address.

Urban wind energy has emerged as an attractive source of distributed generation in cities to achieve sustainable development goals. The advance in technologies for the use of urban wind energy has turned this source into an attractive alternative for the decarbonization of cities and the energy transition. The objectives of this work are (1) to identify the potential of wind energy through numerical weather prediction (NWP) data tools and (2) to identify the roles and responsibilities of the stakeholders involved in the decision-making process. A methodology was developed in two phases and applied to a case study in the Dominican Republic. The first phase consisted of estimating the wind energy potential for the 32 provinces at a height of 10 m using open-access geographic reference systems tools provided by NASA. In the second phase, 28 stakeholders were identified through snowball sampling. The Responsible, Accountable, Consult, and Informed (RACI) matrix tool was applied to identify the roles of the 28 institutions addressed at the country level as relevant in the decision-making process for the energy sector. The annual average wind speed and energy potential for each province were determined. It was found 24 provinces have poor potential, below &lt;4.5 m/s. In the northwest and east is where there is the greatest potential, between 4.83 - 6.63 m/s. The population density was established and was observed that the provinces with greater potential are less densely populated. Through 59 interviews 28 institutions were identified and evaluated due to their relevance in decision-making for the implementation of energy projects. The MEM has strongly categorized as “A”, electricity distribution companies as “R”, energy associations and universities as “C”, and educational and justice institutions as “I”.

Abstract Kidney transplant recipients, because of a weak immune response due to the assumption of immunosuppressant are exposed to the risk of COVID-19 infection. This fact realize the problem on how to treat the severe infection without carrying the risk of acute rejection due to the reduction of the immunosuppressive drugs. The best are the prophylactic measures to be taken before transplantation as vaccination. If the patient is already transplanted, three measures may be undertaken: Vaccination, use of monoclonal antibodies, use of therapeutic antiviral small molecules. Concerning vaccination is still debated which one is the best and how many doses should be given. The surge of new virus variant is the major problem and invites to find new active vaccines. In addition, not all the transplanted patients develop antibodies. The other measure is the use of monoclonal antibodies. They may be used as prophylaxis or in the early stage of the disease. Finally, the antiviral small molecules may be used again as prophylaxis or treatment. Their major drawback are the interference with the immunosuppressive drugs and the fact that some of them cannot be administered to patients with low eGFR.

One of the most important challenges in the Machine and Deep Learning areas today is to build good models using small datasets, because sometimes it is not possible to have large ones. Several techniques have been proposed in the literature to address this challenge. This paper aims at studying the different available Deep Learning techniques and performing a thorough experimentation to analyze which technique or combination thereof improves the performance and effectiveness of the models. A complete comparison with classical Machine Learning techniques was carried out, to contrast the results obtained using both techniques when working with small datasets. Thirteen algorithms were implemented and trained using three different small datasets (MNIST, Fashion MNIST, and CIFAR-10). Each experiment was evaluated using a well-established set of metrics (Accuracy, Precision, Recall, F1, and the Matthews correlation coefficient). The experimentation allowed concluding that it is possible to find a technique or combination of them to mitigate a lack of data, but this depends on the nature of the dataset, the amount of data, and the metrics used to evaluate them.

The effects of rare earth Y content on the microstructure and high-temperature oxidation properties of 47Fe-36Ni-15Cr-1.5Mn alloy at 1000°C were investigated. The results show that 47Fe-36Ni-15Cr-1.5Mn alloy oxidizes at 1000°C under laboratory atmospheric pressure to form an oxide film layer dominated by Cr2O3 and (Fe, Ni, Mn) Cr2O4 spinel, and the oxidation curve of the alloy follows the parabolic law. After the addition of rare earth Y, rare earth phases precipitated along the grain boundaries in the alloy, and the more Y content, the more precipitated phases in the grain boundaries. The alloy with added rare earths was oxidized at a high temperature of 1000 °C for 2160 min, the oxidation law still followed the parabolic law, while the rare earth phase at the grain boundary reacted with the oxygen atoms infiltrated from the outside to generate a rare earth Y-rich oxide residing at the boundary between the grain boundary and the precipitated phase of the alloy. Add 0.5 wt.% rare earth Y 47Fe-36Ni-15Cr-1.5Mn-0.5Y alloy 1000 ° C high temperature oxidation of the formation of spinel oxide crystalline particles, dense and complete oxide film layer, the surface of the addition of a small amount of (0.5 wt.%) rare earth Y after the refinement of the oxide particles, and in the alloy grain boundaries in the form of oxides reside in the alloy to inhibit the cations in the matrix and the oxygen negative ions. and oxygen-negative ions in the alloy matrix, improving the antioxidant performance of the alloy. With the further increase of rare earth Y, during the oxidation of the alloy at high temperature, the precipitation phase at the grain boundary promotes the inward diffusion of oxygen, resulting in the deterioration of the antioxidant property of the alloy.

Survey data from 42 Australian eastern seaboard veterinary practices involving 506 cases are reported with regard to clinical signs, disease severity, mortality, use of pharmaceuticals, and recovery times. New measures of disease severity (visual analogue scales (VAS) and facial expressions) were tested alongside “gold standard” measures (neuromuscular junction (NMJ) scores). Univariable and multivariable logistic regression analyses were conducted to evaluate associations between variables. The VAS scores were progressive, prognostic (especially the respiratory scores) and correlated with the NMJ scores. The presence of inspiratory dyspnoea and crackles on the day of hospitalization, progressing to expiratory dyspnoea and an expiratory wheeze 24 hours later were highly predictive of mortality. Altered facial features on hospital admission were also highly predictive of mortality. The previously used respiratory score (using various clinical signs) was not predictive of mortality. Older animals had a higher mortality rate and no gender or breed susceptibility was found. The only pharmaceuticals that were positively associated with mortality were tick anti-serum and, in severe cases, antibiotics. The use of many pharmaceutical products (acepromazine, atropine, steroids, antihistamines, antiemetics, diuretics and S8 anti-anxiety and sedation drugs) had no effect on mortality. More drug classes were used with increasing clinical severity and specific factors (e.g. vomiting/retching, hydration) affected the period of hospitalisation. Geographic variation in respiratory signs and toxicity scores was evident, whereas mortality and disease severity were not different across regions.

Capsizing accidents are regarded as marine accidents with a high rate of casualties per accident. Approximately 89% of all such accidents occur in small ships (vessels with gross tonnage less than 10 tons). Stability calculations are critical for assessing the risk of capsizing incidents and evaluating a ship's seaworthiness. Despite the high frequency of capsizing accidents involving small ships, they are generally exempt from adhering to stability regulations, thus remaining systemically exposed to the risk of capsizing. Moreover, the absence of essential design documents complicates direct ship stability calculations. This study utilizes hull form feature data—obtained from the general arrangement of small ships—as input for a deep learning model. The model is structured as a multilayer neural network and aims to infer hydrostatic curves, which is required data for stability calculations.

F-type ATP synthases play a key role in oxidative and photophosphorylation processes producing adenosine triphosphate (ATP) for most biochemical reactions in living organisms. In contrast to the mitochondrial FOF1-ATP synthases those of chloroplasts are known to be mostly monomers with approx. 15% fraction of oligomers interacting presumably non-specifically in a thylakoid membrane. To shed light to the nature of this difference we studied interactions of the chloroplast ATP synthases using small-angle X-ray scattering (SAXS) method. Here, we report evidence of I-shaped dimerization of solubilized FOF1-ATP synthases from spinach chloroplasts at different salinity. The structural data were obtained by SAXS and showed dimerization in response to changes in ionic strength. The best model describing SAXS data was two ATP-synthases connected through F1/F1’ parts, presumably via their δ-subunits, forming dimers with the “I” shape. Such I-shaped dimers might possibly connect the neighboring lamellae in thylakoid stacks assuming that the FOF1 monomers comprising such dimers are embedded in different thylakoid membranes. If this type of dimerization exists in nature, it might be one of the pathways of inhibition of chloroplast FOF1-ATP synthase for preventing of ATP hydrolysis in dark, when salinity in plant chloroplasts is rising. Together with a redox switch inserted into a γ-subunit of chloroplast FOF1 and lateral oligomerization, an I-shaped dimerization might comprise a subtle regulatory process of ATP synthesis and stabilize the structure of thylakoid stacks in chloroplasts.

Small boat fishers are often the lifeblood of remote coastal communities in Iceland, contributing to employment, jobs and economic prosperity. This study conducts exploratory but highly practical research into the efficiency of onboard catch handling practices by Icelandic small boat fishers using fish handling tools called automatic jigging machines. Using applied research methods, this study researches whether standardisation of operations could be applied to make catch handling practices on small boats more time and resource efficient, leading to reduced waste, a consistently higher quality product, and potential increases in economic efficiency and sustainability. Thematic analysis, value stream mapping, flow analysis and Kaizen ideology were adopted to identify gaps and continuous improvement opportunities to standardise processes, leading to exemplary performance. Eight core recommendations are identified, seven of which are classed as straight-forward, ‘do now’ measures according to a Kaizen Priority Matrix. These include human and technological interventions in the areas of safety, organisational arrangements, hygiene, fish handling and bleeding, and cooling. Questionnaire responses reveal four main themes of importance to the sub-sector: changes in recent decades; the importance of small boat fishers; education and improvement; and the particularities of the sub-industry. The latter include the perception of a ‘race against time’ to land the catch, an issue that sometimes contributes to sub-optimal catch handling practices. Although this study has decidedly practical connotations for small boat fishers, its outcomes are also likely to be of interest to academics, particularly those focused on the organisational management of natural resources and general applications of the project management methodology and applied research methods as a means of solving practical problems in everyday life.

In the past few decades, the tourism sector has emerged as a significant economic activity in island nations, particularly in tropical regions. However, most of the tropical islands face similar constraints. National and international tourists visit the SIDS including A & N Islands and contribute to the GDP to significant share. The Covid-19 outbreaks in SIDs including A & N islands shows that number of people infected were less as compared to metros or big cities. However, tourism activities completely stopped due to lockdown resulting in decreasing tourist’s arrival, declined GDP and per capita income of SIDs to greater extent. The information gathered from various sources, mass media and net analysed and interpreted in this chapter. Due to Covid-19 tourist’s arrival declined which has serious consequences on the livelihood of islander. Our analysis revealed A&N Islands deficit in energy available at from different sources by 18.26%. However, they are surplus in protein. The burden of high expenditure coupled with poor infrastructure makes them more vulnerable in the circumstance of pandemic outbreaks. This outbreak has created the question of survival due to loss of jobs, halted economic activates, psychological, health unrest and livelihood threats among the depending people of these Island nations. Therefore, government interventions and subsidized package is very much essential to revive the tourism industry.

Exportin-1, the ubiquitous nuclear protein transporter, is widely confirmed as an active chemotherapeutic target in non-small cell lung cancer condition while Juglans mandshurica is a well-studied anticancer plant in some lung cancer cell lines. We intend to find novel exportin-1 inhibitor from Juglans mandshurica with better potential tolerability and pharmaco-dynamo-kinetic properties than the current selective inhibitors of nuclear export in non-small cell lung cancer treatment. Osiris property explorer DataWarrior, Glide standard precision docking, quantum mechanics polarized ligand docking, MMGBSA binding free energy calculations, Jaguar density functional theory analysis, and the online web-based SwissADME were employed respectively in this study to filter the retrieved compounds based on tolerability, toxicity, and Lipinsky’s rule of five violation potential, determine their druggability, establish relative stability of the lead compound in water solvation model, and evaluates druglikeness, lead-likeness, as well as synthetic accessibility of the lead compound. This study reveals eriodictyol as having higher binding free energy (-40 kcal/mol) than that of standard (-39.56 kcal/mol) in exportin-1 active site, better synthetic accessibility score (3.15 versus 3.29), high GI absorption, non-blood brain barrier permeant, lacks Brenk and PAINS alert, obeying Lipinski’s, Ghose’s, Veber’s, Egan’s, and Muegge’s rule of druglikeness and lead-likeness as well as non-cytotoxic to HepG2 cells. We therefore found eriodictyol as a lead-like, non-toxic exportin-1 inhibitor with good predictive stability and pharmacokinetic potential and thus provided data for further validation of eriodictyol as a candidate exportin-1 inhibitor in both preclinical and clinical studies involving lung cancer therapy.

Land degradation is a critical issue globally putting our future generations at risk. The decrease in farm productivity over the years is evidence of land degradation severity in Nepal. Among the many strategies in place, agroforestry, which is an integrated tree-based farming, is widely recommended to address this productivity issue. This paper thoroughly examines what influences the choice of agroforestry adoption by farmers and what discourages the adoption. For this, a total of 288 households were surveyed using a structured questionnaire. Two agroforestry practices were compared with conventional agriculture with the help of the Multinomial Logistic Regression (MNL) model. The likelihood of adoption was found to be influenced by gender; the male-headed households were more likely to adopt the tree-based farming practice. Having a source of off-farm income was positively associated with the adoption decision of farmers. Area of farmland was found being the major constraint to agroforestry adoption for smallholder farmers. Some other variables that affected positively included livestock herd size, provision of extension service, home-to- forest distance, farmers’ group membership and awareness of farmers about environmental benefits of agroforestry. Irrigation was another adoption constraint that the study area farmers were faced with. The households with means of transport and with larger family (household) size were found to be reluctant towards agroforestry adoption. A collective farming practice could be a strategy to engage the smallholder farmers in agroforestry.

Mediterranean catchments are characterized by significant spatial and temporal hydrological variability caused by the interaction of natural as well human-induced abiotic and biotic factors. This study investigates the (non-)linearity rainfall-runoff relationship at multiple temporal scales in representative small Mediterranean catchments (i.e., < 10 km2) to achieve a better understanding of the hydrological response. Rainfall-runoff relationship was evaluated in 44 catchments at annual and event –203 events in 12 of these 44 catchments– scales. A linear rainfall-runoff relation was observed at annual scale with higher scatter in pervious than impervious catchments. Larger scattering was observed at event scale, although pervious lithology and agricultural land use promoted significant rainfall-runoff linear relations in winter and spring. These relationships were particularly analysed during five hydrological years in Es Fangar catchment (3.35 km2; Mallorca, Spain) as a temporal downscaling to assess intra-annual variability in which antecedent wetness conditions played a significant role in runoff generation.

Membranes based on sulfonated synditoactic polystyrene were thoroughly characterized by contrast variation SANS over a wide Q-range in dry and hydrated states. The film samples were prepared by solid-state sulfonation that allowed a uniform sulfonation of only the amorphous phase while preserving the crystallinity of the membrane. The samples were loaded with different guest molecules in either the amorphous (fullerenes) or the crystalline (toluene) regions, in order to vary the neutron contrast or to reproduce the conditions enabling an increased resistance of the membranes to chemical decomposition. The use of uni-axially deformed film samples and contrast variation with different H2O/D2O mixtures allowed for the identification and characterization of different structural levels with sizes between nm and μm, which form and evolve in the membrane morphology in dry and hydrated states and produce scattering features on different detection sectors and at different detection distances after the sample, depending on their size and orientation.

Background: Plasma metabolites are associated with cognitive and physical function in the elderly. Because cerebral small vessel disease (SVD) and neurodegeneration are common causes of cognitive and physical function decline, the primary objective of this study was to investigate the associations of six plasma metabolites (two plasma phosphatidylcholines [PCs]: PC aa C36:5 and PC aa 36:6 and four sphingomyelins [SMs]: SM C26:0, SM [OH] C22:1, SM [OH] C22:2, SM [OH] C24:1) with magnetic resonance imaging (MRI) features of cerebral SVD and neurodegeneration in older adults. Methods: This study included 238 older adults in the Atherosclerosis Risk in Communities study at the fifth exam. Multiple linear regression was used to assess the association of each metabolite (log-transformed) in separate models with MRI measures except lacunar infarcts, for which binary logistic regression was used. Results: Higher concentrations of plasma PC aa C36:5 had adverse associations with MRI features of cerebral SVD (odds ratio of 1.69 [95% confidence interval: 1.01, 2.83] with lacunar infarct, and beta of 0.16 log [cm³] [0.02, 0.30] with log [White Matter Hyperintensities (WMH) volume]) while higher concentrations of 3 plasma SM (OH)s were associated with higher total brain volume (beta of 12.0 cm³ [5.5, 18.6], 11.8 cm³ [5.0, 18.6], and 7.3 cm³ [1.2, 13.5] for SM [OH] C22:1, SM [OH] C22:2, and SM [OH] C24:1, respectively). Conclusions: This study identified associations between certain plasma metabolites and brain MRI measures of SVD and neurodegeneration in older adults, particularly higher SM (OH) concentrations with higher total brain volume.

The aim of this study is to provide the scientists with a straightforward correlation that can be applied for predicting the Fanning friction factor and consequently the pressure drop during blood flow in small caliber vessels. Due to the small diameter of the conduit, the Reynolds numbers are low and thus the flow is laminar. The study has been conducted using CFD simulations validated with relevant experimental data acquired using an appropriate experimental set-up. The experiments concern pressure drop measurement during the flow of a blood analogue that follows the Casson model, i.e. an aqueous glycerol solution that contains a small amount of xanthan gum and exhibits similar behavior to blood, in a smooth, stainless steel microtube (L=5.6cm and D=400 μm). The interpretation of the resulting numerical data led to the proposal of a simplified model that incorporates the effect of the flow rate, the hematocrit value (35-55%) and the vessel diameter (300-1800 μm) and predicts with better than ±10% the Fanning friction factor and consequently the pressure drop during laminar blood flow in small caliber vessels.

Airworthiness certification requires proof of structure strength, which is performed generally through building block approach. To achieve this, representative intermediate scale experiments generated by test benches are in general needed, additionally to material characterization at coupons scale and structure testing at large scale. The VERTEX test bench can generate combined loading of tension/compression-shear-pressure on structural elements and was modelled with Finite Elements to perform virtual testing representative of its intermediate-scale specificity. The numerous bolted joints of the bench were modelled and their behavior identified in previous tests, so the model could quantitatively estimate the transfer function of the bench, which is the relation between the displacements imposed by the jacks and the resulting loads on a given sample. The VERTEX model was identified to represent load shapes and amplitudes on a training set, and was later confronted to a validation set of tests of tension and shear. A model with ideal boundary conditions was also developed for comparison but it failed to predict some load shape specificities and did not give any indication of loading amplitude. Application cases of the developed model are shown to assess a range of virtual testing possibilities.

Management of multiple primary cancers, a not so infrequent event in oncology practice, is a critical issue due to the lack of literature . In this study, we reported the case of a patient with metachronous double metastatic non small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC) who received gefitinib in combination with gemcitabine plus nab-paclitaxel and with mFOLFOX6 in first and second line, respectively. She achieved a progression free survival and an overall survival (OS) of 28 months for NSCLC and PFS-1 and OS of 20 and 13 months, respectively for PDAC. Moreover, the combination of gefitinib and chemotherapies treatments displayed a good safety profile. Given the insignificant frequency of this case, we performed a molecular characterization of both neoplasms with the aim to investigate the existence of particular activated pathways and/or similar immunological mutations. it is interesting to note that two neoplasms shared a commune mutation of B7-H3 gene, with the consecutive impairment of its expressed protein. In both PDAC and NSCLC, the expression of this protein was associated with a worse survival. Since B7-H3 is an anti-apoptotic protein, the reduction of its expression or function should justify a pro-apoptotic activity with a putative justification of the long survival of the patient considered in this report.