Cardiovascular risk factors (CRFs) such as hypertension, high cholesterol, and diabetes are increasingly implicated in cognitive decline and cerebral small vessel disease (cSVD). White matter hyperintensities (WMH), a hallmark of cSVD, are strongly linked to cognitive impairment, but their underlying mechanisms remain unclear. Blood-brain barrier (BBB) dysfunction has been proposed as a potential contributor to WMH development. This study aimed to explore the relationships between CRFs, BBB integrity, and WMH burden. We analyzed 155 participants from the Biomarkers and Cognition Study, Singapore, assessing CRFs through blood tests for glucose and lipid profiles, alongside blood pressure measurements. WMH volume was quantified using MRI, and an in vitro assay evaluated the impact of plasma on BBB integrity using human brain microvascular endothelial cells. Results showed that plasma from participants with higher WMH burden correlated with increased BBB disruption, which was further associated with higher blood pressure, elevated blood glucose, and lipid levels. Both periventricular and subcortical WMH were linked to BBB disruption. These findings suggest that CRFs contribute to BBB dysfunction, promoting WMH development and cognitive decline in cSVD. Further research is needed to clarify the precise mechanisms driving these associations.

With the increasing demand for security surveillance, assisted driving, and remote sensing, target detection networks with rich environmental perception capabilities and high detection accuracy have become a research hotspot. However, detection techniques based on single-modality images face limitations in environmental adaptability, as they are easily affected by lighting conditions, as well as obstacles such as smoke, rain, and vegetation, leading to information loss and failing to meet the required accuracy. To address these issues, we propose a target detection network—IV-YOLO, which integrates features from both visible and infrared images. We built a dual-branch fusion network based on YOLOv8 (You Only Look Once v8) that combines infrared and visible images for target detection. On this foundation, we designed a Bidirectional Pyramid Feature Fusion structure (Bi-Fusion) to fully integrate complementary features from different modalities, reducing detection errors caused by feature redundancy and extracting fine-grained features of small targets through dual-modal fusion. Additionally, we developed the Shuffle-SPP structure, which combines channel and spatial attention mechanisms to enhance focus on deep features and further aggregate upsampling, extracting richer features. To improve the model’s expressive power, we designed a loss function tailored for multi-scale target detection boxes, accelerating the network’s convergence during training. Experimental results show that the proposed IV-YOLO network achieves an average precision (mAP) of 74.6% on the UAV remote sensing dataset, 75.4% on the KAIST pedestrian dataset, and 84.8% on the FLIR dataset. While ensuring detection accuracy, our model significantly reduces computational load, making it well-suited to meet real-time requirements. This architecture is expected to find broad application in fields such as autonomous driving, public safety, and others.

Sublobar resection is a standard surgical procedure for small-sized non-small cell lung cancer (NSCLC). However, clinical role of adjuvant chemotherapy for small-sized NSCLC with pathological lymph node (LN) metastasis after sublobar resection is unknown. National Cancer Database was queried for NSCLC patients between 2004 and 2018. Eligibility included sublobar resection with pathological LN metastasis, R0 resection, Charlson comorbidity score = 0, clinical stage T1a-b, and tumor size ≤ 20 mm. Kaplan-Meier method with log-rank test and multivariable Cox proportional hazards analyses were used for assessing survival. Samples were evaluated before and after propensity score matching (PSM) with respect to age, sex, histologic type, and pathological LN status. Of 810 patients who met the eligibility criteria, 567 (70.0%) underwent adjuvant chemotherapy. After PSM, patients with adjuvant chemotherapy had a significantly longer survival than those without (median survival: 64.3 vs. 34.0 months, hazard ratio for death: 0.61, p < 0.0001). Multivariate analyses after PSM showed that younger age (p = 0.0206), female (p = 0.0005), and adjuvant chemotherapy (p < 0.0001) were independent prognostic factors for longer survival. Adjuvant chemotherapy has a prognostic impact in patients with small-sized NSCLC and pathological lymph node metastasis who undergo sublobar resection.

Major cardiovascular events (MACE) are a cause of major mortality worldwide. The narrowing and blockage of coronary arteries with atherosclerotic plaques is diagnosed and treated with percutaneous coronary intervention (PCI). During this procedure, coronary angiography (CAG) remains the most widely used guidance modality for the evaluation the affected blood vessel diameter in order to decide if intervention with stent colocation is suitable, where small blood vessels (&lt; 2.75 mm) are majorly left untreated; however, small vessel coronary artery disease (SvCAD) is a significant risk factor for recurrence of MACE, and there are some limitations to the use of CAG that could be improved with the use of newer techniques such as intravascular ultrasound (IVUS), although at higher costs, which might explain their underuse. To address this discrepancy and identify specific cases for its use, we conducted a retrospective study in patients who underwent PCI for MACE with at least one small blood vessel affected. The affected small blood vessels’ diameter was obtained with both CAG and IVUS, additionally we underwent a multivariate analysis to identify risk factors associated with a change in diameter. We included information from 48 patients with mean + SD age of 69.1 + 11.9 years and 34% were masculine gender. We found a significant positive low correlation in diameter measurements of small blood vessels (r=0.1242 p=0.014). Mean diameter with CAG and IVUS was 2.1 mm (95% CI 1.9-2.2), and 2.8 (2.8-3.0) the estimated difference was of 0.8 mm (95 % CI 0.7-0.9). In total 37 (77%) of patients had a reclassification of their blood vessels from a small to medium (2.75-3.00 mm) in 21 cases, or even large (&lt;3.00 mm) in 15 cases, after IVUS; this was important for the decision of intervention and stent collocation. The only variable associated with reclassification of blood vessels after adjusted in a multivariate analysis was DT2 (p=0 0.035). Our findings corroborate that blood vessels might appear smaller with CAG, especially in the diabetes population, therefore at least in these cases the use of IVUS is recommended over CAG.

Abstract Cerebral microbleed(s) (CMBs) are increasingly being viewed not only as a marker for cerebral small vessel disease (SVD) but also as having an increased risk for the development of stroke (hemorrhagic/ischemic) and aging-related dementia. Recently, brain endothelial cell activation and dysfunction and blood-brain barrier dysfunction and/or disruption have been shown to be associated with SVD, enlarged perivascular spaces, and the development and evolution of CMBs. CMBs are a known disorder of cerebral microvessels that are visualized as 3-5mm, smooth, round or oval, and hypointense (black) lesions seen only on T2*-weighted gradient recall echo or susceptibility-weighted sequences on MRI images. CMBs (a global problem) are known to occur with high prevalence in community-dwelling older individuals. Since our current global population is the oldest recorded in history and only expected to continue to grow, we can only expect the health care burdens associated with CMBs to also grow. CMBs should raise a red flag regarding the increased risk of large symptomatic neurologic intracerebral hemorrhages. Importantly, CMBs are also currently regarded as markers of diffuse vascular and neurodegenerative brain damage. Thus, it is essential that we try to learn as much as we can about their development, evolution, and their relation to impaired cognition, dementia, and neurodegeneration.

The small-molecule iododiflunisal (IDIF) is a transthyretin (TTR) tetramer stabilizer and acts as a chaperone of the TTR-Amyloid beta interaction. Oral administration of IDIF improves Alzheimer’s Disease (AD)-like pathology in mice, although mechanism of action and pharmacokinetics remain unknown. Radiolabeling IDIF with positron or gamma emitters may aid in the in vivo evaluation of IDIF using non-invasive nuclear imaging techniques. In this work, we report isotopic exchange reaction to obtain IDIF radiolabeled with 18F. [19F/ 18F]exchange reaction over IDIF in dimethylsulfoxide at 160 °C resulted in the formation of [18F]IDIF in 7±3% radiochemical yield in a 20 minutes reaction time, with a final radiochemical purity of >99%. Biodistribution studies after intravenous administration of [18F]IDIF in wild-type mice using positron emission tomography (PET) imaging showed capacity to cross the blood-brain barrier (ca. 1% of injected dose per gram of tissue in the brain at t&gt;10 min post administration), rapid accumulation in the liver, long circulation time and progressive elimination via urine. Our results open opportunities for future studies in larger animal species or human subjects.

The RNA-binding protein Human antigen R (HuR) regulates stability, translation, and nucleus-to-cytoplasm shuttling of its target mRNAs. The protein has been progressively recognized as a relevant therapeutic target for several pathologies like cancer, neurodegeneration, as well as inflammation. Inhibitors of mRNA binding to HuR might thus be beneficial against a variety of diseases. Here we present the rational identification of structurally novel HuR inhibitors. In particular, by combining chemoinformatics approaches, high throughput virtual screening and RNA–protein pull-down assays, we show that the 4-(2-(2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene)hydrazineyl)benzoate ligand exhibits dose-dependent HuR inhibition in binding experiments. Importantly, the chemical scaffold is new with respect to the so-far known HuR inhibitors, opening up a new avenue for the design of pharmaceutical agents targeting this important protein.

Recently, SMR (Small Modular Reactor) is expected to be able to operate flexibly in conjunction with a high renewable energy penetration grid as a result of improved safety and easy power control compared to large nuclear power plants. SMRs such as South Korea’s System-integrated Modular Advanced ReacTor (SMART) are designed to use canned motors (CMs) for their reactor coolant pumps (RCPs) to enhance safety. The CMs passively enhance the reactor’s safety by preventing leakage of radioactive reactor coolant. However, with motor sizes designed to be as small as possible, and the increased air gap of CMs between stator and rotor, starting torque may be insufficiently small compared to that of similar sized induction motors (IMs). Thusly, CMs may require variable frequency drives (VFDs) to start. This paper compares the torque characteristics of CMs with those of IMs for SMART’s RCPs. ETAP is then used to perform motor starting analysis for CMs started with and without VFDs. The results are presented and analyzed to find out if the VFDs deal with the CM starting torque issue.

Skin melanoma presents increasing prevalence and poor outcomes. Progression to aggressive stages is characterized by overexpression of the transcription factor E2F1 and activation of downstream prometastatic gene regulatory networks (GRNs). Appropriate therapeutic manipulation of the E2F1-governed GRNs holds the potential to prevent metastasis however, these networks entail complex feedback and feedforward regulatory motifs among various regulatory layers, which make it difficult to identify druggable components. To this end, computational approaches such as mathematical modeling and virtual screening are important tools to unveil the dynamics of these signaling networks and identify critical components that could be further explored as therapeutic targets. Herein, we integrated a well-established E2F1-mediated epithelial-mesenchymal transition (EMT) map with transcriptomics data from E2F1-expressing melanoma cells to reconstruct a core regulatory network underlying aggressive melanoma. Using logic-based in silico perturbation experiments of a core regulatory network, we identified that simultaneous perturbation of Protein kinase B (AKT1) and oncoprotein murine double minute 2 (MDM2) drastically reduces EMT in melanoma. Using the structures of the two protein signatures, virtual screening strategies were performed with the FDA-approved drug library. Thus, by combining drug repurposing and computer-aided drug design techniques, followed by molecular dynamics simulation analysis identified two potent drugs (Cialis and Finasteride) that can efficiently inhibit AKT1 and MDM2 protein signatures respectively, and with better therapeutic properties. We proposed that these two drugs could be considered for the development of therapeutic strategies for the management of aggressive melanoma.

Since 2020 COVID-19 has caused serious mortality around the world. Given the ambiguity in es-tablishing COVID-19 as the direct cause of death we first investigate the effects of age and sex upon all-cause mortality during 2020 and 2021 in England and Wales. Since infectious agents have their own unique age profile for death, we explore several methods to adjust single year of age deaths in England and Wales during 2019 (the pre-COVID-19 base year) to a pathogen-neutral single year of age baseline. This adjusted base year is then used to confirm the widely reported higher deaths in males for most ages above 43 years in both 2020 and 2021. During 2020 (+ COVID-19 but no vac-cination) both male and female population-adjusted deaths were significantly increased above age 35. A significant reduction in all-cause mortality among both males and females aged 75+ could be demonstrated in 2021 during widespread COVID–19 vaccination, however, below age 75 deaths progressively increased. This finding arises from a mix of vaccination and year of age profiles of deaths for the different SARS-CoV-2 variants. In addition, specific effects for age around puberty were demonstrated where females had higher deaths rather than males. There is evidence that year-of-birth cohorts may also be involved, indicating that immune priming to specific pathogen outbreaks in the past may lead to lower deaths for some birth cohorts. To specifically identify the age profile for the COVID-19 variants in 2020 to 2023, we employ the proportion of total deaths at each age which are potentially due to or ‘with’ COVID-19. The original Wuhan strain, and the Alpha variant show somewhat limited divergence in the age profile with the Alpha variant shifted to a moderately higher proportion of deaths below age 84. The Delta variant specifically targeted persons below age 65. The Omicron variants showed significantly lower proportion of overall mortality, with markedly higher relative proportion of deaths above age 65 steeply increasing with age to a maximum around 100 years of age. A similar age profile for the variants can be seen in the age-banded deaths in US states – although slightly obscured by using age bands rather than single year of age. However, the US data shows that higher male deaths are greatly dependent on age and the COVID-variant. Deaths determined as ‘due to’ COVID-19 (as opposed to ‘involving’ COVID-19) in England and Wales were especially over-estimated in 2021 relative to the change in all-cause mortality. This arose as a by-product of an increase in COVID-19 testing capacity in late 2020. Potential structure-function mechanisms for the year of age specificity of SARS-CoV-2 var-iants are discussed. The question is posed as to whether vaccines based on different variants carry the specific age profile through into the vaccine.

Ral-interacting protein 76 (RLIP76) is a potential factor with vascular endothelial growth factor (VEGF) in the corpus luteum and tumor angiogenesis. RLIP76, VEGF, and hypoxia-inducible factor-1 (HIF-1) are proteins that activate angiogenic functions in tumor and endothelial cells. RLIP76 is a main factor in tumor growth, and VEGF is a major endothelial cell protein for angiogenesis. Also, RLIP76 regulates a small GTPase (R-Ras, oncogene) in cell survival, spreading, and migration. HIF-1 is important in the corpus luteum, tumor angiogenesis, and tumor growth. VEGF and HIF-1 regulate the angiogenic function of RLIP76, and RLIP76 controls vascular growth in endothelial and tumor cells. RLIP76, R-Ras, VEGF, and HIF-1 may be useful in the research of corpus luteum and cancer therapy and the study of mechanisms of tumor angiogenesis. This review will help to elucidate the roles of RLIP76/R-Ras and VEGF via HIF-1 in corpus luteum and tumor angiogenesis, tumorigenesis, and the specific regulation of RLIP76 in luteal, tumor, and endothelial cells. Thus, we reviewed the angiogenesis of the corpus luteum and tumor in the ovarian and tumor microenvironment.

The selenoprotein glutathione peroxidase 4 (GPX4) is one of the main antioxidant mediators in the human body. Its central function involves the reduction of complex hydroperoxides into their respective alcohols often using reduced Glutathione (GSH) as a reducing agent. GPX4 has become a hotspot therapeutic target in biomedical research following its characterization as a chief regulator of ferroptosis, and its subsequent recognition as a specific pharmacological target for the treatment of an extensive variety of human diseases including cancers and neurodegenerative disorders. Several recent studies have provided insights into how GPX4 is distinguished from the rest of the glutathione peroxidase family, the unique biochemical properties of GPX4, how GPX4 is related to lipid peroxidation and ferroptosis, and how the enzyme may be modulated as a potential therapeutic target. This current report aims to review the literature underlying all these insights and present an up-to-date perspective on the current understanding of GPX4 as a potential therapeutic target.

Background: Real-world data on the molecular epidemiology of EGFR resistance mutations at or after progression with first- or second-generation EGFR-TKIs in patients with advanced NSCLC are lacking. Methods: This ongoing observational study was carried out by 23 hospital-based physicians in Greece. The decision to perform Cobas® EGFR Mutation Test v2 in tissue and/or plasma at disease progression was made before enrollment. For patients with negative/inconclusive T790M plasma-based results, tissue re-biopsy could be performed. Results: Ninety-six (96) eligible patients were consecutively enrolled (median age: 67.8 years) between July-2017 and September-2019. Of the patients, 98% were tested upon progression using plasma and 2% using tissue/cytology biopsy. The T790M mutation was detected in 16.0% of liquid biopsies. Tissue re-biopsy was performed in 22.8% of patients with a T790M-negative plasma result. In total, the T790M positivity rate was 21.9%, not differing between patients on first- or second-generation EGFR-TKI. Higher (≥2) ECOG performance status and longer (≥10 months) time to disease progression following EGFR-TKI treatment initiation were associated with T790M positivity. Conclusions: Results from plasma/tissue-cytology samples in a real-world setting, yielded a T790M positivity rate lower than previous reports. Fewer than one in four patients with negative plasma-based testing underwent tissue re-biopsy, indicating the challenges in routine care settings.

Desmoplastic small round cell tumor (DSRCT) is an extremely rare, aggressive sarcoma affecting adolescents and young adults with male predominance. Generally, it originates from serosal surface of abdominal cavity. The hallmark characteristic of DSRCT is the EWSR1-WT1 gene fusion. This translocation up-regulates the expression of PDGFRα, VEGF and other proteins related to tumor and vascular cell proliferation. Current management of DSRCT includes a combination of chemotherapy, radiation and aggressive cytoreductive surgery plus intra-peritoneal hyperthermic chemotherapy (HIPEC). Despite advances in multimodal therapy, outcomes remain poor since the majority of patients present disease recurrence and die within 3 years. The dismal survival makes DSRCT an orphan disease with urgent need of new drugs. The treatment of advanced and recurrent disease with tyrosine kinase inhibitors, such as pazopanib, sunitinib, and mTOR inhibitors have been evaluated in small studies. Recent works using comprehensive molecular profiling of DSRCT identified potential therapeutic targets. In this review, we aim to describe the current studies conducted to better understand DSRCT biology and to explore the new therapeutic strategies under investigation in preclinical models and in early phase clinical trials.

Previously, we demonstrated that IR triggers the invasion/migration of A549 cells via activation of an EGFR–p38/ERK–STAT3/CREB-1–EMT pathway. Here, we have demonstrated the involvement of a novel intracellular signaling mechanism in γ-ionizing radiation (IR)-induced migration/invasion. Expression of receptor-interacting protein (RIP) 1 was initially increased upon exposure of A549, a non-small cell lung cancer (NSCLC) cell line, to IR. IR-induced RIP1 is located downstream of EGFR and involved in the expression/activity of matrix metalloproteases (MMP-2 and MMP-9) and vimentin, suggesting a role in epithelial-mesenchymal transition (EMT). Our experiments showed that IR-induced RIP1 sequentially induces Src-STAT3-EMT to promote invasion/migration. Inhibition of RIP1 kinase activity and expression blocked induction of EMT by IR and suppressed the levels and activities of MMP-2, MMP-9, and vimentin. IR-induced RIP1 activation was additionally associated with stimulation of the transcriptional factor NF-κB. Specifically, exposure to IR triggered NF-κB activation and inhibition of NF-κB suppressed IR-induced RIP1 expression followed by a decrease in invasion/migration as well as EMT. Based on the collective results, we propose that IR concomitantly activates EGFR and NF-κB and subsequently triggers the RIP1–Src/STAT3–EMT pathway, ultimately promoting metastasis.

Integrating ecosystem services (ESs) to delineate ecological functional zones (EFZs) is a fundamental work in terrestrial spatial planning and ecosystem management. However, existing studies have largely overlooked the refinement of EFZs at local scales, which hinders targeted and multi-scale ecosystem management. This study introduced a "two-step refinement zoning method" to address this gap, first using the self-organizing feature mapping method to delineate EFZs based on ESs at a township scale, and then applying hotspot overlay analysis to identify hotspots of dominant ESs within EFZs at a village scale. By overlaying the outcomes of these two steps, EFZs can be further graded by designating villages with hotspots of dominant ESs as level I and those without as level II. The proposed method was applied in Wuhan City, dividing it into five types of EFZs with different ESs combinations and land use compositions. Furthermore, 5.23% of villages were identified as Level I of EFZs, serving as advantageous areas of dominant ESs in the study area. On this basis, diversified management strategies and conservation priorities were proposed. This study provides a theoretical and methodological reference for terrestrial spatial planning and sustainable ecosystem management.

Graphene was synthesized through a two-step pyrolysis method using waste candlenut (Aleurites moluccanus) shells as the precursor. Cerium (Ce)/graphene composites were prepared via an impregnation technique. The resulting graphene and Ce/graphene were characterized using various analytical methods, including Scanning Electron Microscopy with Energy-Dispersive Spectroscopy (SEM-EDS), X-ray Diffraction (XRD), X-ray Photoelectron Spectroscopy (XPS), Transmission Electron Microscopy (TEM), Thermo Gravimetric Analysis (TGA), Fourier Transform Infrared (FTIR) spectroscopy, Cyclic Voltammetry (CV), and Linear Sweep Voltammetry (LSV). The bio-carbon produced predominantly exhibited a graphene structure with flat carbon morphology and an interlayer distance of 0.33 nm. This structural information is supported by XRD data, which shows a broad and weak peak at 2θ = 26° corresponding to the C (002) plane, indicative of graphene presence. FTIR, XPS, and Raman spectroscopy further confirmed the presence of graphene through the detection of Csp2 aromatic bonds and the characteristic D, G, and 2D peaks. Notably, the performance of cerium can be enhanced by the incorporation of graphene, attributed to the large surface area and chemical interactions between Ce and graphene. Consequently, candlenut-derived graphene shows potential as a supportive material for modifying the properties of cerium, thereby opening avenues for various advanced applications, such as sustainable and high-performance energy storage systems.

Civic participation is of great significance to urban management decision-making. In order to facilitate citizens to participate in city management decision-making, this paper proposes a large-scale group decision-making (LSGDM) method based on multi-granular probabilistic linguistic preference relations (MG-PLPRs). First, each decision maker selects a language terms set from the multi-granularity language terms set to represent individual preference relations and the MG-PLPRs are obtained by statistical calculation to represent sub-group’s preferences information. Then, an optimization model based on the expected consistency of PLPR and consensus measure of groups is established to achieving consensus reaching processes, which can ensure satisfactory individual consistency and group consensus. Finally, the validity and applicability of the proposed method is verified by a case of a city "shared garden" site selection with the participation of citizens.

In the rapidly evolving landscape of the AI era, the measurement of Computational Thinking ability among Computer Science (CS) University students is of paramount importance. This study introduces UniCTCheck, a novel method designed to assess the main components of Computational Thinking in CS students. Utilizing two key instruments, namely the web application CTScore and the psychometric scale CTProg, this research aims to precisely evaluate seven core components of Computational Thinking and six programming concepts skills essential for CS students. The study, conducted at Rey Juan Carlos University and Atlantic Technological University Galway, involved a diverse sample of students from different year levels and program specializations. Through a rigorous research design, including sampling strategies and data collection tools, this study seeks to address critical research questions related to measurement of variations in students' Computational Thinking and programming skills by gender, university level, and location. By shedding light on the significance of Computational Thinking and programming in the educational realm, this research contributes to the existing literature and underscores the essential role of computational skills in the modern era.

There is an anecdotal impression that teenage patients report exaggerated postoperative pain scores that do not correlate with their actual level of pain. Nurse and parental perception of teenagers' pain can be complemented by knowledge of patient pain behavior, pain catastrophizing thoughts, anxiety, and mood level. Two hundred two patients completed the study: 56.4% female, 89.6% White, 5.4% Black, and 5% other race. Patient ages ranged from 11 to 17 years (mean = 13.8, SD = 1.9). The patient, the parent, and the nurse completed multiple questionnaires on day one after laparoscopic surgery to assess patient pain. Teenagers and parents (r=0.56) have a high level of agreement, and teenagers and nurses (r=0.47) have a moderate level of agreement on pain scores (p &lt;0.05). The correlation between patient APBQ (Adolescent Pain Behavior Questionnaire) and teenager VAS (Visual Analog Scale ) and between nurse APBQ and teenager VAS, while statistically significant (p &lt; 0.05), is weaker (r range = 0.14-0.17). There is a moderate correlation between teenagers' pain scores and their psychological assessments of anxiety, catastrophic thoughts, and mood (r range= 0.26 – 0.39; p &lt;0.05). A multi-modal evaluation of postoperative pain can be more informative than only assessing self-reported pain scores.

The Universe is treated as an unbound thermodynamic system in which two forces of Nature compete: Attractive gravity loss and repulsive entropic gain. Entropic gain, although not presently considered a force of Nature, is otherwise well known and can be expressed with the gas laws. The Universe at the time of last scattering was all gas. Its instant gain is expressed as gas pressure. When the Gibbs equation is properly applied to this unbound gas, the resulting atomic Hubble parameter is found to be exclusively dependent on baryon density, giving a constant and perpetual two-to-one gain/loss ratio. Instant loss to gravity cannot offset gas pressure in this “thermal equation”. By contrast, the Friedmann equation, a ΛCDM foundation, treats baryon mass as accreted, having little if any entropic gain. These two equations are actually equivalent. Expanding accreted matter at its comoving critical density is herein shown to behave exactly like a freely expanding gas. However, neither equation includes all of today’s Universal kinetic energy, and cannot by themselves fully account for observed stellar movement. The present paper proposes the plausible existence of highly energetic or “suprathermal” free electrons which comprise about half of the intergalactic medium’s kinetic total. It is this suprathermal energy which Λ expresses. The fluid equation, another ΛCDM foundation, eliminates entropic gain from the Gibbs equation. Additionally, rest mass’s Einstein energy E=Mc² is treated as a thermal variable. These two assumptions, isoentropy and energy conflation, led astronomers to populate Λ as they followed the prior art.

In Nigeria, Cervical cancer (CC) and lack of Human Papillomavirus (HPV) awareness poses significant HPV infection risk among women. This study was conducted at Ibrahim Badamasi Babangida (IBB) University in Nigeria; focused on assessing HPV awareness and knowledge, particularly concerning its association with CC and oral contraceptive (OC) pills among students and staff. We adapted and validated a 20-item HPV knowledge scale and explored factors influencing knowledge, vaccination rates, awareness, and the impact of ethnicity on HPV knowledge. Also, due to the non-normality of the knowledge score, non-parametric tests were done. Data were summarized using median and interquartile range (IQR), while categorical data were presented in frequency and percentage distribution. We established the reliability of the 20-item knowledge scale with a strong Cronbach's alpha coefficient of 0.913, indicating internal consistency. However, it revealed a concerning lack of awareness and knowledge about HPV, only 34.8% of participants were aware of HPV infection, and only 25.0% knew about HPV vaccine. Additionally, ethnicity was identified as a significant factor affecting HPV knowledge. Considering these findings, this study emphasizes the need for targeted interventions to enhance HPV awareness and knowledge, particularly among specific ethnic groups. Despite the development and validation of a reliable knowledge scale, the study underscores the importance of educational initiatives to address this knowledge gap, ultimately reducing the risk of HPV infection and CC in Nigeria.

This paper is dedicated to examining dynamic dark energy models in the context of observational constraints and their implications for the universe's future. By integrating theoretical models with various observational data, we aim to provide a comprehensive view of how dynamic dark energy influences cosmic evolution and the universe's fate. This study tests these models against the latest observational evidence, including the Cosmic Microwave Background, supernovae, and large-scale structure surveys, to refine our understanding of the universe's accelerating expansion and the mysterious nature of dark energy.

Background. Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous systemic syn-drome that often coexists with multiple comorbidities. In high-complex COPD patients the role of the Cumulative Illness Rating Scale (CIRS) as a risk predictor of COPD exacerbation is not known. Objective. To determine the effectiveness of the CIRS score in detecting the association of comorbidities and disease severity with the risk of acute exacerbations in COPD patients. Methods. 105 adults with COPD were included in this prospective study. All participants at baseline had at least 2 moderate exacerbations or 1 leading to hospitalization. The primary outcome was a composite of moderate or severe COPD exacerbation during 12-months follow-up. Results. CIRS indices (CIRS total score, Severity Index and Comorbidity Index) showed a positive correlation with mMRC, CAT and a negative correlation with FEV1, FVC, FEV1/FVC. The three CIRS indices were able to predict the 12-month rate of moderate or severe exacerbation (CIRS-Total Score: Hazard Ratio (HR) = 1.12 (95% CI: 1.08-1.21); CIRS-Severity Index: HR = 1.21 (95% CI: 1.12-1-31); CIRS-Comorbidity Index = 1.58 (95% CI: 1.33-1.89)). Conclusions. Among patients with COPD, comorbidity number and severity, assessed by the CIRS score, influence the risk in moderate to severe exacerbations. The CIRS score also correlates with the severity of respiratory symptoms and lung function

Deepfakes are manipulated or altered images, or video, that are created using deep learning models with high levels of photorealism. The two popular methods of producing a deepfake are based on either convolutional neural networks (CNN), or autoencoders. Deepfakes created using CNN comparatively show higher qualities of realism, yet oftentimes leave artifacts and distortions in the generated media that can be detected using machine learning and deep learning algorithms. In recent years, there has been an influx of periocular image and video data because of the increase usage of face masks. By wearing masks, much of what is used for facial recognition is hidden, leaving only the periocular region visible to an observer. This loss of vital information leads to easier misidentification of media, allowing deepfakes to less likely be identified as fake. In this work, feature extraction methods, such as Scale-Invariant Feature Transform (SIFT), Histogram of Oriented Gradients (HOG), and CNN, are used to train an ensemble deep learning model to detect deepfakes in videos on a frame-by-frame level based on the periocular region. Our proposed model is able to distinguish original and manipulated images with accuracies around 98.9 percent, which is an improvement to previous works by combining SIFT and HOG for deepfake detection in convolutional neural networks.

This paper attempts to describe the large-scale (solar system-like, astronomical-scale) systems of the known world using the physical models and mathematical tools of relativistic quantum mechanics. The value of H_x can be introduced and approximated as an analogue of the constant ℏ. Based on the quantum mechanical approach, the proper time scale of the solar system can be determined.

The shape of the knee is a chain-like structure of an ellipsoid. This suggests that, in the latest study, in addition to rolling, there is slippage in the motion of the knee. This paper selects a mechanical braking model for cattle based on two mechanical structures in different directions at the joints. The experimental results show that the modified dynamical system has strong chaotic properties. This can be one of the basis for judging various health states.

The central goal of few-shot scene classification is to learn a model that can generalize well to a novel scene category (UNSEEN) from only one or a few labeled examples. Recent works in the remote sensing (RS) community tackle this challenge by developing algorithms in a meta-learning manner. However, most prior approaches have either focused on rapidly optimizing a meta-learner or aimed at finding good similarity metrics while overlooking the embedding power. Here we propose a novel Task-Adaptive Embedding Learning (TAEL) framework that complements the existing methods by giving full play to feature embedding’s dual roles in few-shot scene classification - representing images and constructing classifiers in the embedding space. First, we design a lightweight network that enriches the diversity and expressive capacity of embeddings by dynamically fusing information from multiple kernels. Second, we present a task-adaptive strategy that helps to generate more discriminative representations by transforming the universal embeddings into task-specific embeddings via a self-attention mechanism. We evaluate our model in the standard few-shot learning setting on two challenging datasets: NWPU-RESISC4 and RSD46-WHU. Experimental results demonstrate that, on all tasks, our method achieves state-of-the-art performance by a significant margin.

Environmental conditions, such as temperature, carbon dioxide, and nutrient availability, are altered by urban conditions at regional scales with potential for impact on tree leaf structure. Our goal was to compare leaf morphological characteristics driven by physiological acclimation in red maple (Acer rubrum L.) trees in deciduous forests embedded in a small (Newark, DE) and a large (Philadelphia, PA) city. The study was conducted in six urban forests on eighteen mature red maple trees in a long-term urban forest network. We hypothesized that red maples in Philadelphia forests compared to Newark forests will have a thicker upper epidermal layer, spongy palisade and mesophyll layer, longer and wider stomates, and lower stomate density. Additionally, we hypothesized that red maples in Philadelphia forests compared to Newark forests will have lower leaf water content and specific leaf area, and greater leaf thickness, fresh leaf weight, dry leaf weight, and leaf dry matter content. Our results for stomate length and stomate width supported our predictions; red maple leaves had longer and wider stomates in Philadelphia forests than in Newark forests. The increased stomate size in red maple trees suggests potential altered gas exchange behavior and mutual abiotic stress mitigation responses in red maple to greater urbanization impacts in Philadelphia forests. This supports previous findings of possible physiological and biochemical acclimation of red maple trees to urban conditions. Furthermore, the findings from this study suggest red maple trees may be a good biomonitor of regional scale impacts in urban environments.

With reference to Planck scale, increasing support for large scale cosmic anisotropy and preferred directions and by considering an increasing ratio of Hubble parameter to angular velocity, right from the beginning of Planck scale, we make an attempt to estimate ordinary matter density ratio, dark matter density ratio, mass, radius, temperature, age and expansion velocity (from and about the baby universe in all directions). We would like suggest that, from the beginning of Planck scale, 1) Dark matter can be considered as a kind of cosmic foam responsible for formation of galaxies. 2) Cosmic angular velocity decreases with square of the decreasing cosmic temperature. 3) Increasing ratio of Hubble parameter to angular velocity plays a crucial role in estimating increasing cosmic expansion velocity and decreasing density ratios of dark matter and ordinary matter. 4) There is no need to consider dark energy for understanding cosmic acceleration.

This article proposes the use of a multi-scale and multi-sensor approach to collect and modelling 3D data concerning wide and complex areas in order to obtain a variety of metric information in the same 3D archive, based on a single coordinate system. The employment of these 3D georeferenced products is multifaceted and the fusion or integration among different sensors data, scales and resolutions is promising and could be useful for the generation of a model that could be defined as hybrid. The correct geometry, accuracy, radiometry and weight of the data models are hereby evaluated comparing integrated processes and results from Terrestrial Laser Scanner (TLS), Mobile Mapping System (MMS), Unmanned Aerial Vehicle (UAV), terrestrial photogrammetry, using Total Station (TS) and Global Navigation Satellite System (GNSS) as topographic survey. The entire analysis underlines the potentiality of the integration and fusion of different solutions and is a crucial part of the “Torino 1911” project whose main purpose is mapping and virtually reconstructing the 1911 Great Exhibition settled in the Valentino Park in Turin (Italy).

Fluctuations of protein three-dimensional structures and large-scale conformational transitions are crucial for the biological function of proteins and their complexes. Experimental studies of such phenomena remain very challenging and therefore molecular modeling can be a good alternative or a valuable supporting tool for the investigation of large molecular systems and long-time events. In this mini-review, we present two alternative approaches to the coarse-grained (CG) modeling of dynamic properties of protein systems. We discuss two CG representations of polypeptide chains used for Monte Carlo dynamics simulations of protein local dynamics and conformational transitions and, on other hand, highly simplified structure-based Elastic Network Models of protein flexibility. In contrast to classical Molecular Dynamics the modeling strategies discussed here allow quite accurate modeling of much larger systems and longer time dynamic phenomena. We briefly describe the main features of these models and outline some of their applications, including modeling of near-native structure fluctuations, sampling of large regions of the protein conformational space, or possible support for the structure prediction of large proteins and their complexes.

A new model of cosmology is proposed, where the state of high energy density commonly associated with the big bang is generated by the collapse of an antineutrino star that has exceeded its Chandrasekhar limit. To allow the first neutrino stars and antineutrino stars to form naturally from an initial quantum vacuum state, matter and antimatter are assumed to gravitationally repel. In this scenario, a degenerate antineutrino star in effective hydrostatic equilibrium has a density that is similar to the dark energy density of the ΛCDM model. When viewed from the core, such a star could today accelerate matter radially and emit the isothermal cosmic microwave background radiation, which addresses the horizon and flatness problems. This model and the ΛCDM model are in similar quantitative agreement with supernova distance measurements. The presented model is also in qualitative agreement with observed large-scale anisotropy and inhomogeneity, which distinguishes it from the ΛCDM model.

In this paper, we will revisit the derivation of Heisenberg's uncertainty principle. We will see how the Heisenberg principle collapses at the Planck scale by introducing a minor modification. The beauty of our suggested modification is that it does not change the main equations in quantum mechanics; it only gives them a Planck scale limit where uncertainty collapses. We suspect that Einstein could have been right after all, when he stated, ``God does not throw dice." His now-famous saying was an expression of his skepticism towards the concept that quantum randomness could be the ruling force, even at the deepest levels of reality. Here we will explore the quantum realm with a fresh perspective, by re-deriving the Heisenberg principle in relation to the Planck scale. We will show how this idea also leads to an upper boundary on uncertainty, in addition to the lower boundary. These upper and lower boundaries are identical for the Planck mass particle; in fact, they are zero, and this highlights the truly unique nature of the Planck mass particle. Further, there may be a close connection between light and the Planck mass particle: In our model, the standard relativistic energy momentum relation also seems to apply to light, while in modern physics light generally stands outside the standard relativistic momentum energy relation. We will also suggest a new way to look at elementary particles, where mass and time are closely related, consistent with some of the recent work in experimental physics. Our model leads to a new time operator that does not appear to be in conflict with the Pauli objection. This indicates that both mass and momentum come in quanta, which are perfectly correlated to an internal Compton `clock' frequency in elementary particles.

Vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) serve an essential role in tumor angiogenesis and have emerged as potential therapeutic targets in lung cancer. This review explores the significance of serum VEGF levels as a predictive biomarker in non-small cell lung cancer (NSCLC). The VEGF family, consisting of VEGFA, VEGFB, VEGFC, VEGFD, and placenta growth factor (PlGF), engages with specific receptors, including tyrosine kinase receptors (VEGFR-1, VEGFR-2, and VEGFR-3) and neuropilin receptors (NRP-1 and NRP-2), to promote angiogenesis and lymphangiogenesis. VEGF-A, the primary component of the VEGF family, binds to VEGFR-2 to stimulate endothelial cell proliferation and migration, while VEGF-B, VEGF-C, and VEGF-D interact with VEGFR-1 and VEGFR-3 to regulate tumor angiogenesis, lymphangiogenesis, and metastasis. The VEGF/VEGFR signaling pathway activates various downstream effectors, including phospholipase Cγ1, MAPK, and PI3K/Akt, which are essential for maintaining vascular homeostasis and promoting angiogenesis. In NSCLC, elevated serum VEGF levels have been observed, and the VEGF/VEGFR axis is frequently impaired, leading to irregular blood vessel formation and metastatic spread. Despite the development of anti-VEGF therapies, their impact on lung cancer outcomes has been limited. Further research is needed to optimize the effectiveness of these treatments and elucidate the potential of serum VEGF as a predictive biomarker in NSCLC.

This paper designs and fabricates a small-type permanent-magnet linear motor and driver for automation applications. It covers structural design, magnetic circuit analysis, control strategies, and hardware development. Magnetic circuit analysis software JMAG is used for flux density distribution, back electromotive force(back-EMF), and electromagnetic force analysis. To address end effects and cogging force, auxiliary core structures and control strategies are proposed. The motor has a three-phase, six-coil, seven-pole configuration, achieving a peak phase voltage of 3.621 V at 1.0 m/s with a total harmonic distortion(THD) of 0.49 % and the voltages of each phase are balancing a phase voltage error of -0.002 V. The average electromagnetic force is 5.46 N/A. The driver uses a three-phase inverter with voltage space vector pulse width modulation(VSVPWM), dq-axes current closed-loop control, electromagnetic force control, and S-curve motion trajectory control. Simulations with JMAG-RT models in MATLAB/Simulink verify the control strategies. A microcontroller (TMS320F280045) serves as the control core, and a magnetic encoder with a 488 nm resolution provides position feedback. Each phase winding has an equivalent resistance of approximately 3.0 Ω and an inductance of approximately 1.98 mH. The S-curve motion trajectory control achieves a maximum position error of approximately 5.0 μm and a speed ripple of approximately 0.03 m/s at steady speed. With cogging force improvement, the maximum electromagnetic force is 4.90 N, and the q-axis current compensates around 1.05 A based on mover position. S-curve motion trajectory control results in highly stable and responsive performance. Practical tests show that the designed small-type permanent-magnet linear motor and its driver provide efficient, stable, and high-precision solutions for automation applications.

The small business sector in Kazakhstan demonstrates dynamic growth, but its sustainable development in modern conditions requires activation from government agencies, society and entrepreneurs themselves The purpose of the article is to study the development of small entrepreneurship in Kazakhstan and develop a mechanism for sustainable development based on network interaction "business entities - society-state" with the identification of priority areas of development based on a rating approach. The methods of bibliographic analysis of scientific literature, statistical, correlation analysis, survey, comparative analysis, ranking based on data normalization were used. The results revealed the need to formalize indicators of sustainable development of the small business sector in strategic development programs; create conditions, support, explain the importance and prospects of investing in sustainable innovations by small businesses; form a balanced strategy for achieving carbon neutrality based on network interaction "business entities - society-state" with the identification of priority areas of development based on a rating approach to ensure transparency and publicity of decisions made. Conclusions are made about the need to popularize sustainable development among business entities, stimulate investment activity through government participation, legislative regulation of public presentation of non-financial reporting, and assist society in the formation of an ESG culture.

Small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) have recently been grouped as lung neuroendocrine carcinomas (NECs). Because these lung NECs are clinically malignant and their treatment strategies differ from those of non-SCLC, the quality of diagnosis has a significant prognostic impact. The diagnosis of LCNEC requires positive immunohistochemical staining with chromogranin A, synaptophysin, and CD56, along with morphological diagnosis, and insulinoma-associated protein 1 (INSM1) has been proposed as an additional marker but sometimes experience difficulty in making the diagnosis. We investigated Musashi-1 as a novel immunohistochemical marker in 42 patients with SCLCs and 44 with LCNECs who underwent lung resection between 1998 and 2020 at our institution. We found Musashi-1 expression in 41 (98%) of 42 SCLCs and 40 (90%) of 44 LCNECs. These findings were similar to CD56 expression and superior to synaptophysin, chromogranin A, and INSM1. Musashi-1 also tended to show more diffuse and intense staining, especially in LCNEC, with more cases staining &gt;10% than any other existing markers (Musashi-1, 77%; INSM1, 45%; chromogranin A, 34%; synaptophysin, 41%; and CD56, 66%). In conclusion, we identified Musashi-1 as a novel immunohistochemical staining marker to aid in the diagnosis of lung NEC.

Besides the increase in global energy demand, access to clean energy, reduction in greenhouse gas emissions caused by conventional power generation sources, energy security, and availability of electricity in remote villages in emerging nations are some of the factors that foster the use of renewable energy sources (RESs) in generating electricity. One of the aims of initiating microgrids (MGs) is to maximize the benefits of RES and alleviate the associated grid integration issues. Microgrids are made up of RES connected to electrical loads within clearly delineated electrical limits that operate as individual controllable units on the electrical network. It can operate in-dependently as well as in connection with the grid. The paper presents an overview of microgrids and investigates the system's performance when connected to and disconnected from the grid. Furthermore, in both modes of operation, the functioning and behavior of system components such as the bidirectional DC-DC converter and energy storage system (ESS) were evaluated. The architecture of the proposed microgrid consists of a small hydropower plant, a wind farm, and a battery energy storage system (BESS). The microgrid under investigation is modeled and simu-lated using MATLAB and Simulink.

The majority of EGFR mutations (85–90%) are exon 19 deletions and L858R point mutation of exon 21, characterized by high sensitivity to EGFR-tyrosine kinase inhibitors (TKIs). Less is known about uncommon mutations (10-15% of EGFR mutations). Predominant mutation types in this category include exon 18 point mutations, exon 21 L861X, exon 20 insertions and exon 20 S768I. This group presents a heterogeneous prevalence, partly due to the different testing methods and to the presence of compound mutation, which in some cases leads to shorter overall survival and different sensitivity to different TKIs than simple mutations. EGFR-TKI sensitivity may also vary depending on the specific mutation and the tertiary structure of the protein. The best strategy remains uncertain and the data of TKIs efficacy are founded of few prospective and some retrospective series. Newer investigational agents are still under study and there are no other approved specific treatment targeting uncommon EGFR mutations. Defining the best treatment option for this patient population remain un unmet medical need. The objective of this review is to evaluate existing data on outcomes, epidemiology and clinical characteristics of lung cancer patients with rare EGFR mutations, with a focus on intracranial activity and response to immunotherapy.

Under the oxidative stress condition, the small RNA (sRNA) Oxys that acts as essential post-transcriptional regulators of gene expression is produced and plays a regulatory function with the assistance of the RNA chaperone Hfq protein. Interestingly, experimental studies found that the N48A mutation of Hfq protein could enhance the binding affinity with OxyS while resulting in defection of gene regulation. But, how the Hfq protein interacts with sRNA Oxys and the origin of the stronger affinity of N48A mutation are both unclear. In this paper, molecular dynamics (MD) simulations were performed on the complex structure of Hfq and OxyS to explore their binding mechanism. The molecular mechanics generalized Born surface area (MM/GBSA) and interaction entropy (IE) method were combined to calculate the binding free energy between Hfq and OxyS sRNA, and the computational result is in excellent correlation with the experimental result. Per-residue decomposition of the binding free energy revealed that the enhanced binding ability of the N48A mutation mainly comes from the increased van der Waals interactions (vdW). This research explores the binding mechanism between Oxys and chaperone protein Hfq, and revealed the origin of the strong binding affinity of N48A mutation. The results provided important insights on the mechanism of gene expression regulation affected by protein mutations.

Lung cancer remains the leading cause of cancer-related death and it is usually diagnosed in advanced stages (stage III or IV). Recently, the availability of targeted strategies and of immunotherapy with checkpoint inhibitors (ICI) has favorably changed patient prognosis. Treatment outcome is closely related to tumor biology and interaction with the host immune microenvironment (TME). Whether for targeted therapies the response relies on the presence of specific genetic alterations in tumor cells, for ICI accurate biomarkers of response are lacking and clinical outcome likely depends on multiple factors, host and tumor-related. This paper is an overview of the ongoing research on predictive factors both from in-vitro/ex-vivo analysis (ranging from conventional pathology to molecular biology) and in-vivo analysis, where molecular imaging is showing an exponential growth and use due to the technological advancement and to the new bioinformatics approaches applied to image analyses that allow specific features recovery in specific tumor subclones.

In contrast to normal cells, tumor cells of multiple entities overexpress the Heat Shock Protein 70 (Hsp70) not only in the cytosol, but also present it on their plasma membrane in a tumor-specific manner. Furthermore, membrane-Hsp70 positive tumor cells actively release Hsp70 into lipid microvesicles termed exosomes into the blood. Due to conformational changes of Hsp70 in the lipid environment, most commercially available antibodies fail to detect membrane-bound and exosomal Hsp70. To fill this gap and to assess the role of exosomal Hsp70 in the circulation as a potential tumor biomarker, we established the novel complete Hsp70 (compHsp70) sandwich ELISA using two monoclonal antibodies (mAbs) that are able to recognize both, free and lipid-associated Hsp70 on the cell surface of viable tumor cells and exosomes. The epitopes of the mAbs cmHsp70.1 (aa 451-461) and cmHsp70.2 (aa 614-623) that are conserved among different species reside in the substrate-binding domain of Hsp70, with measured affinities of 0.42 nM and 0.44 nM, respectively. Validation of the compHsp70 ELISA revealed a high intra- and inter-assay precision, linearity in a concentration range of 1.56 to 25 ng/ml, high recovery rates of ‘spiked’ liposomal Hsp70 (>84%), comparable values between human serum and plasma samples, and no interference by food intake or age of the donors. Hsp70 concentrations in the circulation of patients with glioblastoma, squamous cell or adeno non-small cell lung carcinoma (NSCLC) at diagnosis were significantly higher than those of healthy volunteers. Hsp70 concentrations dropped concomitantly with the decrease in viable tumor mass on irradiation of patients with approximately 20 Gy (range 18 – 22.5 Gy) or after completion of radiotherapy (60 - 70 Gy). In summary, the compHsp70 ELISA presented herein provides a highly sensitive and reliable tool for measuring free and exosomal Hsp70 in liquid biopsies of tumor patients, levels of which can be used as a predictive tumor-specific biomarker, risk assessment and for monitoring therapeutic outcome.

Transfer RNA (tRNA) molecules contain various post-transcriptional modifications that are crucial for tRNA stability, translation efficiency, and fidelity. Besides their canonical roles in translation, tRNAs also originate tRNA-derived small RNAs (tsRNAs), a class of small non-coding RNAs with regulatory functions ranging from translation regulation to gene expression control and cellular stress response. Recent evidence indicates that tsRNAs are also modified, however, the impact of tRNA epitranscriptome deregulation on tsRNAs generation is only now beginning to be uncovered. The 5-methyluridine (m5U) modification at position 54 of cytosolic tRNAs is one of the most common and conserved tRNA modifications among species. The tRNA methyltransferase TRMT2A catalyzes this modification, but its biological role remains mostly unexplored. Here, we show that TRMT2A knockdown in human cells induces m5U54 tRNA hypomodification, resulting in angiogenin (ANG) dependent tsRNA formation. More specifically, m5U54 hypomodification is followed by ANG overexpression and tRNA cleavage near the anticodon, resulting in accumulation of 5’tRNA-derived stress-induced RNAs (5’tiRNAs), in particular 5’tiRNA-GlyGCC and 5’tiRNA-GluCTC. Additionally, transcriptomic analysis confirms that down-regulation of TRMT2A and consequently m5U54 hypomodification impacts the cellular stress response and RNA stability, which is often correlated with tsRNA generation. Accordingly, exposure to oxidative stress conditions induces TRMT2A down-regulation and tsRNA formation in mammalian cells. These results establish a link between tRNA demethylation and ANG-dependent tsRNAs formation and unravel m5U54 as a tRNA cleavage protective mark.

To contribute to small and medium enterprises (SMEs) sustainable transition into the circular economy, the study proposes the activation of organizational learning (OL) processes – denoted here as multi-level knowledge creation, transfer, and retention processes – as a key phase in introducing circular business models (CBMs) at SME and supply chain (SC) level. The research employs a mixed-method approach, using the focus group methodology to identify contextual elements impacting on CBM-related OL processes, and a survey-based evaluation to single out the most frequently used OL processes inside Italian construction SMEs. As main result, a CBM-oriented OL multi-level model offers a fine-grained understanding of contextual elements acting mutually as barriers and drivers for OL processes, as possible OL dynamics among them. The multi-level culture construct – composed of external stakeholders’, SC stakeholders’, and organizational culture – identify the key element to activate CBM-oriented OL processes. Main implications are related to the identification of cultural, structural, regulatory, and process contextual elements across the external, SC, and organizational levels, and their interrelation with applicable intraorganizational and interorganizational learning processes. The proposed model would contribute to an improved implementation of transitioning into the circular economy utilizing sustainable business models in the construction SMEs.

The signal transduction pathways of estrogen receptors (ER) mainly includes gene pathway and non-gene pathway. Studies have shown that the gene pathway of ER is related with the expression of nuclear proteins, and this is the key issue for our current research. With the GEO database analysis, Human centromere protein F (CENPF) is highly expressed in adenocarcinoma of lung (LUAD), and the co-expression of CENPF and ERβ was found in the nucleus of LUAD cells. Meanwhile, CENPF and ERβ2/5 were related with T stage and poor prognosis (P<0.05). Knockdown of CENPF gene significantly inhibited the biological effects of LUAD cells, the tumor growth of mice and the expression of ERβ2/5 (P<0.05). Further, group experiments showed that knockdown CENPF inhibits biological effects of LUAD cells mediated by ERβ pathway. All the results indicated that both CENPF and ERβ2/5 play important roles in the progression of LUAD, and knockdown of CENPF can inhibit the progression of LUAD by inhibiting the expression of ER2/5. Thus, the development of inhibitors against ERβ2/5 subtype and CENPF remained more effective in improving the therapeutic effect of LUAD.

Rice grassy stunt virus (RGSV) a member of Tenuivirus family, is very potent and destructive which effects rice crop in many countries, particularly China. Non coding RNAs have important functions in development and epigenetic regulation of gene expression in numerous organsisms. There is three type of small non coding RNAs have been found in eukaryotes, which are small interferring RNAs (siRNAs), microRNAs (miRNAs) and piwi interacting RNAs (piRNAs). Small RNAs (sRNAs) origination is from the infecting virus which is known as virus-derived small interfering RNAs (vsiRNAs), has responsibility for RNA silencing in plants. Virus-induced gene silencing (VIGS) is mainly dependent on RNA silencing (RNAi). Interestingly, RNA silencing happens in plants during viral infections. RNAi technique showed significant results in Nephotettix cincticeps. RNAi technique demonstrated the gene silencing of planthopper Nilaparvata lugens. The proteins P5, pcf4, Dnj, psn5, and pn6 act as potential movement proteins and serve as silencing suppressors for RGSV. VsiRNAs originate from dsRNA molecules which require Dicer-like (DCL) proteins, RNA dependent RNA polymerase (RdRP) proteins, and Argonaute (AGO) proteins. RdRP uses ssRNA for perfect RNA amplification process and can also be used for DCL dependent secondary vsiRNA formation. VSRs interfere with the movement of signals during silencing mechanism. Moreover, intercellular movement of viruses is facilitated by virus-encoded movement protein. RNAi is found in many eukaryotes which are related to transcriptional or post-transcriptional regulation by gene suppression. Transcription is bidirectional in ssDNA viruses which are originated from dsRNA molecules. In this review, we highlighted the biology of Rice grassy stunt virus and its insect vector and its silencing suppressors. This work will be helpful for plant virologists to understand the whole biogenesis mechanism for rice viruses especially RGSV.

With the sharp increase in the number of vehicles, the issue of parking difficulties has emerged as an urgent challenge that many cities need to address promptly. In the task of predicting large-scale urban parking data, existing research often lacks effective deep learning models and strategies. To tackle this challenge, this paper proposes an innovative framework for predicting large-scale urban parking graphs leveraging real-time service capabilities, aimed at improving the accuracy and efficiency of parking predictions. Specifically, we introduce a graph attention mechanism that assesses the real-time service capabilities of parking lots to construct a dynamic parking graph that accurately reflects real preferences in parking behavior. To effectively handle large-scale parking data, this study combines graph coarsening techniques with temporal convolutional autoencoders to achieve unified dimension reduction of the complex urban parking graph structure and features. Subsequently, we use a spatio-temporal graph convolutional model to make predictions based on the coarsened graph, and a pre-trained autoencoder-decoder module restores the predicted results to their original data dimensions, completing the task. Our methodology has been rigorously tested on a real dataset from parking lots in Shenzhen. The experimental results indicate that compared to traditional parking prediction models, our framework achieves improvements of 46.8% and 30.5% in accuracy and efficiency, respectively. Remarkably, with the expansion of the graph’s scale, our framework’s advantages become even more apparent, showcasing its substantial potential for solving complex urban parking dilemmas in practical scenarios.

A Berry geometrical phase is identified in a strongly metastable system containing dynamically responsive clathrate hydrate structures within a crystal-fluid material. High energy degeneracy in the associated chemistry produces local stability and false vacuum conditions that lead to non-extensive and non-additive contributions in the fundamental thermodynamic relation. Application of Ginzburg-Landau theory and the scaling laws reveals a coherence length and a penetration depth for a macro-scale dual superconductor. The coherence length determines non-extensive volume changes whilst its inverse gives the Higgs mass. The penetration depth determines the extent of QCD vacuum suppression whilst its inverse gives the vector boson mass together with indirect manifestation as non-additive hyperbolic curvature. Simultaneous emergence of the Ginzburg-Landau superconducting phase transition is consistent with gauge-invariant coupling of the scalar field to the Yang-Mills action in QCD. The discovery of an energy gap in the gradient energy term of the system Lagrangian is associated with a critical correlation length revealed in the transition from a gapped to a gapless superconducting state. Together with the emergence and absorption of the Higgs-like scalar field, a mechanism for describing a renormalized QCD mass gap arises.

A novel five-surface phosphor-in-glass (FS-PiG) for high illumination and excellent color uniformity in larger-scale LEDs for sensor light source application is demonstrated. YAG phosphor (Y3Al5O12:Ce3+) was uniformly mixed with ceramic and sintered at 680°C to form a phosphor wafer. A sophisticated laser engraving was employed on the phosphor wafer to form a saddle-shaped large-scale FS-PiG LEDs. The performance of the FS-PiG LEDs exhibited the illumination of 401lm, average color temperature (CCT) of 5488K±110K, and color coordinates (CIE) of (0.3179±0.003, 0.3352±0.003). In contrast to convention single-surface phosphor-in-glass (SS-PiG) LEDs, the performance exhibited the illumination of 380lm, average CCT of 5830K±758K, and CIE of (0.3083±0.07, 0.3172±0.07). These indicated that the performance of the FS-PiG LEDs was higher than the SS-PiG LEDs for illumination, CCT, and CIE of 1.7, 7, and 23 times, respectively. Furthermore, the FS-PiG LEDs demonstrate lower lumen loss of 2% and less chromaticity shift of 5.4x10-3 under accelerated aging at 350°C for 1008 hours, owing to the high ceramic melting temperature of up to 510°C. In this study, the proposed FS-PiG larger-scale LEDs having excellent optical performance and high reliability may be the promising candidates to replace the convention phosphor-in-organic silicone material used in high-power LEDs for the next generation of sensor light sources, display, and headlight applications.

Urban air pollution is a critical global environmental issue, necessitating an understanding of the spatiotemporal characteristics and driving factors for effective environmental protection and urban planning. This study introduced an advanced air quality assessment system that integrates environmental, socio-economic, and urban layout factors, addressing gaps in traditional models that often overlook the impact of urban spatial structures. Analyzing air quality data from Beijing's main urban area (2016-2020) alongside multi-source geographic data, the research develops a comprehensive evaluation system, incorporating 14 key driving factors. Employing Geographically Weighted Regression (GWR) and Multi-scale Geographically Weighted Regression (MGWR), the study quantitatively assessed the influence and spatial heterogeneity of these factors. Findings revealed an annual improvement in air quality, with a U-shaped seasonal pattern and significant spatial clustering (Global Moran’s I = 0.922). The MGWR model, in particular, provided a superior fit over GWR, effectively capturing the spatial variability of factors. Variables such as NDVI), economic output (GDP), and humidity space adjustment capability (HSAC) showed significant positive spatial impacts on air quality, while population density (POP), temperature (TEMP), and road density (RD) exhibited negative effects. These insights enhance the understanding of air pollution dynamics and aid in refining urban planning strategies.

This paper presents the work done to transition the lab scale synthesis (1 g) to a large scale (400 g) synthesis of the 3-5-diamino-1H-Pyrazole Disperazol; a new pharmaceutical for treatment of antibiotic resistant Pseudomonas aeruginosa biofilm infections. The potentially hazardous diazotisation step in the lab scale synthesis was transformed to a safe and easy to handle flow chemistry step. Additionally, the paper presents an OSHA recommended safety assessment of the active compound E, performed by Fauske and Associates, LLC.

This paper aims to demonstrate how the detection of communities for epidemiological networks can be used to reduce the dimensionality of optimal control problems. A range of planted partition stochastic blockmodels are generated, where the underlying communities in the model vary in detectability. A high-performance computing workflow is then used to simulate and estimate reduced model dynamics for the networks, which in turn is used to find optimal control solutions.

A novel five-surface phosphor-in-ceramic (FS-PiC) for high illumination and excellent color uniformity in larger-scale LEDs for sensor light source application is demonstrated. YAG phosphor (Y3Al5O12:Ce3+) was uniformly mixed with ceramic and sintered at 680°C to form a phosphor wafer. A sophisticated laser engraving was employed on the phosphor wafer to form a saddle-shaped large-scale FS-PiC LEDs. The performance of the FS-PiC LEDs exhibited the illumination of 401lm, average color temperature (CCT) of 5488K±110K, and color coordinates (CIE) of (0.3179±0.003, 0.3352±0.003). In contrast to convention single-surface phosphor-in-ceramic (SS-PiC) LEDs, the performance exhibited the illumination of 380lm, average CCT of 5830K±758K, and CIE of (0.3083±0.07, 0.3172±0.07). These indicated that the performance of the FS-PiC LEDs was higher than the SS-PiC LEDs for illumination, CCT, and CIE of 1.1, 7, and 23 times, respectively. Furthermore, the FS-PiC LEDs demonstrate lower lumen loss of 2% and less chromaticity shift of 5.4x10-3 under accelerated aging at 350°C for 1008 hours, owing to the high ceramic melting temperature of up to 510°C. In this study, the proposed FS-PiC larger-scale LEDs having excellent optical performance and high reliability may be the promising candidates to replace the convention phosphor-in-organic silicone material used in high-power LEDs for the next generation of sensor light sources, display, and headlight applications.

The impact of the agriculture net carbon effect is crucial for climate change mitigation, yet research on this topic in China is currently insufficient. In this study, the carbon balance ratio (CBR) is used to characterise the net carbon effect of agriculture, and the spatial Durbin model and threshold regression model were used to empirically analyse the CBR with a sample of 30 provincial-level regions in China from 2004 to 2019. The aim was to investigate the mechanism of the influence of the land management scale (SCALE) of farming on the CBR. The results of the study indicate that national farming generally has a net sink effect, with large changes in interannual fluctuations; the expansion of SCALE has an obvious role in increasing sinks and reducing emissions, and has a positive spatial spillover effect on CBR, with significant spatial heterogeneity. Furthermore, as the SCALE expands, the direction of the influence of rural residents’ income and education level on CBR changes in the opposite direction, showing a significant non-linear relationship characteristic. However, in most areas, the SCALE threshold has not yet been reached, suggesting that the improvement in education levels can still offset the negative impact of economic income growth in the short term. The study recommends paying attention to the role of farmers’ human capital, changing production methods, and implementing carbon peaking and carbon neutrality goals to enhance the net sink effect of the farming industry, which would be achieved by increasing land management scale.

The star matter composed of nucleons deep inside the compact star like a neutron star is believed to be very dense and various new types of concepts and physical phenomena due to the nontrivial strong correlations are naturally expected. Peudo-conformality in dense star matter has been discussed recently assuming the hidden underlying scale symmetry, which is partly supported by the recent discussions of infrared conformal window of QCD. It is found that the appearance of dilaton and the dilatonic mean field calculation of nucleonic matter lead to the density independent nucleon mass at higher density regime than normal nuclear matter density. Non-vanishing constant nucleon mass can be considered as a chiral invariant mass of the parity doublet model, in which the chiral symmetry is manifested even in the massive nucleon sector provided with a parity doubling. In this paper we will discuss how the chiral and scale symmetry are correlated to lead the parity doublet symmetry inside the core of the compact star. A simple schematic model is adopted. The star matter at T=0 is basically composed of the nucleons. As a first approximation, they can be treated as free fermions with the effective mass filled up to fermi surface. There is a nontrivial feature due to the interplay between vector meson and nucleon(or equivalently dilaton, χ). The trace of energy momentum tensor approaches density independent, the pseudo-conformal phase. Local fluctuations inside the star matter will be travelling with the speed of sound which depends on the equation of state. In the pseudo-conformal phase, the speed of sound approaches to the conformal velocity for the scale symmetric matter, vc=13c. The excitations of the parity doublets in the compact star matter as an emerging phenomena in pseudo-conformal phase will be discussed in connection to the chiral symmetry. The possible implication on the corespondence of hadrons to quark degrees of freedom will be briefly discussed.

Microbiomes, comprised of diverse microbial species and viruses, play pivotal roles in human health, environmental processes, and biotechnological applications and interact with themselves, their environment, and hosts via metabolites and signaling molecules. Our understanding of microbiomes is still limited and hampered by their complexity. A concept improving this understanding is systems biology, which focuses on the holistic description of biological systems utilizing experimental and computational methods. An important set of such experimental methods are metaomics methods which analyze microbiomes and output lists of molecular features. These lists of data are integrated, interpreted, and compiled into computational microbiome models, to predict, optimize, and control microbiome behavior. There exists a gap in understanding between microbiologists and modelers/bioinformaticians, stemming from a lack of interdisciplinary knowledge. This knowledge gap hinders the establishment of computational models in microbiome analysis. This review aims to bridge this gap and is tailored for microbiologists, researchers new to microbiome modeling, and bioinformaticians. To achieve this goal, it provides an interdisciplinary overview of microbiome modeling, starting with fundamental knowledge of microbiomes, metagenomics methods, and modeling formalisms. Furthermore, the review explains model building, examples of microbiome model applications for prediction, optimization, and control. It concludes with guidelines, software, and repositories for modeling. Each section provides entry-level information, serving as a valuable resource for comprehending and navigating the complex landscape of microbiome research and modeling.

Leveraging the open-world understanding capacity of large-scale visual-language pre-trained models has become a hot-spot in point cloud classification. Recent approaches rely on transferable visual-language pre-trained models, classifying point clouds by projecting them into 2D images and evaluating consistency with textual prompts. These methods benefit from the robust open-world understanding capabilities of visual-language pre-trained models and require no additional training. However, they face several challenges summarized as prompt ambiguity, image domain gap, view weights confusion, and feature deviation. In response to these challenges, we propose PointBLIP, a zero-training point cloud classification network based on the recently introduced BLIP-2 visual-language model. PointBLIP is adept at processing similarities between multi-images and multi-prompts. We separately introduce a novel method for point cloud zero-shot and few-shot classification, which involves comparing multiple features to achieve effective classification. Simultaneously, we enhance the input data quality for both the image and text sides of PointBLIP. In point cloud zero-shot classification tasks, we outperform state-of-the-art methods on three benchmark datasets. For few-shot classification tasks, to the best of our knowledge, we present the first zero-training few-shot point cloud method, surpassing previous works under the same conditions and showcasing comparable performance to full-training methods.

Interferometric synthetic aperture radar (InSAR) and tomographic SAR measurement techniques are commonly used for the three-dimensional (3D) reconstruction of complex areas, while the effectiveness of these methods relies on the interferometric coherence among SAR images with minimal angular disparities. Radargrammetry exploits stereo image matching to determine the spatial coordinates of corresponding points in two SAR images, and acquire their 3D properties. The performance of the image matching process directly impacts the quality of the resulting digital surface model (DSM). However, the presence of speckle noise, along with dissimilar geometric and radiometric distortions, poses considerable challenges to achieve accurate stereo SAR image matching. To address the aforementioned challenges, this paper proposes a radargrammetric method based on composite registration of multi-aspect SAR images. The proposed method combines coarse registration using scale invariant feature transform (SIFT) with precise registration using normalized cross-correlation (NCC) to achieve accurate registration between multi-aspect SAR images with large disparities. Furthermore, the multi-aspect 3D point clouds are merged by the proposed radargrammetric 3D imaging method, resulting in 3D imaging of target scenes based on multi-aspect SAR images. For validation purpose, this paper presents a comprehensive 3D reconstruction of the Five-hundred-meter Aperture Spherical radio Telescope (FAST) by using Ka-band airborne SAR images. It does not necessitate prior knowledge of the target and is applicable to the detailed 3D imaging of large-scale areas with complex structures. In comparison to other SAR 3D imaging techniques, it reduces the requirements for orbit control and radar system parameters. To sum up, the proposed 3D imaging method with composite registration guarantees imaging efficiency while enhances the imaging accuracy of crucial areas with limited data.

Traveling salesman problems (TSPs) are well-known combinatorial optimization problems, and most existing algorithms are challenging for solving TSPs when its scale is large. To improve the efficiency of solving large-scale TSPs, this work presents a novel adaptive layered clustering framework with improved genetic algorithm (ALC\_IGA). The primary idea behind ALC\_IGA is to break down a large-scale problem into a series of small-scale problems. First, the $k$-means and improved genetic algorithm are used to segment the large-scale TSPs layer by layer and generate the initial solution. Then, the developed two phases simplified $2$-opt algorithm is applied to further improve the quality of the initial solution. The analysis reveals that the computational complexity of the ALC\_IGA is between $O(n\log n)$ and $O(n^2)$. The results of numerical experiments on various TSP instances indicate that, in most situations, the ALC\_IGA surpasses the state-of-the-art algorithms in convergence speed, stability, and solution quality. Specifically, the ALC\_IGA can solve instances with $2 \times 10^5$ nodes within 0.15h, $1.4 \times 10^6$ nodes within 1h, and $2 \times 10^6$ nodes in three dimensions within 1.5h.

Bonding agents (BA) are key compounding ingredients for the correct formulation of composite solid rocket propellants (CSRP). In particular, the addition of BA is essential to achieve suitable mechanical properties of CSRP in terms of adequate tensile strength and elongation at break. It is shown that the polarity of each conventional BA as well as new potential BA can be measured through the Reichardt’s ET(30) polarity scale. Using this criteria it was possible to find a substitute for MAPO (tris-(methylaziridinyl)-phosphine oxide), a conventional BA with the drawback of high toxicity and high reactivity, with TTPT (tris-(pyrrolidine)-phosphine oxide), a completely safe and effective BA. In this work, many other potential BA were evaluated through the Reichardt’s ET(30) polarity scale but only a selection of the potential BA were effectively tested in a standard CSRP. Particular interesting was the evaluation of TTPT vs MAPO showing the ability of the former BA to match the mechanical properties of the latter BA.

Back pain is a common symptom that affects all age groups across the globe, when left untreated may eventually lead to disability. A convenient sample selection method was used in this study due to the global Covid-19 pandemic lockdown which was effective in Turkey during the investigation period. Thus, virtual data collection and health education including some health risks were employed. A total population of two hundred adult women was involved in the study but one hundred and twenty-one responses were collected. Findings show that, for socio-demographic characteristics, the pain was found highest in women between the ages of 41-50 and obese/overweight individuals. Although, there was no significant difference recorded in the marital status category. Moreover, statistical mean differences were detected between the scales for ODI (4.18) and BPFS (6.09). Also, p<0.05, paired sample t-test was 0.001 ODI and 0.001 BPFS after the training exercise. This suggests that exercise training is inversely correlated with pain severity which implies that training has a significant influence on pain intensity. Thus, it could be concluded that there is a relationship between the training exercise and ODI/BPFS.

A multiscale mathematical model is proposed seeking to study the propagation dynamics of the Human Immunodeficiency Virus (HIV) in a group of young people between 15 and 24 years of age, through sexual contact without protection, considering the use of antiretroviral therapy (ART) and therapeutic failure. The model consists in a scale-free complex network that follows a power law, coupled with the immunological dynamics of each individual, that is, it considers the infection by the virus in the immune system of each HIV carrier, through a system of non-linear differential equations that govern the infection’s behavior in the immune system. Propagation of the virus in the network is modelled by taking into account information from the immunological status of each person. The study found that for a population to have high HIV prevalence, it is not necessary at the beginning of the simulation time for the virus to propagate rapidly. In addition, the study proves that with a higher number of sexual partners, there will be greater prevalence of HIV in the population and that the use of ART helps to control the propagation of the infection in the population. As an interesting result, it was also found that there is a higher number of HIV carriers who abandon ART than those who have access to it.

Analyses of the Hubble diagrams are presented for SN1a supernovae and gamma ray bursts in the redshift ranges z = 0.01–1.3 and 0.034–8.1, respectively. Data are presented on the typical z/μ scale and also on the less common yet increasingly sensitive photon flight time t/(z+1) scale. The primary conclusion is that on the basis of the presently accessible data in the redshift range z = 0.01–8.1, the slope of the Hubble diagram is, or is extremely close to, exponential.

This study addresses the latent construct of attitudes towards environmental conservation based on study participant’s responses. We measured and evaluated the latent scale based on an 18-item scale instrument, over four experimental strata (N=945) in the US Virgin Islands and the Caribbean. We estimated the latent scale reliability and validity. We further fitted multiple alternative two-parameter logistic (2PL) and graded response models (GRM) from Item-Response Theory. We finally constructed and fitted equivalent structural and generalized structural equation models (SEM/GSEM) for the attitudinal latent scale. All scale measures (composite, alpha-based, IRT-based and SEM-based) were consistently and reliably valid measures of the study participants’ latent attitudes toward conservation. We found statistically significant differences among participant’s attributes relating to socio-demographic, physical and core environmental characteristics of participants. We assert that the nature of relationship between cognitive attitudes and individual as well as social behavior related to environmental conservation.

ETS exposure has been shown as an important environmental risk factor in vulnerable population groups. The aim of the project is to analyze the relationships among the ETS and behavior and health in 6−15-year-old children in Slovakia. The status of physical and mental health of children in relation to exposure to tobacco smoke was examined in the representative group of 1478 school children. The methods used, included anonymous questionnaires filled in by parents, Columbia Impairment Scale (CIS), Behavior Problem Index (BPI) and anthropometry. The prevalence of passive smoking is the highest in the capital (27%) and southern cities. Significant relationships have been confirmed between ETS and the age, socio-economic status, the incompleteness of the family, the level of mother's education and the significantly higher prevalence of respiratory diseases (26.7%).The relationships of ETS with emotional (CIS scores ≥16) and behavioral functions (BPI score ≥14) were significant in children exposed to mother‘s and father‘s smoking at home. In the multivariate analysis this association was not significant; the factors such as income and completeness of the family were dominant. The results confirmed the impact of ETS and social factors on health state and health behavior and could be the argumentation for legislative changes.

Full-scale/model test comparison studies to validate the traditional ABL wind tunnel simulation technique are reviewed. According to the literature review, notable discrepancies between full-scale measurement results and model test results were observed by most performed comparison studies, but the causes of the observed discrepancies were not revealed in a scientific way by those studies. In this regard, a new research scheme for future full-scale/model test comparison studies is proposed in this article, which utilizes the multiple-fan actively controlled wind tunnel simulation technique. With the new research scheme, future full-scale/model test comparison studies are expected to reasonably disclose the main problems with the traditional ABL wind tunnel simulation technique, and the technique can be improved correspondingly.

The key to simulating soil erosion is to calculate the vegetation cover (C) factor. Methods that apply remote sensing to calculate C factor at regional scale cannot directly use the C factor formula. That is because the C factor formula is obtained by experiment, and needs the coverage ratio data of croplands, woodlands and grasslands at standard plot scale. In this paper, we present a C factor conversion method from a standard plot to a km-sized grid based on large sample theory and multi-scale remote sensing. Results show that: 1) Compared with the existing C factor formula, our method is based on the coverage ratio of croplands, woodlands and grasslands on a km-sized grid, takes the C factor formula obtained from the standard plot experiment and applies it to regional scale. This method improves the applicability of the C factor formula, and can satisfy the need to simulate soil erosion in large areas. 2) The vegetation coverage obtained by remote sensing interpretation is significantly consistent (paired samples t-test, t = −0.03, df = 0.12, 2-tail significance p < 0.05) and significantly correlated with the measured vegetation coverage. 3) The C factor of the study area is smaller in the middle, southern and northern regions, and larger in the eastern and western regions. The main reason for that is the distribution of woodlands, the Hunshandake and Horqin sandy lands and the valleys affected by human activities. 4) The method presented in this paper is more meticulous than the C factor method based on the vegetation index, improves the applicability of the C factor formula, and can be used to simulate soil erosion on large scale and provide strong support for regional soil and water conservation planning.

This systematic review critically examines the adoption and integration of Human Resource Information Systems (HRIS) and Artificial Intelligence (AI) in small and medium-sized enterprises (SMEs), with a focus on enhancing workforce productivity and strategic decision-making. Using the PRISMA framework, 100 research articles from reputable sources such as Google Scholar, Scopus, and Web of Science were analyzed. The analysis reveals that HRIS adoption can improve employee productivity by 29%, decision-making by 20%, and operational efficiency by 26%, highlighting its transformative impact on SMEs. The review identifies major challenges, including high implementation costs, limited IT resources, and integration difficulties with AI and machine learning technologies. Despite these barriers, integrating AI into HRIS presents significant opportunities for SMEs, fostering innovation in talent management, compliance automation, and data-driven decision-making, thus creating a competitive edge in rapidly evolving markets. Actionable insights for practitioners emphasize the need for cost-effective, scalable HRIS solutions tailored to the unique operational needs of SMEs, while researchers are urged to further explore AI-driven HRIS advancements to address current gaps in workforce engagement and performance management. This review offers a comprehensive roadmap for future HRIS innovations and underscores the strategic importance of digital transformation in human resources for sustained SME competitiveness.

The microvessel neurovascular unit with its brain endothelial cell (BEC) and blood-brain barrier remodeling is important in the development of impaired cognition in sporadic or late-onset Alzheimer’s disease (LOAD) and vascular dementia or vascular cognitive impairment and dementia including cerebral amyloid angiopathy in neurodegeneration. LOAD is considered to be the number one cause of dementia globally; however, when one considers the role of mixed dementia (MD) (the combination of both the amyloid cascade hypothesis and the vascular hypothesis of LOAD), it becomes apparent that MD is the number one cause. The microvessel BECs are the first cells in the brain to be exposed to the peripheral neurotoxins of the systemic circulation and are therefore the brain cells at the highest risk for early and chronic injury. Therefore, it is not surprising that microvessel BECs are the first cells to undergo injury and the response to injury wound healing mechanism and remodeling that is excessive and recurrent in the aging process plus other age-related diseases such as cerebro-cardiovascular disease, hypertension, type 2 diabetes mellitus, Parkinson’s disease, plus others. This narrative review explores the intricate relationship between microvessel remodeling, cerebral small vessel disease (SVD), and neurodegeneration as occurs in LOAD. Further, it discusses the current understanding of how microvessel dysfunction, disruption, and pathology contribute to the pathogenesis of LOAD and thus, highlights potential avenues for therapeutic interventions.

The shaft hydropower plant (SHPP) is a novel hydraulic concept for low-head hydropower sites with several environmental and operational advantages over conventional layouts. However, the first two projects implementing this concept have shown comparatively high construction costs and project risks. Therefore, further optimization is required to the economic attractiveness and enabling broader market adoption. Initial model tests recommend a square-shaped shaft inlet with a three-sided approach flow for low-loss and fish-friendly inflow conditions. Yet, this design requires significant space for structural implementation and may be unsuitable for use with multiple shafts or as an extension of non-powered dams and weirs. This research paper presents the application of a computational fluid dynamics simulation setup to evaluate the hydraulic per-formance of various design configurations, especially, alternative design layouts with one-sided approach flow without further physical model tests,. The simulation setup is calibrated against observations including head loss and velocity measurements from the physical model tests, and its satisfactory performance enables the analysis of alternative design layouts. This aims to derive the most significant design parameters for achieving the desired hydraulic conditions at the intake. Increasing the flow depth before the intake and enlarging the inlet area have the most significant impact, while increasing the overflow of the front gate has the least significant effect.. The chosen CFD application is deemed suitable for hydraulic design optimization and provides guidance on the key parameters to focus on for tailored site-specific design development.

Background and objective: Analysis of inflammatory biomarkers, along with the neutrophil/lymphocyte ratio (NLR) or platelets/lymphocyte ratio (PLR), supports the connection between inflammation and carcinogenesis. Methods: We conducted a retrospective observational study at the Clinical County Hospital Mureș, including patients with lung cancer. The parameters analyzed included: histopathological type (NSCLC - squamous cell carcinoma or adenocarcinoma; SCLC), molecular mutations (EGFR, ALK, PD-L1), parameters from the complete blood count, inflammatory parameters and associated comorbidities. Results: 380 patients were included: 115 patients in the cancer group and 265 patients in the control group. Among patients in the lung cancer group, 88 were diagnosed with NSCLC (44 adenocarcinomas, 44 squamous cell carcinomas) and 27 with SCLC. Both NLR and PLR were significantly higher in cancer patients than in the control group (5,30 versus 2,60, p&lt;0,001; 217 versus 136, p&lt; 0.001, respectively). NLR and PLR differs between men and women (p = 0.005, respectively p=0.056). C-reactive protein was not correlated with either NLR (p-value: 0.0669) or PLR (p-value: 0.6733) in lung cancer patients. Conclusion: The NLR and PLR values ​​may serve as new predictive biomarkers for the diagnostic of disease in patients with lung cancer, especially those with NSCLC.

The variability of the material properties of steel from different suppliers causes problems in achieving the required surface quality after turning. Therefore, the manufacturer needs to be able to estimate the resulting quality before starting production, especially if it is an expensive, small-batch production from stainless steel. Predictive models will make it possible to estimate the surface roughness from the mechanical properties of steel in the Mill Test Certificate (MTC) and thus support decision-making about the supplier selection or the acceptance of a material supply. Multivariate second-order polynomial model and feedforward back-propagation Artificial Neural Network (ANN) model were used to enhance the methodological robustness in formulating the decision if the predicted surface roughness is outside the required range, even before accepting the delivery. Both models can accurately predict surface roughness, while the ANN model is more accurate than the polynomial model; however, the predictive model is sensitive to the accuracy of the input data, and the model’s prediction is valid only under precisely defined conditions. The prediction model is used in a step-by-step decision-making procedure, which enables the trained staff to make a quick decision.

Abstract: Epigenetic approaches in direct correlation with assessment of critical genetic mutations in non-small cell lung cancer (NSCLC) are currently very intensive, as the epigenetic components in NSCLC development and progression have attained high recognition. In this level of research, established human NSCLC cell lines as well as experimental animals are widely used to detect novel biomarkers and pharmacological targets to treat NSCLC. The epigenetic background of NSCLC is highly complex and requires precise definition as these phenomena are variable between NSCLC subtypes and systems origin. We engaged an in-depth characterization of non-coding (nc)RNAs prevalent in human KRAS-mutant NSCLC cell lines A549 and H460 and mouse KRAS-mutant NSCLC tissue by Next Generation Sequencing (NGS) and quantitative Real Time PCRs (qPCRs). Also, the effect of transcription factor (TF) LRF, a known epigenetic silencer, was examined on the epigenome modulation. Finally, interacting networks underlying epigenetic variations in NSCLC subtypes were created. Data derived from our study highlights the divergent epigenetic profiles of NSCLC of human and mouse origin, as well as the significant contribution of 12qf1: 109,709,060-109,747,960 mouse chromosomal region to micro-RNA upregulated species. Fur-thermore, the novel epigenetic miR-148b-3p/PVT1/ZBTB7A axis was identified, which differentiates lung adenocarcinoma from large cell lung carcinoma, two characteristic NSCLC subtypes. The detailed recording of epigenetic events in NSCLC and combinational studies including networking between ncRNAs and TFs validate the identification of significant epigenetic features, prevailing in NSCLC subtypes and among experimental models. Our results enrich knowledge in the field and empower research on the epigenetic prognostic biomarkers of the disease and patient-tailored treatments.

Craters are the most prominent geomorphological features on the surface of celestial bodies, which is playing a crucial role in studying the formation and evolution of celestial bodies, as well as in landing and planning for surface exploration. Currently, the main automatic crater detection models and datasets focus on the detection of large and medium craters. In this paper, we created 23 small lunar crater datasets for model training based on the Chang’E-2 (CE-2) DOM, DEM, Slope, and integrated data with 7 kinds of visualization stretching methods. And then, we proposed the YOLO-Crater model for Lunar and Martian small crater detection by replacing EioU and VariFocal loss to solve the crater samples imbalance problem and introducing a CBAM attention mechanism to mitigate interference from the complex extraterrestrial environment. The results show that the accuracy (P = 87.86%, R = 66.04%, and F1 = 75.41%) of the Lunar YOLO-Crater model based on the DOM-MMS (Maximum-Minimum Stretching) dataset is the highest and better than that of YOLOX model. And the Martian YOLO-Crater, trained by the Martian dataset from the 2022 GeoAI Martian Challenge, achieves good performance with P = 88.37%, R = 69.25%, and F1 = 77.65%. It indicates that the YOLO-Crater model has a strong transferability and generalization capability, which can be applied to detect small craters on the Moon and other celestial bodies.

Today, the most powerful approach to detect distant homologs of a protein is based on structure prediction and comparison. Yet this approach is still inapplicable to many viral proteins. Therefore, we developed a powerful sequence-based procedure to identify distant homologs of viral proteins. It relies on 3 main principles: 1) Traces of sequence similarity with a protein can persist beyond the significance cutoff of homology detection programs; 2) Candidate homologs can be identified among proteins with weak sequence similarity to the query, by using "contextual" information, e.g. taxonomy or type of host infected; 3) These candidate homologs can be validated using highly sensitive profile-profile comparison.As a test case, we applied our approach to a protein without known homologs, ORF4 of Lake Sinai virus (which infects bees). We discovered that ORF4 is composed of a domain that has homologs in proteins from >20 taxa of viruses infecting arthropods. We called it “Widespread, Intriguing, Versatile” (WIV) domain because it is found in proteins with a wide variety of domain organizations and functions. For example, WIV is encoded by the NSs protein of tospoviruses, a global threat to food security, which infect plants through arthropod vectors; by the protein encoded by RNA2 ORF1 of chronic bee paralysis virus, a widespread virus of bees; and by various proteins of cypoviruses, which infect the silkworm bombyx mori. WIV has a previously unknown structural fold, according to Alphafold predictions. In some viral species, WIV facilitates infection of arthropods, according to bibliographical evidence

Lung cancer is the most common malignancy across the world. The new era in lung cancer treatments, especially this past decade, has yielded novel categories of targeted therapy for specific mutations and adjuvant therapy, both of which have led to improved survival rates. In the present study, we review the changes and development of treatments, with a special focus on adjuvant therapy using tyrosine kinase inhibitors (TKIs) administered to non-small-cell lung carcinoma patients who had a complete resection of the tumor harboring a mutated epidermal growth factor receptor. The clinical trials are dating from the past (chemotherapy trials), present (TKIs) and future (ongoing trials).

Dynamic contrast-enhanced MRI (DCE-MRI) is increasingly used to quantify and map the spatial distribution of blood-brain barrier (BBB) leakage in neurodegenerative disease, including cerebral small vessel disease and dementia. However, the subtle nature of leakage and resulting small signal changes make quantification challenging. While simplified one-dimensional simulations have probed the impact of noise, scanner drift, and model assumptions, the impact of spatio-temporal effects such as gross motion, k-space sampling and motion artefacts on parametric leakage maps has been overlooked. Moreover, evidence on which to base the design of imaging protocols is lacking due to practical difficulties and the lack of a reference method. To address these problems, we present an open-source computational model of the DCE-MRI acquisition process for generating four-dimensional Digital Reference Objects (DROs), using a high-resolution brain atlas and incorporating realistic patient motion, extra-cerebral signals, noise and k-space sampling. Simulations using the DROs demonstrated a dominant influence of spatio-temporal effects on both the visual appearance of parameter maps and on measured tissue leakage rates. The computational model permits a greater understanding of the sensitivity and limitations of subtle BBB leakage measurement and provides a non-invasive means of testing and optimising imaging protocols for future studies.

Train fault detection primarily relies on the comparative analysis of collected images with standard reference images, making the accurate identification of the collected image types crucial for effective fault detection. Most current systems achieve indirect classification of carriage images by using Automatic Equipment Identification (AEI) devices to recognize carriage identification number information while capturing the carriage images. However, damaged RF tags or blurred characters can hinder these devices, obstructing further train fault analyses. The unique features of carriage linear array images, such as high resolution, extreme aspect ratios, and local non-linear distortions, pose significant challenges to recognition algorithms. This paper proposes a method specifically designed to recognize these types of images. First, we implement an object detection algorithm to locate the positions of key components in carriage linear array images. By leveraging the spatial layout mapping between these key components and the carriage type classification, we simplify the complex image recognition problem into a sparse point set alignment task. To ensure effective registration despite local distortions in the linear array images, we propose a weighted radial basis function. To address the issues of unknown matching relationships and quantity mismatches during point set alignment, the proposed objective function is designed to maximize the similarity between Gaussian mixtures of point sets, thereby determining the RBF weights. Extensive experiments have demonstrated that our algorithm achieves 100% recognition accuracy under local nonlinear scale distortions of less than 15%. The algorithm remains effective even in the presence of some false positives or missed detections in key component object detection results. It can accurately identify the target category from 79 image categories within 24 milliseconds on an i7 CPU without GPU support. It is of great significance to reduce system cost and promote automatic exterior fault detection for train rolling stock.

Bearing fault diagnosis is crucial for ensuring the stable operation of mechanical equipment. With the continuous development of deep learning technology, Convolutional Neural Networks (CNNs) have demonstrated significant advantages in the field of fault diagnosis. This paper proposes a new method that combines various CNN architectures to improve the accuracy of bearing fault diagnosis. We designed five different convolutional network structures, including SerConv, ResConv, One-Shot Aggregation Convolution (OSAConv), Cross-Stage Aggregation Convolution (CSAConv), and MD-DAConv. Experimental results on the Case Western Reserve University (CWRU) bearing dataset show that the proposed method exhibits high accuracy and robustness in fault diagnosis. The results indicate that strategies such as multi-directional, multi-scale, and residual connections play a crucial role in enhancing the depth and breadth of feature extraction, while simple and effective feature fusion and information transmission mechanisms are key to ensuring the robustness and generalization ability of the model.

At 12:28 UTC (8:28 PM, local time) on 15 January 2023, a shallow, moderate earthquake with a magnitude (Mw) of 4.7 and a depth of one (1) kilometer shook the northern part of Leyte Island in the central part of the Philippines. The ground shaking was felt at PHIVOLCS Earthquake Intensity Scale (PEIS) VI, (very strong) equivalent to Modified Mercalli Intensity (MMI) VI in areas along the strike of the Leyte segment of the Philippine Fault. Even though this earthquake is classified as moderate in size, significant geologic, structural, and socio-economic impacts were documented. Most of the earthquake impacts that include surface rupture, liquefaction, and mass movements are limited near the epicentral area. The earthquake produced an 8-km-long surface rupture, the first documented rupture generated by a magnitude &lt;6 along the Philippine Fault, and is unusual in other surface rupturing earthquakes worldwide. It injured 18 persons and damaged 434 residential buildings and 26 public infrastructures which amounts to about 500 thousand US dollars. Structural damages were caused by surface rupture and/or poor engineering construction practices. Analysis of the seismic waveform and recorded peak ground acceleration (PGA) suggests that the subsurface geology influenced the ground motion amplification in an area near the epicenter. Based on the hypocenter, focal mechanism solution, aftershock distribution, and actual field observation, the causative fault for this event is the northern end of the Philippine Fault – Leyte segment. Moderate in size, this earthquake emphasizes the need and importance of documenting moderate-sized earthquakes as a tool and guide for medium and long-term earthquake risk assessment and resiliency.

Rebar cages form the skeletal framework of reinforced concrete structural members. They comprise longitudinal and transverse reinforcing bars, usually connected by tie wires. Past studies have identified tie-wire connections as the "weak links" in large, prefabricated rebar cages, leading to their failure during site handling and construction stages. Recent research has explored the use of mechanical U-bolt connectors to bolster stability and safety of rebar cages while reducing their vulnerability and risk of failure. This paper presents a comprehensive experimental and numerical investigation of a new type of mechanical connector, referred to as "Cage Clamp", to enhance rebar cage stability and safety. Component-level experimental tests are conducted to determine the force-displacement response of Cage Clamp connectors for crossbar connections in different degrees of freedom. The results highlight the remarkable strength and stiffness of Cage Clamp connectors, significantly outperforming traditional tie-wire connections. Furthermore, full-scale experimental tests are performed on a circular underground pile-shaft rebar cage with Cage Clamp connectors to assess its behavior under various site handling conditions. The data obtained from these experiments are used to construct and refine detailed 3D finite element models of the rebar cages, capable of capturing the complex behavior of rebar cages with Cage Clamp connectors. Using the numerical model, a sensitivity analysis is performed to assess the effect of the number of Cage Clamps on the deflection and stability of the rebar cage. The findings show that using cage clamps to connect pick-up rebar with lateral reinforcement at every 8 to 10 feet is sufficient to ensure the stability of the cage during typical site handling conditions. The results of this study serve as a basis for establishing analysis, design, fabrication, and handling guidelines for rebar cages, contributing to safe and efficient construction practices.

To determine the fracture rate of ceramic crowns and causes of ceramic crown failure, this study used keywords—namely “endocrown,” “veneered fixed dental prosthesis,” “monolithic lithium disilicate (LS2),” and “all-ceramic single crown”—to search for articles published in English from 2005 to 2023 in the PubMed electronic database. Rather than using the Boolean logic algorithm between MESH terms and keywords, we accurately calculated the numbers of final clinically tracked cases with crown fractures from the contents of articles. The titles and abstracts of many related articles focused on implant or abutment fracture, while crown fracture was investigated and mentioned only in the main texts of the articles. Our studies included those crowns as well as having more complete data collection. Our search yielded 228, 93, 404, and 358 articles for the keywords “endocrown,” “veneered fixed dental prosthesis,” “monolithic lithium disilicate (LS2),” and “all-ceramic single crown,” respectively. We used the Newcastle–Ottawa Scale (NOS) to assess article quality, and our inclusion criteria were randomized controlled trials (RCT) and cohort study articles involving more than 3 years of follow-up and more than 20 cases. After reviewing, 16 high-quality articles were selected for analysis. The 4.4% crown fracture rate recommended on the basis of most clinical results was achieved in only 6 of the 16 articles. In these 6 articles, the researchers concluded the following reasons that may cause the crown fractures: the thickness of the veneer ceramic material; the connector dimensions; pontic span of the fixed prosthesis; the type of cement; the treatment of the ceramic surface before luting. Other articles inferred that the computer-aided design libraries that were insufficient for the creation of appropriate anatomically supported frameworks for prostheses with ceramic veneers; the thermal expansion coefficient and fracture toughness of the framework material did not match those of the veneer ceramic, resulting in an insufficient area supporting the ceramic veneer then leads to premature crown failure after a long period chewing. The future prospective for material developing could focus on solving those problems and have better clinical results.

Cable-supported façades represent a novel approach in the design and technology of double skin façades (DSF). This type of systems not only offer flexibility in terms of exterior finishes, but also regulates the access of solar radiation, thereby transforming the appearance of the building in response to varying daylight conditions. However, the structural performance of these façades under wind, impact and seismic loads remains an active area of research. The study is a groundbreaking work that experimentally evaluates the wind and seismic behaviour of these type of façades. The methodology used for the evaluation of flexible masonry facades includes laboratory tests analysing the individual capacity of the connections and materials of the system under standardized and non-standardized procedures. A full-scale experimental sub-assembly specimen of a representative module of the façade is also subjected to uniformly distributed pressures of wind load tests as well as hard body and soft body impact tests. The setup considered the border conditions, tension loads, and actual materials. Furthermore, the earthquake assessment includes tests of full-scale specimens subjected to these demands. Research findings allowed the refinement and redesign of the system's components granting the validation of the DSF used as a case study.

Sign Language Recognition (SLR) aims to bridge speech-impaired and general communities by recognizing signs from given videos. Researchers still face challenges developing efficient SLR systems because of the video’s complex background, light illumination, and subject structures. Recently many researchers developed a skeleton-based sign language recognition system to overcome the subject and background variation of hand gesture signs. However, skeleton-based SLR is still under exploration due to the lack of information and annotations on hand key points. More recently, researchers included body and face information with the hand gesture for the SLR, but their performance and efficiency are unsatisfactory. We proposed a Multi-Stream Graph-based Deep Neural Network (SL-GDN) for a skeleton-based SLR system to overcome the problems. The main purpose of the proposed SL-GDN approach is to improve the efficiency and performance of the SLR system with a low computational cost based on the human body pose in the form of 2D landmark locations. In the procedure, firstly, we constructed a skeleton graph based on the selected 27 whole-body key points among 67 key points to solve the inefficiency problems. Then we proposed multi-stream SL-GDN to extract features from the whole-body skeleton graph for four streams. Finally, we concatenated the four different features and applied a classification module to refine the feature and recognize corresponding sign classes. Our data-driven and graph construction method increases the system’s flexibility and brings high generability to adapt various data samples. We used three large-scale benchmark SLR datasets to evaluate the proposed model: WLASL, AUTSL and CSL. The demonstrated performance accuracy table proved the superiority of the proposed model, and we believe this will be considered a great invention in the SLR domain.

In the context of the Education-2030 Framework for Action, an important goal for initial STEM teacher education is to provide professional development on equality and gender awareness. This study explored whether STEM prospective secondary teachers are prepared to implement a sustainable gender-sensitive practice upon graduation. To this end, we cross-culturally validated the TEGEP (Teacher Self-Efficacy for Gender Equality practice) scale and compared STEM student teachers’ perceptions of self-efficacy by country and sex. Participants were 205 STEM (science, technology, engineering, and mathematics) secondary school student teachers (136 Greek and 69 Spanish) drawn from seven public universities (six Greek, one Spanish). Statistical analysis confirmed the structure and factor invariance of the TEGEP across country and between sexes showing evidence that gender equality self-efficacy level is only moderate and that perceived competence in gender knowledge was significantly higher in Greek than in Spanish STEM student teachers, while the latter felt more competent than the Greek in developing values and attitudes in regards to gender. The study provides a cross-validated instrument to measure gender equality self-efficacy in STEM teacher education and evaluate sustainable changes after planned interventions.

The service conditions of underground coal mine equipment are poor, and it is difficult to accurately extract the fault characteristics of rolling bearings. In order to better improve the accuracy of fault identification of rolling bearings, a fault detection method based on multiscale permutation entropy and SOA-SVM is proposed. First, the whale optimization algorithm is used to select the modal analysis number K and the penalty factor α of the variational mode decomposition algorithm. Then, the vibration signal of rolling bearings is dissolved according to the optimized variational mode decomposition algorithm, and the multi-scale permutation entropy of the main intrinsic mode function is calculated. Finally, the feature values of the matrix are entered into the SVM algorithm optimized by the seagull optimization algorithm to obtain the classification result. The experimental results based on the published rolling bearing datasets of Western Reserve University show that the identification success rate of the proposed method can reach 98.75%. The fault detection of the rolling bearings can be completed accurately and efficiently.

There exists an implicit potential limitation in every physical discoveries that has been implemented and understood. However, the limitations can be bounded within a safe limit to prevent any constructing theory to be free from errors. As, it’s the inert nature of the humans, to go far beyond the scope of experimental findings in order to pursue any studies with the sole help of logical reasoning and mathematics, the argument can be prevailed in the form of WEAK Clampdown Effect & STRONG Clampdown Effect. More, the theories are constructed out of physical nature, more the theory gets hypothetical without any finding evidence, but that does or doesn’t actually justify the phenomenon, that too with the more increment of KARDASHEV Scale, more moderate ways of experimentation got developed curbing down the limitations within the human limit of ‘ERRORS’, that does can be neglected by approximation. Relationship being cross-judgmental on the basis of the computational limits and calculation accuracy, leading to a soft singularity, as a warning, that if computer powers cannot be checked on the basis of error approximations, then this may lead to the hitting of a hard singularity, that in phase with the forbidden gap (or after the optimum limit that arises at the core constraints of nature) to prevent the computation being carried off with respect to super-intelligence machines that are cognitive capability oriented future computers responsible for self growth & reproduction with more improvement algorithm, restricting all forms of humanity & constraints the human growth by virtue of limiting capacities of the humans as compared to computers.

Business school curriculums are designed to improve business skills and a student’s eventual workplace performance. In addition to these business skill sets the emerging business environment demands softer skills associated with ethical decision-making and sustainable business practices. Understanding the key influencers of ethical orientation and attitudes towards the environment is the first critical step for curriculum planning designed to develop both ethical decision-making and environmental sensibilities of students in business schools. Using a bivariate regression analysis (OLS) that compared the established New Ecological Paradigm (NEP) scale and the newly introduced Ethical Orientation Scale (EOS), this study assesses environmental eco-consciousness and ethical orientation over time and across varying socio-demographic variables. The study shows first, that in addition to socio-cultural variables, situational factors influence ethical decision-making. Secondly, it illuminates that ethical orientations as measured by the EOS predicts beliefs about the environment as measured by the NEP scale. It further provides evidence of the ethical underpinnings of the New Ecological Paradigm as well as provides initial validation for the new EOS. These outcomes provide additional levers to assist business educators in the creation of high impact teaching strategies to measure and encourage ethical decision-making and sustainable business practices that protect the environment.

According to the Cosmological Principle the Universe is isotropic and no preferred direction would be seen by an observer that might be stationary with respect to the expanding cosmic fluid. However, because of observer’s partaking in the solar system peculiar motion, there would appear in some of the observed properties of the Cosmos a dipole anisotropy, which could in turn be exploited to determine the peculiar motion of the solar system. The dipole anisotropy in the Cosmic Microwave Background Radiation (CMBR) has given a peculiar velocity vector 370 km s−1 along l=264∘,b=48∘. However, some other dipoles, for instance, from the number counts, sky brightness or redshift distributions in large samples of distant Active Galactic Nuclei (AGNs), have yielded values of the peculiar velocity many times larger than that from the CMBR, though surprisingly, in all cases the directions agreed with the CMBR dipole. Here we determine our peculiar motion from a sample of 0.28 million AGNs, selected from the Mid Infra Red Active Galactic Nuclei (MIRAGN) sample comprising more than a million sources. From this, we find a peculiar velocity, which is more than four times the CMBR value, although the direction seems to be within ∼2σ of the CMBR dipole. A genuine value of the solar peculiar velocity should be the same irrespective of the data or the technique employed to estimate it. Therefore, such discordant dipole amplitudes, might mean that the explanation for these dipoles, including that of the CMBR, might in fact be something else. But, the observed fact that the direction in all cases, is the same, though obtained from completely independent surveys using different instruments and techniques, by different sets of people employing different computing routines, might nonetheless indicate that these dipoles are not merely due to some systematics, otherwise why would they all be pointing along the same direction. It might instead suggest a preferred direction in the Universe, implying a genuine anisotropy, which would violate the Cosmological Principle, the core of the modern cosmology.

Despite numerous studies in statistical downscaling methodology, there remains a lack of methods that can downscale from precipitation modeled in global climate models to regional level high resolution gridded precipitation. This paper reports a novel downscaling method using a Generative Adversarial Network (GAN), CliGAN, which can downscale large-scale annual maximum precipitation given by simulation of multiple atmosphere-ocean global climate models (AOGCM) from Coupled Model Inter-comparison Project 6 (CMIP6) to regional-level gridded annual maximum precipitation data. This framework utilizes a convolution encoder-dense decoder network to create a generative network and a similar network to create a critic network. The model is trained using an adversarial training approach. The critic uses the Wasserstein distance loss function and the generator is trained using a combination of adversarial loss Wasserstein distance, structural loss with the multi-scale structural similarity index (MSSIM), and content loss with the Nash-Sutcliff Model Efficiency (NS). The MSSIM index allowed us to gain insight into the model’s regional characteristics and shows that relying exclusively on point-based error functions, widely used in statistical downscaling, may not be enough to reliably simulate regional precipitation characteristics. Further use of structural loss functions within CNN-based downscaling methods may lead to higher quality downscaled climate model products.

Recently, the relationship between emotional arousal and depression has been studied. Focusing on this relationship, we first developed an arousal level voice index (ALVI) to measure arousal levels using the Interactive Emotional Dyadic Motion Capture database. Then, we calculated ALVI from the voices of depressed patients from two hospitals (Ginza Taimei Clinic [GTC] and National Defense Medical College hospital [NDMC]) and compared them with the severity of depression as measured by the Hamilton Rating Scale for Depression (HAM-D). Depending on the HAM-D score, the datasets were classified into a no depression (HAM-D&lt;8) and a depression group (HAM-D≥8) for each hospital. A comparison of the mean ALVI between the groups was performed using the Wilcoxon rank-sum test and a significant difference at the level of 10% (p = 0.094) at GTC and 1% (p = 0.0038) at NDMC was determined. The area under the curve (AUC) of the receiver operating characteristic was 0.66 when categorizing between the two groups for GTC, and the AUC for NDMC was 0.70. The relationship between arousal level and depression severity was indirectly suggested via ALVI.

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

With reference to Planck scale, Mach’s relation, increasing support for large scale cosmic anisotropy and preferred directions and by introducing two new parameters Gamma and Beta, right from the beginning of Planck scale, we make an attempt to estimate ordinary matter density ratio, dark matter density ratio, mass, radius, temperature, age and expansion velocity (from and about the baby universe in all directions). We would like suggest that, from the beginning of Planck scale, 1) Dark matter can be considered as a kind of cosmic foam responsible for formation of galaxies. 2) Cosmic angular velocity is directly proportional to squared cosmic temperature. 3) Ratio of critical temperature to actual temperature plays a heuristic role in understanding ordinary and dark matter density ratios. 4) Cosmic expansion velocity increases with decreasing total matter density ratio. 5) There is no need to consider dark energy for understanding cosmic acceleration.

Studying hydro-meteorological factors variations and its links to large-scale atmospheric circulation systems can facilitate the understanding of the hydrological processes and sustainable water resources management in the source region of the Yangtze River (SRYR). Currently, researches mostly focused on the temporal and spatial variation characteristics in hydro-meteorological factors; however, researches on the hydro-meteorological variations and its links to large-scale atmospheric circulation systems in the SRYR are scarce. Based on long-term hydro-meteorological and reanalysis data, this research investigated multiscale variations of hydro-meteorological factors and its links to large-scale atmospheric circulation characteristic indices during 1957~2012 in the SRYR. The results showed that the amounts of streamflows and precipitation in the SRYR declined during the 1990s. Since the 2000s, the amounts of streamflows and precipitation had increased significantly climate in the SRYR. The change trends of precipitation and streamflows in the SRYR are synergetic at annual and seasonal scales, and have three significant periods, namely 3~5 years, 15–20 years and 30–40 years. The South Asia monsoon (SAM) plays a relatively more important role in the hydro-meteorological factors changes in the SRYR. The relative contributions of SAM to streamflows and precipitation changes were 83.6% and 78%, respectively. During the driest (wettest) year, the SAM is relatively weak (strong), and brings less (more) southwest airflow into the SRYR, less (more) precipitation and streamflows will be generated in the SRYR.

With reference to Planck scale, Mach's relation and by introducing two new parameters Gamma and Beta, right from the beginning of Planck scale, we make an attempt to estimate ordinary matter density ratio, dark matter density ratio, mass, radius, temperature, age and expansion velocity (from and about the Planck mass in all directions). In analogy with currently believed cosmic acceleration, with a decreasing trend of total matter density ratio, cosmic expansion velocity can be shown to be increasing. By considering $H_0\cong 70$ km/sec/Mpc, estimated current cosmic mass, radius, total matter density, expansion velocity, temperature and age are: $4.3352\times {10}^{53}\mathrm{kg},$ $3.207\times {10}^{26}\mathrm{m},$ $3.138\times {10}^{-27}\mathrm{kg}{.\mathrm{m}}^{-3},$ $2.43c,$ $2.721\mathrm{K}$ and $19.78\mathrm{Billion}\mathrm{years}$ respectively. Point to be noted is that, with reference to Planck scale, cosmic temperature seems to be redshifted by a factor ${\left(Z_T\right)}_t\cong \sqrt{1+\ln \left(H_{pl}/H_t\right)}-1$ where $\left(H_{pl},H_t\right)$ represent Planck scale and time dependent Hubble parameters respectively. As a peculiar case, considering the equality of current Hubble parameter and current angular velocity, current cosmic rotational kinetic energy can be estimated to be 0.667 times the current critical energy. It needs further study.

Light and heat resources are ample in Xinjiang plain oasis region. Planting structure is single in irrigation area, which leads to severe seasonal water shortages due to high concentration of water utilization. Therefore, how to make full use of light and heat resources to develop oasis agriculture without expanding planting scale has become the focus of research. The biannual cropping patterns are possible solutions to the problem. Manas River Irrigation area, which is located on the northern slope of Tianshan Mountain in Xinjiang in China is regarded as a typical case study to analyze the suitable planting structure and planting scale for biannual cropping pattern. The effects of optimizing planting patterns on alleviating the contradiction between water supply and water need，and the efficiency of water resources utilization was also studied. The results of the study show that：(1) the suitable planting scales of Manas River irrigation area in wet year (P = 25%), normal year (P = 50%), and low flow year (P = 75%) are about 72.66%, 78.73% and 83.91% of the current planting scale. (2) After the planting structure was optimized, the water use process in the irrigation area extends from May to August at present to April to November. The water use ratio at the peak period of water use decreased from 0.847 to 0.601, and the water use peak was significantly dispersed. (3) Economic benefits per cubic metre of water of the biannual cropping patterns increased from 8.65 yuan·m⁻³ at present to 9.45 yuan·m⁻³, 10.31 yuan·m⁻³ and 11.43 yuan·m⁻³ in wet year (P = 25%), in normal year (P = 50%) and low flow year (P = 75%) respectively, which proved that replanting crops could improve the efficiency of water resources utilization in irrigated areas. Therefore, the optimal planting pattern can be implemented to improve the utilization efficiency of soil and water resources in irrigation area in the arid oasis with single planting pattern with excessive concentration of water use peak and serious water shortage.

Estimating ground surface PM2.5 with fine spatiotemporal resolution is a critical technique for exposure assessments in epidemiological studies of its health risks. Previous studies have utilized monitoring, satellite remote sensing or air quality modeling data to evaluate the spatiotemporal variations of PM2.5 concentrations, but such studies rarely combined these data simultaneously. We develop a three-stage model to fuse PM2.5 monitoring data, satellite-derived aerosol optical depth (AOD) and community multi-scale air quality (CMAQ) simulations together and apply it to estimate daily PM2.5 at a spatial resolution of 0.1˚ over China. Performance of the three-stage model is evaluated using a cross-validation (CV) method step by step. CV results show that the finally fused estimator of PM2.5 is in good agreement with the observational data (RMSE = 23.00 μg/m^3 and R2 = 0.72) and outperforms either AOD-retrieved PM2.5 (R2 = 0.62) or CMAQ simulations (R2 = 0.51). According to step-specific CVs, in data fusion, AOD-retrieved PM2.5 plays a key role to reduce mean bias, whereas CMAQ provides all-spacetime-covered predictions, which avoids sampling bias caused by non-random incompleteness in satellite-derived AOD. Our fused products are more capable than either CMAQ simulations or AOD-based estimates in characterizing the polluting procedure during haze episodes and thus can support both chronic and acute exposure assessments of ambient PM2.5. Based on the products, averaged concentration of annual exposure to PM2.5 was 55.75 μg/m3, while averaged count of polluted days (PM2.5 > 75 μg/m3) was 81, across China during 2014. Fused estimates will be publicly available for future health-related studies.

Goldenhar Syndrome (GS), also known as oculoauriculovertebral spectrum (OVAS), is a rare congenital condition characterized by impaired development of structures such as ears, eyes, nose, palate, lip, mandible, maxilla, and teeth. The etiopathogenesis is multifactorial and dependent on genetic and environmental factors, yet the syndrome has many unknowns. We report a case of a 31-year-old male diagnosed clinically with GS as an infant with an absent left ear, hearing loss, absent left lung lobe, reduced growth of left upper limb, decreased size of left face, absent left kidney, and a missing left thumb, who was seen in the genetic clinic for prenatal genetic counseling. A microarray comparative genome hybridization (aCGH) was performed for copy number abnormalities and targeted NGS panels were performed for hereditary hearing loss and limb/digital malformations. aCGH revealed a 471kb loss at 16p12.2 and a mosaic 7.3Mb gain at 19p12q12. Metaphase FISH confirmed the orientation of 19p12q12 gain as small supernumerary ring chromosome 19. NGS revealed multiple variants (MYH14 c.4001C&gt;T, PDE1C c.8C&gt;T, ADGRV1 c.15502A&gt;G, CDH23 c.8772C&gt;A, MYO3A c.484G&gt;A, ADAMTS10 c.506G&gt;A, CHUK c.1294C&gt;T, CSPP1 c.1972A&gt;G, and TCTN2 c.160G&gt;A). Due to the heterogeneous clinical manifestation and genetic heterogeneity of GS, a comprehensive genetic testing strategy is needed for timely diagnosis and better patient care.

Credit rationing, especially prevalent for smaller firms, impedes economic growth. A Central Bank aligned “not for profit” managed business to business “Stable-Coin” (“Synthetic Central Bank Digital Currency”) providing trade debt liquidity can lower small firm credit rationing. It raises growth by reducing monetary transmission imperfections consequent upon asymmetric information, commercial bank underwriting restrictions, market power dynamics and regulatory distortion. A simple framework is developed to contextualise small firm credit rationing and associated monetary transmission imperfections with broader credit flows into both the real and monetary sectors. Evidence is presented regarding US monetary transmission efficacy to firms, paving the way to proposing a trade debt business to business focused stable-coin to help close credit rationing gaps. Designed to minimise “moral hazard”, the proposed stable-coin provides an additional monetary transmission channel that supplies interest free trade debt funding to firms to support economic activity and raise growth. In addition to helping close the small firm financing gap, the stable-coin provides policy makers with an additional contra-cyclical monetary transmission instrument to minimise real economic disruption consequent upon financial system crises and liquidity events.