Miracle-dz/UniFAR-FTUs huggingface dataset:
Concomitant Inhibition of Cytoprotective Autophagy Augments the Efficacy of Withaferin A in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality, and despite recent advances in early diagnosis and therapeutics, HCC related morbidity and mortality rate continue to rise. Clearly, it is imperative to develop novel effective therapies for HCC to improve long-term survival of HCC patients. We found that Withaferin A (WFA), a bioactive compound derived from Withania somnifera, is an effective agent for HCC inhibition. Interestingly, we observed that in addition to inducing apoptotic cell death, WFA also induces autophagy in HCC cells. Utilizing mRFP-EGFP-LC3B, LC3B-GFP/Lysotracker and LC3B-GFP/Rab7-RFP, we show that WFA induces autophagosomes-lysosomes fusion. WFA-induced autolysosomes exhibit intact protein degradation activity as evident with cathepsin-D activation and DQ-BSA assays. Importantly, we present that inhibiting WFA-induced autophagy either by blocking autophagosome-formation or by elevating lysosomal pH (Chloroquine and Bafilomycin) enhances WFA-induced growth-inhibition and apoptosis, indicating the presence of cytoprotective autophagy. Indeed, WFA and CQ combination shows synergism and higher efficacy in comparison to either monotherapy. Collectively, we reveal that the efficacy of WFA is somewhat diminished by the concomitant induction of cytoprotective autophagy which can be successfully conquered by cotreatment with CQ, and we pave the way for development of a novel combination therapeutic strategy for HCC.
Cellular and Animal Models of Striated Muscle Laminopathies

The lamin A/C (LMNA) gene codes for nuclear intermediate filaments constitutive of the nuclear lamina. LMNA has 12 exons and alternative splicing of exon 10 results in two major isoforms—lamins A and C. Mutations found throughout the LMNA gene cause a group of diseases collectively known as laminopathies, of which the type, diversity, penetrance and severity of phenotypes can vary from one individual to the other, even between individuals carrying the same mutation. The majority of the laminopathies affect cardiac and/or skeletal muscles. The underlying molecular mechanisms contributing to such tissue-specific phenotypes caused by mutations in a ubiquitously expressed gene are not yet well elucidated. This review will explore the different phenotypes observed in established models of striated muscle laminopathies and their respective contributions to advancing our understanding of cardiac and skeletal muscle-related laminopathies. Potential future directions for developing effective treatments for patients with lamin A/C mutation-associated cardiac and/or skeletal muscle conditions will be discussed.
Measurement and Clinical Significance of Lipid Peroxidation as a Biomarker of Oxidative Stress: Oxidative Stress in Diabetes, Atherosclerosis, and Chronic Inflammation

Endothelial dysfunction is one of the initial steps in the pathogenesis of atherosclerosis and development of cardiovascular disease in patients with diabetes mellitus. Several risk factors are associated with endothelial dysfunction and atherosclerosis, such as hypertension, dyslipidaemia, inflammation, oxidative stress, and advanced glycation-end products. Among these risk factors, oxidative stress is the largest contributor to the formation of atherosclerotic plaques. Measurement of reactive oxygen species (ROS) is still difficult, and assays for the measurement of ROS have failed to show a consistent correlation between pathological states and oxidative stress. To solve this problem, this review summarizes the current knowledge on biomarkers of oxidative stress, especially lipid peroxidation, and discusses the roles of oxidative stress, as measured by indices of lipid peroxidation, in diabetes mellitus, atherosclerosis, and chronic inflammation.
Evaluation of a Virus Neutralisation Test for Detection of Rift Valley Fever Antibodies in Suid Sera

Rift Valley fever (RVF) is a vector-borne viral disease of ruminants mainly, and man, characterized by abortions and neonatal deaths in animals and flu-like to more severe symptoms that can result in death in humans. The disease is endemic in Africa, Saudi Arabia and Yemen, and outbreaks occur following proliferation of RVF virus (RVFV) infected mosquito vectors. Vertebrate animal maintenance hosts of RVFV, which serve as a source of virus during inter-epidemic periods remain unknown, with wild and domestic suids being largely overlooked. To address this, we evaluated the virus neutralization test (VNT) for RVF antibody detection in suid sera, as a first step in assessing the role of suids in the epidemiology of RVF in Africa. Testing of experimental and field sera from domestic pigs and warthogs with a commercial RVF competitive antibody ELISA, served as a reference standard against which the VNT results were compared. Results indicate that VNT can detect anti-RVFV antibodies within three days post-infection, has an analytical specificity of 100% and diagnostic sensitivity and specificity of 80% and 97%, respectively. Although labour-intensive and time-consuming, the VNT proved suitable for screening suid sera and plasma for presence of RVFV antibodies in viraemic and recovered animals.
Multi-Cue-Based Circle Detection and Its Application to Robust Extrinsic Calibration of RGB-D Cameras

RGB-Depth (RGB-D) cameras are widely used in computer vision and robotics applications such as 3D modeling and human–computer interaction. To capture 3D information of an object from different viewpoints simultaneously, we need to use multiple RGB-D cameras. To minimize costs, the cameras are often sparsely distributed without shared scene features. Due to the advantage of being visible from different viewpoints, spherical objects have been used for extrinsic calibration of widely-separated cameras. Assuming that the projected shape of the spherical object is circular, this paper presents a multi-cue-based method for detecting circular regions in a single color image. Experimental comparisons with existing methods show that our proposed method accurately detects spherical objects with cluttered backgrounds under different illumination conditions. The circle detection method is then applied to extrinsic calibration of multiple RGB-D cameras, for which we propose to use robust cost functions to reduce errors due to misdetected sphere centers. Through experiments, we show that the proposed method provides accurate calibration results in the presence of outliers and performs better than a least-squares-based method.
Research about DoS Attack against ICPS

This paper studies denial-of-services (DoS) attacks against industrial cyber-physical systems (ICPSs) for which we built a proper ICPS model and attack model. According to the impact of different attack rates on systems, instead of directly studying the time delay caused by the attacks some security zones are identified, which display how a DoS attack destroys the stable status of the ICPS. Research on security zone division is consistent with the fact that ICPSs’ communication devices actually have some capacity for large network traffic. The research on DoS attacks’ impacts on ICPSs by studying their operation conditions in different security zones is simplified further. Then, a detection method and a mimicry security switch strategy are proposed to defend against malicious DoS attacks and bring the ICPS under attack back to normal. Lastly, practical implementation experiments have been carried out to illustrate the effectiveness and efficiency of the method we propose.
A Study of Physical Activity Determinants among High-Risk Hypertensive Filipino and Korean Americans

Physical activity (PA) serves a critical role in maintaining health and preventing chronic diseases, though its influence on high-risk Asian American populations is unclear. The purpose of this study was to determine PA levels among Filipino and Korean Americans at high risk of hypertension and to identify sociodemographic and health-related factors associated with PA levels in these populations. A cross-sectional survey was administered to 137 participants in the Greater Philadelphia Area. Data was collected on PA levels, sociodemographic factors, and health factors. Multinomial logistic regression was conducted to determine predictors associated with low, moderate, and high PA and predictive probabilities were calculated for interaction terms, incorporating ethnicity and blood pressure variables. Overall, 42.33% of participants belonged to the moderately active PA group and 21.90% belonged to the highly active group. In the final multinomial regression model, it was found that having gone to college increased the odds of being in the moderately active PA group (coef. = 1.96, p = 0.034), while having high blood pressure reduced the odds of being in the moderately active PA group (coef. = −2.21, p = 0.022). Lastly, being Korean versus Filipino reduced the odds of being in the highly active category (coef. = −2.89, p = 0.035). Based on predictive probabilities, Koreans and Filipinos with high blood pressure were more likely to belong in the low active PA category (52.31% and 46.33%). These findings highlight the need for culturally relevant PA interventions for promoting and increasing PA levels to prevent and manage hypertension among these populations.
Comparative Design Study for Power Reduction in Organic Optoelectronic Pulse Meter Sensor

This paper demonstrated a new design structure for minimizing the power consumption of a pulse meter. Monolithic devices composed of a red (625 nm) organic light-emitting diode (OLED) and an organic photodiode (OPD) were fabricated on the same substrate. Two organic devices were designed differently. One had a circle-shaped OLED in the center of the device and was surrounded by the OPD, while the other had the opposite structure. The external quantum efficiency (EQE) of the OLED and the OPD were 7% and 37%, respectively. We evaluated and compared the signal-to-noise ratio (SNR) of the photoplethysmogram (PPG) signal on different parts of the body and successfully acquired clear PPG signals at those positions, where the best signal was obtained from the fingertip at a SNR of about 62 dB. The proposed organic pulse meter sensor was operated successfully with a power consumption of 0.1 mW. Eventually, the proposed organic biosensor reduced the power consumption and improved the capability of the pulse meter for long-term use.
Time-Dependent Electric Vehicle Routing Problem with Time Windows and Path Flexibility

With energy and environmental issues becoming increasingly prominent, electric vehicles (EVs) have become the important transportation means in the logistics distribution. In the real-world urban road network, there often exist multiple paths between any two locations (depot, customer, and charging station) since the time-dependent travel times. That is, the travel speed of an EV on each path may be different during different time periods, and thus, this paper explicitly considers path selection between two locations in the time-dependent electric vehicle routing problem with time windows, denoted as path flexibility. Therefore, the integrated decision-making should include not only the routing plan but also the path selection, and the interested problem of this paper is a time-dependent electric vehicle routing problem with time windows and path flexibility (TDEVRP-PF). In order to determine the optimal path between any two locations, an optimization model is established with the goal of minimizing the distance and the battery energy consumption associated with travel speed and cargo load. On the basis of the optimal path model, a 0-1 mixed-integer programming model is then formulated to minimize the total travel distance. Hereinafter, an improved version of the variable neighborhood search (VNS) algorithm is utilized to solve the proposed models, in which multithreading technique is adopted to improve the solution efficiency significantly. Ultimately, several numerical experiments are carried out to test the performance of VNS with a view to the conclusion that the improved VNS is effective in finding high-quality distribution schemes consisted of the distribution routes, traveling paths, and charging plans, which are of practical significance to select and arrange EVs for logistics enterprises.
Convex combinations of centrality measures

ABSTRACT Despite a plethora of centrality measures were proposed, there is no consensus on what centrality is exactly due to the shortcomings each measure has. In this manuscript, we propose to combine centrality measures pertinent to a network by forming their convex combinations. We found that some combinations, induced by regular points, split the nodes into the largest number of classes by their rankings. Moreover, regular points are found with probability and their induced rankings are insensitive to small variation. By contrast, combinations induced by critical points are scarce, but their presence enables the variation in node rankings. We also discuss how optimum combinations could be chosen, while proving various properties of the convex combinations of centrality measures.
The Development of a qPCR Assay to Measure Aspergillus flavus Biomass in Maize and the Use of a Biocontrol Strategy to Limit Aflatoxin Production

Aspergillus flavus colonisation of maize can produce mycotoxins that are detrimental to both human and animal health. Screening of maize lines, resistant to A. flavus infection, together with a biocontrol strategy, could help minimize subsequent aflatoxin contamination. We developed a qPCR assay to measure A. flavus biomass and showed that two African maize lines, GAF4 and KDV1, had different fungal loads for the aflatoxigenic isolate (KSM014), fourteen days after infection. The qPCR assay revealed no significant variation in A. flavus biomass between diseased and non-diseased maize tissues for GAF4, while KDV1 had a significantly higher A. flavus biomass (p < 0.05) in infected shoots and roots compared to the control. The biocontrol strategy using an atoxigenic isolate (KSM012) against the toxigenic isolate (KSM014), showed aflatoxin production inhibition at the co-infection ratio, 50:50 for both maize lines (KDV1 > 99.7% and GAF ≥ 69.4%), as confirmed by bioanalytical techniques. As far as we are aware, this is the first report in Kenya where the biomass of A. flavus from maize tissue was detected and quantified using a qPCR assay. Our results suggest that maize lines, which have adequate resistance to A. flavus, together with the appropriate biocontrol strategy, could limit outbreaks of aflatoxicoses.
Alcohol and substance misuse in the construction industry

This study investigates factors contributing to the menace of alcohol and substance misuse (ASM) in the construction industry, and its mitigation. A sequential exploratory mixed-method design, involving interview and questionnaire, was used for collecting data that were subsequently analysed by thematic analysis, factor analysis and Kruskal–Wallis test. Findings suggest that the problem of ASM is largely caused and exacerbated by mental strain, site working conditions, male dominance and ineffective human resource management. Screening and educational approaches were confirmed as carrot and stick methods for mitigating the menace in the construction industry. The finding implies that by making construction companies more accountable for the well-being of their workers, a change could be brought in the industry. These changes could be incentivized by initiatives like PREVENT to mitigate the crisis currently endemic in construction. The study suggests some practical measures for tackling the menace of ASM that is bedevilling the industry.
Ozone-induced damage of fibrinogen molecules: identification of oxidation sites by high-resolution mass spectrometry

Abstract Fibrinogen is highly susceptible to oxidation compared to other plasma proteins. Fibrinogen oxidation damages its structure and affects the protein function. Ozone-induced oxidative modifications of the fibrinogen Aα, Bβ, and γ polypeptide chains upon addition of various amounts of the oxidiser were studied by mass spectrometry. Amino acid residues located on all three chains and main structural parts of the protein were revealed to be involved in oxidation. The αC-connector was shown to be most vulnerable to oxidation as compared to other structural parts while the E region turned out to be the most protected area of the protein. For the first time, it was established that numerous amino acid residues responsible for the conversion of fibrinogen to fibrin remain unaffected upon fibrinogen oxidation. The data obtained in this study indicate that none of the identified residues, which are considered crucial for the binding of both hole “a” and hole “b” to knob “A” and knob “B”, respectively, as well as those responsible for the thrombin binding to fibrinogen E region, have been subjected to chemical alterations under moderate oxidation. The data on fibrinogen oxidation acquired in the current study enable one to assume that some of the structural fibrinogen parts and easily oxidisable residues could be endowed with antioxidant properties. New findings presented here could be essential for the detection of adaptive molecular mechanisms capable of mitigating the detrimental action of reactive oxygen species (ROS) on the functioning of oxidatively damaged fibrinogen. Data are available via ProteomeXchange with identifier PXD012046. Highlights Various oxidative modifications were detected in fibrinogen by mass spectrometry αC-connector has been shown to be most susceptible to oxidation E region proved to be least vulnerable to the action of the oxidising agent Some of the Met residues in the fibrinogen structure could operate as ROS scavengers
Considerations for Evaluating and Recommending Worker Productivity Outcome Measures: An Update from the OMERACT Worker Productivity Group

Objective. The Outcome Measures in Rheumatology (OMERACT) Worker Productivity Group continues efforts to assess psychometric properties of measures of presenteeism. Methods. Psychometric properties of single-item and dual answer multiitem scales were assessed, as well as methods to evaluate thresholds of meaning. Results. Test-retest reliability and construct validity of single item global measures was moderate to good. The value of measuring both degree of difficulty and amount of time with difficulty in multiitems questionnaires was confirmed. Thresholds of meaning vary depending on methods and external anchors applied. Conclusion. We have advanced our understanding of the performance of presenteeism measures and have developed approaches to describing thresholds of meaning.
Love and incomprehensibility: The hermeneutic labour of caring for and understanding a loved one with psychosis

Informal carers are increasingly involved in supporting people with severe and enduring mental health problems, and carers’ perceptions impact the wellbeing of both parties. However, there is little research on how carers actually make sense of what their loved one is experiencing. Ten carers were interviewed about how they understood a loved one’s psychosis. Data were analysed using a hermeneutic-phenomenological approach. Three themes described the carers’ effortful quest to understand their loved one’s experiences while maintaining their relational bonds. Carers described psychosis as incomprehensible, seeing their loved one as incompatible with the shared world. To overcome this, carers developed hermeneutic ‘mooring points’, making sense of their loved one’s unusual experiences through novel accounts that drew on material or spiritual explanations. The findings suggest that informal carers resist biomedical narratives and develop idiosyncratic understandings of psychosis, in an attempt to maintain relational closeness. We suggest that this process is effortful – it is hermeneutic labour – done in the service of maintaining the caring relationship. Findings imply that services should better acknowledge the bond between carers and care-receivers, and that more relationally oriented approaches should be used to support carers of people experiencing severe mental health problems.
Students’ perceptions and evaluations of plagiarism: Effects of text and context

ABSTRACT As they navigate academic life, students must decide whether the acts of copying they encounter constitute plagiarism, and whether those acts are wrong. The present study investigated students’ perceptions, evaluations, and reasoning about copying. In interviews about hypothetical scenarios involving copying, undergraduates (N = 60) reported whether the characters’ actions constituted plagiarism, whether the actions were wrong, and why. Students’ perceptions varied depending on textual similarity and type of academic task. When students perceived an act as plagiarism, they almost always believed it was wrong. In explaining their evaluations of plagiarism, students commonly referenced concerns about learning consequences, rules, and fairness. As expected, most students expressed uncertainty about what constitutes plagiarism and whether copying was wrong. The findings validate a new method and highlight the need for a situated theoretical model of decision-making that goes beyond stable characteristics and incorporates perceptions, evaluations, and reasoning about specific texts and contexts.
Tau protein aggregates inhibit the protein-folding and vesicular trafficking arms of the cellular proteostasis network

Tauopathies are a diverse class of neurodegenerative diseases characterized by the formation of insoluble tau aggregates and the loss of cellular function and neuronal death. Tau inclusions have been shown to contain a number of proteins, including molecular chaperones, but the consequences of these entrapments are not well established. Here, using a human cell system for seeding-dependent tau aggregation, we demonstrate that the molecular chaperones heat-shock cognate 71-kDa protein (HSC70)/heat-shock protein 70 (HSP70), HSP90, and J-domain co-chaperones are sequestered by tau aggregates. By employing single-cell analysis of protein-folding and clathrin-mediated endocytosis, we show that both chaperone-dependent cellular activities are significantly impaired by tau aggregation and can be reversed by treatment with small-molecule regulators of heat-shock transcription factor 1 (HSF1) proteostasis that induce the expression of cytosolic chaperones. These results reveal that the sequestration of cytoplasmic molecular chaperones by tau aggregates interferes with two arms of the proteostasis network, likely having profound negative consequences for cellular function.