Miracle-dz/UniFAR-FTUs huggingface dataset:
Heparan Sulfate Induces Necroptosis in Murine Cardiomyocytes: A Medical-In silico Approach Combining In vitro Experiments and Machine Learning

Life-threatening cardiomyopathy is a severe, but common, complication associated with severe trauma or sepsis. Several signaling pathways involved in apoptosis and necroptosis are linked to trauma- or sepsis-associated cardiomyopathy. However, the underling causative factors are still debatable. Heparan sulfate (HS) fragments belong to the class of danger/damage-associated molecular patterns liberated from endothelial-bound proteoglycans by heparanase during tissue injury associated with trauma or sepsis. We hypothesized that HS induces apoptosis or necroptosis in murine cardiomyocytes. By using a novel Medical-In silico approach that combines conventional cell culture experiments with machine learning algorithms, we aimed to reduce a significant part of the expensive and time-consuming cell culture experiments and data generation by using computational intelligence (refinement and replacement). Cardiomyocytes exposed to HS showed an activation of the intrinsic apoptosis signal pathway via cytochrome C and the activation of caspase 3 (both p < 0.001). Notably, the exposure of HS resulted in the induction of necroptosis by tumor necrosis factor α and receptor interaction protein 3 (p < 0.05; p < 0.01) and, hence, an increased level of necrotic cardiomyocytes. In conclusion, using this novel Medical-In silico approach, our data suggest (i) that HS induces necroptosis in cardiomyocytes by phosphorylation (activation) of receptor-interacting protein 3, (ii) that HS is a therapeutic target in trauma- or sepsis-associated cardiomyopathy, and (iii) indicate that this proof-of-concept is a first step toward simulating the extent of activated components in the pro-apoptotic pathway induced by HS with only a small data set gained from the in vitro experiments by using machine learning algorithms.
p38 Mitogen-Activated Protein Kinase Mediates Lipopolysaccharide and Tumor Necrosis Factor Alpha Induction of Shiga Toxin 2 Sensitivity in Human Umbilical Vein Endothelial Cells

ABSTRACT Escherichia coli O157:H7 Shiga toxin 2 (Stx2), one of the causative agents of hemolytic-uremic syndrome, is toxic to endothelial cells, including primary cultured human umbilical vein endothelial cells (HUVEC). This sensitivity of cells to Stx2 can be increased with either lipopolysaccharide (LPS) or tumor necrosis factor alpha (TNF-α). The goal of the present study was to identify the intracellular signaling pathway(s) by which LPS and TNF-α sensitize HUVEC to the cytotoxic effects of Stx2. To identify these pathways, specific pharmacological inhibitors and small interfering RNAs were tested with cell viability endpoints. A time course and dose response experiment for HUVEC exposure to LPS and TNF-α showed that a relatively short exposure to either agonist was sufficient to sensitize the cells to Stx2 and that both agonists stimulated intracellular signaling pathways within a short time. Cell viability assays indicated that the p38 mitogen-activated protein kinase (MAPK) inhibitors SB202190 and SB203580 and the general protein synthesis inhibitor cycloheximide inhibited both the LPS and TNF-α sensitization of HUVEC to Stx2, while all other inhibitors tested did not inhibit this sensitization. Additionally, SB202190 reduced the cellular globotriaosylceramide content under LPS- and TNF-α-induced conditions. In conclusion, our results show that LPS and TNF-α induction of Stx2 sensitivity in HUVEC is mediated through a pathway that includes p38 MAPK. These results indicate that inhibition of p38 MAPK in endothelial cells may protect a host from the deleterious effects of Stx2.
THE IMPACT OF FINANCIAL STRUCTURE ON FIRMS’ PROBABILITY OF BANKRUPTCY: A COMPARISON ACROSS WESTERN EUROPE CONVERGENCE REGIONS

The aim of the paper is to investigate the impact of financial structure on firms’ probability of bankruptcy in Western Europe convergence regions. The empirical evidence shows that the financial structure is a key factor explaining firms’ bankruptcy, but while the debt, the cash flow and the profitability ratios are strongly significant in explaining firms’ failure, structure and operational ratios are not relevant factors of bankruptcy. Additional differences arise when we consider the countries separately: while debt and cash flow ratios are significant for bank based economies, they are not significant for market oriented countries.
Multi-focal control of mitochondrial gene expression by oncogenic MYC provides potential therapeutic targets in cancer

Despite ubiquitous activation in human cancer, essential downstream effector pathways of the MYC transcription factor have been difficult to define and target. Using a structure/function-based approach, we identified the mitochondrial RNA polymerase (POLRMT) locus as a critical downstream target of MYC. The multifunctional POLRMT enzyme controls mitochondrial gene expression, a process required both for mitochondrial function and mitochondrial biogenesis. We further demonstrate that inhibition of this newly defined MYC effector pathway causes robust and selective tumor cell apoptosis, via an acute, checkpoint-like mechanism linked to aberrant electron transport chain complex assembly and mitochondrial reactive oxygen species (ROS) production. Fortuitously, MYC-dependent tumor cell death can be induced by inhibiting the mitochondrial gene expression pathway using a variety of strategies, including treatment with FDA-approved antibiotics. In vivo studies using a mouse model of Burkitt's Lymphoma provide pre-clinical evidence that these antibiotics can successfully block progression of MYC-dependent tumors.
Early-Life Selenium Status and Cognitive Function at 5 and 10 Years of Age in Bangladeshi Children

Background: In older adults, selenium status has been positively associated with cognitive function. We recently reported a positive association between maternal selenium status in pregnancy and children’s cognitive function at 1.5 y. Objective: We followed up the children to assess if prenatal and childhood selenium status was associated with cognitive abilities at 5 and 10 y. Methods: This longitudinal cohort study was nested in Maternal and Infant Nutrition Interventions in Matlab (MINIMat), a population-based, randomized supplementation trial in pregnancy in rural Bangladesh. Selenium in maternal blood [erythrocyte fraction (Ery-Se) at baseline] and in child hair and urine was measured using inductively coupled plasma mass spectrometry. Children’s cognition at 5 and 10 y was assessed using the Wechsler Preschool and Primary Scale of Intelligence™ and the Wechsler Intelligence Scale for Children®, respectively. In total, 1,408 children were included. Results: Multivariable-adjusted linear regression analyses showed that prenatal selenium status was positively associated with children’s cognitive function at 5 and 10 y. An increase in maternal Ery-Se from the fifth to the 95th percentile [median: 0. 44μg/g hemoglobin (Hb)] was associated with an increase in full developmental score of 3.5 [95% confidence interval (CI): 0.1, 7.0], corresponding to 0.16 standard deviation (SD) at 5 y, and 8.1 (95% CI: 3.8, 13), corresponding to 0.24 SD at 10 y. In addition, urine and hair selenium concentrations at 5 and 10 y of age were positively associated with cognitive function at 10 y, although associations were inverse for concentrations ≥98th percentile. Some associations were slightly stronger for girls than for boys. Conclusions: Measures of prenatal and childhood (below the 98th percentile) selenium status were associated with higher cognitive function scores at 5 and 10 y of age. https://doi.org/10.1289/EHP1691
Do parasites adopt different strategies in different intermediate hosts? Host size, not host species, influences Coitocaecum parvum (Trematoda) life history strategy, size and egg production

SUMMARY Host exploitation induces host defence responses and competition between parasites, resulting in individual parasites facing highly variable environments. Alternative life strategies may thus be expressed in context-dependent ways, depending on which host species is used and intra-host competition between parasites. Coitocaecum parvum (Trematode) can use facultative progenesis in amphipod intermediate hosts, Paracalliope fluviatilis, to abbreviate its life cycle in response to such environmental factors. Coitocaecum parvum also uses another amphipod host, Paracorophium excavatum, a species widely different in size and ecology from P. fluviatilis. In this study, parasite infection levels and strategies in the two amphipod species were compared to determine whether the adoption of progenesis by C. parvum varied between these two hosts. Potential differences in size and/or egg production between C. parvum individuals according to amphipod host species were also investigated. Results show that C. parvum life strategy was not influenced by host species. In contrast, host size significantly affected C. parvum strategy, size and egg production. Since intra-host interactions between co-infecting parasites also influenced C. parvum strategy, size and fecundity, it is highly likely that within-host resource limitations affect C. parvum life strategy and overall fitness regardless of host species.
The Co-Evolution of Fairness Preferences and Costly Punishment

We study the co-evolutionary emergence of fairness preferences in the form of other-regarding behavior and its effect on the origination of costly punishment behavior in public good games. Our approach closely combines empirical results from three experiments with an evolutionary simulation model. In this way, we try to fill a gap between the evolutionary theoretical literature on cooperation and punishment on the one hand and the empirical findings from experimental economics on the other hand. As a principal result, we show that the evolution among interacting agents inevitably favors a sense for fairness in the form of “disadvantageous inequity aversion”. The evolutionary dominance and stability of disadvantageous inequity aversion is demonstrated by enabling agents to co-evolve with different self- and other-regarding preferences in a competitive environment with limited resources. Disadvantageous inequity aversion leads to the emergence of costly (“altruistic”) punishment behavior and quantitatively explains the level of punishment observed in contemporary lab experiments performed on subjects with a western culture. Our findings corroborate, complement, and interlink the experimental and theoretical literature that has shown the importance of other-regarding behavior in various decision settings.
Too much of a good thing : Long-term treatment with salicylate strengthens outer hair cell function but impairs auditory neural activity Guang

Aspirin has been extensively used in clinical settings. Its side effects on auditory function, including hearing loss and tinnitus, are considered as temporary. A recent promising finding is that chronic treatment with high-dose salicylate (the active ingredient of aspirin) for several weeks enhances expression of the outer hair cell (OHC) motor protein (prestin), resulting in strengthened OHC electromotility and enhanced distortion product otoacoustic emissions (DPOAE). To follow up on these observations, we carried out two studies, one planned study of age-related hearing loss restoration and a second unrelated study of salicylate-induced tinnitus. Rats of different strains and ages were injected with salicylate at a dose of 200 mg/kg/day for 5 days per week for 3 weeks or at higher dose levels (250–350 mg/kg/day) for 4 days per week for 2 weeks. Unexpectedly, while an enhanced or sustained DPOAE was seen, permanent reductions in the amplitude of the cochlear compound action potential (CAP) and the auditory brainstem response (ABR) were often observed after the chronic salicylate treatment. The mechanisms underlying these unexpected, permanent salicylate-induced reductions in neural activity are discussed.
Extraglottic Airways in Tactical Combat Casualty Care

Extraglottic airway (EGA) devices have been used by both physicians and prehospital providers for several decades. The original TCCC Guidelines published in 1996 included a recommendation to use the laryngeal mask airway (LMA) as an option to assist in securing the airway in Tactical Evacuation (TACEVAC) phase of care. A variety of EGAs have been used in combat casualty care over the past 20 years. In 2012, the Committee on TCCC (CoTCCC) and the Defense Health Board (DHB) reaffirmed support for the use of supraglottic airway (SGA) devices in the TACEVAC phase of TCCC, but did not recommend a specific SGA based on the evidence available at that point in time. This paper will use the more inclusive term “extraglottic airway” instead of the term “supragottic airway” used in the DHB memo. Current evidence suggests that the i-gel EGA performs as well or better than the other EGAs available and has other advantages in ease of training, size and weight, cost, safety, and simplicity of use. The gel-filled cuff in the i-gel both eliminates the need for cuff pressure monitoring during flight and reduces the risk of pressure-induced neuropraxia to cranial nerves in the oropharynx as a complication of EGA use. The i-gel thus makes the medic’s tasks simpler and frees him or her from the requirement to carry a cuff manometer as part of the medical kit.
Prediction of ovalling frequency for FRP chimney liners with circumferential stiffeners

ASTM D 5364 requires that the lowest ovalling frequency of a fiberglass reinforced plastic chimney liner shall not be less than 2 Hz. From engineering practices and numerical experiments, the authors find that the frequency calculated in accordance with ASTM D 5364 deviates considerably from results using finite element analysis (FEA). A modified equation has been proposed in this article to better evaluate the lowest ovalling frequency for FRP chimney liners.
Normative Values for Electrochemical Skin Conductance Measurements for Quantitative Assessment of Sudomotor Function in Healthy Indian Adults

Context: Electrochemical skin conductance (ESC) test is a widely accepted objective technique for quantitatively assessing sudomotor dysfunction, which is one of the earliest-detected neurophysiologic abnormalities in diabetic patients with distal symmetric polyneuropathy. Aims: This study aimed to provide normative data for ESC values among healthy Indian participants and assess the potential influence of age, sex, and body mass index (BMI) on ESC measurements. Settings and Design: A sample of 217 healthy participants aged 18–75 years were recruited and assessed for parameters including age, gender, BMI, and ESC measurements of the hands and feet. Statistical Analysis Used: The Shapiro–Wilk test was used to assess the normality of the data. Pearson's correlation was used to evaluate the association between age, gender, and BMI, and ESC measurements. Results: The mean age of the participants was 43.3 ± 13.2 years, and mean BMI was 26.0 ± 4.3 kg/m2. Mean ESC for the hands and feet was 68.9 ± 13.1 and 71 ± 12.9 micro-Siemens, respectively, and there was a significant correlation between values from the right and left hands and feet (r = 0.9, P < 0.0001). A significant correlation was also observed between ESC measurements of the hands and feet (r = 0.94, P < 0.0001). ESC values of both hands and feet declined with age. A weak but significant inverse correlation between ESC and age was observed for the hands (r = 0.02, P = 0.01) and for the feet (r = 0.12, P < 0.0001). There was no significant difference in hand or feet ESC measurement between male and female participants. No significant correlation was observed between BMI and ESC of hands or feet. Only age was identified as a significant determinant of ESC on multivariate logistic regression analysis. Conclusions: Normative values for Indians are lower than that reported for Caucasians.
Resource Sharing of a Computing Access Point for Multi-User Mobile Cloud Offloading with Delay Constraints

We consider a mobile cloud computing system with multiple users, a remote cloud server, and a computing access point (CAP). The CAP serves both as the network access gateway and a computation service provider to the mobile users. It can either process the received tasks from mobile users or offload them to the cloud. We jointly optimize the offloading decisions of all users, together with the allocation of computation and communication resources, to minimize the overall cost of energy consumption, computation, and maximum delay among users. The joint optimization problem is formulated as a mixed-integer program. We show that the problem can be reformulated and transformed into a non-convex quadratically constrained quadratic program, which is NP-hard in general. We then propose an efficient solution to this problem by semidefinite relaxation and a novel randomization mapping method. Furthermore, when there is a strict delay constraint for processing each user's task, we further propose a three-step algorithm to guarantee the feasibility and local optimality of the obtained solution. Our numerical results show that the proposed solutions give nearly optimal performance under a wide range of parameter settings, and the addition of a CAP can significantly reduce the cost of multi-user task offloading compared with conventional mobile cloud computing where only the remote cloud server is available.
Abnormal Alveolar Type 2 Cell Phenotype in AP-3 Mutant Mocha and Pearl Mice- An Electron Microscopy Study

Adaptor protein-3 complex (AP-3), which consists of b3, d, m3, s3 subunits, participates in cargoselective transport from trans Golgi to the lysosome (Dell’Angelica et al., 1998; Hurst et al., 1999). Genetic analyses using AP-3 mutant mice (Odorizzi et al., 1998; Swank et al., 2000) showed that mutations in AP-3d (mocha) and the AP-b3A (pearl) genes resulted in pathogenesis similar to Hermansky Pudlak syndrome (HPS), a recessive inherited disease that is characterized by deficient lysosome functions, hypo pigmentation, prolonged bleeding time, and ceroid deposition. Pulmonary fibrosis has been demonstrated clinically in HPS and is a major cause of morbidity and mortality in these patients (Garay et al., 1978). The purpose of this study was to identify the progressive changes in the ultrastructure of lungs from mocha and pearl mice. The long term goal of this work is to determine if AP-3 mutations in alveolar type 2 cells contribute to pulmonary fibrosis.
Reproductive Success and Nestling Growth of the Baywing Parasitized by Screaming and Shiny Cowbirds

Abstract We studied the breeding biology of the Baywing (Agelaioides badius), a shared host of Screaming (Molothrus rufoaxillaris) and Shiny (M. bonariensis) cowbirds. We monitored 193 nests from December 2002 to March 2007 in the Province of Buenos Aires, Argentina. Baywings used a wide variety of nesting sites, mainly old nests of furnarids. Their breeding season lasted from late November to February and was closely matched by that of Screaming Cowbirds. The breeding season for Shiny Cowbirds started in late September but overlapped that of Baywings. Frequency and intensity of Screaming Cowbird parasitism were 93% and 5 eggs per parasitized nest, while for Shiny Cowbirds they were 16% and 1.4 eggs. Host clutch size was 4.0 ± 0.1 eggs and did not vary with time of breeding. Weight at hatching and age of maximum growth were similar for host and Screaming Cowbird nestlings. Shiny Cowbird nestlings had higher weight at hatching and lower age of maximum growth than the other two species. Screaming and Shiny cowbird nestlings had higher growth rates and asymptotic weights than host nestlings. Sex-specific growth curves of Screaming Cowbirds indicated males had higher growth rate and asymptotic weight than females. Only 19% of the nests produced fledglings. Host egg survival, hatching success, and nestling survival were 0.92, 0.88, and 0.94, respectively. Excluding nest failures, hosts fledged 0.78 chicks per egg laid. Baywings were smaller than Screaming and Shiny cowbirds, and experienced a high frequency and intensity of parasitism. However, the effect of parasitism on host hatching success and chick survival was low and comparable to that observed in larger hosts.
Gaze distribution analysis and saliency prediction across age groups

Knowledge of the human visual system helps to develop better computational models of visual attention. State-of-the-art models have been developed to mimic the visual attention system of young adults that, however, largely ignore the variations that occur with age. In this paper, we investigated how visual scene processing changes with age and we propose an age-adapted framework that helps to develop a computational model that can predict saliency across different age groups. Our analysis uncovers how the explorativeness of an observer varies with age, how well saliency maps of an age group agree with fixation points of observers from the same or different age groups, and how age influences the center bias tendency. We analyzed the eye movement behavior of 82 observers belonging to four age groups while they explored visual scenes. Explorative- ness was quantified in terms of the entropy of a saliency map, and area under the curve (AUC) metrics was used to quantify the agreement analysis and the center bias tendency. Analysis results were used to develop age adapted saliency models. Our results suggest that the proposed age-adapted saliency model outperforms existing saliency models in predicting the regions of interest across age groups.
Journalists and Twitter: How Australian News Organisations Adapt to a New Medium

Twitter has developed an increasingly visible presence in Australian journalism, and in the discussion of news. This article examines the positioning of journalists as ‘personal brands’ on Twitter by documenting the visibility of leading personal and institutional accounts during two major political events in Australia: the Rudd/Gillard leadership spill on 23 June 2010, and the day of the subsequent federal election on 21 August 2010. It highlights the fact that in third-party networks such as Twitter, journalists and news organisations no longer operate solely on their own terms, as they do on their own websites, but gain and maintain prominence in the network and reach for their messages only in concert with other users. It places these observations in a wider context of journalist–audience relations a decade after the emergence of the first citizen journalism websites.