Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular footprints reveal the impact of the protective HLA-A*03 allele in hepatitis C virus infection

Background and aims CD8 T cells are central to the control of hepatitis C virus (HCV) although the key features of a successful CD8 T cell response remain to be defined. In a cohort of Irish women infected by a single source, a strong association between viral clearance and the human lecucocyte (HLA)-A*03 allele has been described, and the aim of this study was to define the protective nature of the associated CD8 T cell response. Methods A sequence-led approach was used to identify HLA-A*03-restricted epitopes. We examine the CD8 T cell response associated with this gene and address the likely mechanism underpinning this protective effect in this special cohort, using viral sequencing, T cell assays and analysis of fitness of viral mutants. Results A strong ‘HLA footprint’ in a novel NS3 epitope (TVYHGAGTK) was observed. A lysine (K) to arginine (R) substitution at position 9 (K1088R) was seen in a significant number of A*03-positive patients (9/12) compared with the control group (1/33, p=0.0003). Threonine (T) was also substituted with alanine (A) at position 8 (T1087A) more frequently in A*03-positive patients (6/12) compared with controls (2/33, p=0.01), and the double substitution of TK to AR was also observed predominantly in HLA-A*03-positive patients (p=0.004). Epitope-specific CD8 T cell responses were observed in 60% of patients three decades after exposure and the mutants selected in vivo impacted on recognition in vitro. Using HCV replicons matched to the viral sequences, viral fitness was found to be markedly reduced by the K1088R substitution but restored by the second substitution T1087A. Conclusions It is proposed that at least part of the protective effect of HLA-A*03 results from targeting of this key epitope in a functional site: the requirement for two mutations to balance fitness and escape provides an initial host advantage. This study highlights the potential protective impact of common HLA-A alleles against persistent viruses, with important implications for HCV vaccine studies.
Evacetrapib: Another CETP Inhibitor for Dyslipidemia With No Clinical Benefit

Evacetrapib is a cholesteryl ester transfer protein (CETP) inhibitor that has been recently studied as a cholesterol modifying agent to reduce cardiovascular risk and mortality in high risk cardiovascular disease patients. Evacetrapib acts to decrease lipid exchange through CETP inhibition. CETP acts to transfer cholesteryl esters from high-density lipoprotein-cholesterol (HDL-C) to low-density lipoprotein cholesterol (LDL-C) and very-low-density lipoprotein (VLDL-C). HDL-C is involved in reverse cholesterol transport and its blood levels have been shown to be inversely correlated with cardiovascular risk. Thus, a pharmacologic agent that can elevate HDL-C has been seen as an exciting area of research. In recent studies, evacetrapib was shown to be safe and efficacious. It produced an increase in HDL-C up to 128% and a 35% decrease in LDL-C, in comparison to placebo. In addition, evacetrapib was also shown to be more potent than previous CETP inhibitors. HDL-C particles treated with evacetrapib remained functional and had improved cholesterol efflux. A previously studied CETP inhibitor, torcetrapib, exhibited side effects of hyperaldosteronism, manifesting in electrolyte disturbances, and hypertension. These detrimental effects were not seen with evacetrapib. Recently, the results of evacetrapib’s phase III ACCELERATE trial showed no significant reduction in major adverse cardiovascular events or mortality, and the drug will not be marketed. Although beneficial cholesterol effects were seen with this drug, more needs to be known to understand what role, if any, evacetrapib has in the reduction of cardiovascular risk.
Hippocampal involvement in detection of deviant auditory and visual stimuli

Recent models of hippocampal function have emphasized its role in processing sequences of events. In this study, we used an oddball task to investigate hippocampal responses to the detection of deviant “target” stimuli that were embedded in a sequence of repetitive “standard” stimuli. Evidence from intracranial event‐related potential studies has suggested a critical role for the hippocampus in oddball tasks. However, functional neuroimaging experiments have failed to detect activation in the hippocampus in response to deviant stimuli. Our study aimed to resolve this discrepancy by using a novel functional magnetic resonance imaging (fMRI) technique that drastically improves signal detection in the hippocampus. Significant hippocampal activation was observed during both auditory and visual oddball tasks. Although there was no difference in the overall level of hippocampal activation in the two modalities, significant modality differences in the profile of activation along the long axis of the hippocampus were observed. In both left and right hippocampi, an anterior‐to‐posterior gradient in the activation (anterior to posterior) was observed during the auditory oddball task, whereas a posterior‐to‐anterior gradient (posterior to anterior) was observed during the visual oddball task. These results indicate that the hippocampus is involved in the detection of deviant stimuli regardless of stimulus modality, and that there are prominent modality differences along the long axis of the hippocampus. The implications of our findings for understanding hippocampal involvement in processing sequences of events are discussed. © 2004 Wiley‐Liss, Inc.
Moving state marine SINS initial alignment based on transformed cubature Kalman filter

In this paper, we propose an initial alignment method for marine strap-down inertial navigation system (SINS) based on transformed cubature Kalman filter (TCKF) under large heading misalignment angle condition, which can alleviate the non-local sampling problem inherent in existing initial alignment method based on cubature Kalman filter (CKF). As can be seen from our simulation results, TCKF outperforms CKF considerably in terms of accuracy and SINS alignment speed.
Half a century of research on the Stroop effect: an integrative review.

The literature on interference in the Stroop Color-Word Task, covering over 50 years and some 400 studies, is organized and reviewed. In so doing, a set of 18 reliable empirical finding is isolated that must be captured by any successful theory of the Stroop effect. Existing theoretical positions are summarized and evaluated in view of this critical evidence and the 2 major candidate theories ―relative speed of processing and automaticity of reading― are found to be wanting. It is concluded that recent theories placing the explanatory weight on parallel processing of the irrelevant and the relevant dimensions are likely to be more sucessful than are earlier theories attempting to locate a single bottleneck in attention
Isolation of Antibiotic-Resistant Bacteria from the Air Plume Downwind of a Swine Confined or Concentrated Animal Feeding Operation

Objective In this study we evaluated the levels of antibiotic- and multidrug-resistant bacteria in bioaerosols upwind, within, and downwind at locations 25 m, 50 m, 100 m, and 150 m from a swine confined animal feeding operation. Design We used Andersen two-stage samplers to collect bacterial samples, the replicate plate method to isolate organisms, and the Kirby-Bauer disk diffusion method to determine antibiotic resistance. Results The percentage of organisms resistant to at least two antibiotic classes and all four classes evaluated were, respectively, 2.1 and 3.0 times higher inside (n = 69) than upwind (n = 59) of the facility. Staphylococcus aureus was the most prevalent organism recovered. Concentrations of antibiotic-resistant S. aureus decreased with increasing distance from the facility. Using Fisher’s exact methods, the change in distribution of antibiotic resistance profiles for each antibiotic was statistically significant (oxytetracycline, p = 0.010; tetracycline, p = 0.014; ampicillin, p = 0.007; erythromycin, p = 0.035); however, this relationship was not seen with lincomycin and penicillin (p > 0.05). In addition, the levels of antibiotic-resistant S. aureus 25 m downwind were significantly greater than the levels from samples taken upwind from the facility for the same four antibiotics (p < 0.05). The percentage of resistant group A streptococci and fecal coliform increased within the facility compared with upwind values for all antibiotics evaluated, except for lincomycin. The percentage of resistant total coliform organisms increased within the facility compared with upwind values for oxytetracycline and tetracycline. Conclusions Bacterial concentrations with multiple antibiotic resistances or multidrug resistance were recovered inside and outside to (at least) 150 m downwind of this facility at higher percentages than upwind. Bacterial concentrations with multiple antibiotic resistances were found within and downwind of the facility even after subtherapeutic antibiotics were discontinued. This could pose a potential human health effect for those who work within or live in close proximity to these facilities.
Assessment of airway function using partial expiratory flow-volume curves: How reliable are measurements of maximal expiratory flow at frc during early infancy?

We investigated the extent to which measurements of maximal expiratory flow at FRC (V EmaxFRC) are influenced by the dynamic increase of FRC in young infants by superimposing partial forced expiratory flow-volume curves on those obtained after lung inflation to 2 kPa (20 cm H2O) in 12 infants during the first month of life. The elastic equilibrium volume (EEV) of the respiratory system was estimated by extrapolating the passive expiratory time constant (obtained after lung inflation but prior to forced deflation) to zero flow. There was a very strong relationship between V EmaxFRC (which ranged from 11 to 190 ml/s) and the extent to which FRC was dynamically increased above EEV (range: 0 to 5 ml/kg), r2 = 0.88. The results of this study suggest that, although V EmaxFRC remains a useful means of measuring peripheral airway function in infants, its values should be interpreted with caution during the neonatal period. In particular, the relatively high V EmaxFRC values reported in healthy newborn infants may reflect differences in breathing strategy rather than airway structure. More meaningful within- and between-infant comparisons of peripheral airway function may be obtained by calculating forced expiratory flows at a fixed interval (e.g., 3 ml/kg) above EEV, rather than at the FRC that is operational at the time of measurement.
MK615, a prospective anti-proliferative agent, enhances CD4/CD8 ratio after exposure to irradiation

Purpose: Recently, it was found that MK615 possessed an anti-proliferative ability on treated cancer cells as a consequence of triterpenoid compounds. It is well known that radiation affects cellular-mediated immunity in cancer patients who are treated with radiotherapy. Similarly, the ability of triterpenoid compounds to enhance the cellular-mediated immunity has been observed. Therefore, in the present study, we attempted to investigate the effect of MK615 on both cancer cells and cellular-mediated immunity after irradiation. Materials and methods: After mice were inoculated with mouse mammary carcinoma (FM3A) cells, they were categorised as follows: Non-treated, irradiated with 5 Gy, treated with 660 μg/day MK615 (MK615, an extract from the Japanese apricot) and lastly exposed to both irradiation and MK615. Afterward, mice were sacrificed and spleens were utilised to measure the cluster of differentiation 4 and 8 (CD4 and CD8) using flowcytometry. Simultaneously, in vitro study, human alveolar basal epithelial carcinomic (A549), mouse lymphoma (EL4) and FM3A cell lines were examined. Growth inhibition was assessed via colony, cell viability and apoptotic assays. Results: The median survival was in favour of the MK615-treated group (26.1 ± 1.9 days) compared with non-treated group (22.3 ± 2.3 days) (p < 0.05). Approximately 50% reduction of the CD4/CD8 ratio was observed following the exposure to irradiation alone. However, this ratio was comparable between the non-treated and both MK615-treated groups. Additionally, only the dual treatment was associated with tumour volume reduction. In contrast, in vitro study showed that MK615 had no significant (p ≥ 0.1) effect on the selected cell lines with or without irradiation. Conclusion: MK615 has a potential to reduce tumour volume and may normalise cellular-mediated immunity level following the exposure to irradiation.
Ward: An Exploratory Study of an Affective Sociotechnical Framework for Addressing Medical Errors

Affective states influence judgment, motivation, risk perceptions, and sense of well-being. Clinicians constantly struggle with negative affective states due to the nature of their work. We propose our framework, the Wearable Avatar Risk Display (WARD), to investigate medical errors from the perspective of affective states' influence. WARD is a dynamic and multimodal mobile affective system that aims for delivering information meaningfully and humanely to clinicians according to their affective states. WARD originates from sociotechnical systems theory and serves two purposes: (1) To guide the development of a test bed of avatars with lifelike behaviors (affective avatars) and (2) To investigate the interplay of clinicians' affects, risk perceptions, and decision-making ability in a healthcare setting. We recently piloted a small exploratory study using Mood Induction Procedures (MIPs), Iowa Gambling Task, and affective avatars to investigate participants' decision-making pattern. Our results indicated that participants did not benefit from our avatars currently. However, correlations analysis and suggestions from participants revealed that there is potential for affective avatars in critical or emergency situations.
Practically Useful: What the Rosetta Protein Modeling Suite Can Do for You

The objective of this review is to enable researchers to use the software package Rosetta for biochemical and biomedicinal studies. We provide a brief review of the six most frequent research problems tackled with Rosetta. For each of these six tasks, we provide a tutorial that illustrates a basic Rosetta protocol. The Rosetta method was originally developed for de novo protein structure prediction and is regularly one of the best performers in the community-wide biennial Critical Assessment of Structure Prediction. Predictions for protein domains with fewer than 125 amino acids regularly have a backbone root-mean-square deviation of better than 5.0 Å. More impressively, there are several cases in which Rosetta has been used to predict structures with atomic level accuracy better than 2.5 Å. In addition to de novo structure prediction, Rosetta also has methods for molecular docking, homology modeling, determining protein structures from sparse experimental NMR or EPR data, and protein design. Rosetta has been used to accurately design a novel protein structure, predict the structure of protein−protein complexes, design altered specificity protein−protein and protein−DNA interactions, and stabilize proteins and protein complexes. Most recently, Rosetta has been used to solve the X-ray crystallographic phase problem.
Cost-Sensitive Structured SVM for Multi-category Domain Adaptation

Domain adaptation addresses the problem of accuracy drop that a classifier may suffer when the training data (source domain) and the testing data (target domain) are drawn from different distributions. In this work, we focus on domain adaptation for structured SVM (SSVM). We propose a cost-sensitive domain adaptation method for SSVM, namely COSS-SSVM. In particular, during the re-training of an adapted classifier based on target and source data, the idea that we explore consists in introducing a non-zero cost even for correctly classified source domain samples. Eventually, we aim to learn a more target-oriented classifier by not rewarding (zero loss) properly classified source-domain training samples. We assess the effectiveness of COSS-SSVM on multi-category object recognition.
Plasma vanadium concentration in manic-depressive illness

SYNOPSIS 133 samples of plasma taken from 9 normal control and 8 manic-depressive subjects were analysed for vanadium by atomic absorption spectrometry. Mean plasma vanadium concentrations were 0·15 μM in normal control, 0·34 μM in manic and 0·28 μM in depressed subjects, and 0·23 μM in manic-depressive subjects after recovery. The differences between normal subjects and manic and recovered subjects were statistically significant. Significant negative correlations were found between plasma vanadium concentration and the ratio of Na–K–Mg ATPase to Mg–ATPase in 2 manic-depressive subjects, but not in normal subjects. The results suggest that vanadium may be a cause of the variations in Na–K–Mg ATPase and sodium pump activity which are associated with manic-depressive illness.
Temperature Increase Negatively Affects the Fatty Acid Bioconversion Capacity of Rainbow Trout (Oncorhynchus mykiss) Fed a Linseed Oil-Based Diet

Aquaculture is meant to provide fish rich in omega-3 long chain polyunsaturated fatty acids (n-3 LC-PUFA). This objective must be reached despite (1) the necessity to replace the finite and limited fish oil in feed production and (2) the increased temperature of the supply water induced by the global warming. The objective of the present paper was to determine to what extent increased water temperature influences the fatty acid bioconversion capacity of rainbow trout (Oncorhynchus mykiss) fed a plant-derived diet. Fish were fed two diets formulated with fish oil (FO) or linseed oil (LO) as only added lipid source at the optimal water temperature of 15°C or at the increased water temperature of 19°C for 60 days. We observed that a temperature increase close to the upper limit of the species temperature tolerance range negatively affected the feed efficiency of rainbow trout fed LO despite a higher feed intake. The negative impact of increased water temperature on fatty acid bioconversion capacity appeared also to be quite clear considering the reduced expression of fatty acid desaturase 2 in liver and intestine and the reduced Δ6 desaturase enzymatic activity in intestinal microsomes. The present results also highlighted a negative impact of increased temperature on the apparent in vivo enzymatic activity of Δ5 and Δ6 desaturases of fish fed LO. Interestingly, this last parameter appeared less affected than those mentioned above. This study highlights that the increased temperature that rainbow trout may face due to global warming could reduce their fatty acid bioconversion capacity. The unavoidable replacement of finite fish oil by more sustainable, readily available and economically viable alternative lipid sources in aquaculture feeds should take this undeniable environmental issue on aquaculture productivity into account.
Pyrolysis process for scrap tires

A process for disposal of scrap tires was developed in which the shredded tires are pyrolyzed in an indirectly heated rotary kiln at 600/sup 0/C to produce mainly fuel oil and char. The operating temperature was determined as the temperature which produces the char that gives carbon black with optimum properties as reinforcing filler for rubber. The oil is condensed in two stages. The gas is used with light oil to heat the kilns. Cost estimates for 4000-14,000 ton/yr plants, balanced against credit for recovered materials and the cost of collecting and transporting scrap tires show an optimum plant size of 7000 tons/yr. A demonstration plant of that size is under construction.
Attributes of God: Conceptual Foundations of a Foundational Belief

Anthropomorphism, or the attribution of human properties to nonhuman entities, is often posited as an explanation for the origin and nature of God concepts, but it remains unclear which human properties we tend to attribute to God and under what conditions. In three studies, participants decided whether two types of human properties-psychological (mind-dependent) properties and physiological (body-dependent) properties-could or could not be attributed to God. In Study 1 (n = 1,525), participants made significantly more psychological attributions than physiological attributions, and the frequency of those attributions was correlated both with participants' religiosity and with their attribution of abstract, theological properties. In Study 2 (n = 99) and Study 3 (n = 138), participants not only showed the same preference for psychological properties but were also significantly faster, more consistent, and more confident when attributing psychological properties to God than when attributing physiological properties. And when denying properties to God, they showed the reverse pattern-that is, they were slower, less consistent, and less confident when denying psychological properties than when denying physiological properties. These patterns were observed both in a predominantly Christian population (Study 2) and a predominantly Hindu population (Study 3). Overall, we argue that God is conceptualized not as a person in general but as an agent in particular, attributed a mind by default but attributed a body only upon further consideration.
Is 21st Century Neuroscience Too Focussed on the Rat/Mouse Model of Brain Function and Dysfunction?

Studies in the basic neurosciences are heavily reliant upon rat and mouse models. The brain is one of the most distinguishing features of the human species, but is enough being done to fully understand the evolution of the human brain and brain diversity in general? Without a clear understanding of the evolution of the nervous system we may be investing a great deal of effort into some limited specific animal models that may prove to be erroneous in terms of the overall usefulness in clinically applied research. Here we present an analysis that demonstrates that 75% of our research efforts are directed to the rat, mouse and human brain, or 0.0001% of the nervous systems on the planet. This extreme bias in research trends may provide a limited scope in the discovery of novel aspects of brain structure and function that would be of importance in understanding both the evolution of the human brain and in selecting appropriate animal models for use in clinically related research. We offer examples both from the historical and recent literature indicating the usefulness of comparative neurobiological investigation in elucidating both normal and abnormal structure and function of the brain.
Traumatic Alterations in GABA Signaling Disrupt Hippocampal Network Activity in the Developing Brain

Severe head trauma causes widespread neuronal shear injuries and acute seizures. Shearing of neural processes might contribute to seizures by disrupting the transmembrane ion gradients that subserve normal synaptic signaling. To test this possibility, we investigated changes in intracellular chloride concentration ([Cl−]i) associated with the widespread neural shear injury induced during preparation of acute brain slices. In hippocampal slices and intact hippocampal preparations from immature CLM-1 mice, increases in [Cl−]i correlated with disruption of neural processes and biomarkers of cell injury. Traumatized neurons with higher [Cl−]i demonstrated excitatory GABA signaling, remained synaptically active, and facilitated network activity as assayed by the frequency of extracellular action potentials and spontaneous network-driven oscillations. These data support a more inhibitory role for GABA in the unperturbed immature brain, demonstrate the utility of the acute brain slice preparation for the study of the consequences of trauma, and provide potential mechanisms for both GABA-mediated excitatory network events in the slice preparation and early post-traumatic seizures.