Miracle-dz/UniFAR-FTUs huggingface dataset:
Clustering HLA Class I Superfamilies Using Structural Interaction Patterns

Human leukocyte antigen (HLA) class I molecules are critical components of the cell-mediated immune system that bind and present intracellular antigenic peptides to CD8+ T cell receptors. To understand the interaction mechanism underlying human leukocyte antigen (HLA) class I specificity in detail, we studied the structural interaction characteristics of 16,393 nonameric peptides binding to 58 HLA-A and -B molecules. Our analysis showed for the first time that HLA-peptide intermolecular bonding patterns vary among different alleles and may be grouped in a superfamily dependent manner. Through the use of these HLA class I ‘fingerprints’, a high resolution HLA class I superfamily classification schema was developed. This classification is capable of separating HLA alleles into well resolved, non-overlapping clusters, which is consistent with known HLA superfamily definitions. Such structural interaction approach serves as an excellent alternative to the traditional methods of HLA superfamily definitions that use peptide binding motifs or receptor information, and will help identify appropriate antigens suitable for broad-based subunit vaccine design.
Personalized Risk Scoring for Critical Care Prognosis Using Mixtures of Gaussian Processes

Objective: In this paper, we develop a personalized real-time risk scoring algorithm that provides timely and granular assessments for the clinical acuity of ward patients based on their (temporal) lab tests and vital signs; the proposed risk scoring system ensures timely intensive care unit admissions for clinically deteriorating patients. Methods: The risk scoring system is based on the idea of sequential hypothesis testing under an uncertain time horizon. The system learns a set of latent patient subtypes from the offline electronic health record data, and trains a mixture of Gaussian Process experts, where each expert models the physiological data streams associated with a specific patient subtype. Transfer learning techniques are used to learn the relationship between a patient's latent subtype and her static admission information (e.g., age, gender, transfer status, ICD-9 codes, etc). Results: Experiments conducted on data from a heterogeneous cohort of 6321 patients admitted to Ronald Reagan UCLA medical center show that our score significantly outperforms the currently deployed risk scores, such as the Rothman index, MEWS, APACHE, and SOFA scores, in terms of timeliness, true positive rate, and positive predictive value. Conclusion: Our results reflect the importance of adopting the concepts of personalized medicine in critical care settings; significant accuracy and timeliness gains can be achieved by accounting for the patients’ heterogeneity. Significance: The proposed risk scoring methodology can confer huge clinical and social benefits on a massive number of critically ill inpatients who exhibit adverse outcomes including, but not limited to, cardiac arrests, respiratory arrests, and septic shocks.
Riesz basis property of a second-order hyperbolic system with collocated scalar input-output

The closed-loop form of a second-order hyperbolic system with scalar collocated sensor/actuator is considered. The Riesz basis property of the system is verified for diagonal semigroups based on an abstract result of one rank perturbation of discrete-type operators in Hilbert spaces. A simplified proof for the abstract result is presented.
Polarization approximations for the macroscopic elastic constants of transversely isotropic multicomponent unidirectional fiber composites

The multicomponent transversely isotropic fiber composites, with unidirectional cylindrical fibers made from different component materials and embedded in a continuous binding matrix, are considered. Hashin–Shtrikman-type polarization trial fields developed earlier by us to bound effective moduli of composites are used to construct polarization approximations for four from the five effective elastic constants of the multicomponent composites, except the longitudinal Young’s modulus, for which the classical volume-weighted-average approximation appears sufficiently accurate and general. The approximations contain certain free parameters. Those parameters can be determined from dilute solutions for circular inclusions, which yield results coincided with Maxwell and Mori–Tanaka approximations in the case, or from the reference effective moduli at some finite volume proportions of the components numerically or experimentally. The simple polarization approximations obey Hashin–Shtrikman bounds over all volume proportions of the components and agree well with numerical results on benchmark models.
An efficient INS/GPS impulse response model for bridging GPS outages

The integration of Inertial Navigation System (INS) and Global Positioning System (GPS) architectures can be achieved through the use of many time-domain filters such as, extended Kalman, unscented Kalman, divided difference, and particle filters. The main objective of these filters is to achieve precise fusion of the data from GPS and INS to provide INS-only navigation solution during GPS outages. The prediction mode performance of all state-of-the-art time-domain filters is poor with significant drift in the INS-only solution. In this paper, a new frequency-domain dynamic response method is proposed to model the INS/GPS system. The input to this dynamic system is the INS-only solution and the output is the INS/GPS integration solution that help derive the transfer function. The discrete Inverse Least Squares Frequency Transform (ILSFT) of the transfer function is applied to estimate the impulse response of the INS/GPS system. It is shown that the long-term motion dynamics are recovered by 72%, 42%, 75%, and 40% for north velocities, east velocities, north positions, and east positions respectively when compared with INS-only solution (prediction mode of the INS/GPS filter).
Infection of human intestinal epithelial cells by invasive bacteria activates NF-κB and increases ICAM-1 expression through NOD1

Background/Aims Nucleotide-binding oligomerization domain 1 (NOD1) is required for primary intestinal epithelial cells (IECs) to respond to natural mucopeptides secreted by gram-negative bacteria. Infection of human IECs with invasive bacteria up-regulates intercellular adhesion molecule-1 (ICAM-1) expression. However, the role of NOD family members in host defense has been largely unknown. The aim of this study was to determine whether there is a functional role for NOD1 in the up-regulation of ICAM-1 expression in invasive bacteria-infected IECs. Methods ICAM-1 mRNA expression was compared between controls, Caco-2 or HT29 cells transfected with an empty vector, and IECs stably transfected with a dominant-negative (DN) NOD1. Expression was compared using qualitative reverse transcription polymerase chain reaction (RT-PCR), real-time RT-PCR, and flow cytometry after infection with enteroinvasive Escherichia coli O29:NM or Shigella flexneri. Nuclear factor kB (NF-κB) activation was determined by electrophoretic mobility shift assays. Results DN NOD1 significantly inhibited the up-regulation of ICAM-1 expression in response to an enteroinvasive bacterial infection. The Caco-2 cells transfected with DN NOD1 manifested marked inhibition of NF-kB activation in response to E. coli O29:NM infection. Conclusions Signaling through NOD1 may play an essential role in neutrophil trafficking following infection with enteroinvasive bacteria.
Preparation and characterisation of calcium phosphate–hyaluronic acid nanocomposite bone cement

In this study, calcium phosphate cements (CPCs) were prepared by using hyaluronic acid (HA) solutions with two different molecular weights. The physical, physicochemical and structural properties of these cements were characterised and compared with those of conventional CPC as control group. Results revealed that the long setting time and the low compressive strength of the CPC could be improved drastically by using HA in the cement composition, in a molecular weight dependent manner. The HA polymer has also a promising effect on cement injectability, which is more considerable in high molecular weight HA. The X-ray diffraction patterns of set cements showed that, in both control group and HA containing cements, primary reactant components were completely converted to nanostructured apatite after soaking in simulated body fluid. This study suggests that calcium phosphate nanocomposite cement obtained by HA solution can be successfully used as injectable bone filler material.
Antidepressants and the risk of suicide, attempted suicide, and overall mortality in a nationwide cohort.

BACKGROUND It is unknown if antidepressant treatment is associated with either increased or decreased risk of suicide. OBJECTIVE To estimate the risk of suicide, attempted suicide, and overall mortality during antidepressant treatments in a real-life setting with high statistical power. DESIGN AND SETTING A cohort study in which all subjects without psychosis, hospitalized because of a suicide attempt from January 1, 1997, to December 31, 2003, in Finland, were followed up through a nationwide computerized database. PARTICIPANTS A total of 15 390 patients with a mean follow-up of 3.4 years. MAIN OUTCOME MEASURES The propensity score-adjusted relative risks (RRs) during monotherapy with the most frequently used antidepressants compared with no antidepressant treatment. RESULTS In the entire cohort, fluoxetine use was associated with the lowest risk (RR, 0.52; 95% confidence interval [CI], 0.30-0.93), and venlafaxine hydrochloride use with the highest risk (RR, 1.61; 95% CI, 1.01-2.57), of suicide. A substantially lower mortality was observed during selective serotonin reuptake inhibitor use (RR, 0.59; 95% CI, 0.49-0.71; P<.001), and this was attributable to a decrease in cardiovascular- and cerebrovascular-related deaths (RR, 0.42; 95% CI, 0.24-0.71; P=.001). Among subjects who had ever used any antidepressant, the current use of medication was associated with a markedly increased risk of attempted suicide (39%, P<.001), but also with a markedly decreased risk of completed suicide (-32%, P=.002) and mortality (-49%, P<.001), when compared with no current use of medication. The results for subjects aged 10 to 19 years were basically the same as those in the total population, except for an increased risk of death with paroxetine hydrochloride use (RR, 5.44; 95% CI, 2.15-13.70; P<.001). CONCLUSIONS Among suicidal subjects who had ever used antidepressants, the current use of any antidepressant was associated with a markedly increased risk of attempted suicide and, at the same time, with a markedly decreased risk of completed suicide and death. Lower mortality was attributable to a decrease in cardiovascular- and cerebrovascular-related deaths during selective serotonin reuptake inhibitor use.
Proliferating or interleukin 1-activated human vascular smooth muscle cells secrete copious interleukin 6.

The cells that make up blood vessel walls appear to participate actively in local immune and inflammatory responses, as well as in certain vascular diseases. We tested here whether smooth muscle cells (SMC) can produce the important inflammatory mediator IL6. Unstimulated SMC in vitro elaborated 5 X 10(3) pg recIL6/24h (i.e., biological activity equivalent to 5 X 10(3) pg recombinant IL6 (recIL6), as determined in B9-assay with a recIL6 standard). Several pathophysiologically relevant factors augmented IL6 release from SMC including 10 micrograms LPS/ml (10(4) pg recIL6), 10 ng tumor necrosis factor/ml (4 X 10(4) pg recIL6), and most notably 10 ng IL1/ml (greater than or equal to 3.2 X 10(5) pg recIL6). Production of IL6 activity corresponded to IL6 mRNA accumulation and de novo synthesis. SMC released newly synthesized IL6 rapidly, as little metabolically labeled material remained cell-associated. In supernatants of IL1-stimulated SMC, IL6 accounted for as much as 4% of the secreted proteins. In normal vessels SMC seldom divide, but SMC proliferation can occur in hypertension or during atherogenesis. We therefore tested the relationship between IL6 production and SMC proliferation in response to platelet-derived growth factor (PDGF) in vitro. Quiescent SMC released scant IL6 activity, whereas PDGF (1-100 ng/ml) produced concentration-dependent and coordinate enhancement of SMC proliferation and IL6 release (linear regression of growth vs. IL6 release yielded r greater than 0.9). IL6 itself neither stimulated nor inhibited SMC growth or IL6 production. Intact medial strips studied in short-term organoid culture produced large quantities of IL6, similar to the results obtained with cultured SMC. These findings illustrate a new function of vascular SMC by which these cells might participate in local immunoregulation and in the pathogenesis of various important vascular diseases as well as in inflammatory responses generally.
Coronavirus minus-strand RNA synthesis and effect of cycloheximide on coronavirus RNA synthesis

The temporal sequence of coronavirus plus-strand and minus-strand RNA synthesis was determined in 17CL1 cells infected with the A59 strain of mouse hepatitis virus (MHV). MHV-induced fusion was prevented by keeping the pH of the medium below pH 6.8. This had no effect on the MHV replication cycle, but gave 5- to 10-fold-greater titers of infectious virus and delayed the detachment of cells from the monolayer which permitted viral RNA synthesis to be studied conveniently until at least 10 h postinfection. Seven species of poly(A)-containing viral RNAs were synthesized at early and late times after infection, in nonequal but constant ratios. MHV minus-strand RNA synthesis was first detected at about 3 h after infection and was found exclusively in the viral replicative intermediates and was not detected in 60S single-stranded form in infected cells. Early in the replication cycle, from 45 to 65% of the [3H]uridine pulse-labeled RF core of purified MHV replicative intermediates was in minus-strand RNA. The rate of minus-strand synthesis peaked at 5 to 6 h postinfection and then declined to about 20% of the maximum rate. The addition of cycloheximide before 3 h postinfection prevented viral RNA synthesis, whereas the addition of cycloheximide after viral RNA synthesis had begun resulted in the inhibition of viral RNA synthesis. The synthesis of both genome and subgenomic mRNAs and of viral minus strands required continued protein synthesis, and minus-strand RNA synthesis was three- to fourfold more sensitive to inhibition by cycloheximide than was plus-strand synthesis.
Towards understanding balancing in exertion games

Playing exertion games with others can be engaging. However, players with different physical skill levels competing against each other can experience reduced engagement because they are either not challenged enough, or challenged too much. Balancing methods can address this; however, there is only limited understanding of balancing in exertion games. In this paper, we identify two distinct dimensional balancing techniques: "internal adjustment" and "external adjustment". We report results from a study where we measured player engagement after applying these adjustments to a digital table tennis game and the traditional table tennis game, finding two disengagement factors: "unexpected physical challenges" and "unacceptable competitive advantage". Based on these factors we derived a set of exertion game design considerations. We conclude that applying digital technology to a physical game can change the required skill level to play the game, and this can affect the impact of these adjustments on player engagement. These results enhances our understanding of balancing in exertion games, supporting the benefits of playing exertion games with others.
Portraits of cyclic pursuit

The study of cyclic pursuit as a means to collective behavior in nature and in artificial multi-agent systems is of current interest. Here we examine the nonlinear closed loop dynamics of planar cyclic pursuit based on the constant bearing (CB) strategy. We show that there exists a family of rectilinear relative equilibria that admit nearby periodic orbits in an appropriate low dimensional space found by methods of symmetry, reduction and constraint. We also demonstrate the existence of other families of rectilinear equilibria that exhibit attractivity or instability.
Alteration in Contractile Responses in Human Detrusor Smooth Muscle from Obstructed Bladders with Overactivity

Introduction: In this study, we aimed to evaluate changes in contractile responses under in vitro conditions in detrusor overactivity (DO) in patients with bladder outflow obstruction (BOO). Materials and Methods: Detrusor strips obtained during open prostatectomy procedure from 16 patients with BOO related to benign prostate hyperplasia were evaluated under in vitro conditions. Patients were assigned to two groups as patients with (DO) and without (no DO) DO. Four detrusor strips were prepared from each bladder in dimensions of 2 × 10 mm, and were suspended in organ bath. Responses to carbachol (10–8 to 10–3M), electrical field stimulation (EFS) (0.5–32 Hz), single-dose adenosine 5′-triphosphate (ATP) (10–3M) and KCl (120 mM) were recorded to evaluate the contractile responses. EFS responses were repeated in the presence of NG-nitro-L-arginine methyl ester (L-NAME; 10 µM) and L-NAME + indomethacin. All responses were expressed as mg tension developed per mg of bladder tissue. Data obtained were compared using independent t test and one-way ANOVA test. Values of p < 0.05 were accepted as statistically significant. Results: Of the 16 patients on whom open prostatectomy was performed because of BOO, 8 of the patients were determined as no DO and 8 as DO. There were no differences between groups regarding age and residual urine. We found statistically significant differences between groups regarding dimensions of prostate, maximum bladder capacity and maximum bladder pressure. In the comparison of cumulative dose of carbachol, it was seen that responses were higher in the DO group, but the differences were not statistically significant. In EFS application, contractile responses were found to increase significantly in the DO group. No changes were observed between groups for ATP and KCl. EFS responses were found to be significantly higher in presence of L-NAME + indomethacin in the no DO group; however, no difference was seen in the DO group. Conclusions: Detrusor contractile responses to EFS increased in patients with BOO in presence of overactivity. These changes in contractile responses are observed possibly as a result of deterioration in neuromodulation, rather than as a result of changes in purinergic or cholinergic receptor sensation or level. We suggest that a noncholinergic-nonpurinergic mechanism can have some effect on these changes.
Predicting reference points and associated uncertainty from life histories for risk and status assessment

To assess status of fish populations and the risks of overexploitation, management bodies compare fishing mortality rates and abundance estimates with reference points (RP). Generic, “data-poor” methods for estimating RP are garnering attention because they are faster and cheaper to implement than those based on extensive life history data. Yet data-poor RP are subject to many unquantified uncertainties. Here, we predict fishing mortality RP based on five levels of increasingly comprehensive data, to quantify effects of parameter and structural uncertainty on RP. Level I RP (least data) are estimated solely from species' maximum size and generic life history relationships, while level V RP (most data) are estimated from population-specific growth and maturity data. By estimating RP at all five data levels, for each of 12 North Sea populations, we demonstrate marked changes in the median RP values, and to a lesser extent uncertainty, when growth parameters come from data rather than life history relationships. As a simple rule, halving the median level I RP gives almost 90% probability that a level V median RP is not exceeded. RP and uncertainty were substantially affected by assumed gear selectivity; plausible changes in selectivity had a greater effect on RP than adding level V data. Calculations of RP using data for successive individual years from 1984 to 2014 showed that the median RP based on data for any given year would often fall outside the range of uncertainty for RP based on data from earlier or later years. This highlighted the benefits of frequent RP updates when suitable data are available. Our approach provides a quantitative method to inform risk-based management and decisions about acceptable targets for data collection and quality. Ultimately, however, the utility and extent of adoption of data-poor methods for estimating RP will depend on the risk aversion of managers.
Diurnal Variation of Pulse Wave Velocity Assessed Non-Invasively by Applanation Tonometry in Young Healthy Men

Purpose Pulse wave velocity (PWV) is at least partially controlled by vascular tone. Vascular tone and underlying physiological processes such as sympathetic activity, plasma catecholamin, and cortisol levels have been shown to follow diurnal variations. Materials and Methods Carotid-to-radial PWV was non-invasively assessed by applanation tonometry in 21 young (26.5 ± 2.3 years) healthy men at three different time points (8:00hr, 12:00hr, 17:00hr) during a day. Additionally, heart rate, systolic, diastolic and mean blood pressure, and radial pulse pressure were assessed at the same time points. Results The mean PWV was significantly higher at 8:00hr compared with the mean PWV assessed at later time points. No significant differences were found between mean PWV at 12:00hr and at 17:00hr. When PWV was corrected for blood pressure, the difference between values at 8:00hr and 12:00hr was no longer significant. Systolic, diastolic and mean blood pressure were significantly lower at 17:00hr compared with those at 8:00hr. Conclusion A small but significant diurnal variation of PWV was observed in young healthy men, which might have been caused at least partly by variations of blood pressure. This finding could be of value, when PWV is used in human research. Thus, in longitudinal investigations the measurements should be performed at similar time points in the course of a day, in order to obtain comparable data. Additionally, our observations ought to be of assistance to studies in which novel pharmacological compounds with activity on the vasculature are investigated.