Miracle-dz/UniFAR-FTUs huggingface dataset:
Gene-Environment Interactions and Familial Relative Risks

Objectives: Parents share genes and environmental exposures with their offspring. Spouses are often unrelated and their excess of genetic sharing is low, but the similar lifestyles of spouses regarding, for example, tobacco consumption may also result in a familial clustering of disease. This study investigates the influence of gene-environment interactions on the relative risks of disease for the offspring and the spouses of affected individuals. Methods: Theoretical models were developed to explore the dependence of familial relative risks on environmental parameters (exposure frequency, relative risk of disease for exposed versus unexposed individuals, extent of environmental sharing), on genetic parameters (allele frequency, genotype relative risk and mode of inheritance), on the number of descendants in exposed versus unexposed individuals, and on the model of gene-environment interaction. Lung cancer was used as an example of a complex disease with smoking as a known risk factor. Results: The parent-offspring and the spouse-spouse relative risks of disease varied widely in the strength of the environmental and genetic components and their degree of interaction. The familial relative risk of lung cancer decreased with increasing smoking prevalence. The relationship between exposure frequency and relative risk was markedly different when genes and environment had similar effects on disease susceptibility. Conclusions: Estimates of the relative risk of disease for varying exposure frequencies may help to assess the relevance of genetic effects in disease etiology. In particular, a positive association between offspring relative risk and exposure frequency may be indicative of genes interacting with environmental factors of similar effect sizes, with the corresponding implications for gene identification studies.
M proteins of group G streptococci: mechanisms of resistance to phagocytosis.

Group G streptococci that express M protein and resist phagocytosis in human blood (virulent strains) were compared with strains of groups G and A that are readily phagocytosed (avirulent). Virulent group G streptococci were less effective (P < .05) as activators of the alternative complement pathway (ACP) than were avirulent streptococci. In immunofluorescence studies, C3 bound more avidly to avirulent than to virulent group G streptococci. Resistance of virulent group G strains to ACP opsonization and to phagocytosis was markedly diminished by removal with pepsin of the type-specific portion of the M molecule. Preincubation with fibrinogen did not diminish ACP activation or C3 binding by virulent group G and A streptococci but did exert an antiphagocytic effect. Given the similarity of M proteins of groups G and A in structure and function, other microbial constituents are likely responsible for differences in the spectra of illnesses attributable to the two serogroups.
Examples, rules, and strategies in the control of dynamic systems.

Two main types of knowledge are considered relevant to successful control of dynamic systems: input-output knowledge (I-O-knowledge), which represents specific input values together with the corresponding output values, and structural knowledge, defined as general knowledge about the variables of a system and their causal relations. While I-O-knowledge has proven important for the control of small systems, structural knowledge is expected to enhance performance when dealing with more complex systems. In an experiment, structural knowledge about a complex system was manipulated. Although the experimental group had better structural knowledge, the control group was equally successful in reaching new goals. That seems to contradict other studies where effects of structural knowledge on performance have been found. To resolve these contradictions, the consideration of a third type of knowledge strategic knowledge is suggested. The postulated effects of different levels of structural and strategic knowledge are explored with a computational model. The three knowledge types are used to interpret the variety of findings within a unitary conceptual framework.
Development of Process Visualisation Systems An Object-Oriented Approach

In this paper a process visualisation development system and its associated development methodology are presented. This methodology is optimised to systems that have complex structure and are built of large number of components belonging to relatively small number of types. In order to handle the complexity, the input requirements of the method is as close to the ”native language” of the application as possible. The elements of the ”native language” are assumed to include engineering drawings and manuals describing the operation of component types the system is built of. Graphics techniques are used to supply the engineering drawings into the development system while not only the required visual appearance is described but the structure of the underlying system is also defined. The elements of engineering drawings are dynamized to animate the graphics presentation to reflect the current state of the monitored system. Component manuals are transformed to interface and state definitions from which a code generator generates a C++ class for each component type. This C++ class must be tuned to reflect the operation of a single component type. From these definitions the development system automatically builds up the complete visualisation program, providing easy and fast application development.
Host immune responses are necessary for density dependence in nematode infections

Nematode infections are subject to density-dependent effects on their establishment, survivorship and fecundity within a host. These effects act to regulate and stabilize the size of nematode populations. Understanding how these density-dependent effects occur is important to guide the development of control strategies against parasitic nematodes and the diseases that they cause. These density-dependent effects have been hypothesized to result from intraspecific competition between parasites for limited resources or from the action of host immune responses. However, no specific evidence exists to distinguish between these two hypotheses. We find that in nematode (Strongyloides ratti) infections, density-dependent effects on parasite establishment, survivorship and fecundity are mediated by the host immune response. These density-dependent effects are only observed late in primary infections and no density-dependent effects are observed in infections in immuno-compromised animals. We find no evidence for intraspecific competition between parasites in experimental infections over a range of doses that encompasses all that is observed in natural infections. We conclude that density-dependent effects due to the immune response will act to regulate S. ratti infections before competition for space or nutrients within the host gut ever occurs.
A note on computing a maximal planar subgraph using PQ-trees

The problem of computing a maximal planar subgraph of a nonplanar graph has been deeply investigated over the last 20 years. Several attempts have been tried to solve the problem with the help of PQ-trees. The latest attempt has been reported by Jayakumar et al. In this paper we show that the algorithm presented by Jayakumar et al. is not correct. We show that it does not necessarily compute a maximal planar subgraph and we note that the same holds for a modified version of the algorithm presented by Kant. Our conclusions most likely suggest not to use PQ-trees at all for this specific problem.
Cloning of Glycerophosphocholine Acyltransferase (GPCAT) from Fungi and Plants

Glycero-3-phosphocholine (GPC), the product of the complete deacylation of phosphatidylcholine (PC), was long thought to not be a substrate for reacylation. However, it was recently shown that cell-free extracts from yeast and plants could acylate GPC with acyl groups from acyl-CoA. By screening enzyme activities of extracts derived from a yeast knock-out collection, we were able to identify and clone the yeast gene (GPC1) encoding the enzyme, named glycerophosphocholine acyltransferase (GPCAT). By homology search, we also identified and cloned GPCAT genes from three plant species. All enzymes utilize acyl-CoA to acylate GPC, forming lyso-PC, and they show broad acyl specificities in both yeast and plants. In addition to acyl-CoA, GPCAT efficiently utilizes LPC and lysophosphatidylethanolamine as acyl donors in the acylation of GPC. GPCAT homologues were found in the major eukaryotic organism groups but not in prokaryotes or chordates. The enzyme forms its own protein family and does not contain any of the acyl binding or lipase motifs that are present in other studied acyltransferases and transacylases. In vivo labeling studies confirm a role for Gpc1p in PC biosynthesis in yeast. It is postulated that GPCATs contribute to the maintenance of PC homeostasis and also have specific functions in acyl editing of PC (e.g. in transferring acyl groups modified at the sn-2 position of PC to the sn-1 position of this molecule in plant cells).
SRY-Box Containing Gene 17 Regulates the Wnt/β-Catenin Signaling Pathway in Oligodendrocyte Progenitor Cells

The SRY-box (Sox) transcription factors regulate oligodendrocyte differentiation, but their signaling targets are largely unknown. We have identified a major signal transduction pathway regulated by Sox containing gene 17 (Sox17) in the oligodendrocyte lineage. Microarray analysis in oligodendrocyte progenitor cells (OPCs) after Sox17 attenuation revealed upregulated genes associated with cell cycle control and activation of the Wingless and integration site (Wnt)/β-catenin pathway. Sox17 knockdown also increases the levels of cyclin D1, Axin2, and activated β-catenin. In OPCs, the expression pattern of Sox17, cyclin D1, and secreted Frizzled-related protein-1 in the presence of platelet-derived growth factor (PDGF) was coordinately accelerated by addition of thyroid hormone, indicating differentiation-induced regulation of Sox17 targets. In developing white matter, decreased total β-catenin, activated β-catenin, and cyclin D1 levels coincided with the peak of Sox17 expression, and immunoprecipitates showed a developmentally regulated interaction among Sox17, T-cell transcription factor 4, and β-catenin proteins. In OPCs, PDGF stimulated phosphorylation of glycogen synthase 3β and the Wnt coreceptor LRP6, and enhanced β-catenin-dependent gene expression. Sox17 overexpression inhibited PDGF-induced TOPFLASH and cyclin D1 promoter activity, and decreased endogenous cyclin D1, activated β-catenin, as well as total β-catenin levels. Recombinant Sox17 prevented Wnt3a from repressing myelin protein expression, and inhibition of Sox17-mediated proteasomal degradation of β-catenin blocked myelin protein induction. These results indicate that Sox17 suppresses cyclin D1 expression and cell proliferation by directly antagonizing β-catenin, whose activity in OPCs is stimulated not only by Wnt3a, but also by PDGF. Our identification of downstream targets of Sox17 thus defines signaling pathways and molecular mechanisms in OPCs that are regulated by Sox17 during cell cycle exit and the onset of differentiation in oligodendrocyte development.
Non-Fatal Gunshot Trauma Among A Sample of Adolescents in Djibouti

Firearm trauma is the second most common cause of serious injury among adolescents in the Republic of Djibouti. The aim of this study was to explore the sociodemographic correlates of serious injury and non-fatal gunshot trauma among adolescents in Djibouti. Using multinomial logistic regression, we compared a sample of adolescents (N = 1,711) who self-reported a non-firearm-related serious injury (n = 587) and those who reported a firearm-related injury (n = 101) with non-injured participants (n = 1,023) during a 12-month recall period. Analyses targeted demographic, behavioral, social, mental health, and family factors. After adjusting for covariates, participants reporting a non-firearm-related serious injury were more likely to report having been involved in physical fights (relative risk ratio [RRR] = 145; confidence interval [CI] = [1.04, 2.02), being bullied (RRR = 2.83; CI = [2.24, 3.56]), feeling lonely (RRR = 1.48; CI = [1.11, 1.96]), having signs of depression (RRR = 1.27; CI = [1.02, 1.58]), and be truant from school (RRR = 1.68; CI = [1.25, 2.28]). Those who reported a gunshot injury recorded being bullied (RRR = 2.83; CI = [1.77, 4.53]) and physically attacked at higher rates (RRR = 1.78; CI = [1.09, 2.89]). Serious injuries, whether firearm related or not, are important threats to adolescent health in Djibouti with potentially serious health-related correlates. More research, particularly multilevel designs, are needed to explain context-relevant factors associated with serious trauma in Djibouti.
A Holistic Approach to ZigBee Performance Enhancement for Home Automation Networks

Wireless home automation networks are gaining importance for smart homes. In this ambit, ZigBee networks play an important role. The ZigBee specification defines a default set of protocol stack parameters and mechanisms that is further refined by the ZigBee Home Automation application profile. In a holistic approach, we analyze how the network performance is affected with the tuning of parameters and mechanisms across multiple layers of the ZigBee protocol stack and investigate possible performance gains by implementing and testing alternative settings. The evaluations are carried out in a testbed of 57 TelosB motes. The results show that considerable performance improvements can be achieved by using alternative protocol stack configurations. From these results, we derive two improved protocol stack configurations for ZigBee wireless home automation networks that are validated in various network scenarios. In our experiments, these improved configurations yield a relative packet delivery ratio increase of up to 33.6%, a delay decrease of up to 66.6% and an improvement of the energy efficiency for battery powered devices of up to 48.7%, obtainable without incurring any overhead to the network.
Voice conversion from non-parallel corpora using variational auto-encoder

We propose a flexible framework for spectral conversion (SC) that facilitates training with unaligned corpora. Many SC frameworks require parallel corpora, phonetic alignments, or explicit frame-wise correspondence for learning conversion functions or for synthesizing a target spectrum with the aid of alignments. However, these requirements gravely limit the scope of practical applications of SC due to scarcity or even unavailability of parallel corpora. We propose an SC framework based on variational auto-encoder which enables us to exploit non-parallel corpora. The framework comprises an encoder that learns speaker-independent phonetic representations and a decoder that learns to reconstruct the designated speaker. It removes the requirement of parallel corpora or phonetic alignments to train a spectral conversion system. We report objective and subjective evaluations to validate our proposed method and compare it to SC methods that have access to aligned corpora.
N-Methyl-D-Aspartic Acid Receptor Activation Downregulates Expression of d Subunit-Containing GABAA Receptors in Cultured Hippocampal Neurons s

Neurosteroids are endogenous allosteric modulators of GABAA receptors (GABARs), and they enhance GABAR-mediated inhibition. However, GABARs expressed on hippocampal dentate granule neurons of epileptic animals are modified such that their neurosteroid sensitivity is reduced and d subunit expression is diminished. We explored the molecular mechanisms triggering this GABAR plasticity. In the cultured hippocampal neurons, treatment with N-methyl-D-aspartic acid (NMDA) (10 mM) for 48 hours reduced the surface expression of d and a4 subunits but did not increase the expression of g2 subunits. The tonic current recorded from neurons in NMDAtreated cultures was reduced, and its neurosteroid modulation was also diminished. In contrast, synaptic inhibition and its modulation by neurosteroids were preserved in these neurons. The time course of NMDA’s effects on surface and total d subunit expression was distinct; shorter (6 hours) treatment decreased surface expression, whereas longer treatment reduced both surface and total expression. Dl-2-amino-5phosphonopentanoic acid (APV) blocked NMDA’s effects on d subunit expression. Chelation of calcium ions by 1,2-bis (2-aminophenoxy)ethane-N,N,N’,N’-tetra-acetic acid tetrakis (acetoxymethyl ester) (BAPTA-AM) or blockade of extracellular signal-regulated kinase (ERK) 1/2 activation by UO126 (1,4diamino-2,3-dicyano-1,4-bis[2-aminophenylthio] butadiene) also prevented the effects of NMDA. Thus, prolonged activation of NMDA receptors in hippocampal neurons reduced GABAR d subunit expression through Ca entry and at least in part by ERK1/2 activation.
Neuron-Specific Expression of Therapeutic Proteins: Evaluation of Different Cellular Promoters in Recombinant Adenoviral Vectors

In order to achieve neuron-restricted expression of antiapoptotic proteins, cellular promoters were investigated for their expression profiles in the context of adenoviral vectors. Both the synapsin 1 gene and the tubulin alpha1 gene promoters were strictly neuron specific in cocultures of primary neurons with their essential feeder cells. The neuron-specific enolase gene promoter exhibited only weak activity in cultured hippocampal neurons and was not neuron specific in preparations of cerebellar granule cells. By attaining virtually 100% transduction efficiency we were able to generate "quasi-transgenic" primary neuron cultures using both differentiated and completely undifferentiated hippocampal neurons. In a functional assay, we used the synapsin promoter to evaluate the effect of Bcl-X(L) overexpression on potassium-withdrawal-induced apoptosis of cerebellar granule neurons. We found nearly complete inhibition of caspase-9 and -3 activation and apoptosis, indicating a major role for mitochondrial pathways in this paradigm of neuronal cell death. The excellent suitability of the synapsin promoter as a strong panneuronal promoter was further demonstrated by its restricted neuronal activity in various brain regions of adult rats in vivo.
Robust control for seeker scan loop using sliding modes

This paper presents robust control of seeker system used in missile target scanning and tracking. The mathematical model for seeker system is considered. A sliding mode controller (SMC) is designed to compensate uncertain coupling effect and external disturbances during scan phase. The model of the plant is based on first-principle method. The dynamic equations of motion are formulated with the assumption that the seeker system is a rigid body with no mass imbalance. These equations of motion are considered in cascade with DC motor equations which provides the actuating torque to the gimbal axes of the seeker system. The performance of the controller is validated in simulations.
Sumoylation of the THO complex regulates the biogenesis of a subset of mRNPs

Assembly of messenger ribonucleoparticles (mRNPs) is a pivotal step in gene expression, but only a few molecular mechanisms contributing to its regulation have been described. Here, through a comprehensive proteomic survey of mRNP assembly, we demonstrate that the SUMO pathway specifically controls the association of the THO complex with mRNPs. We further show that the THO complex, a key player in the interplay between gene expression, mRNA export and genetic stability, is sumoylated on its Hpr1 subunit and that this modification regulates its association with mRNPs. Altered recruitment of the THO complex onto mRNPs in sumoylation-defective mutants does not affect bulk mRNA export or genetic stability, but impairs the expression of acidic stress-induced genes and, consistently, compromises viability in acidic stress conditions. Importantly, inactivation of the nuclear exosome suppresses the phenotypes of the hpr1 non-sumoylatable mutant, showing that SUMO-dependent mRNP assembly is critical to allow a specific subset of mRNPs to escape degradation. This article thus provides the first example of a SUMO-dependent mRNP-assembly event allowing a refined tuning of gene expression, in particular under specific stress conditions.
The impact of pre-injury controlled substance use on clinical outcomes after trauma

BACKGROUND A disproportionately high percentage of trauma patients use controlled substances, and they often co-ingest multiple drugs. Previous studies have evaluated the effect of individual drugs on clinical outcomes after trauma. However, the impact of all drugs included in a comprehensive screening panel has not yet been compared in a single cohort of patients. METHODS All trauma patients who underwent urine drug screens after admission to the LAC + USC Medical Center (January 2008–June 2015) were identified retrospectively. Univariable and multivariable regression analyses determined the significance of all drugs tested in the hospital’s standard toxicology screen (amphetamine, barbiturate, benzodiazepine, cocaine, opiate, phencyclidine) on clinical outcomes. RESULTS A total of 10,166 patients who underwent admission toxicology screening were identified. Although 5,621 patients had completely negative screens, 3,292 patients tested positive for only one drug and 1,253 patients tested for multiple drugs. Univariable analysis indicated that patients who tested positive for multiple drugs had higher rates of operative intervention (p < 0.001), longer hospital stay (p < 0.001), and longer ICU stays (p < 0.001). Multivariable analysis indicated that phencyclidine was associated with higher rates of mortality (p = 0.025) whereas amphetamine was associated with lower rates of mortality (p = 0.012). Higher rates of operative intervention were observed in patients testing positive for amphetamine (p < 0.001), benzodiazepine (p < 0.001), or opiate (p < 0.001). Benzodiazepine use was associated with higher rates of mechanical ventilation (p < 0.001), but use of amphetamines (p = 0.021) or opiates (p < 0.001) was associated with lower rates. CONCLUSIONS Pre-injury use of amphetamine, barbiturate, benzodiazepine, cocaine, opiate, and PCP has a significant and variable impact on clinical outcomes after trauma. Comparing the relative effect of each drug class can help clinicians risk-stratify all trauma patients, including those who test positive for multiple substances. LEVEL OF EVIDENCE Epidemiologic study, level III.
Lossless compression of color mosaic images

We present a low complexity algorithm for lossless compression of color mosaic images generated by a Bayer CCD color filter array. This algorithm is based on an interesting use of the integer wavelet transform followed by a fast adaptive context-based Golomb-Rice coding. The lossless compression performance of the proposed algorithm is apparently the best reported in the literature so far for color mosaic images.