Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of ritonavir on lipids and post-heparin lipase activities in normal subjects

BackgroundIntensive therapy of HIV infection with highly active antiretroviral therapy (HAART) dramatically reduces viral loads and improves immune status. Abnormalities of lipid levels, body fat distribution, and insulin resistance have been commonly reported after starting HAART. Whether the lipid abnormalities result from changes in metabolism after an improvement in HIV status or are partly attributable to the effects of protease inhibitor use is unknown. MethodsTwenty-one healthy volunteers participated in a 2 week double-blind, placebo-controlled study on the effect of the protease inhibitor ritonavir on total lipids, apolipoproteins, and post-heparin plasma lipase activities. ResultsThose taking ritonavir (n = 11) had significantly higher levels of plasma triglyceride, VLDL cholesterol, IDL cholesterol, apolipoprotein B, and lipoprotein (a) compared with placebo (n = 8). HDL cholesterol was lower with therapy as a result of a reduction in HDL3 cholesterol. Post-heparin lipoprotein lipase (LpL) activity did not change but hepatic lipase activity decreased 20% (P < 0.01) in those taking ritonavirrcompared with placebo. Although all lipoprotein subfractions became triglyceride enriched, most of the increase in triglyceride was in VLDL and not in IDL particles. ConclusionTreatment with ritonavir in the absence of HIV infection or changes in body composition results in hypertriglyceridemia that is apparently not mediated by impaired LpL activity or the defective removal of remnant lipoproteins, but could be caused by enhanced formation of VLDL. Long-term studies of patients with HIV infection receiving HAART will be necessary to determine the impact of these drugs and associated dyslipidemia on the risk of coronary artery disease.
Subunit Arrangement in GpsB, a Regulator of Cell Wall Biosynthesis

GpsB, a key regulator of cell division in Gram-positive bacteria, interacts with a key peptidoglycan synthase at the cell division septum, the penicillin binding protein PBP1 (a.k.a. PonA). Bacillus subtilis GpsB has been reported to interact with other components of the cell division machinery, including EzrA, MreC, and PrkC. In this study, we report an analysis of the arrangement of subunits in Listeria monocytogenes GpsB by small-angle X-ray scattering. The resulting model has an elongated shape with residues critical for interaction with PBP1 and the cell membrane clustered at one end of the molecule. Mutations that destabilize the hexameric assembly of the wild-type protein have a gpsB null phenotype, indicating that oligomerization is critical for the correct function of GpsB. We suggest a model in which a single GpsB hexamer can interact with multiple PBP1 molecules and can therefore influence the arrangement of PBP1 molecules within the cell division machinery, a dynamic multiprotein complex called the divisome, consistent with a role for GpsB in modulating the synthesis of the cell wall.
Treatable comorbid conditions and use of VA health care services among patients with dementia.

OBJECTIVE Although dementia is a progressive degenerative disease, treatable comorbid symptoms, such as pain, aggression, depression, and psychosis, occur among more than 60 percent of patients with dementia. Compared with age-matched controls, patients with dementia use 70 percent more health services and account for 50 percent more managed care costs. This prospective study examined the longitudinal relationship between use of health care services and treatable comorbid conditions among patients with dementia. METHODS Ninety-nine patient-caregiver dyads from the Michael E. DeBakey Veterans Affairs (VA) Medical Center in Houston, Texas, completed a one-time interview. Patients' VA records were reviewed one year later to examine the relationships between the study variables and three types of service use: inpatient medical stays, outpatient medical visits, and outpatient psychiatric visits. RESULTS Pain was positively associated with all types of service use. Depression was associated with outpatient psychiatric visits. Psychosis and aggression were not significantly associated with future use of health care services. CONCLUSIONS The results of this study confirm previous findings that pain and depression are associated with increased use of health care services. Although the other treatable comorbid symptoms, with the exception of pain, are associated with increased service use, their impact varies depending on the type of services provided. Interventions to improve the assessment and treatment of comorbid symptoms, especially pain, among patients with dementia may reduce service needs and thus reduce medical care costs.
Program Transformations for Asynchronous and Batched Query Submission

The performance of database/web-service backed applications can be significantly improved by asynchronous submission of queries/requests well ahead of the point where the results are needed, so that results are likely to have been fetched already when they are actually needed. However, manually writing applications to exploit asynchronous query submission is tedious and error-prone. In this paper, we address the issue of automatically transforming a program written assuming synchronous query submission, to one that exploits asynchronous query submission. Our program transformation method is based on data flow analysis and is framed as a set of transformation examples. Our examples can handle query executions within loops, unlike some of the earlier work in this area. We also present a novel approach that, at runtime, can combine multiple asynchronous requests into batches, thereby achieving the benefits of batching in addition to that of asynchronous submission. We have built a tool that implements our transformation techniques on Java programs that use JDBC calls; our tool can be extended to handle Web service calls. We have carried out a detailed experimental study on several real-life applications, which shows the effectiveness of the proposed rewrite techniques, both in terms of their applicability and the performance gains achieved.
Viscoelastic modeling of fiber preform compaction in vacuum infusion process

A woven fabric’s compaction was modeled by using five viscoelastic models – Maxwell, Kelvin-Voigt, Zener, Burgers, and Generalized Maxwell – to reveal the capabilities and limitations of the models. The model parameters were optimized by minimizing the deviation between the model results and experimental data collected in our previous material characterization study mimicking different compaction stages (loading, fiber settling, wetting, unloading, and fiber relaxation) that a fiber structure undergoes during vacuum infusion process. Although Burgers and Generalized Maxwell models have the highest performance due to their almost equal coefficient of determination values, they have diverse characteristics in terms of modeling different stages of compaction. Burgers model allowed modeling the permanent deformation in relaxation stage, but failed in modeling permanent deformation in settling stage. Generalized Maxwell model could do the opposite, i.e. failed in the former and could handle the latter. This study’s major contribution is a holistic numerical approach and its conclusions by modeling all stages of the vacuum infusion process instead of one stage at a time, and thus optimizing only one set of model parameters (constants of springs and dampers) since they do not change with time. The numerical results of different models were fit to the results of a specially designed compaction characterization experiments conducted in our complementary study.
In vitro activity of carumonam

The in vitro activities of carumonam and eight comparative antimicrobial agents were studied. MICs of carumonam were less than or equal to 0.5 microgram/ml for 91% of members of the family Enterobacteriaceae and less than or equal to 16 micrograms/ml for 88% of nonfermenters; gram-positive cocci and anaerobic bacteria were resistant. Combinations of carumonam with piperacillin, nafcillin, or clindamycin were usually indifferent, although synergy between carumonam and piperacillin was observed with 20 (13%) of 155 strains.
Inhibition of misleading heuristics as a core mechanism for typical cognitive development: evidence from behavioural and brain‐imaging studies

Cognitive development is generally conceived as incremental with knowledge of increasing complexity acquired throughout childhood and adolescence. However, several studies have now demonstrated not only that infants possess complex cognitive abilities but also that older children, adolescents, and adults tend to make systematic errors even in simple logical reasoning tasks. Therefore, one of the main issues for any theory of typical cognitive development is to provide an explanation of why at some age and in some contexts children, adolescents, and adults do not express a knowledge or cognitive principle that they already acquired when they were younger. In this review, we present convergent behavioural and neurocognitive evidence that cognitive development is more similar to a non‐linear dynamic system than to a linear, stage‐like system. In this theoretical framework, errors can emerge in problems similar to the ones infants or young children were succeeding when older children, adolescents, and adults rely on a misleading heuristic rather than on the correct logical algorithm to solve such problems. And the core mechanism for overcoming these errors is inhibitory control (i.e. the ability to inhibit the misleading heuristics). Therefore, typical cognitive development relies not only on the ability to acquire knowledge of incremental complexity but also to inhibit previously acquired knowledge.
LANGUAGE DEVELOPMENT

OVERVIEW 296 UNIVERSAL GRAMMAR 297 EMERGENTISM 299 Competition 300 Mechanisms Based on the Body 300 Neural Mechanisms 301 Social Mechanisms 301 Levels and Emergence 302 AUDITORY DEVELOPMENT 303 Distributional Learning 303 Sequential Learning 304 Words as Cues to Segmentation 304 ARTICULATORY DEVELOPMENT 304 Fixed Action Patterns 304 Babbling and Cortical Control 305 Circular Reactions 306 Phonotactic Processes 306 WORD LEARNING 307 Discovering Meanings 308 Initial Episodic Mapping 309 Undergeneralization, Generalization, and Overgeneralization 309 Flexible Learning 310 Children’s Agenda 311 Whorf Versus Humpty Dumpty 311 Learning From Syntactic Contexts 312 Words as Invitations to Learning 312 Competition and Mutual Exclusivity 312 Building Theories 313 Milestones in Vocabulary Growth 313 Models of Word Learning 314 SYNTAX 314 Item-Based Patterns 315 Learning Item-Based Patterns 316 Evidence for Item-Based Patterns 316 Feature-Based Patterns 317 Competition and the LPLA 318 Category-Based Patterns 318 MORPHOLOGY 319 Amalgams 319 MENTAL MODELS 320 Linguistic Relativity 320 Vygotskyan Approaches 321 Perspective Theory 322 Perspective and Gesture 322 CONVERSATION 323 LANGUAGE AND BRAIN 324 Components 325 Auditory Processing 325 Articulatory Processing 325 Lexical Processing 326 Morphological Processing 326 Syntactic Processing 326 Mental Model Processing 327 Conversation Processing 327 Declarative and Procedural Encoding 328 Errors in Connectivity 328 Timeframes 328 MULTILINGUAL DEVELOPMENT 329 Immigrants 330 A Critical Period for Language Learning? 330 SUMMARY 331 OPEN QUESTIONS 331 REFERENCES 331
Optimisation of Fluid Properties and Process Parameters for Batch Slot Die Coating of Dilute Polymer Systems

The effects of viscosity and surface tension are well documented in the case of roll-to-roll slot die systems. However their influence in combination with process parameters for batch scale coaters are less often discussed. Lack of coating uniformity attained using a bespoke slot die coater at the CPI National Printable Electronics Centre led to the requirement for an investigation to identify the sources of error. This project outlines a method used to determine the effects of material and process parameters on coating quality without the requirement for modification of equipment. It also describes the development of a series of versatile formulations containing polyethylene oxide that can be used to mimic similar polymer formulations for cost-effective initial process development of new materials. Various dilute polymer systems were developed whereby solids loading, viscosity and surface tension were all fully controlled. Design of Experiments techniques were employed to determine relationships between parameters and fluid properties. Chosen parameters included coating velocity, coating acceleration, coating gap (gap between slot die lips and substrate), volume infuse (volume of material initially infused) and flow infuse (flow rate of material initially infused). Their effects on coating thickness and thickness uniformity were quantified for the bulk region of the coating, resulting in the development of a statistical model to aid optimisation of parameters for new materials. Surface tension had a minimal effect on coating thickness and uniformity during the screening study so this was not included in the final model. Coating acceleration and flow infuse exhibited a proportional relationship relating to coating thickness uniformity. Volume infuse did not have a significant effect on coating thickness or uniformity. Particular focus was placed on viscosity and coating velocity; in the case of this bespoke tool they were found to be inversely proportional in relation to coating thickness and uniformity. They strongly influenced the flow rate and the resultant coating thickness due to the effects of fluid resistance, though the wet coat thickness parameter was held at a constant value. This suggested that the system does not work by a feedback loop to correct the flow rate for fluid resistance and internal pressure effects. Regardless of this, an operating window was found in which coating thickness and uniformity can be controlled for polymer solutions with a range of viscosities.
Evidence for sex differences in fetal programming of physiological stress reactivity in infancy

Abstract Associations between low birth weight and prenatal anxiety and later psychopathology may arise from programming effects likely to be adaptive under some, but not other, environmental exposures and modified by sex differences. If physiological reactivity, which also confers vulnerability or resilience in an environment-dependent manner, is associated with birth weight and prenatal anxiety, it will be a candidate to mediate the links with psychopathology. From a general population sample of 1,233 first-time mothers recruited at 20 weeks gestation, a sample of 316 stratified by adversity was assessed at 32 weeks and when their infants were aged 29 weeks (N = 271). Prenatal anxiety was assessed by self-report, birth weight from medical records, and vagal reactivity from respiratory sinus arrhythmia during four nonstressful and one stressful (still-face) procedure. Lower birth weight for gestational age predicted higher vagal reactivity only in girls (interaction term, p = .016), and prenatal maternal anxiety predicted lower vagal reactivity only in boys (interaction term, p = .014). These findings are consistent with sex differences in fetal programming, whereby prenatal risks are associated with increased stress reactivity in females but decreased reactivity in males, with distinctive advantages and penalties for each sex.
Site-Specific Effects of PECAM-1 on Atherosclerosis in LDL Receptor–Deficient Mice

Objective—Atherosclerosis is a vascular disease that involves lesion formation at sites of disturbed flow under the influence of genetic and environmental factors. Endothelial expression of adhesion molecules that enable infiltration of immune cells is important for lesion development. Platelet/endothelial cell adhesion molecule-1 (PECAM-1; CD31) is an adhesion and signaling receptor expressed by many cells involved in atherosclerotic lesion development. PECAM-1 transduces signals required for proinflammatory adhesion molecule expression at atherosusceptible sites; thus, it is predicted to be proatherosclerotic. PECAM-1 also inhibits inflammatory responses, on which basis it is predicted to be atheroprotective. Methods and Results—We evaluated herein the effect of PECAM-1 deficiency on development of atherosclerosis in LDL receptor–deficient mice. We found that PECAM-1 has both proatherosclerotic and atheroprotective effects, but that the former dominate in the inner curvature of the aortic arch whereas the latter dominate in the aortic sinus, branching arteries, and descending aorta. Endothelial cell expression of PECAM-1 was sufficient for its atheroprotective effects in the aortic sinus but not in the descending aorta, where the atheroprotective effects of PECAM-1 also required its expression on bone marrow–derived cells. Conclusion—We conclude that PECAM-1 influences initiation and progression of atherosclerosis both positively and negatively, and that it does so in a site-specific manner.
Targeting the Full Length of the Motor End Plate Regions in the Mouse Forelimb Increases the Uptake of Fluoro-Gold into Corresponding Spinal Cord Motor Neurons

Lower motor neuron dysfunction is one of the most debilitating motor conditions. In this regard, transgenic mouse models of various lower motor neuron dysfunctions provide insight into the mechanisms underlying these pathologies and can also aid the development of new therapies. Viral-mediated gene therapy can take advantage of the muscle-motor neuron topographical relationship to shuttle therapeutic genes into specific populations of motor neurons in these mouse models. In this context, motor end plates (MEPs) are highly specialized regions on the skeletal musculature that offer direct access to the pre-synaptic nerve terminals, henceforth to the spinal cord motor neurons. The aim of this study was two-folded. First, it was to characterize the exact position of the MEP regions for several muscles of the mouse forelimb using acetylcholinesterase histochemistry. This MEP-muscle map was then used to guide a series of intramuscular injections of Fluoro-Gold (FG) in order to characterize the distribution of the innervating motor neurons. This analysis revealed that the MEPs are typically organized in an orthogonal fashion across the muscle fibers and extends throughout the full width of each muscle. Furthermore, targeting the full length of the MEP regions gave rise labeled motor neurons that are organized into columns spanning through more spinal cord segments than previously reported. The present analysis suggests that targeting the full width of the muscles’ MEP regions with FG increases the somatic availability of the tracer. This process ensures a greater uptake of the tracer by the pre-synaptic nerve terminals, hence maximizing the labeling in spinal cord motor neurons. This investigation should have positive implications for future studies involving the somatic delivery of therapeutic genes into motor neurons for the treatment of various motor dysfunctions.
Metabolic Changes in Cerebral Cortex, Hippocampus, and Cerebellum During Sustained Bicuculline‐Induced Seizures

Abstract— The objective of the present experiments was to study metabolic correlates to the localization of neuronal lesions during sustained seizures. To that end, status epilepticus was induced by i.v. administration of bicuculline in immobilized and artificially ventilated rats, since this model is known to cause neuronal cell damage in cerebral cortex and hippocampus but not in the cerebellum. After 20 or 120 min of continuous seizure activity, brain tissue was frozen in situ through the skull bone, and samples of cerebral cortex, hippocampus, and cerebellum were collected for analysis of glycolytic metabolites, phosphocreatine (PCr), ATP, ADP, AMP, and cyclic nucleotides. After 20 min of seizure activity, the two “vulnerable” structures (cerebral cortex and hippocampus) and the “resistant” one (cerebellum) showed similar changes in cerebral metabolic state, characterized by decreased tissue concentrations of PCr, ATP, and glycogen, and increased lactate concentrations and lactate/ pyruvate ratios. In all structures, though, the adenylate energy charge remained close to control. At the end of a 2‐h period of status epilepticus, a clear deterioration of the energy state was observed in the cerebral cortex and the hippocampus, but not in the cerebellum. The reduction in adenylate energy charge in the cortex and hippocampus was associated with a seemingly paradoxical decrease in tissue lactate levels and with failure of glycogen resynthesis (cerebral cortex). Experiments with infusion of glucose during the second hour of a 2‐h period of status epilepticus verified that the deterioration of tissue energy state was partly due to reduced substrate supply; however, even in animals with adequate tissue glucose concentrations, the energy charge of the two structures was significantly lowered. The cyclic nucleotides (cAMP and cGMP) behaved differently. Thus, whereas cAMP concentrations were either close to control (hippocampus and cerebellum) or moderately increased (cerebral cortex), the cGMP concentrations remained markedly elevated throughout the seizure period, the largest change being observed in the cerebellum. It is concluded that although the localization of neuronal damage and perturbation of cerebral energy state seem to correlate, the results cannot be taken as. evidence that cellular energy failure is the cause of the damage. Thus, it appears equally probable that the pathologically enhanced neuronal activity (and metabolic rate) underlies both the cell damage and the perturbed metabolic state. The observed changes in cyclic nucleotides do not appear to bear a causal relationship to the mechanisms of damage.
Human Betacoronavirus 2c EMC/2012–related Viruses in Bats, Ghana and Europe

We screened fecal specimens of 4,758 bats from Ghana and 272 bats from 4 European countries for betacoronaviruses. Viruses related to the novel human betacoronavirus EMC/2012 were detected in 46 (24.9%) of 185 Nycteris bats and 40 (14.7%) of 272 Pipistrellus bats. Their genetic relatedness indicated EMC/2012 originated from bats.
A cross-cultural comparison between South African and British students on the Wechsler Adult Intelligence Scales Third Edition (WAIS-III)

There is debate regarding the appropriate use of Western cognitive measures with individuals from very diverse backgrounds to that of the norm population. Given the dated research in this area and the considerable socio-economic changes that South Africa has witnessed over the past 20 years, this paper reports on the use of the Wechsler Adult Intelligence Scale Third Edition (WAIS-III), the most commonly used measure of intelligence, with an English second language, multilingual, low socio-economic group of black, South African university students. Their performance on the WAIS-III was compared to that of a predominantly white, British, monolingual, higher socio-economic group. A multi-group confirmatory factor analysis showed that the WAIS-III lacks measurement invariance between the two groups, suggesting that it may be tapping different constructs in each group. The UK group significantly outperformed the SA group on the knowledge-based verbal, and some non-verbal subtests, while the SA group performed significantly better on measures of Processing Speed (PS). The groups did not differ significantly on the Matrix Reasoning subtest and on those working memory subtests with minimal reliance on language, which appear to be the least culturally biased. Group differences were investigated further in a set of principal components analyses, which revealed that the WAIS-III scores loaded differently for the UK and SA groups. While the SA group appeared to treat the PS subtests differently to those measuring perceptual organization and non-verbal reasoning, the UK group seemed to approach all of these subtests similarly. These results have important implications for the cognitive assessment of individuals from culturally, linguistically, and socio-economically diverse circumstances.