Miracle-dz/UniFAR-FTUs huggingface dataset:
Distinct Cortical Correlates of Autistic versus Antisocial Traits in a Longitudinal Sample of Typically Developing Youth

In humans, behaviors associated with autism and antisociality, disorders characterized by distinct social impairments, can be viewed as quantitative traits that range from frank impairment to normal variation, as found in the general population. Neuroimaging investigations of autism and antisociality demonstrate diagnostically specific aberrant cortical brain structure. However, little is known about structural brain correlates of social behavior in nonclinical populations. Therefore, we sought to determine whether autistic and antisocial traits exhibit dissociable cortical correlates and whether these associations are stable across development among typically developing youth. Three hundred twenty-three typically developing youth (age at first scan: mean = 10.63, SD = 3.71 years) underwent anatomic magnetic resonance imaging (1–6 scans each; total = 742 scans), and provided ratings of autistic and antisocial traits. Higher autistic trait ratings were associated with thinner cortex most prominently in right superior temporal sulcus while higher antisocial trait ratings were associated with thinner cortex in primarily bilateral anterior prefrontal cortices. There was no interaction with age, indicating that these brain–behavior associations were stable across development. Using assessments of both subclinical autistic and subclinical antisocial traits within a large longitudinal sample of typically developing youth, we demonstrate dissociable neuroanatomic correlations that parallel those found in the frank clinical disorders of autism (e.g., superior temporal cortex) and antisociality (e.g., anterior prefrontal cortex). Moreover, these correlations appear to be established in early childhood and remain fixed into early adulthood. These results support the dimensional view of psychopathology and provide neural signatures that can serve as informative endophenotypes for future genetic studies.
Adverse effects & drug load of antiepileptic drugs in patients with epilepsy: Monotherapy versus polytherapy

Background & objectives: Although the need for a combination of antiepileptic drugs (AEDs) in the treatment of epilepsy is well justified, but an associated increase in adverse effects (AEs) lends a restriction to polytherapy. The aim of this study was to evaluate AEs and drug load (prescribed daily dose/defined daily doses) of AEDs in patients with epilepsy (PWE). Methods: Consecutive PWEs attending Epilepsy clinic in a tertiary care hospital in New Delhi, India, were enrolled in the study. Demographic variables, such as age, gender, diagnosis, age at onset of seizures, frequency of seizures, use of all AEDs and adverse event profile (AEP) score were noted. Routine laboratory tests including lipid profile, fasting blood glucose, haematological parameters and liver and kidney function tests were done. Results: A total of 697 consecutive patients were included in this study. Of them, 64.4 per cent were male; mean age was 29.6 ± 10.6 yr. Generalized seizures and focal seizures were recorded in n=386 (55.4%) and n=311 (44.6%), respectively. Monotherapy and polytherapy with two and greater than or equal to three AEDs were prescribed in 264 (37.9%), 243 (34.9%) and 190 (27.2%) patients, respectively. The average AED load, duration of treatment as well as AEP score were found to be significantly higher in combination of greater than or equal to three AEDs as compared to both monotherapy and combination of two AEDs, whereas no significant difference was observed between monotherapy and combination of two AEDs. Patients on monotherapy were in good control of seizures as compared to polytherapy. There was no significant change in biochemical parameters between the groups. Interpretation & conclusions: Polytherapy with combination of greater than or equal to three AEDs was associated with higher AEs and lower seizure control as compared to both monotherapy and combination of two AEDs. AEs did not correlate with AED load, seizure type, gender and age of the patients but were associated with both numbers of AEDs as well as seizure frequency in PWE.
Embedded System Design with Reliability-Centric Optimization

Embedded systems are becoming increasingly popular due to their widespread applications. Hardware/software partitioning with reliability in consideration is becoming one of the most crucial steps in the design of complex embedded systems, especially for safety critical applications. In this paper, a reliability-centric approach is proposed to increase the reliability and decrease the potential errors of the embedded system during the partition stage. We use task graph to model the system function blocks, and treat reliability as the first-class metric during the mathematical formalization and optimization procedure. Experimental evaluations demonstrate that the proposed approach obtains a better solution with the trade off of time, cost and reliability compared to existing partitioning methods, with higher and more accurate reliability characterization for safety-critical systems.
Working memory and sleep in 6- to 13-year-old schoolchildren.

OBJECTIVE To study the associations between sleep quality/quantity and performance in auditory/visual working memory tasks of different load levels. METHOD Sixty schoolchildren aged 6 to 13 years from normal school classes voluntarily participated. Actigraphy measurement was done during a typical school week for 72 consecutive hours. It was timed together with the working memory experiments to obtain information on children's sleep during that period. The n-back task paradigm was used to examine auditory and visual working memory functions. RESULTS Lower sleep efficiency and longer sleep latency were associated with a higher percentage of incorrect responses in working memory tasks at all memory load levels (partial correlations, controlling for age, all p values < .05, except in visual 0-back and auditive 2-back tasks); shorter sleep duration was associated with performing tasks at the highest load level only (partial correlations, controlling for age,p < .05). Also in general linear models (controlling for age, gender, and socioeconomic status), sleep efficiency (F = 11.706, p = .050) and latency (F = 3.588, p = .034) were significantly associated with the mean incorrect response rate in auditory working memory tasks. CONCLUSIONS Sleep quality and quantity affect performance of working memory tasks in school-age children. In children with learning difficulties the possibility of underlying sleep problems should be excluded.
The transferrin–iron import system from pathogenic Neisseria species

Two pathogenic species within the genus Neisseria cause the diseases gonorrhoea and meningitis. While vaccines are available to protect against four N. meningitidis serogroups, there is currently no commercial vaccine to protect against serogroup B or against N. gonorrhoeae. Moreover, the available vaccines have significant limitations and with antibiotic resistance becoming an alarming issue, the search for effective vaccine targets to elicit long‐lasting protection against Neisseria species is becoming more urgent. One strategy for vaccine development has targeted the neisserial iron import systems. Without iron, the Neisseriae cannot survive and, therefore, these iron import systems tend to be relatively well conserved and are promising vaccine targets, having the potential to offer broad protection against both gonococcal and meningococcal infections. These efforts have been boosted by recent reports of the crystal structures of the neisserial receptor proteins TbpA and TbpB, each solved in complex with human transferrin, an iron binding protein normally responsible for delivering iron to human cells. Here, we review the recent structural reports and put them into perspective with available functional studies in order to derive the mechanism(s) for how the pathogenic Neisseriae are able to hijack human iron transport systems for their own survival and pathogenesis.
Relational Theory of Status Hierarchy: An Extension of Gould's Model to Incorporate Multidimensional Choices

Social status hierarchy is a prominent topic in sociology, but a complete theoretical understanding of its process has been lacking. Using game theory and social network theory, Gould showed that status hierarchy can be considered as a type of equilibrium wherein players assign attachments to other players depending on their qualities. However, Gould’s model unrealistically gives limitless attachment resources to each player. We improve Gould’s model by incorporating multidimensional choices that consider resource constraints, including factors of individual quality, social reference, and reciprocity. We find that an individual’s status is determined by the individual’s relative quality in the complete social network (in contrast to Gould’s model, where an individual’s status is dyadically determined). We also demonstrate by agent-based simulation that our model can be based on bounded-rational not hyper-rational players and that it thus has wide applicability to a variety of real world situations. Finally we find that social influence does not always amplify the inequality in the hierarchy, as Gould claimed. In fact, social influence can reduce the inequality in the hierarchy where strong reciprocity conditions are present.
Approximate schedulability analysis

The schedulability analysis problem for many realistic task models is intractable. Therefore, known algorithms either have exponential complexity or at best can be solved in pseudo-polynomial time, thereby restricting application of the concerned models to a large extent. We introduce the notion of "approximate schedulability analysis" and show that if a small amount of "error" (which is specified as an input to the algorithm) can be tolerated in decisions made by the algorithm, then this problem can be solved in polynomial time. Our algorithms are analogous to fully polynomial time approximation schemes in the context of optimization problems. We show that this concept of approximate schedulability analysis is fairly general and can be applied to any task model which satisfies certain "task-independence" assumptions. Lastly, we substantiate our theoretical results with experimental evidence and clearly show tradeoffs between running time of the schedulability analysis and the error incurred for various values of the input error parameter.
Delayed cutaneous hypersensitivity reactions to iodinated contrast media

Contrast-enhanced imaging investigations using iodinated contrast media (ICM) are widely performed [1]. ICM injections are generally well tolerated but adverse reactions may occur. ICM can cause either immediate or non-immediate (more than one hour after exposure) hypersensitivity reactions. Immediate hypersensitivity reactions are the most well-known.Physicians are often less familiar with the delayed hypersensitivity reactions after ICM injection because they usually occur when patients are discharged [. ]
Heuristic thermal sensor allocation methods for overheating detection of real microprocessors

Modern microprocessors utilise embedded thermal sensors to continuously monitor the chip's temperature during runtime. However, the overheating locations change temporally and spatially depending on the various workloads running on the chip. Furthermore, on-chip thermal sensor readings are highly affected by noise due to fabrication fluctuations and randomness, which makes the task of thermal monitoring particularly challenging. In this study, the authors first establish overheating detection models to address the thermal sensor allocation problem under two different conditions when the on-chip thermal sensor observations are corrupted by noise. On this basis, a heuristic method based on genetic algorithm is proposed to find a near-optimal thermal sensor allocation solution, which can make overheating detection probability significantly improved with a greatly reduced execution time. They also propose a hybrid algorithm to identify the optimal thermal sensor placement for each individual chip block or component. Moreover, they develop an oil-based cooling system and utilise infrared thermal imaging techniques to capture the thermal traces of a real dual-core microprocessor when running various workloads. The experiments demonstrate that the authors’ proposed thermal sensor allocation methods obviously outperform several common allocation approaches in terms of overheating detection, which can provide an accurate and reliable thermal monitoring.
The relation between different dimensions of alcohol consumption and burden of disease: an overview.

AIMS As part of a larger study to estimate the global burden of disease and injury attributable to alcohol: to evaluate the evidence for a causal impact of average volume of alcohol consumption and pattern of drinking on diseases and injuries; to quantify relationships identified as causal based on published meta-analyses; to separate the impact on mortality versus morbidity where possible; and to assess the impact of the quality of alcohol on burden of disease. METHODS Systematic literature reviews were used to identify alcohol-related diseases, birth complications and injuries using standard epidemiological criteria to determine causality. The extent of the risk relations was taken from meta-analyses. RESULTS Evidence of a causal impact of average volume of alcohol consumption was found for the following major diseases: tuberculosis, mouth, nasopharynx, other pharynx and oropharynx cancer, oesophageal cancer, colon and rectum cancer, liver cancer, female breast cancer, diabetes mellitus, alcohol use disorders, unipolar depressive disorders, epilepsy, hypertensive heart disease, ischaemic heart disease (IHD), ischaemic and haemorrhagic stroke, conduction disorders and other dysrhythmias, lower respiratory infections (pneumonia), cirrhosis of the liver, preterm birth complications and fetal alcohol syndrome. Dose-response relationships could be quantified for all disease categories except for depressive disorders, with the relative risk increasing with increased level of alcohol consumption for most diseases. Both average volume and drinking pattern were linked causally to IHD, fetal alcohol syndrome and unintentional and intentional injuries. For IHD, ischaemic stroke and diabetes mellitus beneficial effects were observed for patterns of light to moderate drinking without heavy drinking occasions (as defined by 60+ g pure alcohol per day). For several disease and injury categories, the effects were stronger on mortality compared to morbidity. There was insufficient evidence to establish whether quality of alcohol had a major impact on disease burden. CONCLUSIONS Overall, these findings indicate that alcohol impacts many disease outcomes causally, both chronic and acute, and injuries. In addition, a pattern of heavy episodic drinking increases risk for some disease and all injury outcomes. Future studies need to address a number of methodological issues, especially the differential role of average volume versus drinking pattern, in order to obtain more accurate risk estimates and to understand more clearly the nature of alcohol-disease relationships.
Late-onset preeclampsia is associated with an imbalance of angiogenic and anti-angiogenic factors in patients with and without placental lesions consistent with maternal underperfusion

Objective: An imbalance between maternal angiogenic/anti-angiogenic factors concentrations has been observed in preeclampsia (PE) and other obstetrical syndromes. However, the frequency of pathologic findings in the placenta and the changes in maternal plasma angiogenic/anti-angiogenic factor concentrations differ between late- and early-onset PE. The aim of this study was to determine if the maternal plasma concentrations of placental growth factor (PlGF), soluble endoglin (sEng), and soluble vascular endothelial growth factor receptor-1 and 2 (sVEGFR-1 and sVEGFR-2) are different in late-onset PE with and without placental pathologic findings consistent with maternal underperfusion. Study design: A cross-sectional study was conducted including 64 uncomplicated women and 66 women with late-onset PE (>34 weeks) who had blood samples and placenta available for pathologic examination. Patients with late-onset PE were divided into those with and without placental histologic findings consistent with maternal underperfusion as proposed by the Society for Pediatric Pathology. Maternal plasma concentrations of PlGF, sEng, sVEGFR-1 and sVEGRF-2 were determined by ELISA. Non-parametric statistics were used for analysis. Results: 1) the prevalence of placental histological findings consistent with maternal underperfusion among women with late-onset PE was higher than that of those with an uncomplicated pregnancy (47% (31/66) vs. 7.8% (5/64), respectively; p < 0.01); 2) patients with late-onset PE and histological findings consistent with maternal underperfusion had a significantly lower median plasma concentration of PlGF, plasma PlGF/sVEGFR-1 ratio and plasma PlGF/sEng ratio than those with late-onset PE without placental underperfusion lesions (each p < 0.05); 3) the most common pathological findings in the placenta of patient with PE were lesions consistent with villous changes (77%, 24/31); and 4) isolated vascular lesions in the placenta were found only in 2 cases (6.5%), and the rest had a combination of villous and vascular lesions. Conclusions: Nearly half of the patients with late-onset PE have placental lesions consistent with maternal underperfusion. These lesions are associated with an imbalance in the maternal concentration of angiogenic/anti-angiogenic factors. We propose that there is a link between maternal underperfusion and an anti-angiogenic state characterized by the changes in the concentrations of angiogenic and anti-angiogenic factors in women with late onset PE.
Flexibility and design: conformational heterogeneity along the evolutionary trajectory of a redesigned ubiquitin

Summary Although protein design has been used to introduce new functions, designed variants generally only function as well as natural proteins after rounds of laboratory evolution. One possibility for this pattern is that designed mutants frequently sample nonfunctional conformations. To test this idea, we exploited advances in multiconformer modeling of room temperature X-ray data collection on redesigned ubiquitin variants selected for increasing binding affinity to the deubiquitinase USP7. Initial core mutations disrupt natural packing and lead to increased flexibility. Additional, experimentally selected mutations quenched conformational heterogeneity through new stabilizing interactions. Stabilizing interactions, such as cation-pi stacking and ordered waters, which are not included in standard protein design energy functions, can create specific interactions that have long range effects on flexibility across the protein. Our results suggest that increasing flexibility may be a useful strategy to escape local minima during initial directed evolution and protein design steps when creating new functions.
CD11b/CD18 (Mac-1) Is a Novel Surface Receptor for Extracellular Double-Stranded RNA To Mediate Cellular Inflammatory Responses

During viral infection, extracellular dsRNA is a potent signaling molecule that activates many innate immune cells, including macrophages. TLR3 is a well-known receptor for extracellular dsRNA, and internalization of extracellular dsRNA is required for endosomal TLR3 activation. Preserved inflammatory responses of TLR3-deficient macrophages to extracellular dsRNA strongly support a TLR3-independent mechanism in dsRNA-mediated immune responses. The present study demonstrated that CD11b/CD18 (Mac-1 [macrophage-1 Ag]), a surface integrin receptor, recognized extracellular dsRNA and induced macrophage immune responses. CD11b deficiency reduced inflammatory cytokine induction elicited by polyinosinic:polycytidylic acid (poly I:C; a synthetic dsRNA) in mouse sera and livers, as well as in cultured peritoneal macrophages. dsRNA-binding assay and confocal immunofluorescence showed that Mac-1, especially the CD11b subunit, interacted and colocalized with poly I:C on the surface of macrophages. Further mechanistic studies revealed two distinct signaling events following dsRNA recognition by Mac-1. First, Mac-1 facilitated poly I:C internalization through the activation of PI3K signaling and enhanced TLR3-dependent activation of IRF3 in macrophages. Second, poly I:C induced activation of phagocyte NADPH oxidase in a TLR3-independent, but Mac-1–dependent, manner. Subsequently, phagocyte NADPH oxidase–derived intracellular reactive oxygen species activated MAPK and NF-κB pathways. Our results indicate that extracellular dsRNA activates Mac-1 to enhance TLR3-dependent signaling and to trigger TLR3-independent, but Mac-1–dependent, inflammatory oxidative signaling, identifying a novel mechanistic basis for macrophages to recognize extracellular dsRNA to regulate innate immune responses. This study identifies Mac-1 as a novel surface receptor for extracellular dsRNA and implicates it as a potential therapeutic target for virus-related inflammatory diseases.
Administration of a CD25-Directed Immunotoxin, LMB-2, to Patients with Metastatic Melanoma Induces a Selective Partial Reduction in Regulatory T Cells In Vivo1

CD25+CD4+ T regulatory (Treg) cells regulate peripheral self tolerance and possess the ability to suppress antitumor responses, which may in part explain the poor clinical response of cancer patients undergoing active immunization protocols. We have previously shown that in vitro incubation of human PBMC with LMB-2, a CD25-directed immunotoxin, significantly reduced CD25+FOXP3+CD4+ Treg cells without impairing the function of the remaining lymphocytes. In the current study, eight patients with metastatic melanoma were treated with LMB-2 followed by MART-1 and gp100-specific peptide vaccination. LMB-2 administration resulted in a preferential, transient reduction in mean circulating CD25+CD4+ T cell number, from 83 ± 16 cells/μl to a nadir of 17 ± 5 cells/μl, a 79.1% reduction. FOXP3 analysis revealed a less robust depletion with mean FOXP3+CD4+ Treg cell number decreasing from 74 ± 15 cells/μl to 36 ± 8 cells/μl, a 51.4% reduction. FOXP3+CD4+ Treg cells that survived LMB-2-mediated cytotoxicity expressed little or no CD25. Similar to the peripheral blood, immunohistochemical analysis showed a 68.9% mean reduction in FOXP3+CD4+ Treg cell frequency in evaluable lesions. Despite inducing a reduction in Treg cell numbers in vivo, LMB-2 therapy did not augment the immune response to cancer vaccination and no patient experienced an objective response or autoimmunity. These data demonstrate the capacity of a CD25-directed immunotoxin to selectively mediate a transient partial reduction in circulating and tumor-infiltrating Treg cells in vivo, and suggest that more comprehensive Treg cell elimination may be required to bolster antitumor responses in patients with metastatic melanoma.
Trade agreements galore

This book identifies who the key actors are on the stage of international trade policy. It explores what governments regulate by taking an in-depth look at the legal provisions contained in hundreds of economic integration agreements. We line up the arguments for and against regionalism and show how international trade institutions affect world trade. Our results, based on augmented gravity equations and novel, extensive datasets, quantify how much countries gain (or lose) from participating in the World Trade Organisation, the Generalised System of Preferences and other trade agreements. We also illustrate where trade blocs emerge and discuss when and why they change.