Miracle-dz/UniFAR-FTUs huggingface dataset:
Childhood Sexual Abuse Is Highly Associated With HIV Risk-Taking Behavior and Infection Among MSM in the EXPLORE Study

Background:Previous studies have found high rates of childhood sexual abuse (CSA) among US men who have sex with men (MSM). CSA history has been associated with a variety of negative effects later in life including behaviors that place MSM at greater risk for HIV acquisition and transmission. The present analysis is the first to examine the longitudinal association between CSA and HIV infection, unprotected anal sex, and serodiscordant unprotected anal sex, as well as mediators of these relationships among a large sample of HIV-uninfected MSM. Methods:The EXPLORE Study was a behavioral intervention trial conducted in 6 US cities over 48 months with HIV infection as the primary efficacy outcome. Behavioral assessments were done every 6 months via confidential computerized assessments. Longitudinal regression models were constructed, adjusting for randomization arm, geographical location of study site, age at enrollment, education, and race/ethnicity. Results:Of the 4295 participants enrolled, 39.7% had a history of CSA. Participants with a history of CSA [adjusted hazards ratio = 1.30, 95% confidence interval (CI): 1.02 to 1.69] were at increased risk for HIV infection over study follow-up. A significant association was seen between history of CSA and unprotected anal sex (adjusted odds ratio = 1.24, 95% CI: 1.12 to 1.36) and serodiscordant unprotected anal sex (adjusted odds ratio = 1.30, 95% CI: 1.18 to 1.43). Among participants reporting CSA, the EXPLORE intervention had no effect in reducing HIV infection rates. Participants reporting CSA were significantly more likely to have symptoms of depression and use nonprescription drugs. Conclusions:A predictive relationship between a history of CSA and subsequent HIV infection was observed among this large sample of HIV-uninfected MSM. Findings indicate that HIV-uninfected MSM with CSA histories are at greater risk for HIV infection, report higher rates of HIV sexual risk behavior, and may derive less benefit from prevention programs. Future HIV prevention interventions should address the specific mental health concerns of MSM with a history of CSA.
Short term and long term health related quality of life after congenital anorectal malformations and congenital diaphragmatic hernia

Aims: To examine short term and long term health related quality of life (HRQoL) of survivors of congenital anorectal malformations (ARM) and congenital diaphragmatic hernia (CDH), and to compare these patients’ HRQoL with that of the general population. Methods: HRQoL was measured in 286 ARM patients and 111 CDH patients. All patients were administered a symptom checklist and a generic HRQoL measure. For the youngest children (aged 1–4) the TAIQOL (a preliminary version of the TAPQOL) was used, for the other children (aged 5–15) the TACQOL questionnaire, and for adults (aged >16) the SF-36. Results: As appeared from the symptom checklists, many patients remained symptomatic into adulthood. In the youngest ARM patients (aged 1–4 years), generic HRQoL was severely affected, but the older ARM patients showed better HRQoL. In the CDH patients, the influence of symptoms on HRQoL seemed less profound. The instruments we used revealed little difference between adults treated for ARM or CDH and the general population. Conclusions: These results show that for two neonatal surgical procedures, improved survival does not come at the expense of poor HRQoL in adults. Even though there is considerable suffering in terms of both morbidity and mortality in the youngest group, the ultimate prognosis of survivors of the two studied congenital malformations is favourable. This finding can be used to reassure parents of patients in need of neonatal surgery for one of these conditions about the prospects for their child.
UMD (Universal Mutation Database): A generic software to build and analyze locus‐specific databases

The human genome is thought to contain about 80,000 genes and presently only 3,000 are known to be implicated in genetic diseases. In the near future, the entire sequence of the human genome will be available and the development of new methods for point mutation detection will lead to a huge increase in the identification of genes and their mutations associated with genetic diseases as well as cancers, which is growing in frequency in industrial states. The collection of these mutations will be critical for researchers and clinicians to establish genotype/phenotype correlations. Other fields such as molecular epidemiology will also be developed using these new data. Consequently, the future lies not in simple repositories of locus‐specific mutations but in dynamic databases linked to various computerized tools for their analysis and that can be directly queried on‐line. To meet this goal, we devised a generic software called UMD (Universal Mutation Database). It was developed as a generic software to create locus‐specific databases (LSDBs) with the 4th Dimension® package from ACI. This software includes an optimized structure to assist and secure data entry and to allow the input of various clinical data. Thanks to the flexible structure of the UMD software, it has been successfully adapted to nine genes either involved in cancer (APC, P53, RB1, MEN1, SUR1, VHL, and WT1) or in genetic diseases (FBN1 and LDLR). Four new LSDBs are under construction (VLCAD, MCAD, KIR6, and COL4A5). Finally, the data can be transferred to core databases. Hum Mutat 15:86–94, 2000. © 2000 Wiley‐Liss, Inc.
Complement membrane attack complexes activate noncanonical NF-κB by forming an Akt+NIK+ signalosome on Rab5+ endosomes

Significance Complement activation contributes to host defense and immunopathology. We recently discovered that membrane attack complexes (MAC), the terminal effector mechanisms of complement, activate proinflammatory functions in human endothelial cells (ECs) via noncanonical NF-ΚB signaling. Here we elucidate the initial steps of how MACs activate this pathway. MACs formed on the surface of human ECs are rapidly internalized via clathrin-mediated endocytosis into Rab5+ endosomes, which subsequently recruit activated Akt in a Rab5-dependent manner. Akt recruitment results in NIK protein stabilization on the surface of the endosome within 30 min, initiating noncanonical NF-ΚB signaling. MAC internalization in ECs lining human coronary arteries in vivo similarly activates noncanonical NF-ΚB signaling. Our findings suggest new therapeutic targets for controlling complement-mediated inflammation. Complement membrane attack complexes (MACs) promote inflammatory functions in endothelial cells (ECs) by stabilizing NF-κB–inducing kinase (NIK) and activating noncanonical NF-κB signaling. Here we report a novel endosome-based signaling complex induced by MACs to stabilize NIK. We found that, in contrast to cytokine-mediated activation, NIK stabilization by MACs did not involve cIAP2 or TRAF3. Informed by a genome-wide siRNA screen, instead this response required internalization of MACs in a clathrin-, AP2-, and dynamin-dependent manner into Rab5+endosomes, which recruited activated Akt, stabilized NIK, and led to phosphorylation of IκB kinase (IKK)-α. Active Rab5 was required for recruitment of activated Akt to MAC+ endosomes, but not for MAC internalization or for Akt activation. Consistent with these in vitro observations, MAC internalization occurred in human coronary ECs in vivo and was similarly required for NIK stabilization and EC activation. We conclude that MACs activate noncanonical NF-κB by forming a novel Akt+NIK+ signalosome on Rab5+ endosomes.
Optimizing the Stage Resolution in Pipelined SAR ADCs for High-Speed High-Resolution Applications

The successive approximation register (SAR) analog-to-digital converters (ADCs) outperform other types of ADCs on the area and energy efficiency due to its binary searching algorithm, which however has a conversion speed limitation. When pipelining multiple SAR ADCs, the speed is improved, the resolutions in individual stages are relaxed, and the nonidealities from non-first stages are desensitized by the gains preceding them. This brief examines the effects of the stage resolution on linearity, noise, speed, area, and power consumption in pipelined SAR ADCs. Two conclusions are reached. First, under certain cases, a larger resolution per stage improves the ADC linearity without costing the speed of the operational amplifiers (op-amps) used for residue amplifications. However, the stage resolution does not affect the op-amp open-loop gain requirement. Second, for area and power consideration, allocating about one quarter of the overall number of bits to the first stage is optimum in the practical situation that the area and power of the active circuitries are tens or hundreds of times of those of the unit capacitors in the SAR sub-ADCs.
Molecular dynamics study of prolyl oligopeptidase with inhibitor in binding cavity

We used the crystal structure of prolyl oligopeptidase (POP) with bound Z-pro-prolinal (ZPP) inhibitor (Protein Data Bank (PDB) structure 1QFS) to perform an intensive molecular dynamics study of the POP-ZPP complex. We performed 100 ns of simulation with the hemiacetal bond, through which the ZPP is bound to the POP, removed in order to better investigate the binding cavity environment. From basic analysis, measuring the radius of gyration, root mean square deviation, solvent accessible surface area and definition of the secondary structure of protein, we determined that the protein structure is highly stable and maintains its structure over the entire simulation time. This demonstrates that such long time simulations can be performed without the protein structure losing stability. We found that water bridges and hydrogen bonds play a negligible role in binding the ZPP thus indicating the importance of the hemiacetal bond. The two domains of the protein are bound by a set of approximately 12 hydrogen bonds, specific to the particular POP protein.
A NOTE ON THE RATIONALITY TEST

The rationality test is based on regressing the actual series of variable in period t on its forecast formed in period t − 1. The nonrejection of the rationality hypothesis requires expectations' unbiasedness and efficiency. We show that in a model with t − 1 dating, where expectations strongly and positively affect the economy, the rationality test suffers from low power. It provides a high probability of nonrejection of the rationality hypothesis against numerous alternatives for expectations formation. This result is attained because the realization of the economy is driven by the public's expectations, irrespective of how well they are formed, via the structural relationship between them. The parameters in this test are predetermined by the parameters of the structural model, supporting expectations' unbiasedness under reasonable assumptions. Thus, successfully passing the rationality test could be misleading in terms of interpretation of the quality of the expectations and could lead to questionable accuracy of many applications.
Neonatal abstinence syndrome after methadone or buprenorphine exposure.

BACKGROUND Methadone, a full mu-opioid agonist, is the recommended treatment for opioid dependence during pregnancy. However, prenatal exposure to methadone is associated with a neonatal abstinence syndrome (NAS) characterized by central nervous system hyperirritability and autonomic nervous system dysfunction, which often requires medication and extended hospitalization. Buprenorphine, a partial mu-opioid agonist, is an alternative treatment for opioid dependence but has not been extensively studied in pregnancy. METHODS We conducted a double-blind, double-dummy, flexible-dosing, randomized, controlled study in which buprenorphine and methadone were compared for use in the comprehensive care of 175 pregnant women with opioid dependency at eight international sites. Primary outcomes were the number of neonates requiring treatment for NAS, the peak NAS score, the total amount of morphine needed to treat NAS, the length of the hospital stay for neonates, and neonatal head circumference. RESULTS Treatment was discontinued by 16 of the 89 women in the methadone group (18%) and 28 of the 86 women in the buprenorphine group (33%). A comparison of the 131 neonates whose mothers were followed to the end of pregnancy according to treatment group (with 58 exposed to buprenorphine and 73 exposed to methadone) showed that the former group required significantly less morphine (mean dose, 1.1 mg vs. 10.4 mg; P<0.0091), had a significantly shorter hospital stay (10.0 days vs. 17.5 days, P<0.0091), and had a significantly shorter duration of treatment for the neonatal abstinence syndrome (4.1 days vs. 9.9 days, P<0.003125) (P values calculated in accordance with prespecified thresholds for significance). There were no significant differences between groups in other primary or secondary outcomes or in the rates of maternal or neonatal adverse events. CONCLUSIONS These results are consistent with the use of buprenorphine as an acceptable treatment for opioid dependence in pregnant women. (Funded by the National Institute on Drug Abuse; ClinicalTrials.gov number, NCT00271219.).
Significance of background optical properties, time-resolved information and optode arrangement in diffuse optical imaging of term neonates

The significance of accurate knowledge of background optical properties and time-resolved information in reconstructing images of hemodynamic changes in the neonatal brain from diffuse optical imaging data was studied using Monte Carlo (MC) simulation. A segmented anatomical magnetic resonance (MR) image and literature-derived optical properties for each tissue type were used to create a voxel-based anatomical model. Small absorbing perturbations were introduced into the anatomical model to simulate localized hemodynamic responses related to brain activation. Perturbation MC (pMC) was used as the primary method of image reconstruction. For comparison, reconstructions were also performed using the finite element method (FEM) to solve the diffusion approximation (DA) to the radiative transfer equation (RTE). The effect of optode layout was investigated using three different grids. Of the factors studied, the density of the optode grid was found to have the greatest effect on image quality. The use of time-resolved information significantly improved the spatial accuracy with all optode grids. Adequate knowledge and modeling of the optical properties of the background was found to significantly improve the spatial accuracy of the reconstructed images and make the recovery of contrast of absorption changes more consistent over simplified modeling. Localization accuracy of small perturbations was found to be 2–3 mm with accurate a priori knowledge of the background optical properties, when a grid with high optode density (>1 optode cm−2) was used.
Structural conservation of Notch receptors and ligands.

The Notch signalling pathway is an evolutionarily conserved cell-to-cell communication system utilized multiple times and in many tissues during development. The outcome of an interaction between Notch and its ligands is highly influenced by factors both extrinsic and intrinsic to Notch expressing cells, suggesting that Notch functions either directly or in parallel with other signalling systems to regulate cellular differentiation events. Protein domains common to all ligands and receptors of this system suggest conserved functional properties that likely relate to regulatory mechanisms for Notch signalling. Within this review, the known functional properties of these domains are analyzed with respect to their contributions to ligand/receptor interactions and Notch signalling.
Public Sector Pension Plans for Private Sector Workers

It has long been recognized that millions of Americans do not have access to pensions or retirement savings programs at work. Various efforts have been made to address this problem legislatively. None have been particularly successful. The Obama Administration proposed the creation of a federal automatic enrollment Individual Retirement Account (IRA), but Congress would not act. Several states took an interest in the problem but were hindered by a number of problems, most importantly by the question of Employee Retirement Income Security Act of 1974 (ERISA) coverage. President Obama directed the Department of Labor to find a way around the ERISA preemption, which it did by extending the 1975 safe harbor regulations to state-operated payroll deduction IRAs. California’s Auto IRA program became effective on January 1, 2017. Others will soon follow.
Statins suppress interleukin‐6‐induced monocyte chemo‐attractant protein‐1 by inhibiting Janus kinase/signal transducers and activators of transcription pathways in human vascular endothelial cells

Background and purpose: The mechanisms of anti‐inflammatory actions of statins, 3‐hydroxy‐3‐methylglutaryl CoA (HMG‐CoA) reductase inhibitors, remain unclear. We investigated the effects of statins on interleukin (IL)‐6‐induced monocyte chemo‐attractant protein (MCP)‐1 expression and monocyte chemotaxis.
Vectorial solution to double curl equation with generalized coulomb gauge for magneto static problems

In this paper, a solution to the double curl equation with generalized Coulomb gauge is proposed based on the vectorial representation of the magnetic vector potential. Coulomb gauge is applied to remove the null space of the curl operator and hence the uniqueness of the solution is guaranteed. However, as the divergence operator cannot act on the curl-conforming edge basis functions directly, the magnetic vector potential is used to be represented by nodal finite elements. Inspired by the mapping of Whitney forms by mathematical operators and Hodge operators, the divergence of the magnetic vector potential, as a whole, can be approximated by scalar basis functions. Hence, the magnetic vector potential can be expanded by vector basis functions, and the original equation can be rewritten in a generalized form and solved in a more natural and accurate way.
Detection of immunoglobulin gene rearrangement in B lymphoid malignancies by polymerase chain reaction gene amplification

Immunoglobulin heavy chain gene rearrangement serves as a marker of cell lineage and clonality in B lymphoproliferative disorders. We have used polymerase chain reaction (PCR) gene amplification to detect immunoglobulin gene rearrangements involving VH251. a heavy chain variable region preferentially utilized in B lymphoproliferative disorders. Using synthetic amplimers derived from VH251 and the heavy chain joining region, under conditions of high stringency, a homogeneous VH251‐specific fragment of approximately 350 bp could be amplified from leukaemic DNA. Of 53 cases of B lineage acute lymphoblastic leukaemia screened for VH2 51 rearrangement by PCR, 10 were positive. A background level of VH251 rearrangement could also be amplified from normal peripheral blood and bone marrow DNA. but a VH251 rearranged leukaemic clone representing 0‐01% of bone marrow mononuclear cells could be readily detected. The application of PCR to detect immunoglobulin gene rearrangement involving VH251 and potentially other preferentially utilized V regions provides a sensitive method both for tracking malignant B cells and for the study of normal B cell developmental pathways through which B lineage malignancies arise.
Autolytic Properties of Glycopeptide-Intermediate Staphylococcus aureus Mu50

ABSTRACT Whole-cell autolytic activity of prototypical glycopeptide-intermediate Staphylococcus aureus (GISA) Mu50 was reduced versus that of hetero-GISA Mu3 and glycopeptide-susceptible S. aureus, consistent with other GISA strains. In contrast, autolytic activity was relatively high in Mu50 crude cell walls and autolysin extracts against purified cell walls, reflecting the complexities of autolytic activity regulation.
Are the major European wine exporters able to price discriminate across their EU extra wine export destinations

In recent decades, New World has increased its wine export to European markets and became considerable in the global wine competition. However, the export share of traditional wine producers has decreased; Europe still remained market leader on world wine market. Moreover, the global wine market is characterised by progressively concentrated production, France, Italy and Spain accounting for about 50% of world wine production. Consequently, it is important to investigate what kind of pricing strategy the largest wine exporters of the world including France, Italy, Spain, Portugal and Germany can employ in their foreign wine export markets. The pricing behavior of five European wine exporters in their major destination markets is examined using a pricing-to-market (PTM) model for noncompetitive and exchange rate related pricing behaviour between 2000 and 2013. The results suggest that France and Italy were able to pursue price discrimination in many wine export destinations by contrast this advantage was not observable in a case of Spain, Portugal and Germany. The analysis of the asymmetric effects of exchange rates on wine export prices suggests that in many cases the depreciation of Australian, Hong Kong’s; Singapore’s dollar relating to euro had a greater impact than the appreciation while appreciation of Canadian and Singaporean dollar exceeded the effect of depreciation.
Prolonged Kappa Opioid Receptor Phosphorylation Mediated by G-protein Receptor Kinase Underlies Sustained Analgesic Tolerance*

Kappa opioid receptor (KOR) desensitization was previously shown to follow agonist-dependent phosphorylation of serine 369 by G-protein receptor kinase (GRK) and β-arrestin binding in transfected cells. To study the in vivo effects induced by phosphorylation of KOR(S369), C57Bl/6 mice were administered single or repeated doses of the KOR agonist, U50,488, and isolated brain glycoprotein was probed with an antibody, KOR-P, that specifically recognized phosphoserine 369 KOR. Western blot analysis using KOR-P antibody showed that labeling intensity increased after either single or repeated treatment of mice with U50,488 by 59 ± 22% and 101 ± 29%, respectively. In contrast, there was no change in labeling intensity by nonphosphoselective KOR antibodies following acute or chronic in vivo treatment with kappa agonist. Moreover, mice lacking GRK3 showed no increase in KOR-P labeling and developed significantly less analgesic tolerance following treatment with kappa agonist. The result suggests that tolerance to kappa agonists includes phosphorylation of serine 369 within KOR by GRK3. Recovery of analgesic potency and reduction of elevated KOR-P labeling in wild-type mice both required 2 weeks to return to base line. Consistent with these results, in vitro phosphorylation by GRK3 of KOR isolated from tolerant mice resulted in 46 ± 7% less 32P incorporation than in KOR isolated from untreated mice. In addition, in vitro 32P incorporation returned to base line levels only in KOR isolated from tolerant mice allowed to recover for 2 weeks. The coincident reversal of analgesic tolerance and slow return to a basal phosphorylation state matched the regeneration rate of functional kappa receptors following irreversible antagonism and suggested that receptor replacement rather than dephosphorylation was required to restore sensitivity.