Miracle-dz/UniFAR-FTUs huggingface dataset:
Neutralizing antibodies to HIV-1 envelope protect more effectively in vivo than those to the CD4 receptor

Neutralizing antibodies to HIV-1 envelope protect more effectively than an antibody to the CD4 cell receptor in rhesus macaques. Pushing the Envelope of HIV Protection Targeting the HIV envelope (Env) may be the best way to neutralize HIV. Pegu et al. report that broadly neutralizing antibodies to HIV Env provided more efficient protection than antibodies to the cellular receptor CD4 in rhesus macaques. Eliciting broadly neutralizing antibodies is a promising approach to preventing HIV infection. However, the best target for these antibodies has remained a matter of debate. The CD4 receptor is less variable than HIV Env, and antibodies against the CD4 receptor can potently block viral entry in vitro. Yet, when the authors compared the relative efficacy of CD4- and Env-targeting antibodies in preventing against HIV infection in macaques, they found that targeting the HIV Env may be preferable to CD4. HIV-1 infection depends on effective viral entry mediated by the interaction of its envelope (Env) glycoprotein with specific cell surface receptors. Protective antiviral antibodies generated by passive or active immunization must prevent these interactions. Because the HIV-1 Env is highly variable, attention has also focused on blocking the HIV-1 primary cell receptor CD4. We therefore analyzed the in vivo protective efficacy of three potent neutralizing monoclonal antibodies (mAbs) to HIV-1 Env compared to an antibody against the CD4 receptor. Protection was assessed after mucosal challenge of rhesus macaques with simian/HIV (SHIV). Despite its comparable or greater neutralization potency in vitro, the anti-CD4 antibody did not provide effective protection in vivo, whereas the HIV-1–specific mAbs VRC01, 10E8, and PG9, targeting the CD4 binding site, membrane-proximal, and V1V2 glycan Env regions, respectively, conferred complete protection, albeit at different relative potencies. These findings demonstrate the protective efficacy of broadly neutralizing antibodies directed to the HIV-1 Env and suggest that targeting the HIV-1 Env is preferable to the cell surface receptor CD4 for the prevention of HIV-1 transmission.
Observer-Based Adaptive Decentralized Fuzzy Fault-Tolerant Control of Nonlinear Large-Scale Systems With Actuator Failures

This paper investigates the adaptive fuzzy decentralized fault-tolerant control (FTC) problem for a class of nonlinear large-scale systems in strict-feedback form. The considered nonlinear system contains the unknown nonlinear functions, i.e., unmeasured states and actuator faults, which are modeled as both loss of effectiveness and lock-in-place. With the help of fuzzy logic systems to approximate the unknown nonlinear functions, a fuzzy adaptive observer is designed to estimate the unmeasured states. By combining the backstepping technique with the nonlinear FTC theory, a novel adaptive fuzzy decentralized FTC scheme is developed. It is proved that the proposed control approach can guarantee that all the signals of the resulting closed-loop system are bounded, and the tracking errors between the system outputs and the reference signals converge to a small neighborhood of zero by appropriate choice of the design parameters. Simulation results are provided to show the effectiveness of the control approach.
Defective PTEN regulation contributes to B cell hyperresponsiveness in systemic lupus erythematosus

Decreased expression of PTEN regulated by miR-7 contributes to B cell hyperresponsiveness and disturbed B cell homeostasis in SLE. “miR”roring Lupus Control Decreased expression of the B cell signaling inhibitor PTEN may contribute to lupus pathology. Wu et al. found that microRNA (miR)–mediated regulation of PTEN is altered in patients with the autoimmune disease systemic lupus erythematosus (SLE). Patients with SLE have hyperactivated B cells, which results in the production of autoantibodies. The authors found that decreased expression of PTEN in B cells from SLE patients contributes to this B cell hyperactivation. What’s more, they found that PTEN expression in these cells was regulated by miRs, and that blocking miR-7 could restore PTEN expression and function to that of healthy controls. These data support exploring miR-7 and PTEN as therapeutic targets for SLE. PTEN regulates normal signaling through the B cell receptor (BCR). In systemic lupus erythematosus (SLE), enhanced BCR signaling contributes to increased B cell activity, but the role of PTEN in human SLE has remained unclear. We performed fluorescence-activated cell sorting analysis in B cells from SLE patients and found that all SLE B cell subsets, except for memory B cells, showed decreased expression of PTEN compared with B cells from healthy controls. Moreover, the level of PTEN expression was inversely correlated with disease activity. We then explored the mechanisms governing PTEN regulation in SLE B cells. Notably, in normal but not SLE B cells, interleukin-21 (IL-21) induced PTEN expression and suppressed Akt phosphorylation induced by anti–immunoglobulin M and CD40L stimulation. However, this deficit was not primarily at the signaling or the transcriptional level, because IL-21–induced STAT3 (signal transducer and activator of transcription 3) phosphorylation was intact and IL-21 up-regulated PTEN mRNA in SLE B cells. Therefore, we examined the expression of candidate microRNAs (miRs) that could regulate PTEN: SLE B cells were found to express increased levels of miR-7, miR-21, and miR-22. These miRs down-regulated the expression of PTEN, and IL-21 stimulation increased the expression of miR-7 and miR-22 in both normal and SLE B cells. Indeed, a miR-7 antagomir corrected PTEN-related abnormalities in SLE B cells in a manner dependent on PTEN. Therefore, defective miR-7 regulation of PTEN contributes to B cell hyperresponsiveness in SLE and could be a new target of therapeutic intervention.
An Agent-Based Fuzzy Collaborative Intelligence Approach for Precise and Accurate Semiconductor Yield Forecasting

Yield forecasting is an important task for the manufacturer of semiconductors. Owing to the uncertainty in yield learning, it is, however, often difficult to make precise and accurate yield forecasts. To solve this problem, we propose an agent-based fuzzy collaborative intelligence approach that is modified from the fuzzy linear regression and back propagation network approach. In the proposed methodology, software agents rather than domain experts are used to improve the efficiency of collaboration. In addition, an agent decides the adjustable parameters by referencing to others so that the overall prediction performance can be improved in an effective way. In addition, we proposed a simple and effective way to aggregate the fuzzy forecasts by agents. Compared with the fuzzy linear regression and back propagation network approach, the proposed methodology reduced the average range and mean absolute percentage error by 18% and 99%, respectively.
Performance Analysis of Free-Space Optical Systems in Gamma-Gamma Fading

Atmospheric turbulence induced fading is one of the main impairments affecting free-space optics (FSO). Gamma-gamma fading has become the dominant fading model for FSO links because of its excellent agreement with measurement data for a wide range of turbulence conditions. In this paper, we express the bit error rate of intensity modulated FSO with direct detection in single-input single-output and multiple-input multiple-output gamma-gamma fading channels as generalized infinite power series with respect to the signal-to- noise ratio. For fast numerical evaluation these power series are truncated to a finite number of terms and an upper bound for the associated approximation error is provided. Another contribution of this paper is the extension of the well-known RF concepts of diversity and combining gain to FSO and gamma-gamma fading.
Backward Fuzzy Rule Interpolation

Fuzzy rule interpolation offers a useful means to enhancing the robustness of fuzzy models by making inference possible in sparse rule-based systems. However, in real-world applications of interconnected rule bases, situations may arise when certain crucial antecedents are absent from given observations. If such missing antecedents were involved in the subsequent interpolation process, the final conclusion would not be deducible using conventional means. To address this important issue, a new approach named backward fuzzy rule interpolation and extrapolation (BFRIE) is proposed in this paper, allowing the observations, which directly relate to the conclusion to be inferred or interpolated from the known antecedents and conclusion. This approach supports both backward interpolation and extrapolation which involve multiple fuzzy rules, with each having multiple antecedents. As such, it significantly extends the existing fuzzy rule interpolation techniques. In particular, considering that there may be more than one antecedent value missing in an application problem, two methods are proposed in an attempt to perform backward interpolation with multiple missing antecedent values. Algorithms are given to implement the approaches via the use of the scale and move transformation-based fuzzy interpolation. Experimental studies that are based on a real-world scenario are provided to demonstrate the potential and efficacy of the proposed work.
Developing Behavioral Theory With the Systematic Integration of Community Social Capital Concepts

Health behavior theories state that social environments influence health behaviors, but theories of how this occurs are relatively underdeveloped. This article systematically surveys community social capital concepts in health behavior literature and proposes a conceptual framework that integrates these concepts into existing behavioral theory. Fifty-three studies tested associations between community social capital concepts and physical activity (38 studies), smoking (19 studies), and diet (2 studies). Trustworthiness of community members was consistently associated with more health-promoting and less disease-promoting behaviors in 19 studies. Neighborly reciprocity showed mixed results in 10 studies. Reporting a good sense of community was associated with more physical activity in only 5 of 16 studies. Neighborhood collective efficacy, which includes social cohesion and informal social control, was inconsistently associated with behaviors in 22 studies. Behavioral social norms were associated with smoking and physical activity in 2 of 6 studies, and neighborhood modeling of physical activity was associated with increased activity in 12 of 17 studies, with 1 opposing result. This review identifies several community social capital–related concepts that are, at times, associated with both health-promoting and disease-promoting behaviors and often have no associations. Theory explains these findings by describing the relationships and interactions among these concepts. Using these findings, this article proposes a conceptual framework that integrates community social capital concepts into existing behavioral theory. Iterative empirically based theory development is needed to address these concepts, which affect behaviors. These results can also inform theoretically based community-based and socially tailored interventions.
Son preference and fertility in Bangladesh.

Researchers followed 22819 women from Matlab in rural Bangladesh with known sex composition of living children as of July 1982 for 3.5 years. They hypothesized that the effect of son preference on fertility is stronger in a population with adequate and available contraceptive service and relatively high contraceptive prevalence than a population with little to no contraceptive use or access. From July 1982-end of 1984 the contraceptive prevalence rate in the study area climbed from 35%-46%. It ranged from 17-23% in 1983-1985 (less than national average) in the comparison area. 58% of the women had additional children in the study area compared to 69% for the control area. The larger the family size the lower the percentage of women giving birth in both areas. This relationship was especially strong in families with = or + 3 children in the study area. Both areas had an association between sex composition of children and subsequent fertility. Further in both areas the percentage having additional children at each parity level was lower when the number of living sons was higher. this preference was strongest in the study area. For example the percentage difference between women having additional children at parity 2 and no son and those with 2 sons stood at 12% (79% vs. 67%). This difference stood at 4% in the comparison areas (79% vs. 75%). This supported their hypothesis. Overall at parities 70% indicating a strong effect of son preference on fertility in matlab. When women had at least 2 sons at parity 3 and 3 sons at parity 4 they generally did not have any additional children. If they had no daughters at these parities however they tended to have additional children. this indicated a preference for at least 1 living daughter.
Validity and Reliability of a Parental Self-Efficacy Instrument in the Healthy School Start Prevention Trial of Childhood Obesity

Introduction. Measures of parental self-efficacy (PSE) for healthy dietary or physical activity (PA) behaviors in children have been used in several studies; however, further psychometric validation of PSE for these behaviors is needed. The purpose of the present study was to evaluate the psychometric properties of a new PSE instrument. Methods. Mothers (n = 162) of 6-year-old children in the Healthy School Start prevention trial of childhood obesity responded to the instrument and a parent-report questionnaire on diet and PA in children. In addition, PA was objectively assessed by accelerometry. Results. Exploratory factor analysis yielded a structure composed of three factors of PSE for dietary and PA behaviors in children, and PSE was associated with parent-report of these behaviors. Internal consistency was good. Discussion. Preliminary support of the validity and reliability of the PSE instrument was provided. The measure may be useful in prevention and treatment trials of childhood obesity.
Evaluation of a Community Fitness Program for Adolescents with Cerebral Palsy

A community fitness program for adolescents with cerebral palsy was evaluated. Twenty-three subjects (mean age, 14.2 yr) completed a program of aerobics, strength training, and stretching three times a week for 10 weeks. They were tested three times before training, once at the end of the training,
The Association Between Influenza Vaccination and Other Preventative Health Behaviors in a Cohort of Pregnant Women

Objectives. Although pregnant women are a high-priority group for seasonal influenza vaccination, vaccination rates in this population remain below target levels. Previous studies have identified sociodemographic predictors of vaccine choice, but relationships between preconception heath behaviors and seasonal influenza vaccination are poorly understood. This prospective cohort study followed pregnant women during the 2010-2011 influenza season to determine if certain health behaviors were associated with vaccination status. Method. Participants were pregnant women receiving prenatal care from Kaiser Permanente Northwest and Kaiser Permanente Northern California. Women were surveyed about preconception smoking, alcohol consumption, and vitamin/supplement use. Vaccination data were obtained from health plan databases and state immunization records. Results. Data from 1,204 women were included in this analysis. Most participants (1,204; 66.4%) received a seasonal influenza vaccine during the study period. Women vaccinated prior to pregnancy were more likely to use a supplement containing folic acid (80%) or vitamin D (30%) compared with women who were vaccinated during pregnancy (72% and 15%, respectively) or unvaccinated women (62% and 12%, respectively, p < .001). Women vaccinated prior to or during pregnancy were more likely (75%) to have never smoked compared with women who were not vaccinated (70%, p = .005). There were no significant differences in alcohol use or household cigarette smoke exposure by vaccination group. Conclusions. Women who engaged in specific preconception health behaviors were more likely to receive seasonal influenza vaccination. Failure to participate in these health behaviors could alert health care practitioners to patients’ increased risk of remaining unvaccinated during pregnancy.
Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders

Molecular diagnosis of pediatric neurodevelopmental disorders by genomic sequencing is frequently informative and cost-effective and can affect clinical care. The End of the Odyssey? Neurodevelopmental disorders are common in children, but this group of conditions is heterogeneous. Although many of them can be diagnosed by standard clinical testing, more than half of the patients remain undiagnosed despite prolonged and costly evaluations, sometimes termed a “diagnostic Odyssey. ” Now, Soden et al. show that whole-exome or whole-genome sequencing, guided by the acuity of the patients’ conditions, can help solve the medical mystery for many of these children, including some who would otherwise remain undiagnosed, in much less time than traditional testing and with comparable costs. Neurodevelopmental disorders (NDDs) affect more than 3% of children and are attributable to single-gene mutations at more than 1000 loci. Traditional methods yield molecular diagnoses in less than one-half of children with NDD. Whole-genome sequencing (WGS) and whole-exome sequencing (WES) can enable diagnosis of NDD, but their clinical and cost-effectiveness are unknown. One hundred families with 119 children affected by NDD received diagnostic WGS and/or WES of parent-child trios, wherein the sequencing approach was guided by acuity of illness. Forty-five percent received molecular diagnoses. An accelerated sequencing modality, rapid WGS, yielded diagnoses in 73% of families with acutely ill children (11 of 15). Forty percent of families with children with nonacute NDD, followed in ambulatory care clinics (34 of 85), received diagnoses: 33 by WES and 1 by staged WES then WGS. The cost of prior negative tests in the nonacute patients was $19,100 per family, suggesting sequencing to be cost-effective at up to $7640 per family. A change in clinical care or impression of the pathophysiology was reported in 49% of newly diagnosed families. If WES or WGS had been performed at symptom onset, genomic diagnoses may have been made 77 months earlier than occurred in this study. It is suggested that initial diagnostic evaluation of children with NDD should include trio WGS or WES, with extension of accelerated sequencing modalities to high-acuity patients.
Ultrasound scanning in pregnancy: Consumer reactions

Abstract This study assessed the reactions of pregnant women who received ultrasound examination during their pregnancy. The subjects included 30 women who were diagnosed to have raised serum alpha foetoprotein (AFP) in a previous bloodtest and ultrasound scanning was therefore performed to further diagnose foetal abnormalities. Another 30 pregnant women receiving routine scanning for dates also served as subjects. The women were interviewed before and immediately after scanning and a questionnaire was sent to them four weeks after the examination. Results indicated that following scanning the subjects rated the procedure to be less distressing or less physically uncomfortable than they had initially expected. Most of them described the experience as ‘wonderful’ and ‘fine’. The follow-up opinion survey further confirmed that the women were satisfied with the procedures. Their responses highlighted the importance of giving feedback and allowing time to talk to the doctors when such an obstetric procedure w.
IGF2 is an actionable target that identifies a distinct subpopulation of colorectal cancer patients with marginal response to anti-EGFR therapies

Colorectal cancers that display reduced sensitivity to EGFR inhibition and strong IGF2 overexpression can be effectively treated by dual EGFR/IGF2 blockade. Better together Inhibitors of the epidermal growth factor receptor (EGFR) are already used to treat colorectal cancer. Unfortunately, although many patients’ tumors respond to these drugs, most of these responses are only partial and result in a slowing of tumor growth rather than a regression of the cancer. Now, Zanella et al. used a combination of patient samples and mouse xenografts to determine the reasons for the incomplete response to treatment and how it can be overcome. In some cases, more effective treatment just required a more complete inhibition of EGFR. Many of the other cancers overexpressed insulin-like growth factor 2 (IGF2), and the authors discovered that combining inhibitors of EGFR and IGF was an effective way to overcome resistance in these tumors. Among patients with colorectal cancer who benefit from therapy targeted to the epidermal growth factor receptor (EGFR), stable disease (SD) occurs more frequently than massive regressions. Exploring the mechanisms of this incomplete sensitivity to devise more efficacious treatments will likely improve patients’ outcomes. We tested therapies tailored around hypothesis-generating molecular features in patient-derived xenografts (“xenopatients”), which originated from 125 independent samples that did not harbor established resistance-conferring mutations. Samples from xenopatients that responded to cetuximab, an anti-EGFR agent, with disease stabilization displayed high levels of EGFR family ligands and receptors, indicating high EGFR pathway activity. Five of 21 SD models (23.8%) characterized by particularly high expression of EGFR and EGFR family members regressed after intensified EGFR blockade by cetuximab and a small-molecule inhibitor. In addition, a subset of cases in which enhanced EGFR inhibition was unproductive (6 of 16, 37.5%) exhibited marked overexpression of insulin-like growth factor 2 (IGF2). Enrichment of IGF2 overexpressors among cases with SD was demonstrated in the entire xenopatient collection and was confirmed in patients by mining clinical gene expression data sets. In functional studies, IGF2 overproduction attenuated the efficacy of cetuximab. Conversely, interception of IGF2-dependent signaling in IGF2-overexpressing xenopatients potentiated the effects of cetuximab. The clinical implementation of IGF inhibitors awaits reliable predictors of response, but the results of this study suggest rational combination therapies for colorectal cancer and provide evidence for IGF2 as a biomarker of reduced tumor sensitivity to anti-EGFR therapy and a determinant of response to combined IGF2/EGFR targeting.
Risk of breast cancer in relation to cigarette smoking

• To provide additional data on the smoking—breast cancer association, a case-control study of 456 cases of breast cancer and 1693 matched controls was conducted among participants in a cancer screening program. The adjusted risk of breast cancer for current smokers was 1.38 (95% confidence interval, 1.01 to 1.90). Analysis of smoking habits restricted to premenopausal women revealed a risk estimate of 2.33 (confidence interval, 1.10 to 4.96) among current smokers and increasing linear trends in risk for number of cigarettes smoked per day and for number of years of smoking. Although smokers had an earlier natural menopause than nonsmokers, there was no evidence of a protective effect of early menopause after adjustment for other factors. These findings suggest that smoking may increase the incidence of breast cancer, especially in premenopausal women. (Arch Intern Med1988;148:140-144)