Miracle-dz/UniFAR-FTUs huggingface dataset:
Heterogeneous neutralizing antibody and antibody-dependent cell cytotoxicity responses in HIV-1 elite controllers

Objective:To determine the spectrum of antiviral antibodies in HIV-1-infected individuals in whom viral replication is spontaneously undetectable, termed HIV controllers (HICs). Design:Multicenter French trial ANRS EP36 studying the viral control in HICs. Methods:Neutralizing Antibody (nAb) activities (neutralization assay, competition with broadly reactive monoclonal antibodies, and reactivity against the viral MPER gp41 region), FcγR-mediated antiviral activities, antibody-dependent cell cytotoxicity (ADCC), as well as autoantibody levels, were quantified in plasma from 22 controllers and from viremic individuals. The levels of these different antibody responses and HIV-specific CD8 T cell responses quantified by enzyme-linked immunosorbent spot (ELISPOT) IFNγ assay were compared in each controller. Results:The levels of antibody against the gp120 CD4 binding site, gp41, as well as Env epitopes near to the sites bound by broadly nAbs 2F5 and 1b12 were not different between HICs and viremic individuals. We did not find significant autoantibody levels in HICs. The magnitude and breadth of nAbs were heterogeneous in HICs but lower than in viremic individuals. The levels of nAbs using FcγR-mediated assay inhibition were similar in both groups. Regardless of the type of antibody tested, there was no correlation with HIV-specific CD8 T cell responses. ADCC was detectable in all controllers tested and was significantly higher than in viremic individuals (P < 0.0002). Conclusion:There was no single anti-HIV-1 antibody specificity that was a clear correlate of immunity in controllers. Rather, for most antibody types, controllers had the same or lower levels of nAbs than viremic individuals, with the possible exception of ADCC antibodies.
Excitation–Contraction Coupling in Na+–Ca2+ Exchanger Knockout Mice: Reduced Transsarcolemmal Ca2+ Flux

Cardiac-specific Na+–Ca2+ exchanger (NCX) knockout (KO) mice surprisingly survive into adulthood without compensatory changes in protein expression levels. To determine how cardiac function is maintained in the absence of NCX, we investigated membrane currents, intracellular Ca2+, and action potentials (APs) in whole cell patch-clamped myocytes from wild-type (WT) and NCX knockout mice. There was no difference in resting Ca2+ or sarcoplasmic reticular Ca2+ load between KO and WT. During prolonged caffeine exposure, the decrease of the Ca2+ transient was drastically slowed in KO versus WT myocytes, indicating that no alternative Ca2+-extrusion mechanism is upregulated to compensate for the absence of NCX. Peak L-type Ca2+ current (ICa) was reduced by 62% in KO myocytes compared with WT. Nevertheless, the corresponding Ca2+ transients were similar, implying an increase in the gain of excitation–contraction coupling in KO cells. APs recorded from KO cells repolarized more rapidly than in WT. In WT myocytes, applying a KO AP waveform voltage clamp reduced Ca2+ influx via ICa by 59% compared with WT AP waveform clamps. Again, the corresponding Ca2+ transients remained similar. Our findings indicate that NCX KO myocytes limit Ca2+ influx to ≈20% of that in WT by reducing ICa and by abbreviating the AP. Contractility is maintained by an increase in the gain of excitation–contraction coupling resulting from both a more rapid repolarization of the AP and an as yet unidentified AP-independent mechanism.
Linear Precoding for MIMO Systems with Low-Complexity Receivers

This paper considers large multiple-input multiple-output (MIMO) communication systems with linear precoding and linear minimum mean-squared error (LMMSE) equalization based on the iterative conjugate gradient (CG) algorithm. Convergence of the CG algorithm is fast when the eigenvalues of the received signal's covariance matrix are clustered, suggesting that mean-squared error and receiver complexity can be managed with judicious precoder design. In order to accelerate convergence of an iterative CG receiver, we incorporate constraints on two measures of eigenvalue clustering into the precoder design. Closed-form solutions to the optimal precoders are derived using majorization theory and convex optimization techniques. We show that if there are constraints on receiver complexity, the proposed precoders can improve performance for large MIMO systems operating over slowly time-varying fading channels.
On Uniform Global Asymptotic Stability of Nonlinear Discrete-Time Systems With Applications

This paper presents new characterizations of uniform global asymptotic stability for nonlinear and time-varying discrete-time systems. Under mild assumptions, it is shown that weak zero-state detectability is equivalent to uniform global asymptotic stability for globally uniformly stable systems. By employing the notion of reduced limiting systems, another characterization of uniform global asymptotic stability is proposed on the basis of the detectability for the reduced limiting systems associated with the original system. As a by-product, we derive a generalized, discrete-time version of the well-known Krasovskii-LaSalle theorem for general time-varying, not necessarily periodic, systems. Furthermore, we apply the obtained stability results to analyze uniform asymptotic stability of cascaded time-varying systems, and show that some technical assumptions in recent papers can be relaxed. Through a practical application, it is shown that our results play a similar role to the classic LaSalle invariance principle in guaranteeing attractivity, noting that reduced limiting systems are used instead of the original system. To validate the conceptual characterizations, we study the problem of sampled-data stabilization for the benchmark example of nonholonomic mobile robots via the exact discrete-time model rather than approximate models. This case study also reveals that in general, sampled-data systems may become non-periodic even though their original continuous-time system is periodic. A novel sampled-data stabilizer design is proposed using the new stability results and is supported via simulation results
Do mood instability symptoms in epilepsy represent formal bipolar disorder?

We aimed to assess rates of bipolar symptoms versus bipolar disorder in epilepsy, and the effect of bipolar symptoms on quality of life (QOL) in epilepsy. Bipolar, disability, and QOL instruments were administered to 99 tertiary epilepsy center patients. Patients who scored positive on the Mood Disorder Questionnaire (MDQ) also completed depression scales and a structured psychiatric interview. Results indicated MDQ+ patients (10.1%) had worse QOL and more work, social, and family life disruptions. Most MDQ+ patients did not have bipolar disorder. There was close overlap between depressive and bipolar symptomatology. Based on results of this study, bipolar symptom is not synonymous with bipolar disorder. Symptoms picked up by the MDQ may be epilepsy‐related depressive symptoms. Bipolar symptoms are associated with more disability, worse QOL, and may have treatment implications.
Distribution of Target Registration Error for Anisotropic and Inhomogeneous Fiducial Localization Error

In point-based rigid-body registration, target registration error (TRE) is an important measure of the accuracy of the performed registration. The registration's accuracy depends on the fiducial localization error (FLE) which, in turn, is due to the measurement errors in the points (fiducials) used to perform the registration. FLE may have different characteristics and distributions at each point of the registering data sets, and along each orthogonal axis. Previously, the distribution of TRE was estimated based on the assumption that FLE has an independent, identical, and isotropic or anisotropic distribution for each point in the registering data sets. In this article, we present a general solution based on the maximum likelihood (ML) algorithm that estimates the distribution of TRE for the cases where FLE has an independent, identical or inhomogeneous, isotropic or anisotropic, distribution at each point in the registering data sets, and when an algorithm is available that is capable of calculating the optimum registration to first order. Mathematically, we show that the proposed algorithm simplifies to the one proposed by Fitzpatrick and West when FLE has an independent, identical, and isotropic distribution in the registering data sets. Furthermore, we use numerical simulations to show that the proposed algorithm accurately estimates the distribution of TRE when FLE has an independent, inhomogeneous, and anisotropic distribution in the registering data sets.
Radiation-induced mitotic catastrophe in FANCD2 primary fibroblasts

Abstract Purpose: As the Fanconi anemia (FA) pathway is required for appropriate cell cycle progression through mitosis and the completion of cell division, the aim of the present study was to determine the destiny of FA cells after irradiation in vitro and to elucidate any difference in radiosensitivity between FA and control cells. Materials and methods: Analyses of phosphorylated histone H2AX (γ-H2AX) foci, micronuclei formation and cell cycle analysis were performed in unirradiated (0 min) and irradiated primary FA fibroblasts and in a control group at different post-irradiation times (30 min, 2 h, 5 h and 24 h). Results: The accumulation of γ-H2AX foci in irradiated FA fibroblasts was observed. At 24 h post-irradiation, 57% of FA cells were γ-H2AX foci-positive, significantly higher than in the control (p < 0.01). The cell cycle analysis has shown the transient G2/M arrest in irradiated FA fibroblasts. The portion of cells in the G2/M phase showed initial increase at 30 min post-irradiation and afterwards decreased over time reaching the pretreatment level 24 h after irradiation. Irradiated FA fibroblasts progressed to abnormal mitosis, as is shown by the production of cells with different nuclear morphologies from binucleated to multinucleated surrounded with micronuclei, and also by a high percentage of foci-positive micronuclei. The majority of radiation-induced micronuclei were γ-H2AX foci-positive, indicating that radiation-induced micronuclei contain fragments of damaged chromosomes. In contrast, in the control group, most of the micronuclei were classified as γ-H2AX foci-negative, which indicates that cells with unrepaired damage were blocked before entering mitosis. Conclusion: The results clearly indicate that mitotic catastrophe might be an important cell-death mechanism involved in the response of FA fibroblasts to ionizing radiation.
If Programs of Study are the Solution, What is the Problem?

Programs of study are the most recent in a series of federal efforts to create a more transparent and rational system for school-to-work transition for all youth. The current article places this construct in the context of today's labor market and the new focus on college and career readiness for all students. It then provides evidence indicating that all students need a mix of academic, employability, and technical skills to graduate ready for college and careers. Furthermore, it posits that effective programs of study enhance student engagement with school, improve academic and technical achievement, and facilitate students’ transition to continued education beyond high school and into the workplace.
FIREBALL: detector, data acquisition and reduction

The Faint Intergalactic Redshifted Emission Balloon (FIREBALL) had its first scientific flight in June 2009. The instrument combines microchannel plate detector technology with fiber-fed integral field spectroscopy on an unstable stratospheric balloon gondola platform. This unique combination poses a series of calibration and data reduction challenges that must be addressed and resolved to allow for accurate data analysis. We discuss our approach and some of the methods we are employing to accomplish this task.
Caffeine supplementation and peak anaerobic power output

Abstract The aim of this study was to investigate the effects of caffeine supplementation on peak anaerobic power output (Wmax). Using a counterbalanced, randomised, double-blind, placebo-controlled design, 14 well-trained men completed three trials of a protocol consisting of a series of 6-s cycle ergometer sprints, separated by 5-min passive recovery periods. Sprints were performed at progressively increasing torque factors to determine the peak power/torque relationship and Wmax. Apart from Trial 1 (familiarisation), participants ingested a capsule containing 5 mg·kg−1 of caffeine or placebo, one hour before each trial. The effects of caffeine on blood lactate were investigated using capillary samples taken after each sprint. The torque factor which produced Wmax was not significantly different (p ≥ 0.05) between the caffeine (1.15 ± 0.08 N·m·kg−1) and placebo (1.13 ± 0.10 N·m·kg−1) trials. There was, however, a significant effect (p < 0.05) of supplementation on Wmax, with caffeine producing a higher value (1885 ± 303 W) than placebo (1835 ± 290 W). Analysis of the blood lactate data revealed a significant (p < 0.05) torque factor × supplement interaction with values being significantly higher from the sixth sprint (torque factor 1.0 N·m·kg−1) onwards following caffeine supplementation. The results of this study confirm previous reports that caffeine supplementation significantly increases blood lactate and Wmax. These findings may explain why the majority of previous studies, which have used fixed-torque factors of around 0.75 N·m·kg−1 and thereby failing to elicit Wmax, have failed to find an effect of caffeine on sprinting performance.
Project ACTS II: organ donation education for African American adults.

OBJECTIVE Project ACTS "About Choices in Transplantation and Sharing" is a culturally sensitive intervention designed to address organ donation concerns among African American adults. Our study sought to evaluate the efficacy of two versions of the Project ACTS intervention and to determine whether reviewing materials in a group setting would be more effective at increasing participants' interest in organ and tissue donation than allowing participants to review the materials at home with friends and family. DESIGN A pre-post simple factorial experimental design was used to assess differences between intervention package (Project ACTS I vs II) and mode of delivery (group vs take home). METHODS Participants completed a baseline and 1-year follow-up assessment of donation-related knowledge, attitudes, and interest. MAIN OUTCOME MEASURES A summed score that represents participants' interest in being recognized as an organ donor on their driver's license, via donor card, and by talking to family. RESULTS From baseline to follow-up, participants increased their knowledge, attitudes, and interest in being recognized as an organ donor regardless of intervention package (Ps<.05). Regarding setting, participants who reviewed materials in a group setting demonstrated greater increase from baseline to follow-up in interest in organ donation (beta=.22, P<.01) and positive attitudes toward donation (beta=.22, P<.05) than those who were allowed to review materials at home with friends and family. CONCLUSION Project ACTS I and II are equally efficacious; reviewing the intervention in a group setting may be necessary for low vested interest/high ambivalence health behaviors such as organ donation.
Bayesian Estimation of Possibly Similar Yield Densities: Implications for Rating Crop Insurance Contracts

The Agricultural Act of 2014 solidified insurance as the cornerstone of U.S. agricultural policy. The Congressional Budget Office (2014) estimates that this act will increase spending on agricultural insurance programs by $5.7 billion to a total of $89.8 billion over the next decade. In light of the sizable resources directed toward these programs, accurate rating of insurance contracts is of the utmost importance to producers, private insurance companies, and the federal government. Unlike most forms of insurance, agricultural insurance is plagued by a paucity of spatially correlated data. A novel interpretation of Bayesian Model Averaging is used to estimate a set of possibly similar densities that offers greater efficiency if the set of densities are similar while seemingly not losing any if the set of densities are dissimilar. Simulations indicate that finite sample performance—in particular small sample performance—is quite promising. The proposed approach does not require knowledge of the form or extent of any possible similarities, is relatively easy to implement, admits correlated data, and can be used with either parametric or nonparametric estimators. We use the proposed approach to estimate U.S. crop insurance premium rates for area-type programs and develop a test to evaluate its efficacy. An out-of-sample game between private insurance companies and the federal government highlights the policy implications for a variety of crop-state combinations. Consistent with the simulation results, the performance of the proposed approach with respect to rating area-type insurance—in particular small sample performance—remains quite promising.
Simultaneous stimulation of sedoheptulose 1,7‐bisphosphatase, fructose 1,6‐bisphophate aldolase and the photorespiratory glycine decarboxylase‐H protein increases CO 2 assimilation, vegetative biomass and seed yield in Arabidopsis

Summary In this article, we have altered the levels of three different enzymes involved in the Calvin–Benson cycle and photorespiratory pathway. We have generated transgenic Arabidopsis plants with altered combinations of sedoheptulose 1,7‐bisphosphatase (SBPase), fructose 1,6‐bisphophate aldolase (FBPA) and the glycine decarboxylase‐H protein (GDC‐H) gene identified as targets to improve photosynthesis based on previous studies. Here, we show that increasing the levels of the three corresponding proteins, either independently or in combination, significantly increases the quantum efficiency of PSII. Furthermore, photosynthetic measurements demonstrated an increase in the maximum efficiency of CO 2 fixation in lines over‐expressing SBPase and FBPA. Moreover, the co‐expression of GDC‐H with SBPase and FBPA resulted in a cumulative positive impact on leaf area and biomass. Finally, further analysis of transgenic lines revealed a cumulative increase of seed yield in SFH lines grown in high light. These results demonstrate the potential of multigene stacking for improving the productivity of food and energy crops.
In Vivo Efficacy of Measles Virus Fusion Protein-Derived Peptides Is Modulated by the Properties of Self-Assembly and Membrane Residence

ABSTRACT Measles virus (MV) infection is undergoing resurgence and remains one of the leading causes of death among young children worldwide despite the availability of an effective measles vaccine. MV infects its target cells by coordinated action of the MV hemagglutinin (H) and fusion (F) envelope glycoproteins; upon receptor engagement by H, the prefusion F undergoes a structural transition, extending and inserting into the target cell membrane and then refolding into a postfusion structure that fuses the viral and cell membranes. By interfering with this structural transition of F, peptides derived from the heptad repeat (HR) regions of F can inhibit MV infection at the entry stage. In previous work, we have generated potent MV fusion inhibitors by dimerizing the F-derived peptides and conjugating them to cholesterol. We have shown that prophylactic intranasal administration of our lead fusion inhibitor efficiently protects from MV infection in vivo. We show here that peptides tagged with lipophilic moieties self-assemble into nanoparticles until they reach the target cells, where they are integrated into cell membranes. The self-assembly feature enhances biodistribution and the half-life of the peptides, while integration into the target cell membrane increases fusion inhibitor potency. These factors together modulate in vivo efficacy. The results suggest a new framework for developing effective fusion inhibitory peptides. IMPORTANCE Measles virus (MV) infection causes an acute illness that may be associated with infection of the central nervous system (CNS) and severe neurological disease. No specific treatment is available. We have shown that fusion-inhibitory peptides delivered intranasally provide effective prophylaxis against MV infection. We show here that specific biophysical properties regulate the in vivo efficacy of MV F-derived peptides.
Parkinson's disease: imaging update

Purpose of reviewWe aim to review recent neuroimaging contributions to our understanding of the cause and pathogenesis of Parkinson's disease, as well as treatment-related complications of disease, with a focus on functional anatomy and neurochemistry. Recent findingsRecent reports describe altered dopaminergic activity in extrastriatal regions, as well as changes in other monoaminergic systems, such as serotonin. Attempts to correlate altered dopaminergic function with personality traits have also been described in the last year. The role of different markers of presynaptic dopaminergic integrity in the assessment of disease progression is discussed, as is the role of biomarkers in detection of preclinical disease. Cerebral activation studies not only confirm altered function of cortico-striatal-thalamo-cortical loops in Parkinson's, but also emphasize the importance of networks involving the cerebellum. The ability to detect changes in synaptic availability of dopamine using positron emission tomography with [11C]raclopride is reviewed, including the application to detect altered levels of dopamine in response to pharmacological, mechanical and behavioral stimuli. Such studies have been used to identify altered patterns associated with the development of motor fluctuations, as well as a biochemical substrate underlying the placebo effect in Parkinson's. SummaryFunctional imaging studies can provide novel insights into the etiopathogenesis of Parkinson's disease, as well as the mechanisms that contribute to complications of long-term therapy. They also shed light on the mechanisms that may underly behavioral changes and benefit derived from surgical interventions.
Monitoring Pressure Augmentation in Patients With Ischemic Penumbra Using Continuous Electroencephalogram: Three Cases and a Review of the Literature

Background: Continuous electroencephalography (CEEG) is a sensitive, noninvasive surrogate monitor of cerebral blood flow (CBF). Changes in CBF can be seen as changes in the frequencies on the CEEG. This case series suggests that increase in CEEG frequencies may be used to detect improved CBF following pressure augmentation such as with treatment of vasospasm from subarachnoid hemorrhage (SAH) or acute thrombosis from ischemic stroke. The application of this observation to clinical decision-making has not been clearly defined and requires further study. Methods: Case series and imaging. Results: We present 3 patients with ischemic penumbras either from vasospasm from SAH or thrombosis from acute ischemic stroke. All patients were monitored on CEEG and found to have lateralized slowing. During pressure augmentation, the lateralized slowing improved in frequency, which corresponded with improvement in the patients’ neurological examinations. Conclusion: Continuous electroencephalography may be used as a noninvasive monitor to allow for individualization of pressure augmentation in cases of vasospasm from SAH or in cases of acute ischemic strokes. This customized approach may allow for less morbidity associated with pressure augmentation in patients who otherwise may have dysfunction of their intracerebral autoregulation.