Miracle-dz/UniFAR-FTUs huggingface dataset:
Alternative Splicing of FOXP3 Controls Regulatory T Cell Effector Functions and Is Associated With Human Atherosclerotic Plaque Stability

Rationale: Regulatory T (Treg) cells suppress immune responses and have been shown to attenuate atherosclerosis. The Treg cell lineage-specification factor FOXP3 (forkhead box P3) is essential for Treg cells’ ability to uphold immunologic tolerance. In humans, FOXP3 exists in several different isoforms, however, their specific role is poorly understood. Objective: To define the regulation and functions of the 2 major FOXP3 isoforms, FOXP3fl and FOXP3&Dgr;2, as well as to establish whether their expression is associated with the ischemic atherosclerotic disease. Methods and Results: Human primary T cells were transduced with lentiviruses encoding distinct FOXP3 isoforms. The phenotype and function of these cells were analyzed by flow cytometry, in vitro suppression assays and RNA-sequencing. We also assessed the effect of activation on Treg cells isolated from healthy volunteers. Treg cell activation resulted in increased FOXP3 expression that predominantly was made up of FOXP3&Dgr;2. FOXP3&Dgr;2 induced specific transcription of GARP (glycoprotein A repetitions predominant), which functions by tethering the immunosuppressive cytokine TGF (transforming growth factor)-&bgr; to the cell membrane of activated Treg cells. Real-time polymerase chain reaction was used to determine the impact of alternative splicing of FOXP3 in relation with atherosclerotic plaque stability in a cohort of >150 patients that underwent carotid endarterectomy. Plaque instability was associated with a lower FOXP3&Dgr;2 transcript usage, when comparing plaques from patients without symptoms and patients with the occurrence of recent (<1 month) vascular symptoms including minor stroke, transient ischemic attack, or amaurosis fugax. No difference was detected in total levels of FOXP3 mRNA between these 2 groups. Conclusions: These results suggest that activated Treg cells suppress the atherosclerotic disease process and that FOXP3&Dgr;2 controls a transcriptional program that acts protectively in human atherosclerotic plaques.
4D-PET reconstruction using a spline-residue model with spatial and temporal roughness penalties

4D reconstruction of dynamic positron emission tomography (dPET) data can improve the signal-to-noise ratio in reconstructed image sequences by fitting smooth temporal functions to the voxel time-activity-curves (TACs) during the reconstruction, though the optimal choice of function remains an open question. We propose a spline-residue model, which describes TACs as weighted sums of convolutions of the arterial input function with cubic B-spline basis functions. Convolution with the input function constrains the spline-residue model at early time-points, potentially enhancing noise suppression in early time-frames, while still allowing a wide range of TAC descriptions over the entire imaged time-course, thus limiting bias. Spline-residue based 4D-reconstruction is compared to that of a conventional (non-4D) maximum a posteriori (MAP) algorithm, and to 4D-reconstructions based on adaptive-knot cubic B-splines, the spectral model and an irreversible two-tissue compartment (‘2C3K’) model. 4D reconstructions were carried out using a nested-MAP algorithm including spatial and temporal roughness penalties. The algorithms were tested using Monte-Carlo simulated scanner data, generated for a digital thoracic phantom with uptake kinetics based on a dynamic [18F]-Fluromisonidazole scan of a non-small cell lung cancer patient. For every algorithm, parametric maps were calculated by fitting each voxel TAC within a sub-region of the reconstructed images with the 2C3K model. Compared to conventional MAP reconstruction, spline-residue-based 4D reconstruction achieved >50% improvements for five of the eight combinations of the four kinetics parameters for which parametric maps were created with the bias and noise measures used to analyse them, and produced better results for 5/8 combinations than any of the other reconstruction algorithms studied, while spectral model-based 4D reconstruction produced the best results for 2/8. 2C3K model-based 4D reconstruction generated the most biased parametric maps. Inclusion of a temporal roughness penalty function improved the performance of 4D reconstruction based on the cubic B-spline, spectral and spline-residue models.
One-Step Green Hydrothermal Synthesis of Few-Layer Graphene Oxide from Humic Acid

The conventional synthesis route of graphene oxide (GOG), based on Hummers method, suffers from explosion risk, environmental concerns and a tedious synthesis process, which increases production costs and hinders its practical applications. Herein, we report a novel strategy for preparing few-layer graphene oxide (GOH) from humic acid via simple hydrothermal treatment. The formation of GOH is mainly attributed to the hydrolysis, oxidation and aromatization of humic acid under hydrothermal conditions. The as-prepared few-layer GOH has typical morphology (thin and crumpled sheets with the thickness of ~3.2 nm), crystal structure (a Raman ID/IG ratio of 1.09) and chemical composition (an X-ray Photoelectron Spectroscopy (XPS) O/C atomic ratio of 0.36) of few-layer GOG. The thermally reduced GOH (r-GOH) delivers considerable area capacitance of 28 µF·cm−2, high rate capability and low electrochemical resistance as supercapacitor electrodes. The described hydrothermal process shows great promise for the cheap, green and efficient synthesis of few-layer graphene oxide for advanced applications.
The Affordable Care Act’s Impacts on Access to Insurance and Health Care for Low-Income Populations

The Patient Protection and Affordable Care Act (ACA) expands access to health insurance in the United States, and, to date, an estimated 20 million previously uninsured individuals have gained coverage. Understanding the law’s impact on coverage, access, utilization, and health outcomes, especially among low-income populations, is critical to informing ongoing debates about its effectiveness and implementation. Early findings indicate that there have been significant reductions in the rate of uninsurance among the poor and among those who live in Medicaid expansion states. In addition, the law has been associated with increased health care access, affordability, and use of preventive and outpatient services among low-income populations, though impacts on inpatient utilization and health outcomes have been less conclusive. Although these early findings are generally consistent with past coverage expansions, continued monitoring of these domains is essential to understand the long-term impact of the law for underserved populations.
Introduction of a hybrid treatment delivery system used for quality assurance in multi-catheter interstitial brachytherapy

Multi-catheter interstitial brachytherapy (iBT) is a treatment option for breast cancer patients after breast conserving surgery. Typically, only a few additional quality interventions after the first irradiation have been introduced to ensure the planned treatment delivery. Therefore, the purpose of this study is to show the possibilities of an electromagnetic tracking (EMT) system integrated into the afterloader for quality assurance (QA) in high-dose rate (HDR) iBT of patients with breast cancer. The hybrid afterloader system equipped with an electromagnetic sensor was used for all phantom and patient measurements. Phantom measurements were conducted to estimate the quality of different evaluation schemes. After a coherent point drift registration of the EMT traces to the reconstructed catheters based on computed tomograms the dwell positions (DP) were defined. Different fitting and interpolation methods were analyzed for the reconstruction of DPs. All estimated DPs were compared to the DPs defined in treatment planning. Until now, the implant geometry of 20 patients treated with HDR brachytherapy was acquired and explored. Regarding the reconstruction techniques, both fitting and interpolation were able to detect manually introduced shifts and swaps. Nonetheless, interpolation showed superior results (RMSE = 1.27 mm), whereas fitting seemed to be more stable to distortion and motion. The EMT system proved to be beneficial for QA in brachytherapy and furthermore, clinical feasibility was proven.
A Circularly Polarized Octagon-Star-Shaped Microstrip Patch Antenna With Conical Radiation Pattern

A new circularly polarized (CP) microstrip patch antenna with conical radiation pattern is proposed and investigated. The proposed CP antenna has a single feed, a low profile, and a very simple structure. The patch has an octagon-star shape, and can be considered as a superimposition of two square patches. By generating two orthogonal degenerated TM11 modes from the two superimposed square patches, omnidirectional CP radiation is achieved for the proposed antenna. The operation mechanism of the antenna is theoretically explained. A prototype of the proposed antenna is fabricated and measured. Measured results are consistent with the simulated and theoretical results. The antenna can produce a conical CP radiation pattern with a measured average axial ratio (AR) of 1.80 dB in the azimuth plane ( $\theta = 45$ °) and a measured 3-dB AR bandwidth covering the global positioning system L1 band.
Discovery of a Prefusion Respiratory Syncytial Virus F-Specific Monoclonal Antibody That Provides Greater In Vivo Protection than the Murine Precursor of Palivizumab

ABSTRACT Palivizumab, a humanized murine monoclonal antibody that recognizes antigenic site II on both the prefusion (pre-F) and postfusion (post-F) conformations of the respiratory syncytial virus (RSV) F glycoprotein, is the only prophylactic agent approved for use for the treatment of RSV infection. However, its relatively low neutralizing potency and high cost have limited its use to a restricted population of infants at high risk of severe disease. Previously, we isolated a high-potency neutralizing antibody, 5C4, that specifically recognizes antigenic site Ø at the apex of the pre-F protein trimer. We compared in vitro and in vivo the potency and protective efficacy of 5C4 and the murine precursor of palivizumab, antibody 1129. Both antibodies were synthesized on identical murine backbones as either an IgG1 or IgG2a subclass and evaluated for binding to multiple F protein conformations, in vitro inhibition of RSV infection and propagation, and protective efficacy in mice. Although 1129 and 5C4 had similar pre-F protein binding affinities, the 5C4 neutralizing activity was nearly 50-fold greater than that of 1129 in vitro. In BALB/c mice, 5C4 reduced the peak titers of RSV 1,000-fold more than 1129 did in both the upper and lower respiratory tracts. These data indicate that antibodies specific for antigenic site Ø are more efficacious at preventing RSV infection than antibodies specific for antigenic site II. Our data also suggest that site Ø-specific antibodies may be useful for the prevention or treatment of RSV infection and support the use of the pre-F protein as a vaccine antigen. IMPORTANCE There is no vaccine yet available to prevent RSV infection. The use of the licensed antibody palivizumab, which recognizes site II on both the pre-F and post-F proteins, is restricted to prophylaxis in neonates at high risk of severe RSV disease. Recommendations for using passive immunization in the general population or for therapy in immunocompromised persons with persistent infection is limited because of cost, determined from the high doses needed to compensate for its relatively low neutralizing potency. Prior efforts to improve the in vitro potency of site II-specific antibodies did not translate to significant in vivo dose sparing. We isolated a pre-F protein-specific, high-potency neutralizing antibody (5C4) that recognizes antigenic site Ø and compared its efficacy to that of the murine precursor of palivizumab (antibody 1129) matched for isotype and pre-F protein binding affinities. Our findings demonstrate that epitope specificity is an important determinant of antibody neutralizing potency, and defining the mechanisms of neutralization has the potential to identify improved products for the prevention and treatment of RSV infection.
Nonexistence of generalized bent functions and the quadratic norm form equations

We obtain the nonexistence of generalized bent functions (GBFs) from (\ZZ/t\ZZ)^n to \ZZ/t\ZZ (called type [n,t]), for a large new class. Specifically, by showing certain quadratic norm form equations have no integral points, we obtain the universal nonexistence of GBFs with type [n, 2p^e] for all sufficiently large p with respect to n and (p-1)/\ord_2(p), and by computational methods with a well accepted hypothesis (generalized Riemann hypothesis), we also guarantee some nonexistence results for relative small prime p.
Spontaneous and Traumatic Splenic Rupture: Retrospective Clinical, B-Mode and CEUS Analysis in 62 Patients

Abstract Introduction Both B-mode ultrasound and contrast-enhanced ultrasound (CEUS) are well established procedures when diagnosing traumatic splenic ruptures (TSR). To date, there are no data about CEUS patterns in spontaneous splenic ruptures (SSR). It remains unknown whether TSR and SSR differ with respect to clinical characteristics, B-mode and CEUS characteristics. Patients and Methods Between 12/2003 and 2/2010, n=33 SSRs and n=29 TSRs were diagnosed in a tertiary referral center. All patients were examined with B-mode and CEUS, and clinical data and the outcome were retrospectively analyzed. Results Patients with SSR were significantly older than patients with TSR (62 years vs. 44 years; p=0.01). The 4-week mortality was significantly higher in SSR than in TSR (36% vs. 0%; p=0.001). No differences between the grading of TSR and SSR could be shown in B-mode or in CEUS. Notably, CEUS was significantly superior to B-mode with respect to the grading of splenic ruptures (p=0.01). Therefore, therapeutic management was influenced by CEUS. Conclusion There are differences between SSR and TSR, especially concerning clinical data (age, course of disease and mortality). Regarding the sonographic pattern, SSR and TSR show identical grading. When splenic rupture is suspected, CEUS should always be performed to identify patients at risk who require interventional procedures.
Resistance to Glycopeptide Antibiotics in the Teicoplanin Producer Is Mediated by van Gene Homologue Expression Directing the Synthesis of a Modified Cell Wall Peptidoglycan

ABSTRACT Glycopeptide resistance has been studied in detail in enterococci and staphylococci. In these microorganisms, high-level resistance is achieved by replacing the C-terminal d-alanyl-d-alanine of the nascent peptidoglycan with d-alanyl-d-lactate or d-alanyl-d-serine, thus reducing the affinities of glycopeptides for cell wall targets. Reorganization of the cell wall is directed by the expression of the van gene clusters. The identification of van gene homologs in the genomes of several glycopeptide-producing actinomycetes suggests the involvement of a similar self-resistance mechanism to avoid suicide. This report describes a comprehensive study of self-resistance in Actinoplanes teichomyceticus ATCC 31121, the producer of the clinically relevant glycopeptide teicoplanin. A. teichomyceticus ATCC 31121 showed a MIC of teicoplanin of 25 μg/ml and a MIC of vancomycin of 90 μg/ml during vegetative growth. The vanH, vanA, and vanX genes of A. teichomyceticus were found to be organized in an operon whose transcription was constitutive. Analysis of the UDP-linked peptidoglycan precursors revealed the presence of UDP-glycomuramyl pentadepsipeptide terminating in d-alanyl-d-lactate. No trace of precursors ending in d-alanyl-d-alanine was detected. Thus, the van gene complex was transcribed and expressed in the genetic background of A. teichomyceticus and conferred resistance to vancomycin and teicoplanin through the modification of cell wall biosynthesis. During teicoplanin production (maximum productivity, 70 to 80 μg/ml), the MIC of teicoplanin remained in the range of 25 to 35 μg/ml. Teicoplanin-producing cells were found to be tolerant to high concentrations of exogenously added glycopeptides, which were not bactericidal even at 5,000 μg/ml.
Contact‐Free Screening of Atrial Fibrillation by a Smartphone Using Facial Pulsatile Photoplethysmographic Signals

Background We aimed to evaluate a novel method of atrial fibrillation (AF) screening using an iPhone camera to detect and analyze photoplethysmographic signals from the face without physical contact by extracting subtle beat‐to‐beat variations of skin color that reflect the cardiac pulsatile signal. Methods and Results Patients admitted to the cardiology ward of the hospital for clinical reasons were recruited. Simultaneous facial and fingertip photoplethysmographic measurements were obtained from 217 hospital inpatients (mean age, 70.3±13.9 years; 71.4% men) facing the front camera and with an index finger covering the back camera of 2 independent iPhones before a 12‐lead ECG was recorded. Backdrop and background light intensity was monitored during signal acquisition. Three successive 20‐second (total, 60 seconds) recordings were acquired per patient and analyzed for heart rate regularity by Cardiio Rhythm (Cardiio Inc, Cambridge, MA) smartphone application. Pulse irregularity in ≥1 photoplethysmographic readings or 3 uninterpretable photoplethysmographic readings were considered a positive AF screening result. AF was present on 12‐lead ECG in 34.6% (n=75/217) patients. The Cardiio Rhythm facial photoplethysmographic application demonstrated high sensitivity (95%; 95% confidence interval, 87%–98%) and specificity (96%; 95% confidence interval, 91%–98%) in discriminating AF from sinus rhythm compared with 12‐lead ECG. The positive and negative predictive values were 92% (95% confidence interval, 84%–96%) and 97% (95% confidence interval, 93%–99%), respectively. Conclusions Detection of a facial photoplethysmographic signal to determine pulse irregularity attributable to AF is feasible. The Cardiio Rhythm smartphone application showed high sensitivity and specificity, with low negative likelihood ratio for AF from facial photoplethysmographic signals. The convenience of a contact‐free approach is attractive for community screening and has the potential to be useful for distant AF screening.
A Robotic Approach to Understanding the Role and the Mechanism of Vicarious Trial-And-Error in a T-Maze Task

Vicarious trial-and-error (VTE) is a behavior observed in rat experiments that seems to suggest self-conflict. This behavior is seen mainly when the rats are uncertain about making a decision. The presence of VTE is regarded as an indicator of a deliberative decision-making process, that is, searching, predicting, and evaluating outcomes. This process is slower than automated decision-making processes, such as reflex or habituation, but it allows for flexible and ongoing control of behavior. In this study, we propose for the first time a robotic model of VTE to see if VTE can emerge just from a body-environment interaction and to show the underlying mechanism responsible for the observation of VTE and the advantages provided by it. We tried several robots with different parameters, and we have found that they showed three different types of VTE: high numbers of VTE at the beginning of learning, decreasing numbers afterward (similar VTE pattern to experiments with rats), low during the whole learning period, and high numbers all the time. Therefore, we were able to reproduce the phenomenon of VTE in a model robot using only a simple dynamical neural network with Hebbian learning, which suggests that VTE is an emergent property of a plastic and embodied neural network. From a comparison of the three types of VTE, we demonstrated that 1) VTE is associated with chaotic activity of neurons in our model and 2) VTE-showing robots were robust to environmental perturbations. We suggest that the instability of neuronal activity found in VTE allows ongoing learning to rebuild its strategy continuously, which creates robust behavior. Based on these results, we suggest that VTE is caused by a similar mechanism in biology and leads to robust decision making in an analogous way.
Assessing the impacts of global warming on forest pest dynamics

Forest insects and pathogens are the most pervasive and important agents of disturbance in North American forests, affecting an area almost 50 times larger than fire and with an economic impact nearly five times as great. The same attributes that result in an insect herbivore being termed a “pest” predispose it to disruption by climate change, particularly global warming. Although many pest species have co-evolved relationships with forest hosts that may or may not be harmful over the long term, the effects on these relationships may have disastrous consequences. We consider both the data and models necessary to evaluate the impacts of climate change, as well as the assessments that have been made to date. The results indicate that all aspects of insect outbreak behavior will intensify as the climate warms. This reinforces the need for more detailed monitoring and evaluations as climatic events unfold. Luckily, we are well placed to make rapid progress, using software tools, databases, and the models that are already available.
A volitional help sheet to reduce binge drinking in students: a randomized exploratory trial.

AIMS This study tested the ability of a volitional help sheet (VHS) to decrease binge drinking in UK students. METHODS Fifty-six participants were randomly allocated to one of three conditions: control, active control or VHS as part of a questionnaire-based study. RESULTS There were significant decreases in units of alcohol consumed and self-reported binge drinking frequency in the VHS condition, but not in either of the control conditions. CONCLUSIONS The findings support use of the VHS to help people to reduce their alcohol consumption and binge drinking.
Screw dislocation in hcp Ti : DFT dislocation excess energies and metastable core structures

An extensive DFT search of (meta)stable structures of the screw dislocation in hcp-Ti is presented. It reveals that the stable core structures are never basal but always prismatic. This prismatic core dissociates into two partial dislocations in the same or neighboring prismatic planes depending on the initial position of the dislocation line, leading to either a symmetric or an asymmetric core. An alternative way of defining the core region from an electronic structure point of view is also proposed. It evidences clearly the symmetric or asymmetric character of the cores. We then introduce an ansatz for a straightforward and fast calculation of the excess energy, per unit length of dislocation, of a screw dislocation applicable to DFT calculations, in the cluster approach. The method is first validated on calculations of a screw dislocation in hcp-Ti, performed with an EAM potential from which exact excess energies can be extracted. Then, it is shown that it does work in a DFT calculation, through its application to the same screw dislocation in hcp-Ti with an accuracy of 8.4 meV/Å (1.8% of the excess energy for a cluster of 126 atoms per plane normal to the dislocation line). The comparison of the excess energies of the symmetric and assymmetric cores, calculated with the proposed ansatz, reveals that their energy difference is within the uncertainty of the method, which implies that the potential energy surface is very flat and that there could be many metastable core structures in hcp-Ti.