Miracle-dz/UniFAR-FTUs huggingface dataset:
Disruption of chemoreceptor signalling arrays by high levels of CheW, the receptor–kinase coupling protein

During chemotactic signalling by Escherichia coli, the small cytoplasmic CheW protein couples the histidine kinase CheA to chemoreceptor control. Although essential for assembly and operation of receptor signalling complexes, CheW in stoichiometric excess disrupts chemotactic behaviour. To explore the mechanism of the CheW excess effect, we measured the physiological consequences of high cellular levels of wild‐type CheW and of several CheW variants with reduced or enhanced binding affinities for receptor molecules. We found that high levels of CheW interfered with trimer assembly, prevented CheA activation, blocked cluster formation, disrupted chemotactic ability and elevated receptor methylation levels. The severity of these effects paralleled the receptor‐binding affinities of the CheW variants. Because trimer formation may be an obligate step in the assembly of ternary signalling complexes and higher‐order receptor arrays, we suggest that all CheW excess effects stem from disruption of trimer assembly. We propose that the CheW‐binding sites in receptor dimers overlap their trimer contact sites and that high levels of CheW saturate the receptor‐binding sites, preventing trimer assembly. The CheW‐trapped receptor dimers seem to be improved substrates for methyltransferase reactions, but cannot activate CheA or assemble into clusters, processes that are essential for chemotactic signalling.
Targeting the Brain Reservoirs: Toward an HIV Cure

One of the top research priorities of the international AIDS society by the action “Towards an HIV Cure” is the purge or the decrease of the pool of all latently infected cells. This strategy is based on reactivation of latently reservoirs (the shock) followed by an intensifying combination antiretroviral therapy (cART) to kill them (the kill). The central nervous system (CNS) has potential latently infected cells, i.e., perivascular macrophages, microglial cells, and astrocytes that will need to be eliminated. However, the CNS has several characteristics that may preclude the achievement of a cure. In this review, we discuss several limitations to the eradication of brain reservoirs and how we could circumvent these limitations by making it efforts in four directions: (i) designing efficient latency-reversal agents for CNS-cell types, (ii) improving cART by targeting HIV transcription, (iii) improving delivery of HIV drugs in the CNS and in the CNS-cell types, and (iv) developing therapeutic immunization. As a prerequisite to these efforts, we also believe that a better comprehension of molecular mechanisms involved in establishment and persistence of HIV latency in brain reservoirs are essential to design new molecules for strategies aiming to achieve a cure for instance the “shock and kill” strategy.
Adenosine Receptor-Mediated Cardioprotection

Adenosine is a purine nucleoside, which is produced primarily through the metabolism of adenosine triphosphate (ATP), therefore its levels increase during stressful situations when ATP utilization increases. Adenosine exerts potent cardioprotective effects on the ischemic/reperfused heart, reducing reversible and irreversible myocardial injury. Adenosine receptors (ARs) are G-protein-coupled receptors, and 4 subtypes exist—A1, A2A, A2B, and A3, all of which have been shown to be cardioprotective. Adenosine receptors are expressed on multiple cardiac cells, including fibroblasts, endothelial cells, smooth muscle cells, and myocytes. Activation of both A1 and A3 receptors prior to ischemia has been shown in multiple experimental models to reduce ischemia/reperfusion-induced cardiac injury. Additionally, activation of the A2A receptor at the onset of reperfusion has been shown to reduce injury. Most recently, there is evidence that the A2B receptor has cardioprotective effects upon its activation. However, controversy remains regarding the precise timing of activation of these receptors required to induce cardioprotection, as well as their involvement in ischemic preconditioning and postconditioning. Adenosine receptors have been suggested to reduce cell death through actions at the mitochondrial ATP-dependent potassium (KATP) channel, as well as protein kinase C and mitogen-activated protein kinase (MAPK) signaling. Additionally, the ability of ARs to interact has been documented, and several recent reports suggest that these interactions play a role in AR-mediated cardioprotection. This review summarizes the current knowledge of the cardioprotective effects of each AR subtype, as well as the proposed mechanisms of AR cardioprotection. Additionally, the role of AR interactions in cardioprotection is discussed.
Clock rate versus IPC: the end of the road for conventional microarchitectures

The doubling microprocessor performance every three years has been the result of two factors: more transistors per chip and superlinear scaling of the processor dock with technology generation. Our results show that, due to both diminishing improvements in clock rates and poor wire scaling as semiconductor devices shrink, the achievable performance growth of conventional microarchitectures will slow substantially. In this paper, we describe technology-driven models for wire capacitance wire delay, and microarchitectural component delay. Using the results of these models, we measure the simulated performance-estimating both clock rate and IPC-of an aggressive out-of-order microarchitecture as it is scaled from a 250 nm technology to a 35 nm technology. We perform this analysis for three clock scaling targets and two microarchitecture scaling strategies: pipeline scaling and capacity scaling. We find that no scaling strategy permits annual performance improvements of better than 12.5% which is far worse than the annual 50-60% to which we have grown accustomed.
The pharmacology of mesolimbic dopamine neurons: a dual-probe microdialysis study in the ventral tegmental area and nucleus accumbens of the rat brain

Receptor-specific compounds were applied by retrograde microdialysis to the ventral tegmental area (VTA) of the rat brain. The effect of the intrategmental infusions on extracellular dopamine in the ipsilateral nucleus accumbens were recorded with a second microdialysis probe. Intrategmental infusion of muscimol (10–40 microM) or baclofen (50 microM) decreased extracellular dopamine in the nucleus accumbens. Intrategmental infusion of NMDA (1 mM, 15 min) or kainate (50 microM, 15 min) increased extracellular dopamine in the nucleus accumbens. The effects of the excitatory amino acids were suppressed by co-infusion of MK-801 (1 MM), (+)-3-amino-1-hydroxy-2-pyrrolidone [(+)-HA966; 1 mM], (+/-)-3(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP; 100 microM), and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX;300 microM). Intrategmental infusion of of carbachol (50 microM) increased extracellular dopamine in the nucleus accumbens. These results provide evidence for localization of GABAA, GABAB NMDA, non-NMDA, and cholinergic receptors on dopamine neurons in the VTA. Infusions of CPP, (+)-MK-801, (+)-HA966, CNQX, mecamylamine, atropine, or 3-[[(3,4- dichlorophenyl)methyl]propyl](diethoxymethyl) phosphonic acid (CGP 52432) into the VTA did not modify extracellular dopamine in the nucleus accumbens. Infusion of bicuculline (50 microM) and (-)- sulpiride (50 microM) was followed by an increase in extracellular dopamine in the nucleus accumbens. These data suggest that dopamine neurons in the VTA are tonically inhibited by GABA and dopamine by acting on GABAA, and D2 receptors, respectively. A tonic stimulation by glutamatergic or cholinergic neurons was not detected. Finally, results on A10 neurons are compared with earlier data on A9 neurons. A striking difference was found in that GABAA-dopamine interactions are indirect in the substantia nigra and direct in the VTA.
Self-Regulation of Anterior Insula with Real-Time fMRI and Its Behavioral Effects in Obsessive-Compulsive Disorder: A Feasibility Study

Introduction Obsessive-compulsive disorder (OCD) is a common and chronic condition that can have disabling effects throughout the patient's lifespan. Frequent symptoms among OCD patients include fear of contamination and washing compulsions. Several studies have shown a link between contamination fears, disgust over-reactivity, and insula activation in OCD. In concordance with the role of insula in disgust processing, new neural models based on neuroimaging studies suggest that abnormally high activations of insula could be implicated in OCD psychopathology, at least in the subgroup of patients with contamination fears and washing compulsions. Methods In the current study, we used a Brain Computer Interface (BCI) based on real-time functional magnetic resonance imaging (rtfMRI) to aid OCD patients to achieve down-regulation of the Blood Oxygenation Level Dependent (BOLD) signal in anterior insula. Our first aim was to investigate whether patients with contamination obsessions and washing compulsions can learn to volitionally decrease (down-regulate) activity in the insula in the presence of disgust/anxiety provoking stimuli. Our second aim was to evaluate the effect of down-regulation on clinical, behavioural and physiological changes pertaining to OCD symptoms. Hence, several pre- and post-training measures were performed, i.e., confronting the patient with a disgust/anxiety inducing real-world object (Ecological Disgust Test), and subjective rating and physiological responses (heart rate, skin conductance level) of disgust towards provoking pictures. Results Results of this pilot study, performed in 3 patients (2 females), show that OCD patients can gain self-control of the BOLD activity of insula, albeit to different degrees. In two patients positive changes in behaviour in the EDT were observed following the rtfMRI trainings. Behavioural changes were also confirmed by reductions in the negative valence and in the subjective perception of disgust towards symptom provoking images. Conclusion Although preliminary, results of this study confirmed that insula down-regulation is possible in patients suffering from OCD, and that volitional decreases of insula activation could be used for symptom alleviation in this disorder.
A novel portable one lead ECG monitor with low-cost and long-time recording based on NUC501

In this paper, a portable low-cost long- time one lead Electrocardiogram (ECG) Monitor is present, which is powered by one dry battery and based on NUC501. Power management module, analogous amplifier and Advanced RISC Machines (ARM) are used in hardware design. While hardware driver, digital filter, modified baseline drift method and difference threshold method are taken in software structure. The monitor gathers ECG signal through cable from user's body. A prototype instrument has been finally produced and will be put into the clinical environment. The notch filter and median filter are used to process the data. His/her ECG tracing is displayed lively on Liquid Crystal Display (LCD) screen. Also the heart rate is shown precisely on LCD screen and displayed with led flashing. The monitor also can storage and transport data to computer through Universal Serial Bus (USB) cable. While being powered by one dry battery, it works twenty-four hours. If there is any abnormally changes of heart rate, this instrument will be given alarm through the buzzer. The testing results show that this monitor is low power consumption, light-weight, accurate and low-cost. It can care for cardiac patients very good and provide a reliable cost-effective choice for cardio-path.
Calibration of calculable wideband direct feed biconical antenna for EMC measurements

An optimized wideband biconical antenna is presented for EMC measurement which potentially can be used as a standard-reference antenna. The antenna is “direct-fed” (no Balun is needed) with optimized dimension to match with 50 Ω coaxial cable from 200 MHz to 2 GHz. Radiation pattern of the antenna indicates that the common mode current existing on the coaxial cable is negligible. Meanwhile, the biconical antenna has a fixed phase-center for the various frequencies and the related uncertainties can be improved. The antenna factors (AF) of the antenna have been evaluated using analytical and numerical methods. Experimental “Standard Antenna Method SAM” has been used to verify the theoretical results and good agreements were observed.
In our own image? Emotional and neural processing differences when observing human–human vs human–robot interactions

Notwithstanding the significant role that human–robot interactions (HRI) will play in the near future, limited research has explored the neural correlates of feeling eerie in response to social robots. To address this empirical lacuna, the current investigation examined brain activity using functional magnetic resonance imaging while a group of participants (n = 26) viewed a series of human–human interactions (HHI) and HRI. Although brain sites constituting the mentalizing network were found to respond to both types of interactions, systematic neural variation across sites signaled diverging social-cognitive strategies during HHI and HRI processing. Specifically, HHI elicited increased activity in the left temporal–parietal junction indicative of situation-specific mental state attributions, whereas HRI recruited the precuneus and the ventromedial prefrontal cortex (VMPFC) suggestive of script-based social reasoning. Activity in the VMPFC also tracked feelings of eeriness towards HRI in a parametric manner, revealing a potential neural correlate for a phenomenon known as the uncanny valley. By demonstrating how understanding social interactions depends on the kind of agents involved, this study highlights pivotal sub-routes of impression formation and identifies prominent challenges in the use of humanoid robots.
A new verification methodology for complex pipeline behavior

A new test program generation tool, MVpGen, is developed for verifying pipeline design of microprocessors. The only inputs MVpGen requires are pipeline-behavior specifications; it automatically generates test cases at first from pipeline-behavior specifications and then automatically generates test programs corresponding to the test cases. Test programs for verifying complex pipeline behavior such as hazard and branch or hazard and exception, are generated. mVpGen has been integrated into a verification system for verifying RTL descriptions of a real microprocessor design and complex bugs that remained hidden in the RTL descriptions are detected.
Serological survey of hepatitis B immunity in healthcare workers in Catalonia (Spain)

ABSTRACT Healthcare workers (HCW) are exposed to preventable infectious diseases, notably hepatitis B (HB). The aim of this study was to determine the immunity of HCW against hepatitis B. We made a seroprevalence study using a self-administered survey and obtained blood samples. Antibodies against the HB surface antigen (anti-HBs) and against the HB core antigen (anti-HBc) were studied. The odds ratio (OR) and 95% confidence intervals (CI) were calculated. The adjusted OR were calculated using logistic regression. Of the 644 HCW who participated (29.7% physicians, 38.7% nurses, 13.4% other clinical workers and 18.3% non-clinical workers), 46.4% were primary care workers and 53.6% hospital workers. The overall prevalence of anti-HBs was 64.4%. HCW aged <25 y had a significantly higher prevalence (86.7%) than those aged 35–44 y (adjusted OR 3.40; 95% CI 1.06–10.90). The prevalence of anti-HBc was 4.1%, and increased with age. Significant differences were found for HCW aged >44 y with respect to those aged 25–34 y. 75.6% of HCW stated they were vaccinated, but only 39.3% had a vaccination card. In HCW who stated they were unvaccinated, 10.8% had a vaccinated serological pattern (anti-HBc-negative and anti-HBs -positive). Written, updated vaccination records are essential to reliably determine the vaccination status.
The Solar Neighborhood. XLII. Parallax Results from the CTIOPI 0.9 m Program—Identifying New Nearby Subdwarfs Using Tangential Velocities and Locations on the H–R Diagram

Parallaxes, proper motions, and optical photometry are presented for 51 systems consisting of 37 cool subdwarf and 14 additional high proper motion systems. Thirty-seven systems have parallaxes reported for the first time, 15 of which have proper motions of at least 1″ yr−1. The sample includes 22 newly identified cool subdwarfs within 100 pc, of which three are within 25 pc, and an additional five subdwarfs from 100 to 160 pc. Two systems—LSR 1610-0040 AB and LHS 440 AB—are close binaries exhibiting clear astrometric perturbations that will ultimately provide important masses for cool subdwarfs. We use the accurate parallaxes and proper motions provided here, combined with additional data from our program and others, to determine that effectively all nearby stars with tangential velocities greater than 200 km s−1 are subdwarfs. We compare a sample of 167 confirmed cool subdwarfs to nearby main sequence dwarfs and Pleiades members on an observational Hertzsprung–Russell diagram using MV versus (V − Ks) to map trends of age and metallicity. We find that subdwarfs are clearly separated for spectral types K5–M5, indicating that the low metallicities of subdwarfs set them apart in the H–R diagram for (V − Ks) = 3–6. We then apply the tangential velocity cutoff and the subdwarf region of the H–R diagram to stars with parallaxes from Gaia Data Release 1 and the MEarth Project to identify a total of 29 new nearby subdwarf candidates that fall clearly below the main sequence.
Open Ephys: an open-source, plugin-based platform for multichannel electrophysiology

Objective. Closed-loop experiments, in which causal interventions are conditioned on the state of the system under investigation, have become increasingly common in neuroscience. Such experiments can have a high degree of explanatory power, but they require a precise implementation that can be difficult to replicate across laboratories. We sought to overcome this limitation by building open-source software that makes it easier to develop and share algorithms for closed-loop control. Approach. We created the Open Ephys GUI, an open-source platform for multichannel electrophysiology experiments. In addition to the standard ‘open-loop’ visualization and recording functionality, the GUI also includes modules for delivering feedback in response to events detected in the incoming data stream. Importantly, these modules can be built and shared as plugins, which makes it possible for users to extend the functionality of the GUI through a simple API, without having to understand the inner workings of the entire application. Main results. In combination with low-cost, open-source hardware for amplifying and digitizing neural signals, the GUI has been used for closed-loop experiments that perturb the hippocampal theta rhythm in a phase-specific manner. Significance. The Open Ephys GUI is the first widely used application for multichannel electrophysiology that leverages a plugin-based workflow. We hope that it will lower the barrier to entry for electrophysiologists who wish to incorporate real-time feedback into their research.
Neuroblastoma: Effect of genetic factors on prognosis and treatment

Background and Methods. Genetic analysis of tumor tissue has provided considerable insight into mechanisms of malignant transformation and progression. Neuroblastomas have been studied by cytogenetics, flow cytometry, and molecular genetic techniques, and these studies have identified several specific abnormalities that allow subclassification of these tumors into genetic/ clinical subtypes.
Detecting software aging in a cloud computing framework by comparing development versions

Software aging, i.e. degradation of software performance or functionality caused by resource depletion is usually discovered only in the production scenario. This incurs large costs and delays of defect removal and requires provisional solutions such as rejuvenation (controlled restarts). We propose a method for detecting aging problems shortly after their introduction by runtime comparisons of different development versions of the same software. Possible aging issues are discovered by analyzing the differences in runtime traces of selected metrics. The required comparisons are workload-independent which minimizes the additional effort of dedicated stress tests. Consequently, the method requires only minimal changes to the traditional development and testing process. This paves the way to detecting such problems before public releases, greatly reducing the cost of defect fixing. Our study focuses on the memory leaks of Eucalyptus, a popular open source framework for managing cloud computing environments.
A biophysical implementation of a bidirectional graph search algorithm to solve multiple goal navigation tasks

The model presented here extends formal analysis (Hasselmo et al., Neural Networks, 15, pp. 689-707, 2002b) and abstract modelling (Gorchetchnikov and Hasselmo, Neurocomputing, 44-46, pp. 423-427, 2002a) of interactions within the hippocampal area (or other cortical areas), which can be flexibly used to navigate toward any arbitrary goal or multiple goals that change on a trial-by-trial basis. The algorithm is a version of a bidirectional breadth-first graph search implemented in simulated neurons using two flows of neural activity. The new model changes the continuous firing rate neuronal representations (Gorchetchnikov and Hasselmo 2002a) to more detailed compartmental versions with realistic parameters, while preserving the qualitative properties analysed previously (Hasselmo et al., 2002b, Gorchetchnikov and Hasselmo 2002a). The case of multiple goals being present in the environment is studied in this paper. The first set of simulations tests the algorithm in the selection of the closest goal. A small difference in distance between the simulated animal and different goals is sufficient for a correct selection. The second set of simulations studies the behaviour of the model when the goals have different saliences. A small salience-based difference between firing rates of the cells providing goal-related input to the model is sufficient for the selection of a more salient goal. This behaviour was tested in three types of environments: a linear track, a T-maze and an open field. Further investigation of quantitative properties of the model should allow it to handle cases when the exact location of the goal is uncertain.
A dynamical model for generating synthetic electrocardiogram signals

A dynamical model based on three coupled ordinary differential equations is introduced which is capable of generating realistic synthetic electrocardiogram (ECG) signals. The operator can specify the mean and standard deviation of the heart rate, the morphology of the PQRST cycle, and the power spectrum of the RR tachogram. In particular, both respiratory sinus arrhythmia at the high frequencies (HFs) and Mayer waves at the low frequencies (LFs) together with the LF/HF ratio are incorporated in the model. Much of the beat-to-beat variation in morphology and timing of the human ECG, including QT dispersion and R-peak amplitude modulation are shown to result. This model may be employed to assess biomedical signal processing techniques which are used to compute clinical statistics from the ECG.