Miracle-dz/UniFAR-FTUs huggingface dataset:
Output vs. outcome: neurovascular transduction at rest

Microneurography techniques that allow the direct recording of sympathetic nerve activity (SNA) in humans have been used to examine the neural control of cardiovascular regulation in a wide variety of populations. In the context of vascular control, SNA directed at the vasculature within skeletal muscle (muscle SNA; MSNA) occurs in a ‘bursting’ pattern, which is typically quantified as burst frequency (in bursts per minute), burst incidence (in bursts per 100 heart beats), burst amplitude (in arbitrary units) and total activity (frequency × amplitude). Each burst of activity represents the summation of multiple action potentials from multiple neurons, resulting in the downstream release of vasoactive neurotransmitters. However, due to the irregular bursting pattern and relatively low frequency of basal MSNA typically observed in in young, healthy individuals (e.g. 20–30 bursts (100 heart beats)−1; Steinback et al. 2010; Vianna et al. 2012; Fairfax et al. 2013a,b2013b; Tan et al. 2013), the standard metrics of activity are typically averaged over time (minutes) at rest or during the steady state following an initiating stimulus. Due to this limitation, little information is currently available regarding the specific vascular effects of ongoing MSNA (i.e. on a burst-by-burst basis) or the time course of activation in response to various stimuli. A related series of publications, including the recent work published in The Journal of Physiology by Fairfax et al. (2013a), have attempted to address these issues using an adapted approach to measure neurovascular ‘transduction’. The authors have built upon an earlier description of transduction by Wallin & Nerhed (1982) to describe the functional effect of a given burst (or group of bursts) of MSNA on the cardiovascular system. They achieved this by using burst-triggered averaging to define the time course and magnitude of cardiovascular responses (i.e. mean arterial pressure, vascular conductance and cardiac output) over 15 cardiac cycles immediately following a spontaneous sympathetic burst. Categorization of bursts by size and frequency (clusters) was used to evaluate the influence of variations in total MSNA. Furthermore, analysis of the time course of responses following cardiac cycles without bursts and sampling of white noise during random cardiac cycles (with and without bursts) acted as a control analysis. Similar to previous accounts (Wallin & Nerhed, 1982; Vianna et al. 2012; Fairfax et al. 2013b), the authors describe a peak vascular response graded in proportion to the total activity, which occurs approximately five to eight cardiac cycles following a given burst or group of bursts (Fairfax et al. 2013a). In the most recent publication in this series, appearing in The Journal of Physiology, the authors expand upon their previous findings to evaluate the direct contribution of α-receptor-mediated pathways to basal transduction and regional differentiation between upper and lower limbs (Fairfax et al. 2013a).
Differential activation of frontoparietal attention networks by social and symbolic spatial cues

Perception of both gaze-direction and symbolic directional cues (e.g. arrows) orient an observer’s attention toward the indicated location. It is unclear, however, whether these similar behavioral effects are examples of the same attentional phenomenon and, therefore, subserved by the same neural substrate. It has been proposed that gaze, given its evolutionary significance, constitutes a ‘special’ category of spatial cue. As such, it is predicted that the neural systems supporting spatial reorienting will be different for gaze than for non-biological symbols. We tested this prediction using functional magnetic resonance imaging to measure the brain’s response during target localization in which laterally presented targets were preceded by uninformative gaze or arrow cues. Reaction times were faster during valid than invalid trials for both arrow and gaze cues. However, differential patterns of activity were evoked in the brain. Trials including invalid rather than valid arrow cues resulted in a stronger hemodynamic response in the ventral attention network. No such difference was seen during trials including valid and invalid gaze cues. This differential engagement of the ventral reorienting network is consistent with the notion that the facilitation of target detection by gaze cues and arrow cues is subserved by different neural substrates.
Intrapersonal and interpersonal processes of social exclusion

People have a fundamental need to belong with others. Social exclusion impairs this need and has various effects on cognition, affect, and the behavior of excluded individuals. We have previously reported that activity in the dorsal anterior cingulate cortex (dACC) and right ventrolateral prefrontal cortex (rVLPFC) could be a neurocognitive index of social exclusion (Kawamoto et al., 2012). In this article, we provide an integrative framework for understanding occurrences during and after social exclusion, by reviewing neuroimaging, electrophysiological, and behavioral studies of dACC and rVLPFC, within the framework of intrapersonal and interpersonal processes of social exclusion. As a result, we have indicated directions for future studies to further clarify the phenomenon of social exclusion from the following perspectives: (1) constructional elements of social exclusion, (2) detection sensitivity and interpretation bias in social exclusion, (3) development of new methods to assess the reactivity to social exclusion, and (4) sources of social exclusion.
Performance of polar codes for quantum and private classical communication

We analyze the practical performance of quantum polar codes, by computing rigorous bounds on block error probability and by numerically simulating them. We evaluate our bounds for quantum erasure channels with coding block lengths between 210 and 220, and we report the results of simulations for quantum erasure channels, quantum depolarizing channels, and “BB84” channels with coding block lengths up to N = 1024. For quantum erasure channels, we observe that high quantum data rates can be achieved for block error rates Pe ≤ 10-4 and that somewhat lower quantum data rates can be achieved for quantum depolarizing and BB84 channels. Our results here also serve as bounds for and simulations of private classical data transmission over these channels, essentially due to Renes' duality bounds for privacy amplification and classical data transmission of complementary observables. Future work might be able to improve upon our numerical results by employing a polar coding rule other than the heuristic used here.
Effects of Combination of Perindopril, Indapamide, and Calcium Channel Blockers in Patients With Type 2 Diabetes Mellitus: Results From the Action in Diabetes and Vascular Disease: Preterax and Diamicron Controlled Evaluation (ADVANCE) Trial

The objective of the present analysis was to determine the effects of a fixed combination of perindopril and indapamide in combination with calcium channel blockers (CCBs) in patients with type 2 diabetes mellitus. The Action in Diabetes and Vascular Disease: Preterax and Diamicron Controlled Evaluation (ADVANCE) trial was a factorial randomized controlled trial. A total of 11 140 patients with type 2 diabetes mellitus were randomly assigned to fixed combination of perindopril–indapamide (4/1.25 mg) or placebo. Effects of randomized treatment on mortality and major cardiovascular outcomes were examined in subgroups defined by baseline use of CCBs. Patients on CCB at baseline (n=3427) constituted a higher risk group compared with those not on CCB (n=7713), with more extensive use of antihypertensive and other protective therapies. Active treatment reduced the relative risk of death by 28% (95% confidence interval, 10%–43%) among patients with CCB at baseline compared with 5% (−12% to 20%) among those without CCB (P homogeneity=0.02) and 14% (2%–25%) for the whole population. Similarly, the relative risk reduction for major cardiovascular events was 12% (−8% to 28%) versus 6% (−10% to 19%) for those with and without CCB at baseline although the difference was not statistically significant (P homogeneity=0.38). There was no detectable increase in adverse effects in those receiving CCB. The combination of perindopril and indapamide with CCBs seems to provide further protection against mortality in patients with type 2 diabetes mellitus.
Mining Sequence Classifiers for Early Prediction

Supervised learning on sequence data, also known as sequence classification, has been well recognized as an important data mining task with many significant applications. Since temporal order is important in sequence data, in many critical applications of sequence classification such as medical diagnosis and disaster prediction, early prediction is a highly desirable feature of sequence classifiers. In early prediction, a sequence classifier should use a prefix of a sequence as short as possible to make a reasonably accurate prediction. To the best of our knowledge, early prediction on sequence data has not been studied systematically. In this paper, we identify the novel problem of mining sequence classifiers for early prediction. We analyze the problem and the challenges. As the first attempt to tackle the problem, we propose two interesting methods. The sequential classification rule (SCR) method mines a set of sequential classification rules as a classifier. A so-called early-prediction utility is defined and used to select features and rules. The generalized sequential decision tree (GSDT) method adopts a divide-and-conquer strategy to generate a classification model. We conduct an extensive empirical evaluation on several real data sets. Interestingly, our two methods achieve accuracy comparable to that of the stateof-the-art methods, but typically need to use only very short prefixes of the sequences. The results clearly indicate that early prediction is highly feasible and effective.
Climate Change Projected to Exacerbate Impacts of Coastal Eutrophication in the Northern Gulf of Mexico

The continental shelf in the northern Gulf of Mexico experiences expansive seasonal hypoxic conditions and eutrophication-driven acidification in bottom waters. Rising surface ocean temperatures, freshwater and nutrient inputs, and atmospheric CO2 will further exacerbate these conditions. Using a high-resolution, regional circulation-biogeochemical model, we simulated the spatiotemporal dynamics of oxygen and inorganic carbon in the northern Gulf of Mexico under present and a projected future (2100) climate state. Results indicate a modest expansion of the hypoxic zone, but more severe hypoxia and greater exposure to prolonged hypoxic conditions. The main drivers underlying these changes are a reduction in oxygen solubility (accounting for 60–74% of the change) and increased stratification (accounting for less than 40%). pH is projected to decrease across the shelf with lowest values in hypoxic waters where aragonite saturation will approach the saturation limit. In the model simulations, acidification is primarily driven by atmospheric and offshore CO2 levels, while the enhancement in stratification only accounts for 7% or less of the total change in pH. Decreased buffering capacity and increased stratification in the future will enhance respiration-induced acidification (i.e., a decrease in bottom water pH by respired CO2), which will amplify the climate-induced acidification. According to the model, the magnitude of future changes varies significantly from year to year. The largest effects are simulated in years with large freshwater discharge and upwelling-favorable winds. Plain Language Summary The continental shelf in the northern Gulf of Mexico experiences eutrophication-driven seasonal low-oxygen conditions (hypoxia) and acidification (a decrease in bottom water pH by respired CO2). Rising surface ocean temperatures, freshwater and nutrient inputs, and atmospheric CO2 will further exacerbate these conditions. We simulated the variations of oxygen and inorganic carbon in the northern Gulf of Mexico at present and under a projected future (2100) climate state. Results indicate more severe and prolonged periods of hypoxia in the future due to reduced oxygen solubility in warmer waters and increased stratification. pH is projected to decrease significantly with lowest values in low-oxygen waters. Future acidification is primarily driven by rising atmospheric and offshore CO2 levels. A decreased buffering capacity of seawater and increased stratification will enhance respiration-induced acidification, which will further amplify the climate-induced acidification. The magnitude of projected changes varies significantly from year to year, with the largest effects in years with large freshwater discharge and upwelling-favorable winds.
Contribution to the floristic knowledge of the head of the Po Valley (Piedmont, north Italy)

In 2014, the annual field trip of the working group for Floristics, Systematics, and Evolution of the Italian Botanical Society was held in Piemonte (northern Italy), at the head of the Po Valley. This valley, at whose extremity is located the Monviso (3,841 m a.s.l.), belongs to the Cottian Alps about which very little is known from a floristic point of view. An inventory of the taxa of vascular plants collected during the field trip is reported here. The research led to the identification of 3,546 exsiccata , kept in nine public and nine private collections. A total of 669 taxa belonging to 79 plant families were recorded. Six taxa resulted endemic to Italy and three exclusive to Piemonte, while only nine alien species were detected; six taxa are new and five confirmed for the regional flora.
Chemokine receptor CXCR7 mediates human endothelial progenitor cells survival, angiogenesis, but not proliferation

Stromal cell‐derived factor 1 (SDF‐1) is a critical regulator of endothelial progenitor cells (EPCs) mediated physiological and pathologic angiogenesis. It was considered to act via its unique receptor CXCR4 for a long time. CXCR7 is a second, recently identified receptor for SDF‐1, and its role in human EPCs is unclear. In present study, CXCR7 was found to be scarcely expressed on the surface of human EPCs derived from cord blood, but considerable intracellular CXCR7 was detected, which differs from that on EPCs derived from rat bone marrow. CXCR7 failed to support SDF‐1 induced human EPCs migration, proliferation, or nitric oxide (NO) production, but mediated human EPCs survival exclusively. Besides that, CXCR7 mediated EPCs tube formation along with CXCR4. Blocking CXCR7 with its antagonist CCX733 impaired SDF‐1/CXCR4 induced EPCs adhesion to active HUVECs and trans‐endothelial migration. Those results suggested that CXCR7 plays an important role in human cord blood derived EPCs in response to SDF‐1. J. Cell. Biochem. 113: 1437–1446, 2012. © 2011 Wiley Periodicals, Inc.
Glycosaminoglycan Binding Facilitates Entry of a Bacterial Pathogen into Central Nervous Systems

Certain microbes invade brain microvascular endothelial cells (BMECs) to breach the blood-brain barrier (BBB) and establish central nervous system (CNS) infection. Here we use the leading meningitis pathogen group B Streptococcus (GBS) together with insect and mammalian infection models to probe a potential role of glycosaminoglycan (GAG) interactions in the pathogenesis of CNS entry. Site-directed mutagenesis of a GAG-binding domain of the surface GBS alpha C protein impeded GBS penetration of the Drosophila BBB in vivo and diminished GBS adherence to and invasion of human BMECs in vitro. Conversely, genetic impairment of GAG expression in flies or mice reduced GBS dissemination into the brain. These complementary approaches identify a role for bacterial-GAG interactions in the pathogenesis of CNS infection. Our results also highlight how the simpler yet genetically conserved Drosophila GAG pathways can provide a model organism to screen candidate molecules that can interrupt pathogen-GAG interactions for future therapeutic applications.
A Mechanistic Paradigm for Broad-Spectrum Antivirals that Target Virus-Cell Fusion

LJ001 is a lipophilic thiazolidine derivative that inhibits the entry of numerous enveloped viruses at non-cytotoxic concentrations (IC50≤0.5 µM), and was posited to exploit the physiological difference between static viral membranes and biogenic cellular membranes. We now report on the molecular mechanism that results in LJ001's specific inhibition of virus-cell fusion. The antiviral activity of LJ001 was light-dependent, required the presence of molecular oxygen, and was reversed by singlet oxygen (1O2) quenchers, qualifying LJ001 as a type II photosensitizer. Unsaturated phospholipids were the main target modified by LJ001-generated 1O2. Hydroxylated fatty acid species were detected in model and viral membranes treated with LJ001, but not its inactive molecular analog, LJ025. 1O2-mediated allylic hydroxylation of unsaturated phospholipids leads to a trans-isomerization of the double bond and concurrent formation of a hydroxyl group in the middle of the hydrophobic lipid bilayer. LJ001-induced 1O2-mediated lipid oxidation negatively impacts on the biophysical properties of viral membranes (membrane curvature and fluidity) critical for productive virus-cell membrane fusion. LJ001 did not mediate any apparent damage on biogenic cellular membranes, likely due to multiple endogenous cytoprotection mechanisms against phospholipid hydroperoxides. Based on our understanding of LJ001's mechanism of action, we designed a new class of membrane-intercalating photosensitizers to overcome LJ001's limitations for use as an in vivo antiviral agent. Structure activity relationship (SAR) studies led to a novel class of compounds (oxazolidine-2,4-dithiones) with (1) 100-fold improved in vitro potency (IC50<10 nM), (2) red-shifted absorption spectra (for better tissue penetration), (3) increased quantum yield (efficiency of 1O2 generation), and (4) 10–100-fold improved bioavailability. Candidate compounds in our new series moderately but significantly (p≤0.01) delayed the time to death in a murine lethal challenge model of Rift Valley Fever Virus (RVFV). The viral membrane may be a viable target for broad-spectrum antivirals that target virus-cell fusion.
Regulation of Ras Exchange Factors and Cellular Localization of Ras Activation by Lipid Messengers in T Cells

The Ras-MAPK signaling pathway is highly conserved throughout evolution and is activated downstream of a wide range of receptor stimuli. Ras guanine nucleotide exchange factors (RasGEFs) catalyze GTP loading of Ras and play a pivotal role in regulating receptor-ligand induced Ras activity. In T cells, three families of functionally important RasGEFs are expressed: RasGRF, RasGRP, and Son of Sevenless (SOS)-family GEFs. Early on it was recognized that Ras activation is critical for T cell development and that the RasGEFs play an important role herein. More recent work has revealed that nuances in Ras activation appear to significantly impact T cell development and selection. These nuances include distinct biochemical patterns of analog versus digital Ras activation, differences in cellular localization of Ras activation, and intricate interplays between the RasGEFs during distinct T cell developmental stages as revealed by various new mouse models. In many instances, the exact nature of these nuances in Ras activation or how these may result from fine-tuning of the RasGEFs is not understood. One large group of biomolecules critically involved in the control of RasGEFs functions are lipid second messengers. Multiple, yet distinct lipid products are generated following T cell receptor (TCR) stimulation and bind to different domains in the RasGRP and SOS RasGEFs to facilitate the activation of the membrane-anchored Ras GTPases. In this review we highlight how different lipid-based elements are generated by various enzymes downstream of the TCR and other receptors and how these dynamic and interrelated lipid products may fine-tune Ras activation by RasGEFs in developing T cells.
On the limits of communication with low-precision analog-to-digital conversion at the receiver

As communication systems scale up in speed and bandwidth, the cost and power consumption of high-precision (e.g., 8-12 bits) analog-to-digital conversion (ADC) becomes the limiting factor in modern transceiver architectures based on digital signal processing. In this work, we explore the impact of lowering the precision of the ADC on the performance of the communication link. Specifically, we evaluate the communication limits imposed by low-precision ADC (e.g., 1-3 bits) for transmission over the real discrete-time additive white Gaussian noise (AWGN) channel, under an average power constraint on the input. For an ADC with K quantization bins (i.e., a precision of log2 K bits), we show that the input distribution need not have any more than K+1 mass points to achieve the channel capacity. For 2-bin (1-bit) symmetric quantization, this result is tightened to show that binary antipodal signaling is optimum for any signal-to- noise ratio (SNR). For multi-bit quantization, a dual formulation of the channel capacity problem is used to obtain tight upper bounds on the capacity. The cutting-plane algorithm is employed to compute the capacity numerically, and the results obtained are used to make the following encouraging observations : (a) up to a moderately high SNR of 20 dB, 2-3 bit quantization results in only 10-20% reduction of spectral efficiency compared to unquantized observations, (b) standard equiprobable pulse amplitude modulated input with quantizer thresholds set to implement maximum likelihood hard decisions is asymptotically optimum at high SNR, and works well at low to moderate SNRs as well.
Cost of noninfectious comorbidities in patients with HIV

Objectives We hypothesized that the increased prevalence of noninfectious comorbidities (NICMs) observed among HIV-infected patients may result in increased direct costs of medical care compared to the general population. Our objective was to provide estimates of and describe factors contributing to direct costs for medical care among HIV-infected patients, focusing on NICM care expenditure. Methods A case-control study analyzing direct medical care costs in 2009. Antiretroviral therapy (ART)-experienced HIV-infected patients (cases) were compared to age, sex, and race-matched adults from the general population, included in the CINECA ARNO database (controls). NICMs evaluated included cardiovascular disease, hypertension, diabetes mellitus, bone fractures, and renal failure. Medical care cost information evaluated included pharmacy, outpatient, and inpatient hospital expenditures. Linear regression models were constructed to evaluate predictors of total care cost for the controls and cases. Results There were 2854 cases and 8562 controls. Mean age was 46 years and 37% were women. We analyzed data from 29,275 drug prescription records. Positive predictors of health care cost in the overall population: HIV infection (β = 2878; confidence interval (CI) = 2001–3755); polypathology (β = 8911; CI = 8356–9466); age (β = 62; CI = 45–79); and ART exposure (β = 18,773; CI = 17,873–19,672). Predictors of health care cost among cases: Center for Disease Control group C (β = 1548; CI = 330–2766); polypathology (β = 11,081; CI = 9447–12,716); age < 50 years (β = 1903; CI = 542–3264); protease inhibitor exposure (per month of use; β = 69; CI = 53–85); CD4 count < 200 cells/mm3 (β = 5438; CI = 3082–7795); and ART drug change (per change; β = 911; CI = 716–1106). Conclusion Total cost of medical care is higher in cases than controls. Lower medical costs associated with higher CD4 strata are offset by increases in the care costs needed for advancing age, particularly for NICMs.