Miracle-dz/UniFAR-FTUs huggingface dataset:
A mechanistic description of gating of the human cardiac ryanodine receptor in a regulated minimal environment

Cardiac muscle contraction, triggered by the action potential, is mediated by the release of Ca2+ from the sarcoplasmic reticulum through ryanodine receptor (RyR)2 channels. In situ, RyR2 gating is modulated by numerous physiological and pharmacological agents, and altered RyR2 function underlies the occurrence of arrhythmias in both inherited and acquired diseases. To understand fully the mechanisms underpinning the regulation of RyR2 in the normal heart and how these systems are altered in pathological conditions, we must first gain a detailed knowledge of the fundamental processes of RyR2 gating. In this investigation, we provide key novel mechanistic insights into the physical reality of RyR2 gating revealed by new experimental and analytical approaches. We have examined in detail the single-channel gating kinetics of the purified human RyR2 when activated by cytosolic Ca2+ in a stringently regulated environment where the modulatory influence of factors external to the channel were minimized. The resulting gating schemes are based on an accurate description of single-channel kinetics using hidden Markov model analysis and reveal several novel aspects of RyR2 gating behavior: (a) constitutive gating is observed as unliganded opening events; (b) binding of Ca2+ to the channel stabilizes it in different open states; (c) RyR2 exists in two preopening closed conformations in equilibrium, one of which binds Ca2+ more readily than the other; (d) the gating of RyR2 when bound to Ca2+ can be described by a kinetic scheme incorporating bursts; and (e) analysis of flicker closing events within bursts reveals gating activity that is not influenced by ligand binding. The gating schemes generated in this investigation provide a framework for future studies in which the mechanisms of action of key physiological regulatory factors, disease-linked mutations, and potential therapeutic compounds can be described precisely.
Tuberculosis transmission to young children in a South African community: modeling household and community infection risks.

BACKGROUND Tuberculosis transmission is determined by contact between infectious and susceptible individuals. A recent study reported a 4% annual risk of child tuberculosis infection in a southern African township. A model was used to explore the interactions between prevalence of adult tuberculosis infection, adult-to-child contacts, and household ventilation, which could result in such a high annual risk of tuberculosis infection. METHODS Number of residents per household and tuberculosis incidence were derived from a household census and community tuberculosis registers. Using the Wells-Riley equation and probability analyses of contact between infectious adults with tuberculosis and preschool children, we estimated the annual risk of tuberculosis infection within and outside of the home. RESULTS There was a mean of 2.2 adults per child-containing household with a 1.35% annual adult smear-positive tuberculosis notification rate. The maximal household annual risk of tuberculosis infection was 3%, which was primarily determined by the number of resident adults. Transmission risk outside the home increased with increasing number of households visited. Transmission probabilities were sensitive to exposure time, ventilation, and period of adult infectivity. The benefits of increased ventilation were greatest when the period of infectivity was reduced. Similar reductions in household transmission could be achieved by increasing ventilation from 2 to 6 air changes/hour or by separating child and adult sleeping areas. CONCLUSIONS The annual risk of tuberculosis infection of preschool children predominantly results from infectious residents in the home. However, even with limited social interactions, a substantial proportion of transmissions may occur from nonresident adults. The benefits of increased ventilation are maximized when the period of infectivity is reduced by prompt treatment of source cases.
Live-Cell Analysis of a Green Fluorescent Protein-Tagged Herpes Simplex Virus Infection

ABSTRACT Many stages of the herpes simplex virus maturation pathway have not yet been defined. In particular, little is known about the assembly of the virion tegument compartment and its subsequent incorporation into maturing virus particles. Here we describe the construction of a herpes simplex virus type 1 (HSV-1) recombinant in which we have replaced the gene encoding a major tegument protein, VP22, with a gene expressing a green fluorescent protein (GFP)-VP22 fusion protein (GFP-22). We show that this virus has growth properties identical to those of the parental virus and that newly synthesized GFP-22 is detectable in live cells as early as 3 h postinfection. Moreover, we show that GFP-22 is incorporated into the HSV-1 virion as efficiently as VP22, resulting in particles which are visible by fluorescence microscopy. Consequently, we have used time lapse confocal microscopy to monitor GFP-22 in live-cell infection, and we present time lapse animations of GFP-22 localization throughout the virus life cycle. These animations demonstrate that GFP-22 is present in a diffuse cytoplasmic location when it is initially expressed but evolves into particulate material which travels through an exclusively cytoplasmic pathway to the cell periphery. In this way, we have for the first time visualized the trafficking of a herpesvirus structural component within live, infected cells.
Current Science on Consumer Use of Mobile Health for Cardiovascular Disease Prevention: A Scientific Statement From the American Heart Association.

Although mortality for cardiovascular disease (CVD) has declined for several decades, heart disease and stroke continue to be the leading causes of death, disability, and high healthcare costs. Unhealthy behaviors related to CVD risk (eg, smoking, sedentary lifestyle, and unhealthful eating habits) remain highly prevalent. The high rates of overweight, obesity, and type 2 diabetes mellitus (T2DM); the persistent presence of uncontrolled hypertension; lipid levels not at target; and the ≈18% of adults who continue to smoke cigarettes pose formidable challenges for achieving improved cardiovascular health.1,2 It is apparent that the performance of healthful behaviors related to the management of CVD risk factors has become an increasingly important facet of the prevention and management of CVD.3 In 2010, the American Heart Association (AHA) made a transformative shift in its strategic plan and added the concept of cardiovascular health.2 To operationalize this concept, the AHA targeted 4 health behaviors in the 2020 Strategic Impact Goals: reduction in smoking and weight, healthful eating, and promotion of regular physical activity. Three health indicators also were included: glucose, blood pressure (BP), and cholesterol. On the basis of the AHA Life’s Simple 7 metrics for improved cardiovascular health, 30% have not reached the target levels for lipids or BP. National Health and Nutrition Examination Survey (NHANES) data revealed that people who met ≥6 of the cardiovascular health metrics had a significantly better risk profile (hazard ratio for all-cause mortality, 0.49) compared with individuals who had achieved only 1 metric or none.2 The studies reviewed in this statement targeted these behaviors (ie, smoking, physical activity, healthful eating, and maintaining a healthful weight) and cardiovascular health indicators (ie, blood …
Seasonal Variation in TP53 R249S-Mutated Serum DNA with Aflatoxin Exposure and Hepatitis B Virus Infection

Background: Chronic hepatitis B virus (HBV) infection and dietary aflatoxin B1 (AFB1) exposure are etiological factors for hepatocellular carcinoma (HCC) in countries with hot, humid climates. HCC often harbors a TP53 (tumor protein p53) mutation at codon 249 (R249S). In chronic carriers, 1762T/1764A mutations in the HBV X gene are associated with increased HCC risk. Both mutations have been detected in circulating cell-free DNA (CFDNA) from asymptomatic HBV carriers. Objective: We evaluated seasonal variation in R249S and HBV in relation to AFB1 exposure. Methods: R249S was quantitated by mass spectrometry in CFDNA in a cross-sectional survey of 473 asymptomatic subjects (237 HBV carriers and 236 noncarriers) recruited in three villages in the Gambia over a 10-month period. 1762T/1764A HBV mutations were detected by quantitative polymerase chain reaction. In addition, the HBV S gene was sequenced in 99 subjects positive for HBV surface antigen (HBsAg). Results: We observed a seasonal variation of serum R249S levels. Positivity for R249S and average concentration were significantly higher in HBsAg-positive subjects surveyed during April–July (61%; 5,690 ± 11,300 R249S copies/mL serum) than in those surveyed October–March [32% and 480 ± 1,030 copies/mL serum (odds ratio = 3.59; 95% confidence interval: 2.05, 6.30; p < 0.001)]. Positivity for HBV e antigen (HBeAg) (a marker of HBV replication) and viral DNA load also varied seasonally, with 15–30% of subjects surveyed between April and June HBeAg positive, compared with < 10% surveyed during other months. We detected 1762T/1764A mutations in 8% of carriers, half of whom were positive for R249S. We found HBV genotype E in 95 of 99 HBsAg-positive subjects. Conclusion: R249S is detectable in CFDNA of asymptomatic subjects. Evidence of temporal and quantitative variations suggests an interaction among AFB1 exposure, HBV positivity, and replication on TP53 mutation formation or persistence.
A hard day’s night: a longitudinal study on the relationships among job demands and job control, sleep quality and fatigue

This prospective four‐wave study examined (i) the causal direction of the longitudinal relations among job demands, job control, sleep quality and fatigue; and (ii) the effects of stability and change in demand–control history on the development of sleep quality and fatigue. Based on results of a four‐wave complete panel study among 1163 Dutch employees, we found significant effects of job demands and job control on sleep quality and fatigue across a 1‐year time lag, supporting the strain hypothesis (Demand–Control model; Karasek and Theorell, Basic Books, New York, 1990). No reversed or reciprocal causal patterns were detected. Furthermore, our results revealed that cumulative exposure to a high‐strain work environment (characterized by high job demands and low job control) was associated with elevated levels of sleep‐related complaints. Cumulative exposure to a low‐strain work environment (i.e. low job demands and high job control) was associated with the highest sleep quality and lowest level of fatigue. Our results revealed further that changes in exposure history were related to changes in reported sleep quality and fatigue across time. As expected, a transition from a non‐high‐strain towards a high‐strain job was associated with a significant increase in sleep‐related complaints; conversely, a transition towards a non‐high‐strain job was not related to an improvement in sleep‐related problems.
XSEED: Accurate and Fast Cardinality Estimation for XPath Queries

We propose XSEED, a synopsis of path queries for cardinality estimation that is accurate, robust, efficient, and adaptive to memory budgets. XSEED starts from a very small kernel, and then incrementally updates information of the synopsis. With such an incremental construction, a synopsis structure can be dynamically configured to accommodate different memory budgets. Cardinality estimation based on XSEED can be performed very efficiently and accurately. Extensive experiments on both synthetic and real data sets show that even with less memory, XSEED could achieve accuracy that is an order of magnitude better than that of other synopsis structures. The cardinality estimation time is under 2% of the actual querying time for a wide range of queries in all test cases.
Modeling cardiorespiratory interaction during human sleep with complex networks

Human sleep comprises several stages including wake, rapid-eye-movement sleep, light sleep, and deep sleep. Cardiorespiratory activity has been shown to correlate with sleep stages due to the regulation of autonomic nervous system. Here, the cardiorespiratory interaction (CRI) during sleep is analyzed using a visibility graph (VG) method that represents the CRI time series in complex networks. We demonstrate that the dynamics of the interaction between heartbeats and respiration can be revealed by VG-based networks, whereby sleep stages can be characterized and differentiated.
Household Food Insecurity and Dietary Intake among Mexican-American Women Participating in Federal Food Assistance Programs

Purpose. To explore the association between food insecurity and dietary intake among Mexican-American women after controlling for sociocultural and economic factors including participation in federal food assistance programs. Design. Cross-sectional. Setting. Three cities in Texas. Subjects. Seven hundred seven Mexican-American women (26–44 years). Measures. Demographics, anthropometrics, acculturation, and food security status were obtained using validated measures. Dietary intake was assessed by a 24-hour dietary food record. Analysis. Logistic regression was used to examine the association between individual and household characteristics on food security status. One-way analysis of covariance tested the association between food security status and dietary intake after adjusting for sociodemographic variables, acculturation, body mass index, participation in federal food assistance programs, and energy intake. Results. About 77% of food-insecure women participated in at least one federal food assistance program. Each additional child in the household increased the odds of being food insecure by 25%. A higher proportion of obese women was found in the food-insecure group. No significant differences in dietary intake were found by food security status. Conclusion. Food insecurity did not negatively influence dietary intake independently of women's participation in federal food assistance programs. Food security did not ensure consumption of nutritionally adequate foods. Educational and food assistance programs need to be optimized to facilitate enrollment and improve the nutritional status of this ethnic group, food secure or not.
Association Between Serum Cytokine Profiles and Clearance or Persistence of High-Risk Human Papillomavirus Infection: A Prospective Study

Introduction: The cytokines that may be associated with the clearance or persistence of high-risk human papillomavirus (HPV) infection in patients with mild dysplasia or less of the uterine cervix were determined. Methods: A prospective study of 160 patients who harbored high-risk HPV with histologically confirmed mild dysplasia or less between January 2006 and August 2008 was performed. All patients were followed up at every 4 months during the first year. Human papillomavirus DNA tests by the Hybrid Capture 2 method (Digene, Gaithersburg, Md) were performed at every visit on all patients. Blood sampling was performed in all patients at their initial visit, and an enzyme-linked immunosorbent assay was used to measure the serum levels of interferon γ, tumor necrosis factor &agr;, and interleukins 6 and 10. Results: Of the 160 patients, 107 (66.9%) had clearance of HPV infection after 12 months of follow-up. The median age of patients in the persistence group was significantly higher than that of patients in the clearance group (47 vs 38 years, respectively; range, 21-77 vs 21-71 years, respectively; P = 0.0009). In univariate analysis, the number of patients with serum negative for tumor necrosis factor &agr; was significantly higher in the clearance group than the persistence group (P = 0.0363). However, in multivariate logistic regression analysis, all 4 cytokines failed to show any significant association with the clearance or persistence of HPV infection. Conclusions: The baseline serum cytokine levels were not associated with the clearance or persistence of HPV infection. Systemic immunity may not influence the natural history of HPV infection.
A Dual‐Label Immunofluorometric Assay for Human Osteocalcin

Circulating human osteocalcin (hOC) has been shown to be comprised of two main forms: the intact 1–49 form and the proteolytic N‐terminal midfragment (N‐mid) spanning amino acid residues 1–43 or 1–44. We used three monoclonal antibodies (MAbs) raised against hOC and bovine osteocalcin in developing a dual‐label assay for the simultaneous measurement of the proportions of the intact and N‐mid forms in serum samples. The assay is based on time‐resolved fluorescence utilizing differently labeled tracer MAbs. Biotinylated MAb 2H9 is used as a capture antibody for both the intact hOC and the N‐mid. Tracer MAb 6F9 labeled with a Europium(III)‐chelate binds to the N‐mid and the intact hOC, whereas tracer MAb 3G8 labeled with a Terbium(III)‐chelate binds to the intact hOC only. The simultaneous binding of the antibodies was tested by comparing full‐length hOC purified from human bone and hOC shortened from the C terminus by four amino acid residues with carboxypeptidase Y. Serum hOC measurements with the dual‐label assay were in agreement with the corresponding single‐label assays (r = 0.96 for intact + N‐mid assays and r = 0.81 for intact assays, n = 91). The lower correlation between the intact assays was attributable to proteolytic susceptibility of the intact form due to one additional freezing and thawing cycle in carrying out the dual‐label assay. As measured with the dual‐label assay, the levels (mean ± SD) of serum intact + N‐mid OC were 6.2 ± 2.1 ng/ml in the premenopausal group (n = 44), 13.9 ± 4.9 ng/ml in the postmenopausal group without hormone replacement therapy (HRT; n = 13), and 7.5 ± 3.4 ng/ml in the postmenopausal group with HRT (n = 13). The levels of intact hOC in the same groups were 4.8 ± 1.4 ng/ml, 9.8 ± 2.9 ng/ml, and 5.3 ± 2.1 ng/ml, respectively. Whether the main forms of OC or their relative proportions in serum can be used for predicting bone diseases or for monitoring the progression and management of diseases awaits further investigations.
Decoding the Infant Mind: Multichannel Pattern Analysis (MCPA) using fNIRS

The MRI environment restricts the types of populations and tasks that can be studied by cognitive neuroscientists (e.g., young infants, face-to-face communication). FNIRS is a neuroimaging modality that records the same physiological signal as fMRI but without the constraints of MRI, and with better spatial localization than EEG. However, research in the fNIRS community largely lacks the analytic sophistication of analogous fMRI work, restricting the application of this imaging technology. The current paper presents a method of multivariate pattern analysis for fNIRS that allows the authors to decode the infant mind (a key fNIRS population). Specifically, multi-channel pattern analysis (MCPA) employs a correlation-based decoding method where a group model is constructed for all infants except one; both average patterns (i.e., infant-level) and single trial patterns (i.e., trial-level) of activation are decoded. Between subjects decoding is a particularly difficult task, because each infant has their own somewhat idiosyncratic patterns of neural activation. The fact that our method succeeds at across-subject decoding demonstrates the presence of group-level multi-channel regularities across infants. The code for implementing these analyses has been made readily available online to facilitate the quick adoption of this method to advance the methodological tools available to the fNIRS researcher.
Cancer in Kidney Transplantation

Cancer in the transplanted kidney is rare, and its clinical and surgical management can be controversial. We report 3 cases of cancer in renal transplantation (1 case of renal cell carcinoma and 2 cases of transitional cell carcinoma) and their treatment. Our data and those reported in the literature suggest that these cancers can be treated like a neoplasm in the general population. However, a higher number of cases and longer follow-up periods are necessary to confirm our findings.
Interventional Ultrasound in Pregnant Macaques: Embryonic/Fetal Applications

Similarities in developmental biology between human and nonhuman primates have resulted in the use of macaque species as models in perinatal research. Studies have frequently included invasive surgical procedures or may have required “blind” injections. Several techniques have been established in human subjects using ultrasound as a guide such as cordocentesis and fetal therapy. These techniques have been applied to the nonhuman primate laboratory setting, which significantly decreases the risk of pregnancy loss due to experimental intervention.
Visualizing complex dynamics in many-core accelerator architectures

While many-core accelerator architectures, such as today's Graphics Processing Units (GPUs), offer orders of magnitude more raw computing power than contemporary CPUs, their massive parallelism often produces complex dynamic behaviors even with the simplest applications. Using a fixed set of hardware or simulator performance counters to quantify behavior over a large interval of time such as an entire application execution run or program phase may not capture this behavior. Software and/or hardware designers may consequently miss out on opportunities to optimize for better performance. Similarly, significant effort may be expended to find metrics that explain anomalous behavior in architecture design studies. Moreover, the increasing complexity of applications developed for today's GPU has created additional difficulties for software developers when attempting to identify bottlenecks of an application for optimization. This paper presents a novel GPU performance visualization tool, AerialVision, to address these two problems. It interfaces with the GPGPU-Sim simulator to capture and visualize the dynamic behavior of a GPU architecture throughout an application run. Similar to existing performance analysis tools for CPUs, it can annotate individual lines of source code with performance statistics to simplify the bottleneck identification process. To provide further insight, AerialVision introduces a novel methodology to relate pathological dynamic architectural behaviors resulting in performance loss with the part of the source code that is responsible. By rapidly providing insight into complex dynamic behavior, AerialVision enables research on improving many-core accelerator architectures and will help ensure applications written for these architectures reach their full performance potential.
Social Discounting under Risk

As a measure of how prosocial behavior depends on social distance, social discounting is defined as the decrease in generosity between the decision maker and the recipient as the social distance increases. While risk is a ubiquitous part of modern life, there is limited research on the relationship between risk and prosocial behavior. In the present experiment, we empirically test whether risk has an influence on social discounting. We use the choice titration procedure to examine this effect. Our data show that independent of risk, participants are less eager to forego money and exhibit more selfishness toward a specific person when the social distance increases; these findings are reflected in the hyperbolic model. Interestingly, risk influences the shape of the social discounting function, which is reflected in the notable different discount rates. Individuals who make decisions under risk yield a smaller discount rate than those who make decisions without risk, i.e., under risk subjects reduce less their generosity as a function of the social distance. Furthermore, this distinct type of generosity occurs typically among individuals with 10-distance recipients but not with the closest- and furthest-social-distance recipients.