Miracle-dz/UniFAR-FTUs huggingface dataset:
Integration of Calcium and Cyclic AMP Signaling Pathways by 14-3-3

ABSTRACT Calcium-stimulated nuclear factor of activated T cells (NFAT) transcription activity at the interleukin-2 promoter is negatively regulated by cyclic AMP (cAMP). This effect of cAMP is mediated, in part, by protein kinase A phosphorylation of NFAT. The mechanism of regulation involves the creation of a phosphorylation-dependent binding site for 14-3-3. Decreased NFAT phosphorylation caused by the calcium-stimulated phosphatase calcineurin, or mutation of the PKA phosphorylation sites, disrupted 14-3-3 binding and increased NFAT transcription activity. In contrast, NFAT phosphorylation caused by cAMP increased 14-3-3 binding and reduced NFAT transcription activity. The regulated interaction between NFAT and 14-3-3 provides a mechanism for the integration of calcium and cAMP signaling pathways.
Deletion of Ptpn11 (Shp2) in Cardiomyocytes Causes Dilated Cardiomyopathy via Effects on the Extracellular Signal–Regulated Kinase/Mitogen-Activated Protein Kinase and RhoA Signaling Pathways

Background— Heart failure is the leading cause of death in the United States. By delineating the pathways that regulate cardiomyocyte function, we can better understand the pathogenesis of cardiac disease. Many cardiomyocyte signaling pathways activate protein tyrosine kinases. However, the role of specific protein tyrosine phosphatases (PTPs) in these pathways is unknown. Methods and Results— Here, we show that mice with muscle-specific deletion of Ptpn11, the gene encoding the SH2 domain–containing PTP Shp2, rapidly develop a compensated dilated cardiomyopathy without an intervening hypertrophic phase, with signs of cardiac dysfunction appearing by the second postnatal month. Shp2-deficient primary cardiomyocytes are defective in extracellular signal–regulated kinase/mitogen-activated protein kinase (Erk/MAPK) activation in response to a variety of soluble agonists and pressure overload but show hyperactivation of the RhoA signaling pathway. Treatment of primary cardiomyocytes with Erk1/2- and RhoA pathway–specific inhibitors suggests that both abnormal Erk/MAPK and RhoA activities contribute to the dilated phenotype of Shp2-deficient hearts. Conclusions— Our results identify Shp2 as the first PTP with a critical role in adult cardiac function, indicate that in the absence of Shp2 cardiac hypertrophy does not occur in response to pressure overload, and demonstrate that the cardioprotective role of Shp2 is mediated via control of both the Erk/MAPK and RhoA signaling pathways.
Microtubule binding protein PACRG plays a role in regulating specific ciliary dyneins during microtubule sliding

The complex waveforms characteristic of motile eukaryotic cilia and flagella are produced by the temporally and spatially regulated action of multiple dynein subforms generating sliding between subsets of axonemal microtubules. Multiple protein complexes have been identified that are associated with the doublet microtubules and that mediate regulatory signals between key axonemal structures, such as the radial spokes and central apparatus, and the dynein arm motors; these complexes include the N‐DRC, MIA, and CSC complexes. Previous studies have shown that PACRG (parkin co‐regulated gene) forms a complex that is anchored to the axonemal doublet microtubules. Loss of PACRG causes defects in ciliary motility and cilia related diseases. Here, we use an in vitro microtubule sliding assay to demonstrate that PACRG and its interactors are part of a signaling pathway that includes the central apparatus, radial spokes and specific inner dynein arm subforms to control dynein‐driven microtubule sliding. Using a biochemical approach, our studies also indicate that PACRG interacts with the radial spokes. © 2016 Wiley Periodicals, Inc.
Individual Differences in Stressor-Evoked Blood Pressure Reactivity Vary with Activation, Volume, and Functional Connectivity of the Amygdala

Individuals who exhibit exaggerated blood pressure reactions to psychological stressors are at risk for hypertension, ventricular hypertrophy, and premature atherosclerosis; however, the neural systems mediating exaggerated blood pressure reactivity and associated cardiovascular risk in humans remain poorly defined. Animal models indicate that the amygdala orchestrates stressor-evoked blood pressure reactions via reciprocal signaling with corticolimbic and brainstem cardiovascular-regulatory circuits. Based on these models, we used a multimodal neuroimaging approach to determine whether human individual differences in stressor-evoked blood pressure reactivity vary with amygdala activation, gray matter volume, and functional connectivity with corticolimbic and brainstem areas implicated in stressor processing and cardiovascular regulation. We monitored mean arterial pressure (MAP) and concurrent functional magnetic resonance imaging BOLD signal changes in healthy young individuals while they completed a Stroop color-word stressor task, validated previously in epidemiological studies of cardiovascular risk. Individuals exhibiting greater stressor-evoked MAP reactivity showed (1) greater amygdala activation, (2) lower amygdala gray matter volume, and (3) stronger positive functional connectivity between the amygdala and perigenual anterior cingulate cortex and brainstem pons. Individual differences in amygdala activation, gray matter volume, and functional connectivity with corticolimbic and brainstem circuits may partly underpin cardiovascular disease risk by impacting stressor-evoked blood pressure reactivity.
Comparing acquisition of and preference for manual signs, picture exchange, and speech-generating devices in nine children with autism spectrum disorder

Abstract Objective: To compare how quickly children with autism spectrum disorder (ASD) acquired manual signs, picture exchange, and an iPad®/iPod®-based speech-generating device (SGD) and to compare if children showed a preference for one of these options. Method: Nine children with ASD and limited communication skills received intervention to teach requesting preferred stimuli using manual signs, picture exchange, and a SGD. Intervention was evaluated in a non-concurrent multiple-baseline across participants and alternating treatments design. Results: Five children learned all three systems to criterion. Four children required fewer sessions to learn the SGD compared to manual signs and picture exchange. Eight children demonstrated a preference for the SGD. Conclusion: The results support previous studies that demonstrate children with ASD can learn manual signs, picture exchange, and an iPad®/iPod®-based SGD to request preferred stimuli. Most children showed a preference for the SGD. For some children, acquisition may be quicker when learning a preferred option.
SIMULATIONS OF WINDS OF WEAK-LINED T TAURI STARS: THE MAGNETIC FIELD GEOMETRY AND THE INFLUENCE OF THE WIND ON GIANT PLANET MIGRATION

By means of numerical simulations, we investigate magnetized stellar winds of pre-main-sequence stars. In particular, we analyze under which circumstances these stars will present elongated magnetic features (e.g., helmet streamers, slingshot prominences, etc). We focus on weak-lined T Tauri stars, as the presence of the tenuous accretion disk is not expected to have strong influence on the structure of the stellar wind. We show that the plasma-β parameter (the ratio of thermal to magnetic energy densities) is a decisive factor in defining the magnetic configuration of the stellar wind. Using initial parameters within the observed range for these stars, we show that the coronal magnetic field configuration can vary between a dipole-like configuration and a configuration with strong collimated polar lines and closed streamers at the equator (multicomponent configuration for the magnetic field). We show that elongated magnetic features will only be present if the plasma-β parameter at the coronal base is β0 ≪ 1. Using our self-consistent three-dimensional magnetohydrodynamics model, we estimate for these stellar winds the timescale of planet migration due to drag forces exerted by the stellar wind on a hot-Jupiter. In contrast to the findings of Lovelace et al., who estimated such timescales using the Weber and Davis model, our model suggests that the stellar wind of these multicomponent coronae are not expected to have significant influence on hot-Jupiters migration. Further simulations are necessary to investigate this result under more intense surface magnetic field strengths (∼2–3 kG) and higher coronal base densities, as well as in a tilted stellar magnetosphere.
Regional and racial differences among stroke victims in the United States

Examination of the 1980 age‐adjusted mortality data by geographic region shows that death rates for black males and females are higher in the Southeast than in other parts of the United States. The reason for these higher death rates was sought by examining the NHANES II data. The prevalence of hypertension among black females was significantly higher in the Southeast (44%) than in all other regions (34%). The prevalence of hypertension among males, both black and white, and among white females in the Southeast was similar to that in all other regions. Although black and white hypertensives in the Southeast were as aware of their condition as hypertensives in the rest of the nation, the rate of hypertension control among black females in the Southeast was significantly lower than elsewhere. In addition, both male and female black hypertensives in the Southeast were more likely to be obese than their counterparts in the other regions. Analysis of smoking patterns showed that among hypertensives in the Southeast, only white males had higher rates of smoking than their counterparts elsewhere in the United States.
Predicting the 30-Year Risk of Cardiovascular Disease: The Framingham Heart Study

Background— Present cardiovascular disease (CVD) risk prediction algorithms were developed for a ≤10-year follow up period. Clustering of risk factors at younger ages and increasing life expectancy suggest the need for longer-term risk prediction tools. Methods and Results— We prospectively followed 4506 participants (2333 women) of the Framingham Offspring cohort aged 20 to 59 years and free of CVD and cancer at baseline examination in 1971–1974 for the development of “hard” CVD events (coronary death, myocardial infarction, stroke). We used a modified Cox model that allows adjustment for competing risk of noncardiovascular death to construct a prediction algorithm for 30-year risk of hard CVD. Cross-validated survival C statistic and calibration &khgr;2 were used to assess model performance. The 30-year hard CVD event rates adjusted for the competing risk of death were 7.6% for women and 18.3% for men. Standard risk factors (male sex, systolic blood pressure, antihypertensive treatment, total and high-density lipoprotein cholesterol, smoking, and diabetes mellitus), measured at baseline, were significantly related to the incidence of hard CVD and remained significant when updated regularly on follow-up. Body mass index was associated positively with 30-year risk of hard CVD only in models that did not update risk factors. Model performance was excellent as indicated by cross-validated discrimination C=0.803 and calibration &khgr;2=4.25 (P=0.894). In contrast, 30-year risk predictions based on different applications of 10-year functions proved inadequate. Conclusions— Standard risk factors remain strong predictors of hard CVD over extended follow-up. Thirty-year risk prediction functions offer additional risk burden information that complements that of 10-year functions.
Use of Large Databases to Identify Trends in the Behavior of Ferritic Steels

In this paper we explore the crucial role played by the use of large databases in the identification, development, and refinement of models that describe the toughness behavior of ferritic steels. Specifically, we seek to emphasize and illustrate the point that when physical models are calibrated using large databases this process can reveal trends not previously seen, or foreseen. In support of this idea two examples are cited. First, the evidence for a CVE master curve in fracture mode transition is reviewed, as a counterpoint to the commonly held belief that each Charpy tanh transition curve is unique, with little commonality even within specific alloys, let alone across all ferritic steels. Second, new evidence is presented that the degree of prior hardening experienced by a ferritic steel has a systematic effect on the scatter exhibited by KJc data. This evidence suggests that the KJc Master Curve model, in which the scatter of KJc follows a Weibull distribution having a Kmin = 20 MPa√m and a slope (scatter magnitude) of 4, requires refinement, especially for the higher To values characteristic of steels that have been hardened by, for example, neutron irradiation damage.Copyright © 2009 by ASME
Green Engineered Polypropylene Biodegradable Fibers Through Blending with Recycled Poly(lactic) Acid Plastic Wastes

The modification of polypropylene (PP) fibers via blending with recycled poly(lactic) acid (r-PLA) flakes by a melt spinning method was investigated. Mechanical and morphological properties, biodegradability, differential scanning calorimetery (DSC) analysis, and dyeing behavior were carried out for physical and structural characterization of the fiber samples. The results showed that the PP/r-PLA blend fibers with the different blend ratios could be successfully melt spun along with suitable continuity. Acceptable tenacity and initial modulus and suitable biodegradability were obtained for the modified PP fibers. Dye uptake of the modified PP fiber samples was improved and the washing and light fastness of some them were excellent.
Reducing the impact bias in judgments of post-decisional affect: Distraction or task interference?

People overestimate their affective reactions to future events and decisions — a phenomenon that has been termed “impact bias. ” Evidence suggests that completing a diary detailing events contemporaneous with the focal one de-biases judgments of affect. It is generally assumed that this is because diary completion helps people to realize that they will be distracted from the focal event. However, there is another possibility: de-biasing may occur because diary completion interferes with the processing responsible for the bias. In a first experiment, we showed that diary completion also lowers affect associated with past decisions. In a second experiment, we showed that solving anagrams has the same effect. A third experiment demonstrates that this is not because affect judgments are influenced by mood changes brought about by solving anagrams. Indeed, monitoring moods lowered affect in the same way as diary completion. It appears that cognitive tasks of any sort interfere with the processing required by judgments of affect.
Silymarin augments human cervical cancer HeLa cell apoptosis via P38/JNK MAPK pathways in serum-free medium

Silymarin was proved to have a protective effect of UV-induced A375-S2 cell apoptosis in our previous research. In this study, its pro-apoptotic and anti-apoptotic activities on human cervical cancer (HeLa) cells in vitro were investigated. Silymarin induced HeLa cell death through both apoptotic and necrotic pathways. At low doses (below 80 μmol l− 1), it induced cell apoptosis, but caused necrosis at high dose (160 μmol l− 1). Silymarin induced typical chromatin condensation and nuclear fragmentation as a hallmark of apoptosis. In this case, mitochondrial Bcl-2 family, Bcl-2 and Bax, were not involved in apoptotic effects; however, silymarin-induced cell death was regulated by the activation of p38 and JNK MAPKs. We also found that pan-caspase inhibitor and caspase-3 inhibitor could not antagonise silymarin-induced apoptosis. Therefore, silymarin induced and augmented HeLa cell apoptosis through p38/JNK MAPKs in the serum-free medium.
Design lessons from mainstream motion-based games for exergames for older adults

Availability of commodity gaming devices for bodily input has sparked new interest in serious games for rehabilitation and the treatment of age-related diseases. This leads to the idea of creating games for the daily use to prevent the age-related loss of certain abilities. In a qualitative in-depth field study, we visited senior participants at their homes over the course of three full days. During this time they played a selection of off-the-shelf games titles that included game controls that can be seen also as physical exercises. We discuss our qualitative findings and formulate design lessons to consider when developing games for older adults: favor progress over challenge, prevent overexertion, prevent health risks, decreased reaction times, design for adaptability, and prefer realistic scenarios and mechanics over fantasy settings.
Drug-Related Mitochondrial Optic Neuropathies

Background: There is a group of optic neuropathies of either genetic or acquired origin characterized by similar clinical manifestations with preferential involvement of the papillomacular bundle (PMB). PMB fibers are most susceptible to injury as they are small, unmyelinated, and have high-energy demands. These optic neuropathies share a presumed common pathophysiology of mitochondrial dysfunction. Evidence Acquisition: A variety of medications cause optic neuropathy by interfering with mitochondrial function. The evidence linking these therapeutic agents as a cause of mitochondrial optic neuropathy (MON) is well established in some and less certain in others. The differential diagnosis includes other optic nerve disorders producing bilateral, symmetric visual loss, including certain nutritional deficiencies, toxins, and genetic diseases. Results: Ethambutol, chloramphenicol, linezolid, erythromycin, streptomycin, and antiretroviral drugs can cause drug-related MON. In many cases, drug toxicity is dose and duration dependent, and discontinuation of the drug in a timely manner can lead to significant visual recovery. Conclusions: Mitochondrial optic neuropathies are increasingly recognized as a spectrum of conditions that reach a similar end point by compromising a common pathway of mitochondrial dysfunction. Clinicians should be aware of drugs that can cause a MON. Prompt recognition of this association is critical in preventing irreversible, profound visual loss.
Income shocks and HIV in Sub-Saharan Africa

Poverty is commonly cited as a key driver of the HIV/AIDS epidemic, yet little causal evidence exists linking economic conditions to actual disease outcomes. Using data on more than 200,000 individuals across 19 Sub-Saharan African countries, we present evidence that negative income shocks can lead to substantial increases in HIV prevalence, particularly for women in rural areas. Building on recent work showing that income shortfalls can induce some women to engage in higher-risk sex, we match data on individuals' HIV status from the Demographic and Health Surveys to data on recent variation in local rainfall, a primary (and exogenous) source of variation in income for rural households in Africa. We find that infection rates for women (men) in HIV-endemic rural areas increase significantly by 14 percent (11 percent) for every drought event experienced in the previous 10 years. Further analysis suggests that women most affected by the shocks (that is, those engaged in agriculture) are driving the women's results; these women are partnering with men least affected (those employed outside agriculture). Our findings suggest a role for formal insurance and social safety nets in tackling the HIV/AIDS epidemic.
Neutron Diffraction Measurements of Deformation and Recrystallization Textures in Cold Wire-Drawn Copper

The crystallographic texture of electrolytic tough pitch copper has been investigated by neutron diffraction after deformation by cold wire-drawing (reduction of area between 51 and 94 %) and after static recrystallization. The deformation texture characterized by a strong <111> fiber is reinforced with increasing strain, while the volume fraction of <100> fiber is reduced. In turn, we show that the <100> fiber is strongly reinforced after recrystallization when intensity of the <100> maxima increases with the level of deformation. Since the <111> fiber disappears first during annealing, the static recrystallization has been followed “in situ” by measurements of the diffracted intensity evolution in the center of the {111} pole figure. From these experimental data and taking into account the Arrhenius equation, the activation energy of the recrystallization process has been determined for each deformation rate.
A Review on the Role of Vibrational Spectroscopy as An Analytical Method to Measure Starch Biochemical and Biophysical Properties in Cereals and Starchy Foods

Starch is the major component of cereal grains and starchy foods, and changes in its biophysical and biochemical properties (e.g., amylose, amylopectin, pasting, gelatinization, viscosity) will have a direct effect on its end use properties (e.g., bread, malt, polymers). The use of rapid and non-destructive methods to study and monitor starch properties, such as gelatinization, retrogradation, water absorption in cereals and starchy foods, is of great interest in order to improve and assess their quality. In recent years, near infrared reflectance (NIR) and mid infrared (MIR) spectroscopy have been explored to predict several quality parameters, such as those generated by instrumental methods commonly used in routine analysis like the rapid visco analyser (RVA) or viscometers. In this review, applications of both NIR and MIR spectroscopy to measure and monitor starch biochemical (amylose, amylopectin, starch) and biophysical properties (e.g., pasting properties) will be presented and discussed.
A Bayesian Account of Visual–Vestibular Interactions in the Rod-and-Frame Task

Abstract Panoramic visual cues, as generated by the objects in the environment, provide the brain with important information about gravity direction. To derive an optimal, i.e., Bayesian, estimate of gravity direction, the brain must combine panoramic information with gravity information detected by the vestibular system. Here, we examined the individual sensory contributions to this estimate psychometrically. We asked human subjects to judge the orientation (clockwise or counterclockwise relative to gravity) of a briefly flashed luminous rod, presented within an oriented square frame (rod-in-frame). Vestibular contributions were manipulated by tilting the subject’s head, whereas visual contributions were manipulated by changing the viewing distance of the rod and frame. Results show a cyclical modulation of the frame-induced bias in perceived verticality across a 90° range of frame orientations. The magnitude of this bias decreased significantly with larger viewing distance, as if visual reliability was reduced. Biases increased significantly when the head was tilted, as if vestibular reliability was reduced. A Bayesian optimal integration model, with distinct vertical and horizontal panoramic weights, a gain factor to allow for visual reliability changes, and ocular counterroll in response to head tilt, provided a good fit to the data. We conclude that subjects flexibly weigh visual panoramic and vestibular information based on their orientation-dependent reliability, resulting in the observed verticality biases and the associated response variabilities.
Strawman Specification for TCP Friendly ( Reliable ) Multicast Congestion Control ( TFMCC )

This document presents a strawman specification for TCP-Friendly Multicast Congestion Control (TFMCC). It is not a standard of any form. We do not suggest basing products on this specification. Eventually, if further research shows this specification to perform acceptably, we envisage moving this document into the IETF for standardization, but the document is not currently at this stage. Many people have contributed to this specification in one form or another by the time it is ready for standardization we hope that many more people will have contributed ideas and performed simulation work to test the details.