Miracle-dz/UniFAR-FTUs huggingface dataset:
Stac3 enhances expression of human CaV1.1 in Xenopus oocytes and reveals gating pore currents in HypoPP mutant channels

Mutations of CaV1.1, the pore-forming subunit of the L-type Ca2+ channel in skeletal muscle, are an established cause of hypokalemic periodic paralysis (HypoPP). However, functional assessment of HypoPP mutant channels has been hampered by difficulties in achieving sufficient plasma membrane expression in cells that are not of muscle origin. In this study, we show that coexpression of Stac3 dramatically increases the expression of human CaV1.1 (plus &agr;2-&dgr;1b and &bgr;1a subunits) at the plasma membrane of Xenopus laevis oocytes. In voltage-clamp studies with the cut-open oocyte clamp, we observe ionic currents on the order of 1 &mgr;A and gating charge displacements of ∼0.5–1 nC. Importantly, this high expression level is sufficient to ascertain whether HypoPP mutant channels are leaky because of missense mutations at arginine residues in S4 segments of the voltage sensor domains. We show that R528H and R528G in S4 of domain II both support gating pore currents, but unlike other R/H HypoPP mutations, R528H does not conduct protons. Stac3-enhanced membrane expression of CaV1.1 in oocytes increases the throughput for functional studies of disease-associated mutations and is a new platform for investigating the voltage-dependent properties of CaV1.1 without the complexity of the transverse tubule network in skeletal muscle.
The Effect of Technology-Mediated Diabetes Prevention Interventions on Weight: A Meta-Analysis

Background Lifestyle interventions targeting weight loss, such as those delivered through the Diabetes Prevention Program, reduce the risk of developing type 2 diabetes. Technology-mediated interventions may be an option to help overcome barriers to program delivery, and to disseminate diabetes prevention programs on a larger scale. Objective We conducted a meta-analysis to evaluate the effect of such technology-mediated interventions on weight loss. Methods In this meta-analysis, six databases were searched to identify studies reporting weight change that used technology to mediate diet and exercise interventions, and targeted individuals at high risk for developing type 2 diabetes. Studies published between January 1, 2002 and August 4, 2016 were included. Results The search identified 1196 citations. Of those, 15 studies met the inclusion criteria and evaluated 18 technology-mediated intervention arms delivered to a total of 2774 participants. Study duration ranged from 12 weeks to 2 years. A random-effects meta-analysis showed a pooled weight loss effect of 3.76 kilograms (95% CI 2.8-4.7; P<.001) for the interventions. Several studies also reported improved glycemic control following the intervention. The small sample sizes and heterogeneity of the trials precluded an evaluation of which technology-mediated intervention method was most efficacious. Conclusions Technology-mediated diabetes prevention programs can result in clinically significant amounts of weight loss, as well as improvements in glycaemia in patients with prediabetes. Due to their potential for large-scale implementation, these interventions will play an important role in the dissemination of diabetes prevention programs.
Female Field Crickets Incur Increased Parasitism Risk When Near Preferred Song

Female animals often prefer males with conspicuous traits because these males provide direct or indirect benefits. Conspicuous male traits, however, can attract predators. This not only increases the risk of predation for conspicuous males but also for the females that prefer them. In the variable field cricket, Gryllus lineaticeps, males that produce preferred song types provide females with greater material benefits, but they are also more likely to attract lethal parasitoid flies. First, we conducted a field experiment that tested the hypothesis that females have a greater risk of fly parasitism when in association with preferred high chirp rate males. Females were nearly twice as likely to be parasitized when caged with high chirp rate song than when caged with low chirp rate song. Females may thus be forced to trade off the quality of the benefits they receive from mating with preferred males and the risk of being killed by a predator when near these males. Second, we assessed female parasitism rates in a natural population. Up to 6% of the females were parasitized in field samples. Because the females we collected could have become parasitized had they not been collected, this provides a minimum estimate of the female parasitism rate in the field. In a laboratory study, we found no difference in the proportion of time parasitized and unparasitized females spent hiding under shelters; thus, differences in activity patterns do not appear to have biased our estimate of female parasitism rates. Overall, our results suggest that female association costs have the potential to shape the evolution of female mating preferences.
Topographic gravity modeling for global Bouguer maps to degree 2160: Validation of spectral and spatial domain forward modeling techniques at the 10 microGal level

Over the past years, spectral techniques have become a standard to model Earth's global gravity field to 10 km scales, with the EGM2008 geopotential model being a prominent example. For some geophysical applications of EGM2008, particularly Bouguer gravity computation with spectral techniques, a topographic potential model of adequate resolution is required. However, current topographic potential models have not yet been successfully validated to degree 2160, and notable discrepancies between spectral modeling and Newtonian (numerical) integration well beyond the 10 mGal level have been reported. Here we accurately compute and validate gravity implied by a degree 2160 model of Earth's topographic masses. Our experiments are based on two key strategies, both of which require advanced computational resources. First, we construct a spectrally complete model of the gravity field which is generated by the degree 2160 Earth topography model. This involves expansion of the topographic potential to the 15th integer power of the topography and modeling of short‐scale gravity signals to ultrahigh degree of 21,600, translating into unprecedented fine scales of 1 km. Second, we apply Newtonian integration in the space domain with high spatial resolution to reduce discretization errors. Our numerical study demonstrates excellent agreement (8 μGgal RMS) between gravity from both forward modeling techniques and provides insight into the convergence process associated with spectral modeling of gravity signals at very short scales (few km). As key conclusion, our work successfully validates the spectral domain forward modeling technique for degree 2160 topography and increases the confidence in new high‐resolution global Bouguer gravity maps.
Allosteric modulation of cardiac myosin dynamics by omecamtiv mecarbil

New promising avenues for the pharmacological treatment of skeletal and heart muscle diseases rely on direct sarcomeric modulators, which are molecules that can directly bind to sarcomeric proteins and either inhibit or enhance their activity. A recent breakthrough has been the discovery of the myosin activator omecamtiv mecarbil (OM), which has been shown to increase the power output of the cardiac muscle and is currently in clinical trials for the treatment of heart failure. While the overall effect of OM on the mechano-chemical cycle of myosin is to increase the fraction of myosin molecules in the sarcomere that are strongly bound to actin, the molecular basis of its action is still not completely clear. We present here a Molecular Dynamics study of the motor domain of human cardiac myosin bound to OM, where the effects of the drug on the dynamical properties of the protein are investigated for the first time with atomistic resolution. We found that OM has a double effect on myosin dynamics, inducing a) an increased coupling of the motions of the converter and lever arm subdomains to the rest of the protein and b) a rewiring of the network of dynamic correlations, which produces preferential communication pathways between the OM binding site and distant functional regions. The location of the residues responsible for these effects suggests possible strategies for the future development of improved drugs and the targeting of specific cardiomyopathy-related mutations.
Register sharing for equality prediction

Recently, Value Prediction (VP) has been gaining renewed traction in the research community. VP speculates on the result of instructions to increase Instruction Level Parallelism (ILP). In most embodiments, VP requires large tables to track predictions for many static instructions. However, in many cases, it is possible to detect that the result of an instruction is produced by an older inflight instruction, but not to predict the result itself. Consequently it is possible to rely on predicting register equality and handle speculation through the renamer. To do so, we propose to use Distance Prediction, a technique that was previously used to perform Speculative Memory Bypassing (short-circuiting def-store-load-use chains). Distance Prediction attempts to determine how many instructions separate the instruction of interest and the most recent older instruction that produced the same result. With this information, the physical register identifier of the older instruction can be retrieved from the ROB and provided to the renamer. In this paper, we first quantify the performance gains brought by renaming-based register equality prediction and regular VP on SPEC benchmarks. Second, we study the overlap between the two different schemes and show that those mechanisms often capture different behavior.
Application of polyethylene sheath and swelling powder against water treeing

It is feasible to calculate the water permeation into a cable with a plastic jacket and a swelling tape underneath. The combination of a PVC jacket and swelling tape hardly gives any relief. However, MDPE jackets are certainly promising. If cables are operated with a low load the jackets are approximately isothermal. In that case, they can be adequately protected against water by means of a combination of a jacket with low water permeability and a water absorber within the jacket, e.g. swelling tape. At high load, the temperature gradient makes the water intrusion faster, but the humidity remains lower. Therefore, possibly the critical relative humidity level of 70-75% within the jacket will not be reached.
Adjudicating between face-coding models with individual-face fMRI responses

The perceptual representation of individual faces is often explained with reference to a norm-based face space. In such spaces, individuals are encoded as vectors where identity is primarily conveyed by direction and distinctiveness by eccentricity. Here we measured human fMRI responses and psychophysical similarity judgments of individual face exemplars, which were generated as realistic 3D animations using a computer-graphics model. We developed and evaluated multiple neurobiologically plausible computational models, each of which predicts a representational distance matrix and a regional-mean activation profile for 24 face stimuli. In the fusiform face area, a face-space coding model with sigmoidal ramp tuning provided a better account of the data than one based on exemplar tuning. However, an image-processing model with weighted banks of Gabor filters performed similarly. Accounting for the data required the inclusion of a measurement-level population averaging mechanism that approximates how fMRI voxels locally average distinct neuronal tunings. Our study demonstrates the importance of comparing multiple models and of modeling the measurement process in computational neuroimaging. Author Summary Humans recognize conspecifics by their faces. Understanding how faces are recognized is an open computational problem with relevance to theories of perception, social cognition, and the engineering of computer vision systems. Here we measured brain activity with functional MRI while human participants viewed individual faces. We developed multiple computational models inspired by known response preferences of single neurons in the primate visual cortex. We then compared these neuronal models to patterns of brain activity corresponding to individual faces. The data were consistent with a model where neurons respond to directions in a high-dimensional space of faces. It also proved essential to model how functional MRI voxels locally average the responses of tens of thousands of neurons. The study highlights the challenges in adjudicating between alternative computational theories of visual information processing.
Adaptive visual tracking and recognition using particle filters

This paper presents an improved method for simultaneous tracking and recognition of human faces from video, where a time series model is used to resolve the uncertainties in tracking and recognition. The improvements mainly arise from three aspects: (i) modeling the inter-frame appearance changes within the video sequence using an adaptive appearance model and an adaptive-velocity motion model; (ii) modeling the appearance changes between the video frames and gallery images by constructing intra- and extra-personal spaces; and (iii) utilization of the fact that the gallery images are in frontal views. By embedding them in a particle filter, we are able to achieve a stabilized tracker and an accurate recognizer when confronted by pose and illumination variations.
Pattern of Alcohol Consumption by Young People from North Eastern Portugal

Abstract Alcohol is the most used psychoactive substance among adolescents, is an important public health problem and a major risk factor for the health of this group. This study is regarding to the pattern of alcohol consumption by adolescents. Descriptive, correlational and cross-sectional study, with a sample of 378 adolescents, which are attending three high schools, in north-eastern Portugal. In the data collection we used a questionnaire. Data was analysed using SPSS. The prevalence of alcohol is 86.8%. The mean score of Alcohol Use Disorders Identification Test (AUDIT) was 3.53±4.525 points. The vast majority of participants were located in the non-excessive alcohol consumption area (91.3%). The pattern of alcohol consumption differs significantly between gender (Wald: p ≤ 0,004) and the religious practice (Wald: p ≤ 0,027), with greater percentage of boys and students who did not practice any religion in excessive consumers. The prevalence of alcohol consumers is high. The proportion of young people with excessive consumption in our sample is lower than in other studies, but shows that there is a group of adolescents in excessive consumption. It found a relationship between consumption pattern, gender and religious practice. These results justify the development of public health interventions.
Dynamic Emotional and Neural Responses to Music Depend on Performance Expression and Listener Experience

Apart from its natural relevance to cognition, music provides a window into the intimate relationships between production, perception, experience, and emotion. Here, emotional responses and neural activity were observed as they evolved together with stimulus parameters over several minutes. Participants listened to a skilled music performance that included the natural fluctuations in timing and sound intensity that musicians use to evoke emotional responses. A mechanical performance of the same piece served as a control. Before and after fMRI scanning, participants reported real-time emotional responses on a 2-dimensional rating scale (arousal and valence) as they listened to each performance. During fMRI scanning, participants listened without reporting emotional responses. Limbic and paralimbic brain areas responded to the expressive dynamics of human music performance, and both emotion and reward related activations during music listening were dependent upon musical training. Moreover, dynamic changes in timing predicted ratings of emotional arousal, as well as real-time changes in neural activity. BOLD signal changes correlated with expressive timing fluctuations in cortical and subcortical motor areas consistent with pulse perception, and in a network consistent with the human mirror neuron system. These findings show that expressive music performance evokes emotion and reward related neural activations, and that music's affective impact on the brains of listeners is altered by musical training. Our observations are consistent with the idea that music performance evokes an emotional response through a form of empathy that is based, at least in part, on the perception of movement and on violations of pulse-based temporal expectancies.
Airport Detection on Optical Satellite Images Using Deep Convolutional Neural Networks

This letter proposes a method using convolutional neural networks (CNNs) for airport detection on optical satellite images. To efficiently build a deep CNN with limited satellite image samples, a transfer learning approach had been employed by sharing the common image features of the natural images. To decrease the computing cost, an efficient region proposal method had been proposed based on the prior knowledge of the line segments distribution in an airport. The transfer learning ability on deep CNN for airport detection on satellite images had been first evaluated in this letter. The proposed method was tested on an image data set, including 170 different airports and 30 nonairports. The detection rate could reach 88.8% in experiments with seconds’ computation time, which showed a great improvement over other the state-of-the-art methods.
A critique of the historical‐fire‐regime concept in conservation

Prescribed fire is widely accepted as a conservation tool because fire is essential to the maintenance of native biodiversity in many terrestrial communities. Approaches to this land‐management technique vary greatly among continents, and sharing knowledge internationally can inform application of prescribed fire worldwide. In North America, decisions about how and when to apply prescribed fire are typically based on the historical‐fire‐regime concept (HFRC), which holds that replicating the pattern of fires ignited by lightning or preindustrial humans best promotes native species in fire‐prone regions. The HFRC rests on 3 assumptions: it is possible to infer historical fire regimes accurately; fire‐suppressed communities are ecologically degraded; and reinstating historical fire regimes is the best course of action despite the global shift toward novel abiotic and biotic conditions. We examined the underpinnings of these assumptions by conducting a literature review on the use of historical fire regimes to inform the application of prescribed fire. We found that the practice of inferring historical fire regimes for entire regions or ecosystems often entails substantial uncertainty and can yield equivocal results; ecological outcomes of fire suppression are complex and may not equate to degradation, depending on the ecosystem and context; and habitat fragmentation, invasive species, and other modern factors can interact with fire to produce novel and in some cases negative ecological outcomes. It is therefore unlikely that all 3 assumptions will be fully upheld for any landscape in which prescribed fire is being applied. Although the HFRC is a valuable starting point, it should not be viewed as the sole basis for developing prescribed fire programs. Rather, fire prescriptions should also account for other specific, measurable ecological parameters on a case‐by‐case basis. To best achieve conservation goals, researchers should seek to understand contemporary fire–biota interactions across trophic levels, functional groups, spatial and temporal scales, and management contexts.
Surfactant protein-D deficiency suppresses systemic inflammation and reduces atherosclerosis in ApoE knockout mice

Aims Although surfactant protein-D (SP-D) is a pneumoprotein that is predominantly synthesized by type II epithelial cells in the lung, individuals with increased circulating levels of SP-D are at an elevated risk of mortality from ischemic heart disease. Whether SP-D contributes directly to atherosclerosis is unknown. We determined the effects of SP-D gene deletion in a mouse model of atherosclerosis. Methods and results SP-D knockout (KO) mice were crossed with hyperlipidemic and atherosclerosis-prone apolipoprotein E (ApoE) KO mice to generate SP-D/ApoE double knockout (DKO) mice. Mice were placed on a high-fat diet for 12 weeks beginning at 8 weeks of age. Compared with ApoE KO mice, SP-D/ApoE DKO mice had significantly less atherosclerosis with reduced macrophage accumulation, decreased local macrophage proliferation, and increased smooth muscle cell coverage in plaques. Interestingly, SP-D deficiency worsened hypercholesterolemia and induced obesity and insulin resistance but suppressed plasma interleukin-6 (IL-6) levels. SP-D deficiency also reduced blood monocytes and neutrophils counts in ApoE KO mice. Conclusion SP-D deficiency reduces atherosclerosis in part by decreasing the accumulation and proliferation of macrophages and by reducing IL-6 levels systemically. SP-D is a promising therapeutic target for cachectic COPD patients with elevated circulating SP-D levels who are at increased risk of cardiovascular morbidity and mortality.
Retrospective analysis of survival in patients with leptomeningeal carcinomatosis from lung adenocarcinoma treated with erlotinib and gefitinib

Background Leptomeningeal carcinomatosis is a relatively rare metastatic form of non-small cell lung cancer, which can impact prognosis. There is an increasing need for selecting suitable epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors among those currently included in standard care for EGFR mutation-positive patients. We compared the efficacy of gefitinib and erlotinib in survival of patients with leptomeningeal carcinomatosis. Patients and methods The medical records of 269 patients who received tyrosine kinase inhibitors at a single center were retrospectively reviewed. Overall, 22 patients (8.2%) were treated with tyrosine kinase inhibitors for leptomeningeal carcinomatosis from non-small cell lung cancer with EGFR mutation between 2006 and 2016. Time to death from leptomeningeal carcinomatosis diagnosis was compared between the gefitinib and erlotinib groups. Results Gefitinib and erlotinib were administrated to 5 and 17 patients, respectively. Median progression-free survival was longer in the erlotinib group than in the gefitinib group (6.60 vs 2.12 months, P = 0.07). Overall survival was more than twice as long in the erlotinib arm compared with that in the gefitinib arm (7.20 vs 2.99 months, P = 0.32). Response in patients with exon 19 deletion was better than in those with exon 21 mutation (overall survival, 7.20 and 5.62 months, respectively, P = 0.12). Conclusions Erlotinib seemed more effective than gefitinib in prolonging survival in leptomeningeal carcinomatosis from EGFR mutation-positive non-small cell lung cancer and may be particularly beneficial in patients with EGFR exon 19 mutations, warranting further studies.