Miracle-dz/UniFAR-FTUs huggingface dataset:
No Apparent Requirement for Neuronal Sodium Channels in Excitation-Contraction Coupling in Rat Ventricular Myocytes

The majority of Na channels in the heart are composed of the tetrodotoxin (TTX)-resistant (KD, 2 to 6 &mgr;mol/L) “cardiac” NaV1.5 isoform; however, TTX-sensitive (KD, 1 to 25 nmol/L) “neuronal” Na channel isoforms have recently been detected in several cardiac preparations. In the present study, we determined the functional subcellular localization of Na channel isoforms (according to their TTX sensitivity) in rat ventricular myocytes by recording INa in control and detubulated myocytes. We found that TTX-sensitive INa (KD, ≈8.8 nmol/L) makes up 14±3% of total INa in control and ≤4% in detubulated myocytes and calculated that ≈80% of TTX-sensitive INa is located in the t-tubules, where it generates ≈1/3 of t-tubular INa. In contrast, TTX-resistant INa is located predominantly (≈78%) at the surface membrane. We also investigated the possible contribution of TTX-sensitive INa to excitation-contraction coupling, using 200 nmol/L TTX to selectively block TTX-sensitive INa. TTX decreased the rate of depolarization of the action potential by 10% but did not delay the rise of systolic Ca2+ in the center of the cell (transverse confocal line scan), suggesting that TTX-sensitive INa does not play a role in synchronizing Ca2+ release at the t-tubules; the amplitude of the Ca2+ transient and contraction were also unchanged by 200 nmol/L TTX. The quantity of charge entering via ICa elicited by control or TTX action potential waveforms was similar, suggesting that the trigger for Ca2+ release is not altered by blocking TTX-sensitive INa. We conclude that neuronal INa is concentrated at the t-tubules, but there is no evidence of a requirement for these channels in normal excitation-contraction coupling in ventricular myocytes.
The combined effect of triple therapy with rosiglitazone, metformin, and insulin aspart in type 2 diabetic patients.

OBJECTIVE Type 2 diabetes is caused by reduced insulin secretion and insulin resistance in skeletal muscle and liver. We tested the combination therapy with insulin aspart, rosiglitazone, and metformin with the purpose of treating all three defects in order to test the hypothesis that this "triple therapy" will normalize glucose metabolism. RESEARCH DESIGN AND METHODS Sixteen obese type 2 diabetic outpatients on human NPH or MIX (regular + NPH insulin) insulin twice daily were randomized to either triple therapy, i.e., insulin aspart (a rapid-acting insulin analog) at meals, metformin (which improves hepatic insulin sensitivity), and rosiglitazone (which improves peripheral insulin sensitivity), or to continue their NPH or MIX insulin twice daily for 6 months. Insulin doses were adjusted in both groups based on algorithms. HbA(1c), insulin dose, hypoglycemic episodes, insulin sensitivity (clamp), hepatic glucose production (tracer), and diurnal profiles of plasma glucose and insulin were used in evaluating treatment. RESULTS In the triple therapy group, HbA(1c) declined from 8.8 to 6.8% (P < 0.01) without inducing severe hypoglycemic events. Postprandial hyperglycemia was generally avoided, and the diurnal profile of serum insulin showed fast and high peaks without any need to increase insulin dose. In the control group, the insulin dose was increased by 50%, but nevertheless both HbA(1c) and 24-h blood glucose profiles remained unchanged. Insulin sensitivity improved in both skeletal muscle and the liver in the triple therapy group, whereas no change was observed in the control group. CONCLUSIONS We conclude that treatment of the three major pathophysiological defects in type 2 diabetic subjects by triple therapy significantly improved glucose metabolism in obese type 2 diabetic subjects.
The discovery of an expanding X-ray source in the HH 154 protostellar jet

Context. Protostellar jets are a new class of X-ray sources which has been discovered with both XMM-Newton and Chandra. The mechanism responsible for the X-ray emission is still not clear. Self-shocking in jets, shocks where the jet hits the surrounding medium, reflected or scattered stellar X-ray emission have all been invoked as possible explanations. Aims. One key diagnostic discriminating among physical emission mechanisms is the motion of the X-ray source: hydrodynamical numerical models of continuous protostellar jets plowing through a uniform medium show an X-ray emitting shock front moving at several hundreds km s -1 . In the nearest X-ray emitting protostellar jet, HH 154, this is detectable, with the spatial resolution of the Chandra X-ray observatory, over a few years baseline, allowing a robust discrimination among different mechanisms. Methods. We have performed, in October 2005, a deep Chandra X-ray observation of HH 154. Comparison with the previous (2001) Chandra observation allows to detect proper motion down to the level predicted by models of X-ray emitting shocks in the jet. Results. The 2005 Chandra observation of HH 154 shows unexpected morphological changes of the X-ray emission in comparison with the 2001 data. Two components are present: a stronger, point-like component with no detectable motion and a weaker component which has expanded in size by approximately 300 AU over the 4 years time base of the two observations. This expansion corresponds to approximately 500 km s -1 , very close to the velocity of the X-ray emitting shock in the simple theoretical models. Conclusions. The 2005 data show a more complex system than initially thought (and modeled), with multiple components with different properties. The observed morphology is possibly indicating a pulsed jet propagating through a non-homogeneous medium, likely with medium density decreasing with distance from the driving source. Detailed theoretical modeling and deeper X-ray observations will be needed to understand the physics of this fascinating class of sources.
Effects of neuromuscular lags on controlling contact transitions

We present a numerical exploration of contact transitions with the fingertip. When picking up objects our fingertips must make contact at specific locations, and—upon contact—maintain posture while producing well-directed force vectors. However, the joint torques for moving the fingertip towards a surface (τm) are different from those for producing static force vectors (τf). We previously described the neural control of such abrupt transitions in humans, and found that unavoidable errors arise because sensorimotor time delays and lags prevent an instantaneous switch between different torques. Here, we use numerical optimization on a finger model to reveal physical bounds for controlling such rapid contact transitions. Resembling human data, it is necessary to anticipatorily switch joint torques to τf at about 30 ms before contact to minimize the initial misdirection of the fingertip force vector. This anticipatory strategy arises in our deterministic model from neuromuscular lags, and not from optimizing for robustness to noise/uncertainties. Importantly, the optimal solution also leads to a trade-off between the speed of force magnitude increase versus the accuracy of initial force direction. This is an alternative to prevailing theories that propose multiplicative noise in muscles as the driver of speed–accuracy trade-offs. We instead find that the speed–accuracy trade-off arises solely from neuromuscular lags. Finally, because our model intentionally uses idealized assumptions, its agreement with human data suggests that the biological system is controlled in a way that approaches the physical boundaries of performance.
Optimal Belief Approximation

In Bayesian statistics probability distributions express beliefs. However, for many problems the beliefs cannot be computed analytically and approximations of beliefs are needed. We seek a loss function that quantifies how "embarrassing" it is to communicate a given approximation. We reproduce and discuss an old proof showing that there is only one ranking under the requirements that (1) the best ranked approximation is the non-approximated belief and (2) that the ranking judges approximations only by their predictions for actual outcomes. The loss function that is obtained in the derivation is equal to the Kullback-Leibler divergence when normalized. This loss function is frequently used in the literature. However, there seems to be confusion about the correct order in which its functional arguments, the approximated and non-approximated beliefs, should be used. The correct order ensures that the recipient of a communication is only deprived of the minimal amount of information. We hope that the elementary derivation settles the apparent confusion. For example when approximating beliefs with Gaussian distributions the optimal approximation is given by moment matching. This is in contrast to many suggested computational schemes.
Year‐round optical properties and source characterization of Arctic organic carbon aerosols on the North Slope Alaska

Long‐term data on organic aerosol concentration and optical properties are needed in the Arctic to improve characterization of radiative forcing by atmospheric aerosols. This study presents the seasonal trends (summer 2012 to summer 2013) of organic carbon (OC) and water‐soluble organic carbon (WSOC) along with optical properties of light‐absorbing OC from a yearlong sampling campaign in Utqiaġvik, AK. Ambient OC concentrations for the year range from 0.008 ± 0.002 μg m−3 to 0.95 ± 0.06 μg m−3 with peaks in late summer, early fall, and late winter. On average, WSOC accounted for 57 ± 11% of the total OC burden throughout the sampling campaign, which is consistent with previous WSOC values. In order to understand the potential radiative impacts of light‐absorbing OC, the light absorption properties of WSOC were determined. Seasonal averaging revealed that the highest average mass absorption efficiency value of 1.54 ± 0.75 m2 g−1 was in the fall, with an annual range of 0.70 ± 0.44 to 1.54 ± 0.75 m2 g−1. To quantify the contributions of fossil and contemporary carbon sources to OC, radiocarbon abundance measurements were performed. For OC, fossil contributions were the greatest for select samples in the fall at 61.4 ± 9.8%, with contemporary contributions dominating OC in the spring and summer (68.9 ± 9.8% and 64.8 ± 9.8%, respectively). Back trajectories identified five major source regions to Utqiaġvik throughout the year, with a marine influence from the Arctic Ocean potentially present in all seasons. All these results point to impact from primary and secondary sources of OC in the Arctic.
Performance evaluation of Speex audio codec for wireless communication networks

This paper provides a scheme where Speex audio codec was used in a wireless mobile communication network for the transmission of voice. The data gathered is visualised and compared with traditional AMR audio codec. The document concludes by stating that Speex presents itself as a better alternative to traditional AMR technology in the wireless field.
Computer Science in High Performance Sport - Applications and Implications for Professional Coaching (Dagstuhl Seminar 13272)

This report documents the program and the outcomes of Dagstuhl Seminar 13272 "Computer Science in High Performance Sport - Applications and Implications for Professional Coaching". There were 25 presentations organized into 5 sessions over the course of three days focusing on various aspects on the relevance, applications and current issues pertaining to computer science in sport and it's applications for professional coaching. In each session were covered a miscellaneous of topics which looked at broad topics ranging from hardware devices for mobile coaching, modelling sports as dynamical systems, use of neural networks in performance analysis as well as theoretical issues in human movement science, and serious games. Once again the Dagstuhl seminar concept provided benefits for the experts from different fields and countries that otherwise would hardly meet and have the opportunity to exchange their ideas in an informal fashion way. Several ideas were presented to try to reduce the gap between sport science and high performance coaching and new projects were discussed among the participants, such as the agreement to build a data repository in order facilitate the collaboration between different institutions with common and complementary research topics or framework in performance analysis.
CONE: Zero-Calibration Accurate Confidence Estimation for Indoor Localization Systems

Accurate estimation of the confidence of an indoor localization system is crucial for a number of applications including crowd-sensing applications, map-matching services, and probabilistic location fusion techniques; all of which lead to an enhanced user experience. Current approaches for quantifying the output accuracy of a localization system in real-time either do not provide a distance metric, require an extensive training process, and/or are tailored to a specific localization system. In this paper, we present the design, implementation, and evaluation of CONE: a novel calibration-free accurate confidence estimation system that can work in real-time with any location determination system. CONE builds on a sound theoretical model that allows it to trade the required user confidence with tight bound on the estimated confidence radius. We also introduce a new metric for evaluating confidence estimation systems that can capture new aspects of their performance. Evaluation of CONE on Android phones in a typical testbed using the iBeacons BLE technology with a side-by-side comparison with traditional confidence estimation techniques shows that CONE can achieve a consistent median absolute error difference accuracy of less than 2.7m while estimating the user position more than 80% of the time within the confidence circle. This is significantly better than the state-of-the-art confidence estimation systems that are tailored to the specific localization system in use. Moreover, CONE does not require any calibration and therefore provides a scalable and ubiquitous confidence estimation system for pervasive applications.
Functional modules integrating essential cellular functions are predictive of the response of leukaemia cells to DNA damage

MOTIVATION Childhood B-precursor lymphoblastic leukaemia (ALL) is the most common paediatric malignancy. Despite the fact that 80% of ALL patients respond to anti-cancer drugs, the patho-physiology of this disease is still not fully understood. mRNA expression-profiling studies that have been performed have not yet provided novel insights into the mechanisms behind cellular response to DNA damage. More powerful data analysis techniques may be required for identifying novel functional pathways involved in the cellular responses to DNA damage. RESULTS In order to explore the possibility that unforeseen biological processes may be involved in the response to DNA damage, we have developed and applied a novel procedure for the identification of functional modules in ALL cells. We have discovered that the overall activity of functional modules integrating protein degradation and mRNA processing is predictive of response to DNA damage. AVAILABILITY Supplementary material including R code, additional results, experimental datasets, as well as a detailed description of the methodology are available at http://www.bip. bham.ac. uk/vivo/fumo.html. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Interpreting Fuzzy Models: the Discriminative Power of Input Features

An important part of the interpretation of a decision process lies on the ascertainment of the influence of the input features, that is, of how much the implemented model relies on a given input feature to perform the desired task. Recently data analysis techniques based on fuzzy logic have gained attention because of their interpretability. Many real-world applications, however, have very high dimensionality and require very complex decision borders. In this case the number of fuzzy rules can proliferate and the easy interpretability of the fuzzy model can progressively disappear. A method is presented that quantifies the discriminative power of the input features in a fuzzy model. The proposed quantification helps the interpretation of fuzzy models built on high dimensional and very fragmented training sets. First, a measure of the information contained in the fuzzy model is defined on the basis of its fuzzy rules. The classification is then performed along one of the input features. That is the fuzzy rules are split according to that feature''s linguistic values. For each linguistic value, a fuzzy sub-model is generated from the original fuzzy model. The average information contained in these sub-models is measured and the relative comparison with the information measure of the original fuzzy model quantifies the information gain that derives from the classification performed on the selected input feature. This information gain characterizes the discriminative power of the input features and allows better insights into the selected fuzzy classification strategy, even in very high dimensional cases, and consequently a possible reduction of the input dimension. Several artificial and real-world data analysis are reported as examples, in order to illustrate the characteristics and potentialities of the proposed algorithm. As real-world examples, the most informative electrocardiographic measures are detected for an arrhythmia classification problem and the role of duration, amplitude and pitch variations of syllabic nuclei in English spoken sentences is investigated for prosodic stress classification.
Carmustine-Induced Phosphatidylserine Translocation in the Erythrocyte Membrane

The nitrosourea alkylating agent, carmustine, is used as chemotherapeutic drug in several malignancies. The substance triggers tumor cell apoptosis. Side effects of carmustine include myelotoxicity with anemia. At least in theory, anemia could partly be due to stimulation of eryptosis, the suicidal death of erythrocytes, characterized by cell shrinkage and breakdown of phosphatidylserine asymmetry of the cell membrane with phosphatidylserine exposure at the erythrocyte surface. Stimulators of eryptosis include increase of cytosolic Ca2+ activity ([Ca2+]i). The present study tested whether carmustine triggers eryptosis. To this end [Ca2+]i was estimated from Fluo3 fluorescence, cell volume from forward scatter, phosphatidylserine exposure from annexin V binding, and hemolysis from hemoglobin release. As a result a 48 h exposure to carmustine (≥25 µM) significantly increased [Ca2+]i, decreased forward scatter and increased annexin V binding. The effect on annexin V binding was significantly blunted in the absence of extracellular Ca2+. In conclusion, carmustine stimulates eryptosis at least partially by increasing cytosolic Ca2+ activity.
Nonhomologous RNA recombination in tombusviruses: generation and evolution of defective interfering RNAs by stepwise deletions

We used a protoplast system to study the mechanisms involved in the generation and evolution of defective interfering (DI) RNAs of tomato bushy stunt tombusvirus (TBSV). Synthetic transcripts corresponding to different naturally occurring TBSV DI RNAs, or to various artificially constructed TBSV defective RNAs, were analyzed. The relative levels of competitiveness of different DI RNAs were determined by coinoculating their corresponding transcripts into protoplasts along with helper genomic RNA transcripts and monitoring the level of DI RNA accumulation. Further studies were performed to assess the contribution of naked DI RNA stability and DI RNA encapsidation efficiency to the observed levels of competitiveness. In addition, the ability of various defective RNAs to evolve to alternative forms was tested by serially passaging protoplast infections initiated with transcripts corresponding to helper genomic RNA and a single type of defective RNA. These studies, and the analysis of the sequences of observed recombinants, indicate that (i) replication competence is a major factor dictating DI RNA competitiveness and is likely a primary determinant in DI RNA evolution, (ii) DI RNAs are capable of evolving to both smaller and larger forms, and the rates at which various transitions occur differ, (iii) DI RNA-DI RNA recombination and/or rearrangement is responsible for the formation of the evolved RNA molecules which were examined, and (iv) sequence complementarities between positive- and negative-sense strands in the regions of the junctions suggest that, in some cases, base pairing between an incomplete replicase-associated nascent strand and acceptor template may mediate selection of recombination sites. On the basis of our data, we propose a stepwise deletion model to describe the temporal order of events leading to the formation of tombusvirus DI RNAs.
Periventricular nodular heterotopia and cardiovascular defects.

BACKGROUND Periventricular nodular heterotopia (PNH) is a rare congenital anomaly of the brain presenting as nodular heterotopia along the paraventricular region. Ten cases of PNH complicated by aortic aneurysm have been reported in the literature, and 9 of them also had symptoms of Ehlers-Danlos syndrome (EDS). This study investigated the association of PNH and cardiovascular anomalies in Asians. METHODS Patients with a diagnosis of brain heterotopia on magnetic resonance imaging at Chang Gung Memorial Hospital between 1994 and 2010 were screened for both typical PNH and cardiovascular anomalies. The family members of the index cases were also evaluated. RESULTS One family (5 patients) and a sporadic case were found to have both typical PNH and cardiovascular anomalies. Two of them had aortic root aneurysm, one had aortic regurgitation, and one had minor valvular disease. Two patients had a history of seizures, but none of them had EDS. CONCLUSIONS Clinical heterogeneity exists in the patients with PNH. Overlap in the symptoms of PNH, cardiovascular anomalies, aortic aneurysm, and EDS were reviewed. EDS is unusual in Asians with PNH. Aortic aneurysm and other valvular heart diseases are common cardiovascular anomalies in PNH patients.
Thalassemia in the Next Millennium: Keynote Address a

Abstract: Over the next decade it will be essential to make the thalassemia problem more visible to governments and international health agencies that are involved in health care in the emerging countries. This will require detailed population surveys to determine the gene frequencies of the important forms of thalassemia, together with a better understanding of their natural history and of the factors that modify their clinical phenotypes. In particular, more needs to be learnt about the natural history and ways of managing the intermediate forms of β thalassemia. While research should continue towards definitive forms of treatment it is important, in the meantime, to pursue the development of cheap and safe oral chelating agents and to carry out clinical trials of drugs that may interact one with another to elevate the level of fetal hemoglobin, particularly in patients with different types of β thalassemia intermedia. The partial control of the disease by carrier detection and prenatal diagnosis will only be feasible in emerging countries if it is possible to obtain the financial support of the major international agencies and the cooperation of their governments and communities; the remarkable success of this approach in some of the Mediterranean islands is a good example of what can be achieved.
Real-time perception-guided motion planning for a personal robot

This paper presents significant steps towards the online integration of 3D perception and manipulation for personal robotics applications. We propose a modular and distributed architecture, which seamlessly integrates the creation of 3D maps for collision detection and semantic annotations, with a real-time motion replanning framework. To validate our system, we present results obtained during a comprehensive mobile manipulation scenario, which includes the fusion of the above components with a higher level executive.