Miracle-dz/UniFAR-FTUs huggingface dataset:
External triggers of onset of myocardial infarction – an update

Abstract Coronary heart disease is one of the leading causes of death in both industrialised and developing countries. About two thirds of all coronary deaths occur outside the hospital and before any medical care can be reached. Therefore, the prevention of coronary events appears to be of utmost importance. Rupture of an atherosclerotic plaque and subsequent coronary thrombosis is the most common underlying pathophysiological mechanism of coronary events. External stresses or ‘triggers’ imposing on coronary plaques may precipitate plaque rupture. External triggers include physical activity, various emotional stresses, eating, environmental factors, and sexual activity. The increased relative risk of myocardial infarction may be induced by external triggers via the activation of internal triggering mechanisms such as biomechanical and hemodynamic stresses and changes in platelet aggregability and blood viscosity. Recent prospective studies have confirmed the results of earlier retrospective studies and have, similarly, shown the importance of external triggers in increasing the risk of myocardial infarction and other coronary events. Particularly, sedentary individuals with underlying coronary heart disease appear to be at risk when exposed to external triggers. Regular physical activity, on the other hand, is a protective factor against the increased risk associated with external triggers. However, health education needs to be provided about the risks associated with strenuous exercise in untrained individuals. Apart from lifestyle factors, pharmacological protection of the population at risk during vulnerable periods plays an important role as well. Medication such as beta-blockers and aspirin may lower the increased risk of coronary events during exposure to external triggers. Also, further research is needed with regard to psychosocial stressors and their potential role as external triggers of myocardial infarction and other coronary events.
Guidelines for defining benchmark problems in Genetic Programming

The field of Genetic Programming has recently seen a surge of attention to the fact that benchmarking and comparison of approaches is often done in non-standard ways, using poorly designed comparison problems. We raise some issues concerning the design of benchmarks, within the domain of symbolic regression, through experimental evidence. A set of guidelines is provided, aiming towards careful definition and use of artificial functions as symbolic regression benchmarks.
Geophysical and Geochemical Evidence for Deep Temperature Variations Beneath Mid-Ocean Ridges

Deep, Driving Temperatures Convection in Earth's mantle is largely controlled by the physical properties of the mantle such as density and viscosity. Because these factors are influenced by both temperature and composition, it has been difficult to ascribe one as the primary control over mantle convection or explain the long-wavelength features associated with mid-ocean ridges. Examining correlations between a global seismic velocity model with constraints on the depth and geochemical signature of mid-ocean ridges, Dalton et al. (p. 80; see the Perspective by Kelley) suggest that large temperature variations extending into the upper mantle explain most of the geophysical and geochemical observations. Moreover, the analysis provides support for deeply rooted mantle plumes as the source of hot spot volcanism. Temperature variations in the upper mantle drive mantle convection. [Also see Perspective by Kelley] The temperature and composition of Earth’s mantle control fundamental planetary properties, including the vigor of mantle convection and the depths of the ocean basins. Seismic wave velocities, ocean ridge depths, and the composition of mid-ocean ridge basalts can all be used to determine variations in mantle temperature and composition, yet are typically considered in isolation. We show that correlations among these three data sets are consistent with 250°C variation extending to depths >400 kilometers and are inconsistent with variations in mantle composition at constant temperature. Anomalously hot ridge segments are located near hot spots, confirming a deep mantle-plume origin for hot spot volcanism. Chemical heterogeneity may contribute to scatter about the global trend. The coherent temperature signal provides a thermal calibration scale for interpreting seismic velocities located distant from ridges.
Structure of a Class C GPCR Metabotropic Glutamate Receptor 1 Bound to an Allosteric Modulator

Completing the Set G protein–coupled receptors (GPCRs) are membrane proteins that transduce extracellular signals to activate diverse signaling pathways. Significant insight into GPCR function has come from structures of three of four classes of GPCRs—A, B, and Frizzled. Wu et al. (p. 58, published online 6 March) complete the picture by reporting the structure of metabotropic glutamate receptor 1, a class C GPCR. The structure shows differences in the seven-transmembrane (7TM) domain between class C and other classes; however, the overall fold is preserved. Class C GPCRs are known to form dimers through their extracellular domains; however, the structure suggests additional interactions between the 7TM domains mediated by cholesterol. Insight into the activation mechanism of a human neuronal G protein–coupled receptor. The excitatory neurotransmitter glutamate induces modulatory actions via the metabotropic glutamate receptors (mGlus), which are class C G protein–coupled receptors (GPCRs). We determined the structure of the human mGlu1 receptor seven-transmembrane (7TM) domain bound to a negative allosteric modulator, FITM, at a resolution of 2.8 angstroms. The modulator binding site partially overlaps with the orthosteric binding sites of class A GPCRs but is more restricted than most other GPCRs. We observed a parallel 7TM dimer mediated by cholesterols, which suggests that signaling initiated by glutamate’s interaction with the extracellular domain might be mediated via 7TM interactions within the full-length receptor dimer. A combination of crystallography, structure-activity relationships, mutagenesis, and full-length dimer modeling provides insights about the allosteric modulation and activation mechanism of class C GPCRs.
Thermohaline circulation crisis and impacts during the mid-Pleistocene transition

Circulating between different cycles Around a million years ago, large-scale ocean circulation changed dramatically during the switch from ∼41,000- to ∼100,000-year long glacial cycles. Pena and Goldstein analyzed the isotopic composition of neodymium in marine sediments from the South Atlantic. The results suggest how the contributions of deep water from northern and southern sources varied across the transition. The boundary between the two glacial states appears to have been marked by a dramatic weakening, perhaps even a shutdown, of deep-water currents. Science, this issue p. 318 Marine thermohaline circulation changed markedly during the mid-Pleistocene transition. The mid-Pleistocene transition (MPT) marked a fundamental change in glacial-interglacial periodicity, when it increased from ~41-thousand-year to 100-thousand-year cycles and developed higher-amplitude climate variability without substantial changes in the Milankovitch forcing. Here, we document, by using Nd isotopes, a major disruption of the ocean thermohaline circulation (THC) system during the MPT between marine isotope stages (MISs) 25 and 21 at ~950 to 860 thousand years ago, which effectively marks the first 100-thousand-year cycle, including an exceptional weakening through a critical interglacial (MIS 23) at ~900 thousand years ago. Its recovery into the post-MPT 100-thousand-year world is characterized by continued weak glacial THC. The MPT ocean circulation crisis facilitated the coeval drawdown of atmospheric CO2 and high-latitude ice sheet growth, generating the conditions that stabilized 100-thousand-year cycles.
Response to Caputo and Bernardi, Acta Physiologica Scandinavica

Dear Sirs, In contrast to our conclusion, Dr Caputo advocates the use of gamma hydroxybutyric acid (GHB) in the treatment of alcohol-dependent patients. He refers to a recent study comparing GHB and naltrexone in maintaining alcohol abstinence in 35 detoxified alcohol-dependent outpatients (1). This study reports a significant difference (P 1⁄4 0.02) in the number of abstinent patients between the GHB and the naltrexone groups after 3 months of treatment. However, (i) this study was open label, (ii) does not provide basic information such as method of randomization and power calculation, and (iii) does not analyze data using the intention-to-treat principle despite the fact that eight patients (23%) withdrew from this relatively small study (1). Other oft-quoted studies indicating a role for GHB in the treatment of alcohol dependence include open label studies without a control group (2, 3), and a randomized, open label study in alcohol-dependent outpatients comparing a GHB-treated group (n 1⁄4 30) with a diazepam-treated control group (n 1⁄4 30) (4). The authors conclude that GHB is as effective as benzodiazepine in the management of alcohol withdrawal syndrome. However, this study did not report the method of randomization, power calculation, and did not use an intention-to-treat principle when analyzing the outcome despite a dropout rate of 26.6% in the diazepam-treated group and of 13.3% in the GHB-treated group (4). We have identified two short-term randomized, double-blind studies assessing the effect of GHB on withdrawal in alcohol-dependent patients. One very small study in 23 patients (placebo, n 1⁄4 12; GHB, n 1⁄4 11) showed a significant effect on withdrawal up to 7 h after drug/placebo intake (5). The other was a larger study of low dose GHB (50 mg/kg, n 1⁄4 33), high-dose GHB (100 mg/kg, n 1⁄4 32), and clomethiazole (1000 mg/day, n 1⁄4 33) (6). There was no difference between the three arms in rating of alcohol withdrawal symptoms after 6 days of treatment (6), indicating that GHB has a short-term, dose-independent efficacy comparable to clomethiazole. Only one medium-term, randomized, doubleblind study of GHB in the treatment of alcohol dependence was identified (7). Out of 82 patients included in the study, 71 completed (placebo, n 1⁄4 35; GHB, n 1⁄4 36). Alcohol consumption was selfreported, and more patients reported abstinence from drinking in the GHB-treated group (n 1⁄4 11) compared to two in the placebo group (7). However, this study did not state (i) the primary and secondary outcome of the trial or (ii) method of randomization, nor did it use the intention-to-treat principle when analyzing data (7). Therefore, we find that the results on GHB are still too preliminary to recommend GHB for the treatment of alcohol-dependent patients, especially given the abuse potential of the drug.
Neonatal therapeutic hypothermia-associated hypomagnesemia during parenteral nutrition therapy.

BACKGROUND Hypoxic-ischemic encephalopathy (HIE) is a significant cause of morbidity and mortality in the neonatal population. Total body cooling in term infants who meet the criteria for moderate to severe HIE has been shown to be neuroprotective. A decreased core body temperature is known to affect kinetic properties of many enzyme systems in which magnesium is a cofactor. Maintenance of magnesium during therapeutic hypothermia appears to play an important role in neuroprotection. Currently, there are no studies evaluating the effects that therapeutic hypothermia in neonates has on serum magnesium levels and implications for parenteral nutrition (PN) management. Our hypothesis was that neonatal hypothermia would result in hypomagnesemia and require magnesium therapy. METHODS Laboratory measurement of serum magnesium was obtained in all infants during the cooling process. RESULTS Serum magnesium was depressed (<1.6 mg/dL) in 80% of the infants cooled despite administration of standard PN and required additional magnesium supplementation. CONCLUSION Further studies are needed to determine the target magnesium required for PN in hypothermic therapy.
Collaborative multilevel adaptation in distributed mobile applications

The next years will be characterized by high levels of heterogeneity and interactions among devices connected to global networks. The first researches involving wide-area distributed systems answered many questions concerning resource management, although they fail in treating questions related to heterogeneity and dynamic adaptation. More recent works, through technologies like CORBA and Java/Jini, deal with heterogeneity problem, but do not deepen into adaptability aspects. In this article, we present the ISAM architecture. ISAM is a middleware directed to resource management in heterogeneous networks, supporting physical and logical mobilities, dynamic adaptation and the execution of distributed mobile applications based on components. In order to achieve its goal, ISAM uses, as strategy, an integrated environment that: (a) provides a programming paradigm and its execution environment; (b) handles the adaptation process through a multilevel collaborative model, in which both the system and the application contribute.
Keeping us on track: a national program to reduce impaired driving in the United States

In January 1995, a bold new national goal was established to reduce alcohol-related traffic fatalities in the United States of America to no more than 11 000 by the year 2005. It is well known that a combination of effective laws, highly publicized enforcement, public information and education, and practical alternatives to drinking and driving are the keys to substantially reducing the impaired driving problem in the US. If we are really serious about achieving the goal by the year 2005, there are existing laws that can be implemented in every state, enforcement program strategies that will deter people from drinking and driving in the first place, public information campaigns that will raise the public consciousness of the problem, and transportation alternatives that will make it easier for certain segments of society to change their behavior. Many of these strategies have already helped reduce alcohol-related traffic fatalities in the US from an estimated 25 165 in 1982 to 22 084 in 1990 to 16 653 in 2000. What will it take? It will take the political will of the US Congress, the new administration, federal, state and local officials, and the general public to make it happen. While there are arguments against some of these measures, they are cost-effective and the majority of American people favor them.
Traditional and novel tools to probe the mitochondrial metabolism in health and disease

Mitochondrial metabolism links energy production to other essential cellular processes such as signaling, cellular differentiation, and apoptosis. In addition to producing adenosine triphosphate (ATP) as an energy source, mitochondria are responsible for the synthesis of a myriad of important metabolites and cofactors such as tetrahydrofolate, α‐ketoacids, steroids, aminolevulinic acid, biotin, lipoic acid, acetyl‐CoA, iron‐sulfur clusters, heme, and ubiquinone. Furthermore, mitochondria and their metabolism have been implicated in aging and several human diseases, including inherited mitochondrial disorders, cardiac dysfunction, heart failure, neurodegenerative diseases, diabetes, and cancer. Therefore, there is great interest in understanding mitochondrial metabolism and the complex relationship it has with other cellular processes. A large number of studies on mitochondrial metabolism have been conducted in the last 50 years, taking a broad range of approaches. In this review, we summarize and discuss the most commonly used tools that have been used to study different aspects of the metabolism of mitochondria: ranging from dyes that monitor changes in the mitochondrial membrane potential and pharmacological tools to study respiration or ATP synthesis, to more modern tools such as genetically encoded biosensors and trans‐omic approaches enabled by recent advances in mass spectrometry, computation, and other technologies. These tools have allowed the large number of studies that have shaped our current understanding of mitochondrial metabolism. WIREs Syst Biol Med 2017, 9:e1373. doi: 10.1002/wsbm.1373
Accelerating Hydrocodes with OpenACC, OpenCL and CUDA

Hardware accelerators such as GPGPUs are becoming increasingly common in HPC platforms and their use is widely recognised as being one of the most promising approaches for reaching exascale levels of performance. Large HPC centres, such as AWE, have made huge investments in maintaining their existing scientific software codebases, the vast majority of which were not designed to effectively utilise accelerator devices. Consequently, HPC centres will have to decide how to develop their existing applications to take best advantage of future HPC system architectures. Given limited development and financial resources, it is unlikely that all potential approaches will be evaluated for each application. We are interested in how this decision making can be improved, and this work seeks to directly evaluate three candidate technologies-OpenACC, OpenCL and CUDA-in terms of performance, programmer productivity, and portability using a recently developed Lagrangian-Eulerian explicit hydrodynamics mini-application. We find that OpenACC is an extremely viable programming model for accelerator devices, improving programmer productivity and achieving better performance than OpenCL and CUDA.
Surveying the landscape of optogenetic methods for detection of protein–protein interactions

Mapping the protein–protein interaction (PPi) landscape is of critical importance to furthering our understanding how cells and organisms function. Optogenetic methods, that is, approaches that utilize genetically encoded fluorophores or fluorogenic enzyme reactions, uniquely enable the visualization of biochemical phenomena in live cells with high spatial and temporal accuracy. Applying optogenetic methods to the detection of PPis requires the engineering of protein‐based systems in which an optical signal undergoes a substantial change when the two proteins of interest interact. In recent years, researchers have developed a number of creative and effective optogenetic methods that achieve this goal, and used them to further elaborate our map of the PPi landscape. In this review, we provide an introduction to the general principles of optogenetic PPi detection, and then provide a number of representative examples of how these principles have been applied. We have organized this review by categorizing methods based on whether the signal generated is reversible or irreversible in nature, and whether the signal is localized or nonlocalized at the subcellular site of the PPi. We discuss these techniques giving both their benefits and drawbacks to enable rational choices about their potential use.
Adapting learning classifier systems to symbolic regression

Genetic programming (GP) approaches have been widely studied for symbolic regression problems and have achieved substantial progress. This work investigates the effectiveness of niching property and multiple learned solutions of a Learning Classifier System (LCS) to symbolic regression benchmark problems. Specifically, an XCS with real-valued interval based conditions and code fragmented action termed as XCS-SR is proposed for tackling symbolic regression problem. This is the first LCS ever to address the problem of symbolic regression. The results on nine standard symbolic regression benchmarks show that the proposed XCS-SR method consistently obtains statistically better results on a majority of the benchmarks, in terms of average absolute error together with an increased number of exact solutions as compared with the GP benchmark.
Inviwo - An extensible, multi-purpose visualization framework

To enable visualization research impacting other scientific domains, the availability of easy-to-use visualization frameworks is essential. Nevertheless, an easy-to-use system also has to be adapted to the capabilities of modern hardware architectures, as only this allows for realizing interactive visualizations. With this trade-off in mind, we have designed and realized the cross-platform Inviwo (Interactive Visualization Workshop) visualization framework, that supports both interactive visualization research as well as efficient visualization application development and deployment. In this poster we give an overview of the architecture behind Inviwo, and show how its design enables us and other researchers to realize their visualization ideas efficiently. Inviwo consists of a modern and lightweight, graphics independent core, which is extended by optional modules that encapsulate visualization algorithms, well-known utility libraries and commonly used parallel-processing APIs (such as OpenGL and OpenCL). The core enables a simplistic structure for creating bridges between the different modules regarding data transfer across architecture and devices with an easy-to-use screen graph and minimalistic programming. Making the base structures in a modern way while providing intuitive methods of extending the functionality and creating modules based on other modules, we hope that Inviwo can help the visualization community to perform research through a rapid-prototyping design and GUI, while at the same time allowing users to take advantage of the results implemented in the system in any way they desire later on. Inviwo is publicly available at www.inviwo. org, and can be used freely by anyone under a permissive free software license (Simplified BSD).
Orthotic Management of Children with Cerebral Palsy

The International Classification of Functioning, Disability and Health (ICF) distinguishes impairments of body structure from activity limitations and participation exclusions. By definition, the impairment known as cerebral palsy (CP) describes damage to the immature brain resulting in problems with balance, coordination, and movement. Understanding the effects of such a complex condition is a constant challenge to developing treatment regimens to improve the health of children with CP. A consensus for describing the primary neurological impairment has been presented by the group for the Surveillance of Cerebral Palsy in Europe (SCPE). The impact of skeletal growth during childhood can compound the primary problem if muscles fail to lengthen in proportion to their adjacent long bones. Therefore, although CP is by definition a static neurological lesion, the phenotype has also been labeled with the secondary impairment of a ‘progressive neuromuscular deformity. ’ Children with CP are often limited in their activities because of primary and secondary impairments. A valid and reliable means of measuring functional limitations in children with CP is now possible using the Gross Motor Function Classification System (GMFCS) for children up to 12 years old. The GMFCS enables clinicians to describe the severity of a child’s functional limitations in one of five levels. Children in Level I are only mildly affected and can achieve most the activities of their age-matched healthy counterparts, with only modest qualitative differences. Conversely, children in Level V are the most limited in their activities and have little ability to control their head and trunk posture to counter the effects of the motor impairment and gravity. Rates of functional limitation in mobility, manual dexterity, speech, and vision, and to a lesser extent hearing and cognition, have been shown to correlate with GMFCS level.