Miracle-dz/UniFAR-FTUs huggingface dataset:
Therapeutic Approaches to Genetic Ion Channelopathies and Perspectives in Drug Discovery

In the human genome more than 400 genes encode ion channels, which are transmembrane proteins mediating ion fluxes across membranes. Being expressed in all cell types, they are involved in almost all physiological processes, including sense perception, neurotransmission, muscle contraction, secretion, immune response, cell proliferation, and differentiation. Due to the widespread tissue distribution of ion channels and their physiological functions, mutations in genes encoding ion channel subunits, or their interacting proteins, are responsible for inherited ion channelopathies. These diseases can range from common to very rare disorders and their severity can be mild, disabling, or life-threatening. In spite of this, ion channels are the primary target of only about 5% of the marketed drugs suggesting their potential in drug discovery. The current review summarizes the therapeutic management of the principal ion channelopathies of central and peripheral nervous system, heart, kidney, bone, skeletal muscle and pancreas, resulting from mutations in calcium, sodium, potassium, and chloride ion channels. For most channelopathies the therapy is mainly empirical and symptomatic, often limited by lack of efficacy and tolerability for a significant number of patients. Other channelopathies can exploit ion channel targeted drugs, such as marketed sodium channel blockers. Developing new and more specific therapeutic approaches is therefore required. To this aim, a major advancement in the pharmacotherapy of channelopathies has been the discovery that ion channel mutations lead to change in biophysics that can in turn specifically modify the sensitivity to drugs: this opens the way to a pharmacogenetics strategy, allowing the development of a personalized therapy with increased efficacy and reduced side effects. In addition, the identification of disease modifiers in ion channelopathies appears an alternative strategy to discover novel druggable targets.
Short-Term Trends in Heart Failure–Related Hospitalizations in a High-Risk State

Objectives We sought to determine whether there are signs of improvement in the rates of heart failure (HF) hospitalizations given the recent reports of improvement in national trends. Methods HF admissions data from the Tennessee Hospital Discharge Data System were analyzed. Results Hospitalization for primary diagnosis of HF (HFPD) in adults (aged 20 years old or older) decreased from 4.5% in 2006 to 4.2% in 2008. Similarly, age-adjusted HF hospitalization (per 10,000 population) declined by 19.1% (from 45.5 in 2006 to 36.8 in 2008). The age-adjusted rates remain higher among blacks than whites and higher among men than women. Notably, the rate ratio of black-to-white men ages 20 to 34 years admitted with HFPD increased from 8.5 in 2006 to 11.1 in 2008; similarly, the adjusted odds ratios for HFPD were 4.75 (95% confidence interval 3.29–6.86) and 5.61 (95% confidence interval 3.70–8.49), respectively. There was, however, a significant improvement in odds ratio for HF rates among young black women, as evidenced by a decrease from 4.60 to 3.97 (aged 20–34 years) and 4.21 to 3.12 (aged 35–44 years) between 2006 and 2008, respectively. Among patients aged 20 to 34 and 35 to 44 years, hypertension was the strongest independent predictor for HF. Diabetes and myocardial infarction emerged as predictors for HF among patients aged 35 years and older. Conclusions The overall rate of HF hospitalization declined during the period surveyed, but the persistent disproportionate involvement of blacks with evidence of worsening among younger black men, requires close attention.
Non-planar target for multi-camera network calibration

Rapid calibration of multi-camera systems using planar targets is typically impractical. Here we report a non-planar target for rapid calibration of inward-looking visual sensor networks (VSNs), designed using a novel VSN simulator and verified experimentally. The target consists of a large central sphere, surrounded by several smaller, rigidly mounted spheres. Rotation about an axis through the center of this sphere changes the location of the outer spheres, while keeping a fixed reference point in the center to permit extrinsic parameter extraction. Using the simulation, different target configurations are tested for field-of-view (FOV) coverage for each camera. Experimental results using a constructed operational prototype are consistent with traditional planar target calibrations, but require only a single view of the target to extract the intrinsic parameters.
The true complexity of a system of linear equations

In this paper we look for conditions that are sufficient to guarantee that a subset A of a finite Abelian group G contains the ‘expected’ number of linear configurations of a given type. The simplest non‐trivial result of this kind is the well‐known fact that if G has odd order, A has density α and all Fourier coefficients of the characteristic function of A are significantly smaller than α (except the one at zero, which equals α), then A contains approximately α3|G|2 triples of the form (a, a+d, a+2d). This is ‘expected’ in the sense that a random set A of density α has approximately α3|G|2 such triples with very high probability. More generally, it was shown by the first author (in the case G = ℤN for N prime, but the proof generalizes) that a set A of density α has about αk|G|2 arithmetic progressions of length k if the characteristic function of A is almost as small as it can be, given its density, in a norm that is now called the Uk−1‐norm. When investigating linear equations in the primes, Green and Tao found the most general statement that follows from the technique used to prove this result, introducing a notion that they call the complexity of a system of linear forms. They prove that if A has almost minimal Uk+1‐norm, then it has the expected number of linear configurations of a given type, provided that the associated complexity is at most k. The main result of this paper is that the converse is not true: in particular there are certain systems of complexity 2 that are controlled by the U2‐norm, whereas the result of Green and Tao requires the stronger hypothesis of U3‐control. We say that a system of m linear forms L1, …, Lm in d variables with integer coeffcients has true complexity k if k is the smallest positive integer such that, for any set A of density α and almost minimal Uk+1‐norm, the number of d‐tuples (x1, …, xd) such that Li(x1, …, xd) ∈ A for every i is approximately αm|G|d. We conjecture that the true complexity k is the smallest positive integer s for which the functions L1s+1, … ,Lms+1 are linearly independent. Using the ‘quadratic Fourier analysis’ of Green and Tao we prove this conjecture in the case where the complexity of the system (in Green and Tao's sense) is 2, s=1 and G is the group 𝔽pn for some fixed odd prime p. A closely related result in ergodic theory was recently proved independently by Leibman. We end the paper by discussing the connections between his result and ours.
The relationship between freshman student retention and use of an online parent portal

iv DEDICATION . vi ACKNOWLEDGEMENTS . vii LIST OF TABLES . x LIST OF FIGURES . xi LIST OF ABBREVIATIONS . xii LIST OF SYMBOLS . xiv CHAPTER
Autoencoding Evolutionary Search With Learning Across Heterogeneous Problems

To enhance the search performance of evolutionary algorithms, reusing knowledge captured from past optimization experiences along the search process has been proposed in the literature, and demonstrated much promise. In the literature, there are generally three types of approaches for reusing knowledge from past search experiences, namely exact storage and reuse of past solutions, the reuse of model-based information, and the reuse of structured knowledge captured from past optimized solutions. In this paper, we focus on the third type of knowledge reuse for enhancing evolutionary search. In contrast to existing works, here we focus on knowledge transfer across heterogeneous continuous optimization problems with diverse properties, such as problem dimension, number of objectives, etc., that cannot be handled by existing approaches. In particular, we propose a novel autoencoding evolutionary search paradigm with learning capability across heterogeneous problems. The essential ingredient for learning structured knowledge from search experience in our proposed paradigm is a single layer denoising autoencoder (DA), which is able to build the connections between problem domains by treating past optimized solutions as the corrupted version of the solutions for the newly encountered problem. Further, as the derived DA holds a closed-form solution, the corresponding reusing of knowledge from past search experiences will not bring much additional computational burden on the evolutionary search. To evaluate the proposed search paradigm, comprehensive empirical studies on the complex multiobjective optimization problems are presented, along with a real-world case study from the fiber-reinforced polymer composites manufacturing industry.
L1-Norm Distance Linear Discriminant Analysis Based on an Effective Iterative Algorithm

Recent works have proposed two L1-norm distance measure-based linear discriminant analysis (LDA) methods, L1-LD and LDA-L1, which aim to promote the robustness of the conventional LDA against outliers. In LDA-L1, a gradient ascending iterative algorithm is applied, which, however, suffers from the choice of stepwise. In L1-LDA, an alternating optimization strategy is proposed to overcome this problem. In this paper, however, we show that due to the use of this strategy, L1-LDA is accompanied with some serious problems that hinder the derivation of the optimal discrimination for data. Then, we propose an effective iterative framework to solve a general L1-norm minimization–maximization (minmax) problem. Based on the framework, we further develop a effective L1-norm distance-based LDA (called L1-ELDA) method. Theoretical insights into the convergence and effectiveness of our algorithm are provided and further verified by extensive experimental results on image databases.
Beyond ERPs: Oscillatory neuronal dynamics

Since the initial report on the existence of electrical activity stemming from the brain in 1875 by Richard Caton (Caton, 1875), researchers have been intrigued for more than half a century by the strikingly ubiquitousness of rhythmic, oscillatory activity in EEG recordings. In the early reports on EEG, a particularly counterintuitive finding was that the observed oscillations seemed to disappear upon sensory stimulation. Adolf Beck, one of the pioneers of EEG research, struggled with the interpretation of this observation, as evidenced in the following passage from his Ph. D. thesis:
Rifampicin reduces plasma concentrations of moxifloxacin in patients with tuberculosis.

BACKGROUND The long duration of the current tuberculosis (TB) treatment is demanding and warrants the development of new drugs. Moxifloxacin shows promising results and may be combined with rifampicin to shorten the duration of TB treatment. Rifampicin induces the phase II metabolic enzymes that are involved in the biotransformation of moxifloxacin. Therefore, the interaction between rifampicin and moxifloxacin should be investigated. PATIENTS AND METHODS Nineteen Indonesian patients with pulmonary TB who were in the last month of their TB treatment completed a 1-arm, 2-period, fixed-order pharmacokinetic study. In phase 1 of the study, they received 400 mg of moxifloxacin every day for 5 days in addition to 450 mg of rifampicin and 600 mg of isoniazid 3 times per week. In phase 2 of the study, after a 1-month washout period, patients received moxifloxacin for another 5 days (without rifampicin and isoniazid). A 24-h pharmacokinetic curve for moxifloxacin was recorded on the last day of both study periods, and its pharmacokinetic parameters were evaluated for an interaction with rifampicin, using a bioequivalence approach. RESULTS Coadministration of moxifloxacin with rifampicin and isoniazid resulted in an almost uniform decrease in moxifloxacin exposure (in 18 of 19 patients). The geometric means for the ratio of phase 1 area under the curve to phase 2 area under the curve and for the ratio of phase 1 peak plasma concentration to phase 2 peak plasma concentration were 0.69 (90% confidence interval, 0.65-0.74) and 0.68 (90% confidence interval, 0.64-0.73), respectively. The median time to reach peak plasma concentration for moxifloxacin was prolonged from 1 h to 2.5 h when combined with rifampicin and isoniazid (P=.003). CONCLUSIONS Coadministration of moxifloxacin with intermittently administered rifampicin and isoniazid results in reduced moxifloxacin plasma concentrations, which is most likely the result of induced glucuronidation or sulphation by rifampicin. Further studies are warranted to evaluate the impact of the interaction on the outcome of TB treatment.
A computer vision system for automated grading of rough hardwood lumber using a knowledge-based approach

A computer vision system that locates and identifies grading defects in rough hardwood lumber in a species-independent manner is described in detail. It consists of a low-level module that performs segmentation and extracts region properties, and a high-level module that identifies the type of defect present in each of the regions passed from the low-level module and extracts the appropriate characteristics associated with each defect. The system has been designed using a knowledge-based approach using a blackboard framework and has been tested on a number of boards from four hardwood species. The current system can detect four of the most common types of defects: knots, holes, wane, and splits/checks. Although it has limited recognition capabilities, the results suggest that species-independent methods can be found for accomplishing the required tasks. <<ETX>>
Dynamic based control strategy for haptic devices

Transparency is a key performance measure for haptic devices. In this paper, we investigate a control strategy to increase the transparency of a haptic device. This control strategy is based on careful analysis of the dynamics of the haptic device, computed torque feed forward control and current feedback based force control. The inverse dynamic equation of motion for the device is derived using Lagrangian formalism and the dominating terms are identified for some representative motion trajectories. The user contact dynamic model is identified using experiments on the device with different users. A PI controller using motor current measurements is used to follow the reference force from the virtual environment. Experimental results illustrate the effectiveness of the control strategy.
The Wiley Blackwell handbook of mindfulness

The Wiley Blackwell Handbook of Mindfulness brings together the latest multi-disciplinary research on mindfulness from a group of international scholars: • Examines the origins and key theories of the two dominant Western approaches to mindfulness • Compares, contrasts, and integrates insights from the social psychological and Eastern-derived perspectives • Discusses the implications for mindfulness across a range of fields, including consciousness and cognition, education, creativity, leadership and organizational behavior, law, medical practice and therapy, well-being, and sports • 2 Volumes
Semantic Inference at the Lexical-Syntactic Level for Textual Entailment Recognition

We present a new framework for textual entailment, which provides a modular integration between knowledge-based exact inference and cost-based approximate matching. Diverse types of knowledge are uniformly represented as entailment rules, which were acquired both manually and automatically. Our proof system operates directly on parse trees, and infers new trees by applying entailment rules, aiming to strictly generate the target hypothesis from the source text. In order to cope with inevitable knowledge gaps, a cost function is used to measure the remaining "distance" from the hypothesis.
Combustion engine modelling using an evolving local model network

In this paper a new evolving parameter estimation algorithm for a local model network under special consideration of combustion engine modelling is presented. For practical applications computational speed, incorporation of prior knowledge and the interpretability of the local models is of great interest. Accordingly, a robust and efficient online training algorithm with a particular focus on computational requirements involved in dynamic system identification of complex nonlinear processes is presented. The incremental construction of the model tree allows to gradually increase the model complexity while a proper initialisation of new model parameters is easily possible. The proposed evolving local model network is validated using real measurement data from a state-of-the-art 4-cylinder EURO5 diesel engine.
I222 Neuraminidase Mutations Further Reduce Oseltamivir Susceptibility of Indonesian Clade 2.1 Highly Pathogenic Avian Influenza A(H5N1) Viruses

We have tested the susceptibility to neuraminidase inhibitors of 155 clade 2.1 H5N1 viruses from Indonesia, isolated between 2006–2008 as well as 12 clade 1 isolates from Thailand and Cambodia from 2004–2007 using a fluorometric MUNANA-based enzyme inhibition assay. The Thailand and Cambodian clade 1 isolates tested here were all susceptible to oseltamivir and zanamivir, and sequence comparison indicated that reduced oseltamivir susceptibility we observed previously with clade 1 Cambodian isolates correlated with an S246G neuraminidase mutation. Eight Indonesian viruses (5%), all bearing I222 neuraminidase mutations, were identified as mild to extreme outliers for oseltamivir based on statistical analysis by box plots. IC50s were from 50 to 500-fold higher than the reference clade 1 virus from Viet Nam, ranging from 43–75 nM for I222T/V mutants and from 268–349 nM for I222M mutants. All eight viruses were from different geographic locales; all I222M variants were from central Sumatra. None of the H5N1 isolates tested demonstrated reduced susceptibility to zanamivir (IC50s all <5 nM). All I222 mutants showed loss of slow binding specifically for oseltamivir in an IC50 kinetics assay. We identified four other Indonesian isolates with higher IC50s which also demonstrated loss of slow binding, including one virus with an I117V mutation. There was a minimal effect on the binding of zanamivir and peramivir for all isolates tested. As H5N1 remains a potential pandemic threat, the incidence of mutations conferring reduced oseltamivir susceptibility is concerning and emphasizes the need for greater surveillance of drug susceptibility.
Prasugrel Compared With High Loading– and Maintenance–Dose Clopidogrel in Patients With Planned Percutaneous Coronary Intervention: The Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation–Thrombolysis in Myocardial Infarction 44 Trial

Background— The increasing use of higher-than-approved doses of clopidogrel in clinical practice is based in part on the desire for greater levels of inhibition of platelet aggregation (IPA). Prasugrel is a new thienopyridine that is more potent than standard-dose clopidogrel in healthy subjects and patients with stable coronary artery disease. The relative antiplatelet effects of prasugrel versus high-dose clopidogrel in percutaneous coronary intervention patients are unknown. Methods and Results— Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation–Thrombolysis in Myocardial Infarction 44 (PRINCIPLE-TIMI 44) was a randomized, double-blind, 2-phase crossover study of prasugrel compared with high-dose clopidogrel in patients undergoing cardiac catheterization for planned percutaneous coronary intervention. The primary end point of the loading-dose phase (prasugrel 60 mg versus clopidogrel 600 mg) was IPA with 20 &mgr;mol/L ADP at 6 hours. Patients with percutaneous coronary intervention entered the maintenance-dose phase, a 28-day crossover comparison of prasugrel 10 mg/d versus clopidogrel 150 mg/d with a primary end point of IPA after 14 days of either drug. In this study, 201 subjects were randomized. IPA at 6 hours was significantly higher in subjects receiving prasugrel (mean±SD, 74.8±13.0%) compared with clopidogrel (31.8±21.1%; P<0.0001). During the maintenance-dose phase, IPA with 20 &mgr;mol/L ADP was higher in subjects receiving prasugrel (61.3±17.8%) compared with clopidogrel (46.1±21.3%; P<0.0001). Results were consistent across all key secondary end points; significant differences emerged by 30 minutes and persisted across all time points. Conclusions— Among patients undergoing cardiac catheterization with planned percutaneous coronary intervention, loading with 60 mg prasugrel resulted in greater platelet inhibition than a 600-mg clopidogrel loading dose. Maintenance therapy with prasugrel 10 mg/d resulted in a greater antiplatelet effect than 150 mg/d clopidogrel.
Artificial Beings: the Conscience of a Conscious Machine

It is almost universally agreed that consciousness and possession of a conscience are essential characteristics of human intelligence. While some believe it to be impossible to create artificial beings possessing these traits, and conclude that ultimate major goal of Artificial Intelligence is hopeless, this book demonstrates that not only is it possible to create entities with capabilities in both areas, but that they demonstrate them in ways different from our own, thereby showing a new kind of consciousness. This latter characteristic affords such entities performance beyond the reach of humans, not for lack of intelligence, but because human intelligence depends on networks of neurons which impose processing restrictions which do not apply to computers. At the beginning of the investigation of the creation of an artificial being, the main goal was not to study the possibility of whether a conscious machine would possess a conscience. However, experimental data indicate that many characteristics implemented to improve efficiency in such systems are linked to these capacities. This implies that when they are present it is because they are essential to the desired performance improvement. Moreover, since the goal is not to imitate human behavior, some of these structural characteristics are different from those displayed by the neurons of the human brain - suggesting that we are at the threshold of a new scientific field, artificial cognition, which formalizes methods for giving cognitive capabilities to artificial entities through the full use of the computational power of machines.
Schedule-Based Robotic Search for Multiple Residents in a Retirement Home Environment

In this paper we address the planning problem of a robot searching for multiple residents in a retirement home in order to remind them of an upcoming multi-person recreational activity before a given deadline. We introduce a novel Multi-User Schedule Based (M-USB) Search approach which generates a high-level-plan to maximize the number of residents that are found within the given time frame. From the schedules of the residents, the layout of the retirement home environment as well as direct observations by the robot, we obtain spatio-temporal likelihood functions for the individual residents. The main contribution of our work is the development of a novel approach to compute a reward to find a search plan for the robot using: 1) the likelihood functions, 2) the availabilities of the residents, and 3) the order in which the residents should be found. Simulations were conducted on a floor of a real retirement home to compare our proposed M-USB Search approach to a Weighted Informed Walk and a Random Walk. Our results show that the proposed M-USB Search finds residents in a shorter amount of time by visiting fewer rooms when compared to the other approaches.