Miracle-dz/UniFAR-FTUs huggingface dataset:
An Adaptive Dynamic Extensible Processor

This paper describes an approach for adaptive dynamic instruction set extension, tuning processors to specific applications. These new instructions are generated after production. The processor has two modes: training mode and normal mode. The application-specific instructions are extracted from the critical portions of the code detected by a profiler at training mode. At normal mode they are executed on a reconfigurable coarse grain accelerator. The sequencer decides when, which custom instruction should be executed. In this methodology there is no need to a new compiler and extra opcodes. Two methods are proposed for finding critical regions of the code. Keyword Extensible Processor, Hot Spots, Online Profiling, Custom Instruction, Reconfigurable Accelerator
Forecasting Software Aging of Service-Oriented Application Server Based on Wavelet Network with Adaptive Genetic Algorithm

Web services are gaining acceptance as a standards-based approach for integrating loosely coupled services. Achieving high levels of reliability and availability of service-oriented application server in spite of service or infrastructure failures poses new challenges. According to the characteristic of performance parameters of service-oriented application sever, a new software aging forecasting model based on wavelet network is proposed. The dimensionality of input variables is reduced by principal component analysis, and the structure and parameters of wavelet network are optimized with genetic algorithm and evolutionary programming. The objective is to observe and model the existing systematic parameter data series of service-oriented application server to forecast accurately future unknown data values. By the model, we can get the aging threshold before application server fails and rejuvenate the application server in autonomic ways before observed systematic parameter value reaches the threshold. The experiments are carried out to validate the efficiency of the proposed model and show that the aging forecasting model based on wavelet network with adaptive genetic algorithm is superior to the BP neural network model and wavelet network model in the aspects of convergence rate and forecasting precision.
Sex differences in blood pressure after stroke: a systematic review and meta-analysis.

OBJECTIVES Evidence about sex differences in blood pressure (BP) at the time of acute stroke presentation is scarce. We aimed to summarize available data on sex differences in BP at the time of acute stroke presentation, including stratification by prior history of hypertension and stroke subtype. METHODS We performed a systematic literature search across MEDLINE and Embase, from inception to 21 December 2018, to identify all population-based observational studies that reported BP at the time of acute stroke presentation. We extracted data on patient demographics, stroke-type (ischaemic or haemorrhagic), stroke severity, vascular risk factors, and SBP and DBP at the time of stroke presentation. Wherever possible, data were pooled for meta-analysis with weighted mean difference (WMD) and corresponding 95% confidence intervals (CI) using random effects meta-analysis. RESULTS We included 128 138 stroke patients from 43 studies. Women had higher SBP at presentation than men (WMD, 1.46; 95% CI, 0.65-2.26); this difference was significant in ischaemic stroke (1.49; 0.25-2.72 mmHg), but not in intracerebral haemorrhage (0.19; -4.21 to 4.59 mmHg). Meta regression show that sex differences in SBP were consistent with increasing age, stroke severity, other comorbidities and medication history. CONCLUSION This systematic review and meta-analysis indicates that women have higher SBP at the time of presentation with acute stroke. These differences are consistent with sex differences in hypertension patterns in older age, and may be explained by the fact that women are more likely to have a premorbid hypertension. This highlights the need for effective sex-specific blood pressure control in patients at high risk for stroke.
The benefits of maternal effects in novel and in stable environments

Natural selection favours phenotypes that match prevailing ecological conditions. A rapid process of adaptation is therefore required in changing environments. Maternal effects can facilitate such responses, but it is currently poorly understood under which circumstances maternal effects may accelerate or slow down the rate of phenotypic evolution. Here, we use a quantitative genetic model, including phenotypic plasticity and maternal effects, to suggest that the relationship between fitness and phenotypic variance plays an important role. Intuitive expectations that positive maternal effects are beneficial are supported following an extreme environmental shift, but, if too strong, that shift can also generate oscillatory dynamics that overshoot the optimal phenotype. In a stable environment, negative maternal effects that slow phenotypic evolution actually minimize variance around the optimum phenotype and thus maximize population mean fitness.
Analysis of internal timings and clock rates of TerraSAR-X

Due to the indirect measurement principle of radar on base of signal travel time, a very precise calibration of the sensor's internal clock with regard to clock rate and potential time offsets relative to the Coordinated Universal Time is an essential prerequisite for accurate pixel localization in Synthetic Aperture Radar. Giving special considerations on this aspect, we developed two algorithms that improve the already high localization accuracy of TerraSAR-X: The either one very precisely determines the true oscillator clock rate, while the other one effectively refines the accuracy of time annotation. Experimental analyses evaluate the obtained improvements in localization accuracy from both techniques.
N-glycan Cryptic Antigens as Active Immunological Targets in Prostate Cancer Patients

Although tumor-associated abnormal glycosylation has been recognized for decades, information regarding host recognition of the evolving tumor glycome remains elusive. We report here a carbohydrate microarray analysis of a number of tumor-associated carbohydrates for their serum antibody reactivities and potential immunogenicity in humans. These are the precursors, cores and internal sequences of N-glycans. They are usually masked by other sugar moieties and belong to a class of glyco-antigens that are normally “cryptic”. However, viral expression of these carbohydrates may trigger host immune responses. For examples, HIV-1 and SARS-CoV display Man9 clusters and tri- or multi-antennary type II (Galβ1→4GlcNAc) chains (Tri/m-II), respectively; viral neutralizing antibodies often target these sugar moieties. We asked, therefore, whether prostate tumor expression of corresponding carbohydrates triggers antibody responses in vivo. Using carbohydrate microarrays, we analyzed a panel of human sera, including 17 samples from prostate cancer patients and 12 from men with Benign Prostatic Hyperplasia (BPH). We observed that IgG antibodies targeting the Man9- or Tri-/m-II-autoantigens are readily detectable in the sera of men with BPH, as well as those with cancer. Importantly, these antibody activities were selectively increased in prostate cancer patients. Thus, human immune systems actively recognize these N-glycan cryptic carbohydrates and produce targeting antibodies. This finding shads a light on a class of previously less studied immunological targets of human cancers. Identifying the diagnostic, prognostic and therapeutic values of these targets will require further investigation.
Temperature- and Touch-Sensitive Neurons Couple CNG and TRPV Channel Activities to Control Heat Avoidance in Caenorhabditis elegans

Background Any organism depends on its ability to sense temperature and avoid noxious heat. The nematode Caenorhabditis elegans responds to noxious temperatures exceeding ∼35°C and also senses changes in its environmental temperature in the range between 15 and 25°C. The neural circuits and molecular mechanisms involved in thermotaxis have been successfully studied, whereas details of the thermal avoidance behavior remain elusive. In this work, we investigate neurological and molecular aspects of thermonociception using genetic, cell biological and physiological approaches. Methodology/Principal Findings We show here that the thermosensory neurons AFD, in addition to sensing temperature within the range within which the animals can thrive, also contribute to the sensation of noxious temperatures resulting in a reflex-like escape reaction. Distinct sets of interneurons are involved in transmitting thermonociception and thermotaxis, respectively. Loss of AFD is partially compensated by the activity of a pair of multidendritic, polymodal neurons, FLP, whereas laser ablation of both types of neurons abrogated the heat response in the head of the animals almost completely. A third pair of heat sensory neurons, PHC, is situated in the tail. We find that the thermal avoidance response requires the cell autonomous function of cGMP dependent Cyclic Nucleotide-Gated (CNG) channels in AFD, and the heat- and capsaicin-sensitive Transient Receptor Potential Vanilloid (TRPV) channels in the FLP and PHC sensory neurons. Conclusions/Significance Our results identify distinct thermal responses mediated by a single neuron, but also show that parallel nociceptor circuits and molecules may be used as back-up strategies to guarantee fast and efficient responses to potentially detrimental stimuli.
The Robustness of Outputs With Respect to Disturbances for Boolean Control Networks

In this brief, we investigate the robustness of outputs with respect to disturbances for Boolean control networks (BCNs) by semi-tensor product (STP) of matrices. First, BCNs are converted into the corresponding algebraic forms by STP, then two sufficient conditions for the robustness are derived. Moreover, the corresponding permutation system and permutation graph are constructed. It is proven that if there exist controllers such that the outputs of permutation systems are robust with respect to disturbances, then there must also exist controllers such that the outputs of the corresponding original systems achieve robustness with respect to disturbances. One effective method is proposed to construct controllers to achieve robustness. Examples are also provided to illustrate the correctness of the obtained results.
Assessing pragmatic language in autism spectrum disorder: the Yale in vivo Pragmatic Protocol.

PURPOSE This study compared pragmatic language in youths (9-17 years) with autism spectrum disorder (ASD) and those with typical development (TD) on the Yale in vivo Pragmatic Protocol (YiPP), a semistructured, dynamic conversational assessment. METHOD Participants (n = 118) were divided into groups based on age and diagnosis. Each completed the YiPP, which included 4 pragmatic domains (discourse management, communicative functions, conversational repair, presupposition). The participant's response to each probe was scored correct or incorrect; incorrect scores elicited cues from the examiner, and level of cue required for a correction was also scored. RESULTS The YiPP showed high reliability and internal consistency, with moderate concurrent validity, sensitivity, and specificity. The group with ASD performed worse overall on YiPP probes compared to their TD counterparts on both error (d = 0.96) and cue (d = 0.91) scores. Item analyses revealed greater gaps between older students with ASD and their TD peers than between the 2 younger groups. CONCLUSIONS These data suggest that a probe measure designed to assess pragmatic abilities in children with ASD within a conversational context has some validity for contributing to diagnostic classification and can identify specific areas of pragmatic vulnerabilities as part of a clinical assessment.
A Randomized Crossover Study to Assess the Usability of Two New Vision Tests in Patients with Low Vision.

SIGNIFICANCE Well-established charts such as Early Treatment Diabetic Retinopathy Study are able to quantify visual acuity (VA) with a low cutoff of 1.6 logMAR. Below this point, nonquantitative measures, such as count fingers, hand movements, and light perception, are used. There is a need for more reproducible, comparable, and reliable ways to measure VA changes in this patient cohort. PURPOSE The purpose of this study was to examine and compare the ability of the Berkeley Rudimentary Vision Test (BRVT) and the Freiburg Acuity Test (FrACT) to quantify VA in low-vision patients who score nonnumerical VAs in standard charts. METHODS Fifty adult participants with VA ≤1.0 logMAR in both eyes were recruited from the Oxford Eye Hospital, Oxford, United Kingdom. Correlation between FrACT and BRVT results and the correlation between VA and daily living activities were analyzed statistically. Potential predictors of differences were investigated. RESULTS The BRVT was significantly faster to conduct (P = .002), but FrACT was able to quantify vision numerically in a greater proportion of eyes. The κ agreement between tests was 0.26. The difference increased systematically with the VA reduction (P < .0001). The Bland-Altman analysis showed a skew to measurement of lower logMAR VA indicating better vision measured on the FrACT. The only significant predictor of difference between the tests was binocular VA (coefficient, -0.445; P = .001). CONCLUSIONS Both tests are suitable for a very low-vision population. The BRVT is a faster test to administer, but FrACT provides a numerical result in more eyes. The poor intertest repeatability indicates that they cannot be used interchangeably. The BRVT generally reported poorer vision than did the FrACT. The medium of presentation, such as a computer screen or externally lit print medium, is likely to be the biggest factor in these differences and warrants further investigation.
Glucocorticoid treatment alleviates dystrophic myofiber pathology by activation of the calcineurin/NF‐AT pathway

Duchenne muscular dystrophy (DMD) is a progressive and ultimately fatal skeletal muscle disease. Currently, the most effective therapy is the administration of a subclass of glucocorticoids, most notably deflazacort. Although deflazacort treatment can attenuate DMD progression, extend ambulation, and maintain muscle strength, the mechanism of its action remains unknown. Prior observations have shown that activation of a JNK1‐mediated signal transduction cascade contributes to the progression of the DMD phenotype, in part by phosphorylation and inhibition of a calcineurin sensitive NF‐ATc1 transcription factor. Here, we observed that deflazacort treatment restored myocyte viability in muscle cells with constitutive activation of JNK1 and in dystrophic mdx mice. However, deflazacort treatment did not alter JNK1 activity itself, but rather led to an increase in the activity of the calcineurin phosphatase and an up‐regulation of NF‐ATc1‐dependent gene expression. The prophylactic effect of deflazacort treatment was associated with increased expression of NF‐ATc1 target genes such as the dystrophin homologue utrophin. Moreover, the muscle sparing effects of deflazacort were completely abolished when used in conjunction with the calcineurin inhibitor cyclosporine. Collectively, these results show that deflazacort attenuates loss of dystrophic myofiber integrity by up‐regulating the activity of the phosphatase calcineurin, which in turn negates JNK1 inhibition of NF‐ATc1‐mediated phosphorylation and nuclear exclusion of NF‐ATc1.
Multi‐target attention and visual short‐term memory capacity are closely linked in the intraparietal sulcus

The existing literature suggests a critical role for both the right intraparietal sulcus (IPS) and the right temporo‐parietal junction (TPJ) in our ability to attend to multiple simultaneously‐presented lateralized targets (multi‐target attention), and the failure of this ability in extinction patients. Currently, however, the precise role of each of these areas in multi‐target attention is unclear. In this study, we combined the theory of visual attention (TVA) with functional magnetic resonance imaging (fMRI) guided continuous theta burst stimulation (cTBS) in neurologically healthy subjects to directly investigate the role of the right IPS and TPJ in multi‐target attention. Our results show that cTBS at an area of the right IPS associated with multi‐target attention elicits a reduction of visual short‐term memory capacity. This suggests that the right IPS is associated with a general capacity‐limited encoding mechanism that is engaged regardless of whether targets have to be attended or remembered. Curiously, however, cTBS to the right IPS failed to elicit extinction‐like behavior in our study, supporting previous suggestions that different areas of the right IPS may provide different contributions to multi‐target attention. CTBS to the right TPJ failed to induce a change in either TVA parameters or extinction‐like behavior.
Modelling clinical data shows active tissue concentration of daclatasvir is 10-fold lower than its plasma concentration.

OBJECTIVES Daclatasvir is a highly potent inhibitor of hepatitis C virus. We estimated the active tissue concentration of daclatasvir in vivo. METHODS We developed a mathematical model incorporating pharmacokinetic/pharmacodynamic and viral dynamics. By fitting the model to clinical data reported previously, we estimated the ratio between plasma drug concentration and active tissue concentration in vivo. RESULTS The modelling results show that the active tissue concentration of daclatasvir is ∼9% of the concentration measured in plasma (95% CI 1%-29%). CONCLUSIONS Using plasma concentrations as surrogates for clinical recommendations may lead to substantial underestimation of the risk of resistance.
Utilizing a Mobile Health Intervention to Manage Hypertension in an Underserved Community

This 6-month pilot randomized controlled trial examined the effectiveness of a Mobile Health (mHealth) intervention for hypertension self-monitoring and management in an underserved urban community. The four health outcomes measured included changes in systolic and diastolic blood pressure (BP), BP monitoring adherence, perceived medication adherence self-efficacy, and health-related quality of life. Thirty participants were randomly assigned to the mHealth group or a standard follow-up group; 25 participants completed the study. The mHealth group had statistically significant improvement in systolic BP decrease (p = .01). The mHealth group had better adherence to BP monitoring and improved perceived medication adherence self-efficacy at 6 months, compared with the standard follow-up group. The results suggest that an mHealth intervention has the potential to facilitate hypertension management in underserved urban communities.
ATP-Sensitive potassium channels: a review of their cardioprotective pharmacology.

ATP-sensitive potassium channels (K(ATP)) have been thought to be a mediator of cardioprotection for the last ten years. Significant progress has been made in learning the pharmacology of this channel as well as its molecular regulation with regard to cardioprotection. K(ATP)openers as a class protect ischemic/reperfused myocardium and appear to do so by conservation of energy. The reduced rate of ATP hydrolysis during ischemia exerted by these openers is not due to a cardioplegic effect and is independent of action potential shortening. Compounds have been synthesized which retain the cardioprotective effects of first generation K(ATP)openers, but are devoid of vasodilator and cardiac sarcolemmal potassium outward currents. These results suggest receptor or channel subtypes. Recent pharmacologic and molecular biology studies suggest the activation of mitochondrial K(ATP)as the relevant cardioprotective site. Implications of these results for future drug discovery and preconditioning are discussed.
Prodrugs for targeted cancer therapy

ABSTRACT Introduction: Prodrugs have been used to improve the selectivity and efficacy of cancer therapy by targeting unique abnormal markers that are overexpressed by cancer cells and are absent in normal tissues. In this context, different strategies have been exploited and new ones are being developed each year. Areas covered: In this review, an integrated view of the potential use of prodrugs in targeted cancer therapy is provided. Passive and active strategies are discussed in light of the advantages of each one and some successful examples are provided, as well as the clinical status of several prodrugs. Among them, antibody-drug conjugates (ADCs) are the most commonly used. However, several drawbacks, including limited prodrug uptake, poor pharmacokinetics, immunogenicity problems, difficulties in selective targeting and gene expression, and optimized bystander effects limit their clinical applications. Expert opinion: Despite the efforts of different companies and research groups, several drawbacks, such as the lack of relevant in vivo models, complexity of the human metabolism, and economic limitations, have hampered the development of new prodrugs for targeted cancer therapy. As a result, we believe that the combination of prodrugs with cancer nanotechnology and other newly developed approaches, such as aptamer-conjugated nanomaterials, are efficient strategies. Trial registration: ClinicalTrials.gov identifier: NCT02049905. Trial registration: ClinicalTrials.gov identifier: NCT02049905. Trial registration: ClinicalTrials.gov identifier: NCT02014844. Trial registration: ClinicalTrials.gov identifier: NCT02029430. Trial registration: ClinicalTrials.gov identifier: NCT01706835.
Appropriately Incorporating Statistical Significance in PMI

Two recent measures incorporate the notion of statistical significance in basic PMI formulation. In some tasks, we find that the new measures perform worse than the PMI. Our analysis shows that while the basic ideas in incorporating statistical significance in PMI are reasonable, they have been applied slightly inappropriately. By fixing this, we get new measures that improve performance over not just PMI but on other popular co-occurrence measures as well. In fact, the revised measures perform reasonably well compared with more resource intensive non co-occurrence based methods also.
Relation between Unification Problem and Intruder Deduction Problem

Intruder deduction problem constitutes the first step in cryptographic protocols verification for a passive intruder. In the case of an active intruder, we know that undecidability of the unification problem implies undecidability of the secrecy problem. In this paper, we analyze the link between the unification problem and the intruder deduction problem. Through examples using equational theories, we show that these two problems are not linked. We present situations where one problem is decidable and the other one is not, or the both are decidable or not. All these examples prove that the two problems are independent for a passive intruder.