Miracle-dz/UniFAR-FTUs huggingface dataset:
Parallel algorithms for verification on large systems

The model-checking problem is the question whether a given system model satisfies a property. The property is usually given as formula of a temporal logic, and the system model as labelled transition system. However, the well-known state-space explosion effect is responsible for yielding transition systems of exponential size when compared to their description, and common sequential algorithms often are not capable to solve the model-checking problem with resources available on a single computer. In this thesis, we develop parallel and, in particular, distributed algorithms which exploit the combined resources of a network of commodity workstations to solve problem instances which are beyond the capabilities of today’s sequential algorithms. Specifically, our algorithms solve the model-checking problem for two important fragments of the μ-calculus which subsume many well-known temporal logics (CTL, LTL, CTL∗). We describe our algorithms based on a characterization of the problem at hand in terms of two-player games. The underlying data structure, the game graph, is colored according to the player who has a winning strategy from the current game configuration. Finally, the color of the initial configuration tells who is the winner of the game, and thus whether the transition system satisfies the property or not. Through experimentation, we found that our algorithms scale well, and are able to solve the largest problem instances of the VLTS benchmark suite. In a second part, we investigate ways to efficiently generate (low-level) transition systems suitable for many verification tools from compact high-level descriptions of the input model. We propose a virtual-machine based approach, which uses an intermediate format to break the translation from high-level to low-level representations of a model into two steps. This well-known compiler technique simplifies the translation and still is very fast in practice. We show the practicality of our approach through the example of a compiler for the PROMELA modelling language which targets our intermediate language—the virtualmachine’s byte-code. With a comparison of benchmarks, we show that our approach is competitive to state-of-the-art tools like SPIN in speed, with additional advantages, like easier reusability, and application as component in distributed model-checking algorithms like the ones we proposed earlier.
Phosphatidylinositol 3-Kinase and Ca2+ Influx Dependence for Ligand-stimulated Internalization of the c-Kit Receptor*

We have evaluated the role of phosphatidylinositol 3-kinase (PI3-kinase) and Ca2+influx in ligand-stimulated internalization of the c-Kit receptor. The wild type (wt) c-Kit receptor and YF719, a mutant receptor in which the SH2-mediated binding site for the p85 subunit of PI3-kinase is disrupted, were expressed in DA-1 cells. YF719 internalized with similar kinetics as wt c-Kit although the receptor remained localized close to the plasma membrane. However, in the absence of extracellular Ca2+, or in the presence of the competitive Ca2+ influx blocker Ni2+, the YF719 mutant failed to internalize. Failure to internalize in the absence of Ca2+ was also observed for the wt c-Kit receptor in cells that were pretreated with the PI3-kinase inhibitor, wortmannin. Following stimulation with ligand, clathrin heavy chains were found to co-immunoprecipitate with c-Kit. However, under conditions in which PI3-kinase activity is inhibited and Ca2+ influx is blocked, clathrin failed to co-immunoprecipitate with c-Kit. Our results demonstrate that both Ca2+ influx and PI3-kinase activity influence c-Kit endocytosis, and inhibition of these two signals disrupts the earliest stages of ligand-mediated internalization.
A review of interventions in the parent‐child relationship informed by attachment theory

Bowlby's attachment theory has inspired a dramatic shift in the way we understand the development of the early relationship between infant and caregiver(s). Though almost all infants develop an attachment relationship to their primary caregiver(s), not all of them are able to use their caregiver(s) as a secure base or haven of safety from which to explore the world. Mary Ainsworth was the first to describe in detail the aspects of the caregiving system that are most important for the development of the attachment relationship. During the last decade several studies have started to evaluate the possibility that insensitive and perhaps even inadequate parenting can be effectively ameliorated by interventions. The present article sketches the theory behind attachment‐based interventions and reviews the evidence for the effectiveness of such interventions. Finally, the article gives examples of successful preventive as well as therapeutic interventions.
Combination 5-fluoruracil/cisplatinum versus 5-fluoruracil/leucovorin adjuvant chemotherapy efficacy for R0 gastric resection in locally invasive gastric cancer.

BACKGROUND The efficacy of adjuvant chemotherapy for advance resectable gastric cancer is controversial. Recently, less than 20% of the patients that received surgery can survive locally advance gastric cancer for 5 years. The purpose of the present study was to compare the therapeutic efficacy of the combination 5-fluoruracil (5-FU) with cisplatinum based and single 5-FU based regimen for the treatment of gastric cancer after post-operative gastric resection. MATERIAL AND METHOD Patients were recruited if they underwent curative RO gastric resection surgery with standard Dl or D2 lymph node dissection. Between 2002 and 2007, we conducted a cohort study, and collected prospective data of 88 patients with advanced gastric cancer They were analyzed for median survival time and rate, recurrence rate, and chemotherapy toxicity prevalence. The median survival time was the primary study endpoint. The median survival time was compared between groups by a log-rank test. RESULTS In the present study, combined 5-FU based regimen did not show a significantly superior survival time to single 5-FU regimen, both poor stage groups had better median survival in both combined 5-FU and single 5-FU regimen when compared to surgery. There was more than 50 months median survival in the first group, and 52 months in the latter However, in cisplatinum with 5-FU group, there are only a small number of signet ring cells. In addition, those have poorer clinical profile before treatment (p = 0.003). No difference on mortality rate related to toxicity. CONCLUSION Both regimens are useful regimens with efficient benefit for gastric cancer patients as well as a cheaper regimen than other new combination drug regimens. However second line drug or other combined second generation based chemotherapy regimen that has similar action to cisplatinum such as oxaliplatin may be safer for toxicity, and may get better out outcome. 5-FU regimen is still the reference group in future clinical trial for advanced gastric cancer treatment. The value of any new adjuvant treatment approach could be proven by a randomized study comparing it with cisplatinum based regimen plus 5-FU or single 5-FU regimen.
A sequential design to estimate sensitivity and specificity of a diagnostic or screening test

We consider efficient study designs to estimate sensitivity and specificity of a candidate diagnostic or screening test. Our focus is the setting in which the candidate test is inexpensive to administer compared to evaluation of disease status, and the test results, available in a large cohort, can be used as a basis for sampling subjects for verification of disease status. We examine designs in which disease status is verified in a sample chosen so as to optimize estimation of either sensitivity or specificity. We then propose a sequential design in which the first step of sampling is conducted to efficiently estimate specificity. If the candidate test is determined to be of sufficient specificity, then step two of sampling is conducted to estimate sensitivity. We propose estimators based on this sequential sampling scheme, and show that the performance of these estimators is excellent. We develop sample size calculations for the sequential design, and show that this design, in most situations, compares favourably in terms of expected sample size to a fixed size design. Copyright © 2005 John Wiley & Sons, Ltd.
Enhancing Quality of Provider Practices for Older Adults in the Emergency Department (EQUiPPED)

EQUiPPED is a multicomponent quality improvement initiative combining education, electronic clinical decision support, and individual provider feedback to influence prescribing and improve medication safety for older adults. The objective here was to evaluate the effectiveness and sustainability of EQUiPPED to reduce the use of potentially inappropriate medications (PIMs), as defined by the American Geriatrics Society 2012 Beers Criteria, prescribed to older Veterans at the time of emergency department (ED) discharge. This evaluation represents a pre‐ and post‐intervention comparison of PIM prescriptions at 4 urban Veteran Affairs (VA) Medical Center EDs. Poisson regression was used to compare the number of PIMs prescribed to Veterans 65 years or older discharged from the ED for at least 6 months prior to the first EQUiPPED intervention at each site and for at least 12 months following the final EQUiPPED intervention. The implementation timeline varied by site depending on local resources. All 4 sites showed a significant and sustained reduction in use of PIMs. The proportion of PIMs at site one decreased from 11.9% (SD 1.8) pre‐EQUiPPED to 5.1% (SD 1.4) post‐EQUiPPED (P < .0001); site 2 from 8.2% (SD 0.8) pre to 4.5% (SD 1.0) post (P < .0001); site 3 from 8.9% (SD 1.9) pre to 6.1% (SD 1.7) post (P = .0007); and site 4 from 7.4% (SD 1.7) pre to 5.7% (SD 0.8) post (P = .04). These results suggest a multicomponent program to influence provider prescribing behavior leads to safer prescribing for older adults discharged from the ED and is sustainable across multiple VA ED sites.
Non-constrained monitoring of systolic blood pressure on a weighing scale

In this study, we developed a novel technique for estimating non-constrained and cuffless blood pressure (BP) that was based on electrocardiogram (ECG) and ballistocardiogram (BCG). The BCG was non-invasively measured using a common electronic weighing scale when a subject was standing on it. The ECG was measured using three different methods: on the chest using Ag/AgCl electrodes, on the hands using dry electrodes and on the feet also using dry electrodes. For a BP correlated parameter, a time interval parameter, which was defined as the time difference between the ECG R-peak and BCG J-peak, was employed for evaluating and estimating beat-to-beat BP. Under a BP varying experiment with a Valsalva manoeuvre, the R–J intervals were extracted at every beat cycle and a systolic blood pressure (SBP) estimation equation was established using linear regression analysis for each subject. In the case of feet delivered ECG (F-ECG), an ensemble average technique synchronized at the BCG J-peak point was applied to extract the ECG signal from the feet. The performance of the proposed method was evaluated using Finapres, a non-invasive blood pressure measurement system, as a reference BP signal, and a scatter plot was used to find the regression line between the reference values and estimated BPs. A moving-window averaging technique was applied to remove the high-frequency noise in the R–J intervals and was applied to enhance the accuracy of the SBP estimation. For all individuals, the estimated SBP was similar to the measured SBP with a reliable correlation, which makes the proposed method suitable for use in a home healthcare system to monitor blood pressure on a weighing scale at the same time as measuring weight.
Reform of Physical Education Teaching and Cultivation of Life - long Sports Consciousness in Higher Vocational Colleges

With the continuous development of the times, competition among talents has become ever more intense. How to develop close to the needs of the community with a variety of talents, it becomes very important. In this case, we can only college sports education and lifelong sports education combined, can be achieved. Through the clarification and exposition of the relationship between the two, we can identify students in the important stage of life foundation, continue to learn, the school must cultivate professional students of lifelong physical education awareness, in order to promote higher education In the reform of physical education.
Spatially structured metapopulation models: global and local assessment of metapopulation capacity.

We model metapopulation dynamics in finite networks of discrete habitat patches with given areas and spatial locations. We define and analyze two simple and ecologically intuitive measures of the capacity of the habitat patch network to support a viable metapopulation. Metapopulation persistence capacity lambda(M) defines the threshold condition for long-term metapopulation persistence as lambda(M)>delta, where delta is defined by the extinction and colonization rate parameters of the focal species. Metapopulation invasion capacity lambda(I) sets the condition for successful invasion of an empty network from one small local population as lambda(I)>delta. The metapopulation capacities lambda(M) and lambda(I) are defined as the leading eigenvalue or a comparable quantity of an appropriate "landscape" matrix. Based on these definitions, we present a classification of a very general class of deterministic, continuous-time and discrete-time metapopulation models. Two specific models are analyzed in greater detail: a spatially realistic version of the continuous-time Levins model and the discrete-time incidence function model with propagule size-dependent colonization rate and a rescue effect. In both models we assume that the extinction rate increases with decreasing patch area and that the colonization rate increases with patch connectivity. In the spatially realistic Levins model, the two types of metapopulation capacities coincide, whereas the incidence function model possesses a strong Allee effect characterized by lambda(I)=0. For these two models, we show that the metapopulation capacities can be considered as simple sums of contributions from individual habitat patches, given by the elements of the leading eigenvector or comparable quantities. We may therefore assess the significance of particular habitat patches, including new patches that might be added to the network, for the metapopulation capacities of the network as a whole. We derive useful approximations for both the threshold conditions and the equilibrium states in the two models. The metapopulation capacities and the measures of the dynamic significance of particular patches can be calculated for real patch networks for applications in metapopulation ecology, landscape ecology, and conservation biology.
Alzheimer's Disease Therapeutics: New Approaches to an Ageing Problem

Abnormal proteinaceous deposits are found in the brain of patients with many different neurodegenerative diseases. In many of these diseases, the production of the deposits is probably associated with disease pathogenesis. In Alzheimer's disease (AD), the amyloid protein (Aβ), is produced by the action of enzymes known as secretases, which cleave the β‐amyloid protein precursor. Aβ is secreted from cells in the brain, after which it oligomerizes and is deposited in the extracellular compartment of the brain to form amyloid plaques and amyloid angiopathy. Targeting the production of Aβ and its aggregation is now a key strategy in the development of novel therapeutic agents for the treatment of AD. This review examines the potential of immunization strategies, cholesterol‐lowering drugs, protease inhibitors and nicotinic drugs for the treatment of AD. IUBMB Life, 56: 203‐208, 2004
Physicochemical Properties, Pharmacokinetics, and Pharmacodynamics of a Reformulated Microemulsion Propofol in Rats

Background:A newly developed microemulsion propofol consisted of 10% purified poloxamer 188 and 0.7% polyethylene glycol 660 hydroxystearate. The authors studied the physicochemical properties, aqueous free propofol concentration, and plasma bradykinin generation. Pharmacokinetics and pharmacodynamics were also evaluated in rats. Methods:The pH, particle size, and osmolarity of microemulsion propofol were measured using a pH meter, particle size analyzer, and cryoscopic osmometer, respectively. The aqueous free propofol and plasma bradykinin were measured by a dialysis method and radioimmunoassay, respectively. Microemulsion propofol was administered by zero-order infusion of 0.5, 1.0, and 1.5 mg · kg−1 · min−1 for 20 min in 30 rats. The electroencephalographic approximate entropy was used as a surrogate measure of propofol effect. Results:The pH, osmolarity, and particle size of microemulsion propofol are 7.5, 280 mOsm/l, and 67.0 ± 28.5 nm, respectively. The aqueous free propofol concentration in microemulsion propofol was 63.3 ± 1.2 μg/ml. When mixed with human blood, microemulsion propofol did not generate bradykinin in plasma. Although microemulsion propofol had nonlinear pharmacokinetics, a two-compartment model with linear pharmacokinetics best described the time course of the propofol concentration as follows: V1 = 0.143 l/kg, k10 = 0.175 min−1, k12 = 0.126 min−1, k21 = 0.043 min−1. The pharmacodynamic parameters in a sigmoid Emax model were as follows: E0 = 1.18, Emax = 0.636, Ce50 = 1.87 μg/ml, γ = 1.28, ke0 = 1.02 min−1. Conclusions:Microemulsion propofol produced a high concentration of free propofol in the aqueous phase. For the applied dose range, microemulsion propofol showed nonlinear pharmacokinetics.
FPGA Implementation of a Tone-Based Flight Termination System in a Software-Defined Radio Platform

This paper outlines the design and implementation of a tone-based flight termination system (FTS) in a software-defined radio (SDR) platform. It is completely a novel implementation of an analog FTS in an SDR platform of NI Flex-RIO system. This single platform based design appears as a substitute for the previously used multiple platforms based complex system. Ruggedization and relevance design methods are required for the FTS design. Hence, the blueprint of the FTS is carried out in a field-programmable gate array. It ensures reconfigurable, interoperable operations with precise, reliable, and future upgradable implementation. Efficient optimization methods have been adopted to minimize the use of hardware resources. LabVIEW, a graphical programming language, is used for rapid prototyping. The validation of the system was done both in subsystem level as well as the integrated level at real-time mission scenario.
Investigation of Established Genetic Risk Variants for Glioma in Prediagnostic Samples from a Population-Based Nested Case–Control Study

Background: Although glioma etiology is poorly understood in general, growing evidence indicates a genetic component. Four large genome-wide association studies (GWAS) have linked common genetic variants with an increased glioma risk. However, to date, these studies are based largely on a case–control design, where cases have been recruited at the time of or after diagnosis. They may therefore suffer from a degree of survival bias, introduced when rapidly fatal cases are not included. Methods: To confirm glioma risk variants in a prospective setting, we have analyzed 11 previously identified risk variants in a set of prediagnostic serum samples with 598 cases and 595 matched controls. Serum samples were acquired from The Janus Serum Bank, a Norwegian population-based biobank reserved for cancer research. Results: We confirmed the association with glioma risk for variants within five genomic regions: 8q24.21 (CCDC26), 9p21.3 (CDKN2B-AS1), 11q23.3 (PHLDB1), 17p13.1 (TP53), and 20q13.33 (RTEL1). However, previously identified risk variants within the 7p11.2 (EGFR) region were not confirmed by this study. Conclusions: Our results indicate that the risk variants that were confirmed by this study are truly associated with glioma risk and may, consequently, affect gliomagenesis. Though the lack of positive confirmation of EGFR risk variants may be attributable to relatively limited statistical power, it nevertheless raises the question whether they truly are risk variants or markers for glioma prognosis. Impact: Our findings indicate the need for further studies to clarify the role of glioma risk loci with respect to prolonged survival versus etiology. Cancer Epidemiol Biomarkers Prev; 24(5); 810–6. ©2015 AACR.
Cloning, expression, and nucleotide sequence of a Staphylococcus aureus gene (fbpA) encoding a fibrinogen-binding protein

Septicemia due to Staphylococcus aureus often begins as a focal infection (e.g., colonized wounds or catheters) from which the organism gains access to the bloodstream. On the basis of recent data from this laboratory, it is likely that S. aureus colonizes catheters and endothelium by using a fibrinogen-binding protein to mediate adhesion to fibrinogen-coated surfaces. To characterize the fibrinogen-reactive protein, we screened a lambda Zap library of S. aureus DB, a clinical isolate, for clones that were reactive with fibrinogen. Of 100,000 plaques screened, 3 were found to react with fibrinogen on immunoblots. Plasmid DNA prepared from clones 14, 30, and 36, upon digestion with EcoR1, which released the insert, revealed fragments of 4.6, 3.6, and 3.2 kb, respectively. To identify the cloned protein expressed in E. coli, cells were fractionated into periplasmic, membrane, and cytoplasmic fractions. Expression studies of clone 14, which comprised approximately two-thirds of the mature molecule, including the C terminus, revealed a 34-kDa fibrinogen-reactive protein in both the periplasmic and membrane fractions. This protein, designated FbpA, could be partially purified on a fibrinogen column. By using both clones 14 and 36 as templates, the complete DNA sequence of the fibrinogen-binding protein was obtained, yielding a molecule with a predicted size of 69,991 Da. Although sequence analysis revealed a high degree of homology with coagulase, there is a unique sequence of 11 amino acids that is not found in three known coagulases as well as two recently cloned fibrinogen-binding proteins. This unique sequence shares homology with a cell wall anchor motif found in other gram-positive surface proteins.
Local TAT-p27Kip1 fusion protein inhibits cell proliferation in rat carotid arteries.

INTRODUCTION p27(Kip1) is a cyclin kinase inhibitor that induces cell cycle arrest. In this study, the efficacy of fusion protein TAT- p27(Kip1) to inhibit cell proliferation in rat perivascular injured carotid arteries was tested. METHODS The cDNA of p27(Kip1) and GFP (green fluorescein protein) fused to the TAT epitope, which allows cell penetration, yielded TAT-p27 (Kip1) and TAT-GFP fusion proteins. In vitro biological activity on cell proliferation was evaluated by [(3)H] thymidine DNA incorporation in rabbit aortic endothelial cells (REC). An in vivo model used a silicone collar filled with saline positioned around the carotid vessel for 14 days to produce an increased adventitia cross-sectional area. RESULTS TAT-p27(Kip1) inhibited REC proliferation in vitro using either 100, 200, and 500 nM compared to control (88.2 +/- 4.4, 81.3 +/- 7, 71.9 +/- 4.2 vs. 100 +/- 6.7%, N = 3, respectively, p < 0.05). This response was stable for purified proteins stored at -20*C for at least 23 days. In vivo , TAT-p27(Kip1) solution reduced adventitia cross-sectional area in a dose-dependent manner compared to TAT-GFP (area in mm(2) - TAT-p27(Kip1): 200 nM, 0.160 +/- 0.018; 500 nM, 0.050 +/- 0.005 vs. TAT-GFP: 500 nM, 0.595 +/- 0.066 vs. the contralateral: 0.047 +/- 0.005, N = 7, p < 0.01). CONCLUSION Taken together, these results provide evidence that TAT-p27(Kip1) can inhibit vascular cells proliferation. It is the first successful demonstration that the cell permeable TAT-p27(Kip1) has potential as a vascular anti-proliferative agent.