Miracle-dz/UniFAR-FTUs huggingface dataset:
Screening of Specific Inhibitors for Human Carboxylesterases or Arylacetamide Deacetylase

Esterases catalyze the hydrolysis of therapeutic drugs containing esters or amides in their structures. Human carboxylesterase (CES) and arylacetamide deacetylase (AADAC) are the major enzymes that catalyze the hydrolysis of drugs in the liver. Characterization of the enzyme(s) responsible for drug metabolism is required in drug development and to realize optimal drug therapy. Because multiple enzymes may show a metabolic potency for a given compound, inhibition studies using chemical inhibitors are useful tools to determine the contribution of each enzyme in human tissue preparations. The purpose of this study was to find specific inhibitors for human CES1, CES2, and AADAC. We screened 542 chemicals for the inhibition potency toward hydrolase activities of p-nitrophenyl acetate by recombinant CES1, CES2, and AADAC. We found that digitonin and telmisartan specifically inhibited CES1 and CES2 enzyme activity, respectively. Vinblastine potently inhibited both AADAC and CES2, but no specific inhibitor of AADAC was found. The inhibitory potency and specificity of these compounds were also evaluated by monitoring the effects on hydrolase activity of probe compounds of each enzyme (CES1: lidocaine, CES2: CPT-11, AADAC: phenacetin) in human liver microsomes. Telmisartan and vinblastine strongly inhibited the hydrolysis of CPT-11 and/or phenacetin, but digitonin did not strongly inhibit the hydrolysis of lidocaine, indicating that the inhibitory potency of digitonin was different between recombinant CES1 and liver microsomes. Although we could not find a specific inhibitor of AADAC, the combined use of telmisartan and vinblastine could predict the responsibility of human AADAC to drug hydrolysis.
Research in Physical Medicine and Rehabilitation: V. Data Entry and Early Exploratory Data Analysis

The process of data entry and initial analysis to locate data errors is described. Basic terms are defined and a simple method of entering data by using word processing software is illustrated. Data checking is done by using visual check of the raw data. Statistical programs are then used to locate possible data errors by finding data points (outliers) that are very different from the average. Special graphic output of statistical programs, scatterplots and box and whisker plots can be used to further locate questionable data. Examples of data entry forms and annotated step by step data cleaning with the use of inexpensive programs for personal computers are presented.
Effect of magnesium infusion on thoracic epidural analgesia

Introduction: Patients of lung volume reduction surgery (LVRS) having an ASA status III or more are likely to be further downgraded by surgery to critical levels of pulmonary function. Aim: To compare the efficacy of thoracic epidural block with (0.125%) bupivacaine, fentanyl combination and (0.125%) bupivacaine, fentanyl combination with adjunctive intravenous magnesium infusion for the relief of postoperative pain in patients undergoing LVRS. Methods: Patients were operated under general anesthesia. Thirty minutes before the anticipated completion of skin closure in both groups, (Group A and Group B) 7 ml of (0.125%) bupivacaine calculated as 1.5 ml/thoracic segment space for achieving analgesia in dermatomes of T4, T5, T6, T7, and T8 segments, along with fentanyl 50 μg (0.5 ml), was administered through the catheter, activating the epidural block, and the time was noted. Thereafter, in patients of Group A, magnesium sulfate injection 30 mg/kg i.v. bolus was followed by infusion of magnesium sulfate at 10 mg/kg/hr and continued up to 24 hours. Group B was treated as control. Results and Analysis: A significant increase in the mean and maximum duration of analgesia in Group A in comparison with Group B (P<0.05) was observed. Total epidural dose of fentanyl and bupivacaine required in Group A was significantly lower in comparison with Group B in 24 hours. Discussion: Requirement of total doses of local anesthetics along with opioids could be minimized by magnesium infusion; therefore, the further downgradation of patients of LVRS may be prevented. Conclusion: Intravenous magnesium can prolong opioid-induced analgesia while minimizing nausea, pruritus, and somnolence.
Preliminary results to define an active multispectral imager for gunshot residues patterns visualization

In incidents involving gunshot wounds, for short range target shooting only, gunshot residues (GSR) are projected on the target and a distinct pattern around the bullet entrance hole may be observed by the forensic experts. A careful analysis of this pattern is often carried out in order to determine the muzzle-to-target distance and angle, and draw some conclusions about the nature of the firearm. However, seeing and recording gunshot residue patterns can be difficult especially if the victim's clothing is dark. The main goal of our study is to develop a multispectral laser imaging device able to reveal gunshot residue patterns on many kinds of clothes, which provide a fast result. The first stage before developing this device is to acquire and analyze hyperspectral images taken on samples in order to select the best spectral bands to use and to develop the appropriate processing to enhance the pattern.
Flow-dependent cellular mechanotransduction in atherosclerosis

Summary Atherosclerosis depends on risk factors such as hyperlipidemia, smoking, hypertension and diabetes. Although these risk factors are relatively constant throughout the arterial circulation, atherosclerotic plaques occur at specific sites where flow patterns are disturbed, with lower overall magnitude and complex changes in speed and direction. Research over the past few decades has provided new insights into the cellular mechanisms of force transduction and how mechanical effects act in concert with conventional risk factors to mediate plaque formation and progression. This Commentary summarizes our current understanding of how mechanotransduction pathways synergize with conventional risk factors in atherosclerosis. We attempt to integrate cellular studies with animal and clinical data, and highlight major questions that need to be answered to develop more effective therapies.
Suppression of Extracellular Signal-Regulated Kinase Activity in Herpes Simplex Virus 1-Infected Cells by the Us3 Protein Kinase

ABSTRACT Host mitogen-activated protein kinases (MAPKs) are deregulated by herpes simplex virus 1 (HSV-1). Unlike p38 MAPK and Jun N-terminal protein kinase (JNK), which require ICP27 for their activation early in infection, extracellular signal-regulated kinase (ERK) activity is suppressed by an unknown mechanism. Here, we establish that HSV-1-induced suppression of ERK activity requires viral gene expression, occurs with delayed-early kinetics, and requires the functional virus-encoded Us3 Ser/Thr protein kinase. Finally, Us3 expression in uninfected cells was necessary and sufficient to suppress ERK activity in the absence of any other virus-encoded gene products. This demonstrates that inhibition of ERK activity in HSV-1-infected cells is an intrinsic Us3 function and defines a new role for this alphaherpesvirus Us3 kinase in regulating MAPK activation in infected cells.
Challenges for Optically Enabled High-Radix Switches for Data Center Networks

We discuss challenges for optically enabled high-radix switches in data centers. We highlight the clear advantages of using high-radix switches and explain why coupling such switches with midboard optics can be a winning solution. We further analyze the trends in pluggable transceivers and data center switches and indicate that if current scaling trends are set to continue, very different hardware, software, and architectures should be adopted to support future data centers networks.
A real-time image feature vector generator employing functional cache memory for edge flags

A feature-vector-generation VLSI architecture has been developed aiming at building real-time image recognition systems based on the directional edge based algorithm. The functional cache memory developed in the present work cyclically buffers newly extracted edge flags from an input image, while supplying edge flags to a vector generation circuitry. As a result, it has become possible to generate a 64-dimetional feature vector in every cycle of operation. The chip was designed in a 0.18-µm 5-metal CMOS technology and sent to fabrication, and correct operation of the entire system was confirmed by Nanosim simulation. The architecture enables us to generate 3.9 × 107 feature vectors/sec (@100MHz), which is 5 × 103 times faster than the software processing using 2.16-GHz processor.
Transgenic plants in the biopharmaceutical market

Many of our ‘small-molecule-drugs’ are natural products from plants, or are synthetic compounds based on molecules found naturally in plants. However, the vast majority of the protein therapeutics (or biopharmaceuticals) we use are from animal or human sources, and are produced commercially in microbial or mammalian bioreactor systems. Over the last few years, it has become clear that plants have great potential for the production of human proteins and other protein-based therapeutic entities. Plants offer the prospect of inexpensive biopharmaceutical production without sacrificing product quality or safety, and following the success of several plant-derived technical proteins, the first therapeutic products are now approaching the market. In this review, the different plant-based production systems are discussed and the merits of transgenic plants are evaluated compared with other platforms. A detailed discussion is provided of the development issues that remain to be addressed before plants become an acceptable mainstream production technology. The many different proteins that have already been produced using plants are described, and a sketch of the current market and the activities of the key players is provided. Despite the currently unclear regulatory framework and general industry inertia, the benefits of plant-derived pharmaceuticals are now bringing the prospect of inexpensive veterinary and human medicines closer than ever before.
Testing the hypothesis of tissue selectivity: the intersection–union test and a Bayesian approach

Motivation: Finding genes that are preferentially expressed in a particular tissue or condition is a problem that cannot be solved by standard statistical testing procedures. A relatively unknown procedure that can be used is the intersection–union test (IUT). However, two disadvantages of the IUT are that it is conservative and it conveys only the information of the least differing target tissue–other tissue pair. Results: We propose a Bayesian procedure that quantifies how much evidence there is in the overall expression profile for selective over-expression. In a small simulation study, it is shown that the proposed method outperforms the IUT when it comes to finding selectively expressed genes. An application to publicly available data consisting of 22 tissues shows that the Bayesian method indeed selects genes with functions that reflect the specific tissue functions. The proposed method can also be used to find genes that are underexpressed in a particular tissue. Availability: Both MATLAB and R code that implement the IUT and the Bayesian procedure in an efficient way, can be downloaded at http://ppw.kuleuven. be/okp/software/BayesianIUT/. Contact: katrijn.vandeun@psy.kuleuven. be
Galaxy pairs in the Sloan Digital Sky Survey – XI. A new method for measuring the influence of the closest companion out to wide separations

We describe a statistical approach for measuring the influence that a galaxy's closest companion has on the galaxy's properties out to arbitrarily wide separations. We begin by identifying the closest companion for every galaxy in a large spectroscopic sample of Sloan Digital Sky Survey galaxies. We then characterize the local environment of each galaxy by using the number of galaxies within 2 Mpc and by determining the isolation of the galaxy pair from other neighbouring galaxies. We introduce a sophisticated algorithm for creating a statistical control sample for each galaxy, matching on stellar mass, redshift, local density and isolation. Unlike traditional studies of close galaxy pairs, this approach is effective in a wide range of environments, regardless of how faraway the closest companion is (although a very distant closest companion is unlikely to have a measurable influence on the galaxy in question). We apply this methodology to measurements of galaxy asymmetry, and find that the presence of nearby companions drives a clear enhancement in galaxy asymmetries. The asymmetry excess peaks at the smallest projected separations (<10 kpc), where the mean asymmetry is enhanced by a factor of 2.0 ± 0.2. Enhancements in mean asymmetry decline as pair separation increases, but remain statistically significant (1σ–2σ) out to projected separations of at least 50 kpc.
Robustness Evaluation of High-Voltage Press-Pack IGBT Modules in Enhanced Short-Circuit Test

This paper deals with the evaluation of robustness of high-power press-pack insulated-gate bipolar transistor modules under short-circuit conditions. The severity of the tests is usually related to the achievement of the real failure mode which drives the device to withstand a big amount of energy. The most well-known methods to evaluate the robustness of the devices have been analyzed and improved in order to operate with the highest achievable di/dt and to consequently emulate the real circuit setup and failure mode. Experimental tests will be shown and evaluated under different voltage and temperature conditions. The tests described in this paper have been targeted to evaluate the capability of the device to withstand extremely severe conditions when they are used in a high-power converter. A driving protection feature dealing with the target of improving the functionality of protection against failure will be also described.
Incidence and prevalence of idiopathic pulmonary fibrosis.

RATIONALE Idiopathic pulmonary fibrosis is a chronic interstitial lung disease of unknown etiology; its epidemiology in the United States has not been well characterized. OBJECTIVE To estimate the annual incidence and prevalence of idiopathic pulmonary fibrosis in the United States. METHODS Retrospective cohort design utilizing a large health care claims database spanning the period January 1996 through December 2000. MEASUREMENTS AND MAIN RESULTS Persons with idiopathic pulmonary fibrosis were identified based on diagnosis and procedure codes. Using broad case-finding criteria, prevalence was estimated to range from 4.0 per 100,000 persons aged 18 to 34 yr to 227.2 per 100,000 among those 75 yr or older; annual incidence was estimated to range from 1.2 to 76.4 per 100,000. Using narrow case-finding criteria, prevalence ranged from 0.8 to 64.7 per 100,000 persons; comparable figures for incidence were 0.4 to 27.1 per 100,000 persons. Extrapolating these rates to the overall United States' population, prevalence was estimated to be 42.7 per 100,000 (incidence, 16.3 per 100,000) using broad criteria; with narrow criteria, prevalence was estimated to be 14.0 per 100,000 (incidence, 6.8 per 100,000). CONCLUSIONS Our results suggest that idiopathic pulmonary fibrosis is probably more common in the United States than previously reported.
A Structural Approach for Transistor Circuit Synthesis

This paper presents a structural approach for synthesizing arbitrary multi-output multi-stage static CMOS circuits at the transistor level, targeting the reduction of transistor counts. To make the problem tractable, the solution space is restricted to the circuit structures which can be obtained by performing algebraic transformations on an arbitrary prime-and-irredundant two-level circuit. The proposed algorithm is guaranteed to find the optimal solution within the solution space. The circuit structures are implicitly enumerated via structural transformations on a single graph structure, then a dynamic-programming based algorithm efficiently finds the minimum solution among them. Experimental results on a benchmark suite targeting standard cell implementations demonstrate the feasibility and effectiveness of the proposed approach. We also demonstrated the efficiency of the proposed algorithm by a numerical analysis on randomly-generated problems.
The effect of diesel exhaust emission on blood brain barrier integrity and function

II ACKNOWLEDGEMENTS . V STATEMENT OF CONTRIBUTION . VI ABBREVIATIONS . VII TABLE OF CONTENTS . VIII CHAPTER 1: LITERATURE REVIEW . 2 1. AIR POLLUTION . 2 1.1 Air pollution definition, composition and sources . 2 1.2 Ambient air quality standards . 3 1.3 Particulate matter composition and classification . 4 1.4 Diesel exhaust and Diesel exhaust particulate . 6 1.5 Diesel exhaust and health effects . 10 1.5. 1 Diesel exhaust and foetal, infantile development . 10 1.5. 2 Diesel exhaust and cancers . 11 1.5. 3 Diesel exhaust and respiratory effects . 12 1.5. 4 Diesel exhaust and cardiovascular effects . 13 1.5. 5 Diesel exhaust and CNS effects . 14 1.6 Diesel exhaust and CNS . 17 1.6. 1 Diesel exhaust/Diesel exhaust particle mechanisms of action on CNS . 17 1.6. 1.1 Inflammatory response induced by diesel exhaust/diesel exhaust particle . 17 1.6. 1.2 Oxidative stress induced by diesel exhaust particle . 19 1.6. 2 Passage of diesel exhaust particle to CNS . 20 1.6. 2.1 Peripheral pathway.21 1.6. 2.2 Direct pathway . 21 1.6. 3 Brain cellular mediators of DEP-induced CNS pathology . 22 1.6. 3.1 Diesel exhaust and blood brain barrier. 22 1.6. 3.2 Diesel exhaust and glial cells . 26 INTRODUCTION AND STRUCTURE OF THESIS . 29
Positive Diversifying Selection on the Plasmodium falciparum surf4.1 Gene in Thailand

Plasmodium falciparum SURFIN4.1 is a type I transmembrane protein thought to locate on the merozoite surface and to be responsible for a reversible adherence to the erythrocyte before invasion. In this study, we evaluated surf4.1 gene segment encoding extracellular region for polymorphism, the signature of positive selection, the degree of linkage disequilibrium, and temporal change in allele frequency distribution in P. falciparum isolates from Thailand in 1988–89, 2003, and 2005. We found that SURFIN4.1 is highly polymorphic, particularly at the C-terminal side of the variable region located just before a predicted transmembrane region. A signature of positive diversifying selection on the variable region was detected by multiple tests and, to a lesser extent, on conserved N-terminally located cysteine-rich domain by Tajima’s D test. Linkage disequilibrium between sites over a long distance (> 1.5 kb) was detected, and multiple SURFIN4.1 haplotype sequences detected in 1988/89 still circulated in 2003. Few of the single amino acid polymorphism allele frequency distributions were significantly different between the 1988/89 and 2003 groups, suggesting that the frequency distribution of SURFIN4.1 extracellular region remained stable over 14 years.
Adaptively Learning Local Shape Statistics for Prostate Segmentation in Ultrasound

Automatic segmentation of the prostate from 2-D transrectal ultrasound (TRUS) is a highly desired tool in many clinical applications. However, it is a very challenging task, especially for segmenting the base and apex of the prostate due to the large shape variations in those areas compared to the midgland, which leads many existing segmentation methods to fail. To address the problem, this paper presents a novel TRUS video segmentation algorithm using both global population-based and patient-specific local shape statistics as shape constraint. By adaptively learning shape statistics in a local neighborhood during the segmentation process, the algorithm can effectively capture the patient-specific shape statistics and quickly adapt to the local shape changes in the base and apex areas. The learned shape statistics is then used as the shape constraint in a deformable model for TRUS video segmentation. The proposed method can robustly segment the entire gland of the prostate with significantly improved performance in the base and apex regions, compared to other previously reported methods. Our method was evaluated using 19 video sequences obtained from different patients and the average mean absolute distance error was 1.65 0.47 mm.
An AC Josephson voltage standard system for frequencies up to the kHz range tested in an industrial environment

This paper describes the performance of a new turn-key AC quantum voltmeter, an AC Josephson voltage standard system, used for calibration of common DC and AC voltage standards. The capabilities and handling of the system in an industrial environment were investigated and are discussed here. Several Fluke 5700A series calibrators were tested and their voltage and frequency dependence is characterized in the range of DC to 1 kHz with amplitudes up to 10 V. The combined measurement uncertainty for AC measurements was determined to be less than 1 μV/V.
Neuromuscular Blocking Agents and Neuromuscular Dysfunction Acquired in Critical Illness: A Systematic Review and Meta-Analysis

Objective:The relationship between neuromuscular blocking agents and neuromuscular dysfunction acquired in critical illness remains unclear. We examined the association between neuromuscular blocking agents and ICU-acquired weakness, critical illness polyneuropathy, and critical illness myopathy. Data Sources:PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health Literature, and bibliographies of included studies were searched from database inception until September 24, 2015. Study Selection:Randomized controlled trials and prospective observational studies examining the association between neuromuscular blocking agents and ICU-acquired weakness, critical illness polyneuropathy, or critical illness myopathy. Data Extraction:One author screened titles/abstracts. Two authors independently reviewed full text and extracted data from included studies. Meta-analysis was performed using the DerSimonian-Laird random effects model (OpenMetaAnalyst 10.10 for OS.X). We assessed reporting bias with funnel plots and heterogeneity with the I2 statistic. Data Synthesis:Of 2,170 titles/abstracts screened, 99 full texts were selected for review, yielding one randomized controlled trial and 18 prospective observational studies, for a total of 2,254 patients. The randomized controlled trial did not show an association between neuromuscular blocking agents and neuromuscular dysfunction acquired in critical illness (odds ratio, 1.21; 95% CI, 0.67–2.19), but pooled data from all included studies suggested a modest association (odds ratio, 1.25; 95% CI, 1.06–1.48; I2 = 16%). Funnel plots suggested reporting bias, and sensitivity analyses showed a disproportionate contribution from critical illness polyneuropathy/critical illness myopathy and severe sepsis/septic shock studies. Conclusions:This meta-analysis suggests a modest association between neuromuscular blocking agents and neuromuscular dysfunction acquired in critical illness; limitations include studies with a high risk of bias and a disproportionate contribution from studies examining patients for critical illness polyneuropathy/critical illness myopathy and those with severe sepsis/septic shock.