Miracle-dz/UniFAR-FTUs huggingface dataset:
Learning and Confirming with Preclinical Studies: Modeling and Simulation in the Discovery of GDC-0917, an Inhibitor of Apoptosis Proteins Antagonist

The application of modeling and simulation techniques is increasingly common in the preclinical stages of the drug development process. GDC-0917 [(S)-1-((S)-2-cyclohexyl-2-((S)-2-(methylamino)propanamido)acetyl)-N-(2-(oxazol-2-yl)-4-phenylthiazol-5-yl)pyrrolidine-2-carboxamide] is a potent second-generation antagonist of inhibitor of apoptosis (IAP) proteins that is being developed for the treatment of various cancers. GDC-0917 has low to moderate clearance in the mouse (12.0 ml/min/kg), rat (27.0 ml/min/kg), and dog (15.3 ml/min/kg), and high clearance in the monkey (67.6 ml/min/kg). Accordingly, oral bioavailability was lowest in monkeys compared with other species. Based on our experience with a prototype molecule with similar structure, in vitro–in vivo extrapolation was used to predict a moderate clearance (11.5 ml/min/kg) in humans. The predicted human volume of distribution was estimated using simple allometry at 6.69 l/kg. Translational pharmacokinetic-pharmacodynamic (PK-PD) analysis using results from MDA-MB-231-X1.1 breast cancer xenograft studies and predicted human pharmacokinetics suggests that ED50 and ED90 targets can be achieved in humans using acceptable doses (72 mg and 660 mg, respectively) and under an acceptable time frame. The relationship between GDC-0917 concentrations and pharmacodynamic response (cIAP1 degradation) was characterized using an in vitro peripheral blood mononuclear cell immunoassay. Simulations of human GDC-0917 plasma concentration-time profile and cIAP1 degradation at the 5-mg starting dose in the phase 1 clinical trial agreed well with observations. This work shows the importance of leveraging information from prototype molecules and illustrates how modeling and simulation can be used to add value to preclinical studies in the early stages of the drug development process.
High-risk sexual behavior and condom use among gay and bisexual African-American men.

OBJECTIVES Little is known about the human immunodeficiency virus (HIV) high-risk sexual practices of gay and bisexual African-American men. These data are needed so that better interventions can be developed and implemented in this population. METHODS The frequency and correlates of unprotected anal intercourse were examined among 250 gay and bisexual African-American men in the San Francisco Bay Area. The cohort was recruited in 1990 from bars, bathhouses, and erotic bookstores, and through African-American gay organizations, street outreach, advertisements in gay mainstream and African-American newspapers, health clinics, and personal referral from other participants. RESULTS More than 50% of the men in our sample reported having unprotected anal intercourse in the past 6 months, a considerably higher percentage than that among gay White men in San Francisco through 1988 and 1989. Men who practiced unprotected anal intercourse were more likely to be poor, to have been paid for sex, or to have used injection drugs; to have a higher perceived risk of HIV infection; and to report less social support for concerns about risky sexual behavior. Condom norms, condom efficacy, and negative expectations about using condoms predicted these men's failure to use them. CONCLUSION In the second decade of the acquired immunodeficiency syndrome epidemic, risk reduction programs are still needed for gay and bisexual African-American men.
Chemical composition and biological activities of the essential oil from Rubus pungens var. oldhamii

Abstract This paper presents a study on chemical composition, antimicrobial, antioxidant and tyrosinase inhibitory properties of the essential oil from leaves of Rubus pungens var. oldhamii (REO). The major component of the REO is sesquiterpenes (36.04%), which consists of 1,5-Cyclooctadiene,3-(1-me thylallyl)-(8CI)(17.66%), 5,6-Diethenyl-1-methylcyclohexene (12%), (+) – γ-Elemene (10.48%) and β-Caryophyllene (8.39%). The REO is shown to be moderately active against Staphylococcus aureus, Aspergillus niger and Penicillium glaucum, and has weak antioxidant activity in 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Furthermore, tyrosinase inhibition was investigated against monophenolase (L-tyrosine). IC50 values of REO and arbutin were found 0.923 and 0.657 mg/mL, respectively. The REO exerted potential antityrosinase activity. Our test results indicated that the REO was rich in sesquiterpenes, and also exhibited good antityrosinase activity, and moderate antimicrobial activity against pathogenic micro-organisms. The REO can be used as a natural source of promising antimicrobial and tyrosinase inhibiting agent.
A Molecular Platform in Neurons Regulates Inflammation after Spinal Cord Injury

Vigorous immune responses are induced in the immune privileged CNS by injury and disease, but the molecular mechanisms regulating innate immunity in the CNS are poorly defined. The inflammatory response initiated by spinal cord injury (SCI) involves activation of interleukin-1β (IL-1β) that contributes to secondary cell death. In the peripheral immune response, the inflammasome activates caspase-1 to process proinflammatory cytokines, but the regulation of trauma-induced inflammation in the CNS is not clearly understood. Here we show that a molecular platform [NALP1 (NAcht leucine-rich-repeat protein 1) inflammasome] consisting of caspase-1, caspase-11, ASC (apoptosis-associated speck-like protein containing a caspase-activating recruitment domain), and NALP1 is expressed in neurons of the normal rat spinal cord and forms a protein assembly with the X-linked inhibitor of apoptosis protein (XIAP). Moderate cervical contusive SCI induced processing of IL-1β, IL-18, activation of caspase-1, cleavage of XIAP, and promoted assembly of the multiprotein complex. Anti-ASC neutralizing antibodies administered to injured rats entered spinal cord neurons via a mechanism that was sensitive to carbenoxolone. Therapeutic neutralization of ASC reduced caspase-1 activation, XIAP cleavage, and interleukin processing, resulting in significant tissue sparing and functional improvement. Thus, rat spinal cord neurons contain a caspase-1, pro-ILβ, and pro-IL-18 activating complex different from the human NALP1 inflammasome that constitutes an important arm of the innate CNS inflammatory response after SCI.
Searching for susceptibility genes for psychosis in late-onset Alzheimer's disease

A number of behavioural symptoms are commonly displayed by Alzheimer's disease (AD) sufferers. Behavioural disturbances in AD can include affective symptoms, agitation, aggression and psychosis (Burns et al. 1990a Burns et al. 1990b Burns et al. 1990c). Alois Alzheimer was the first to document psychosis in the disease bearing his name, during his description of the clinical presentation of a patient upon admission to the Frankfurt asylum in 1906 (Alzheimer 1995 Schneider and Dagerman 2004).
A Robust Multi-Orientation Gabor Based System for Discriminating Touching White and Red Cells in Microscopic Blood Image

In many image analysis systems, segmentation is the first step. So its accuracy impacts on whole system efficiency. In normal human blood microscopic image, which contains white and red blood cells, because of high accumulation of red cells, there exist touch and overlap between these cells. They are two difficult issues in image segmentation which common segmentation algorithms cannot overcome them. Red cell has fine texture while white cell has coarse one, so texture is a very good discriminating feature for segmentation of blood cells. Gabor filters are one of the most powerful methods for texture segmentation. Blood image don't have regular textures. Common Gabor filter banks are suitable for regular texture segmentation. So we have employed a Gabor filter bank including many orientations and few frequencies in combination with sigmoid function for blood image segmentation. Results show that our approach is efficient
Psychological need fulfillment as a mediator of the relationship between transformational leadership and positive job attitudes

Purpose – The purpose of this paper is to explore the possible mediating role of need fulfilment in the relationship between transformational leadership and employee job attitudes (job satisfaction and dedication). Design/methodology/approach – The two samples include both cross-sectional and diary data. The cross-sectional sample (sample 1) consisted of 661 employees from various organizations. In the diary study (sample 2), 65 employees completed a daily questionnaire on five consecutive working days, yielding 325 measurement points in total. The authors analyzed the data using structural equation modeling (Mplus 5) and multilevel analyses (MLwiN 2.20). Findings – As hypothesized, support for full mediation of the relationship between transformational leadership and positive job attitudes through the fulfilment of psychological needs were found both on a general level and on a daily basis. Originality/value – The paper is based on a multi study approach and empirically addresses the link between transfo.
DETERMINISTIC TEST PATTERN GENERATOR DESIGN WITH GENETIC ALGORITHM APPROACH

The paper presents an automatic technique for structure optimization of a deterministic test pattern generator (TPG). The TPG is composed of a linear register and a non-linear combinational function that can invert any bit in the generated patterns. Consequently, any arbitrary test sequence can be produced. This kind of a TPG is suitable for on-line built-in self-test (BIST) implementations where a set of deterministic test patterns is required. In order to reduce the gate count of the BIST structure a genetic algorithm (GA) is employed. In contrast to conventional approaches, a GA concurrently optimizes multiple parameters that influence the final solution. Experimental results on ISCAS benchmarks demonstrate the efficiency of the approach. K e y w o r d s: test pattern generator, design, evolutionary technique, genetic algorithm, optimization 1 INTRODUCTION Testing of integrated circuits and systems has nowadays become a difficult problem for which conventional test approaches often prove to be inadequate. Part of the difficulties arises from the fact that the number of transistors in a chip increases faster than the pin count and consequently internal chip modules become increasingly difficult to access. Limited number of I/O pins represents a bottleneck in testing of complex embedded cores where transfers of large amounts of test patterns and test results between the automatic test equipment (ATE) and the unit-under-test (UUT) are required, [1]. One of the alternative solutions is to implement a built-in self-test (BIST) of the UUT, [2], with on-chip test pattern generation (TPG) and on-chip output response analysis logic. In this way, communication with external ATE is reduced to test initiation and transfer of test results [3]. The approach, however, also has some disadvantages. BIST implementation inevitably leads to area overhead, which typically results in performance penalties due to longer signal routing paths resulting from the inclusion of the BIST circuitry in the design. Minimization of the BIST logic is one of the commonly addressed problems in practice. In the paper an approach for the generation of deterministic TPG logic based on a Linear Feedback Shift Register (LFSR) composed of D-type and T-type flip-flops is described [4]. The use of LFSR for TPG eliminates the need of a ROM for storing the seeds since the LFSR itself jumps from a state to the next required state (seed) by inverting the logic value of some of the bits of its next
Speed Control of Switched Reluctance Motor Using Soft Computing Technique for Industrial Applications

This paper presents a new converter for switched reluctance motor for controlling the speed using soft computing technique like Fuzzy Logic Controller (FLC). The operating modes of proposed converter circuit are discussed. The proposed converter is capable of minimizing the torque ripple because of its faster excitation and demagnetization nature and also improving the average torque when compared to the conventional converter circuit. Fuzzy Logic Controller has becoming an important methodology in control engineering. The FLC has fast response, easily modified, cheaper to implement and does not require any mathematical modeling, perfect speed tracking with no peak overshoot compared to the conventional controller. The objective of this paper is to achieve a desired speed response with effective controller. The effectiveness of the proposed system is verified by using simulation. The simulation results are carried out by using MATLAB/SIMULINK and the corresponding results are presented.
CEFF: An efficient approach for traffic anomaly detection and classification

Nowadays, there are two major challenges to detect traffic anomalies in a large scale network. One is how to handle huge amounts of traffic data when we detect traffic anomalies in a network, and the other is how to carry out fast and detailed detection and classification. To address these two challenges, we propose a Change based Effective Frequent flow Features approach (CEFF), which can quickly obtain the anomaly detection and classification results by scanning the flow data only once. We implement CEFF for both offline and online detection and classification in Spark, a popular big data processing platform. Besides, we evaluate CEFF using China Telecom NetFlow format data in experiments, and make comparisons between CEFF and Shannon entropy based method, which has been proved to be effective for traffic anomaly detection. The experiment results show that CEFF has excellent performance in traffic anomaly detection and classification.
Performance Analysis of Energy Detection for MIMO Decision Fusion in Wireless Sensor Networks Over Arbitrary Fading Channels

In this paper, we consider a wireless sensor network (WSN) with sensors simultaneously reporting their decision to a fusion center (FC) equipped with multiple antennas. A Gaussian mixture channel model is used to obtain a general fading characterization of the channels ensemble between the sensors and the FC. Energy detection is studied as an appealing low-complexity sub-optimal alternative to the (computationally expensive) optimal test based on log-likelihood ratio. Closed-form theoretical performance is obtained for the energy test and furthermore asymptotic analysis for both tests is derived in order to provide a detailed characterization of large-system scenarios. Finally, the simulation results are provided to confirm the theoretical results and compare performance trends of the two tests.
A FIELD EVALUATION OF FOUR LARVAL MOSQUITO CONTROL METHODS IN URBAN CATCH BASINS

ABSTRACT Effective control of mosquitoes in rural Midwestern communities that lack organized mosquito control districts would be aided by baseline data on optimal breeding sites, interannual effects of climate on population emergence and abundance, and efficacy of various control options under field conditions. During 19 surveillance weeks in the summer of 2005, we sampled 100 catch basins each week that were distributed among 10 study zones. Catch basins within each study zone were subjected to 1 of 4 different mosquito control methods or were left untreated. Of the 10 study zones, 5 were in high-intensity urban areas and 5 in low-intensity urban areas. During the study period, treatment of urban catch basins with Altosid® XR extended residual briquets resulted in a 69.5% reduction in mosquito larvae numbers. However, the product did not provide sustained treatment for the 120–150 days suggested by the manufacturer. Vectolex®WSP, when applied according to manufacturer's suggestions, resulted in a 73.4% reduction in mosquito larvae. VectolexWSP effectiveness was impacted by heavy rainfalls early in the surveillance period. Cleaning catch basins once or twice during the surveillance period resulted in a 40.1% and a 39.9% reduction in mosquito larvae, respectively. Catch basins in high-intensity urban areas comprised 27.7% of the total collection compared to 72.3% from low-intensity urban areas. The AltosidXR extended residual briquets and the VectolexWSP products both impacted the number of mosquito larvae collected. However, a single treatment to control mosquitoes in this study area may not be sufficient. We suggest that treatment of urban catch basins is optimized when accompanied by a comprehensive surveillance plan, and that a combination of treatments or multiple treatments during the season may be necessary to mitigate risks of vector-borne infectious diseases in areas with similar climate and precipitation trends.
Integrating Anomaly Diagnosis Techniques into Spreadsheet Environments

Although spreadsheets are often faulty, end-users like them for their flexibility. Most existing approaches to spreadsheet diagnosis are fully automated and use static analysis techniques to find anomalies in formulas or methods to derive test cases without user interaction. The few more interactive approaches are based on values already present in spreadsheets as well. In our work, we advance the idea of testing spreadsheets with user-defined test scenarios but encourage visually aided creation of independent test cases by separating the definition of test scenarios from the specific values present in the spreadsheet - just like test code is separated from production code in professional software. We combine the testing approach with static analysis and integrate it into a common visual spreadsheet environment named SIFEI. It supports users in interactively creating, executing, and analyzing their own test scenarios with a number of visual markers. Findings from two qualitative studies indicate that the concept is suitable for casual spreadsheet users.
Ultrasound strain imaging based on information theoretic delay estimation

Ultrasound strain imaging has great importance as tumor or cancerous tissues are much stiffer than normal tissues. Estimations of strain calculating the time delays between consecutive ultrasound echo signals are common approaches in quasi-static elastography. Because of the ill posed nature of strain images, the ultrasound strain estimation still remains challenging. In this paper, we present an iterative strain estimator that uses mutual information between stochastic pre and post compressed radio frequency (RF) signals to define time delays. For each RF signal, a past and future is defined by cutting sample sequences into two parts. The time delay is considered to be the time shift between the cutting moments for which the mutual information between both past vectors and future vectors reaches a minimum. Displacement calculation with this time delay provides effective strain estimation for small strains. A synthetic phantom of tissue with tumor is modeled using the finite element method (FEM) and the pre-/post-compressed RF signals are generated using ultrasound simulation package Field II. Using these simulated RF data displacements and strain of deformation are calculated in MATLAB. The Contrast to Noise Ratio (CNR) and Signal to Noise Ratio (SNR) are found better compared to conventional cross-correlation method. This algorithm can detect inclusions having echogenicity very close to that of the surrounding tissues and hence can be useful for detection of tumors or cancers.
Review of anthropometric factors and breast cancer risk

Epidemiological evidence implicating anthropometric risk factors in breast cancer aetiology is accumulating. For premenopausal women, breast cancer risk increases with increasing height, but decreases with higher weight or body mass index, and no association with increased central adiposity exists. For postmenopausal women, an increased risk of breast cancer is found with increasing levels of all the anthropometric variables including height, weight, body mass index, waist–hip ratio, waist circumference and weight gain. Weight loss appears to decrease risk, particularly if it occurs later in life. Breast size may be a risk factor for breast cancer, however, the current evidence is inconclusive. Several hypothesized biologic mechanisms exist to explain how anthropometric factors influence breast cancer risk. Obesity may increase levels of circulating endogenous sex hormones, insulin and insulin‐like growth factors that all, in turn, increase breast cancer risk. Genetic predisposition to obesity and to specific body fat distributions are also implicated. With obesity, there are increased levels of fat tissue that can store toxins and can serve as a continuous source of carcinogens. Recommendations for future research on anthropometric factors and breast cancer are provided. Sufficient evidence exists to support strategies to avoid weight gain throughout life as a means of reducing postmenopausal breast cancer risk.
A Formal Model of Planning for Concurrency

While classical planning is still mostly concerned with sequential plans, numerous realistic domains are inherently concurrent. Especially planning for multi-agent systems necessitates a clear formal concept of plans in such domains. This paper presents a basic semantic model for concurrent plans using actions with arbitrary effects over time and shared accesses to resources. Two complementary forms of event interaction, asynchronous and synchronous concurrency, are formally described that allow to automatically compute complex joint effects of concurrent actions if possible, but also to explicitly specify combined effects that are not derivable from the single events. According to the formal model, a description language for concurrent domains is defined. The language BTPL (Basic Temporal Planning Language) allows also for rich specifications of initial and goal situations including triggered or exogenous events over time. BTPL is downward compatible to PDDL and may therefore be helpful in bringing classical and multi-agent planning closer together.
The political economy of concurrent partners: toward a history of sex–love–gift connections in the time of AIDS

Over the last decade, one of the most influential explanations for high HIV prevalence in sub-Saharan Africa is the existence of sexual networks characterised by concurrent partners. Recently, however, a growing number of scholars have challenged the evidential basis for the concurrency argument. While this dispute has led to a call for more sophisticated quantitative methods to measure concurrency, this article widens the discussion to emphasise the political economic roots and qualitative dimension of concurrent partnered relations. Specifically, the paper argues for the importance of situating concurrency within key historical processes and, to that end, gives special consideration to the growth of ‘transactional sex' – non-prostitute but material relations between men and women. Critics of the concurrency–HIV thesis have sometimes dismissed as anecdotal accounts of sex–gift exchanges in Africa. Yet by exploring through an ethnographic/historical lens the changing configuration of sex, love and gifts in South Africa, this article illuminates different manifestations of concurrency, including connections between concurrency and condom use.