Miracle-dz/UniFAR-FTUs huggingface dataset:
Species differences in metabolism of EPZ015666, an oxetane-containing protein arginine methyltransferase-5 (PRMT5) inhibitor

Abstract 1. Metabolite profiling and identification studies were conducted to understand the cross-species differences in the metabolic clearance of EPZ015666, a first-in-class protein arginine methyltransferase-5 (PRMT5) inhibitor, with anti-proliferative effects in preclinical models of Mantle Cell Lymphoma. EPZ015666 exhibited low clearance in human, mouse and rat liver microsomes, in part by introduction of a 3-substituted oxetane ring on the molecule. In contrast, a higher clearance was observed in dog liver microsomes (DLM) that translated to a higher in vivo clearance in dog compared with rodent. 2. Structure elucidation via high resolution, accurate mass LC-MSn revealed that the prominent metabolites of EPZ015666 were present in hepatocytes from all species, with the highest turnover rate in dogs. M1 and M2 resulted from oxidative oxetane ring scission, whereas M3 resulted from loss of the oxetane ring via an N-dealkylation reaction. 3. The formation of M1 and M2 in DLM was significantly abrogated in the presence of the specific CYP2D inhibitor, quinidine, and to a lesser extent by the CYP3A inhibitor, ketoconazole, corroborating data from human recombinant isozymes. 4. Our data indicate a marked species difference in the metabolism of the PRMT5 inhibitor EPZ015666, with oxetane ring scission the predominant metabolic pathway in dog mediated largely by CYP2D.
HW/SW-database-codesign for compressed bitmap index processing

Compressed bitmap indices are heavily used in scientific and commercial database systems because they largely improve query performance for various workloads. Early research focused on finding tailor-made index compression schemes that are amenable for modern processors. Improving performance further typically comes at the expense of a lower compression rate, which is in many applications not acceptable because of memory limitations. Alternatively, tailor-made hardware allows to achieve a performance that can only hardly be reached with software running on general-purpose CPUs. In this paper, we will show how to create a custom instruction set framework for compressed bitmap processing that is generic enough to implement most of the major compressed bitmap indices. For evaluation, we implemented WAH, PLWAH, and COMPAX operations using our framework and compared the resulting implementation to multiple state-of-the-art processors. We show that the custom-made bitmap processor achieves speedups of up to one order of magnitude by also using two orders of magnitude less energy compared to a modern energy-efficient Intel processor. Finally, we discuss how to embed our processor with database-specific instruction sets into database system environments.
Radiation‐induced bystander effects in malignant trophoblast cells are independent from gap junctional communication

It is controversially discussed that irradiation induces bystander effects via gap junction channels and/or diffusible cellular factors such as nitric oxide or cytokines excreted from the cells into the environment. But up to now the molecular mechanism leading to a bystander response is not well understood. To discriminate between both mechanisms of bystander response, (i) mediated by gap junctional communication and/or (ii) mediated by diffusible molecules, we used non‐communicating Jeg3 malignant trophoblast cells transfected with inducible gap junction proteins, connexin43 and connexin26, respectively, based on the Tet‐On system. We co‐cultivated X‐ray irradiated and non‐irradiated bystander Jeg3 cells for 4 h, separated both cell populations by flow cytometry and evaluated the expression of activated p53 by Western blot analysis. The experimental design was proven with communicating versus non‐communicating Jeg3 cells. Interestingly, our results revealed a bystander effect which was independent from gap junctional communication properties and the connexin isoform expressed. Therefore, it seems more likely that the bystander effect is not mediated via gap junction channels but rather by paracrine mechanisms via excreted molecules in Jeg3 cells. J. Cell. Biochem. 103: 149–161, 2008. © 2007 Wiley‐Liss, Inc.
Extracts from fermented black soybean milk exhibit antioxidant and cytotoxic activities.

Summary In this study, ethanol extracts from 2-day fermented black soybean milk (FBE) by immobilized Rhizopus oligosporus NTU5 have been evaluated for both antioxidant and cytotoxic activities. The results reveal that a 2-day FBE had strong 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging effect (76 %). The extracts were further fractionated by silica gel column chromatography and an unknown compound, FBE5-A, was obtained, which exhibited strong antioxidant activity. IC50 of the DPPH scavenging effect of FBE5-A was 7.5 mg/mL, which is stronger than a commonly used antioxidant, vitamin E (a-tocopherol; 17.4 mg/mL), and similar to vitamin C (ascorbic acid; 7.6 mg/mL). The cytotoxic test demonstrated that extracts of 2-day fermented broth exhibited selective cytotoxic activity towards human carcinoma cells, Hep 3B (IC50=150.2 mg/mL), and did not affect normal human lung fibroblasts, MRC-5 (p<0.05). The results indicate the potential applications of fermented black soybean milk as functional food, pharmaceutical or cancer therapy formula.
Seeing the Forest through the Trees

1 Georgia Institute of Technology, Sam Nunn School of International Affairs, Atlanta, GA 30332, USA. Email: d.muchlinski@unsw.edu. au 2 Arizona State University—School of Politics and Global Studies, Tempe, AZ 85287, USA. Email: david.siroky@asu.edu 3 Arizona State University—Computer Science and Engineering, Tempe, AZ 85281, USA. Email: jingrui.he@asu.edu 4 Johns Hopkins University—Political Science and SAIS, Baltimore, MD 21218, USA. Email: matthew.kocher@jhu.edu
GENERALIZED MEASURES OF FUZZY DIRECTED-DIVERGENCE, TOTAL AMBIGUITY AND INFORMATION IMPROVEMENT

Uncertainty and fuzziness are the basic nature of human thinking and of many real world objectives. In the present communication, we have introduced two new generalized measures of fuzzy directed divergence with the proof of their validity. Further, we studied some measures of total ambiguity and new generalized measures of fuzzy information improvement. We have also discussed particular cases of corresponding directed divergence and symmetric divergence.
Urokinase expression and binding activity associated with the transforming growth factor β1‐induced migratory and invasive phenotype of mouse epidermal keratinocytes

Transforming growth factor β1(TGF‐β1) is a stimulator of malignant progression in mouse skin carcinogenesis. TGF‐β1 exerts a differential effect on cultured nontumorigenic (MCA3D cell line) and transformed (PDV cell line) keratinocytes. Whereas MCA3D cells are growth arrested and committed to die in the presence of the factor, it induces a reversible epithelial‐fibroblastic conversion in PDV cells. This conversion is associated in vivo with a squamous‐spindle cell carcinoma transition. Here we have investigated the role of urokinase (uPA) during malignant progression of transformed epidermal keratinocytes. We show that the levels of uPA expression/secretion, and the uPA binding activity to the cell surface, correlate with the invasive and malignant potentials of mouse epidermal cell lines. TGF‐β1 enhanced uPA production, the number of uPA cell surface binding sites, and the expression of the plasminogen activator inhibitor PAI‐1, in transformed PDV cells, but had no major effect on nontumorigenic MCA3D keratinocytes. Increased uPA production depended on the presence of the factor in the culture medium and occurred concomitantly to the stimulation of the migratory and invasive abilities of PDV cells. Synthetic peptides containing the amino terminal sequence of the mature mouse uPA inhibited the binding of uPA to the cell surface and decreased TGF‐β1‐induced cell motility and invasiveness. These results demonstrate that the uPA system mediates at least part of the migratory and invasive phenotype induced by TGF‐β1 in transformed keratinocytes, and suggest a role for uPA on the changes that lead to the appearance of spindle carcinomas. J. Cell. Biochem. 74:61–73, 1999. © 1999 Wiley‐Liss, Inc.
A Dipole Excited Ultrawideband Dielectric Rod Antenna With Reflector

A novel very compact ultrawideband dielectric rod antenna with metallic reflector is presented. The desired HE11 mode on the rod is excited by a biconical dipole fed by a broadband tapered microstrip line balun. The input reflection remains below -10 dB from 3 up to 20 GHz. The antenna exhibits a flat gain larger than 7 dBi over the whole ultrawideband frequency range from 3 to 10 GHz approved by the Federal Communication Commission. An almost constant transient performance over a wide azimuth angle of plusmn40deg is obtained with small dispersion.
Development of a PCR-based method for detection of pathogenic Yersinia enterocolitica in pork

Thisted Lambertz, S. 2005. Development of a PCR-based method for detection of pathogenic Yersinia enterocolitica in pork. Doctor s dissertation. ISSN 1652-6880, ISBN 91-576-6922-8 During the last decade, Yersinia enterocolitica has been reported to cause between 500 and 800 cases of human gastroenteritis per year in Sweden. As pigs are the only animals in human food production that regularly harbour the pathogen, pork is probably an important source of infection. Earlier it has only rarely been possible to recover the bacterium from pork, but in the last few years this was made possible by DNA-based technology. In this project, a PCR-based method for the detection of pathogenic Y. enterocolitica in pork was developed. The chromosome-located gene attachment invasion locus (ail) was chosen as the PCRtarget. The ail PCR assay was evaluated according to criteria for a standardised PCR-based method set by the European research project FOOD-PCR. In a trial involving 14 European laboratories, the ail PCR assay showed high repeatability and robustness. The complete PCR-based method comprises a sample treatment step prior to the ail PCR assay. The assay consists of either one (single) or two (nested) PCR analyses and an internal amplification control for monitoring false-negative results. The detection limit of the complete (single) PCR method, using inoculated enriched homogenates, was established to 10 cfu or less per gram. An increased sensitivity in the form of a nested PCR was required to enable detection of the bacterium in naturally contaminated pork. This is in practice very important. Finally, for characterisation of isolated strains, a multiplex PCR assay was developed, directed towards four different virulence-associated genes (yst, rfbC, ail and virF). As presence or absence of the four PCR targets was established, the following groups were identified: pathogenic Y. enterocolitica 4/O:3 strains, pathogenic Y. enterocolitica serotypes other than 4/O:3, Y. pseudotuberculosis strains and nonpathogenic strains. The method does not allow for confirmation of the viability of the pathogen, the reason being that the bacterium cannot be isolated by traditional culture. The method can therefore preferably be used where information about viability is not important, for example in studies to identify the critical points during slaughter, important to limit contamination by the bacterium.
5 Years of 'Papyrusing' - Migrating Industrial Development from a Proprietary Commercial Tool to Papyrus (Invited Presentation)

Five years ago, Ericsson decided to investigate the possibility of replacing a proprietary commercial UML modeling tool, used at the core of one of its internal toolchains, with an open source alternative based on Papyrus. The motivation for this switch was manifold, including cost, technology integration and community activity. It was clear from the outset that significant effort would be required to make Papyrus into a tool usable in large-scale industrial projects. This journey took time and dedication from both the Ericsson and the Papyrus development teams, but we have now reached the point where deployment has begun. In this paper we provide an experience report from the last five years.
Assessing the sensitivity to usage profile changes in test planning

Software reliability is an important characteristic for most systems, but due to its dynamic properties it is hard to assess until very late in the development. Nevertheless, the testing must be planned to meet the reliability requirements. In test planning, the notion of usage coverage may be used as an indicator of reliability as they are correlated with each other. When the testing is planned, the test cases to be run and the usage profile are derived. The usage profile is estimated using the available information of the expected usage. There are therefore some uncertainties in the estimated usage profile. The paper presents and evaluates a method for analysing the impact of uncertainties in the usage profile on the usage coverage. The method is applied during test planning to evaluate how sensitive the usage coverage is to usage profile uncertainties. Different usage profiles are simulated using the expected usage profile and an uncertainty expressed as a percentage value or a range within which the changed usage profile may vary. Test cases are derived from the expected usage profile and the resulting usage coverage is estimated for each simulated usage profile. Thus the impact in the usage coverage can be analysed. The presented analysis method is illustrated with an example system. One of the conclusions from this first study of the method is that the sparseness of the usage profile, which is defined by limitations in the usage pattern, reduces the impact of the usage profile uncertainties. Further, the number of test cases is an important factor in the sensitivity to uncertainties in the usage profile.
Computational Modeling Studies in Sinoatrial Node Cells

The sinoatrial node (SAN) cells generate the spontane-ous pacing activity in the heart. These cells are biologic oscillators with interesting intrinsic nonlinear behaviors. The pacemaker cells have been of great interest to experi-mentalists and theoreticians. The nonlinear dynamic properties of these biologic oscillators continue to be studied in mathematical models
Designing Efficient Security Technique for Data Storage in Cloud Computing

Cloud computing is an environment in which data owner move data from local system to cloud storage, next job of cloud service provider (CSP) to store that data and provide it to the user on their demand. In this simplest environment exist various security risk on cloud storage because it consist sensitive data of owner, sometime it may happened cloud services provide is dishonest. On the brief view it is clear there is various risk on cloud data storage. In this paper firstly introduce recycle storage method for reliability of data and for improving the performance and security concern proposed audit storage system. Index termCloud computing, security risk, recycle storage, audit storage.
Global wavelet analysis of impure chaotic dynamics

In this paper we introduce the spectral complex index in order to characterize the variability pattern of different chaotic dynamics. This index is obtained from the global wavelet analysis (GWA) of a chaotic signal with impurities (a stochastic noise component). The parameter is defined as the absolute distance between the powers with and without impurity (following the same principle of the KL divergence but not in the full entropic definition). The results suggest that, due to the Global Wavelet Spectrum logarithmic properties, this new spectral method provides a high sensitive measure for characterization of at least three different properties of the underlying dynamical process such as (i) the intrinsic noise level, (ii) the nature of the nonlinear deterministic rule (discrete or continuous) and (iii) the presence or not of spatial correlation.
Impairment of Proliferating Cell Nuclear Antigen-dependent Apurinic/Apyrimidinic Site Repair on Linear DNA*

Repair of apurinic/apyrimidinic (AP) sites by mammalian cell extracts was compared using circular and linear DNA substrates. Extracts prepared from DNA polymerase β (polβ)-proficient mouse fibroblasts repaired AP sites on both circular and linear DNA. However, extracts from the isogenic polβ-knockout cells repaired AP sites on circular DNA but not efficiently on linear DNA. The circularity-dependent repair by the polβ-knockout cell extract was completely inhibited by anti-proliferating cell nuclear antigen (PCNA) antibody but fully restored by addition of purified PCNA. Pretreatment of the linear DNA with AP endonuclease did not improve repair, indicating that impairment of AP site repair on linear DNA by polβ-knockout cell extracts is not due to inefficiency of damage incision but rather to deficiency at the subsequent steps. These results indicate that AP sites can be repaired on circular DNA by the PCNA-dependent pathway in addition to the polβ-dependent pathway and that the PCNA-dependent repair mechanism is poorly functional on linear DNA in vitro.
Hybrid HDFS: decreasing energy consumption and speeding up Hadoop using SSDs

Apache Hadoop has evolved significantly over the last years, with more than 60 releases bringing new features. By implementing the MapReduce programming paradigm and leveraging HDFS, its distributed file system, Hadoop has become a reliable and fault tolerant middleware for parallel and distributed computing over large datasets. Nevertheless, Hadoop may struggle under certain workloads, resulting in poor performance and high energy consumption. Users increasingly demand that high performance computing solutions being to address sustainability and limit power consumption. In this paper, we introduce HDFSH , a hybrid storage mechanism for HDFS, which uses a combination of Hard Disks and Solid-State Disks to achieve higher performance while saving power in Hadoop computations. HDFSH brings to middleware the best from HDs (affordable cost per GB and high storage capacity) and SSDs (high throughput and low energy consumption) in a configurable fashion, using dedicated storage zones for each storage device type. We implemented our mechanism as a block placement policy for HDFS, and assessed it over six recent releases of the Hadoop project, representing different designs of the Hadoop middleware. Results indicate that our approach increases overall job performance while decreasing the energy consumption under most hybrid configurations evaluated. Our results also showed that in many cases storing only part of the data in SSDs results in significant energy savings and execution speedups.
Cooperative spectrum sensing using frequency domain correlation detection

This paper presents a cooperative spectrum sensing scheme for cognitive radio based on the FFT energy detection. The proposed cooperative sensing scheme utilizes the cross correlation between the output of the sensor of interest and composite output of other sensors. Simulation results show that the proposed cooperative sensing scheme is superior to conventional cooperative sensing using frequency domain correlation detection.
Use of Queuing Models to Estimate Delay Savings from 4D Trajectory Precision

The potential benefit from introducing trajectory based operations into the NAS is estimated in this paper. Delay predictions of a stochastic and a deterministic queuing model, which represent high and low levels of trajectory uncertainty, are compared. It is found that delay savings are on the order of 35% in the average case, Delay predictions from the various models are found to be strongly collinear over a wide range of congestion levels.
Sequential Quadratic Programming and Simulating Annealing techniques to calculate optimized Air Quality control policies

In this work the air quality control problem is formalized through a two-objective approach. The objectives considered are (a) the emission reduction cost and (b) the Air Quality Index. The control variables are the precursor emission reductions due to application of available technologies. The nonlinear relationship linking air quality objective and precursor emissions is described by artificial neural networks, identified by processing deterministic Chemical Transport Modeling system simulations. This paper presents the comparison of the optimization problem results computed by means of different procedures: the Sequential Quadratic Programming and the Simulating Annealing. The test case of a polluted domain in Northern Italy is shown.
SOA-Based WDM Metro Ring Networks With Link Control Technologies

We experimentally study the performance of wavelength-division-multiplexing (WDM) metro/access ring networks, based on semiconductor optical amplifiers (SOAs), considering several gain control techniques. We show that gain control through link-control (LC) channel or amplified spontaneous emission (ASE) power recirculation, effectively used in erbium-doped fiber amplifier-based WDM ring networks, introduces serious penalties due to intensity noise transfer, and cannot be used in short-span SOA-based WDM rings. On the other hand, we observe a net benefit using LC channel and ASE extraction for short span rings and a limited WDM channel number, compared with linear operating conditions. An effective optical signal-to-noise ratio improvement of 2.1 dB has been achieved with LC channel extraction with respect to linear operation, for a 4 x 13.5 dB span ring with eight WDM channels. For spans longer than 15 dB, system performance in gain-controlled rings is found to be similar to noncontrolled ones.
Driver Behavior Comparison Between Static and Dynamic Simulation for Advanced Driving Maneuvers

In advanced driving maneuvers, such as a slalom maneuver, it is assumed that drivers use all the available cues to optimize their driving performance. For example, in curve driving, drivers use lateral acceleration to adjust car velocity. The same result can be found in driving simulation. However, for comparable curves, drivers drove faster in fixed-base simulators than when actually driving a car. This difference in driving behavior decreases with the use of inertial motion feedback in simulators. The literature suggests that the beneficial effect of inertial cues in driving behavior increases with the difficulty of the maneuver. Therefore, for an extreme maneuver such as a fast slalom, a change in driving behavior is expected when a fixed-base condition is compared to a condition with inertial motion. It is hypothesized that driving behavior in a simulator changes when motion cues are present in extreme maneuvers. To test the hypothesis, a comparison between No-Motion and Motion car driving simulation was done, by measuring driving behavior in a fast slalom. A within-subjects design was used, with 20 subjects driving the fast slalom in both conditions. The average speed during the Motion condition was significantly lower than the average speed during the No-Motion condition. The same was found for the peak lateral acceleration generated by the car model. A power spectral density analysis performed on the steering wheel angle signal showed different control input behavior between the two experimental conditions. In addition, the results from a paired comparison showed that subjects preferred driving with motion feedback. From the lower driving speed and different control input on the steering wheel, we concluded that motion feedback led to a significant change in driving behavior.