Miracle-dz/UniFAR-FTUs huggingface dataset:
Metastatic castration-resistant prostate cancer reveals intrapatient similarity and interpatient heterogeneity of therapeutic kinase targets

Significance Metastatic castration-resistant prostate cancer (CRPC) remains incurable due to the lack of effective therapies. The need to identify new actionable targets in CRPC is crucial as we begin to examine the resistance mechanisms related to androgen withdrawal. Here, we report an unbiased quantitative phosphoproteomic approach to identify druggable kinases in metastatic CRPC. These kinase activation patterns revealed intrapatient similarity and interpatient heterogeneity across a large panel of targets. Interestingly, these kinase activities are not a result of mutation but rather pathway activation within the tumors themselves. The observation that similar kinase activities are present in most if not all anatomically disparate metastatic lesions from the same patient suggests that CRPC patients may benefit from individualized, targeted combination therapies. In prostate cancer, multiple metastases from the same patient share similar copy number, mutational status, erythroblast transformation specific (ETS) rearrangements, and methylation patterns supporting their clonal origins. Whether actionable targets such as tyrosine kinases are also similarly expressed and activated in anatomically distinct metastatic lesions of the same patient is not known. We evaluated active kinases using phosphotyrosine peptide enrichment and quantitative mass spectrometry to identify druggable targets in metastatic castration-resistant prostate cancer obtained at rapid autopsy. We identified distinct phosphopeptide patterns in metastatic tissues compared with treatment-naive primary prostate tissue and prostate cancer cell line-derived xenografts. Evaluation of metastatic castration-resistant prostate cancer samples for tyrosine phosphorylation and upstream kinase targets revealed SRC, epidermal growth factor receptor (EGFR), rearranged during transfection (RET), anaplastic lymphoma kinase (ALK), and MAPK1/3 and other activities while exhibiting intrapatient similarity and interpatient heterogeneity. Phosphoproteomic analyses and identification of kinase activation states in metastatic castration-resistant prostate cancer patients have allowed for the prioritization of kinases for further clinical evaluation.
A Memetic Algorithm for closest string problem and farthest string problem

Sequences consensus problems are especially important in studying molecular evolution, protein structures, and drug target design. In this paper, we work on two of these problems, namely closest string problem and farthest string problem. These problems are NP-hard, and none of exact algorithms already proposed to solve them is in polynomial time. Many non-exact algorithms have been proposed which try to obtain ‘good’ solutions in acceptable time for these problems. In this paper, a Memetic Algorithm (MA) is proposed for the closest string problem, which outperforms the existing algorithms. We then extend the proposed algorithm to address the farthest string problem.
A resource discovery mechanism integrating P2P and Grid

Aiming to overcome the shortcomings of Grid resource discovery, this paper presents a Grid resource discovery model with different layers, which adopts P2P (Peer-to-Peer) technology in Grid resource discovery mechanism. The model includes three layers based on three different peers: the Super peer_Agent, Super Peer and Ordinary peer. According to the model, this paper produces a novel Grid resource discovery algorithm, which adopts Keywords Mach algorithm based on Hash Table, employees TF_IDF to product resource keywords, locates and search s resource based on Consistent Hashing Chord, access lower latency and higher credibility peer by ant colony algorithm based on adaptively adjusting pheromone. It is testified by simulation implement that the algorithm can find the most suitable resources and improve resource discovery efficiency.
Correctly rounded architectures for Floating-Point multi-operand addition and dot-product computation

This study presents hardware architectures performing correctly rounded Floating-Point (FP) multioperand addition and dot-product computation, both of which are widely used in various fields, such as scientific computing, digital signal processing, and 3D graphic applications. A novel realignment method is proposed to solve the catastrophic cancellation and multi-sticky bits. Only one rounding operation is performed in both of the proposed FP multi-operand adder and dot-product computation unit. Implementation results show that our architectures not only can produce correctly rounded results, whose errors are less than 0.5 ULP (Unit in the Last Place), but also have reduced delay comparing with the traditional network architecture, which uses 2-operand FP adders and multipliers to perform multi-operand addition and dot-product computation.
InAlAs/InGaAs/InP MODFET's with uniform threshold voltage obtained by selective wet gate recess

Excellent uniformity in the threshold voltage, transconductance, and current-gain cutoff frequency of InAlAs/InGaAs/InP MODFETs has been achieved using a selective wet gate recess process. An etch rate ratio of 25 was achieved for InGaAs over InAlAs using a 1:1 citric acid:H/sub 2/O/sub 2/ solution. By using this solution for gate recessing, the authors have achieved a threshold voltage standard deviation of 15 mV and a transconductance standard deviation of 15 mS/mm for devices across a quarter of a 2-in-diameter wafer. The average threshold voltage, transconductance, and current-gain cutoff frequency of 1.0- mu m gate-length devices were -234 mV, 355 mS/mm, and 32 GHz, respectively. <<ETX>>
Understanding Leaders' Proactivity from a Goal-Process View and with Multisource Ratings

In this chapter, we empirically examine leaders’ proactivity by taking the goal-process view of proactivity and from a multiple-rating source perspective. We proposed five behavioral indicators (envisioning and following goals, planning, solving problems, creating ideas, and championing change) to evaluate the key stages in the process of achieving proactive goals. We collected 360-degree ratings from leaders themselves, their supervisors, colleagues, and subordinates on these key indicators. The specific aim of this study is to (1) assess factorial validity of these five proactivity-related constructs, and (2) gauge whether different rater groups have consistent or different views in evaluating target leaders’ proactivity. Data were collected from a total of 535 part-time EMBA students, and data were analyzed by a Correlated Trait-Uncorrelated Method (CTUM) model. Results showed that (1) the five proactivity-related indicators were highly intercorrelated and can be influenced by a higher-order proactivity factor, and (2) ratings on the same construct but from different raters consistently converged on the same factor, revealing that different raters have a consistent perception in evaluating leaders’ multiple dimensions of proactivity.
Oral vaccination with an attenuated Salmonella typhimurium strain expressing Borrelia burgdorferi OspA prevents murine Lyme borreliosis

Borrelia burgdorferi is the causative agent of Lyme disease. In the mouse model, protection is correlated with the development of antibodies to a major outer surface protein, OspA. In this study, we expressed OspA in an attenuated strain of Salmonella typhimurium and tested the efficacy of the transformed strain in protecting against disease. We show that mice inoculated by gavage developed high titers of anti-OspA antibodies and were protected against an intradermal challenge with the spirochete.
Determining the value of a corporate reuse program

Reuse metrics must accurately reflect the amount of effort saved. One must have realistic measures to ensure the credibility of the value placed on reuse and to separate reuse benefits from those of other technologies also competing for limited investment dollars. The paper defines a reuse metric and return on investment (ROI) model at IBM that distinguishes reuse savings and benefits from those already gained through accepted software engineering techniques. Used in conjunction with a planned reuse program, the potential of reuse serves as a powerful motivator. They derive three reuse metrics from readily available software data elements and use these metrics in return on investment model that establishes a sound business justification for reuse. <<ETX>>
The role of inhibitory dynamics in the loss and reemergence of macropodoid tooth traits

The reversibility of phenotypic evolution is likely to be strongly influenced by the ability of underlying developmental systems to generate ancestral traits. However, few studies have quantitatively linked these developmental dynamics to traits that reevolve. In this study, we assess how changes in the inhibitory cascade, a developmental system that regulates relative tooth size in mammals, influenced the loss and reversals of the posthypocristid, a molar tooth crest, in the kangaroo superfamily Macropodoidea. We find that posthypocristid loss is linked with reduced levels of posterior molar inhibition, potentially driven by selection for lophodont, higher‐crowned molar teeth. There is strong support for two posthypocristid reversals, each occurring after more than 15 million years of absence, in large‐bodied species of Macropus, and two giant extinct species of short‐faced sthenurine kangaroo (Procoptodon). We find that whereas primitive posthypocristid expression is linked to higher levels of posterior molar inhibition, reemergence is tied to a relative increase in third molar size associated with increasing body mass, producing molar phenotypes similar to those in mouse where the ectodysplasin pathway is upregulated. We argue that although shifts in the inhibitory cascade may enable reemergence, dietary ecology may limit the frequency of phylogenetic reversal.
Tourism experiences through the eyes of a child

ABSTRACT Children are viewed typically as unsophisticated or incompetent research respondents. We challenge these assumptions by collecting data directly from 39 children, aged 9 and 10 years, which captures how they experience their holiday destination through ‘real time’ recordings. The findings reveal that children like to be physically active, have freedom and safety to play and make new friends independently. Holidays represent time spent with family and offer an escape from everyday routines and environments. Conversely, children dislike bad weather and queuing in traffic, restaurants and attractions; journeys are spoiled by travel sickness. This paper makes a number of major contributions to existing research. It adds to our understanding of the physical and emotional proximity of tourism experiences within an age specific context. It explores children's views and opinions as articulated by themselves and not adult proxies. It provides ‘real time’ data on tourism experiences, rather than using recollections.
Classification Of Multitemporal Remote-Sensing Images By A Fuzzy Fusion Of Spectral And Spatio-Temporal Contextual Information

A fuzzy-logic approach to the classification of multitemporal, multisensor remote-sensing images is proposed. The approach is based on a fuzzy fusion of three basic sources of information: spectral, spatial and temporal contextual information sources. It aims at improving the accuracy over that of single-time noncontextual classification. Single-time class posterior probabilities, which are used to represent spectral information, are estimated by Multilayer Perceptron neural networks trained for each single-time image, thus making the approach applicable to multisensor data. Both the spatial and temporal kinds of contextual information are derived from the single-time classification maps obtained by the neural networks. The expert's knowledge of possible transitions between classes at two different times is exploited to extract temporal contextual information. The three kinds of information are then fuzzified in order to apply a fuzzy reasoning rule for their fusion. Fuzzy reasoning is based on the "MAX" fuzzy operator and on information about class prior probabilities. Finally, the class with the largest fuzzy output value is selected for each pixel in order to provide the final classification map. Experimental results on a multitemporal data set consisting of two multisensor (Landsat TM and ERS-1 SAR) images are reported. The accuracy of the proposed fuzzy spatio-temporal contextual classifier is compared with those obtained by the Multilayer Perceptron neural networks and a reference classification approach based on Markov Random Fields (MRFs). Results show the benefit of adding spatio-temporal contextual information to the classification scheme, and suggest that the proposed approach represents an interesting alternative to the MRF-based approach, in particular, in terms of simplicity.
Radiation pressure acceleration by ultraintense laser pulses

The future applications of the short-duration, multi-MeV ion beams produced in the interaction of high-intensity laser pulses with solid targets will require improvements in the conversion efficiency, peak ion energy, beam monochromaticity and collimation. Regimes based on radiation pressure acceleration (RPA) might be the dominant ones at ultrahigh intensities and most suitable for specific applications. This regime may be reached with present-day intensities using circularly polarized (CP) pulses thanks to the suppression of fast electron generation, so that RPA dominates over sheath acceleration at any intensity. We present a brief review of a previous work on RPA with CP pulses and a few recent results. Parametric studies in one dimension were performed to identify the optimal thickness of foil targets for RPA and to study the effect of a short-scalelength preplasma. Three-dimensional simulations show the importance of ‘flat-top’ radial intensity profiles to minimize the rarefaction of thin targets and address the issue of angular momentum conservation and absorption.
Wild-type p53 regulates its own transcription in a cell-type specific manner.

Wild-type (w.t.) p53 acts as a transcriptional regulator that binds to DNA and modulates transcription of several promoters. Wild-type p53 has also been shown to autoregulate its own transcription. There is no agreement, however, on whether w.t. p53 has trans-activates or downregulates its own transcription. To further explore the transcriptional autoregulation of the p53 gene, we analyzed the effect of w.t. p53 on its own promoter in different cell lines that do not express p53. A DNA domain within the human p53 promoter (-48 to -23) with the structure of ATGGGATTGGGGTTTTCCCCTCCCAT shares 8 of 10 nucleotides sequence homology with the p53 binding motif. When the human p53 promoter that included this domain was linked to a chloramphenicol acetyltransferase (CAT) gene and coexpressed with w.t. or mutated p53 in cells lacking p53 protein, w.t. p53 down-regulated its own promoter in SAOS-2 and K562 cells, but not in DP15 cells. We were unable to detect direct interaction of p53 with its promoter or to domain -48 to -23 following transfection of these cells with w.t. p53. A different pattern of protein--DNA complexes was observed, however, between the p53 promoter and nuclear extracts from SAOS-2 and DP15 cells following transfection with w.t. p53. These data suggest that w.t. p53 autoregulates its own promoter indirectly and in a cell type-specific manner.
CUHK System for the Spoken Web Search task at Mediaeval 2012

This paper describes our systems submitted to the spoken web search (SWS) task at MediaEval 2012. All the systems were based on a new framework which is modied from the posteriorgram-based template matching approach. This framework employs parallel tokenizers to convert audio data into posteriorgrams, and then combine the distance matrices from the posteriorgrams of dierent tokenizers to derive a combined distance matrix. Lastly dynamic time warping (DTW) is applied to the combined distance matrix to detect the possible occurrences of the query terms. For this SWS task, we used three types of tokenizers, namely Gaussian mixture model (GMM) tokenizer, acoustic segment model (ASM) tokenizer, and phoneme recognizers of rich-resource languages. Pseudo-relevance feedback (PRF) and score normalization were also used in some of the systems.
Practical design of multi-channel oversampled warped cosine-modulated filter banks

A practical approach to optimal design of multichannel oversampled warped cosine-modulated filter banks (CMFB) is proposed. Warped CMFB is obtained by all- pass transformation of uniform CMFB. The paper addresses the problems of minimization amplitude distortion and suppression of aliasing components emerged due to oversampling of filter bank channel signals. Pro- posed optimization-based design considerably reduces distortions of overall filter bank transfer function taking into account channel subsampling ratios.
Genetic Diversity and Population Structure of Theileria annulata in Oman

Background Theileriosis, caused by a number of species within the genus Theileria, is a common disease of livestock in Oman. It is a major constraint to the development of the livestock industry due to a high rate of morbidity and mortality in both cattle and sheep. Since little is currently known about the genetic diversity of the parasites causing theileriosis in Oman, the present study was designed to address this issue with specific regard to T. annulata in cattle. Methods Blood samples were collected from cattle from four geographically distinct regions in Oman for genetic analysis of the Theileria annulata population. Ten genetic markers (micro- and mini-satellites) representing all four chromosomes of T. annulata were applied to these samples using a combination of PCR amplification and fragment analysis. The resultant genetic data was analysed to provide a first insight into the structure of the T. annulata population in Oman. Results We applied ten micro- and mini-satellite markers to a total of 310 samples obtained from different regions (174 [56%] from Dhofar, 68 [22%] from Dhira, 44 [14.5%] from Batinah and 24 [8%] from Sharqia). A high degree of allelic diversity was observed among the four parasite populations. Expected heterozygosity for each site ranged from 0.816 to 0.854. A high multiplicity of infection was observed in individual hosts, with an average of 3.3 to 3.4 alleles per locus, in samples derived from Batinah, Dhofar and Sharqia regions. In samples from Dhira region, an average of 2.9 alleles per locus was observed. Mild but statistically significant linkage disequilibrium between pairs of markers was observed in populations from three of the four regions. In contrast, when the analysis was performed at farm level, no significant linkage disequilibrium was observed. Finally, no significant genetic differentiation was seen between the four populations, with most pair-wise FST values being less than 0.03. Slightly higher FST values (GST’ = 0.075, θ = 0.07) were detected when the data for T. annulata parasites in Oman was compared with that previously generated for Turkey and Tunisia. Conclusion Genetic analyses of T. annulata samples representing four geographical regions in Oman revealed a high level of genetic diversity in the parasite population. There was little evidence of genetic differentiation between parasites from different regions, and a high level of genetic diversity was maintained within each sub-population. These findings are consistent with a high parasite transmission rate and frequent movement of animals between different regions in Oman.
Scheduling and Source Control with Average Queue-Length Control in Cellular Networks

In this paper, a scheduling problem is considered in the cellular network where there exist CBR (constant bit rate) users requiring exact minimum average throughput and delay guarantee, and EMG (elastic with minimum guarantee) users requiring minimum average throughput and delay guarantee and more throughput if possible. We first define a new utility function of average queue length. Based on the new queue utility function and the throughput utility function proposed before, we design a 2-dimensional weight function that will be used in our scheduling algorithm, and suggest a source control algorithm that can work with the scheduling algorithm. We show through simulations that the proposed algorithm guarantees the QoS (quality of service) requirements of CBR and EMG users.
Optimization of Opportunity-Based Software Rejuvenation Policy

This paper deals with the optimization problem to determine the software rejuvenation time in the software system degraded by aging-related bugs. In particular, we discuss the opportunity-based policy where the execution of software rejuvenation is limited on a time sequence of opportunities, and the software rejuvenation is performed at the first opportunity after the rejuvenation time. Based on the semi-Markov model presented by Dohi et al. 2001, we derive a sufficient condition for the optimal rejuvenation time under the opportunity-based policy.
Localization of computer acoustic signal source

Plenty of devices emanate acoustic signal, which is not necessarily located in the hearing range. Attacks on this side channel develop, from distinguishing sounds of mechanical key pressing on the keyboard up to processor's instruction recognition. In the case of complex analysis of electronic components emanation, the daunting challenge is to locate the precise source of the sound. Sound emanation can be the result of changes in power of power supply circuit. This paper studies behavior of inductors and capacitors within the LC-circuit of voltage regulator and corresponding changes in power consumption in relation to executing instructions.