Large Number Of Hits Research Articles

A 2-D Clustering Algorithm for Data Reconstruction in Vertex Detector of ILC

On the vertex detector of the International Linear Collider, a large number of hits are generated by the charged particles coming from the beam background. These charged particles produce large angles of incidence and generate elongated clusters. The CMOS pixel sensor (CPS) which would contain on-chip artificial neural networks could tag and remove these clusters to reduce the data flow of the detector system. The clustering procedure is the first step of data preprocessing. The conventional clustering algorithm is not suitable for on-chip integration since it requires sequential and iterative processing. In this article, a 2-D real-time clustering algorithm is proposed. The clustering algorithm is tested by 4500 frames of pixel values (12 bit/pixel) from MIMOSA-18. The clustering algorithm is implemented using Very High-Speed Integrated Circuit Hardware Description Language (VHDL), synthesized for different windows, multiplexers, and analog-to-digital converter (ADC) resolution. Power consumption and the occupied surface of the clustering implementation are presented. This implementation provides a possibility to integrate the clustering procedure into a CPS.

Cracking the WHIP: An Evaluation of Baseball’s Hall of Fame Pitchers

Walks plus hits per inning pitched (WHIP) is a key performance metric for pitchers in Major League Baseball (MLB). The authors analyze WHIP and its two components, walks and hits, to determine whether Hall of Fame pitcher performance has changed over time since the Hall of Fame’s first induction in 1936. All inducted pitchers are divided into four roughly equal groups. The results reveal that pitchers inducted between 1936 and 1959 gave up significantly fewer walks per inning pitched while pitchers inducted between 1960 and 1979 gave up significantly more hits per inning pitched. However, in general, WHIP displays no statistically significant trend over time, as the small number of walks per inning pitched among early inductees is offset by a large number of hits given up per inning pitched among later inductees.

Bivariate normal distribution for finding inliers in Hough space for a Time Projection Chamber

A Time Projection Chamber (TPC) is foreseen as the main tracking detector for the International Large Detector (ILD), one of the two detectors for the next candidate collider named International Linear Collider (ILC) [1].GridPix, a combination of a micropattern gaseous detector with a pixelized readout, is one of the candidate readout systems for the TPC [2] [3]. One of the challenges in the track reconstruction is the large number of individual hits along a track (around 100 per cm). Due to the small pixel size of 55 x 55 μ m2 , the distance between the individual ionization processes in the gas is larger than the size of the pixels. Consequently, the hits in the GridPix are not contiguous. This leads to the challenge of assigning the individual hits to the correct track. Hits within a given distance from a reconstructed track are called inliers. Consequently, finding inliers within the large number of hits and in the presence of noise is difficult for pattern recognition. This difficulty is increased by diffusion effects in the TPC.One of the current algorithms which are utilized for track finding is the Hough transform. Using a bivariate normal distribution based on the covariance matrix calculated from the diffusion effect improves collecting inliers in the Hough space directly [5].

A High-Content, Phenotypic Screen Identifies Fluorouridine as an Inhibitor of Pyoverdine Biosynthesis and Pseudomonas aeruginosa Virulence.

Pseudomonas aeruginosa is an opportunistic pathogen that causes severe health problems. Despite intensive investigation, many aspects of microbial virulence remain poorly understood. We used a high-throughput, high-content, whole-organism, phenotypic screen to identify small molecules that inhibit P.aeruginosa virulence in Caenorhabditis elegans. Approximately half of the hits were known antimicrobials. A large number of hits were nonantimicrobial bioactive compounds, including the cancer chemotherapeutic 5-fluorouracil. We determined that 5-fluorouracil both transiently inhibits bacterial growth and reduces pyoverdine biosynthesis. Pyoverdine is a siderophore that regulates the expression of several virulence determinants and is critical for pathogenesis in mammals. We show that 5-fluorouridine, a downstream metabolite of 5-fluorouracil, is responsible for inhibiting pyoverdine biosynthesis. We also show that 5-fluorouridine, in contrast to 5-fluorouracil, is a genuine antivirulence compound, with no bacteriostatic or bactericidal activity. To our knowledge, this is the first report utilizing a whole-organism screen to identify novel compounds with antivirulent properties effective against P.aeruginosa. IMPORTANCE Despite intense research effort from scientists and the advent of the molecular age of biomedical research, many of the mechanisms that underlie pathogenesis are still understood poorly, if at all. The opportunistic human pathogen Pseudomonas aeruginosa causes a variety of soft tissue infections and is responsible for over 50,000 hospital-acquired infections per year. In addition, P.aeruginosa exhibits a striking degree of innate and acquired antimicrobial resistance, complicating treatment. It is increasingly important to understand P.aeruginosa virulence. In an effort to gain this information in an unbiased fashion, we used a high-throughput phenotypic screen to identify small molecules that disrupted bacterial pathogenesis and increased host survival using the model nematode Caenorhabditis elegans. This method led to the unexpected discovery that addition of a modified nucleotide, 5-fluorouridine, disrupted bacterial RNA metabolism and inhibited synthesis of pyoverdine, a critical toxin. Our results demonstrate that this compound specifically functions as an antivirulent.

QUANTIFYING THE RISK OF ABNORMAL NEUROPHYSIOLOGY AS A RESULT OF SUB-CONCUSSIVE BLOWS IN HIGH SCHOOL FOOTBALL ATHLETES

BackgroundRecent work suggests that repetitive sub-concussive head impacts may contribute to long-term neurodegeneration; however, the risk thresholds for sub-concussive injury are unknown.ObjectiveTo evaluate the risk of developing abnormal neurophysiology due...

Primer-BLAST: A tool to design target-specific primers for polymerase chain reaction

BackgroundChoosing appropriate primers is probably the single most important factor affecting the polymerase chain reaction (PCR). Specific amplification of the intended target requires that primers do not have matches to other targets in certain orientations and within certain distances that allow undesired amplification. The process of designing specific primers typically involves two stages. First, the primers flanking regions of interest are generated either manually or using software tools; then they are searched against an appropriate nucleotide sequence database using tools such as BLAST to examine the potential targets. However, the latter is not an easy process as one needs to examine many details between primers and targets, such as the number and the positions of matched bases, the primer orientations and distance between forward and reverse primers. The complexity of such analysis usually makes this a time-consuming and very difficult task for users, especially when the primers have a large number of hits. Furthermore, although the BLAST program has been widely used for primer target detection, it is in fact not an ideal tool for this purpose as BLAST is a local alignment algorithm and does not necessarily return complete match information over the entire primer range.ResultsWe present a new software tool called Primer-BLAST to alleviate the difficulty in designing target-specific primers. This tool combines BLAST with a global alignment algorithm to ensure a full primer-target alignment and is sensitive enough to detect targets that have a significant number of mismatches to primers. Primer-BLAST allows users to design new target-specific primers in one step as well as to check the specificity of pre-existing primers. Primer-BLAST also supports placing primers based on exon/intron locations and excluding single nucleotide polymorphism (SNP) sites in primers.ConclusionsWe describe a robust and fully implemented general purpose primer design tool that designs target-specific PCR primers. Primer-BLAST offers flexible options to adjust the specificity threshold and other primer properties. This tool is publicly available at http://www.ncbi.nlm.nih.gov/tools/primer-blast.

Innovations and communication through innovative users: An exploratory mechanism of social networking website

The study focuses on which users to target and why and how to inspire their participation by applying combination of von Hippel's lead user and user innovation toolkits with Rogers’ innovation diffusion theories. After an investigation of a social networking website, this study finds that individuals with large number of hits are highly active users of new functions. Moreover, they are likely to use toolkits to customize their personal uses and respond to others’ problems. Therefore, they garner appreciation from others in return, achieve higher ranks in the top hit parade, and obtain better-expected benefits from the website's incentive compensation. This study also evaluates the toolkits’ efficacy in the Web 2.0 context and finds that they are not equivalents. This research offers insights useful for web service providers to target innovative users and create an environment using web toolkits to induce user-generated innovation and achieve better effect of innovation communication.

Supporting the education evidence portal via text mining

The UK Education Evidence Portal (eep) provides a single, searchable, point of access to the contents of the websites of 33 organizations relating to education, with the aim of revolutionizing work practices for the education community. Use of the portal alleviates the need to spend time searching multiple resources to find relevant information. However, the combined content of the websites of interest is still very large (over 500 000 documents and growing). This means that searches using the portal can produce very large numbers of hits. As users often have limited time, they would benefit from enhanced methods of performing searches and viewing results, allowing them to drill down to information of interest more efficiently, without having to sift through potentially long lists of irrelevant documents. The Joint Information Systems Committee (JISC)-funded ASSIST project has produced a prototype web interface to demonstrate the applicability of integrating a number of text-mining tools and methods into the eep, to facilitate an enhanced searching, browsing and document-viewing experience. New features include automatic classification of documents according to a taxonomy, automatic clustering of search results according to similar document content, and automatic identification and highlighting of key terms within documents.

ChemInform Abstract: Application of Nearest-Neighbor and Cluster Analyses in Pharmaceutical Lead Discovery.

High throughput screening (HTS) programs based on diverse collections of compounds can rapidly identify leads for potential drug candidates. In cases where the compound collection is truly diverse, one may only identify a few compounds of interest. However, where a large number of hits are identified, it becomes necessary to examine the structures to determine the true number of compound classes involved so that follow-up studies may be conducted as efficiently as possible. In this case, cluster analysis is applied to determine the structural relationship among HTS hits. To efficiently expand around the region of the hit (or a class of hits) in chemical space, we have applied nearest neighbors analysis1 to select additional compounds from collections of a large number of commercial vendors, achieving an average hit rate in excess of 15%. Applying these techniques in a number of different cases, we obtained results that are useful for subsequent investigations of hits from HTS and other relevant molecular ...

Using proteomics to mine genome sequences.

We present a method for mining unannotated or annotated genome sequences with proteomic data to identify open reading frames. The region of a genome coding for a protein sequence is identified by using information from the analysis of proteins and peptides with MALDI-TOF mass spectrometry. The raw genome sequence or any unassembled contigs of an organism are theoretically cleaved into a number of equal sized but overlapping fragments, and these are then translated in all six frames into a series of virtual proteins. Each virtual protein is then subjected to a theoretical enzymatic digestion. Standard proteomic sample preparation methods are used to separate, array, and digest the proteins of interest to peptides. The masses of the resulting peptides are measured using mass spectrometry and compared to the theoretical peptide masses of the virtual proteins. The region of the genome responsible for coding for a particular protein can then be identified when there are a large number of hits between peptides from the protein and peptides from the virtual protein. The method makes no assumptions about the location of a protein in a particular gene sequence or the positions or types of start and stop codons. To illustrate this approach, all 773 proteins of Pseudomonas aeruginosa contained in SWISS-PROT were used to theoretically test the method and optimize parameters. Increasing the size of the virtual proteins results in an overall improvement in the ability to detect the coding region, at the cost of decreasing the sensitivity of the method for smaller proteins. Increasing the minimum number of matching peptides, lowering the mass error tolerance, or increasing the signal-to-noise ratio of the simulated mass spectrum, improves the ability to detect coding regions. The method is further demonstrated on experimental data from Mycobacterium tuberculosis and is also shown to work with eukaryotic organisms (e.g., Homo sapiens).

Request Distribution Mechanisms for a Large E-Commerce Site

For any popular e-commerce site getting very large number of hits, single monolithic webserver is not capable of giving good performance. To achieve good performance, and also fault tolerance, etc, cluster or set of clusters of servers is used for handling the high request rate. Every incoming request should be served by one of the servers in the cluster. This process requires request distribution, i.e. directing request for some resource to one of the servers capable of satisfying this request. This paper reviews mechanisms for directing a client request to one of the servers. The applicability and limitations of various request distribution mechanisms are also discussed.

MED21/393: ICD as a Search Tool for Medical Internet Resources

IntroductionThe Internet offers information on specific diseases on WWW-server distributed over the entire world. Selecting the appropriate information resource is a non-trivial task. Several approaches (like MeSH, MedPix) exist to describe the contents of Web pages. However, the majority of the Web sites do not make use of these schemas. Automatic (or semi-automatic) linking of medical records to information resources on the internet is not sufficiently supported. ICD (International Classification of Diseases) is the standard for coding the diagnosis in medical records. The purpose of this study was to evaluate the feasibility of ICD - based search tools.MethodsA general ICD Meta-Search Engine (ICD-Search) was established to perform ICD-based Internet searches. From the records of the Großhadern University Hospital, the 20 most frequent diagnosis were selected. The diseases are coded with ICD-9 by the medical personnel of the hospital. The English version of the ICD-9 was chosen for performing the internet study. General search engines (Yahoo, Lycos, AltaVista) were used to retrieve medical information corresponding to the selected ICD codes. The first 50 hits were included in the study. The Web pages were scored according to accessibility (information could be retrieved) of the Web pages and the contents (reflects ICD code). The quality of information (current state of knowledge, complete information, comprehensive presentation) was not take into account. Also the results of the different search engines were compared. This study was repeated with specialized medical search engines (MedHunt) . Scoring of the results was performed accordingly.ResultsBoth Lycos and AltaVista searched resulted in a large number of hits. The range for AltaVista was between 114.440 (Coronary atherosclerosis) and 405.770 (Alcohol dependence syndrome). The Lycos search resulted in no categories and four sites (Coronary atherosclerosis) and one site for Alcohol dependence syndrome. MedHunt found 131 corresponding sites for Coronary atherosclerosis and 112 for Alcohol dependence syndrome. The median scores for Lycos and Altavista were in the same order with some extreme low scores for AltaVista on selected diseases. Lycos, in general, scored better than Lycos and AltaVista but show a low number of hits for several diseases. MedHunt produced both good scores and a sufficient number of hits. The results from Lycos and AltaVista were compared. It showed, that only 15% of the web pages were found by both search engines.ConclusionAll search engines found Internet sites that corresponded to the selected ICD-codes. The standard vocabulary provided by ICD proved to be a good basis for linking medical diagnosis with Internet Web sites. Specialized medical search engines perform better than general ones. Search engines, that also give information on the quality of information, offer additional value.

Application of nearest-neighbor and cluster analyses in pharmaceutical lead discovery.

High throughput screening (HTS) programs based on diverse collections of compounds can rapidly identify leads for potential drug candidates. In cases where the compound collection is truly diverse, one may only identify a few compounds of interest. However, where a large number of hits are identified, it becomes necessary to examine the structures to determine the true number of compound classes involved so that follow-up studies may be conducted as efficiently as possible. In this case, cluster analysis is applied to determine the structural relationship among HTS hits. To efficiently expand around the region of the hit (or a class of hits) in chemical space, we have applied nearest neighbors analysis to select additional compounds from collections of a large number of commercial vendors, achieving an average hit rate in excess of 15%. Applying these techniques in a number of different cases, we obtained results that are useful for subsequent investigations of hits from HTS and other relevant molecular structures from the literature.

Microdosimetry of alpha-emitting bone seekers.

Microdosimetric probability distributions of specific energy f(z) in cell nuclei at alpha-contaminated bone surfaces are determined. The calculations are based on autoradiographic measurements of specific endosteal surface activities of rats injected with 239-Pu. The effect of a variation of the surface activity and target density and a correlation of both is discussed. A mathematical description of trabecular bone remodeling is given and the dependence of specific energy deposition on remodeling processes is demonstrated. For non-age-dependent remodeling and relatively large numbers of hits (greater than 20) the main contribution to the variation of f(z) comes from the variation of residual lifetimes and specific surface activities. With small numbers of hits (less than 1) the variation is mainly determined by the Poisson hit statistics and the width of the single event spectrum.

Electiveness of photorepair, influence of dark-repair on shape of dose—response curves, and high-dose decline, in UV-induced colour mutations of serratia

Strain CV of Serratia marcescens mutates by UV with high frequency to 3 groups of mutants (w, h, s) differing in colour from the red wild-type. The mutational dose—response curve has a curvature corresponding to about 3 hits. It reaches a peak and declines at high doses. Inactivation curves have a broad shoulder and mostly, but not always, a break to a lesser slope at UV doses near the peak of mutations. Photoreactivation (PR) gives a dose reduction of about 2 for both inactivation and mutation including the break and peak. The dose curve with PR for w-mutations shows 1 hit-, and the other types 2-hit curvature leading to a change of mutation spectrum with dose due to PR. The UV-sensitive mutant uvs21 of CV has a survival curve with a small shoulder and a long upward concavity without a break, and the mutation curve is of the one-hit type without a peak and decline. PR gives a dose reduction of 12 for inactivation and of 7.5 for mutation. The 3-hit mutation curve of CV is interpreted by assuming that 2 further hits are required to protect the 1-hit pre-mutations from being abolished by the repair lacking in uvs21. UV induction of SOS repair cannot be responsible for the 3-hit curvature because UVR of phages and induction of prophage are already saturated at rather low doses. High-dose decline (HDD) of mutations in CV is probably caused neiher by a fraction of UV-resistant cells in the population nor by post-mutational selective inhibition of growth of mutants by UV-inactivated neighbour cells. As HDD is not observed in uvs21, possibly the non-mutagenic repair lacking from uvs21 interferes with the mutation finishing processes at high doses in the repair-proficient strain CV. However, UV induction of this interference cannot be a one-hit process but requires a very large number of hits.