Signaling Network Assessment of Mutations and Copy Number Variations Predicts Breast Cancer Subtype-specific Drug Targets

Individual cancer cells carry a bewildering number of distinct genomic alterations i.e., copy number variations and mutations, making it a challenge to uncover genomic-driven mechanisms governing tumorigenesis. Here we performed exome-sequencing on several breast cancer cell lines which represent two subtypes, luminal and basal. We integrated this sequencing data, and functional RNAi screening data (i.e., for identifying genes which are essential for cell proliferation and survival), onto a human signaling network. Two subtype-specific networks were identified, which potentially represent core-signaling mechanisms underlying tumorigenesis. Within both networks, we found that genes were differentially affected in different cell lines; i.e., in some cell lines a gene was identified through RNAi screening whereas in others it was genomically altered. Interestingly, we found that highly connected network genes could be used to correctly classify breast tumors into subtypes based on genomic alterations. Further, the networks effectively predicted subtype-specific drug targets, which were experimentally validated.Comment: 4 figs, more related papers at http://www.cancer-systemsbiology.org, appears in Cell Reports, 201

Crop phenology and LANDSAT-based irrigated lands inventory in the high plains

The activity concentrated on identifying crop and irrigation data sources for the eight states within the High Plains Aquifer and making contacts concerning the nature of these data. A mail questionnaire was developed to gather specific data not routinely reported through standard data collection channels. Input/output routines were designed for High Plains crop and irrigation data and initial statistical data on crops were input to computer files

Collaboration on reference to objects that are not mutually known

In conversation, a person sometimes has to refer to an object that is not previously known to the other participant. We present a plan-based model of how agents collaborate on reference of this sort. In making a reference, an agent uses the most salient attributes of the referent. In understanding a reference, an agent determines his confidence in its adequacy as a means of identifying the referent. To collaborate, the agents use judgment, suggestion, and elaboration moves to refashion an inadequate referring expression.Comment: 6 pages, to appear in proceedings of COLING-94, LaTeX (now uses fullname.sty, fullname.bst

Stroke units: The implementation of a complex intervention

This article reports on selected findings from an action research study that looked at the lessons learnt from setting up a new in-patient stroke service in a London teaching hospital. Key participants in the design and evaluation of this 2-year study included members of the multi-professional stroke team and support staff within the unit, the hospital management team and representatives of patients and carers. Mixed methods (focus groups, indepth interviews, audits, documentary analysis, participant observation field notes) were used to generate data. Findings demonstrated positive change overtime with four main themes emerging from the process: building a team; developing practice-based knowledge and skills in stroke; valuing the central role of the nurse in stroke care; and creating an organisational climate for supporting change. The interplay of these non-linear, but interrelated factors is supported by complexity theory, which includes exploration of how the sum of a whole can be more than its constituent parts. Findings are likely to be of interest to practitioners, managers and policy makers interested in supporting change in a learning organisation

WaveCNV: allele-specific copy number alterations in primary tumors and xenograft models from next-generation sequencing.

MotivationCopy number variations (CNVs) are a major source of genomic variability and are especially significant in cancer. Until recently microarray technologies have been used to characterize CNVs in genomes. However, advances in next-generation sequencing technology offer significant opportunities to deduce copy number directly from genome sequencing data. Unfortunately cancer genomes differ from normal genomes in several aspects that make them far less amenable to copy number detection. For example, cancer genomes are often aneuploid and an admixture of diploid/non-tumor cell fractions. Also patient-derived xenograft models can be laden with mouse contamination that strongly affects accurate assignment of copy number. Hence, there is a need to develop analytical tools that can take into account cancer-specific parameters for detecting CNVs directly from genome sequencing data.ResultsWe have developed WaveCNV, a software package to identify copy number alterations by detecting breakpoints of CNVs using translation-invariant discrete wavelet transforms and assign digitized copy numbers to each event using next-generation sequencing data. We also assign alleles specifying the chromosomal ratio following duplication/loss. We verified copy number calls using both microarray (correlation coefficient 0.97) and quantitative polymerase chain reaction (correlation coefficient 0.94) and found them to be highly concordant. We demonstrate its utility in pancreatic primary and xenograft sequencing data.Availability and implementationSource code and executables are available at https://github.com/WaveCNV. The segmentation algorithm is implemented in MATLAB, and copy number assignment is implemented [email protected] informationSupplementary data are available at Bioinformatics online

EVALUATION INFORMATION SYSTEM DELIVERY PT. RST CARGO INTERNATIONAL

The purpose of this study was to evaluate the application of general controls and application controls on the sale of information systems as a basis to support and produce accurate information in decision-making. The research methodology used was the literature research, field research consisting of interviews and observations, questionnaires, analysis and auditing method that I use is Auditing Around the Computer. The research literature sourced from reference books, interviews conducted by asking questions to the audit, the observation is done by making a list of questions intended for the use of the system and the analysis is done by analyzing the findings of the evaluation and identifying the strengths and weaknesses of internal control. From this analysis, the findings obtained advantages and disadvantages of internal control. Weaknesses are found to be expressed in the form of finding problems, risks and recommendations as a follow- improvement. Conclusions derived from the results of the evaluation for management control and operational security in information systems delivery PT. RST International Cargo are still some shortcomings , while in applications such as boundary control, input and output can meet and support the delivery of PT. RST Cargo Internationa

Synthesizing and tuning chemical reaction networks with specified behaviours

We consider how to generate chemical reaction networks (CRNs) from functional specifications. We propose a two-stage approach that combines synthesis by satisfiability modulo theories and Markov chain Monte Carlo based optimisation. First, we identify candidate CRNs that have the possibility to produce correct computations for a given finite set of inputs. We then optimise the reaction rates of each CRN using a combination of stochastic search techniques applied to the chemical master equation, simultaneously improving the of correct behaviour and ruling out spurious solutions. In addition, we use techniques from continuous time Markov chain theory to study the expected termination time for each CRN. We illustrate our approach by identifying CRNs for majority decision-making and division computation, which includes the identification of both known and unknown networks.Comment: 17 pages, 6 figures, appeared the proceedings of the 21st conference on DNA Computing and Molecular Programming, 201

Copy That: Guidelines for Replicating Programs to Prevent Teen Pregnancy

Published jointly with The National Campaign to Prevent Teen Pregnancy, this report provides guidance about the replication of effective pregnancy prevention programs. It urges stakeholders to ask a variety of key questions when considering replication: Is the program effective? (What kind of evaluation has been done and what did it show?) What are the essential elements that make the program effective? Is the program ready to be replicated (with clear documentation)? And what is the replication plan? The report gleans lessons from the replication experiences of three programs: The Teen Outreach Program, The CAS-Carrera Program, and Plain Talk, whose national replication is being managed by P/PV

Use of magnetic resonance angiography to select candidates with recently symptomatic carotid stenosis for surgery: systematic review

Objective To determine if sufficient evidence exists to support the use of magnetic resonance angiography as a means of selecting patients with recently symptomatic high grade carotid stenosis for surgery. Design Systematic review of published research on the diagnostic performance of magnetic resonance angiography, 1990-9. Main outcome measures Performance characteristics of diagnostic test. Results 126 potentially relevant articles were identified, but many articles failed to examine die performance of magnetic resonance angiography as a diagnostic test at the surgical decision thresholds used in major clinical trials on endarterectomy. 26 articles were included in a meta-analysis that showed a maximal joint sensitivity and specificity of 99% (95% confidence interval 98% to 100%) for identifying 70-99% stenosis and 90% (81% to 99%) for identifying 50-99% stenosis. Only four articles evaluated contrast enhanced magnetic resonance angiography. Conclusions Magnetic resonance angiography is accurate for selecting patients for carotid endarterectomy at the surgical decision thresholds established in the major endarterectomy trials, but the evidence is not very robust because of the heterogeneity of the studies included. Research is to determine the diagnostic performance of the most recent developments in magnetic resonance angiography, including contrast enhanced techniques, as well as to assess the impact of magnetic resonance angiography on surgical decision making and outcomes