TCGAbiolinks: an R/Bioconductor package for integrative analysis of TCGA data

PubMed Central

Colaprico, Antonio; Silva, Tiago C.; Olsen, Catharina; Garofano, Luciano; Cava, Claudia; Garolini, Davide; Sabedot, Thais S.; Malta, Tathiane M.; Pagnotta, Stefano M.; Castiglioni, Isabella; Ceccarelli, Michele; Bontempi, Gianluca; Noushmehr, Houtan

2016-01-01

The Cancer Genome Atlas (TCGA) research network has made public a large collection of clinical and molecular phenotypes of more than 10 000 tumor patients across 33 different tumor types. Using this cohort, TCGA has published over 20 marker papers detailing the genomic and epigenomic alterations associated with these tumor types. Although many important discoveries have been made by TCGA's research network, opportunities still exist to implement novel methods, thereby elucidating new biological pathways and diagnostic markers. However, mining the TCGA data presents several bioinformatics challenges, such as data retrieval and integration with clinical data and other molecular data types (e.g. RNA and DNA methylation). We developed an R/Bioconductor package called TCGAbiolinks to address these challenges and offer bioinformatics solutions by using a guided workflow to allow users to query, download and perform integrative analyses of TCGA data. We combined methods from computer science and statistics into the pipeline and incorporated methodologies developed in previous TCGA marker studies and in our own group. Using four different TCGA tumor types (Kidney, Brain, Breast and Colon) as examples, we provide case studies to illustrate examples of reproducibility, integrative analysis and utilization of different Bioconductor packages to advance and accelerate novel discoveries. PMID:26704973

Paul Spellman, Ph.D., Talks about TCGA at AACR 2011 - TCGA

Cancer.gov

Dr. Paul Spellman talks about The Cancer Genome Atlas (TCGA) and how this could help further the treatment of cancer. TCGA is a project working to catalog genetic mutations responsible for cancer. Clinicians are sequencing the genomes of patients with any of 20 different cancers and hope that this could target clinical trials at the specific patient sub-groups that would benefit most. Dr. Spellman explains how an increasing number of laboratories are becoming able to conduct genome sequencing and contribute to the TCGA project, discusses how clinicians could apply the findings in practice to decide on treatment and effect patient outlook and suggests that in future patients may start to request for their genome to be sequenced in order to aid their treatment.

Genomic underpinnings of brain tumors - TCGA

Cancer.gov

TCGA researchers analyzed nearly 300 cases of diffuse low- and intermediate-grade gliomas, which together comprise lower-grade gliomas. LGGs occur mainly in adults and include astrocytomas, oligodendrogliomas and oligoastrocytomas.

Looking Across Many Cancer Genomes - TCGA

Cancer.gov

TCGA researchers have developed a formal project for a cross tumor analysis, called Pan-Cancer. Its goal is to assemble TCGA’s wealth of data across tumor types, analyze and interpret those data, and finally, make both the analyses and the data freely available.

Disease Risk Score (DRS) as a Confounder Summary Method: Systematic Review and Recommendations

PubMed Central

Tadrous, Mina; Gagne, Joshua J.; Stürmer, Til; Cadarette, Suzanne M.

2013-01-01

Purpose To systematically examine trends and applications of the disease risk score (DRS) as a confounder summary method. Methods We completed a systematic search of MEDLINE and Web of Science® to identify all English language articles that applied DRS methods. We tabulated the number of publications by year and type (empirical application, methodological contribution, or review paper) and summarized methods used in empirical applications overall and by publication year (<2000, ≥2000). Results Of 714 unique articles identified, 97 examined DRS methods and 86 were empirical applications. We observed a bimodal distribution in the number of publications over time, with a peak 1979-1980, and resurgence since 2000. The majority of applications with methodological detail derived DRS using logistic regression (47%), used DRS as a categorical variable in regression (93%), and applied DRS in a non-experimental cohort (47%) or case-control (42%) study. Few studies examined effect modification by outcome risk (23%). Conclusion Use of DRS methods has increased yet remains low. Comparative effectiveness research may benefit from more DRS applications, particularly to examine effect modification by outcome risk. Standardized terminology may facilitate identification, application, and comprehension of DRS methods. More research is needed to support the application of DRS methods, particularly in case-control studies. PMID:23172692

Genomic features of lobular breast carcinoma - TCGA

Cancer.gov

Investigators with The Cancer Genome Atlas (TCGA) Research Network have identified molecular characteristics of a type of breast cancer, invasive lobular carcinoma (ILC), that distinguishes it from invasive ductal carcinoma (IDC), the most common invasive breast cancer subtype.

OncDRS: An integrative clinical and genomic data platform for enabling translational research and precision medicine

PubMed Central

Orechia, John; Pathak, Ameet; Shi, Yunling; Nawani, Aniket; Belozerov, Andrey; Fontes, Caitlin; Lakhiani, Camille; Jawale, Chetan; Patel, Chetansharan; Quinn, Daniel; Botvinnik, Dmitry; Mei, Eddie; Cotter, Elizabeth; Byleckie, James; Ullman-Cullere, Mollie; Chhetri, Padam; Chalasani, Poornima; Karnam, Purushotham; Beaudoin, Ronald; Sahu, Sandeep; Belozerova, Yelena; Mathew, Jomol P.

2015-01-01

We live in the genomic era of medicine, where a patient's genomic/molecular data is becoming increasingly important for disease diagnosis, identification of targeted therapy, and risk assessment for adverse reactions. However, decoding the genomic test results and integrating it with clinical data for retrospective studies and cohort identification for prospective clinical trials is still a challenging task. In order to overcome these barriers, we developed an overarching enterprise informatics framework for translational research and personalized medicine called Synergistic Patient and Research Knowledge Systems (SPARKS) and a suite of tools called Oncology Data Retrieval Systems (OncDRS). OncDRS enables seamless data integration, secure and self-navigated query and extraction of clinical and genomic data from heterogeneous sources. Within a year of release, the system has facilitated more than 1500 research queries and has delivered data for more than 50 research studies. PMID:27054074

TSVdb: a web-tool for TCGA splicing variants analysis.

PubMed

Sun, Wenjie; Duan, Ting; Ye, Panmeng; Chen, Kelie; Zhang, Guanling; Lai, Maode; Zhang, Honghe

2018-05-29

Collaborative projects such as The Cancer Genome Atlas (TCGA) have generated various -omics and clinical data on cancer. Many computational tools have been developed to facilitate the study of the molecular characterization of tumors using data from the TCGA. Alternative splicing of a gene produces splicing variants, and accumulating evidence has revealed its essential role in cancer-related processes, implying the urgent need to discover tumor-specific isoforms and uncover their potential functions in tumorigenesis. We developed TSVdb, a web-based tool, to explore alternative splicing based on TCGA samples with 30 clinical variables from 33 tumors. TSVdb has an integrated and well-proportioned interface for visualization of the clinical data, gene expression, usage of exons/junctions and splicing patterns. Researchers can interpret the isoform expression variations between or across clinical subgroups and estimate the relationships between isoforms and patient prognosis. TSVdb is available at http://www.tsvdb.com , and the source code is available at https://github.com/wenjie1991/TSVdb . TSVdb will inspire oncologists and accelerate isoform-level advances in cancer research.

Web-TCGA: an online platform for integrated analysis of molecular cancer data sets.

PubMed

Deng, Mario; Brägelmann, Johannes; Schultze, Joachim L; Perner, Sven

2016-02-06

The Cancer Genome Atlas (TCGA) is a pool of molecular data sets publicly accessible and freely available to cancer researchers anywhere around the world. However, wide spread use is limited since an advanced knowledge of statistics and statistical software is required. In order to improve accessibility we created Web-TCGA, a web based, freely accessible online tool, which can also be run in a private instance, for integrated analysis of molecular cancer data sets provided by TCGA. In contrast to already available tools, Web-TCGA utilizes different methods for analysis and visualization of TCGA data, allowing users to generate global molecular profiles across different cancer entities simultaneously. In addition to global molecular profiles, Web-TCGA offers highly detailed gene and tumor entity centric analysis by providing interactive tables and views. As a supplement to other already available tools, such as cBioPortal (Sci Signal 6:pl1, 2013, Cancer Discov 2:401-4, 2012), Web-TCGA is offering an analysis service, which does not require any installation or configuration, for molecular data sets available at the TCGA. Individual processing requests (queries) are generated by the user for mutation, methylation, expression and copy number variation (CNV) analyses. The user can focus analyses on results from single genes and cancer entities or perform a global analysis (multiple cancer entities and genes simultaneously).

Looking Across Many Cancer Genomes - TCGA

Cancer.gov

TCGA's Pan-Cancer project publishes its integrative analysis of TCGA cancer types. The Pan-cancer project's goal is to assemble TCGA’s wealth of data across tumor types, analyze and interpret those data, and finally, make both the analyses and the data freely available.

TopFed: TCGA tailored federated query processing and linking to LOD.

PubMed

Saleem, Muhammad; Padmanabhuni, Shanmukha S; Ngomo, Axel-Cyrille Ngonga; Iqbal, Aftab; Almeida, Jonas S; Decker, Stefan; Deus, Helena F

2014-01-01

The Cancer Genome Atlas (TCGA) is a multidisciplinary, multi-institutional effort to catalogue genetic mutations responsible for cancer using genome analysis techniques. One of the aims of this project is to create a comprehensive and open repository of cancer related molecular analysis, to be exploited by bioinformaticians towards advancing cancer knowledge. However, devising bioinformatics applications to analyse such large dataset is still challenging, as it often requires downloading large archives and parsing the relevant text files. Therefore, it is making it difficult to enable virtual data integration in order to collect the critical co-variates necessary for analysis. We address these issues by transforming the TCGA data into the Semantic Web standard Resource Description Format (RDF), link it to relevant datasets in the Linked Open Data (LOD) cloud and further propose an efficient data distribution strategy to host the resulting 20.4 billion triples data via several SPARQL endpoints. Having the TCGA data distributed across multiple SPARQL endpoints, we enable biomedical scientists to query and retrieve information from these SPARQL endpoints by proposing a TCGA tailored federated SPARQL query processing engine named TopFed. We compare TopFed with a well established federation engine FedX in terms of source selection and query execution time by using 10 different federated SPARQL queries with varying requirements. Our evaluation results show that TopFed selects on average less than half of the sources (with 100% recall) with query execution time equal to one third to that of FedX. With TopFed, we aim to offer biomedical scientists a single-point-of-access through which distributed TCGA data can be accessed in unison. We believe the proposed system can greatly help researchers in the biomedical domain to carry out their research effectively with TCGA as the amount and diversity of data exceeds the ability of local resources to handle its retrieval and

Phlebotomy and the Amish Inspired this Geneticist - TCGA

Cancer.gov

Dr. Stacey Gabriel began her career in genetics while working on a rare disease in the Amish. Learn more about her experience witnessing the human element of genetics in this TCGA in Action Researcher Profile.

Using Forensics to Untangle Batch Effects in TCGA Data - TCGA

Cancer.gov

Rehan Akbani, Ph.D., and colleagues at the University of Texas MD Anderson Cancer Center developed a tool called MBatch to detect, diagnose, and correct batch effects in TCGA data. Read more about batch effects in this Case Study.

TCGA study identifies genomic features of cervical cancer

Cancer.gov

Investigators with The Cancer Genome Atlas (TCGA) Research Network have identified novel genomic and molecular characteristics of cervical cancer that will aid in subclassification of the disease and may help target therapies that are most appropriate for each patient.

New study reveals relatively few mutations in AML genomes - TCGA

Cancer.gov

Investigators for The Cancer Genome Atlas (TCGA) Research Network have detailed and broadly classified the genomic alterations that frequently underlie the development of acute myeloid leukemia (AML).

TCGA's Pan-Cancer Efforts and Expansion to Include Whole Genome Sequence - TCGA

Cancer.gov

Carolyn Hutter, Ph.D., Program Director of NHGRI's Division of Genomic Medicine, discusses the expansion of TCGA's Pan-Cancer efforts to include the Pan-Cancer Analysis of Whole Genomes (PAWG) project.

AACR 2010: Strategy for Mapping of 20 Cancers - TCGA

Cancer.gov

TCGA held an NCI-sponsored session at the American Association for Cancer Research's (AACR) 101st Annual Meeting 2010 to address the program’s Phase II structure and strategies for sample acquisition, evolving technologies, data management and analysis.

Proteome Characterization Centers - TCGA

Cancer.gov

The centers, a component of NCI’s Clinical Proteomic Tumor Analysis Consortium, will analyze a subset of TCGA samples to define proteins translated from cancer genomes and their related biological processes.

Brad Ozenberger, Ph.D., Presents the Achievements of The Cancer Genome Atlas During its Early Years - TCGA

Cancer.gov

Dr. Brad Ozenberger, former TCGA Program Director for the National Human Genome Research Institute, describes the goals and achievements of TCGA during its pilot phase, which involved the genomic characterization of brain, ovarian, and lung cancers.

David Haussler, Ph.D., Lectures on Cancer Genomics - TCGA

Cancer.gov

In this lecture, Dr. David Haussler provides a historical overview of the field of genomics leading up to TCGA, including the Cancer Genomics Hub at the University of California, Santa Cruz, and the TCGA Pan-Cancer initiative.

TCGA and Its Vital Role in Understanding the Landscape of Somatic Alterations in Cancer - TCGA

Cancer.gov

Dr. Stephen Chanock, M.D., Director of the Division of Cancer Epidemiology & Genetics at the NCI, discusses how TCGA provides a strong foundation for understanding key biological alterations in cancer.

TCGA2BED: extracting, extending, integrating, and querying The Cancer Genome Atlas.

PubMed

Cumbo, Fabio; Fiscon, Giulia; Ceri, Stefano; Masseroli, Marco; Weitschek, Emanuel

2017-01-03

Data extraction and integration methods are becoming essential to effectively access and take advantage of the huge amounts of heterogeneous genomics and clinical data increasingly available. In this work, we focus on The Cancer Genome Atlas, a comprehensive archive of tumoral data containing the results of high-throughout experiments, mainly Next Generation Sequencing, for more than 30 cancer types. We propose TCGA2BED a software tool to search and retrieve TCGA data, and convert them in the structured BED format for their seamless use and integration. Additionally, it supports the conversion in CSV, GTF, JSON, and XML standard formats. Furthermore, TCGA2BED extends TCGA data with information extracted from other genomic databases (i.e., NCBI Entrez Gene, HGNC, UCSC, and miRBase). We also provide and maintain an automatically updated data repository with publicly available Copy Number Variation, DNA-methylation, DNA-seq, miRNA-seq, and RNA-seq (V1,V2) experimental data of TCGA converted into the BED format, and their associated clinical and biospecimen meta data in attribute-value text format. The availability of the valuable TCGA data in BED format reduces the time spent in taking advantage of them: it is possible to efficiently and effectively deal with huge amounts of cancer genomic data integratively, and to search, retrieve and extend them with additional information. The BED format facilitates the investigators allowing several knowledge discovery analyses on all tumor types in TCGA with the final aim of understanding pathological mechanisms and aiding cancer treatments.

Pan-cancer analysis reveals technical artifacts in TCGA germline variant calls.

PubMed

Buckley, Alexandra R; Standish, Kristopher A; Bhutani, Kunal; Ideker, Trey; Lasken, Roger S; Carter, Hannah; Harismendy, Olivier; Schork, Nicholas J

2017-06-12

Cancer research to date has largely focused on somatically acquired genetic aberrations. In contrast, the degree to which germline, or inherited, variation contributes to tumorigenesis remains unclear, possibly due to a lack of accessible germline variant data. Here we called germline variants on 9618 cases from The Cancer Genome Atlas (TCGA) database representing 31 cancer types. We identified batch effects affecting loss of function (LOF) variant calls that can be traced back to differences in the way the sequence data were generated both within and across cancer types. Overall, LOF indel calls were more sensitive to technical artifacts than LOF Single Nucleotide Variant (SNV) calls. In particular, whole genome amplification of DNA prior to sequencing led to an artificially increased burden of LOF indel calls, which confounded association analyses relating germline variants to tumor type despite stringent indel filtering strategies. The samples affected by these technical artifacts include all acute myeloid leukemia and practically all ovarian cancer samples. We demonstrate how technical artifacts induced by whole genome amplification of DNA can lead to false positive germline-tumor type associations and suggest TCGA whole genome amplified samples be used with caution. This study draws attention to the need to be sensitive to problems associated with a lack of uniformity in data generation in TCGA data.

B-CAN: a resource sharing platform to improve the operation, visualization and integrated analysis of TCGA breast cancer data.

PubMed

Wen, Can-Hong; Ou, Shao-Min; Guo, Xiao-Bo; Liu, Chen-Feng; Shen, Yan-Bo; You, Na; Cai, Wei-Hong; Shen, Wen-Jun; Wang, Xue-Qin; Tan, Hai-Zhu

2017-12-12

Breast cancer is a high-risk heterogeneous disease with myriad subtypes and complicated biological features. The Cancer Genome Atlas (TCGA) breast cancer database provides researchers with the large-scale genome and clinical data via web portals and FTP services. Researchers are able to gain new insights into their related fields, and evaluate experimental discoveries with TCGA. However, it is difficult for researchers who have little experience with database and bioinformatics to access and operate on because of TCGA's complex data format and diverse files. For ease of use, we build the breast cancer (B-CAN) platform, which enables data customization, data visualization, and private data center. The B-CAN platform runs on Apache server and interacts with the backstage of MySQL database by PHP. Users can customize data based on their needs by combining tables from original TCGA database and selecting variables from each table. The private data center is applicable for private data and two types of customized data. A key feature of the B-CAN is that it provides single table display and multiple table display. Customized data with one barcode corresponding to many records and processed customized data are allowed in Multiple Tables Display. The B-CAN is an intuitive and high-efficient data-sharing platform.

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics.

PubMed

Liu, Jianfang; Lichtenberg, Tara; Hoadley, Katherine A; Poisson, Laila M; Lazar, Alexander J; Cherniack, Andrew D; Kovatich, Albert J; Benz, Christopher C; Levine, Douglas A; Lee, Adrian V; Omberg, Larsson; Wolf, Denise M; Shriver, Craig D; Thorsson, Vesteinn; Hu, Hai

2018-04-05

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Copyright © 2018 Elsevier Inc. All rights reserved.

DrsG from Streptococcus dysgalactiae subsp. equisimilis Inhibits the Antimicrobial Peptide LL-37

PubMed Central

Smyth, Danielle; Cameron, Ainslie; Davies, Mark R.; McNeilly, Celia; Hafner, Louise; Sriprakash, Kadaba S.

2014-01-01

SIC and DRS are related proteins present in only 4 of the >200 Streptococcus pyogenes emm types. These proteins inhibit complement-mediated lysis and/or the activity of certain antimicrobial peptides (AMPs). A gene encoding a homologue of these proteins, herein called DrsG, has been identified in the related bacterium Streptococcus dysgalactiae subsp. equisimilis. Here we show that geographically dispersed isolates representing 14 of 50 emm types examined possess variants of drsG. However, not all isolates within the drsG-positive emm types possess the gene. Sequence comparisons also revealed a high degree of conservation in different S. dysgalactiae subsp. equisimilis emm types. To examine the biological activity of DrsG, recombinant versions of two major DrsG variants, DrsGS and DrsGL, were expressed and purified. Western blot analysis using antisera raised to these proteins demonstrated both variants to be expressed and secreted into culture supernatants. Unlike SIC, but similar to DRS, DrsG does not inhibit complement-mediated lysis. However, like both SIC and DRS, DrsG is a ligand of the cathelicidin LL-37 and is inhibitory to its bactericidal activity in in vitro assays. Conservation of prolines in the C-terminal region also suggests that these residues are important in the biology of this family of proteins. This is the first report demonstrating the activity of an AMP-inhibitory protein in S. dysgalactiae subsp. equisimilis and suggests that inhibition of AMP activity is the primary function of this family of proteins. The acquisition of the complement-inhibitory activity of SIC may reflect its continuing evolution. PMID:24664506

The Cancer Digital Slide Archive - TCGA

Cancer.gov

Dr. David Gutman and Dr. Lee Cooper developed The Cancer Digital Slide Archive (CDSA), a web platform for accessing pathology slide images of TCGA samples. Find out how they did it and how to use the CDSA website in this Case Study.

CCG Programs with Clinical Data will Build on the Success of TCGA

Cancer.gov

Though TCGA will wrap up in 2016 with a concluding symposium, cancer genomics projects built upon the success of TCGA will continue to play a major part in the NCI’s mission to better understand and treat cancer in the years to come.

Cloud Technology May Widen Genomic Bottleneck - TCGA

Cancer.gov

Computational biologist Dr. Ilya Shmulevich suggests that renting cloud computing power might widen the bottleneck for analyzing genomic data. Learn more about his experience with the Cloud in this TCGA in Action Case Study.

AACR 2013: Review of Data Dissemination - TCGA

Cancer.gov

The session will report TCGA's progress toward the 25 tumor project goal, the expansion to include over a dozen rare malignancies, as part of TCGA’s Rare Tumor Project, and beginning analysis across tumor types.

Home - The Cancer Genome Atlas - Cancer Genome - TCGA

Cancer.gov

The Cancer Genome Atlas (TCGA) is a comprehensive and coordinated effort to accelerate our understanding of the molecular basis of cancer through the application of genome analysis technologies, including large-scale genome sequencing.

Positron lifetime setup based on DRS4 evaluation board

NASA Astrophysics Data System (ADS)

Petriska, M.; Sojak, S.; Slugeň, V.

2014-04-01

A digital positron lifetime setup based on DRS4 evaluation board designed at the Paul Scherrer Institute has been constructed and tested in the Positron annihilation laboratory Slovak University of Technology Bratislava. The high bandwidth, low power consumption and short readout time make DRS4 chip attractive for positron annihilation lifetime (PALS) setup, replacing traditional ADCs and TDCs. A software for PALS setup online and offline pulse analysis was developed with Qt,Qwt and ALGLIB libraries.

TCGA bladder cancer study reveals potential drug targets

Cancer.gov

Investigators with TCGA have identified new potential therapeutic targets for a major form of bladder cancer, including important genes and pathways that are disrupted in the disease. They also discovered that, at the molecular level, some subtypes of bla

Studying the Genetic Basis of Kidney Cancer - TCGA

Cancer.gov

Dr. Marston Linehan, NCI's Chief of Urologic Surgery, has spent the last several decades studying kidney cancer genes and treating kidney cancer patients. Learn more about his experience as a kidney cancer physician scientist and TCGA contributor in this

B-CAN: a resource sharing platform to improve the operation, visualization and integrated analysis of TCGA breast cancer data

PubMed Central

Wen, Can-Hong; Ou, Shao-Min; Guo, Xiao-Bo; Liu, Chen-Feng; Shen, Yan-Bo; You, Na; Cai, Wei-Hong; Shen, Wen-Jun; Wang, Xue-Qin; Tan, Hai-Zhu

2017-01-01

Breast cancer is a high-risk heterogeneous disease with myriad subtypes and complicated biological features. The Cancer Genome Atlas (TCGA) breast cancer database provides researchers with the large-scale genome and clinical data via web portals and FTP services. Researchers are able to gain new insights into their related fields, and evaluate experimental discoveries with TCGA. However, it is difficult for researchers who have little experience with database and bioinformatics to access and operate on because of TCGA’s complex data format and diverse files. For ease of use, we build the breast cancer (B-CAN) platform, which enables data customization, data visualization, and private data center. The B-CAN platform runs on Apache server and interacts with the backstage of MySQL database by PHP. Users can customize data based on their needs by combining tables from original TCGA database and selecting variables from each table. The private data center is applicable for private data and two types of customized data. A key feature of the B-CAN is that it provides single table display and multiple table display. Customized data with one barcode corresponding to many records and processed customized data are allowed in Multiple Tables Display. The B-CAN is an intuitive and high-efficient data-sharing platform. PMID:29312567

Steps Towards Precision Medicine: Utilizing FFPE Specimens - TCGA

Cancer.gov

Roy W. Tarnuzzer, Ph.D., the Biospecimen Core Resource Program Manager at the TCGA Program Office, provides an overview of the Formalin-fixed Paraffin Pilot Project, an initiative to investigate best practices for use of FFPE specimens in genomic studies.

Transcultural and psychometric validation of the Dispositional Resilience Scale (DRS-15) in Chinese adult women.

PubMed

Wong, Janet Yuen-Ha; Fong, Daniel Yee-Tak; Choi, Anna Wai-Man; Chan, Claudia Kor-Yee; Tiwari, Agnes; Chan, Ko Ling; Lai, Vincent; Logan, Tk; Bartone, Paul

2014-11-01

The aim of this study was to report translation and transcultural adaptation of the 15-item Dispositional Resilience Scale in traditional Chinese (C-DRS-15) and evaluate its psychometric properties. The DRS is a self-report instrument that measures psychological hardiness. We followed an international standard of cross-cultural translation and validation of patient-reported outcome measures to create the Chinese version. Then, the translated C-DRS-15 was validated on 542 Chinese women from a population-based sample in Hong Kong. The internal consistency and criterion-related validity were investigated. Exploratory and confirmatory factor analysis revealed that the C-DRS-15 was supported by a modified three-factor structure in our Chinese sample (RMSEA = .06, CFI = .94, TLI = .92, and SRMR = .06). The reliability (Cronbach's α coefficient = .78) and validity were satisfactory. Total resilience score was negatively correlated with depression (p < .001), with non-depressed women scoring higher on the C-DRS-15. The C-DRS-15 was demonstrated to be a reliable and valid measurement to assess hardiness in Chinese women.

TU-CD-BRB-07: Identification of Associations Between Radiologist-Annotated Imaging Features and Genomic Alterations in Breast Invasive Carcinoma, a TCGA Phenotype Research Group Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rao, A; Net, J; Brandt, K

2015-06-15

Purpose: To determine associations between radiologist-annotated MRI features and genomic measurements in breast invasive carcinoma (BRCA) from the Cancer Genome Atlas (TCGA). Methods: 98 TCGA patients with BRCA were assessed by a panel of radiologists (TCGA Breast Phenotype Research Group) based on a variety of mass and non-mass features according to the Breast Imaging Reporting and Data System (BI-RADS). Batch corrected gene expression data was obtained from the TCGA Data Portal. The Kruskal-Wallis test was used to assess correlations between categorical image features and tumor-derived genomic features (such as gene pathway activity, copy number and mutation characteristics). Image-derived features weremore » also correlated with estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu) status. Multiple hypothesis correction was done using Benjamini-Hochberg FDR. Associations at an FDR of 0.1 were selected for interpretation. Results: ER status was associated with rim enhancement and peritumoral edema. PR status was associated with internal enhancement. Several components of the PI3K/Akt pathway were associated with rim enhancement as well as heterogeneity. In addition, several components of cell cycle regulation and cell division were associated with imaging characteristics.TP53 and GATA3 mutations were associated with lesion size. MRI features associated with TP53 mutation status were rim enhancement and peritumoral edema. Rim enhancement was associated with activity of RB1, PIK3R1, MAP3K1, AKT1,PI3K, and PIK3CA. Margin status was associated with HIF1A/ARNT, Ras/ GTP/PI3K, KRAS, and GADD45A. Axillary lymphadenopathy was associated with RB1 and BCL2L1. Peritumoral edema was associated with Aurora A/GADD45A, BCL2L1, CCNE1, and FOXA1. Heterogeneous internal nonmass enhancement was associated with EGFR, PI3K, AKT1, HF/MET, and EGFR/Erbb4/neuregulin 1. Diffuse nonmass enhancement was associated with HGF/MET/MUC20

Identification of druggable cancer driver genes amplified across TCGA datasets.

PubMed

Chen, Ying; McGee, Jeremy; Chen, Xianming; Doman, Thompson N; Gong, Xueqian; Zhang, Youyan; Hamm, Nicole; Ma, Xiwen; Higgs, Richard E; Bhagwat, Shripad V; Buchanan, Sean; Peng, Sheng-Bin; Staschke, Kirk A; Yadav, Vipin; Yue, Yong; Kouros-Mehr, Hosein

2014-01-01

The Cancer Genome Atlas (TCGA) projects have advanced our understanding of the driver mutations, genetic backgrounds, and key pathways activated across cancer types. Analysis of TCGA datasets have mostly focused on somatic mutations and translocations, with less emphasis placed on gene amplifications. Here we describe a bioinformatics screening strategy to identify putative cancer driver genes amplified across TCGA datasets. We carried out GISTIC2 analysis of TCGA datasets spanning 16 cancer subtypes and identified 486 genes that were amplified in two or more datasets. The list was narrowed to 75 cancer-associated genes with potential "druggable" properties. The majority of the genes were localized to 14 amplicons spread across the genome. To identify potential cancer driver genes, we analyzed gene copy number and mRNA expression data from individual patient samples and identified 42 putative cancer driver genes linked to diverse oncogenic processes. Oncogenic activity was further validated by siRNA/shRNA knockdown and by referencing the Project Achilles datasets. The amplified genes represented a number of gene families, including epigenetic regulators, cell cycle-associated genes, DNA damage response/repair genes, metabolic regulators, and genes linked to the Wnt, Notch, Hedgehog, JAK/STAT, NF-KB and MAPK signaling pathways. Among the 42 putative driver genes were known driver genes, such as EGFR, ERBB2 and PIK3CA. Wild-type KRAS was amplified in several cancer types, and KRAS-amplified cancer cell lines were most sensitive to KRAS shRNA, suggesting that KRAS amplification was an independent oncogenic event. A number of MAP kinase adapters were co-amplified with their receptor tyrosine kinases, such as the FGFR adapter FRS2 and the EGFR family adapters GRB2 and GRB7. The ubiquitin-like ligase DCUN1D1 and the histone methyltransferase NSD3 were also identified as novel putative cancer driver genes. We discuss the patient tailoring implications for existing cancer

Identification of Druggable Cancer Driver Genes Amplified across TCGA Datasets

PubMed Central

Chen, Ying; McGee, Jeremy; Chen, Xianming; Doman, Thompson N.; Gong, Xueqian; Zhang, Youyan; Hamm, Nicole; Ma, Xiwen; Higgs, Richard E.; Bhagwat, Shripad V.; Buchanan, Sean; Peng, Sheng-Bin; Staschke, Kirk A.; Yadav, Vipin; Yue, Yong; Kouros-Mehr, Hosein

2014-01-01

The Cancer Genome Atlas (TCGA) projects have advanced our understanding of the driver mutations, genetic backgrounds, and key pathways activated across cancer types. Analysis of TCGA datasets have mostly focused on somatic mutations and translocations, with less emphasis placed on gene amplifications. Here we describe a bioinformatics screening strategy to identify putative cancer driver genes amplified across TCGA datasets. We carried out GISTIC2 analysis of TCGA datasets spanning 14 cancer subtypes and identified 461 genes that were amplified in two or more datasets. The list was narrowed to 73 cancer-associated genes with potential “druggable” properties. The majority of the genes were localized to 14 amplicons spread across the genome. To identify potential cancer driver genes, we analyzed gene copy number and mRNA expression data from individual patient samples and identified 40 putative cancer driver genes linked to diverse oncogenic processes. Oncogenic activity was further validated by siRNA/shRNA knockdown and by referencing the Project Achilles datasets. The amplified genes represented a number of gene families, including epigenetic regulators, cell cycle-associated genes, DNA damage response/repair genes, metabolic regulators, and genes linked to the Wnt, Notch, Hedgehog, JAK/STAT, NF-KB and MAPK signaling pathways. Among the 40 putative driver genes were known driver genes, such as EGFR, ERBB2 and PIK3CA. Wild-type KRAS was amplified in several cancer types, and KRAS-amplified cancer cell lines were most sensitive to KRAS shRNA, suggesting that KRAS amplification was an independent oncogenic event. A number of MAP kinase adapters were co-amplified with their receptor tyrosine kinases, such as the FGFR adapter FRS2 and the EGFR family adapter GRB7. The ubiquitin-like ligase DCUN1D1 and the histone methyltransferase NSD3 were also identified as novel putative cancer driver genes. We discuss the patient tailoring implications for existing cancer drug

DRS is far less divergent than streptococcal inhibitor of complement of group A streptococcus.

PubMed

Sagar, Vivek; Kumar, Rajesh; Ganguly, Nirmal K; Menon, Thangam; Chakraborti, Anuradha

2007-04-01

When 100 group A streptococcus isolates were screened, drs, a variant of sic, was identified in emm12 and emm55 isolates. Molecular characterization showed that the drs gene sequence is highly conserved, unlike the sic gene sequence. However, the variation in gene size observed was due to the presence of extra internal repeat sequences.

DRS Is Far Less Divergent than Streptococcal Inhibitor of Complement of Group A Streptococcus▿

PubMed Central

Sagar, Vivek; Kumar, Rajesh; Ganguly, Nirmal K.; Menon, Thangam; Chakraborti, Anuradha

2007-01-01

When 100 group A streptococcus isolates were screened, drs, a variant of sic, was identified in emm12 and emm55 isolates. Molecular characterization showed that the drs gene sequence is highly conserved, unlike the sic gene sequence. However, the variation in gene size observed was due to the presence of extra internal repeat sequences. PMID:17237170

Factor analysis of the Colombian translation of the Delirium Rating Scale (DRS), Revised-98.

PubMed

Franco, José G; Trzepacz, Paula T; Mejía, Mario A; Ochoa, Sol B

2009-01-01

The phenomenology of delirium needs further elucidation using validated tools. The authors sought to derive valid factors from the Delirium Rating Scale (DRS), Revised -98. A factor analysis of the DRS-R-98 was performed among 161 medical-surgical patients. Scores ranged from 0 to 7 in 120 patients (74.53%; no delirium), 8 to 13 in 19 (11.80%; subclinical/prodromal delirium), and > or = 14 in 22 (13.66%; delirium). The DSM-IV-TR delirium incidence was 19.87%. The first two rotated factors explained 63.37% of the variance and may correspond to Cognition and Psychosis/Agitation factors. The dimension of motor retardation loaded with cognitive items. Motor agitation and retardation clustered with inattention, which is the cardinal symptom of delirium. The DRS-R-98 has good construct validity in this Latino population.

Characterization of a Complement-Binding Protein, DRS, from Strains of Streptococcus pyogenes Containing the emm12 and emm55 Genes

PubMed Central

Binks, Michael; Sriprakash, K. S.

2004-01-01

An extracellular protein of Streptococcus pyogenes, streptococcal inhibitor of complement (SIC), and its variant, called DRS (distantly related to SIC), are expressed by some S. pyogenes strains. SIC from type 1 (M1) isolates of S. pyogenes interferes with complement-mediated cell lysis, reportedly via its interaction with complement proteins. In this study we demonstrate that S. pyogenes strains carrying emm12 and emm55 (the genes for the M12 and M55 proteins, respectively) express and secrete DRS. This protein, like SIC, binds to the C6 and C7 complement proteins, and competition enzyme-linked immunosorbent assay experiments demonstrate that DRS competes with SIC for C6 and C7 binding. Similarly, SIC competes with DRS for binding to the complement proteins. Despite this, the recombinant DRS preparation showed no significant effect on complement function, as determined by lysis of sensitized sheep erythrocytes. Furthermore, the presence of DRS is not inhibitory to SIC activity. PMID:15213143

Characterization of a complement-binding protein, DRS, from strains of Streptococcus pyogenes containing the emm12 and emm55 genes.

PubMed

Binks, Michael; Sriprakash, K S

2004-07-01

An extracellular protein of Streptococcus pyogenes, streptococcal inhibitor of complement (SIC), and its variant, called DRS (distantly related to SIC), are expressed by some S. pyogenes strains. SIC from type 1 (M1) isolates of S. pyogenes interferes with complement-mediated cell lysis, reportedly via its interaction with complement proteins. In this study we demonstrate that S. pyogenes strains carrying emm12 and emm55 (the genes for the M12 and M55 proteins, respectively) express and secrete DRS. This protein, like SIC, binds to the C6 and C7 complement proteins, and competition enzyme-linked immunosorbent assay experiments demonstrate that DRS competes with SIC for C6 and C7 binding. Similarly, SIC competes with DRS for binding to the complement proteins. Despite this, the recombinant DRS preparation showed no significant effect on complement function, as determined by lysis of sensitized sheep erythrocytes. Furthermore, the presence of DRS is not inhibitory to SIC activity.

Mattis dementia rating scale (DRS) normative data for the brazilian middle-age and elderly populations.

PubMed

Foss, Maria Paula; de Carvalho, Viviane Amaral; Machado, Thais Helena; Dos Reis, Geraldo Cássio; Tumas, Vitor; Caramelli, Paulo; Nitrini, Ricardo; Porto, Cláudia Sellitto

2013-01-01

To expand norms for the Mattis Dementia Rating Scale (DRS) for the Brazilian middle-age and elderly populations. The DRS was administered to 502 individuals without cognitive deficits, 312 women and 190 men, aged 50 years or over and with educational level ranging from 0 to 13 years or more. The sample was composed of subjects who participated in other studies, from Caeté (Minas Gerais state), Ribeirão Preto (São Paulo state) and São Paulo (São Paulo state). Participants were divided into four schooling groups (illiterate, 1 to 4 years, 5 to 12 years and 13 years or more). The subjects were divided into four groups according to age (50 to 60, 61 to 70, 71 to 80, and 80 years or over). Normative data for DRS scores are expressed as percentile values. The group with lowest schooling and subjects older than 80 years had the worst scores. As expected, age and education were strongly correlated with DRS scores. Illiterates and older old individuals performed worse than the other groups. These data might help to improve the accuracy of the diagnosis of cognitive impairment and dementia in Brazilian middle-age and elderly populations.

Phosphatidylserine Stimulation of Drs2p·Cdc50p Lipid Translocase Dephosphorylation Is Controlled by Phosphatidylinositol-4-phosphate*

PubMed Central

Jacquot, Aurore; Montigny, Cédric; Hennrich, Hanka; Barry, Raphaëlle; le Maire, Marc; Jaxel, Christine; Holthuis, Joost; Champeil, Philippe; Lenoir, Guillaume

2012-01-01

Here, Drs2p, a yeast lipid translocase that belongs to the family of P4-type ATPases, was overexpressed in the yeast Saccharomyces cerevisiae together with Cdc50p, its glycosylated partner, as a result of the design of a novel co-expression vector. The resulting high yield allowed us, using crude membranes or detergent-solubilized membranes, to measure the formation from [γ-32P]ATP of a 32P-labeled transient phosphoenzyme at the catalytic site of Drs2p. Formation of this phosphoenzyme could be detected only if Cdc50p was co-expressed with Drs2p but was not dependent on full glycosylation of Cdc50p. It was inhibited by orthovanadate and fluoride compounds. In crude membranes, the phosphoenzyme formed at steady state at 4 °C displayed ADP-insensitive but temperature-sensitive decay. Solubilizing concentrations of dodecyl maltoside left this decay rate almost unaltered, whereas several other detergents accelerated it. Unexpectedly, the dephosphorylation rate for the solubilized Drs2p·Cdc50p complex was inhibited by the addition of phosphatidylserine. Phosphatidylserine exerted its anticipated accelerating effect on the dephosphorylation of Drs2p·Cdc50p complex only in the additional presence of phosphatidylinositol-4-phosphate. These results explain why phosphatidylinositol-4-phosphate tightly controls Drs2p-catalyzed lipid transport and establish the functional relevance of the Drs2p·Cdc50p complex overexpressed here. PMID:22351780

Serum-based six-miRNA signature as a potential marker for EC diagnosis: Comparison with TCGA miRNAseq dataset and identification of miRNA-mRNA target pairs by integrated analysis of TCGA miRNAseq and RNAseq datasets.

PubMed

Sharma, Priyanka; Saraya, Anoop; Sharma, Rinu

2018-01-30

To evaluate the diagnostic potential of a six microRNAs (miRNAs) panel consisting of miR-21, miR-144, miR-107, miR-342, miR-93 and miR-152 for esophageal cancer (EC) detection. The expression of miRNAs was analyzed in EC sera samples using quantitative real-time PCR. Risk score analysis was performed and linear regression models were then fitted to generate the six-miRNA panel. In addition, we made an effort to identify significantly dysregulated miRNAs and mRNAs in EC using the Cancer Genome Atlas (TCGA) miRNAseq and RNAseq datasets, respectively. Further, we identified significantly correlated miRNA-mRNA target pairs by integrating TCGA EC miRNAseq dataset with RNAseq dataset. The panel of circulating miRNAs showed enhanced sensitivity (87.5%) and specificity (90.48%) in terms of discriminating EC patients from normal subjects (area under the curve [AUC] = 0.968). Pathway enrichment analysis for potential targets of six miRNAs revealed 48 significant (P < 0.05) pathways, viz. pathways in cancer, mRNA surveillance, MAPK, Wnt, mTOR signaling, and so on. The expression data for mRNAs and miRNAs, downloaded from TCGA database, lead to identification of 2309 differentially expressed genes and 189 miRNAs. Gene ontology and pathway enrichment analysis showed that cell-cycle processes were most significantly enriched for differentially expressed mRNA. Integrated analysis of TCGA miRNAseq and RNAseq datasets resulted in identification of 53 063 significantly and negatively correlated miRNA-mRNA pairs. In summary, a novel and highly sensitive signature of serum miRNAs was identified for EC detection. Moreover, this is the first report identifying miRNA-mRNA target pairs from EC TCGA dataset, thus providing a comprehensive resource for understanding the interactions existing between miRNA and their target mRNAs in EC. © 2018 John Wiley & Sons Australia, Ltd.

Mattis dementia rating scale (DRS) normative data for the brazilian middle-age and elderly populations

PubMed Central

Foss, Maria Paula; de Carvalho, Viviane Amaral; Machado, Thais Helena; dos Reis, Geraldo Cássio; Tumas, Vitor; Caramelli, Paulo; Nitrini, Ricardo; Porto, Cláudia Sellitto

2013-01-01

OBJECTIVE To expand norms for the Mattis Dementia Rating Scale (DRS) for the Brazilian middle-age and elderly populations. METHODS The DRS was administered to 502 individuals without cognitive deficits, 312 women and 190 men, aged 50 years or over and with educational level ranging from 0 to 13 years or more. The sample was composed of subjects who participated in other studies, from Caeté (Minas Gerais state), Ribeirão Preto (São Paulo state) and São Paulo (São Paulo state). Participants were divided into four schooling groups (illiterate, 1 to 4 years, 5 to 12 years and 13 years or more). The subjects were divided into four groups according to age (50 to 60, 61 to 70, 71 to 80, and 80 years or over). RESULTS Normative data for DRS scores are expressed as percentile values. The group with lowest schooling and subjects older than 80 years had the worst scores. CONCLUSION As expected, age and education were strongly correlated with DRS scores. Illiterates and older old individuals performed worse than the other groups. These data might help to improve the accuracy of the diagnosis of cognitive impairment and dementia in Brazilian middle-age and elderly populations. PMID:29213861

Cancer Digital Slide Archive: an informatics resource to support integrated in silico analysis of TCGA pathology data

PubMed Central

Gutman, David A; Cobb, Jake; Somanna, Dhananjaya; Park, Yuna; Wang, Fusheng; Kurc, Tahsin; Saltz, Joel H; Brat, Daniel J; Cooper, Lee A D

2013-01-01

Background The integration and visualization of multimodal datasets is a common challenge in biomedical informatics. Several recent studies of The Cancer Genome Atlas (TCGA) data have illustrated important relationships between morphology observed in whole-slide images, outcome, and genetic events. The pairing of genomics and rich clinical descriptions with whole-slide imaging provided by TCGA presents a unique opportunity to perform these correlative studies. However, better tools are needed to integrate the vast and disparate data types. Objective To build an integrated web-based platform supporting whole-slide pathology image visualization and data integration. Materials and methods All images and genomic data were directly obtained from the TCGA and National Cancer Institute (NCI) websites. Results The Cancer Digital Slide Archive (CDSA) produced is accessible to the public (http://cancer.digitalslidearchive.net) and currently hosts more than 20 000 whole-slide images from 22 cancer types. Discussion The capabilities of CDSA are demonstrated using TCGA datasets to integrate pathology imaging with associated clinical, genomic and MRI measurements in glioblastomas and can be extended to other tumor types. CDSA also allows URL-based sharing of whole-slide images, and has preliminary support for directly sharing regions of interest and other annotations. Images can also be selected on the basis of other metadata, such as mutational profile, patient age, and other relevant characteristics. Conclusions With the increasing availability of whole-slide scanners, analysis of digitized pathology images will become increasingly important in linking morphologic observations with genomic and clinical endpoints. PMID:23893318

Functional analysis of overexpressed PtDRS1 involved in abiotic stresses enhances growth in transgenic poplar.

PubMed

Mohammadi, Kourosh; Movahedi, Ali; Maleki, Samaneh Sadat; Sun, Weibo; Zhang, Jiaxin; Almasi Zadeh Yaghuti, Amir; Nourmohammadi, Saeed; Zhuge, Qiang

2018-05-01

Drought and salinity are two main abiotic stressors that can disrupt plant growth and survival. Various biotechnological approaches have been used to alleviate the problem of drought stress by improving water stress resistance in forestry and agriculture. The drought sensitive 1 (DRS1) gene acts as a regulator of drought stress, identified in human, yeast and some model plants, such as Arabidopsis thaliana, but there have been no reports of DRS1 transformation in poplar plants to date. In this study, we transformed the DRS1 gene from Populus trichocarpa into Populus deltoides × Populus euramericana 'Nanlin895' using Agrobacterium tumefaciens-mediated transformation. We confirmed that the DRS1 gene was transformed into 'Nanlin895' poplar genomes using reverse transcription polymerase chain reaction (PCR), multiplex PCR, real-time PCR, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. All transformed and wild-type (WT) plants were then transferred into a greenhouse for complementary experiments. We analyzed the physiological and biochemical responses of transgenic plants under drought and salt stresses in the greenhouse, and the results were compared with control WT plants. Responses to abiotic stress were greater in transgenic plants compared with WT. Based on our results, introduction of the DRS1 gene into poplar 'Nanlin895' plants significantly enhanced the resistance of those plants to water deficit and high salinity, allowing higher growth rates of roots and shoots in those plants. Additionally, the clawed root rate increased in transformed poplars grown in culture media or in soil, and improved survival under drought and salt stress conditions. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Predictors of Performance on the MMSE and the DRS-2 Among American Indian Elders

PubMed Central

Jervis, Lori L.; Fickenscher, Alexandra; Beals, Janette; Cullum, C. Munro; Novins, Douglas K.; Manson, Spero M.; Arciniegas, David B.

2015-01-01

Little is known about factors that predict older American Indians’ performance on cognitive tests. This study examined 137 American Indian elders’ performance on the MMSE and the Dementia Rating Scale—Second Edition (DRS-2). Multivariate regression identified younger age, more education, not receiving Supplemental Security Income, and frequent receipt of needed health care as predictors of better performance on the MMSE. Better performance on the DRS-2 was predicted by more education, boarding school attendance, not receiving Supplemental Security Income, and frequent receipt of needed health care. This study points to the importance of economic and educational factors on cognitive test performance among American Indian elders. PMID:21037127

Predictors of performance on the MMSE and the DRS-2 among American Indian elders.

PubMed

Jervis, Lori L; Fickenscher, Alexandra; Beals, Janette; Cullum, C Munro; Novins, Douglas K; Manson, Spero M; Arciniegas, David B

2010-01-01

Little is known about factors that predict older American Indians' performance on cognitive tests. This study examined 137 American Indian elders' performance on the MMSE and the Dementia Rating Scale-Second Edition (DRS-2). Multivariate regression identified younger age, more education, not receiving Supplemental Security Income, and frequent receipt of needed health care as predictors of better performance on the MMSE. Better performance on the DRS-2 was predicted by more education, boarding school attendance, not receiving Supplemental Security Income, and frequent receipt of needed health care. This study points to the importance of economic and educational factors on cognitive test performance among American Indian elders.

TCGA divides gastric cancer into four molecular subtypes: implications for individualized therapeutics.

PubMed

Zhang, Wei

2014-10-01

Gastric cancer is a leading cause of cancer deaths in the world. The treatment of gastric cancer is challenging because of its highly heterogeneous etiology and clinical characteristics. Recent genomic and molecular characterization of gastric cancer, especially the findings reported by the Cancer Genome Atlas (TCGA), have shed light on the heterogeneity and potential targeted therapeutics for four different subtypes of gastric cancer.

Colloid micro-Newton thruster development for the ST7-DRS and LISA missions

NASA Technical Reports Server (NTRS)

Ziemer, John K.; Gamero-Castano, Manuel; Hruby, Vlad; Spence, Doug; Demmons, Nate; McCormick, Ryan; Roy, Tom

2005-01-01

We present recent progress and development of the Busek Colloid Micro-Newton Thruster (CMNT) for the Space Technology 7 Disturbance Reduction System (ST7-DRS) and Laser Interferometer Space Antenna (LISA) Missions.

38. View of DRS 1, 2, and 3 (structure nos. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

38. View of DRS 1, 2, and 3 (structure nos. 735, 736, and 737) console fault locator for beam power status, radio frequency (RF) and intermediate frequency (IF) fault conditions, RF switches status and TR status. - Clear Air Force Station, Ballistic Missile Early Warning System Site II, One mile west of mile marker 293.5 on Parks Highway, 5 miles southwest of Anderson, Anderson, Denali Borough, AK

CAC-DRS: Coronary Artery Calcium Data and Reporting System. An expert consensus document of the Society of Cardiovascular Computed Tomography (SCCT).

PubMed

Hecht, Harvey S; Blaha, Michael J; Kazerooni, Ella A; Cury, Ricardo C; Budoff, Matt; Leipsic, Jonathon; Shaw, Leslee

2018-03-30

The goal of CAC-DRS: Coronary Artery Calcium Data and Reporting System is to create a standardized method to communicate findings of CAC scanning on all noncontrast CT scans, irrespective of the indication, in order to facilitate clinical decision-making, with recommendations for subsequent patient management. The CAC-DRS classification is applied on a per-patient basis and represents the total calcium score and the number of involved arteries. General recommendations are provided for further management of patients with different degrees of calcified plaque burden based on CAC-DRS classification. In addition, CAC-DRS will provide a framework of standardization that may benefit quality assurance and tracking patient outcomes with the potential to ultimately result in improved quality of care. Copyright © 2018 Society of Cardiovascular Computed Tomography. All rights reserved.

[Value of DC and DRs in prediction of cardiovascular events in acute myocardial infarction patients].

PubMed

Gao, L; Chen, Y D; Shi, Y J; Xue, H; Wang, J L

2016-05-24

To investigate the value of deceleration capacity of rate (DC) and heart rate deceleration runs(DRs) in predicting cardiovascular events in patient with acute myocardial infarction (AMI). This study included 166 patients with AMI, who underwent ECG with sinus rhythm.These patients were followed-up for major adverse cardiac events (MACE). The receiver operating characteristic curve (ROC) was drawn to determine the best values for estimating the MACE. The mean follow-up time was (20.5±2.8) months, with 13 cases of cardiac death.There was statistically significant difference of DC, DRs and standard diviation of NN intervals(SDNN-24) between the death group and survival group.The area under the curve (AUC) of DC, DR4 and DR8 were larger than SDNN-24 (0.874, 0.804 vs 0.727). The values of DC, DR2, DR4 and root mean square of the successive differences(RMSSD) in the group of patients who underwent cardiac adverse events were smaller than the group of patients who didn't, and the AUC of DC was slightly higher than that of RMSSD. DC and DRs have important predictive value for cardiac death and MACE and can screen high-risk patients in patients with AMI.

TCGA Workflow: Analyze cancer genomics and epigenomics data using Bioconductor packages

PubMed Central

Bontempi, Gianluca; Ceccarelli, Michele; Noushmehr, Houtan

2016-01-01

Biotechnological advances in sequencing have led to an explosion of publicly available data via large international consortia such as The Cancer Genome Atlas (TCGA), The Encyclopedia of DNA Elements (ENCODE), and The NIH Roadmap Epigenomics Mapping Consortium (Roadmap). These projects have provided unprecedented opportunities to interrogate the epigenome of cultured cancer cell lines as well as normal and tumor tissues with high genomic resolution. The Bioconductor project offers more than 1,000 open-source software and statistical packages to analyze high-throughput genomic data. However, most packages are designed for specific data types (e.g. expression, epigenetics, genomics) and there is no one comprehensive tool that provides a complete integrative analysis of the resources and data provided by all three public projects. A need to create an integration of these different analyses was recently proposed. In this workflow, we provide a series of biologically focused integrative analyses of different molecular data. We describe how to download, process and prepare TCGA data and by harnessing several key Bioconductor packages, we describe how to extract biologically meaningful genomic and epigenomic data. Using Roadmap and ENCODE data, we provide a work plan to identify biologically relevant functional epigenomic elements associated with cancer. To illustrate our workflow, we analyzed two types of brain tumors: low-grade glioma (LGG) versus high-grade glioma (glioblastoma multiform or GBM). This workflow introduces the following Bioconductor packages: AnnotationHub, ChIPSeeker, ComplexHeatmap, pathview, ELMER, GAIA, MINET, RTCGAToolbox,  TCGAbiolinks. PMID:28232861

TCGA Workflow: Analyze cancer genomics and epigenomics data using Bioconductor packages.

PubMed

Silva, Tiago C; Colaprico, Antonio; Olsen, Catharina; D'Angelo, Fulvio; Bontempi, Gianluca; Ceccarelli, Michele; Noushmehr, Houtan

2016-01-01

Biotechnological advances in sequencing have led to an explosion of publicly available data via large international consortia such as The Cancer Genome Atlas (TCGA), The Encyclopedia of DNA Elements (ENCODE), and The NIH Roadmap Epigenomics Mapping Consortium (Roadmap). These projects have provided unprecedented opportunities to interrogate the epigenome of cultured cancer cell lines as well as normal and tumor tissues with high genomic resolution. The Bioconductor project offers more than 1,000 open-source software and statistical packages to analyze high-throughput genomic data. However, most packages are designed for specific data types (e.g. expression, epigenetics, genomics) and there is no one comprehensive tool that provides a complete integrative analysis of the resources and data provided by all three public projects. A need to create an integration of these different analyses was recently proposed. In this workflow, we provide a series of biologically focused integrative analyses of different molecular data. We describe how to download, process and prepare TCGA data and by harnessing several key Bioconductor packages, we describe how to extract biologically meaningful genomic and epigenomic data. Using Roadmap and ENCODE data, we provide a work plan to identify biologically relevant functional epigenomic elements associated with cancer. To illustrate our workflow, we analyzed two types of brain tumors: low-grade glioma (LGG) versus high-grade glioma (glioblastoma multiform or GBM). This workflow introduces the following Bioconductor packages: AnnotationHub, ChIPSeeker, ComplexHeatmap, pathview, ELMER, GAIA, MINET, RTCGAToolbox,  TCGAbiolinks.

A comparison of delirium diagnosis in elderly medical inpatients using the CAM, DRS-R98, DSM-IV and DSM-5 criteria.

PubMed

Adamis, Dimitrios; Rooney, Siobhan; Meagher, David; Mulligan, Owen; McCarthy, Geraldine

2015-06-01

The recently published DSM-5 criteria for delirium may lead to different case identification and rates of delirium than previous classifications. The aims of this study are to determine how the new DSM-5 criteria compare with DSM-IV in identification of delirium in elderly medical inpatients and to investigate the agreement between different methods, using CAM, DRS-R98, DSM-IV, and DSM-5 criteria. Prospective, observational study of elderly patients aged 70+ admitted under the acute medical teams in a regional general hospital. Each participant was assessed within 3 days of admission using the DSM-5, and DSM-IV criteria plus the DRS-R98, and CAM scales. We assessed 200 patients [mean age 81.1±6.5; 50% female; pre-existing cognitive impairment in 63%]. The prevalence rates of delirium for each diagnostic method were: 13.0% (n = 26) for DSM-5; 19.5% (n = 39) for DSM-IV; 13.5% (n = 27) for DRS-R98 and 17.0%, (n = 34) for CAM. Using tetrachoric correlation coefficients the agreement between DSM-5 and DSM-IV was statistically significant (ρtetr = 0.64, SE = 0.1, p < 0.0001). Similar significant agreement was found between the four methods. DSM-IV is the most inclusive diagnostic method for delirium, while DSM-5 is the most restrictive. In addition, these classification systems identify different cases of delirium. This could have clinical, financial, and research implications. However, both classification systems have significant agreement in the identification of the same concept (delirium). Clarity of diagnosis is required for classification but also further research considering the relevance in predicting outcomes can allow for more detailed evaluation of the DSM-5 criteria.

Mining TCGA Data Using Boolean Implications

PubMed Central

Sinha, Subarna; Tsang, Emily K.; Zeng, Haoyang; Meister, Michela; Dill, David L.

2014-01-01

Boolean implications (if-then rules) provide a conceptually simple, uniform and highly scalable way to find associations between pairs of random variables. In this paper, we propose to use Boolean implications to find relationships between variables of different data types (mutation, copy number alteration, DNA methylation and gene expression) from the glioblastoma (GBM) and ovarian serous cystadenoma (OV) data sets from The Cancer Genome Atlas (TCGA). We find hundreds of thousands of Boolean implications from these data sets. A direct comparison of the relationships found by Boolean implications and those found by commonly used methods for mining associations show that existing methods would miss relationships found by Boolean implications. Furthermore, many relationships exposed by Boolean implications reflect important aspects of cancer biology. Examples of our findings include cis relationships between copy number alteration, DNA methylation and expression of genes, a new hierarchy of mutations and recurrent copy number alterations, loss-of-heterozygosity of well-known tumor suppressors, and the hypermethylation phenotype associated with IDH1 mutations in GBM. The Boolean implication results used in the paper can be accessed at http://crookneck.stanford.edu/microarray/TCGANetworks/. PMID:25054200

'Combined reflectance stratigraphy' - subdivision of loess successions by diffuse reflectance spectrometry (DRS)

NASA Astrophysics Data System (ADS)

Szeberényi, Jozsef; Bradak-Hayashi, Balázs; Kiss, Klaudia; Kovács, József; Varga, György; Balázs, Réka; Szalai, Zoltán; Viczián, István

2016-04-01

The different varieties of loess (and intercalated paleosol layers) together constitute one of the most widespread terrestrial sediments, which was deposited, altered, and redeposited in the course of the changing climatic conditions of the Pleistocene. To reveal more information about Pleistocene climate cycles and/or environments the detailed lithostratigraphical subdivision and classification of the loess variations and paleosols are necessary. Beside the numerous method such as various field measurements, semi-quantitative tests and laboratory investigations, diffuse reflectance spectroscopy (DRS) is one of the well applied method on loess/paleosol sequences. Generally, DRS has been used to separate the detrital and pedogenic mineral component of the loess sections by the hematite/goethite ratio. DRS also has been applied as a joint method of various environmental magnetic investigations such as magnetic susceptibility- and isothermal remanent magnetization measurements. In our study the so-called "combined reflectance stratigraphy method" were developed. At First, complex mathematical method was applied to compare the results of the spectral reflectance measurements. One of the most preferred multivariate methods is cluster analysis. Its scope is to group and compare the loess variations and paleosol based on the similarity and common properties of their reflectance curves. In the Second, beside the basic subdivision of the profiles by the different reflectance curves of the layers, the most characteristic wavelength section of the reflectance curve was determined. This sections played the most important role during the classification of the different materials of the section. The reflectance value of individual samples, belonged to the characteristic wavelength were depicted in the function of depth and well correlated with other proxies like grain size distribution and magnetic susceptibility data. The results of the correlation showed the significance of

Evaluating the Prognostic Value of microRNA-203 in Solid Tumors Based on a Meta-Analysis and the Cancer Genome Atlas (TCGA) Datasets.

PubMed

Shao, Yingjie; Gu, Wendong; Ning, Zhonghua; Song, Xing; Pei, Honglei; Jiang, Jingting

2017-01-01

It has been reported that miR-203 expression was aberrant in various types of cancers, and it could be used as a prognostic biomarker. Therefore, in this study, we aimed to evaluate the prognostic value of miR-203 expression in solid tumors by using meta-analysis and The Cancer Genome Atlas (TCGA) datasets. By doing a literature research in PubMed, Embase and the Cochrane Library (last update by December 2016), we were able to identify the studies assessing the prognostic role of miR-203 in various tumors. We then used TCGA datasets to validate the results of meta-analysis. 33 studies from 26 articles were qualified and enrolled in this meta-analysis. Pooled analyses showed that higher expression of miR-203 in tissues couldn't predict poor overall survival (OS) and progression-free survival (PFS) in solid tumors. However, the results of subgroup analyses revealed that the upregulation of tissue miR-203 expression was associated with poor OS in colorectal cancer (hazard ratio (HR)=1.81, 95% confidence intervals (CI) 1.31-2.49; P<0.001), pancreatic cancer (HR=1.19, 95% CI 1.09-1.31; P<0.001) and ovarian cancer (HR=1.85, 95% CI 1.45-2.37; P<0.001); but it had opposite association in liver cancer (HR=0.52, 95% CI 0.28-0.97; P=0.040) and esophageal cancer (HR=0.41, 95% CI 0.25-0.66; P<0.001). Based on TCGA datasets, we found the same results for pancreatic cancer and esophageal cancer, but not for colorectal cancer and liver cancer. Moreover, patients with high circulating miR-203 in blood had significantly poor OS and PFS in colorectal cancer and breast cancer. Our study showed that the prognostic values of tissue miR-203 varied in different tumor types. In addition, the upregulation of circulating miR-203 in blood was associated with poor prognosis in colorectal cancer and breast cancer. © 2017 The Author(s)Published by S. Karger AG, Basel.

Children and young adults in a prolonged unconscious state after severe brain injury: long-term functional outcome as measured by the DRS and the GOSE after early intensive neurorehabilitation.

PubMed

Eilander, H J; Timmerman, R B W; Scheirs, J G M; Van Heugten, C M; De Kort, P L M; Prevo, A J H

2007-01-01

To investigate the long-term (2-15 years) functional outcome of children and young adults who received an early intensive neurorehabilitation programme (EINP) after a prolonged period of unconsciousness due to severe brain injury; to differentiate between traumatic brain injury (TBI) and non-traumatic brain injury (nTBI); and to compare the results on two different outcome scales: the Disability Rating Scale (DRS) and the Glasgow Outcome Scale Extended (GOSE). One hundred and forty-five patients, who were admitted to EINP between December 1987 and January 2001. The Post-Acute Level of Consciousness scale (PALOC-s), the DRS, including categorized scores (DRScat), and the GOSE. The long-term functional level of 90 patients could be determined, of whom 25 were deceased. The mean DRS-score of the surviving patients was 6.8 (SD = 6.6); the mean score on the GOSE was 4.5 (SD = 1.7). There was a significant difference in the outcome amongst traumatic and non-traumatic patients (t88 = 4.21; p < 0.01). The correlation between the DRS and the GOSE was high (Spearman rho = 0.85; p < 0.01), as well as the correlation between the categorized scores of the DRS and the GOSE (Spearman rho = 0.81; p < 0.01). The distribution of outcome scores on the DRScat is more diverse than on the GOSE. Especially item 7 of the DRS, measuring functional independence, showed considerable variance in discriminating between different outcome levels. More patients with TBI than expected reached a (semi-) independent level of functioning, indicating a possible effect of EINP. Patients suffering from nTBI did not demonstrate these outcome levels. Only a few patients stayed in a vegetative state for more than a couple of years. In this cohort of severe brain-injured young people, the DRS offered the best investigative possibilities for long-term level of functioning.

A comparison of outcomes according to different diagnostic systems for delirium (DSM-5, DSM-IV, CAM, and DRS-R98).

PubMed

Adamis, Dimitrios; Meagher, David; Rooney, Siobhan; Mulligan, Owen; McCarthy, Geraldine

2018-04-01

ABSTRACTStudies indicate that DSM-5 criteria for delirium are relatively restrictive, and identify different cases of delirium compared with previous systems. We evaluate four outcomes of delirium (mortality, length of hospital stay, institutionalization, and cognitive improvement) in relation to delirium defined by different DSM classification systems.Prospective, longitudinal study of patients aged 70+ admitted to medical wards of a general hospital. Participants were assessed up to a maximum of four times during two weeks, using DSM-5 and DSM-IV criteria, DRS-R98 and CAM scales as proxies for DSM III-R and DSM III.Of the 200 assessed patients (mean age 81.1, SD = 6.5; and 50% female) during hospitalization, delirium was identified in 41 (20.5%) using DSM-5, 45 (22.5%) according to DSM-IV, 46 (23%) with CAM positive, and 37 (18.5%) with DRS-R98 severity score >15. Mortality was significantly associated with delirium according to any classification system, but those identified with DSM-5 were at greater risk. Length of stay was significantly longer for those with DSM-IV delirium. Discharge to a care home was associated only with DRS-R98 defined delirium. Cognitive improvement was only associated with CAM and DSM-IV. Different classification systems for delirium identify populations with different outcomes.

Characterization of consecutive Streptococcus pyogenes isolates from patients with pharyngitis and bacteriological treatment failure: special reference to prtF1 and sic / drs.

PubMed

Brandt, C M; Allerberger, F; Spellerberg, B; Holland, R; Lütticken, R; Haase, G

2001-02-15

To analyze bacteriological treatment failure in streptococcal pharyngitis, 40 consecutive Streptococcus pyogenes isolates from 18 patients were characterized. For 17 patients, isolates were indistinguishable with respect to emm type, random amplified polymorphic DNA pattern, and presence of prtF1 encoding the fibronectin-binding protein F1. prtF1 was detected only in the 11 isolates (4 patients) with emm12 and in the single isolate with emm6. Further analysis by vir(mga) regulon typing, sequencing of sic encoding the streptococcal inhibitor of complement from 19 isolates with emm1 (9 patients), and sequencing of drs (distantly related sic) from 11 isolates with emm12 revealed distinct sic alleles with insertions and/or deletions in sic that corresponded to differences in restriction patterns of the vir(mga) regulon only for paired isolates of 2 patients. Among isolates with emm12, 2 novel drs alleles were found. Analysis of these data suggests that neither the presence of prtF1 nor the diversification of sic / drs is required for the persistence of S. pyogenes in pharyngitis.

Reinvigorating GBM Research with Hope for Therapies - TCGA

Cancer.gov

Dr. Antonio Iavarone and his research group at Columbia University have discovered the first recurrent gene fusion in glioblastoma. Find out how they did it and potential implications in this Case Study.

Clinical value of miR-182-5p in lung squamous cell carcinoma: a study combining data from TCGA, GEO, and RT-qPCR validation.

PubMed

Luo, Jie; Shi, Ke; Yin, Shu-Ya; Tang, Rui-Xue; Chen, Wen-Jie; Huang, Lin-Zhen; Gan, Ting-Qing; Cai, Zheng-Wen; Chen, Gang

2018-04-10

MiR-182-5p, as a member of miRNA family, can be detected in lung cancer and plays an important role in lung cancer. To explore the clinical value of miR-182-5p in lung squamous cell carcinoma (LUSC) and to unveil the molecular mechanism of LUSC. The clinical value of miR-182-5p in LUSC was investigated by collecting and calculating data from The Cancer Genome Atlas (TCGA) database, the Gene Expression Omnibus (GEO) database, and real-time quantitative polymerase chain reaction (RT-qPCR). Twelve prediction platforms were used to predict the target genes of miR-182-5p. Protein-protein interaction (PPI) networks and gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to explore the molecular mechanism of LUSC. The expression of miR-182-5p was significantly over-expressed in LUSC than in non-cancerous tissues, as evidenced by various approaches, including the TCGA database, GEO microarrays, RT-qPCR, and a comprehensive meta-analysis of 501 LUSC cases and 148 non-cancerous cases. Furthermore, a total of 81 potential target genes were chosen from the union of predicted genes and the TCGA database. GO and KEGG analyses demonstrated that the target genes are involved in pathways related to biological processes. PPIs revealed the relationships between these genes, with EPAS1, PRKCE, NR3C1, and RHOB being located in the center of the PPI network. MiR-182-5p upregulation greatly contributes to LUSC and may serve as a biomarker in LUSC.

TCGA analysis of adrenocortical carcinoma - TCGA

Cancer.gov

In the most comprehensive molecular characterization to date of adrenocortical carcinoma, a rare cancer of the adrenal cortex, researchers extensively analyzed 91 cases for alterations in the tumor genomes.

Utility of miR‑133a‑3p as a diagnostic indicator for hepatocellular carcinoma: An investigation combined with GEO, TCGA, meta‑analysis and bioinformatics.

PubMed

Liang, Hai-Wei; Yang, Xia; Wen, Dong-Yue; Gao, Li; Zhang, Xiang-Yu; Ye, Zhi-Hua; Luo, Jie; Li, Zu-Yun; He, Yun; Pang, Yu-Yan; Chen, Gang

2018-01-01

Increasing evidence has demonstrated that microRNA (miR)‑133a‑3p is an important regulator of hepatocellular carcinoma (HCC). In the present study, the diagnostic role of miR‑133a‑3p in HCC, and the potential functional pathways, were both explored based on publicly available data. Eligible microarray datasets were collected from NCBI Gene Expression Omnibus (GEO) database and ArrayExpress database. The data related to HCC and matched adjacent normal tissues were also downloaded from The Cancer Genome Atlas (TCGA). Published studies reporting the association between miR‑133a‑3p expression and HCC were reviewed from multiple databases. By combining the data derived from three sources (GEO, TCGA and published studies), the authors analyzed the comprehensive relationship between miR‑133a‑3p expression and clinicopathological features of HCC. Eventually, putative targets of miR‑133a‑3p in HCC were selected for further bioinformatics prediction. A total of eight published microarray datasets were gathered, and the pooled results demonstrated that the expression of miR‑133a‑3p in the tumor group was lower than that in normal groups [standardized mean difference (SMD)=‑0.54; 95% confidence interval (CI), ‑0.74 to ‑0.35; P<0.001]. Consistently, the level of miR‑133a‑1 in HCC was reduced markedly compared to normal tissues (P<0.001) based on TCGA data, and the AUC value of low miR‑133a‑1 expression for HCC diagnosis was 0.670 (P<0.001). Furthermore, the combined SMD of all datasets (GEO, TCGA and literature) suggested that significant difference was observed between the HCC group and the normal control group, and lower miR‑133a‑3p expression in HCC group was noted (SMD=‑0.69; 95% CI, ‑1.10 to ‑0.29; P=0.001). In addition, the authors discovered five key genes of the calcium signaling pathway (NOS1, ADRA1A, ADRA1B, ADRA1D and TBXA2R) that may probably be targeted by miR‑133a‑3p in HCC. The study reveals that miR‑133a‑3p

Characterization of the gene encoding pinin/DRS/memA and evidence for its potential tumor suppressor function.

PubMed

Shi, Y; Ouyang, P; Sugrue, S P

2000-01-13

Several cell adhesion-related proteins have been shown to act as tumor-suppressors (TS) in the neoplastic progression of epithelial-derived tumors. Pinin/DRS/memA was first identified in our laboratory and it was shown to be a cell adhesion-related molecule. Our previous study demonstrated that restoration of pinin expression in transformed cells not only positively influenced cellular adhesive properties but also reversed the transformed phenotype to more epithelial-like. Here, we show by FISH analysis that the gene locus for pinin is within 14q13. The alignment of the pinin gene with STS markers localized the gene to the previously identified TS locus D14S75-D14S288. Northern analyses revealed diminished pinin mRNA in renal cell carcinomas (RCC) and certain cancer cell lines. Immunohistochemical examination of tumor samples demonstrated absent or greatly reduced pinin in transitional cell carcinoma (TCC) and RCC tumors. TCC-derived J82 cells as well as EcR-293 cells transfected with full-length pinin cDNA demonstrated inhibition of anchorage-independent growth of cells in soft agar. Furthermore, methylation analyses revealed that aberrant methylation of pinin CpG islands was correlated with decreased/absent pinin expression in a subset of tumor tissues. These data lend significant support to the hypothesis that pinin/DRS/memA may act as a tumor suppressor in certain types of cancers.

Down-regulation of miR-146a-5p and its potential targets in hepatocellular carcinoma validated by a TCGA- and GEO-based study.

PubMed

Zhang, Xin; Ye, Zhi-Hua; Liang, Hai-Wei; Ren, Fang-Hui; Li, Ping; Dang, Yi-Wu; Chen, Gang

2017-04-01

Our previous research has demonstrated that miR-146a-5p is down-regulated in hepatocellular carcinoma (HCC) and might play a tumor-suppressive role. In this study, we sought to validate the decreased expression with a larger cohort and to explore potential molecular mechanisms. GEO and TCGA databases were used to gather miR-146a-5p expression data in HCC, which included 762 HCC and 454 noncancerous liver tissues. A meta-analysis of the GEO-based microarrays, TCGA-based RNA-seq data, and additional qRT-PCR data validated the down-regulation of miR-146a-5p in HCC and no publication bias was observed. Integrated genes were generated by overlapping miR-146a-5p-related genes from predicted and formerly reported HCC-related genes using natural language processing. The overlaps were comprehensively analyzed to discover the potential gene signatures, regulatory pathways, and networks of miR-146a-5p in HCC. A total of 251 miR-146a-5p potential target genes were predicted by bioinformatics platforms and 104 genes were considered as both HCC- and miR-146a-5p-related overlaps. RAC1 was the most connected hub gene for miR-146a-5p and four pathways with high enrichment (VEGF signaling pathway, adherens junction, toll-like receptor signaling pathway, and neurotrophin signaling pathway) were denoted for the overlapped genes. The down-regulation of miR-146a-5p in HCC has been validated with the most complete data possible. The potential gene signatures, regulatory pathways, and networks identified for miR-146a-5p in HCC could prove useful for molecular-targeted diagnostics and therapeutics.

Investigation of miR-136-5p key target genes and pathways in lung squamous cell cancer based on TCGA database and bioinformatics analysis.

PubMed

Xie, Zu-Cheng; Li, Tian-Tian; Gan, Bin-Liang; Gao, Xiang; Gao, Li; Chen, Gang; Hu, Xiao-Hua

2018-05-01

Lung squamous cell cancer (LUSC) is a common but challenging malignancy. It is important to illuminate the molecular mechanism of LUSC. Thus, we aim to explore the molecular mechanism of miR-136-5p in relation to LUSC. We used the Cancer Genome Atlas (TCGA) database to investigate the expression of miR-136-5p in relation to LUSC. Then, we identified the possible miR-136-5p target genes through intersection of the predicted miR-136-5p target genes and LUSC upregulated genes from TCGA. Bioinformatics analysis was performed to determine the key miR-136-5p targets and pathways associated with LUSC. Finally, the expression of hub genes, correlation between miR-136-5p and hub genes, and expected significance of hub genes were evaluated via the TCGA and Genotype-Tissue Expression (GTEx) project. MiR-136-5p was significantly downregulated in LUSC patients. Glucuronidation, glucuronosyltransferase, and the retinoic acid metabolic process were the most enriched metabolic interactions in LUSC patients. Ascorbate and aldarate metabolism, pentose and glucuronate interconversions, and retinol metabolism were identified as crucial pathways. Seven hub genes (UGT1A1, UGT1A3, UGT1A6, UGT1A7, UGT1A10, SRD5A1, and ADH7) were found to be upregulated, and UGT1A1, UGT1A3, UGT1A6, UGT1A7, and ADH7 were negatively correlated with miR-136-5p. UGT1A7 and ADH7 were the most significantly involved miR-136-5p target genes, and high expression of these genes was correlated with better overall survival and disease-free survival of LUSC patients. Downregulated miR-136-5p may target UGT1A7 and ADH7 and participate in ascorbate and aldarate metabolism, pentose and glucuronate interconversions, and retinol metabolism. High expression of UGT1A7 and ADH7 may indicate better prognosis of LUSC patients. Copyright © 2018. Published by Elsevier GmbH.

Molecular and structural determinants of adamantyl susceptibility to HLA-DRs allelic variants: an in silico approach to understand the mechanism of MLEs

NASA Astrophysics Data System (ADS)

Zaheer-ul-Haq; Khan, Waqasuddin

2011-01-01

Class II major histocompatibility complex (MHC II) molecules as expressed by antigen-presenting cells are heterodimeric cell-surface glycoprotein receptors that are fundamental in initiating and propagating an immune response by presenting tumor-associated antigenic peptides to CD4+/TH cells. The loading efficiency of such peptides can be improved by small organic compounds (MHC Loading Enhancers—MLEs), that convert the non-receptive peptide conformation of MHC II to a peptide-receptive conformation. In a reversible reaction, these compounds open up the binding site of MHC II molecules by specific interactions with a yet undefined pocket. Here, we performed molecular docking and molecular dynamics simulation studies of adamantyl compounds on the predicted cavity around the P1 pocket of 2 allelic variants of HLA-DRs. The purpose was to investigate the suitability of adamantyl compounds as MLEs at the dimorphic β86 position. Docking studies revealed that besides numerous molecular interactions formed by the adamantyl compounds, Asnβ82, Tyrβ83, and Thrβ90 are the crucial amino acid residues that are characterized as the "sensors" of peptide loading. Molecular dynamics simulation studies exposed the dynamical structural changes that HLA-DRs adopted as a response to binding of 3-(1-adamantyl)-5-hydrazidocarbonyl-1H-pyrazole (AdCaPy). The conformations of AdCaPy complexed with the Glyβ86 HLA-DR allelic variant are well correlated with the stabilized form of peptide-loaded HLA-DRs, further confirming the role of AdCaPy as a MLE. Hydrogen bonding interaction analysis clearly demonstrated that after making suitable contacts with AdCaPy, HLA-DR changes its local conformation. However, AdCaPy complexed with HLA-DR having Valβ86 at the dimorphic position did not accommodate AdCaPy as MLE due to steric hindrance caused by the valine.

Fully automatic GBM segmentation in the TCGA-GBM dataset: Prognosis and correlation with VASARI features.

PubMed

Rios Velazquez, Emmanuel; Meier, Raphael; Dunn, William D; Alexander, Brian; Wiest, Roland; Bauer, Stefan; Gutman, David A; Reyes, Mauricio; Aerts, Hugo J W L

2015-11-18

Reproducible definition and quantification of imaging biomarkers is essential. We evaluated a fully automatic MR-based segmentation method by comparing it to manually defined sub-volumes by experienced radiologists in the TCGA-GBM dataset, in terms of sub-volume prognosis and association with VASARI features. MRI sets of 109 GBM patients were downloaded from the Cancer Imaging archive. GBM sub-compartments were defined manually and automatically using the Brain Tumor Image Analysis (BraTumIA). Spearman's correlation was used to evaluate the agreement with VASARI features. Prognostic significance was assessed using the C-index. Auto-segmented sub-volumes showed moderate to high agreement with manually delineated volumes (range (r): 0.4 - 0.86). Also, the auto and manual volumes showed similar correlation with VASARI features (auto r = 0.35, 0.43 and 0.36; manual r = 0.17, 0.67, 0.41, for contrast-enhancing, necrosis and edema, respectively). The auto-segmented contrast-enhancing volume and post-contrast abnormal volume showed the highest AUC (0.66, CI: 0.55-0.77 and 0.65, CI: 0.54-0.76), comparable to manually defined volumes (0.64, CI: 0.53-0.75 and 0.63, CI: 0.52-0.74, respectively). BraTumIA and manual tumor sub-compartments showed comparable performance in terms of prognosis and correlation with VASARI features. This method can enable more reproducible definition and quantification of imaging based biomarkers and has potential in high-throughput medical imaging research.

Long noncoding RNA CYTOR in cancer: A TCGA data review.

PubMed

Liang, Jiayu; Wei, Xin; Liu, Zhihong; Cao, Dehong; Tang, Yongquan; Zou, Zijun; Zhou, Chuan; Lu, Yiping

2018-08-01

Increasing evidence has shown the critical role of long non-coding RNA cytoskeleton regulator (CYTOR) in cancers. The expression of CYTOR is reported to be up-regulated in many kinds of cancers, such as gastric cancer, hepatocellular carcinoma, colon cancer, lung adenocarcinoma, oesophageal squamous cell carcinoma and renal cell carcinoma. Here, we summarized related studies and performed a meta-analysis to investigate the prognostic value of CYTOR in multiple cancers. Eligible studies were retrieved from PubMed, Embase and Cochrane Library databases, and the role of CYTOR in cancers was evaluated by pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs). The results were further validated using The Cancer Genome Atlas (TCGA) dataset. Our results showed that elevated CYTOR expression was significantly associated with poor prognosis in cancer patients (overall survival, HR = 2.03, 95% CI = 1.73-2.38, P < 0.00001). In addition, increased CYTOR expression is associated with lymph node metastasis (OR = 2.76, 95% CI = 1.28-5.95, P = 0.01), advanced TNM stage (OR = 2.23, 95% CI = 1.48-3.38, P = 0.001) and higher tumour grade (OR = 1.54, 95% CI = 1.03-2.29, P = 0.04). Overall, this study indicates that CYTOR may serve as a prognostic biomarker for cancer patients during the follow-up. Copyright © 2018 Elsevier B.V. All rights reserved.

Role of miR-1 expression in clear cell renal cell carcinoma (ccRCC): A bioinformatics study based on GEO, ArrayExpress microarrays and TCGA database.

PubMed

Yan, Hai-Biao; Huang, Jia-Cheng; Chen, You-Rong; Yao, Jian-Ni; Cen, Wei-Ning; Li, Jia-Yi; Jiang, Yi-Fan; Chen, Gang; Li, Sheng-Hua

2018-02-01

To investigate the clinical value and potential molecular mechanisms of miR-1 in clear cell renal cell carcinoma (ccRCC). We searched the Gene Expression Omnibus (GEO), ArrayExpress, several online publication databases and the Cancer Genome Atlas (TCGA). Continuous variable meta-analysis and diagnostic meta-analysis were conducted, both in Stata 14, to show the expression of miR-1 in ccRCC. Furthermore, we acquired the potential targets of miR-1 from datasets that transfected miR-1 into ccRCC cells, online prediction databases, differentially expressed genes from TCGA and literature. Subsequently bioinformatics analysis based on aforementioned selected target genes was conducted. The combined effect was -0.92 with the 95% confidence interval (CI) of -1.08 to -0.77 based on fixed effect model (I 2  = 81.3%, P < 0.001). No publication bias was found in our investigation. Sensitivity analysis showed that GSE47582 and 2 TCGA studies might cause heterogeneity. After eliminating them, the combined effect was -0.47 (95%CI: -0.78, -0.16) with I 2  = 18.3%. As for the diagnostic meta-analysis, the combined sensitivity and specificity were 0.90 (95%CI: 0.61, 0.98) and 0.63 (95%CI: 0.39, 0.82). The area under the curve (AUC) in the summarized receiver operating characteristic (SROC) curve was 0.83 (95%CI: 0.80, 0.86). No publication bias was found (P = 0.15). We finally got 67 genes which were defined the promising target genes of miR-1 in ccRCC. The most three significant KEGG pathways based on the aforementioned genes were Complement and coagulation cascades, ECM-receptor interaction and Focal adhesion. The downregulation of miR-1 might play an important role in ccRCC by targeting its target genes. Copyright © 2017 Elsevier GmbH. All rights reserved.

Matching on the Disease Risk Score in Comparative Effectiveness Research of New Treatments

PubMed Central

Wyss, Richard; Ellis, Alan R.; Brookhart, M. Alan; Funk, Michele Jonsson; Girman, Cynthia J.; Simpson, Ross J.; Stürmer, Til

2016-01-01

Purpose We use simulations and an empirical example to evaluate the performance of disease risk score (DRS) matching compared with propensity score (PS) matching when controlling large numbers of covariates in settings involving newly introduced treatments. Methods We simulated a dichotomous treatment, a dichotomous outcome, and 100 baseline covariates that included both continuous and dichotomous random variables. For the empirical example, we evaluated the comparative effectiveness of dabigatran versus warfarin in preventing combined ischemic stroke and all-cause mortality. We matched treatment groups on a historically estimated DRS and again on the PS. We controlled for a high-dimensional set of covariates using 20% and 1% samples of Medicare claims data from October 2010 through December 2012. Results In simulations, matching on the DRS versus the PS generally yielded matches for more treated individuals and improved precision of the effect estimate. For the empirical example, PS and DRS matching in the 20% sample resulted in similar hazard ratios (0.88 and 0.87) and standard errors (0.04 for both methods). In the 1% sample, PS matching resulted in matches for only 92.0% of the treated population and a hazard ratio and standard error of 0.89 and 0.19, respectively, while DRS matching resulted in matches for 98.5% and a hazard ratio and standard error of 0.85 and 0.16, respectively. Conclusions When PS distributions are separated, DRS matching can improve the precision of effect estimates and allow researchers to evaluate the treatment effect in a larger proportion of the treated population. However, accurately modeling the DRS can be challenging compared with the PS. PMID:26112690

Matching on the disease risk score in comparative effectiveness research of new treatments.

PubMed

Wyss, Richard; Ellis, Alan R; Brookhart, M Alan; Jonsson Funk, Michele; Girman, Cynthia J; Simpson, Ross J; Stürmer, Til

2015-09-01

We use simulations and an empirical example to evaluate the performance of disease risk score (DRS) matching compared with propensity score (PS) matching when controlling large numbers of covariates in settings involving newly introduced treatments. We simulated a dichotomous treatment, a dichotomous outcome, and 100 baseline covariates that included both continuous and dichotomous random variables. For the empirical example, we evaluated the comparative effectiveness of dabigatran versus warfarin in preventing combined ischemic stroke and all-cause mortality. We matched treatment groups on a historically estimated DRS and again on the PS. We controlled for a high-dimensional set of covariates using 20% and 1% samples of Medicare claims data from October 2010 through December 2012. In simulations, matching on the DRS versus the PS generally yielded matches for more treated individuals and improved precision of the effect estimate. For the empirical example, PS and DRS matching in the 20% sample resulted in similar hazard ratios (0.88 and 0.87) and standard errors (0.04 for both methods). In the 1% sample, PS matching resulted in matches for only 92.0% of the treated population and a hazard ratio and standard error of 0.89 and 0.19, respectively, while DRS matching resulted in matches for 98.5% and a hazard ratio and standard error of 0.85 and 0.16, respectively. When PS distributions are separated, DRS matching can improve the precision of effect estimates and allow researchers to evaluate the treatment effect in a larger proportion of the treated population. However, accurately modeling the DRS can be challenging compared with the PS. Copyright © 2015 John Wiley & Sons, Ltd.

Overexpression of LncRNA HOTAIR is Associated with Poor Prognosis in Thyroid Carcinoma: A Study Based on TCGA and GEO Data.

PubMed

Li, Hong-Mei; Yang, Hong; Wen, Dong-Yue; Luo, Yi-Huan; Liang, Chun-Yan; Pan, Deng-Hua; Ma, Wei; Chen, Gang; He, Yun; Chen, Jun-Qiang

2017-05-01

The role of long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) in thyroid carcinoma (TC) remains unclear. The current study was aimed to assess the clinical value of HOTAIR expression levels in TC based on publically available data and to evaluate its potential signaling pathways. The expression data of HOTAIR and clinical information concerning TC were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. Furthermore, 3 online biological databases, Starbase, Cbioportal, and Multi Experiment Matrix, were used to identify HOTAIR-related genes in TC. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Panther pathway analyses were then undertaken to study the most enriched signaling pathways in TC (EASE score<0.1, Bonferroni<0.05). The TCGA results demonstrated that the expression level of HOTAIR in TC tissues was significantly increased compared with non-cancerous tissues (p<0.001). HOTAIR over-expression was significantly associated with poor survival in TC patients (p=0.03). Meta-analyses of GEO datasets revealed a trend consistent with the above results on HOTAIR expression levels in TC (SMD=0.23; 95%CI, 0.00-0.45; p=0.047). Finally, the results of functional analysis for HOTAIR-related genes indicated that HOTAIR might participate in tumorigenesis via the Wnt signaling pathway. In conclusion, our study demonstrates that HOTAIR may be involved in thyroid carcinogenesis, and the over-expression of HOTAIR could act as a biomarker associated with a poor outcome in TC patients. Moreover, the Wnt signaling pathway may be the key pathway regulated by HOTAIR in TC. © Georg Thieme Verlag KG Stuttgart · New York.

NCI Expands Repository of Cancer Research Models

Cancer.gov

NCI is expanding its Patient-Derived Models Repository (PDMR), which generates and distributes models like patient-derived xenografts and organoids. In this Cancer Currents Q&A with Drs. Yvonne Evrard and James Doroshow, learn how the expansion can help cancer researchers make more rapid progress.

Study reveals potentially prognostic gene, metabolism changes in kidney cancers | Center for Cancer Research

Cancer.gov

The Cancer Genome Atlas Research Network investigators, including CCR scientists, identified genetic and metabolic pathway changes linked to reduced survival of patients within and across subtypes of renal cell carcinoma (RCC), a type of kidney cancer. The study, published April 5, 2018, in Cell Reports, is part of The Cancer Genome Atlas (TCGA) Program, a joint effort of the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI).

Probing the electronic structure and photoactivation process of nitrogen-doped TiO2 using DRS, PL, and EPR.

PubMed

Zhang, Zizhong; Long, Jinlin; Xie, Xiuqiang; Lin, Huan; Zhou, Yangen; Yuan, Rusheng; Dai, Wenxin; Ding, Zhengxin; Wang, Xuxu; Fu, Xianzhi

2012-04-23

The electronic structure and photoactivation process in N-doped TiO(2) is investigated. Diffuse reflectance spectroscopy (DRS), photoluminescence (PL), and electron paramagnetic resonance (EPR) are employed to monitor the change of optical absorption ability and the formation of N species and defects in the heat- and photoinduced N-doped TiO(2) catalyst. Under thermal treatment below 573 K in vacuum, no nitrogen dopant is removed from the doped samples but oxygen vacancies and Ti(3+) states are formed to enhance the optical absorption in the visible-light region, especially at wavelengths above 500 nm with increasing temperature. In the photoactivation processes of N-doped TiO(2), the DRS absorption and PL emission in the visible spectral region of 450-700 nm increase with prolonged irradiation time. The EPR results reveal that paramagnetic nitrogen species (N(s)·, oxygen vacancies with one electron (V(o)·), and Ti(3+) ions are produced with light irradiation and the intensity of N(s)· species is dependent on the excitation light wavelength and power. The combined characterization results confirm that the energy level of doped N species is localized above the valence band of TiO(2) corresponding to the main absorption band at 410 nm of N-doped TiO(2), but oxygen vacancies and Ti(3+) states as defects contribute to the visible-light absorption above 500 nm in the overall absorption of the doped samples. Thus, a detailed picture of the electronic structure of N-doped TiO(2) is proposed and discussed. On the other hand, the transfer of charge carriers between nitrogen species and defects is reversible on the catalyst surface. The presence of oxygen-vacancy-related defects leads to quenching of paramagnetic N(s)· species but they stabilize the active nitrogen species N(s)(-). Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Study reveals potentially prognostic gene, metabolism changes in kidney cancers | Center for Cancer Research

Cancer.gov

The Cancer Genome Atlas Research Network investigators, including CCR scientists, identified genetic and metabolic pathway changes linked to reduced survival of patients within and across subtypes of renal cell carcinoma (RCC), a type of kidney cancer. The study, published April 5, 2018, in Cell Reports, is part of The Cancer Genome Atlas (TCGA) Program, a joint effort of the

A physician faces her own ovarian cancer | Center for Cancer Research

Cancer.gov

Drs. Tracie Miller and Steve Lipshultz have spent their careers caring for pediatric patients and conducting research at well-known medical institutions across the country. In some ways, those years of providing patient care and conducting medical research prepared the couple for Tracie’s ovarian cancer diagnosis, and in other ways, it didn’t.

Symptom profile and etiology of delirium in a referral population in northern india: factor analysis of the DRS-R98.

PubMed

Mattoo, Surendra K; Grover, Sandeep; Chakravarty, Kaustav; Trzepacz, Paula T; Meagher, David J; Gupta, Nitin

2012-01-01

Delirium is understudied in developing countries, where there tends to be a lower proportion of older persons and comorbid dementia. The authors assessed 100 consecutive cases of DSM-IV delirium (patients' mean age: 44.4 [standard deviation: 19.4] years; mean DRS-R98 score: 25.6 [3.6]) referred to an adult Consultation-Liaison Psychiatry service in Northern India. Disturbances of attention, orientation, visuospatial ability, and sleep disturbance were the most frequent symptoms, followed by language, thought-process abnormality, and motor agitation. A three-factor solution was identified, representing domains for cognition, higher-order thinking, and circadian rhythm/psychosis. These domains can guide studies addressing the relationship between symptom profile, therapeutic needs, and outcomes and are consistent with core domains previously identified in other countries.

Molecular heterogeneity at the network level: high-dimensional testing, clustering and a TCGA case study.

PubMed

Städler, Nicolas; Dondelinger, Frank; Hill, Steven M; Akbani, Rehan; Lu, Yiling; Mills, Gordon B; Mukherjee, Sach

2017-09-15

Molecular pathways and networks play a key role in basic and disease biology. An emerging notion is that networks encoding patterns of molecular interplay may themselves differ between contexts, such as cell type, tissue or disease (sub)type. However, while statistical testing of differences in mean expression levels has been extensively studied, testing of network differences remains challenging. Furthermore, since network differences could provide important and biologically interpretable information to identify molecular subgroups, there is a need to consider the unsupervised task of learning subgroups and networks that define them. This is a nontrivial clustering problem, with neither subgroups nor subgroup-specific networks known at the outset. We leverage recent ideas from high-dimensional statistics for testing and clustering in the network biology setting. The methods we describe can be applied directly to most continuous molecular measurements and networks do not need to be specified beforehand. We illustrate the ideas and methods in a case study using protein data from The Cancer Genome Atlas (TCGA). This provides evidence that patterns of interplay between signalling proteins differ significantly between cancer types. Furthermore, we show how the proposed approaches can be used to learn subtypes and the molecular networks that define them. As the Bioconductor package nethet. staedler.n@gmail.com or sach.mukherjee@dzne.de. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

[Implications of TCGA Network Data on 2nd Generation Immunotherapy Concepts Based on PD-L1 and PD-1 Target Structures].

PubMed

Peters, I; Tezval, H; Kramer, M W; Wolters, M; Grünwald, V; Kuczyk, M A; Serth, J

2015-11-01

The era of cytokines, given to patients with metastatic renal cell carcinoma (mRCC) as part of an unspecific immunomodulatory treatment concept, seems to have ended with the introduction of targeted therapies. However, preliminary data from studies on treatment with checkpoint inhibitors (e. g. anti-PD-1 and anti-PD-L1) may point the way to second-generation immunotherapy. The rationale of such immunomodulatory treatment is to stop or interrupt the tumour from "escaping" the body's immune defence. Thompson et al. report that increased protein expression of PD-L1 (CD274/ B7-H1) in tumour cells and tumour-infiltrating immune cells (TILs; lymphocytes and histiocytes) is associated with unfavourable clinical pathological parameters as well as poor survival. In small pilot groups of mRCC patients it was found that increased PD-L1 protein expression in tumours and TILs may be correlated with the objective response to anti-PD-1 treatment. Sometimes, however, a very wide variety of response rates was observed, which raises the question if this can be explained by individual expression levels of PD-L1 (CD 274) or PD-1 (PDCD1).Recently published data from the Cancer Genome Atlas (TCGA) Kidney Renal Clear Cell Carcinoma (KIRC) Network now provide a genome-wide data base that allows us to review or validate the molecular results obtained in clear cell renal cell carcinomas (ccRCC) to date.In this study, we analysed the TCGA KIRC mRNA expression data for PD-L1 and PD-1 for a possible association with clinical pathological parameters and the survival of 417 ccRCC patients.The mRNA expression of PD-L1 in primary nephrectomy specimens revealed no significant association with unfavourable clinical parameters. Interestingly, though, a positive correlation with patient survival was found (HR=0,59, p=0,006).These results, which partly contradict the concept applied to date, point out the necessity to ascertain the characteristics of PD-L1 and PD-1 expression at mRNA and protein

Research on the Technology of Item Writing.

DTIC Science & Technology

1979-06-01

research contract, Drs. Roid and Haladyna were . invited by Academic Press towrite a book intended for educational research- ers on the technology of...STATE SYSTEM OF HIGHER EDUCATION MONMOUTH UNCLSSIFED 6 ROWD ET AL. JUN 79 MDA983-77-C-O9 FG /2 N ;1.3 ~~ 10 1 Z:1.0 °°11U 11111.25 ,.1. :: liii...11111--- 1111- ~MICROCOPY RESOLUTION TEST CHART NATIONAL BUR[AU OF STANDARDS i96 A %* 9 "... ;- .. RESEARCH ON THE TECHNOLOGY OF ITEM WRITING 0 Gale Roid

Hypervelocity Expansion Facility for Fundamental High-Enthalpy Research

DTIC Science & Technology

2017-02-27

RESEARCH Submitted by Drs. R. Bowersox,1 E. White1 and S. North2 E. Marcotte,1 G. Aguilar,1 A. Pages1 1Aerospace Engineering and 2Chemistry...bowersox@tamu.edu (979) 845-4184 710 HRBB, 3141-TAMU Texas A&M University College Station, TX 77843 To Dr. Knox T. Millsaps Director...Office of Naval Research (ONR) 875 N. Randolph Street, Suite 1425 Arlington, VA 22203-1995 Feb 27, 2017 2 ABSTRACT The objective for

Photodetector timing research at Fermilab

DOE PAGES

Ramberg, E.; Ronzhin, A.; Albrow, M.; ...

2011-01-01

We describe here the outlines of research undertaken by Fermilab into timing characteristics of photodetectors. We describe our experimental method and give benchtop results on the timing resolution of micro-channel plate photomultipliers (MCP-PMT) and silicon photomultipliers (SiPM). In addition, we describe results of various configurations of these detectors, along with quartz radiators, in particle test beams at Fermilab. Results for timing of scintillator light using the DRS4 high speed digitizer are also presented.

Neil Hayes, M.D., M.P.H., Explains TCGA Findings on GBM Subtypes - TCGA

Cancer.gov

New findings by researchers at UNC Lineberger Comprehensive Cancer Center suggest that the most common form of malignant brain cancer in adults, glioblastoma multiforme (GBM), is probably not a single disease but a set of diseases, each with a distinct underlying molecular disease process. The study was published by Cell Press in the January issue of the journal Cancer Cell and the researchers are part of the The Cancer Genome Atlas.

Compassion and Curiosity - TCGA

Cancer.gov

William Kim, M.D., is motivated by two things: compassion and curiosity. Dr. Kim has taken these dual motivations and created a career in which he cares directly for patients and spearheads research that may lead to improved treatment options.

Integrated Cancer Research in Five Thematic Areas in Interest

DTIC Science & Technology

2005-07-01

Professor of Urology (on-going RSU), Howard Crawford, PhD, Assistant Professor of Pharmacological Sciences (on-going RSU), Marjana Maletic- Savatic ...young scientists. Drs. Adler, Crawford, Maletic- Savatic received base support from this mechanism as they further develop their research programs...Mirjana Maletic- Savatic , MD-PhD, Assistant Professor Neurology: Human Neural Stem Cells - In Vivo Models for Cerebral Carcinoma The study of human

[Research progress in molecular classification of gastric cancer].

PubMed

Zhou, Menglong; Li, Guichao; Zhang, Zhen

2016-09-25

Gastric cancer(GC) is a highly heterogeneous malignancy. The present widely used histopathological classifications have gradually failed to meet the needs of individualized diagnosis and treatment. Development of technologies such as microarray and next-generation sequencing (NGS) has allowed GC to be studied at the molecular level. Mechanisms about tumorigenesis and progression of GC can be elucidated in the aspects of gene mutations, chromosomal alterations, transcriptional and epigenetic changes, on the basis of which GC can be divided into several subtypes. The classifications of Tan's, Lei's, TCGA and ACRG are relatively comprehensive. Especially the TCGA and ACRG classifications have large sample size and abundant molecular profiling data, thus, the genomic characteristics of GC can be depicted more accurately. However, significant differences between both classifications still exist so that they cannot be substituted for each other. So far there is no widely accepted molecular classification of GC. Compared with TCGA classification, ACRG system may have more clinical significance in Chinese GC patients since the samples are mostly from Asian population and show better association with prognosis. The molecular classification of GC may provide the theoretical and experimental basis for early diagnosis, therapeutic efficacy prediction and treatment stratification while their clinical application is still limited. Future work should involve the application of molecular classifications in the clinical settings for improving the medical management of GC.

Stages of Se adsorption on Au(111): A combined XPS, LEED, TOF-DRS, and DFT study

NASA Astrophysics Data System (ADS)

Ruano, G.; Tosi, E.; Sanchez, E.; Abufager, P.; Martiarena, M. L.; Grizzi, O.; Zampieri, G.

2017-08-01

We have studied the adsorption of Se on the surface Au(111) using XPS, TOF-DRS, LEED and DFT calculations. The use of a doser that operates in vacuum allowed us to investigate all the stages of the adsorption from the clean surface up to the formation of multilayers. In the monolayer regime we have found two ordered phases with distinctive LEED patterns. The LEED pattern of the first phase presents three fractional spots arranged symmetrically around the positions of the spots in a √3x√3 pattern. The analysis of this pattern suggests the formation of either a nxn superstructure of √3x√3 domains with n=19 or n=22, or that the adsorption occurs without removing the 22x√3 herringbone reconstruction of the gold surface. This last possibility is in accordance with DFT calculations which show that the charge transfer to a Se adsorbate might not be enough to destabilize the surface reconstruction. Increasing the coverage, beyond 0.3 ML a new LEED pattern appears with broad spots which upon annealing at 150 °C become well defined indicating a 1×8 periodicity. At the highest doses we have observed the formation of multilayers with no discernible LEED pattern. The comparison with adsorption experiments carried out in liquid solutions show similarities and also some important differences.

Disease risk score as a confounder summary method: systematic review and recommendations.

PubMed

Tadrous, Mina; Gagne, Joshua J; Stürmer, Til; Cadarette, Suzanne M

2013-02-01

To systematically examine trends and applications of the disease risk score (DRS) as a confounder summary method. We completed a systematic search of MEDLINE and Web of Science® to identify all English language articles that applied DRS methods. We tabulated the number of publications by year and type (empirical application, methodological contribution, or review paper) and summarized methods used in empirical applications overall and by publication year (<2000, ≥2000). Of 714 unique articles identified, 97 examined DRS methods and 86 were empirical applications. We observed a bimodal distribution in the number of publications over time, with a peak 1979-1980, and resurgence since 2000. The majority of applications with methodological detail derived DRS using logistic regression (47%), used DRS as a categorical variable in regression (93%), and applied DRS in a non-experimental cohort (47%) or case-control (42%) study. Few studies examined effect modification by outcome risk (23%). Use of DRS methods has increased yet remains low. Comparative effectiveness research may benefit from more DRS applications, particularly to examine effect modification by outcome risk. Standardized terminology may facilitate identification, application, and comprehension of DRS methods. More research is needed to support the application of DRS methods, particularly in case-control studies. Copyright © 2012 John Wiley & Sons, Ltd.

UCSC Xena | Informatics Technology for Cancer Research (ITCR)

Cancer.gov

UCSC Xena securely analyzes and visualizes your private functional genomics data set in the context of public and shared genomic/phenotypic data sets such as TCGA, ICGC, TARGET, GTEx, and GA4GH (TOIL).

[Food industry funding and epidemiologic research in public health nutrition].

PubMed

Navarrete-Muñoz, Eva María; Tardón, Adonina; Romaguera, Dora; Martínez-González, Miguel Ángel; Vioque, Jesús

The interests of the food industry to fund nutrition and health research are not limited to promoting scientific advances. Recently, several systematic reviews conducted about the effect of sugar-sweetened beverages and health outcomes have shown some biased conclusions in studies that acknowledge industry sponsorship. In this context, the Nutrition Working Group of the Spanish Epidemiology Society presented a scientific session entitled Food industry and epidemiologic research at its annual meeting. In a round table, four experts in nutrition research presented their points of view about whether the food industry should fund nutrition-related research and the related potential conflicts of interest of the food industry. All the experts agreed not only on defending independence in nutritional epidemiology regarding the design, interpretation and conclusion of their studies but also on the crucial need for guaranteed scientific rigor, scientific quality of the results and measures to protect studies against potential biases related to the conflicts of interest of funding by the food industry. Drs Pérez-Farinós and Romaguera believe that the most effective way to prevent conflicts of interest would be not to allow the food industry to fund nutrition research; Drs Marcos and Martínez-González suggested the need to establish mechanisms and strategies to prevent the potential influences of the food industry in selecting researchers or institutional sponsorship and in the analysis and results of the studies, to ensure maximum independence for researchers, as well as their professional ethics. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

Viral expression associated with gastrointestinal adenocarcinomas in TCGA high-throughput sequencing data

PubMed Central

2013-01-01

Background Up to 20% of cancers worldwide are thought to be associated with microbial pathogens, including bacteria and viruses. The widely used methods of viral infection detection are usually limited to a few a priori suspected viruses in one cancer type. To our knowledge, there have not been many broad screening approaches to address this problem more comprehensively. Methods In this study, we performed a comprehensive screening for viruses in nine common cancers using a multistep computational approach. Tumor transcriptome and genome sequencing data were available from The Cancer Genome Atlas (TCGA). Nine hundred fifty eight primary tumors in nine common cancers with poor prognosis were screened against a non-redundant database of virus sequences. DNA sequences from normal matched tissue specimens were used as controls to test whether each virus is associated with tumors. Results We identified human papilloma virus type 18 (HPV-18) and four human herpes viruses (HHV) types 4, 5, 6B, and 8, also known as EBV, CMV, roseola virus, and KSHV, in colon, rectal, and stomach adenocarcinomas. In total, 59% of screened gastrointestinal adenocarcinomas (GIA) were positive for at least one virus: 26% for EBV, 21% for CMV, 7% for HHV-6B, and 20% for HPV-18. Over 20% of tumors were co-infected with multiple viruses. Two viruses (EBV and CMV) were statistically significantly associated with colorectal cancers when compared to the matched healthy tissues from the same individuals (p = 0.02 and 0.03, respectively). HPV-18 was not detected in DNA, and thus, no association testing was possible. Nevertheless, HPV-18 expression patterns suggest viral integration in the host genome, consistent with the potentially oncogenic nature of HPV-18 in colorectal adenocarcinomas. The estimated counts of viral copies were below one per cell for all identified viruses and approached the detection limit. Conclusions Our comprehensive screening for viruses in multiple cancer types using next

TU-AB-BRA-11: Evaluation of Fully Automatic Volumetric GBM Segmentation in the TCGA-GBM Dataset: Prognosis and Correlation with VASARI Features

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rios Velazquez, E; Meier, R; Dunn, W

Purpose: Reproducible definition and quantification of imaging biomarkers is essential. We evaluated a fully automatic MR-based segmentation method by comparing it to manually defined sub-volumes by experienced radiologists in the TCGA-GBM dataset, in terms of sub-volume prognosis and association with VASARI features. Methods: MRI sets of 67 GBM patients were downloaded from the Cancer Imaging archive. GBM sub-compartments were defined manually and automatically using the Brain Tumor Image Analysis (BraTumIA), including necrosis, edema, contrast enhancing and non-enhancing tumor. Spearman’s correlation was used to evaluate the agreement with VASARI features. Prognostic significance was assessed using the C-index. Results: Auto-segmented sub-volumes showedmore » high agreement with manually delineated volumes (range (r): 0.65 – 0.91). Also showed higher correlation with VASARI features (auto r = 0.35, 0.60 and 0.59; manual r = 0.29, 0.50, 0.43, for contrast-enhancing, necrosis and edema, respectively). The contrast-enhancing volume and post-contrast abnormal volume showed the highest C-index (0.73 and 0.72), comparable to manually defined volumes (p = 0.22 and p = 0.07, respectively). The non-enhancing region defined by BraTumIA showed a significantly higher prognostic value (CI = 0.71) than the edema (CI = 0.60), both of which could not be distinguished by manual delineation. Conclusion: BraTumIA tumor sub-compartments showed higher correlation with VASARI data, and equivalent performance in terms of prognosis compared to manual sub-volumes. This method can enable more reproducible definition and quantification of imaging based biomarkers and has a large potential in high-throughput medical imaging research.« less

Cancer in silico drug discovery: a systems biology tool for identifying candidate drugs to target specific molecular tumor subtypes.

PubMed

San Lucas, F Anthony; Fowler, Jerry; Chang, Kyle; Kopetz, Scott; Vilar, Eduardo; Scheet, Paul

2014-12-01

Large-scale cancer datasets such as The Cancer Genome Atlas (TCGA) allow researchers to profile tumors based on a wide range of clinical and molecular characteristics. Subsequently, TCGA-derived gene expression profiles can be analyzed with the Connectivity Map (CMap) to find candidate drugs to target tumors with specific clinical phenotypes or molecular characteristics. This represents a powerful computational approach for candidate drug identification, but due to the complexity of TCGA and technology differences between CMap and TCGA experiments, such analyses are challenging to conduct and reproduce. We present Cancer in silico Drug Discovery (CiDD; scheet.org/software), a computational drug discovery platform that addresses these challenges. CiDD integrates data from TCGA, CMap, and Cancer Cell Line Encyclopedia (CCLE) to perform computational drug discovery experiments, generating hypotheses for the following three general problems: (i) determining whether specific clinical phenotypes or molecular characteristics are associated with unique gene expression signatures; (ii) finding candidate drugs to repress these expression signatures; and (iii) identifying cell lines that resemble the tumors being studied for subsequent in vitro experiments. The primary input to CiDD is a clinical or molecular characteristic. The output is a biologically annotated list of candidate drugs and a list of cell lines for in vitro experimentation. We applied CiDD to identify candidate drugs to treat colorectal cancers harboring mutations in BRAF. CiDD identified EGFR and proteasome inhibitors, while proposing five cell lines for in vitro testing. CiDD facilitates phenotype-driven, systematic drug discovery based on clinical and molecular data from TCGA. ©2014 American Association for Cancer Research.

TCGA Third Annual Scientific Symposium - TCGA

Cancer.gov

Monday, May 12 - Tuesday, May 13, 2014 National Institutes of Health, Bethesda, Md. This open scientific meeting will consist of collaborative workshops, poster sessions, and plenary sessions. Registration is now open.

Further Confirmation of Germline Glioma Risk Variant rs78378222 in TP53 and Its Implication in Tumor Tissues via Integrative Analysis of TCGA Data

PubMed Central

Wang, Zhaoming; Rajaraman, Preetha; Melin, Beatrice S.; Chung, Charles C.; Zhang, Weijia; McKean-Cowdin, Roberta; Michaud, Dominique; Yeager, Meredith; Ahlbom, Anders; Albanes, Demetrius; Andersson, Ulrika; Beane Freeman, Laura E.; Buring, Julie E.; Butler, Mary Ann; Carreón, Tania; Feychting, Maria; Gapstur, Susan M.; Gaziano, J. Michael; Giles, Graham G.; Hallmans, Goran; Henriksson, Roger; Hoffman-Bolton, Judith; Inskip, Peter D.; Kitahara, Cari M.; Le Marchand, Loic; Linet, Martha S.; Li, Shengchao; Peters, Ulrike; Purdue, Mark P.; Rothman, Nathaniel; Ruder, Avima M.; Sesso, Howard D.; Severi, Gianluca; Stampfer, Meir; Stevens, Victoria L.; Visvanathan, Kala; Wang, Sophia S.; White, Emily; Zeleniuch-Jacquotte, Anne; Hoover, Robert; Fraumeni, Joseph F.; Chatterjee, Nilanjan; Hartge, Patricia; Chanock, Stephen J.

2016-01-01

We confirmed strong association of rs78378222:A>C (per allele odds ratio [OR] = 3.14; P = 6.48 × 10−11), a germline rare single-nucleotide polymorphism (SNP) in TP53, via imputation of a genome-wide association study of glioma (1,856 cases and 4,955 controls). We subsequently performed integrative analyses on the Cancer Genome Atlas (TCGA) data for GBM (glioblastoma multiforme) and LUAD (lung adenocarcinoma). Based on SNP data, we imputed genotypes for rs78378222 and selected individuals carrying rare risk allele (C). Using RNA sequencing data, we observed aberrant transcripts with ~3 kb longer than normal for those individuals. Using exome sequencing data, we further showed that loss of haplotype carrying common protective allele (A) occurred somatically in GBM but not in LUAD. Our bioinformatic analysis suggests rare risk allele (C) disrupts mRNA termination, and an allelic loss of a genomic region harboring common protective allele (A) occurs during tumor initiation or progression for glioma. PMID:25907361

Cancers Selected for Study - TCGA

Cancer.gov

The Cancer Genome Atlas researchers are mapping the genetic changes in 33 cancers. Find out which cancers have been selected for study, the criteria for selection and the scientific questions being asked about each cancer.

Genomic Data Commons launches - TCGA

Cancer.gov

The Genomic Data Commons (GDC), a unified data system that promotes sharing of genomic and clinical data between researchers, launched today with a visit from Vice President Joe Biden to the operations center at the University of Chicago.

QFD-ANP Approach for the Conceptual Design of Research Vessels: A Case Study

NASA Astrophysics Data System (ADS)

Venkata Subbaiah, Kambagowni; Yeshwanth Sai, Koneru; Suresh, Challa

2016-10-01

Conceptual design is a subset of concept art wherein a new idea of product is created instead of a visual representation which would directly be used in a final product. The purpose is to understand the needs of conceptual design which are being used in engineering designs and to clarify the current conceptual design practice. Quality function deployment (QFD) is a customer oriented design approach for developing new or improved products and services to enhance customer satisfaction. House of quality (HOQ) has been traditionally used as planning tool of QFD which translates customer requirements (CRs) into design requirements (DRs). Factor analysis is carried out in order to reduce the CR portions of HOQ. The analytical hierarchical process is employed to obtain the priority ratings of CR's which are used in constructing HOQ. This paper mainly discusses about the conceptual design of an oceanographic research vessel using analytical network process (ANP) technique. Finally the QFD-ANP integrated methodology helps to establish the importance ratings of DRs.

Clinical Value of miR-101-3p and Biological Analysis of its Prospective Targets in Breast Cancer: A Study Based on The Cancer Genome Atlas (TCGA) and Bioinformatics.

PubMed

Li, Chun-Yao; Xiong, Dan-Dan; Huang, Chun-Qin; He, Rong-Quan; Liang, Hai-Wei; Pan, Deng-Hua; Wang, Han-Lin; Wang, Yi-Wen; Zhu, Hua-Wei; Chen, Gang

2017-04-18

BACKGROUND MiR-101-3p can promote apoptosis and inhibit proliferation, invasion, and metastasis in breast cancer (BC) cells. However, its mechanisms in BC are not fully understood. Therefore, a comprehensive analysis of the target genes, pathways, and networks of miR-101-3p in BC is necessary. MATERIAL AND METHODS The miR-101 profiles for 781 patients with BC from The Cancer Genome Atlas (TCGA) were analyzed. Gene expression profiling of GSE31397 with miR-101-3p transfected MCF-7 cells and scramble control cells was downloaded from Gene Expression Omnibus (GEO), and the differentially expressed genes (DEGs) were identified. The potential genes targeted by miR-101-3p were also predicted. Gene Ontology (GO) and pathway and network analyses were constructed for the DEGs and predicted genes. RESULTS In the TCGA data, a low level of miR-101-2 expression might represent a diagnostic (AUC: 0.63) marker, and the miR-101-1 was a prognostic (HR=1.79) marker. MiR-101-1 was linked to the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), and miR-101-2 was associated with the tumor (T), lymph node (N), and metastasis (M) stages of BC. Moreover, 427 genes were selected from the 921 DEGs in GEO and the 7924 potential target genes from the prediction databases. These genes were related to transcription, metabolism, biosynthesis, and proliferation. The results were also significantly enriched in the VEGF, mTOR, focal adhesion, Wnt, and chemokine signaling pathways. CONCLUSIONS MiR-101-1 and miR-101-2 may be prospective biomarkers for the prognosis and diagnosis of BC, respectively, and are associated with diverse clinical parameters. The target genes of miR-101-3p regulate the development and progression of BC. These results provide insight into the pathogenic mechanism and potential therapies for BC.

Clinical research in small genomically stratified patient populations.

PubMed

Martin-Liberal, J; Rodon, J

2017-07-01

The paradigm of early drug development in cancer is shifting from 'histology-oriented' to 'molecularly oriented' clinical trials. This change can be attributed to the vast amount of tumour biology knowledge generated by large international research initiatives such as The Cancer Genome Atlas (TCGA) and the use of next generation sequencing (NGS) techniques developed in recent years. However, targeting infrequent molecular alterations entails a series of special challenges. The optimal molecular profiling method, the lack of standardised biological thresholds, inter- and intra-tumor heterogeneity, availability of enough tumour material, correct clinical trials design, attrition rate, logistics or costs are only some of the issues that need to be taken into consideration in clinical research in small genomically stratified patient populations. This article examines the most relevant challenges inherent to clinical research in these populations. Moreover, perspectives from the Academia point of view are reviewed as well as initiatives to be taken in forthcoming years. Copyright © 2017 Elsevier Ltd. All rights reserved.

Exploratory and Confirmatory Factor Analysis of the Decision Regret Scale in Recipients of Internal Cardioverter Defibrillators

PubMed Central

Hickman, Ronald L.; Pinto, Melissa D.; Lee, Eunsuk; Daly, Barbara J.

2015-01-01

The Decision Regret Scale (DRS) is a five-item instrument that captures an individual’s regret associated with a healthcare decision. Cross-sectional data were collected from 109 cardiac patients who decided to receive an internal cardioverter defibrillator (ICD). Exploratory and confirmatory factor analyses, assessments of the internal reliability consistency (α = .86), and discriminant validity established the DRS as a reliable and valid measure of decision regret in ICD recipients. The DRS, a psychometrically sound instrument, has relevance for clinicians and researchers vested in optimizing the decisional outcomes of ICD recipients. Future research is needed to examine the reliability and validity of the DRS in a larger and more diverse sample of ICD recipients. PMID:22679707

New noninvasive approach assessing in vivo sun protection factor (SPF) using diffuse reflectance spectroscopy (DRS) and in vitro transmission.

PubMed

Ruvolo Junior, Eduardo; Kollias, Nikiforos; Cole, Curtis

2014-08-01

In the past 56 years, many different in vitro methodologies have been developed and published to assess the sun protection factor (SPF) of products, but there is no method that has 1:1 correlation with in vivo measurements. Spectroscopic techniques have been used to noninvasively assess the UVA protection factor with good correlation to in vivo UVA-PF methodologies. To assess the SPF of sunscreen product by diffuse reflectance spectroscopy (DRS) technique, it is necessary to also determine the absorbance spectrum of the test material in the UVB portion of the spectrum (290-320 nm). However, because of the high absorbance characteristics of the stratum corneum and epidermis, the human skin does not remit enough UVB radiation to be used to measure the absorption spectrum of the applied product on skin. In this work, we present a new method combining the evaluation of the absolute UVA absorption spectrum, as measured by DRS with the spectral absorbance 'shape' of the UVB absorbance of the test material as determined with current in vitro thin film spectroscopy. The measurement of the in vivo UVA absorption spectrum involves the assessment of the remitted intensity of monochromatic UVA radiation (320-400 nm) before and after a sunscreen product was applied on skin using a spectrofluorimeter Fluorolog 3, FL3-22 (Yvon Horiba, Edison, NJ, USA). The probe geometry assures that light scattering products as well as colored products may be correctly assessed. This methodology has been extensively tested, validated, and reported in the literature. The in vitro absorption spectrum of the sunscreen samples and polyvinyl chloride (PVC) films 'surrogate' sunscreen standards were measured using Labsphere® UV-2000S (Labsphere, North Sutton, NH, USA). Sunscreens samples were tested using PMMA Helioplates (Helioscience, Marseille, France) as substrates. The UVB absorbance spectrum (Labsphere) is 'attached' to the UVA absorbance spectrum (diffuse reflectance) with the UVB

The BioMedical Evidence Graph (BMEG) | Informatics Technology for Cancer Research (ITCR)

Cancer.gov

The BMEG is a Cancer Data integration Platform that utilizes methods collected from DREAM challenges and applied to large datasets, such as the TCGA, and makes them avalible for analysis using a high performance graph database

Mixed methods research in the development and evaluation of complex interventions in palliative and end-of-life care: report on the MORECare consensus exercise.

PubMed

Farquhar, Morag; Preston, Nancy; Evans, Catherine J; Grande, Gunn; Short, Vicky; Benalia, Hamid; Higginson, Irene J; Todd, Chris

2013-12-01

Complex interventions are common in palliative and end-of-life care. Mixed methods approaches sit well within the multiphase model of complex intervention development and evaluation. Generic mixed methods guidance is useful but additional challenges in the research design and operationalization within palliative and end-of-life care may have an impact on the use of mixed methods. The objective of the study was to develop guidance on the best methods for combining quantitative and qualitative methods for health and social care intervention development and evaluation in palliative and end-of-life care. A one-day workshop was held where experts participated in facilitated groups using Transparent Expert Consultation to generate items for potential recommendations. Agreement and consensus were then sought on nine draft recommendations (DRs) in a follow-up exercise. There was at least moderate agreement with most of the DRs, although consensus was low. Strongest agreement was with DR1 (usefulness of mixed methods to palliative and end-of-life care) and DR5 (importance of attention to respondent burden), and least agreement was with DR2 (use of theoretical perspectives) and DR6 (therapeutic effects of research interviews). Narrative comments enabled recommendation refinement. Two fully endorsed, five partially endorsed, and two refined DRs emerged. The relationship of these nine to six key challenges of palliative and end-of-life care research was analyzed. There is a need for further discussion of these recommendations and their contribution to methodology. The recommendations should be considered when designing and operationalizing mixed methods studies of complex interventions in palliative care, and because they may have wider relevance, should be considered for other applications.

CAS-viewer: web-based tool for splicing-guided integrative analysis of multi-omics cancer data.

PubMed

Han, Seonggyun; Kim, Dongwook; Kim, Youngjun; Choi, Kanghoon; Miller, Jason E; Kim, Dokyoon; Lee, Younghee

2018-04-20

The Cancer Genome Atlas (TCGA) project is a public resource that provides transcriptomic, DNA sequence, methylation, and clinical data for 33 cancer types. Transforming the large size and high complexity of TCGA cancer genome data into integrated knowledge can be useful to promote cancer research. Alternative splicing (AS) is a key regulatory mechanism of genes in human cancer development and in the interaction with epigenetic factors. Therefore, AS-guided integration of existing TCGA data sets will make it easier to gain insight into the genetic architecture of cancer risk and related outcomes. There are already existing tools analyzing and visualizing alternative mRNA splicing patterns for large-scale RNA-seq experiments. However, these existing web-based tools are limited to the analysis of individual TCGA data sets at a time, such as only transcriptomic information. We implemented CAS-viewer (integrative analysis of Cancer genome data based on Alternative Splicing), a web-based tool leveraging multi-cancer omics data from TCGA. It illustrates alternative mRNA splicing patterns along with methylation, miRNAs, and SNPs, and then provides an analysis tool to link differential transcript expression ratio to methylation, miRNA, and splicing regulatory elements for 33 cancer types. Moreover, one can analyze AS patterns with clinical data to identify potential transcripts associated with different survival outcome for each cancer. CAS-viewer is a web-based application for transcript isoform-driven integration of multi-omics data in multiple cancer types and will aid in the visualization and possible discovery of biomarkers for cancer by integrating multi-omics data from TCGA.

TCGA study of genetic drivers of melanoma - TCGA

Cancer.gov

A comprehensive analysis of the genome of cutaneous melanoma has provided new insights into the roles of frequently mutated cancer genes and other genomic alterations that drive the development of this disease.

Diffuse Reflectance Spectroscopy (DRS) of radiation-induced re-oxygenation in sensitive and resistant head and neck tumor xenografts

NASA Astrophysics Data System (ADS)

Dadgar, Sina; Rodríguez Troncoso, Joel; Rajaram, Narasimhan

2018-02-01

Currently, anatomical assessment of tumor volume performed several weeks after completion of treatment is the clinical standard to determine whether a cancer patient has responded to a treatment. However, functional changes within the tumor could potentially provide information regarding treatment resistance or response much earlier than anatomical changes. We have used diffuse reflectance spectroscopy to assess the short and long-term re-oxygenation kinetics of a human head and neck squamous cell carcinoma xenografts in response to radiation therapy. First, we injected UM-SCC-22B cell line into the flank of 50 mice to grow xenografts. Once the tumor volume reached 200 mm3 (designated as Day 1), the mice were distributed into radiation and control groups. Members of radiation group underwent a clinical dose of radiation of 2 Gy/day on Days 1, 4, 7, and 10 for a cumulative dose of 8 Gy. DRS spectra of these tumors were collected for 14 days during and after therapy, and the collected spectra of each tumor were converted to its optical properties using a lookup table-base inverse model. We found statistically significant differences in tumor growth rate between two groups which is in indication of the sensitivity of this cell line to radiation. We further acquired significantly different contents of hemoglobin and scattering magnitude and size in two groups. The scattering has previously been associated with necrosis. We furthermore found significantly different time-dependent changes in vascular oxygenation and tumor hemoglobin concentration in post-radiation days.

Mixed Methods Research in the Development and Evaluation of Complex Interventions in Palliative and End-of-Life Care: Report on the MORECare Consensus Exercise

PubMed Central

Preston, Nancy; Evans, Catherine J.; Grande, Gunn; Short, Vicky; Benalia, Hamid; Higginson, Irene J.; Todd, on behalf of MORECare, Chris

2013-01-01

Abstract Background: Complex interventions are common in palliative and end-of-life care. Mixed methods approaches sit well within the multiphase model of complex intervention development and evaluation. Generic mixed methods guidance is useful but additional challenges in the research design and operationalization within palliative and end-of-life care may have an impact on the use of mixed methods. Objective: The objective of the study was to develop guidance on the best methods for combining quantitative and qualitative methods for health and social care intervention development and evaluation in palliative and end-of-life care. Methods: A one-day workshop was held where experts participated in facilitated groups using Transparent Expert Consultation to generate items for potential recommendations. Agreement and consensus were then sought on nine draft recommendations (DRs) in a follow-up exercise. Results: There was at least moderate agreement with most of the DRs, although consensus was low. Strongest agreement was with DR1 (usefulness of mixed methods to palliative and end-of-life care) and DR5 (importance of attention to respondent burden), and least agreement was with DR2 (use of theoretical perspectives) and DR6 (therapeutic effects of research interviews). Narrative comments enabled recommendation refinement. Two fully endorsed, five partially endorsed, and two refined DRs emerged. The relationship of these nine to six key challenges of palliative and end-of-life care research was analyzed. Conclusions: There is a need for further discussion of these recommendations and their contribution to methodology. The recommendations should be considered when designing and operationalizing mixed methods studies of complex interventions in palliative care, and because they may have wider relevance, should be considered for other applications. PMID:24195755

Infrared Submillimeter and Radio Astronomy Research and Analysis Program

NASA Technical Reports Server (NTRS)

Traub, Wesley A.

2000-01-01

This program entitled "Infrared Submillimeter and Radio Astronomy Research and Analysis Program" with NASA-Ames Research Center (ARC) was proposed by the Smithsonian Astrophysical Observatory (SAO) to cover three years. Due to funding constraints only the first year installment of $18,436 was funded, but this funding was spread out over two years to try to maximize the benefit to the program. During the tenure of this contact, the investigators at the SAO, Drs. Wesley A. Traub and Nathaniel P. Carleton, worked with the investigators at ARC, Drs. Jesse Bregman and Fred Wittebom, on the following three main areas: 1. Rapid scanning SAO and ARC collaborated on purchasing and constructing a Rapid Scan Platform for the delay arm of the Infrared-Optical Telescope Array (IOTA) interferometer on Mt. Hopkins, Arizona. The Rapid Scan Platform was tested and improved by the addition of stiffening plates which eliminated a very small but noticeable bending of the metal platform at the micro-meter level. 2. Star tracking Bregman and Wittebom conducted a study of the IOTA CCD-based star tracker system, by constructing a device to simulate star motion having a specified frequency and amplitude of motion, and by examining the response of the tracker to this simulated star input. 3. Fringe tracking. ARC, and in particular Dr. Robert Mah, developed a fringe-packet tracking algorithm, based on data that Bregman and Witteborn obtained on IOTA. The algorithm was tested in the laboratory at ARC, and found to work well for both strong and weak fringes.

Restoration of bighorn sheep metapopulations in and near 15 national parks: Conservation of severely fragmented species; Volume II, Synopsis of research findings

USGS Publications Warehouse

Singer, Francis J.; Gudorf, Michelle A.

1999-01-01

The research studies were conducted by scientists from the Biological Resources Division of the USGS (fonnerly NBS) (11 research studies), university-based scientists (Univ. of Wyoming- 2 studies, University of Colorado- 1, Colorado State University- 2, University of California, White Mountain Center- 1, Northern Arizona University - 1, Montana State University - 1) and by state agency veterinarians: Drs. Beth Williams of Wyoming, Mike Miller of Colorado, and Terry Spraker of Colorado State University. Only the highlights of these research studies are presented below. Full research reports are available in Volume III of this series.

Cancer systems biology: signal processing for cancer research

PubMed Central

Yli-Harja, Olli; Ylipää, Antti; Nykter, Matti; Zhang, Wei

2011-01-01

In this editorial we introduce the research paradigms of signal processing in the era of systems biology. Signal processing is a field of science traditionally focused on modeling electronic and communications systems, but recently it has turned to biological applications with astounding results. The essence of signal processing is to describe the natural world by mathematical models and then, based on these models, develop efficient computational tools for solving engineering problems. Here, we underline, with examples, the endless possibilities which arise when the battle-hardened tools of engineering are applied to solve the problems that have tormented cancer researchers. Based on this approach, a new field has emerged, called cancer systems biology. Despite its short history, cancer systems biology has already produced several success stories tackling previously impracticable problems. Perhaps most importantly, it has been accepted as an integral part of the major endeavors of cancer research, such as analyzing the genomic and epigenomic data produced by The Cancer Genome Atlas (TCGA) project. Finally, we show that signal processing and cancer research, two fields that are seemingly distant from each other, have merged into a field that is indeed more than the sum of its parts. PMID:21439242

A Most Interesting Man of Science: The Life and Research of Richard Rozzell Fay.

PubMed

Sisneros, Joseph A

2016-01-01

On May 25, 2013, a special symposium was held at the Mote Marine Laboratory in Sarasota, FL to honor the outstanding careers of Drs. Richard R. Fay and Arthur N. Popper, a "dynamic duo" of scientists who were pioneers in the field of contemporary fish hearing and bioacoustics. The present article details the research, academic life, and "other side" of Richard Rozzell Fay, a most interesting man of science who is known to all as a kind, gentle, wise, and introspective scientist.

The Cancer Genome Atlas Clinical Explorer: a web and mobile interface for identifying clinical-genomic driver associations.

PubMed

Lee, HoJoon; Palm, Jennifer; Grimes, Susan M; Ji, Hanlee P

2015-10-27

include clinical stage or smoking history. The Cancer Genome Atlas Clinical Explorer enables the cancer research community and others to explore clinically relevant associations inferred from TCGA data. With its accessible web and mobile interface, users can examine queries and test hypothesis regarding genomic/proteomic alterations across a broad spectrum of malignancies.

A conversation with Drs. Kaplan and Moser about conflicting data, confusing results, and some recent treatment recommendations for the management of hypertension.

PubMed

Post, Wendy; Moser, Marvin; Kaplan, Norman

2005-10-01

Following a hypertension symposium in Baltimore, MD, on June 1, 2005, Dr. Wendy Post from the Johns Hopkins University School of Medicine, Baltimore, MD, had the opportunity to interview two of the outstanding hypertension experts in the United States on several controversial issues in hypertension management. Dr. Norman Kaplan is Clinical Professor of Medicine at the Southwestern Health Science Center in Dallas, TX, and Dr. Marvin Moser is Clinical Professor of Medicine at the Yale University School of Medicine, New Haven, CT. Both have been leaders in the field of hypertension treatment and education for more than 40 years. Dr. Kaplan's book Clinical Hypertension has been a standard textbook since 1973 and is now in its ninth edition. Dr. Marvin Moser was the Senior Medical Consultant to the National High Blood Pressure Education Program from 1974 to 2002 and was Chairman of the first Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure and a member of the six subsequent committees. His book Clinical Management of Hypertension is in its seventh edition. Drs. Moser and Kaplan were corecipients of the 2004 International Society of Hypertension Award for Outstanding Contributions to Hypertension Treatment and Education and have lectured extensively throughout the United States and overseas.

Potential targets for lung squamous cell carcinoma

Cancer.gov

Researchers have identified potential therapeutic targets in lung squamous cell carcinoma, the second most common form of lung cancer. The Cancer Genome Atlas (TCGA) Research Network study comprehensively characterized the lung squamous cell carcinoma gen

Integrative Bioinformatics and Functional Analyses of GEO, ENCODE, and TCGA Reveal FADD as a Direct Target of the Tumor Suppressor BRCA1.

PubMed

Nguyen, Dinh-Duc; Lee, Dong Gyu; Kim, Sinae; Kang, Keunsoo; Rhee, Je-Keun; Chang, Suhwan

2018-05-14

BRCA1 is a multifunctional tumor suppressor involved in several essential cellular processes. Although many of these functions are driven by or related to its transcriptional/epigenetic regulator activity, there has been no genome-wide study to reveal the transcriptional/epigenetic targets of BRCA1. Therefore, we conducted a comprehensive analysis of genomics/transcriptomics data to identify novel BRCA1 target genes. We first analyzed ENCODE data with BRCA1 chromatin immunoprecipitation (ChIP)-sequencing results and identified a set of genes with a promoter occupied by BRCA1. We collected 3085 loci with a BRCA1 ChIP signal from four cell lines and calculated the distance between the loci and the nearest gene transcription start site (TSS). Overall, 66.5% of the BRCA1-bound loci fell into a 2-kb region around the TSS, suggesting a role in transcriptional regulation. We selected 45 candidate genes based on gene expression correlation data, obtained from two GEO (Gene Expression Omnibus) datasets and TCGA data of human breast cancer, compared to BRCA1 expression levels. Among them, we further tested three genes ( MEIS2 , CKS1B and FADD ) and verified FADD as a novel direct target of BRCA1 by ChIP, RT-PCR, and a luciferase reporter assay. Collectively, our data demonstrate genome-wide transcriptional regulation by BRCA1 and suggest target genes as biomarker candidates for BRCA1-associated breast cancer.

TCGA study improves understanding of thyroid cancer genetics - TCGA

Cancer.gov

A comprehensive analysis of the genomes of nearly 500 papillary thyroid carcinomas has provided new insights into the roles of frequently mutated cancer genes and other genomic alterations that drive disease development.

The Cancer Genome Atlas Pan-Cancer analysis project.

PubMed

Weinstein, John N; Collisson, Eric A; Mills, Gordon B; Shaw, Kenna R Mills; Ozenberger, Brad A; Ellrott, Kyle; Shmulevich, Ilya; Sander, Chris; Stuart, Joshua M

2013-10-01

The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile.

Antitumor and Angiostatic Activities of the Antimicrobial Peptide Dermaseptin B2

PubMed Central

van Zoggel, Hanneke; Carpentier, Gilles; Dos Santos, Célia; Hamma-Kourbali, Yamina; Courty, José; Amiche, Mohamed; Delbé, Jean

2012-01-01

Recently, we have found that the skin secretions of the Amazonian tree frog Phyllomedusa bicolor contains molecules with antitumor and angiostatic activities and identified one of them as the antimicrobial peptide dermaseptin (Drs) B2. In the present study we further explored the in vitro and in vivo antitumor activity of this molecule and investigated its mechanism of action. We showed that Drs B2 inhibits the proliferation and colony formation of various human tumor cell types, and the proliferation and capillary formation of endothelial cells in vitro. Furthermore, Drs B2 inhibited tumor growth of the human prostate adenocarcinoma cell line PC3 in a xenograft model in vivo. Research on the mechanism of action of Drs B2 on tumor PC3 cells demonstrated a rapid increasing amount of cytosolic lactate dehydrogenase, no activation of caspase-3, and no changes in mitochondrial membrane potential. Confocal microscopy analysis revealed that Drs B2 can interact with the tumor cell surface, aggregate and penetrate the cells. These data together indicate that Drs B2 does not act by apoptosis but possibly by necrosis. In conclusion, Drs B2 could be considered as an interesting and promising pharmacological and therapeutic leader molecule for the treatment of cancer. PMID:23028527

Antitumor and angiostatic activities of the antimicrobial peptide dermaseptin B2.

PubMed

van Zoggel, Hanneke; Carpentier, Gilles; Dos Santos, Célia; Hamma-Kourbali, Yamina; Courty, José; Amiche, Mohamed; Delbé, Jean

2012-01-01

Recently, we have found that the skin secretions of the Amazonian tree frog Phyllomedusa bicolor contains molecules with antitumor and angiostatic activities and identified one of them as the antimicrobial peptide dermaseptin (Drs) B2. In the present study we further explored the in vitro and in vivo antitumor activity of this molecule and investigated its mechanism of action. We showed that Drs B2 inhibits the proliferation and colony formation of various human tumor cell types, and the proliferation and capillary formation of endothelial cells in vitro. Furthermore, Drs B2 inhibited tumor growth of the human prostate adenocarcinoma cell line PC3 in a xenograft model in vivo. Research on the mechanism of action of Drs B2 on tumor PC3 cells demonstrated a rapid increasing amount of cytosolic lactate dehydrogenase, no activation of caspase-3, and no changes in mitochondrial membrane potential. Confocal microscopy analysis revealed that Drs B2 can interact with the tumor cell surface, aggregate and penetrate the cells. These data together indicate that Drs B2 does not act by apoptosis but possibly by necrosis. In conclusion, Drs B2 could be considered as an interesting and promising pharmacological and therapeutic leader molecule for the treatment of cancer.

TU-CD-BRB-04: Automated Radiomic Features Complement the Prognostic Value of VASARI in the TCGA-GBM Dataset

DOE Office of Scientific and Technical Information (OSTI.GOV)

Velazquez, E Rios; Narayan, V; Grossmann, P

2015-06-15

Purpose: To compare the complementary prognostic value of automated Radiomic features to that of radiologist-annotated VASARI features in TCGA-GBM MRI dataset. Methods: For 96 GBM patients, pre-operative MRI images were obtained from The Cancer Imaging Archive. The abnormal tumor bulks were manually defined on post-contrast T1w images. The contrast-enhancing and necrotic regions were segmented using FAST. From these sub-volumes and the total abnormal tumor bulk, a set of Radiomic features quantifying phenotypic differences based on the tumor intensity, shape and texture, were extracted from the post-contrast T1w images. Minimum-redundancy-maximum-relevance (MRMR) was used to identify the most informative Radiomic, VASARI andmore » combined Radiomic-VASARI features in 70% of the dataset (training-set). Multivariate Cox-proportional hazards models were evaluated in 30% of the dataset (validation-set) using the C-index for OS. A bootstrap procedure was used to assess significance while comparing the C-Indices of the different models. Results: Overall, the Radiomic features showed a moderate correlation with the radiologist-annotated VASARI features (r = −0.37 – 0.49); however that correlation was stronger for the Tumor Diameter and Proportion of Necrosis VASARI features (r = −0.71 – 0.69). After MRMR feature selection, the best-performing Radiomic, VASARI, and Radiomic-VASARI Cox-PH models showed a validation C-index of 0.56 (p = NS), 0.58 (p = NS) and 0.65 (p = 0.01), respectively. The combined Radiomic-VASARI model C-index was significantly higher than that obtained from either the Radiomic or VASARI model alone (p = <0.001). Conclusion: Quantitative volumetric and textural Radiomic features complement the qualitative and semi-quantitative annotated VASARI feature set. The prognostic value of informative qualitative VASARI features such as Eloquent Brain and Multifocality is increased with the addition of quantitative volumetric and textural features from

Performance of the disease risk score in a cohort study with policy-induced selection bias.

PubMed

Tadrous, Mina; Mamdani, Muhammad M; Juurlink, David N; Krahn, Murray D; Lévesque, Linda E; Cadarette, Suzanne M

2015-11-01

To examine the performance of the disease risk score (DRS) in a cohort study with evidence of policy-induced selection bias. We examined two cohorts of new users of bisphosphonates. Estimates for 1-year hip fracture rates between agents using DRS, exposure propensity scores and traditional multivariable analysis were compared. The results for the cohort with no evidence of policy-induced selection bias showed little variation across analyses (-4.1-2.0%). Analysis of the cohort with evidence of policy-induced selection bias showed greater variation (-13.5-8.1%), with the greatest difference seen with DRS analyses. Our findings suggest that caution may be warranted when using DRS methods in cohort studies with policy-induced selection bias, further research is needed.

Associations Among Indicators of Depression in Medicaid-Eligible Community-Dwelling Older Adults

PubMed Central

Byma, Elizabeth A.

2013-01-01

Purpose: The purpose of this research was to examine associations among 2 separate Minimum Data Set-Home Care (MDS-HC) depression measures (the Depression Rating Scale [DRS] and medical diagnosis of depression) with billed antidepressant medications in Medicaid paid claim files. Design and Methods: The sample for this cross-sectional research included 3,041 Medicaid-eligible older adult participants in a Home and Community Based Waiver Program and used data from the MDS-HC, Version 1 and Medicaid Paid Claim Files. Sensitivity and specificity analyses, receiver operating characteristic (ROC) curve analysis, and t tests were utilized. Results: DRS scoring indicated that 15.4% of participants had behaviors indicative of depression, whereas 42% had a medical diagnosis of depression noted in the MDS-HC. Of those with a medical diagnosis of depression, 51% had a prescribed antidepressant medication. ROC analysis suggested that the DRS was a poor distinguisher of participants with and without a medical diagnosis of depression or prescribed antidepressant medications. Implications: Approximately half of Medicaid-eligible older adults medically diagnosed with depression were treated pharmacologically. Longitudinal research is recommended to assess responsiveness of the DRS over time to pharmacological and psychotherapeutic interventions for depression. PMID:23103523

Development of the psychometric property of a Minimum Data-Set-Based Depression Rating Scale for use in long-term care facilities in Taiwan.

PubMed

Hsiao, C Y; Lan, C F; Chang, P L; Li, I C

2015-01-01

Our aim is to develop the psychometric property of the Minimum Data-Set-Based Depression Rating Scale (MDS-DRS) to ensure its use to assess service needs and guide care plans for institutionalized residents. 378 residents were recruited from the Haoran Senior Citizen Home in northern Taiwan. The MDS-DRS and GDS-SF were used to identify observable features of depression symptoms in the elderly residents. A total of 378 residents participated in this study. The receiver operating characteristic (ROC) curve indicated that the MDS-DRS has a 43.3% sensitivity and a 90.6% specificity when screening for depression symptoms. The total variance, explained by the two factors 'sadness' and 'distress,' was 58.1% based on the factor analysis. Reliable assessment tools for nurses are important because they allow the early detection of depression symptoms. The MDS-DRS items perform as well as the GDS-SF items in detecting depression symptoms. Furthermore, the MDS-DRS has the advantage of providing information to staff about care process implementation, which can facilitate the identification of areas that need improvement. Further research is needed to validate the use of the MDS-DRS in long-term care facilities.

[A history of the research on bone metabolism for the past 50 years in Japan and a memory of Dr. Hirotoshi Morii].

PubMed

Suda, Tatsuo

2011-12-01

It has been 20 years since the monthly Journal "CLINICAL CALCIUM" was published in November, 1991. This review Journal edited by Drs. Hirotoshi Morii and Yoshio Yazaki has contributed a lot to the understanding of the importance of calcium in bone and cardiovascular systems. This article describes a history of the research on bone metabolism for the past 50 years in Japan. Also, a memory of my dear friend, Hirotoshi Morii, is retraced.

CPTAC Releases Largest-Ever Breast Cancer Proteome Dataset from Previously Genome Characterized Tumors | Office of Cancer Clinical Proteomics Research

Cancer.gov

National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) scientists have released a dataset of proteins and  phosphopeptides identified through deep proteomic and phosphoproteomic analysis of breast tumor samples, previously genomically analyzed by The Cancer Genome Atlas (TCGA).

Non-synonymous variations in cancer and their effects on the human proteome: workflow for NGS data biocuration and proteome-wide analysis of TCGA data.

PubMed

Cole, Charles; Krampis, Konstantinos; Karagiannis, Konstantinos; Almeida, Jonas S; Faison, William J; Motwani, Mona; Wan, Quan; Golikov, Anton; Pan, Yang; Simonyan, Vahan; Mazumder, Raja

2014-01-27

Next-generation sequencing (NGS) technologies have resulted in petabytes of scattered data, decentralized in archives, databases and sometimes in isolated hard-disks which are inaccessible for browsing and analysis. It is expected that curated secondary databases will help organize some of this Big Data thereby allowing users better navigate, search and compute on it. To address the above challenge, we have implemented a NGS biocuration workflow and are analyzing short read sequences and associated metadata from cancer patients to better understand the human variome. Curation of variation and other related information from control (normal tissue) and case (tumor) samples will provide comprehensive background information that can be used in genomic medicine research and application studies. Our approach includes a CloudBioLinux Virtual Machine which is used upstream of an integrated High-performance Integrated Virtual Environment (HIVE) that encapsulates Curated Short Read archive (CSR) and a proteome-wide variation effect analysis tool (SNVDis). As a proof-of-concept, we have curated and analyzed control and case breast cancer datasets from the NCI cancer genomics program - The Cancer Genome Atlas (TCGA). Our efforts include reviewing and recording in CSR available clinical information on patients, mapping of the reads to the reference followed by identification of non-synonymous Single Nucleotide Variations (nsSNVs) and integrating the data with tools that allow analysis of effect nsSNVs on the human proteome. Furthermore, we have also developed a novel phylogenetic analysis algorithm that uses SNV positions and can be used to classify the patient population. The workflow described here lays the foundation for analysis of short read sequence data to identify rare and novel SNVs that are not present in dbSNP and therefore provides a more comprehensive understanding of the human variome. Variation results for single genes as well as the entire study are available

Non-synonymous variations in cancer and their effects on the human proteome: workflow for NGS data biocuration and proteome-wide analysis of TCGA data

PubMed Central

2014-01-01

Background Next-generation sequencing (NGS) technologies have resulted in petabytes of scattered data, decentralized in archives, databases and sometimes in isolated hard-disks which are inaccessible for browsing and analysis. It is expected that curated secondary databases will help organize some of this Big Data thereby allowing users better navigate, search and compute on it. Results To address the above challenge, we have implemented a NGS biocuration workflow and are analyzing short read sequences and associated metadata from cancer patients to better understand the human variome. Curation of variation and other related information from control (normal tissue) and case (tumor) samples will provide comprehensive background information that can be used in genomic medicine research and application studies. Our approach includes a CloudBioLinux Virtual Machine which is used upstream of an integrated High-performance Integrated Virtual Environment (HIVE) that encapsulates Curated Short Read archive (CSR) and a proteome-wide variation effect analysis tool (SNVDis). As a proof-of-concept, we have curated and analyzed control and case breast cancer datasets from the NCI cancer genomics program - The Cancer Genome Atlas (TCGA). Our efforts include reviewing and recording in CSR available clinical information on patients, mapping of the reads to the reference followed by identification of non-synonymous Single Nucleotide Variations (nsSNVs) and integrating the data with tools that allow analysis of effect nsSNVs on the human proteome. Furthermore, we have also developed a novel phylogenetic analysis algorithm that uses SNV positions and can be used to classify the patient population. The workflow described here lays the foundation for analysis of short read sequence data to identify rare and novel SNVs that are not present in dbSNP and therefore provides a more comprehensive understanding of the human variome. Variation results for single genes as well as the entire

Urban STEM Education: A Unique Summer Experience

ERIC Educational Resources Information Center

White, David W.

2013-01-01

In April of 2010, the author was approached to write a proposal that would provide grant money for a summer program to take place at the Florida Agricultural and Mechanical University's Developmental Research School (FAMU DRS). The FAMU DRS functions as a normal K-12 school; however, it is administered by the Florida A&M University College of…

Dental Health Services Research Unit celebrates 30 years: Report of conference to mark the 30th anniversary of the Dental Health Services Research Unit (DHSRU) at Dundee, held on 1st December 2008.

PubMed

Eaton, Kenneth A; Pitts, Nigel B

2009-04-01

Over the years, several members of the staff of the Dental Health Services Research Unit (DHSRU) at Dundee have published papers in Primary Dental Care. Furthermore, its Director, Professor Nigel Pitts, together with Drs Jan Clarkson and Gail Topping have co-edited a number of the Faculty of General Dental Practice (UK)'s standards manuals and contributed to others. It had been suggested to the Unit by several parties that, having been in funded existence for some 30 years, it would be appropriate to mark this anniversary with a conference to explore 'Dental Health Services Research: After 30 years, what was the impact, what have we learned and where are we going?' So, following a range of consultations, the conference was convened at the West Park Conference Centre in Dundee with a mixed audience representing both dental research and dental practice.

Military Suicide Research Consortium

DTIC Science & Technology

2015-10-01

support face-to- face therapy away from the clinic, the CT or DBT clinician often will implement a physical “hope kit” or “hope box” with the patient (Berk...Assessments within Suicide-Specific Group Therapy Treatment for Veterans: A Pilot Study, Drs. Lori Johnson and David Jobes, Robley Rex VAMC, $429,801...40,160 o Longitudinal Assessment of Physical Activity and Suicide Risk, Dr. Collin Davidson, Denver VAMC, $46,665  The MSRC offers annual Dissertation

Toward a Comprehensive Genomic Analysis of Cancer - TCGA

Cancer.gov

The National Cancer Institute (NCI) and National Human Genome Research Institute (NHGRI) convened a "Toward a Comprehensive Genomic Analysis of Cancer" workshop in Washington, D.C. This workshop brought together physicians, basic scientists and other members of the U.S. and international cancer communities to assist in outlining the most effective strategies for the development of a successful project. Information about this workshop is reported in the Executive Summary.

Genomic features of lobular breast carcinoma

Cancer.gov

Investigators with The Cancer Genome Atlas (TCGA) Research Network have identified molecular characteristics of a type of breast cancer, invasive lobular carcinoma (ILC), that distinguishes it from invasive ductal carcinoma (IDC), the most common invasive breast cancer subtype.

First Large-Scale Proteogenomic Study of Breast Cancer Provides Insight into Potential Therapeutic Targets | Office of Cancer Clinical Proteomics Research

Cancer.gov

News Release: May 25, 2016 — Building on data from The Cancer Genome Atlas (TCGA) project, a multi-institutional team of scientists has completed the first large-scale “proteogenomic” study of breast cancer, linking DNA mutations to protein signaling and helping pinpoint the genes that drive cancer.

Cobalt ferrite nano-composite coated on glass by Doctor Blade method for photo-catalytic degradation of an azo textile dye Reactive Red 4: XRD, FESEM and DRS investigations.

PubMed

Habibi, Mohammad Hossein; Parhizkar, Janan

2015-11-05

Cobalt ferrite nano-composite was prepared by hydrothermal route using cobalt nitrate, iron nitrate and ethylene glycol as chelating agent. The nano-composite was coated on glass by Doctor Blade method and annealed at 300 °C. The structural, optical, and photocatalytic properties have been studied by powder X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM) and UV-visible spectroscopy (UV-Vis DRS). Powder XRD analysis confirmed formation of CoFe2O4 spinel phase. The estimated particle size from FESEM data was 50 nm. The calculated energy band gaps, obtained by Tauc relation from UV-Vis absorption spectra was 1.3 eV. Photocatalytic degradation of Reactive Red 4 as an azo textile was investigated in aqueous solution under irradiation showed 68.0% degradation of the dye within 100 min. The experimental enhanced activity compare to pure Fe2O3 can be ascribed to the formation of composite, which was mainly attributable to the transfer of electron and hole to the surface of composite and hinder the electron hole recombination. Copyright © 2015 Elsevier B.V. All rights reserved.

The drosomycin multigene family: three-disulfide variants from Drosophila takahashii possess antibacterial activity

PubMed Central

Gao, Bin; Zhu, Shunyi

2016-01-01

Drosomycin (DRS) is a strictly antifungal peptide in Drosophila melanogaster, which contains four disulfide bridges (DBs) with three buried in molecular interior and one exposed on molecular surface to tie the amino- and carboxyl-termini of the molecule together (called wrapper disulfide bridge, WDB). Based on computational analysis of genomes of Drosophila species belonging to the Oriental lineage, we identified a new multigene family of DRS in Drosphila takahashii that includes a total of 11 DRS-encoding genes (termed DtDRS-1 to DtDRS-11) and a pseudogene. Phylogenetic tree and synteny analyses reveal orthologous relationship between DtDRSs and DRSs, indicating that orthologous genes of DRS-1, DRS-2, DRS-3 and DRS-6 have undergone duplication in D. takahashii and three amplifications (DtDRS-9 to DtDRS-11) of DRS-3 have lost WDB. Among the 11 genes, five are transcriptionally active in adult fruitflies. The ortholog of DRS (DtDRS-1) shows high structural and functional similarity to DRS while two WDB-deficient members display antibacterial activity accompanying complete loss or remarkable reduction of antifungal activity. To the best of our knowledge, this is the first report on the presence of three-disulfide antibacterial DRSs in a specific Drosophila species, suggesting a potential role of DB loss in neofunctionalization of a protein via structural adjustment. PMID:27562645

MATE (Mentale Aspecten van Team Effectiviteit) (MATE (Mental Aspects of Team Effectiveness))

DTIC Science & Technology

2008-05-01

0 Auteur (s) drs. J.P. van Meer drs. MI. 1 ’ IIart0 drs. 1. van der 16. Rubricering rapport Ongerubriceerd Vastgesteld door Ikol drs. L.A. de Vos...team Auteur (s) Teamntraining drs. J.P. van Meer drs. M.H.E. I Hart Programmanummer Projectnummer drs. 1. van der Beijl V406 015.34095 Rubricering...Murphy & Cleveland (1995) geven inzicht in de tearngedragingen die meetbaar zijn en de theorie over Shared Mental Models (Espevik et al, 2006) laat zien

The benefits of looking across many cancer genomes

Cancer.gov

Cancer is not a single entity, but rather, it is more than one hundred complex and distinct diseases, with most cancer types demanding a unique treatment strategy. TCGA researchers have developed a formal project for a cross tumor analysis, called Pan-Can

Rare kidney tumor provides insight on metabolic changes

Cancer.gov

Researchers in The Cancer Genome Atlas (TCGA) Network have uncovered a number of new findings about the biology and development of a rare form of kidney cancer. They found that the disease – chromophobe renal cell carcinoma – stems in part from alteratio

Communication and Decision Making in Cancer Care: Setting Research Priorities for Decision Support/Patients’ Decision Aids

PubMed Central

Barnato, Amber E.; Llewellyn-Thomas, Hilary A.; Peters, Ellen M.; Siminoff, Laura; Collins, E. Dale; Barry, Michael J.

2013-01-01

The following is a summary report from a special symposium, entitled “Translating Research into Practice: Setting a Research Agenda for Clinical Decision Tools in Cancer Prevention, Early Detection, and Treatment”, that was held on October 23, 2005 in San Francisco at the Annual Meeting of the Society for Medical Decision Making (SMDM). The symposium was designed to answer the question: “What are the top two research priorities in the field of patients’ cancer-related decision aids?” After introductory remarks by Dr. Barry, each of four panelists–Drs. Hilary Llewellyn-Thomas, Ellen Peters, Laura Siminoff, and Dale Collins–addressed the question and provided their rationale during prepared remarks. The moderator, Dr. Michael Barry, then facilitated a discussion between the panelists, with input from the audience, to further explore and add to the various proposed research questions. Finally, Dr. Amber Barnato conducted a simple vote count (see Table 1) to prioritize the panelists’ and the audience’s recommendations. PMID:17873249

Cancer Genomics: Integrative and Scalable Solutions in R / Bioconductor | Informatics Technology for Cancer Research (ITCR)

Cancer.gov

This proposal develops scalable R / Bioconductor software infrastructure and data resources to integrate complex, heterogeneous, and large cancer genomic experiments. The falling cost of genomic assays facilitates collection of multiple data types (e.g., gene and transcript expression, structural variation, copy number, methylation, and microRNA data) from a set of clinical specimens. Furthermore, substantial resources are now available from large consortium activities like The Cancer Genome Atlas (TCGA).

Molecular Pathology of Patient Tumors, Patient-Derived Xenografts, and Cancer Cell Lines.

PubMed

Guo, Sheng; Qian, Wubin; Cai, Jie; Zhang, Likun; Wery, Jean-Pierre; Li, Qi-Xiang

2016-08-15

The Cancer Genome Atlas (TCGA) project has generated abundant genomic data for human cancers of various histopathology types and enabled exploring cancer molecular pathology per big data approach. We developed a new algorithm based on most differentially expressed genes (DEG) per pairwise comparisons to calculate correlation coefficients to be used to quantify similarity within and between cancer types. We systematically compared TCGA cancers, demonstrating high correlation within types and low correlation between types, thus establishing molecular specificity of cancer types and an alternative diagnostic method largely equivalent to histopathology. Different coefficients for different cancers in study may reveal that the degree of the within-type homogeneity varies by cancer types. We also performed the same calculation using the TCGA-derived DEGs on patient-derived xenografts (PDX) of different histopathology types corresponding to the TCGA types, as well as on cancer cell lines. We, for the first time, demonstrated highly similar patterns for within- and between-type correlation between PDXs and patient samples in a systematic study, confirming the high relevance of PDXs as surrogate experimental models for human diseases. In contrast, cancer cell lines have drastically reduced expression similarity to both PDXs and patient samples. The studies also revealed high similarity between some types, for example, LUSC and HNSCC, but low similarity between certain subtypes, for example, LUAD and LUSC. Our newly developed algorithm seems to be a practical diagnostic method to classify and reclassify a disease, either human or xenograft, with better accuracy than traditional histopathology. Cancer Res; 76(16); 4619-26. ©2016 AACR. ©2016 American Association for Cancer Research.

A self-updating road map of The Cancer Genome Atlas.

PubMed

Robbins, David E; Grüneberg, Alexander; Deus, Helena F; Tanik, Murat M; Almeida, Jonas S

2013-05-15

Since 2011, The Cancer Genome Atlas' (TCGA) files have been accessible through HTTP from a public site, creating entirely new possibilities for cancer informatics by enhancing data discovery and retrieval. Significantly, these enhancements enable the reporting of analysis results that can be fully traced to and reproduced using their source data. However, to realize this possibility, a continually updated road map of files in the TCGA is required. Creation of such a road map represents a significant data modeling challenge, due to the size and fluidity of this resource: each of the 33 cancer types is instantiated in only partially overlapping sets of analytical platforms, while the number of data files available doubles approximately every 7 months. We developed an engine to index and annotate the TCGA files, relying exclusively on third-generation web technologies (Web 3.0). Specifically, this engine uses JavaScript in conjunction with the World Wide Web Consortium's (W3C) Resource Description Framework (RDF), and SPARQL, the query language for RDF, to capture metadata of files in the TCGA open-access HTTP directory. The resulting index may be queried using SPARQL, and enables file-level provenance annotations as well as discovery of arbitrary subsets of files, based on their metadata, using web standard languages. In turn, these abilities enhance the reproducibility and distribution of novel results delivered as elements of a web-based computational ecosystem. The development of the TCGA Roadmap engine was found to provide specific clues about how biomedical big data initiatives should be exposed as public resources for exploratory analysis, data mining and reproducible research. These specific design elements align with the concept of knowledge reengineering and represent a sharp departure from top-down approaches in grid initiatives such as CaBIG. They also present a much more interoperable and reproducible alternative to the still pervasive use of data portals

CPTAC Releases Largest-Ever Colorectal Cancer Proteome Dataset from Previously Genome Characterized Tumors | Office of Cancer Clinical Proteomics Research

Cancer.gov

On September 4, 2013, NCI’s Clinical Proteomics Tumor Analysis Consortium (CPTAC) publicly released proteomic data produced from colorectal tumor samples previously analyzed by The Cancer Genome Atlas (TCGA).  This is the initial release of proteomic tumor data designed to complement genomic data on the same tumors. The data is publicly available at the CPTAC data portal.

Genomic understanding of glioblastoma expanded

Cancer.gov

Glioblastoma multiforme (GBM) was the first cancer type to be systematically studied by TCGA in 2008. In a new, complementary report, TCGA experts examined more than 590 GBM samples--the largest to date utilizing genomic characterization techniques and ne

NIH Fellows Award for Research Excellence (FARE) Presentations by Drs. Sklavos, Gu, and Camargo

Cancer.gov

Sklavos: Anti-Müllerian Hormone Deficiency in Inherited Bone Marrow Failure Syndromes, Gu: Time to first cigarette after waking and lung cancer Camargo: Epstein-Barr virus (EBV) and gastric cancer: epidemiological findings from the NCI International EBV-G

P4-ATPase Requirement for AP-1/Clathrin Function in Protein Transport from the trans-Golgi Network and Early Endosomes

PubMed Central

Liu, Ke; Surendhran, Kavitha; Nothwehr, Steven F.

2008-01-01

Drs2p is a resident type 4 P-type ATPase (P4-ATPase) and potential phospholipid translocase of the trans-Golgi network (TGN) where it has been implicated in clathrin function. However, precise protein transport pathways requiring Drs2p and how it contributes to clathrin-coated vesicle budding remain unclear. Here we show a functional codependence between Drs2p and the AP-1 clathrin adaptor in protein sorting at the TGN and early endosomes of Saccharomyces cerevisiae. Genetic criteria indicate that Drs2p and AP-1 operate in the same pathway and that AP-1 requires Drs2p for function. In addition, we show that loss of AP-1 markedly increases Drs2p trafficking to the plasma membrane, but does not perturb retrieval of Drs2p from the early endosome back to the TGN. Thus AP-1 is required at the TGN to sort Drs2p out of the exocytic pathway, presumably for delivery to the early endosome. Moreover, a conditional allele that inactivates Drs2p phospholipid translocase (flippase) activity disrupts its own transport in this AP-1 pathway. Drs2p physically interacts with AP-1; however, AP-1 and clathrin are both recruited normally to the TGN in drs2Δ cells. These results imply that Drs2p acts independently of coat recruitment to facilitate AP-1/clathrin-coated vesicle budding from the TGN. PMID:18508916

CPTAC Releases Largest-Ever Ovarian Cancer Proteome Dataset from Previously Genome Characterized Tumors | Office of Cancer Clinical Proteomics Research

Cancer.gov

National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) scientists have just released a comprehensive dataset of the proteomic analysis of high grade serous ovarian tumor samples, previously genomically analyzed by The Cancer Genome Atlas (TCGA).  This is one of the largest public datasets covering the proteome, phosphoproteome and glycoproteome with complementary deep genomic sequencing data on the same tumor.

Systemic analysis of different colorectal cancer cell lines and TCGA datasets identified IGF-1R/EGFR-PPAR-CASPASE axis as important indicator for radiotherapy sensitivity.

PubMed

Chen, Lin; Zhu, Zhe; Gao, Wei; Jiang, Qixin; Yu, Jiangming; Fu, Chuangang

2017-09-05

Insulin-like growth factor 1 receptor (IGF-1R) is proved to contribute the development of many types of cancers. But, little is known about its roles in radio-resistance of colorectal cancer (CRC). Here, we demonstrated that low IGF-1R expression value was associated with the better radiotherapy sensitivity of CRC. Besides, through Quantitative Real-time PCR (qRT-PCR), the elevated expression value of epidermal growth factor receptor (EGFR) was observed in CRC cell lines (HT29, RKO) with high radio-sensitivity compared with those with low sensitivity (SW480, LOVO). The irradiation induced apoptosis rates of wild type and EGFR agonist (EGF) or IGF-1R inhibitor (NVP-ADW742) treated HT29 and SW480 cells were quantified by flow cytometry. As a result, the apoptosis rate of EGF and NVP-ADW742 treated HT29 cells was significantly higher than that of those wild type ones, which indicated that high EGFR and low IGF-1R expression level in CRC was associated with the high sensitivity to radiotherapy. We next conducted systemic bioinformatics analysis of genome-wide expression profiles of CRC samples from the Cancer Genome Atlas (TCGA). Differential expression analysis between IGF-1R and EGFR abnormal CRC samples, i.e. CRC samples with higher IGF-1R and lower EGFR expression levels based on their median expression values, and the rest of CRC samples identified potential genes contribute to radiotherapy sensitivity. Functional enrichment of analysis of those differential expression genes (DEGs) in the Database for Annotation, Visualization and Integrated Discovery (DAVID) indicated PPAR signaling pathway as an important pathway for the radio-resistance of CRC. Our study identified the potential biomarkers for the rational selection of radiotherapy for CRC patients. Copyright © 2017 Elsevier B.V. All rights reserved.

The Impact of the Cancer Genome Atlas on Lung Cancer

PubMed Central

Chang, Jeremy Tzu-Huai; Lee, Yee-Ming; Huang, R. Stephanie

2015-01-01

The Cancer Genome Atlas (TCGA) has profiled over 10,000 samples derived from 33 types of cancer to date, with the goal of improving our understanding of the molecular basis of cancer and advancing our ability to diagnose, treat, and prevent cancer. This review focuses on lung cancer as it is the leading cause of cancer-related mortality worldwide in both men and women. Particularly, non-small cell lung cancers (including lung adenocarcinoma and lung squamous cell carcinoma) were evaluated. Our goal is to demonstrate the impact of TCGA on lung cancer research under four themes: namely, diagnostic markers, disease progression markers, novel therapeutic targets, and novel tools. Examples were given related to DNA mutation, copy number variation, mRNA, and microRNA expression along with methylation profiling. PMID:26318634

Impact of aging on host immune response and survival in melanoma: an analysis of 3 patient cohorts.

PubMed

Weiss, Sarah A; Han, Joseph; Darvishian, Farbod; Tchack, Jeremy; Han, Sung Won; Malecek, Karolina; Krogsgaard, Michelle; Osman, Iman; Zhong, Judy

2016-10-19

Age has been reported as an independent prognostic factor for melanoma-specific survival (MSS). We tested the hypothesis that age impacts the host anti-tumor immune response, accounting for age-specific survival outcomes in three unique melanoma patient cohorts. We queried the U.S. population-based Surveillance, Epidemiology, and End Results Program (SEER), the prospective tertiary care hospital-based Interdisciplinary Melanoma Cooperative Group (IMCG) biorepository, and the Cancer Genome Atlas (TCGA) biospecimen database to test the association of patient age at time of melanoma diagnosis with clinicopathologic features and survival outcomes. Age groups were defined as ≤45 (young), 46-65 (intermediate), and >65 (older). Each age group in the IMCG and TCGA cohorts was stratified by tumor infiltrating lymphocyte (TIL) measurements and tested for association with MSS. Differential expression of 594 immunoregulatory genes was assessed in a subset of primary melanomas in the IMCG and TCGA cohorts using an integrative pathway analysis. We analyzed 304, 476 (SEER), 1241 (IMCG), and 292 (TCGA) patients. Increasing age at melanoma diagnosis in both the SEER and IMCG cohorts demonstrated a positive correlation with tumor thickness, ulceration, stage, and mortality, however age in the TCGA cohort did not correlate with mortality. Older age was associated with shorter MSS in all three cohorts. When the young age group in both the IMCG and TCGA cohorts was stratified by TIL status, there were no differences in MSS. However, older IMCG patients with brisk TILs and intermediate aged TCGA patients with high lymphocyte scores (3-6) had improved MSS. Gene expression analysis revealed top pathways (T cell trafficking, communication, and differentiation) and top upstream regulators (CD3, CD28, IFNG, and STAT3) that significantly changed with age in 84 IMCG and 43 TCGA primary melanomas. Older age at time of melanoma diagnosis is associated with shorter MSS, however age

What works to increase attendance for diabetic retinopathy screening? An evidence synthesis and economic analysis.

PubMed

Lawrenson, John G; Graham-Rowe, Ella; Lorencatto, Fabiana; Rice, Stephen; Bunce, Catey; Francis, Jill J; Burr, Jennifer M; Aluko, Patricia; Vale, Luke; Peto, Tunde; Presseau, Justin; Ivers, Noah M; Grimshaw, Jeremy M

2018-05-01

and of 'restructuring the social environment' (RD 0.19, 95% CI 0.12 to 0.26) and 'credible source' (RD 0.16, 95% CI 0.08 to 0.24) in interventions targeting HCPs. Phase 2 - 3457 studies were screened, of which 65 non-randomised studies were included in the review. The following theoretical domains were likely to influence attendance: 'environmental context and resources', 'social influences', 'knowledge', 'memory, attention and decision processes', 'beliefs about consequences' and 'emotions'. Phase 3 - mapping identified that interventions included BCTs targeting important barriers to/enablers of DRS attendance. However, BCTs targeting emotional factors around DRS were under-represented. QI components were unlikely to be cost-effective whereas BCTs with a high probability (≥ 0.975) of being cost-effective at a societal willingness-to-pay threshold of £20,000 per QALY included 'goal-setting (outcome)', 'feedback on outcomes of behaviour', 'social support' and 'information about health consequences'. Cost-effectiveness increased when DRS attendance was lower and with longer screening intervals. Quality improvement/BCT coding was dependent on descriptions of intervention content in primary sources; methods for the identification of coherence of BCTs require improvement. Randomised controlled trial evidence indicates that QI interventions incorporating specific BCT components are associated with meaningful improvements in DRS attendance compared with usual care. Interventions generally used appropriate BCTs that target important barriers to screening attendance, with a high probability of being cost-effective. Research is needed to optimise BCTs or BCT combinations that seek to improve DRS attendance at an acceptable cost. BCTs targeting emotional factors represent a missed opportunity to improve attendance and should be tested in future studies. This study is registered as PROSPERO CRD42016044157 and PROSPERO CRD42016032990. The National Institute for Health

Object-oriented regression for building predictive models with high dimensional omics data from translational studies.

PubMed

Zhao, Lue Ping; Bolouri, Hamid

2016-04-01

Maturing omics technologies enable researchers to generate high dimension omics data (HDOD) routinely in translational clinical studies. In the field of oncology, The Cancer Genome Atlas (TCGA) provided funding support to researchers to generate different types of omics data on a common set of biospecimens with accompanying clinical data and has made the data available for the research community to mine. One important application, and the focus of this manuscript, is to build predictive models for prognostic outcomes based on HDOD. To complement prevailing regression-based approaches, we propose to use an object-oriented regression (OOR) methodology to identify exemplars specified by HDOD patterns and to assess their associations with prognostic outcome. Through computing patient's similarities to these exemplars, the OOR-based predictive model produces a risk estimate using a patient's HDOD. The primary advantages of OOR are twofold: reducing the penalty of high dimensionality and retaining the interpretability to clinical practitioners. To illustrate its utility, we apply OOR to gene expression data from non-small cell lung cancer patients in TCGA and build a predictive model for prognostic survivorship among stage I patients, i.e., we stratify these patients by their prognostic survival risks beyond histological classifications. Identification of these high-risk patients helps oncologists to develop effective treatment protocols and post-treatment disease management plans. Using the TCGA data, the total sample is divided into training and validation data sets. After building up a predictive model in the training set, we compute risk scores from the predictive model, and validate associations of risk scores with prognostic outcome in the validation data (P-value=0.015). Copyright © 2016 Elsevier Inc. All rights reserved.

Object-Oriented Regression for Building Predictive Models with High Dimensional Omics Data from Translational Studies

PubMed Central

Zhao, Lue Ping; Bolouri, Hamid

2016-01-01

Maturing omics technologies enable researchers to generate high dimension omics data (HDOD) routinely in translational clinical studies. In the field of oncology, The Cancer Genome Atlas (TCGA) provided funding support to researchers to generate different types of omics data on a common set of biospecimens with accompanying clinical data and to make the data available for the research community to mine. One important application, and the focus of this manuscript, is to build predictive models for prognostic outcomes based on HDOD. To complement prevailing regression-based approaches, we propose to use an object-oriented regression (OOR) methodology to identify exemplars specified by HDOD patterns and to assess their associations with prognostic outcome. Through computing patient’s similarities to these exemplars, the OOR-based predictive model produces a risk estimate using a patient’s HDOD. The primary advantages of OOR are twofold: reducing the penalty of high dimensionality and retaining the interpretability to clinical practitioners. To illustrate its utility, we apply OOR to gene expression data from non-small cell lung cancer patients in TCGA and build a predictive model for prognostic survivorship among stage I patients, i.e., we stratify these patients by their prognostic survival risks beyond histological classifications. Identification of these high-risk patients helps oncologists to develop effective treatment protocols and post-treatment disease management plans. Using the TCGA data, the total sample is divided into training and validation data sets. After building up a predictive model in the training set, we compute risk scores from the predictive model, and validate associations of risk scores with prognostic outcome in the validation data (p=0.015). PMID:26972839

Lineage fate of ductular reactions in liver injury and carcinogenesis.

PubMed

Jörs, Simone; Jeliazkova, Petia; Ringelhan, Marc; Thalhammer, Julian; Dürl, Stephanie; Ferrer, Jorge; Sander, Maike; Heikenwalder, Mathias; Schmid, Roland M; Siveke, Jens T; Geisler, Fabian

2015-06-01

Ductular reactions (DRs) are observed in virtually all forms of human liver disease; however, the histogenesis and function of DRs in liver injury are not entirely understood. It is widely believed that DRs contain bipotential liver progenitor cells (LPCs) that serve as an emergency cell pool to regenerate both cholangiocytes and hepatocytes and may eventually give rise to hepatocellular carcinoma (HCC). Here, we used a murine model that allows highly efficient and specific lineage labeling of the biliary compartment to analyze the histogenesis of DRs and their potential contribution to liver regeneration and carcinogenesis. In multiple experimental and genetic liver injury models, biliary cells were the predominant precursors of DRs but lacked substantial capacity to produce new hepatocytes, even when liver injuries were prolonged up to 12 months. Genetic modulation of NOTCH and/or WNT/β-catenin signaling within lineage-tagged DRs impaired DR expansion but failed to redirect DRs from biliary differentiation toward the hepatocyte lineage. Further, lineage-labeled DRs did not produce tumors in genetic and chemical HCC mouse models. In summary, we found no evidence in our system to support mouse biliary-derived DRs as an LPC pool to replenish hepatocytes in a quantitatively relevant way in injury or evidence that DRs give rise to HCCs.

Association of Cognitive and Noncognitive Symptoms of Delirium: A Study from Consultation-liaison Psychiatry Set-up.

PubMed

Grover, Sandeep; Mehra, Aseem; Chakrabarti, Subho; Avasthi, Ajit

2016-12-01

This study aims to evaluate the cognitive functions of patients with delirium using Hindi Mental Status Examination (HMSE), to study the correlation of cognitive functions assessed by HMSE with noncognitive symptoms as assessed using Delirium Rating Scale-Revised 1998 (DRS-R-98) and to study the association of cognitive functions assessed using HMSE and DRS-R98. A total of 76 consecutive patients fulfilling the diagnosis of delirium were evaluated on DRS-R-98, HMSE, and Short Informant Questionnaire on Cognitive Decline in the Elderly (retrospective IQCODE). The mean DRS-R-98 score 33.9 (standard deviation [SD] - 7.2) and the mean DRS-R-98 severity score was 25.9 (SD - 7.2). The mean score on HMSE was 19.3 (7.98). There were significant correlations of all the domains of HMSE with DRS-R-98 total score, DRS-R-98 severity score, DRS-R-98 cognitive subscale score, DRS-R-98 noncognitive domain subscale score, and DRS severity score without attention score. When the association of each item of DRS-R-98 and HMSE was evaluated, except for the items of delusions, lability of affect and motor retardation, there were significant negative association between all the items of DRS-R-98 and HMSE, indicating that higher severity of cognitive symptoms as assessed on HMSE is associated with higher severity of all the cognitive symptoms and most of the noncognitive symptoms as assessed by DRS-R-98. The present study suggests that attention deficits in patients with delirium influence the severity of cognitive and noncognitive symptoms of delirium. Further, the present study suggests an increase in the severity of cognitive symptoms in other domains is also associated with an increase in the severity of noncognitive symptoms of delirium.

Abducens Nerve in Patients with Type 3 Duane’s Retraction Syndrome

PubMed Central

Hwang, Jeong-Min

2016-01-01

Background We have previously reported that the presence of the abducens nerve was variable in patients with type 3 Duane’s retraction syndrome (DRS), being present in 2 of 5 eyes (40%) and absent in 3 (60%) on magnetic resonance imaging (MRI). The previous study included only 5 eyes with unilateral DRS type 3. Objectives To supplement existing scarce pathologic information by evaluating the presence of the abducens nerve using high resolution thin-section MRI system in a larger number of patients with DRS type 3, thus to provide further insight into the pathogenesis of DRS. Data Extraction A retrospective review of medical records on ophthalmologic examination and high resolution thin-section MRI at the brainstem level and orbit was performed. A total of 31 patients who showed the typical signs of DRS type 3, including abduction and adduction deficit, globe retraction, narrowing of fissure on adduction and upshoot and/or downshoot, were included. The abducens nerve and any other extraocular muscle abnormalities discovered by MRI were noted. Results DRS was unilateral in 26 patients (84%) and bilateral in 5 patients (16%). Two out of 5 bilateral patients had DRS type 3 in the right eye and DRS type 1 in the left eye. Of the 34 affected orbits with DRS type 3 in 31 patients, the abducens nerve was absent or hypoplastic in 31 eyes (91%) and present in 3 eyes (9%). Patients with a present abducens nerve showed more limitation in adduction compared to patients with an absent abducens nerve (P = 0.030). Conclusions The abducens nerve is absent or hypoplastic in 91% of DRS type 3. Patients with a present abducens nerve showed more prominent limitation of adduction. As DRS type 3 partly share the same pathophysiology with type 1 and 2 DRS, the classification of DRS may have to be revised according to MRI findings. PMID:27352171

Molecular classification of gastric adenocarcinoma: translating new insights from the cancer genome atlas research network.

PubMed

Sunakawa, Yu; Lenz, Heinz-Josef

2015-04-01

Gastric cancer is a heterogenous cancer, which may be classified into several distinct subtypes based on pathology and epidemiology, each with different initiating pathological processes and each possibly having different tumor biology. A classification of gastric cancer should be important to select patients who can benefit from the targeted therapies or to precisely predict prognosis. The Cancer Genome Atlas (TCGA) study collaborated with previous reports regarding subtyping gastric cancer but also proposed a refined classification based on molecular characteristics. The addition of the new molecular classification strategy to a current classical subtyping may be a promising option, particularly stratification by Epstein-Barr virus (EBV) and microsatellite instability (MSI) statuses. According to TCGA study, EBV gastric cancer patients may benefit the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) antibodies or phosphoinositide 3-kinase (PI3K) inhibitors which are now being developed. The discoveries of predictive biomarkers should improve patient care and individualized medicine in the management since the targeted therapies may have the potential to change the landscape of gastric cancer treatment, moreover leading to both better understanding of the heterogeneity and better outcomes. Patient enrichment by predictive biomarkers for new treatment strategies will be critical to improve clinical outcomes. Additionally, liquid biopsies will be able to enable us to monitor in real-time molecular escape mechanism, resulting in better treatment strategies.

Studies of the antitumor mechanism of action of dermaseptin B2, a multifunctional cationic antimicrobial peptide, reveal a partial implication of cell surface glycosaminoglycans.

PubMed

Dos Santos, Célia; Hamadat, Sabah; Le Saux, Karen; Newton, Clara; Mazouni, Meriem; Zargarian, Loussiné; Miro-Padovani, Mickael; Zadigue, Patricia; Delbé, Jean; Hamma-Kourbali, Yamina; Amiche, Mohamed

2017-01-01

Dermaseptin-B2 (DRS-B2) is a multifunctional cationic antimicrobial peptide (CAP) isolated from frog skin secretion. We previously reported that DRS-B2 possesses anticancer and antiangiogenic activities in vitro and in vivo. In the present study, we evaluated the antiproliferative activity of DRS-B2 on numerous tumor cell lines, its cell internalization and studies of its molecular partners as well as their influences on its structure. Confocal microscopy using ([Alexa594]-(Cys0)-DRS-B2) shows that in sensitive human tumor cells (PC3), DRS-B2 seems to accumulate rapidly at the cytoplasmic membranes and enters the cytoplasm and the nucleus, while in less sensitive tumor cells (U87MG), DRS-B2 is found packed in vesicles at the cell membrane. Furthermore FACS analysis shows that PC3 cells viability decreases after DRS-B2 treatment while U87 MG seems to be unaffected. However, "pull down" experiments performed with total protein pools from PC3 or U87MG cells and the comparison between the antiproliferative effect of DRS-B2 and its synthetic analog containing all D-amino acids suggest the absence of a stereo-selective protein receptor. Pretreatment of PC3 cells with sodium chlorate, decreases the antiproliferative activity of DRS-B2. This activity is partially restored after addition of exogenous chondroitin sulfate C (CS-C). Moreover, we demonstrate that at nanomolar concentrations CS-C potentiates the antiproliferative effect of DRS-B2. These results highlight the partial implication of glycosaminoglycans in the mechanism of antiproliferative action of DRS-B2. Structural analysis of DRS-B2 by circular dichroism in the presence of increasing concentration of CS-C shows that DRS-B2 adopts an α-helical structure. Finally, structure-activity-relationship studies suggest a key role of the W residue in position 3 of the DRS-B2 sequence for its antiproliferative activity.

Studies of the antitumor mechanism of action of dermaseptin B2, a multifunctional cationic antimicrobial peptide, reveal a partial implication of cell surface glycosaminoglycans

PubMed Central

Dos Santos, Célia; Hamadat, Sabah; Le Saux, Karen; Newton, Clara; Mazouni, Meriem; Zargarian, Loussiné; Miro-Padovani, Mickael; Zadigue, Patricia; Delbé, Jean; Hamma-Kourbali, Yamina

2017-01-01

Dermaseptin-B2 (DRS-B2) is a multifunctional cationic antimicrobial peptide (CAP) isolated from frog skin secretion. We previously reported that DRS-B2 possesses anticancer and antiangiogenic activities in vitro and in vivo. In the present study, we evaluated the antiproliferative activity of DRS-B2 on numerous tumor cell lines, its cell internalization and studies of its molecular partners as well as their influences on its structure. Confocal microscopy using ([Alexa594]-(Cys0)-DRS-B2) shows that in sensitive human tumor cells (PC3), DRS-B2 seems to accumulate rapidly at the cytoplasmic membranes and enters the cytoplasm and the nucleus, while in less sensitive tumor cells (U87MG), DRS-B2 is found packed in vesicles at the cell membrane. Furthermore FACS analysis shows that PC3 cells viability decreases after DRS-B2 treatment while U87 MG seems to be unaffected. However, "pull down" experiments performed with total protein pools from PC3 or U87MG cells and the comparison between the antiproliferative effect of DRS-B2 and its synthetic analog containing all D-amino acids suggest the absence of a stereo-selective protein receptor. Pretreatment of PC3 cells with sodium chlorate, decreases the antiproliferative activity of DRS-B2. This activity is partially restored after addition of exogenous chondroitin sulfate C (CS-C). Moreover, we demonstrate that at nanomolar concentrations CS-C potentiates the antiproliferative effect of DRS-B2. These results highlight the partial implication of glycosaminoglycans in the mechanism of antiproliferative action of DRS-B2. Structural analysis of DRS-B2 by circular dichroism in the presence of increasing concentration of CS-C shows that DRS-B2 adopts an α-helical structure. Finally, structure-activity-relationship studies suggest a key role of the W residue in position 3 of the DRS-B2 sequence for its antiproliferative activity. PMID:28797092

Useful marker of oscillatory lung function in methacholine challenge test-comparison of reactance and resistance with dose-response slope.

PubMed

Yoon, Jung Won; Shin, Youn Ho; Jee, Hye Mi; Chang, Sun Jung; Baek, Ji Hyeon; Choi, Sun Hee; Kim, Hyeong Yun; Han, Man Yong

2014-06-01

There are few studies focusing on the comparison of resistance (Rrs) and reactance (Xrs) in impulse oscillometry system (IOS) in the bronchial challenge test using dose-response slope (DRS), a quantitative index of bronchial hyperresponsiveness. We conducted a case-control study of 144 asthmatic and 218 non-asthmatic children to compare the diagnostic accuracy of two-point linear DRS for FEV1 , Rrs5 , and Xrs5 (DRS_FEV1 , DRS_Rrs5 , and DRS_Xrs5 ) and assessed various diagnostic cut-off points of provocation concentrations (PC) using receiver operating characteristic (ROC) curves. DRS_FEV1 had a stronger correlation with DRS_Xrs5 (r = 0.739, P < 0.001) than with DRS_Rrs5 (r = 0.652, P < 0.001) and the area under the ROC curves of DRS_Xrs5 (0.737) was similar to that of DRS_FEV1 (0.732) and higher than that of DRS_Rrs5 (0.668). The area under the ROC curves in order of greater value was as follows: absolute change of Xrs5 (Abs_Xrs5 ) (0.759) > percent change of FEV1 (Pch_FEV1 ) (0.735) > Pch_Xrs5 (0.727) > Abs_Rrs5 (0.690) > Pch_Rrs5 (0.630). PC78 _Xrs5 and PC0.17 _Xrs5 of IOS showed considerably good sensitivity and specificity comparable to those of PC20 _FEV1 by spirometry. Additional 18 (13%) children who showed normal spirometric measures were identified as asthmatics with the use of IOS. The utility of the DRS_Xrs5 to differentiate asthmatics from controls was comparable to that of the DRS_FEV1 and better than that of the DRS_Rrs5 . In addition, IOS could detect additional asthmatic patients who did not show positive responses in spirometry. © 2013 Wiley Periodicals, Inc.

Performance of the Delirium Rating Scale-Revised-98 Against Different Delirium Diagnostic Criteria in a Population With a High Prevalence of Dementia.

PubMed

Sepulveda, Esteban; Franco, José G; Trzepacz, Paula T; Gaviria, Ana M; Viñuelas, Eva; Palma, José; Ferré, Gisela; Grau, Imma; Vilella, Elisabet

2015-01-01

Delirium diagnosis in elderly is often complicated by underlying dementia. We evaluated performance of the Delirium Rating Scale-Revised-98 (DRS-R98) in patients with high dementia prevalence and also assessed concordance among past and current diagnostic criteria for delirium. Cross-sectional analysis of newly admitted patients to a skilled nursing facility over 6 months, who were rated within 24-48 hours after admission. Interview for Diagnostic and Statistical Manual of Mental Disorders, 3rd edition-R (DSM)-III-R, DSM-IV, DSM-5, and International Classification of Diseases 10th edition delirium ratings, administration of the DRS-R98, and assessment of dementia using the Informant Questionnaire on Cognitive Decline in the Elderly were independently performed by 3 researchers. Discriminant analyses (receiver operating characteristics curves) were used to study DRS-R98 accuracy against different diagnostic criteria. Hanley and McNeil test compared the area under the curve for DRS-R98's discriminant performance for all diagnostic criteria. Dementia was present in 85/125 (68.0%) subjects, and 36/125 (28.8%) met criteria for delirium by at least 1 classification system, whereas only 19/36 (52.8%) did by all. DSM-III-R diagnosed the most as delirious (27.2%), followed by DSM-5 (24.8%), DSM-IV-TR (22.4%), and International Classification of Diseases 10th edition (16%). DRS-R98 had the highest AUC when discriminating DSM-III-R delirium (92.9%), followed by DSM-IV (92.4%), DSM-5 (91%), and International Classification of Diseases 10th edition (90.5%), without statistical differences among them. The best DRS-R98 cutoff score was ≥14.5 for all diagnostic systems except International Classification of Diseases 10th edition (≥15.5). There is a low concordance across diagnostic systems for identification of delirium. The DRS-R98 performs well despite differences across classification systems perhaps because it broadly assesses phenomenology, even in this population with a

Anorectal stimulation causes increased colonic motor activity in subjects with spinal cord injury.

PubMed

Korsten, Mark A; Singal, Ashwani K; Monga, Amit; Chaparala, Geeta; Khan, Amir M; Palmon, Ron; Mendoza, John Reagan D; Lirio, Juan P; Rosman, Alan S; Spungen, Ann; Bauman, William A

2007-01-01

Difficulty with evacuation (DWE) is a major problem after spinal cord injury (SCI). Stimulation of the anal canal and lower rectum, accomplished using a gloved finger (so-called digital rectal stimulation or DRS) is often used as an adjunct to laxatives and enemas to facilitate bowel evacuation. However, the basis for the efficacy of DRS is not known. This study assessed the effect of DRS on colonic motility. Six subjects with SCI were studied several hours after a bowel care session. Colonic motility was assessed using a manometric catheter (affixed endoscopically to the splenic flexure) at baseline, during DRS, and after DRS. In addition, evacuation of barium oatmeal paste (with the consistency of stool and introduced into the rectum and descending colon) was assessed simultaneously using fluoroscopic techniques. The mean number (+/- SEM) of peristaltic waves per minute increased from 0 at baseline to 1.9 (+/- 0.5/min) during DRS and 1.5 (+/- 0.3/min) during the period immediately after cessation of DRS (P < 0.05). The mean amplitude (+/- SEM) of the peristaltic contractions was 43.4 (+/- 2.2) mmHg. The frequency of contractions, as well as amplitude of contractions, during or immediately after DRS was not significantly different. These manometric changes in response to DRS were accompanied by expulsion of barium oatmeal paste in every subject by the fifth DRS. DRS causes left-sided colonic activity in subjects with SCI. At least in part, an anorectal colonic reflex that results in enhanced contractions of the descending colon and rectum may contribute to bowel evacuation in individuals with SCI.

A self-updating road map of The Cancer Genome Atlas

PubMed Central

Robbins, David E.; Grüneberg, Alexander; Deus, Helena F.; Tanik, Murat M.; Almeida, Jonas S.

2013-01-01

Motivation: Since 2011, The Cancer Genome Atlas’ (TCGA) files have been accessible through HTTP from a public site, creating entirely new possibilities for cancer informatics by enhancing data discovery and retrieval. Significantly, these enhancements enable the reporting of analysis results that can be fully traced to and reproduced using their source data. However, to realize this possibility, a continually updated road map of files in the TCGA is required. Creation of such a road map represents a significant data modeling challenge, due to the size and fluidity of this resource: each of the 33 cancer types is instantiated in only partially overlapping sets of analytical platforms, while the number of data files available doubles approximately every 7 months. Results: We developed an engine to index and annotate the TCGA files, relying exclusively on third-generation web technologies (Web 3.0). Specifically, this engine uses JavaScript in conjunction with the World Wide Web Consortium’s (W3C) Resource Description Framework (RDF), and SPARQL, the query language for RDF, to capture metadata of files in the TCGA open-access HTTP directory. The resulting index may be queried using SPARQL, and enables file-level provenance annotations as well as discovery of arbitrary subsets of files, based on their metadata, using web standard languages. In turn, these abilities enhance the reproducibility and distribution of novel results delivered as elements of a web-based computational ecosystem. The development of the TCGA Roadmap engine was found to provide specific clues about how biomedical big data initiatives should be exposed as public resources for exploratory analysis, data mining and reproducible research. These specific design elements align with the concept of knowledge reengineering and represent a sharp departure from top-down approaches in grid initiatives such as CaBIG. They also present a much more interoperable and reproducible alternative to the still

Effects on survival of BAP1 and PBRM1 mutations in sporadic clear-cell renal-cell carcinoma: a retrospective analysis with independent validation.

PubMed

Kapur, Payal; Peña-Llopis, Samuel; Christie, Alana; Zhrebker, Leah; Pavía-Jiménez, Andrea; Rathmell, W Kimryn; Xie, Xian-Jin; Brugarolas, James

2013-02-01

% CI 0·3-3·8, for the UTSW cohort, and 0·2 years, 0·0-1·2, for the TCGA cohort). Our findings identify mutation-defined subtypes of clear-cell renal-cell carcinoma with distinct clinical outcomes, a high-risk BAP1-mutant group and a favourable PBRM1-mutant group. These data establish the basis for a molecular genetic classification of clear-cell renal-cell carcinoma that could influence treatment decisions in the future. The existence of different molecular subtypes with disparate outcomes should be considered in the design and assessment of clinical studies. Cancer Prevention and Research Institution of Texas and National Cancer Institute. Copyright © 2013 Elsevier Ltd. All rights reserved.

Commentary on "Effects on survival of BAP1 and PBRM1 mutations in sporadic clear-cell renal-cell carcinoma: a retrospective analysis with independent validation." Kapur P, Peña-Llopis S, Christie A, Zhrebker L, Pavía-Jiménez A, Rathmell WK, Xie XJ, Brugarolas J. Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX. Lancet Oncol 2013; 14(2):159-67. [Epub 2013 Jan 16]. doi: 10.1016/S1470-2045(12)70584-3.

PubMed

Boorjian, Stephen

2014-08-01

% CI 0·3-3·8, for the UTSW cohort, and 0·2 years, 0·0-1·2, for the TCGA cohort). Our findings identify mutation-defined subtypes of clear-cell renal-cell carcinoma with distinct clinical outcomes, a high-risk BAP1-mutant group and a favourable PBRM1-mutant group. These data establish the basis for a molecular genetic classification of clear-cell renal-cell carcinoma that could influence treatment decisions in the future. The existence of different molecular subtypes with disparate outcomes should be considered in the design and assessment of clinical studies. Cancer Prevention and Research Institution of Texas and National Cancer Institute. Copyright © 2014 Elsevier Inc. All rights reserved.

Sea Basing Logistiek

DTIC Science & Technology

2007-11-01

athankelijkheden, de hoeveelheid situatie? Auteur (s) ir. P.L.H. Cleophas drs. M.H.M. Delmee PROGRAMMA PROJECT drs. S. Hoesmans drs. P.G.M. van Scheepstal drs...hiertussen een aanvullende belangrijke schakel. In theorie worden binnen de CLAS en CZSK verschillende methoden voor het plannen van een operatie gehanteerd...J.H.A.Blokker MCM drs P.G.M. van Scheepstal Afdelingshoofd Auteur 72/72 TNO-rapport I TNO-DV 2007 A452 TNO-rapport I TNO-DV 2007 A452 Bijlage A 11/4 A Fysiek

Regulatory interactions between long noncoding RNA LINC00968 and miR-9-3p in non-small cell lung cancer: A bioinformatic analysis based on miRNA microarray, GEO and TCGA.

PubMed

Li, Dong-Yao; Chen, Wen-Jie; Shang, Jun; Chen, Gang; Li, Shi-Kang

2018-06-01

Long non-coding RNAs (lncRNAs) have been demonstrated to mediate carcinogenesis in various types of cancer. However, the regulatory role of lncRNA LINC00968 in lung adenocarcinoma remains unclear. The microRNA (miRNA) expression in LINC00968-overexpressing human lung adenocarcinoma A549 cells was detected using miRNA microarray analysis. miR-9-3p was selected for further analysis, and its expression was verified in the Gene Expression Omnibus (GEO) database. In addition, the regulatory axis of LINC00968 was validated using The Cancer Genome Atlas (TCGA) database. Results of the GEO database indicated miR-9-3p expression in lung adenocarcinoma was significantly higher compared with normal tissues. Functional enrichment analyses of the target genes of miR-9-3p indicated protein binding and the AMP-activated protein kinase pathway were the most enriched Gene Ontology and KEGG terms, respectively. Combining target genes with the correlated genes of LINC00968 and miR-9-3p, 120 objective genes were obtained, which were used to construct a protein-protein interaction (PPI) network. Cyclin A2 (CCNA2) was identified to have a vital role in the PPI network. Significant correlations were detected between LINC00968, miR-9-3p and CCNA2 in lung adenocarcinoma. The LINC00968/miR-9-3p/CCNA2 regulatory axis provides a new foundation for further evaluating the regulatory mechanisms of LINC00968 in lung adenocarcinoma.

Effect of annealing temperature on optical properties of binary zinc tin oxide nano-composite prepared by sol-gel route using simple precursors: structural and optical studies by DRS, FT-IR, XRD, FESEM investigations.

PubMed

Habibi, Mohammad Hossein; Mardani, Maryam

2015-02-25

Binary zinc tin oxide nano-composite was synthesized by a facile sol-gel method using simple precursors from the solutions consisting of zinc acetate, tin(IV) chloride and ethanol. Effect of annealing temperature on optical and structural properties was investigated using X-ray diffraction (XRD), diffuse reflectance spectra (DRS), field emission scanning electron microscopy (FESEM) and Fourier transform infrared spectroscopy (FTIR). XRD results revealed the existence of the ZnO and SnO2 phases. FESEM results showed that binary zinc tin oxide nano-composites ranges from 56 to 60 nm in diameter at 400°C and 500°C annealing temperatures respectively. The optical band gap was increased from 2.72 eV to 3.11 eV with the increasing of the annealing temperature. FTIR results confirmed the presence of zinc oxide and tin oxide and the broad absorption peaks at 3426 and 1602 cm(-1) can be ascribed to the vibration of absorptive water, and the absorption peaks at 546, 1038 and 1410 cm(-1) are due to the vibration of Zn-O or Sn-O groups in binary zinc tin oxide. Copyright © 2014 Elsevier B.V. All rights reserved.

New research on the origin of mottled clay in Quaternary basins in the coastal area of south China

NASA Astrophysics Data System (ADS)

Wang, Jing; Chen, Zhen; Gao, Quanzhou; Chen, Guoneng

2018-06-01

Last Glacial Maximum (LGM) mottled clay occurs widely in Late Quaternary basins in south China coastal areas. Current research attributes its origin to exposure weathering of Late Pleistocene marine/fluvial deposits during the LGM. However, field data suggest that this is not the case as there is no gradual transition in lithology, grain size, structure and material composition among these layers. Instead, the mottled clay possesses sedimentary characteristics of exotic dust. In this study, three typical drill cores in the Pearl River Delta were studied using grain size analysis, diffuse reflection spectroscopy (DRS) and geochemical analysis to ascertain the clay's sedimentary characteristics and origin. Grain size distribution patterns and parameters of the mottled clay were similar to those of a typical loess, indicating aeolian origin. In DRS curves, the peak height of hematite > goethite, indicating that the mottled clay had not experienced strong hydration and constitutes a continental product. This conforms to a typical loess but differs from the underlying marine/fluvial deposits. The chemical composition of the mottled clay was homogeneous in the vertical and planar directions. Upper continental crust (UCC) normalized curves of major and trace elements of the mottled clay were close to the average UCC and were consistent with typical aeolian deposits. The spatial and temporal distribution characteristics and relationship with the underlying layer suggest that the mottled clay was a loess-like deposit during the LGM and its mottled structure originated from strong modification of oxidation during the postglacial period after homogeneous dust had accumulated.

Clinical value of survivin and its underlying mechanism in ovarian cancer: A bioinformatics study based on GEO and TCGA data mining.

PubMed

Li, Xiao-Jiao; Pang, Jin-Shu; Li, Yao-Mei; Ahmed, Farah Abdirahman; He, Rong-Quan; Ma, Jie; Ma, Fu-Chao; Chen, Gang

2018-03-01

An increasing number of studies have confirmed that survivin (BIRC5) plays essential roles in ovarian cancer. Nevertheless, inconsistent or controversial results exist in some studies. In the present study, we sought to determine the clinical significance of survivin and its potential molecular pathways. The correlation between survivin (BIRC5) expression and diagnostic value, prognostic value and clinicopathological features was assessed by meta-analysis with more than 4000 patients from literature, GEO and TCGA. In addition, the potential molecular mechanism of survivin in ovarian cancer was also determined. The pooled sensitivity and specificity were 0.71 (95%CI: 0.68-0.74) and 0.97 (95%CI: 0.94-0.98), respectively. The AUC of sROC was 0.8765. The results showed that there was also a significant relationship between survivin expression and poor overall survival (HR: 1.24, 95%CI: 1.14-1.35, p < 0.001), disease-free survival (HR: 1.53, 95%CI: 0.57-4.09, p < 0.001), as well as higher recurrence rate (HR: 1.11, 95%CI: 0.97-1.27). Moreover, survivin expression was also associated with tumor progression (cancerous vs. benign, OR: 11.29, 95%CI: 8.96-14.24, p < 0.001), TNM stage (III + IV vs. I + II, OR: 5.38, 95%CI: 4.16-6.97, p < 0.001), histological grades (G3 vs. G1 ∼ G2, OR: 4.36, 95%CI: 3.29-5.77, p < 0.001), and lymphatic metastasis (metastasis vs. non-metastasis, 3.35, 95%CI 2.36-4.75, p < 0.001). Bioinformatics analysis revealed the 50 most frequently altered neighboring genes of survivin in OC, and then Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted. GO analysis showed that these genes were related to signal conduction, cell cycle, apoptosis, and metabolism. KEGG pathways analysis indicated that these genes were primarily enriched in mitotic prometaphase, PLK1 signaling events and the regulation of glucokinase by the glucokinase regulatory protein. Survivin (BIRC5) expression

Anorectal Stimulation Causes Increased Colonic Motor Activity in Subjects With Spinal Cord Injury

PubMed Central

Korsten, Mark A; Singal, Ashwani K; Monga, Amit; Chaparala, Geeta; Khan, Amir M; Palmon, Ron; Mendoza, John Reagan D; Lirio, Juan P; Rosman, Alan S; Spungen, Ann; Bauman, William A

2007-01-01

Background: Difficulty with evacuation (DWE) is a major problem after spinal cord injury (SCI). Stimulation of the anal canal and lower rectum, accomplished using a gloved finger (so-called digital rectal stimulation or DRS) is often used as an adjunct to laxatives and enemas to facilitate bowel evacuation. However, the basis for the efficacy of DRS is not known. This study assessed the effect of DRS on colonic motility. Methods: Six subjects with SCI were studied several hours after a bowel care session. Colonic motility was assessed using a manometric catheter (affixed endoscopically to the splenic flexure) at baseline, during DRS, and after DRS. In addition, evacuation of barium oatmeal paste (with the consistency of stool and introduced into the rectum and descending colon) was assessed simultaneously using fluoroscopic techniques. Results: The mean number (± SEM) of peristaltic waves per minute increased from 0 at baseline to 1.9 (±0.5/min) during DRS and 1.5 (±0.3/min) during the period immediately after cessation of DRS (P < 0.05). The mean amplitude (±SEM) of the peristaltic contractions was 43.4 (±2.2) mmHg. The frequency of contractions, as well as amplitude of contractions, during or immediately after DRS was not significantly different. These manometric changes in response to DRS were accompanied by expulsion of barium oatmeal paste in every subject by the fifth DRS. Conclusions: DRS causes left-sided colonic activity in subjects with SCI. At least in part, an anorectal colonic reflex that results in enhanced contractions of the descending colon and rectum may contribute to bowel evacuation in individuals with SCI. PMID:17385267

Superiority of delayed risk stratification in differentiated thyroid cancer after total thyroidectomy and radioactive iodine ablation.

PubMed

Hong, Chae Moon; Lee, Won Kee; Jeong, Shin Young; Lee, Sang-Woo; Ahn, Byeong-Cheol; Lee, Jaetae

2014-11-01

The aim of this study was to validate the effectiveness of delayed risk stratification (DRS) in predicting structural progression and compare the predictive value of American Thyroid Association (ATA) risk stratification with that of DRS in patients with differentiated thyroid cancer (DTC). A total of 398 patients with DTC who underwent surgery followed by radioactive iodine ablation were enrolled. Patients were categorized as having excellent response, acceptable response, biochemical incomplete response, or structural incomplete response at 8-15 months' evaluation after radioactive iodine ablation for DRS. Effectiveness of DRS was evaluated according to structural progression-free survival (PFS; median follow-up, 10.7 years). A total of 229 patients (57.5%) were classified as having excellent response, 78 (19.6%) as having acceptable response, 62 (15.6%) as having biochemical incomplete response, and 29 patients (7.3%) as having structural incomplete response. After DRS, 60.2% of intermediate-risk patients and 20.5% of high-risk patients were shifted to the excellent response category. Sixty-nine patients (17.3%) showed structural progression. DRS showed statistical difference in PFS (hazard ratio, 4.268; 95% confidence interval, 3.258-5.477; P<0.001). In multivariate analysis of ATA risk stratification and DRS, DRS was significantly associated with PFS (hazard ratio, 4.383; 95% confidence interval, 3.250-5.912; P<0.001), but ATA risk stratification was not. There was no significant difference in deviances between the use of DRS alone and the use of both DRS and ATA risk stratification (χ=0.103, d.f.=1, P=0.748). DRS is superior to ATA risk stratification in predicting structural disease progression for DTC patients.

Network Meta-Analysis on the Effects of DNA Damage Response-Related Gene Mutations on Overall Survival of Breast Cancer Based on TCGA Database.

PubMed

Liu, Chang; Chang, Hong; Li, Xiao-Han; Qi, Ya-Fei; Wang, Jin-Ou; Zhang, Ying; Yang, Xiang-Hong

2017-12-01

The study was conducted for comparing the effects of 12 DNA damage response gene mutations (CHEK1, CHEK2, RAD51, BRCA1, BRCA2, MLH1, MSH2, ATM, ATR, MDC1, PARP1, and FANCF) on the overall survival (OS) of breast cancer (BC) patients. We searched the Cancer Genome Atlas (TCGA) database from inception to September 2016. Studies that investigated the association between 12 DNA damage responses related genes and BC consolidated into this Network meta-analysis, by comparing directly or indirectly to evaluate the hazard rate (HR) value and the surface under the cumulative sequence ranking curves (SUCRA). In total four articles were involved. Our results demonstrated 12 DNA damage response gene mutations were associated to the poor prognosis of BC patients (CHEK1: HR = 9.9, 95%CI = 3.6-26.0; CHEK2: HR = 6.9, 95%CI = 3.1-15.0; RAD51: HR = 5.8, 95%CI = 2.2-15.0; BRCA1: HR = 2.8, 95%CI = 1.3-6.1; BRCA2: HR = 3.9, 95%CI = 2.0-7.7; MLH1: HR = 11.0, 95%CI = 3.4-33.0; MSH2: HR = 6.5, 95%CI = 2.1-20.0; ATM: HR = 5.6, 95%CI = 2.6-12.0; ATR: HR = 2.9, 95%CI = 1.3-6.9; MDC1: HR = 15.0, 95%CI = 5.0-45.0; PARP1: HR = 3.4, 95%CI = 1.8-6.6; FANCF: HR = 6.0, 95%CI = 1.8-20.0). SUCRA results revealed that the mutation of MDC1 gene was related to the worst prognosis in patients with BC (SUCRA = 17.32%). DNA damage response gene mutations were associated to the poor prognosis in patients with BC and the BC patients with MDC1 gene mutation had the worst prognosis. J. Cell. Biochem. 118: 4728-4734, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Relationship between the baseline alveolar volume-to-total lung capacity ratio and airway responsiveness.

PubMed

Kaminsky, David A; Daud, Anees; Chapman, David G

2014-10-01

Ventilation heterogeneity (VH) has been linked to airway responsiveness (AR) based on various measures of VH involving inert gas washout, forced oscillation and lung imaging. We explore whether VH at baseline, as measured by the simple ratio of single breath alveolar volume to plethysmographically determined total lung capacity (VA/TLC), would correlate with AR as measured by methacholine challenge testing. We analysed data from spirometry, lung volumes, diffusing capacity and methacholine challenge to derive the VA/TLC and the dose-response slope (DRS) of forced expiratory volume in 1 s (DRS-FEV1) during methacholine challenge from 136 patients. We separated out airway closure versus narrowing by examining the DRS for forced vital capacity (DRS-FVC) and the DRS for FEV1/FVC (DRS-FEV1/FVC), respectively. Similarly, we calculated the DRS for sGaw (DRS-sGaw) as another measure of airway narrowing. We performed statistical analysis using Spearman rank correlation and multifactor linear regression using a backward stepwise modelling procedure. We found that the DRS-FEV1 correlated with baseline VA/TLC (rho = -0.26, P < 0.01), and VA/TLC and FEV1 were independently associated with DRS-FEV1 (R(2)  = 0.14, P = 0.01). In addition, VA/TLC was associated with both airway narrowing and closure in response to methacholine. These results confirm that baseline VA/TLC is associated with AR, and reflects both airway closure and airway narrowing following methacholine challenge. © 2014 Asian Pacific Society of Respirology.

Young Investigator Perspectives. Teaching and the postdoctoral experience: impact on transition to faculty positions.

PubMed

Uno, Jennifer; Walton, Kristen L W

2014-05-01

This editorial continues with our Young Investigator Perspectives series. Drs. Uno and Walton are young investigators who hold faculty positions. They completed a K12 postdoctoral program through the IRACDA (Individual Research and Career Development Award) program sponsored through the NIGMS institute at NIH. IRACDA programs exist at multiple institutions in the USA to combine postdoctoral training with formal training in academic skills and teaching at partner institutions. I thank Drs. Walton and Uno for a thoughtful perspective on how this experience shaped their career goals to combine teaching and research and inspire undergraduates to science careers. Given the current national dialog on broadening career paths and outcomes for PhD scientists, this is a timely perspective. -P. Kay Lund.

Comparison of Accuracy of Diabetes Risk Score and Components of the Metabolic Syndrome in Assessing Risk of Incident Type 2 Diabetes in Inter99 Cohort

PubMed Central

Shafizadeh, Tracy B.; Moler, Edward J.; Kolberg, Janice A.; Nguyen, Uyen Thao; Hansen, Torben; Jorgensen, Torben; Pedersen, Oluf; Borch-Johnsen, Knut

2011-01-01

Background Given the increasing worldwide incidence of diabetes, methods to assess diabetes risk which would identify those at highest risk are needed. We compared two risk-stratification approaches for incident type 2 diabetes mellitus (T2DM); factors of metabolic syndrome (MetS) and a previously developed diabetes risk score, PreDx® Diabetes Risk Score (DRS). DRS assesses 5 yr risk of incident T2DM based on the measurement of 7 biomarkers in fasting blood. Methodology/Principal Findings DRS was evaluated in baseline serum samples from 4,128 non-diabetic subjects in the Inter99 cohort (Danes aged 30–60) for whom diabetes outcomes at 5 years were known. Subjects were classified as having MetS based on the presence of at least 3 MetS risk factors in baseline clinical data. The sensitivity and false positive rate for predicting diabetes using MetS was compared to DRS. When the sensitivity was fixed to match MetS, DRS had a significantly lower false positive rate. Similarly, when the false positive rate was fixed to match MetS, DRS had a significantly higher specificity. In further analyses, subjects were classified by presence of 0–2, 3 or 4–5 risk factors with matching proportions of subjects distributed among three DRS groups. Comparison between the two risk stratification schemes, MetS risk factors and DRS, were evaluated using Net Reclassification Improvement (NRI). Comparing risk stratification by DRS to MetS factors in the total population, the NRI was 0.146 (p = 0.008) demonstrating DRS provides significantly improved stratification. Additionally, the relative risk of T2DM differed by 15 fold between the low and high DRS risk groups, but only 8-fold between the low and high risk MetS groups. Conclusions/Significance DRS provides a more accurate assessment of risk for diabetes than MetS. This improved performance may allow clinicians to focus preventive strategies on those most in need of urgent intervention. PMID:21829540

Exploring cancer genomic data from the cancer genome atlas project.

PubMed

Lee, Ju-Seog

2016-11-01

The Cancer Genome Atlas (TCGA) has compiled genomic, epigenomic, and proteomic data from more than 10,000 samples derived from 33 types of cancer, aiming to improve our understanding of the molecular basis of cancer development. Availability of these genome-wide information provides an unprecedented opportunity for uncovering new key regulators of signaling pathways or new roles of pre-existing members in pathways. To take advantage of the advancement, it will be necessary to learn systematic approaches that can help to uncover novel genes reflecting genetic alterations, prognosis, or response to treatments. This minireview describes the updated status of TCGA project and explains how to use TCGA data. [BMB Reports 2016; 49(11): 607-611].

Major depressive disorder with psychotic features may lead to misdiagnosis of dementia: a case report and review of the literature.

PubMed

Wagner, Gerhardt S; McClintock, Shawn M; Rosenquist, Peter B; McCall, W Vaughn; Kahn, David A

2011-11-01

Major depressive disorder (MDD) with psychotic features is relatively frequent in patients with greater depressive symptom severity and is associated with a poorer course of illness and greater functional impairment than MDD without psychotic features. Multiple studies have found that patients with psychotic mood disorders demonstrate significantly poorer cognitive performance in a variety of areas than those with nonpsychotic mood disorders. The Mini Mental State Examination (MMSE) and the Dementia Rating Scale, Second Edition (DRS-2) are widely used to measure cognitive functions in research on MDD with psychotic features. Established total raw score cut-offs of 24 on the MMSE and 137 on the DRS-2 in published manuals suggest possible global cognitive impairment and dementia, respectively. Limited research is available on these suggested cut-offs for patients with MDD with psychotic features. We document the therapeutic benefit of electroconvulsive therapy (ECT), which is usually associated with short-term cognitive impairment, in a 68-year-old woman with psychotic depression whose MMSE and DRS-2 scores initially suggested possible global cognitive impairment and dementia. Over the course of four ECT treatments, the patient's MMSE scores progressively increased. After the second ECT treatment, the patient no longer met criteria for global cognitive impairment. With each treatment, depression severity, measured by the 24-item Hamilton Rating Scale for Depression, improved sequentially. Thus, the suggested cut-off scores for the MMSE and the DRS-2 in patients with MDD with psychotic features may in some cases produce false-positive indications of dementia.

Activity of binary mixtures of drospirenone with progesterone and 17α-ethinylestradiol in vitro and in vivo.

PubMed

Rossier, Nadine Madeleine; Chew, Geraldine; Zhang, Kun; Riva, Francesco; Fent, Karl

2016-05-01

Despite potential exposure of aquatic organisms to mixtures of steroid hormones, very little is known on their joint activity in fish. Drospirenone (DRS) is a new synthetic progestin used in contraceptive pills in combination with 17α-ethinylestradiol (EE2). Here we systematically analyzed effects of DRS in binary mixtures with progesterone (P4) and EE2. First, we determined the in vitro activity of single compounds in recombinant yeast assays that express the human progesterone, androgen, or estrogen receptor, followed by determination of mixture activities of DRS and P4, DRS and EE2, as well as medroxyprogesterone acetate (MPA) and dydrogesterone (DDG). Mixtures of DRS and P4, as well as of DRS and EE2 showed additive progestogenic and androgenic activities. However, DDG and MPA showed non-additive progestogenic and androgenic activities. We then analyzed the in vivo activity of single compounds and mixtures of DRS and P4, as well as DRS and EE2, by assessing transcriptional changes of up to 14 selected target genes in zebrafish embryos at 48h post fertilization (hpf), and in eleuthero-embryos at 96hpf and 144hpf. DRS, P4, and EE2 led to significant transcriptional alteration of genes, including those encoding hormone receptors (pgr, esr1), a steroidogenic enzyme (hsd17b3), and estrogenic markers (vtg1, cyp19b), in particular at 144 hpf. In general, DRS showed stronger transcriptional changes than P4. In mixtures of DRS and P4, they were mainly non-additive (antagonistic interaction). In mixtures of DRS and EE2, transcriptional responses of esr1, vtg1 and cyp19b were dominated by EE2, suggesting an antagonistic interaction or independent action. Equi-effective mixtures of DRS and EE2, based on progesterone receptor transcripts, showed antagonistic interactions. Our data suggest that interactions in mixtures assessed in vitro in recombinant yeast cannot be translated to the in vivo situation. The receptor-based responses did not correspond well to the

Comparison of primary position measurements and abduction deficit between type 1 Duane syndrome and sixth cranial nerve palsy.

PubMed

Batra, Noopur Nikki; Arnoldi, Kyle; Reynolds, James D; Strominger, Mitchell B

2011-06-01

Unilateral Duane retraction syndrome type 1 (DRS-I) and unilateral sixth nerve palsy (6NP) present with limitation of abduction, incomitant esotropia, and frequently, a compensatory head turn. The purpose of this study was to compare the mean primary position measurement and to correlate this with the abduction deficit to determine if these measurements may be used to differentiate between the 2 conditions when other clinical signs of DRS-I (globe retraction, changes in lid fissure height, and upshoots/downshoots) are subtle. A database search of patients examined over a 5-year period revealed 69 cases of DRS-I and 62 cases of unilateral 6NP. Primary position measurements both at distance and near and limitation of abduction on version testing were recorded and compared. Mean abduction deficit was -3.5 ± 0.1 for DRS-I and -2.6 ± 0.2 for 6NP (P = 0.0004). Mean esotropia at near was 8.4 ± 1.1 prism diopters (PD) for DRS-I and 27.2 ± 2.4 PD for 6NP (P < 0.0001). Mean esotropia at distance was 10.3 ± 1.3 PD for DRS-I and 36.4 ± 2.4 PD for 6NP (P < 0.0001). The mean distance-near disparity for DRS-I was 1.94 ± 0.62 PD and 9.19 ± 1.28 PD for 6NP (P < 0.0001). The age-group of ≤2 years consisted of 23 DRS-I and only 2 6NP cases. The age-group between >2 years and <18 years had 41 DRS-I and 16 6NP cases, respectively. Finally, the age-group of ≥18 years had only 5 DRS-I and 44 6NP cases (P < 0.0001). Patients with DRS-I showed greater abduction deficit yet significantly less esotropia in primary position than those with 6NP. Patients with 6NP were more likely to have a significant distance-near disparity. In addition, patients with DRS-I tended to be younger than those with 6NP. This report documents that DRS-I and 6NP can be differentiated based on magnitude of primary position esotropia, comparison of primary position esotropia with severity of abduction deficit, distance-near disparity, and patient age.

Subsyndromal delirium compared with delirium, dementia, and subjects without delirium or dementia in elderly general hospital admissions and nursing home residents.

PubMed

Sepulveda, Esteban; Leonard, Maeve; Franco, Jose G; Adamis, Dimitrios; McCarthy, Geraldine; Dunne, Colum; Trzepacz, Paula T; Gaviria, Ana M; de Pablo, Joan; Vilella, Elisabet; Meagher, David J

2017-01-01

Subsyndromal delirium (SSD) complicates diagnosis of delirium and dementia, although there is little research comparing their symptom profiles. Cross-sectional study of 400 elderly patients' admission to a general hospital or nursing home diagnosed with delirium, SSD, dementia, or no-delirium/no-dementia (NDND). Symptom profiles were assessed using the Delirium Rating Scale-Revised-98 (DRS-R98). Twenty percent patients had delirium, 19.3% had SSD, 29.8% had dementia-only, and 31% had NDND. Eighty-one percent of subsyndromal and 76% of delirium groups had comorbid dementia. DRS-R98 scores showed ascending severity from NDND < dementia-only < SSD < delirium. DRS-R98 scores for items evaluating the three core symptom domains (cognitive, higher-order thinking, and circadian) distinguished SSD from delirium and both from nondelirium groups. DRS-R98 profiles were essentially the same in delirium and SSD subgroups with or without dementia, although total scale scores were generally higher when in comorbid subgroups. SSD shared characteristic core domain symptoms with delirium, which distinguished each from nondelirium groups, although severity was intermediate in the subsyndromal group. Delirium core symptoms overshadowed the dementia phenotype when comorbid. Milder disturbances of delirium core domain symptoms are highly suggestive of SSD.

Dynamics of controllably induced bruises assessed by diffuse reflectance spectroscopy and pulsed photothermal radiometry

NASA Astrophysics Data System (ADS)

Marin, Ana; Milanič, Matija; Verdel, Nina; Vidovič, Luka; Majaron, Boris

2018-02-01

Combination of diffuse reflectance spectroscopy (DRS) and pulsed photothermal radiometry (PPTR) was recently successfully used to study evolution of accidental traumatic bruises. Yet, accidental bruises introduce many unknowns into the evolution analysis and thus a more controllable and repeatable approach for bruising is desired. In this study, evolution of bruises induced by aluminum projectiles of known mass and velocity were studied by DRS and PPTR. Bruises were induced on volar forearm skin of two healthy volunteers. Inverse Monte Carlo including four-layer skin model, was used to analyze the DRS and PPTR data to determine skin chromophores, their concentrations and depths. For bruise analysis, a bruise model was constructed and evolved according to hemoglobin diffusion kinetics. Bruise analysis of PPTR signals yielded bruise evolution parameters, most importantly hemoglobin diffusion constant, hemoglobin decomposition time and blood pool depth. The study results show that chronological tracking of hemoglobin decomposition can be assessed by the combined DRS and PPTR technique on induced bruise. Parameters of individual bruises were compared and two trends in chronological behavior of hemoglobin decomposition time discerned. Changes in bruise diffuse reflectance spectra were noted. Induced bruise parameters, however, still showed some scatter and thus further research is needed to reduce bruise variability.

Down syndrome: national conference on patient registries, research databases, and biobanks.

PubMed

Oster-Granite, Mary Lou; Parisi, Melissa A; Abbeduto, Leonard; Berlin, Dorit S; Bodine, Cathy; Bynum, Dana; Capone, George; Collier, Elaine; Hall, Dan; Kaeser, Lisa; Kaufmann, Petra; Krischer, Jeffrey; Livingston, Michelle; McCabe, Linda L; Pace, Jill; Pfenninger, Karl; Rasmussen, Sonja A; Reeves, Roger H; Rubinstein, Yaffa; Sherman, Stephanie; Terry, Sharon F; Whitten, Michelle Sie; Williams, Stephen; McCabe, Edward R B; Maddox, Yvonne T

2011-01-01

A December 2010 meeting, "Down Syndrome: National Conference on Patient Registries, Research Databases, and Biobanks," was jointly sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at the National Institutes of Health (NIH) in Bethesda, MD, and the Global Down Syndrome Foundation (GDSF)/Linda Crnic Institute for Down Syndrome based in Denver, CO. Approximately 70 attendees and organizers from various advocacy groups, federal agencies (Centers for Disease Control and Prevention, and various NIH Institutes, Centers, and Offices), members of industry, clinicians, and researchers from various academic institutions were greeted by Drs. Yvonne Maddox, Deputy Director of NICHD, and Edward McCabe, Executive Director of the Linda Crnic Institute for Down Syndrome. They charged the participants to focus on the separate issues of contact registries, research databases, and biobanks through both podium presentations and breakout session discussions. Among the breakout groups for each of the major sessions, participants were asked to generate responses to questions posed by the organizers concerning these three research resources as they related to Down syndrome and then to report back to the group at large with a summary of their discussions. This report represents a synthesis of the discussions and suggested approaches formulated by the group as a whole. Copyright © 2011. Published by Elsevier Inc. All rights reserved.

Doctoral profile of the medical radiation sciences: a baseline for Australia and New Zealand.

PubMed

Ekpo, Ernest U; Snaith, Beverly; Harris, Martine A; McEntee, Mark F

2017-09-01

Research is critical to evidence-based practice, and the rapid developments in technology provide opportunities to innovate and improve practice. Little is known about the research profile of the medical radiation science (MRS) profession in Australia and New Zealand (NZ). This study provides a baseline of their doctoral activity. A cross-sectional survey of MRS professionals in Australia and NZ holding a doctorate or undertaking doctoral studies, was performed using an online tool (Bristol Online Survey ® , Bristol, UK). A chain-referral sampling technique was adopted for data collection. An email invitation with a link to the survey was generated and distributed through email and social media. The survey contained questions related to participant demographics, doctoral status, qualification route, funding and employment. There were 63 responses to the survey comprising 50.8% diagnostic radiographers (DRs; n = 32), 23.8% radiation therapists (RTs; n = 15), with the remaining 25.4% (n = 16) equally split between sonographers and nuclear medicine technologists (NMTs). A total of 40 (63.5%) of respondents had completed their doctoral qualification. In NZ, only DRs held a doctoral award constituting 0.3% of DRs and 0.2% of the total registered MRS population. In Australia, there was a greater proportion of doctoral NMTs (n = 8/1098; 0.7%) than RTs (n = 15/2394; 0.6%) and DRs (n = 27/12,001; 0.2%). Similar to other countries, findings show a very small percentage of doctoral MRS professionals in Australia and NZ. Strategies to engage and support individuals in research, up to and beyond doctoral study, need to be embedded in practice. © 2017 The Authors. Journal of Medical Radiation Sciences published by John Wiley & Sons Australia, Ltd on behalf of Australian Society of Medical Imaging and Radiation Therapy and New Zealand Institute of Medical Radiation Technology.

Levels of personality functioning and their association with clinical features and interpersonal functioning in patients with personality disorders.

PubMed

Lowyck, Benedicte; Luyten, Patrick; Verhaest, Yannic; Vandeneede, Bart; Vermote, Rudi

2013-06-01

Recently, the DSM-5 Personality and Personality Disorders Work Group has proposed a multiple level approach toward the classification and diagnosis of personality disorders (PDs), with the first level entailing a rating of impairments in levels of personality functioning. Although a number of measures that assess levels of personality functioning have been validated, given its prominent status in the DSM-5 proposal and contemporary theories of personality pathology, the Work Group has called for more research in this area (e.g., Bender, Morey, & Skodol, 2011). In response to this call, this study investigates the relationship between two major, well-validated dimensional measures of levels of personality functioning, that is, the Differentiation-Relatedness Scale (DR-S; Diamond, Blatt, Stayner, & Kaslow, 1991), as scored on the Object Relations Inventory (ORI; Blatt, Wein, Chevron, & Quinlan, 1979), and the Inventory of Personality Organization (IPO; Lenzenweger, Clarkin, Kernberg, & Foelsch, 2001), a self-report instrument, and their relationship with different measures of clinical and interpersonal functioning in 70 patients with a PD. First, results showed that higher levels of differentiation and relatedness of descriptions of self and significant others, and of the self in particular, were negatively related to indices of personality functioning as assessed by the IPO. Lower levels of personality functioning, as measured with both the DR-S and the IPO, were positively related to severity of depression, symptomatic distress, self-harm, and interpersonal problems. Finally, results showed that the DR-S and the IPO independently predicted clinical features and interpersonal functioning. Hence, this study lends further support for the concurrent and predictive validity of the DR-S and the IPO in assessing levels of personality functioning. However, more research concerning the validity of these measures in assessing levels of personality functioning is needed

The Cancer Genome Atlas Pan-Cancer Analysis Project

PubMed Central

Weinstein, John N.; Collisson, Eric A.; Mills, Gordon B.; Shaw, Kenna M.; Ozenberger, Brad A.; Ellrott, Kyle; Shmulevich, Ilya; Sander, Chris; Stuart, Joshua M.

2014-01-01

Cancer can take hundreds of different forms depending on the location, cell of origin and spectrum of genomic alterations that promote oncogenesis and affect therapeutic response. Although many genomic events with direct phenotypic impact have been identified, much of the complex molecular landscape remains incompletely charted for most cancer lineages. For that reason, The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumours to discover molecular aberrations at the DNA, RNA, protein, and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences, and emergent themes across tumour lineages. The Pan-Cancer initiative compares the first twelve tumour types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumour types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. PMID:24071849

Predictive validity of disability rating scale in determining functional outcome in patients with severe traumatic brain injury.

PubMed

Deepika, Akhil; Devi, B Indira; Shukla, Dhaval

2017-01-01

Most patients with severe traumatic brain injury (TBI) are discharged when they have still not recovered completely. Many such patients are not available for follow up. We conducted this study to determine whether the condition at discharge from acute care setting, as assessed with disability rating scale (DRS), correlates with functional outcome at follow up. This study was conducted at a Neurosurgical intensive care unit (ICU) of a tertiary care referral center. This was a prospective observational study. Patients admitted to ICU with a diagnosis of severe TBI were enrolled for the study. On the day of discharge, all patients underwent DRS assessment. A final assessment was performed using Glasgow outcome scale extended (GOSE) at 6 months after discharge from the hospital. The correlation between the DRS scores at the time of discharge with DRS scores and GOSE categories at 6 months after discharge was determined using Spearman's rho correlation coefficient. A total of 88 patients were recruited for the study. The correlation coefficient of DRS at discharge for DRS at 6 months was 0.536 and for GOSE was -0.553. The area under the curve of DRS score at discharge for predicting unfavorable outcome and mortality at 6 months was 0.770 and 0.820, respectively. The predictive validity of DRS is fair to good in determining GOSE at follow-up. Pending availability of a more accurate outcome assessment tool, DRS at discharge can be used as a surrogate outcome for GOSE at follow up.

Conference Proceedings: “Down Syndrome: National Conference on Patient Registries, Research Databases, and Biobanks”

PubMed Central

Oster-Granite, Mary Lou; Parisi, Melissa A.; Abbeduto, Leonard; Berlin, Dorit S.; Bodine, Cathy; Bynum, Dana; Capone, George; Collier, Elaine; Hall, Dan; Kaeser, Lisa; Kaufmann, Petra; Krischer, Jeffrey; Livingston, Michelle; McCabe, Linda L.; Pace, Jill; Pfenninger, Karl; Rasmussen, Sonja A.; Reeves, Roger H.; Rubinstein, Yaffa; Sherman, Stephanie; Terry, Sharon F.; Whitten, Michelle Sie; Williams, Stephen; McCabe, Edward R.B.; Maddox, Yvonne T.

2011-01-01

A December 2010 meeting, “Down Syndrome: National Conference on Patient Registries, Research Databases, and Biobanks,” was jointly sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at the National Institutes of Health (NIH) in Bethesda, MD, and the Global Down Syndrome Foundation (GDSF)/Linda Crnic Institute for Down Syndrome based in Denver, CO. Approximately 70 attendees and organizers from various advocacy groups, federal agencies (Centers for Disease Control and Prevention, and various NIH Institutes, Centers, and Offices), members of industry, clinicians, and researchers from various academic institutions were greeted by Drs. Yvonne Maddox, Deputy Director of NICHD, and Edward McCabe, Executive Director of the Linda Crnic Institute for Down Syndrome. They charged the participants to focus on the separate issues of contact registries, research databases, and biobanks through both podium presentations and breakout session discussions. Among the breakout groups for each of the major sessions, participants were asked to generate responses to questions posed by the organizers concerning these three research resources as they related to Down syndrome and then to report back to the group at large with a summary of their discussions. This report represents a synthesis of the discussions and suggested approaches formulated by the group as a whole. PMID:21835664

2013 Schroth faces of the future symposium to highlight early career professionals in Mycology

USDA-ARS?s Scientific Manuscript database

The 2013 Schroth Faces of the Future symposium was created to recognize early career professionals (those within 10 years of graduation) who represent the future in their field via innovative research. For this year, future faces in mycology research were recognized. Drs. Jason Slot, Erica Goss, Jam...

Architecting Human Operator Trust in Automation to Improve System Effectiveness in Multiple Unmanned Aerial Vehicles (UAV) Control

DTIC Science & Technology

2009-03-01

like to extend our appreciation to our research sponsor Dr. Janet Miller from the Air Force Research Labs, and her colleague Dr. Cheryl Batchelor, for...for single-operator control of multiple UAVs. Drs. Brian Tsou, Lamar Warfield , Justin Estepp and Benjamin Knott , meanwhile, contributed to our

Linking International Cancer Screening Efforts

Cancer.gov

Drs. Sudha Sivaram and Steve Taplin speak at the International Cancer Screening Network (ICSN) Meeting, which brings together individuals involved in cancer screening research and cancer screening programs from the ICSN’s member countries.

Korean version of the delirium rating scale-revised-98: reliability and validity.

PubMed

Lee, Yanghyun; Ryu, Jian; Lee, Jinyoung; Kim, Hwi-Jung; Shin, Im Hee; Kim, Jeong-Lan; Trzepacz, Paula T

2011-03-01

The aims of the present study were 1) to standardize the validity and reliability of the Korean version of Delirium Rating Scale-Revised-98 (DRS-R98-K) and 2) to establish the optimum cut-off value, sensitivity, and specificity for discriminating delirium from other non-delirious psychiatric conditions. Using DSM-IV criteria, 157 subjects (69 delirium, 29 dementia, 32 schizophrenia, and 27 other psychiatric patients) were enrolled. Subjects were evaluated using DRS-R98-K, DRS-K, Mini-Mental State Examination (MMSE-K), and Clinical Global Impression-Severity (CGI-S) scale. DRS-R98-K total and severity scores showed high correlations with DRS-K. They were significantly different across all groups (p=0.000). However, neither MMSE-K nor CGI-S distinguished delirium from dementia. All DRS-R98-K diagnostic items (#14-16) and items #1 and 2 significantly discriminated delirium from dementia. Cronbach's alpha coefficient revealed high internal consistency for DRS-R98-K total (r=0.91) and severity (r=0.89) scales. Interrater reliability (ICC between 0.96 and 1) was very high. Using receiver operating characteristic analysis, the area under the curve of DRS-R98-K total score was 0.948 between the delirium group and all other groups and 0.873 between the delirium and dementia groups. The best cut-off scores in DRS-R98-K total score were 18.5 and 19.5 between the delirium and the other three groups and 20.5 between the delirium and dementia groups. We demonstrated that DRS-R98-K is a valid and reliable instrument for assessing delirium severity and diagnosis and discriminating delirium from dementia and other psychiatric disorders in Korean patients.

Reliability and Validity of a Brief Questionnaire to Assess Calcium Intake in Female Collegiate Athletes

PubMed Central

Ward, Kenneth D.; Hunt, Kami Mays; Berg, Melanie Burstyne; Slawson, Deborah A.; Vukadinovich, Christopher M.; McClanahan, Barbara S.; Clemens, Linda H.

2016-01-01

Calcium intake often is inadequate in female collegiate athletes, increasing the risk for training injuries and future osteoporosis. Thus, a brief and accurate assessment tool to quickly measure calcium intake in athletes is needed. We evaluated the reliability and validity, compared to 6 days of diet records (DRs), of the Rapid Assessment Method (RAM), a self-administered calcium checklist (14). Seventy-six female collegiate athletes (mean age = 18.8 yrs, range = 17–21; 97% Caucasian) were recruited from basketball, cross-country, field hockey, soccer, and volleyball teams. Athletes completed a RAM at the start of the training season to assess calcium intake during the past week. Two weeks later, a second RAM was completed to assess reliability, and athletes began 6 days of diet records (DRs) collection. At completion of DRs, athletes completed a final RAM, corresponding to the same time period as DRs, to assess agreement between the 2 instruments. The RAM demonstrated adequate test-retest reliability over 2 weeks (n = 56; Intraclass correlation [ICC] = .54, p < .0001) and adequate agreement with DRs (n = 34; ICC = .41, p = .0067). Calcium intake was below recommended levels, and mean estimates did not differ significantly on the RAM (823 ± 387 mg/d) and DRs (822 ± 330 mg/d; p = .988). Adequacy of calcium intake from both DRs and the RAM was classified as “inadequate” (<1000 mg/d) and “adequate” (≥1000 mg/d). Agreement between the RAM and DRs for adequacy classification was fair (ICC = .30, p = .042), with the RAM identifying 84% of athletes judged to have inadequate calcium intake based on DRs. The RAM briefly and accurately estimates calcium intake in female collegiate athletes compared to DRs. PMID:15118194

Which Genes Drive Cancers? - TCGA

Cancer.gov

Associate Professor of Medicine at the Dana-Farber Cancer Institute, William Hahn, describes the method his lab has developed to tease apart the crucial driver mutations from passenger mutations in ovarian cancer.

Advancing The Cancer Genome Atlas glioma MRI collections with expert segmentation labels and radiomic features

PubMed Central

Bakas, Spyridon; Akbari, Hamed; Sotiras, Aristeidis; Bilello, Michel; Rozycki, Martin; Kirby, Justin S.; Freymann, John B.; Farahani, Keyvan; Davatzikos, Christos

2017-01-01

Gliomas belong to a group of central nervous system tumors, and consist of various sub-regions. Gold standard labeling of these sub-regions in radiographic imaging is essential for both clinical and computational studies, including radiomic and radiogenomic analyses. Towards this end, we release segmentation labels and radiomic features for all pre-operative multimodal magnetic resonance imaging (MRI) (n=243) of the multi-institutional glioma collections of The Cancer Genome Atlas (TCGA), publicly available in The Cancer Imaging Archive (TCIA). Pre-operative scans were identified in both glioblastoma (TCGA-GBM, n=135) and low-grade-glioma (TCGA-LGG, n=108) collections via radiological assessment. The glioma sub-region labels were produced by an automated state-of-the-art method and manually revised by an expert board-certified neuroradiologist. An extensive panel of radiomic features was extracted based on the manually-revised labels. This set of labels and features should enable i) direct utilization of the TCGA/TCIA glioma collections towards repeatable, reproducible and comparative quantitative studies leading to new predictive, prognostic, and diagnostic assessments, as well as ii) performance evaluation of computer-aided segmentation methods, and comparison to our state-of-the-art method. PMID:28872634

Branched-chain amino acids may improve recovery from a vegetative or minimally conscious state in patients with traumatic brain injury: a pilot study.

PubMed

Aquilani, Roberto; Boselli, Mirella; Boschi, Federica; Viglio, Simona; Iadarola, Paolo; Dossena, Maurizia; Pastoris, Ornella; Verri, Manuela

2008-09-01

To investigate whether supplementation with branched-chain amino acids (BCAAs) may improve recovery of patients with a posttraumatic vegetative or minimally conscious state. Patients were randomly assigned to 15 days of intravenous BCAA supplementation (n=22; 19.6g/d) or an isonitrogenous placebo (n=19). Tertiary care rehabilitation setting. Patients (N=41; 29 men, 12 women; mean age, 49.5+/-21 y) with a posttraumatic vegetative or minimally conscious state, 47+/-24 days after the index traumatic event. Supplementation with BCAAs. Disability Rating Scale (DRS) as log(10)DRS. Fifteen days after admission to the rehabilitation department, the log(10)DRS score improved significantly only in patients who had received BCAAs (log(10)DRS score, 1.365+/-0.08 to 1.294+/-0.05; P<.001), while the log(10)DRS score in the placebo recipients remained virtually unchanged (log(10)DRS score, 1.373+/-0.03 to 1.37+/-0.03; P not significant). The difference in improvement of log(10)DRS score between the 2 groups was highly significant (P<.000). Moreover, 68.2% (n=15) of treated patients achieved a log(10)DRS point score of .477 or higher (3 as geometric mean) that allowed them to exit the vegetative or minimally conscious state. Supplemented BCAAs may improve the recovery from a vegetative or minimally conscious state in patients with posttraumatic vegetative or minimally conscious state.

From a PI’s perspective: How we made a T2 success

USDA-ARS?s Scientific Manuscript database

A team of scientists (Drs. Ariel A. Szogi, Matias B. Vanotti, and Patrick G. Hunt) from the Agricultural Research Service (ARS) - Coastal Plains, Soil, Water & Plant Research Center in Florence, S.C., invented a new treatment process, called “quick wash,” to extract and recover phosphorus from poult...

Integration of Multi-Modal Biomedical Data to Predict Cancer Grade and Patient Survival.

PubMed

Phan, John H; Hoffman, Ryan; Kothari, Sonal; Wu, Po-Yen; Wang, May D

2016-02-01

The Big Data era in Biomedical research has resulted in large-cohort data repositories such as The Cancer Genome Atlas (TCGA). These repositories routinely contain hundreds of matched patient samples for genomic, proteomic, imaging, and clinical data modalities, enabling holistic and multi-modal integrative analysis of human disease. Using TCGA renal and ovarian cancer data, we conducted a novel investigation of multi-modal data integration by combining histopathological image and RNA-seq data. We compared the performances of two integrative prediction methods: majority vote and stacked generalization. Results indicate that integration of multiple data modalities improves prediction of cancer grade and outcome. Specifically, stacked generalization, a method that integrates multiple data modalities to produce a single prediction result, outperforms both single-data-modality prediction and majority vote. Moreover, stacked generalization reveals the contribution of each data modality (and specific features within each data modality) to the final prediction result and may provide biological insights to explain prediction performance.

Exposing the cancer genome atlas as a SPARQL endpoint.

PubMed

Deus, Helena F; Veiga, Diogo F; Freire, Pablo R; Weinstein, John N; Mills, Gordon B; Almeida, Jonas S

2010-12-01

The Cancer Genome Atlas (TCGA) is a multidisciplinary, multi-institutional effort to characterize several types of cancer. Datasets from biomedical domains such as TCGA present a particularly challenging task for those interested in dynamically aggregating its results because the data sources are typically both heterogeneous and distributed. The Linked Data best practices offer a solution to integrate and discover data with those characteristics, namely through exposure of data as Web services supporting SPARQL, the Resource Description Framework query language. Most SPARQL endpoints, however, cannot easily be queried by data experts. Furthermore, exposing experimental data as SPARQL endpoints remains a challenging task because, in most cases, data must first be converted to Resource Description Framework triples. In line with those requirements, we have developed an infrastructure to expose clinical, demographic and molecular data elements generated by TCGA as a SPARQL endpoint by assigning elements to entities of the Simple Sloppy Semantic Database (S3DB) management model. All components of the infrastructure are available as independent Representational State Transfer (REST) Web services to encourage reusability, and a simple interface was developed to automatically assemble SPARQL queries by navigating a representation of the TCGA domain. A key feature of the proposed solution that greatly facilitates assembly of SPARQL queries is the distinction between the TCGA domain descriptors and data elements. Furthermore, the use of the S3DB management model as a mediator enables queries to both public and protected data without the need for prior submission to a single data source. Copyright © 2010 Elsevier Inc. All rights reserved.

Exposing the cancer genome atlas as a SPARQL endpoint

PubMed Central

Deus, Helena F.; Veiga, Diogo F.; Freire, Pablo R.; Weinstein, John N.; Mills, Gordon B.; Almeida, Jonas S.

2011-01-01

The Cancer Genome Atlas (TCGA) is a multidisciplinary, multi-institutional effort to characterize several types of cancer. Datasets from biomedical domains such as TCGA present a particularly challenging task for those interested in dynamically aggregating its results because the data sources are typically both heterogeneous and distributed. The Linked Data best practices offer a solution to integrate and discover data with those characteristics, namely through exposure of data as Web services supporting SPARQL, the Resource Description Framework query language. Most SPARQL endpoints, however, cannot easily be queried by data experts. Furthermore, exposing experimental data as SPARQL endpoints remains a challenging task because, in most cases, data must first be converted to Resource Description Framework triples. In line with those requirements, we have developed an infrastructure to expose clinical, demographic and molecular data elements generated by TCGA as a SPARQL endpoint by assigning elements to entities of the Simple Sloppy Semantic Database (S3DB) management model. All components of the infrastructure are available as independent Representational State Transfer (REST) Web services to encourage reusability, and a simple interface was developed to automatically assemble SPARQL queries by navigating a representation of the TCGA domain. A key feature of the proposed solution that greatly facilitates assembly of SPARQL queries is the distinction between the TCGA domain descriptors and data elements. Furthermore, the use of the S3DB management model as a mediator enables queries to both public and protected data without the need for prior submission to a single data source. PMID:20851208

Duane retraction syndrome on the Arabian Peninsula.

PubMed

Khan, Arif O; Oystreck, Darren T; Wilken, Keith; Akbar, Fatima

2007-01-01

To describe the clinical features of patients from the Arabian Peninsula with Duane retraction syndrome (DRS). Retrospective chart review of patients referred to the King Khaled Eye Specialist Hospital in Riyadh, Saudi Arabia from 1982 to 2003 with a diagnosis of DRS. Patients having had prior strabismus surgery were excluded. Of 404 DRS patients, 347 (86%) were unilateral, 57 (14%) were bilateral, and 111 (27%) had amblyopia. There were 221 (55%) females and 182 (45%) males. The Huber classification was as follows: 315 (78%) Type I, 16 (4%) Type II, and 77 (19%) Type III. Of the 57 bilateral cases, 25 (44%) were female and 32 (56%) were male. Overall, the clinical features of DRS patients referred to a Riyadh eye hospital are similar to those reported in series throughout the world. However, our referred bilateral DRS patients are more commonly male. The clinical features of bilateral DRS deserve further worldwide study.

Integrative Behavioral Couple Therapy: Theoretical Background, Empirical Research, and Dissemination.

PubMed

Roddy, McKenzie K; Nowlan, Kathryn M; Doss, Brian D; Christensen, Andrew

2016-09-01

Integrative Behavioral Couple Therapy (IBCT), developed by Drs. Andrew Christensen and Neil Jacobson, builds off the tradition of behavioral couple therapy by including acceptance strategies as key components of treatment. Results from a large randomized clinical trial of IBCT indicate that it yields large and significant gains in relationship satisfaction. Furthermore, these benefits have been shown to persist for at least 5 years after treatment for the average couple. Not only does IBCT positively impact relationship constructs such as satisfaction and communication, but the benefits of therapy extend to individual, co-parenting, and child functioning. Moreover, IBCT has been shown to operate through the putative mechanisms of improvements in emotional acceptance, behavior change, and communication. IBCT was chosen for nationwide training and dissemination through the Veteran Affairs Medical Centers. Furthermore, the principles of IBCT have been translated into a web-based intervention for distressed couples, OurRelationship.com. IBCT is continuing to evolve and grow as research and technologies allow for continued evaluation and dissemination of this well-supported theoretical model. © 2016 Family Process Institute.

Relationship between cognitive and non-cognitive symptoms of delirium.

PubMed

Rajlakshmi, Aarya Krishnan; Mattoo, Surendra Kumar; Grover, Sandeep

2013-04-01

To study relationship between the cognitive and the non-cognitive symptoms of delirium. Eighty-four patients referred to psychiatry liaison services and met DSM-IVTR criteria of delirium were assessed using the Delirium Rating Scale Revised-1998 (DRSR-98) and Cognitive Test for Delirium (CTD). The mean DRS-R-98 severity score was 17.19 and DRS-R-98 total score was 23.36. The mean total score on CTD was 11.75. The mean scores on CTD were highest for comprehension (3.47) and lowest for vigilance (1.71). Poor attention was associated with significantly higher motor retardation and higher DRS-R-98 severity scores minus the attention scores. There were no significant differences between those with and without poor attention. Higher attention deficits were associated with higher dysfunction on all other domains of cognition on CTD. There was significant correlation between cognitive functions as assessed on CTD and total DRS-R-98 score, DRS-R-98 severity score and DRS-R-98 severity score without the attention item score. However, few correlations emerged between CTD domains and CTD total scores with cognitive symptom total score of DRS-R-98 (items 9-13) and non-cognitive symptom total score of DRS-R-98 (items 1-8). Our study suggests that in delirium, cognitive deficits are quite prevalent and correlate with overall severity of delirium. Attention deficit is a core symptom of delirium. Copyright © 2012 Elsevier B.V. All rights reserved.

A radiosensitivity gene signature and PD-L1 status predict clinical outcome of patients with invasive breast carcinoma in The Cancer Genome Atlas (TCGA) dataset.

PubMed

Jang, Bum-Sup; Kim, In Ah

2017-09-01

We investigated the link between the radiosensitivity gene signature and programmed cell death ligand 1 (PD-L1) status and clinical outcome in order to identify a group of patients that would possibly receive clinical benefit of radiotherapy (RT) combined with anti-PD1/PD-L1 therapy. We validated the identified gene signature related to radiosensitivity and analyzed the PD-L1 status of invasive breast cancer in The Cancer Genome Atlas (TCGA) dataset. To validate the gene signature, 1045 patients were selected and divided into two clusters using a consensus clustering algorithm based on their radiosensitive (RS) or radioresistant (RR) designation according to their prognosis. Patients were also stratified as PD-L1-high or PD-L1-low based on the median value of CD274 mRNA expression level as surrogates of PD-L1. Patents assigned to the RS group had decreased risk of recurrence-free survival (RFS) rate than patients in the RR group by univariate analysis (HR 0.45, 95% CI 0.25-0.81, p=0.008) only when treated with RT. The RS group was independently associated with the PD-L1-high group, and CD274 mRNA expression was significantly higher in the RS group (p<0.001) than the RR group. In the PD-L1-high group, the RS group was associated with better RFS compared to the RR group (HR 0.37, 95% CI 0.16-0.87, p=0.022) in multivariate analysis. The level of PD-L1 expression may represent the immunogenicity of tumors, and thus, we speculated that the PD-L1-high group had more immunogenic tumors, which could be more sensitive to radiation-induced immunologic cell death. We first evaluated the predictive value of the radiosensitivity gene signature and described a relationship with this radiosensitivity gene signature and PD-L1. The radiosensitivity gene signature and PD-L1 status were important factors for prediction of the clinical outcome of RT in patients with invasive breast cancer and may be used for selecting patients who will benefit from RT combined with anti-PD1/PDL1

Gardasil® and Cervarix® | NCI Technology Transfer Center | TTC

Cancer.gov

Vaccine for human papilloma virus (HPV) to protect from cancers Key elements of the technology for Gardasil® and Cervarix originated from the HPV research of the laboratory of Drs. Douglas Lowy and John Schiller of the NCI.

Registration open for "Cancer and Immunotherapy: From Conception to Delivery" symposium | Center for Cancer Research

Cancer.gov

The Annual Immunology Symposium, sponsored by the CCR’s Center of Excellence in Immunology will be held this fall on October 12-13th in Masur and Lipsett Auditorium in Building 10.  This year’s theme is "Cancer Immunology and Immunotherapy:  From Conception to Delivery", and the symposium will be chaired by Drs. Nicholas Restifo and Steve Rosenberg.  Learn more...

VarDict: a novel and versatile variant caller for next-generation sequencing in cancer research

PubMed Central

Lai, Zhongwu; Markovets, Aleksandra; Ahdesmaki, Miika; Chapman, Brad; Hofmann, Oliver; McEwen, Robert; Johnson, Justin; Dougherty, Brian; Barrett, J. Carl; Dry, Jonathan R.

2016-01-01

Abstract Accurate variant calling in next generation sequencing (NGS) is critical to understand cancer genomes better. Here we present VarDict, a novel and versatile variant caller for both DNA- and RNA-sequencing data. VarDict simultaneously calls SNV, MNV, InDels, complex and structural variants, expanding the detected genetic driver landscape of tumors. It performs local realignments on the fly for more accurate allele frequency estimation. VarDict performance scales linearly to sequencing depth, enabling ultra-deep sequencing used to explore tumor evolution or detect tumor DNA circulating in blood. In addition, VarDict performs amplicon aware variant calling for polymerase chain reaction (PCR)-based targeted sequencing often used in diagnostic settings, and is able to detect PCR artifacts. Finally, VarDict also detects differences in somatic and loss of heterozygosity variants between paired samples. VarDict reprocessing of The Cancer Genome Atlas (TCGA) Lung Adenocarcinoma dataset called known driver mutations in KRAS, EGFR, BRAF, PIK3CA and MET in 16% more patients than previously published variant calls. We believe VarDict will greatly facilitate application of NGS in clinical cancer research. PMID:27060149

A novel optimised and validated method for analysis of multi-residues of pesticides in fruits and vegetables by microwave-assisted extraction (MAE)-dispersive solid-phase extraction (d-SPE)-retention time locked (RTL)-gas chromatography-mass spectrometry with Deconvolution reporting software (DRS).

PubMed

Satpathy, Gouri; Tyagi, Yogesh Kumar; Gupta, Rajinder Kumar

2011-08-01

A rapid, effective and ecofriendly method for sensitive screening and quantification of 72 pesticides residue in fruits and vegetables, by microwave-assisted extraction (MAE) followed by dispersive solid-phase extraction (d-SPE), retention time locked (RTL) capillary gas-chromatographic separation in trace ion mode mass spectrometric determination has been validated as per ISO/IEC: 17025:2005. Identification and reporting with total and extracted ion chromatograms were facilitated to a great extent by Deconvolution reporting software (DRS). For all compounds LOD were 0.002-0.02mg/kg and LOQ were 0.025-0.100mg/kg. Correlation coefficients of the calibration curves in the range of 0.025-0.50mg/kg were >0.993. To validate matrix effects repeatability, reproducibility, recovery and overall uncertainty were calculated for the 35 matrices at 0.025, 0.050 and 0.100mg/kg. Recovery ranged between 72% and 114% with RSD of <20% for repeatability and intermediate precision. The reproducibility of the method was evaluated by an inter laboratory participation and Z score obtained within ±2. Copyright © 2011 Elsevier Ltd. All rights reserved.

Augmented superior rectus transposition procedure in Duane retraction syndrome compared with sixth nerve palsy.

PubMed

Akbari, Mohammadreza; Shomali, Setareh; Mirmohammadsadeghi, Arash; Fard, Masoud Aghsaei

2018-05-01

Superior rectus transposition (SRT) with medial rectus recession has been used for the treatment of sixth nerve palsy and esotropic Duane retraction syndrome (DRS). The purpose of this study was to compare the results of augmented SRT (with scleral fixation) without medial rectus recession in DRS and sixth nerve palsy. Patients with unilateral esotropic DRS (DRS group) and sixth nerve palsy were included in this prospective, comparative study and underwent SRT. Preoperative forced duction testing was negative or slightly positive in both groups. Prospective measurements were compared between the two groups. There were 11 patients in the DRS group and 11 patients in the sixth nerve palsy group. The mean preoperative esotropia decreased from 20.9 ± 6.0 prism diopter (PD) at far to 13.2 ± 5.8 PD in the DRS group (P = 0.003). The same measurement improved from 28.0 ± 8.5 PD to 8.4 ± 7.3 PD in the sixth nerve palsy group (P = 0.003). In the sixth nerve palsy group, the improvement in primary gaze esotropia and abnormal head posture was more than the DRS group (Both P < 0.001).The average dose effect for SRT was 7.8 ± 2.2 PD in the DRS group and 19.2 ± 4.6 PD in the sixth nerve palsy group. Although objective intorsion was significantly induced after SRT, subjective torsion was not significant after surgery in both groups. SRT appears to be more effective in improving primary gaze deviation and head posture in sixth nerve palsy compared with DRS. Subjective torsional and vertical diplopia were rare in both groups.

Crystal structure of human cytosolic aspartyl-tRNA synthetase, a component of multi-tRNA synthetase complex

PubMed Central

Kim, Kyung Rok; Park, Sang Ho; Kim, Hyoun Sook; Rhee, Kyung Hee; Kim, Byung-Gyu; Kim, Dae Gyu; Park, Mi Seul; Kim, Hyun-Jung; Kim, Sunghoon; Han, Byung Woo

2013-01-01

Human cytosolic aspartyl-tRNA synthetase (DRS) catalyzes the attachment of the amino acid aspartic acid to its cognate tRNA and it is a component of the multi-tRNA synthetase complex (MSC) which has been known to be involved in unexpected signaling pathways. Here, we report the crystal structure of DRS at a resolution of 2.25 Å. DRS is a homodimer with a dimer interface of 3750.5 Å2 which comprises 16.6% of the monomeric surface area. Our structure reveals the C-terminal end of the N-helix which is considered as a unique addition in DRS, and its conformation further supports the switching model of the N-helix for the transfer of tRNAAsp to elongation factor 1α. From our analyses of the crystal structure and post-translational modification of DRS, we suggest that the phosphorylation of Ser146 provokes the separation of DRS from the MSC and provides the binding site for an interaction partner with unforeseen functions. PMID:23609930

Convergent Validity, Concurrent Validity, and Diagnostic Accuracy of the interRAI Depression Rating Scale.

PubMed

Penny, Katherine; Barron, Alex; Higgins, Ann-Marie; Gee, Susan; Croucher, Matthew; Cheung, Gary

2016-09-19

Depression Rating Scale (DRS) is one of the clinical outcome measures of the International Resident Assessment Instrument (interRAI) assessment. The primary aim of this study is to investigate the diagnostic accuracy and concurrent validity of the 3-day assessment window version of the DRS. The performance of DRS was compared with a gold standard clinical diagnosis of depression in 92 patients (age ≥65) who had interRAI version 9.1 Home Care assessment completed within 30 days of discharge from psychogeriatric inpatient care or memory clinic assessment. The DRS had poor diagnostic accuracy for depression diagnosis with an area under the curve of 0.68 (95% confidence interval [CI] = 0.57-0.77). The DRS score had a poor to moderate correlation with the Health of the Nation Outcome Scale 65+ depression item score (r s = 0.30, 95% CI = 0.09-0.48, P = .006). This study and the existing literature raise concerns that the DRS is not an adequate measure of depression. © The Author(s) 2016.

Crystal structure of human cytosolic aspartyl-tRNA synthetase, a component of multi-tRNA synthetase complex.

PubMed

Kim, Kyung Rok; Park, Sang Ho; Kim, Hyoun Sook; Rhee, Kyung Hee; Kim, Byung-Gyu; Kim, Dae Gyu; Park, Mi Seul; Kim, Hyun-Jung; Kim, Sunghoon; Han, Byung Woo

2013-10-01

Human cytosolic aspartyl-tRNA synthetase (DRS) catalyzes the attachment of the amino acid aspartic acid to its cognate tRNA and it is a component of the multi-tRNA synthetase complex (MSC) which has been known to be involved in unexpected signaling pathways. Here, we report the crystal structure of DRS at a resolution of 2.25 Å. DRS is a homodimer with a dimer interface of 3750.5 Å(2) which comprises 16.6% of the monomeric surface area. Our structure reveals the C-terminal end of the N-helix which is considered as a unique addition in DRS, and its conformation further supports the switching model of the N-helix for the transfer of tRNA(Asp) to elongation factor 1α. From our analyses of the crystal structure and post-translational modification of DRS, we suggest that the phosphorylation of Ser146 provokes the separation of DRS from the MSC and provides the binding site for an interaction partner with unforeseen functions. Copyright © 2013 Wiley Periodicals, Inc.

Delayed risk stratification, to include the response to initial treatment (surgery and radioiodine ablation), has better outcome predictivity in differentiated thyroid cancer patients.

PubMed

Castagna, Maria Grazia; Maino, Fabio; Cipri, Claudia; Belardini, Valentina; Theodoropoulou, Alexandra; Cevenini, Gabriele; Pacini, Furio

2011-09-01

After initial treatment, differentiated thyroid cancer (DTC) patients are stratified as low and high risk based on clinical/pathological features. Recently, a risk stratification based on additional clinical data accumulated during follow-up has been proposed. To evaluate the predictive value of delayed risk stratification (DRS) obtained at the time of the first diagnostic control (8-12 months after initial treatment). We reviewed 512 patients with DTC whose risk assessment was initially defined according to the American (ATA) and European Thyroid Association (ETA) guidelines. At the time of the first control, 8-12 months after initial treatment, patients were re-stratified according to their clinical status: DRS. Using DRS, about 50% of ATA/ETA intermediate/high-risk patients moved to DRS low-risk category, while about 10% of ATA/ETA low-risk patients moved to DRS high-risk category. The ability of the DRS to predict the final outcome was superior to that of ATA and ETA. Positive and negative predictive values for both ATA (39.2 and 90.6% respectively) and ETA (38.4 and 91.3% respectively) were significantly lower than that observed with the DRS (72.8 and 96.3% respectively, P<0.05). The observed variance in predicting final outcome was 25.4% for ATA, 19.1% for ETA, and 62.1% for DRS. Delaying the risk stratification of DTC patients at a time when the response to surgery and radioiodine ablation is evident allows to better define individual risk and to better modulate the subsequent follow-up.

Performance of Disease Risk Score Matching in Nested Case-Control Studies: A Simulation Study.

PubMed

Desai, Rishi J; Glynn, Robert J; Wang, Shirley; Gagne, Joshua J

2016-05-15

In a case-control study, matching on a disease risk score (DRS), which includes many confounders, should theoretically result in greater precision than matching on only a few confounders; however, this has not been investigated. We simulated 1,000 hypothetical cohorts with a binary exposure, a time-to-event outcome, and 13 covariates. Each cohort comprised 2 subcohorts of 10,000 patients each: a historical subcohort and a concurrent subcohort. DRS were estimated in the historical subcohorts and applied to the concurrent subcohorts. Nested case-control studies were conducted in the concurrent subcohorts using incidence density sampling with 2 strategies-matching on age and sex, with adjustment for additional confounders, and matching on DRS-followed by conditional logistic regression for 9 outcome-exposure incidence scenarios. In all scenarios, DRS matching yielded lower average standard errors and mean squared errors than did matching on age and sex. In 6 scenarios, DRS matching also resulted in greater empirical power. DRS matching resulted in less relative bias than did matching on age and sex at lower outcome incidences but more relative bias at higher incidences. Post-hoc analysis revealed that the effect of DRS model misspecification might be more pronounced at higher outcome incidences, resulting in higher relative bias. These results suggest that DRS matching might increase the statistical efficiency of case-control studies, particularly when the outcome is rare. © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Regulation of Breast Cancer Stem Cell by Tissue Rigidity

DTIC Science & Technology

2015-06-01

analysis. The TCGA breast cancer gene expression data set (TCGA BRCA G4502A_07_3) was downloaded from the UCSC Cancer Genome Browser (https:// genome ...Public Release; Distribution Unlimited The views, opinions and/or findings contained in this report are those of the author(s) and should not be...construed as an official Department of the Army position, policy or decision unless so designated by other documentation. Report Documentation Page Form

Rapid identification of oil-contaminated soils using visible near-infrared diffuse reflectance spectroscopy.

PubMed

Chakraborty, Somsubhra; Weindorf, David C; Morgan, Cristine L S; Ge, Yufeng; Galbraith, John M; Li, Bin; Kahlon, Charanjit S

2010-01-01

In the United States, petroleum extraction, refinement, and transportation present countless opportunities for spillage mishaps. A method for rapid field appraisal and mapping of petroleum hydrocarbon-contaminated soils for environmental cleanup purposes would be useful. Visible near-infrared (VisNIR, 350-2500 nm) diffuse reflectance spectroscopy (DRS) is a rapid, nondestructive, proximal-sensing technique that has proven adept at quantifying soil properties in situ. The objective of this study was to determine the prediction accuracy of VisNIR DRS in quantifying petroleum hydrocarbons in contaminated soils. Forty-six soil samples (including both contaminated and reference samples) were collected from six different parishes in Louisiana. Each soil sample was scanned using VisNIR DRS at three combinations of moisture content and pretreatment: (i) field-moist intact aggregates, (ii) air-dried intact aggregates, (iii) and air-dried ground soil (sieved through a 2-mm sieve). The VisNIR spectra of soil samples were used to predict total petroleum hydrocarbon (TPH) content in the soil using partial least squares (PLS) regression and boosted regression tree (BRT) models. Each model was validated with 30% of the samples that were randomly selected and not used in the calibration model. The field-moist intact scan proved best for predicting TPH content with a validation r2 of 0.64 and relative percent difference (RPD) of 1.70. Because VisNIR DRS was promising for rapidly predicting soil petroleum hydrocarbon content, future research is warranted to evaluate the methodology for identifying petroleum contaminated soils.

Skin collagen can be accurately quantified through noninvasive optical method: Validation on a swine study.

PubMed

Tzeng, S-Y; Kuo, T-Y; Hu, S-B; Chen, Y-W; Lin, Y-L; Chu, K-Y; Tseng, S-H

2018-02-01

Diffuse reflectance spectroscopy (DRS) is a noninvasive optical technology characterized by relatively low system cost and high efficiency. In our previous study, we quantified the relative concentration of collagen for the individual keloid patient. However, no actual value of collagen concentration can prove the reliability of collagen detection by our DRS system. Skin-mimicking phantoms were prepared using different collagen and coffee concentrations, and their chromophore concentrations were quantified using the DRS system to analyze the influence of collagen and other chromophores. Moreover, we used the animal study to compare the DRS system with the collagen evaluation of biopsy section by second-harmonic generation (SHG) microscopy at four different skin parts. In the phantom study, the result showed that coffee chromophore did not severely interfere with collagen concentration recovery. In the animal study, a positive correlation (r=.902) between the DRS system and collagen evaluation with SHG microscopy was found. We have demonstrated that the DRS system can quantify the actual values of collagen concentration and excluded the interference of other chromophores in skin-mimicking phantoms. Furthermore, a high positive correlation was found in the animal study with SHG microscopy. We consider that the DRS is a potential technique and can evaluate skin condition objectively. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The “Dry-Run” Analysis: A Method for Evaluating Risk Scores for Confounding Control

PubMed Central

Wyss, Richard; Hansen, Ben B.; Ellis, Alan R.; Gagne, Joshua J.; Desai, Rishi J.; Glynn, Robert J.; Stürmer, Til

2017-01-01

Abstract A propensity score (PS) model's ability to control confounding can be assessed by evaluating covariate balance across exposure groups after PS adjustment. The optimal strategy for evaluating a disease risk score (DRS) model's ability to control confounding is less clear. DRS models cannot be evaluated through balance checks within the full population, and they are usually assessed through prediction diagnostics and goodness-of-fit tests. A proposed alternative is the “dry-run” analysis, which divides the unexposed population into “pseudo-exposed” and “pseudo-unexposed” groups so that differences on observed covariates resemble differences between the actual exposed and unexposed populations. With no exposure effect separating the pseudo-exposed and pseudo-unexposed groups, a DRS model is evaluated by its ability to retrieve an unconfounded null estimate after adjustment in this pseudo-population. We used simulations and an empirical example to compare traditional DRS performance metrics with the dry-run validation. In simulations, the dry run often improved assessment of confounding control, compared with the C statistic and goodness-of-fit tests. In the empirical example, PS and DRS matching gave similar results and showed good performance in terms of covariate balance (PS matching) and controlling confounding in the dry-run analysis (DRS matching). The dry-run analysis may prove useful in evaluating confounding control through DRS models. PMID:28338910

NCI Blog Post: CPTAC, the Complementary Sibling of TCGA (An Interview with Dr. Henry Rodriguez about NCI’s Proteomics Program) | Office of Cancer Clinical Proteomics Research

Cancer.gov

What is proteomics? Proteomics is a highly automated and rapid method for measuring all the proteins in a biological sample. Proteins are the molecules that actually do most of the work inside a cell. When researchers develop cancer drugs, those drugs typically target proteins, so scientists and clinicians really have to understand what the proteins are doing. Proteomics researchers are now able to measure up to 10,000 proteins per tumor sample.

P06.19 TERT promoter mutation is an independent prognostic factor in 1p/19q co-deleted oligodendrogliomas: a POLA network study

PubMed Central

Alentorn, A.; Carpentier, C.; Labreche, K.; Ducray, F.; Dehais, C.; Mokhtari, K.; Uro-Coste, E.; Figarella-Branger, D.; Delattre, J.; Idbaih, A.

2016-01-01

independent favorable prognostic factor in the POLA cohort (p=0.037, HR=3.7 (1.1–13)) and in the TCGA dataset (p=0.01, HR=9.8 (1.6–60)). Conclusion: This study identifies TERTp mutation as a novel independent prognostic biomarker in oligodendrogliomas toward a better stratification of this tumor type. Acknowledgements: The results shown here are in whole or part based upon data generated by the TCGA Research Network: http://cancergenome.nih.gov/. La Ligue Nationale Contre La Cancer. The Institut Universitaire de Cancérologie (IUC). The program Investissements d’avenir” ANR-10-IAIHU-06. POLA network is supported by Institut National du Cancer.

Accuracy of Answers Provided by Digital/Face-to-Face Reference Services in Japanese Public Libraries and Q & A Sites

ERIC Educational Resources Information Center

Tsuji, Keita; To, Haruna; Hara, Atsuyuki

2011-01-01

We asked the same 60 questions using DRS (digital reference services) in Japanese public libraries, face-to-face reference services and Q & A (question and answer) sites. It was found that: (1) The correct answer ratio of DRS is higher than that of Q & A sites; (2) DRS takes longer to provide answers as compared to Q & A sites; and (3)…

Promoter Methylation of PTEN Is a Significant Prognostic Factor in Melanoma Survival.

PubMed

Roh, Mi Ryung; Gupta, Sameer; Park, Kyu-Hyun; Chung, Kee Yang; Lauss, Martin; Flaherty, Keith T; Jönsson, Göran; Rha, Sun Young; Tsao, Hensin

2016-05-01

Structural compromise of the tumor suppressor gene, phosphatase and tensin homolog (PTEN), occurs in 10% of melanoma specimens, and loss of PTEN expression through DNA methylation of the PTEN promoter region has also been reported in a number of other malignancies. However, the role of PTEN promoter methylation in melanoma is not well understood. We thus sought to elucidate the prevalence of PTEN promoter methylation in melanoma specimens, its relationship to clinical features, and its impact on the outcome of patients with melanoma. PTEN promoter methylation data were acquired from an archived primary Korean melanoma cohort (KMC) of 158 patients and, for validation, 234 patients from The Cancer Genome Atlas melanoma (TCGA-MEL) cohort. Hierarchical clustering was performed to identify PTEN "high methylated" and "low methylated" samples. Subsequently, differences in clinical features and outcomes based on PTEN promoter methylation status were then analyzed using SPSS and R. In the KMC, all tumors were acquired from primary tumors and 65.7% (n = 105) were acral or mucosal by site, whereas in the TCGA-MEL cohort, 90.5% of the tumors were from regional lymph node and distant metastatic lesions. Overall, 17.7% and 45.7% of the specimens harbored BRAF mutations in the KMC and TCGA-MEL cohort, respectively. Neuroblastoma RAS viral oncogene homolog was mutated in 12.2% and 26.9% of the tumors in the KMC and TCGA-MEL cohort, respectively. In the KMC, 31 cases (19.6%) were included in the high methylated group versus 142 cases (60.7%) in the TCGA-MEL cohort (P < 0.001). Multivariate Cox-regression analysis revealed promoter methylation of PTEN to be an independent negative prognostic factor for survival in both the KMC (hazard ratio 3.76, 95% confidence interval = 1.24-11.12, P = 0.017) and TCGA-MEL cohort (HR 1.88, 95% confidence interval = 1.13-3.12, P = 0.015). Our results indicate that PTEN promoter methylation is an independent predictor for impaired survival in

College Board Response to "Harvard Educational Review" Article by Santelices and Wilson

ERIC Educational Resources Information Center

College Board, 2010

2010-01-01

This is the College Board's response to a research article by Drs. Maria Veronica Santelices and Mark Wilson in the Harvard Educational Review, entitled "Unfair Treatment? The Case of Freedle, the SAT, and the Standardization Approach to Differential Item Functioning" (see EJ930622).

A Gene Expression Profile of BRCAness That Predicts for Responsiveness to Platinum and PARP Inhibitors

DTIC Science & Technology

2017-02-01

To) 15 July 2010 – 2 Nov.2016 4 . TITLE AND SUBTITLE A Gene Expression Profile of BRCAness That Predicts for Responsiveness to Platinum and PARP...resistance in vitro, and to investigate the mechanism for this effect. The major goal for Aim 4 was to determine the reproducibility of the BRCAness...we used the epithelial ovarian cancer (EOC) dataset from The Cancer Genome Atlas (TCGA) ( 4 ). The TCGA dataset is a unique tool for these studies as

MiR-26a downregulates retinoblastoma in colorectal cancer.

PubMed

López-Urrutia, Eduardo; Coronel-Hernández, Jossimar; García-Castillo, Verónica; Contreras-Romero, Carlos; Martínez-Gutierrez, Antonio; Estrada-Galicia, Diana; Terrazas, Luis Ignacio; López-Camarillo, César; Maldonado-Martínez, Hector; Jacobo-Herrera, Nadia; Pérez-Plasencia, Carlos

2017-04-01

MicroRNAs are non-coding short RNAs that target the 3' untranslated region of messenger RNAs (mRNAs) and lead to their degradation or to translational repression. Several microRNAs have been designated as oncomirs, owing to their regulating tumor suppressor genes. Interestingly, a few of them have been found to target multiple genes whose simultaneous suppression contributes to the development of a tumoral phenotype. Here, we have showed that miR-26a is overexpressed in colorectal cancer data obtained from TCGA Research Network and in human colon cancer pathological specimens; moreover, an orthotopic in vivo model of colon cancer showed overexpression of miR-26a, while Rb1 expression inversely correlated to miR-26a in TCGA Research Network data, pathological samples, and the in vivo model. Then, by means of luciferase assay, we demonstrated that miR-26a targets the 3' untranslated region of Rb1 mRNA directly. This is, to our knowledge, the first report of miR-26a targeting Rb1 in colon cancer. The results of this study suggested that miR-26a could serve as a progression biomarker in colorectal cancer. Further validation studies are still needed to confirm our findings.

I. 'Street of twins': multiple births in Cuba II. The Cuban twin registry: an update / twin research reports: cord entanglement; heritability of clubfoot; school separation / twins and twin researchers in the news: reunited at seventy-eight; basketball duo dissolved; delivered holding hands; the better brew; award winners.

PubMed

Segal, Nancy L; Marcheco-Teruel, Beatriz

2014-08-01

I was part of a people-to-people tour of Havana, Cuba during the first week in April 2014. Among the many highlights of that adventure were an informal meeting with Dr Beatriz Marcheco-Teruel, from Cuba's National Center for Medical Genetics, and a visit to the famous 'Street of Twins'. A fortuitous meeting with parents of twins in the fishing town of Jaimanitas was also an extraordinary event. The Cuban experience is followed by summaries of recent twin research, covering umbilical cord entanglement, the heritability of clubfoot and school separation policies for twins. Media reports include twins reunited at age 78, the future of UCLA's twin basketball players, MZ twins born holding hands, a twin conflict over beer and a pair of American Psychological Association honors for Drs Nancy L. Segal and Thomas J. Bouchard, Jr.

Scalable Open Science Approach for Mutation Calling of Tumor Exomes Using Multiple Genomic Pipelines.

PubMed

Ellrott, Kyle; Bailey, Matthew H; Saksena, Gordon; Covington, Kyle R; Kandoth, Cyriac; Stewart, Chip; Hess, Julian; Ma, Singer; Chiotti, Kami E; McLellan, Michael; Sofia, Heidi J; Hutter, Carolyn; Getz, Gad; Wheeler, David; Ding, Li

2018-03-28

The Cancer Genome Atlas (TCGA) cancer genomics dataset includes over 10,000 tumor-normal exome pairs across 33 different cancer types, in total >400 TB of raw data files requiring analysis. Here we describe the Multi-Center Mutation Calling in Multiple Cancers project, our effort to generate a comprehensive encyclopedia of somatic mutation calls for the TCGA data to enable robust cross-tumor-type analyses. Our approach accounts for variance and batch effects introduced by the rapid advancement of DNA extraction, hybridization-capture, sequencing, and analysis methods over time. We present best practices for applying an ensemble of seven mutation-calling algorithms with scoring and artifact filtering. The dataset created by this analysis includes 3.5 million somatic variants and forms the basis for PanCan Atlas papers. The results have been made available to the research community along with the methods used to generate them. This project is the result of collaboration from a number of institutes and demonstrates how team science drives extremely large genomics projects. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Confounder summary scores when comparing the effects of multiple drug exposures.

PubMed

Cadarette, Suzanne M; Gagne, Joshua J; Solomon, Daniel H; Katz, Jeffrey N; Stürmer, Til

2010-01-01

Little information is available comparing methods to adjust for confounding when considering multiple drug exposures. We compared three analytic strategies to control for confounding based on measured variables: conventional multivariable, exposure propensity score (EPS), and disease risk score (DRS). Each method was applied to a dataset (2000-2006) recently used to examine the comparative effectiveness of four drugs. The relative effectiveness of risedronate, nasal calcitonin, and raloxifene in preventing non-vertebral fracture, were each compared to alendronate. EPSs were derived both by using multinomial logistic regression (single model EPS) and by three separate logistic regression models (separate model EPS). DRSs were derived and event rates compared using Cox proportional hazard models. DRSs derived among the entire cohort (full cohort DRS) was compared to DRSs derived only among the referent alendronate (unexposed cohort DRS). Less than 8% deviation from the base estimate (conventional multivariable) was observed applying single model EPS, separate model EPS or full cohort DRS. Applying the unexposed cohort DRS when background risk for fracture differed between comparison drug exposure cohorts resulted in -7 to + 13% deviation from our base estimate. With sufficient numbers of exposed and outcomes, either conventional multivariable, EPS or full cohort DRS may be used to adjust for confounding to compare the effects of multiple drug exposures. However, our data also suggest that unexposed cohort DRS may be problematic when background risks differ between referent and exposed groups. Further empirical and simulation studies will help to clarify the generalizability of our findings.

Sulfur Mustard Induces Apoptosis in Cultured Normal Human Airway Epithelial Cells: Evidence of a Dominant Caspase-8-Mediated Pathway and Differential Cellular Responses

DTIC Science & Technology

2008-01-01

proteases that cleave their substrates after aspartic acid residues (cysteine aspartase). Thus, in these assays, free fluorescent AMC, generated as a...for her technical assistance and also thank Drs. Alan Brimfield and Clarence A. Broomfield of the US Army Medical Research Institute of Chemical

Drs. Smith Brothers: dental surgeons of Calcutta.

PubMed

Sanjeev, Kumar

2014-01-01

During the British raj, India attracted dental practitioners from all over the world who set up practices in the Presidency towns of Calcutta, Bombay, Madras and Bangalore. Lured by the abundant opportunity to make good money, these mercenary but courageous dentists counted Viceroys, Indian royalty and political leaders amongst their clients. Some, like the famous American Smith Brothers of Calcutta, were sought after even by the rulers of neighboring countries. Dr. Mark Smith's hazardous visit to the Amir of Afghanistan made worldwide headlines more than 100 years ago for the fabulous fee he was paid for the dental treatment. This paper briefly describes the exploits and experiences of the Smith brothers while in India.

Predicting functional ability in mild cognitive impairment with the Dementia Rating Scale-2.

PubMed

Greenaway, Melanie C; Duncan, Noah L; Hanna, Sherrie; Smith, Glenn E

2012-06-01

We examined the utility of cognitive evaluation to predict instrumental activities of daily living (IADLs) and decisional ability in Mild Cognitive Impairment (MCI). Sixty-seven individuals with single-domain amnestic MCI were administered the Dementia Rating Scale-2 (DRS-2) as well as the Everyday Cognition assessment form to assess functional ability. The DRS-2 Total Scores and Initiation/Perseveration and Memory subscales were found to be predictive of IADLs, with Total Scores accounting for 19% of the variance in IADL performance on average. In addition, the DRS-2 Initiation/Perseveration and Total Scores were predictive of ability to understand information, and the DRS-2 Conceptualization helped predict ability to communicate with others, both key variables in decision-making ability. These findings suggest that performance on the DRS-2, and specific subscales related to executive function and memory, is significantly related to IADLs in individuals with MCI. These cognitive measures are also associated with decision-making-related abilities in MCI.

Discharge rates in electromyography distinguish early between peripheral and central paresis.

PubMed

Jürgens, Tim P; Puchner, Christoph; Schulte-Mattler, Wilhelm J

2012-10-01

Abnormally increased discharge rates (DRs) of motor unit potentials on concentric needle electromyography (CNEMG) indicate a loss of motor units in peripheral neurogenic lesions. To determine when increased DRs occur during the course of a peripheral nerve lesion, we retrospectively analyzed CNEMG recordings of 19 patients with acute weakness of peripheral origin. The initial CNEMG studies took place from 3.7 hours to 10 days after the onset of the lesion. Abnormally increased DRs (≥20/s) were found in all but 1 of the muscles in which MRC grade was <4. Peripheral neurogenic damage was confirmed in all patients thereafter. The DRs depended on neither the kind of lesion nor the time between onset and CNEMG examination. The measurement of DRs of motor unit potentials is helpful immediately after a sudden paresis of MRC grade 3 or worse to differentiate between a central and a peripheral lesion. Copyright © 2012 Wiley Periodicals, Inc.

Splenium microstructure is related to two dimensions of reading skill.

PubMed

Frye, Richard E; Hasan, Khader; Xue, Lian; Strickland, David; Malmberg, Benjamin; Liederman, Jacqueline; Papanicolaou, Andrew

2008-10-29

Inconsistent differences in the corpus callosum (CC) structure between dyslexic readers (DRs) and typical readers (TRs) have been reported. We examine differences in CC splenium microstructure and the association of splenium microstructure with reading-related skills. Nine DRs and 18 TRs completed a reading skills battery and diffusion tensor imaging. DRs had higher splenium fractional anisotropy (FA) and axial diffusivity (LA) as compared with TRs. Retrieval of orthographic information from the language lexicon was negatively associated with FA and LA within both reading groups. Phonological awareness was positively associated with splenium FA and LA in TRs but not DRs. This study suggests two white matter pathways that may be differentially associated with reading skills in the CC splenium.

Proteogenomic characterization of human colon and rectal cancer

PubMed Central

Zhang, Bing; Wang, Jing; Wang, Xiaojing; Zhu, Jing; Liu, Qi; Shi, Zhiao; Chambers, Matthew C.; Zimmerman, Lisa J.; Shaddox, Kent F.; Kim, Sangtae; Davies, Sherri R.; Wang, Sean; Wang, Pei; Kinsinger, Christopher R.; Rivers, Robert C.; Rodriguez, Henry; Townsend, R. Reid; Ellis, Matthew J.C.; Carr, Steven A.; Tabb, David L.; Coffey, Robert J.; Slebos, Robbert J.C.; Liebler, Daniel C.

2014-01-01

Summary We analyzed proteomes of colon and rectal tumors previously characterized by the Cancer Genome Atlas (TCGA) and performed integrated proteogenomic analyses. Somatic variants displayed reduced protein abundance compared to germline variants. mRNA transcript abundance did not reliably predict protein abundance differences between tumors. Proteomics identified five proteomic subtypes in the TCGA cohort, two of which overlapped with the TCGA “MSI/CIMP” transcriptomic subtype, but had distinct mutation, methylation, and protein expression patterns associated with different clinical outcomes. Although copy number alterations showed strong cis- and trans-effects on mRNA abundance, relatively few of these extend to the protein level. Thus, proteomics data enabled prioritization of candidate driver genes. The chromosome 20q amplicon was associated with the largest global changes at both mRNA and protein levels; proteomics data highlighted potential 20q candidates including HNF4A, TOMM34 and SRC. Integrated proteogenomic analysis provides functional context to interpret genomic abnormalities and affords a new paradigm for understanding cancer biology. PMID:25043054

Systems 2020

DTIC Science & Technology

2012-03-22

USC Team Members: SERC Research Council Dr. Abhi Deshmukh , Purdue Dr. Michael Griffin. U. Alabama-Huntsville Dr. Barry Horowitz, U. Virginia Dr...Areas ................................................. 34 3.2.1 Affordability, Agility, and Resilience (Barry Boehm and Abhi Deshmukh , Leads...statement was reinterpreted to involve the SERC Research Council (Drs. Deshmukh , Griffin, Horowitz, Rouse, and Wade, with Dr. Boehm as chair) in defining

Using Quantile and Asymmetric Least Squares Regression for Optimal Risk Adjustment.

PubMed

Lorenz, Normann

2017-06-01

In this paper, we analyze optimal risk adjustment for direct risk selection (DRS). Integrating insurers' activities for risk selection into a discrete choice model of individuals' health insurance choice shows that DRS has the structure of a contest. For the contest success function (csf) used in most of the contest literature (the Tullock-csf), optimal transfers for a risk adjustment scheme have to be determined by means of a restricted quantile regression, irrespective of whether insurers are primarily engaged in positive DRS (attracting low risks) or negative DRS (repelling high risks). This is at odds with the common practice of determining transfers by means of a least squares regression. However, this common practice can be rationalized for a new csf, but only if positive and negative DRSs are equally important; if they are not, optimal transfers have to be calculated by means of a restricted asymmetric least squares regression. Using data from German and Swiss health insurers, we find considerable differences between the three types of regressions. Optimal transfers therefore critically depend on which csf represents insurers' incentives for DRS and, if it is not the Tullock-csf, whether insurers are primarily engaged in positive or negative DRS. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Are mutagenic non D-loop direct repeat motifs in mitochondrial DNA under a negative selection pressure?

PubMed Central

Lakshmanan, Lakshmi Narayanan; Gruber, Jan; Halliwell, Barry; Gunawan, Rudiyanto

2015-01-01

Non D-loop direct repeats (DRs) in mitochondrial DNA (mtDNA) have been commonly implicated in the mutagenesis of mtDNA deletions associated with neuromuscular disease and ageing. Further, these DRs have been hypothesized to put a constraint on the lifespan of mammals and are under a negative selection pressure. Using a compendium of 294 mammalian mtDNA, we re-examined the relationship between species lifespan and the mutagenicity of such DRs. Contradicting the prevailing hypotheses, we found no significant evidence that long-lived mammals possess fewer mutagenic DRs than short-lived mammals. By comparing DR counts in human mtDNA with those in selectively randomized sequences, we also showed that the number of DRs in human mtDNA is primarily determined by global mtDNA properties, such as the bias in synonymous codon usage (SCU) and nucleotide composition. We found that SCU bias in mtDNA positively correlates with DR counts, where repeated usage of a subset of codons leads to more frequent DR occurrences. While bias in SCU and nucleotide composition has been attributed to nucleotide mutational bias, mammalian mtDNA still exhibit higher SCU bias and DR counts than expected from such mutational bias, suggesting a lack of negative selection against non D-loop DRs. PMID:25855815

Validation of a multimarker model for assessing risk of type 2 diabetes from a five-year prospective study of 6784 Danish people (Inter99).

PubMed

Urdea, Mickey; Kolberg, Janice; Wilber, Judith; Gerwien, Robert; Moler, Edward; Rowe, Michael; Jorgensen, Paul; Hansen, Torben; Pedersen, Oluf; Jørgensen, Torben; Borch-Johnsen, Knut

2009-07-01

Improved identification of subjects at high risk for development of type 2 diabetes would allow preventive interventions to be targeted toward individuals most likely to benefit. In previous research, predictive biomarkers were identified and used to develop multivariate models to assess an individual's risk of developing diabetes. Here we describe the training and validation of the PreDx Diabetes Risk Score (DRS) model in a clinical laboratory setting using baseline serum samples from subjects in the Inter99 cohort, a population-based primary prevention study of cardiovascular disease. Among 6784 subjects free of diabetes at baseline, 215 subjects progressed to diabetes (converters) during five years of follow-up. A nested case-control study was performed using serum samples from 202 converters and 597 randomly selected nonconverters. Samples were randomly assigned to equally sized training and validation sets. Seven biomarkers were measured using assays developed for use in a clinical reference laboratory. The PreDx DRS model performed better on the training set (area under the curve [AUC] = 0.837) than fasting plasma glucose alone (AUC = 0.779). When applied to the sequestered validation set, the PreDx DRS showed the same performance (AUC = 0.838), thus validating the model. This model had a better AUC than any other single measure from a fasting sample. Moreover, the model provided further risk stratification among high-risk subpopulations with impaired fasting glucose or metabolic syndrome. The PreDx DRS provides the absolute risk of diabetes conversion in five years for subjects identified to be "at risk" using the clinical factors. Copyright 2009 Diabetes Technology Society.

The Value of DNA Sequencing - TCGA

Cancer.gov

DNA sequencing: what it tells us about DNA changes in cancer, how looking across many tumors will help to identify meaningful changes and potential drug targets, and how genomics is changing the way we think about cancer.

Mapping International Cancer Activities – Global Cancer Project Map Launch

Cancer.gov

CGH’s Dr. Sudha Sivaram, Dr. Makeda Williams, and Ms. Kalina Duncan have partnered with Drs. Ami Bhatt and Franklin Huang at Global Oncology, Inc. (GO) to develop the Global Cancer Project Map - a web-based tool designed to facilitate cancer research and control activity planning.

Evaluation of Psychological Hardiness and Coping Style as Risk/Resilience Factors for Health Risk Behaviour

DTIC Science & Technology

2011-04-01

205 RESEARCH DESIGN & METHODS Objective/Hypothesis: The objective of the study is to evaluate the utility of a short hardiness-resilience...problems. Study Design & Methods : This research will evaluate the utility of hardiness, as measured by the DRS-15R, as a screening tool for...may take a toll on defense workers. This research points the way to new approaches for early identification of military workers at risk for stress

HPMSS(High Precision Magnetic Survey System) and InterRidge

NASA Astrophysics Data System (ADS)

Isezaki, N.; Sayanagi, K.

2012-12-01

From the beginning of 1990s to the beginning of 2000s, the Japanese group of IntreRidge conducted many cruises for three component magnetic survey using Shipboard Three Component Magnetometer (STCM) and Deep Towed Three Component Magnetometer (DTCM) in the world wide oceans. We have been developing HPMSS during this time with support of Dr.Tamaki(the late representative of InterRidge Japan) who understood the advantages of three component geomagnetic anomalies (TCGA). TCGA measured by STCM determines the direction of geomagnetic anomaly lineations precisely at every point where TCGA were observed, which playes the important role in magnetic anomaly lineation analysis. Even in the beginning of 2000s, almost all marine magnetic scientists believed that the total intensity anomly (TIA) is the better data than TCGA for analysis because the scalar magnetometers (e.g. proton precession magnetometer) have the better accuracy than any other magnetometers (e.g.flux gate magnetometer (FGM)). We employed the high accrate gyroscope (e.g.ring lase gyroscope (RLG)/optical fiber gyroscope (OFG)) to improve the accuracy of STCM/DTCM equipped with FGM. Moreover we employed accurate and precise FGM which was selected among the market. Finally we developed the new magnetic survey system with high precision usable as airborn, shipboard and dee-ptowed magnetometers which we call HPMSS(High Precision Magnetic Survey System). As an optional equipment, we use LAN to communicate between a data aquisiitin part and a data logging part, and GPS for a position fix. For the deep-towed survey, we use the acoustic position fix (super short base line method) and the acoustic communication to monitor the DTCM status. First we used HPMSS to obtain the magnetization structure of the volcanic island, Aogashima located 300km south of Tokyo using a hellcopter in 2006 and 2009. Next we used HPMSS installed in DTCM in 2010,2011 and 2012 using R/V Bosei-maru belonging to Tokai University. Also we used

Next-generation sequencing of translocation renal cell carcinoma reveals novel RNA splicing partners and frequent mutations of chromatin-remodeling genes.

PubMed

Malouf, Gabriel G; Su, Xiaoping; Yao, Hui; Gao, Jianjun; Xiong, Liangwen; He, Qiuming; Compérat, Eva; Couturier, Jérôme; Molinié, Vincent; Escudier, Bernard; Camparo, Philippe; Doss, Denaha J; Thompson, Erika J; Khayat, David; Wood, Christopher G; Yu, Willie; Teh, Bin T; Weinstein, John; Tannir, Nizar M

2014-08-01

MITF/TFE translocation renal cell carcinoma (TRCC) is a rare subtype of kidney cancer. Its incidence and the genome-wide characterization of its genetic origin have not been fully elucidated. We performed RNA and exome sequencing on an exploratory set of TRCC (n = 7), and validated our findings using The Cancer Genome Atlas (TCGA) clear-cell RCC (ccRCC) dataset (n = 460). Using the TCGA dataset, we identified seven TRCC (1.5%) cases and determined their genomic profile. We discovered three novel partners of MITF/TFE (LUC7L3, KHSRP, and KHDRBS2) that are involved in RNA splicing. TRCC displayed a unique gene expression signature as compared with other RCC types, and showed activation of MITF, the transforming growth factor β1 and the PI3K complex targets. Genes differentially spliced between TRCC and other RCC types were enriched for MITF and ID2 targets. Exome sequencing of TRCC revealed a distinct mutational spectrum as compared with ccRCC, with frequent mutations in chromatin-remodeling genes (six of eight cases, three of which were from the TCGA). In two cases, we identified mutations in INO80D, an ATP-dependent chromatin-remodeling gene, previously shown to control the amplitude of the S phase. Knockdown of INO80D decreased cell proliferation in a novel cell line bearing LUC7L3-TFE3 translocation. This genome-wide study defines the incidence of TRCC within a ccRCC-directed project and expands the genomic spectrum of TRCC by identifying novel MITF/TFE partners involved in RNA splicing and frequent mutations in chromatin-remodeling genes. ©2014 American Association for Cancer Research.

Super-resolution Microscopical Localization of Dopamine Receptors 1 and 2 in Rat Hippocampal Synaptosomes.

PubMed

Miklosi, Andras G; Del Favero, Giorgia; Bulat, Tanja; Höger, Harald; Shigemoto, Ryuichi; Marko, Doris; Lubec, Gert

2018-06-01

Although dopamine receptors D1 and D2 play key roles in hippocampal function, their synaptic localization within the hippocampus has not been fully elucidated. In order to understand precise functions of pre- or postsynaptic dopamine receptors (DRs), the development of protocols to differentiate pre- and postsynaptic DRs is essential. So far, most studies on determination and quantification of DRs did not discriminate between subsynaptic localization. Therefore, the aim of the study was to generate a robust workflow for the localization of DRs. This work provides the basis for future work on hippocampal DRs, in light that DRs may have different functions at pre- or postsynaptic sites. Synaptosomes from rat hippocampi isolated by a sucrose gradient protocol were prepared for super-resolution direct stochastic optical reconstruction microscopy (dSTORM) using Bassoon as a presynaptic zone and Homer1 as postsynaptic density marker. Direct labeling of primary validated antibodies against dopamine receptors D1 (D1R) and D2 (D2R) with Alexa Fluor 594 enabled unequivocal assignment of D1R and D2R to both, pre- and postsynaptic sites. D1R immunoreactivity clusters were observed within the presynaptic active zone as well as at perisynaptic sites at the edge of the presynaptic active zone. The results may be useful for the interpretation of previous studies and the design of future work on DRs in the hippocampus. Moreover, the reduction of the complexity of brain tissue by the use of synaptosomal preparations and dSTORM technology may represent a useful tool for synaptic localization of brain proteins.

Synergistic effects of acyclovir and 3, 19-isopropylideneandrographolide on herpes simplex virus wild types and drug-resistant strains.

PubMed

Priengprom, Thongkoon; Ekalaksananan, Tipaya; Kongyingyoes, Bunkerd; Suebsasana, Supawadee; Aromdee, Chantana; Pientong, Chamsai

2015-03-11

An andrographolide analogue, 3, 19-isopropylideneandrographolide (IPAD), exerts an inhibitory effect on replication of wild-type herpes simplex virus serotype 1 (HSV-1). In this study, we examined the anti-viral activity of IPAD on HSV wild types (HSV-1 strain KOS and HSV-2 clinical isolate) and HSV-1 drug-resistant strains (DRs). Synergistic effects of IPAD with acyclovir (ACV) were also evaluated. MTT and cytopathic effect (CPE) reduction assays were performed to determine cytotoxicity and anti-viral activities, respectively. A combination assay was used to determine synergistic effects of IPAD and ACV. Presence of viral DNA and protein in experimental cells was investigated using the polymerase chain reaction and western blotting, respectively. A non-cytotoxic concentration of IPAD (20.50 μM) completely inhibited CPE formation induced by HSV wild types and HSV-1 DRs after viral entry into the cells. The anti-HSV activities included inhibition of viral DNA and protein synthesis. The minimum inhibitory concentrations of ACV for HSV wild types and HSV-1 DRs were 20.20 and 2,220.00 μM, respectively. Combination of ACV with IPAD showed synergistic effects in inhibition of CPE formation, viral DNA and protein synthesis by HSV wild types as well as HSV-1 DRs. For the synergistic effects on HSV wild types and HSV-1 DRs, the effective concentrations of ACV were reduced. These results showed the inhibitory potential of IPAD on HSV wild types and HSV-1 DRs and suggested that IPAD could be used in combination with ACV for treatment of HSV-1 DRs infections.

Methylphenidate Transdermal System: A Multisite, Open-Label Study of Dermal Reactions in Pediatric Patients Diagnosed With ADHD

PubMed Central

Squires, Liza; Li, Yunfeng; Civil, Richard; Paller, Amy S.

2010-01-01

Objective: To characterize dermal reactions and examine methylphenidate (MPH) sensitization in subjects receiving methylphenidate transdermal system (MTS). Method: This multicenter, open-label, dose-optimization study utilized MTS doses of 10, 15, 20, and 30 mg in children aged 6 to 12 years, inclusive (N = 305), with a DSM-IV-TR primary diagnosis of attention-deficit/hyperactivity disorder. The study was conducted between January 8, 2007, and August 23, 2007. Subjects wore MTS on their hips for 9 hours per day, alternating sides daily for a total of 7 weeks. Assessments included the Experience of Discomfort scale, Transdermal System Adherence scale, and Dermal Response Scale (DRS; 0 = no irritation, 7 = strong reaction). On-study reevaluations were conducted to characterize DRS scores ≥ 4. Epicutaneous allergy patch testing was conducted for DRS scores ≥ 6, persistent DRS scores ≥ 4, DRS score increase following an assessment of ≥ 4, or DRS scores of 4 or 5 following elective discontinuation. Results: Approximately half of subjects experienced definite erythema at the patch site that generally dissipated within 24 hours. Four subjects experienced a DRS score of 4 (1%): erythema in 1 subject resolved on study treatment, 2 cases resolved poststudy and subjects tolerated oral MPH, and 1 subject discontinued treatment. The latter subject was referred for patch testing and was diagnosed with allergic contact sensitization to MPH. Conclusions: Few severe dermal effects were seen with MTS treatment. Dermal reactions were characterized as contact dermatitis and dissipated rapidly. On patch testing, 1 subject (0.3%) manifested sensitization to MPH. Trial Registration: clinicaltrials.gov Identifier: NCT00434213 PMID:21494336

The Oregon Studies in Educational Research, Development, Diffusion, and Evaluational Volume III: Conceptual Frameworks for Viewing Educational RDD&E. Final Report.

ERIC Educational Resources Information Center

Schalock, H. Del, Ed.; Sell, G. Roger, Ed.

This volume represents the output of a yearlong effort to clarify and firm the conceptual base that underlies educational RDD&E. It contains three commissioned papers authored by Drs. Hendrik D. Gideonse, Gene V Glass and Blaine R. Worthen, and by Leslie J. Briggs and one paper prepared by H. Del Schalock and G. Roger Sell of the staff of the…

Demonstration of Dispersive Rarefaction Shocks in Hollow Elliptical Cylinder Chains

NASA Astrophysics Data System (ADS)

Kim, H.; Kim, E.; Chong, C.; Kevrekidis, P. G.; Yang, J.

2018-05-01

We report an experimental and numerical demonstration of dispersive rarefaction shocks (DRS) in a 3D-printed soft chain of hollow elliptical cylinders. We find that, in contrast to conventional nonlinear waves, these DRS have their lower amplitude components travel faster, while the higher amplitude ones propagate slower. This results in the backward-tilted shape of the front of the wave (the rarefaction segment) and the breakage of wave tails into a modulated waveform (the dispersive shock segment). Examining the DRS under various impact conditions, we find the counterintuitive feature that the higher striker velocity causes the slower propagation of the DRS. These unique features can be useful for mitigating impact controllably and efficiently without relying on material damping or plasticity effects.

Demonstration of Dispersive Rarefaction Shocks in Hollow Elliptical Cylinder Chains.

PubMed

Kim, H; Kim, E; Chong, C; Kevrekidis, P G; Yang, J

2018-05-11

We report an experimental and numerical demonstration of dispersive rarefaction shocks (DRS) in a 3D-printed soft chain of hollow elliptical cylinders. We find that, in contrast to conventional nonlinear waves, these DRS have their lower amplitude components travel faster, while the higher amplitude ones propagate slower. This results in the backward-tilted shape of the front of the wave (the rarefaction segment) and the breakage of wave tails into a modulated waveform (the dispersive shock segment). Examining the DRS under various impact conditions, we find the counterintuitive feature that the higher striker velocity causes the slower propagation of the DRS. These unique features can be useful for mitigating impact controllably and efficiently without relying on material damping or plasticity effects.

Acquire an Bruker Dimension FastScan (trademark) Atomic Force Microscope (AFM) for Materials, Physical and Biological Science Research and Education

DTIC Science & Technology

2016-04-14

two super users, Drs. Biswajit Sannigrahi and Guangchang Zhou were trained by the Senior Engineer for Product Service, Dr. Teddy Huang from the... Engineering : The number of undergraduates funded by your agreement who graduated during this period and intend to work for the Department of Defense The...science, mathematics, engineering or technology fields: Student Metrics This section only applies to graduating undergraduates supported by this

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Yitan; Xu, Yanxun; Helseth, Donald L.

Background: Genetic interactions play a critical role in cancer development. Existing knowledge about cancer genetic interactions is incomplete, especially lacking evidences derived from large-scale cancer genomics data. The Cancer Genome Atlas (TCGA) produces multimodal measurements across genomics and features of thousands of tumors, which provide an unprecedented opportunity to investigate the interplays of genes in cancer. Methods: We introduce Zodiac, a computational tool and resource to integrate existing knowledge about cancer genetic interactions with new information contained in TCGA data. It is an evolution of existing knowledge by treating it as a prior graph, integrating it with a likelihood modelmore » derived by Bayesian graphical model based on TCGA data, and producing a posterior graph as updated and data-enhanced knowledge. In short, Zodiac realizes “Prior interaction map + TCGA data → Posterior interaction map.” Results: Zodiac provides molecular interactions for about 200 million pairs of genes. All the results are generated from a big-data analysis and organized into a comprehensive database allowing customized search. In addition, Zodiac provides data processing and analysis tools that allow users to customize the prior networks and update the genetic pathways of their interest. Zodiac is publicly available at www.compgenome.org/ZODIAC. Conclusions: Zodiac recapitulates and extends existing knowledge of molecular interactions in cancer. It can be used to explore novel gene-gene interactions, transcriptional regulation, and other types of molecular interplays in cancer.« less

Evaluation of hierarchical models for integrative genomic analyses.

PubMed

Denis, Marie; Tadesse, Mahlet G

2016-03-01

Advances in high-throughput technologies have led to the acquisition of various types of -omic data on the same biological samples. Each data type gives independent and complementary information that can explain the biological mechanisms of interest. While several studies performing independent analyses of each dataset have led to significant results, a better understanding of complex biological mechanisms requires an integrative analysis of different sources of data. Flexible modeling approaches, based on penalized likelihood methods and expectation-maximization (EM) algorithms, are studied and tested under various biological relationship scenarios between the different molecular features and their effects on a clinical outcome. The models are applied to genomic datasets from two cancer types in the Cancer Genome Atlas project: glioblastoma multiforme and ovarian serous cystadenocarcinoma. The integrative models lead to improved model fit and predictive performance. They also provide a better understanding of the biological mechanisms underlying patients' survival. Source code implementing the integrative models is freely available at https://github.com/mgt000/IntegrativeAnalysis along with example datasets and sample R script applying the models to these data. The TCGA datasets used for analysis are publicly available at https://tcga-data.nci.nih.gov/tcga/tcgaDownload.jsp marie.denis@cirad.fr or mgt26@georgetown.edu Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Comparison of indium-labeled-leukocyte imaging with sequential technetium-gallium scanning in the diagnosis of low-grade musculoskeletal sepsis. A prospective study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Merkel, K.D.; Brown, M.L.; Dewanjee, M.K.

We prospectively compared sequential technetium-gallium imaging with indium-labeled-leukocyte imaging in fifty patients with suspected low-grade musculoskeletal sepsis. Adequate images and follow-up examinations were obtained for forty-two patients. The presence or absence of low-grade sepsis was confirmed by histological and bacteriological examinations of tissue specimens taken at surgery in thirty of the forty-two patients. In these thirty patients, the sensitivity of sequential Tc-Ga imaging was 48 per cent, the specificity was 86 per cent, and the accuracy was 57 per cent, whereas the sensitivity of the indium-labeled-leukocyte technique was 83 per cent, the specificity was 86 per cent, and the accuracymore » was 83 per cent. When the additional twelve patients for whom surgery was deemed unnecessary were considered, the sensitivity of sequential Tc-Ga imaging was 50 per cent, the specificity was 78 per cent, and the accuracy was 62 per cent, as compared with a sensitivity of 83 per cent, a specificity of 94 per cent, and an accuracy of 88 per cent with the indium-labeled-leukocyte method. In patients with a prosthesis the indium-labeled-leukocyte image was 94 per cent accurate, compared with 75 per cent accuracy for sequential Tc-Ga imaging. Statistical analysis of these data demonstrated that the indium-labeled-leukocyte technique was superior to sequential Tc-Ga imaging in detecting areas of low-grade musculoskeletal sepsis.« less

Portable handheld diffuse reflectance spectroscopy system for clinical evaluation of skin: a pilot study in psoriasis patients

PubMed Central

Tzeng, Shih-Yu; Guo, Jean-Yan; Yang, Chao-Chun; Hsu, Chao-Kai; Huang, Hung Ji; Chou, Shih-Jie; Hwang, Chi-Hung; Tseng, Sheng-Hao

2016-01-01

Diffuse reflectance spectroscopy (DRS) has been utilized to study biological tissues for a variety of applications. However, many DRS systems are not designed for handheld use and/or relatively expensive which limit the extensive clinical use of this technique. In this paper, we report a handheld, low-cost DRS system consisting of a light source, optical switch, and a spectrometer, that can precisely quantify the optical properties of tissue samples in the clinical setting. The handheld DRS system was employed to determine the skin chromophore concentrations, absorption and scattering properties of 11 patients with psoriasis. The measurement results were compared to the clinical severity of psoriasis as evaluated by dermatologist using PASI (Psoriasis Area and Severity Index) scores. Our statistical analyses indicated that the handheld DRS system could be a useful non-invasive tool for objective evaluation of the severity of psoriasis. It is expected that the handheld system can be used for the objective evaluation and monitoring of various skin diseases such as keloid and psoriasis. PMID:26977366

Integrative, multimodal analysis of glioblastoma using TCGA molecular data, pathology images, and clinical outcomes.

PubMed

Kong, Jun; Cooper, Lee A D; Wang, Fusheng; Gutman, David A; Gao, Jingjing; Chisolm, Candace; Sharma, Ashish; Pan, Tony; Van Meir, Erwin G; Kurc, Tahsin M; Moreno, Carlos S; Saltz, Joel H; Brat, Daniel J

2011-12-01

Multimodal, multiscale data synthesis is becoming increasingly critical for successful translational biomedical research. In this letter, we present a large-scale investigative initiative on glioblastoma, a high-grade brain tumor, with complementary data types using in silico approaches. We integrate and analyze data from The Cancer Genome Atlas Project on glioblastoma that includes novel nuclear phenotypic data derived from microscopic slides, genotypic signatures described by transcriptional class and genetic alterations, and clinical outcomes defined by response to therapy and patient survival. Our preliminary results demonstrate numerous clinically and biologically significant correlations across multiple data types, revealing the power of in silico multimodal data integration for cancer research.

A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers. | Office of Cancer Genomics

Cancer.gov

We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique molecular features, clinically significant subtypes, and potential therapeutic targets. We found 61 somatic copy-number alterations (SCNAs) and 46 significantly mutated genes (SMGs). Eleven SCNAs and 11 SMGs had not been identified in previous TCGA studies of the individual tumor types. We found functionally significant estrogen receptor-regulated long non-coding RNAs (lncRNAs) and gene/lncRNA interaction networks.

Prediction of Ba, Co and Ni for tropical soils using diffuse reflectance spectroscopy and X-ray fluorescence spectroscopy

NASA Astrophysics Data System (ADS)

Arantes Camargo, Livia; Marques Júnior, José; Reynaldo Ferracciú Alleoni, Luís; Tadeu Pereira, Gener; De Bortoli Teixeira, Daniel; Santos Rabelo de Souza Bahia, Angélica

2017-04-01

Environmental impact assessments may be assisted by spatial characterization of potentially toxic elements (PTEs). Diffuse reflectance spectroscopy (DRS) and X-ray fluorescence spectroscopy (XRF) are rapid, non-destructive, low-cost, prediction tools for a simultaneous characterization of different soil attributes. Although low concentrations of PTEs might preclude the observation of spectral features, their contents can be predicted using spectroscopy by exploring the existing relationship between the PTEs and soil attributes with spectral features. This study aimed to evaluate, in three geomorphic surfaces of Oxisols, the capacity for predicting PTEs (Ba, Co, and Ni) and their spatial variability by means of diffuse reflectance spectroscopy (DRS) and X-ray fluorescence spectroscopy (XRF). For that, soil samples were collected from three geomorphic surfaces and analyzed for chemical, physical, and mineralogical properties, and then analyzed in DRS (visible + near infrared - VIS+NIR and medium infrared - MIR) and XRF equipment. PTE prediction models were calibrated using partial least squares regression (PLSR). PTE spatial distribution maps were built using the values calculated by the calibrated models that reached the best accuracy using geostatistics. PTE prediction models were satisfactorily calibrated using MIR DRS for Ba, and Co (residual prediction deviation - RPD > 3.0), Vis DRS for Ni (RPD > 2.0) and FRX for all the studied PTEs (RPD > 1.8). DRS- and XRF-predicted values allowed the characterization and the understanding of spatial variability of the studied PTEs.

Smartphone spectrometer for non-invasive diffuse reflectance spectroscopy based hemoglobin sensing (Conference Presentation)

NASA Astrophysics Data System (ADS)

Edwards, Perry S.

2016-10-01

Fiber-optic based diffuse reflectance spectroscopy (DRS) is shown to be a highly specific and highly sensitive method for non-invasive detection of various cancers (e.g. cervical and oral) as well as many other diseases. Fiber-optic DRS diagnosis relies on non-invasive biomarker detection (e.g. oxy- and deoxy-hemoglobin) and can be done without the need for sophisticated laboratory analysis of samples. Thus, it is highly amenable for clinical adoption especially in resource scarce regions that have limited access to such developed laboratory infrastructure. Despite the demonstrated effectiveness of fiber-optic DRS, such systems remain cost prohibitive in many of these regions, mainly due to the use of bulky and expensive spectrometers. Here, a fiber-optic DRS system is coupled to a smartphone spectrometer and is proposed as a low-cost solution for non-invasive tissue hemoglobin sensing. The performance of the system is assessed by measuring tissue phantoms with varying hemoglobin concentrations. A DRS retrieval algorithm is used to extract hemoglobin parameters from the measurements and determine the accuracy of the system. The results are then compared with those of a previously reported fiber-optic DRS system which is based on a larger more expensive spectrometer system. The preliminary results are encouraging and indicate the potential of the smartphone spectrometer as a viable low-cost option for non-invasive tissue hemoglobin sensing.

Duane's retraction syndrome: its sensory features.

PubMed

Tomaç, Suhan; Mutlu, Fatih Mehmet; Altinsoy, Halil Ibrahim

2007-11-01

To investigate binocularity in Duane's retraction syndrome (DRS) and to evaluate whether or not there is a relationship between the sensory and clinical features of the syndrome. Clinical and sensory findings of 29 patients with DRS were recorded. Binocularity was tested with the Bagolini glasses (BG), Worth four-dot (W4D), TNO and the stereo-fly plate of the Titmus test. Twenty-four (83%) patients showed fusion with the BG at near and 23 (79%) had fusion at distance. With the W4D, 23 (79%) patients had fusion at near and 19 (65%) had fusion at distance. Seven (24%) patients demonstrated normal stereoacuity, 15 (52%) had reduced stereoacuity and the remaining seven (24%) patients had no measurable stereoacuity. In patients without stereoacuity, amblyopia (p < 0.001), type 2 and 3 DRS (p = 0.031) and exotropia (p = 0.003) in primary position were more common than in those with reduced or with normal stereoacuity. Restriction of ocular ductions was also more severe in patients without stereoacuity than in those with reduced or normal stereoacuity (p = 0.019, p = 0.016). Patients with type 2 and 3 DRS were significantly more likely to have amblyopia (p = 0.037), large-angle heterotropia (p = 0.005) in primary position, upshoot or downshoot (p = 0.010) than those with type 1 DRS. Although approximately 75% of DRS patients had fusion and measurable stereoacuity, only 25% demonstrated normal binocularity. This report provides new data on the relationship of sensory features to most of the clinical findings of this syndrome. Sensory features, as well as most clinical features of the syndrome, are better in patients with type 1 DRS.

Two novel CHN1 mutations in two families with Duane’s retraction syndrome

PubMed Central

Chan, Wai-Man; Miyake, Noriko; Zhu-Tam, Lily; Andrews, Caroline; Engle, Elizabeth C.

2012-01-01

Objective To determine the genetic cause of Duane’s retraction syndrome (DRS) in two families segregating DRS as an autosomal dominant trait. Method Members of two unrelated pedigrees were enrolled in an ongoing genetic study. Linkage analysis was performed using fluorescent microsatellite markers flanking the CHN1 locus. Probands and family members were screened for CHN1 mutations. Results Of the six clinically affected individuals in the two pedigrees, three have bilateral and three have unilateral DRS. Both pedigrees are consistent with linkage to the DURS2 locus, one with complete and one with incomplete penetrance. Sequence analysis revealed the pedigrees segregate novel heterozygous missense CHN1 mutations, c.422C>T and c.754C>T, predicted to result in α2-chimaerin amino acid substitutions P141L and P252S, respectively. Conclusion Genetic analysis of two pedigrees segregating nonsyndromic DRS reveals two novel mutations in CHN1, bringing the number of DRS pedigrees know to harbor CHN1 mutations, and the number of unique CHN1 mutations, from seven to nine. Both mutations identified in this study alter residues that participate in intramolecular interactions that stabilize the inactive, closed conformation of α2-chimerin, and thus are predicted to result in its hyper-activation. Moreover, amino acid residue P252 was altered to a different residue in a previously reported DRS pedigree; thus, this is the first report of two CHN1 mutations altering the same residue, further supporting a gain-of-function etiology. Clinical Relevance Members of families segregating DRS as an autosomal dominant trait should be screened for mutations in the CHN1 gene, enhancing genetic counseling and permitting earlier diagnosis. PMID:21555619

Regression Analysis of Combined Gene Expression Regulation in Acute Myeloid Leukemia

PubMed Central

Li, Yue; Liang, Minggao; Zhang, Zhaolei

2014-01-01

Gene expression is a combinatorial function of genetic/epigenetic factors such as copy number variation (CNV), DNA methylation (DM), transcription factors (TF) occupancy, and microRNA (miRNA) post-transcriptional regulation. At the maturity of microarray/sequencing technologies, large amounts of data measuring the genome-wide signals of those factors became available from Encyclopedia of DNA Elements (ENCODE) and The Cancer Genome Atlas (TCGA). However, there is a lack of an integrative model to take full advantage of these rich yet heterogeneous data. To this end, we developed RACER (Regression Analysis of Combined Expression Regulation), which fits the mRNA expression as response using as explanatory variables, the TF data from ENCODE, and CNV, DM, miRNA expression signals from TCGA. Briefly, RACER first infers the sample-specific regulatory activities by TFs and miRNAs, which are then used as inputs to infer specific TF/miRNA-gene interactions. Such a two-stage regression framework circumvents a common difficulty in integrating ENCODE data measured in generic cell-line with the sample-specific TCGA measurements. As a case study, we integrated Acute Myeloid Leukemia (AML) data from TCGA and the related TF binding data measured in K562 from ENCODE. As a proof-of-concept, we first verified our model formalism by 10-fold cross-validation on predicting gene expression. We next evaluated RACER on recovering known regulatory interactions, and demonstrated its superior statistical power over existing methods in detecting known miRNA/TF targets. Additionally, we developed a feature selection procedure, which identified 18 regulators, whose activities clustered consistently with cytogenetic risk groups. One of the selected regulators is miR-548p, whose inferred targets were significantly enriched for leukemia-related pathway, implicating its novel role in AML pathogenesis. Moreover, survival analysis using the inferred activities identified C-Fos as a potential AML

Duane's retraction syndrome: a retrospective review from Kathmandu, Nepal.

PubMed

Shrestha, Gauri Shankar; Sharma, Ananda Kumar

2012-01-01

  The aim was to study the clinical characteristics of Duane's retraction syndrome (DRS) in Nepalese patients.   Medical records from 52 cases of DRS from May 2003 to April 2010 were retrospectively reviewed for age, gender, laterality and clinical characteristics. Forty-one case records (78.8 per cent) that had complete clinical findings were considered for further evaluation. Examination included visual acuity by Snellen chart, refraction, associated horizontal and vertical strabismus in primary gaze, upshoot and downshoot on attempted adduction, binocular vision assessed with the Worth four-dot test on adopted gaze and stereopsis examined with the Titmus stereo test.   DRS type I was the most common type observed in 73.2 per cent of cases, followed by DRS type II (14.6 per cent) and DRS type III (12.2 per cent). It was more common in female patients (58.5 per cent) than male patients (χ(2) = 4.6, df = 1, p = 0.03). DRS was more common in the left eye (68.3 per cent) than the right eye and unilaterally present in 95.1 per cent of subjects. In primary gaze, orthotropia (41.5 per cent) was more common than exotropia (34.1 per cent) and esotropia (24.4 per cent) and vertical strabismus was present in 24.4 per cent of subjects. Upshoot and downshoot on attempted adduction was seen in 14.6 and 9.8 per cent, respectively. Binocular single vision was present in 68.3 per cent of subjects by Worth four-dot test at near. Stereopsis of 3,000 seconds of arc was present in 9.8 per cent, 100 to 200 seconds of arc in 14.6 per cent and 40 to 60 seconds of arc in 43.9 per cent with the Titmus stereo test.   DRS is more common in female patients and the left eye. DRS type I is the most common type. © 2011 The Authors. Clinical and Experimental Optometry © 2011 Optometrists Association Australia.

Novel Approaches to Preventing Urinary Tract Infection in Women

DTIC Science & Technology

1998-09-01

tract tissue (kidney). (4) Establishment of a collaboration with Drs. M. Juliana McElrath and Florian Hladik of the Fred Hutchison Cancer Research...liver, A. Hamers , W. Gaastra, 20. Levery, S. B., M. E. Salyan, S. J. Steele, R. Kannagi, S. Dasgupta, J. L. K.-A. Karlsson, and S. Normark. 1990

DNA replication stress and cancer chemotherapy.

PubMed

Kitao, Hiroyuki; Iimori, Makoto; Kataoka, Yuki; Wakasa, Takeshi; Tokunaga, Eriko; Saeki, Hiroshi; Oki, Eiji; Maehara, Yoshihiko

2018-02-01

DNA replication is one of the fundamental biological processes in which dysregulation can cause genome instability. This instability is one of the hallmarks of cancer and confers genetic diversity during tumorigenesis. Numerous experimental and clinical studies have indicated that most tumors have experienced and overcome the stresses caused by the perturbation of DNA replication, which is also referred to as DNA replication stress (DRS). When we consider therapeutic approaches for tumors, it is important to exploit the differences in DRS between tumor and normal cells. In this review, we introduce the current understanding of DRS in tumors and discuss the underlying mechanism of cancer therapy from the aspect of DRS. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Prospective observational study of delirium recovery trajectories and associated short-term outcomes in older adults admitted to a specialized delirium unit.

PubMed

Lam, Ching-yu; Tay, Laura; Chan, Mark; Ding, Yew Yoong; Chong, Mei Sian

2014-09-01

To describe the recovery trajectories of delirium and to determine factors predicting the course of recovery and adverse outcome. A prospective observational study. Geriatric monitoring unit (GMU), a five-bed unit specializing in managing older adults with delirium. Individuals admitted to the GMU between December 2010 and August 2012 (N = 234; mean age 84.1 ± 7.4). Information was collected on demographic characteristics; comorbidities; severity of illness; functional status; and daily cognitive, Delirium Rating Scale, Revised-98 (DRS-R98) severity, and functional scoring. Resolution of delirium, and thus GMU discharge, was determined according to clinical assessment. The primary outcome was residual subsyndromal delirium (SSD) (DRS-R98 severity ≥13) upon GMU discharge. Univariate and multivariate methods were used to determine the predictors of residual SSD and adverse outcomes (inpatient mortality and incident nursing home admission upon discharge). Participants with residual SSD had a slower recovery in terms of delirium severity, cognition, and functional status than those with no residual SSD. Residual SSD predictors included underlying dementia, admission DRS-R98 severity, DRS-R98 severity on Day 1 minus Day 3 of GMU stay, and admission modified Barthel Index. Only presence of residual SSD at discharge predicted adverse outcomes (odds ratio = 5.27, 95% confidence interval = 1.43-19.47). Individuals with residual SSD had prolonged recovery trajectory of delirium. These new insights into the recovery trajectories of delirium may help formulate early discharge planning and provide the basis for future research on delirium treatment. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

Validation of a Multimarker Model for Assessing Risk of Type 2 Diabetes from a Five-Year Prospective Study of 6784 Danish People (Inter99)

PubMed Central

Urdea, Mickey; Kolberg, Janice; Wilber, Judith; Gerwien, Robert; Moler, Edward; Rowe, Michael; Jorgensen, Paul; Hansen, Torben; Pedersen, Oluf; Jørgensen, Torben; Borch-Johnsen, Knut

2009-01-01

Background Improved identification of subjects at high risk for development of type 2 diabetes would allow preventive interventions to be targeted toward individuals most likely to benefit. In previous research, predictive biomarkers were identified and used to develop multivariate models to assess an individual's risk of developing diabetes. Here we describe the training and validation of the PreDx™ Diabetes Risk Score (DRS) model in a clinical laboratory setting using baseline serum samples from subjects in the Inter99 cohort, a population-based primary prevention study of cardiovascular disease. Methods Among 6784 subjects free of diabetes at baseline, 215 subjects progressed to diabetes (converters) during five years of follow-up. A nested case-control study was performed using serum samples from 202 converters and 597 randomly selected nonconverters. Samples were randomly assigned to equally sized training and validation sets. Seven biomarkers were measured using assays developed for use in a clinical reference laboratory. Results The PreDx DRS model performed better on the training set (area under the curve [AUC] = 0.837) than fasting plasma glucose alone (AUC = 0.779). When applied to the sequestered validation set, the PreDx DRS showed the same performance (AUC = 0.838), thus validating the model. This model had a better AUC than any other single measure from a fasting sample. Moreover, the model provided further risk stratification among high-risk subpopulations with impaired fasting glucose or metabolic syndrome. Conclusions The PreDx DRS provides the absolute risk of diabetes conversion in five years for subjects identified to be “at risk” using the clinical factors. PMID:20144324

Role of miR-452-5p in the tumorigenesis of prostate cancer: A study based on the Cancer Genome Atl(TCGA), Gene Expression Omnibus (GEO), and bioinformatics analysis.

PubMed

Gao, Li; Zhang, Li-Jie; Li, Sheng-Hua; Wei, Li-Li; Luo, Bin; He, Rong-Quan; Xia, Shuang

2018-03-06

MiR-452-5p has been reported to be down-regulated in prostate cancer, affecting the development of this type of cancer. However, the molecular mechanism of miR-452-5p in prostate cancer remains unclear. Therefore, we investigated the network of target genes of miR-452-5p in prostate cancer using bioinformatics analyses. We first analyzed the expression profiles and prognostic value of miR-452-5p in prostate cancer tissues from a public database. Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), PANTHER pathway analyses, and a disease ontology (DG) analysis were performed to find the molecular functions of the target genes from GSE datasets and miRWalk. Finally, we validated hub genes from the protein-protein interaction (PPI) networks of the target genes in the Human Protein Atlas (HPA) database and Gene Expression Profiling Interactive Analysis (GEPIA). Narrowing down the optimal target genes was conducted by seeking the common parts of up-regulated genes from GEPIA, down-regulated genes from GSE datasets, and predicted genes in miRWalk. Based on mining of GEO and ArrayExpress microarray chips and miRNA-Seq data in the TCGA database, which includes 1007 prostate cancer samples and 387 non-cancer samples, miR-452-5p is shown to be down-regulated in prostate cancer. GO, KEGG, and PANTHER pathway analyses suggested that the target genes might participate in important biological processes, such as transforming growth factor beta signaling and the positive regulation of brown fat cell differentiation and mesenchymal cell differentiation, as well as the Ras signaling pathway and pathways regulating the pluripotency of stem cells and arrhythmogenic right ventricular cardiomyopathy (ARVC). Nine genes-GABBR, PNISR, NTSR1, DOCK1, EREG, SFRP1, PTGS2, LEF1, and BMP2-were defined as hub genes in the PPI network. Three genes-FAM174B, SLC30A4, and SLIT1-were jointly shared by GEPIA, the GSE datasets, and miRWalk. Down-regulated miR-452-5p might play an

Unifying cancer and normal RNA sequencing data from different sources

PubMed Central

Wang, Qingguo; Armenia, Joshua; Zhang, Chao; Penson, Alexander V.; Reznik, Ed; Zhang, Liguo; Minet, Thais; Ochoa, Angelica; Gross, Benjamin E.; Iacobuzio-Donahue, Christine A.; Betel, Doron; Taylor, Barry S.; Gao, Jianjiong; Schultz, Nikolaus

2018-01-01

Driven by the recent advances of next generation sequencing (NGS) technologies and an urgent need to decode complex human diseases, a multitude of large-scale studies were conducted recently that have resulted in an unprecedented volume of whole transcriptome sequencing (RNA-seq) data, such as the Genotype Tissue Expression project (GTEx) and The Cancer Genome Atlas (TCGA). While these data offer new opportunities to identify the mechanisms underlying disease, the comparison of data from different sources remains challenging, due to differences in sample and data processing. Here, we developed a pipeline that processes and unifies RNA-seq data from different studies, which includes uniform realignment, gene expression quantification, and batch effect removal. We find that uniform alignment and quantification is not sufficient when combining RNA-seq data from different sources and that the removal of other batch effects is essential to facilitate data comparison. We have processed data from GTEx and TCGA and successfully corrected for study-specific biases, enabling comparative analysis between TCGA and GTEx. The normalized datasets are available for download on figshare. PMID:29664468

Molecular approaches for classifying endometrial carcinoma.

PubMed

Piulats, Josep M; Guerra, Esther; Gil-Martín, Marta; Roman-Canal, Berta; Gatius, Sonia; Sanz-Pamplona, Rebeca; Velasco, Ana; Vidal, August; Matias-Guiu, Xavier

2017-04-01

Endometrial carcinoma is the most common cancer of the female genital tract. This review article discusses the usefulness of molecular techniques to classify endometrial carcinoma. Any proposal for molecular classification of neoplasms should integrate morphological features of the tumors. For that reason, we start with the current histological classification of endometrial carcinoma, by discussing the correlation between genotype and phenotype, and the most significant recent improvements. Then, we comment on some of the possible flaws of this classification, by discussing also the value of molecular pathology in improving them, including interobserver variation in pathologic interpretation of high grade tumors. Third, we discuss the importance of applying TCGA molecular approach to clinical practice. We also comment on the impact of intratumor heterogeneity in classification, and finally, we will discuss briefly, the usefulness of TCGA classification in tailoring immunotherapy in endometrial cancer patients. We suggest combining pathologic classification and the surrogate TCGA molecular classification for high-grade endometrial carcinomas, as an option to improve assessment of prognosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Quality Assurance of Cancer Study Common Data Elements Using A Post-Coordination Approach

PubMed Central

Jiang, Guoqian; Solbrig, Harold R.; Prud’hommeaux, Eric; Tao, Cui; Weng, Chunhua; Chute, Christopher G.

2015-01-01

Domain-specific common data elements (CDEs) are emerging as an effective approach to standards-based clinical research data storage and retrieval. A limiting factor, however, is the lack of robust automated quality assurance (QA) tools for the CDEs in clinical study domains. The objectives of the present study are to prototype and evaluate a QA tool for the study of cancer CDEs using a post-coordination approach. The study starts by integrating the NCI caDSR CDEs and The Cancer Genome Atlas (TCGA) data dictionaries in a single Resource Description Framework (RDF) data store. We designed a compositional expression pattern based on the Data Element Concept model structure informed by ISO/IEC 11179, and developed a transformation tool that converts the pattern-based compositional expressions into the Web Ontology Language (OWL) syntax. Invoking reasoning and explanation services, we tested the system utilizing the CDEs extracted from two TCGA clinical cancer study domains. The system could automatically identify duplicate CDEs, and detect CDE modeling errors. In conclusion, compositional expressions not only enable reuse of existing ontology codes to define new domain concepts, but also provide an automated mechanism for QA of terminological annotations for CDEs. PMID:26958201

Diffuse Reflectance Spectroscopy for Surface Measurement of Liver Pathology.

PubMed

Nilsson, Jan H; Reistad, Nina; Brange, Hannes; Öberg, Carl-Fredrik; Sturesson, Christian

2017-01-01

Liver parenchymal injuries such as steatosis, steatohepatitis, fibrosis, and sinusoidal obstruction syndrome can lead to increased morbidity and liver failure after liver resection. Diffuse reflectance spectroscopy (DRS) is an optical measuring method that is fast, convenient, and established. DRS has previously been used on the liver with an invasive technique consisting of a needle that is inserted into the parenchyma. We developed a DRS system with a hand-held probe that is applied to the liver surface. In this study, we investigated the impact of the liver capsule on DRS measurements and whether liver surface measurements are representative of the whole liver. We also wanted to confirm that we could discriminate between tumor and liver parenchyma by DRS. The instrumentation setup consisted of a light source, a fiber-optic contact probe, and two spectrometers connected to a computer. Patients scheduled for liver resection due to hepatic malignancy were included, and DRS measurements were performed on the excised liver part with and without the liver capsule and alongside a newly cut surface. To estimate the scattering parameters and tissue chromophore volume fractions, including blood, bile, and fat, the measured diffuse reflectance spectra were applied to an analytical model. In total, 960 DRS spectra from the excised liver tissue of 18 patients were analyzed. All factors analyzed regarding tumor versus liver tissue were significantly different. When measuring through the capsule, the blood volume fraction was found to be 8.4 ± 3.5%, the lipid volume fraction was 9.9 ± 4.7%, and the bile volume fraction was 8.2 ± 4.6%. No differences could be found between surface measurements and cross-sectional measurements. In measurements with/without the liver capsule, the differences in volume fraction were 1.63% (0.75-2.77), -0.54% (-2.97 to 0.32), and -0.15% (-1.06 to 1.24) for blood, lipid, and bile, respectively. This study shows that it is possible to manage DRS

Regeneration of hepatocyte 'buds' in cirrhosis from intrabiliary stem cells.

PubMed

Falkowski, Olga; An, Hee Jung; Ianus, I Andreea; Chiriboga, Luis; Yee, Herman; West, A Brian; Theise, Neil D

2003-09-01

In massive hepatic necrosis, hepatic stem cells constitute a canal of Hering derived, cytokeratin 19 (CK19) positive 'ductular reaction' (DR). Whether DRs in cirrhosis are activated stem cells (so called 'buds') or biliary metaplasia of cholestatic, injured hepatocytes is still debated. We investigate derivation of intraseptal hepatocytes (ISHs) from DRs and from the biliary tree in cirrhosis. Explants of hepatitis B and C, alcohol, primary biliary cirrhosis and primary sclerosing cholangitis-related cirrhosis were examined. ISHs were quantified and their associations with DRs and cholestasis recorded. 3D-reconstruction of ISHs and nearby bile ducts was performed in blocks from hepatitis C and primary sclerosing cholangitis cirrhosis. Seven hundred seventy five/830 (94%) ISHs were associated with CK19 positive DRs. ISHs without ductular reactions were more likely to show cholestatic features (P<0.0001). In 3D, ISHs were seen to bud directly from the biliary tree. In summary: ISHs: (1) are usually associated with stem cell-like DRs; (2) are rarely cholestatic, leaving the associated DRs unexplained; and (3) are linked to the biliary tree in 3D. Dynamic proliferation rates in hepatitis C over time suggest that hepatocyte replication diminishes in late stages, with an associated activation of the biliary stem cell compartment. We therefore suggest that the biliary tree, from at least its smaller branches up to the canals of Hering, are composed of or at least harbor facultative hepatic stem cells, and that ISH largely represent 'buds' of newly formed hepatocytes.

Evaluation of Decision Rules in a Tiered Assessment of Inhalation Exposure to Nanomaterials.

PubMed

Brouwer, Derk; Boessen, Ruud; van Duuren-Stuurman, Birgit; Bard, Delphine; Moehlmann, Carsten; Bekker, Cindy; Fransman, Wouter; Klein Entink, Rinke

2016-10-01

Tiered or stepwise approaches to assess occupational exposure to nano-objects, and their agglomerates and aggregates have been proposed, which require decision rules (DRs) to move to a next tier, or terminate the assessment. In a desk study the performance of a number of DRs based on the evaluation of results from direct reading instruments was investigated by both statistical simulations and the application of the DRs to real workplace data sets. A statistical model that accounts for autocorrelation patterns in time-series, i.e. autoregressive integrated moving average (ARIMA), was used as 'gold' standard. The simulations showed that none of the proposed DRs covered the entire range of simulated scenarios with respect to the ARIMA model parameters, however, a combined DR showed a slightly better agreement. Application of the DRs to real workplace datasets (n = 117) revealed sensitivity up to 0.72, whereas the lowest observed specificity was 0.95. The selection of the most appropriate DR is very much dependent on the consequences of the decision, i.e. ruling in or ruling out of scenarios for further evaluation. Since a basic assessment may also comprise of other type of measurements and information, an evaluation logic was proposed which embeds the DRs, but furthermore supports decision making in view of a tiered-approach exposure assessment. © The Author 2016. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

Dynamic Control System Performance during Commissioning of the Space Technology 7-Disturbance Reduction System Experiment of LISA Pathfinder

NASA Technical Reports Server (NTRS)

Hsu, Oscar; Maghami, Peiman; O’Donnell, James R., Jr.; Ziemer, John; Romero-Wolf, Andrew

2017-01-01

The Space Technology-7 Disturbance Reduction System (DRS) launched aboard the European Space Agencys LISA Pathfinder spacecraft on December 3, 2015, after more than a decade in development. DRS consists of three prima-ry components: an Integrated Avionics Unit (IAU), Colloidal MicroNewton Thrusters, and Dynamic Control System (DCS) algorithms implemented on the IAU. During the portions of the mission in which the DRS was under control, the DCS was responsible for controlling the spacecraft and the free-floating test masses that were part of the LISA Test Package. The commissioning period was originally divided into two periods: before propulsion separation and after pro-pulsion separation. A recommissioning period was added after an anomaly oc-curred in the thruster system. The paper will describe the activities used to com-mission DRS, present results from the commissioning of the DCS and the re-commissioning activities performed after the thruster anomaly.

Purification of a phospholipase A2 from Daboia russelii siamensis venom with anticancer effects

PubMed Central

Khunsap, Suchitra; Pakmanee, Narumol; Khow, Orawan; Chanhome, Lawan; Sitprija, Visith; Suntravat, Montamas; Lucena, Sara E; Perez, John C; Sánchez, Elda E

2011-01-01

Venom phospholipases A2 (PLA2) are associated with neurotoxic, myotoxic, cardiotoxic, platelet aggregation, and edema activities. A PLA2 (Drs-PLA2) was purified from Daboia russelii siamensis venom by a two-step purification procedure consisting of size-exclusion, followed by anion exchange high performance liquid chromatography (HPLC). The molecular weight of the Drs-PLA2 was 13,679Da, which was determined by MALDI-TOF mass spectrometry. Its N-terminal amino acid sequence was homologous to basic PLA2s of viperid snake venoms. The Drs-PLA2 had indirect hemolytic and anticoagulant activities, cytotoxic activity with a CC50 of 65.8nM, and inhibited SK-MEL-28 cell migration with an IC50 of 25.6nM. In addition, the Drs-PLA2 inhibited the colonization of B16F10 cells in lungs of BALB/c mice by ∼65%. PMID:22091349

Dynamic Control System Performance during Commissioning of the Space Technology 7-Disturbance Reduction System Experiment of LISA Pathfinder

NASA Technical Reports Server (NTRS)

Hsu, Oscar; Maghami, Peiman; O’Donnell, James R., Jr.; Ziemer, John; Romero-Wolf, Andrew

2017-01-01

The Space Technology-7 Disturbance Reduction System (DRS) launched aboard the European Space Agency's LISA Pathfinder spacecraft on December 3, 2015, after more than a decade in development. DRS consists of three primary components: an Integrated Avionics Unit (IAU), Colloidal MicroNewton Thrusters, and Dynamic Control System (DCS) algorithms implemented on the IAU. During the portions of the mission in which the DRS was under control, the DCS was responsible for controlling the spacecraft and the free-floating test masses that were part of the LISA Test Package. The commissioning period was originally divided into two periods: before propulsion separation and after propulsion separation. A recommissioning period was added after an anomaly occurred in the thruster system. The paper will describe the activities used to commission DRS, present results from the commissioning of the DCS and the recommissioning activities per-formed after the thruster anomaly.

A new paradigm of dielectric relaxation spectroscopy for non-invasive detection of breast abnormalities: a preliminary feasibility analysis

NASA Astrophysics Data System (ADS)

Dhurjaty, Sreeram; Qiu, Yuchen; Tan, Maxine; Qian, Wei; Zheng, Bin

2016-03-01

In order to improve efficacy of screening mammography, in recent years, we have been investigating the feasibility of applying a resonance-frequency based electrical impedance spectroscopy (REIS) technology to noninvasively detect breast abnormalities that may lead to the development of cancer in the near-term. Despite promising study-results, we found that REIS suffered from relatively poor reproducibility due to perturbations in electrode placement, contact pressure variation on the breast, as well as variation of the resonating inductor. To overcome this limitation, in this study, we propose and analyze a new paradigm of Dielectric Relaxation Spectroscopy (DRS) that measures polarization-lag of dielectric signals in breast-capacitance when excited by the pulses or sine waves. Unlike conventional DRS that operates using the signals at very high frequencies (GHz) to examine changes in polarization, our new method detects and characterizes the dielectric properties of tissue at low frequencies (<=10 MHz) due to the advent of inexpensive oscillators that are accurate to 1 pico-second (used in GPS receivers) as well as measurement of amplitudes of 1 ppm or better. From theoretical analysis, we have proved that the sensitivity of new DRS in detecting permittivity of water increased by >=80 times as compared to conventional DRS, which operates at frequencies around 4GHz. By analyzing and comparing the relationship between the new DRS and REIS, we found that this DRS has potential advantages in enhancing repeatability from various readings, including temperature-insensitive detection, and yielding higher resolution or sensitivity (up to 100 Femtofarads).

Attitudes, access and anguish: a qualitative interview study of staff and patients' experiences of diabetic retinopathy screening.

PubMed

Hipwell, A E; Sturt, J; Lindenmeyer, A; Stratton, I; Gadsby, R; O'Hare, P; Scanlon, P H

2014-12-15

To examine the experiences of patients, health professionals and screeners; their interactions with and understandings of diabetic retinopathy screening (DRS); and how these influence uptake. Purposive, qualitative design using multiperspectival, semistructured interviews and thematic analysis. Three UK Screening Programme regions with different service-delivery modes, minority ethnic and deprivation levels across rural, urban and inner-city areas, in general practitioner practices and patients' homes. 62 including 38 patients (22 regular-screening attenders, 16 non-regular attenders) and 24 professionals (15 primary care professionals and 9 screeners). Antecedents to attendance included knowledge about diabetic retinopathy and screening; antecedents to non-attendance included psychological, pragmatic and social factors. Confusion between photographs taken at routine eye tests and DRS photographs was identified. The differing regional invitation methods and screening locations were discussed, with convenience and transport safety being over-riding considerations for patients. Some patients mentioned significant pain and visual disturbance from mydriasis drops as a deterrent to attendance. In this, the first study to consider multiperspectival experiential accounts, we identified that proactive coordination of care involving patients, primary care and screening programmes, prior to, during and after screening is required. Multiple factors, prior to, during and after screening, are involved in the attendance and non-attendance for DRS. Further research is needed to establish whether patient self-management educational interventions and the pharmacological reformulation of shorter acting mydriasis drops, may improve uptake of DRS. This might, in turn, reduce preventable vision loss and its associated costs to individuals and their families, and to health and social care providers, reducing current inequalities. Published by the BMJ Publishing Group Limited. For

Development of receiving-detecting circuit for digital radiographic systems with improved spatial resolution

NASA Astrophysics Data System (ADS)

Ryzhikov, Volodymir D.; Opolonin, Oleksandr D.; Galkin, Serhiy M.; Voronkin, Yevheniy F.; Lysetska, Olena K.; Kostyukevych, Serhiy A.

2009-08-01

Detection of X-ray radiation by digital radiographic systems (DRS) is realized using multi-element detector arrays of scintillator-photodiode (S-PD) type. Accounting for our experience in development of X-ray introscopy systems, possibilities can be found for improvement of DRS detection efficiency. Namely, a more efficient use of the dynamic range of the analog-to-digit converter by means of instrumental compensation of scatter of detector characteristics and smaller apertures of individual detection channels. However, smaller apertures lead to lower levels of useful signals, and a problem emerges of signal interference over neighboring channels, which is related to optical separation of the scintillation elements. Also, more compact arrangement of electronic components of preamplifiers is achieved. The latter problem is solved by using multi-channel (from 32 to 1024 channels) photoreceiving devices (PRD). PRD has a set of photosensitive elements formed on one crystal, as well as shift registers ensuring preliminary amplification of signals and series connection to one outlet. The work envisages creation of receiving-detecting circuit (RDC) with improved spatial resolution (ISR) with the aim of producing advanced DRS with improved characteristics: density resolution better than 0.9%, and detecting ability allowing detection of θ 0.5 mm steel wire behind 6 mm steel. The work will result in the development of RDC with ISR (800-200 microns). In combination with various ionizing radiation sources and scanning mechanisms this will allow creation of DRS for many tasks of non-destructive testing (NDT) and technical diagnostics (TD), in particular, for check-up of pipelines, objects of oil and gas industries, etc. This work was supported by the Ministry of Education and Science of Ukraine, the U.S. Civilian Research and Development Foundation (CRDF), and by the NATO Science for Peace and Security Program (Project SfP-982823).

Nutrition Frontiers - Summer 2016 | Division of Cancer Prevention

Cancer.gov

Volume 7, Issue 3 The summer issue of Nutrition Frontiers showcases the combined effects of ursolic acid and resveratrol for skin cancer, the potential chemopreventive effects of the dietary supplement 4-MU, and a method to monitor a heterocyclic aromatic amine in dyed hair. Learn about our spotlight investigators, Drs. Michael Caligiuri and Jianhua Yu, and their research on

Exploration of the Central Dogma at the Interface of Chemistry and Biology

PubMed Central

Zhou, Alice Qinhua

2010-01-01

Ever since the term “central dogma” was coined in 1958, researchers have sought to control information flow from nucleic acids to proteins. Talks delivered by Drs. Anna Pyle and Hiroaki Suga at this year’s Chemical Biology Symposium at Yale in May 2010 applauded recent advances in this area, at the interface between chemistry and biology. PMID:20885900

75 FR 42471 - Self-Regulatory Organizations; NYSE Arca, Inc.; Order Granting Accelerated Approval of Proposed...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-21

... Commission (``Commission''), pursuant to Section 19(b)(1) of the Securities Exchange Act of 1934 (``Act'') \\1... addition includes other Depositary Receipts (``DRs''), which include Global Depositary Receipts (``GDRs''), Euro Depositary Receipts (``Euro DRs'') and New York Shares (``NYSs'').\\6\\ \\4\\ The Trust is registered...

Simultaneous Occurrence of Duane Retraction Syndrome with Marfan Syndrome

PubMed Central

Kothari, Mihir; Manurung, Florence; Mithiya, Bhavesh

2011-01-01

Marfan syndrome (MFS) is an autosomal dominant disorder of connective tissue, while Duane retraction syndrome (DRS) is a congenital cranial dysinnervation disorder (CCDD) which can be transmitted as autosomal dominant disorder in 5–10% of patients. In this paper, we present an 8-year-old girl who presented with left eye DRS and bilateral subluxation of the lens associated with MFS in absence of familial involvement. To our knowledge this is the first case report of DRS with MFS. The occurrence of these syndromes together is very rare and appears to be coincidental. PMID:22606474

Duane retraction syndrome: causes, effects and management strategies

PubMed Central

Kekunnaya, Ramesh; Negalur, Mithila

2017-01-01

Duane retraction syndrome (DRS) is a congenital eye movement anomaly characterized by variable horizontal duction deficits, with narrowing of the palpebral fissure and globe retraction on attempted adduction, occasionally accompanied by upshoot or down-shoot. The etiopathogenesis of this condition can be explained by a spectrum of mechanical, innervational, neurologic and genetic abnormalities occurring independently or which influence each other giving rise to patterns of clinical presentations along with a complex set of ocular and systemic anomalies. Huber type I DRS is the most common form of DRS with an earlier presentation, while Huber type II is the least common presentation. Usually, patients with unilateral type I Duane syndrome have esotropia more frequently than exotropia, those with type II have exotropia and those with type III have esotropia and exotropia occurring equally common. Cases of bilateral DRS may have variable presentation depending upon the type of presentation in each eye. As regards its management, DRS classification based on primary position deviation as esotropic, exotropic or orthotropic is more relevant than Huber’s classification before planning surgery. Surgical approach to these patients is challenging and must be individualized based on the amount of ocular deviation, abnormal head position, associated globe retraction and overshoots. PMID:29133973

Elimination of single-beam substitution error in diffuse reflectance measurements using an integrating sphere.

PubMed

Vidovic, Luka; Majaron, Boris

2014-02-01

Diffuse reflectance spectra (DRS) of biological samples are commonly measured using an integrating sphere (IS). To account for the incident light spectrum, measurement begins by placing a highly reflective white standard against the IS sample opening and collecting the reflected light. After replacing the white standard with the test sample of interest, DRS of the latter is determined as the ratio of the two values at each involved wavelength. However, such a substitution may alter the fluence rate inside the IS. This leads to distortion of measured DRS, which is known as single-beam substitution error (SBSE). Barring the use of more complex experimental setups, the literature states that only approximate corrections of the SBSE are possible, e.g., by using look-up tables generated with calibrated low-reflectivity standards. We present a practical method for elimination of SBSE when using IS equipped with an additional reference port. Two additional measurements performed at this port enable a rigorous elimination of SBSE. Our experimental characterization of SBSE is replicated by theoretical derivation. This offers an alternative possibility of computational removal of SBSE based on advance characterization of a specific DRS setup. The influence of SBSE on quantitative analysis of DRS is illustrated in one application example.

The Space Technology-7 Disturbance Reduction System Precision Control Flight Validation Experiment Control System Design

NASA Technical Reports Server (NTRS)

O'Donnell, James R.; Hsu, Oscar C.; Maghami, Peirman G.; Markley, F. Landis

2006-01-01

As originally proposed, the Space Technology-7 Disturbance Reduction System (DRS) project, managed out of the Jet Propulsion Laboratory, was designed to validate technologies required for future missions such as the Laser Interferometer Space Antenna (LISA). The two technologies to be demonstrated by DRS were Gravitational Reference Sensors (GRSs) and Colloidal MicroNewton Thrusters (CMNTs). Control algorithms being designed by the Dynamic Control System (DCS) team at the Goddard Space Flight Center would control the spacecraft so that it flew about a freely-floating GRS test mass, keeping it centered within its housing. For programmatic reasons, the GRSs were descoped from DRS. The primary goals of the new mission are to validate the performance of the CMNTs and to demonstrate precise spacecraft position control. DRS will fly as a part of the European Space Agency (ESA) LISA Pathfinder (LPF) spacecraft along with a similar ESA experiment, the LISA Technology Package (LTP). With no GRS, the DCS attitude and drag-free control systems make use of the sensor being developed by ESA as a part of the LTP. The control system is designed to maintain the spacecraft s position with respect to the test mass, to within 10 nm/the square root of Hz over the DRS science frequency band of 1 to 30 mHz.

Transcriptional diversity of long-term glioblastoma survivors

PubMed Central

Gerber, Naamit K.; Goenka, Anuj; Turcan, Sevin; Reyngold, Marsha; Makarov, Vladimir; Kannan, Kasthuri; Beal, Kathryn; Omuro, Antonio; Yamada, Yoshiya; Gutin, Phillip; Brennan, Cameron W.; Huse, Jason T.; Chan, Timothy A.

2014-01-01

Background Glioblastoma (GBM) is a highly aggressive type of glioma with poor prognosis. However, a small number of patients live much longer than the median survival. A better understanding of these long-term survivors (LTSs) may provide important insight into the biology of GBM. Methods We identified 7 patients with GBM, treated at Memorial Sloan-Kettering Cancer Center (MSKCC), with survival >48 months. We characterized the transcriptome of each patient and determined rates of MGMT promoter methylation and IDH1 and IDH2 mutational status. We identified LTSs in 2 independent cohorts (The Cancer Genome Atlas [TCGA] and NCI Repository for Molecular Brain Neoplasia Data [REMBRANDT]) and analyzed the transcriptomal characteristics of these LTSs. Results The median overall survival of our cohort was 62.5 months. LTSs were distributed between the proneural (n = 2), neural (n = 2), classical (n = 2), and mesenchymal (n = 1) subtypes. Similarly, LTS in the TCGA and REMBRANDT cohorts demonstrated diverse transcriptomal subclassification identities. The majority of the MSKCC LTSs (71%) were found to have methylation of the MGMT promoter. None of the patients had an IDH1 or IDH2 mutation, and IDH mutation occurred in a minority of the TCGA LTSs as well. A set of 60 genes was found to be differentially expressed in the MSKCC and TCGA LTSs. Conclusions While IDH mutant proneural tumors impart a better prognosis in the short-term, survival beyond 4 years does not require IDH mutation and is not dictated by a single transcriptional subclass. In contrast, MGMT methylation continues to have strong prognostic value for survival beyond 4 years. These findings have substantial impact for understanding GBM biology and progression. PMID:24662514

TCGA study of genetic drivers of melanoma

Cancer.gov

A comprehensive analysis of the genome of cutaneous melanoma has provided new insights into the roles of frequently mutated cancer genes and other genomic alterations that drive the development of this disease.

Augmenting cognitive architectures to support diagrammatic imagination.

PubMed

Chandrasekaran, Balakrishnan; Banerjee, Bonny; Kurup, Unmesh; Lele, Omkar

2011-10-01

Diagrams are a form of spatial representation that supports reasoning and problem solving. Even when diagrams are external, not to mention when there are no external representations, problem solving often calls for internal representations, that is, representations in cognition, of diagrammatic elements and internal perceptions on them. General cognitive architectures--Soar and ACT-R, to name the most prominent--do not have representations and operations to support diagrammatic reasoning. In this article, we examine some requirements for such internal representations and processes in cognitive architectures. We discuss the degree to which DRS, our earlier proposal for such an internal representation for diagrams, meets these requirements. In DRS, the diagrams are not raw images, but a composition of objects that can be individuated and thus symbolized, while, unlike traditional symbols, the referent of the symbol is an object that retains its perceptual essence, namely, its spatiality. This duality provides a way to resolve what anti-imagists thought was a contradiction in mental imagery: the compositionality of mental images that seemed to be unique to symbol systems, and their support of a perceptual experience of images and some types of perception on them. We briefly review the use of DRS to augment Soar and ACT-R with a diagrammatic representation component. We identify issues for further research. Copyright © 2011 Cognitive Science Society, Inc.

Prognostic value of DNA repair based stratification of hepatocellular carcinoma

PubMed Central

Lin, Zhuo; Xu, Shi-Hao; Wang, Hai-Qing; Cai, Yi-Jing; Ying, Li; Song, Mei; Wang, Yu-Qun; Du, Shan-Jie; Shi, Ke-Qing; Zhou, Meng-Tao

2016-01-01

Aberrant activation of DNA repair is frequently associated with tumor progression and response to therapy in hepatocellular carcinoma (HCC). Bioinformatics analyses of HCC data in the Cancer Genome Atlas (TCGA) were performed to define DNA repair based molecular classification that could predict the prognosis of patients with HCC. Furthermore, we tested its predictive performance in 120 independent cases. Four molecular subgroups were identified on the basis of coordinate DNA repair cluster (CDRC) comprising 15 genes in TCGA dataset. Increasing expression of CDRC genes were significantly associated with TP53 mutation. High CDRC was significantly correlated with advanced tumor grades, advanced pathological stage and increased vascular invasion rate. Multivariate Cox regression analysis indicated that the molecular subgrouping was an independent prognostic parameter for both overall survival (p = 0.004, hazard ratio (HR): 2.989) and tumor-free survival (p = 0.049, HR: 3.366) in TCGA dataset. Similar results were also obtained by analyzing the independent cohort. These data suggest that distinct dysregulation of DNA repair constituents based molecular classes in HCC would be useful for predicting prognosis and designing clinical trials for targeted therapy. PMID:27174663

Efficient exploration of pan-cancer networks by generalized covariance selection and interactive web content

PubMed Central

Kling, Teresia; Johansson, Patrik; Sanchez, José; Marinescu, Voichita D.; Jörnsten, Rebecka; Nelander, Sven

2015-01-01

Statistical network modeling techniques are increasingly important tools to analyze cancer genomics data. However, current tools and resources are not designed to work across multiple diagnoses and technical platforms, thus limiting their applicability to comprehensive pan-cancer datasets such as The Cancer Genome Atlas (TCGA). To address this, we describe a new data driven modeling method, based on generalized Sparse Inverse Covariance Selection (SICS). The method integrates genetic, epigenetic and transcriptional data from multiple cancers, to define links that are present in multiple cancers, a subset of cancers, or a single cancer. It is shown to be statistically robust and effective at detecting direct pathway links in data from TCGA. To facilitate interpretation of the results, we introduce a publicly accessible tool (cancerlandscapes.org), in which the derived networks are explored as interactive web content, linked to several pathway and pharmacological databases. To evaluate the performance of the method, we constructed a model for eight TCGA cancers, using data from 3900 patients. The model rediscovered known mechanisms and contained interesting predictions. Possible applications include prediction of regulatory relationships, comparison of network modules across multiple forms of cancer and identification of drug targets. PMID:25953855

The Automated Self-Administered 24-Hour Dietary Recall for Children, 2012 Version, for Youth Aged 9 to 11 Years: A Validation Study.

PubMed

Diep, Cassandra S; Hingle, Melanie; Chen, Tzu-An; Dadabhoy, Hafza R; Beltran, Alicia; Baranowski, Janice; Subar, Amy F; Baranowski, Tom

2015-10-01

Valid methods of diet assessment are important for nutrition research and practice, but can be difficult with children. To validate the 2012 version of the Automated Self-Administered 24-Hour Dietary Recall for Children (ASA24-Kids-2012), a self-administered web-based 24-hour dietary recall (24hDR) instrument, among children aged 9 to 11 years, in two sites. Quasiexperimental. In one site, trained staff members observed and recorded foods and drinks consumed by children (n=38) during school lunch. The next day, the observed children completed both ASA24-Kids-2012 and an interviewer-administered 24hDR in a randomized order. Procedures in a second site (n=31) were similar, except observations occurred during dinner in a community location. Foods were classified as matches (reported and consumed), intrusions (reported, but not consumed), or omissions (not reported, but consumed) for each participant. Rates of matches, intrusions, and omissions were calculated. Rates were compared between each recall method using repeated measures analysis of covariance. For matched foods, the authors determined correlation coefficients between observed and reported serving sizes. Match, intrusion, and omission rates between ASA24-Kids-2012 and observed intakes in Site 1 were 37%, 27%, and 35%, respectively. Comparable rates for interviewer-administered 24hDRs were 57%, 20%, and 23%, respectively. In Site 2, match, intrusion, and omission rates between ASA24-Kids-2012 and observed intakes were 53%, 12%, and 36%, respectively, vs 76% matches, 9% intrusions, and 15% omissions for interviewer-administered 24hDRs. The relationship strength between reported and observed serving sizes for matched foods was 0.18 in Site 1 and 0.09 in Site 2 for ASA24-Kids-2012, and 0.46 in Site 1 and 0.11 in Site 2 for interviewer-administered 24hDRs. ASA24-Kids-2012 was less accurate than interviewer-administered 24hDRs when compared with observed intakes, but both performed poorly. Additional research

A validation study of the Automated Self-Administered 24-Hour Dietary Recall for Children (ASA24-Kids) among 9 to 11-year-old youth

PubMed Central

Diep, Cassandra S.; Hingle, Melanie; Chen, Tzu-An; Dadabhoy, Hafza R.; Beltran, Alicia; Baranowski, Janice; Subar, Amy F.; Baranowski, Tom

2015-01-01

Background Valid methods of diet assessment are important for nutrition research and practice but can be difficult with children. Objective To validate ASA24-Kids-2012, a self-administered web-based 24-hour dietary recall (24hDR) among 9-11-year-old children, in two sites. Design Quasi-experimental Participants/setting In one site, trained staff observed and recorded foods and drinks consumed by children (n=38) during school lunch. The next day, the observed children completed both ASA24-Kids-2012 and an interviewer-administered 24hDR in a randomized order. Procedures in a second site (n=31) were similar, except observations occurred during dinner in a community location. Statistical analyses Foods were classified as matches (reported and consumed), intrusions (reported, but not consumed), or omissions (not reported, but consumed) for each participant. Rates of matches, intrusions, and omissions were calculated. Rates were compared between each recall method using repeated measures analysis of covariance. For matched foods, the authors determined correlation coefficients between observed and reported serving sizes. Results Match, intrusion, and omission rates between ASA24-Kids-2012 and observed intakes in site 1 were 37%, 27%, and 35%, respectively. Comparable rates for interviewer-administered 24hDRs were 57%, 20%, and 23%, respectively. In site 2, match, intrusion, and omission rates between ASA24-Kids-2012 and observed intakes were 53%, 12%, and 36%, respectively, vs. 76% matches, 9% intrusions, and 15% omissions for interviewer-administered 24hDRs. The relationship strength between reported and observed serving sizes for matched foods was 0.18 in site 1 and 0.09 in site 2 for ASA24-Kids-2012, and 0.46 in site 1 and 0.11 in site 2 for interviewer-administered 24hDRs. Conclusions ASA24-Kids-2012 was less accurate than interviewer-administered 24hDRs when compared to observed intakes, but both performed poorly. Additional research should assess the age at which

Molecular Mobility in Hyperbranched Polymers and Their Interaction with an Epoxy Matrix

PubMed Central

Román, Frida; Colomer, Pere; Calventus, Yolanda; Hutchinson, John M.

2016-01-01

The molecular mobility related to the glass transition and secondary relaxations in a hyperbranched polyethyleneimine, HBPEI, and its relaxation behaviour when incorporated into an epoxy resin matrix are investigated by dielectric relaxation spectroscopy (DRS) and dynamic mechanical analysis (DMA). Three systems are analysed: HBPEI, epoxy and an epoxy/HBPEI mixture, denoted ELP. The DRS behaviour is monitored in the ELP system in three stages: prior to curing, during curing, and in the fully cured system. In the stage prior to curing, DRS measurements show three dipolar relaxations: γ, β and α, for all systems (HBPEI, epoxy and ELP). The α-relaxation for the ELP system deviates significantly from that for HBPEI, but superposes on that for the epoxy resin. The fully cured thermoset displays both β- and α-relaxations. In DMA measurements, both α- and β-relaxations are observed in all systems and in both the uncured and fully cured systems, similar to the behaviour identified by DRS. PMID:28773319

Diabetes abolishes the cardioprotection induced by sevoflurane postconditioning in the rat heart in vivo: roles of glycogen synthase kinase-3β and its upstream pathways.

PubMed

Tai, Wenjun; Shi, Enyi; Yan, Lihui; Jiang, Xiaojing; Ma, Hong; Ai, Chunyu

2012-11-01

We measured the cardioprotection afforded by sevoflurane postconditioning in streptozotocin-induced diabetic rats (DRs) and determined the roles of glycogen synthase kinase (GSK), phosphatidylinositol-3-kinase/Akt, and extracellular signal-regulated kinase (ERK1/2) in such a procedure. DRs and nondiabetic rats (NDRs) were subjected to a 30-min coronary artery occlusion followed by a 120-min reperfusion. Postconditioning was achieved by inhalation of 1 minimum alveolar concentration sevoflurane at the first 5 min of reperfusion. The infarct size was determined by triphenyltetrazolium chloride staining. Expressions of GSK-3β, Akt, and ERK1/2 were measured using Western blotting. In NDRs, the infarct size was significantly decreased from 53.4% ± 7.6% to 34.9% ± 5.6% by sevoflurane postconditioning (P < 0.01). Such an anti-infarct effect was abolished completely in the DRs, as evidenced by a similar infarct size observed between the sevoflurane-treated and untreated DRs (49.3% ± 8.6% and 49.6% ± 9.3%, respectively, P > 0.05). Direct inhibition of GSK-3β by injection of SB216763 just before the start of reperfusion induced equivalent infarct-sparing effects in both NDRs (37.8% ± 3.9% and 53.4% ± 7.6% in SB216763-treated and untreated NDRs, respectively; P < 0.01) and DRs (38.8% ± 3.2% and 49.3% ± 8.6% in SB216763-treated and untreated DRs, respectively; P < 0.05). Sevoflurane postconditioning remarkably enhanced the phosphorylation of GSK-3β Ser(9), Akt Ser(473), and ERK1/2 in NDRs, which were blocked in DRs. The cardioprotection induced by sevoflurane postconditioning is abolished by diabetes. This might be due to the impairment of phosphorylation of GSK-3β and its upstream signaling pathways of phosphatidylinositol-3-kinase/Akt and ERK1/2 in the presence of diabetes. Copyright © 2012 Elsevier Inc. All rights reserved.

Implications of High-Frequency Cochlear Dead Regions for Fitting Hearing Aids to Adults with Mild to Moderately-Severe Hearing Loss

PubMed Central

Cox, Robyn M.; Johnson, Jani A.; Alexander, Genevieve C.

2012-01-01

Short Summary It has been suggested that existence of high-frequency cochlear dead regions (DRs) has implications for hearing aid fitting, and that the optimal amount of high-frequency gain is reduced for these patients. This investigation used laboratory and field measurements to examine the effectiveness of reduced high-frequency gain in typical hearing aid users with high-frequency DRs. Both types of data revealed that speech understanding was better with the evidence-based prescription than with reduced high-frequency gain, and that this was seen for listeners with and without DRs. Nevertheless, subjects did not always prefer the amplification condition that produced better speech understanding. PMID:22555183

ChimerDB 3.0: an enhanced database for fusion genes from cancer transcriptome and literature data mining.

PubMed

Lee, Myunggyo; Lee, Kyubum; Yu, Namhee; Jang, Insu; Choi, Ikjung; Kim, Pora; Jang, Ye Eun; Kim, Byounggun; Kim, Sunkyu; Lee, Byungwook; Kang, Jaewoo; Lee, Sanghyuk

2017-01-04

Fusion gene is an important class of therapeutic targets and prognostic markers in cancer. ChimerDB is a comprehensive database of fusion genes encompassing analysis of deep sequencing data and manual curations. In this update, the database coverage was enhanced considerably by adding two new modules of The Cancer Genome Atlas (TCGA) RNA-Seq analysis and PubMed abstract mining. ChimerDB 3.0 is composed of three modules of ChimerKB, ChimerPub and ChimerSeq. ChimerKB represents a knowledgebase including 1066 fusion genes with manual curation that were compiled from public resources of fusion genes with experimental evidences. ChimerPub includes 2767 fusion genes obtained from text mining of PubMed abstracts. ChimerSeq module is designed to archive the fusion candidates from deep sequencing data. Importantly, we have analyzed RNA-Seq data of the TCGA project covering 4569 patients in 23 cancer types using two reliable programs of FusionScan and TopHat-Fusion. The new user interface supports diverse search options and graphic representation of fusion gene structure. ChimerDB 3.0 is available at http://ercsb.ewha.ac.kr/fusiongene/. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Early Life Processes, Endocrine Mediators and Number of Susceptible Cells in Relation to Breast Cancer Risk

DTIC Science & Technology

2006-04-01

Epidemiology, Dept. of Medicine, Karolinska Institutet / Karolinska University Hospital, SE-171 76 Stockholm, Sweden. Timetable of research...in adult life” CP2 PI: Prof. Per Hall, Dept. of Medical Epidemiology and Biostatistics, Karolinska Institutet , P.O. Box 281, SE-171 77 Stockholm...subjects. We have established collaboration with the Department of Radiology, Karolinska University Hospital. Drs. Gunilla Svane and Edward Azavedo

Models & Methods in SCOPE A Status Report

DTIC Science & Technology

2008-04-01

Projecttitel april 2008 Soldaat Optreden Scope Consolidatie Auteur (s) drs. E.M. Ubink Programmanummer Projectnummer dr. W.A. Lotens V707 032.13 114 drs...starvation. The fat and protein involved is handled through the muscle equation. Excess glucose production is converted to body fat. In theory body fat is

PODCAST: From Lost in Translation to Paradise Found: Enabling Protein Biomarker Method Transfer by Mass Spectrometry | Office of Cancer Clinical Proteomics Research

Cancer.gov

Translation of novel biomarkers into clinical care for the evaluation of therapeutic safety and efficacy has been slow, partly attributable to the cost and complexity of immunoassay development.  The potential for liquid chromatography-tandem mass spectrometry (LC-MS/MS) to streamline the translation of novel protein biomarkers is profound.  Drs. Henry Rodriguez and Andrew Hoofnagle discuss what the future may be for clinical proteomics. This is an American Association for Clinical Chemistry (AACC) podcast.

Light distribution modulated diffuse reflectance spectroscopy.

PubMed

Huang, Pin-Yuan; Chien, Chun-Yu; Sheu, Chia-Rong; Chen, Yu-Wen; Tseng, Sheng-Hao

2016-06-01

Typically, a diffuse reflectance spectroscopy (DRS) system employing a continuous wave light source would need to acquire diffuse reflectances measured at multiple source-detector separations for determining the absorption and reduced scattering coefficients of turbid samples. This results in a multi-fiber probe structure and an indefinite probing depth. Here we present a novel DRS method that can utilize a few diffuse reflectances measured at one source-detector separation for recovering the optical properties of samples. The core of innovation is a liquid crystal (LC) cell whose scattering property can be modulated by the bias voltage. By placing the LC cell between the light source and the sample, the spatial distribution of light in the sample can be varied as the scattering property of the LC cell modulated by the bias voltage, and this would induce intensity variation of the collected diffuse reflectance. From a series of Monte Carlo simulations and phantom measurements, we found that this new light distribution modulated DRS (LDM DRS) system was capable of accurately recover the absorption and scattering coefficients of turbid samples and its probing depth only varied by less than 3% over the full bias voltage variation range. Our results suggest that this LDM DRS platform could be developed to various low-cost, efficient, and compact systems for in-vivo superficial tissue investigation.

Light distribution modulated diffuse reflectance spectroscopy

PubMed Central

Huang, Pin-Yuan; Chien, Chun-Yu; Sheu, Chia-Rong; Chen, Yu-Wen; Tseng, Sheng-Hao

2016-01-01

Typically, a diffuse reflectance spectroscopy (DRS) system employing a continuous wave light source would need to acquire diffuse reflectances measured at multiple source-detector separations for determining the absorption and reduced scattering coefficients of turbid samples. This results in a multi-fiber probe structure and an indefinite probing depth. Here we present a novel DRS method that can utilize a few diffuse reflectances measured at one source-detector separation for recovering the optical properties of samples. The core of innovation is a liquid crystal (LC) cell whose scattering property can be modulated by the bias voltage. By placing the LC cell between the light source and the sample, the spatial distribution of light in the sample can be varied as the scattering property of the LC cell modulated by the bias voltage, and this would induce intensity variation of the collected diffuse reflectance. From a series of Monte Carlo simulations and phantom measurements, we found that this new light distribution modulated DRS (LDM DRS) system was capable of accurately recover the absorption and scattering coefficients of turbid samples and its probing depth only varied by less than 3% over the full bias voltage variation range. Our results suggest that this LDM DRS platform could be developed to various low-cost, efficient, and compact systems for in-vivo superficial tissue investigation. PMID:27375931

Diffuse optical monitoring of peripheral tissues during uncontrolled internal hemorrhage in a porcine model

PubMed Central

Vishwanath, Karthik; Gurjar, Rajan; Wolf, David; Riccardi, Suzannah; Duggan, Michael; King, David

2018-01-01

Reliable, continuous and noninvasive blood flow and hemoglobin monitoring in trauma patients remains a critical, but generally unachieved goal. Two optical sensing methods - diffuse correlation spectroscopy (DCS) and diffuse reflectance spectroscopy (DRS) – are used to monitor and detect internal hemorrhage. Specifically, we investigate if cutaneous perfusion measurements acquired using DCS and DRS in peripheral (thighs and ear-lobe) tissues could detect severe hemorrhagic shock in a porcine model. Four animals underwent high-grade hepato-portal injury in a closed abdomen, to induce uncontrolled hemorrhage and were subsequently allowed to bleed for 10 minutes before fluid resuscitation. DRS and DCS measurements of cutaneous blood flow were acquired using fiber optical probes placed on the thigh and earlobe of the animals and were obtained repeatedly starting from 1 to 5 minutes pre-injury, up to several minutes post shock. Clear changes were observed in measured optical spectra across all animals at both sites. DCS-derived cutaneous blood flow decreased sharply during hemorrhage, while DRS-derived vascular saturation and hemoglobin paralleled cardiac output. All derived optical parameters had the steepest changes during the rapid initial hemorrhage unambiguously. This suggests that a combined DCS and DRS based device might provide an easy-to-use, non-invasive, internal-hemorrhage detection system that can be used across a wide array of clinical settings. PMID:29552394

Salt Lake Skills Center Handicapped Advocacy Program. Summary Report.

ERIC Educational Resources Information Center

Hall, Bo; Armstrong, Terry L.

The Handicapped Advocacy Program (HAP) is an advocacy service for individuals with disabilities who are sponsored in skills training by the Utah Division of Rehabilitation Services (DRS). It has developed a system whereby DRS clients can be tracked throughout their tenure at the Salt Lake Skills Center. Other services include Skills Center…

Analysis of single nucleotide variants of HFE gene and association to survival in The Cancer Genome Atlas GBM data

PubMed Central

Zhang, Bo; Liu, Dajiang J.; Muscat, Joshua E.; Langan, Sara T.; Connor, James R.

2017-01-01

Human hemochromatosis protein (HFE) is involved in iron metabolism. Two major HFE polymorphisms, H63D and C282Y, have been associated with an increased risk of cancers. Previously, we reported decreased gender effects in overall survival based on H63D or C282Y HFE polymorphisms patients with glioblastoma multiforme (GBM). However, the effect of other single nucleotide variation (SNV) in the HFE gene on the cancer development and progression has not been systematically studied. To expand our finding in a larger sample, and to identify other HFE SNV, we analyzed the frequency of somatic SNV in HFE gene and its relationship to survival in GBM patients using The Cancer Genome Atlas (TCGA) GBM (Caucasian only) database. We found 9 SNVs with increased frequency in blood normal of TCGA GBM patients compared to the 1000Genome. Among 9 SNVs, 7 SNVs were located in the intron and 2 SNVs (i.e., H63D, C282Y) in the exon of HFE gene. The statistical analysis demonstrated that blood normal samples of TCGA GBM have more H63D (p = 0.0002, 95% Confidence interval (CI): 0.2119–0.3223) or C282Y (p = 0.0129, 95% CI: 0.0474–0.1159) HFE polymorphisms than 1000Genome. The Kaplan-Meier survival curve for the 264 GBM samples revealed no difference between wild type (WT) HFE and H63D, and WT HFE and C282Y GBM patients. In addition, there was no difference in the survival of male/female GBM patients based on HFE genotype. There was no correlation between HFE expression and survival. In conclusion, the current results suggest that somatic HFE polymorphisms do not impact GBM patients’ survival in the TCGA data set of GBM. PMID:28358914

Analysis of single nucleotide variants of HFE gene and association to survival in The Cancer Genome Atlas GBM data.

PubMed

Lee, Sang Y; Zhu, Junjia; Salzberg, Anna C; Zhang, Bo; Liu, Dajiang J; Muscat, Joshua E; Langan, Sara T; Connor, James R

2017-01-01

Human hemochromatosis protein (HFE) is involved in iron metabolism. Two major HFE polymorphisms, H63D and C282Y, have been associated with an increased risk of cancers. Previously, we reported decreased gender effects in overall survival based on H63D or C282Y HFE polymorphisms patients with glioblastoma multiforme (GBM). However, the effect of other single nucleotide variation (SNV) in the HFE gene on the cancer development and progression has not been systematically studied. To expand our finding in a larger sample, and to identify other HFE SNV, we analyzed the frequency of somatic SNV in HFE gene and its relationship to survival in GBM patients using The Cancer Genome Atlas (TCGA) GBM (Caucasian only) database. We found 9 SNVs with increased frequency in blood normal of TCGA GBM patients compared to the 1000Genome. Among 9 SNVs, 7 SNVs were located in the intron and 2 SNVs (i.e., H63D, C282Y) in the exon of HFE gene. The statistical analysis demonstrated that blood normal samples of TCGA GBM have more H63D (p = 0.0002, 95% Confidence interval (CI): 0.2119-0.3223) or C282Y (p = 0.0129, 95% CI: 0.0474-0.1159) HFE polymorphisms than 1000Genome. The Kaplan-Meier survival curve for the 264 GBM samples revealed no difference between wild type (WT) HFE and H63D, and WT HFE and C282Y GBM patients. In addition, there was no difference in the survival of male/female GBM patients based on HFE genotype. There was no correlation between HFE expression and survival. In conclusion, the current results suggest that somatic HFE polymorphisms do not impact GBM patients' survival in the TCGA data set of GBM.

FGFR3, as a receptor tyrosine kinase, is associated with differentiated biological functions and improved survival of glioma patients

PubMed Central

Wang, Zheng; Zhang, Chuanbao; Sun, Lihua; Liang, Jingshan; Liu, Xing; Li, Guanzhang; Yao, Kun; Zhang, Wei; Jiang, Tao

2016-01-01

Background Activation of receptor tyrosine kinases is common in Malignancies. FGFR3 fusion with TACC3 has been reported to have transforming effects in primary glioblastoma and display oncogenic activity in vitro and in vivo. We set out to investigate the role of FGFR3 in glioma through transcriptomic analysis. Results FGFR3 increased in Classical subtype and Neural subtype consistently in CGGA and TCGA cohort. Similar patterns of FGFR3 distribution through subtypes were observed in CGGA and TCGA samples. Gene ontology analysis was performed with genes that were significantly correlated with FGFR3 expression. We found that positively associated biological processes of FGFR3 were focused on differentiated cellular functions and neuronal activities, while negatively correlated biological processes focused on mitosis and cell cycle phase. Clinical investigation showed that higher FGFR3 expression predicted improved survival for glioma patients, especially in Proneural subtype. Moreover, FGFR3 showed very limited relevance with other receptor tyrosine kinases in glioma at transcriptome level. Materials and Methods FGFR3 expression data of glioma was obtained from Chinese Glioma Genome Atlas (CGGA) and TCGA (The Cancer Genome Atlas). In total, RNA sequencing data of 325 glioma samples and mRNA microarray data of 301 samples from CGGA dataset were enrolled into this study. To consolidate the findings that we have revealed in CGGA dataset, RNA-seq data of 672 glioma samples from TCGA dataset were used as a validation cohort. R language was used as the main tool to perform statistical analysis and graphical work. Conclusions FGFR3 expression increased in classical and neural subtypes and was associated with differentiated cellular functions. FGFR3 showed very limited correlation with other common receptor tyrosine kinases, and predicted improved survival for glioma patients. PMID:27829236

Transcriptional diversity of long-term glioblastoma survivors.

PubMed

Gerber, Naamit K; Goenka, Anuj; Turcan, Sevin; Reyngold, Marsha; Makarov, Vladimir; Kannan, Kasthuri; Beal, Kathryn; Omuro, Antonio; Yamada, Yoshiya; Gutin, Phillip; Brennan, Cameron W; Huse, Jason T; Chan, Timothy A

2014-09-01

Glioblastoma (GBM) is a highly aggressive type of glioma with poor prognosis. However, a small number of patients live much longer than the median survival. A better understanding of these long-term survivors (LTSs) may provide important insight into the biology of GBM. We identified 7 patients with GBM, treated at Memorial Sloan-Kettering Cancer Center (MSKCC), with survival >48 months. We characterized the transcriptome of each patient and determined rates of MGMT promoter methylation and IDH1 and IDH2 mutational status. We identified LTSs in 2 independent cohorts (The Cancer Genome Atlas [TCGA] and NCI Repository for Molecular Brain Neoplasia Data [REMBRANDT]) and analyzed the transcriptomal characteristics of these LTSs. The median overall survival of our cohort was 62.5 months. LTSs were distributed between the proneural (n = 2), neural (n = 2), classical (n = 2), and mesenchymal (n = 1) subtypes. Similarly, LTS in the TCGA and REMBRANDT cohorts demonstrated diverse transcriptomal subclassification identities. The majority of the MSKCC LTSs (71%) were found to have methylation of the MGMT promoter. None of the patients had an IDH1 or IDH2 mutation, and IDH mutation occurred in a minority of the TCGA LTSs as well. A set of 60 genes was found to be differentially expressed in the MSKCC and TCGA LTSs. While IDH mutant proneural tumors impart a better prognosis in the short-term, survival beyond 4 years does not require IDH mutation and is not dictated by a single transcriptional subclass. In contrast, MGMT methylation continues to have strong prognostic value for survival beyond 4 years. These findings have substantial impact for understanding GBM biology and progression. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

[Bioinformatics on vascular invasion markers in hepatocellular carcinoma via Big-Data analysis].

PubMed

Chen, Q; Qiu, X Q

2017-04-10

Objective: To investigate the biomarkers in hepatocellular carcinoma and their prognostic value via GEO (Gene Expression Omnibus) and TCGA (The Cancer Genome Atlas) database. Methods: Datasets of hepatocellular carcinoma were downloaded from GEO (GSE67140) and TCGA. MicroRNA in SNU423, SNU449, HepG2, Hep3B, SNU398 cell lines which had low or high invasion capabilities were investigated and verified, in 81 patients with and 91 without vascular invasion hepatocellular carcinoma. The prognostic value of these microRNAs were studied via TCGA database,obtained from 362 patients with hepatocellular carcinoma, through Kaplan-Meier and Multivariate Cox proportional hazard analysis. Target genes were analyzed by GO and KEGG. Results: Expressions of hsa-mir-1180, hsa-mir-149, hsa-mir-744 and hsa-mir-940 were all up regulated in high invasion capable cell lines (SNU423, SNU449) and vascular invasion patients with hepatocellular carcinoma (logFC>1, P <0.05). Results from the Survival analysis showed that hsa-mir-1180 ( HR =1.623, 95 % CI : 1.114-2.365, P =0.012), hsa-mir-149 ( HR =2.400, 95 % CI : 1.639-3.514) and hsa-mir-940 ( HR =1.704, 95 %CI : 1.188-2.443, P =0.004) were independent risk factors on the prognosis of patients with hepatocellular carcinoma ( P <0.05). The mechanism might be related to factors as immune response, focal adhesion and adherence junction signaling pathways. Conclusion: With TCGA and GEO data mining, we found that hsa-mir-1180, hsa-mir-149, hsa-mir-744 and hsa-mir-940 were all highly related to the prognosis of hepatocellular carcinoma, that enabled it to be used to further study the biomarkers related to the prognosis of hepatocellular carcinoma.

FGFR3, as a receptor tyrosine kinase, is associated with differentiated biological functions and improved survival of glioma patients.

PubMed

Wang, Zheng; Zhang, Chuanbao; Sun, Lihua; Liang, Jingshan; Liu, Xing; Li, Guanzhang; Yao, Kun; Zhang, Wei; Jiang, Tao

2016-12-20

Activation of receptor tyrosine kinases is common in Malignancies. FGFR3 fusion with TACC3 has been reported to have transforming effects in primary glioblastoma and display oncogenic activity in vitro and in vivo. We set out to investigate the role of FGFR3 in glioma through transcriptomic analysis. FGFR3 increased in Classical subtype and Neural subtype consistently in CGGA and TCGA cohort. Similar patterns of FGFR3 distribution through subtypes were observed in CGGA and TCGA samples. Gene ontology analysis was performed with genes that were significantly correlated with FGFR3 expression. We found that positively associated biological processes of FGFR3 were focused on differentiated cellular functions and neuronal activities, while negatively correlated biological processes focused on mitosis and cell cycle phase. Clinical investigation showed that higher FGFR3 expression predicted improved survival for glioma patients, especially in Proneural subtype. Moreover, FGFR3 showed very limited relevance with other receptor tyrosine kinases in glioma at transcriptome level. FGFR3 expression data of glioma was obtained from Chinese Glioma Genome Atlas (CGGA) and TCGA (The Cancer Genome Atlas). In total, RNA sequencing data of 325 glioma samples and mRNA microarray data of 301 samples from CGGA dataset were enrolled into this study. To consolidate the findings that we have revealed in CGGA dataset, RNA-seq data of 672 glioma samples from TCGA dataset were used as a validation cohort. R language was used as the main tool to perform statistical analysis and graphical work. FGFR3 expression increased in classical and neural subtypes and was associated with differentiated cellular functions. FGFR3 showed very limited correlation with other common receptor tyrosine kinases, and predicted improved survival for glioma patients.

The current status of immunotoxins: an overview of experimental and clinical studies as presented at the Third International Symposium on Immunotoxins.

PubMed

Uckun, F M; Frankel, A

1993-02-01

The Third International Symposium on Immunotoxins was held on June 19-21, 1992 in Orlando, Florida. This symposium was sponsored by NATO, NIH, Pierce Chemical Company, Walt Disney Cancer Institute at Florida Hospital, Duke Comprehensive Cancer Center, Xoma, Immunogen, Seragen, Bristol-Myers Squibb, Chiron, Ortho Biotech, Upjohn, Merck Sharp & Dohme Research Laboratories, Abbot Laboratories, Lilly Research Laboratories, and Evans & Sutherland. The Pierce Immunotoxin Award which recognizes outstanding contributions to immunotoxin research and development, was presented to Drs David FitzGerald, Fatih Uckun, David Eisenberg, and Ira Wool, for their contributions to the immunotoxin field.

In Situ Effective Diffusion Coefficient Profiles in Live Biofilms Using Pulsed-Field Gradient Nuclear Magnetic Resonance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Renslow, Ryan S.; Majors, Paul D.; McLean, Jeffrey S.

2010-08-15

Diffusive mass transfer in biofilms is characterized by the effective diffusion coefficient. It is well-documented that the effective diffusion coefficient can vary by location in a biofilm. The current literature is dominated by effective diffusion coefficient measurements for distinct cell clusters and stratified biofilms showing this spatial variation. Regardless of whether distinct cell clusters or surface-averaging methods are used, position-dependent measurements of the effective diffusion coefficient are currently: 1) invasive to the biofilm, 2) performed under unnatural conditions, 3) lethal to cells, and/or 4) spatially restricted to only certain regions of the biofilm. Invasive measurements can lead to inaccurate resultsmore » and prohibit further (time dependent) measurements which are important for the mathematical modeling of biofilms. In this study our goals were to: 1) measure the effective diffusion coefficient for water in live biofilms, 2) monitor how the effective diffusion coefficient changes over time under growth conditions, and 3) correlate the effective diffusion coefficient with depth in the biofilm. We measured in situ two-dimensional effective diffusion coefficient maps within Shewanella oneidensis MR-1biofilms using pulsed-field gradient nuclear magnetic resonance methods, and used them to calculate surface-averaged relative effective diffusion coefficient (Drs) profiles. We found that 1) Drs decreased from the top of the biofilm to the bottom, 2) Drs profiles differed for biofilms of different ages, 3) Drs profiles changed over time and generally decreased with time, 4) all the biofilms showed very similar Drs profiles near the top of the biofilm, and 5) the Drs profile near the bottom of the biofilm was different for each biofilm. Practically, our results demonstrate that advanced biofilm models should use a variable effective diffusivity which changes with time and location in the biofilm.« less

Treatment of denture-related stomatitis improves endothelial function assessed by flow-mediated vascular dilation.

PubMed

Osmenda, Grzegorz; Maciąg, Joanna; Wilk, Grzegorz; Maciąg, Anna; Nowakowski, Daniel; Loster, Jolanta; Dembowska, Elżbieta; Robertson, Douglas; Guzik, Tomasz; Cześnikiewicz-Guzik, Marta

2017-02-01

The presence of oral inflammation has recently been linked with the pathogenesis of cardiovascular diseases. While numerous studies have described links between periodontitis and endothelial dysfunction, little is known about the influence of denture-related stomatitis (DRS) on cardiovascular risk. Therefore, the aim of this study was to determine whether the treatment of DRS can lead to improvement of the clinical measures of vascular dysfunction. The DRS patients were treated with a local oral antifungal agent for 3 weeks. Blood pressure, flow-mediated dilatation (FMD) and nitroglycerine-mediated vascular dilatation (NMD) were measured during three study visits: before treatment, one day and two months after conclusion of antifungal therapy. Flow-mediated dilatation measurements showed significant improvement of endothelial function 2 months after treatment (FMD median 5%, 95 CI: 3-8.3 vs. 11%, 95% CI: 8.8-14.4; p < 0.01), while there was no difference in control, endothelium-independent vasorelaxations (NMD; median = 15.3%, 95% CI: 10.8-19.3 vs. 12.7%, 95% CI: 10.6-15; p = 0.3). Other cardiovascular parameters such as systolic (median = 125 mm Hg; 95% CI: 116-129 vs. 120 mm Hg, 95% CI: 116-126; p = 0.1) as well as diastolic blood pressure and heart rate (median = 65.5 bpm, 95% CI: 56.7-77.7 vs. 71 bpm, 95% CI: 66.7-75; p = 0.5) did not change during or after the treatment. Treatment of DRS is associated with improvement of endothelial function. Since endothelial dysfunction is known to precede the development of severe cardiovascular disorders such as atherosclerosis and hypertension, patients should be more carefully screened for DRS in general dental practice, and immediate DRS treatment should be advised.

The diagnosis, prevalence and outcome of delirium in a cohort of older people with mental health problems on general hospital wards.

PubMed

Whittamore, Kathy H; Goldberg, Sarah E; Gladman, John R F; Bradshaw, Lucy E; Jones, Rob G; Harwood, Rowan H

2014-01-01

This paper aimed to measure the prevalence and outcomes of delirium for patients over 70 admitted to a general hospital for acute medical care and to assess the validity of the Delirium Rating Scale-Revised-98 (DRS-R-98) in this setting. Prospective study in a British acute general hospital providing sole emergency medical services for its locality. We screened consecutive patients over 70 with an unplanned emergency hospital admission and recruited a cohort of 249 patients likely to have mental health problems. They were assessed for health status at baseline and followed over 6 months. A sub-sample of 93 participants was assessed clinically for delirium. 27% (95% confidence interval (CI) 23-31) of all older medical patients admitted to hospital had DRS-diagnosed delirium, and 41% (95% CI 37-45) had dementia (including 19% with co-morbid delirium and dementia). Compared with clinician diagnosis, DRS-R-98 sensitivity was at least 0.75, specificity 0.71. Compared with reversible cognitive impairment, sensitivity was at least 0.50, specificity 0.67. DRS-diagnosed delirium was associated with cognitive impairment, mood, behavioural and psychological symptoms, activities of daily living, and number of drugs prescribed, supporting construct validity. Of those with DRS-diagnosed delirium, 37% died within 6 months (relative risk 1.4, 95% CI 0.97-2.2), 43% had reversible cognitive impairment, but only 25% had clinically important recovery in activities of daily living. Behavioural and psychological symptoms were common and mostly resolved, but new symptoms frequently developed. Delirium is common. Some, but not all, features are reversible. DRS-R-98 has reasonable validity in populations where co-morbid dementia is prevalent. Copyright © 2013 John Wiley & Sons, Ltd.

76 FR 35896 - Agency Information Collection Activities; Proposed Collection; Comment Request; Guidance for...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-20

... information by August 19, 2011. ADDRESSES: Submit electronic comments on the collection of information to http... Estimate: Based on the number of requests for tier one and tier two DRs received by FDA since the guidance... requests for tier one and tier two DRs. FDA estimates the burden of this collection of information as...

Pioneer Valley Life Sciences Institute Program in Endocrinology and Metabolism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schneyer, Alan; Brown, Melissa; Schwartz, Lawrence

2012-04-24

Specific Aim - To determine the role of TGFBeta superfamily ligands in regulating Beta-cell function, proliferation, and survival (Drs. Schneyer and Brown) Specific Aim - To determine the feasibility of using respiratory activity and extracellular acidification rates of myoblasts to decipher the state of insulin resistance in cultured myoblastsMyoblast physiology (Drs. Schwartz and Yadava)

Development and Validation of a Quantitative Food Frequency Questionnaire among Rural- and Urban-Dwelling Adults in Colombia

ERIC Educational Resources Information Center

Dehghan, Mahshid; Lopez Jaramillo, Patricio; Duenas, Ruby; Anaya, Lilliam Lima; Garcia, Ronald G.; Zhang, Xiaohe; Islam, Shofiqul; Merchant, Anwar T.

2012-01-01

Objective: To validate a food frequency questionnaire (FFQ) against multiple 24-hour dietary recalls (DRs) that could be used for Colombian adults. Methods: A convenience sample of 219 individuals participated in the study. The validity of the FFQ was evaluated against multiple DRs. Four dietary recalls were collected during the year, and an FFQ…

A new time calibration method for switched-capacitor-array-based waveform samplers

NASA Astrophysics Data System (ADS)

Kim, H.; Chen, C.-T.; Eclov, N.; Ronzhin, A.; Murat, P.; Ramberg, E.; Los, S.; Moses, W.; Choong, W.-S.; Kao, C.-M.

2014-12-01

We have developed a new time calibration method for the DRS4 waveform sampler that enables us to precisely measure the non-uniform sampling interval inherent in the switched-capacitor cells of the DRS4. The method uses the proportionality between the differential amplitude and sampling interval of adjacent switched-capacitor cells responding to a sawtooth-shape pulse. In the experiment, a sawtooth-shape pulse with a 40 ns period generated by a Tektronix AWG7102 is fed to a DRS4 evaluation board for calibrating the sampling intervals of all 1024 cells individually. The electronic time resolution of the DRS4 evaluation board with the new time calibration is measured to be 2.4 ps RMS by using two simultaneous Gaussian pulses with 2.35 ns full-width at half-maximum and applying a Gaussian fit. The time resolution dependencies on the time difference with the new time calibration are measured and compared to results obtained by another method. The new method could be applicable for other switched-capacitor-array technology-based waveform samplers for precise time calibration.

A New Time Calibration Method for Switched-capacitor-array-based Waveform Samplers.

PubMed

Kim, H; Chen, C-T; Eclov, N; Ronzhin, A; Murat, P; Ramberg, E; Los, S; Moses, W; Choong, W-S; Kao, C-M

2014-12-11

We have developed a new time calibration method for the DRS4 waveform sampler that enables us to precisely measure the non-uniform sampling interval inherent in the switched-capacitor cells of the DRS4. The method uses the proportionality between the differential amplitude and sampling interval of adjacent switched-capacitor cells responding to a sawtooth-shape pulse. In the experiment, a sawtooth-shape pulse with a 40 ns period generated by a Tektronix AWG7102 is fed to a DRS4 evaluation board for calibrating the sampling intervals of all 1024 cells individually. The electronic time resolution of the DRS4 evaluation board with the new time calibration is measured to be ~2.4 ps RMS by using two simultaneous Gaussian pulses with 2.35 ns full-width at half-maximum and applying a Gaussian fit. The time resolution dependencies on the time difference with the new time calibration are measured and compared to results obtained by another method. The new method could be applicable for other switched-capacitor-array technology-based waveform samplers for precise time calibration.

A New Time Calibration Method for Switched-capacitor-array-based Waveform Samplers

PubMed Central

Kim, H.; Chen, C.-T.; Eclov, N.; Ronzhin, A.; Murat, P.; Ramberg, E.; Los, S.; Moses, W.; Choong, W.-S.; Kao, C.-M.

2014-01-01

We have developed a new time calibration method for the DRS4 waveform sampler that enables us to precisely measure the non-uniform sampling interval inherent in the switched-capacitor cells of the DRS4. The method uses the proportionality between the differential amplitude and sampling interval of adjacent switched-capacitor cells responding to a sawtooth-shape pulse. In the experiment, a sawtooth-shape pulse with a 40 ns period generated by a Tektronix AWG7102 is fed to a DRS4 evaluation board for calibrating the sampling intervals of all 1024 cells individually. The electronic time resolution of the DRS4 evaluation board with the new time calibration is measured to be ~2.4 ps RMS by using two simultaneous Gaussian pulses with 2.35 ns full-width at half-maximum and applying a Gaussian fit. The time resolution dependencies on the time difference with the new time calibration are measured and compared to results obtained by another method. The new method could be applicable for other switched-capacitor-array technology-based waveform samplers for precise time calibration. PMID:25506113

Experimental investigation of the glass transition of polystyrene thin films in a broad frequency range

NASA Astrophysics Data System (ADS)

Inoue, Rintaro; Kanaya, Toshiji; Yamada, Takeshi; Shibata, Kaoru; Fukao, Koji

2018-01-01

In this study, we investigate the α process of a polystyrene thin film using inelastic neutron scattering (INS), dielectric relaxation spectroscopy (DRS), and thermal expansion spectroscopy (TES). The DRS and TES measurements exhibited a decrease in glass transition temperature (Tg) with film thickness. On the other hand, an increase in Tg was observed in INS studies. In order to interpret this contradiction, we investigated the temperature dependence of the peak frequency (fm) of the α process probed by DRS and TES. The experiments revealed an increase in the peak frequency (fm) with decreasing film thickness in the frequency region. This observation is consistent with the observed decrease in Tg with thickness. Interestingly, the increase in Tg with film thickness was confirmed by fitting the temperature dependence measurements of the peak frequency with the Vogel-Fulcher-Tammann equation, within the frequency region probed by INS. The discrepancy between INS and DRS or TES descriptions of the α process is likely to be attributed to a decrease in the apparent activation energy with film thickness and reduced mobility, due to the impenetrable wall effect.

Development of a hybrid proximal sensing method for rapid identification of petroleum contaminated soils.

PubMed

Chakraborty, Somsubhra; Weindorf, David C; Li, Bin; Ali Aldabaa, Abdalsamad Abdalsatar; Ghosh, Rakesh Kumar; Paul, Sathi; Nasim Ali, Md

2015-05-01

Using 108 petroleum contaminated soil samples, this pilot study proposed a new analytical approach of combining visible near-infrared diffuse reflectance spectroscopy (VisNIR DRS) and portable X-ray fluorescence spectrometry (PXRF) for rapid and improved quantification of soil petroleum contamination. Results indicated that an advanced fused model where VisNIR DRS spectra-based penalized spline regression (PSR) was used to predict total petroleum hydrocarbon followed by PXRF elemental data-based random forest regression was used to model the PSR residuals, it outperformed (R(2)=0.78, residual prediction deviation (RPD)=2.19) all other models tested, even producing better generalization than using VisNIR DRS alone (RPD's of 1.64, 1.86, and 1.96 for random forest, penalized spline regression, and partial least squares regression, respectively). Additionally, unsupervised principal component analysis using the PXRF+VisNIR DRS system qualitatively separated contaminated soils from control samples. Fusion of PXRF elemental data and VisNIR derivative spectra produced an optimized model for total petroleum hydrocarbon quantification in soils. Copyright © 2015 Elsevier B.V. All rights reserved.

Further support for using the dementia rating scale in the assessment of neuro-cognitive functions of individuals with mental retardation.

PubMed

McDaniel, W F; McLaughlin, T

2000-02-01

The utility of the Dementia Rating Scale (DRS) when administered to individuals with mental retardation (MR) was examined. Our sample was comprised of individuals residing in an intermediate care facility in the southeastern United States, included individuals diagnosed with mild, moderate, or severe MR, and consisted of both Caucasians (50%) and individuals of African-American descent (50%). Descriptive statistics for the DRS Total Score and five subtests (e. g., Attention, Initiation/Perseveration, Construction, Conceptualization, and Memory) obtained from our sample of individuals with mild MR compared favorably with previously published values. The group with mild MR performed significantly better than the group with moderate MR on the Total Score and all subtests except Construction, and the group with moderate MR performed significantly better than individuals with severe MR on all measures. These results show that the DRS can provide information about the cognitive strengths and weaknesses of individuals with mental retardation, and they show that the DRS can be administered to a wide range of individuals diagnosed with MR.

Study on the Spectral Mixing Model for Mineral Pigments Based on Derivative of Ratio Spectroscopy-Take Vermilion and Stone Yellow for Example

NASA Astrophysics Data System (ADS)

Zhao, H.; Hao, Y.; Liu, X.; Hou, M.; Zhao, X.

2018-04-01

Hyperspectral remote sensing is a completely non-invasive technology for measurement of cultural relics, and has been successfully applied in identification and analysis of pigments of Chinese historical paintings. Although the phenomenon of mixing pigments is very usual in Chinese historical paintings, the quantitative analysis of the mixing pigments in the ancient paintings is still unsolved. In this research, we took two typical mineral pigments, vermilion and stone yellow as example, made precisely mixed samples using these two kinds of pigments, and measured their spectra in the laboratory. For the mixing spectra, both fully constrained least square (FCLS) method and derivative of ratio spectroscopy (DRS) were performed. Experimental results showed that the mixing spectra of vermilion and stone yellow had strong nonlinear mixing characteristics, but at some bands linear unmixing could also achieve satisfactory results. DRS using strong linear bands can reach much higher accuracy than that of FCLS using full bands.

A framework for organizing cancer-related variations from existing databases, publications and NGS data using a High-performance Integrated Virtual Environment (HIVE).

PubMed

Wu, Tsung-Jung; Shamsaddini, Amirhossein; Pan, Yang; Smith, Krista; Crichton, Daniel J; Simonyan, Vahan; Mazumder, Raja

2014-01-01

Years of sequence feature curation by UniProtKB/Swiss-Prot, PIR-PSD, NCBI-CDD, RefSeq and other database biocurators has led to a rich repository of information on functional sites of genes and proteins. This information along with variation-related annotation can be used to scan human short sequence reads from next-generation sequencing (NGS) pipelines for presence of non-synonymous single-nucleotide variations (nsSNVs) that affect functional sites. This and similar workflows are becoming more important because thousands of NGS data sets are being made available through projects such as The Cancer Genome Atlas (TCGA), and researchers want to evaluate their biomarkers in genomic data. BioMuta, an integrated sequence feature database, provides a framework for automated and manual curation and integration of cancer-related sequence features so that they can be used in NGS analysis pipelines. Sequence feature information in BioMuta is collected from the Catalogue of Somatic Mutations in Cancer (COSMIC), ClinVar, UniProtKB and through biocuration of information available from publications. Additionally, nsSNVs identified through automated analysis of NGS data from TCGA are also included in the database. Because of the petabytes of data and information present in NGS primary repositories, a platform HIVE (High-performance Integrated Virtual Environment) for storing, analyzing, computing and curating NGS data and associated metadata has been developed. Using HIVE, 31 979 nsSNVs were identified in TCGA-derived NGS data from breast cancer patients. All variations identified through this process are stored in a Curated Short Read archive, and the nsSNVs from the tumor samples are included in BioMuta. Currently, BioMuta has 26 cancer types with 13 896 small-scale and 308 986 large-scale study-derived variations. Integration of variation data allows identifications of novel or common nsSNVs that can be prioritized in validation studies. Database URL: BioMuta: http

PITX3 promoter methylation is a prognostic biomarker for biochemical recurrence-free survival in prostate cancer patients after radical prostatectomy.

PubMed

Holmes, Emily Eva; Goltz, Diane; Sailer, Verena; Jung, Maria; Meller, Sebastian; Uhl, Barbara; Dietrich, Jörn; Röhler, Magda; Ellinger, Jörg; Kristiansen, Glen; Dietrich, Dimo

2016-01-01

Molecular biomarkers that might help to distinguish between more aggressive and clinically insignificant prostate cancers (PCa) are still urgently needed. Aberrant DNA methylation as a common molecular alteration in PCa seems to be a promising source for such biomarkers. In this study, PITX3 DNA methylation ( mPITX3 ) and its potential role as a prognostic biomarker were investigated. Furthermore, m PITX3 was analyzed in combination with the established PCa methylation biomarker PITX2 ( mPITX2 ). mPITX3 and mPITX2 were assessed by a quantitative real-time PCR and by means of the Infinium HumanMethylation450 BeadChip. BeadChip data were obtained from The Cancer Genome Atlas (TCGA) Research Network. DNA methylation differences between normal adjacent, benign hyperplastic, and carcinomatous prostate tissues were examined in the TCGA dataset as well as in prostatectomy specimens from the University Hospital Bonn. Retrospective analyses of biochemical recurrence (BCR) were conducted in a training cohort ( n  = 498) from the TCGA and an independent validation cohort ( n  = 300) from the University Hospital Bonn. All patients received radical prostatectomy. In PCa tissue, mPITX3 was increased significantly compared to normal and benign hyperplastic tissue. In univariate Cox proportional hazards analyses, mPITX3 showed a significant prognostic value for BCR (training cohort: hazard ratio (HR) = 1.83 (95 % CI 1.07-3.11), p  = 0.027; validation cohort: HR = 2.56 (95 % CI 1.44-4.54), p  = 0.001). A combined evaluation with PITX2 methylation further revealed that hypermethylation of a single PITX gene member (either PITX2 or PITX3 ) identifies an intermediate risk group. PITX3 DNA methylation alone and in combination with PITX2 is a promising biomarker for the risk stratification of PCa patients and adds relevant prognostic information to common clinically implemented parameters. Further studies are required to determine whether the results are

Efficacy and safety of haloperidol versus atypical antipsychotic medications in the treatment of delirium.

PubMed

Yoon, Hyung-Jun; Park, Kyoung-Min; Choi, Won-Jung; Choi, Soo-Hee; Park, Jin-Young; Kim, Jae-Jin; Seok, Jeong-Ho

2013-09-30

Most previous studies on the efficacy of antipsychotic medication for the treatment of delirium have reported that there is no significant difference between typical and atypical antipsychotic medications. It is known, however, that older age might be a predictor of poor response to antipsychotics in the treatment of delirium. The objective of this study was to compare the efficacy and safety of haloperidol versus three atypical antipsychotic medications (risperidone, olanzapine, and quetiapine) for the treatment of delirium with consideration of patient age. This study was a 6-day, prospective, comparative clinical observational study of haloperidol versus atypical antipsychotic medications (risperidone, olanzapine, and quetiapine) in patients with delirium at a tertiary level hospital. The subjects were referred to the consultation-liaison psychiatric service for management of delirium and were screened before enrollment in this study. A total of 80 subjects were assigned to receive either haloperidol (N = 23), risperidone (N = 21), olanzapine (N = 18), or quetiapine (N = 18). The efficacy was evaluated using the Korean version of the Delirium Rating Scale-Revised-98 (DRS-K) and the Korean version of the Mini Mental Status Examination (K-MMSE). The safety was evaluated by the Udvalg Kliniske Undersogelser side effect rating scale. There were no significant differences in mean DRS-K severity or K-MMSE scores among the four groups at baseline. In all groups, the DRS-K severity score decreased and the K-MMSE score increased significantly over the study period. However, there were no significant differences in the improvement of DRS-K or K-MMSE scores among the four groups. Similarly, cognitive and non-cognitive subscale DRS-K scores decreased regardless of the treatment group. The treatment response rate was lower in patients over 75 years old than in patients under 75 years old. Particularly, the response rate to olanzapine was poorer in the older age group

Biomarkers for Early Detection of Clinically Relevant Prostate Cancer: A Multi-Institutional Validation Trial

DTIC Science & Technology

2015-10-01

Suzanne Kolb 12 Project Role: Project Coordinator Researcher Identifier (e.g. ORCID ID): N/A Nearest person month worked: 5 person months...Contribution to Project: Ms. Kolb works under the direction of Drs. Lin and Newcomb to fulfill daily fiscal and administrative functions of the...program. She monitors subaward budgets, provides logistical support. Ms. Kolb works closely with the PASS Deputy Director to maintain IRB files

Biomarkers for Early Detection of Clinically Relevant Prostate Cancer: A Multi-Institutional Validation Trial

DTIC Science & Technology

2015-10-01

Name: Suzanne Kolb 12 Project Role: Project Coordinator Researcher Identifier (e.g. ORCID ID): N/A Nearest person month worked: 5 person...months Contribution to Project: Ms. Kolb works under the direction of Drs. Lin and Newcomb to fulfill daily fiscal and administrative functions of the...program. She monitors subaward budgets, provides logistical support. Ms. Kolb works closely with the PASS Deputy Director to maintain IRB files

Remarks on the physiological effects of defoliation on sugar maple and some impacts on syrup production

Treesearch

Philip M. Wargo

1991-01-01

The information I am going to present today is a conglomeration of some of the research on the effects of defoliation that has been done on sugar maple and oak. It involves work done by Drs. David Houston, Johnson Parker, Robert Gregory and me. Dr. Houston, a plant pathologist, and Dr. Parker, a plant physiologist, work with the USDA Forest Service in Hamden, Ct.; Dr....

Conformation, orientation, and adsorption kinetics of dermaseptin B2 onto synthetic supports at aqueous/solid interface.

PubMed

Noinville, S; Bruston, F; El Amri, C; Baron, D; Nicolas, P

2003-08-01

The antimicrobial activity of cationic amphipathic peptides is due mainly to the adsorption of peptides onto target membranes, which can be modulated by such physicochemical parameters as charge and hydrophobicity. We investigated the structure of dermaseptin B2 (Drs B2) at the aqueous/synthetic solid support interface and its adsorption kinetics using attenuated total reflection Fourier transform infrared spectroscopy and surface plasmon resonance. We determined the conformation and affinity of Drs B2 adsorbed onto negatively charged (silica or dextran) and hydrophobic supports. Synthetic supports of differing hydrophobicity were obtained by modifying silica or gold with omega-functionalized alkylsilanes (bromo, vinyl, phenyl, methyl) or alkylthiols. The peptide molecules adsorbed onto negatively charged supports mostly had a beta-type conformation. In contrast, a monolayer of Drs B2, mainly in the alpha-helical conformation, was adsorbed irreversibly onto the hydrophobic synthetic supports. The conformational changes during formation of the adsorbed monolayer were monitored by two-dimensional Fourier transform infrared spectroscopy correlation; they showed the influence of peptide-peptide interactions on alpha-helix folding on the most hydrophobic support. The orientation of the alpha-helical Drs B2 with respect to the hydrophobic support was determined by polarized attenuated total reflection; it was around 15 +/- 5 degrees. This orientation was confirmed and illustrated by a molecular dynamics study. These combined data demonstrate that specific chemical environments influence the structure of Drs B2, which could explain the many functions of antimicrobial peptides.

Risk Score Algorithm for Treatment of Persistent Apical Periodontitis

PubMed Central

Yu, V.S.; Khin, L.W.; Hsu, C.S.; Yee, R.; Messer, H.H.

2014-01-01

Persistent apical periodontitis related to a nonvital tooth that does not resolve following root canal treatment may be compatible with health and may not require further intervention. This research aimed to develop a Deterioration Risk Score (DRS) to differentiate lesions requiring further intervention from lesions likely to be compatible with health. In this cross-sectional study, patient records (2003-2008) were screened for root-filled teeth with periapical radiolucency visible on periapical radiographs taken at treatment and at recruitment at least 4 yr later. The final sample consisted of 228 lesions in 182 patients. Potential demographic and treatment risk factors were screened against 3 categorical outcomes (improved/unchanged/deteriorated), and a multivariate independent multinomial probit regression model was built. A 5-level DRS was constructed by summing values of adjusted regression coefficients in the model, based on predicted probabilities of deterioration. Most lesions (127, 55.7%) had improved over time, while 32 (14.0%) remained unchanged, and 69 (30.3%) had deteriorated. Significant predictors of deterioration were as follows: time since treatment (relative risk [RR]: 1.11, 95% confidence interval [CI]: 1.01-1.22, p = .030, rounded beta value = 1, for every year increase after 4 yr), current pain (RR: 3.79, 95% CI: 1.48-9.70, p = .005, rounded beta value = 13), sinus tract present (RR: 4.13, 95% CI: 1.11-15.29, p = .034, rounded beta value = 14), and lesion size (RR: 7.20, 95% CI: 3.70-14.02, p < .001, rounded beta value = 20). Persistent apical periodontitis with DRS <15 represented very low risk; 15-20, low risk; 21-30, moderate risk; 31-40, high risk; and >40, very high risk. DRS could help the clinician identify persistent apical periodontitis at low risk for deterioration, and it would not require intervention. When validated, this tool could reduce the risk of overtreatment and contribute toward targeted care and better efficiency in the

Neurological Outcome Scale for Traumatic Brain Injury: III. Criterion-Related Validity and Sensitivity to Change in the NABIS Hypothermia-II Clinical Trial

PubMed Central

Wilde, Elisabeth A.; Moretti, Paolo; MacLeod, Marianne C.; Pedroza, Claudia; Drever, Pamala; Fourwinds, Sierra; Frisby, Melisa L.; Beers, Sue R.; Scott, James N.; Hunter, Jill V.; Traipe, Elfrides; Valadka, Alex B.; Okonkwo, David O.; Zygun, David A.; Puccio, Ava M.; Clifton, Guy L.

2013-01-01

Abstract The Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI) is a measure assessing neurological functioning in patients with TBI. We hypothesized that the NOS-TBI would exhibit adequate concurrent and predictive validity and demonstrate more sensitivity to change, compared with other well-established outcome measures. We analyzed data from the National Acute Brain Injury Study: Hypothermia-II clinical trial. Participants were 16–45 years of age with severe TBI assessed at 1, 3, 6, and 12 months postinjury. For analysis of criterion-related validity (concurrent and predictive), Spearman's rank-order correlations were calculated between the NOS-TBI and the Glasgow Outcome Scale (GOS), GOS-Extended (GOS-E), Disability Rating Scale (DRS), and Neurobehavioral Rating Scale-Revised (NRS-R). Concurrent validity was demonstrated through significant correlations between the NOS-TBI and GOS, GOS-E, DRS, and NRS-R measured contemporaneously at 3, 6, and 12 months postinjury (all p<0.0013). For prediction analyses, the multiplicity-adjusted p value using the false discovery rate was <0.015. The 1-month NOS-TBI score was a significant predictor of outcome in the GOS, GOS-E, and DRS at 3 and 6 months postinjury (all p<0.015). The 3-month NOS-TBI significantly predicted GOS, GOS-E, DRS, and NRS-R outcomes at 6 and 12 months postinjury (all p<0.0015). Sensitivity to change was analyzed using Wilcoxon's signed rank-sum test of subsamples demonstrating no change in the GOS or GOS-E between 3 and 6 months. The NOS-TBI demonstrated higher sensitivity to change, compared with the GOS (p<0.038) and GOS-E (p<0.016). In summary, the NOS-TBI demonstrated adequate concurrent and predictive validity as well as sensitivity to change, compared with gold-standard outcome measures. The NOS-TBI may enhance prediction of outcome in clinical practice and measurement of outcome in TBI research. PMID:23617608

Development and initial validation of the NCCN/FACT symptom index for advanced kidney cancer.

PubMed

Rothrock, Nan E; Jensen, Sally E; Beaumont, Jennifer L; Abernethy, Amy P; Jacobsen, Paul B; Syrjala, Karen; Cella, David

2013-01-01

There is a need for a brief symptom index for advanced kidney cancer that includes perspectives of both patients and clinicians and is consistent with the Food and Drug Administration's guidance for patient-reported outcome measures. This study developed and examined the preliminary reliability and validity of the new National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy (FACT)-Kidney Symptom Index 19. Fifty patients with advanced kidney cancer provided open-ended and survey responses ranking their most important symptoms. Responses were reconciled with published clinician reports of the most important symptoms. Ten experienced oncologists rated symptoms as disease- or treatment-related. Patients completed quality-of-life and performance status measures. A 19-item index was produced from symptoms that were rated as most important by patients or clinicians. It includes three subscales: disease-related symptoms (DRS), treatment side effects (TSE), and general function and well-being (FWB). Internal consistency was good for the full instrument (α = 0.83), the DRS subscale (α = 0.76), and the FWB subscale (α = 0.78) but lower for the TSE subscale (α = 0.59). Convergent validity was demonstrated through correlations with the FACT-General. Patients with differing performance status were distinguished by the total score (F2,47 = 17.37; P < .0001), the DRS subscale (F2,47 = 14.22; P < .0001), and the FWB subscale (F2,47 = 13.40; P < .0001) but not the TSE subscale (F2,47 =1.48; P = 0.2380). The National Comprehensive Cancer Network/FACT-Kidney Symptom Index 19 combines symptoms deemed most important by patients and clinicians. Preliminary evidence suggests that the total score and DRS and FWB subscales are reliable and valid as summary indexes. The TSE subscale may be least relevant given the advent of newer therapies. Copyright © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All

Connecting genomic alterations to cancer biology with proteomics: the NCI Clinical Proteomic Tumor Analysis Consortium.

PubMed

Ellis, Matthew J; Gillette, Michael; Carr, Steven A; Paulovich, Amanda G; Smith, Richard D; Rodland, Karin K; Townsend, R Reid; Kinsinger, Christopher; Mesri, Mehdi; Rodriguez, Henry; Liebler, Daniel C

2013-10-01

The National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium is applying the latest generation of proteomic technologies to genomically annotated tumors from The Cancer Genome Atlas (TCGA) program, a joint initiative of the NCI and the National Human Genome Research Institute. By providing a fully integrated accounting of DNA, RNA, and protein abnormalities in individual tumors, these datasets will illuminate the complex relationship between genomic abnormalities and cancer phenotypes, thus producing biologic insights as well as a wave of novel candidate biomarkers and therapeutic targets amenable to verification using targeted mass spectrometry methods. ©2013 AACR.

Centralized vs decentralized options for an European Data Relay Satellite system

NASA Astrophysics Data System (ADS)

Saint Aubert, S.; Hervieux, M.; Perbos, J. L.; Saggese, E.; Soprano, C.

1985-10-01

The European Data Relay Satellite (DRS) is now being planned to support future European missions in the nineties and in particular the various elements of the in-orbit infrastructure. Studies are being conducted to investigate the usefulness of the relay system as well as to provide the basis for issuing technical specifications for a development and launch in 1993. This paper presents the results of a study issued by ESA on possible options for a DRS System, concentrating on the comparison between a centralized and a decentralized data distribution concept. After recalling the space programs foreseen in Europe, the paper discusses the architecture and design of the various elements of the System: space segment, DRS ground segment, and user ground segment for different options of data dissemination.

Centralized vs decentralized options for a european data relay satellite system

NASA Astrophysics Data System (ADS)

Aubert, Ph. Saint; Hervieux, M.; Perbos, J. L.; Saggese, E.; Soprano, C.

The European Data Relay Satellite (DRS) is now being planned to support future European missions in the nineties and in particular the various elements of the in-orbit infrastructure. Studies are being conducted to investigate the usefulness of the Relay System as well as to provide the basis for issuing technical specifications for a development and launch in 1993. This paper presents the results of a study issued by ESA on possible options for a DRS System, concentrating on the comparison between a centralized and a decentralized data distribution concept. After recalling the space programmes foreseen in Europe, the paper discusses the architecture and design of the various elements of the System: space segment, DRS ground segment and user ground segment for different options of data dissemination.

A new time calibration method for switched-capacitor-array-based waveform samplers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, H.; Chen, C. -T.; Eclov, N.

2014-08-24

Here we have developed a new time calibration method for the DRS4 waveform sampler that enables us to precisely measure the non-uniform sampling interval inherent in the switched-capacitor cells of the DRS4. The method uses the proportionality between the differential amplitude and sampling interval of adjacent switched-capacitor cells responding to a sawtooth-shape pulse. In the experiment, a sawtooth-shape pulse with a 40 ns period generated by a Tektronix AWG7102 is fed to a DRS4 evaluation board for calibrating the sampling intervals of all 1024 cells individually. The electronic time resolution of the DRS4 evaluation board with the new time calibrationmore » is measured to be ~2.4 ps RMS by using two simultaneous Gaussian pulses with 2.35 ns full-width at half-maximum and applying a Gaussian fit. The time resolution dependencies on the time difference with the new time calibration are measured and compared to results obtained by another method. Ultimately, the new method could be applicable for other switched-capacitor-array technology-based waveform samplers for precise time calibration.« less

The Space Technology-7 Disturbance Reduction Systems

NASA Technical Reports Server (NTRS)

ODonnell, James R., Jr.; Hsu, Oscar C.; Hanson, John; Hruby, Vlad

2004-01-01

The Space Technology 7 Disturbance Reduction System (DRS) is an in-space technology demonstration designed to validate technologies that are required for future missions such as the Laser Interferometer Space Antenna (LISA) and the Micro-Arcsecond X-ray Imaging Mission (MAXIM). The primary sensors that will be used by DRS are two Gravitational Reference Sensors (GRSs) being developed by Stanford University. DRS will control the spacecraft so that it flies about one of the freely-floating Gravitational Reference Sensor test masses, keeping it centered within its housing. The other GRS serves as a cross-reference for the first as well as being used as a reference for .the spacecraft s attitude control. Colloidal MicroNewton Thrusters being developed by the Busek Co. will be used to control the spacecraft's position and attitude using a six degree-of-freedom Dynamic Control System being developed by Goddard Space Flight Center. A laser interferometer being built by the Jet Propulsion Laboratory will be used to help validate the results of the experiment. The DRS will be launched in 2008 on the European Space Agency (ESA) LISA Pathfinder spacecraft along with a similar ESA experiment, the LISA Test Package.

Modified Y-splitting Procedure for the Treatment of Duane Retraction Syndrome.

PubMed

Altıntaş, Ayşe Gül; Arifoğlu, Hasan Basri; Köklü, Şükrü Gültekin

2015-08-01

To present the outcomes of modified lateral rectus Y-splitting combined with either unilateral or bilateral horizontal rectus recession in Duane Retraction Syndrome (DRS) with significant upshoot or downshoot. A total of 12 patients including 10 patients with Type I DRS and 2 with Type III DRS underwent modified Y-splitting surgery. Amount of additional recessions varied with the degree of preoperative deviation by intraoperative adjustable suture technique. Preoperatively 3 patients had esotropia (ET), 6 had exotropia (XT), and 3 patients had orthotropia. The mean preoperative deviation was 19.3 prism diopters (PD) (range, 18-20 PD) in ET patients and 19.2 PD (range, 16-20 PD) in XT patients. Postoperatively, all patients had significant correction in horizontal deviation and aligned within 4 PD of orthotropia, and no patients exhibited abnormal head posture. Co-contraction and globe retraction were markedly reduced and abnormal ocular vertical movement disappeared or significantly decreased in all cases. No patients experienced recurrence of ocular motility disorders in the mean 26-month (range, 13-66 months) follow-up period. Modified Y-splitting surgery combined with co-contracting horizontal muscle recession technique seems to be a safe and effective treatment in DRS.

Django Remote Submission

DOE Office of Scientific and Technical Information (OSTI.GOV)

Doucet, Mathieu; Hobson, Tanner C.; Ferraz Leal, Ricardo Miguel

The Django Remote Submission (DRS) is a Django (Django, n.d.) application to manage long running job submission, including starting the job, saving logs, and storing results. It is an independent project available as a standalone pypi package (PyPi, n.d.). It can be easily integrated in any Django project. The source code is freely available as a GitHub repository (django-remote-submission, n.d.). To run the jobs in background, DRS takes advantage of Celery (Celery, n.d.), a powerful asynchronous job queue used for running tasks in the background, and the Redis Server (Redis, n.d.), an in-memory data structure store. Celery uses brokers tomore » pass messages between a Django Project and the Celery workers. Redis is the message broker of DRS. In addition DRS provides real time monitoring of the progress of Jobs and associated logs. Through the Django Channels project (Channels, n.d.), and the usage of Web Sockets, it is possible to asynchronously display the Job Status and the live Job output (standard output and standard error) on a web page.« less

Duane retraction syndrome in a patient with Duchenne muscular dystrophy.

PubMed

Bosley, Thomas M; Salih, Mustafa A; Alkhalidi, Hisham; Oystreck, Darren T; El Khashab, Heba Y; Kondkar, Altaf A; Abu-Amero, Khaled K

2016-09-01

We describe the clinical features of a boy with bilateral Duane retraction syndrome (DRS), Duchenne muscular dystrophy (DMD), and other medical problems. The child was followed-up for five years; his chart was reviewed, including the results of a muscle biopsy and genetic testing. Multiplex ligation-dependent probe amplification (MLPA) was used to interrogate deletions/duplications in the dystrophin gene. The proband had bilateral DRS with otherwise normal ocular motility; he also had developmental delay, mild mental retardation, and seizures. Clinical diagnosis of DMD included progressive proximal weakness, highly elevated creatine kinase levels, and a muscle biopsy showing significant dystrophic changes including contracted, degenerative, and regenerative fibers, and negative dystrophin immunostaining. MLPA documented duplication of exons 3 and 4 of the dystrophin gene. This boy is the third patient to be reported with DRS and DMD, the second with bilateral DRS and the only one with other neurologic features. Mutated dystrophin is present in extraocular muscles and in the central nervous system (CNS) in DMD, leaving open the question of whether this co-occurrence is the result of the genetic muscle abnormality, CNS effects caused by dystrophin mutations, or chance.

Django Remote Submission

DOE PAGES

Doucet, Mathieu; Hobson, Tanner C.; Ferraz Leal, Ricardo Miguel

2017-08-01

The Django Remote Submission (DRS) is a Django (Django, n.d.) application to manage long running job submission, including starting the job, saving logs, and storing results. It is an independent project available as a standalone pypi package (PyPi, n.d.). It can be easily integrated in any Django project. The source code is freely available as a GitHub repository (django-remote-submission, n.d.). To run the jobs in background, DRS takes advantage of Celery (Celery, n.d.), a powerful asynchronous job queue used for running tasks in the background, and the Redis Server (Redis, n.d.), an in-memory data structure store. Celery uses brokers tomore » pass messages between a Django Project and the Celery workers. Redis is the message broker of DRS. In addition DRS provides real time monitoring of the progress of Jobs and associated logs. Through the Django Channels project (Channels, n.d.), and the usage of Web Sockets, it is possible to asynchronously display the Job Status and the live Job output (standard output and standard error) on a web page.« less

Larval dispersal underlies demographically important inter-system connectivity in a Great Lakes yellow perch (Perca flavescens) population

USGS Publications Warehouse

Brodnik, Reed M.; Fraker, Michael E.; Anderson, Eric J.; Carreon-Martinez, Lucia; DeVanna, Kristen M.; Heath, Dan D.; Reichert, Julie M.; Roseman, Edward F.; Ludsin, Stuart A.

2016-01-01

Ability to quantify connectivity among spawning subpopulations and their relative contribution of recruits to the broader population is a critical fisheries management need. By combining microsatellite and age information from larval yellow perch (Perca flavescens) collected in the Lake St. Clair – Detroit River system (SC-DRS) and western Lake Erie with a hydrodynamic backtracking approach, we quantified subpopulation structure, connectivity, and contributions of recruits to the juvenile stage in western Lake Erie during 2006-2007. After finding weak (yet stable) genetic structure between the SC-DRS and two western Lake Erie subpopulations, microsatellites also revealed measurable recruitment of SC-DRS larvae to the juvenile stage in western Lake Erie (17-21% during 2006-2007). Consideration of pre-collection larval dispersal trajectories, using hydrodynamic backtracking, increased estimated contributions to 65% in 2006 and 57% in 2007. Our findings highlight the value of complementing subpopulation discrimination methods with hydrodynamic predictions of larval dispersal by revealing the SC-DRS as a source of recruits to western Lake Erie and also showing that connectivity through larval dispersal can affect the structure and dynamics of large-lake fish populations.

Plant Growth Regulators as Potential Tools in Aquatic Plant Management: Efficacy and Persistence in Small-Scale Tests

DTIC Science & Technology

1994-01-01

gratefully acknowledge the support of the Waterways Experi- ment Station and Drs. Howard Westerdahl and Kurt Getsinger as this research was being conducted...E. Westerdahl , eds., Plant Growth Regulator Society of America, San Antonio, TX, 127-45. Anderson, L. W. J., and Dechoretz, N. (1988). "Bensulfuron...Vegetation Management. J. E. Kaufman and H. E. Westerdahl , eds., Plant Growth Regulator Society of America, San Antonio, TX, 155-86. Herbicide Handbook

Utility of CRISPR/Cas9 systems in hematology research.

PubMed

Lucas, Daniel; O'Leary, Heather A; Ebert, Benjamin L; Cowan, Chad A; Tremblay, Cedric S

2017-10-01

Since the end of the 20th century, novel approaches have emerged to manipulate experimental models of hematological disorders so that they more accurately mirror what is observed in the clinical setting. Despite these technological advances, the characterization of crucial genes for benign or malignant hematological disorders remains challenging, given the dynamic nature of the hematopoietic system and the genetic heterogeneity of these disorders. To overcome this limitation, genome-editing technologies have been developed to manipulate the genome specifically via deletion, insertion, or modification of targeted loci. These technologies have progressed swiftly, allowing their common use to investigate genetic function in experimental hematology. Among them, homologous-recombination-mediated targeting technologies have facilitated the manipulation of specific loci by generating knock-out and knock-in models. Despite promoting significant advances in our understanding of the molecular mechanisms involved in hematology, these inefficient, time-consuming, and labor-intensive approaches did not permit the development of cellular or animal models, recapitulating the complexity of hematological disorders. On October 26, 2016, Drs. Ben Ebert and Chad Cowan shared their knowledge of and experience with the utilization of CRISPR for models of myeloid malignancy, disease, and novel therapeutics in an International Society for Experimental Hematology webinar titled "Utility of CRISPR/Cas9 Systems in Hematology Research." Here, we provide an overview of the topics they covered, including their insights into the novel applications of the technique and its strengths and limitations. Copyright © 2017 ISEH – Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

LinkedOmics: analyzing multi-omics data within and across 32 cancer types.

PubMed

Vasaikar, Suhas V; Straub, Peter; Wang, Jing; Zhang, Bing

2018-01-04

The LinkedOmics database contains multi-omics data and clinical data for 32 cancer types and a total of 11 158 patients from The Cancer Genome Atlas (TCGA) project. It is also the first multi-omics database that integrates mass spectrometry (MS)-based global proteomics data generated by the Clinical Proteomic Tumor Analysis Consortium (CPTAC) on selected TCGA tumor samples. In total, LinkedOmics has more than a billion data points. To allow comprehensive analysis of these data, we developed three analysis modules in the LinkedOmics web application. The LinkFinder module allows flexible exploration of associations between a molecular or clinical attribute of interest and all other attributes, providing the opportunity to analyze and visualize associations between billions of attribute pairs for each cancer cohort. The LinkCompare module enables easy comparison of the associations identified by LinkFinder, which is particularly useful in multi-omics and pan-cancer analyses. The LinkInterpreter module transforms identified associations into biological understanding through pathway and network analysis. Using five case studies, we demonstrate that LinkedOmics provides a unique platform for biologists and clinicians to access, analyze and compare cancer multi-omics data within and across tumor types. LinkedOmics is freely available at http://www.linkedomics.org. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

GenomeVIP: a cloud platform for genomic variant discovery and interpretation

PubMed Central

Mashl, R. Jay; Scott, Adam D.; Huang, Kuan-lin; Wyczalkowski, Matthew A.; Yoon, Christopher J.; Niu, Beifang; DeNardo, Erin; Yellapantula, Venkata D.; Handsaker, Robert E.; Chen, Ken; Koboldt, Daniel C.; Ye, Kai; Fenyö, David; Raphael, Benjamin J.; Wendl, Michael C.; Ding, Li

2017-01-01

Identifying genomic variants is a fundamental first step toward the understanding of the role of inherited and acquired variation in disease. The accelerating growth in the corpus of sequencing data that underpins such analysis is making the data-download bottleneck more evident, placing substantial burdens on the research community to keep pace. As a result, the search for alternative approaches to the traditional “download and analyze” paradigm on local computing resources has led to a rapidly growing demand for cloud-computing solutions for genomics analysis. Here, we introduce the Genome Variant Investigation Platform (GenomeVIP), an open-source framework for performing genomics variant discovery and annotation using cloud- or local high-performance computing infrastructure. GenomeVIP orchestrates the analysis of whole-genome and exome sequence data using a set of robust and popular task-specific tools, including VarScan, GATK, Pindel, BreakDancer, Strelka, and Genome STRiP, through a web interface. GenomeVIP has been used for genomic analysis in large-data projects such as the TCGA PanCanAtlas and in other projects, such as the ICGC Pilots, CPTAC, ICGC-TCGA DREAM Challenges, and the 1000 Genomes SV Project. Here, we demonstrate GenomeVIP's ability to provide high-confidence annotated somatic, germline, and de novo variants of potential biological significance using publicly available data sets. PMID:28522612

Genetic drivers of papillary renal cell carcinoma - TCGA

Cancer.gov

A comprehensive genomic analysis of 161 tumors from people with papillary renal cell carcinoma (PRCC) – the second most common form of kidney cancer –provided insights into the molecular basis of this cancer and may inform its classification and treatment.

The mitochondrial disulfide relay system protein GFER is mutated in autosomal-recessive myopathy with cataract and combined respiratory-chain deficiency.

PubMed

Di Fonzo, Alessio; Ronchi, Dario; Lodi, Tiziana; Fassone, Elisa; Tigano, Marco; Lamperti, Costanza; Corti, Stefania; Bordoni, Andreina; Fortunato, Francesco; Nizzardo, Monica; Napoli, Laura; Donadoni, Chiara; Salani, Sabrina; Saladino, Francesca; Moggio, Maurizio; Bresolin, Nereo; Ferrero, Iliana; Comi, Giacomo P

2009-05-01

A disulfide relay system (DRS) was recently identified in the yeast mitochondrial intermembrane space (IMS) that consists of two essential components: the sulfhydryl oxidase Erv1 and the redox-regulated import receptor Mia40. The DRS drives the import of cysteine-rich proteins into the IMS via an oxidative folding mechanism. Erv1p is reoxidized within this system, transferring its electrons to molecular oxygen through interactions with cytochrome c and cytochrome c oxidase (COX), thereby linking the DRS to the respiratory chain. The role of the human Erv1 ortholog, GFER, in the DRS has been poorly explored. Using homozygosity mapping, we discovered that a mutation in the GFER gene causes an infantile mitochondrial disorder. Three children born to healthy consanguineous parents presented with progressive myopathy and partial combined respiratory-chain deficiency, congenital cataract, sensorineural hearing loss, and developmental delay. The consequences of the mutation at the level of the patient's muscle tissue and fibroblasts were 1) a reduction in complex I, II, and IV activity; 2) a lower cysteine-rich protein content; 3) abnormal ultrastructural morphology of the mitochondria, with enlargement of the IMS space; and 4) accelerated time-dependent accumulation of multiple mtDNA deletions. Moreover, the Saccharomyces cerevisiae erv1(R182H) mutant strain reproduced the complex IV activity defect and exhibited genetic instability of the mtDNA and mitochondrial morphological defects. These findings shed light on the mechanisms of mitochondrial biogenesis, establish the role of GFER in the human DRS, and promote an understanding of the pathogenesis of a new mitochondrial disease.

The Mitochondrial Disulfide Relay System Protein GFER Is Mutated in Autosomal-Recessive Myopathy with Cataract and Combined Respiratory-Chain Deficiency

PubMed Central

Di Fonzo, Alessio; Ronchi, Dario; Lodi, Tiziana; Fassone, Elisa; Tigano, Marco; Lamperti, Costanza; Corti, Stefania; Bordoni, Andreina; Fortunato, Francesco; Nizzardo, Monica; Napoli, Laura; Donadoni, Chiara; Salani, Sabrina; Saladino, Francesca; Moggio, Maurizio; Bresolin, Nereo; Ferrero, Iliana; Comi, Giacomo P.

2009-01-01

A disulfide relay system (DRS) was recently identified in the yeast mitochondrial intermembrane space (IMS) that consists of two essential components: the sulfhydryl oxidase Erv1 and the redox-regulated import receptor Mia40. The DRS drives the import of cysteine-rich proteins into the IMS via an oxidative folding mechanism. Erv1p is reoxidized within this system, transferring its electrons to molecular oxygen through interactions with cytochrome c and cytochrome c oxidase (COX), thereby linking the DRS to the respiratory chain. The role of the human Erv1 ortholog, GFER, in the DRS has been poorly explored. Using homozygosity mapping, we discovered that a mutation in the GFER gene causes an infantile mitochondrial disorder. Three children born to healthy consanguineous parents presented with progressive myopathy and partial combined respiratory-chain deficiency, congenital cataract, sensorineural hearing loss, and developmental delay. The consequences of the mutation at the level of the patient's muscle tissue and fibroblasts were 1) a reduction in complex I, II, and IV activity; 2) a lower cysteine-rich protein content; 3) abnormal ultrastructural morphology of the mitochondria, with enlargement of the IMS space; and 4) accelerated time-dependent accumulation of multiple mtDNA deletions. Moreover, the Saccharomyces cerevisiae erv1R182H mutant strain reproduced the complex IV activity defect and exhibited genetic instability of the mtDNA and mitochondrial morphological defects. These findings shed light on the mechanisms of mitochondrial biogenesis, establish the role of GFER in the human DRS, and promote an understanding of the pathogenesis of a new mitochondrial disease. PMID:19409522

Low-cost uncooled VOx infrared camera development

NASA Astrophysics Data System (ADS)

Li, Chuan; Han, C. J.; Skidmore, George D.; Cook, Grady; Kubala, Kenny; Bates, Robert; Temple, Dorota; Lannon, John; Hilton, Allan; Glukh, Konstantin; Hardy, Busbee

2013-06-01

The DRS Tamarisk® 320 camera, introduced in 2011, is a low cost commercial camera based on the 17 µm pixel pitch 320×240 VOx microbolometer technology. A higher resolution 17 µm pixel pitch 640×480 Tamarisk®640 has also been developed and is now in production serving the commercial markets. Recently, under the DARPA sponsored Low Cost Thermal Imager-Manufacturing (LCTI-M) program and internal project, DRS is leading a team of industrial experts from FiveFocal, RTI International and MEMSCAP to develop a small form factor uncooled infrared camera for the military and commercial markets. The objective of the DARPA LCTI-M program is to develop a low SWaP camera (<3.5 cm3 in volume and <500 mW in power consumption) that costs less than US $500 based on a 10,000 units per month production rate. To meet this challenge, DRS is developing several innovative technologies including a small pixel pitch 640×512 VOx uncooled detector, an advanced digital ROIC and low power miniature camera electronics. In addition, DRS and its partners are developing innovative manufacturing processes to reduce production cycle time and costs including wafer scale optic and vacuum packaging manufacturing and a 3-dimensional integrated camera assembly. This paper provides an overview of the DRS Tamarisk® project and LCTI-M related uncooled technology development activities. Highlights of recent progress and challenges will also be discussed. It should be noted that BAE Systems and Raytheon Vision Systems are also participants of the DARPA LCTI-M program.

A prospective analysis of the role of cognition in three models of aging and schizophrenia.

PubMed

Cohen, Carl I; Murante, Tessa

2017-07-02

This study uses longitudinal data from a sample of older adults with schizophrenia spectrum disorder (OAS) to examine the role of cognition in 3 models of aging and schizophrenia-accelerated aging, paradoxical aging, and heterogeneity of course-and their clinical relevance. The sample consisted of 103 community-dwelling persons aged 55 and over (mean=61years) with early-onset schizophrenia. Mean follow-up was 52.5months (range: 12-116months); 55% were men; 55% were white. We identified 21 potential predictor variables and used the Dementia Rating Scale (DRS) to assess cognition. There were no significant differences in the DRS at baseline (T1) and follow-up (T2). However, 20%, 22% and 58% of persons exhibited >0.5 effect size increase or decrease, or no change in their DRS scores, respectively; 19% were rapid decliners (>-2.11pts/year) and 19% were rapid improvers (>+2.11pts/year). In multivariable analysis, there were 3 predictors of higher DRS (T2): DRS (T1), decline in anxiety score, and race (white). The heterogeneity model best characterized the trajectory of cognition in later life. The accelerated aging model did not represent typical cognitive trajectories since most individuals were stable or improved. The heterogeneous trajectories made it difficult to generalize about cognition's role in the paradoxical aging model. Despite the paucity of predictors, our findings suggested that it may be clinically productive to enlist remediation strategies that target anxiety and cognition, and direct more attention to non-white OAS. Copyright © 2017. Published by Elsevier B.V.

Colloid Microthruster Flight Performance Results from Space Technology 7 Disturbance Reduction System

NASA Technical Reports Server (NTRS)

Ziemer, John; Marrese-Reading, Colleen; Dunn, Charley; Romero-Wolf, Andrew; Cutler, Curt; Javidnia, Shahram; Li, Thanh; Li, Irena; Franklin, Garth; Barela, Phil;

Ex ante Implementatietoetsing van Beleid, Een Methodiek Gebaseerd op Synergie Tussen Risicomanagement en Verandermanagement (Ex Ante Test for Policy Implementation - A Method Based Upon Synergy Between Risk Management an Change Management)

DTIC Science & Technology

2006-12-01

ante implementatietoetsing van beleid Een methodiek gebaseerd op synergie tussen risicomnanagemnent en verandermanagemnent Datuni december 2006 Auteur (s...te analyseren. Het de resultaten van de interviews gebruikct bij de theorie van risicomanagement en project Verandermanagernent bij de de ontwikkehing...Opdrachtnummer Hoewel expliciet is gekeken naar voorbeelden van risico’s bij Datum december 2006 Auteur (s) PROGRAMMA PR03ECT drs. R.C.T. de Haas drs

rTMS: A Treatment to Restore Function After Severe TBI

DTIC Science & Technology

2016-10-01

of rTMS-induced neurobehavioral effects measured with the Disability Rating Scale. Aim II will determine the presence, direction and sustainability...Aim IV addresses the need to confirm rTMS safety for severe TBI. 15. SUBJECT TERMS Disability Rating Scale (DRS), Neurobehavioral, Repetitive...rTMS sessions. The Disability Rating Scale (DRS) will be used at four time points to measure neurobehavioral recovery slopes. Net neural effects

Prevalence of Anti-Tuberculosis Drug Resistance in Foreign-Born Tuberculosis Cases in the U.S. and in Their Countries of Origin

PubMed Central

Taylor, Allison B.; Kurbatova, Ekaterina V.; Cegielski, J. Peter

2012-01-01

Background Foreign-born individuals comprise >50% of tuberculosis (TB) cases in the U.S. Since anti-TB drug resistance is more common in most other countries, when evaluating a foreign-born individual for TB, one must consider the risk of drug resistance. Naturally, clinicians query The Global Project on Anti-tuberculosis Drug Resistance Surveillance (Global DRS) which provides population-based data on the prevalence of anti-TB drug resistance in 127 countries starting in 1994. However, foreign-born persons in the U.S. are a biased sample of the population of their countries of origin, and Global DRS data may not accurately predict their risk of drug resistance. Since implementing drug resistance surveillance in 1993, the U.S. National TB Surveillance System (NTSS) has accumulated systematic data on over 130,000 foreign-born TB cases from more than 200 countries and territories. Our objective was to determine whether the prevalence of drug resistance among foreign-born TB cases correlates better with data from the Global DRS or with data on foreign-born TB cases in the NTSS. Methods and Findings We compared the prevalence of resistance to isoniazid and rifampin among foreign-born TB cases in the U.S., 2007–2009, with US NTSS data from 1993 to 2006 and with Global DRS data from 1994–2007 visually with scatterplots and statistically with correlation and linear regression analyses. Among foreign-born TB cases in the U.S., 2007–2009, the prevalence of isoniazid resistance and multidrug resistance (MDR, i.e. resistance to isoniazid and rifampin), correlated much better with 1993–2006 US surveillance data (isoniazid: r = 0.95, P<.001, MDR: r = 0.75, P<.001) than with Global DRS data, 1994–2007 (isoniazid: r = 0.55, P = .001; MDR: r = 0.50, P<.001). Conclusion Since 1993, the US NTSS has accumulated sufficient data on foreign-born TB cases to estimate the risk of drug resistance among such individuals better than data from the Global DRS

Combined image and genomic analysis of high-grade serous ovarian cancer reveals PTEN loss as a common driver event and prognostic classifier.

PubMed

Martins, Filipe C; Santiago, Ines de; Trinh, Anne; Xian, Jian; Guo, Anne; Sayal, Karen; Jimenez-Linan, Mercedes; Deen, Suha; Driver, Kristy; Mack, Marie; Aslop, Jennifer; Pharoah, Paul D; Markowetz, Florian; Brenton, James D

2014-12-17

TP53 and BRCA1/2 mutations are the main drivers in high-grade serous ovarian carcinoma (HGSOC). We hypothesise that combining tissue phenotypes from image analysis of tumour sections with genomic profiles could reveal other significant driver events. Automatic estimates of stromal content combined with genomic analysis of TCGA HGSOC tumours show that stroma strongly biases estimates of PTEN expression. Tumour-specific PTEN expression was tested in two independent cohorts using tissue microarrays containing 521 cases of HGSOC. PTEN loss or downregulation occurred in 77% of the first cohort by immunofluorescence and 52% of the validation group by immunohistochemistry, and is associated with worse survival in a multivariate Cox-regression model adjusted for study site, age, stage and grade. Reanalysis of TCGA data shows that hemizygous loss of PTEN is common (36%) and expression of PTEN and expression of androgen receptor are positively associated. Low androgen receptor expression was associated with reduced survival in data from TCGA and immunohistochemical analysis of the first cohort. PTEN loss is a common event in HGSOC and defines a subgroup with significantly worse prognosis, suggesting the rational use of drugs to target PI3K and androgen receptor pathways for HGSOC. This work shows that integrative approaches combining tissue phenotypes from images with genomic analysis can resolve confounding effects of tissue heterogeneity and should be used to identify new drivers in other cancers.

PREFACE: 2nd International Conference and Young Scientist School ''Magnetic resonance imaging in biomedical research''

NASA Astrophysics Data System (ADS)

Naumova, A. V.; Khodanovich, M. Y.; Yarnykh, V. L.

2016-02-01

The Second International Conference and Young Scientist School ''Magnetic resonance imaging in biomedical research'' was held on the campus of the National Research Tomsk State University (Tomsk, Russia) on September 7-9, 2015. The conference was focused on magnetic resonance imaging (MRI) applications for biomedical research. The main goal was to bring together basic scientists, clinical researchers and developers of new MRI techniques to bridge the gap between clinical/research needs and advanced technological solutions. The conference fostered research and development in basic and clinical MR science and its application to health care. It also had an educational purpose to promote understanding of cutting-edge MR developments. The conference provided an opportunity for researchers and clinicians to present their recent theoretical developments, practical applications, and to discuss unsolved problems. The program of the conference was divided into three main topics. First day of the conference was devoted to educational lectures on the fundamentals of MRI physics and image acquisition/reconstruction techniques, including recent developments in quantitative MRI. The second day was focused on developments and applications of new contrast agents. Multinuclear and spectroscopic acquisitions as well as functional MRI were presented during the third day of the conference. We would like to highlight the main developments presented at the conference and introduce the prominent speakers. The keynote speaker of the conference Dr. Vasily Yarnykh (University of Washington, Seattle, USA) presented a recently developed MRI method, macromolecular proton fraction (MPF) mapping, as a unique tool for modifying image contrast and a unique tool for quantification of the myelin content in neural tissues. Professor Yury Pirogov (Lomonosov Moscow State University) described development of new fluorocarbon compounds and applications for biomedicine. Drs. Julia Velikina and Alexey

Dopamine, T cells and multiple sclerosis (MS).

PubMed

Levite, Mia; Marino, Franca; Cosentino, Marco

2017-05-01

Dopamine is a key neurotransmitter that induces critical effects in the nervous system and in many peripheral organs, via 5 dopamine receptors (DRs): D1R-D5R. Dopamine also induces many direct and very potent effects on many DR-expressing immune cells, primarily T cells and dendritic cells. In this review, we focus only on dopamine receptors, effects and production in T cells. Dopamine by itself (at an optimal concentration of~0.1 nM) induces multiple function of resting normal human T cells, among them: T cell adhesion, chemotactic migration, homing, cytokine secretion and others. Interestingly, dopamine activates resting effector T cells (Teffs), but suppresses regulatory T cells (Tregs), and both effects lead eventually to Teff activation. Dopamine-induced effects on T cells are dynamic, context-sensitive and determined by the: T cell activation state, T cell type, DR type, and dopamine concentration. Dopamine itself, and also few dopaminergic molecules/ drugs that are in clinical use for cardiac, neurological and other non-immune indications, have direct effects on human T cells (summarized in this review). These dopaminergic drugs include: dopamine = intropin, L-DOPA, bromocriptine, pramipexole, pergolide, haloperidol, pimozide, and amantadine. Other dopaminergic drugs were not yet tested for their direct effects on T cells. Extensive evidence in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) show dopaminergic dysregulations in T cells in these diseases: D1-like DRs are decreased in Teffs of MS patients, and dopamine does not affect these cells. In contrast, D1-like DRs are increased in Tregs of MS patients, possibly causing functional Treg impairment in MS. Treatment of MS patients with interferon β (IFN-β) increases D1-like DRs and decreases D2-like DRs in Teffs, decreases D1-like DRs in Tregs, and most important: restores responsiveness of patient's Teffs to dopamine. DR agonists and antagonists confer some benefits in

Patient-reported outcomes in a phase iii study of everolimus versus placebo in patients with metastatic carcinoma of the kidney that has progressed on vascular endothelial growth factor receptor tyrosine kinase inhibitor therapy.

PubMed

Beaumont, Jennifer L; Butt, Zeeshan; Baladi, Jeanfrancois; Motzer, Robert J; Haas, Tomas; Hollaender, Norbert; Kay, Andrea; Cella, David

2011-01-01

A phase III, randomized, double-blind, placebo-controlled trial was conducted in patients with metastatic renal cell carcinoma. The focus of this paper is to evaluate the patient-reported outcomes. Patients were randomly assigned (2:1) to receive oral everolimus 10 mg once daily or placebo. The Functional Assessment of Cancer Therapy Kidney Symptom Index-Disease-Related Symptoms (FKSI-DRS) and European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 were administered before randomization and on day 1 of each cycle. The FKSI-DRS and the EORTC QLQ-C30 Physical Functioning and Global Quality of Life scores were the primary endpoints examined. Longitudinal models were used to compare treatment arms. Sensitivity analyses were conducted to explore the impact of missing data assumptions. Longitudinal trends for FKSI-DRS scores did not differ by treatment arm. Taking nonignorable missing data into account, there were significant differences between treatment arms in the trend over time for physical functioning and global quality of life, with the everolimus arm exhibiting greater decreases. All three of these measures of health-related quality of life were significantly related to progression-free survival. There was no evidence of a difference between everolimus and placebo in longitudinal patterns of disease-related symptoms, and little difference between the arms in physical functioning or global quality of life trends. This supports the conclusion that delay in tumor progression demonstrated by everolimus is associated with minimal impact on symptoms, physical functioning, or quality of life, as reported by patients.

Patient-Reported Outcomes in a Phase III Study of Everolimus Versus Placebo in Patients with Metastatic Carcinoma of the Kidney That Has Progressed on Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy

PubMed Central

Butt, Zeeshan; Baladi, Jeanfrancois; Motzer, Robert J.; Haas, Tomas; Hollaender, Norbert; Kay, Andrea; Cella, David

2011-01-01

Purpose. A phase III, randomized, double-blind, placebo-controlled trial was conducted in patients with metastatic renal cell carcinoma. The focus of this paper is to evaluate the patient-reported outcomes. Methods. Patients were randomly assigned (2:1) to receive oral everolimus 10 mg once daily or placebo. The Functional Assessment of Cancer Therapy Kidney Symptom Index—Disease-Related Symptoms (FKSI-DRS) and European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 were administered before randomization and on day 1 of each cycle. The FKSI-DRS and the EORTC QLQ-C30 Physical Functioning and Global Quality of Life scores were the primary endpoints examined. Longitudinal models were used to compare treatment arms. Sensitivity analyses were conducted to explore the impact of missing data assumptions. Results. Longitudinal trends for FKSI-DRS scores did not differ by treatment arm. Taking nonignorable missing data into account, there were significant differences between treatment arms in the trend over time for physical functioning and global quality of life, with the everolimus arm exhibiting greater decreases. All three of these measures of health-related quality of life were significantly related to progression-free survival. Conclusions. There was no evidence of a difference between everolimus and placebo in longitudinal patterns of disease-related symptoms, and little difference between the arms in physical functioning or global quality of life trends. This supports the conclusion that delay in tumor progression demonstrated by everolimus is associated with minimal impact on symptoms, physical functioning, or quality of life, as reported by patients. PMID:21459902

Development of GNSS PWV information management system for very short-term weather forecast in the Korean Peninsula

NASA Astrophysics Data System (ADS)

Park, Han-Earl; Yoon, Ha Su; Yoo, Sung-Moon; Cho, Jungho

2017-04-01

Over the past decade, Global Navigation Satellite System (GNSS) was in the spotlight as a meteorological research tool. The Korea Astronomy and Space Science Institute (KASI) developed a GNSS precipitable water vapor (PWV) information management system to apply PWV to practical applications, such as very short-term weather forecast. The system consists of a DPR, DRS, and TEV, which are divided functionally. The DPR processes GNSS data using the Bernese GNSS software and then retrieves PWV from zenith total delay (ZTD) with the optimized mean temperature equation for the Korean Peninsula. The DRS collects data from eighty permanent GNSS stations in the southern part of the Korean Peninsula and provides the PWV retrieved from GNSS data to a user. The TEV is in charge of redundancy of the DPR. The whole process is performed in near real-time where the delay is ten minutes. The validity of the GNSS PWV was proved by means of a comparison with radiosonde data. In the experiment of numerical weather prediction model, the GNSS PWV was utilized as the initial value of the Weather Research & Forecasting (WRF) model for heavy rainfall event. As a result, we found that the forecasting capability of the WRF is improved by data assimilation of GNSS PWV.

Introduction to Special Series: The Great Debate—Evaluating the Health Implications of Positive Psychology

PubMed Central

Miller, Suzanne M.; Christensen, Alan J.

2010-01-01

Background In recent years, investigators have focused increased attention on positive psychology constructs and their associations with health outcomes, such as morbidity, mortality, and adaptation to illness. The database regarding some of these concepts and models has grown appreciably, but work in this area has been subject to controversy. Purpose This special series of papers offers contrasting perspectives regarding research on positive psychology and health. Both proponents and critics were invited to review recent developments concerning a number of positive constructs that have been evaluated in the oncology literature and in health research, more generally. Methods Papers are presented in the format of a debate. Significant advances are reviewed by one set of investigators, Drs, Lisa G. Aspinwall and Richard G. Tedeschi, while shortcomings and concerns are highlighted by another set of investigators, Drs. James C. Coyne and Howard Tennen. Each of these review papers is followed by a rebuttal by the opposing side. A commentary on the exchange is provided by Dr. Sherri Sheinfeld Gorin. Results These papers address a range of important considerations regarding conceptualization of constructs, methodological rigor, dissemination of findings, and implications for practice. Conclusion The critiques and recommendations offered in these papers may help inform future efforts in this area, as the field continues to evolve. PMID:20306165

Validation of SCT Methylation as a Hallmark Biomarker for Lung Cancers.

PubMed

Zhang, Yu-An; Ma, Xiaotu; Sathe, Adwait; Fujimoto, Junya; Wistuba, Ignacio; Lam, Stephen; Yatabe, Yasushi; Wang, Yi-Wei; Stastny, Victor; Gao, Boning; Larsen, Jill E; Girard, Luc; Liu, Xiaoyun; Song, Kai; Behrens, Carmen; Kalhor, Neda; Xie, Yang; Zhang, Michael Q; Minna, John D; Gazdar, Adi F

2016-03-01

The human secretin gene (SCT) encodes secretin, a hormone with limited tissue distribution. Analysis of the 450k methylation array data in The Cancer Genome Atlas (TCGA) indicated that the SCT promoter region is differentially hypermethylated in lung cancer. Our purpose was to validate SCT methylation as a potential biomarker for lung cancer. We analyzed data from TCGA and developed and applied SCT-specific bisulfite DNA sequencing and quantitative methylation-specific polymerase chain reaction assays. The analyses of TCGA 450K data for 801 samples showed that SCT hypermethylation has an area under the curve (AUC) value greater than 0.98 that can be used to distinguish lung adenocarcinomas or squamous cell carcinomas from nonmalignant lung tissue. Bisulfite sequencing of lung cancer cell lines and normal blood cells allowed us to confirm that SCT methylation is highly discriminative. By applying a quantitative methylation-specific polymerase chain reaction assay, we found that SCT hypermethylation is frequently detected in all major subtypes of malignant non-small cell lung cancer (AUC = 0.92, n = 108) and small cell lung cancer (AUC = 0.93, n = 40) but is less frequent in lung carcinoids (AUC = 0.54, n = 20). SCT hypermethylation appeared in samples of lung carcinoma in situ during multistage pathogenesis and increased in invasive samples. Further analyses of TCGA 450k data showed that SCT hypermethylation is highly discriminative in most other types of malignant tumors but less frequent in low-grade malignant tumors. The only normal tissue with a high level of methylation was the placenta. Our findings demonstrated that SCT methylation is a highly discriminative biomarker for lung and other malignant tumors, is less frequent in low-grade malignant tumors (including lung carcinoids), and appears at the carcinoma in situ stage. Copyright © 2015 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

TET2 binds the androgen receptor and loss is associated with prostate cancer

PubMed Central

Nickerson, ML; Das, S; Im, KM; Turan, S; Berndt, SI; Li, H; Lou, H; Brodie, SA; Billaud, JN; Zhang, T; Bouk, AJ; Butcher, D; Wang, Z; Sun, L; Misner, K; Tan, W; Esnakula, A; Esposito, D; Huang, WY; Hoover, RN; Tucker, MA; Keller, JR; Boland, J; Brown, K; Anderson, SK; Moore, LE; Isaacs, WB; Chanock, SJ; Yeager, M; Dean, M; Andresson, T

2016-01-01

Genetic alterations associated with prostate cancer (PCa) may be identified by sequencing metastatic tumor genomes to identify molecular markers at this lethal stage of disease. Previously, we characterized somatic alterations in metastatic tumors in the methylcytosine dioxygenase ten-eleven translocation 2 (TET2), which is altered in 5–15% of myeloid, kidney, colon and prostate cancers. Genome-wide association studies previously identified non-coding risk variants associated with PCa and melanoma. We performed fine-mapping of PCa risk across TET2 using genotypes from the PEGASUS case-control cohort and identified six new risk variants in introns 1 and 2. Oligonucleotides containing two risk variants were bound by the transcription factor octamer-binding protein 1 (Oct1/POU2F1) and TET2 and Oct1 expression were positively correlated in prostate tumors. TET2 is expressed in normal prostate tissue and reduced in a subset of tumors from the Cancer Genome Atlas (TCGA). Small interfering RNA (siRNA)-mediated TET2 knockdown (KD) increases LNCaP cell proliferation, migration, and wound healing, verifying loss drives a cancer phenotype. Endogenous TET2 bound the androgen receptor (AR) and AR-coactivator proteins in LNCaP cell extracts, and TET2 KD increases prostate-specific antigen (KLK3/PSA) expression. Published data reveal TET2 binding sites and hydroxymethylcytosine (hmC) proximal to KLK3. A gene co-expression network identified using TCGA prostate tumor RNA-sequencing identifies co-regulated cancer genes associated with 2-oxoglutarate (2-OG) and succinate metabolism, including TET2, lysine demethylase (KDM) KDM6A, BRCA1-associated BAP1, and citric acid cycle enzymes IDH1/2, SDHA/B, and FH. The co-expression signature is conserved across 31 TCGA cancers suggesting a putative role for TET2 as an energy sensor (of 2-OG) that modifies aspects of androgen-AR signaling. Decreased TET2 mRNA expression in TCGA PCa tumors is strongly associated with reduced patient survival

Endometrial and acute myeloid leukemia cancer genomes characterized

Cancer.gov

Two studies from The Cancer Genome Atlas (TCGA) program reveal details about the genomic landscapes of acute myeloid leukemia (AML) and endometrial cancer. Both provide new insights into the molecular underpinnings of these cancers.

Respiratory medicine and research at McGill University: A historical perspective

PubMed Central

Martin, James G; Schwartzman, Kevin

2015-01-01

The history of respiratory medicine and research at McGill University (Montreal, Quebec) is tightly linked with the growth of academic medicine within its teaching hospitals. Dr Jonathan Meakins, a McGill medical graduate, was recruited to the Royal Victoria Hospital in 1924; as McGill’s first full-time clinical professor and Physician-in-Chief at the Royal Victoria Hospital. His focus on respiratory medicine led to the publication of his first book, Respiratory Function in Disease, in 1925. Meakins moved clinical laboratories from the Department of Pathology and placed them within the hospital. As such, he was responsible for the development of hospital-based research. Dr Ronald Christie was recruited as a postdoctoral fellow by Meakins in the early 1930s. After his fellowship, he returned to Britain but came back to McGill from St Bartholomew’s Hospital (London, United Kingdom) to become Chair of the Department of Medicine in 1955; he occupied the post for 10 years. He published extensively on the mechanical properties of the lung in common diseases such as emphysema and heart failure. Dr David Bates was among Dr Christie’s notable recruits; Bates in turn, recruited Drs Maurice McGregor, Margaret Becklake, William Thurlbeck, Joseph Milic-Emili, Nicholas Anthonisen, Charles Bryan and Peter Macklem. Bates published extensively in the area of respiratory physiology and, with Macklem and Christie, coauthored the book Respiratory Function in Disease, which integrated physiology into the analysis of disease. Dr JA Peter Paré joined the attending staff of the Royal Victoria Hospital and the Royal Edward Laurentian Hospital in 1949. A consummate clinician and teacher, he worked closely with Dr Robert Fraser, the Chair of Radiology, to write the reference text Diagnosis of Diseases of the Chest. This was a sentinel contribution in its focus on radiographic findings as the foundation for a systematic approach to diagnosis, and the correlation of these findings with

Decreased expression of serine protease inhibitor family G1 (SERPING1) in prostate cancer can help distinguish high-risk prostate cancer and predicts malignant progression.

PubMed

Peng, Shengmeng; Du, Tao; Wu, Wanhua; Chen, Xianju; Lai, Yiming; Zhu, Dingjun; Wang, Qiong; Ma, Xiaoming; Lin, Chunhao; Li, Zean; Guo, Zhenghui; Huang, Hai

2018-06-11

The aim of this study was to investigate the associations of serine proteinase inhibitor family G1 (SERPING1) down-regulation with poor prognosis in patients with prostate cancer (PCa). Furthermore, we aim to find more novel and effective PCa molecular markers to provide an early screening of PCa, distinguish patients with aggressive PCa, predict the prognosis, or reduce the economic burden of PCa. SERPING1 protein expression in both human PCa and normal prostate tissues was detected by immunohistochemical staining, which intensity was analyzed in association with clinical pathological parameters such Gleason score, pathological grade, clinical stage, tumor stage, lymph node metastasis, and distant metastasis. Moreover, we used The Cancer Genome Atlas (TCGA) Database, Taylor Database, and Oncomine dataset to validate our immunohistochemical results and investigated the value of SERPING1 in PCa at mRNA level. Kaplan-Meier analysis and Cox regression analysis were performed to evaluate the relationship between SERPING1 and prognosis of patients with PCa. The outcome showed that SERPING1 was expressed mainly in cytoplasm of grand cells of prostate tissue and was significantly expressed less in PCa (P<0.001). Furthermore, in the tissue microarray of our samples, decreasing expression of SERPING1 was correlated with the higher Gleason score (P = 0.004), the higher pathological grade (P = 0.01) and the advanced tumor stage (P = 0.005) at protein level. In TCGA dataset and Taylor Dataset, low-expressed SERPING1 was correlated with the younger patient (P = 0.02 in TCGA, P = 0.044 in Taylor) and the higher Gleason score (P = 0.019 in TCGA, P<0.001 in Taylor) at mRNA level. Kaplan-Meier analysis revealed that the lower mRNA of SERPING1 predicted lower overall survivals (P = 0.027 in TCGA), lower disease-free survival (P = 0.029) and lower biochemical recurrence-free survival (P = 0.011 in Taylor). Data from Oncomine database shown that SERPING1 low expression implying higher

Modeling Approach for Oxygen Exchange in the Human Lung under Hypobaric Conditions

DTIC Science & Technology

2001-06-01

Operational Medical Issues in Hypo-and Hyperbaric Conditions [les Questions medicales a caractere oprationel liees aux conditions hypobares ou hyperbares ] To...under Hypobaric Conditions DISTRIBUTION: Approved for public release, distribution unlimited This paper is part of the following report: TITLE...Approach for Oxygen Exchange in the Human Lung under Hypobaric Conditions Ing J.P.F. Lindhout*, Drs M. van de Graaff*, Ir Drs R.C. van de Graaff*, Dr

Regeneration of the Adult Rat Spinal Cord in Response to Ensheathing Cells and Methylprednisolone

DTIC Science & Technology

2002-01-01

me in academics and research, and also as my friend. I thank Dr. Linda L. Porter, for her continuous efforts on my behalf as the Chairperson of...and Spinal Cord Injury Program. We are grateful to Drs. Barbara S. Bregman and Linda L. Porter for their wonderful suggestions and guidance; to Anna...ES, Pietronigro DD, Seligman ML (1980) The free radical pathology and the microcirculation in the major central nervous system disorders. Acta

STRUCTURAL SCALE LIFE PREDICTION OF AERO STRUCTURES EXPERIENCING COMBINED EXTREME ENVIRONMENTS

DTIC Science & Technology

2017-07-01

representation is converted into a tetrahedral FE mesh using the software DREAM .3D. Due to a special voxel-identification scheme the FE mesh includes...research team met with DREAM .3D developers at AFRL (Drs. Mike Groeber and Sean Donegan) to discuss possible solutions. Together, the group proposed the...development of a DREAM .3D extension that can leverage the topological data structure within DREAM .3D instead of relying on an image-based

Development and Validation of Methods for Applying Pharmacokinetic Data in Risk Assessment. Volume 3. Tetrachloroethylene

DTIC Science & Technology

1990-12-01

Armstrong Aerospace Medical Research Laboratory, Wright Paterson Air Force Base, and Drs. Melvin Andersen and Michael Cargas , formerly with the Harry G...based on the arterial blood concentration surrogate were more III-1-10 similar to those de ’!ved in the traditional manner than were the estimates based on...pharmacokinetic modeling. Prepared by Office of Risk Analysis, Oak Ridge National L-ioratory, Oak Pidge, Tenn.zsee. Prepared under Contract No. DE -ACO5-84

Relation between the Fluctuating Wall Pressure and the Turbulent Structure of a Boundary Layer on a Cylinder in Axial Flow

DTIC Science & Technology

1993-08-12

Shop for their expert assistance during thze design ard development ur the wind tunnel and experimental apparatus; Drs. Alan L. Kistler, Seth Lichter...vertical wind tunnel was designed and built for this research. I With the test section in a vertical orientation, gravity effects leading to cylinder sag...were eliminated. The overall design and layout of the wind tunnel, as well as specific design features incorporated into the wind tunnel to satisfy

Evaporation from Sand

DTIC Science & Technology

1992-04-01

Instituuts Advies R2ad PML Prof. dr. U.A.Th. Brinkanl~ 36. Direactur van het Medisch Biologisch Laboratorium TNO Prof.Dr. W.R.F. Notten 37. Directeur...Grootsdialige Rampenbestrijdcing Ministerie van Binnenlandsc Zaken Drs. H. Evers 9. Adviseur van het Prins Maurits Laboratorium TWO Prot. Dr. J.M. van...Rossum, 10. Adyisew, van het Prins Maurits Laboratorium TWO Chernisdie Research Prof.Dr. G. Dijkstra 11. H~ur. NBC DMKIJOMAT/KIO Ir. AAM. Slagveer 12

Management of Duane retraction syndrome with prismatic glasses

PubMed Central

Aygit, Ebru Demet; Kocamaz, Murat; Inal, Asli; Fazil, Korhan; Ocak, Osman Bulut; Akar, Serpil; Gokyigit, Birsen

2017-01-01

Purpose To report the results of using prismatic glasses for Duane retraction syndrome (DRS). Methods Data were obtained from the records of patients who were evaluated during the year 2000 in the Strabismus Unit of the Beyoglu Eye Training and Research Hospital. The average follow-up was 12.2±17.7 months. In all cases, 2 main variables were evaluated: horizontal deviation in the primary position and face turn. Prismatic glasses were provided to patients according to the degree of shift in the primary position. Results The mean age of patients was 11.2 years. An analysis was performed on the data collected from 12 cases; 7 patients were females (58.3%) and 5 were males (41.7%), with 11 (91.7%) cases being of type I DRS. All 12 patients had abnormal head posture (face turn) and an angle of mean deviation equaling 10 PD (prism dioptri). Conclusion Treatment was individualized on a case-by-case basis. Prismatic glasses are useful for eliminating abnormal head posture and ocular misalignment in selected cases. PMID:28442887

Notch Signaling Activation Is Associated with Patient Mortality and Increased FGF1-Mediated Invasion in Squamous Cell Carcinoma of the Oral Cavity.

PubMed

Weaver, Alice N; Burch, M Benjamin; Cooper, Tiffiny S; Della Manna, Deborah L; Wei, Shi; Ojesina, Akinyemi I; Rosenthal, Eben L; Yang, Eddy S

2016-09-01

Oral squamous cell carcinoma (OSCC) is a cancer subtype that lacks validated prognostic and therapeutic biomarkers, and human papillomavirus status has not proven beneficial in predicting patient outcomes. A gene expression pathway analysis was conducted using OSCC patient specimens to identify molecular targets that may improve management of this disease. RNA was isolated from 19 OSCCs treated surgically at the University of Alabama at Birmingham (UAB; Birmingham, AL) and evaluated using the NanoString nCounter system. Results were confirmed using the oral cavity subdivision of the Head and Neck Squamous Cell Carcinoma Cancer (HNSCC) study generated by The Cancer Genome Atlas (TCGA) Research Network. Further characterization of the in vitro phenotype produced by Notch pathway activation in HNSCC cell lines included gene expression, proliferation, cell cycle, migration, invasion, and radiosensitivity. In both UAB and TCGA samples, Notch pathway upregulation was significantly correlated with patient mortality status and with expression of the proinvasive gene FGF1 In vitro Notch activation in HNSCC cells increased transcription of FGF1 and induced a marked increase in cell migration and invasion, which was fully abrogated by FGF1 knockdown. These results reveal that increased Notch pathway signaling plays a role in cancer progression and patient outcomes in OSCC. Accordingly, the Notch-FGF interaction should be further studied as a prognostic biomarker and potential therapeutic target for OSCC. Patients with squamous cell carcinoma of the oral cavity who succumb to their disease are more likely to have upregulated Notch signaling, which may mediate a more invasive phenotype through increased FGF1 transcription. Mol Cancer Res; 14(9); 883-91. ©2016 AACR. ©2016 American Association for Cancer Research.

Predicted impact of extending the screening interval for diabetic retinopathy: the Scottish Diabetic Retinopathy Screening programme.

PubMed

Looker, H C; Nyangoma, S O; Cromie, D T; Olson, J A; Leese, G P; Philip, S; Black, M W; Doig, J; Lee, N; Briggs, A; Hothersall, E J; Morris, A D; Lindsay, R S; McKnight, J A; Pearson, D W M; Sattar, N A; Wild, S H; McKeigue, P; Colhoun, H M

2013-08-01

The aim of our study was to identify subgroups of patients attending the Scottish Diabetic Retinopathy Screening (DRS) programme who might safely move from annual to two yearly retinopathy screening. This was a retrospective cohort study of screening data from the DRS programme collected between 2005 and 2011 for people aged ≥12 years with type 1 or type 2 diabetes in Scotland. We used hidden Markov models to calculate the probabilities of transitions to referable diabetic retinopathy (referable background or proliferative retinopathy) or referable maculopathy. The study included 155,114 individuals with no referable diabetic retinopathy or maculopathy at their first DRS examination and with one or more further DRS examinations. There were 11,275 incident cases of referable diabetic eye disease (9,204 referable maculopathy, 2,071 referable background or proliferative retinopathy). The observed transitions to referable background or proliferative retinopathy were lower for people with no visible retinopathy vs mild background retinopathy at their prior examination (respectively, 1.2% vs 8.1% for type 1 diabetes and 0.6% vs 5.1% for type 2 diabetes). The lowest probability for transitioning to referable background or proliferative retinopathy was among people with two consecutive screens showing no visible retinopathy, where the probability was <0.3% for type 1 and <0.2% for type 2 diabetes at 2 years. Transition rates to referable diabetic eye disease were lowest among people with type 2 diabetes and two consecutive screens showing no visible retinopathy. If such people had been offered two yearly screening the DRS service would have needed to screen 40% fewer people in 2009.

Rapid Identification of Mycobacteria and Drug-Resistant Mycobacterium tuberculosis by Use of a Single Multiplex PCR and DNA Sequencing

PubMed Central

Pérez-Osorio, Ailyn C.; Boyle, David S.; Ingham, Zachary K.; Ostash, Alla; Gautom, Romesh K.; Colombel, Craig; Houze, Yolanda

2012-01-01

Tuberculosis (TB) remains a significant global health problem for which rapid diagnosis is critical to both treatment and control. This report describes a multiplex PCR method, the Mycobacterial IDentification and Drug Resistance Screen (MID-DRS) assay, which allows identification of members of the Mycobacterium tuberculosis complex (MTBC) and the simultaneous amplification of targets for sequencing-based drug resistance screening of rifampin-resistant (rifampinr), isoniazidr, and pyrazinamider TB. Additionally, the same multiplex reaction amplifies a specific 16S rRNA gene target for rapid identification of M. avium complex (MAC) and a region of the heat shock protein 65 gene (hsp65) for further DNA sequencing-based confirmation or identification of other mycobacterial species. Comparison of preliminary results generated with MID-DRS versus culture-based methods for a total of 188 bacterial isolates demonstrated MID-DRS sensitivity and specificity as 100% and 96.8% for MTBC identification; 100% and 98.3% for MAC identification; 97.4% and 98.7% for rifampinr TB identification; 60.6% and 100% for isoniazidr TB identification; and 75.0% and 98.1% for pyrazinamider TB identification. The performance of the MID-DRS was also tested on acid-fast-bacterium (AFB)-positive clinical specimens, resulting in sensitivity and specificity of 100% and 78.6% for detection of MTBC and 100% and 97.8% for detection of MAC. In conclusion, use of the MID-DRS reduces the time necessary for initial identification and drug resistance screening of TB specimens to as little as 2 days. Since all targets needed for completing the assay are included in a single PCR amplification step, assay costs, preparation time, and risks due to user errors are also reduced. PMID:22162548

Determinants of Regret in Elderly Dialysis Patients.

PubMed

Tan, Edlyn Gui Fang; Teo, Irene; Finkelstein, Eric A; Chan, Choong Meng

2018-05-07

In Singapore, most elderly end stage renal disease (ESRD) patients choose dialysis over palliative management. However, dialysis may not be the optimal treatment option given only moderate survival benefits and high costs and treatment burden compared to non-dialysis management. Elderly patients may therefore come to regret this decision. This study investigated (1) extent of patients' decision regret after starting dialysis, and (2) potentially modifiable predictors of regret: satisfaction with chronic kidney disease education, decisional conflict, and decision-making involvement. Cross-sectional study of 103 dialysis patients above 70 years old surveyed at Singapore General Hospital's renal medicine clinics between March and June 2017. Participants reported their levels of decision regret on the Decision Regret Scale (DRS), retrospective decisional conflict on the Decisional Conflict Scale, information satisfaction, and decision-making involvement. 81% of participants reported no decision regret (DRS score <50), 11% ambivalence (DRS =50), and 8% regret (DRS >50). In individual DRS items, 19% felt dialysis had done them harm and 16% would not make the same decision again. In multivariable analyses, lower information satisfaction [b = -0.07 (95% CI: -0.13, -0.01)] and decisional conflict [b = 0.004 (95% CI: 0.002, 0.006)] were significantly associated with decision regret. Although majority of elderly dialysis patients were comfortable with their decision to start dialysis, a proportion was ambivalent or regretted this choice. Regret was more likely among those who experienced decisional conflict and/or expressed poorer information satisfaction. Healthcare professionals should recognize these risk factors and take steps to minimize chances of regret among this population subset. This article is protected by copyright. All rights reserved.

Microcirculation assessment using an individualized model for diffuse reflectance spectroscopy and conventional laser Doppler flowmetry

NASA Astrophysics Data System (ADS)

Strömberg, Tomas; Karlsson, Hanna; Fredriksson, Ingemar; Nyström, Fredrik H.; Larsson, Marcus

2014-05-01

Microvascular assessment would benefit from co-registration of blood flow and hemoglobin oxygenation dynamics during stimulus response tests. We used a fiber-optic probe for simultaneous recording of white light diffuse reflectance (DRS; 475-850 nm) and laser Doppler flowmetry (LDF; 780 nm) spectra at two source-detector distances (0.4 and 1.2 mm). An inverse Monte Carlo algorithm, based on a multiparameter three-layer adaptive skin model, was used for analyzing DRS data. LDF spectra were conventionally processed for perfusion. The system was evaluated on volar forearm recordings of 33 healthy subjects during a 5-min systolic occlusion protocol. The calibration scheme and the optimal adaptive skin model fitted DRS spectra at both distances within 10%. During occlusion, perfusion decreased within 5 s while oxygenation decreased slowly (mean time constant 61 s dissociation of oxygen from hemoglobin). After occlusion release, perfusion and oxygenation increased within 3 s (inflow of oxygenized blood). The increased perfusion was due to increased blood tissue fraction and speed. The supranormal hemoglobin oxygenation indicates a blood flow in excess of metabolic demands. In conclusion, by integrating DRS and LDF in a fiber-optic probe, a powerful tool for assessment of blood flow and oxygenation in the same microvascular bed has been presented.

Dopamine D2 receptor availability is linked to hippocampal–caudate functional connectivity and episodic memory

PubMed Central

Nyberg, Lars; Karalija, Nina; Salami, Alireza; Andersson, Micael; Wåhlin, Anders; Kaboovand, Neda; Köhncke, Ylva; Axelsson, Jan; Rieckmann, Anna; Papenberg, Goran; Garrett, Douglas D.; Riklund, Katrine; Lövdén, Martin; Bäckman, Lars

2016-01-01

D1 and D2 dopamine receptors (D1DRs and D2DRs) may contribute differently to various aspects of memory and cognition. The D1DR system has been linked to functions supported by the prefrontal cortex. By contrast, the role of the D2DR system is less clear, although it has been hypothesized that D2DRs make a specific contribution to hippocampus-based cognitive functions. Here we present results from 181 healthy adults between 64 and 68 y of age who underwent comprehensive assessment of episodic memory, working memory, and processing speed, along with MRI and D2DR assessment with [11C]raclopride and PET. Caudate D2DR availability was positively associated with episodic memory but not with working memory or speed. Whole-brain analyses further revealed a relation between hippocampal D2DR availability and episodic memory. Hippocampal and caudate D2DR availability were interrelated, and functional MRI-based resting-state functional connectivity between the ventral caudate and medial temporal cortex increased as a function of caudate D2DR availability. Collectively, these findings indicate that D2DRs make a specific contribution to hippocampus-based cognition by influencing striatal and hippocampal regions, and their interactions. PMID:27339132

Microcirculation assessment using an individualized model for diffuse reflectance spectroscopy and conventional laser Doppler flowmetry.

PubMed

Strömberg, Tomas; Karlsson, Hanna; Fredriksson, Ingemar; Nyström, Fredrik H; Larsson, Marcus

2014-05-01

Microvascular assessment would benefit from co-registration of blood flow and hemoglobin oxygenation dynamics during stimulus response tests. We used a fiber-optic probe for simultaneous recording of white light diffuse reflectance (DRS; 475-850 nm) and laser Doppler flowmetry (LDF; 780 nm) spectra at two source-detector distances (0.4 and 1.2 mm). An inverse Monte Carlo algorithm, based on a multiparameter three-layer adaptive skin model, was used for analyzing DRS data. LDF spectra were conventionally processed for perfusion. The system was evaluated on volar forearm recordings of 33 healthy subjects during a 5-min systolic occlusion protocol. The calibration scheme and the optimal adaptive skin model fitted DRS spectra at both distances within 10%. During occlusion, perfusion decreased within 5 s while oxygenation decreased slowly (mean time constant 61 s; dissociation of oxygen from hemoglobin). After occlusion release, perfusion and oxygenation increased within 3 s (inflow of oxygenized blood). The increased perfusion was due to increased blood tissue fraction and speed. The supranormal hemoglobin oxygenation indicates a blood flow in excess of metabolic demands. In conclusion, by integrating DRS and LDF in a fiber-optic probe, a powerful tool for assessment of blood flow and oxygenation in the same microvascular bed has been presented.

Immobilization of cationic antimicrobial peptides and natural cashew gum in nanosheet systems for the investigation of anti-leishmanial activity.

PubMed

Bittencourt, Clicia Ramos; de Oliveira Farias, Emanuel Airton; Bezerra, Karla Costa; Véras, Leiz Maria Costa; Silva, Vladimir Costa; Costa, Carlos Henrique Nery; Bemquerer, Marcelo P; Silva, Luciano Paulino; Souza de Almeida Leite, José Roberto de; Eiras, Carla

2016-02-01

This report details the development of thin films containing an antimicrobial peptide, specifically, dermaseptin 01 (GLWSTIKQKGKEAAIAAA-KAAGQAALGAL-NH2, [DRS 01]), and a natural polysaccharide, for a novel application in detecting the presence of Leishmania cells and maintaining anti-leishmanial activity. The peptide DRS 01 was immobilized in conjunction with natural cashew gum (CG) onto an indium tin oxide (ITO) substrate using the Layer-by-Layer (LbL) deposition technique. The LbL film ITO/CG/DRS 01, containing DRS 01 as the outer layer, was capable of detecting the presence of Leishmania cells and acting as an anti-leishmanial system. Detection was performed using cyclic voltammetry (CV) in phosphate buffer (pH7.2) in the presence of promastigote cells (0-10(7)cells/mL). The results showed a linear and inversely proportional relation between the concentration of Leishmania infantum protozoan cells and the measured current values obtained for the films, which was attributed to the effect of peptide-induced lysis of the cell membrane, and resulted in freed residues that were adsorbed on the electrode surface. With this, the paper shows a method using thin films with this new material to demonstrate the anti-leishmanial activity in vitro models of carpet-like mechanisms. Copyright © 2015 Elsevier B.V. All rights reserved.

18-Degree-of-Freedom Controller Design for the ST7 Disturbance Reduction System

NASA Technical Reports Server (NTRS)

Markley, F. L.; Maghami, P. G.; Houghton, M. B.; Hsu, O. C.

2003-01-01

This paper presents the overall design and analysis process of the spacecraft controller being developed at NASA's Goddard Space Flight Center to close the loop between the GRS and the micro-newton colloidal thrusters. The essential dynamics of the ST7-DRS are captured in a simulation including eighteen rigid-body dynamic degrees of freedom: three translations and three rotations for the spacecraft and for each test mass. The ST7 DRS comprises three control systems: the attitude control system (ACS) to maintain a sun-pointing attitude; the drag free control (DFC) to center the spacecraft about the test masses; and the test mass suspension control. This paper summarizes the control design and analysis of the ST7-DRS 18-DOF model, and is an extension of previous analyses employing a 7-DOF planar model of ST-7.

Temperature dependences of characteristics of 2,5-hexanediol and 1,2,6-hexanetriol cluster structures according to dielectric radiospectroscopy

NASA Astrophysics Data System (ADS)

Usacheva, T. M.; Zhuravlev, V. I.

2013-03-01

Dielectric radiospectra (DRS) of 2,5-hexanediol and 1,2,6-hexanetriol at frequencies of 1 MHz, 9.375, 36.885, and 74.569 GHz in a temperature range of 303-423 K (above the glass transition temperatures) are studied. Experimental DRS are analyzed using the Dissado-Hill (DH) cluster model. The dependence of the equilibrium and relaxation characteristics of DRS on the number of OH groups is studied. The dipole moments of the clusters are calculated. The change in the orientation of the dipole moments of the molecules in the cluster during the rearranging of its structure is characterized through the unit vector of the longitudinal component of dipole moment M e of the cluster. The relation between a change in the Onsager-Kirkwood-Fröhlich correlation factor and the behavior of M e is shown.

AOIPS data base management systems support for GARP data sets

NASA Technical Reports Server (NTRS)

Gary, J. P.

1977-01-01

A data base management system is identified, developed to provide flexible access to data sets produced by GARP during its data systems tests. The content and coverage of the data base are defined and a computer-aided, interactive information storage and retrieval system, implemented to facilitate access to user specified data subsets, is described. The computer programs developed to provide the capability were implemented on the highly interactive, minicomputer-based AOIPS and are referred to as the data retrieval system (DRS). Implemented as a user interactive but menu guided system, the DRS permits users to inventory the data tape library and create duplicate or subset data sets based on a user selected window defined by time and latitude/longitude boundaries. The DRS permits users to select, display, or produce formatted hard copy of individual data items contained within the data records.

Diffuse Reflectance Spectroscopy and Colorimetry as a Diagnostic Tool for Acanthosis Nigricans

NASA Astrophysics Data System (ADS)

Pattamadilok, Bensachee; Devpura, Suneetha; Syed, Zain U.; Vemulapalli, Pranita; Henderson, Marsha; Rehse, Steven J.; Hamzavi, Iltefat; Mahmoud, Bassel H.; Lim, Henry W.; Naik, Ratna

2011-03-01

The purpose of this study was to quantify skin color changes due to Acanthosis Nigricans, a disorder common among prediabetic and obese individuals. The non-invasive optical technique diffuse reflectance spectroscopy (DRS) was used to determine skin melanin, oxyhemoglobin and deoxyhemoglobin content through the measured absorption spectrum. Colorimetery was used to measure skin color based on the standard Tristimulus values (L*, a*, and b*). Data was obtained from eight patients, spanning eight months of treatment. Measurements were obtained from lesion tissue on the neck and healthy skin was used as a control. L*, a* and b* values showed significant differences between lesion and normal controls, whereas melanin was the only parameter which showed statistical significant differences in DRS measurements. Future work will use more sensitive chemometric methods to increase diagnostic accuracy based on the raw spectra of the DRS.

Underground Explosions

DTIC Science & Technology

2015-09-09

AVC‐VTN‐15‐G06 “Underground  Explosions”  By  Vitaly  V. Adushkin and Alexander...Language Book "UNDERGROUND EXPLOSIONS" Drs. Vitaly V. Adushkin and Alexander A. Spivak Dr. Anastasia Stroujkova and Professor Paul Richards Weston...SAQMMA13M2475 DOS/AVC/MNA UNLIMITED “Underground Explosions”, a Russian language book authored by Drs. Vitaly V. Adushkin and Alexander A. Spivak has been

Downregulated CDKN1C/p57kip2 drives tumorigenesis and associates with poor overall survival in breast cancer.

PubMed

Qiu, Zhu; Li, Yunhai; Zeng, Beilei; Guan, Xiaoqin; Li, Hongzhong

2018-02-26

CDKN1C, also known as p57 kip2 , is considered to be a potential tumor suppressor implicated in several kinds of human cancers. However, the current knowledge of CDKN1C in breast cancer remains obscure. In the present study, we demonstrated that CDKN1C was dramatically downregulated in breast cancer compared with normal tissues by using real-time quantitative polymerase chain reaction, western blot and two public data portals: The Cancer Genome Atlas (TCGA) and Oncomine datasets. Moreover, the expression of CDKN1C was correlated with age and tumor size in the TCGA cohort containing 708 cases of breast cancer. Low expression of CDKN1C was significantly associated with poor overall survival (OS) in the TCGA cohort and validated cohort composed of 1402 patients. Multivariate Cox regression analysis indicated that CDKN1C was an independent prognostic factor for worse OS (HR = 1.78, 95% CI: 1.09-2.89, p = 0.020). Furthermore, gene set enrichment analysis (GSEA) revealed that CDKN1C was significantly correlated with gene signatures involving DNA repair, cell cycle, glycolysis, adipogenesis, and two critical signaling pathways mTORC1 and PI3K/Akt/mTOR. In conclusion, our data suggested an essential role of CDKN1C in the tumorgenesis of breast cancer. Targeting CDKN1C may be a promising strategy for anticancer therapeutics. Copyright © 2018 Elsevier Inc. All rights reserved.

Promoter methylation of the immune checkpoint receptor PD-1 (PDCD1) is an independent prognostic biomarker for biochemical recurrence-free survival in prostate cancer patients following radical prostatectomy.

PubMed

Goltz, Diane; Gevensleben, Heidrun; Dietrich, Jörn; Ellinger, Jörg; Landsberg, Jennifer; Kristiansen, Glen; Dietrich, Dimo

2016-01-01

Biomarkers that facilitate the prediction of disease recurrence in prostate cancer (PCa) may enable physicians to personalize treatment for individual patients. In the current study, PD-1 ( PDCD1 ) promoter methylation was assessed in a cohort of 498 PCa patients included in The Cancer Genome Atlas (TCGA) and a second cohort of 300 PCa cases treated at the University Hospital of Bonn. In the TCGA cohort, the PD-1 promoter was significantly hypermethylated in carcinomas versus normal prostatic epithelium (55.5% vs. 38.2%, p < 0.001) and PD-1 methylation ( mPD-1 ) inversely correlated with PD-1 mRNA expression in PCa (Spearman's ρ = -0.415, p < 0.001). In both cohorts, mPD-1 significantly correlated with preoperative prostate specific antigen (PSA). In univariate Cox Proportional Hazard analysis, mPD-1 served as a significant prognostic factor for biochemical recurrence (BCR)-free survival (Hazard ratio: HR = 2.35 [1.35-4.10], p = 0.003, n = 410) in the TCGA cohort. In multivariate analysis, mPD-1 was shown to add significant independent prognostic information adjunct to pathologic tumor category (pT) and Gleason grading group (HR = 2.08 [1.16-3.74], p = 0.014, n = 350). PD-1 promoter methylation analyses could thus potentially aid the identification of patients which might benefit from adjuvant treatment after radical prostatectomy. Moreover, our data suggest an intrinsic role of PD-1 in PCa carcinogenesis and disease progression, which needs to be addressed in future studies.

NRAO Astronomer Wins Max-Planck Research Award

NASA Astrophysics Data System (ADS)

2005-04-01

galaxies. "The phone call from Prof. Fruehwald, president of the Humboldt Foundation, was quite a shock, and overwhelming, but much appreciated," Carilli said. "Now I just have to make good on their investment. Fortunately, I have a lot of help. I consider this award a recognition of our team's efforts over the last few years." The team includes collaborators in Bonn, Profs. Karl Menten and Frank Bertoldi; Heidelberg, Drs. Fabian Walter and Eva Schinnerer; and in France, Dr. Pierre Cox and Prof. Alain Omont. Carilli added: "In an era of big international telescope projects, I think we have set the standard for successful international research collaborations. These folks are not only my professional colleagues, but good friends." Carilli received a B.A. in Physics and Astronomy from the University of Pennsylvania and, in 1989, a Ph.D. in Physics from the Massachusetts Institute of Technology. After serving in research positions at NRAO in Socorro, the Harvard-Smithsonian Center for Astrophysics, and Leiden Observatory in the Netherlands, Carilli joined NRAO's permanent scientific staff in 1996. He also was a visiting Humboldt fellow in Bonn in 1999. He serves on a number of scientific advisory committees, and recently was chair of the international science advisory committee for the Square Kilometer Array project. He has co-edited five books and authored numerous research papers in a wide variety of scientific journals. The National Radio Astronomy Observatory is a facility of the National Science Foundation, operated under cooperative agreement by Associated Universities, Inc.

A benders decomposition approach to multiarea stochastic distributed utility planning

NASA Astrophysics Data System (ADS)

McCusker, Susan Ann

individual models. These constraints are presented as a heuristic for the given examples; future research will investigate conditions for convergence. A ten-year multi-area example demonstrates the decomposition approach and suggests the ability of DRs and new transmission to modify capacity additions and production costs by changing demand and power flows. Results demonstrate that DR and new transmission options may lead to greater capacity additions, but resulting production cost savings more than offset extra capacity costs.

Movement, Transport, and Scour of Particulate Organic Matter and Aquatic Invertebrates Downstream from a Peaking Hydropower Project.

DTIC Science & Technology

1983-05-01

tigations, Clemson, S. C . 29631 and U. S. Army ED- It. REPORT DATE gineer Waterways Experiment Station, Environmental May 1983 Laboratory, P. 0. Box 631...ON eport) Washington, D. C . 20314 Unclassified I&. NMITORING AGENCY NAME & ADORVESS( Idfieuf orn o C ..,bDIMi OW~~ IS. DECkASFCTO(ONRDN W DISTRIBUTION...Reservoir Research Program, U. S. Fish and Wildlife Ser- vice, Clemson, S. C .; and Drs. John Nestler and Gary Saul, EL, WES. Preparation of this report

Optical signature of nerve tissue-Exploratory ex vivo study comparing optical, histological, and molecular characteristics of different adipose and nerve tissues.

PubMed

Balthasar, Andrea J R; Bydlon, Torre M; Ippel, Hans; van der Voort, Marjolein; Hendriks, Benno H W; Lucassen, Gerald W; van Geffen, Geert-Jan; van Kleef, Maarten; van Dijk, Paul; Lataster, Arno

2018-05-14

During several anesthesiological procedures, needles are inserted through the skin of a patient to target nerves. In most cases, the needle traverses several tissues-skin, subcutaneous adipose tissue, muscles, nerves, and blood vessels-to reach the target nerve. A clear identification of the target nerve can improve the success of the nerve block and reduce the rate of complications. This may be accomplished with diffuse reflectance spectroscopy (DRS) which can provide a quantitative measure of the tissue composition. The goal of the current study was to further explore the morphological, biological, chemical, and optical characteristics of the tissues encountered during needle insertion to improve future DRS classification algorithms. To compare characteristics of nerve tissue (sciatic nerve) and adipose tissues, the following techniques were used: histology, DRS, absorption spectrophotometry, high-resolution magic-angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy, and solution 2D 13 C- 1 H heteronuclear single-quantum coherence spectroscopy. Tissues from five human freshly frozen cadavers were examined. Histology clearly highlights a higher density of cellular nuclei, collagen, and cytoplasm in fascicular nerve tissue (IFAS). IFAS showed lower absorption of light around 1200 nm and 1750 nm, higher absorption around 1500 nm and 2000 nm, and a shift in the peak observed around 1000 nm. DRS measurements showed a higher water percentage and collagen concentration in IFAS and a lower fat percentage compared to all other tissues. The scattering parameter (b) was highest in IFAS. The HR-MAS NMR data showed three extra chemical peak shifts in IFAS tissue. Collagen, water, and cellular nuclei concentration are clearly different between nerve fascicular tissue and other adipose tissue and explain some of the differences observed in the optical absorption, DRS, and HR-NMR spectra of these tissues. Some differences observed between fascicular

A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers.

PubMed

Berger, Ashton C; Korkut, Anil; Kanchi, Rupa S; Hegde, Apurva M; Lenoir, Walter; Liu, Wenbin; Liu, Yuexin; Fan, Huihui; Shen, Hui; Ravikumar, Visweswaran; Rao, Arvind; Schultz, Andre; Li, Xubin; Sumazin, Pavel; Williams, Cecilia; Mestdagh, Pieter; Gunaratne, Preethi H; Yau, Christina; Bowlby, Reanne; Robertson, A Gordon; Tiezzi, Daniel G; Wang, Chen; Cherniack, Andrew D; Godwin, Andrew K; Kuderer, Nicole M; Rader, Janet S; Zuna, Rosemary E; Sood, Anil K; Lazar, Alexander J; Ojesina, Akinyemi I; Adebamowo, Clement; Adebamowo, Sally N; Baggerly, Keith A; Chen, Ting-Wen; Chiu, Hua-Sheng; Lefever, Steve; Liu, Liang; MacKenzie, Karen; Orsulic, Sandra; Roszik, Jason; Shelley, Carl Simon; Song, Qianqian; Vellano, Christopher P; Wentzensen, Nicolas; Weinstein, John N; Mills, Gordon B; Levine, Douglas A; Akbani, Rehan

2018-04-09

We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique molecular features, clinically significant subtypes, and potential therapeutic targets. We found 61 somatic copy-number alterations (SCNAs) and 46 significantly mutated genes (SMGs). Eleven SCNAs and 11 SMGs had not been identified in previous TCGA studies of the individual tumor types. We found functionally significant estrogen receptor-regulated long non-coding RNAs (lncRNAs) and gene/lncRNA interaction networks. Pathway analysis identified subtypes with high leukocyte infiltration, raising potential implications for immunotherapy. Using 16 key molecular features, we identified five prognostic subtypes and developed a decision tree that classified patients into the subtypes based on just six features that are assessable in clinical laboratories. Copyright © 2018 Elsevier Inc. All rights reserved.

Commentary on: "An integrated metabolic atlas of clear cell renal cell carcinoma." Hakimi AA, Reznik E, Lee CH, Creighton CJ, Brannon AR, Luna A, Aksoy BA, Liu EM, Shen R, Lee W, Chen Y, Stirdivant SM, Russo P, Chen YB, Tickoo SK, Reuter VE, Cheng EH, Sander C, Hsieh JJ.: Cancer Cell. 2016 Jan 11;29(1):104-16.

PubMed

Lee, Byron H

2017-09-01

Dysregulated metabolism is a hallmark of cancer, manifested through alterations in metabolites. We performed metabolomic profiling on 138 matched clear cell renal cell carcinoma (ccRCC)/normal tissue pairs and found that ccRCC is characterized by broad shifts in central carbon metabolism, one-carbon metabolism, and antioxidant response. Tumor progression and metastasis were associated with metabolite increases in glutathione and cysteine/methionine metabolism pathways. We develop an analytic pipeline and visualization tool (metabolograms) to bridge the gap between TCGA transcriptomic profiling and our metabolomic data, which enables us to assemble an integrated pathway-level metabolic atlas and to demonstrate discordance between transcriptome and metabolome. Lastly, expression profiling was performed on a high-glutathione cluster, which corresponds to a poor-survival subgroup in the ccRCC TCGA cohort. Copyright © 2017 Elsevier Inc. All rights reserved.

Enhancing Exposure Therapy for PTSD: Virtual Reality and Imaginal Exposure with a Cognitive Enhancer

DTIC Science & Technology

2015-10-01

VA, Dr. Rachel Stewart (formerly Rachel Robertson) began an emergency medical/ maternity leave on 8/19/13. At the present time, Dr. Stewart’s return...part-time to fulfill her duties. At NICoE, Dr. Suzanne Leaman returned from her maternity leave on 4/29/13. At USC, Jack Mondonedo returned from... maternity leave . Drs. Maryrose Gerardi (Emory) and Judith Cukor (Cornell) participated in a conference call with Drs. Holloway, Riggs, and Adamson on 12/13

Tussenrapportage Validatie Onderwijsvernieuwingen (Validation Assistant in Instructional Design)

DTIC Science & Technology

2007-05-01

validatie onderwij svemieuwingen D)atum mei 2007 Auteur (s) drs. J.P. van Meer drs. G,J. Veldhuis dr. M.L. van Ernmerik M.G. van Schaik Rubricering...als doel om nog beter is het van belang dat het maken van keuzes Auteur (s) passende adviezen te kunnen genereren. binnen een moeilijk grijpbaar...benaderd door de theorie achter de onderwijsconcepten te toetsen aan het oordeel van de expert. Er zijn echter beperkingen in deze opzet denkbaar die

Fe-oxide mineralogy of the Jiujiang red earth sediments and implications for Quaternary climate change, southern China.

PubMed

Yin, Ke; Hong, Hanlie; Algeo, Thomas J; Churchman, Gordon Jock; Li, Zhaohui; Zhu, Zongmin; Fang, Qian; Zhao, Lulu; Wang, Chaowen; Ji, Kaipeng; Lei, Weidong; Duan, Zhenggang

2018-02-26

Diffuse reflectance spectrophotometry (DRS) is a new, fast, and reliable method to characterize Fe-oxides in soils. The Fe-oxide mineralogy of the Jiujiang red earth sediments was investigated using DRS to investigate the climate evolution of southern China since the mid-Pleistocene. The DRS results show that hematite/(hematite + goethite) ratios [Hm/(Hm + Gt)] exhibit an upward decreasing trend within the Jiujiang section, suggesting a gradual climate change from warm and humid in the middle Pleistocene to cooler and drier in the late Pleistocene. Upsection trends toward higher (orthoclase + plagioclase)/quartz ratios [(Or + Pl)/Q] and magnetic susceptibility values (χ lf ) support this inference, which accords with global climate trends at that time. However, higher-frequency climatic subcycles observed in loess sections of northern China are not evident in the Jiujiang records, indicating a relatively lower climate sensitivity of the red earth sediments in southern China.

Delirium in elderly people: a study of a psychiatric liaison service in north India.

PubMed

Grover, Sandeep; Kate, Natasha; Agarwal, Munish; Mattoo, Surendra Kumar; Avasthi, Ajit; Malhotra, Savita; Kulhara, Parmanand; Chakrabarti, Subho; Basu, Debasish

2012-01-01

Very few studies from India have studied the phenomenology of delirium. The aim of the present study was to study the phenomenology as measured using the Delirium Rating Scale-Revised-98 (DRS-R98), the associated etiologies and the outcome of delirium among the elderly participants seen by the consultation-liaison psychiatric service in India. In addition, an attempt was made to study the factor structure of symptoms using principal components analysis. The case notes of 109 elderly patients referred to psychiatry liaison services were reviewed. The mean age of the sample was 73.35 years (SD: 7.44; range 65-95 years) and two-thirds of the sample had hospital emergent delirium. The mean DRS-R98 severity score was 18.77 and the DRS-R98 total score was 24.81. In 15 patients the DRS-R98 scores were in the subsyndromal range. Among the various symptoms present, most patients had sleep-wake cycle disturbance, disturbance in orientation, attention and short-term memory impairments, fluctuation of symptoms, temporal onset of symptoms and a physical disorder. Principal components analysis identified three factors which explained 43.5% of variance of symptomatology and it yielded a three-factor structure. Endocrine/metabolic disturbances were the commonest associated etiological category with delirium. The mean hospital stay after being referred to psychiatry referral services was 8.89 days, after which delirium improved in 58.7% of cases. The mortality rate during the inpatient stay was 16.5%. Results suggest that the symptoms of delirium as assessed by DRS-R98 separate out into a three-factor structure. Delirium is commonly associated with metabolic endocrine disturbances and about one-sixth of the patients die during the short inpatient stay.

Data Sets from Major NCI Initiaves

Cancer.gov

The NCI Data Catalog includes links to data collections produced by major NCI initiatives and other widely used data sets, including animal models, human tumor cell lines, epidemiology data sets, genomics data sets from TCGA, TARGET, COSMIC, GSK, NCI60.

The Dynamic Range for Korean Standard Sentence Material: A Gender Comparison in a Male and a Female Speakers.

PubMed

Park, Kyeong-Yeon; Jin, In-Ki

2015-09-01

The purpose of this study was to identify differences between the dynamic ranges (DRs) of male and female speakers using Korean standard sentence material. Consideration was especially given to effects within the predefined segmentalized frequency-bands. We used Korean standard sentence lists for adults as stimuli. Each sentence was normalized to a root-mean-square of 65 dB sound pressure level. The sentences were then modified to ensure there were no pauses, and the modified sentences were passed through a filter bank in order to perform the frequency analysis. Finally, the DR was quantified using a histogram that showed the cumulative envelope distribution levels of the speech in each frequency band. In DRs that were averaged across all frequency bands, there were no significant differences between the male and the female speakers. However, when considering effects within the predefined frequency bands, there were significant differences in several frequency bands between the DRs of male speech and those of female speech. This study shows that the DR of speech for the male speaker differed from the female speaker in nine frequency bands among 21 frequency bands. These observed differences suggest that a standardized DR of male speech in the band-audibility function of the speech intelligibility index may differ from that of female speech derived in the same way. Further studies are required to derive standardized DRs for Korean speakers.

Diffusion in biofilms respiring on electrodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Renslow, Ryan S.; Babauta, Jerome T.; Majors, Paul D.

2012-11-15

The goal of this study was to measure spatially and temporally resolved effective diffusion coefficients (De) in biofilms respiring on electrodes. Two model electrochemically active biofilms, Geobacter sulfurreducens PCA and Shewanella oneidensis MR-1, were investigated. A novel nuclear magnetic resonance microimaging perfusion probe capable of simultaneous electrochemical and pulsed-field gradient nuclear magnetic resonance (PFG-NMR) techniques was used. PFG-NMR allowed for noninvasive, nondestructive, high spatial resolution in situ De measurements in living biofilms respiring on electrodes. The electrodes were polarized so that they would act as the sole terminal electron acceptor for microbial metabolism. We present our results as both two-dimensionalmore » De heat maps and surface-averaged relative effective diffusion coefficient (Drs) depth profiles. We found that (1) Drs decreases with depth in G. sulfurreducens biofilms, following a sigmoid shape; (2) Drs at a given location decreases with G. sulfurreducens biofilm age; (3) average De and Drs profiles in G. sulfurreducens biofilms are lower than those in S. oneidensis biofilms—the G. sulfurreducens biofilms studied here were on average 10 times denser than the S. oneidensis biofilms; and (4) halting the respiration of a G. sulfurreducens biofilm decreases the De values. Density, reflected by De, plays a major role in the extracellular electron transfer strategies of electrochemically active biofilms.« less

Diversified clinical presentations associated with a novel sal-like 4 gene mutation in a Chinese pedigree with Duane retraction syndrome.

PubMed

Yang, Ming-ming; Ho, Mary; Lau, Henry H W; Tam, Pancy O S; Young, Alvin L; Pang, Chi Pui; Yip, Wilson W K; Chen, LiJia

2013-01-01

To determine the underlying genetic cause of Duane retraction syndrome (DRS) in a non-consanguineous Chinese Han family. Detailed ophthalmic and physical examinations were performed on all members from a pedigree with DRS. All exons and their adjacent splicing junctions of the sal-like 4 (SALL4) gene were amplified with polymerase chain reaction and analyzed with direct sequencing in all the recruited family members and 200 unrelated control subjects. Clinical examination revealed a broad spectrum of phenotypes in the DRS family. Mutation analysis of SALL4 identified a novel heterozygous duplication mutation, c.1919dupT, which was completely cosegregated with the disease in the family and absent in controls. This mutation was predicted to cause a frameshift, introducing a premature stop codon, when translated, resulting in a truncated SALL4 protein, i.e., p.Met640IlefsX25. Bioinformatics analysis showed that the affected region of SALL4 shared a highly conserved sequence across different species. Diversified clinical manifestations were observed in the c.1919dupT carriers of the family. We identified a novel truncating mutation in the SALL4 gene that leads to diversified clinical features of DRS in a Chinese family. This mutation is predicted to result in a truncated SALL4 protein affecting two functional domains and cause disease development due to haploinsufficiency through nonsense-mediated mRNA decay.

Feasibility of quantitative diffuse reflectance spectroscopy for targeted measurement of renal ischemia during laparoscopic partial nephrectomy.

PubMed

Goel, Utsav O; Maddox, Michael M; Elfer, Katherine N; Dorsey, Philip J; Wang, Mei; McCaslin, Ian Ross; Brown, J Quincy; Lee, Benjamin R

2014-01-01

Reduction of warm ischemia time during partial nephrectomy (PN) is critical to minimizing ischemic damage and improving postoperative kidney function, while maintaining tumor resection efficacy. Recently, methods for localizing the effects of warm ischemia to the region of the tumor via selective clamping of higher-order segmental artery branches have been shown to have superior outcomes compared with clamping the main renal artery. However, artery identification can prolong operative time and increase the blood loss and reduce the positive effects of selective ischemia. Quantitative diffuse reflectance spectroscopy (DRS) can provide a convenient, real-time means to aid in artery identification during laparoscopic PN. The feasibility of quantitative DRS for real-time longitudinal measurement of tissue perfusion and vascular oxygenation in laparoscopic nephrectomy was investigated in vivo in six Yorkshire swine kidneys (n=three animals ). DRS allowed for rapid identification of ischemic areas after selective vessel occlusion. In addition, the rates of ischemia induction and recovery were compared for main renal artery versus tertiary segmental artery occlusion, and it was found that the tertiary segmental artery occlusion trends toward faster recovery after ischemia, which suggests a potential benefit of selective ischemia. Quantitative DRS could provide a convenient and fast tool for artery identification and evaluation of the depth, spatial extent, and duration of selective tissue ischemia in laparoscopic PN.

Environmental Progestins Progesterone and Drospirenone Alter the Circadian Rhythm Network in Zebrafish (Danio rerio).

PubMed

Zhao, Yanbin; Castiglioni, Sara; Fent, Karl

2015-08-18

Progestins alter hormone homeostasis and may result in reproductive effects in humans and animals. Thus far, studies in fish have focused on the hypothalamic-pituitary-gonadal (HPG)-axis and reproduction, but other effects have little been investigated. Here we report that progesterone (P4) and drospirenone (DRS) interfere with regulation of the circadian rhythm in fish. Breeding pairs of adult zebrafish were exposed to P4 and DRS at concentrations between 7 and 13 650 ng/L for 21 days. Transcriptional analysis revealed significant and dose-dependent alterations of the circadian rhythm network in the brain with little effects in the gonads. Significant alterations of many target transcripts occurred even at environmental relevant concentrations of 7 ng/L P4 and at 99 ng/L DRS. They were fully consistent with the well-described circadian rhythm negative/positive feedback loops. Transcriptional alterations of the circadian rhythm network were correlated with those in the HPG-Liver-axis. Fecundity was decreased at 742 (P4) and 2763 (DRS) ng/L. Dose-dependent alterations in the circadian rhythm network were also observed in F1 eleuthero-embryos. Our results suggest a potential target of environmental progestins, the circadian rhythm network, in addition to the adverse reproductive effects. Forthcoming studies should show whether the transcriptional alterations in circadian rhythm translate into physiological effects.

Geochemical baseline level and function and contamination of phosphorus in Liao River Watershed sediments of China.

PubMed

Liu, Shaoqing; Wang, Jing; Lin, Chunye; He, Mengchang; Liu, Xitao

2013-10-15

The quantitative assessment of P contamination in sediments is a challenge due to sediment heterogeneity and the lacking of geochemical background or baseline levels. In this study, a procedure was proposed to determine the average P background level and P geochemical baseline level (GBL) and develop P geochemical baseline functions (GBF) for riverbed sediments of the Liao River Watershed (LRW). The LRW has two river systems - the Liao River System (LRS) and the Daliao River System (DRS). Eighty-eight samples were collected and analyzed for P, Al, Fe, Ca, organic matter, pH, and texture. The results show that Fe can be used as a better particle-size proxy to construct the GBF of P (P (mg/kg) = 39.98 + 166.19 × Fe (%), R(2) = 0.835, n = 66). The GBL of P was 675 mg/kg, while the average background level of P was 355 mg/kg. Noting that many large cities are located in the DRS watershed, most of the contaminated sites were located within the DRS and the riverbed sediments were more contaminated by P in the DRS watershed than in the LRS watershed. The geochemical background and baseline information of P are of great importance in managing P levels within the LRW. Copyright © 2013 Elsevier Ltd. All rights reserved.

Feasibility of quantitative diffuse reflectance spectroscopy for targeted measurement of renal ischemia during laparoscopic partial nephrectomy

NASA Astrophysics Data System (ADS)

Goel, Utsav O.; Maddox, Michael M.; Elfer, Katherine N.; Dorsey, Philip J.; Wang, Mei; McCaslin, Ian Ross; Brown, J. Quincy; Lee, Benjamin R.

2014-10-01

Reduction of warm ischemia time during partial nephrectomy (PN) is critical to minimizing ischemic damage and improving postoperative kidney function, while maintaining tumor resection efficacy. Recently, methods for localizing the effects of warm ischemia to the region of the tumor via selective clamping of higher-order segmental artery branches have been shown to have superior outcomes compared with clamping the main renal artery. However, artery identification can prolong operative time and increase the blood loss and reduce the positive effects of selective ischemia. Quantitative diffuse reflectance spectroscopy (DRS) can provide a convenient, real-time means to aid in artery identification during laparoscopic PN. The feasibility of quantitative DRS for real-time longitudinal measurement of tissue perfusion and vascular oxygenation in laparoscopic nephrectomy was investigated in vivo in six Yorkshire swine kidneys (n=three animals). DRS allowed for rapid identification of ischemic areas after selective vessel occlusion. In addition, the rates of ischemia induction and recovery were compared for main renal artery versus tertiary segmental artery occlusion, and it was found that the tertiary segmental artery occlusion trends toward faster recovery after ischemia, which suggests a potential benefit of selective ischemia. Quantitative DRS could provide a convenient and fast tool for artery identification and evaluation of the depth, spatial extent, and duration of selective tissue ischemia in laparoscopic PN.

Orion Nebula and Planetary Nebulae

NASA Technical Reports Server (NTRS)

Dufour, Reginald J.

1998-01-01

This report summarizes the research performed at Rice University related to NASA-Ames University consortium grant NCC2-5199 during the two year period 1996 September 1 through 1998 August 31. The research program, titled Orion Nebula and Planetary Nebulae, involved the analysis of Hubble Space Telescope (HST) imagery and spectroscopy of the Orion Nebula and of the planetary nebulae NGC 6818 and NGC 6210. In addition, we analyzed infrared spectra of the Orion Nebula taken with the Infrared Space Observatory (ISO) The primary collaborators at NASA-Ames were Drs. R. H. Rubin, A. G. C. M. Tielens, S. W. J. Colgan, and S. D. Lord (Tielens & Lord has since changed institutions). Other collaborators include Drs. P. G. Martin (CITA, Toronto), G. J. Ferland (U. KY), J. A. Baldwin (CTIO, Chile), J. J. Hester (ASU), D. K. Walter (SCSU), and P. Harrington (U. MD). In addition to the Principal Investigator, Professor Reginald J. Dufour of the Department of Space Physics & Astronomy, the research also involved two students, Mr. Matthew Browning and Mr. Brent Buckalew. Mr. Browning will be graduating from Rice in 1999 May with a B.A. degree in Physics and Mr. Buckalew continues as a graduate student in our department, having recently received a NASA GSRP research fellowship (sponsored by Ames). The collaboration was very productive, with two refereed papers already appearing in the literature, several others in preparation, numerous meeting presentations and two press releases. Some of our research accomplishments are highlighted below. Attached to the report are copies of the two major publications. Note that this research continues to date and related extensions of it recently has been awarded time with the HST for 1999-2000.

Generating a focused view of disease ontology cancer terms for pan-cancer data integration and analysis

PubMed Central

Wu, Tsung-Jung; Schriml, Lynn M.; Chen, Qing-Rong; Colbert, Maureen; Crichton, Daniel J.; Finney, Richard; Hu, Ying; Kibbe, Warren A.; Kincaid, Heather; Meerzaman, Daoud; Mitraka, Elvira; Pan, Yang; Smith, Krista M.; Srivastava, Sudhir; Ward, Sari; Yan, Cheng; Mazumder, Raja

2015-01-01

Bio-ontologies provide terminologies for the scientific community to describe biomedical entities in a standardized manner. There are multiple initiatives that are developing biomedical terminologies for the purpose of providing better annotation, data integration and mining capabilities. Terminology resources devised for multiple purposes inherently diverge in content and structure. A major issue of biomedical data integration is the development of overlapping terms, ambiguous classifications and inconsistencies represented across databases and publications. The disease ontology (DO) was developed over the past decade to address data integration, standardization and annotation issues for human disease data. We have established a DO cancer project to be a focused view of cancer terms within the DO. The DO cancer project mapped 386 cancer terms from the Catalogue of Somatic Mutations in Cancer (COSMIC), The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium, Therapeutically Applicable Research to Generate Effective Treatments, Integrative Oncogenomics and the Early Detection Research Network into a cohesive set of 187 DO terms represented by 63 top-level DO cancer terms. For example, the COSMIC term ‘kidney, NS, carcinoma, clear_cell_renal_cell_carcinoma’ and TCGA term ‘Kidney renal clear cell carcinoma’ were both grouped to the term ‘Disease Ontology Identification (DOID):4467 / renal clear cell carcinoma’ which was mapped to the TopNodes_DOcancerslim term ‘DOID:263 / kidney cancer’. Mapping of diverse cancer terms to DO and the use of top level terms (DO slims) will enable pan-cancer analysis across datasets generated from any of the cancer term sources where pan-cancer means including or relating to all or multiple types of cancer. The terms can be browsed from the DO web site (http://www.disease-ontology.org) and downloaded from the DO’s Apache Subversion or GitHub repositories. Database URL: http://www.disease-ontology.org PMID

Bats, cyanide, and gold mining

USGS Publications Warehouse

Clark, Donald R.

1991-01-01

Although the boom days of prospectors and gold nuggets are long gone, modern technology enables gold to continue to be extracted from ore. Unfortunately, the extraction method has often been disastrous for bats and other wildlife, an issue I first became aware of in early 1989. Phone calls from Drs. Merlin Tuttle and Elizabeth Pierson, a BCI member and bat researcher from Berkeley, California, alerted me that bats were dying from apparent cyanide poisoning at gold mines in the western United States.

Monitoring of caffeine consumption effect on skin blood properties by diffuse reflectance spectroscopy

NASA Astrophysics Data System (ADS)

Milanic, Matija; Marin, Ana; Stergar, Jost; Verdel, Nina; Majaron, Boris

2017-07-01

Caffeine is the most widely consumed psychoactive substance in the world. It affects many tissues and organs, in particular central nervous system, heart, and blood vessels. The effect of caffeine on vascular smooth muscle cells is an initial transient contraction followed by significant vasodilatation. In this study we investigate the use of diffuse reflectance spectroscopy (DRS) for monitoring of vascular changes in human skin induced by caffeine consumption. DRS spectra were recorded on volar sides of the forearms of ten healthy volunteers at time delays of 0, 30, 60, 120, and 180 minutes after consumption of caffeine, while one subject served as a negative control. Analytical diffusion approximation solutions for diffuse reflectance from three-layer structures were used to assess skin composition (e.g., dermal blood volume fraction and oxygen saturation) by fitting to experimental data. The results demonstrate that cutaneous vasodynamics induced by caffeine consumption can be monitored by DRS, while changes in the control subject not consuming caffeine were insignificant.

Effects of Moquiniastrum polymorphum ssp floccosum ethnolic extract on colorectal carcinogenesis induced by 1,2-dimethylhydrazine.

PubMed

Limeiras, S M A; Oliveira, B C; Pessatto, L R; Pesarini, J R; Kassuya, C A L; Monreal, A C D; Cantero, W B; Antoniolli-Silva, R; Antoniolli-Silva, A C M B; Stefanello, M E A; Oliveira, R J

2017-03-16

The objective of this study was to evaluate the effect of Moquiniastrum polymorphum ssp floccosum ethanolic extract (MPEE) on 1,2 dimethylhydrazine (DMH)-induced colorectal carcinogenesis in mice. Forty-two male Swiss mice (Mus musculus) were subdivided into six groups (N = 7/group): negative control, DMH, MPEE, pre-treatment, simultaneous, and post-treatment. Results showed that MPEE has antigenotoxic potential on the tested protocols pre- and silmultaneous treatment, and the percent damage reductions (%DRs) were 81.88 and 93.12%, respectively. The micronucleus test demonstrated that MPEE has great antimutagenic activity, with %DRs higher than 77.09 in the associated groups. The aberrant crypt focus assay demonstrated anticarcinogenic potential of MPEE as the associated groups showed %DRs that ranged from 62.13 to 95.14%. The study shows that MPEE is nontoxic and has chemopreventive and anticarcinogenic activity, thus it may prove to be a promising medicinal plant in view of its demonstrated properties.

Relative validity of a food frequency questionnaire to identify dietary patterns in an adult Mexican population.

PubMed

Denova-Gutiérrez, Edgar; Tucker, Katherine L; Salmerón, Jorge; Flores, Mario; Barquera, Simón

2016-01-01

To examine the validity of a semi-quantitative food frequency questionnaire (SFFQ) to identify dietary patterns in an adult Mexican population. A 140-item SFFQ and two 24-hour dietary recalls (24DRs) were administered. Foods were categorized into 29 food groups used to derive dietary patterns via factor analysis. Pearson and intraclass correlations coefficients between dietary pattern scores identified from the SFFQ and 24DRs were assessed. Pattern 1 was high in snacks, fast food, soft drinks, processed meats and refined grains; pattern 2 was high in fresh vegetables, fresh fruits, and dairy products; and pattern 3 was high in legumes, eggs, sweetened foods and sugars. Pearson correlation coefficients between the SFFQ and the 24DRs for these patterns were 0.66 (P<0.001), 0.41 (P<0.001) and 0.29 (P=0.193) respectively. Our data indicate reasonable validity of the SFFQ, using factor analysis, to derive major dietary patterns in comparison with two 24DR.

Validity of a food frequency questionnaire to assess food intake in Mexican adolescent and adult population.

PubMed

Denova-Gutiérrez, Edgar; Ramírez-Silva, Ivonne; Rodríguez-Ramírez, Sonia; Jiménez-Aguilar, Alejandra; Shamah-Levy, Teresa; Rivera-Dommarco, Juan A

2016-01-01

To assess the validity of a 140-item semiquantitative food frequency questionnaire (SFFQ), in Mexican adolescents and adults. Dietary intakes using a SFFQ and two 24-hour dietary recalls (24DRs), in nonconsecutive days during the same week were measured from 178 adolescents and 230 adults participating in the Mexican National Health and Nutrition Survey-2012.Validity was evaluated using correlation coefficients (CC),deattenuated CC, linear regression models, cross-classification analysis, and the Bland-Altman method. In adults, deattenuated correlation coefficients between the SFFQ and the 24DRs ranged from 0.30 for folate to 0.61 for saturated fat. In addition, 63% adults and 62% adolescents were classified in the same and adjacent quartile of nutrient intake when comparing data from SFFQ and 24DRs. The SFFQ had moderate validity for energy, macronutrients and micronutrients. It also had good validity to rank individuals according to their dietary intake of different nutrients.

Diffuse reflectance spectroscopy of liver tissue

NASA Astrophysics Data System (ADS)

Reistad, Nina; Nilsson, Jan; Vilhelmsson Timmermand, Oskar; Sturesson, Christian; Andersson-Engels, Stefan

2015-06-01

Diffuse reflectance spectroscopy (DRS) with a fiber-optic contact probe is a cost-effective, rapid, and non-invasive optical method used to extract diagnosis information of tissue. By combining commercially available VIS- and NIR-spectrometers with various fiber-optic contact-probes, we have access to the full wavelength range from around 400 to 1600 nm. Using this flexible and portable spectroscopy system, we have acquired ex-vivo DRS-spectra from murine, porcine, and human liver tissue. For extracting the tissue optical properties from the measured spectra, we have employed and compared predictions from two models for light propagation in tissue, diffusion theory model (DT) and Monte Carlo simulations (MC). The focus in this work is on the capacity of this DRS-technique in discriminating metastatic tumor tissue from normal liver tissue as well as in assessing and characterizing damage to non-malignant liver tissue induced by preoperative chemotherapy for colorectal liver metastases.

Agarose hydrogel induced MCF-7 and BMG-1 cell line progressive 3D and 3D revert cultures.

PubMed

Subramaniyan, Aishwarya; Ravi, Maddaly

2018-04-01

3D culture systems have enhanced the utility of cancer cell lines as they are considered closer to the in vivo systems. A variety of changes are induced in cells cultured in 3D systems; an apparent and striking feature being the spontaneous acquisition of distinct morphological entities. 3D reverts (3DRs) can be obtained by introducing 3D aggregates in scaffold/matrix-free culture units. It could be seen that the two cell lines used in this study exhibited differences in 3DR structures, though both were cultured on agarose hydrogels. Also, differences in 3DR formation, growth and survival were different. While 3D aggregates of several cell lines have been reported for a variety of studies, there are no studies that describe or utilize 3DRs. 3DRs can provide insights into complex events that can occur in cancer cells; especially as material to study metastasis, migration, and invasion. © 2017 Wiley Periodicals, Inc.

Stephen Baylin, M.D., Explains Genetics and Epigenetics - TCGA

Cancer.gov

Stephen Baylin, M.D., at the Johns Hopkins Kimmel Cancer Center discusses the how alterations in the DNA code are deciphered in a combined effort with The Cancer Genome Atlas at the National Cancer Institute to decode the brain cancer genome.

It’s alive: microbes and cells in human milk and their potential benefits to mother and infant.

PubMed

Bode, Lars; McGuire, Mark; Rodriguez, Juan M; Geddes, Donna T; Hassiotou, Foteini; Hartmann, Peter E; McGuire, Michelle K

2014-09-01

Human milk is the optimal source of nutrition for the nursing infant. Classically, the nutrients (water, protein, lipid, carbohydrate, vitamins, and minerals) were studied as the critical components of milk serving the growth needs of the infant for optimum growth. However, human milk contains factors other than the classically defined nutrients for which researchers are investigating potential roles in infant and maternal health, development, and well-being. The symposium addressed some of the exciting factors being studied, including microbes and maternal cells found within milk. Drs. Michelle McGuire and Juan M. Rodríguez addressed the presence of a bacterial community in human milk produced by healthy and mastitic mothers, potential sources of those bacteria, and the impact of milk-derived bacteria on the nursing infant. Drs. Donna Geddes, Peter Hartmann, and Foteini Hassiotou discussed the potential importance of maternal cells. For years, immune cells were known to be present in human milk, but recent evidence suggests that their impact is as much on the infant as on the health of the lactating mammary gland. Finally, the existence of highly plastic stem cells in human milk opens doors for previously unforeseen developmental “training” of the nursing infant.

Monitoring radionuclide contamination in the unsaturated zone - Lessons learned at the Amargosa Desert Research Site, Nye County, Nevada

USGS Publications Warehouse

Stonestrom, David A.; Abraham, Jared D.; Andraski, Brian J.; Baker, Ronald J.; Mayers, C. Justin; Michel, Robert L.; Prudic, David E.; Striegl, Robert G.; Walvoord, Michelle Ann

2004-01-01

Contaminant-transport processes are being investigated at the U.S. Geological Survey’s Amargosa Desert Research Site (A DRS), adjacent to the Nation’s first commercial disposal facility for low-level radioactive waste. Gases containing tritium and radiocarbon are migrating through a 110-m thick unsaturated zone from unlined trenches that received waste from 1962 to 1992. Results relevant to long- term monitoring of radionuclides are summarized as follows. Contaminant plumes have unexpected histories and spatial configurations due to uncertainties in the: (1) geologic framework, (2) biochemical reactions involving waste components, (3) interactions between plume components and unsaturated-zone materials, (4) disposal practices, and (5) physical transport processes. Information on plume dynamics depends on ex-situ wet-chemical techniques because in-situ sensors for the radionuclides of interest do not exist. As at other radioactive-waste disposal facilities, radionuclides at the ADRS are mixed with varying amounts of volatile organic compounds (VOCs). Carbon-dioxide and VOC anomalies provide proxies for radioactive contamination. Contaminants in the unsaturated zone migrate along preferential pathways. Effective monitoring thus requires accurate geologic characterization. Direct- current electrical-resistivity imaging successfully mapped geologic units controlling preferential transport at the ADRS. Direct sampling of water from the unsaturated zone is complex and time consuming. Sampling plant water is an efficient alternative for mapping shallow tritium contamination.

Critical comparison of diffuse reflectance spectroscopy and colorimetry as dermatological diagnostic tools for acanthosis nigricans: a chemometric approach.

PubMed

Devpura, Suneetha; Pattamadilok, Bensachee; Syed, Zain U; Vemulapalli, Pranita; Henderson, Marsha; Rehse, Steven J; Hamzavi, Iltefat; Lim, Henry W; Naik, Ratna

2011-06-01

Quantification of skin changes due to acanthosis nigricans (AN), a disorder common among insulin-resistant diabetic and obese individuals, was investigated using two optical techniques: diffuse reflectance spectroscopy (DRS) and colorimetry. Measurements were obtained from AN lesions on the neck and two control sites of eight AN patients. A principal component/discriminant function analysis successfully differentiated between AN lesion and normal skin with 87.7% sensitivity and 94.8% specificity in DRS measurements and 97.2% sensitivity and 96.4% specificity in colorimetry measurements.

Critical comparison of diffuse reflectance spectroscopy and colorimetry as dermatological diagnostic tools for acanthosis nigricans: a chemometric approach

PubMed Central

Devpura, Suneetha; Pattamadilok, Bensachee; Syed, Zain U.; Vemulapalli, Pranita; Henderson, Marsha; Rehse, Steven J.; Hamzavi, Iltefat; Lim, Henry W.; Naik, Ratna

2011-01-01

Quantification of skin changes due to acanthosis nigricans (AN), a disorder common among insulin-resistant diabetic and obese individuals, was investigated using two optical techniques: diffuse reflectance spectroscopy (DRS) and colorimetry. Measurements were obtained from AN lesions on the neck and two control sites of eight AN patients. A principal component/discriminant function analysis successfully differentiated between AN lesion and normal skin with 87.7% sensitivity and 94.8% specificity in DRS measurements and 97.2% sensitivity and 96.4% specificity in colorimetry measurements. PMID:21698027

Reduction in expression of the benign AR transcriptome is a hallmark of localised prostate cancer progression.

PubMed

Stuchbery, Ryan; Macintyre, Geoff; Cmero, Marek; Harewood, Laurence M; Peters, Justin S; Costello, Anthony J; Hovens, Christopher M; Corcoran, Niall M

2016-05-24

Despite the importance of androgen receptor (AR) signalling to prostate cancer development, little is known about how this signalling pathway changes with increasing grade and stage of the disease. To explore changes in the normal AR transcriptome in localised prostate cancer, and its relation to adverse pathological features and disease recurrence. Publically accessible human prostate cancer expression arrays as well as RNA sequencing data from the prostate TCGA. Tumour associated PSA and PSAD were calculated for a large cohort of men (n=1108) undergoing prostatectomy. We performed a meta-analysis of the expression of an androgen-regulated gene set across datasets using Oncomine. Differential expression of selected genes in the prostate TCGA database was probed using the edgeR Bioconductor package. Changes in tumour PSA density with stage and grade were assessed by Student's t-test, and its association with biochemical recurrence explored by Kaplan-Meier curves and Cox regression. Meta-analysis revealed a systematic decline in the expression of a previously identified benign prostate androgen-regulated gene set with increasing tumour grade, reaching significance in nine of 25 genes tested despite increasing AR expression. These results were confirmed in a large independent dataset from the TCGA. At the protein level, when serum PSA was corrected for tumour volume, significantly lower levels were observed with increasing tumour grade and stage, and predicted disease recurrence. Lower PSA secretion-per-tumour-volume is associated with increasing grade and stage of prostate cancer, has prognostic relevance, and reflects a systematic perturbation of androgen signalling.

Building a semantic web-based metadata repository for facilitating detailed clinical modeling in cancer genome studies.

PubMed

Sharma, Deepak K; Solbrig, Harold R; Tao, Cui; Weng, Chunhua; Chute, Christopher G; Jiang, Guoqian

2017-06-05

Detailed Clinical Models (DCMs) have been regarded as the basis for retaining computable meaning when data are exchanged between heterogeneous computer systems. To better support clinical cancer data capturing and reporting, there is an emerging need to develop informatics solutions for standards-based clinical models in cancer study domains. The objective of the study is to develop and evaluate a cancer genome study metadata management system that serves as a key infrastructure in supporting clinical information modeling in cancer genome study domains. We leveraged a Semantic Web-based metadata repository enhanced with both ISO11179 metadata standard and Clinical Information Modeling Initiative (CIMI) Reference Model. We used the common data elements (CDEs) defined in The Cancer Genome Atlas (TCGA) data dictionary, and extracted the metadata of the CDEs using the NCI Cancer Data Standards Repository (caDSR) CDE dataset rendered in the Resource Description Framework (RDF). The ITEM/ITEM_GROUP pattern defined in the latest CIMI Reference Model is used to represent reusable model elements (mini-Archetypes). We produced a metadata repository with 38 clinical cancer genome study domains, comprising a rich collection of mini-Archetype pattern instances. We performed a case study of the domain "clinical pharmaceutical" in the TCGA data dictionary and demonstrated enriched data elements in the metadata repository are very useful in support of building detailed clinical models. Our informatics approach leveraging Semantic Web technologies provides an effective way to build a CIMI-compliant metadata repository that would facilitate the detailed clinical modeling to support use cases beyond TCGA in clinical cancer study domains.

Promoter methylation of the immune checkpoint receptor PD-1 (PDCD1) is an independent prognostic biomarker for biochemical recurrence-free survival in prostate cancer patients following radical prostatectomy

PubMed Central

Goltz, Diane; Gevensleben, Heidrun; Dietrich, Jörn; Ellinger, Jörg; Landsberg, Jennifer; Kristiansen, Glen; Dietrich, Dimo

2016-01-01

ABSTRACT Biomarkers that facilitate the prediction of disease recurrence in prostate cancer (PCa) may enable physicians to personalize treatment for individual patients. In the current study, PD-1 (PDCD1) promoter methylation was assessed in a cohort of 498 PCa patients included in The Cancer Genome Atlas (TCGA) and a second cohort of 300 PCa cases treated at the University Hospital of Bonn. In the TCGA cohort, the PD-1 promoter was significantly hypermethylated in carcinomas versus normal prostatic epithelium (55.5% vs. 38.2%, p < 0.001) and PD-1 methylation (mPD-1) inversely correlated with PD-1 mRNA expression in PCa (Spearman's ρ = −0.415, p < 0.001). In both cohorts, mPD-1 significantly correlated with preoperative prostate specific antigen (PSA). In univariate Cox Proportional Hazard analysis, mPD-1 served as a significant prognostic factor for biochemical recurrence (BCR)-free survival (Hazard ratio: HR = 2.35 [1.35–4.10], p = 0.003, n = 410) in the TCGA cohort. In multivariate analysis, mPD-1 was shown to add significant independent prognostic information adjunct to pathologic tumor category (pT) and Gleason grading group (HR = 2.08 [1.16–3.74], p = 0.014, n = 350). PD-1 promoter methylation analyses could thus potentially aid the identification of patients which might benefit from adjuvant treatment after radical prostatectomy. Moreover, our data suggest an intrinsic role of PD-1 in PCa carcinogenesis and disease progression, which needs to be addressed in future studies. PMID:27853645

Dynamic Control System Mode Performance of the Space Technology-7 Disturbance Reduction System

NASA Technical Reports Server (NTRS)

O'Donnell, James R., Jr.; Hsu, Oscar; Maghami, Peiman

2017-01-01

The Space Technology-7 (ST-7) Disturbance Reduction System (DRS) is an experiment package aboard the European Space Agency (ESA) LISA Pathfinder spacecraft, launched on December 3, 2015. DRS consists of three primary components: Colloidal MicroNewton Thrusters (CMNTs), an Integrated Avionics Unit (IAU), and flight-software implementing the Command and Data Handling (C&DH) and Dynamic Control System (DCS) algorithms. The CMNTs were designed to provide thrust from 5 to 30 micro Newton, with thrust controllability and resolution of 0.1 micro Newton and thrust noise of 0.1 micro Newton/(square root of (Hz)) in the measurement band from 1-30 mHz. The IAU hosts the C&DH and DCS flight software, as well as interfaces with both the CMNT electronics and the LISA Pathfinder spacecraft. When in control, the DCS uses star tracker attitude data and capacitive or optically-measured position and attitude information from LISA Pathfinder and the LISA Technology Package (LTP) to control the attitude and position of the spacecraft and the two test masses inside the LTP. After completion of the nominal ESA LISA Pathfinder mission, the DRS experiment was commissioned followed by its nominal mission. DRS operations extended over the next five months, interspersed with station keeping, anomaly resolution, and periods where control was handed back to LISA Pathfinder for them to conduct further experiments. The primary DRS mission ended on December 6, 2016, with the experiment meeting all of its Level 1 requirements. The DCS, developed at the NASA Goddard Space Flight Center, consists of five spacecraft control modes and six test mass control modes, combined into six 'DRS Mission Modes'. Attitude Control and Zero-G were primarily used to control the spacecraft during initial handover and during many of the CMNT characterization experiments. The other Mission Modes, Drag Free Low Force, 18-DOF Transitional, and 18-DOF, were used to provide drag-free control of the spacecraft about the test

Seroprevalence of Streptococcal Inhibitor of Complement (SIC) suggests association of streptococcal infection with chronic kidney disease

PubMed Central

2013-01-01

Background Group A streptococcus (GAS) is an etiological agent for the immune mediated sequela post streptococcal glomerulonephritis (PSGN). In some populations PSGN is recognized as a risk factor for chronic kidney disease (CKD) and end-stage renal disease (ESRD). It was found that a significantly greater proportion of subjects with past history of PSGN than without the history exhibited seroreactions to streptococcal antigens called streptococcal inhibitor of complement (SIC) and to distantly related SIC (DRS). These antigens are expressed by major PSGN-associated GAS types. We therefore predicted that in populations such as India, which is endemic for streptococcal diseases and which has high prevalence of CKD and ESRD, greater proportions of CKD and ESRD patients exhibit seroreaction to SIC and DRS than healthy controls. Methods To test this we conducted a SIC and DRS seroprevalence study in subjects from Mumbai area. We recruited 100 CKD, 70 ESRD and 70 healthy individuals. Results Nineteen and 35.7% of CKD and ESRD subjects respectively were SIC antibody-positive, whereas only 7% of healthy cohort was seropositive to SIC. Furthermore, significantly greater proportion of the ESRD patients than the CKD patients is seropositive to SIC (p=0.02; odds ratio 2.37). No association was found between the renal diseases and DRS-antibody-positivity. Conclusions Past infection with SIC-positive GAS is a risk factor for CKD and ESRD in Mumbai population. Furthermore, SIC seropositivity is predictive of poor prognosis of CKD patients. PMID:23642030

Quantitative skin color measurements in acanthosis nigricans patients: colorimetry and diffuse reflectance spectroscopy.

PubMed

Pattamadilok, Bensachee; Devpura, Suneetha; Syed, Zain U; Agbai, Oma N; Vemulapalli, Pranita; Henderson, Marsha; Rehse, Steven J; Mahmoud, Bassel H; Lim, Henry W; Naik, Ratna; Hamzavi, Iltefat H

2012-08-01

Tristimulus colorimetry and diffuse reflectance spectroscopy (DRS) are white-light skin reflectance techniques used to measure the intensity of skin pigmentation. The tristimulus colorimeter is an instrument that measures a perceived color and the DRS instrument measures biological chromophores of the skin, including oxy- and deoxyhemoglobin, melanin and scattering. Data gathered from these tools can be used to understand morphological changes induced in skin chromophores due to conditions of the skin or their treatments. The purpose of this study was to evaluate the use of these two instruments in color measurements of acanthosis nigricans (AN) lesions. Eight patients with hyperinsulinemia and clinically diagnosable AN were seen monthly. Skin pigmentation was measured at three sites: the inner forearm, the medial aspect of the posterior neck, and anterior neck unaffected by AN. Of the three, measured tristimulus L*a*b* color parameters, the luminosity parameter L* was found to most reliably distinguish lesion from normally pigmented skin. The DRS instrument was able to characterize a lesion on the basis of the calculated melanin concentration, though melanin is a weak indicator of skin change and not a reliable measure to be used independently. Calculated oxyhemoglobin and deoxyhemoglobin concentrations were not found to be reliable indicators of AN. Tristimulus colorimetry may provide reliable methods for respectively quantifying and characterizing the objective color change in AN, while DRS may be useful in characterizing changes in skin melanin content associated with this skin condition. © 2012 John Wiley & Sons A/S.

Mobile fiber-optic sensor for detection of oral and cervical cancer in the developing world.

PubMed

Yu, Bing; Nagarajan, Vivek Krishna; Ferris, Daron G

2015-01-01

Oral and cervical cancers are a growing global health problem that disproportionately impacts women and men living in the developing world. The high death rate in developing countries is largely due to the fact that these countries do not have the appropriate medical infrastructure and resources to support the organized screening and diagnostic programs that are available in the developed world. Diffuse reflectance spectroscopy (DRS) with a fiber-optic probe can noninvasively quantify the optical properties of epithelial tissues and has shown the potential as a cost-effective, easy-to-use, and sensitive tool for diagnosis of early precancerous changes in the cervix and oral cavity. However, current fiber-optic DRS systems have not been designed to be robust and reliable for use in developing countries. They are subject to various sources of systematic or random errors, arising from the uncontrolled probe-tissue interface and lack of real-time calibration, use bulky and expensive optical components, and require extensive training. This chapter describes a portable DRS device that is specifically designed for detection of oral and cervical cancers in resource-poor settings. The device uses an innovative smart fiber-optic probe to eliminate operator bias, state-of-the-art photonics components to reduce size and power consumption, and automated software to reduce the need of operator training. The size and cost of the smart fiber-optic DRS system may be further reduced by incorporating a smartphone based spectrometer.

Reduced arterial stiffness may contribute to angiotensin-converting enzyme inhibitor induced improvements in walking time in peripheral arterial disease patients: Retraction.

PubMed

2015-12-01

J Hypertension 2008, 26:1037–1042. The following authors, Drs A.M. Dart, A. Lawler, P.A. Blombery, Prof. B.A. Kingwell, have requested retraction of a paper by A.A. Ahimastos et al. An investigation by the Research Conduct Office of the Baker Heart and Diabetes Institute found irregularities in a study, including falsification of patients' records and misrepresentation of results, from which this article was derived. On the basis of this investigation the Baker Heart and Diabetes Institute strongly supports retraction and points out the co-authors asking for retraction were found not be involved in the research misconduct. The article is retracted.

Improving care transitions through meaningful use stage 2: continuity of care document.

PubMed

Murphy, Lyn Stankiewicz; Wilson, Marisa L; Newhouse, Robin P

2013-02-01

In this department, Drs Murphy, Wilson, and Newhouse highlight hot topics in nursing outcomes, research, and evidence-based practice relevant to the nurse administrator. The goal is to discuss the practical implications for nurse leaders in diverse healthcare settings. Content includes evidence-based projects and decision making, locating measurement tools for quality improvement and safety projects, using outcome measures to evaluate quality, practice implications of administrative research, and exemplars of projects that demon strate innovative approaches to organizational problems. In this article, the authors describe the elements of continuity of care documentation, how sharing information can improve the quality and safety of care transitions and the implications for nurse executives.

Center for Evaluation of Resilience Programs

DTIC Science & Technology

2014-10-14

Research Institutes  Yearly Report, W81XWH-11-2-0173| 14 October 2014 | Page 6 John Doyle  California Institute of  Technology     Citation...Efficacy Scale” or “SSE” or “Dispositional Resilience Scale” or “DRS-15” or “ Metacognitive Awareness Inventory” or “Attention Network Test” or “ANT” or...be reproduced, stored or transmitted, in any form or by any other means, with the prior permission in writing of the publisher, or in the case of

PEST domain mutations in Notch receptors comprise an oncogenic driver segment in triple-negative breast cancer sensitive to a γ-secretase inhibitor.

PubMed

Wang, Kai; Zhang, Qin; Li, Danan; Ching, Keith; Zhang, Cathy; Zheng, Xianxian; Ozeck, Mark; Shi, Stephanie; Li, Xiaorong; Wang, Hui; Rejto, Paul; Christensen, James; Olson, Peter

2015-03-15

To identify and characterize novel, activating mutations in Notch receptors in breast cancer and to determine response to the gamma secretase inhibitor (GSI) PF-03084014. We used several computational approaches, including novel algorithms, to analyze next-generation sequencing data and related omic datasets from The Cancer Genome Atlas (TCGA) breast cancer cohort. Patient-derived xenograft (PDX) models were sequenced, and Notch-mutant models were treated with PF-03084014. Gene-expression and functional analyses were performed to study the mechanism of activation through mutation and inhibition by PF-03084014. We identified mutations within and upstream of the PEST domains of NOTCH1, NOTCH2, and NOTCH3 in the TCGA dataset. Mutations occurred via several genetic mechanisms and compromised the function of the PEST domain, a negative regulatory domain commonly mutated in other cancers. Focal amplifications of NOTCH2 and NOTCH3 were also observed, as were heterodimerization or extracellular domain mutations at lower incidence. Mutations and amplifications often activated the Notch pathway as evidenced by increased expression of canonical Notch target genes, and functional mutations were significantly enriched in the triple-negative breast cancer subtype (TNBC). PDX models were also identified that harbored PEST domain mutations, and these models were highly sensitive to PF-03084014. This work suggests that Notch-altered breast cancer constitutes a bona fide oncogenic driver segment with the most common alteration being PEST domain mutations present in multiple Notch receptors. Importantly, functional studies suggest that this newly identified class can be targeted with Notch inhibitors, including GSIs. ©2015 American Association for Cancer Research.

Cells redox environment modulates BRCA1 expression and DNA homologous recombination repair.

PubMed

Wilson, Aaron; Yakovlev, Vasily A

2016-12-01

Cancer development and progression have been linked to oxidative stress, a condition characterized by unbalanced increase in ROS and RNS production. The main endogenous initiators of the redox imbalance in cancer cells are defective mitochondria, elevated NOX activity, and uncoupled NOS3. Traditionally, most attention has been paid to direct oxidative damage to DNA by certain ROS. However, increase in oxidative DNA lesions does not always lead to malignancy. Hence, additional ROS-dependent, pro-carcinogenic mechanisms must be important. Our recent study demonstrated that Tyr nitration of PP2A stimulates its activity and leads to downregulation of BRCA1 expression. This provides a mechanism for chromosomal instability essential for tumor progression. In the present work, we demonstrated that inhibition of ROS production by generating mitochondrial-electron-transport-deficient cell lines (ρ 0 cells) or by inhibition of NOX activity with a selective peptide inhibitor significantly reduced PP2A Tyr nitration and its activity in different cancer cell lines. As a result of the decreased PP2A activity, BRCA1 expression was restored along with a significantly enhanced level of DNA HRR. We used TCGA database to analyze the correlation between expressions of the NOX regulatory subunits, NOS isoforms, and BRCA1 in the 3 cancer research studies: breast invasive carcinoma, ovarian cystadenocarcinoma, and lung adenocarcinoma. TCGA database analysis demonstrated that the high expression levels of most of the NOX regulatory subunits responsible for stimulation of NOX1-NOX4 were associated with significant downregulation of BRCA1 expression. Copyright © 2016. Published by Elsevier Inc.

Figure 4 from Integrative Genomics Viewer: Visualizing Big Data | Office of Cancer Genomics

Cancer.gov

Gene-list view of genomic data. The gene-list view allows users to compare data across a set of loci. The data in this figure includes copy number, mutation, and clinical data from 202 glioblastoma samples from TCGA. Adapted from Figure 7; Thorvaldsdottir H et al. 2012

Perspective on Oncogenic Processes at the End of the Beginning of Cancer Genomics.

PubMed

Ding, Li; Bailey, Matthew H; Porta-Pardo, Eduard; Thorsson, Vesteinn; Colaprico, Antonio; Bertrand, Denis; Gibbs, David L; Weerasinghe, Amila; Huang, Kuan-Lin; Tokheim, Collin; Cortés-Ciriano, Isidro; Jayasinghe, Reyka; Chen, Feng; Yu, Lihua; Sun, Sam; Olsen, Catharina; Kim, Jaegil; Taylor, Alison M; Cherniack, Andrew D; Akbani, Rehan; Suphavilai, Chayaporn; Nagarajan, Niranjan; Stuart, Joshua M; Mills, Gordon B; Wyczalkowski, Matthew A; Vincent, Benjamin G; Hutter, Carolyn M; Zenklusen, Jean Claude; Hoadley, Katherine A; Wendl, Michael C; Shmulevich, Llya; Lazar, Alexander J; Wheeler, David A; Getz, Gad

2018-04-05

The Cancer Genome Atlas (TCGA) has catalyzed systematic characterization of diverse genomic alterations underlying human cancers. At this historic junction marking the completion of genomic characterization of over 11,000 tumors from 33 cancer types, we present our current understanding of the molecular processes governing oncogenesis. We illustrate our insights into cancer through synthesis of the findings of the TCGA PanCancer Atlas project on three facets of oncogenesis: (1) somatic driver mutations, germline pathogenic variants, and their interactions in the tumor; (2) the influence of the tumor genome and epigenome on transcriptome and proteome; and (3) the relationship between tumor and the microenvironment, including implications for drugs targeting driver events and immunotherapies. These results will anchor future characterization of rare and common tumor types, primary and relapsed tumors, and cancers across ancestry groups and will guide the deployment of clinical genomic sequencing. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Proteogenomic characterization of human colon and rectal cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Bing; Wang, Jing; Wang, Xiaojing

2014-09-18

We analyzed proteomes of colon and rectal tumors previously characterized by the Cancer Genome Atlas (TCGA) and performed integrated proteogenomic analyses. Protein sequence variants encoded by somatic genomic variations displayed reduced expression compared to protein variants encoded by germline variations. mRNA transcript abundance did not reliably predict protein expression differences between tumors. Proteomics identified five protein expression subtypes, two of which were associated with the TCGA "MSI/CIMP" transcriptional subtype, but had distinct mutation and methylation patterns and associated with different clinical outcomes. Although CNAs showed strong cis- and trans-effects on mRNA expression, relatively few of these extend to the proteinmore » level. Thus, proteomics data enabled prioritization of candidate driver genes. Our analyses identified HNF4A, a novel candidate driver gene in tumors with chromosome 20q amplifications. Integrated proteogenomic analysis provides functional context to interpret genomic abnormalities and affords novel insights into cancer biology.« less

Stratocumulus Precipitation and Entrainment Experiment (SPEE) Field Campaign Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Albrecht, Bruce; Ghate, Virendra; CADeddu, Maria

2016-06-01

The scientific focus of this project was to examine precipitation and entrainment processes in marine stratocumulus clouds. The entrainment studies focused on characterizing cloud turbulence at cloud top using Doppler cloud radar observations. The precipitation studies focused on characterizing the precipitation and the macroscopic properties (cloud thickness, and liquid water path) of the clouds. This project will contribute to the U.S. Department of Energy (DOE) Atmospheric Radiation Measurement (ARM) Climate Research Facility’s overall objective of providing the remote-sensing observations needed to improve the representation of key cloud processes in climate models. It will be of direct relevance to the componentsmore » of ARM dealing with entrainment and precipitation processes in stratiform clouds. Further, the radar observing techniques that will be used in this study were developed using ARM Southern Great Plains (SGP) facility observations under Atmospheric System Research (ASR) support. The observing systems operating automatously from a site located just north of the Center for Interdisciplinary Remotely-Piloted Aircraft Studies (CIRPAS) aircraft hangar in Marina, California during the period of 1 May to 4 November 2015 included: 1. Microwave radiometer: ARM Microwave Radiometer, 3-Channel (MWR3C) with channels centered at 23.834, 30, and 89 GHz; supported by Dr. Maria Cadeddu. 2. Cloud Radar: CIRPAS 95 GHz Frequency Modulated Continuous Wave (FMCW) Cloud Radar (Centroid Frequency Chirp Rate [CFCR]); operations overseen by Drs. Ghate and Albrecht. 3. Ceilometer: Vaisala CK-14; operations overseen by Drs. Ghate and Albrecht.« less

Mammalian RAD52 Functions in Break-Induced Replication Repair of Collapsed DNA Replication Forks.

PubMed

Sotiriou, Sotirios K; Kamileri, Irene; Lugli, Natalia; Evangelou, Konstantinos; Da-Ré, Caterina; Huber, Florian; Padayachy, Laura; Tardy, Sebastien; Nicati, Noemie L; Barriot, Samia; Ochs, Fena; Lukas, Claudia; Lukas, Jiri; Gorgoulis, Vassilis G; Scapozza, Leonardo; Halazonetis, Thanos D

2016-12-15

Human cancers are characterized by the presence of oncogene-induced DNA replication stress (DRS), making them dependent on repair pathways such as break-induced replication (BIR) for damaged DNA replication forks. To better understand BIR, we performed a targeted siRNA screen for genes whose depletion inhibited G1 to S phase progression when oncogenic cyclin E was overexpressed. RAD52, a gene dispensable for normal development in mice, was among the top hits. In cells in which fork collapse was induced by oncogenes or chemicals, the Rad52 protein localized to DRS foci. Depletion of Rad52 by siRNA or knockout of the gene by CRISPR/Cas9 compromised restart of collapsed forks and led to DNA damage in cells experiencing DRS. Furthermore, in cancer-prone, heterozygous APC mutant mice, homozygous deletion of the Rad52 gene suppressed tumor growth and prolonged lifespan. We therefore propose that mammalian RAD52 facilitates repair of collapsed DNA replication forks in cancer cells. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Postoperative full abduction in a patient of Duane retraction syndrome without an abducens nerve: a case report.

PubMed

Kim, Jae Hyoung; Hwang, Jeong-Min

2017-05-19

Duane retraction syndrome (DRS) consists of abduction deficit, globe retraction and upshoots or downshoots with adduction. The abducens nerve on the affected side is absent in type 1 DRS. After bilateral medial rectus muscle recession in unilateral type 1 DRS may improve the abduction limitation, but still more than -3 limitation remains. A 6-month-old boy presented with esotropia which had been noticed in early infancy. He showed limited abduction, fissure narrowing on attempted adduction and a small upshoot OS. Left abducens nerve was not identified on magnetic resonance imaging compatible with Duane retraction syndrome type 1. He showed full abduction after bilateral medial rectus recession of 6.0 mm at the age of 9 months, and remained orthotropia with full abduction OU 2 years postoperatively. He is my only patient with Duane retraction syndrome who showed full abduction after bilateral medial rectus recession. A patient with the type 1 Duane retraction syndrome rarely may show full abduction after bilateral medial rectus recession mimicking infantile esotropia.

Heart rate deceleration runs for postinfarction risk prediction.

PubMed

Guzik, Przemyslaw; Piskorski, Jaroslaw; Barthel, Petra; Bauer, Axel; Müller, Alexander; Junk, Nadine; Ulm, Kurt; Malik, Marek; Schmidt, Georg

2012-01-01

A method for counting episodes of uninterrupted beat-to-beat heart rate decelerations was developed. The method was set up and evaluated using 24-hour electrocardiogram Holter recordings of 1455 (training sample) and 946 (validation sample) postinfarction patients. During a median follow-up of 24 months, 70, 46, and 19 patients of the training sample suffered from total, cardiac, and sudden cardiac mortality, respectively. In the validation sample, these numbers were 39, 25, and 15. Episodes of consecutive beat-to-beat heart rate decelerations (deceleration runs [DRs]) were characterized by their length. Deceleration runs of 2 to 10 cycles were significantly less frequent in nonsurvivors. Multivariate model of DRs of 2, 4, and 8 cycles identified low-, intermediate-, and high-risk groups. In these groups of the training sample, the total mortalities were 1.8%, 6.1%, and 24%, respectively. In the validation sample, these numbers were 1.8%, 4.1%, and 21.9%. Infrequent DRs during 24-hour Holter indicate high risk of postinfarction mortality. Copyright © 2012 Elsevier Inc. All rights reserved.

Diffuse reflectance spectroscopy and optical polarization imaging of in-vivo biological tissue

NASA Astrophysics Data System (ADS)

Mora-Núñez, A.; Castillejos, Y.; García-Torales, G.; Martínez-Ponce, G.

2013-11-01

A number of optical techniques have been reported in the scientific literature as accomplishable methodologies to diagnose diseases in biological tissue, for instance, diffuse reflectance spectroscopy (DRS) and optical polarization imaging (OPI). The skin is the largest organ in the body and consists of three primary layers, namely, the epidermis (the outermost layer exposed to the world), the dermis, and the hypodermis. The epidermis changes from to site to site, mainly because of difference in hydration. A lower water content increase light scattering and reduce the penetration depth of radiation. In this work, two hairless mice have been selected to evaluate their skin features by using DRS and OPI. Four areas of the specimen body were chosen to realize the comparison: back, abdomen, tail, and head. From DRS, it was possible to distinguish the skin nature because of different blood irrigation at dermis. In the other hand, OPI shows pseudo-depolarizing regions in the measured Mueller images related to a spatially varying propagation of the scattered light. This provides information about the cell size in the irradiated skin.

Intermediate Experimental Vehicle, ESA Programme Supersonic Transonic Aerodynamics

NASA Astrophysics Data System (ADS)

Sjors, Karin; Olsson, Jorgen; Maseland, Hans; de Cock, Koen; Dutheil, Sylvain; Bouleuc, Laurent; Cantinaud, Olivier; Tribot, Jean-Pierre; Mareschi, Vincenzo; Ferrarella, Daniella, Rufolo, Giuseppe

2011-05-01

The IXV project objectives are the design, development, manufacture and on ground and in flight verification of an autonomous European lifting and aerodynamically controlled re-entry system, which is highly flexible and manoeuvrable. The IXV vehicle is planned to be recovered in supersonic regime by means of a Descent and Recovery System (DRS). In that context, a specific aerodynamic identification was carried in order to provide data to be used for consolidating the AEDB (AErodynamic Data Base) and as inputs for the DRS sub-system activities. During the phase C2, a wind tunnel campaign was carried out at for the Mach number range M=1.7 to M=0.3 together with computational fluid dynamics simulation. The main objectives were to assess the aerodynamic forces and moments assuming high aileron setting in supersonic regime and to get preliminary aerodynamic data in subsonic regime to be used as input by the DRS team. The logic and the main results of these activities are presented and discussed in this paper.

Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer. | Office of Cancer Genomics

Cancer.gov

We report a comprehensive analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC-signature mutagenesis. Clustering by mutation signature identified a high-mutation subset with 75% 5-year survival.

Comparative analyses of gene copy number and mRNA expression in GBM tumors and GBM xenografts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hodgson, J. Graeme; Yeh, Ru-Fang; Ray, Amrita

2009-04-03

Development of model systems that recapitulate the molecular heterogeneity observed among glioblastoma multiforme (GBM) tumors will expedite the testing of targeted molecular therapeutic strategies for GBM treatment. In this study, we profiled DNA copy number and mRNA expression in 21 independent GBM tumor lines maintained as subcutaneous xenografts (GBMX), and compared GBMX molecular signatures to those observed in GBM clinical specimens derived from the Cancer Genome Atlas (TCGA). The predominant copy number signature in both tumor groups was defined by chromosome-7 gain/chromosome-10 loss, a poor-prognosis genetic signature. We also observed, at frequencies similar to that detected in TCGA GBM tumors,more » genomic amplification and overexpression of known GBM oncogenes, such as EGFR, MDM2, CDK6, and MYCN, and novel genes, including NUP107, SLC35E3, MMP1, MMP13, and DDX1. The transcriptional signature of GBMX tumors, which was stable over multiple subcutaneous passages, was defined by overexpression of genes involved in M phase, DNA replication, and chromosome organization (MRC) and was highly similar to the poor-prognosis mitosis and cell-cycle module (MCM) in GBM. Assessment of gene expression in TCGA-derived GBMs revealed overexpression of MRC cancer genes AURKB, BIRC5, CCNB1, CCNB2, CDC2, CDK2, and FOXM1, which form a transcriptional network important for G2/M progression and/or checkpoint activation. Our study supports propagation of GBM tumors as subcutaneous xenografts as a useful approach for sustaining key molecular characteristics of patient tumors, and highlights therapeutic opportunities conferred by this GBMX tumor panel for testing targeted therapeutic strategies for GBM treatment.« less

An eleven gene molecular signature for extra-capsular spread in oral squamous cell carcinoma serves as a prognosticator of outcome in patients without nodal metastases.

PubMed

Wang, Weining; Lim, Weng Khong; Leong, Hui Sun; Chong, Fui Teen; Lim, Tony K H; Tan, Daniel S W; Teh, Bin Tean; Iyer, N Gopalakrishna

2015-04-01

Extracapsular spread (ECS) is an important prognostic factor for oral squamous cell carcinoma (OSCC) and is used to guide management. In this study, we aimed to identify an expression profile signature for ECS in node-positive OSCC using data derived from two different sources: a cohort of OSCC patients from our institution (National Cancer Centre Singapore) and The Cancer Genome Atlas (TCGA) head and neck squamous cell carcinoma (HNSCC) cohort. We also sought to determine if this signature could serve as a prognostic factor in node negative cancers. Patients with a histological diagnosis of OSCC were identified from an institutional database and fresh tumor samples were retrieved. RNA was extracted and gene expression profiling was performed using the Affymetrix GeneChip Human Genome U133 Plus 2.0 microarray platform. RNA sequence data and corresponding clinical data for the TCGA HNSCC cohort were downloaded from the TCGA Data Portal. All data analyses were conducted using R package and SPSS. We identified an 11 gene signature (GGH, MTFR1, CDKN3, PSRC1, SMIM3, CA9, IRX4, CPA3, ZSCAN16, CBX7 and ZFP3) which was robust in segregating tumors by ECS status. In node negative patients, patients harboring this ECS signature had a significantly worse overall survival (p=0.04). An eleven gene signature for ECS was derived. Our results also suggest that this signature is prognostic in a separate subset of patients with no nodal metastasis Further validation of this signature on other datasets and immunohistochemical studies are required to establish utility of this signature in stratifying early stage OSCC patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Co-expression of mitosis-regulating genes contributes to malignant progression and prognosis in oligodendrogliomas

PubMed Central

Liu, Yanwei; Hu, Huimin; Zhang, Chuanbao; Wang, Haoyuan; Zhang, Wenlong; Wang, Zheng; Li, Mingyang; Zhang, Wei; Zhou, Dabiao; Jiang, Tao

2015-01-01

The clinical prognosis of patients with glioma is determined by tumor grades, but tumors of different subtypes with equal malignancy grade usually have different prognosis that is largely determined by genetic abnormalities. Oligodendrogliomas (ODs) are the second most common type of gliomas. In this study, integrative analyses found that distribution of TCGA transcriptomic subtypes was associated with grade progression in ODs. To identify critical gene(s) associated with tumor grades and TCGA subtypes, we analyzed 34 normal brain tissue (NBT), 146 WHO grade II and 130 grade III ODs by microarray and RNA sequencing, and identified a co-expression network of six genes (AURKA, NDC80,CENPK, KIAA0101, TIMELESS and MELK) that was associated with tumor grades and TCGA subtypes as well as Ki-67 expression. Validation of the six genes was performed by qPCR in additional 28 ODs. Importantly, these genes also were validated in four high-grade recurrent gliomas and the initial lower-grade gliomas resected from the same patients. Finally, the RNA data on two genes with the highest discrimination potential (AURKA and NDC80) and Ki-67 were validated on an independent cohort (5 NBTs and 86 ODs) by immunohistochemistry. Knockdown of AURKA and NDC80 by siRNAs suppressed Ki-67 expression and proliferation of gliomas cells. Survival analysis showed that high expression of the six genes corporately indicated a poor survival outcome. Correlation and protein interaction analysis provided further evidence for this co-expression network. These data suggest that the co-expression of the six mitosis-regulating genes was associated with malignant progression and prognosis in ODs. PMID:26468983

GAB2 Amplification in Squamous Cell Lung Cancer of Non-Smokers

PubMed Central

2017-01-01

Lung squamous cell cancer (SCC) is typically found in smokers and has a very low incidence in non-smokers, indicating differences in the tumor biology of lung SCC in smokers and non-smokers. However, the specific mutations that drive tumor growth in non-smokers have not been identified. To identify mutations in lung SCC of non-smokers, we performed a genetic analysis using arrays comparative genomic hybridization (ArrayCGH). We analyzed 19 patients with lung SCC who underwent surgical treatment between April 2005 and April 2015. Clinical characteristics were reviewed, and DNA was extracted from fresh frozen lung cancer specimens. All of copy number alterations from ArrayCGH were validated using The Cancer Genome Atlas (TCGA) copy number variation (CNV) data of lung SCC. We examined the frequency of copy number changes according to the smoking status (non-smoker [n = 8] or smoker [n = 11]). We identified 16 significantly altered regions from ArrayCGH data, three gain and four loss regions overlapped with the TCGA lung squamous cell carcinoma (LUSC) patients. Within these overlapped significant regions, we detected 15 genes that have been reported in the Cancer Gene census. We also found that the proto-oncogene GAB2 (11q14.1) was significantly amplified in non-smokers patients and vice versa in both ArrayCGH and TCGA data. Immunohistochemical analyses showed that GAB2 protein was relatively upregulated in non-smoker than smoker tissues (37.5% vs. 9.0%, P = 0.007). GAB2 amplification may have an important role in the development of lung SCC in non-smokers. GAB2 may represent a potential biomarker for lung SCC in non-smokers. PMID:28960030

Renal Cell Carcinoma With Chromosome 6p Amplification Including the TFEB Gene: A Novel Mechanism of Tumor Pathogenesis?

PubMed

Williamson, Sean R; Grignon, David J; Cheng, Liang; Favazza, Laura; Gondim, Dibson D; Carskadon, Shannon; Gupta, Nilesh S; Chitale, Dhananjay A; Kalyana-Sundaram, Shanker; Palanisamy, Nallasivam

2017-03-01

Amplification of chromosome 6p has been implicated in aggressive behavior in several cancers, but has not been characterized in renal cell carcinoma (RCC). We identified 9 renal tumors with amplification of chromosome 6p including the TFEB gene, 3 by fluorescence in situ hybridization, and 6 from the Cancer Genome Atlas (TCGA) databases. Patients' ages were 28 to 78 years (median, 61 y). Most tumors were high stage (7/9 pT3a, 2/9 pN1). Using immunohistochemistry, 2/4 were positive for melanocytic markers and cathepsin K. Novel TFEB fusions were reported by TCGA in 2; however, due to a small composition of fusion transcripts compared with full-length transcripts (0.5/174 and 3.3/132 FPKM), we hypothesize that these represent secondary fusions due to amplification. Five specimens (4 TCGA, 1 fluorescence in situ hybridization) had concurrent chromosome 3p copy number loss or VHL deletion. However, these did not resemble clear cell RCC, had negative carbonic anhydrase IX labeling, lacked VHL mutation, and had papillary or unclassified histology (2/4 had gain of chromosome 7 or 17). One tumor each had somatic FH mutation and SMARCB1 mutation. Chromosome 6p amplification including TFEB is a previously unrecognized cytogenetic alteration in RCC, associated with heterogenous tubulopapillary eosinophilic and clear cell histology. The combined constellation of features does not fit cleanly into an existing tumor category (unclassified), most closely resembling papillary or translocation RCC. The tendency for high tumor stage, varied tubulopapillary morphology, and a subset with melanocytic marker positivity suggests the possibility of a unique tumor type, despite some variation in appearance and genetics.

Amplification of the NSD3-BRD4-CHD8 pathway in pelvic high-grade serous carcinomas of tubo-ovarian and endometrial origin.

PubMed

Jones, Derek H; Lin, Douglas I

2017-08-01

Identification of novel therapeutics in pelvic high-grade serous carcinoma (HGSC) has been hampered by a paucity of actionable point mutations in target genes. The aim of the present study was to investigate the extent of amplification of the therapeutically targetable NSD3-CHD8-BRD4 pathway in pelvic HGSC, and to determine whether amplification is associated with worse prognosis. The Cancer Genome Atlas (TCGA) ovarian and endometrial cancer cohorts were retrospectively analyzed via online data-mining tools to test the association of NSD3 , CHD8 and BRD4 genomic alterations with survival of pelvic HGSC patients. It was demonstrated that amplification of the NSD3-CHD8-BRD4 pathway in the ovarian HGSC cohort (observed in 18% of the cases, 88/489) was significantly associated with worse overall and progression-free survival compared with non-amplified cases. In addition, amplification of NSD3 , CHD8 and BRD4 also occurred in 9% (21/232) of overall endometrial cancer TCGA cases, which was associated with worse overall survival. In the endometrial cancer TCGA cohort, NSD3 , CHD8 and BRD4 amplification occurred specifically in the serous carcinoma (25%, 13/53) and 'serous-like' copy number high endometrial carcinoma (33%, 20/60) subgroups, compared with the polymerase e (0%, 0/17), microsatellite instability high (0%, 0/65) or low copy number (1%, 1/90) subgroups. These findings support the hypothesis that amplification of the NSD3-BRD4-CDH8 axis is frequent in pelvic HGSC of both ovarian and endometrial origin, and that this pathway is potentially targetable in a subset of HGSC patients.

National Medal of Technology Awarded to NCI Drs. Lowy and Schiller

Cancer.gov

President Obama announced that two NCI scientists would be recipients of the National Medal of Technology and Innovation -- the nation's highest honor for technological achievement. The honorees, John Schiller, Ph.D., Laboratory of Cellular Oncology (LCO)

CFD Validation for Hypersonic Flight: Real Gas Flows

DTIC Science & Technology

2006-01-01

Calculations Two research groups contributed results to this test case. The group of Drs. Marco Marini and Salvatore Borelli from the Italian Aerospace...and Borelli ran calculations at four test con- ditions, and we simulated Run 46, which is the high- enthalpy air case. The test section conditions were...N2 at ρ∞ = 3.31 g/cm3, T∞ = 556 K, u∞ = 4450 m/s. Run 46: Air at ρ∞ = 3.28 g/cm3, T∞ = 672 K, u∞ = 4480 m/s. Marini and Borelli used grids of 144× 40

Cost-effectiveness analysis of an early-initiated, continuous chain of rehabilitation after severe traumatic brain injury.

PubMed

Andelic, Nada; Ye, Jiajia; Tornas, Sveinung; Roe, Cecilie; Lu, Juan; Bautz-Holter, Erik; Moger, Tron; Sigurdardottir, Solrun; Schanke, Anne-Kristine; Aas, Eline

2014-07-15

The aim of this study is to estimate the long-term cost-effectiveness of two different rehabilitation trajectories after severe traumatic brain injury (sTBI). A decision tree model compared hospitalization costs, health effects, and incremental cost-effectiveness ratios (ICER) of a continuous chain versus a broken chain of rehabilitation. The expected costs were estimated by the reimbursement system using diagnosis-related group and based on point estimates of the Disability Rating Scale (DRS); the health effects were measured by means of area under the curve (AUC). The incremental health benefit was estimated as the difference in the AUCs between the chains. Lower values on the DRS scale indicate better health; thus, smaller AUCs were preferred. The modeled population was a cohort of 59 patients with sTBI (30 in continuous chain; 29 in broken chain) with 6-weeks, 1-year, and 5-year post-injury follow-ups. Regarding the DRS estimates, 5-year AUCs were 19.40 (continuous chain) and 23.46 (broken chain). Across 5 years, the continuous chain of rehabilitation had lower costs and better health effects. By replacing the broken chain with the continuous chain, NOK 37.000 could be saved and 4.06 DRS points gained. By means of probabilistic sensitivity analysis, the majority of ICER estimates (67% of the Monte Carlo simulations) indicated that a continuous chain of rehabilitation was less costly and more effective. These findings indicate that the trajectory of continuous rehabilitation represents a dominant strategy in that it reduces costs and improves outcomes after sTBI under reasonable assumptions.

On the use and misuse of scalar scores of confounders in design and analysis of observational studies.

PubMed

Pfeiffer, R M; Riedl, R

2015-08-15

We assess the asymptotic bias of estimates of exposure effects conditional on covariates when summary scores of confounders, instead of the confounders themselves, are used to analyze observational data. First, we study regression models for cohort data that are adjusted for summary scores. Second, we derive the asymptotic bias for case-control studies when cases and controls are matched on a summary score, and then analyzed either using conditional logistic regression or by unconditional logistic regression adjusted for the summary score. Two scores, the propensity score (PS) and the disease risk score (DRS) are studied in detail. For cohort analysis, when regression models are adjusted for the PS, the estimated conditional treatment effect is unbiased only for linear models, or at the null for non-linear models. Adjustment of cohort data for DRS yields unbiased estimates only for linear regression; all other estimates of exposure effects are biased. Matching cases and controls on DRS and analyzing them using conditional logistic regression yields unbiased estimates of exposure effect, whereas adjusting for the DRS in unconditional logistic regression yields biased estimates, even under the null hypothesis of no association. Matching cases and controls on the PS yield unbiased estimates only under the null for both conditional and unconditional logistic regression, adjusted for the PS. We study the bias for various confounding scenarios and compare our asymptotic results with those from simulations with limited sample sizes. To create realistic correlations among multiple confounders, we also based simulations on a real dataset. Copyright © 2015 John Wiley & Sons, Ltd.

Clinical evaluation of the 3M Littmann Electronic Stethoscope Model 3200 in 150 cats.

PubMed

Blass, Keith A; Schober, Karsten E; Bonagura, John D; Scansen, Brian A; Visser, Lance C; Lu, Jennifer; Smith, Danielle N; Ward, Jessica L

2013-10-01

Detection of murmurs and gallops may help to identify cats with heart disease. However, auscultatory findings may be subject to clinically relevant observer variation. The objective of this study was to evaluate an electronic stethoscope (ES) in cats. We hypothesized that the ES would perform at least as well as a conventional stethoscope (CS) in the detection of abnormal heart sounds. One hundred and fifty consecutive cats undergoing echocardiography were enrolled prospectively. Cats were ausculted with a CS (WA Tycos Harvey Elite) by two observers, and heart sounds were recorded digitally using an ES (3M Littmann Stethoscope Model 3200) for off-line analysis. Echocardiography was used as the clinical standard method for validation of auscultatory findings. Additionally, digital recordings (DRs) were assessed by eight independent observers with various levels of expertise, and compared using interclass correlation and Cohen's weighted kappa analyses. Using the CS, a heart murmur (n = 88 cats) or gallop sound (n = 17) was identified in 105 cats, whereas 45 cats lacked abnormal heart sounds. There was good total agreement (83-90%) between the two observers using the CS. In contrast, there was only moderate agreement (P <0.001) between results from the CS and the DRs for murmurs, and poor agreement for gallops. The CS was more sensitive compared with the DRs with regard to murmurs and gallops. Agreement among the eight observers was good-to-excellent for murmur detection (81%). In conclusion, DRs made with the ES are less sensitive but comparably specific to a CS at detecting abnormal heart sounds in cats.

Interventions to increase attendance for diabetic retinopathy screening.

PubMed

Lawrenson, John G; Graham-Rowe, Ella; Lorencatto, Fabiana; Burr, Jennifer; Bunce, Catey; Francis, Jillian J; Aluko, Patricia; Rice, Stephen; Vale, Luke; Peto, Tunde; Presseau, Justin; Ivers, Noah; Grimshaw, Jeremy M

2018-01-15

Despite evidence supporting the effectiveness of diabetic retinopathy screening (DRS) in reducing the risk of sight loss, attendance for screening is consistently below recommended levels. The primary objective of the review was to assess the effectiveness of quality improvement (QI) interventions that seek to increase attendance for DRS in people with type 1 and type 2 diabetes.Secondary objectives were:To use validated taxonomies of QI intervention strategies and behaviour change techniques (BCTs) to code the description of interventions in the included studies and determine whether interventions that include particular QI strategies or component BCTs are more effective in increasing screening attendance;To explore heterogeneity in effect size within and between studies to identify potential explanatory factors for variability in effect size;To explore differential effects in subgroups to provide information on how equity of screening attendance could be improved;To critically appraise and summarise current evidence on the resource use, costs and cost effectiveness. We searched the Cochrane Library, MEDLINE, Embase, PsycINFO, Web of Science, ProQuest Family Health, OpenGrey, the ISRCTN, ClinicalTrials.gov, and the WHO ICTRP to identify randomised controlled trials (RCTs) that were designed to improve attendance for DRS or were evaluating general quality improvement (QI) strategies for diabetes care and reported the effect of the intervention on DRS attendance. We searched the resources on 13 February 2017. We did not use any date or language restrictions in the searches. We included RCTs that compared any QI intervention to usual care or a more intensive (stepped) intervention versus a less intensive intervention. We coded the QI strategy using a modification of the taxonomy developed by Cochrane Effective Practice and Organisation of Care (EPOC) and BCTs using the BCT Taxonomy version 1 (BCTTv1). We used Place of residence, Race

Figure 2 from Integrative Genomics Viewer: Visualizing Big Data | Office of Cancer Genomics

Cancer.gov

Grouping and sorting genomic data in IGV. The IGV user interface displaying 202 glioblastoma samples from TCGA. Samples are grouped by tumor subtype (second annotation column) and data type (first annotation column) and sorted by copy number of the EGFR locus (middle column). Adapted from Figure 1; Robinson et al. 2011

To Boldly Go. America's Next Era in Space: New Frontiers in Climate Research

NASA Technical Reports Server (NTRS)

1995-01-01

Dr. France Cordova, NASA's Chief Scientist, chaired this, the fourth seminar in the NASA Administrator's Seminar Series. She introduced NASA Administrator, Daniel S. Goldin, who greeted the attendees, and in his opening remarks said that human beings have a need to understand the what and why of the forces of nature and of people, and the stresses on the planet Earth. The first speaker, Dr. Ellen Mosley-Thompson of Ohio State University discussed the many things that scientists have learned from ice cores obtained in Peru and the Antarctic. The next speaker, Dr. Michael McElroy of Harvard University, is active in environmental research. He noted that insurance companies need to know more about the physics and chemistry of weather in order to avoid bankruptcy; that the greenhouse effect, which is good because it reflects heat, is being changed, and we don't know the rules. In the discussion that followed, Goldin asked if the present technology for measuring circulation of air and water and contents of the atmosphere is worth the cost. Drs. McElroy and Mosley-Thompson noted that the historic record in an ice core is endangered by ice melts; that in the last 10 years we've learned that tropics change; that the water vapor in the tropics is critical right now; that clouds absorb short-wave radiation; and that there is a need to improve measurements of atmospheric contents, the development of models, and the understanding of basic physics. We also need to understand parameters for detecting climate change, water, water temperature, and be able to provide fundamental information. Additional information is included in the original extended abstract.

2K09 and thereafter : the coming era of integrative bioinformatics, systems biology and intelligent computing for functional genomics and personalized medicine research.

PubMed

Yang, Jack Y; Niemierko, Andrzej; Bajcsy, Ruzena; Xu, Dong; Athey, Brian D; Zhang, Aidong; Ersoy, Okan K; Li, Guo-Zheng; Borodovsky, Mark; Zhang, Joe C; Arabnia, Hamid R; Deng, Youping; Dunker, A Keith; Liu, Yunlong; Ghafoor, Arif

2010-12-01

Significant interest exists in establishing synergistic research in bioinformatics, systems biology and intelligent computing. Supported by the United States National Science Foundation (NSF), International Society of Intelligent Biological Medicine (http://www.ISIBM.org), International Journal of Computational Biology and Drug Design (IJCBDD) and International Journal of Functional Informatics and Personalized Medicine, the ISIBM International Joint Conferences on Bioinformatics, Systems Biology and Intelligent Computing (ISIBM IJCBS 2009) attracted more than 300 papers and 400 researchers and medical doctors world-wide. It was the only inter/multidisciplinary conference aimed to promote synergistic research and education in bioinformatics, systems biology and intelligent computing. The conference committee was very grateful for the valuable advice and suggestions from honorary chairs, steering committee members and scientific leaders including Dr. Michael S. Waterman (USC, Member of United States National Academy of Sciences), Dr. Chih-Ming Ho (UCLA, Member of United States National Academy of Engineering and Academician of Academia Sinica), Dr. Wing H. Wong (Stanford, Member of United States National Academy of Sciences), Dr. Ruzena Bajcsy (UC Berkeley, Member of United States National Academy of Engineering and Member of United States Institute of Medicine of the National Academies), Dr. Mary Qu Yang (United States National Institutes of Health and Oak Ridge, DOE), Dr. Andrzej Niemierko (Harvard), Dr. A. Keith Dunker (Indiana), Dr. Brian D. Athey (Michigan), Dr. Weida Tong (FDA, United States Department of Health and Human Services), Dr. Cathy H. Wu (Georgetown), Dr. Dong Xu (Missouri), Drs. Arif Ghafoor and Okan K Ersoy (Purdue), Dr. Mark Borodovsky (Georgia Tech, President of ISIBM), Dr. Hamid R. Arabnia (UGA, Vice-President of ISIBM), and other scientific leaders. The committee presented the 2009 ISIBM Outstanding Achievement Awards to Dr. Joydeep Ghosh (UT

2K09 and thereafter : the coming era of integrative bioinformatics, systems biology and intelligent computing for functional genomics and personalized medicine research

PubMed Central

2010-01-01

Significant interest exists in establishing synergistic research in bioinformatics, systems biology and intelligent computing. Supported by the United States National Science Foundation (NSF), International Society of Intelligent Biological Medicine (http://www.ISIBM.org), International Journal of Computational Biology and Drug Design (IJCBDD) and International Journal of Functional Informatics and Personalized Medicine, the ISIBM International Joint Conferences on Bioinformatics, Systems Biology and Intelligent Computing (ISIBM IJCBS 2009) attracted more than 300 papers and 400 researchers and medical doctors world-wide. It was the only inter/multidisciplinary conference aimed to promote synergistic research and education in bioinformatics, systems biology and intelligent computing. The conference committee was very grateful for the valuable advice and suggestions from honorary chairs, steering committee members and scientific leaders including Dr. Michael S. Waterman (USC, Member of United States National Academy of Sciences), Dr. Chih-Ming Ho (UCLA, Member of United States National Academy of Engineering and Academician of Academia Sinica), Dr. Wing H. Wong (Stanford, Member of United States National Academy of Sciences), Dr. Ruzena Bajcsy (UC Berkeley, Member of United States National Academy of Engineering and Member of United States Institute of Medicine of the National Academies), Dr. Mary Qu Yang (United States National Institutes of Health and Oak Ridge, DOE), Dr. Andrzej Niemierko (Harvard), Dr. A. Keith Dunker (Indiana), Dr. Brian D. Athey (Michigan), Dr. Weida Tong (FDA, United States Department of Health and Human Services), Dr. Cathy H. Wu (Georgetown), Dr. Dong Xu (Missouri), Drs. Arif Ghafoor and Okan K Ersoy (Purdue), Dr. Mark Borodovsky (Georgia Tech, President of ISIBM), Dr. Hamid R. Arabnia (UGA, Vice-President of ISIBM), and other scientific leaders. The committee presented the 2009 ISIBM Outstanding Achievement Awards to Dr. Joydeep Ghosh (UT

Synthesis, characterizations and anti-bacterial activities of pure and Ag doped CdO nanoparticles by chemical precipitation method

NASA Astrophysics Data System (ADS)

Sivakumar, S.; Venkatesan, A.; Soundhirarajan, P.; Khatiwada, Chandra Prasad

2015-02-01

In the present study, synthesized pure and Ag (1%, 2%, and 3%) doped Cadmium Oxide (CdO) nanoparticles by chemical precipitation method. Then, the synthesized products were characterized by thermo gravimetric-differential thermal analysis (TG-DTA), X-ray diffraction (XRD) analysis, Fourier transform infrared (FT-IR) spectroscopy, Ultra violet-Vis diffused reflectance spectroscopy (UV-Vis-DRS), Scanning electron microscopy (SEM), Energy dispersive X-rays (EDX) spectroscopy, and anti-bacterial activities, respectively. The transition temperatures and phase transitions of Cd(OH)2 to CdO at 400 °C was confirmed by TG-DTA analysis. The XRD patterns show the cubic shape and average particle sizes are 21, 40, 34, and 37 nm, respectively for pure and Ag doped samples. FT-IR study confirmed the presence of CdO and Ag at 677 and 459 cm-1, respectively. UV-Vis-DRS study shows the variation on direct and indirect band gaps. The surface morphologies and elemental analysis have been confirmed from SEM and with EDX. In addition, the synthesized products have been characterized by antibacterial activities against Gram-positive and negative bacteria. Further, the present investigation suggests that CdO nanoparticles have the great potential applications on various industrial and medical fields of research.

Leveraging Large-Scale Cancer Genomics Datasets for Germline Discovery - TCGA

Cancer.gov

The session will review how data types have changed over time, focusing on how next-generation sequencing is being employed to yield more precise information about the underlying genomic variation that influences tumor etiology and biology.

A Panel of Novel Detection and Prognostic Methylated DNA Markers in Primary Non-Small Cell Lung Cancer and Serum DNA.

PubMed

Ooki, Akira; Maleki, Zahra; Tsay, Jun-Chieh J; Goparaju, Chandra; Brait, Mariana; Turaga, Nitesh; Nam, Hae-Seong; Rom, William N; Pass, Harvey I; Sidransky, David; Guerrero-Preston, Rafael; Hoque, Mohammad Obaidul

2017-11-15

Purpose: To establish a novel panel of cancer-specific methylated genes for cancer detection and prognostic stratification of early-stage non-small cell lung cancer (NSCLC). Experimental Design: Identification of differentially methylated regions (DMR) was performed with bumphunter on "The Cancer Genome Atlas (TCGA)" dataset, and clinical utility was assessed using quantitative methylation-specific PCR assay in multiple sets of primary NSCLC and body fluids that included serum, pleural effusion, and ascites samples. Results: A methylation panel of 6 genes ( CDO1, HOXA9, AJAP1, PTGDR, UNCX , and MARCH11 ) was selected from TCGA dataset. Promoter methylation of the gene panel was detected in 92.2% (83/90) of the training cohort with a specificity of 72.0% (18/25) and in 93.0% (40/43) of an independent cohort of stage IA primary NSCLC. In serum samples from the later 43 stage IA subjects and population-matched 42 control subjects, the gene panel yielded a sensitivity of 72.1% (31/41) and specificity of 71.4% (30/42). Similar diagnostic accuracy was observed in pleural effusion and ascites samples. A prognostic risk category based on the methylation status of CDO1, HOXA9, PTGDR , and AJAP1 refined the risk stratification for outcomes as an independent prognostic factor for an early-stage disease. Moreover, the paralog group for HOXA9, predominantly overexpressed in subjects with HOXA9 methylation, showed poor outcomes. Conclusions: Promoter methylation of a panel of 6 genes has potential for use as a biomarker for early cancer detection and to predict prognosis at the time of diagnosis. Clin Cancer Res; 23(22); 7141-52. ©2017 AACR . ©2017 American Association for Cancer Research.

Diagnostic accuracy of Onen's Alternative Grading System combined with Doppler evaluation of ureteral jets as an alternative in the diagnosis of obstructive hydronephrosis in children.

PubMed

de Bessa, Jose; Rodrigues, Cicilia M; Chammas, Maria Cristina; Miranda, Eduardo P; Gomes, Cristiano M; Moscardi, Paulo R; Bessa, Marcia C; Molina, Carlos A; Tiraboschi, Ricardo B; Netto, Jose M; Denes, Francisco T

2018-01-01

Ureteropelvic junction obstruction (UPJO) is a common congenital anomaly leading to varying degrees of hydronephrosis (HN), ranging from no apparent effect on the renal function to atrophy. Evaluation of these children is based on Diuretic Renal Scintigraphy (DRS) and Ultrasonography (US). Recent studies have suggested that new parameters of conventional and color Doppler ultrasonography (CDUS) may be useful in discriminating which kidneys are obstructed. The present study aims to assess the diagnostic accuracy of such parameters in the diagnosis of obstruction in children with UPJO. We evaluated 44 patients (33 boys) with a mean age of 6.53 ± 4.39 years diagnosed with unilateral high-grade hydronephrosis (SFU grades 3 and 4). All underwent DRS and index tests (conventional US and CDUS to evaluate ureteral jets frequency) within a maximum interval of two weeks. Hydronephrotic units were reclassified according to the alternative grading system (AGS) proposed by Onen et al. Obstruction in the DRS was defined as a differential renal function <40% on the affected side and/or features indicating poor drainage function like T1/2 >20 minutes after the administration of furosemide, and a plateau or ascending pattern of the excretion curve. Nineteen hydronephrotic units (43.1%) were obstructed. Some degree of cortical atrophy-grades 3 (segmental) or 4 (diffuse)-was present in those obstructed units. AGS grades had 100% sensitivity, 76% of specificity and 86.4% of accuracy. The absence of ureteral jets had a sensitivity of 73.68%, a specificity of 100% with an accuracy of 88.6%. When we analyzed the two aspects together and considered obstructed the renal units classified as AGS grade 3 or 4 with no jets, sensitivity increased to 78.9%, accuracy to 92%, remaining with a maximum specificity of 100%. These features combined would allow us to avoid performing DRS in 61% of our patients, leaving more invasive tests to inconclusive cases. Although DRS remains the mainstay to

Diffuse near-infrared reflectance spectroscopy during heatstroke in a mouse model: pilot study.

PubMed

Abookasis, David; Zafrir, Elad; Nesher, Elimelech; Pinhasov, Albert; Sternklar, Shmuel; Mathews, Marlon S

2012-10-01

Heatstroke, a form of hyperthermia, is a life-threatening condition characterized by an elevated core body temperature that rises above 40°C (104°F) and central nervous system dysfunction that results in delirium, convulsions, or coma. Without emergency treatment, the victim lapses into a coma and death soon follows. The study presented was conducted with a diffuse reflectance spectroscopy (DRS) setup to assess the effects of brain dysfunction that occurred during heatstroke in mice model (n=6). It was hypothesized that DRS can be utilized in small animal studies to monitor change in internal brain tissue temperature during heatstroke injury since it induces a sequence of pathologic changes that change the tissue composition and structure. Heatstroke was induced by exposure of the mice body under general anesthesia, to a high ambient temperature. A type of DRS in which the brain tissue was illuminated through the intact scalp with a broadband light source and diffuse reflected spectra was employed, taking in the spectral region between 650 and 1000 nm and acquired at an angle of 90 deg at a position on the scalp ∼12  mm from the illumination site. The temperature at the onset of the experiment was ∼34°C (rectal temperature) with increasing intervals of 1°C until mouse death. The increase in temperature caused optical scattering signal changes consistent with a structural alteration of brain tissue, ultimately resulting in death. We have found that the peak absorbance intensity and its second derivative at specific wavelengths correlate well with temperature with an exponential dependence. Based on these findings, in order to estimate the influence of temperature on the internal brain tissue a reflectance-temperature index was established and was seen to correlate as well with measured temperature. Overall, results indicate variations in neural tissue properties during heatstroke and the feasibility to monitor and assess internal temperature variations

Text Mining Effectively Scores and Ranks the Literature for Improving Chemical-Gene-Disease Curation at the Comparative Toxicogenomics Database

PubMed Central

Johnson, Robin J.; Lay, Jean M.; Lennon-Hopkins, Kelley; Saraceni-Richards, Cynthia; Sciaky, Daniela; Murphy, Cynthia Grondin; Mattingly, Carolyn J.

2013-01-01

The Comparative Toxicogenomics Database (CTD; http://ctdbase.org/) is a public resource that curates interactions between environmental chemicals and gene products, and their relationships to diseases, as a means of understanding the effects of environmental chemicals on human health. CTD provides a triad of core information in the form of chemical-gene, chemical-disease, and gene-disease interactions that are manually curated from scientific articles. To increase the efficiency, productivity, and data coverage of manual curation, we have leveraged text mining to help rank and prioritize the triaged literature. Here, we describe our text-mining process that computes and assigns each article a document relevancy score (DRS), wherein a high DRS suggests that an article is more likely to be relevant for curation at CTD. We evaluated our process by first text mining a corpus of 14,904 articles triaged for seven heavy metals (cadmium, cobalt, copper, lead, manganese, mercury, and nickel). Based upon initial analysis, a representative subset corpus of 3,583 articles was then selected from the 14,094 articles and sent to five CTD biocurators for review. The resulting curation of these 3,583 articles was analyzed for a variety of parameters, including article relevancy, novel data content, interaction yield rate, mean average precision, and biological and toxicological interpretability. We show that for all measured parameters, the DRS is an effective indicator for scoring and improving the ranking of literature for the curation of chemical-gene-disease information at CTD. Here, we demonstrate how fully incorporating text mining-based DRS scoring into our curation pipeline enhances manual curation by prioritizing more relevant articles, thereby increasing data content, productivity, and efficiency. PMID:23613709

Dual-modality smartphone endoscope for cervical pre-cancer detection (Conference Presentation)

NASA Astrophysics Data System (ADS)

Hong, Xiangqian; Yu, Bing

2017-02-01

Early detection is the key to the prevention of cervical cancer. There is an urgent need for a portable, affordable, and easy-to-use device for cervical pre-cancer detection, especially in low-resource settings. We have developed a dual-modality fiber-optic endoscope system (SmartME) that integrates high-resolution fluorescence imaging (FLI) and quantitative diffuse reflectance spectroscopy (DRS) onto a smartphone platform. The SmartME consists of a smartphone, a miniature fiber-optic endoscope, a phone attachment containing imaging optics, and a smartphone application (app). FLI is obtained by painting the tissue with a contrast agent (e.g., proflavine), illuminating the tissue and collecting its fluorescence images through an imaging bundle that is coupled to the phone camera. DRS is achieved by using a white LED, attaching additional source and detection fibers to the imaging bundle, and converting the phone camera into a spectrometer. The app collects images/spectra and transmits them to a remote server for analysis to extract the tissue parameters, including nuclear-to-cytoplasm ratio (calculated from FLI), concentrations of oxyhemoglobin (HbO2) and deoxyhemoglobin (Hb) as well as scattering (measured by DRS). These parameters can be used to detect cervical dysplasia. Our preliminary studies have demonstrated that the SmartME can clearly visualize the nuclei in living cells and in vivo biological samples, with a high spatial resolution of 3.1μm. The device can also measure tissue absorption and scattering properties with comparable accuracy to those of a benchtop DRS system. The SmartME has great potential to provide a compact, affordable, and `smart' solution for early detection of neoplastic changes in cervix.

Sensing vascularization of ex-vivo produced oral mucosal equivalent (EVPOME) skin grafts in nude mice using optical spectroscopy

NASA Astrophysics Data System (ADS)

Vishwanath, Karthik; Gurjar, Rajan; Kuo, Shiuhyang; Fasi, Anthony; Kim, Roderick; Riccardi, Suzannah; Feinberg, Stephen E.; Wolf, David E.

2014-03-01

Repair of soft tissue defects of the lips as seen in complex maxillofacial injuries, requires pre-vascularized multi-tissue composite grafts. Protocols for fabrication of human ex-vivo produced oral mucosal equivalents (EVPOME) composed of epithelial cells and a dermal equivalent are available to create prelaminated flaps for grafting in patients. However, invivo assessment of neovascularization of the buried prelaminated flaps remains clinically challenging. Here, we use diffuse reflectance spectroscopy (DRS) and diffuse correlation spectroscopy (DCS) to non-invasively quantify longitudinal changes in the vessel density and blood-flow within EVPOME grafts implanted in the backs of SCID mice and subsequently to determine the utility of these optical techniques for assessing vascularization of implanted grafts. 20 animals were implanted with EVPOME grafts (1x1x0.05 cm3) in their backs. DRS and DCS measurements were obtained from each animal both atop the graft site and far away from the graft site, at one week post-implantation, each week, for four consecutive weeks. DRS spectra were analyzed using an inverse Monte Carlo model to extract tissue absorption and scattering coefficients, which were then used to extract blood flow information by fitting the experimental DCS traces. There were clear differences in the mean optical parameters (averaged across all mice) at the graft site vs. the off-site measurements. Both the total hemoglobin concentration (from DRS) and the relative blood flow (from DCS) peaked at week 3 at the graft site and declined to the off-site values by week 4. The optical parameters remained relatively constant throughout 4 weeks for the off-site measurements.