Investigation of internalization and cytotoxicity of 125I-[Tyr3]-octreotide in NCI-H446 cell line

International Nuclear Information System (INIS)

Sun Junjie; Fan Wo; Xu Yujie; Zhang Youjiu; Zhu Ran; Hu Mingjiang

2004-01-01

Objective: To investigate the [Tyr 3 ]-octreotide (TOC) internalizing capacity of NCI-H446 cell line, and the cytotoxicity of 125 I-TOC in NCI-H446 cell line. To assess the therapeutic radiopharmaceutical potentiality of 125 I-TOC for the somatostatin receptor (SSTR) positive tumor. Methods: NCI-H446 cells were incubated together with 125 I-TOC for different periods of time, the amount of internalized 125 I-TOC and the 125 I-TOC bound on the cellular nucleus were detected with γ counter, respectively. The viability of the cells was analyzed by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay at different time points with various doses of 125 I-TOC, free 125 I and TOC. Results: 125 I-TOC was internalized into the nucleus and bound on the nucleus in a time-dependent manner. 125 I-TOC bound on the nucleus increased to the highest level at 24 h, the amount of nucleus bound 125 I-TOC at 24 h was 7 times higher than that at 0.5 h. Cytotoxicity of 125 I-TOC in SSTR positive NCI-H446 cells was also dose- and time-dependent. The supreme effect of cytotoxicity was found at 96 h with 74 kBq 125 I-TOC, the survival ratio of cells was reduced to (44.8 ± 7.2)%. Conclusions: 125 I-TOC can be internalized into SSTR positive cells mediated by SSTR. The NCI-H446 cells can be killed by Auger electron emitting from 125 I-TOC. Effect of cytotoxicity showed dose- and time-dependent

NCI designated cancer center funding not influenced by organizational structure.

Science.gov (United States)

Wolfe, Margaret E; Yagoda, Daniel; Thurman, Paul W; Luna, Jorge M; Figg, William Douglas

2009-05-01

National Cancer Institutes (NCI) designated cancer centers use one of three organizational structures. The hypothesis of this study is that there are differences in the amount of annual NCI funding per faculty member based on a cancer center's organizational structure. The study also considers the impact of secondary factors (i.e., the existence of a clinical program, the region and the size of the city in which the cancer center is located) on funding and the number of Howard Hughes Medical Institute (HHMI) investigators at each cancer center. Of the 63 cancer centers, 44 use a matrix structure, 16 have a freestanding structure, and three have a Department of Oncology structure. Kruskal-Wallis tests reveal no statistically significant differences in the amount of funding per faculty member or the number of HHMI investigators between centers with a matrix, freestanding or Department of Oncology structure. Online research and telephone interviews with each cancer center were used to gather information, including: organizational structure, the presence of a clinical program, the number of faculty members, and the number of Howard Hughes Medical Institute investigators. Statistical tests were used to assess the impact which organizational structure has on the amount of funding per faculty member and number of HHMI investigators. While the results seem to suggest that the organizational structure of a given cancer center does not impact the amount of NCI funding or number of HHMI investigators which it attracts, the existence of this relationship is likely masked by the small sample size in this study. Further studies may be appropriate to examine the effect organizational structure has on other measurements which are relevant to cancer centers, such as quality and quantity of research produced.

International Fellows of NCI at Frederick | Poster

Science.gov (United States)

Each year, the Employee Diversity Team (EDT) acknowledges members of the NCI at Frederick Community for their achievements and contributions towards the mission of facility.  Historically, the team has profiled the “Women of NCI at Frederick,” but this year, the team decided to instead shed light on the diverse and successful individuals who make up the international fellows community.

Photo dynamics of BLUF domain mutant H44R of AppA from Rhodobacter sphaeroides

Energy Technology Data Exchange (ETDEWEB)

Zirak, P. [Institut II - Experimentelle und Angewandte Physik, Universitaet Regensburg, Universitaetstrasse 31, D-93053 Regensburg (Germany); Penzkofer, A. [Institut II - Experimentelle und Angewandte Physik, Universitaet Regensburg, Universitaetstrasse 31, D-93053 Regensburg (Germany)], E-mail: alfons.penzkofer@physik.uni-regensburg.de; Hegemann, P.; Mathes, T. [Institut fuer Biologie, Experimentelle Biophysik, Humboldt-Universitaet zu Berlin, Invalidenstr. 42, D-10115 Berlin (Germany)

2007-05-21

The photo-cycle dynamics of the H44R mutant of the BLUF domain of the transcriptional anti-repressor protein AppA (AppA-H44R) from the non-sulfur anoxyphototropic purple bacterium Rhodobacter sphaeroides is studied in order to gain information on the involvement of His44 in the photo-cyclic mechanism of the AppA BLUF domain and to add information to the involved processes. The amino acid residue histidine at position 44 is replaced by arginine. A 12 nm red-shifted signalling state is formed upon blue-light excitation, while in wild-type AppA (AppA-wt) the red-shift is 16 nm. The recovery to the receptor dark state is approximately a factor of 2.5 faster ({tau}{sub rec} {approx} 6.5 min) than the recovery of the wild-type counterpart. Extended light exposure of the mutant causes photo-degradation of flavin (mainly free flavin conversion to lumichrome and re-equilibration between free and non-covalently bound flavin) and protein aggregation (showing up as light scattering). No photo-degradation was observed for AppA-wt. The quantum efficiency of signalling-state formation determined by intensity dependent absorption measurements is found to be {phi}{sub s} {approx} 0.3 (for AppA-wt: {phi}{sub s} {approx} 0.24). A two-component single-exponential fluorescence relaxation was observed, which is interpreted as fast fluorescence quenching to an equilibrium value by photo-induced electron transfer followed by slower fluorescence decay due to charge recombination. Based on the experimental findings, an extended photo-cycle model for BLUF domains is proposed.

NCI at Frederick Ebola Response Team | Poster

Science.gov (United States)

Editor’s note: This article was adapted from the Employee Diversity Team’s display case exhibit “Recognizing the NCI at Frederick Ebola Response Team,” in the lobby of Building 549. The Poster staff recognizes that this article does not include everyone who was involved in the response to the Ebola crisis, both at NCI at Frederick and in Africa. When the Ebola crisis broke out

IJUE. Tema 3. Les competències de la Unió Europea

OpenAIRE

Torres Pérez, María

2018-01-01

PowerPoint del Tema 3 de la asignatura "Institucions Jurídiques de la Unió Europea". Curso académico 2017-2018. Tema 3. Les competències de la Unió Europea. 1. L’atribució de competències a la Unió Europea. 2. La delimitació de les competències a la Unió Europea. 3. Els principis que regeixen l’exercici de les competències. 4. L’exercici de les competències de la Unió per “alguns Estats membres”.

An NCI perspective on creating sustainable biospecimen resources.

Science.gov (United States)

Vaught, Jimmie; Rogers, Joyce; Myers, Kimberly; Lim, Mark David; Lockhart, Nicole; Moore, Helen; Sawyer, Sherilyn; Furman, Jeffrey L; Compton, Carolyn

2011-01-01

High-quality biospecimens with appropriate clinical annotation are critical in the era of personalized medicine. It is now widely recognized that biospecimen resources need to be developed and operated under established scientific, technical, business, and ethical/legal standards. To date, such standards have not been widely practiced, resulting in variable biospecimen quality that may compromise research efforts. The National Cancer Institute (NCI) Office of Biorepositories and Biospecimen Research (OBBR) was established in 2005 to coordinate NCI's biospecimen resource activities and address those issues that affect access to the high-quality specimens and data necessary for its research enterprises as well as the broader translational research field. OBBR and the NCI Biorepository Coordinating Committee developed NCI's "Best Practices for Biospecimen Resources" after consultation with a broad array of experts. A Biospecimen Research Network was established to fund research to develop additional evidence-based practices. Although these initiatives will improve the overall availability of high-quality specimens and data for cancer research, OBBR has been authorized to implement a national biobanking effort, cancer HUman Biobank (caHUB). caHUB will address systematically the gaps in knowledge needed to improve the state-of-the-science and strengthen the standards for human biobanking. This commentary outlines the progressive efforts by NCI in technical, governance, and economic considerations that will be important as the new caHUB enterprise is undertaken.

Curcumin Inhibits Growth of Human NCI-H292 Lung Squamous Cell Carcinoma Cells by Increasing FOXA2 Expression

Directory of Open Access Journals (Sweden)

Lingling Tang

2018-02-01

Full Text Available Lung squamous cell carcinoma (LSCC is a common histological lung cancer subtype, but unlike lung adenocarcinoma, limited therapeutic options are available for treatment. Curcumin, a natural compound, may have anticancer effects in various cancer cells, but how it may be used to treat LSCC has not been well studied. Here, we applied curcumin to a human NCI-H292 LSCC cell line to test anticancer effects and explored underlying potential mechanisms of action. Curcumin treatment inhibited NCI-H292 cell growth and increased FOXA2 expression in a time-dependent manner. FOXA2 expression was decreased in LSCC tissues compared with adjacent normal tissues and knockdown of FOXA2 increased NCI-H292 cells proliferation. Inhibition of cell proliferation by curcumin was attenuated by FOXA2 knockdown. Moreover inhibition of STAT3 pathways by curcumin increased FOXA2 expression in NCI-H292 cells whereas a STAT3 activator (IL-6 significantly inhibited curcumin-induced FOXA2 expression. Also, SOCS1 and SOCS3, negative regulators of STAT3 activity, were upregulated by curcumin treatment. Thus, curcumin inhibited human NCI-H292 cells growth by increasing FOXA2 expression via regulation of STAT3 signaling pathways.

DNA fingerprinting of the NCI-60 cell line panel.

Science.gov (United States)

Lorenzi, Philip L; Reinhold, William C; Varma, Sudhir; Hutchinson, Amy A; Pommier, Yves; Chanock, Stephen J; Weinstein, John N

2009-04-01

The National Cancer Institute's NCI-60 cell line panel, the most extensively characterized set of cells in existence and a public resource, is frequently used as a screening tool for drug discovery. Because many laboratories around the world rely on data from the NCI-60 cells, confirmation of their genetic identities represents an essential step in validating results from them. Given the consequences of cell line contamination or misidentification, quality control measures should routinely include DNA fingerprinting. We have, therefore, used standard DNA microsatellite short tandem repeats to profile the NCI-60, and the resulting DNA fingerprints are provided here as a reference. Consistent with previous reports, the fingerprints suggest that several NCI-60 lines have common origins: the melanoma lines MDA-MB-435, MDA-N, and M14; the central nervous system lines U251 and SNB-19; the ovarian lines OVCAR-8 and OVCAR-8/ADR (also called NCI/ADR); and the prostate lines DU-145, DU-145 (ATCC), and RC0.1. Those lines also show that the ability to connect two fingerprints to the same origin is not affected by stable transfection or by the development of multidrug resistance. As expected, DNA fingerprints were not able to distinguish different tissues-of-origin. The fingerprints serve principally as a barcodes.

NCI Pediatric Preclinical Testing Consortium

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NCI has awarded grants to five research teams to participate in its Pediatric Preclinical Testing Consortium, which is intended to help to prioritize which agents to pursue in pediatric clinical trials.

NCI's Role in Immunotherapy Research

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... Reporting & Auditing Grant Transfer Grant Closeout Contracts & Small Business Training Cancer Training at NCI (Intramural) Resources for ... promising immunotherapies to the clinic more efficiently and cost effectively. For ... of the checkpoint inhibitor pembrolizumab in patients with ...

Mechanism of gene transfection by polyamidoamine (PAMAM) dendrimers modified with ornithine residues.

Science.gov (United States)

Kumar, Ajay; Yellepeddi, Venkata K; Vangara, Kiran K; Strychar, Kevin B; Palakurthi, Srinath

2011-11-01

The aim of this study was to prepare and investigate the mechanism of uptake of the dendriplexes prepared with ornithine-conjugated polyamidoamine (PAMAM) G4 dendrimers. Ornithine-conjugated PAMAMG4 dendrimers were prepared by Fmoc synthesis. A comparative transfection study in NCI H157G cells and polyamine transport-deficient cell line NCI H157R was performed to confirm the role of the polyamine transporter system (PAT) in the dendriplex uptake. Transfection efficiency significantly increased with increase in generation number and extent of ornithine conjugation. Transfection efficiency of the PAMAMG4-ORN60 dendrimers significantly decreased in presence of excess of ornithine (P dendrimers. Transfection efficiency of PAMAMG4-ORN60 was significantly low in NCI H157R (31.66 ± 3.95%, RFU: 17.87 ± 1.34) as compared to NCI H157G cell line (63.07 ± 6.8%, relative fluorescence units (RFU): 23.28 ± 0.66). Results indicate the role of PAT in addition to charge-mediated endocytosis in the internalization of ornithine-conjugated PAMAMG4 dendrimers. Cytotoxicity analysis (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay) in human embryonic kidney cell line (HEK) 293T cells showed that the dendriplexes were non-toxic at N/P 10.

NCI-MATCH Trial Links Targeted Drugs to Mutations

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Investigators for the nationwide trial, NCI-MATCH: Molecular Analysis for Therapy Choice, announced that the trial will seek to determine whether targeted therapies for people whose tumors have specific gene mutations will be effective regardless of their cancer type. NCI-MATCH will incorporate more than 20 different study drugs or drug combinations, each targeting a specific gene mutation, in order to match each patient in the trial with a therapy that targets a molecular abnormality in their tumor.

NCI Takes Back the Defelice Cup at Ninth Annual Golf Tournament | Poster

Science.gov (United States)

By Ashley DeVine, Staff Writer After being down by a point in the morning, NCI reclaimed the Defelice Cup trophy from Leidos Biomedical Research, with a final score of 12 ½ to 11 ½, at the ninth annual Ronald H. Defelice Golf Tournament, held Oct. 13. “The tightest matches in the nine-year history of this cup competition resulted in a narrow victory for NCI and allowed NCI to

Find an NCI-Designated Cancer Center

Science.gov (United States)

Find the locations of NCI-designated cancer centers by area, region, state, or name that includes contact information to help health care providers and cancer patients with referrals to clinical trials.

NCI's Transdisciplinary High Performance Scientific Data Platform

Science.gov (United States)

Evans, Ben; Antony, Joseph; Bastrakova, Irina; Car, Nicholas; Cox, Simon; Druken, Kelsey; Evans, Bradley; Fraser, Ryan; Ip, Alex; Kemp, Carina; King, Edward; Minchin, Stuart; Larraondo, Pablo; Pugh, Tim; Richards, Clare; Santana, Fabiana; Smillie, Jon; Trenham, Claire; Wang, Jingbo; Wyborn, Lesley

2016-04-01

The Australian National Computational Infrastructure (NCI) manages Earth Systems data collections sourced from several domains and organisations onto a single High Performance Data (HPD) Node to further Australia's national priority research and innovation agenda. The NCI HPD Node has rapidly established its value, currently managing over 10 PBytes of datasets from collections that span a wide range of disciplines including climate, weather, environment, geoscience, geophysics, water resources and social sciences. Importantly, in order to facilitate broad user uptake, maximise reuse and enable transdisciplinary access through software and standardised interfaces, the datasets, associated information systems and processes have been incorporated into the design and operation of a unified platform that NCI has called, the National Environmental Research Data Interoperability Platform (NERDIP). The key goal of the NERDIP is to regularise data access so that it is easily discoverable, interoperable for different domains and enabled for high performance methods. It adopts and implements international standards and data conventions, and promotes scientific integrity within a high performance computing and data analysis environment. NCI has established a rich and flexible computing environment to access to this data, through the NCI supercomputer; a private cloud that supports both domain focused virtual laboratories and in-common interactive analysis interfaces; as well as remotely through scalable data services. Data collections of this importance must be managed with careful consideration of both their current use and the needs of the end-communities, as well as its future potential use, such as transitioning to more advanced software and improved methods. It is therefore critical that the data platform is both well-managed and trusted for stable production use (including transparency and reproducibility), agile enough to incorporate new technological advances and

76 FR 28439 - Submission for OMB Review; Comment Request; NCI Cancer Genetics Services Directory Web-Based...

Science.gov (United States)

2011-05-17

...; Comment Request; NCI Cancer Genetics Services Directory Web-Based Application Form and Update Mailer... currently valid OMB control number. Proposed Collection: Title: NCI Cancer Genetics Services Directory Web... included in the NCI Cancer Genetics Services Directory on NCI's Cancer.gov Web site. The information...

DISSENYAR EXPERIÈNCIES AMB VALOR TURÍSTIC: PAISATGES URBANS

Directory of Open Access Journals (Sweden)

Francesc Fusté

2015-10-01

Full Text Available Aquest article tracta sobre les possibilitats que la creació d’experiències té en relació al desenvolupament empresarial i regional, gràcies a la tematització del sector turístic i la modificació intencional de l’entorn, tant cultural com natural. El paisatge caracteritza els espais en funció de la seva configuració territorial i també arquitectònica i urbana. Les estructures arquitectòniques, els esdeveniments i les activitats que impliquen la participació activa dels usuaris són la clau de l’èxit del disseny de les experiències amb un valor afegit, on les noves tecnologies ajuden a emfatitzar-ne l’impacte. Sigui com sigui, convertir els llocs en experiències tant pels residents com pels visitants.

NCI Scientists Awarded National Medal of Technology and Innovation by President Obama | Poster

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Two NCI scientists received the National Medal of Technology and Innovation, the nation’s highest honor for technological achievement. The award was announced by President Obama in October. The honorees, John Schiller, Ph.D., Laboratory of Cellular Oncology (LCO), Center for Cancer Research, NCI, and Douglas Lowy, M.D., also from LCO and NCI deputy director, received their medals at a White House ceremony on Nov. 20.

Selected Publications by the NCI Director

Science.gov (United States)

Dr. Norman Sharpless's written work on cancer research appears in many leading scientific journals, as well as a variety of other publications. This page lists some of the articles published by Dr. Sharpless since becoming NCI director.

Mechanisms of Cancer - Annual Plan

Science.gov (United States)

NCI works to understand the mechanisms of cancer cell growth, survival, and metastasis. Get more information on how NCI supports basic scientific research that will lead to new ways to prevent, detect, and treat cancer.

Avaluació de competències professionalitzadores en els estudis de grau de comunicació audiovisual

Directory of Open Access Journals (Sweden)

Marina Romeo

2017-01-01

Full Text Available Els recents canvis en la formació universitària han comportat un destacable nivell de professionalització dels estudis i una constant adequació a les demandes socials. En aquest sentit, una de les necessitats per a la formació universitària a l'àrea de la comunicació audiovisual és desenvolupar en els estudiants competències professionalitzadores que els permetin trobar nínxols d'ocupació en un mercat altament competitiu i sotmès a canvis continus. Aquesta recerca té per objecte crear una rúbrica que permeti avaluar l'aprenentatge professionalitzador en els estudis de grau en comunicació audiovisual (CAV que es desenvolupen a Espanya. Per desenvolupar-la hem comptat amb ocupadors i acadèmics experts de l'àmbit de la comunicació audiovisual triats de forma intencional. La rúbrica final desenvolupada, a més de permetre avaluar el grau d'adquisició de les competències professionalitzadores en CAV, permet dibuixar un mapa clar de l'organització i adequació dels processos i metodologies docents. En aquest sentit, la rúbrica pot ser un instrument pedagògic clau per a una futura promoció d'estudiants, i es pot convertir en un instrument que afavoreixi l'avaluació formativa dels alumnes.

Invention Development Program Helps Nurture NCI at Frederick Technologies | Poster

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The Invention Development Fund (IDF) was piloted by the Technology Transfer Center (TTC) in 2014 to facilitate the commercial development of NCI technologies. The IDF received a second round of funding from the NCI Office of the Director and the Office of Budget and Management to establish the Invention Development Program (IDP) for fiscal year 2016. The IDP is using these funds to help advance a second set of inventions.

About TTC | NCI Technology Transfer Center | TTC

Science.gov (United States)

The TTC facilitates licensing and co-development partnerships between biomedical industry, academia, and government agencies and the research laboratories of the NCI and nine other institutes and centers of NIH.

Life Outside NCI | Cancer Prevention Fellowship Program

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The CPFP Office is located at the NCI facilities in Rockville, Maryland, near the Nation’s Capital. With the convenient Metro subway reaching throughout the metropolitan area, transportation is within easy reach.

At NCI, Supporting the Best Science

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Yesterday, at the AACR annual meeting, Dr. Doug Lowy spoke directly to the research community about his goals as NCI Acting Director. Dr. Lowy said that he plans to continue many of the programs launched by his predecessor, Dr. Harold Varmus, and to sharp

Robert Wiltrout Says Goodbye to NCI in 2015 | Poster

Science.gov (United States)

After 34 years at NCI, Robert Wiltrout, Ph.D., said he is looking forward to trading his I-270 commute for another type of commute: exploring the waterways of Maryland, Alaska, and Wyoming to fulfill his love of fishing. Wiltrout officially retired as director of the NCI Center for Cancer Research (CCR) on July 2 of last year. Throughout his college academic career, Wiltrout had an interest in science, but it was not until he was working on a research project for his master’s degree that he considered a career in scientific research.

NCI's national environmental research data collection: metadata management built on standards and preparing for the semantic web

Science.gov (United States)

Wang, Jingbo; Bastrakova, Irina; Evans, Ben; Gohar, Kashif; Santana, Fabiana; Wyborn, Lesley

2015-04-01

National Computational Infrastructure (NCI) manages national environmental research data collections (10+ PB) as part of its specialized high performance data node of the Research Data Storage Infrastructure (RDSI) program. We manage 40+ data collections using NCI's Data Management Plan (DMP), which is compatible with the ISO 19100 metadata standards. We utilize ISO standards to make sure our metadata is transferable and interoperable for sharing and harvesting. The DMP is used along with metadata from the data itself, to create a hierarchy of data collection, dataset and time series catalogues that is then exposed through GeoNetwork for standard discoverability. This hierarchy catalogues are linked using a parent-child relationship. The hierarchical infrastructure of our GeoNetwork catalogues system aims to address both discoverability and in-house administrative use-cases. At NCI, we are currently improving the metadata interoperability in our catalogue by linking with standardized community vocabulary services. These emerging vocabulary services are being established to help harmonise data from different national and international scientific communities. One such vocabulary service is currently being established by the Australian National Data Services (ANDS). Data citation is another important aspect of the NCI data infrastructure, which allows tracking of data usage and infrastructure investment, encourage data sharing, and increasing trust in research that is reliant on these data collections. We incorporate the standard vocabularies into the data citation metadata so that the data citation become machine readable and semantically friendly for web-search purpose as well. By standardizing our metadata structure across our entire data corpus, we are laying the foundation to enable the application of appropriate semantic mechanisms to enhance discovery and analysis of NCI's national environmental research data information. We expect that this will further

Human Monoclonal Antibodies Targeting Glypican-2 in Neuroblastoma | NCI Technology Transfer Center | TTC

Science.gov (United States)

Researchers at the National Cancer Institute’s Laboratory of Molecular Biology (NCI LMB) have developed and isolated several single domain monoclonal human antibodies against GPC2. NCI seeks parties interested in licensing or co-developing GPC2 antibodies and/or conjugates.

Les competències. La doctrina del Tribunal sobre la definició de les competències. Les competències exclusives, les compartides i les executives. - Las competencias. La doctrina del Tribunal sobre la definición de las competencias. Competencias exclusivas, compartidas y ejecutivas.

Directory of Open Access Journals (Sweden)

Ramon Riu

2010-07-01

Full Text Available La doctrina de la Sentència 31/2010 sobre la definició estatutària de les categories competencials (251-257 Mercè Barceló i SerramaleraLa doctrina del Tribunal Constitucional sobre la definició de competències. Les competències exclusives, les compartides i les executives (258-261Antoni Bayona RocamoraLa doctrina de la Sentència 31/2010 sobre les competències executives (Xavier Bernadí GilLa doctrina del Tribunal sobre la definició de les competències. Les ompetències exclusives, les compartides i les executives (270-276Marc Carrillo LópezEls efectes de la Sentència sobre la definició estatutària de les competències: la «devaluació» jurídica dels estatuts d’autonomia (277-281Mercè Corretja TorrensLes categories funcionals de competències a l’Estatut d’autonomia de Catalunya. Comentaris a la Sentència 31/2010 (282-287Ramon Riu FortunyTipologia de les competències. El seu abast funcional: els articles 110 a 112 (288-294Joaquín Tornos Massostenella e no enmendalla (262-269 La doctrina de la Sentencia 31/2010 sobre la definición estatutaria de las categorías competenciales (251-257Mercè Barceló i SerramaleraLa doctrina del Tribunal Constitucional sobre la definición de competencias. Las competencias exclusivas, las compartidas y las ejecutivas (258-261Antoni Bayona RocamoraLa doctrina de la Sentencia 31/2010 sobre las competencias ejecutivas (sostenella e no enmendalla (262-270 Xavier Bernadí GilLa doctrina del Tribunal sobre la definición de las competencias. Las competencias exclusivas, las compartidas y las ejecutivas (271-277Marc Carrillo LópezLos efectos de la Sentencia sobre la definición estatutaria de las competencias:la «devaluación» jurídica de los estatutos de autonomía (278-283Mercè Corretja TorrensLas categorías funcionales de competencias en el Estatuto de Autonomía de Cataluña. Comentarios a la Sentencia 31/2010 (284-289Ramon Riu FortunyTipología de las competencias. Su alcance

Preclinical evaluation of melanocortin-1 receptor (MC1-R) specific 68Ga- and 44Sc-labeled DOTA-NAPamide in melanoma imaging.

Science.gov (United States)

Nagy, Gábor; Dénes, Noémi; Kis, Adrienn; Szabó, Judit P; Berényi, Ervin; Garai, Ildikó; Bai, Péter; Hajdu, István; Szikra, Dezső; Trencsényi, György

2017-08-30

Alpha melanocyte stimulating hormone (α-MSH) enhances melanogenesis in melanoma malignum by binding to melanocortin-1 receptors (MC1-R). Earlier studies demonstrated that alpha-MSH analog NAPamide molecule specifically binds to MC1-R receptor. Radiolabeled NAPamide is a promising radiotracer for the non-invasive detection of melanin producing melanoma tumors by Positron Emission Tomography (PET). In this present study the MC1-R selectivity of the newly developed Sc-44-labeled DOTA-NAPamide was investigated in vitro and in vivo using melanoma tumors. DOTA-NAPamide was labeled with Ga-68 and Sc-44 radionuclides. The MC1-R specificity of Ga-68- and Sc-44-labeled DOTA-NAPamide was investigated in vitro and in vivo using MC1-R positive (B16-F10) and negative (A375) melanoma cell lines. For in vivo imaging studies B16-F10 and A375 tumor-bearing mice were injected with 44 Sc/ 68 Ga-DOTA-NAPamide (in blocking studies with α-MSH) and whole body PET/MRI scans were acquired. Radiotracer uptake was expressed in terms of standardized uptake values (SUVs). 44 Sc/ 68 Ga-labeled DOTA-NAPamide were produced with high specific activity (approx. 19 GBq/μmol) and with excellent radiochemical purity (99%DOTA-NAPamide (SUVmean: 0.38±0.02), and Sc-44-DOTA-NAPamide (SUVmean: 0.52±0.13) uptake was observed in subcutaneously growing B16-F10 tumors, than in receptor negative A375 tumors, where the SUVmean values of Ga-68-DOTA-NAPamide and Sc-44-DOTA-NAPamide were 0.04±0.01 and 0.07±0.01, respectively. Tumor-to-muscle (T/M SUVmean) ratios were approximately 15-fold higher in B16-F10 tumor-bearing mice, than that of A375 tumors, and this difference was also significant (p≤0.01) using both radiotracers after 60 min incubation time. Our newly synthesized 44 Sc-labeled DOTA-NAPamide probe showed excellent binding properties to melanocortin-1 receptor (MC1-R) positive melanoma cell and tumors. Due to its high specificity and sensitivity 44 Sc-DOTA-NAPamide is a promising radiotracer in

NCI International EBV-Gastric Cancer Consortium

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A collaboration among NCI and extramural investigators, established by DCEG in 2006, that utilizes data and biospecimens from completed and ongoing case series and observational studies of gastric cancer to replicate and extend findings from previous studies hindered by small numbers of EBV-positive cases, and to stimulate multidisciplinary research in this area.

Spatial patterns of FUS-immunoreactive neuronal cytoplasmic inclusions (NCI) in neuronal intermediate filament inclusion disease (NIFID).

Science.gov (United States)

Armstrong, Richard A; Gearing, Marla; Bigio, Eileen H; Cruz-Sanchez, Felix F; Duyckaerts, Charles; Mackenzie, Ian R A; Perry, Robert H; Skullerud, Kari; Yokoo, Hideaki; Cairns, Nigel J

2011-11-01

Neuronal intermediate filament inclusion disease (NIFID), a rare form of frontotemporal lobar degeneration (FTLD), is characterized neuropathologically by focal atrophy of the frontal and temporal lobes, neuronal loss, gliosis, and neuronal cytoplasmic inclusions (NCI) containing epitopes of ubiquitin and neuronal intermediate filament (IF) proteins. Recently, the 'fused in sarcoma' (FUS) protein (encoded by the FUS gene) has been shown to be a component of the inclusions of NIFID. To further characterize FUS proteinopathy in NIFID, we studied the spatial patterns of the FUS-immunoreactive NCI in frontal and temporal cortex of 10 cases. In the cerebral cortex, sectors CA1/2 of the hippocampus, and the dentate gyrus (DG), the FUS-immunoreactive NCI were frequently clustered and the clusters were regularly distributed parallel to the tissue boundary. In a proportion of cortical gyri, cluster size of the NCI approximated to those of the columns of cells was associated with the cortico-cortical projections. There were no significant differences in the frequency of different types of spatial patterns with disease duration or disease stage. Clusters of NCI in the upper and lower cortex were significantly larger using FUS compared with phosphorylated, neurofilament heavy polypeptide (NEFH) or α-internexin (INA) immunohistochemistry (IHC). We concluded: (1) FUS-immunoreactive NCI exhibit similar spatial patterns to analogous inclusions in the tauopathies and synucleinopathies, (2) clusters of FUS-immunoreactive NCI are larger than those revealed by NEFH or ΙΝΑ, and (3) the spatial patterns of the FUS-immunoreactive NCI suggest the degeneration of the cortico-cortical projections in NIFID.

Molecular mechanism for the action of the anti-CD44 monoclonal antibody MEM-85

Czech Academy of Sciences Publication Activity Database

Škerlová, Jana; Král, Vlastimil; Kachala, M.; Fábry, Milan; Bumba, Ladislav; Svergun, D.I.; Tosner, Z.; Veverka, V.; Řezáčová, Pavlína

2015-01-01

Roč. 191, č. 2 (2015), s. 214-223 ISSN 1047-8477 R&D Projects: GA ČR(CZ) GA15-11851S EU Projects: European Commission 264257 Institutional support: RVO:68378050 ; RVO:61388971 Keywords : CD44 * Epitope mapping * Monoclonal antibody * MEM-85 * SAXS * NMR Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.570, year: 2015

College Graduate with NCI Internship Gains Experience, Carries Chemistry into Medicine | Poster

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For Jennifer Marshall, the skills learned through an internship at the National Cancer Institute (NCI) at Frederick have prepared her for the next step of her life—medical school. Marshall, who will be attending the West Virginia University School of Medicine in the fall, spent three summers in NCI at Frederick’s Summer Internship Program expanding her love and passion for

NCI Releases Video: Proteogenomics Research - On the Frontier of Precision Medicine | Office of Cancer Clinical Proteomics Research

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The Clinical Proteomic Tumor Analysis Consortium (CPTAC) of the National Cancer Institute (NCI), part of the National Institutes of Health, announces the release of an educational video titled “Proteogenomics Research: On the Frontier of Precision Medicine."  Launched at the HUPO2017 Global Leadership Gala Dinner, catalyzed in part by the Cancer Moonshot initiative and featuring as keynote speaker the 47th Vice President of the United States of America Joseph R.

Vaccine for BK Polyomavirus-associated Infections in Transplant Recipients | NCI Technology Transfer Center | TTC

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NCI researches identified a BK polyomavirus (BKV) virulent strain that causes chronic urinary tract infections, and the development of vaccine and therapeutic methods that would block BKV pathogenesis. The NCI Laboratory of Cellular Oncology, seek parties to license or co-develop this technology.

The NCI Digital Divide Pilot Projects: implications for cancer education.

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Kreps, Gary L; Gustafson, David; Salovey, Peter; Perocchia, Rosemarie Slevin; Wilbright, Wayne; Bright, Mary Anne; Muha, Cathy

2007-01-01

The National Cancer Institute (NCI) supported four innovative demonstration research projects, "The Digital Divide Pilot Projects," to test new strategies for disseminating health information via computer to vulnerable consumers. These projects involved active research collaborations between the NCI's Cancer Information Service (CIS) and regional cancer control researchers to field test new approaches for enhancing cancer communication in vulnerable communities. The projects were able to use computers to successfully disseminate relevant cancer information to vulnerable populations. These demonstration research projects suggested effective new strategies for using communication technologies to educate underserved populations about cancer prevention, control, and care.

Hyaluronate fragments reverse skin atrophy by a CD44-dependent mechanism.

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Gürkan Kaya

2006-12-01

Full Text Available BACKGROUND: Skin atrophy is a common manifestation of aging and is frequently accompanied by ulceration and delayed wound healing. With an increasingly aging patient population, management of skin atrophy is becoming a major challenge in the clinic, particularly in light of the fact that there are no effective therapeutic options at present. METHODS AND FINDINGS: Atrophic skin displays a decreased hyaluronate (HA content and expression of the major cell-surface hyaluronate receptor, CD44. In an effort to develop a therapeutic strategy for skin atrophy, we addressed the effect of topical administration of defined-size HA fragments (HAF on skin trophicity. Treatment of primary keratinocyte cultures with intermediate-size HAF (HAFi; 50,000-400,000 Da but not with small-size HAF (HAFs; 400,000 Da induced wild-type (wt but not CD44-deficient (CD44-/- keratinocyte proliferation. Topical application of HAFi caused marked epidermal hyperplasia in wt but not in CD44-/- mice, and significant skin thickening in patients with age- or corticosteroid-related skin atrophy. The effect of HAFi on keratinocyte proliferation was abrogated by antibodies against heparin-binding epidermal growth factor (HB-EGF and its receptor, erbB1, which form a complex with a particular isoform of CD44 (CD44v3, and by tissue inhibitor of metalloproteinase-3 (TIMP-3. CONCLUSIONS: Our observations provide a novel CD44-dependent mechanism for HA oligosaccharide-induced keratinocyte proliferation and suggest that topical HAFi application may provide an attractive therapeutic option in human skin atrophy.

Published Research - NCI Alliance for Nanotechnology in Cancer

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The NCI Alliance for Nanotechnology in Cancer has published much exciting and impactful research over the years. Find here a list of all of these listed in PubMed and others across the field of Cancer Nanotechnology.

Tumor therapy with 125I-octreotide and 125I-UdR

International Nuclear Information System (INIS)

Fan, W.; Zhu, R.; Yang, C.; Sun, J.J.; Xu, Y.J.; Zhang, Y.J.; Wu, M.J.; Wang, D.J.

2005-01-01

Purpose: To determine the tumor cell damage effect with Auger-electron emitter 125 I in different chemical states. Methods: (1) [Tyr 3 ] octreotide (TOC) and UdR are labeled with 125 I,respectively. (2) Receptor analysis of 125 I-TOC on small cell lung cancer (SCLC) NCI-H446 cell lines is performed comparing with normal lymph cells. NCI-H446 cells added various dose of 125 I-TOC are incubated for different time with 125 I-Nal and non-labeled TOC as control. The capacity of NCI-H446 cell lines bound and internalization of 125 I TOC are determined. The radiation damage of tumor cells is measured by MTF methods. (3) The killing effects of 125 I-UdR in human pancreatic cancer cell line Bax-Pc and Sca-BER bladder carcinoma cells are evaluated with the similar methods. I-UdR penetrating into the Sca-BER cell nucleus is observed with confocal microscope. The grow suppression and clonogenic formation of Sca-BER cells after incubation with 125 I-UdR are analyzed. Proliferation fraction and S phase cell fraction of Sca-BER cell added 125 I-UdR is measured with flow cytometric analysis. Results: (1) Kd=(0.56∼2.0) x 10 -11 mol/L and B max =(1.17∼2.0) x 10 5 cell site are obtained by receptor analysis of 125 I-TOC on NCI-H446 cells. Comparatively, the difference between total binding and non-specific binding is low and there is no saturation of specific binding for normal lymphocyte. About 50% of 125 I-TOC is internalized into the NCI-H446 cell nucleus at 24h after incubation. The damige of NCI-H446 cells by 125 I-TOC is clearly observed. (2) The penetration amount of 125 I-UdR into cell nucleus increases with the incubate time when the concentration of 125 I-UdR is in the range of 10∼500 kBq/mL and reaches the peak fraction of 94% at 36 h after incubation. The radioactivity of 125 I-UdR is then achieved equelibration and no more increased with time. The linear correlation with γ=0.867∼0.978 between the concentration of 125 I-UdR in cell nucleus and the incubation time

Time, Concentration, and pH-Dependent Transport and Uptake of Anthocyanins in a Human Gastric Epithelial (NCI-N87 Cell Line

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Allison A. Atnip

2017-02-01

Full Text Available Anthocyanins are the largest class of water soluble plant pigments and a common part of the human diet. They may have many potential health benefits, including antioxidant, anti-inflammatory, anti-cancer, and cardioprotective activities. However, anthocyanin metabolism is not well understood. Studies suggest that anthocyanins absorption may occur in the stomach, in which the acidic pH favors anthocyanin stability. A gastric epithelial cell line (NCI-N87 has been used to study the behavior of anthocyanins at a pH range of 3.0–7.4. This work examines the effects of time (0–3 h, concentration (50–1500 µM, and pH (3.0, 5.0, 7.4 on the transport and uptake of anthocyanins using NCI-N87 cells. Anthocyanins were transported from the apical to basolateral side of NCI-N87 cells in time and dose dependent manners. Over the treatment time of 3 h the rate of transport increased, especially with higher anthocyanin concentrations. The non-linear rate of transport may suggest an active mechanism for the transport of anthocyanins across the NCI-N87 monolayer. At apical pH 3.0, higher anthocyanin transport was observed compared to pH 5.0 and 7.4. Reduced transport of anthocyanins was found to occur at apical pH 5.0.

NCI intramural research highlighted at 2014 AACR meeting

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This year’s American Association for Cancer Research meeting featured plenary talks by two NCI scientists, Steven Rosenberg, M.D., and Louis Staudt, M.D., Ph.D., that highlighted the challenges in developing varied and potentially synergistic treatments f

NCI Core Open House Shines Spotlight on Supportive Science and Basic Research | Poster

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The lobby of Building 549 at NCI at Frederick bustled with activity for two hours on Tuesday, May 1, as several dozen scientists and staff gathered for the NCI Core Open House. The event aimed to encourage discussion and educate visitors about the capabilities of the cores, laboratories, and facilities that offer support to NCI’s Center for Cancer Research.

Pharmacologically directed strategies in academic anticancer drug discovery based on the European NCI compounds initiative.

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Hendriks, Hans R; Govaerts, Anne-Sophie; Fichtner, Iduna; Burtles, Sally; Westwell, Andrew D; Peters, Godefridus J

2017-07-11

The European NCI compounds programme, a joint initiative of the EORTC Research Branch, Cancer Research Campaign and the US National Cancer Institute, was initiated in 1993. The objective was to help the NCI in reducing the backlog of in vivo testing of potential anticancer compounds, synthesised in Europe that emerged from the NCI in vitro 60-cell screen. Over a period of more than twenty years the EORTC-Cancer Research Campaign panel reviewed ∼2000 compounds of which 95 were selected for further evaluation. Selected compounds were stepwise developed with clear go/no go decision points using a pharmacologically directed programme. This approach eliminated quickly compounds with unsuitable pharmacological properties. A few compounds went into Phase I clinical evaluation. The lessons learned and many of the principles outlined in the paper can easily be applied to current and future drug discovery and development programmes. Changes in the review panel, restrictions regarding numbers and types of compounds tested in the NCI in vitro screen and the appearance of targeted agents led to the discontinuation of the European NCI programme in 2017 and its transformation into an academic platform of excellence for anticancer drug discovery and development within the EORTC-PAMM group. This group remains open for advice and collaboration with interested parties in the field of cancer pharmacology.

Tartrate-resistant acid phosphatase (TRAP/ACP5) promotes metastasis-related properties via TGFβ2/TβR and CD44 in MDA-MB-231 breast cancer cells.

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Reithmeier, Anja; Panizza, Elena; Krumpel, Michael; Orre, Lukas M; Branca, Rui M M; Lehtiö, Janne; Ek-Rylander, Barbro; Andersson, Göran

2017-09-15

inhibition demonstrated that TRAP-dependent migration and proliferation is regulated via TGFβ2/TβR, whereas proliferation beyond basal levels is regulated through CD44. Altogether, TRAP promotes metastasis-related cell properties in MDA-MB-231 breast cancer cells via TGFβ2/TβR and CD44, thereby identifying a potential signaling mechanism associated to TRAP action in breast cancer cells.

UNC Cancer Center Director to Lead NCI.

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2017-08-01

President Donald Trump has selected Norman "Ned" Sharpless, MD, director of the University of North Carolina Lineberger Comprehensive Cancer Center, to lead the NCI. The news was met with widespread approval among cancer researchers, who view Sharpless as a strong communicator who can ably represent the needs of the cancer community in the face of proposed funding cuts. ©2017 American Association for Cancer Research.

Creating Start-up Companies around NCI Inventions | Poster

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By Karen Surabian, Thomas Stackhouse, and Rose Freel, Contributing Writers, and Rosemarie Truman, Guest Writer The National Cancer Institute (NCI), led by the Technology Transfer Center (TTC),  the Avon Foundation, and The Center for Advancing Innovation have partnered to create a “first-of-a-kind” Breast Cancer Start-up Challenge.

Molecular mechanism for the action of the anti-CD44 monoclonal antibody MEM-85

Czech Academy of Sciences Publication Activity Database

Škerlová, Jana; Král, V.; Kachala, M.; Fábry, M.; Bumba, L.; Svergun, D. I.; Tošner, Z.; Veverka, Václav; Řezáčová, Pavlína

2015-01-01

Roč. 191, č. 2 (2015), s. 214-223 ISSN 1047-8477 R&D Projects: GA MŠk(CZ) LK11205; GA MŠk(CZ) LO1304 Institutional support: RVO:61388963 Keywords : CD44 * epitope mapping * monoclonal antibody * MEM-85 * NMR * SAXS Subject RIV: CE - Biochemistry Impact factor: 2.570, year: 2015

Help NCI at Frederick “Knock Out Hunger” | Poster

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NCI at Frederick is once again participating in the Feds Feed Families initiative, an annual food drive that addresses severe shortages of non-perishable items in food banks across D.C., Maryland, and Virginia during the summer months, when giving is at its lowest.

Phenethyl Isothiocyanate Induces Apoptotic Cell Death Through the Mitochondria-dependent Pathway in Gefitinib-resistant NCI-H460 Human Lung Cancer Cells In Vitro.

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Hsia, Te-Chun; Huang, Yi-Ping; Jiang, Yi-Wen; Chen, Hsin-Yu; Cheng, Zheng-Yu; Hsiao, Yung-Ting; Chen, Cheng-Yen; Peng, Shu-Fen; Chueh, Fu-Shin; Chou, Yu-Cheng; Chung, Jing-Gung

2018-04-01

Some lung cancer patients treated with gefitinib develop resistance to this drug resulting in unsatisfactory treatment outcomes. Phenethyl isothiocyanate (PEITC), present in our common cruciferous vegetables, exhibits anticancer activities in many human cancer cell lines. Currently, there is no available information on the possible modification of gefitinib resistance of lung cancer in vitro by PEITC. Thus, the effects of PEITC on gefitinib resistant lung cancer NCI-H460 cells were investigated in vitro. The total cell viability, apoptotic cell death, production of reactive oxygen species (ROS) and Ca 2+ , levels of mitochondria membrane potential (ΔΨ m ) and caspase-3, -8 and -9 activities were measured by flow cytometry assay. PEITC induced chromatin condensation was examined by DAPI staining. PEITC-induced cell morphological changes, decreased total viable cell number and induced apoptotic cell death in NCI-H460 and NCI-H460/G cells. PEITC decreased ROS production in NCI-H460 cells, but increased production in NCI-H460/G cells. PEITC increased Ca 2+ production, decreased the levels of ΔΨ m and increased caspase-3, -8 and -9 activities in both NCI-H460 and NCI-H460/G cells. Western blotting was used to examine the effect of apoptotic cell death associated protein expression in NCI-H460 NCI-H460/G cells after exposure to PEITC. Results showed that PEITC increased expression of cleaved caspase-3, PARP, GADD153, Endo G and pro-apoptotic protein Bax in NCI-H460/G cells. Based on these results, we suggest that PEITC induces apoptotic cell death via the caspase- and mitochondria-dependent pathway in NCI-H460/G cells. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

77 FR 2734 - Proposed Collection; Comment Request: Solar Cell: A Mobile UV Manager for Smart Phones (NCI)

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2012-01-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Proposed Collection; Comment Request: Solar Cell: A Mobile UV Manager for Smart Phones (NCI) SUMMARY: In compliance with the... Manager for Smart Phones (NCI). Type of Information Collection Request: New. Need and Use of Information...

The generalizability of NCI-sponsored clinical trials accrual among women with gynecologic malignancies.

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Mishkin, Grace; Minasian, Lori M; Kohn, Elise C; Noone, Anne-Michelle; Temkin, Sarah M

2016-12-01

Enrollment of a representative population to cancer clinical trials ensures scientific reliability and generalizability of results. This study evaluated the similarity of patients enrolled in NCI-supported group gynecologic cancer trials to the incident US population. Accrual to NCI-sponsored ovarian, uterine, and cervical cancer treatment trials between 2003 and 2012 were examined. Race, ethnicity, age, and insurance status were compared to the analogous US patient population estimated using adjusted SEER incidence data. There were 18,913 accruals to 156 NCI-sponsored gynecologic cancer treatment trials, ovarian (56%), uterine (32%), and cervical cancers (12%). Ovarian cancer trials included the least racial, ethnic and age diversity. Black women were notably underrepresented in ovarian trials (4% versus 11%). Hispanic patients were underrepresented in ovarian and uterine trials (4% and 5% versus 18% and 19%, respectively), but not in cervical cancer trials (14 versus 11%). Elderly patients were underrepresented in each disease area, with the greatest underrepresentation seen in ovarian cancer patients over the age of 75 (7% versus 29%). Privately insured women were overrepresented among accrued ovarian cancer patients (87% versus 76%), and the uninsured were overrepresented among women with uterine or cervical cancers. These patterns did not change over time. Several notable differences were observed between the patients accrued to NCI funded trials and the incident population. Improving representation of racial and ethnic minorities and elderly patients on cancer clinical trials continues to be a challenge and priority. Copyright © 2016 Elsevier Inc. All rights reserved.

Regular paths in SparQL: querying the NCI Thesaurus.

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Detwiler, Landon T; Suciu, Dan; Brinkley, James F

2008-11-06

OWL, the Web Ontology Language, provides syntax and semantics for representing knowledge for the semantic web. Many of the constructs of OWL have a basis in the field of description logics. While the formal underpinnings of description logics have lead to a highly computable language, it has come at a cognitive cost. OWL ontologies are often unintuitive to readers lacking a strong logic background. In this work we describe GLEEN, a regular path expression library, which extends the RDF query language SparQL to support complex path expressions over OWL and other RDF-based ontologies. We illustrate the utility of GLEEN by showing how it can be used in a query-based approach to defining simpler, more intuitive views of OWL ontologies. In particular we show how relatively simple GLEEN-enhanced SparQL queries can create views of the OWL version of the NCI Thesaurus that match the views generated by the web-based NCI browser.

Synergistic Effect of Subtoxic-dose Cisplatin and TRAIL to Mediate Apoptosis by Down-regulating Decoy Receptor 2 and Up-regulating Caspase-8, Caspase-9 and Bax Expression on NCI-H460 and A549 Cells

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Xiaoyan Zhang

2013-05-01

Full Text Available Objective(s: Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL can selectively induce apoptosis in tumor cells, more than half of tumors including non-small cell lung cancer (NSCLC exhibit TRAIL-resistance. The purpose of this study was to determine whether subtoxic-dose cisplatin and TRAIL could synergistically enhance apoptosis on NSCLC cells and investigate its underlying mechanisms. Materials and Methods:NCI-H460 and A549 cells were treated with TRAIL alone, cisplatin alone or combination treatment in this study. The cytotoxicity was evaluated according to Sulforhodamine B assay, and apoptosis was examined using Hoechst 33342 staining and flow cytometry. The mRNA and protein levels of TRAIL receptors and apoptotic proteins including caspase-8, caspase-9, Bcl-2 and Bax were determined by RT-PCR and Western blotting, respectively. Results:Our results showed that NCI-H460 cells were sensitive to TRAIL, whereas A549 cells were resistant. However, subtoxic-dose cisplatin could enhance the both cells to TRAIL-mediated cell proliferation inhibition and apoptosis. The underlying mechanisms might be associated with the down-regulation of DcR2 and up-regulation of Caspase-8, Caspase-9 and Bax. Conclusion:Subtoxic-dose cisplatin could enhance both TRAIL- sensitive and TRAIL- resistant NSCLC cells to TRAIL-mediated apoptosis. These findings motivated further studies to evaluate such a combinatory therapeutic strategy against NSCLC in the animal models.

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

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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.

The NCI Alliance for Nanotechnology in Cancer: achievement and path forward.

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Ptak, Krzysztof; Farrell, Dorothy; Panaro, Nicholas J; Grodzinski, Piotr; Barker, Anna D

2010-01-01

Nanotechnology is a 'disruptive technology', which can lead to a generation of new diagnostic and therapeutic products, resulting in dramatically improved cancer outcomes. The National Cancer Institute (NCI) of National Institutes of Health explores innovative approaches to multidisciplinary research allowing for a convergence of molecular biology, oncology, physics, chemistry, and engineering and leading to the development of clinically worthy technological approaches. These initiatives include programmatic efforts to enable nanotechnology as a driver of advances in clinical oncology and cancer research, known collectively as the NCI Alliance for Nanotechnology in Cancer (ANC). Over the last 5 years, ANC has demonstrated that multidisciplinary approach catalyzes scientific developments and advances clinical translation in cancer nanotechnology. The research conducted by ANC members has improved diagnostic assays and imaging agents, leading to the development of point-of-care diagnostics, identification and validation of numerous biomarkers for novel diagnostic assays, and the development of multifunctional agents for imaging and therapy. Numerous nanotechnology-based technologies developed by ANC researchers are entering clinical trials. NCI has re-issued ANC program for next 5 years signaling that it continues to have high expectations for cancer nanotechnology's impact on clinical practice. The goals of the next phase will be to broaden access to cancer nanotechnology research through greater clinical translation and outreach to the patient and clinical communities and to support development of entirely new models of cancer care.

How You Can Partner with NIH | NCI Technology Transfer Center | TTC

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NCI Technology Transfer Center (TTC) provides an array of agreements to support the National Cancer Institute's partnering. Deciding which type of agreement to use can be a challenge: CRADA, MTA, collaboration, agreement, CTA, Materials-CRADA

History of the Diet History Questionnaire (DHQ) | EGRP/DCCPS/NCI/NIH

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Learn about the evolution of the Diet History Questionnaire (DHQ), developed by the National Cancer Institute (NCI) initially in 2001, to the DHQ II in 2010, up to the present version, DHQ III, launched in 2018.

Russian delegation visits NIH and NCI to discuss research collaboration

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The NCI Center for Global Health hosted a delegation from the Russian Foundation for Basic Research to discuss ongoing and future collaborations in cancer research. The delegation was accompanied by representatives from the US Embassy in Moscow and the Embassy of the Russian Federation in Washington DC.

NIH Employee Invention Report (EIR) | NCI Technology Transfer Center | TTC

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NIH researchers must immediately contact their Laboratory or Branch Chief and inform him or her of a possible invention, and then consult with your NCI TTC Technology Transfer Manager about submitting an Employee Invention Report (EIR) Form. | [google6f4cd5334ac394ab.html

CellMiner: a relational database and query tool for the NCI-60 cancer cell lines

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Reinhold William C

2009-06-01

Full Text Available Abstract Background Advances in the high-throughput omic technologies have made it possible to profile cells in a large number of ways at the DNA, RNA, protein, chromosomal, functional, and pharmacological levels. A persistent problem is that some classes of molecular data are labeled with gene identifiers, others with transcript or protein identifiers, and still others with chromosomal locations. What has lagged behind is the ability to integrate the resulting data to uncover complex relationships and patterns. Those issues are reflected in full form by molecular profile data on the panel of 60 diverse human cancer cell lines (the NCI-60 used since 1990 by the U.S. National Cancer Institute to screen compounds for anticancer activity. To our knowledge, CellMiner is the first online database resource for integration of the diverse molecular types of NCI-60 and related meta data. Description CellMiner enables scientists to perform advanced querying of molecular information on NCI-60 (and additional types through a single web interface. CellMiner is a freely available tool that organizes and stores raw and normalized data that represent multiple types of molecular characterizations at the DNA, RNA, protein, and pharmacological levels. Annotations for each project, along with associated metadata on the samples and datasets, are stored in a MySQL database and linked to the molecular profile data. Data can be queried and downloaded along with comprehensive information on experimental and analytic methods for each data set. A Data Intersection tool allows selection of a list of genes (proteins in common between two or more data sets and outputs the data for those genes (proteins in the respective sets. In addition to its role as an integrative resource for the NCI-60, the CellMiner package also serves as a shell for incorporation of molecular profile data on other cell or tissue sample types. Conclusion CellMiner is a relational database tool for

Like a Good Neighbor, NCI-Frederick Is There | Poster

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The main campus of the National Cancer Institute at Frederick is an island of sorts: 68 acres of land that was once part of Fort Detrick. Accessing NCI property means passing through the Fort Detrick gates and crossing the post. While the campus is surrounded by the military installation, is protected by NIH police, and doesn’t allow the use of tobacco products, it is not a

Resveratrol enhances radiosensitivity of human non-small cell lung cancer NCI-H838 cells accompanied by inhibition of nuclear factor-kappa B activation

International Nuclear Information System (INIS)

Liao, Hui-Fen; Kuo Cheng-Deng; Yang, Yuh-Cheng; Lin, Chin-Ping; Tai, Hung-Chi; Chen, Yu-Jen; Chen, Yu-Yawn

2005-01-01

Resveratrol, a polyphenol in red wine, possesses many pharmacological activities including cardio-protection, chemoprevention, anti-tumor effects, and nuclear factor-kappa B (NF-κB) inactivation. The present study was designed to evaluate the effects and possible mechanism of resveratrol in enhancing radiosensitivity of lung cancer cells. Human non-small cell lung cancer NCI-H838 cells were irradiated with or without resveratrol pretreatment. The surviving fraction and sensitizer enhancement ratio (SER) were estimated by using a colony formation assay and linear-quadratic model. The cell-cycle distribution was evaluated by using prospidium iodide staining and flow cytometry. An enzyme-linked immunosorbent assay (ELISA)-based assay with immobilized oligonucleotide was performed to assess the DNA binding activity of NF-κB. Resveratrol had no direct growth-inhibitory effect on NCI-H838 cells treated for 24 hours with doses up to 25 μM. Pretreatment with resveratrol significantly enhanced cell killing by radiation, with an SER up to 2.2. Radiation activated NF-κB, an effect reversed by resveratrol pretreatment. Resveratrol resulted in a decrease of cells in the G 0 /G 1 phase and an increase in the S phase. Our results demonstrate that resveratrol enhances the radiosensitivity of NCI-H838 cells accompanied by NF-κB inhibition and S-phase arrest. (author)

Best Performers Announced for the NCI-CPTAC DREAM Proteogenomics Computational Challenge | Office of Cancer Clinical Proteomics Research

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The National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) is pleased to announce that teams led by Jaewoo Kang (Korea University), and Yuanfang Guan with Hongyang Li (University of Michigan) as the best performers of the NCI-CPTAC DREAM Proteogenomics Computational Challenge. Over 500 participants from 20 countries registered for the Challenge, which offered $25,000 in cash awards contributed by the NVIDIA Foundation through its Compute the Cure initiative.

Direct cortical hemodynamic mapping of somatotopy of pig nostril sensation by functional near-infrared cortical imaging (fNCI).

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Uga, Minako; Saito, Toshiyuki; Sano, Toshifumi; Yokota, Hidenori; Oguro, Keiji; Rizki, Edmi Edison; Mizutani, Tsutomu; Katura, Takusige; Dan, Ippeita; Watanabe, Eiju

2014-05-01

Functional near-infrared spectroscopy (fNIRS) is a neuroimaging technique for the noninvasive monitoring of human brain activation states utilizing the coupling between neural activity and regional cerebral hemodynamics. Illuminators and detectors, together constituting optodes, are placed on the scalp, but due to the presence of head tissues, an inter-optode distance of more than 2.5cm is necessary to detect cortical signals. Although direct cortical monitoring with fNIRS has been pursued, a high-resolution visualization of hemodynamic changes associated with sensory, motor and cognitive neural responses directly from the cortical surface has yet to be realized. To acquire robust information on the hemodynamics of the cortex, devoid of signal complications in transcranial measurement, we devised a functional near-infrared cortical imaging (fNCI) technique. Here we demonstrate the first direct functional measurement of temporal and spatial patterns of cortical hemodynamics using the fNCI technique. For fNCI, inter-optode distance was set at 5mm, and light leakage from illuminators was prevented by a special optode holder made of a light-shielding rubber sheet. fNCI successfully detected the somatotopy of pig nostril sensation, as assessed in comparison with concurrent and sequential somatosensory-evoked potential (SEP) measurements on the same stimulation sites. Accordingly, the fNCI system realized a direct cortical hemodynamic measurement with a spatial resolution comparable to that of SEP mapping on the rostral region of the pig brain. This study provides an important initial step toward realizing functional cortical hemodynamic monitoring during neurosurgery of human brains. Copyright © 2014. Published by Elsevier Inc.

NCI and the Chinese Academy of Medical Sciences Sign Statement of Intent

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Today the National Cancer Institute (NCI) and the Cancer Institute/Hospital of the Chinese Academy of Medical Sciences (CICAMS) signed a statement of intent to share an interest in fostering collaborative biomedical research in oncology and a common goal

Craig Reynolds, Ph.D., to Retire as NCI Associate Director for Frederick | Poster

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On December 2, Craig Reynolds, Ph.D., director, Office of Scientific Operations, and NCI associate director for Frederick, will put the finishing touches on a 37-year career with the National Cancer Institute.

Mechanism of blood pressure and R-R variability: insights from ganglion blockade in humans

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Zhang, Rong; Iwasaki, Kenichi; Zuckerman, Julie H.; Behbehani, Khosrow; Crandall, Craig G.; Levine, Benjamin D.; Blomqvist, C. G. (Principal Investigator)

2002-01-01

Spontaneous blood pressure (BP) and R-R variability are used frequently as 'windows' into cardiovascular control mechanisms. However, the origin of these rhythmic fluctuations is not completely understood. In this study, with ganglion blockade, we evaluated the role of autonomic neural activity versus other 'non-neural' factors in the origin of BP and R-R variability in humans. Beat-to-beat BP, R-R interval and respiratory excursions were recorded in ten healthy subjects (aged 30 +/- 6 years) before and after ganglion blockade with trimethaphan. The spectral power of these variables was calculated in the very low (0.0078-0.05 Hz), low (0.05-0.15 Hz) and high (0.15-0.35 Hz) frequency ranges. The relationship between systolic BP and R-R variability was examined by cross-spectral analysis. After blockade, R-R variability was virtually abolished at all frequencies; however, respiration and high frequency BP variability remained unchanged. Very low and low frequency BP variability was reduced substantially by 84 and 69 %, respectively, but still persisted. Transfer function gain between systolic BP and R-R interval variability decreased by 92 and 88 % at low and high frequencies, respectively, while the phase changed from negative to positive values at the high frequencies. These data suggest that under supine resting conditions with spontaneous breathing: (1) R-R variability at all measured frequencies is predominantly controlled by autonomic neural activity; (2) BP variability at high frequencies (> 0.15 Hz) is mediated largely, if not exclusively, by mechanical effects of respiration on intrathoracic pressure and/or cardiac filling; (3) BP variability at very low and low frequencies (rhythmicity; and (4) the dynamic relationship between BP and R-R variability as quantified by transfer function analysis is determined predominantly by autonomic neural activity rather than other, non-neural factors.

New Phone System Coming to NCI Campus at Frederick | Poster

Science.gov (United States)

By Travis Fouche and Trent McKee, Guest Writers Beginning in September, phones at the NCI Campus at Frederick will begin to be replaced, as the project to upgrade the current phone system ramps up. Over the next 16 months, the Information Systems Program (ISP) will be working with Facilities Maintenance and Engineering and Computer & Statistical Services to replace the current

Basic mechanisms of rTMS: Implications in Parkinson's disease

Directory of Open Access Journals (Sweden)

Arias-Carrión Oscar

2008-04-01

Full Text Available Abstract Background Basic and clinical research suggests a potential role for repetitive transcranial magnetic stimulation (rTMS in the treatment of Parkinson's disease. However, compared to the growing number of clinical studies on its putative therapeutic properties, the studies on the basic mechanisms of rTMS are surprisingly scarce. Results Animal studies have broadened our understanding of how rTMS affects brain circuits and the causal chain in brain-behavior relationships. The observed changes are thought to be to neurotransmitter release, transsynaptic efficiency, signaling pathways and gene transcription. Furthermore, recent studies suggest that rTMS induces neurogenesis, neuronal viability and secretion of neuroprotective molecules. Conclusion The mechanisms underlying the disease-modifying effects of these and related rTMS in animals are the principle subject of the current review. The possible applications for treatment of Parkinson's disease are discussed.

Cancer communication science funding trends, 2000-2012.

Science.gov (United States)

Ramírez, A Susana; Galica, Kasia; Blake, Kelly D; Chou, Wen-Ying Sylvia; Hesse, Bradford W

2013-12-01

Since 2000, the field of health communication has grown tremendously, owing largely to research funding by the National Cancer Institute (NCI). This study provides an overview of cancer communication science funding trends in the past decade. We conducted an analysis of communication-related grant applications submitted to the NCI in fiscal years 2000-2012. Using 103 keywords related to health communication, data were extracted from the Portfolio Management Application, a grants management application used at NCI. Automated coding described key grant characteristics such as mechanism and review study section. Manual coding determined funding across the cancer control continuum, by cancer site, and by cancer risk factors. A total of 3307 unique grant applications met initial inclusion criteria; 1013 of these were funded over the 12-year period. The top funded grant mechanisms were the R01, R21, and R03. Applications were largely investigator-initiated proposals as opposed to responses to particular funding opportunity announcements. Among funded communication research, the top risk factor being studied was tobacco, and across the cancer control continuum, cancer prevention was the most common stage investigated. NCI support of cancer communication research has been an important source of growth for health communication science over the last 12 years. The analysis' findings describe NCI's priorities in cancer communication science and suggest areas for future investments.

A Gene-Based Prognostic for Hepatocellular Carcinoma Patient Response to Adjuvant Transcatheter Arterial Chemoembolization | NCI Technology Transfer Center | TTC

Science.gov (United States)

The gold standard of care for hepatocellular carcinoma patients with intermediate- to locally advanced tumors is transcatheter arterial chemoembolization (TACE), a procedure whereby the tumor is targeted both with local chemotherapy and restriction of local blood supply. NCI scientists have identified a 14-gene signature predictive of response to TACE, and NCI seeks licensees or co-development partners to develop the technology toward commercialization.

It’s Easy to Recycle at NCI at Frederick | Poster

Science.gov (United States)

From 2013 through the first quarter of 2018, NCI at Frederick has recycled over 1,667 tons of material, while incinerating or landfilling over 4,273 tons of trash. This earns us a recycling rate close to 28 percent, which is below the national average of 32 percent, according to the Environmental Protection Agency, and well below our goal of 50 percent. (These numbers only

Analysis of 125I-[Tyr3] octreotide receptors of NCI-H466 cell line

International Nuclear Information System (INIS)

Sun Junjie; Fan Wo; Xu Yujie; Zhang Youjiu; Zhu Ran

2002-01-01

Objective: To study the affinity of small cell lung carcinoma to [Tyr 3 ] octreotide (TOC). Methods: Taking 125 I-[Tyr 3 ] octreotide (labeled by chloramine-T method), as the ligand, small cell lung carcinoma NCI-H466 cell line was inspected for the receptor-binding points and affinity constant. Results: The radio-chemical purity of 125 I-TOC purified through sephadex G-10 was higher than 95%. Receptor analysis study showed that the expression of somatostatin receptors on NCI-H446 cells was numerous (Bmax = 1.17 x 10 5 /cell) with strong affinity to 125 I-TOC (Kd = 0.56 nM). Conclusion: Labeled TOC could be used for small cell lung carcinoma receptor imaging and radio-pharmaceutical therapy

Tendències en el disseny metodològic de recerca sobre l’avaluació de competències a l’educació superior

Directory of Open Access Journals (Sweden)

Karina Angélica Villegas Sandoval

2017-01-01

Full Text Available L’article té com a finalitat descriure i analitzar les metodologies d'investigació utilitzades per estudis recents que aborden el tema de l’avaluació per competències a l’educació superior i la formació docent, per tal de detectar les tendències en el disseny metodològic i orientar futurs projectes d'investigació sobre aquest tema. El mètode de treball que s'ha seguit per dur a terme aquest estudi és l’anàlisi de contingut de 22 documents trobats a Dialnet. Els resultats mostren que les investigacions que tracten el tema assenyalat han anat en augment en els últims tretze anys, i es destaca el canvi de metodologia utilitzada, amb dissenys majoritàriament descriptius i avaluatius. Al seu torn, però, crida l'atenció que un gran nombre d'estudis no expliquen ni el mètode ni el disseny d'investigació que han aplicat. Es conclou que és important que les investigacions presentin un apartat que al·ludeixi al disseny metodològic a fi d’afavorir la comprensió del lector dels processos d'indagació que s'han dut a terme.

Program Spotlight: Ground Broken for NCI-supported Cancer Treatment Center in Puerto Rico

Science.gov (United States)

Dr. Sanya A. Springfield represented NCI at the groundbreaking ceremonies for the University of Puerto Rico (UPR) cancer hospital. In her remarks, she acknowledged the driving force behind this development is the UPR and the MD Anderson Cancer Center partnership.

Softball Games Bring NCI and Leidos Biomed Employees Together | Poster

Science.gov (United States)

NCI and Leidos Biomed employees took to the fields at Nallin Pond for the third annual slow-pitch softball games on August 26. The series attracted 54 employees who were divided into four teams, Red, Blue, Gray, and White, and they were cheered on by about 40 enthusiastic spectators. In the first set of games, the Gray team defeated the Blue team, 15–8, and the White team

Vaccines for HIV | NCI Technology Transfer Center | TTC

Science.gov (United States)

The development of an effective HIV vaccine has been an ongoing area of research. The high variability in HIV-1 virus strains has represented a major challenge in successful development. Ideally, an effective candidate vaccine would provide protection against the majority of clades of HIV. Two major hurdles to overcome are immunodominance and sequence diversity. This vaccine utilizes a strategy for overcoming these two issues by identifying the conserved regions of the virus and exploiting them for use in a targeted therapy. NCI seeks licensees and/or research collaborators to commercialize this technology, which has been validated in macaque models.

Hexamethoxylated Monocarbonyl Analogues of Curcumin Cause G2/M Cell Cycle Arrest in NCI-H460 Cells via Michael Acceptor-Dependent Redox Intervention.

Science.gov (United States)

Li, Yan; Zhang, Li-Ping; Dai, Fang; Yan, Wen-Jing; Wang, Hai-Bo; Tu, Zhi-Shan; Zhou, Bo

2015-09-09

Curcumin, derived from the dietary spice turmeric, holds promise for cancer prevention. This prompts much interest in investigating the action mechanisms of curcumin and its analogues. Two symmetrical hexamethoxy-diarylpentadienones (1 and 2) as cucumin analogues were reported to possess significantly enhanced cytotoxicity compared with the parent molecule. However, the detailed mechanisms remain unclear. In this study, compounds 1 and 2 were identified as the G2/M cell cycle arrest agents to mediate the cytotoxicity toward NCI-H460 cells via Michael acceptor-dependent redox intervention. Compared with curcumin, they could more easily induce a burst of reactive oxygen species (ROS) and collapse of the redox buffering system. One possible reason is that they could more effectively target intracellular TrxR to convert this antioxidant enzyme into a ROS promoter. Additionally, they caused up-regulation of p53 and p21 and down-regulation of redox-sensitive Cdc25C along with cyclin B1/Cdk1 in a Michael acceptor- and ROS-dependent fashion. Interestingly, in comparison with compound 2, compound 1 displayed a relatively weak ability to generate ROS but increased cell cycle arrest activity and cytotoxicity probably due to its Michael acceptor-dependent microtubule-destabilizing effect and greater GST-inhibitory activity, as well as its enhanced cellular uptake. This work provides useful information for understanding Michael acceptor-dependent and redox-mediated cytotoxic mechanisms of curcumin and its active analogues.

Prostate Cancer Cell Growth: Stimulatory Role of Neurotensin and Mechanism of Inhibition by Flavonoids as Related to Protein Kinase C

Science.gov (United States)

2010-01-01

cell lines (NCI-N417, NCI-H345, NCI-N592) were found to convert exogenous NT into the fragments NT1 –8 and NT9–13, reflecting the presence of...secrete NT. However, exogenous NT was degraded primarily to NT1 –11, consistent with the presence of neutral endopeptidase 3.4.24.11 in these cells . This...TITLE: Prostate Cancer Cell Growth: Stimulatory Role of Neurotensin and Mechanism of Inhibition by Flavonoids as Related to Protein Kinase C

NCI's High Performance Computing (HPC) and High Performance Data (HPD) Computing Platform for Environmental and Earth System Data Science

Science.gov (United States)

Evans, Ben; Allen, Chris; Antony, Joseph; Bastrakova, Irina; Gohar, Kashif; Porter, David; Pugh, Tim; Santana, Fabiana; Smillie, Jon; Trenham, Claire; Wang, Jingbo; Wyborn, Lesley

2015-04-01

The National Computational Infrastructure (NCI) has established a powerful and flexible in-situ petascale computational environment to enable both high performance computing and Data-intensive Science across a wide spectrum of national environmental and earth science data collections - in particular climate, observational data and geoscientific assets. This paper examines 1) the computational environments that supports the modelling and data processing pipelines, 2) the analysis environments and methods to support data analysis, and 3) the progress so far to harmonise the underlying data collections for future interdisciplinary research across these large volume data collections. NCI has established 10+ PBytes of major national and international data collections from both the government and research sectors based on six themes: 1) weather, climate, and earth system science model simulations, 2) marine and earth observations, 3) geosciences, 4) terrestrial ecosystems, 5) water and hydrology, and 6) astronomy, social and biosciences. Collectively they span the lithosphere, crust, biosphere, hydrosphere, troposphere, and stratosphere. The data is largely sourced from NCI's partners (which include the custodians of many of the major Australian national-scale scientific collections), leading research communities, and collaborating overseas organisations. New infrastructures created at NCI mean the data collections are now accessible within an integrated High Performance Computing and Data (HPC-HPD) environment - a 1.2 PFlop supercomputer (Raijin), a HPC class 3000 core OpenStack cloud system and several highly connected large-scale high-bandwidth Lustre filesystems. The hardware was designed at inception to ensure that it would allow the layered software environment to flexibly accommodate the advancement of future data science. New approaches to software technology and data models have also had to be developed to enable access to these large and exponentially

44th Aerospace Mechanisms Symposium

Science.gov (United States)

Boesiger, Edward A. (Compiler)

2018-01-01

The Aerospace Mechanisms Symposium (AMS) provides a unique forum for those active in the design, production and use of aerospace mechanisms. A major focus is the reporting of problems and solutions associated with the development and flight certification of new mechanisms.

The nature of hydrogen bonding in R-2(2)(8) crystal motifs - a computational exploration

Czech Academy of Sciences Publication Activity Database

Deepa, Palanisamy; Solomon, R. V.; Vedha, S. A.; Kolandaivel, P.; Venuvanalingam, P.

2014-01-01

Roč. 112, č. 24 (2014), s. 3195-3205 ISSN 0026-8976 Institutional support: RVO:61388963 Keywords : NCI plot * hydrogen bonds * R-2(2)(8) motif * organic crystals * NBO * QTAIM analysis Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.720, year: 2014

NCI and the Chinese National Cancer Center pursue new collaborations in cancer research

Science.gov (United States)

CGH Director, Dr. Ted Trimble, and East Asia Program Director, Dr. Ann Chao, traveled to Beijing with Mr. Matthew Brown from the Department of Health and Human Services Office of Global Affairs to attend the Joint Meeting of the NCC and the U.S. NCI.

Ratio Based Biomarkers for the Prediction of Cancer Survival | NCI Technology Transfer Center | TTC

Science.gov (United States)

The NCI seeks licensees or co-development partners for this technology, which describes compositions, methods and kits for identifying, characterizing biomolecules expressed in a sample that are associated with the presence, the development, or progression of cancer.

Anàlisi forense d'evidències digitals

OpenAIRE

Bonachera López, Esteban

2014-01-01

L'objectiu principal d'aquest projecte consisteix en la realització de l'anàlisi forense del disc dur i de la memòria RAM d'un ordinador personal, en concret un Netbook, vinculat a una possible conducta delictiva. També s'inclou en l'anàlisi una base de dades del conegut programari WhatsApp extreta d'un smartphone. Per realitzar aquesta tasca s'utilitzaran eines específiques per localitzar les evidències digitals que puguin demostrar els presumptes delictes. El objetivo principal de este p...

Mission & Role | NCI Technology Transfer Center | TTC

Science.gov (United States)

The NCI TTC serves as the focal point for implementing the Federal Technology Transfer Act to utilize patents as incentive for commercial development of technologies and to establish research collaborations and licensing among academia, federal laboratories, non-profit organizations, and industry. The TTC supports technology development activities for the National Cancer Institute and nine other NIH Institutes and Centers. TTC staff negotiate co-development agreements and licenses with universities, non-profit organizations, and pharmaceutical and biotechnology companies to ensure compliance with Federal statutes, regulations and the policies of the National Institutes of Health. TTC also reviews employee invention reports and makes recommendations concerning filing of domestic and foreign patent applications. | [google6f4cd5334ac394ab.html

NCI at Frederick Employees Receive Awards at the Spring Research Festival | Poster

Science.gov (United States)

NCI and Frederick National Laboratory staff members were among those honored at the Spring Research Festival Awards Ceremony on May 28. The ceremony was the culmination of the festival, which was sponsored by the National Interagency Confederation for Biological Research (NICBR), May 4–7. Maj. Gen. Brian Lein, commanding general, U.S. Army Medical Research and Materiel Command

Silica-Coated Nanodiamonds for Imaging and Delivery of Therapeutic Agents | NCI Technology Transfer Center | TTC

Science.gov (United States)

The NCI Radiation Oncology Branch and the NHLBI Laboratory of Single Molecule Biophysics seek parties to co-develop fluorescent nanodiamonds for use as in vivo and in vitro optical tracking probes toward commercialization.

76 FR 14034 - Proposed Collection; Comment Request; NCI Cancer Genetics Services Directory Web-Based...

Science.gov (United States)

2011-03-15

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Proposed Collection; Comment Request; NCI Cancer Genetics Services Directory Web-Based Application Form and Update Mailer Summary: In... Cancer Genetics Services Directory Web-based Application Form and Update Mailer. [[Page 14035

THE NCI STUDIES ON RADIATION DOSES AND CANCER RISKS IN THE MARSHALL ISLANDS ASSOCIATED WITH EXPOSURE TO RADIOACTIVE FALLOUT

OpenAIRE

Simon, Steven L.

2012-01-01

The U.S. National Cancer Institute (NCI, National Institutes of Health) was requested by the U.S. Congress in 2004 to assess the number of radiation-related illnesses to be expected among the people of the Marshall Islands from nuclear tests conducted there during 1946-1958. A thorough analysis conducted by the NCI concluded that 20 of the 66 nuclear devices tested in or near the Marshall Islands resulted in measurable fallout deposition on one or more of the inhabited atolls of the Marshall ...

Food Science and Technology Abstracts (FSTA): guia ràpida. Gener 2011

OpenAIRE

Universitat de Barcelona. CRAI

2011-01-01

Guia ràpida de la base de dades bibliogràfica (FSTA) d'àmbit mundial sobre ciència, tecnologia i química alimentària, nutrició i salut humana, biotecnologia i toxicologia. Buida prop de 1800 revistes especialitzades, monografies, conferències, tesis, patents, legislació, etc. publicats en unes 40 llengües.

Paracytosis of Haemophilus influenzae through cell layers of NCI-H292 lung epithelial cells

NARCIS (Netherlands)

van Schilfgaarde, M.; van Alphen, L.; Eijk, P.; Everts, V.; Dankert, J.

1995-01-01

Haemophilus influenzae penetrates the respiratory epithelium during carriage and invasive disease, including respiratory tract infections. We developed an in vitro model system consisting of lung epithelial NCI-H292 cells on permeable supports to study the passage of H. influenzae through lung

NCI Requests Targets for Monoclonal Antibody Production and Characterization | Office of Cancer Clinical Proteomics Research

Science.gov (United States)

In an effort to provide well-characterized monoclonal antibodies to the scientific community, NCI's Antibody Characterization Program requests cancer-related protein targets for affinity production and distribution. Submissions will be accepted through July 9, 2012.

Microsoft Office 365 Deployment Continues through June at NCI at Frederick | Poster

Science.gov (United States)

The latest Microsoft suite, Office 365 (O365), is being deployed to all NCI at Frederick computers during the months of May and June to comply with federal mandates. The suite includes the latest versions of Word, Excel, Outlook, PowerPoint, and Skype for Business, along with cloud-based capabilities. These cloud-based capabilities will help meet the federal mandates that

Puerto Rico NCI Community Oncology Research Program Minority/Underserved | Division of Cancer Prevention

Science.gov (United States)

The Puerto Rico NCI Community Oncology Research Program (PRNCORP) will be the principal organization in the island that promotes cancer prevention, control and screening/post-treatment surveillance clinical trials. It will conduct cancer care delivery research and will provide access to treatment and imaging clinical trials conducted under the reorganization of the National

Inactivated Tianjin strain, a novel genotype of Sendai virus, induces apoptosis in HeLa, NCI-H446 and Hep3B cells.

Science.gov (United States)

Chen, Jun; Han, Han; Wang, Bin; Shi, Liying

2016-07-01

The Sendai virus strain Tianjin is a novel genotype of the Sendai virus. In previous studies, ultraviolet-inactivated Sendai virus strain Tianjin (UV-Tianjin) demonstrated antitumor effects on human breast cancer cells. The aim of the present study was to investigate the in vitro antitumor effects of UV-Tianjin on the human cervical carcinoma HeLa, human small cell lung cancer NCI-H446 and human hepatocellular carcinoma Hep 3B cell lines, and the possible underlying mechanisms of these antitumor effects. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay revealed that UV-Tianjin treatment inhibited the proliferation of HeLa, NCI-H446 and Hep 3B cells in a dose- and time-dependent manner. Hoechst and Annexin V-fluorescein isothiocyanate/propidium iodide double staining indicated that UV-Tianjin induced dose-dependent apoptosis in all three cell lines with the most significant effect observed in the HeLa cell line. In the HeLa cell line, UV-Tianjin-induced apoptosis was further confirmed by the disruption of the mitochondria membrane potential and the activation of caspases, as demonstrated by fluorescent cationic dye and colorimetric assays, respectively. In addition, western blot analysis revealed that UV-Tianjin treatment resulted in significant upregulation of cytochrome c , apoptosis protease activating factor-1, Fas, Fas ligand and Fas-associated protein with death domain, and activated caspase-9, -8 and -3 in HeLa cells. Based on these results, it is hypothesized that UV-Tianjin exhibits anticancer activity in HeLa, NCI-H446 and Hep 3B cell lines via the induction of apoptosis. In conclusion, the results of the present study indicate that in the HeLa cell line, intrinsic and extrinsic apoptotic pathways may be involved in UV-Tianjin-induced apoptosis.

Protective mechanism against cancer found in progeria patient cells

Science.gov (United States)

NCI scientists have studied cells of patients with an extremely rare genetic disease that is characterized by drastic premature aging and discovered a new protective cellular mechanism against cancer. They found that cells from patients with Hutchinson Gi

Composite Control of the n–link Chained Mechanical Systems

Czech Academy of Sciences Publication Activity Database

Zikmund, Jiří

2008-01-01

Roč. 44, č. 5 (2008), s. 664-684 ISSN 0023-5954 R&D Projects: GA ČR(CZ) GA102/08/0186 Institutional research plan: CEZ:AV0Z10750506 Keywords : nonlinear systems * exact linearization * underactuated mechanical systems Subject RIV: BC - Control Systems Theory Impact factor: 0.281, year: 2008

75 FR 46945 - Proposed Collection; Comment Request; the Drug Accountability Record (Form NIH 2564) (NCI)

Science.gov (United States)

2010-08-04

... Request; the Drug Accountability Record (Form NIH 2564) (NCI) SUMMARY: In compliance with the requirement... Management and Budget (OMB) for review and approval. Proposed Collection Title: The Drug Accountability... agent accountability. In order to fulfill these requirements, a standard Investigational Drug...

78 FR 2678 - Proposed Collection; Comment Request (60-Day FRN): The National Cancer Institute (NCI...

Science.gov (United States)

2013-01-14

... Request (60-Day FRN): The National Cancer Institute (NCI) SmokefreeTXT (Text Message) Program Evaluation..., Behavioral Scientist/ Health Science Administrator, Division of Cancer Control and Population Sciences, 6130... text message smoking cessation intervention designed for young adult smokers ages 18-29. The Smokefree...

NCI Requests Cancer Targets for Monoclonal Antibody Production and Characterization | Office of Cancer Clinical Proteomics Research

Science.gov (United States)

In an effort to provide well-characterized monoclonal antibodies to the scientific community, NCI's Antibody Characterization Program requests cancer-related protein targets for affinity production and distribution. Submissions will be accepted through July 11, 2014.

R&W Club Frederick Hosts Second Annual Car Show | Poster

Science.gov (United States)

A 1994 Ford Thunderbird, a 2006 Porsche 911-S, and a 1996 Chevy Camaro Z28 were just a few of the rides on display this summer at R&W Club Frederick’s second annual Car and Motorcycle Show. “It’s a chance to raise money for a good cause,” said Geoff Seidel, one of the organizers of the event and program director for the Coordinating Center for Clinical Trials, NCI Office of

78 FR 53763 - Proposed Collection; 60-day Comment Request Cancer Trials Support Unit (CTSU) (NCI)

Science.gov (United States)

2013-08-30

... proposed data collection projects, the National Cancer Institute (NCI), National Institutes of Health (NIH), will publish periodic summaries of proposed projects to be submitted to the Office of Management and... proposed collection of information, including the validity of the methodology and assumptions used; (3...

Highlights of recent developments and trends in cancer nanotechnology research--view from NCI Alliance for Nanotechnology in Cancer.

Science.gov (United States)

Hull, L C; Farrell, D; Grodzinski, P

2014-01-01

Although the incidence of cancer and cancer related deaths in the United States has decreased over the past two decades due to improvements in early detection and treatment, cancer still is responsible for a quarter of the deaths in this country. There is much room for improvement on the standard treatments currently available and the National Cancer Institute (NCI) has recognized the potential for nanotechnology and nanomaterials in this area. The NCI Alliance for Nanotechnology in Cancer was formed in 2004 to support multidisciplinary researchers in the application of nanotechnology to cancer diagnosis and treatment. The researchers in the Alliance have been productive in generating innovative solutions to some of the central issues of cancer treatment including how to detect tumors earlier, how to target cancer cells specifically, and how to improve the therapeutic index of existing chemotherapies and radiotherapy treatments. Highly creative ideas are being pursued where novelty in nanomaterial development enables new modalities of detection or therapy. This review highlights some of the innovative materials approaches being pursued by researchers funded by the NCI Alliance. Their discoveries to improve the functionality of nanoparticles for medical applications includes the generation of new platforms, improvements in the manufacturing of nanoparticles and determining the underlying reasons for the movement of nanoparticles in the blood. © 2013.

Variations in Mre11/Rad50/Nbs1 status and DNA damage-induced S-phase arrest in the cell lines of the NCI60 panel

Directory of Open Access Journals (Sweden)

Eastman Alan

2011-05-01

Full Text Available Abstract Background The Mre11/Rad50/Nbs1 (MRN complex is a regulator of cell cycle checkpoints and DNA repair. Defects in MRN can lead to defective S-phase arrest when cells are damaged. Such defects may elicit sensitivity to selected drugs providing a chemical synthetic lethal interaction that could be used to target therapy to tumors with these defects. The goal of this study was to identify these defects in the NCI60 panel of cell lines and identify compounds that might elicit selective cytotoxicity. Methods We screened the NCI60 panel in search of cell lines that express low levels of MRN proteins, or that fail to arrest in S-phase in response to the topisomerase I inhibitor SN38. The NCI COMPARE program was used to discover compounds that preferentially target cells with these phenotypes. Results HCT116 cells were initially identified as defective in MRN and S phase arrest. Transfection with Mre11 also elevated Rad50 and Nbs1, and rescued the defective S-phase arrest. Cells of the NCI60 panel exhibited a large range of protein expression but a strong correlation existed between Mre11, Rad50 and Nbs1 consistent with complex formation determining protein stability. Mre11 mRNA correlated best with protein level suggesting it was the primary determinant of the overall level of the complex. Three other cell lines failed to arrest in response to SN38, two of which also had low MRN. However, other cell lines with low MRN still arrested suggesting low MRN does not predict an inability to arrest. Many compounds, including a family of benzothiazoles, correlated with the failure to arrest in S phase. The activity of benzothiazoles has been attributed to metabolic activation and DNA alkylation, but we note several cell lines in which sensitivity does not correlate with metabolism. We propose that the checkpoint defect imposes an additional mechanism of sensitivity on cells. Conclusions We have identified cells with possible defects in the MRN complex

Variations in Mre11/Rad50/Nbs1 status and DNA damage-induced S-phase arrest in the cell lines of the NCI60 panel

International Nuclear Information System (INIS)

Garner, Kristen M; Eastman, Alan

2011-01-01

The Mre11/Rad50/Nbs1 (MRN) complex is a regulator of cell cycle checkpoints and DNA repair. Defects in MRN can lead to defective S-phase arrest when cells are damaged. Such defects may elicit sensitivity to selected drugs providing a chemical synthetic lethal interaction that could be used to target therapy to tumors with these defects. The goal of this study was to identify these defects in the NCI60 panel of cell lines and identify compounds that might elicit selective cytotoxicity. We screened the NCI60 panel in search of cell lines that express low levels of MRN proteins, or that fail to arrest in S-phase in response to the topisomerase I inhibitor SN38. The NCI COMPARE program was used to discover compounds that preferentially target cells with these phenotypes. HCT116 cells were initially identified as defective in MRN and S phase arrest. Transfection with Mre11 also elevated Rad50 and Nbs1, and rescued the defective S-phase arrest. Cells of the NCI60 panel exhibited a large range of protein expression but a strong correlation existed between Mre11, Rad50 and Nbs1 consistent with complex formation determining protein stability. Mre11 mRNA correlated best with protein level suggesting it was the primary determinant of the overall level of the complex. Three other cell lines failed to arrest in response to SN38, two of which also had low MRN. However, other cell lines with low MRN still arrested suggesting low MRN does not predict an inability to arrest. Many compounds, including a family of benzothiazoles, correlated with the failure to arrest in S phase. The activity of benzothiazoles has been attributed to metabolic activation and DNA alkylation, but we note several cell lines in which sensitivity does not correlate with metabolism. We propose that the checkpoint defect imposes an additional mechanism of sensitivity on cells. We have identified cells with possible defects in the MRN complex and S phase arrest, and a series of compounds that may

NCI Think Tank Concerning the Identifiability of Biospecimens and “-Omic” Data

OpenAIRE

Weil, Carol J.; Mechanic, Leah E.; Green, Tiffany; Kinsinger, Christopher; Lockhart, Nicole C.; Nelson, Stefanie A.; Rodriguez, Laura L.; Buccini, Laura D.

2013-01-01

On June 11 and 12, 2012, the National Cancer Institute (NCI) hosted a think tank concerning the identifiability of biospecimens and “omic” Data in order to explore challenges surrounding this complex and multifaceted topic. The think tank brought together forty-six leaders from several fields, including cancer genomics, bioinformatics, human subject protection, patient advocacy, and commercial genetics. The first day involved presentations regarding the state of the science of re-identificati...

75 FR 61763 - Submission of OMB Review; Comment Request; Drug Accountability Record (Form NIH 2564) (NCI)

Science.gov (United States)

2010-10-06

...; Comment Request; Drug Accountability Record (Form NIH 2564) (NCI) SUMMARY: In compliance with the..., 2011, unless it displays a valid OMB control number. Proposed Collection: Title: Drug Accountability... accountability. In order to fulfill these requirements, a standard Investigational Drug Accountability Report...

Photoactivatable Lipid-based Nanoparticles as a Vehicle for Dual Agent Delivery | NCI Technology Transfer Center | TTC

Science.gov (United States)

Researchers at the National Cancer Institute (NCI) RNA Biology Laboratory have developed nanoparticles that can deliver an agent (i.e., therapeutic or imaging) and release the agent upon targeted photoactivation allowing for controlled temporal and localized release of the agent.

Test de visualitat: les preferències del bon disseny

Directory of Open Access Journals (Sweden)

Quim Merino

2014-07-01

Full Text Available Aquest article pretén donar notícia de la investigació dirigida pel Grup de Recerca en Publicitat i Relacions Públiques (en endavant, GRP de la Universitat Autònoma de Barcelona duta a terme pels autors d'aquesta ressenya. El treball s'emmarca en una activitat de l'assignatura de Disseny en Publicitat i Relacions Públiques del Grau en Publicitat i Relacions Públiques de la UAB. L'objectiu del treball és constatar les preferències del consumidor davant diferents estímuls formals del disseny gràfic en publicitat

Differential regulation of human 3β-hydroxysteroid dehydrogenase type 2 for steroid hormone biosynthesis by starvation and cyclic AMP stimulation: studies in the human adrenal NCI-H295R cell model.

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Sameer Udhane

Full Text Available Human steroid biosynthesis depends on a specifically regulated cascade of enzymes including 3β-hydroxysteroid dehydrogenases (HSD3Bs. Type 2 HSD3B catalyzes the conversion of pregnenolone, 17α-hydroxypregnenolone and dehydroepiandrosterone to progesterone, 17α-hydroxyprogesterone and androstenedione in the human adrenal cortex and the gonads but the exact regulation of this enzyme is unknown. Therefore, specific downregulation of HSD3B2 at adrenarche around age 6-8 years and characteristic upregulation of HSD3B2 in the ovaries of women suffering from the polycystic ovary syndrome remain unexplained prompting us to study the regulation of HSD3B2 in adrenal NCI-H295R cells. Our studies confirm that the HSD3B2 promoter is regulated by transcription factors GATA, Nur77 and SF1/LRH1 in concert and that the NBRE/Nur77 site is crucial for hormonal stimulation with cAMP. In fact, these three transcription factors together were able to transactivate the HSD3B2 promoter in placental JEG3 cells which normally do not express HSD3B2. By contrast, epigenetic mechanisms such as methylation and acetylation seem not involved in controlling HSD3B2 expression. Cyclic AMP was found to exert differential effects on HSD3B2 when comparing short (acute versus long-term (chronic stimulation. Short cAMP stimulation inhibited HSD3B2 activity directly possibly due to regulation at co-factor or substrate level or posttranslational modification of the protein. Long cAMP stimulation attenuated HSD3B2 inhibition and increased HSD3B2 expression through transcriptional regulation. Although PKA and MAPK pathways are obvious candidates for possibly transmitting the cAMP signal to HSD3B2, our studies using PKA and MEK1/2 inhibitors revealed no such downstream signaling of cAMP. However, both signaling pathways were clearly regulating HSD3B2 expression.

Reducing Friction: An Update on the NCIP Open Development Initiative - NCI BioMedical Informatics Blog

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NCIP has migrated 132 repositories from the NCI subversion repository to our public NCIP GitHub channel with the goal of facilitating third party contributions to the existing code base. Within the GitHub environment, we are advocating use of the GitHub “fork and pull” model.

CD44v10, osteopontin and lymphoma growth retardation by a CD44v10-specific antibody.

Science.gov (United States)

Megaptche, Amelie Pajip; Erb, Ulrike; Büchler, Markus Wolfgang; Zöller, Margot

2014-09-01

Blockade of CD44 is considered a therapeutic option for the elimination of leukemia-initiating cells. However, the application of anti-panCD44 can be burdened by severe side effects. We determined whether these side effects could be avoided by replacing anti-panCD44 with CD44 variant isoform (CD44v)-specific antibodies in CD44v-positive hematological malignancies using the EL4 thymoma and CD44v10-transfected EL4 (EL4-v10) as models. Subcutaneous growth of EL4 and EL4-v10 was equally well inhibited by the anti-panCD44 and anti-CD44v10 antibodies, respectively. Ex vivo analysis indicated that natural killer cytotoxicity and antibody-dependent cellular cytotoxicity were the main effector mechanisms. Under local inflammation, the efficacy of anti-CD44v10 prolonged the survival time twofold compared with untreated, EL4-v10 tumor-bearing mice, and this was due to inflammation-induced expression of osteopontin (OPN). A high level of OPN in EL4-v10 tumors supported leukocyte recruitment and tumor-infiltrating T-cell activation. Taken together, in hematological malignancies expressing CD44v, anti-panCD44 can be replaced by CD44v-specific antibodies without a loss in efficacy. Furthermore, CD44v10-specific antibodies appear particularly advantageous in cutaneous leukemia therapy, as CD44v10 binding of OPN drives leukocyte recruitment and activation.

77 FR 4334 - Proposed Collection; Comment Request; Solar Cell: A Mobile UV Manager for Smart Phones (NCI)

Science.gov (United States)

2012-01-27

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Proposed Collection; Comment Request; Solar Cell: A Mobile UV Manager for Smart Phones (NCI) SUMMARY: In compliance with the... Manager for Smart Phones [[Page 4335

P44/WDR77 restricts the sensitivity of proliferating cells to TGFβ signaling

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Yi, Pengfei [Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, Hubei 430022 (China); Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 (United States); Gao, Shen [Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 (United States); Gu, Zhongping [Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038 (China); Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 (United States); Huang, Tao [Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Road, Wuhan, Hubei 430022 (China); Wang, Zhengxin, E-mail: zhenwang@mdanderson.org [Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 (United States)

2014-07-18

Highlights: • P44/WDR77 causes proliferating cells to become non-responsive to TGFβ signaling. • P44/WDR77 down-regulates TβRII and TβR2 expression. • P44/WDR77 down-regulated TGFβ signaling correlates with lung tumorigenesis. - Abstract: We previously reported that a novel WD-40 domain-containing protein, p44/WDR77, drives quiescent epithelial cells to re-enter the cell cycle and plays an essential role for growth of lung and prostate cancer cells. Transforming growth factor beta (TGFβ) signaling is important in the maintenance of non-transformed cells in the quiescent or slowly cycling stage. However, both non-transformed proliferating cells and human cancer cells are non-responsive to endogenous TGFβ signaling. The mechanism by which proliferating cells become refractory to TGFβ inhibition is not well established. Here, we found that silencing p44/WDR77 increased cellular sensitivity to TGFβ signaling and that this was inversely correlated with decreased cell proliferation. Smad2 or 3 phosphorylation, TGFβ-mediated transcription, and TGFβ2 and TGFβ receptor type II (TβRII) expression were dramatically induced by silencing of p44/WDR77. These data support the hypothesis that p44/WDR77 down-regulates the expression of the TGFβ ligand and its receptor, thereby leading to a cellular non-response to TGFβ signaling. Finally, we found that p44/WDR77 expression was correlated with cell proliferation and decreased TGFβ signaling during lung tumorigenesis. Together, these results suggest that p44/WDR77 expression causes the non-sensitivity of proliferating cells to TGFβ signaling, thereby contributing to cellular proliferation during lung tumorigenesis.

Lithiation of prochiral 2,2'-dichloro-5,5'-dibromo-4,4'-bipyridine as a tool for the synthesis of chiral polyhalogenated 4,4'-bipyridines.

Science.gov (United States)

Mamane, Victor; Aubert, Emmanuel; Peluso, Paola; Cossu, Sergio

2013-08-02

Lithiation of the achiral tetrahalogenated 4,4'-bipyridine 1 with alkyllithiums was investigated. n-BuLi was found to induce either the chlorine-directed deprotolithiation reaction alone or with a concomitant halogen-lithium exchange furnishing after iodine trapping chiral 4,4'-bipyridines 2 and 6, respectively. The role of n-BuLi in the deprotolithiation process of 1 was elucidated on the basis of isolated secondary derivatives. After deprotolithiation, the lithiated species could be trapped by different electrophiles such as MeI, TMSCl, MeSSMe, R3SnCl (R = Me or n-Bu), and PPh2Cl. Moreover, 4,4'-bipyridine 2 was submitted to cross-coupling reactions (Suzuki and Sonogashira) which occurred selectively at the carbon-iodine bond. All compounds of this new family of atropisomeric 4,4'-bipyridines were separated by chiral HPLC (high-performance liquid chromatography), and the absolute configurations of obtained enantiomers were mainly assigned by XRD (X-ray diffraction) using anomalous dispersion.

Improving global data infrastructures for more effective and scalable analysis of Earth and environmental data: the Australian NCI NERDIP Approach

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Evans, Ben; Wyborn, Lesley; Druken, Kelsey; Richards, Clare; Trenham, Claire; Wang, Jingbo; Rozas Larraondo, Pablo; Steer, Adam; Smillie, Jon

2017-04-01

The National Computational Infrastructure (NCI) facility hosts one of Australia's largest repositories (10+ PBytes) of research data collections spanning datasets from climate, coasts, oceans, and geophysics through to astronomy, bioinformatics, and the social sciences domains. The data are obtained from national and international sources, spanning a wide range of gridded and ungridded (i.e., line surveys, point clouds) data, and raster imagery, as well as diverse coordinate reference projections and resolutions. Rather than managing these data assets as a digital library, whereby users can discover and download files to personal servers (similar to borrowing 'books' from a 'library'), NCI has built an extensive and well-integrated research data platform, the National Environmental Research Data Interoperability Platform (NERDIP, http://nci.org.au/data-collections/nerdip/). The NERDIP architecture enables programmatic access to data via standards-compliant services for high performance data analysis, and provides a flexible cloud-based environment to facilitate the next generation of transdisciplinary scientific research across all data domains. To improve use of modern scalable data infrastructures that are focused on efficient data analysis, the data organisation needs to be carefully managed including performance evaluations of projections and coordinate systems, data encoding standards and formats. A complication is that we have often found multiple domain vocabularies and ontologies are associated with equivalent datasets. It is not practical for individual dataset managers to determine which standards are best to apply to their dataset as this could impact accessibility and interoperability. Instead, they need to work with data custodians across interrelated communities and, in partnership with the data repository, the international scientific community to determine the most useful approach. For the data repository, this approach is essential to enable

An OmpA family protein, a target of the GinI/GinR quorum-sensing system in Gluconacetobacter intermedius, controls acetic acid fermentation.

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Iida, Aya; Ohnishi, Yasuo; Horinouchi, Sueharu

2008-07-01

Via N-acylhomoserine lactones, the GinI/GinR quorum-sensing system in Gluconacetobacter intermedius NCI1051, a gram-negative acetic acid bacterium, represses acetic acid and gluconic acid fermentation. Two-dimensional polyacrylamide gel electrophoretic analysis of protein profiles of strain NCI1051 and ginI and ginR mutants identified a protein that was produced in response to the GinI/GinR regulatory system. Cloning and nucleotide sequencing of the gene encoding this protein revealed that it encoded an OmpA family protein, named GmpA. gmpA was a member of the gene cluster containing three adjacent homologous genes, gmpA to gmpC, the organization of which appeared to be unique to vinegar producers, including "Gluconacetobacter polyoxogenes." In addition, GmpA was unique among the OmpA family proteins in that its N-terminal membrane domain forming eight antiparallel transmembrane beta-strands contained an extra sequence in one of the surface-exposed loops. Transcriptional analysis showed that only gmpA of the three adjacent gmp genes was activated by the GinI/GinR quorum-sensing system. However, gmpA was not controlled directly by GinR but was controlled by an 89-amino-acid protein, GinA, a target of this quorum-sensing system. A gmpA mutant grew more rapidly in the presence of 2% (vol/vol) ethanol and accumulated acetic acid and gluconic acid in greater final yields than strain NCI1051. Thus, GmpA plays a role in repressing oxidative fermentation, including acetic acid fermentation, which is unique to acetic acid bacteria and allows ATP synthesis via ethanol oxidation. Consistent with the involvement of gmpA in oxidative fermentation, its transcription was also enhanced by ethanol and acetic acid.

Transcriptional Mechanisms Controlling miR-375 Gene Expression in the Pancreas

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Tali Avnit-Sagi

2012-01-01

Full Text Available MicroRNAs (miRNAs are a class of small non-coding RNAs that play an important role in mediating a broad and expanding range of biological activities. miR-375 is expressed selectively in the pancreas. We have previously shown that selective expression of miR-375 in pancreatic beta cells is controlled by transcriptional mechanisms operating through a TATA box-containing promoter. Expression of miR-375 has been reported in non-beta cells within the endocrine pancreas, and indeed inactivation of miR-375 leads to perturbation in cell mass and number of both alpha and beta cells. Consistent with its expression throughout the endocrine pancreas, we now show that the promoter of the miR-375 gene shows selective activity in pancreatic endocrine alpha cells, comparable to that observed in beta cells. We previously identified a novel negative regulatory element located downstream of the miR-375 gene transcription start site. By generating luciferase reporter genes, we now show that the sequence is functional also when positioned upstream of a heterologous promoter, thus proving that the repressor effect is mediated at least in part at the level of transcription. Further characterization of the transcriptional control mechanism regulating expression of miR-375 and other pancreatic miRNAs will contribute to a better understanding of pancreas development and function.

Mechanism research of miR-181 regulating human lens epithelial cell apoptosis

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Yu Qin

2015-05-01

Full Text Available AIM: To investigate the expression of miR-181 in the lens tissue of cataract and the regulating mechanism of miR-181 on apoptosis of human lens epithelial cell.METHODS:Real time q-PCR was used to measure the expression of miR-181 in the anterior lens capsules of age-related cataract and human lens epithelial cell apoptosis model. miR-181 mimic and inhibitor were transfected using Lipofectamine 2 000 to regulate the expression of miR-181, and then Real time q-PCR was used to verify transfection efficiency. Flow cytometry was used to detect the change of cell apoptosis rate. RESULTS: Compared with control group, the expression of miR-181 was significantly higher in both the anterior lens capsules of age-related cataract and human lens epithelial cell apoptosis model; the relative expression of miR-181 in lens epithelial cells transfected with miR-181 mimic was increased, whereas decreased in cells transfected with miR-181 inhibitor; the apoptosis rate of cells transfected with miR-181 mimic was increased, while reduced in miR-181 inhibitor group. Each result was statistically significant(PCONCLUSION: High expression of miR-181 is detected in anterior lens capsule of age-related cataract. miR-181 might play a certain role in the pathogenesis of cataract via promoting human lens epithelial cell apoptosis. miR-181 probably becomes a new approach for the nonoperative treatment of cataract, but the concrete mechanism still needs to be further studied.

R&W Club Frederick Hosts Second Annual Golf Tourney for The Children’s Inn | Poster

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By Carolynne Keenan, Contributing Writer On Sept. 8, more than 40 NCI at Frederick and Leidos Biomedical Research employees, along with family and friends, swapped work clothes for golf gear at Maryland National Golf Club in Middletown. The golfers didn’t just play for fun; they participated in the second annual R&W Club Frederick Golf Tournament to support The Children’s Inn

An OmpA Family Protein, a Target of the GinI/GinR Quorum-Sensing System in Gluconacetobacter intermedius, Controls Acetic Acid Fermentation▿ †

Science.gov (United States)

Iida, Aya; Ohnishi, Yasuo; Horinouchi, Sueharu

2008-01-01

Via N-acylhomoserine lactones, the GinI/GinR quorum-sensing system in Gluconacetobacter intermedius NCI1051, a gram-negative acetic acid bacterium, represses acetic acid and gluconic acid fermentation. Two-dimensional polyacrylamide gel electrophoretic analysis of protein profiles of strain NCI1051 and ginI and ginR mutants identified a protein that was produced in response to the GinI/GinR regulatory system. Cloning and nucleotide sequencing of the gene encoding this protein revealed that it encoded an OmpA family protein, named GmpA. gmpA was a member of the gene cluster containing three adjacent homologous genes, gmpA to gmpC, the organization of which appeared to be unique to vinegar producers, including “Gluconacetobacter polyoxogenes.” In addition, GmpA was unique among the OmpA family proteins in that its N-terminal membrane domain forming eight antiparallel transmembrane β-strands contained an extra sequence in one of the surface-exposed loops. Transcriptional analysis showed that only gmpA of the three adjacent gmp genes was activated by the GinI/GinR quorum-sensing system. However, gmpA was not controlled directly by GinR but was controlled by an 89-amino-acid protein, GinA, a target of this quorum-sensing system. A gmpA mutant grew more rapidly in the presence of 2% (vol/vol) ethanol and accumulated acetic acid and gluconic acid in greater final yields than strain NCI1051. Thus, GmpA plays a role in repressing oxidative fermentation, including acetic acid fermentation, which is unique to acetic acid bacteria and allows ATP synthesis via ethanol oxidation. Consistent with the involvement of gmpA in oxidative fermentation, its transcription was also enhanced by ethanol and acetic acid. PMID:18487322

The national cancer institute (NCI) and cancer biology in a 'post genome world'

International Nuclear Information System (INIS)

Klausner, Richard D.

1996-01-01

The National Cancer Institute (NCI) exists to reduce the burden of all cancers through research and discovery. Extensive restructuring of the NCI over the past year has been aimed at assuring that the institution functions in all ways to promote opportunities for discovery in the laboratory, in the clinic, and in the community. To do this well requires the difficult and almost paradoxical problem of planning for scientific discovery which, in turn is based on the freedom to pursue the unanticipated. The intellectual and structural landscape of science is changing and it places new challenges, new demands and new opportunities for facilitating discovery. The nature of cancer as a disease of genomic instability and of accumulated genetic change, coupled with a possibility of the development of new technologies for reading, utilizing, interpreting and manipulating the genome of single cells, provides unprecedented opportunities for a new type of high through-put biology that will change the nature of discovery, cancer detection, diagnosis, prognosis, therapeutic decision-making and therapeutic discovery. To capture these new opportunities will require attention to be paid to integrate the development of technology and new scientific discoveries with the ability to apply advances rapidly and efficiently through clinical trials

NCI Workshop Report: Clinical and Computational Requirements for Correlating Imaging Phenotypes with Genomics Signatures

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Rivka Colen

2014-10-01

Full Text Available The National Cancer Institute (NCI Cancer Imaging Program organized two related workshops on June 26–27, 2013, entitled “Correlating Imaging Phenotypes with Genomics Signatures Research” and “Scalable Computational Resources as Required for Imaging-Genomics Decision Support Systems.” The first workshop focused on clinical and scientific requirements, exploring our knowledge of phenotypic characteristics of cancer biological properties to determine whether the field is sufficiently advanced to correlate with imaging phenotypes that underpin genomics and clinical outcomes, and exploring new scientific methods to extract phenotypic features from medical images and relate them to genomics analyses. The second workshop focused on computational methods that explore informatics and computational requirements to extract phenotypic features from medical images and relate them to genomics analyses and improve the accessibility and speed of dissemination of existing NIH resources. These workshops linked clinical and scientific requirements of currently known phenotypic and genotypic cancer biology characteristics with imaging phenotypes that underpin genomics and clinical outcomes. The group generated a set of recommendations to NCI leadership and the research community that encourage and support development of the emerging radiogenomics research field to address short-and longer-term goals in cancer research.

Diarachidonoylphosphoethanolamine induces apoptosis of malignant pleural mesothelioma cells through a Trx/ASK1/p38 MAPK pathway

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Ayako Tsuchiya

2015-11-01

Full Text Available 1,2-Diarachidonoyl-sn-glycero-3-phosphoethanolamine (DAPE induces both necrosis/necroptosis and apoptosis of NCI-H28 malignant pleural mesothelioma (MPM cells. The present study was conducted to understand the mechanism for DAPE-induced apoptosis of NCI-H28 cells. DAPE induced caspase-independent apoptosis of NCI-H28 malignant pleural mesothelioma (MPM cells, and the effect of DAPE was prevented by antioxidants or an inhibitor of NADPH oxidase (NOX. DAPE generated reactive oxygen species (ROS and inhibited activity of thioredoxin (Trx reductase (TrxR. DAPE decreased an association of apoptosis signal-regulating kinase 1 (ASK1 with thioredoxin (Trx, thereby releasing ASK1. DAPE activated p38 mitogen-activated protein kinase (MAPK, which was inhibited by an antioxidant or knocking-down ASK1. In addition, DAPE-induced NCI-H28 cell death was also prevented by knocking-down ASK1. Taken together, the results of the present study indicate that DAPE stimulates NOX-mediated ROS production and suppresses TrxR activity, resulting in the decrease of reduced Trx and the dissociation of ASK1 from a complex with Trx, allowing sequential activation of ASK1 and p38 MAPK, to induce apoptosis of NCI-H28 MPM cells.

Diarachidonoylphosphoethanolamine induces apoptosis of malignant pleural mesothelioma cells through a Trx/ASK1/p38 MAPK pathway.

Science.gov (United States)

Tsuchiya, Ayako; Kaku, Yoshiko; Nakano, Takashi; Nishizaki, Tomoyuki

2015-11-01

1,2-Diarachidonoyl-sn-glycero-3-phosphoethanolamine (DAPE) induces both necrosis/necroptosis and apoptosis of NCI-H28 malignant pleural mesothelioma (MPM) cells. The present study was conducted to understand the mechanism for DAPE-induced apoptosis of NCI-H28 cells. DAPE induced caspase-independent apoptosis of NCI-H28 malignant pleural mesothelioma (MPM) cells, and the effect of DAPE was prevented by antioxidants or an inhibitor of NADPH oxidase (NOX). DAPE generated reactive oxygen species (ROS) and inhibited activity of thioredoxin (Trx) reductase (TrxR). DAPE decreased an association of apoptosis signal-regulating kinase 1 (ASK1) with thioredoxin (Trx), thereby releasing ASK1. DAPE activated p38 mitogen-activated protein kinase (MAPK), which was inhibited by an antioxidant or knocking-down ASK1. In addition, DAPE-induced NCI-H28 cell death was also prevented by knocking-down ASK1. Taken together, the results of the present study indicate that DAPE stimulates NOX-mediated ROS production and suppresses TrxR activity, resulting in the decrease of reduced Trx and the dissociation of ASK1 from a complex with Trx, allowing sequential activation of ASK1 and p38 MAPK, to induce apoptosis of NCI-H28 MPM cells. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Deletion of A44L, A46R and C12L Vaccinia Virus Genes from the MVA Genome Improved the Vector Immunogenicity by Modifying the Innate Immune Response Generating Enhanced and Optimized Specific T-Cell Responses

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María Pía Holgado

2016-05-01

Full Text Available MVA is an attenuated vector that still retains immunomodulatory genes. We have previously reported its optimization after deleting the C12L gene, coding for the IL-18 binding-protein. Here, we analyzed the immunogenicity of MVA vectors harboring the simultaneous deletion of A44L, related to steroid synthesis and A46R, a TLR-signaling inhibitor (MVAΔA44L-A46R; or also including a deletion of C12L (MVAΔC12L/ΔA44L-A46R. The absence of biological activities of the deleted genes in the MVA vectors was demonstrated. Adaptive T-cell responses against VACV epitopes, evaluated in spleen and draining lymph-nodes of C57Bl/6 mice at acute/memory phases, were of higher magnitude in those animals that received deleted MVAs compared to MVAwt. MVAΔC12L/ΔA44L-A46R generated cellular specific memory responses of higher quality characterized by bifunctionality (CD107a/b+/IFN-γ+ and proliferation capacity. Deletion of selected genes from MVA generated innate immune responses with higher levels of determining cytokines related to T-cell response generation, such as IL-12, IFN-γ, as well as IL-1β and IFN-β. This study describes for the first time that simultaneous deletion of the A44L, A46R and C12L genes from MVA improved its immunogenicity by enhancing the host adaptive and innate immune responses, suggesting that this approach comprises an appropriate strategy to increase the MVA vaccine potential.

Alternatively spliced CD44 isoforms containing exon v10 promote cellular adhesion through the recognition of chondroitin sulfate-modified CD44

NARCIS (Netherlands)

Chiu, R K; Droll, A; Dougherty, S T; Carpenito, C; Cooper, D L; Dougherty, G J

1999-01-01

Correlations have been noted between the expression of certain alternatively spliced CD44 isoforms and the metastatic propensity of various histologically distinct tumor cell types. The precise mechanism by which particular CD44 isoforms contribute to the metastatic process is, however, unclear. In

NCI-FDA Interagency Oncology Task Force Workshop Provides Guidance for Analytical Validation of Protein-based Multiplex Assays | Office of Cancer Clinical Proteomics Research

Science.gov (United States)

An NCI-FDA Interagency Oncology Task Force (IOTF) Molecular Diagnostics Workshop was held on October 30, 2008 in Cambridge, MA, to discuss requirements for analytical validation of protein-based multiplex technologies in the context of its intended use. This workshop developed through NCI's Clinical Proteomic Technologies for Cancer initiative and the FDA focused on technology-specific analytical validation processes to be addressed prior to use in clinical settings. In making this workshop unique, a case study approach was used to discuss issues related to

44 CFR 206.367 - Loan repayment.

Science.gov (United States)

2010-10-01

... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Loan repayment. 206.367 Section 206.367 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... interest, P=the principal amount disbursed; R=the interest rate of the loan; and, T=the outstanding term in...

NCI Statement on the U.S. Surgeon General's "Call to Action to Prevent Skin Cancer"

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As the Federal Government's principal agency for cancer research and training, the National Cancer Institute (NCI) endorses the U.S. Surgeon General’s “Call to Action to Prevent Skin Cancer,” which provides a comprehensive evaluation of the current state of skin cancer prevention efforts in the United States and recommends actions for improvement in the future.

L’avaluació de competències a l’Educació Superior: el cas d’un màster universitari

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Xavier Ma. Triadó i Ivern

2013-01-01

Full Text Available La implantació de les competències és una tasca que ha anat incorporant-se paulatinament pels docents de la universitat espanyola amb l’entrada en vigor del EEES. Tot i això, encara s’està lluny d’aconseguir nivells òptims d’avaluació de les mateixes. Aquest article permet reflexionar sobre algunes bones practiques al respecte i sobre les dificultats i limitacions que apareixen en voler implementar un canvi en les metodologies docents, en el marc d’un màster universitari. Els resultats indiquen el grau en què s’han avaluat i adquirit tant les competències genèriques com especifiques en l’educació superior.

Structure of the transcriptional regulator LmrR and its mechanism of multidrug recognition

NARCIS (Netherlands)

Madoori, Pramod Kumar; Agustiandari, Herfita; Driessen, Arnold J. M.; Thunnissen, Andy-Mark W. H.

2009-01-01

LmrR is a PadR-related transcriptional repressor that regulates the production of LmrCD, a major multidrug ABC transporter in Lactococcus lactis. Transcriptional regulation is presumed to follow a drug-sensitive induction mechanism involving the direct binding of transporter ligands to LmrR. Here,

A novel mechanism of regulating breast cancer cell migration via palmitoylation-dependent alterations in the lipid raft affiliation of CD44.

Science.gov (United States)

Babina, Irina S; McSherry, Elaine A; Donatello, Simona; Hill, Arnold D K; Hopkins, Ann M

2014-02-10

, the relevance of these findings is underscored by the fact that levels of palmitoylated CD44 were lower in primary cultures from invasive ductal carcinomas relative to non-tumour tissue, while CD44 co-localisation with a lipid raft marker was less in invasive ductal carcinoma relative to ductal carcinoma in situ cultures. Our results support a novel mechanism whereby CD44 palmitoylation and consequent lipid raft affiliation inversely regulate breast cancer cell migration, and may act as a new therapeutic target in breast cancer metastasis.

The corticotropin-releasing factor-like diuretic hormone 44 (DH44) and kinin neuropeptides modulate desiccation and starvation tolerance in Drosophila melanogaster.

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Cannell, Elizabeth; Dornan, Anthony J; Halberg, Kenneth A; Terhzaz, Selim; Dow, Julian A T; Davies, Shireen-A

2016-06-01

Malpighian tubules are critical organs for epithelial fluid transport and stress tolerance in insects, and are under neuroendocrine control by multiple neuropeptides secreted by identified neurons. Here, we demonstrate roles for CRF-like diuretic hormone 44 (DH44) and Drosophila melanogaster kinin (Drome-kinin, DK) in desiccation and starvation tolerance. Gene expression and labelled DH44 ligand binding data, as well as highly selective knockdowns and/or neuronal ablations of DH44 in neurons of the pars intercerebralis and DH44 receptor (DH44-R2) in Malpighian tubule principal cells, indicate that suppression of DH44 signalling improves desiccation tolerance of the intact fly. Drome-kinin receptor, encoded by the leucokinin receptor gene, LKR, is expressed in DH44 neurons as well as in stellate cells of the Malpighian tubules. LKR knockdown in DH44-expressing neurons reduces Malpighian tubule-specific LKR, suggesting interactions between DH44 and LK signalling pathways. Finally, although a role for DK in desiccation tolerance was not defined, we demonstrate a novel role for Malpighian tubule cell-specific LKR in starvation tolerance. Starvation increases gene expression of epithelial LKR. Also, Malpighian tubule stellate cell-specific knockdown of LKR significantly reduced starvation tolerance, demonstrating a role for neuropeptide signalling during starvation stress. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

44 CFR 13.44 - Termination for convenience.

Science.gov (United States)

2010-10-01

... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Termination for convenience. 13.44 Section 13.44 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY... § 13.44 Termination for convenience. Except as provided in § 13.43 awards may be terminated in whole or...

Metformin synergistically enhances antiproliferative effects of cisplatin and etoposide in NCI-H460 human lung cancer cells

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Sarah Fernandes Teixeira

2013-12-01

Full Text Available OBJECTIVE: To test the effectiveness of combining conventional antineoplastic drugs (cisplatin and etoposide with metformin in the treatment of non-small cell lung cancer in the NCI-H460 cell line, in order to develop new therapeutic options with high efficacy and low toxicity.METHODS: We used the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay and calculated the combination index for the drugs studied.RESULTS: We found that the use of metformin as monotherapy reduced the metabolic viability of the cell line studied. Combining metformin with cisplatin or etoposide produced a synergistic effect and was more effective than was the use of cisplatin or etoposide as monotherapy.CONCLUSIONS: Metformin, due to its independent effects on liver kinase B1, had antiproliferative effects on the NCI-H460 cell line. When metformin was combined with cisplatin or etoposide, the cell death rate was even higher.

ERK phosphorylation is predictive of resistance to IGF-1R inhibition in small cell lung cancer.

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Zinn, Rebekah L; Gardner, Eric E; Marchionni, Luigi; Murphy, Sara C; Dobromilskaya, Irina; Hann, Christine L; Rudin, Charles M

2013-06-01

New therapies are critically needed to improve the outcome for patients with small cell lung cancer (SCLC). Insulin-like growth factor 1 receptor (IGF-1R) inhibition is a potential treatment strategy for SCLC: the IGF-1R pathway is commonly upregulated in SCLC and has been associated with inhibition of apoptosis and stimulation of proliferation through downstream signaling pathways, including phosphatidylinositol-3-kinase-Akt and mitogen-activated protein kinase. To evaluate potential determinants of response to IGF-1R inhibition, we assessed the relative sensitivity of 19 SCLC cell lines to OSI-906, a small molecule inhibitor of IGF-1R, and the closely related insulin receptor. Approximately one third of these cell lines were sensitive to OSI-906, with an IC50 OSI-906. Interestingly, OSI-906 sensitive lines expressed significantly lower levels of baseline phospho-ERK relative to resistant lines (P = 0.006). OSI-906 treatment resulted in dose-dependent inhibition of phospho-IGF-1R and phospho-Akt in both sensitive and resistant cell lines, but induced apoptosis and cell-cycle arrest only in sensitive lines. We tested the in vivo efficacy of OSI-906 using an NCI-H187 xenograft model and two SCLC patient xenografts in mice. OSI-906 treatment resulted in 50% tumor growth inhibition in NCI-H187 and 30% inhibition in the primary patient xenograft models compared with mock-treated animals. Taken together our data support IGF-1R inhibition as a viable treatment strategy for a defined subset of SCLC and suggest that low pretreatment levels of phospho-ERK may be indicative of sensitivity to this therapeutic approach. ©2013 AACR

Bibliography on Cold Regions Science and Technology. Volume 44, Part 1, 1990

Science.gov (United States)

1990-12-01

Institute, Information. (Prostaia sistema poiska snegolavinnol thesis. Refs. p.342 -358. Tokyo Quarterly reports. Feb. 1988, 29(l), p.9. S. rcferativnot...down this area toward the cna plateau. ot maud toc Clayton. L., ct al, Geological Society of America. 44-2077 d i t t r t u Urnioirs, 1989, No.173, 80p...pro rosion, Heat transfer, Solutions, Air conditioning. Japan-Sapporo. toc &on, and operator training. 130 CRREL BIBLIOGRAPHY 44-3050 44-3054 44.3062

Enhanced Missing Proteins Detection in NCI60 Cell Lines Using an Integrative Search Engine Approach.

Science.gov (United States)

Guruceaga, Elizabeth; Garin-Muga, Alba; Prieto, Gorka; Bejarano, Bartolomé; Marcilla, Miguel; Marín-Vicente, Consuelo; Perez-Riverol, Yasset; Casal, J Ignacio; Vizcaíno, Juan Antonio; Corrales, Fernando J; Segura, Victor

2017-12-01

The Human Proteome Project (HPP) aims deciphering the complete map of the human proteome. In the past few years, significant efforts of the HPP teams have been dedicated to the experimental detection of the missing proteins, which lack reliable mass spectrometry evidence of their existence. In this endeavor, an in depth analysis of shotgun experiments might represent a valuable resource to select a biological matrix in design validation experiments. In this work, we used all the proteomic experiments from the NCI60 cell lines and applied an integrative approach based on the results obtained from Comet, Mascot, OMSSA, and X!Tandem. This workflow benefits from the complementarity of these search engines to increase the proteome coverage. Five missing proteins C-HPP guidelines compliant were identified, although further validation is needed. Moreover, 165 missing proteins were detected with only one unique peptide, and their functional analysis supported their participation in cellular pathways as was also proposed in other studies. Finally, we performed a combined analysis of the gene expression levels and the proteomic identifications from the common cell lines between the NCI60 and the CCLE project to suggest alternatives for further validation of missing protein observations.

Game Analysis on Influence Mechanism of Equity Incentive on R&D Investments

OpenAIRE

Cao Wen; Li Yuewen

2014-01-01

A game model between shareholders and manager is built to analyze influence mechanism of equity incentive on R&D investments based on principal-agent theory. Research shows that there are inverted U-shaped relationships between equity incentive and R&D investments, the modest equity should be gave for stimulate manager.

Hyaluronan-CD44v3 Interaction with Oct4-Sox2-Nanog Promotes miR-302 Expression Leading to Self-renewal, Clonal Formation, and Cisplatin Resistance in Cancer Stem Cells from Head and Neck Squamous Cell Carcinoma*

Science.gov (United States)

Bourguignon, Lilly Y. W.; Wong, Gabriel; Earle, Christine; Chen, Liqun

2012-01-01

Human head and neck squamous cell carcinoma (HNSCC) is a highly malignant cancer associated with major morbidity and mortality. In this study, we determined that human HNSCC-derived HSC-3 cells contain a subpopulation of cancer stem cells (CSCs) characterized by high levels of CD44v3 and aldehyde dehydrogenase-1 (ALDH1) expression. These tumor cells also express several stem cell markers (the transcription factors Oct4, Sox2, and Nanog) and display the hallmark CSC properties of self-renewal/clonal formation and the ability to generate heterogeneous cell populations. Importantly, hyaluronan (HA) stimulates the CD44v3 (an HA receptor) interaction with Oct4-Sox2-Nanog leading to both a complex formation and the nuclear translocation of three CSC transcription factors. Further analysis reveals that microRNA-302 (miR-302) is controlled by an upstream promoter containing Oct4-Sox2-Nanog-binding sites, whereas chromatin immunoprecipitation (ChIP) assays demonstrate that stimulation of miR-302 expression by HA-CD44 is Oct4-Sox2-Nanog-dependent in HNSCC-specific CSCs. This process results in suppression of several epigenetic regulators (AOF1/AOF2 and DNMT1) and the up-regulation of several survival proteins (cIAP-1, cIAP-2, and XIAP) leading to self-renewal, clonal formation, and cisplatin resistance. These CSCs were transfected with a specific anti-miR-302 inhibitor to silence miR-302 expression and block its target functions. Our results demonstrate that the anti-miR-302 inhibitor not only enhances the expression of AOF1/AOF2 and DNMT1 but also abrogates the production of cIAP-1, cIAP-2, and XIAP and HA-CD44v3-mediated cancer stem cell functions. Taken together, these findings strongly support the contention that the HA-induced CD44v3 interaction with Oct4-Sox2-Nanog signaling plays a pivotal role in miR-302 production leading to AOF1/AOF2/DNMT1 down-regulation and survival of protein activation. All of these events are critically important for the acquisition of cancer

Hyaluronan-CD44v3 interaction with Oct4-Sox2-Nanog promotes miR-302 expression leading to self-renewal, clonal formation, and cisplatin resistance in cancer stem cells from head and neck squamous cell carcinoma.

Science.gov (United States)

Bourguignon, Lilly Y W; Wong, Gabriel; Earle, Christine; Chen, Liqun

2012-09-21

Human head and neck squamous cell carcinoma (HNSCC) is a highly malignant cancer associated with major morbidity and mortality. In this study, we determined that human HNSCC-derived HSC-3 cells contain a subpopulation of cancer stem cells (CSCs) characterized by high levels of CD44v3 and aldehyde dehydrogenase-1 (ALDH1) expression. These tumor cells also express several stem cell markers (the transcription factors Oct4, Sox2, and Nanog) and display the hallmark CSC properties of self-renewal/clonal formation and the ability to generate heterogeneous cell populations. Importantly, hyaluronan (HA) stimulates the CD44v3 (an HA receptor) interaction with Oct4-Sox2-Nanog leading to both a complex formation and the nuclear translocation of three CSC transcription factors. Further analysis reveals that microRNA-302 (miR-302) is controlled by an upstream promoter containing Oct4-Sox2-Nanog-binding sites, whereas chromatin immunoprecipitation (ChIP) assays demonstrate that stimulation of miR-302 expression by HA-CD44 is Oct4-Sox2-Nanog-dependent in HNSCC-specific CSCs. This process results in suppression of several epigenetic regulators (AOF1/AOF2 and DNMT1) and the up-regulation of several survival proteins (cIAP-1, cIAP-2, and XIAP) leading to self-renewal, clonal formation, and cisplatin resistance. These CSCs were transfected with a specific anti-miR-302 inhibitor to silence miR-302 expression and block its target functions. Our results demonstrate that the anti-miR-302 inhibitor not only enhances the expression of AOF1/AOF2 and DNMT1 but also abrogates the production of cIAP-1, cIAP-2, and XIAP and HA-CD44v3-mediated cancer stem cell functions. Taken together, these findings strongly support the contention that the HA-induced CD44v3 interaction with Oct4-Sox2-Nanog signaling plays a pivotal role in miR-302 production leading to AOF1/AOF2/DNMT1 down-regulation and survival of protein activation. All of these events are critically important for the acquisition of cancer

Persistent Identifier Practice for Big Data Management at NCI

Directory of Open Access Journals (Sweden)

Jingbo Wang

2017-04-01

Full Text Available The National Computational Infrastructure (NCI manages over 10 PB research data, which is co-located with the high performance computer (Raijin and an HPC class 3000 core OpenStack cloud system (Tenjin. In support of this integrated High Performance Computing/High Performance Data (HPC/HPD infrastructure, NCI’s data management practices includes building catalogues, DOI minting, data curation, data publishing, and data delivery through a variety of data services. The metadata catalogues, DOIs, THREDDS, and Vocabularies, all use different Uniform Resource Locator (URL styles. A Persistent IDentifier (PID service provides an important utility to manage URLs in a consistent, controlled and monitored manner to support the robustness of our national ‘Big Data’ infrastructure. In this paper we demonstrate NCI’s approach of utilising the NCI’s 'PID Service 'to consistently manage its persistent identifiers with various applications.

Mechanical and IL-1β Responsive miR-365 Contributes to Osteoarthritis Development by Targeting Histone Deacetylase 4

Directory of Open Access Journals (Sweden)

Xu Yang

2016-03-01

Full Text Available Mechanical stress plays an important role in the initiation and progression of osteoarthritis. Studies show that excessive mechanical stress can directly damage the cartilage extracellular matrix and shift the balance in chondrocytes to favor catabolic activity over anabolism. However, the underlying mechanism remains unknown. MicroRNAs (miRNAs are emerging as important regulators in osteoarthritis pathogenesis. We have found that mechanical loading up-regulated microRNA miR-365 in growth plate chondrocytes, which promotes chondrocyte differentiation. Here, we explored the role of the mechanical responsive microRNA miR-365 in pathogenesis of osteoarthritis (OA. We found that miR-365 was up-regulated by cyclic loading and IL-1β stimulation in articular chondrocytes through a mechanism that involved the transcription factor NF-κB. miR-365 expressed significant higher level in rat anterior cruciate ligament (ACL surgery induced OA cartilage as well as human OA cartilage from primary OA patients and traumatic OA Patients. Overexpression of miR-365 in chondrocytes increases gene expression of matrix degrading enzyme matrix metallopeptidase 13 (MMP13 and collagen type X (Col X. The increase in miR-365 expression in OA cartilage and in response to IL-1 may contribute to the abnormal gene expression pattern characteristic of OA. Inhibition of miR-365 down-regulated IL-1β induced MMP13 and Col X gene expression. We further showed histone deacetylase 4 (HDAC4 is a direct target of miR-365, which mediates mechanical stress and inflammation in OA pathogenesis. Thus, miR-365 is a critical regulator of mechanical stress and pro-inflammatory responses, which contributes cartilage catabolism. Manipulation of the expression of miR-365 in articular chondrocytes by miR-365 inhibitor may be a potent therapeutic target for the prevention and treatment of osteoarthritis.

Malalties de transmissió sexual a urgències pediàtriques

OpenAIRE

Díaz Sabogal, Diana; Curcoy Barcenilla, Ana Isabel; Trenchs Sainz de la Maza, Victoria; Giménez Roca, Clara; Luaces Cubells, Carles

2014-01-01

Determinar les característiques dels pacients diag- nosticats de malalties de transmissió sexual (MTS) a urgèn- cies i establir la freqüència en què són degudes a abús sexual. Mètode. Estudi retrospectiu fet entre el gener del 2007 i el desembre del 2011. S'inclouen els pacients menors de 18 anys diagnosticats a urgències d'MTS -infecció per Neisse- ria gonorrhoeae, Chlamydia trachomatis, Treponema palli- dum, , virus d'immunodeficiència humana (VIH), virus del pa- pil loma humà (VPH) i virus...

Structure of the transcriptional regulator LmrR and its mechanism of multidrug recognition.

Science.gov (United States)

Madoori, Pramod Kumar; Agustiandari, Herfita; Driessen, Arnold J M; Thunnissen, Andy-Mark W H

2009-01-21

LmrR is a PadR-related transcriptional repressor that regulates the production of LmrCD, a major multidrug ABC transporter in Lactococcus lactis. Transcriptional regulation is presumed to follow a drug-sensitive induction mechanism involving the direct binding of transporter ligands to LmrR. Here, we present crystal structures of LmrR in an apo state and in two drug-bound states complexed with Hoechst 33342 and daunomycin. LmrR shows a common topology containing a typical beta-winged helix-turn-helix domain with an additional C-terminal helix involved in dimerization. Its dimeric organization is highly unusual with a flat-shaped hydrophobic pore at the dimer centre serving as a multidrug-binding site. The drugs bind in a similar manner with their aromatic rings sandwiched in between the indole groups of two dimer-related tryptophan residues. Multidrug recognition is facilitated by conformational plasticity and the absence of drug-specific hydrogen bonds. Combined analyses using site-directed mutagenesis, fluorescence-based drug binding and protein-DNA gel shift assays reveal an allosteric coupling between the multidrug- and DNA-binding sites of LmrR that most likely has a function in the induction mechanism.

NCI Research Specialist Award (R50)

Science.gov (United States)

Award enables scientists to pursue stable research careers within an existing cancer research program, but not serve as independent investigators. Letter of Intent due: January 2, 2017 Application due: February 2, 2017

R&W Club Frederick Hosts 4th Annual Golf Tournament Benefiting The Children’s Inn at NIH | Poster

Science.gov (United States)

The R&W Club Frederick’s 4th Annual Golf Tournament to benefit the Children’s Inn at NIH teed off on time despite cloudy weather and scattered showers. Employees from NCI at Frederick, the main NIH campus, and Leidos Biomed, along with family and friends, came to enjoy an afternoon at the beautiful Maryland National Golf Club in Middletown and to support a wonderful charity.

Unified Singularity Modeling and Reconfiguration of 3rTPS Metamorphic Parallel Mechanisms with Parallel Constraint Screws

Directory of Open Access Journals (Sweden)

Yufeng Zhuang

2015-01-01

Full Text Available This paper presents a unified singularity modeling and reconfiguration analysis of variable topologies of a class of metamorphic parallel mechanisms with parallel constraint screws. The new parallel mechanisms consist of three reconfigurable rTPS limbs that have two working phases stemming from the reconfigurable Hooke (rT joint. While one phase has full mobility, the other supplies a constraint force to the platform. Based on these, the platform constraint screw systems show that the new metamorphic parallel mechanisms have four topologies by altering the limb phases with mobility change among 1R2T (one rotation with two translations, 2R2T, and 3R2T and mobility 6. Geometric conditions of the mechanism design are investigated with some special topologies illustrated considering the limb arrangement. Following this and the actuation scheme analysis, a unified Jacobian matrix is formed using screw theory to include the change between geometric constraints and actuation constraints in the topology reconfiguration. Various singular configurations are identified by analyzing screw dependency in the Jacobian matrix. The work in this paper provides basis for singularity-free workspace analysis and optimal design of the class of metamorphic parallel mechanisms with parallel constraint screws which shows simple geometric constraints with potential simple kinematics and dynamics properties.

Macro-Micro Linkages and the Role of Mechanisms in Social Stratification Research

Czech Academy of Sciences Publication Activity Database

Veselý, Arnošt; Smith, Michael

2008-01-01

Roč. 44, č. 3 (2008), s. 491-509 ISSN 0038-0288 R&D Projects: GA ČR GA403/08/0109; GA MPS(CZ) 1J/005/04-DP2 Institutional research plan: CEZ:AV0Z70280505 Keywords : Social stratification research * stratification processes * social mechanisms Subject RIV: AO - Sociology, Demography Impact factor: 0.427, year: 2008 http://dlib.lib.cas.cz/3508/

NCI Helps Children’s Hospital of Philadelphia to Identify and Treat New Target in Pediatric Cancer | Poster

Science.gov (United States)

There may be a new, more effective method for treating high-risk neuroblastoma, according to scientists at the Children’s Hospital of Philadelphia and collaborators in the Cancer and Inflammation Program at NCI at Frederick. Together, the groups published a study describing a previously unrecognized protein on neuroblastoma cells, called GPC2, as well as the creation of a

Soluble interleukin 6 receptor (sIL-6R) mediates colonic tumor cell adherence to the vascular endothelium: a mechanism for metastatic initiation?

LENUS (Irish Health Repository)

Dowdall, J F

2012-02-03

The mechanisms by which surgery increases metastatic proliferation remain poorly characterized, although endotoxin and immunocytes play a role. Recent evidence suggests that endothelial adherence of tumor cells may be important in the formation of metastases. Soluble receptors of interleukin-6 (sIL-6R) shed by activated neutrophils exert IL-6 effects on endothelial cells, which are unresponsive under normal circumstances. This study examined the hypothesis that sIL-6R released by surgical stress increases tumor cell adherence to the endothelium. Neutrophils (PMN) were stimulated with lipopolysaccharide, C-reactive protein (CRP), and tumor necrosis factor-alpha. Soluble IL-6R release was measured by enzyme-linked immunosorbent assay. Colonic tumor cells transfected with green fluorescent protein and endothelial cells were exposed to sIL-6R, and tumor cell adherence and transmigration were measured by fluorescence microscopy. Basal release of sIL-6R from PMN was 44.7 +\\/- 8.2 pg\\/ml at 60 min. This was significantly increased by endotoxin and CRP (131 +\\/- 16.8 and 84.1 +\\/- 5.3, respectively; both P < 0.05). However, tumor necrosis factor-alpha did not significantly alter sIL-6R release. Endothelial and tumor cell exposure to sIL-6R increased tumor cell adherence by 71.3% within 2 h but did not significantly increase transmigration, even at 6 h. Mediators of surgical stress induce neutrophil release of a soluble receptor for IL-6 that enhances colon cancer cell endothelial adherence. Since adherence to the endothelium is now considered to be a key event in metastatic genesis, these findings have important implications for colon cancer treatment strategies.

Defended to the Nines: 25 Years of Resistance Gene Cloning Identifies Nine Mechanisms for R Protein Function.

Science.gov (United States)

Kourelis, Jiorgos; van der Hoorn, Renier A L

2018-02-01

Plants have many, highly variable resistance ( R ) gene loci, which provide resistance to a variety of pathogens. The first R gene to be cloned, maize ( Zea mays ) Hm1 , was published over 25 years ago, and since then, many different R genes have been identified and isolated. The encoded proteins have provided clues to the diverse molecular mechanisms underlying immunity. Here, we present a meta-analysis of 314 cloned R genes. The majority of R genes encode cell surface or intracellular receptors, and we distinguish nine molecular mechanisms by which R proteins can elevate or trigger disease resistance: direct (1) or indirect (2) perception of pathogen-derived molecules on the cell surface by receptor-like proteins and receptor-like kinases; direct (3) or indirect (4) intracellular detection of pathogen-derived molecules by nucleotide binding, leucine-rich repeat receptors, or detection through integrated domains (5); perception of transcription activator-like effectors through activation of executor genes (6); and active (7), passive (8), or host reprogramming-mediated (9) loss of susceptibility. Although the molecular mechanisms underlying the functions of R genes are only understood for a small proportion of known R genes, a clearer understanding of mechanisms is emerging and will be crucial for rational engineering and deployment of novel R genes. © 2018 American Society of Plant Biologists. All rights reserved.

Genome-wide identification and characterization of R2R3MYB family in Rosaceae.

Science.gov (United States)

González, Máximo; Carrasco, Basilio; Salazar, Erika

2016-09-01

Transcription factors R2R3MYB family have been associated with the control of secondary metabolites, development of structures, cold tolerance and response to biotic and abiotic stress, among others. In recent years, genomes of Rosaceae botanical family are available. Although this information has been used to study the karyotype evolution of these species from an ancestral genome, there are no studies that treat the evolution and diversity of gene families present in these species or in the botanical family. Here we present the first comparative study of the R2R3MYB subfamily of transcription factors in three species of Rosaceae family (Malus domestica, Prunus persica and Fragaria vesca). We described 186, 98 and 86 non-redundant gene models for apple, peach and strawberry, respectively. In this research, we analyzed the intron-exon structure and genomic distribution of R2R3MYB families mentioned above. The phylogenetic comparisons revealed putative functions of some R2R3MYB transcription factors. This analysis found 44 functional subgroups, seven of which were unique for Rosaceae. In addition, our results showed a highly collinearity among some genes revealing the existence of conserved gene models between the three species studied. Although some gene models in these species have been validated under several approaches, more research in the Rosaceae family is necessary to determine gene expression patterns in specific tissues and development stages to facilitate understanding of the regulatory and biochemical mechanism in this botanical family.

Expression of CD44 3'-untranslated region regulates endogenous microRNA functions in tumorigenesis and angiogenesis.

Science.gov (United States)

Jeyapalan, Zina; Deng, Zhaoqun; Shatseva, Tatiana; Fang, Ling; He, Chengyan; Yang, Burton B

2011-04-01

The non-coding 3'-untranslated region (UTR) plays an important role in the regulation of microRNA (miRNA) functions, since it can bind and inactivate multiple miRNAs. Here, we show the 3'-UTR of CD44 is able to antagonize cytoplasmic miRNAs, and result in the increased translation of CD44 and downstream target mRNA, CDC42. A series of cell function assays in the human breast cancer cell line, MT-1, have shown that the CD44 3'-UTR inhibits proliferation, colony formation and tumor growth. Furthermore, it modulated endothelial cell activities, favored angiogenesis, induced tumor cell apoptosis and increased sensitivity to Docetaxel. These results are due to the interaction of the CD44 3'-UTR with multiple miRNAs. Computational algorithms have predicted three miRNAs, miR-216a, miR-330 and miR-608, can bind to both the CD44 and CDC42 3'-UTRs. This was confirmed with luciferase assays, western blotting and immunohistochemical staining and correlated with a series of siRNA assays. Thus, the non-coding CD44 3'-UTR serves as a competitor for miRNA binding and subsequently inactivates miRNA functions, by freeing the target mRNAs from being repressed.

Well-posedness of a thermo-mechanical model for shape memory alloys under tension

Czech Academy of Sciences Publication Activity Database

Krejčí, Pavel; Stefanelli, U.

2010-01-01

Roč. 44, č. 6 (2010), s. 1239-1253 ISSN 0764-583X R&D Projects: GA ČR GAP201/10/2315 Institutional research plan: CEZ:AV0Z10190503 Keywords : shape memory alloys * thermo-mechanics * well-posedness * hysteresis operator Subject RIV: BA - General Mathematics Impact factor: 1.202, year: 2010 http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=8129335

Defended to the Nines: 25 Years of Resistance Gene Cloning Identifies Nine Mechanisms for R Protein Function[OPEN

Science.gov (United States)

2018-01-01

Plants have many, highly variable resistance (R) gene loci, which provide resistance to a variety of pathogens. The first R gene to be cloned, maize (Zea mays) Hm1, was published over 25 years ago, and since then, many different R genes have been identified and isolated. The encoded proteins have provided clues to the diverse molecular mechanisms underlying immunity. Here, we present a meta-analysis of 314 cloned R genes. The majority of R genes encode cell surface or intracellular receptors, and we distinguish nine molecular mechanisms by which R proteins can elevate or trigger disease resistance: direct (1) or indirect (2) perception of pathogen-derived molecules on the cell surface by receptor-like proteins and receptor-like kinases; direct (3) or indirect (4) intracellular detection of pathogen-derived molecules by nucleotide binding, leucine-rich repeat receptors, or detection through integrated domains (5); perception of transcription activator-like effectors through activation of executor genes (6); and active (7), passive (8), or host reprogramming-mediated (9) loss of susceptibility. Although the molecular mechanisms underlying the functions of R genes are only understood for a small proportion of known R genes, a clearer understanding of mechanisms is emerging and will be crucial for rational engineering and deployment of novel R genes. PMID:29382771

Plant collecting program in Southeast Asia under the sponsorship of the United States National Cancer Institute (NCI) (1986-1991)

NARCIS (Netherlands)

Soejarto, D.D.

1992-01-01

Under the funding from the United States National Cancer Institute (NCI)¹, a program was undertaken to collect plant samples in Southeast Asia to be tested for their cancer- and AIDS-arresting properties, for the period of September 1, 1986 through August 31, 1991. The program was implemented with

Experimental study on the killing effects of 125IUdR to human glioma cells in vitro

International Nuclear Information System (INIS)

Li Jinquan; Bao Yaodong; Zhou Dai; Cui Gang; Wang Bocheng; Jiang Yimin; Wang Haiqiu; Wu Yiwei

2001-01-01

The 125 IUdR-uptake profile and the cytocidal effects of 125 IUdR on human cerebral glioma (SHG44) cells were estimated after incubation with 125 IUdR. The killing effects of 125 IUdR comparing with Na 125 I on SHG44 were estimated by colony forming method. The results showed that the amounts of 125 IUdR uptake by SHG44 were growing with the rate of dose of 125 IUdR in the medium, relation factor r = 0.9917. Also the concentration of 125 IUdR uptake by SHG44 was time-dependent, relation factor r = 0.9859. As the concentration in SHG44 growing, the inhibition effects became stronger, relation factor r = - 0.9736. The LD 50 was 8.7 +- 0.12 kBq/ml. The concentration of radioactivity ingestion was significantly stronger in 125 IUdR group than that in Na 125 I group. The surviving fraction was significantly different between in the 125 IUdR group and in Na 125 I group at the concentration point 9.0 kBq/ml. 125 IUdR may be incorporated in SHG44 cell, and the concentration of 125 IUdR ingestion by SHG44 was influenced with the dose in the medium and the culturing time. The prohibitive effects of 125 IUdR on SHG44 cell were obvious. The prohibition effects were significantly stronger in 125 IUdR group than that in Na 125 I group. 125 IUdR may be a kind of potential drug in the therapy of human cerebral glioma

Decreased glucose uptake by hyperglycemia is regulated by different mechanisms in human cancer cells and monocytes

International Nuclear Information System (INIS)

Kim, Chae Kyun; Chung, June Key; Lee, Yong Jin; Hong, Mee Kyoung; Jeong, Jae Min; Lee, Dong Soo; Lee, Myung Chul

2002-01-01

To clarify the difference in glucose uptake between human cancer cells and monocytes, we studied ( 18 F) fluorodeoxyglucose (FDG) uptake in three human colon cancer cell lines (SNU-C2A, SNU-C4, SNU-C5), one human lung cancer cell line (NCI-H522), and human peripheral blood monocytes. The FDG uptake of both cancer cells and monocytes was increased in glucose-free medium, but decreased in the medium containing 16.7 mM glucose (hyperglycemic). The level of Glut1 mRNA decreased in human colon cancer cells and NCI-H522 under hyperglycemic condition. Glut1 protein expression was also decreased in the four human cancer cell lines under hyperglycemic condition, whereas it was consistently undetectable in monocytes. SNU-C2A, SNU-C4 and NCI-H522 showed a similar level of hexokinase activity (7.5-10.8 mU/mg), while SNU-C5 and moncytes showed lower range of hexokinase activity (4.3-6.5 mU/mg). These data suggest that glucose uptake is regulated by different mechanisms in human cancer cells and monocytes

The Effectiveness of Different Mechanisms for Integrating Marketing and R&D

NARCIS (Netherlands)

M.A.A.M. Leenders (Mark); B. Wierenga (Berend)

2001-01-01

textabstractThe integration of marketing and R&D is a major concern for companies that want to improve their new product performance (NPP). In order to integrate, companies are using mechanisms such as physical proximity, cross-functional teams, and job rotation. This study examines the relative

Preliminary crystallographic studies of yeast mitochondrial peripheral membrane protein Tim44p

Energy Technology Data Exchange (ETDEWEB)

Josyula, Ratnakar [Department of Cell Biology, Center for Biophysical Sciences and Engineering, University of Alabama at Birmingham (United States); Jin, Zhongmin [SER-CAT, APS, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, IL 60439 (United States); McCombs, Deborah; DeLucas, Lawrence [Center for Biophysical Sciences and Engineering, University of Alabama at Birmingham (United States); Sha, Bingdong, E-mail: bdsha@uab.edu [Department of Cell Biology, Center for Biophysical Sciences and Engineering, University of Alabama at Birmingham (United States)

2006-02-01

Tim44p is an essential mitochondrial peripheral membrane protein. To investigate the mechanism by which Tim44p functions in the TIM23 translocon to deliver the mitochondrial protein precursors, the yeast Tim44p has been crystallized. Protein translocations across mitochondrial membranes play critical roles in mitochondrion biogenesis. Protein transport from the cell cytosol to the mitochondrial matrix is carried out by the translocase of the outer membrane (TOM) complex and the translocase of the inner membrane (TIM) complexes. Tim44p is an essential mitochondrial peripheral membrane protein and a major component of the TIM23 translocon. To investigate the mechanism by which Tim44p functions in the TIM23 translocon to deliver the mitochondrial protein precursors, the yeast Tim44p was crystallized. The crystals diffract to 3.2 Å using a synchrotron X-ray source and belong to space group P6{sub 3}22, with unit-cell parameters a = 124.25, c = 77.83 Å. There is one Tim44p molecule in one asymmetric unit, which corresponds to a solvent content of approximately 43%. Structure determination by MAD methods is under way.

Identification of the Molecular Mechanisms Responsible for the Inhibition of Homing of AML Cells Triggered by CD44-Ligation

KAUST Repository

Al-Jifri, Ablah

2011-08-03

Acute Myeloid Leukemia (AML) is a cancerous disease that is defined by the inability to produce functional and mature blood cells, as well as the uncontrolled proliferation due to failure to undergo apoptosis of abnormal cells. The most common therapy for Leukemia, chemotherapy, has proven only to be partially efficient since it does not target the leukemic stem cells (LSCs) that have a high self-renewal and repopulation capacity and result in remission of the disease. Therefore targeting LSCs will provide more efficient therapy. One way to achieve this would be to inhibit their homing capability to the bone marrow. It has recently been shown that CD44, an adhesive molecule, plays a crucial role in cell trafficking and lodgement of both normal and leukemic stem cells. More importantly anti-CD44 monoclonal antibodies, along with its ability to induce differentiation of leukemic blasts, it inhibits specifically the homing capacity of LSCs to their micro-environmental niches. However, these molecular mechanisms that underlie the inhibition of homing have yet to be determined. To address these questions we conducted in vitro adhesion and blot-rolling assays to analyze the adherence and rolling capacity of these LSCs before and after treatment with anti-CD44 monoclonal antibody (mAb). Since glycosyltransferases play a crucial role in post translational carbohydrate decoration on adhesion molecules, we analyzed the expression (using quantitative PCR) of the different glycosyltransferases expressed in LSC\\'s before and after CD44 ligation (mAb treatment). Furthermore, we analyzed differentiation by flow cytometric analysis of treated and non-treated LSC\\'s. We anticipate that our results will set forth new insights into targeted therapies for AML.

R K Laxman

Indian Academy of Sciences (India)

Home; Journals; Resonance – Journal of Science Education. R K Laxman. Articles written in Resonance – Journal of Science Education. Volume 1 Issue 4 April 1996 pp 4-4 Science Smiles. Chief Editor's column / Science Smiles · R K Laxman · More Details Fulltext PDF. Volume 1 Issue 5 May 1996 pp 3-3 Science Smiles.

miR-375 is highly expressed and possibly transactivated by achaete-scute complex homolog 1 in small-cell lung cancer cells

Institute of Scientific and Technical Information of China (English)

Huijie Zhao; Lei Zhu; Yujuan Jin; Hongbin Ji; Xiumin Yan; Xueliang Zhu

2012-01-01

In this study,we identified five miRNAs highly expressed in the small-cell lung cancer (SCLC) cell line NCI-H209.Among them,the expression levels of miR-375 were dramatically elevated in all SCLC cell lines examined,coincident with the expression of the transcription factor achaete-scute complex homolog 1 (ASCL1).Moreover,miR-375 was upregulated and correlated with ASCL1 in the cell lines generated from mouse SCLC-like tumors as well.Dual-luciferase assays further showed that ASCL1 activated the expression of miR-375 by binding to the three E-box elements in the miR-375 promoter.These results imply a role of ASCL1 in SCLC via the upregulation of miR-375.

Expression of CD44 3′-untranslated region regulates endogenous microRNA functions in tumorigenesis and angiogenesis

Science.gov (United States)

Jeyapalan, Zina; Deng, Zhaoqun; Shatseva, Tatiana; Fang, Ling; He, Chengyan; Yang, Burton B.

2011-01-01

The non-coding 3′-untranslated region (UTR) plays an important role in the regulation of microRNA (miRNA) functions, since it can bind and inactivate multiple miRNAs. Here, we show the 3′-UTR of CD44 is able to antagonize cytoplasmic miRNAs, and result in the increased translation of CD44 and downstream target mRNA, CDC42. A series of cell function assays in the human breast cancer cell line, MT-1, have shown that the CD44 3′-UTR inhibits proliferation, colony formation and tumor growth. Furthermore, it modulated endothelial cell activities, favored angiogenesis, induced tumor cell apoptosis and increased sensitivity to Docetaxel. These results are due to the interaction of the CD44 3′-UTR with multiple miRNAs. Computational algorithms have predicted three miRNAs, miR-216a, miR-330 and miR-608, can bind to both the CD44 and CDC42 3′-UTRs. This was confirmed with luciferase assays, western blotting and immunohistochemical staining and correlated with a series of siRNA assays. Thus, the non-coding CD44 3′-UTR serves as a competitor for miRNA binding and subsequently inactivates miRNA functions, by freeing the target mRNAs from being repressed. PMID:21149267

NCI's Distributed Geospatial Data Server

Science.gov (United States)

Larraondo, P. R.; Evans, B. J. K.; Antony, J.

2016-12-01

Earth systems, environmental and geophysics datasets are an extremely valuable source of information about the state and evolution of the Earth. However, different disciplines and applications require this data to be post-processed in different ways before it can be used. For researchers experimenting with algorithms across large datasets or combining multiple data sets, the traditional approach to batch data processing and storing all the output for later analysis rapidly becomes unfeasible, and often requires additional work to publish for others to use. Recent developments on distributed computing using interactive access to significant cloud infrastructure opens the door for new ways of processing data on demand, hence alleviating the need for storage space for each individual copy of each product. The Australian National Computational Infrastructure (NCI) has developed a highly distributed geospatial data server which supports interactive processing of large geospatial data products, including satellite Earth Observation data and global model data, using flexible user-defined functions. This system dynamically and efficiently distributes the required computations among cloud nodes and thus provides a scalable analysis capability. In many cases this completely alleviates the need to preprocess and store the data as products. This system presents a standards-compliant interface, allowing ready accessibility for users of the data. Typical data wrangling problems such as handling different file formats and data types, or harmonising the coordinate projections or temporal and spatial resolutions, can now be handled automatically by this service. The geospatial data server exposes functionality for specifying how the data should be aggregated and transformed. The resulting products can be served using several standards such as the Open Geospatial Consortium's (OGC) Web Map Service (WMS) or Web Feature Service (WFS), Open Street Map tiles, or raw binary arrays under

Effect of bcl-2 antisense oligodexynucleotides on chemotherapy efficacy of Vp-16 on human small cell lung cancer cell line NCI-H69

International Nuclear Information System (INIS)

He Wenqian; Liu Zhonghua

2007-01-01

Objective: To study the effect of bcl-2 antisense oligodexynucleotides on chemotherapy efficacy of Vp-16 on human small cell lung cancer cell line NCI-H69. Methods: Cultured NCI-H69 cells were derided into 4 groups: bcl-2 antisense oligodexynucleotides (ASODN) added, sense oligodexynucleotides (SODN) added, nonsense oligodexynucleotides (NSODN) added and control (no nucleotides added), the oligodexynucleotides were transfected into the cultured cells with oligofectamine. The cellular expression of Bcl-2 protein 72h later was examined with Western-Blot. The four different groups of cultured tumor cells were treated with etopside(Vp-16) at different concentrations (0, 0.25, 0.5, 1.0, 2.0 and 4.0 μg/ml) for 48hr then the cell survival fraction was assessed with MTY test. Results: The apoptotic rate of cells in the ASODN group was significantly higher than that of the control group, also, the survival fraction of cells in ASODN group was significantly lower than that of the control group. The Bcl-2 protein expression in ASODN group was significantly lower than that in the control group, but no inhibition was observed in SODN and NSODN groups. Conclusion: The bcl-2 ASODN could enhance the sensitivity to chemotherapy with Vp-16 in small cell lung cancer cell line NCI-H69 by effectively blocking bcl-2 gene expression. (authors)

Computational Environments and Analysis methods available on the NCI High Performance Computing (HPC) and High Performance Data (HPD) Platform

Science.gov (United States)

Evans, B. J. K.; Foster, C.; Minchin, S. A.; Pugh, T.; Lewis, A.; Wyborn, L. A.; Evans, B. J.; Uhlherr, A.

2014-12-01

The National Computational Infrastructure (NCI) has established a powerful in-situ computational environment to enable both high performance computing and data-intensive science across a wide spectrum of national environmental data collections - in particular climate, observational data and geoscientific assets. This paper examines 1) the computational environments that supports the modelling and data processing pipelines, 2) the analysis environments and methods to support data analysis, and 3) the progress in addressing harmonisation of the underlying data collections for future transdisciplinary research that enable accurate climate projections. NCI makes available 10+ PB major data collections from both the government and research sectors based on six themes: 1) weather, climate, and earth system science model simulations, 2) marine and earth observations, 3) geosciences, 4) terrestrial ecosystems, 5) water and hydrology, and 6) astronomy, social and biosciences. Collectively they span the lithosphere, crust, biosphere, hydrosphere, troposphere, and stratosphere. The data is largely sourced from NCI's partners (which include the custodians of many of the national scientific records), major research communities, and collaborating overseas organisations. The data is accessible within an integrated HPC-HPD environment - a 1.2 PFlop supercomputer (Raijin), a HPC class 3000 core OpenStack cloud system and several highly connected large scale and high-bandwidth Lustre filesystems. This computational environment supports a catalogue of integrated reusable software and workflows from earth system and ecosystem modelling, weather research, satellite and other observed data processing and analysis. To enable transdisciplinary research on this scale, data needs to be harmonised so that researchers can readily apply techniques and software across the corpus of data available and not be constrained to work within artificial disciplinary boundaries. Future challenges will

NCI Funding Trends and Priorities in Physical Activity and Energy Balance Research Among Cancer Survivors.

Science.gov (United States)

Alfano, Catherine M; Bluethmann, Shirley M; Tesauro, Gina; Perna, Frank; Agurs-Collins, Tanya; Elena, Joanne W; Ross, Sharon A; O'Connell, Mary; Bowles, Heather R; Greenberg, Deborah; Nebeling, Linda

2016-01-01

There is considerable evidence that a healthy lifestyle consisting of physical activity, healthy diet, and weight control is associated with reduced risk of morbidity and mortality after cancer. However, these behavioral interventions are not widely adopted in practice or community settings. Integrating heath behavior change interventions into standard survivorship care for the growing number of cancer survivors requires an understanding of the current state of the science and a coordinated scientific agenda for the future with focused attention in several priority areas. To facilitate this goal, this paper presents trends over the past decade of the National Cancer Institute (NCI) research portfolio, fiscal year 2004 to 2014, by funding mechanism, research focus, research design and methodology, primary study exposures and outcomes, and study team expertise and composition. These data inform a prioritized research agenda for the next decade focused on demonstrating value and feasibility and creating desire for health behavior change interventions at multiple levels including the survivor, clinician, and healthcare payer to facilitate the development and implementation of appropriately targeted, adaptive, effective, and sustainable programs for all survivors. Published by Oxford University Press (2015). This work is written by (a) US Government employee(s) and is in the public domain in the US.

NCI-60 whole exome sequencing and pharmacological CellMiner analyses.

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William C Reinhold

Full Text Available Exome sequencing provides unprecedented insights into cancer biology and pharmacological response. Here we assess these two parameters for the NCI-60, which is among the richest genomic and pharmacological publicly available cancer cell line databases. Homozygous genetic variants that putatively affect protein function were identified in 1,199 genes (approximately 6% of all genes. Variants that are either enriched or depleted compared to non-cancerous genomes, and thus may be influential in cancer progression and differential drug response were identified for 2,546 genes. Potential gene knockouts are made available. Assessment of cell line response to 19,940 compounds, including 110 FDA-approved drugs, reveals ≈80-fold range in resistance versus sensitivity response across cell lines. 103,422 gene variants were significantly correlated with at least one compound (at p<0.0002. These include genes of known pharmacological importance such as IGF1R, BRAF, RAD52, MTOR, STAT2 and TSC2 as well as a large number of candidate genes such as NOM1, TLL2, and XDH. We introduce two new web-based CellMiner applications that enable exploration of variant-to-compound relationships for a broad range of researchers, especially those without bioinformatics support. The first tool, "Genetic variant versus drug visualization", provides a visualization of significant correlations between drug activity-gene variant combinations. Examples are given for the known vemurafenib-BRAF, and novel ifosfamide-RAD52 pairings. The second, "Genetic variant summation" allows an assessment of cumulative genetic variations for up to 150 combined genes together; and is designed to identify the variant burden for molecular pathways or functional grouping of genes. An example of its use is provided for the EGFR-ERBB2 pathway gene variant data and the identification of correlated EGFR, ERBB2, MTOR, BRAF, MEK and ERK inhibitors. The new tools are implemented as an updated web-based Cell

Synthesis and physico-chemical properties of (R,S)-6-ditrideuteriomethylamino-4,4-diphenylheptan-3-one hydrochloride (methadone-d6)

International Nuclear Information System (INIS)

Gerardy, B.M.; Poupaert, J.H.; Vandervorst, D.; Dumont, P.; Declerq, J.-P.; Meerssche, M. van; Portoghese, P.S.

1985-01-01

A reaction sequence is described to synthesize (R,S)-6-ditrideuteriomethylamino-4,4-diphenylheptan-3-one hydrochloride (methado-ne-d 6 .HC1) in 10.5% overall yield starting from dimethylamine-d 6 hydrochloride. While methadone-d 6 .HC1 had rather similar physicochemical properties compared to methadone.HC1 in the solid phase, a divergent behaviour was observed in solution (pKa, chromatographic and 13 C-NMR data). A higher basicity along with a more important hydrophilicity were observed for the d 6 -derivative. A 13 C-NMR study showed significant differences in the 13 C chemical shifts, which were attributed in part to the intrinsic nature of D itself and in part to a conformational perturbation. The longer duration of antinociceptive action, along with higher tsub(1/2) and clearance, and the depression of the metabolic N-demethylation process were the only biological properties modified by the deuteration. (author)

MO-E-BRF-01: Research Opportunities in Technology for Innovation in Radiation Oncology (Highlight of ASTRO NCI 2013 Workshop)

International Nuclear Information System (INIS)

Hahn, S; Jaffray, D; Chetty, I; Benedict, S

2014-01-01

Radiotherapy is one of the most effective treatments for solid tumors, in large part due to significant technological advances associated with, for instance, the ability to target tumors to very high levels of accuracy (within millimeters). Technological advances have played a central role in the success of radiation therapy as an oncologic treatment option for patients. ASTRO, AAPM and NCI sponsored a workshop “Technology for Innovation in Radiation Oncology” at the NCI campus in Bethesda, MD on June 13–14, 2013. The purpose of this workshop was to bring together expert clinicians and scientists to discuss the role of disruptive technologies in radiation oncology, in particular with regard to how they are being developed and translated to clinical practice in the face of current and future challenges and opportunities. The technologies discussed encompassed imaging and delivery aspects, along with methods to enable/facilitate application of them in the clinic. Measures for assessment of the performance of these technologies, such as techniques to validate quantitative imaging, were reviewed. Novel delivery technologies, incorporating efficient and safe delivery mechanisms enabled by development of tools for process automation and the associated field of oncology informatics formed one of the central themes of the workshop. The discussion on disruptive technologies was grounded in the need for evidence of efficacy. Scientists in the areas of technology assessment and bioinformatics provided expert views on different approaches toward evaluation of technology efficacy. Clinicians well versed in clinical trials incorporating disruptive technologies (e.g. SBRT for early stage lung cancer) discussed the important role of these technologies in significantly improving local tumor control and survival for these cohorts of patients. Recommendations summary focused on the opportunities associated with translating the technologies into the clinic and assessing their

MO-E-BRF-01: Research Opportunities in Technology for Innovation in Radiation Oncology (Highlight of ASTRO NCI 2013 Workshop)

Energy Technology Data Exchange (ETDEWEB)

Hahn, S [University of Pennsylvania, Philadelphia, PA (United States); Jaffray, D [Princess Margaret Hospital, Toronto, ON (Canada); Chetty, I [Henry Ford Health System, Detroit, MI (United States); Benedict, S [UC Davis Cancer Center, Sacramento, CA (United States)

2014-06-15

Radiotherapy is one of the most effective treatments for solid tumors, in large part due to significant technological advances associated with, for instance, the ability to target tumors to very high levels of accuracy (within millimeters). Technological advances have played a central role in the success of radiation therapy as an oncologic treatment option for patients. ASTRO, AAPM and NCI sponsored a workshop “Technology for Innovation in Radiation Oncology” at the NCI campus in Bethesda, MD on June 13–14, 2013. The purpose of this workshop was to bring together expert clinicians and scientists to discuss the role of disruptive technologies in radiation oncology, in particular with regard to how they are being developed and translated to clinical practice in the face of current and future challenges and opportunities. The technologies discussed encompassed imaging and delivery aspects, along with methods to enable/facilitate application of them in the clinic. Measures for assessment of the performance of these technologies, such as techniques to validate quantitative imaging, were reviewed. Novel delivery technologies, incorporating efficient and safe delivery mechanisms enabled by development of tools for process automation and the associated field of oncology informatics formed one of the central themes of the workshop. The discussion on disruptive technologies was grounded in the need for evidence of efficacy. Scientists in the areas of technology assessment and bioinformatics provided expert views on different approaches toward evaluation of technology efficacy. Clinicians well versed in clinical trials incorporating disruptive technologies (e.g. SBRT for early stage lung cancer) discussed the important role of these technologies in significantly improving local tumor control and survival for these cohorts of patients. Recommendations summary focused on the opportunities associated with translating the technologies into the clinic and assessing their

Overexpression of CD44 accompanies acquired tamoxifen resistance in MCF7 cells and augments their sensitivity to the stromal factors, heregulin and hyaluronan

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Hiscox Stephen

2012-10-01

Full Text Available Abstract Background Acquired resistance to endocrine therapy in breast cancer is a significant problem with relapse being associated with local and/or regional recurrence and frequent distant metastases. Breast cancer cell models reveal that endocrine resistance is accompanied by a gain in aggressive behaviour driven in part through altered growth factor receptor signalling, particularly involving erbB family receptors. Recently we identified that CD44, a transmembrane cell adhesion receptor known to interact with growth factor receptors, is upregulated in tamoxifen-resistant (TamR MCF7 breast cancer cells. The purpose of this study was to explore the consequences of CD44 upregulation in an MCF7 cell model of acquired tamoxifen resistance, specifically with respect to the hypothesis that CD44 may influence erbB activity to promote an adverse phenotype. Methods CD44 expression in MCF7 and TamR cells was assessed by RT-PCR, Western blotting and immunocytochemistry. Immunofluorescence and immunoprecipitation studies revealed CD44-erbB associations. TamR cells (± siRNA-mediated CD44 suppression or MCF7 cells (± transfection with the CD44 gene were treated with the CD44 ligand, hyaluronon (HA, or heregulin and their in vitro growth (MTT, migration (Boyden chamber and wound healing and invasion (Matrigel transwell migration determined. erbB signalling was assessed using Western blotting. The effect of HA on erbB family dimerisation in TamR cells was determined by immunoprecipitation in the presence or absence of CD44 siRNA. Results TamR cells overexpressed CD44 where it was seen to associate with erbB2 at the cell surface. siRNA-mediated suppression of CD44 in TamR cells significantly attenuated their response to heregulin, inhibiting heregulin-induced cell migration and invasion. Furthermore, TamR cells exhibited enhanced sensitivity to HA, with HA treatment resulting in modulation of erbB dimerisation, ligand-independent activation of erbB2

Overexpression of CD44 accompanies acquired tamoxifen resistance in MCF7 cells and augments their sensitivity to the stromal factors, heregulin and hyaluronan

International Nuclear Information System (INIS)

Hiscox, Stephen; Gee, Julia; Baruha, Bedanta; Smith, Chris; Bellerby, Rebecca; Goddard, Lindy; Jordan, Nicola; Poghosyan, Zaruhi; Nicholson, Robert I; Barrett-Lee, Peter

2012-01-01

Acquired resistance to endocrine therapy in breast cancer is a significant problem with relapse being associated with local and/or regional recurrence and frequent distant metastases. Breast cancer cell models reveal that endocrine resistance is accompanied by a gain in aggressive behaviour driven in part through altered growth factor receptor signalling, particularly involving erbB family receptors. Recently we identified that CD44, a transmembrane cell adhesion receptor known to interact with growth factor receptors, is upregulated in tamoxifen-resistant (TamR) MCF7 breast cancer cells. The purpose of this study was to explore the consequences of CD44 upregulation in an MCF7 cell model of acquired tamoxifen resistance, specifically with respect to the hypothesis that CD44 may influence erbB activity to promote an adverse phenotype. CD44 expression in MCF7 and TamR cells was assessed by RT-PCR, Western blotting and immunocytochemistry. Immunofluorescence and immunoprecipitation studies revealed CD44-erbB associations. TamR cells (± siRNA-mediated CD44 suppression) or MCF7 cells (± transfection with the CD44 gene) were treated with the CD44 ligand, hyaluronon (HA), or heregulin and their in vitro growth (MTT), migration (Boyden chamber and wound healing) and invasion (Matrigel transwell migration) determined. erbB signalling was assessed using Western blotting. The effect of HA on erbB family dimerisation in TamR cells was determined by immunoprecipitation in the presence or absence of CD44 siRNA. TamR cells overexpressed CD44 where it was seen to associate with erbB2 at the cell surface. siRNA-mediated suppression of CD44 in TamR cells significantly attenuated their response to heregulin, inhibiting heregulin-induced cell migration and invasion. Furthermore, TamR cells exhibited enhanced sensitivity to HA, with HA treatment resulting in modulation of erbB dimerisation, ligand-independent activation of erbB2 and EGFR and induction of cell migration

18FDG-PET predicts pharmacodynamic response to OSI-906, a dual IGF-1R/IR inhibitor, in preclinical mouse models of lung cancer.

Science.gov (United States)

McKinley, Eliot T; Bugaj, Joseph E; Zhao, Ping; Guleryuz, Saffet; Mantis, Christine; Gokhale, Prafulla C; Wild, Robert; Manning, H Charles

2011-05-15

To evaluate 2-deoxy-2-[(18)F]fluoro-d-glucose positron emission tomography imaging ((18)FDG-PET) as a predictive, noninvasive, pharmacodynamic (PD) biomarker of response following administration of a small-molecule insulin-like growth factor-1 receptor and insulin receptor (IGF-1R/IR) inhibitor, OSI-906. In vitro uptake studies of (3)H-2-deoxy glucose following OSI-906 exposure were conducted evaluating correlation of dose with inhibition of IGF-1R/IR as well as markers of downstream pathways and glucose metabolism. Similarly, in vivo PD effects were evaluated in human tumor cell line xenografts propagated in athymic nude mice by (18)FDG-PET at 2, 4, and 24 hours following a single treatment of OSI-906 for the correlation of inhibition of receptor targets and downstream markers. Uptake of (3)H-2-deoxy glucose and (18)FDG was significantly diminished following OSI-906 exposure in sensitive tumor cells and subcutaneous xenografts (NCI-H292) but not in an insensitive model lacking IGF-1R expression (NCI-H441). Diminished PD (18)FDG-PET, collected immediately following the initial treatment agreed with inhibition of pIGF-1R/pIR, reduced PI3K (phosphoinositide 3-kinase) and MAPK (mitogen activated protein kinase) pathway activity, and predicted tumor growth arrest as measured by high-resolution ultrasound imaging. (18)FDG-PET seems to serve as a rapid, noninvasive PD marker of IGF-1R/IR inhibition following a single dose of OSI-906 and should be explored clinically as a predictive clinical biomarker in patients undergoing IGF-1R/IR-directed cancer therapy. ©2011 AACR.

Structure and Mechanism of Receptoe Sharing by the IL-10R2 Common Chain

Energy Technology Data Exchange (ETDEWEB)

Yoon, Sung-il; Jones, Brandi C.; Logsdon, Naomi J.; Harris, Bethany D.; Deshpande, Ashlesha; Radaeva, Svetlana; Halloran, Brian A.; Gao, Bin; Walter, Mark R. (NIH); (UAB)

2010-06-14

IL-10R2 is a shared cell surface receptor required for the activation of five class 2 cytokines (IL-10, IL-22, IL-26, IL-28, and IL-29) that play critical roles in host defense. To define the molecular mechanisms that regulate its promiscuous binding, we have determined the crystal structure of the IL-10R2 ectodomain at 2.14 {angstrom} resolution. IL-10R2 residues required for binding were identified by alanine scanning and used to derive computational models of IL-10/IL-10R1/IL-10R2 and IL-22/IL-22R1/IL-10R2 ternary complexes. The models reveal a conserved binding epitope that is surrounded by two clefts that accommodate the structural and chemical diversity of the cytokines. These results provide a structural framework for interpreting IL-10R2 single nucleotide polymorphisms associated with human disease.

Structure and Mechanism of Receptor Sharing by the IL-10R2 Common Chain

Energy Technology Data Exchange (ETDEWEB)

Yoon, Sung-il; Jones, Brandi C.; Logsdon, Naomi J.; Harris, Bethany D.; Deshpande, Ashlesha; Radaeva, Svetlana; Halloran, Brian A.; Gao, Bin; Walter, Mark R. (NIH); (UAB)

2010-07-19

IL-10R2 is a shared cell surface receptor required for the activation of five class 2 cytokines (IL-10, IL-22, IL-26, IL-28, and IL-29) that play critical roles in host defense. To define the molecular mechanisms that regulate its promiscuous binding, we have determined the crystal structure of the IL-10R2 ectodomain at 2.14 {angstrom} resolution. IL-10R2 residues required for binding were identified by alanine scanning and used to derive computational models of IL-10/IL-10R1/IL-10R2 and IL-22/IL-22R1/IL-10R2 ternary complexes. The models reveal a conserved binding epitope that is surrounded by two clefts that accommodate the structural and chemical diversity of the cytokines. These results provide a structural framework for interpreting IL-10R2 single nucleotide polymorphisms associated with human disease.

Decreased glucose uptake by hyperglycemia is regulated by different mechanisms in human cancer cells and monocytes

Energy Technology Data Exchange (ETDEWEB)

Kim, Chae Kyun; Chung, June Key; Lee, Yong Jin; Hong, Mee Kyoung; Jeong, Jae Min; Lee, Dong Soo; Lee, Myung Chul [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

2002-04-01

To clarify the difference in glucose uptake between human cancer cells and monocytes, we studied ({sup 18}F) fluorodeoxyglucose (FDG) uptake in three human colon cancer cell lines (SNU-C2A, SNU-C4, SNU-C5), one human lung cancer cell line (NCI-H522), and human peripheral blood monocytes. The FDG uptake of both cancer cells and monocytes was increased in glucose-free medium, but decreased in the medium containing 16.7 mM glucose (hyperglycemic). The level of Glut1 mRNA decreased in human colon cancer cells and NCI-H522 under hyperglycemic condition. Glut1 protein expression was also decreased in the four human cancer cell lines under hyperglycemic condition, whereas it was consistently undetectable in monocytes. SNU-C2A, SNU-C4 and NCI-H522 showed a similar level of hexokinase activity (7.5-10.8 mU/mg), while SNU-C5 and moncytes showed lower range of hexokinase activity (4.3-6.5 mU/mg). These data suggest that glucose uptake is regulated by different mechanisms in human cancer cells and monocytes.

Incorporació de petites seqüències de cinema comercial en l’ensenyament de les drogodependències. Assaig pilot en l'assignatura de Toxicologia

Directory of Open Access Journals (Sweden)

Miguel Rodamilans-Pérez

2013-01-01

Full Text Available El Grup d'Innovació Docent Orfila, en el seu projecte per millorar la qualitat de la docència, està assajant la utilització del cinema amb finalitat didàctica. El material didàctic que hem desenvolupat en aquest projecte són petites seqüències de pel·lícules comercials de 3 a 5 minuts, per ser utilitzades com a elements il·lustratius del procés addictiu. Se seleccionen escenes de la filmografia i s'adeqüen als nostres programes docents. Es recull l'opinió dels professors participants, així com la dels alumnes, mitjançant una entrevista personal i una enquesta d'opinió, respectivament.De les entrevistes als professors i de les enquestes d'opinió dels alumnes, es dedueix un alt grau de satisfacció.

Deciphering Dimerization Modes of PAS Domains: Computational and Experimental Analyses of the AhR:ARNT Complex Reveal New Insights Into the Mechanisms of AhR Transformation.

Science.gov (United States)

Corrada, Dario; Soshilov, Anatoly A; Denison, Michael S; Bonati, Laura

2016-06-01

The Aryl hydrocarbon Receptor (AhR) is a transcription factor that mediates the biochemical response to xenobiotics and the toxic effects of a number of environmental contaminants, including dioxins. Recently, endogenous regulatory roles for the AhR in normal physiology and development have also been reported, thus extending the interest in understanding its molecular mechanisms of activation. Since dimerization with the AhR Nuclear Translocator (ARNT) protein, occurring through the Helix-Loop-Helix (HLH) and PER-ARNT-SIM (PAS) domains, is needed to convert the AhR into its transcriptionally active form, deciphering the AhR:ARNT dimerization mode would provide insights into the mechanisms of AhR transformation. Here we present homology models of the murine AhR:ARNT PAS domain dimer developed using recently available X-ray structures of other bHLH-PAS protein dimers. Due to the different reciprocal orientation and interaction surfaces in the different template dimers, two alternative models were developed for both the PAS-A and PAS-B dimers and they were characterized by combining a number of computational evaluations. Both well-established hot spot prediction methods and new approaches to analyze individual residue and residue-pairwise contributions to the MM-GBSA binding free energies were adopted to predict residues critical for dimer stabilization. On this basis, a mutagenesis strategy for both the murine AhR and ARNT proteins was designed and ligand-dependent DNA binding ability of the AhR:ARNT heterodimer mutants was evaluated. While functional analysis disfavored the HIF2α:ARNT heterodimer-based PAS-B model, most mutants derived from the CLOCK:BMAL1-based AhR:ARNT dimer models of both the PAS-A and the PAS-B dramatically decreased the levels of DNA binding, suggesting this latter model as the most suitable for describing AhR:ARNT dimerization. These novel results open new research directions focused at elucidating basic molecular mechanisms underlying the

Deciphering Dimerization Modes of PAS Domains: Computational and Experimental Analyses of the AhR:ARNT Complex Reveal New Insights Into the Mechanisms of AhR Transformation.

Directory of Open Access Journals (Sweden)

Dario Corrada

2016-06-01

Full Text Available The Aryl hydrocarbon Receptor (AhR is a transcription factor that mediates the biochemical response to xenobiotics and the toxic effects of a number of environmental contaminants, including dioxins. Recently, endogenous regulatory roles for the AhR in normal physiology and development have also been reported, thus extending the interest in understanding its molecular mechanisms of activation. Since dimerization with the AhR Nuclear Translocator (ARNT protein, occurring through the Helix-Loop-Helix (HLH and PER-ARNT-SIM (PAS domains, is needed to convert the AhR into its transcriptionally active form, deciphering the AhR:ARNT dimerization mode would provide insights into the mechanisms of AhR transformation. Here we present homology models of the murine AhR:ARNT PAS domain dimer developed using recently available X-ray structures of other bHLH-PAS protein dimers. Due to the different reciprocal orientation and interaction surfaces in the different template dimers, two alternative models were developed for both the PAS-A and PAS-B dimers and they were characterized by combining a number of computational evaluations. Both well-established hot spot prediction methods and new approaches to analyze individual residue and residue-pairwise contributions to the MM-GBSA binding free energies were adopted to predict residues critical for dimer stabilization. On this basis, a mutagenesis strategy for both the murine AhR and ARNT proteins was designed and ligand-dependent DNA binding ability of the AhR:ARNT heterodimer mutants was evaluated. While functional analysis disfavored the HIF2α:ARNT heterodimer-based PAS-B model, most mutants derived from the CLOCK:BMAL1-based AhR:ARNT dimer models of both the PAS-A and the PAS-B dramatically decreased the levels of DNA binding, suggesting this latter model as the most suitable for describing AhR:ARNT dimerization. These novel results open new research directions focused at elucidating basic molecular mechanisms

Aprenentatge cooperatiu interdisciplinari i rúbriques per a la millora del procés d'ensenyament-aprenentatge

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Beatriz Corchuelo Martínez-Azúa

2016-06-01

Full Text Available L'adaptació dels títols a l'Espai Europeu d'Educació Superior (EEES suposa l'ocasió de millorar l'educació integral dels alumnes, orientant les accions docents cap al desenvolupament de competències. L'adquisició de competències exigeix la incorporació de metodologies docents actives que permetin la generació enfront de la mera transmissió de coneixements. Així mateix, nombrosos estudis adverteixen de l'escassa transferència existent en els coneixements tractats en les assignatures quan es consideren de manera individual. El treball interdisciplinari constitueix una valuosa eina perquè els estudiants facin connexions, plantegin i trobin respostes a situacions problemàtiques i ajustin el seu aprenentatge a un coneixement integral. Pel que s'ha vist la necessitat de desenvolupar, en el currículum formatiu de l'alumne, aproximacions interdisciplinàries.Tenint en compte aquests aspectes, s'ha realitzat una experiència d'innovació docent universitària de caràcter interdisciplinari en la qual s'integren els continguts i competències de diverses assignatures per abordar el procés de solució de problemes econòmics. S'ha treballat la interdisciplinaritat amb tècniques d'aprenentatge cooperatiu. La interacció d’aquests aspectes és la raó por la quual hem denominat a l'experiència “Aprenentatge Cooperatiu Interdisciplinari” (ACI. L'avaluació de l'aprenentatge es realitza de forma individual, (mitjançant heteroevaluació i coevaluació, i grupal, (mitjançant rúbriques i coevaluació.Els resultats mostren diversos aspectes: 1 La metodologia ACI no solament permet formar en continguts sinó també en competències. 2 La interconnexió entre assignatures ha permès que els alumnes ajuste n els seus aprenentatges cap a un coneixement més integral. 3 La unió de les diferents innovacions docents ha repercutit positivament en la motivació de l'alumnat. 4 S'han assolit resultats d'aprenentatge positius en l'alumnat, majors

Characterisation of glufosinate resistance mechanisms in Eleusine indica.

Science.gov (United States)

Jalaludin, Adam; Yu, Qin; Zoellner, Peter; Beffa, Roland; Powles, Stephen B

2017-06-01

An Eleusine indica population has evolved resistance to glufosinate, a major post-emergence herbicide of global agriculture. This population was analysed for target-site (glutamine synthetase) and non-target-site (glufosinate uptake, translocation and metabolism) resistance mechanisms. Glutamine synthetase (GS) activity extracted from susceptible (S) and resistant (R*) plants was equally sensitive to glufosinate inhibition, with IC 50 values of 0.85 mm and 0.99 mm, respectively. The extractable GS activity was also similar in S and R* samples. Foliar uptake of [ 14 C]-glufosinate did not differ in S and R* plants, nor did glufosinate net uptake in leaf discs. Translocation of [ 14 C]-glufosinate into untreated shoots and roots was also similar in both populations, with 44% to 47% of the herbicide translocated out from the treated leaf 24 h after treatment. The HPLC and LC-MS analysis of glufosinate metabolism revealed no major metabolites in S or R* leaf tissue. Glufosinate resistance in this resistant population is not due to an insensitive GS, or increased activity, or altered glufosinate uptake and translocation, or enhanced glufosinate metabolism. Thus, target-site resistance is likely excluded and the exact resistance mechanism(s) remain to be determined. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Les experiències artístiques en l'espai públic. Art efímer com a catàlisi de la vida urbana

Directory of Open Access Journals (Sweden)

Lucila Urda Peña

2016-06-01

Full Text Available L'art efímer urbà, com a corrent d'expressió de pensament col·lectiu és una font de generació de projectes comunitaris en què els ciutadans poden recuperar "l'experiència de ciutat". La profusió de diverses manifestacions d'art efímer en ciutats de tot el món des de començaments del segle XXI està tenint conseqüències en l'espai urbà tant a nivell local com a nivell global. Una d'elles és la transformació del paisatge urbà, cada vegada més considerat com a escenari visible en projectes de regeneració urbana. A més de la transformació física també es produeixen canvis en les dinàmiques urbanes ja que els efectes de les intervencions tenen conseqüències més enllà dels canvis d'imatge. Els efectes socioeconòmics locals o fins i tot globals de les transformacions lligades a l'art efímer són cada vegada més evidents. Aquest article relata l'origen i desenvolupament de diverses manifestacions artístiques urbanes i reflexiona sobre les seves conseqüències en la vida urbana com a eina de transformació física i social.

Improving clinical research and cancer care delivery in community settings: evaluating the NCI community cancer centers program.

Science.gov (United States)

Clauser, Steven B; Johnson, Maureen R; O'Brien, Donna M; Beveridge, Joy M; Fennell, Mary L; Kaluzny, Arnold D

2009-09-26

In this article, we describe the National Cancer Institute (NCI) Community Cancer Centers Program (NCCCP) pilot and the evaluation designed to assess its role, function, and relevance to the NCI's research mission. In doing so, we describe the evolution of and rationale for the NCCCP concept, participating sites' characteristics, its multi-faceted aims to enhance clinical research and quality of care in community settings, and the role of strategic partnerships, both within and outside of the NCCCP network, in achieving program objectives. The evaluation of the NCCCP is conceptualized as a mixed method multi-layered assessment of organizational innovation and performance which includes mapping the evolution of site development as a means of understanding the inter- and intra-organizational change in the pilot, and the application of specific evaluation metrics for assessing the implementation, operations, and performance of the NCCCP pilot. The assessment of the cost of the pilot as an additional means of informing the longer-term feasibility and sustainability of the program is also discussed. The NCCCP is a major systems-level set of organizational innovations to enhance clinical research and care delivery in diverse communities across the United States. Assessment of the extent to which the program achieves its aims will depend on a full understanding of how individual, organizational, and environmental factors align (or fail to align) to achieve these improvements, and at what cost.

Quantification of Biodegradation: Applied Example on Oil Seeps in Armàncies Fm, Southeastern Pyrenees

OpenAIRE

Permanyer, Albert; Caja, Miguel Ángel

2005-01-01

La presencia de petróleo expulsado directamente de la roca madre de la Formación Armàncies, constituye un caso único para el estudio de los procesos de biodegradación aeróbica en petróleo. El estado de degradación bacteriana es moderado y está principalmente limitado a la alteración de n-alcanos, isoprenoides y algunos aromáticos. La cuantificación ha sido realizada mediante el contenido en sulfuro y con los marcadores moleculares de la fracción aromática. Los resultados obtenidos...

Insights into the catalytic mechanism of dehydrogenase BphB: A quantum mechanics/molecular mechanics study.

Science.gov (United States)

Zhang, Ruiming; Shi, Xiangli; Sun, Yanhui; Zhang, Qingzhu; Wang, Wenxing

2018-05-17

The present study delineated the dehydrogenation mechanism of cis-2,3-dihydro-2,3-dihydroxybiphenyl (2,3-DDBPH) and cis-2,3-dihydro-2,3-dihydroxy-4,4'-dichlorobiphenyl (2,3-DD-4,4'-DBPH) by Pandoraea pnomenusa strain B-356 cis-2,3-dihydro-2,3-dihydroxybiphenyl dehydrogenase (BphB) in atomistic detail. The enzymatic process was investigated by a combined quantum mechanics/molecular mechanics (QM/MM) approach. Five different snapshots were extracted and calculated, which revealed that the Boltzmann-weighted average barriers of 2,3-DDBPH and 2,3-DD-4,4'-DBPH dehydrogenation processes are 10.7 and 11.5 kcal mol -1 , respectively. The established dehydrogenation mechanism provides new insight into the degradation processes of other chlorinated 2,3-DDBPH. In addition to Asn115, Ser142, and Lys149, the importance of Ile 89, Asn143, Pro184, Met 187, Thr189, and Lue 191 during the dehydrogenation process of 2,3-DDBPH and 2,3-DD-4,4'-DBPH were also highlighted to search for promising mutation targets for improving the catalytic efficiency of BphB. Copyright © 2018. Published by Elsevier Ltd.

Lipid raft association restricts CD44-ezrin interaction and promotion of breast cancer cell migration.

LENUS (Irish Health Repository)

Donatello, Simona

2012-12-01

Cancer cell migration is an early event in metastasis, the main cause of breast cancer-related deaths. Cholesterol-enriched membrane domains called lipid rafts influence the function of many molecules, including the raft-associated protein CD44. We describe a novel mechanism whereby rafts regulate interactions between CD44 and its binding partner ezrin in migrating breast cancer cells. Specifically, in nonmigrating cells, CD44 and ezrin localized to different membranous compartments: CD44 predominantly in rafts, and ezrin in nonraft compartments. After the induction of migration (either nonspecific or CD44-driven), CD44 affiliation with lipid rafts was decreased. This was accompanied by increased coprecipitation of CD44 and active (threonine-phosphorylated) ezrin-radixin-moesin (ERM) proteins in nonraft compartments and increased colocalization of CD44 with the nonraft protein, transferrin receptor. Pharmacological raft disruption using methyl-β-cyclodextrin also increased CD44-ezrin coprecipitation and colocalization, further suggesting that CD44 interacts with ezrin outside rafts during migration. Conversely, promoting CD44 retention inside lipid rafts by pharmacological inhibition of depalmitoylation virtually abolished CD44-ezrin interactions. However, transient single or double knockdown of flotillin-1 or caveolin-1 was not sufficient to increase cell migration over a short time course, suggesting complex crosstalk mechanisms. We propose a new model for CD44-dependent breast cancer cell migration, where CD44 must relocalize outside lipid rafts to drive cell migration. This could have implications for rafts as pharmacological targets to down-regulate cancer cell migration.

Lipid Raft Association Restricts CD44-Ezrin Interaction and Promotion of Breast Cancer Cell Migration

Science.gov (United States)

Donatello, Simona; Babina, Irina S.; Hazelwood, Lee D.; Hill, Arnold D.K.; Nabi, Ivan R.; Hopkins, Ann M.

2012-01-01

Cancer cell migration is an early event in metastasis, the main cause of breast cancer-related deaths. Cholesterol-enriched membrane domains called lipid rafts influence the function of many molecules, including the raft-associated protein CD44. We describe a novel mechanism whereby rafts regulate interactions between CD44 and its binding partner ezrin in migrating breast cancer cells. Specifically, in nonmigrating cells, CD44 and ezrin localized to different membranous compartments: CD44 predominantly in rafts, and ezrin in nonraft compartments. After the induction of migration (either nonspecific or CD44-driven), CD44 affiliation with lipid rafts was decreased. This was accompanied by increased coprecipitation of CD44 and active (threonine-phosphorylated) ezrin-radixin-moesin (ERM) proteins in nonraft compartments and increased colocalization of CD44 with the nonraft protein, transferrin receptor. Pharmacological raft disruption using methyl-β-cyclodextrin also increased CD44-ezrin coprecipitation and colocalization, further suggesting that CD44 interacts with ezrin outside rafts during migration. Conversely, promoting CD44 retention inside lipid rafts by pharmacological inhibition of depalmitoylation virtually abolished CD44-ezrin interactions. However, transient single or double knockdown of flotillin-1 or caveolin-1 was not sufficient to increase cell migration over a short time course, suggesting complex crosstalk mechanisms. We propose a new model for CD44-dependent breast cancer cell migration, where CD44 must relocalize outside lipid rafts to drive cell migration. This could have implications for rafts as pharmacological targets to down-regulate cancer cell migration. PMID:23031255

Vectors to Increase Production Efficiency of Inducible Pluripotent Stem Cell (iPSC) | NCI Technology Transfer Center | TTC

Science.gov (United States)

This invention describes the discovery that specific p53 isoform increase the number of inducible pluripotent stem cells (iPS). It is known that the activity of p53 regulates the self-renewal and pluripotency of normal and cancer stem cells, and also affects re-programming efficiency of iPS cells. This p53 isoform-based technology provides a more natural process of increasing iPS cell production than previous methods of decreasing p53. NCI seeks licensees for this technology.

ANIONIC POLYMERIZATION OF ALKYL METHACRYLATES INITIATED BY nBuCu(NCy2)Li

Institute of Scientific and Technical Information of China (English)

Bing-yong Han; Jian-guo Liang; Jian-min Lu; Feng An; Wan-tai Yang

2009-01-01

Anionic polymerization of methyl methacrylate (MMA), n-butyl methacrylate (nBMA) and glycidyl methacrylate (GMA) initiated by nBuCu(NCy2)Li (1) in tetrahydrofuran (THF) at -50℃ to -10℃ was investigated. It was found that the polymerization of MMA and nBMA initiated by 1 proceeded quantitatively in THF to afford PMMA and PBMA with polydispersity index 1.15-1.30 and nearly 100% initiator efficiencies at -10℃. The molecular weights increased linearly with the ratio of [monomer]/[1]. However, a post-polymerization experiment carried out on this system revealed a double polymer peak by GPC when fresh monomer was added after an interval of 10 rain. Polymerization of styrene could be initiated by 1, but the initiator efficiency was low.

CALCULATION ALGORITHM FOR STUDYING EFFORTS IN THE 4R SPHERICAL QUADRILATERAL MECHANISMS BECAUSE OF TECHNICAL DEVIATIONS

Directory of Open Access Journals (Sweden)

Ion BULAC

2013-05-01

Full Text Available Due to technical deviations, in the elements of the 4R spatial spherical mechanism appear efforts thatadditionally loads the mechanism, efforts that can be determined with the calculation algorithm that will bepresented in this paper

ACToR Chemical Structure processing using Open Source ...

Science.gov (United States)

ACToR (Aggregated Computational Toxicology Resource) is a centralized database repository developed by the National Center for Computational Toxicology (NCCT) at the U.S. Environmental Protection Agency (EPA). Free and open source tools were used to compile toxicity data from over 1,950 public sources. ACToR contains chemical structure information and toxicological data for over 558,000 unique chemicals. The database primarily includes data from NCCT research programs, in vivo toxicity data from ToxRef, human exposure data from ExpoCast, high-throughput screening data from ToxCast and high quality chemical structure information from the EPA DSSTox program. The DSSTox database is a chemical structure inventory for the NCCT programs and currently has about 16,000 unique structures. Included are also data from PubChem, ChemSpider, USDA, FDA, NIH and several other public data sources. ACToR has been a resource to various international and national research groups. Most of our recent efforts on ACToR are focused on improving the structural identifiers and Physico-Chemical properties of the chemicals in the database. Organizing this huge collection of data and improving the chemical structure quality of the database has posed some major challenges. Workflows have been developed to process structures, calculate chemical properties and identify relationships between CAS numbers. The Structure processing workflow integrates web services (PubChem and NIH NCI Cactus) to d

The role of endogenous and exogenous mechanisms in the formation of R&D networks

Science.gov (United States)

Tomasello, Mario V.; Perra, Nicola; Tessone, Claudio J.; Karsai, Márton; Schweitzer, Frank

2014-01-01

We develop an agent-based model of strategic link formation in Research and Development (R&D) networks. Empirical evidence has shown that the growth of these networks is driven by mechanisms which are both endogenous to the system (that is, depending on existing alliances patterns) and exogenous (that is, driven by an exploratory search for newcomer firms). Extant research to date has not investigated both mechanisms simultaneously in a comparative manner. To overcome this limitation, we develop a general modeling framework to shed light on the relative importance of these two mechanisms. We test our model against a comprehensive dataset, listing cross-country and cross-sectoral R&D alliances from 1984 to 2009. Our results show that by fitting only three macroscopic properties of the network topology, this framework is able to reproduce a number of micro-level measures, including the distributions of degree, local clustering, path length and component size, and the emergence of network clusters. Furthermore, by estimating the link probabilities towards newcomers and established firms from the data, we find that endogenous mechanisms are predominant over the exogenous ones in the network formation, thus quantifying the importance of existing structures in selecting partner firms. PMID:25022561

The role of endogenous and exogenous mechanisms in the formation of R&D networks

Science.gov (United States)

Tomasello, Mario V.; Perra, Nicola; Tessone, Claudio J.; Karsai, Márton; Schweitzer, Frank

2014-07-01

We develop an agent-based model of strategic link formation in Research and Development (R&D) networks. Empirical evidence has shown that the growth of these networks is driven by mechanisms which are both endogenous to the system (that is, depending on existing alliances patterns) and exogenous (that is, driven by an exploratory search for newcomer firms). Extant research to date has not investigated both mechanisms simultaneously in a comparative manner. To overcome this limitation, we develop a general modeling framework to shed light on the relative importance of these two mechanisms. We test our model against a comprehensive dataset, listing cross-country and cross-sectoral R&D alliances from 1984 to 2009. Our results show that by fitting only three macroscopic properties of the network topology, this framework is able to reproduce a number of micro-level measures, including the distributions of degree, local clustering, path length and component size, and the emergence of network clusters. Furthermore, by estimating the link probabilities towards newcomers and established firms from the data, we find that endogenous mechanisms are predominant over the exogenous ones in the network formation, thus quantifying the importance of existing structures in selecting partner firms.

R-parity Conservation via the Stueckelberg Mechanism: LHC and Dark Matter Signals

CERN Document Server

Feldman, Daniel; Nath, Pran

2012-01-01

We investigate the connection between the conservation of R-parity in supersymmetry and the Stueckelberg mechanism for the mass generation of the B-L vector gauge boson. It is shown that with universal boundary conditions for soft terms of sfermions in each family at the high scale and with the Stueckelberg mechanism for generating mass for the B-L gauge boson present in the theory, electric charge conservation guarantees the conservation of R-parity in the minimal B-L extended supersymmetric standard model. We also discuss non-minimal extensions. This includes extensions where the gauge symmetries arise with an additional U(1)_{B-L} x U(1)_X, where U(1)_X is a hidden sector gauge group. In this case the presence of the additional U(1)_X allows for a Z' gauge boson mass with B-L interactions to lie in the sub-TeV region overcoming the multi-TeV LEP constraints. The possible tests of the models at colliders and in dark matter experiments are analyzed including signals of a low mass Z' resonance and the product...

Synthesis of symmetrical 2,2',4,4'-tetrasubstituted [4,4'-bithiazole]-5,5'(4H,4'H)-diones and their reactions with some nucleophiles

DEFF Research Database (Denmark)

Andersen, Kenneth K.; Bray, Diana D.; Kjær, Anders

1997-01-01

steric factors. X-Ray crystallography established the structure of the dehydrodimer (4R*,4R'*)-2,2'-diethoxy-4,4'-dibenzyl-[4,4'-bithiazole]-5,5'(4H,4 'H)-dione. One stereoisomer of 2,2'-diphenyl-4,4'-dimethyl-[4,4'-bithiazole]-5,5'(4H,4'H)-dione and a mixture of the stereoisomers 2,2'-diphenyl-4......-carboxylic acid and piperidylamide, was established by X-ray crystallography. Treatment of stereoisomeric mixtures of 2,2'-diethoxy-4,4'-bithiazolones with HCl in benzene gave the corresponding racemic and meso bis-(N-carboxythioanhydride)s. A stereoisomeric mixture of the bis...

CD44 antibodies and immune thrombocytopenia in the amelioration of murine inflammatory arthritis.

Directory of Open Access Journals (Sweden)

Patrick J Mott

Full Text Available Antibodies to CD44 have been used to successfully ameliorate murine models of autoimmune disease. The most often studied disease model has been murine inflammatory arthritis, where a clear mechanism for the efficacy of CD44 antibodies has not been established. We have recently shown in a murine passive-model of the autoimmune disease immune thrombocytopenia (ITP that some CD44 antibodies themselves can induce thrombocytopenia in mice, and the CD44 antibody causing the most severe thrombocytopenia (IM7, also is known to be highly effective in ameliorating murine models of arthritis. Recent work in the K/BxN serum-induced model of arthritis demonstrated that antibody-induced thrombocytopenia reduced arthritis, causing us to question whether CD44 antibodies might primarily ameliorate arthritis through their thrombocytopenic effect. We evaluated IM7, IRAWB14.4, 5035-41.1D, KM201, KM114, and KM81, and found that while all could induce thrombocytopenia, the degree of protection against serum-induced arthritis was not closely related to the length or severity of the thrombocytopenia. CD44 antibody treatment was also able to reverse established inflammation, while thrombocytopenia induced by an anti-platelet antibody targeting the GPIIbIIIa platelet antigen, could not mediate this effect. While CD44 antibody-induced thrombocytopenia may contribute to some of its therapeutic effect against the initiation of arthritis, for established disease there are likely other mechanisms contributing to its efficacy. Humans are not known to express CD44 on platelets, and are therefore unlikely to develop thrombocytopenia after CD44 antibody treatment. An understanding of the relationship between arthritis, thrombocytopenia, and CD44 antibody treatment remains critical for continued development of CD44 antibody therapeutics.

The role of electrostatics in TrxR electron transfer mechanism: A computational approach.

Science.gov (United States)

Teixeira, Vitor H; Capacho, Ana Sofia C; Machuqueiro, Miguel

2016-12-01

Thioredoxin reductase (TrxR) is an important enzyme in the control of the intracellular reduced redox environment. It transfers electrons from NADPH to several molecules, including its natural partner, thioredoxin. Although there is a generally accepted model describing how the electrons are transferred along TrxR, which involves a flexible arm working as a "shuttle," the molecular details of such mechanism are not completely understood. In this work, we use molecular dynamics simulations with Poisson-Boltzmann/Monte Carlo pKa calculations to investigate the role of electrostatics in the electron transfer mechanism. We observed that the combination of redox/protonation states of the N-terminal (FAD and Cys59/64) and C-terminal (Cys497/Selenocysteine498) redox centers defines the preferred relative positions and allows for the flexible arm to work as the desired "shuttle." Changing the redox/ionization states of those key players, leads to electrostatic triggers pushing the arm into the pocket when oxidized, and pulling it out, once it has been reduced. The calculated pKa values for Cys497 and Selenocysteine498 are 9.7 and 5.8, respectively, confirming that the selenocysteine is indeed deprotonated at physiological pH. This can be an important advantage in terms of reactivity (thiolate/selenolate are more nucleophilic than thiol/selenol) and ability to work as an electrostatic trigger (the "shuttle" mechanism) and may be the reason why TrxR uses selenium instead of sulfur. Proteins 2016; 84:1836-1843. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

44 CFR 208.44 - Reimbursement for other costs.

Science.gov (United States)

2010-10-01

... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Reimbursement for other costs... Cooperative Agreements § 208.44 Reimbursement for other costs. (a) Except as allowed under paragraph (b) of this section, DHS will not reimburse other costs incurred preceding, during or upon the conclusion of...

The Transcriptome of the Reference Potato Genome Solanum tuberosum Group Phureja Clone DM1-3 516R44

Science.gov (United States)

Massa, Alicia N.; Childs, Kevin L.; Lin, Haining; Bryan, Glenn J.; Giuliano, Giovanni; Buell, C. Robin

2011-01-01

Advances in molecular breeding in potato have been limited by its complex biological system, which includes vegetative propagation, autotetraploidy, and extreme heterozygosity. The availability of the potato genome and accompanying gene complement with corresponding gene structure, location, and functional annotation are powerful resources for understanding this complex plant and advancing molecular breeding efforts. Here, we report a reference for the potato transcriptome using 32 tissues and growth conditions from the doubled monoploid Solanum tuberosum Group Phureja clone DM1-3 516R44 for which a genome sequence is available. Analysis of greater than 550 million RNA-Seq reads permitted the detection and quantification of expression levels of over 22,000 genes. Hierarchical clustering and principal component analyses captured the biological variability that accounts for gene expression differences among tissues suggesting tissue-specific gene expression, and genes with tissue or condition restricted expression. Using gene co-expression network analysis, we identified 18 gene modules that represent tissue-specific transcriptional networks of major potato organs and developmental stages. This information provides a powerful resource for potato research as well as studies on other members of the Solanaceae family. PMID:22046362

[Effect of Evn-50 on cell growth and apoptosis in tamoxifen-resistance human breast cancer cell line MCF-7/TAM-R].

Science.gov (United States)

Hu, Hui-yong; Zhou, Jun; Wan, Fang; Dong, Li-feng; Zhang, Feng; Wang, Yi-ke; Chen, Fang-fang; Chen, Yi-ding

2012-09-01

To investigate the effect of Evn-50 extracted from Vitex negundo on human breast cancer cell line MCF-7 and MCF-7/TAM-R cells in vitro. MCF-7 and tamoxifen-resistant MCF-7/TAM-R cells were treated with Evn-50,tamoxifen or combination of Evn-50 and tamoxifen. Cell proliferation inhibition rates were determined by MTT assay. The apoptosis rate and the change of cell cycle were detected by PI staining flow cytometry. Protein expression of phospho-MAPK 44/42 (Thr202/Tyr204),MAPK P44/42, phospho-AKT (Ser473) and AKT were detected with Western blotting. The viability of MCF-7 cells was decreased in combination group [(28.65 ±11.43)%] and Evn-50 group [(53.02 ±15.14)%] compared with TAM group (PTAM-R in combination group [(42.11 ±14.30)%] was significantly lower than that in TAM group [(92.18 ±13.16)%] (PTAM-R cells,the expression of phosphorylation of AKT and MAPK44/42 protein was not changed in Evn-50 or TAM alone group,but significantly inhibited in the combination group at 72 h. Evn-50 can inhibit cell growth and induce apoptosis in MCF-7 and MCF-7/TAM-R cells,it can reverse tamoxifen-resistance of MCF-7/TAM-R cells.The mechanisms may be related to the down-regulation of phosphorylated ERK1/2 in MAPK signal pathway and phosphorylated AKT in AKT signal pathway.

Effect of Naphthalene and Salicylate Analogues on the Bioluminescence of Bioreporter Pseudomonas Fluorescens HK44.

Czech Academy of Sciences Publication Activity Database

Trögl, Josef; Kuncová, Gabriela; Kubicová, L.; Pařík, P.; Hálová, Jaroslava; Demnerová, K.; Ripp, S.; Sayler, G. S.

2007-01-01

Roč. 52, 1 (2007) , s. 3-14 ISSN 0015-5632 R&D Projects: GA ČR(CZ) GA104/05/2637; GA ČR(CZ) GA203/06/1244 Institutional research plan: CEZ:AV0Z40720504; CEZ:AV0Z40320502 Keywords : pseudomonas fluorescens HK44 * bioluminescence * bioluminescence Subject RIV: CE - Biochemistry Impact factor: 0.989, year: 2007

Selective agonists at group II metabotropic glutamate receptors: synthesis, stereochemistry, and molecular pharmacology of (S)- and (R)-2-amino-4-(4-hydroxy[1,2,5]thiadiazol-3-yl)butyric acid

DEFF Research Database (Denmark)

Clausen, Rasmus P; Bräuner-Osborne, Hans; Greenwood, Jeremy R

2002-01-01

Homologation of analogues of the central excitatory neurotransmitter glutamic acid (Glu), in which the distal carboxy group has been bioisosterically replaced by acidic heterocyclic units, has previously provided subtype selective ligands for metabotropic Glu receptors (mGluRs). The (S......)-form of the 1,2,5-thiadiazol-3-ol Glu analogue, 2-amino-3-(4-hydroxy[1,2,5]thiadiazol-3-yl)propionic acid (TDPA, 6), is an 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) receptor agonist, which in addition stereospecifically activates group I mGluRs. We have now synthesized the (S)- and (R......)-forms of 2-amino-4-(4-hydroxy[1,2,5]thiadiazol-3-yl)butyric acid (homo-TDPA, 7) and shown that whereas neither enantiomer interacts with AMPA receptors, (S)- and (R)-7 appear to be selective and equipotent agonists at group II mGluRs as represented by the mGluR2 subtype. The activities of (S)- and (R)-7...

Evaluation of the UF/NCI hybrid computational phantoms for use in organ dosimetry of pediatric patients undergoing fluoroscopically guided cardiac procedures

Science.gov (United States)

Marshall, Emily L.; Borrego, David; Tran, Trung; Fudge, James C.; Bolch, Wesley E.

2018-03-01

Epidemiologic data demonstrate that pediatric patients face a higher relative risk of radiation induced cancers than their adult counterparts at equivalent exposures. Infants and children with congenital heart defects are a critical patient population exposed to ionizing radiation during life-saving procedures. These patients will likely incur numerous procedures throughout their lifespan, each time increasing their cumulative radiation absorbed dose. As continued improvements in long-term prognosis of congenital heart defect patients is achieved, a better understanding of organ radiation dose following treatment becomes increasingly vital. Dosimetry of these patients can be accomplished using Monte Carlo radiation transport simulations, coupled with modern anatomical patient models. The aim of this study was to evaluate the performance of the University of Florida/National Cancer Institute (UF/NCI) pediatric hybrid computational phantom library for organ dose assessment of patients that have undergone fluoroscopically guided cardiac catheterizations. In this study, two types of simulations were modeled. A dose assessment was performed on 29 patient-specific voxel phantoms (taken as representing the patient’s true anatomy), height/weight-matched hybrid library phantoms, and age-matched reference phantoms. Two exposure studies were conducted for each phantom type. First, a parametric study was constructed by the attending pediatric interventional cardiologist at the University of Florida to model the range of parameters seen clinically. Second, four clinical cardiac procedures were simulated based upon internal logfiles captured by a Toshiba Infinix-i Cardiac Bi-Plane fluoroscopic unit. Performance of the phantom library was quantified by computing both the percent difference in individual organ doses, as well as the organ dose root mean square values for overall phantom assessment between the matched phantoms (UF/NCI library or reference) and the patient

CD44 is involved in mineralization of dental pulp cells.

Science.gov (United States)

Chen, Kuan-Liang; Huang, Yu-Yuan; Lung, Jrhau; Yeh, Ying-Yi; Yuan, Kuo

2013-03-01

CD44 is a transmembrane glycoprotein with various biological functions. Histologic studies have shown that CD44 is strongly expressed in odontoblasts at the appositional stage of tooth development. We investigated whether CD44 is involved in the mineralization of dental pulp cells. Ten human third molars with incomplete root formation were collected and processed for immunohistochemistry of CD44. Dental pulp cells isolated from another 5 human third molars were assayed for their viability, alkaline phosphatase activity, and alizarin red staining in vitro after silencing stably their expression of CD44 by using the short hairpin RNA technique. The CD44 knockdown cells were cultured on a collagen sponge and transplanted subcutaneously into the dorsal surfaces of immunocompromised mice. After 6 weeks, the subcutaneous tissues were processed for alizarin red staining and immunohistochemistry of human specific antigen. The dental pulp cells transduced with control short hairpin RNA were used as the control in all assays. CD44 is expressed in odontogenic cells with active mineral deposition during tooth development. Odontoblasts in the root ends of immature teeth express a stronger CD44 signal compared with those in the crown portion. When CD44 expression was stably suppressed in dental pulp cells, their mineralization activities were substantially decreased in both in vitro and in vivo assays. CD44 may play a crucial role in the initial mineralization of tooth-associated structures. However, further studies are required to clarify the underlying mechanisms. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

AtMYB44 regulates WRKY70 expression and modulates antagonistic interaction between salicylic acid and jasmonic acid signaling.

Science.gov (United States)

Shim, Jae Sung; Jung, Choonkyun; Lee, Sangjoon; Min, Kyunghun; Lee, Yin-Won; Choi, Yeonhee; Lee, Jong Seob; Song, Jong Tae; Kim, Ju-Kon; Choi, Yang Do

2013-02-01

The role of AtMYB44, an R2R3 MYB transcription factor, in signaling mediated by jasmonic acid (JA) and salicylic acid (SA) is examined. AtMYB44 is induced by JA through CORONATINE INSENSITIVE 1 (COI1). AtMYB44 over-expression down-regulated defense responses against the necrotrophic pathogen Alternaria brassicicola, but up-regulated WRKY70 and PR genes, leading to enhanced resistance to the biotrophic pathogen Pseudomonas syringae pv. tomato DC3000. The knockout mutant atmyb44 shows opposite effects. Induction of WRKY70 by SA is reduced in atmyb44 and npr1-1 mutants, and is totally abolished in atmyb44 npr1-1 double mutants, showing that WRKY70 is regulated independently through both NPR1 and AtMYB44. AtMYB44 over-expression does not change SA content, but AtMYB44 over-expression phenotypes, such as retarded growth, up-regulated PR1 and down-regulated PDF1.2 are reversed by SA depletion. The wrky70 mutation suppressed AtMYB44 over-expression phenotypes, including up-regulation of PR1 expression and down-regulation of PDF1.2 expression. β-estradiol-induced expression of AtMYB44 led to WRKY70 activation and thus PR1 activation. AtMYB44 binds to the WRKY70 promoter region, indicating that AtMYB44 acts as a transcriptional activator of WRKY70 by directly binding to a conserved sequence element in the WRKY70 promoter. These results demonstrate that AtMYB44 modulates antagonistic interaction by activating SA-mediated defenses and repressing JA-mediated defenses through direct control of WRKY70. © 2012 The Authors The Plant Journal © 2012 Blackwell Publishing Ltd.

Danusertib, a potent pan-Aurora kinase and ABL kinase inhibitor, induces cell cycle arrest and programmed cell death and inhibits epithelial to mesenchymal transition involving the PI3K/Akt/mTOR-mediated signaling pathway in human gastric cancer AGS and NCI-N78 cells

Directory of Open Access Journals (Sweden)

Yuan CX

2015-03-01

Full Text Available Chun-Xiu Yuan,1,2 Zhi-Wei Zhou,2,3 Yin-Xue Yang,4 Zhi-Xu He,3 Xueji Zhang,5 Dong Wang,6 Tianxing Yang,7 Si-Yuan Pan,8 Xiao-Wu Chen,9 Shu-Feng Zhou2 1Department of Oncology, General Hospital, Ningxia Medical University, Yinchuan, People’s Republic of China; 2Department of Pharmaceutical Science, College of Pharmacy, University of South Florida, Tampa, FL, USA; 3Guizhou Provincial Key Laboratory for Regenerative Medicine, Stem Cell and Tissue Engineering Research Center and Sino-US Joint Laboratory for Medical Sciences, Guiyang Medical University, Guiyang, 4Department of Colorectal Surgery, General Hospital, Ningxia Medical University, Yinchuan, 5Research Center for Bioengineering and Sensing Technology, University of Science and Technology Beijing, 6Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People’s Republic of China; 7Department of Internal Medicine, University of Utah and Salt Lake Veterans Affairs Medical Center, Salt Lake City, UT, USA; 8Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 9Department of General Surgery, The First People’s Hospital of Shunde, Southern Medical University, Shunde, People’s Republic of China Abstract: Gastric cancer is the second leading cause of cancer-related death worldwide, with a poor response to current chemotherapy. Danusertib is a pan-inhibitor of the Aurora kinases and a third-generation Bcr-Abl tyrosine kinase inhibitor with potent anticancer effects, but its antitumor effect and underlying mechanisms in the treatment of human gastric cancer are unknown. This study aimed to investigate the effects of danusertib on cell growth, apoptosis, autophagy, and epithelial to mesenchymal transition and the molecular mechanisms involved in human gastric cancer AGS and NCI-N78 cells. The results showed that danusertib had potent growth-inhibitory, apoptosis-inducing, and

Mechanical reinforcement of Bioglass (R)-based scaffolds by novel polyvinyl-alcohol/microfibrillated cellulose composite coating

Czech Academy of Sciences Publication Activity Database

Bertolla, Luca; Dlouhý, Ivo; Philippart, A.; Boccaccini, A. R.

2014-01-01

Roč. 118, MAR (2014), s. 204-207 ISSN 0167-577X R&D Projects: GA MŠk(CZ) ED1.1.00/02.0068 EU Projects: European Commission(XE) 264526 - GLACERCO Institutional support: RVO:68081723 Keywords : bioactive glass * mechanical properties * scaffolds * cellulose * coatings Subject RIV: JL - Materials Fatigue, Friction Mechanics Impact factor: 2.489, year: 2014

El procés d'avaluació i intervenció psicològica a pacients amb trastorns per abús d' alcohol i/o altres substàncies psicotròpiques

OpenAIRE

Trasovares Navarrete, María Victoria

2004-01-01

Aquest treball, realitzat al Centre d'Atenció i Seguiment de Drogodependències (CASD) de Nou Barris, ha tingut com a objectiu principal observar el rol del psicòleg clínic en el procés d'avaluació i intervenció psicoterapèutica en pacients que presenten un trastorn per dependència de substàncies psicotròpiques. Este trabajo, realizado en el Centro de Atención y Seguimiento de Drogodependencias (CASD) de Nou Barris, ha tenido como principal objetivo observar el rol del psicólogo clínico en ...

Genetic resistance in experimental autoimmune encephalomyelitis. I. Analysis of the mechanism of LeR resistance using radiation chimeras

International Nuclear Information System (INIS)

Pelfrey, C.M.; Waxman, F.J.; Whitacre, C.C.

1989-01-01

Experimental autoimmune encephalomyelitis (EAE) is a cell-mediated autoimmune disease of the central nervous system that has been extensively studied in the rat. The Lewis rat is highly susceptible to the induction of EAE, while the Lewis resistant (LeR) rat is known to be resistant. In this paper, we demonstrate that the LeR rat, which was derived from the Lewis strain by inbreeding of fully resistant animals, is histocompatible with the Lewis strain. Radiation chimeras, a tool for distinguishing between immunologic and nonimmunologic resistance mechanisms, were utilized to analyze the cellular mechanisms involved in genetic resistance to EAE. By transplanting bone marrow cells from LeR rats into irradiated Lewis recipients, Lewis rats were rendered resistant to EAE induction. Likewise, transplanting Lewis bone marrow cells into irradiated LeR recipients rendered LeR rats susceptible. Mixed lymphoid cell chimeras using bone marrow, spleen, and thymus cells in Lewis recipient rats revealed individual lymphoid cell types and cell interactions that significantly affected the incidence and severity of EAE. Our results suggest that LeR resistance is mediated by hematopoietic/immune cells, and that cells located in the spleen appear to play a critical role in the resistance/susceptibility to EAE induction. Depletion of splenic adherent cells did not change the patterns of EAE resistance. In vivo cell mixing studies suggested the presence of a suppressor cell population in the LeR spleen preparations which exerted an inhibitory effect on Lewis autoimmune responses. Thus, the mechanism of LeR resistance appears to be different from that in other EAE-resistant animals

Protocol per a la implantació d’eines didàctiques virtuals: competències i habilitats adquirides pels estudiants

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Laura Guitart Tarrés

2011-06-01

Full Text Available L’adaptació al nou espai europeu d’educació superior (EEES ha plantejat alguns canvis en l’enfocament de la formació universitària al nostre país. On abans era el docent el protagonista, ara és l’estudiant el que pren el rol d’actor principal de la seva formació, i l’aprenentatge s’orienta cap a una autonomia i reflexió més grans. En aquest escenari, les noves tecnologies ofereixen un ampli ventall d’opcions per millorar els processos formatius. En aquests sentit, el Grup d’Innovació Docent G•IDEA ha participat activament en aquest procés d’adaptació des de ja fa uns quants anys, i ha creat una sèrie de recursos docents digitals que han estat àmpliament provats en diversos ensenyaments de la Facultat d’Economia i Empresa de la Universitat de Barcelona. L’objectiu d’aquest article és presentar el protocol dissenyat per l’equip d’investigadors del G•IDEA per implantar aquestes eines didàctiques (webquestes i exercicis tutoritzats, i també els resultats d’una enquesta de satisfacció sobre les competències i habilitats adquirides pels nostres estudiants en la utilització dels recursos. Els resultats mostren, d’una banda, que no ha estat possible crear un mateix protocol aplicable a tots els recursos, a causa de les diferències en els objectius didàctics de les distintes eines docents implantades. D’altra banda, la valoració que els estudiants fan de la utilització de les eines és molt positiva, tot i que hi ha algunes diferències entre els recursos analitzats. Conèixer la valoració que l’alumnat fa d’aquests recursos permet al grup d’investigadors poder-los millorar i adequar al perfil dels estudiants perquè aquests en puguin treure el màxim profit possible.

NCI Program for Natural Product Discovery: A Publicly-Accessible Library of Natural Product Fractions for High-Throughput Screening.

Science.gov (United States)

Thornburg, Christopher C; Britt, John R; Evans, Jason R; Akee, Rhone K; Whitt, James A; Trinh, Spencer K; Harris, Matthew J; Thompson, Jerell R; Ewing, Teresa L; Shipley, Suzanne M; Grothaus, Paul G; Newman, David J; Schneider, Joel P; Grkovic, Tanja; O'Keefe, Barry R

2018-06-13

The US National Cancer Institute's (NCI) Natural Product Repository is one of the world's largest, most diverse collections of natural products containing over 230,000 unique extracts derived from plant, marine, and microbial organisms that have been collected from biodiverse regions throughout the world. Importantly, this national resource is available to the research community for the screening of extracts and the isolation of bioactive natural products. However, despite the success of natural products in drug discovery, compatibility issues that make extracts challenging for liquid handling systems, extended timelines that complicate natural product-based drug discovery efforts and the presence of pan-assay interfering compounds have reduced enthusiasm for the high-throughput screening (HTS) of crude natural product extract libraries in targeted assay systems. To address these limitations, the NCI Program for Natural Product Discovery (NPNPD), a newly launched, national program to advance natural product discovery technologies and facilitate the discovery of structurally defined, validated lead molecules ready for translation will create a prefractionated library from over 125,000 natural product extracts with the aim of producing a publicly-accessible, HTS-amenable library of >1,000,000 fractions. This library, representing perhaps the largest accumulation of natural-product based fractions in the world, will be made available free of charge in 384-well plates for screening against all disease states in an effort to reinvigorate natural product-based drug discovery.

Improving clinical research and cancer care delivery in community settings: evaluating the NCI community cancer centers program

Directory of Open Access Journals (Sweden)

Fennell Mary L

2009-09-01

Full Text Available Abstract Background In this article, we describe the National Cancer Institute (NCI Community Cancer Centers Program (NCCCP pilot and the evaluation designed to assess its role, function, and relevance to the NCI's research mission. In doing so, we describe the evolution of and rationale for the NCCCP concept, participating sites' characteristics, its multi-faceted aims to enhance clinical research and quality of care in community settings, and the role of strategic partnerships, both within and outside of the NCCCP network, in achieving program objectives. Discussion The evaluation of the NCCCP is conceptualized as a mixed method multi-layered assessment of organizational innovation and performance which includes mapping the evolution of site development as a means of understanding the inter- and intra-organizational change in the pilot, and the application of specific evaluation metrics for assessing the implementation, operations, and performance of the NCCCP pilot. The assessment of the cost of the pilot as an additional means of informing the longer-term feasibility and sustainability of the program is also discussed. Summary The NCCCP is a major systems-level set of organizational innovations to enhance clinical research and care delivery in diverse communities across the United States. Assessment of the extent to which the program achieves its aims will depend on a full understanding of how individual, organizational, and environmental factors align (or fail to align to achieve these improvements, and at what cost.

Study of rNIS as a reporter gene monitoring rBMSC transplanted to rat myocardium

International Nuclear Information System (INIS)

Hu Shou; Lan Xiaoli; Cao Wei; Cao Guoxiang; Zhang Guopeng; Zhang Binqing; Wu Tao; Chang Wei; Zhang Yongxue

2010-01-01

Objective: To investigate the feasibility of rat sodium/iodide symporter (rNIS) as a reporter gene monitoring rat bone marrow mesenchymal cells (rBMSC) transplanted to rat myocardium in vivo. Methods: Recombinated adenovirus vector was constructed by rNIS/enhanced green fluorescence protein (EGFP) (Ad-rNIS/EGFP). rBMSC transfected by Ad-rNIS/EGFP were studied using fluorescence microscope. Fifteen rats were transplanted with rBMSC and randomly divided into three groups: rNIS group (with rNIS transfection), blocked group (with rNIS transfection) by oral intake of perchloric sodium before planar imaging (GE Millennium MPR SPECT), and control group (without rNIS transfection). All rats underwent 99 Tc m -pertechnetate planar imaging. The biological distribution of 99 Tc m -pertechnetate was studied. The expressions of rNIS gene and protein in myocardium were measured by real time polymerase chain reaction (PCR) and western blot, respectively. The expressions of CD 29 , CD 44 , CD 90 , CD 11 b, CD 34 and CD 45 were measured by immunohistochemistry. Results: rBMSC transfected by Ad-rNIS/EGFP showed EGFP expression under fluorescence microscope. The transplanted rat myocardium could be visualized on 99 Tc m -pertechnetate planar imaging in rNIS group. The relative uptake ratio (R heart /R hmb , RUR) was 6.7 ±0.4. RUR in control group (3.0 ±0.2) was lower than that in rNIS group (t =2.78, P=0.03). The percentage injection dose per gram of tissue (% ID/g) of the transplanted myocardium was 60.2 ± 20.8 in rNIS group, which was higher than that (2.5 ± 0.4) % ID/g of control group ( t = 7.13, P 29 , CD 44 and CD 90 were positive, CD 45 and CD 45 negative CD 11 b mildly positive in the myocardium transplanted with infective rBMSC. Conclusion: rNIS can efficiently monitor rBMSC transplanted to rat myocardium. (authors)

Theoretical analysis of the binding of iron(III) protoporphyrin IX to 4-methoxyacetophenone thiosemicarbazone via DFT-D3, MEP, QTAIM, NCI, ELF, and LOL studies.

Science.gov (United States)

Nkungli, Nyiang Kennet; Ghogomu, Julius Numbonui

2017-07-01

Thiosemicarbazones display diverse pharmacological properties, including antimalarial activities. Their pharmacological activities have been studied in depth, but little of this research has focused on their antimalarial mode of action. To elucidate this antimalarial mechanism, we investigated the nature of the interactions between iron(III) protoporphyrin IX (Fe(III)PPIX) and the thione-thiol tautomers of 4-methoxyacetophenone thiosemicarbazone (MAPTSC). Dispersion-corrected density functional theory (DFT-D3), the quantum theory of atoms in molecules (QTAIM), the noncovalent interaction (NCI) index, the electron localization function (ELF), the localized orbital locator (LOL), and thermodynamic calculations were employed in this work. Fe(III)PPIX-MAPTSC binding is expected to inhibit hemozoin formation, thereby preventing Fe(III)PPIX detoxification in plasmodia. Preliminary studies geared toward the identification of atomic binding sites in the thione-thiol tautomers of MAPTSC were carried out using molecular electrostatic potential (MEP) maps and conceptual DFT-based local reactivity indices. The thionic sulfur and the 2 N-azomethine nitrogen/thiol sulfur of, respectively, the thione and thiol tautomers of MAPTSC were identified as the most favorable nucleophilic sites for electrophilic attack. The negative values of the computed Fe(III)PPIX-MAPTSC binding energies, enthalpies, and Gibbs free energies are indicative of the existence and stability of Fe(III)PPIX-MAPTSC complexes. MAPTSC-Fe(III) coordinate bonds and strong hydrogen bonds (N-H···O) between the NH 2 group in MAPTSC and the C=O group in one propionate side chain of Fe(III)PPIX are crucial to Fe(III)PPIX-MAPTSC binding. QTAIM, NCI, ELF, and LOL analyses revealed a subtle interplay of weak noncovalent interactions dominated by dispersive-like van der Waals interactions between Fe(III)PPIX and MAPTSC that stabilize the Fe(III)PPIX-MAPTSC complexes.

E.S.R. studies of mechanisms of radiation protection effect by cysteine and cystine

International Nuclear Information System (INIS)

Xue-Peng, L.; Tie-Cheng, T.; Nian-Yun, L.

1981-01-01

By means of E.S.R. the repair mechanism of radiation induced spin transfer from dTMP to cysteine in binary system dTMP-cysteine has been confirmed. Furthermore, a new marked radiation protection effect, exerted by cysteine or cystine on thymine irradiated and observed at low temperature, has been detected. Another sort of fast protection mechanism, including electron transfer and excitation transfer, has been proposed, based on recent advances of primary radiation process of pyrimidine bases and analysed by molecular orbital theory. This fast radiation protection mechanism provides the possibility to utilize electrophilic sulfhydryl protectors for realizing excellent protection effect. (author)

Identification of a Bis-guanylhydrazone [4,4'-Diacetyldiphenylurea-bis(guanylhydrazone); NSC 109555] as a novel chemotype for inhibition of Chk2 kinase.

Science.gov (United States)

Jobson, Andrew G; Cardellina, John H; Scudiero, Dominic; Kondapaka, Sudhir; Zhang, Hongliang; Kim, Hijoo; Shoemaker, Robert; Pommier, Yves

2007-10-01

Chk2 is a protein kinase involved in the ATM-dependent checkpoint pathway (http://discover.nci.nih.gov/mim). This pathway is activated by genomic instability and DNA damage and results in either cell cycle arrest, to allow DNA repair to occur, or cell death (apoptosis). Chk2 is activated by ATM-mediated phosphorylation and autophosphorylation and in turn phosphorylates its downstream targets (Cdc25A, Cdc25C, BRCA1, p53, Hdmx, E2F1, PP2A, and PML). Inhibition of Chk2 has been proposed to sensitize p53-deficient cells as well as protect normal tissue after exposure to DNA-damaging agents. We have developed a drug-screening program for specific Chk2 inhibitors using a fluorescence polarization assay, immobilized metal ion affinity-based fluorescence polarization (IMAP). This assay detects the degree of phosphorylation of a fluorescently linked substrate by Chk2. From a screen of over 100,000 compounds from the NCI Developmental Therapeutics Program, we identified a bis-guanylhydrazone [4,4'-diacetyldiphenylureabis(guanylhydrazone); NSC 109555] as a lead compound. In vitro data show the specific inhibition of Chk2 kinase activity by NSC 109555 using in vitro kinase assays and kinase-profiling experiments. NSC 109555 was shown to be a competitive inhibitor of Chk2 with respect to ATP, which was supported by docking of NSC 109555 into the ATP binding pocket of the Chk2 catalytic domain. The potency of NSC 109555 was comparable with that of other known Chk2 inhibitors, such as debromohymenialdisine and 2-arylbenzimidazole. These data define a novel chemotype for the development of potent and selective inhibitors of Chk2. This class of drugs may ultimately be useful in combination with current DNA-damaging agents used in the clinic.

The mechanism of three-body process of energy transfer from excited xenon atoms to molecules

International Nuclear Information System (INIS)

Wojciechowski, K.; Forys, M.

1999-01-01

The mechanism of energy transfer from Xe(6 s[3/2] 1 ) resonance state (E=8.44 eV) and higher excited Xe(6p, 6p', 6 d) atoms produced in pulse radiolysis to molecules have been discussed. The analysis of the kinetic data for these processes shows that in the sensitized photolysis and radiolysis of Xe-M mixtures the excited atoms decay in 'ordinary' two-body reaction: Xe(6s[3/2] 1 0 )+M→products (r.1) and in fast 'accelerated' third order process: Xe(6s[3/2] 1 0 )+M+Xe→products (r.2) The discussion shows that three-body process occurs via reactions: Xe(6s[3/2] 1 0 )+Xe k w ↔ k d Xe 2 ** (r.2a) Xe 2 **+M k q →[Xe 2 M]*→products (r.2b) It was shown that this mechanism concerns also higher excited Xe atoms and can explain a similar process in He-M mixtures and suggests that it is a general mechanism of energy transfer in all irradiated rare gas-molecule systems

The NCI High Performance Computing (HPC) and High Performance Data (HPD) Platform to Support the Analysis of Petascale Environmental Data Collections

Science.gov (United States)

Evans, B. J. K.; Pugh, T.; Wyborn, L. A.; Porter, D.; Allen, C.; Smillie, J.; Antony, J.; Trenham, C.; Evans, B. J.; Beckett, D.; Erwin, T.; King, E.; Hodge, J.; Woodcock, R.; Fraser, R.; Lescinsky, D. T.

2014-12-01

The National Computational Infrastructure (NCI) has co-located a priority set of national data assets within a HPC research platform. This powerful in-situ computational platform has been created to help serve and analyse the massive amounts of data across the spectrum of environmental collections - in particular the climate, observational data and geoscientific domains. This paper examines the infrastructure, innovation and opportunity for this significant research platform. NCI currently manages nationally significant data collections (10+ PB) categorised as 1) earth system sciences, climate and weather model data assets and products, 2) earth and marine observations and products, 3) geosciences, 4) terrestrial ecosystem, 5) water management and hydrology, and 6) astronomy, social science and biosciences. The data is largely sourced from the NCI partners (who include the custodians of many of the national scientific records), major research communities, and collaborating overseas organisations. By co-locating these large valuable data assets, new opportunities have arisen by harmonising the data collections, making a powerful transdisciplinary research platformThe data is accessible within an integrated HPC-HPD environment - a 1.2 PFlop supercomputer (Raijin), a HPC class 3000 core OpenStack cloud system and several highly connected large scale and high-bandwidth Lustre filesystems. New scientific software, cloud-scale techniques, server-side visualisation and data services have been harnessed and integrated into the platform, so that analysis is performed seamlessly across the traditional boundaries of the underlying data domains. Characterisation of the techniques along with performance profiling ensures scalability of each software component, all of which can either be enhanced or replaced through future improvements. A Development-to-Operations (DevOps) framework has also been implemented to manage the scale of the software complexity alone. This ensures that

Brucella BioR Regulator Defines a Complex Regulatory Mechanism for Bacterial Biotin Metabolism

Science.gov (United States)

Xu, Jie; Zhang, Huimin; Srinivas, Swaminath

2013-01-01

The enzyme cofactor biotin (vitamin H or B7) is an energetically expensive molecule whose de novo biosynthesis requires 20 ATP equivalents. It seems quite likely that diverse mechanisms have evolved to tightly regulate its biosynthesis. Unlike the model regulator BirA, a bifunctional biotin protein ligase with the capability of repressing the biotin biosynthetic pathway, BioR has been recently reported by us as an alternative machinery and a new type of GntR family transcriptional factor that can repress the expression of the bioBFDAZ operon in the plant pathogen Agrobacterium tumefaciens. However, quite unusually, a closely related human pathogen, Brucella melitensis, has four putative BioR-binding sites (both bioR and bioY possess one site in the promoter region, whereas the bioBFDAZ [bio] operon contains two tandem BioR boxes). This raised the question of whether BioR mediates the complex regulatory network of biotin metabolism. Here, we report that this is the case. The B. melitensis BioR ortholog was overexpressed and purified to homogeneity, and its solution structure was found to be dimeric. Functional complementation in a bioR isogenic mutant of A. tumefaciens elucidated that Brucella BioR is a functional repressor. Electrophoretic mobility shift assays demonstrated that the four predicted BioR sites of Brucella plus the BioR site of A. tumefaciens can all interact with the Brucella BioR protein. In a reporter strain that we developed on the basis of a double mutant of A. tumefaciens (the ΔbioR ΔbioBFDA mutant), the β-galactosidase (β-Gal) activity of three plasmid-borne transcriptional fusions (bioBbme-lacZ, bioYbme-lacZ, and bioRbme-lacZ) was dramatically decreased upon overexpression of Brucella bioR. Real-time quantitative PCR analyses showed that the expression of bioBFDA and bioY is significantly elevated upon removal of bioR from B. melitensis. Together, we conclude that Brucella BioR is not only a negative autoregulator but also a repressor of

Mechanical response of shock conditioned HPNS-5 (R-1) grout

International Nuclear Information System (INIS)

Plannerer, H.N.

1997-01-01

HPNS-5 (R-1) grout is a portland cement formulated mix designed for use as a rigid containment plug in vertical boreholes at the Nevada Test Site. Coincident with field testing of this grout in 1991 and 1992 , two arums of the grout mix were collected and positioned in the by pass drift of the DISTANT ZENITH event to expose the grout to passage of a nuclear driven stress wave. The drums were later retrieved to determine the mechanical behavior of the shock conditioned grout. Sealed hollow tubes positioned within the grout-filled drums to detect ductile flow on passage of the stress wave were found partially to completely filled with HPNS-5 grout following the experiment. Static mechanical tests support the evidence for ductile flow and place the transition from brittle fracture failure to ductile behavior in the shock conditioned grout at a confining stress between ambient and 5 MPa (725 psi). Uniaxial and triaxial tests delineated a stress-strain field for interstice collapse that interposes between the mechanics of linear elastic deformation and dilatancy. Hydrostatic stress loading between 25 MPa (3.6 ksi) and 60 MPa (8.7 ksi) results in a significant change of permanent set from 1% to greater than 15% volume strain

Mechanism of Metal Ion Activation of the Diphtheria Toxin Repressor DtxR

Energy Technology Data Exchange (ETDEWEB)

D' Aquino,J.; Tetenbaum-Novatt, J.; White, A.; Berkovitch, F.; Ringe, D.

2005-01-01

The diphtheria toxin repressor (DtxR) is a metal ion-activated transcriptional regulator that has been linked to the virulence of Corynebacterium diphtheriae. Structure determination has shown that there are two metal ion binding sites per repressor monomer, and site-directed mutagenesis has demonstrated that binding site 2 (primary) is essential for recognition of the target DNA repressor, leaving the role of binding site 1 (ancillary) unclear. Calorimetric techniques have demonstrated that although binding site 1 (ancillary) has high affinity for metal ion with a binding constant of 2 x 10{sup -7}, binding site 2 (primary) is a low-affinity binding site with a binding constant of 6.3 x 10{sup -4}. These two binding sites act in an independent fashion, and their contribution can be easily dissected by traditional mutational analysis. Our results clearly demonstrate that binding site 1 (ancillary) is the first one to be occupied during metal ion activation, playing a critical role in stabilization of the repressor. In addition, structural data obtained for the mutants Ni-DtxR(H79A, C102D), reported here, and the previously reported DtxR(H79A) have allowed us to propose a mechanism of metal activation for DtxR.

Comparison of R6 and A16 J estimation methods under combined mechanical and thermal loads with FE results

International Nuclear Information System (INIS)

Nam, Hyun-Suk; Oh, Chang-Young; Kim, Yun-Jae; Jerng, Dong Wook; Ainsworth, Robert A.; Budden, Peter J.; Marie, Stéphane

2015-01-01

This paper compares elastic–plastic values of J calculated using the methods in the UK R6 and the French A16 fitness-for-service procedures with FE results for a vessel with a circumferential surface crack under axial tension and a radial thermal gradient. In the FE analyses, the relative magnitudes and loading sequence of mechanical and thermal loads are systematically varied, together with the material strain hardening exponent. Fully circumferential and semi-elliptical surface crack with two relative crack depths are considered. It is found that the R6 estimates are overall accurate but can be non-conservative at large L_r. The A16 estimates are more conservative than the R6 estimates at small L_r but are conservative even at large L_r. Possible sources of conservatism and non-conservatism in R6 and A16 are discussed. - Highlights: • Accuracy of existing J estimation methods for combined mechanical and thermal loading are compared with FE results. • The methods in the UK R6 and the French A16 procedures are considered. • The R6 estimates are overall accurate but can be non-conservative at large L_r. • The A16 estimates are more conservative than the R6 estimates at small L_r but are conservative even at large L_r. • Possible sources of conservatism and non-conservatism in R6 and A16 are discussed.

The HMGA1 Pseudogene 7 Induces miR-483 and miR-675 Upregulation by Activating Egr1 through a ceRNA Mechanism

Directory of Open Access Journals (Sweden)

Marco De Martino

2017-11-01

Full Text Available Several studies have established that pseudogene mRNAs can work as competing endogenous RNAs and, when deregulated, play a key role in the onset of human neoplasias. Recently, we have isolated two HMGA1 pseudogenes, HMGA1P6 and HMGA1P7. These pseudogenes have a critical role in cancer progression, acting as micro RNA (miRNA sponges for HMGA1 and other cancer-related genes. HMGA1 pseudogenes were found overexpressed in several human carcinomas, and their expression levels positively correlate with an advanced cancer stage and a poor prognosis. In order to investigate the molecular alterations following HMGA1 pseudogene 7 overexpression, we carried out miRNA sequencing analysis on HMGA1P7 overexpressing mouse embryonic fibroblasts. Intriguingly, the most upregulated miRNAs were miR-483 and miR-675 that have been described as key regulators in cancer progression. Here, we report that HMGA1P7 upregulates miR-483 and miR-675 through a competing endogenous RNA mechanism with Egr1, a transcriptional factor that positively regulates miR-483 and miR-675 expression.

Late toxicity results of the GORTEC 94-01 randomized trial comparing radiotherapy with concomitant radiochemotherapy for advanced-stage oropharynx carcinoma: comparison of LENT/SOMA, RTOG/EORTC, and NCI-CTC scoring systems

International Nuclear Information System (INIS)

Denis, Fabrice; Garaud, Pascal; Bardet, Etienne; Alfonsi, Marc; Sire, Christian; Germain, Thierry; Bergerot, Philippe; Rhein, Beatrix; Tortochaux, Jacques; Oudinot, Patrick; Calais, Gilles

2003-01-01

Purpose: To prospectively assess 5-year late toxicity in patients treated by concomitant radiochemotherapy for locally advanced oropharynx carcinoma using three different toxicity scales. Methods and Materials: A total of 226 patients were entered in a Phase III multicenter, randomized trial comparing radiotherapy alone (70 Gy in 35 fractions: Arm A) with concomitant radiochemotherapy (70 Gy in 35 fractions with three cycles of a 4-day regimen containing carboplatin and 5-fluorouracil: Arm B). Five living patients, free of local or distant recurrences, could not be evaluated for late toxicity. Forty-four patients were eligible for late toxicity with a median follow-up of 5 years. Late toxicity was evaluated by the radiation oncologist using a large questionnaire containing 120 mixed items of three scales (NCI-CTC, LENT/SOMA, and RTOG). The data were then transposed on separate scales using corresponding grades. Results: The 5-year overall survival rate was 22% in Arm B and 16% in Arm A (p=0.05). The 5-year locoregional control rate was 48% in Arm B and 25% in Arm A (p=0.002). The spinal cord was not affected by the concomitant adjunct of chemotherapy, and no deaths were caused by late toxicity. Using the three late toxicity scales, 100% of the patients treated with the combined modality (Arm B) developed one or more late complications vs. 94% in the radiotherapy-alone arm (Arm A). The difference was not statistically significant. The most commonly damaged organs (all Grade 1-4) were the salivary glands (100% in Arm B vs. 82% in Arm A, p<0.05), skin (78% vs. 47%, p<0.05), teeth (67% vs. 18%, p<0.05), mucosa (59% vs. 63% p = not significant), and mandible (44% vs. 12%, p<0.05). One or more Grade 3-4 complications occurred in 82% of the patients in Arm B vs. 47% in Arm A (p=0.02) but concerned only the teeth. The correlation between the RTOG and LENT/SOMA scale and between the NCI-CTC and LENT/SOMA scale were low for Grade 1-4 toxicity (near 30%). The transposability

Association of a single nucleotide polymorphic variation in the human chromosome 19q13.3 with drug responses in the NCI60 cell lines

DEFF Research Database (Denmark)

Nissen, K.K.; Vogel, Ulla Birgitte; Nexo, B.A.

2009-01-01

the correlations between the responses of the NCI60 cells to different anticancer drugs and their respective alleles of five DNA polymorphisms located in a cancer-related chromosomal area. One polymorphism, located in the 5' noncoding region of the gene ASE-1, alias CD3EAP, proved to be associated with drug...

Comparison of 44-hour and fixed 24-hour ambulatory blood pressure monitoring in dialysis patients.

Science.gov (United States)

Liu, Wenjin; Ye, Hong; Tang, Bing; Sun, Zhiping; Wen, Ping; Wu, Wenhui; Bian, Xueqing; Shen, Xia; Yang, Junwei

2014-01-01

The two most commonly used strategies to evaluate dialysis patients' blood pressure (BP) level are 44-hour and 24-hour ambulatory blood pressure monitoring (ABPM). The objective of this study was to find an appropriate 24-hour period that correlated well with the 44-hour BP level and determine the differences between these strategies. In a group of 51 dialysis patients, the authors performed 44-hour ABPM and extracted data for a fixed 24-hour ABPM. The fixed 24-hour ABPM started at 6 am on the nondialysis day. A strong correlation was found between all parameters of 44-hour and the fixed 24-hour ABPM, with paired sample t test showing only small magnitude changes in a few parameters. Both 24-hour ABPM and 44-hour ABPM were superior to clinic BP in predicting left ventricular mass index (LVMI) by multiple regression analysis. It was found that 44-hour ambulatory arterial stiffness index (AASI), but not 24-hour AASI, had a positive association with LVMI (r=0.328, P=.021). However, after adjustment for 44-hour systolic blood pressure, this association disappeared. Fixed 24-hour ABPM is a good surrogate of 44-hour ABPM to some extent, while 44-hour ABPM can provide more accurate and detailed information. ©2013 Wiley Periodicals, Inc.

The natural cytokinin 2OH3MeOBAR induces cell death by a mechanism that is different from that of the „classical“ cytokinin ribosides

Czech Academy of Sciences Publication Activity Database

Voller, Jiří; Béres, T.; Zatloukal, M.; Kaminski, P. A.; Niemann, P.; Doležal, K.; Džubák, P.; Hajdúch, M.; Strnad, Miroslav

2017-01-01

Roč. 136, APR (2017), s. 156-164 ISSN 0031-9422 R&D Projects: GA MŠk(CZ) LO1204; GA MŠk(CZ) LO1304; GA MŠk(CZ) LM2015064; GA MŠk LM2015063; GA ČR GA14-19590S Institutional support: RVO:61389030 Keywords : myeloid-leukemia cells * kinetin-riboside * hl-60 cells * cancer-cells * in-vitro * apoptosis * gene * rcl * identification * lines * Phytohormone * Cytokinin * Leukemia * Cancer * Apoptosis * NCI60 panel Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Plant sciences, botany Impact factor: 3.205, year: 2016

Downregulation of CD44 reduces doxorubicin resistance of CD44+CD24- breast cancer cells

Directory of Open Access Journals (Sweden)

Phuc PV

2011-06-01

Full Text Available Pham Van Phuc, Phan Lu Chinh Nhan, Truong Hai Nhung, Nguyen Thanh Tam, Nguyen Minh Hoang, Vuong Gia Tue, Duong Thanh Thuy, Phan Kim NgocLaboratory of Stem Cell Research and Application, University of Science, Vietnam National University, Ho Chi Minh, VietnamBackground: Cells within breast cancer stem cell populations have been confirmed to have a CD44+CD24- phenotype. Strong expression of CD44 plays a critical role in numerous types of human cancers. CD44 is involved in cell differentiation, adhesion, and metastasis of cancer cells.Methods: In this study, we reduced CD44 expression in CD44+CD24- breast cancer stem cells and investigated their sensitivity to an antitumor drug. The CD44+CD24- breast cancer stem cells were isolated from breast tumors; CD44 expression was downregulated with siRNAs followed by treatment with different concentrations of the antitumor drug.Results: The proliferation of CD44 downregulated CD44+CD24- breast cancer stem cells was decreased after drug treatment. We noticed treated cells were more sensitive to doxorubicin, even at low doses, compared with the control groups.Conclusions: It would appear that expression of CD44 is integral among the CD44+CD24- cell population. Reducing the expression level of CD44, combined with doxorubicin treatment, yields promising results for eradicating breast cancer stem cells in vitro. This study opens a new direction in treating breast cancer through gene therapy in conjunction with chemotherapy.Keywords: antitumor drugs, breast cancer stem cells, CD44, CD44+CD24- cells, doxorubicin

Big Five Inventory: Základní psychometrické charakteristiky české verze BFI-44 a BFI-10

Czech Academy of Sciences Publication Activity Database

Hřebíčková, Martina; Jelínek, Martin; Blatný, Marek; Brom, C.; Burešová, I.; Graf, Sylvie; Mejzlíková, T.; Vazsonyi, A. T.; Zábrodská, Kateřina

2016-01-01

Roč. 60, č. 6 (2016), s. 567-583 ISSN 0009-062X R&D Projects: GA ČR GA13-25656S; GA ČR GA14-02098S Institutional support: RVO:68081740 Keywords : Five Factor Model * Big Five Inventory * BFI-44 * BFI-10 * psychometric properties Subject RIV: AN - Psychology Impact factor: 0.242, year: 2016

Managing creative team performance in virtual environments : An empirical study in 44 R&D teams

NARCIS (Netherlands)

Kratzer, J.; Leenders, R.Th.A.J.; van Engelen, J.M.L.

Creative performance in R&D is of vital importance to organizations. Because R&D usually is organized in teams, the management of creative performance inherently refers to the team level creative performance. Over the last decades, R&D teams have become increasingly virtual. In this article we

Molecular and biochemical analyses of the GH44 module of CbMan5B/Cel44A, a bifunctional enzyme from the hyperthermophilic bacterium Caldicellulosiruptor bescii.

Science.gov (United States)

Ye, Libin; Su, Xiaoyun; Schmitz, George E; Moon, Young Hwan; Zhang, Jing; Mackie, Roderick I; Cann, Isaac K O

2012-10-01

A large polypeptide encoded in the genome of the thermophilic bacterium Caldicellulosiruptor bescii was determined to consist of two glycoside hydrolase (GH) modules separated by two carbohydrate-binding modules (CBMs). Based on the detection of mannanase and endoglucanase activities in the N-terminal GH5 and the C-terminal GH44 module, respectively, the protein was designated CbMan5B/Cel44A. A GH5 module with >99% identity from the same organism was characterized previously (X. Su, R. I. Mackie, and I. K. Cann, Appl. Environ. Microbiol. 78:2230-2240, 2012); therefore, attention was focused on CbMan5A/Cel44A-TM2 (or TM2), which harbors the GH44 module and the two CBMs. On cellulosic substrates, TM2 had an optimal temperature and pH of 85°C and 5.0, respectively. Although the amino acid sequence of the GH44 module of TM2 was similar to those of other GH44 modules that hydrolyzed cello-oligosaccharides, cellulose, lichenan, and xyloglucan, it was unique that TM2 also displayed modest activity on mannose-configured substrates and xylan. The TM2 protein also degraded Avicel with higher specific activity than activities reported for its homologs. The GH44 catalytic module is composed of a TIM-like domain and a β-sandwich domain, which consists of one β-sheet at the N terminus and nine β-sheets at the C terminus. Deletion of one or more β-sheets from the β-sandwich domain resulted in insoluble proteins, suggesting that the β-sandwich domain is essential for proper folding of the polypeptide. Combining TM2 with three other endoglucanases from C. bescii led to modest synergistic activities during degradation of cellulose, and based on our results, we propose a model for cellulose hydrolysis and utilization by C. bescii.

Revealing the mechanisms of protein disorder and N-glycosylation in CD44-hyaluronan binding using molecular simulation

Directory of Open Access Journals (Sweden)

Olgun eGuvench

2015-06-01

Full Text Available The extracellular N-terminal hyaluronan binding domain (HABD of CD44 is a small globular domain that confers hyaluronan (HA binding functionality to this large transmembrane glycoprotein. When recombinantly expressed by itself, HABD exists as a globular water-soluble protein that retains the capacity to bind HA. This has enabled atomic-resolution structural biology experiments that have revealed the structure of HABD and its binding mode with oligomeric HA. Such experiments have also pointed to an order-to-disorder transition in HABD that is associated with HA binding. However, it had remained unclear how this structural transition was involved in binding since it occurs in a region of HABD distant from the HA-binding site. Furthermore, HABD is known to be N-glycosylated, and such glycosylation can diminish HA binding when the associated N-glycans are capped with sialic acid residues. The intrinsic flexibility of disordered proteins and of N-glycans makes it difficult to apply experimental structural biology approaches to probe the molecular mechanisms of how the order-to-disorder transition and N-glycosylation can modulate HA binding by HABD. We review recent results from molecular dynamics simulations that provide atomic-resolution mechanistic understanding of such modulation to help bridge gaps between existing experimental binding and structural biology data. Findings from these simulations include: Tyr42 may function as a molecular switch that converts the HA binding site from a low affinity to a high affinity state; in the partially-disordered form of HABD, basic amino acids in the C-terminal region can gain sufficient mobility to form direct contacts with bound HA to further stabilize binding; and terminal sialic acids on covalently-attached N-glycans can form charge-paired hydrogen bonding interactions with basic amino acids that could otherwise bind to HA, thereby blocking HA binding to glycosylated CD44 HABD.

A Micro-Grid Simulator Tool (SGridSim) using Effective Node-to-Node Complex Impedance (EN2NCI) Models

Energy Technology Data Exchange (ETDEWEB)

Udhay Ravishankar; Milos manic

2013-08-01

This paper presents a micro-grid simulator tool useful for implementing and testing multi-agent controllers (SGridSim). As a common engineering practice it is important to have a tool that simplifies the modeling of the salient features of a desired system. In electric micro-grids, these salient features are the voltage and power distributions within the micro-grid. Current simplified electric power grid simulator tools such as PowerWorld, PowerSim, Gridlab, etc, model only the power distribution features of a desired micro-grid. Other power grid simulators such as Simulink, Modelica, etc, use detailed modeling to accommodate the voltage distribution features. This paper presents a SGridSim micro-grid simulator tool that simplifies the modeling of both the voltage and power distribution features in a desired micro-grid. The SGridSim tool accomplishes this simplified modeling by using Effective Node-to-Node Complex Impedance (EN2NCI) models of components that typically make-up a micro-grid. The term EN2NCI models means that the impedance based components of a micro-grid are modeled as single impedances tied between their respective voltage nodes on the micro-grid. Hence the benefit of the presented SGridSim tool are 1) simulation of a micro-grid is performed strictly in the complex-domain; 2) faster simulation of a micro-grid by avoiding the simulation of detailed transients. An example micro-grid model was built using the SGridSim tool and tested to simulate both the voltage and power distribution features with a total absolute relative error of less than 6%.

Microstructure, mechanical properties, in vitro degradation and cytotoxicity evaluations of Mg-1.5Y-1.2Zn-0.44Zr alloys for biodegradable metallic implants.

Science.gov (United States)

Fan, Jun; Qiu, Xin; Niu, Xiaodong; Tian, Zheng; Sun, Wei; Liu, Xiaojuan; Li, Yangde; Li, Weirong; Meng, Jian

2013-05-01

Mg-1.5Y-1.2Zn-0.44Zr alloys were newly developed as degradable metallic biomaterials. A comprehensive investigation of the microstructure, mechanical properties, in vitro degradation assessments and in vitro cytotoxicity evaluations of the as-cast state, as-heat treated state and as-extruded state alloys was done. The microstructure observations show that the Mg-1.5Y-1.2Zn-0.44Zr alloys are mainly composed of the matrix α-Mg phases and the Mg12ZnY secondary phases (LPS structure). The hot extrusion method significantly refined the grains and eliminated the defects of both as-cast and heat treated alloys and thereby contributed to the better mechanical properties and biodegradation resistance. The values of tensile strength and tensile yield strength of the alloy in the as-extruded condition are about 236 and 178 MPa respectively, with an excellent elongation of 28%. Meanwhile, the value of compressive strength is about 471 MPa and the value of bending strength is about 501 MPa. The superior bending strength further demonstrates the excellent ductility of the hot extruded alloys. The results of immersion tests and electrochemical measurements in the SBF indicate that a protective film precipitated on the alloy's surface with the extension of degradation. The protective film contains Mg(OH)2 and hydroxyapatite (HA) which can reinforce osteoblast activity and promote good biocompatibility. No significant cytotoxicity towards L-929 cells was detected and the immersion extracts of alloy samples could enhance the cell proliferation with time in the cytotoxicity evaluations, implying that the Mg-1.5Y-1.2Zn-0.44Zr alloys have the potential to be used for biomedical applications. Copyright © 2013 Elsevier B.V. All rights reserved.

The utilization of websites for fundraising by NCI-designated cancer centers: Examining the capacity for dialogic communication with prospective donors.

Science.gov (United States)

Erwin, Cathleen O; Dias, Ashley M

2016-01-01

The study employs a dialogic public relations framework to explore the utilization of the Internet for fundraising by nonprofit health care organizations-specifically, NCI-designated cancer centers. Cancer centers have been noted for effective websites and for being highly engaged in fundraising, which is characterized as relationship marketing. Results indicate all but one cancer center use websites and social media for fundraising but are limited in capacity for two-way symmetrical dialogue. Results are discussed and recommendations are made for future research.

Detecting Role Errors in the Gene Hierarchy of the NCI Thesaurus

Directory of Open Access Journals (Sweden)

Yehoshua Perl

2008-01-01

Full Text Available Gene terminologies are playing an increasingly important role in the ever-growing field of genomic research. While errors in large, complex terminologies are inevitable, gene terminologies are even more susceptible to them due to the rapid growth of genomic knowledge and the nature of its discovery. It is therefore very important to establish quality- assurance protocols for such genomic-knowledge repositories. Different kinds of terminologies oftentimes require auditing methodologies adapted to their particular structures. In light of this, an auditing methodology tailored to the characteristics of the NCI Thesaurus’s (NCIT’s Gene hierarchy is presented. The Gene hierarchy is of particular interest to the NCIT’s designers due to the primary role of genomics in current cancer research. This multiphase methodology focuses on detecting role-errors, such as missing roles or roles with incorrect or incomplete target structures, occurring within that hierarchy. The methodology is based on two kinds of abstraction networks, called taxonomies, that highlight the role distribution among concepts within the IS-A (subsumption hierarchy. These abstract views tend to highlight portions of the hierarchy having a higher concentration of errors. The errors found during an application of the methodology

Generation of insulin-producing cells from rat mesenchymal stem cells using an aminopyrrole derivative XW4.4.

Science.gov (United States)

Ouyang, Jingfeng; Huang, Wei; Yu, Wanwan; Xiong, Wei; Mula, Ramanjaneya V R; Zou, Hongbin; Yu, Yongping

2014-02-05

Type 1 diabetes mellitus (T1DM), a multisystem disease with both biochemical and anatomical/structural consequences, is a major health concern worldwide. Pancreatic islet transplantation provides a promising treatment for T1DM. However, the limited availability of islet tissue or new sources of insulin producing cells (IPCs) that are responsive to glucose hinder this promising approach. Though slow, the development of pancreatic beta-cell lines from rodent or human origin has been steadily progressing. Bone marrow-derived mesenchymal stem cells (MSCs) are multipotent, culture-expanded, non-hematopoietic cells that are currently being investigated as a novel cellular therapy. The in vitro differentiation potential of IPCs has raised hopes for a treatment of clinical diseases associated with autoimmunity. We screened for small molecules that induce pancreatic differentiation of IPCs. There are some compounds which showed positive effects on the DTZ staining. The aminopyrrole derivative compound XW4.4 which shows the best activity among them was found to induce pancreatic differentiation of rat MSCs (rMSCs). The in vitro studies indicated that treatment of rMSCs with compound XW4.4 resulted in differentiated cells with characteristics of IPCs including islet-like clusters, spherical, grape-like morphology, insulin secretion, positive for dithizone, glucose stimulation and expression of pancreatic endocrine cell marker genes. The data has also suggested that hepatocyte nuclear factor 3β (HNF 3β) may be involved in pancreatic differentiation of rMSCs when treated with XW4.4. Results indicate that XW4.4 induced rMSCs support the efforts to derive functional IPCs and serve as a means to alleviate limitations surrounding islet cell transplantation in the treatment of T1DM. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Lung cancer tumorigenicity and drug resistance are maintained through ALDH(hi)CD44(hi) tumor initiating cells.

Science.gov (United States)

Liu, Jing; Xiao, Zhijie; Wong, Sunny Kit-Man; Tin, Vicky Pui-Chi; Ho, Ka-Yan; Wang, Junwen; Sham, Mai-Har; Wong, Maria Pik

2013-10-01

Limited improvement in long term survival of lung cancer patients has been achieved by conventional chemotherapy or targeted therapy. To explore the potentials of tumor initiating cells (TIC)-directed therapy, it is essential to identify the cell targets and understand their maintenance mechanisms. We have analyzed the performance of ALDH/CD44 co-expression as TIC markers and treatment targets of lung cancer using well-validated in vitro and in vivo analyses in multiple established and patient-derived lung cancer cells. The ALDH(hi)CD44(hi) subset showed the highest enhancement of stem cell phenotypic properties compared to ALDH(hi)CD44(lo), ALDH(lo)CD44(hi), ALDH(lo)CD44(lo) cells and unsorted controls. They showed higher invasion capacities, pluripotency genes and epithelial-mesenchymal transition transcription factors expression, lower intercellular adhesion protein expression and higher G2/M phase cell cycle fraction. In immunosuppressed mice, the ALDH(hi)CD44(hi)xenografts showed the highest tumor induction frequency, serial transplantability, shortest latency, largest volume and highest growth rates. Inhibition of sonic Hedgehog and Notch developmental pathways reduced ALDH+CD44+ compartment. Chemotherapy and targeted therapy resulted in higher AALDH(hi)CD44(hi) subset viability and ALDH(lo)CD44(lo) subset apoptosis fraction. ALDH inhibition and CD44 knockdown led to reduced stemness gene expression and sensitization to drug treatment. In accordance, clinical lung cancers containing a higher abundance of ALDH and CD44-coexpressing cells was associated with lower recurrence-free survival. Together, results suggested theALDH(hi)CD44(hi)compartment was the cellular mediator of tumorigenicity and drug resistance. Further investigation of the regulatory mechanisms underlying ALDH(hi)CD44(hi)TIC maintenance would be beneficial for the development of long term lung cancer control.

Incidència i consequències de les caigudes en les persones grans que viuen a la comunitat

OpenAIRE

Salvà, Antoni

2016-01-01

ANTECEDENTS I OBJECTIUS: Avaluar la incidència de les caigudes en funció dels factors sociodemogràfics i de salut, i determinar llurs conseqüències físiques, psicològiques i socials. Desenvolupar una nova eina d'avaluació del factor de risc amb l'objectiu d'assolir una intervenció preventiva multifactorial. METODOLOGIA: Estudi poblacional prospectiu, que inclou una cohort representativa de 448 persones grans, de 65 anys o més, que viuen a la ciutat de Mataró (Espanya). Hem fet una avaluació b...

Endoplasmic reticulum stress increases AT1R mRNA expression via TIA-1-dependent mechanism.

Science.gov (United States)

Backlund, Michael; Paukku, Kirsi; Kontula, Kimmo K; Lehtonen, Jukka Y A

2016-04-20

As the formation of ribonucleoprotein complexes is a major mechanism of angiotensin II type 1 receptor (AT1R) regulation, we sought to identify novel AT1R mRNA binding proteins. By affinity purification and mass spectroscopy, we identified TIA-1. This interaction was confirmed by colocalization of AT1R mRNA and TIA-1 by FISH and immunofluorescence microscopy. In immunoprecipitates of endogenous TIA- 1, reverse transcription-PCR amplified AT1R mRNA. TIA-1 has two binding sites within AT1R 3'-UTR. The binding site proximal to the coding region is glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-dependent whereas the distal binding site is not. TIA-1 functions as a part of endoplasmic reticulum (ER) stress response leading to stress granule (SG) formation and translational silencing. We and others have shown that AT1R expression is increased by ER stress-inducing factors. In unstressed cells, TIA-1 binds to AT1R mRNA and decreases AT1R protein expression. Fluorescence microscopy shows that ER stress induced by thapsigargin leads to the transfer of TIA-1 to SGs. In FISH analysis AT1R mRNA remains in the cytoplasm and no longer colocalizes with TIA-1. Thus, release of TIA-1-mediated suppression by ER stress increases AT1R protein expression. In conclusion, AT1R mRNA is regulated by TIA-1 in a ER stress-dependent manner. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Transfer reaction measurements and the stellar nucleosynthesis of 26Al and 44Ti

CERN Document Server

AUTHOR|(CDS)2086831

Progress in the description of stellar evolution is driven by the collaborative effort of nuclear physics, astrophysics and astronomy. Using those developments, the theory of the origin of elements in the Universe is challenged. This thesis addresses the problem behind the abundance of 44Ti and the origin of 26Al. The mismatch between the predicted abundance of 44Ti as produced by the only sites known to be able to create 44Ti, core collapse supernovae (CCSNe), and the observations, highlight the current uncertainty that exists in the physics of these stars. Several satellite based gamma-ray observations of the isotope 44Ti have been reported in recent times and conrm the disagreement. As the amount of this isotope in stellar ejecta is thought to critically depend on the explosion mechanism, the ability to accurately model the observed abundance would be a pivotal step towards validating that theory. The most in influential reaction to the amount of 44Ti in supernovae is 44Ti(alpha, p)47V. Here we report on a...

Cocrystals of kaempferol, quercetin and myricetin with 4,4‧-bipyridine: Crystal structures, analyses of intermolecular interactions and antibacterial properties

Science.gov (United States)

Zhang, Yu-Nan; Yin, He-Mei; Zhang, Yu; Zhang, Da-Jun; Su, Xin; Kuang, Hai-Xue

2017-02-01

With an aim to explore the interactions of Osbnd H⋯N between hydroxyl moiety of the flavonoids and the pyridyl ring of N-containing aromatic amines, three flavonols with varying B-ring-hydroxyl groups (kaempferol, quercetin, and myricetin) were selected to combine with 4,4‧-bipyridine. As a result, three new cocrystals of flavonols were obtained with a solution evaporation approach. These three cocrystals were characterized by single crystal X-ray diffraction, XPRD, IR and NMR methods. The resulting cocrystals were kaempferol: 4,4‧-bipyridine (2:1) (KAE·BPY·2H2O), quercetin: 4,4‧-bipyridine (1:1.5) (QUE·BPY), and myricetin: 4,4‧-bipyridine (1:2) (MYR·BPY·H2O). Structural analyses show that an array of hydrogen bonds and π-π stacking interactions interconnect the molecules to form a two-dimensional (2D) supramolecular layer in KAE·BPY·2H2O, QUE·BPY, and MYR·BPY·H2O. In the three cocrystals, they present as three different synthons-ⅠR88(58), Ⅳ R44(42) and, Ⅶ R66(29) with 4,4‧-bipyridine, respectively-which may yield a strategy for constructing the supramolecule. Cocrystals of flavonols combined with N-containing aromatic amines, 7-OH, B-ring-hydroxyl number and/or the location of the flavonols to play a significant part in extending the dimensionality of the cocrystals. The resulting motif formation and crystal packing in these flavonols cocrystals has combined with N-containing aromatic amines. Additionally, the antibacterial properties of the three cocrystals against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) have been investigated.

Immunohistochemical expression of CD44s in human neuroblastic tumors: Moroccan experience and highlights on current data

Science.gov (United States)

2013-01-01

�cembre 2010, a été réalisé. Résultats Nos résultats ont mis en évidence l’association des TNPs n’exprimant pas le CD44s avec une perte de différenciation et une progression tumorale et nous avons rapporté une association significative entre l’absence d’expression du CD44s et la présence de métastases. Nous avons également constaté que l’expression du CD44s définit des sous-groupes de patients dans les tumeurs n’amplifiant pas le MYCN, comme en témoigne son association avec les stades INSS bas, l’absence de métastases et l’histologie favorable de Shimada. Discussion Ces résultats appuient l’hypothèse du rôle de la glycoprotéine CD44s dans le potentiel de croissance invasive des cellules néoplasiques et suggèrent que son expression pourrait être prise en considération dans des voies thérapeutiques ciblant les métastases. PMID:23445749

Clinical relevance of microRNA miR-21, miR-31, miR-92a, miR-101, miR-106a and miR-145 in colorectal cancer

International Nuclear Information System (INIS)

Schee, Kristina; Boye, Kjetil; Abrahamsen, Torveig Weum; Fodstad, Øystein; Flatmark, Kjersti

2012-01-01

MicroRNAs (miRNAs) regulate gene expression by binding to mRNA, and can function as oncogenes or tumor suppressors depending on the target. In this study, using qRT-PCR, we examined the expression of six miRNAs (miR-21, miR-31, miR-92a, miR-101, miR-106a and miR-145) in tumors from 193 prospectively recruited patients with colorectal cancer, and associations with clinicopathological parameters and patient outcome were analyzed. The miRNAs were chosen based on previous studies for their biomarker potential and suggested biological relevance in colorectal cancer. The miRNA expression was examined by qRT-PCR. Associations between miRNA expression and clinicopathological variables were explored using Mann–Whitney U and Kruskal-Wallis test while survival was estimated using the Kaplan-Meier method and compared using the log-rank test. MiR-101 was hardly expressed in the tumor samples, while for the other miRNAs, variable expression levels and expression ranges were observed, with miR-21 being most abundantly expressed relative to the reference (RNU44). In our study cohort, major clinical significance was demonstrated only for miR-31, as high expression was associated with advanced tumor stage and poor differentiation. No significant associations were found between expression of the investigated miRNAs and metastasis-free or overall survival. Investigating the expression of six miRNAs previously identified as candidate biomarkers in colorectal cancer, few clinically relevant associations were detected in our patient cohort. Our results emphasize the importance of validating potential tumor markers in independent patient cohorts, and indicate that the role of miRNAs as colorectal cancer biomarkers is still undetermined

CD44-engineered mesoporous silica nanoparticles for overcoming multidrug resistance in breast cancer

International Nuclear Information System (INIS)

Wang, Xin; Liu, Ying; Wang, Shouju; Shi, Donghong; Zhou, Xianguang; Wang, Chunyan; Wu, Jiang; Zeng, Zhiyong; Li, Yanjun; Sun, Jing; Wang, Jiandong; Zhang, Longjiang; Teng, Zhaogang; Lu, Guangming

2015-01-01

Graphical abstract: - Highlights: • CD44-engineered mesoporous silica nanoparticles are synthesized. • The mechanism of CD44-engineered mesoporous silica nanoparticles is revealed. • This new delivery system increased the drug accumulation in vitro and in vivo. • This new delivery system offers an effective approach to treat multidrug resistance. - Abstract: Multidrug resistance is a major impediment for the successful chemotherapy in breast cancer. CD44 is over-expressed in multidrug resistant human breast cancer cells. CD44 monoclonal antibody exhibits anticancer potential by inhibiting proliferation and regulating P-glycoprotein-mediated drug efflux activity in multidrug resistant cells. Thereby, CD44 monoclonal antibody in combination with chemotherapeutic drug might be result in enhancing chemosensitivity and overcoming multidrug resistance. The purpose of this study is to investigate the effects of the CD44 monoclonal antibody functionalized mesoporous silica nanoparticles containing doxorubicin on human breast resistant cancer MCF-7 cells. The data showed that CD44-modified mesoporous silica nanoparticles increased cytotoxicity and enhanced the downregulation of P-glycoprotein in comparison to CD44 antibody. Moreover, CD44-engineered mesoporous silica nanoparticles provided active target, which promoted more cellular uptake of DOX in the resistant cells and more retention of DOX in tumor tissues than unengineered counterpart. Animal studies of the resistant breast cancer xenografts demonstrated that CD44-engineered drug delivery system remarkably induced apoptosis and inhibited the tumor growth. Our results indicated that the CD44-engineered mesoporous silica nanoparticle-based drug delivery system offers an effective approach to overcome multidrug resistance in human breast cancer

LFI 30 and 44 GHz receivers Back-End Modules

International Nuclear Information System (INIS)

Artal, E; Aja, B; Fuente, M L de la; Pascual, J P; Mediavilla, A; Martinez-Gonzalez, E; Pradell, L; Paco, P de; Bara, M; Blanco, E; GarcIa, E; Davis, R; Kettle, D; Roddis, N; Wilkinson, A; Bersanelli, M; Mennella, A; Tomasi, M; Butler, R C; Cuttaia, F

2009-01-01

The 30 and 44 GHz Back End Modules (BEM) for the Planck Low Frequency Instrument are broadband receivers (20% relative bandwidth) working at room temperature. The signals coming from the Front End Module are amplified, band pass filtered and finally converted to DC by a detector diode. Each receiver has two identical branches following the differential scheme of the Planck radiometers. The BEM design is based on MMIC Low Noise Amplifiers using GaAs P-HEMT devices, microstrip filters and Schottky diode detectors. Their manufacturing development has included elegant breadboard prototypes and finally qualification and flight model units. Electrical, mechanical and environmental tests were carried out for the characterization and verification of the manufactured BEMs. A description of the 30 and 44 GHz Back End Modules of Planck-LFI radiometers is given, with details of the tests done to determine their electrical and environmental performances. The electrical performances of the 30 and 44 GHz Back End Modules: frequency response, effective bandwidth, equivalent noise temperature, 1/f noise and linearity are presented.

La colección ibero-balear de Meloidae Gyllenhal, 1810 (Coleoptera, Tenebrionoidea del Museu de Ciències Naturals de Barcelona

Directory of Open Access Journals (Sweden)

Prieto, M.

2016-12-01

Full Text Available The Ibero-Balearic collection of Meloidae Gyllenhal, 1810 (Coleoptera, Tenebrionoidea of the Museu de Ciències Naturals de Barcelona A commented catalogue of the Ibero-Balearic collection of Meloidae Gyllenhal, 1810 housed in the Museu de Ciències Naturals de Barcelona is presented. The studied material consists of 2,129 specimens belonging to 49 of 64 species from the Iberian peninsula and the Balearic Islands. The temporal coverage of the collection extends from the last decades of the nineteenth century to the present time. Revision, documentation, and computerization of the material have been made, resulting in 963 collection records (June 2014. For each lot, the catalogue includes the register number, geographical data, collection date, collector or origin of the collection, and number of specimens. Information about taxonomy and distribution of the species is also given. Chorological novelties are provided, extending the distribution areas for most species. The importance of the collection for the knowledge of the Ibero-Balearic fauna of Meloidae is discussed, particularly concerning the area of Catalonia (northeastern Iberian peninsula as it accounts for 60% of the records. Some rare or particularly interesting species in the collection are highlighted, as are those requiring protection measures in Spain and Catalonia. The catalogue also shows a brief gallery of photographs that includes four type specimens.

CdS decorated rGO containing PVDF electrospun fiber based piezoelectric nanogenerator for mechanical energy harvesting application

Science.gov (United States)

Roy, Krittish; Mandal, Dipankar

2018-04-01

In this work, we demonstrate a simple and facile route ofcadmium sulfide (CdS) nanoparticle (NPs) grafted reduced graphene oxide (rGO) synthesis. It is found that a pinch (0.25 wt%) of as synthesisedCdS/rGOnanocompositecan induce more than 90% of electroactive phases in the electrospunpoly(vinylidene fluoride) (PVDF) nanofiber. Moreover, CdS/rGO nanocomposite doped PVDF nanofiber based nanogenerator (NG) can generate an output voltage of approximately 4 V upon repetitive finger imparting. Thus, the NG can be used as a mechanical energy harvester and power source for portable electronic and optoelectronic wearable devices.

Effects of CD44 Ligation on Signaling and Metabolic Pathways in Acute Myeloid Leukemia

KAUST Repository

Madhoun, Nour Y.

2017-04-01

Acute myeloid leukemia (AML) is characterized by a blockage in the differentiation of myeloid cells at different stages. CD44-ligation using anti-CD44 monoclonal antibodies (mAbs) has been shown to reverse the blockage of differentiation and to inhibit the proliferation of blasts in most AML-subtypes. However, the molecular mechanisms underlying this property have not been fully elucidated. Here, we sought to I) analyze the effects of anti-CD44 mAbs on downstream signaling pathways, including the ERK1/2 (extracellular signal-regulated kinase 1 and 2) and mTOR (mammalian target of rapamycin) pathways and II) use state-of-the-art Nuclear Magnetic Resonance (NMR) technology to determine the global metabolic changes during differentiation induction of AML cells using anti-CD44 mAbs and other two previously reported differentiation agents. In the first objective (Chapter 4), our studies provide evidence that CD44-ligation with specific mAbs in AML cells induced an increase in ERK1/2 phosphorylation. The use of the MEK inhibitor (U0126) significantly inhibited the CD44-induced differentiation of HL60 cells, suggesting that ERK1/2 is critical for the CD44-triggered differentiation in AML. In addition, this was accompanied by a marked decrease in the phosphorylation of the mTORC1 and mTORC2 complexes, which are strongly correlated with the inhibition of the PI3K/Akt pathway. In the second objective (Chapter 5), 1H NMR experiments demonstrated that considerable changes in the metabolic profiles of HL60 cells were induced in response to each differentiation agent. These most notable metabolites that significantly changed upon CD44 ligation were involved in the tricarboxylic acid (TCA) cycle and glycolysis such as, succinate, fumarate and lactate. Therefore, we sought to analyze the mechanisms underlying their alterations. Our results revealed that anti-CD44 mAbs treatment induced upregulation in fumarate hydratase (FH) expression and its activity which was accompanied by a

Spectroscopic study of the extremely fast rotating star 44 Geminorum

Czech Academy of Sciences Publication Activity Database

Iliev, L.; Vennes, Stephane; Kawka, Adela; Kubát, Jiří; Németh, Péter; Borisov, G.; Kraus, Michaela

2012-01-01

Roč. 18, č. 12012 (2012), s. 20-28 ISSN 1313-2709 R&D Projects: GA AV ČR(CZ) IAA300030908; GA AV ČR IAA301630901; GA ČR GAP209/10/0967 Institutional support: RVO:67985815 Keywords : Be stars * emission line * fundamental parameter Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics

miR126-5p down-regulation facilitates axon degeneration and NMJ disruption via a non-cell-autonomous mechanism in ALS.

Science.gov (United States)

Maimon, Roy; Ionescu, Ariel; Bonnie, Avichai; Sweetat, Sahar; Wald-Altman, Shane; Inbar, Shani; Gradus, Tal; Trotti, Davide; Weil, Miguel; Behar, Oded; Perlson, Eran

2018-05-17

Axon degeneration and disruption of neuromuscular junctions (NMJs) are key events in Amyotrophic Lateral Sclerosis (ALS) pathology. Although the disease's etiology is not fully understood, it is thought to involve a non-cell-autonomous mechanism and alterations in RNA metabolism. Here, we identified reduced levels of miR-126-5p in pre-symptomatic ALS male mice models, and an increase in its targets: axon destabilizing type-3 Semaphorins and their co-receptor Neuropilins. Utilizing compartmentalized in vitro co-cultures, we demonstrated that myocytes expressing diverse ALS-causing mutations promote axon degeneration and NMJ dysfunction, which were inhibited by applying Neuropilin1 (NRP1) blocking antibody. Finally, overexpressing miR126-5p is sufficient to transiently rescue axon degeneration and NMJ disruption both in vitro and in vivo Thus, we demonstrate a novel mechanism underlying ALS pathology, in which alterations in miR126-5p facilitate a non-cell-autonomous mechanism of motor neuron degeneration in ALS. SIGNIFICANCE STATEMENT In spite of some progress, currently no effective treatment is available for ALS. We suggest a novel regulatory role for miR126-5p in ALS and demonstrate for the first time a mechanism by which alterations in miR126-5p contribute to axon degeneration and NMJ disruption observed in ALS. We show that miR126-5p is altered in ALS models and that it can modulate Sema3 and NRP protein expression. Furthermore, NRP1 elevations in motor neurons and muscle secretion of Sema3A contribute to axon degeneration and NMJ disruption in ALS. Finally, overexpressing miR126-5p is sufficient to transiently rescue NMJ disruption and axon degeneration both in vitro and in vivo. Copyright © 2018 Maimon et al.

Experimental investigation on transformation, reorientation and plasticity of Ni47Ti44Nb9 SMA under biaxial thermal–mechanical loading

International Nuclear Information System (INIS)

Chen, Xiang; Peng, Xianghe; Chen, Bin; Han, Jia; Zeng, Zhongmin; Hu, Ning

2015-01-01

The constitutive behavior of shape memory alloy (SMA) Ni 47 Ti 44 Nb 9 specimens subjected to different thermal–mechanical loading histories was investigated experimentally. This involved the application of strain by different proportional or non-proportional paths in the biaxial ϵ−γ plane at −60 °C (M s + 30 °C), the interaction between stress-induced martensitic transformation, reorientation and plastic deformation, temperature-induced reverse martensitic transformation and strain recovery. The results show that the equivalent stress–strain curves, as well as the pure shear and pure tensile curves, depend strongly on the thermal–mechanical loading history. For specimens deformed previously to the same equivalent strains by different paths, the equivalent recovery strains after unloading are similar, as are the spans between the reverse transformation start and final temperatures. The activated martensite variants depend strongly on loading history. The recovery of the axial strain component and that of the shear strain component due to reverse transformation occur synchronously and develop along the shortest path in the ϵ−γ plane. The results may provide some new and useful information on the effects of transformation, plasticity and loading paths for further studies and applications of such materials. (paper)

Diversity of off-shell twisted (4,4) multiplets in SU(2)xSU(2) harmonic superspace

International Nuclear Information System (INIS)

Ivanov, E.A.; Sutulin, A.O.

2004-01-01

We elaborate on four different types of twisted N=(4,4) supermultiplets in the SU(2)xSU(2), 2D harmonic superspace. In the conventional N=(4,4), 2D superspace they are described by the superfields q ia , q Ia , q IA , subjected to proper differential constraints, (i, I, a, A) being the doublet indices of four groups SU(2) which form the full R-symmetry group SO(4) L xSO(4) R of N=(4,4) supersymmetry. We construct the torsionful off-shell sigma-model actions for each type of these multiplets, as well as the corresponding invariant mass terms, in an analytic subspace of the SU(2)xSU(2) harmonic superspace. As an instructive example, N=(4,4) superconformal extension of the SU(2)xU(1) WZNW sigma-model action and its massive deformation are presented for the multiplet q iA . We prove that N=(4,4) supersymmetry requires the general sigma-model action of pair of different multiplets to split into a sum of sigma-model actions of each multiplet. This phenomenon also persists if a larger number of non-equivalent multiplets are simultaneously included. We show that different multiplets may interact with each other only through mixed mass terms which can be set up for multiplets belonging to 'self-dual' pairs (q ia , q IA ) and (q Ia , q iA ). The multiplets from different pairs cannot interact at all. For a 'self-dual' pair of the twisted multiplets we give the most general form of the on-shell scalar potential

Bibliography of Soviet Laser Developments, Number 44 November - December 1979.

Science.gov (United States)

1980-08-13

from quantum noise. Acta physica polonica , v. A44, no. 6, 1979, 945-948. (RZhF, 11/79, 1ID1396) 196. Izraylev, F.M., and D.L. Shepelyanskiy (79...thermodynamics for matter plus radiation system with quadrupole interactions. Acta physica polonica , v. A55, no. 3, 1979, 413-417. (RZhF, 11/79...PSS (PSSAB) Physica Status Solidi (A). Applied Research (PSSBB) Physica Status Solidi (B). Basic Research r£i. (PRTEA) Pribory i tekhnika eksperimenta

Measurement of the $^{44}$Ti($\\alpha$,p)$^{47}$V reaction cross section, of relevance to $\\gamma$-ray observation of core collapse supernovae, using reclaimed $^{44}$Ti

CERN Multimedia

Despite decades of research, fundamental uncertainties remain in the underlying explosion mechanism of core collapse supernovae. One of the most direct methods that might help resolve this problem is a comparison of the predicted to the observed flux of $\\gamma$-rays due to decay of $^{44}$Ti produced in the explosion, as it is believed this could reveal the location of the mass cut, a key hydrodynamical property of the explosion. Such a study is at present limited by the uncertainty in the $^{44}$Ti($\\alpha$,p)$^{47}$V reaction rate. In this experiment we propose to measure the cross section for this reaction at astrophysically relevant energies. The single previous measurement of this reaction was limited to higher energies due to low beam intensities. Here, a more intense beam will be employed, generated from $^{44}$Ti reclaimed as part of the ERAWAST project at PSI.

Using the Principles of F.A.I.R Data to Improve the Measure of Value of Big Data and Big Data Repositories

Science.gov (United States)

Richards, C. J.; Wyborn, L. A.; Evans, B. J. K.; Wang, J.; Druken, K. A.; Smillie, J.; Pringle, S.

2017-12-01

In a data-intensive world, finding the right data can be time-consuming and, when found, may involve compromises on quality and often considerable extra effort to wrangle it into shape. This is particularly true as users are exploring new and innovative ways of working with data from different sources and scientific domains. It is recognised that the effort and specialist knowledge required to transform datasets to meet these requirements goes beyond the reasonable remit of a single research project or research community. Instead, Government investments in national collaborations like the Australian National University's National Computational Infrastructure (NCI), provide a sustainable way to bring together and transform disparate data collections from a range of disciplines in ways which enable new and innovative analysis and use. With these goals in mind, the NCI established a Data Quality Strategy (DQS) for managing 10PB of reference data collections with a particular focus on improving data use and reuse across scientific domains, making the data suitable for use in a high-end computational and data-intensive environment, and supporting programmatic access for a range of applications. Evaluating how effectively we're achivieving these goals and maintaining ongoing funding requires demonstration of the value and impact of these data collections. Standard approaches to measuring data value involve basic measures of `data usage' or make an attempt to track data to `research outcomes'. While useful, these measures fail to capture the value of the level of curation or quality assurance in making the data available. To fill this gap, NCI has developed a 3-tiered approach to measuring the return on investment which broadens the concept of value to include improvements in access to and use of the data. Key to this approach was integrating the guiding principles of the Force 11 community's F.A.I.R data into the DQS because it provides a community-driven standards

Detection of high CD44 expression in oral cancers using the novel monoclonal antibody, C44Mab-5

Directory of Open Access Journals (Sweden)

Shinji Yamada

2018-07-01

Full Text Available CD44 is a transmembrane glycoprotein that regulates a variety of genes related to cell-adhesion, migration, proliferation, differentiation, and survival. A large number of alternative splicing isoforms of CD44, containing various combinations of alternative exons, have been reported. CD44 standard (CD44s, which lacks variant exons, is widely expressed on the surface of most tissues and all hematopoietic cells. In contrast, CD44 variant isoforms show tissue-specific expression patterns and have been extensively studied as both prognostic markers and therapeutic targets in cancer and other diseases. In this study, we immunized mice with CHO-K1 cell lines overexpressing CD44v3-10 to obtain novel anti-CD44 mAbs. One of the clones, C44Mab-5 (IgG1, kappa, recognized both CD44s and CD44v3-10. C44Mab-5 also reacted with oral cancer cells such as Ca9-22, HO-1-u-1, SAS, HSC-2, HSC-3, and HSC-4 using flow cytometry. Moreover, immunohistochemical analysis revealed that C44Mab-5 detected 166/182 (91.2% of oral cancers. These results suggest that the C44Mab-5 antibody may be useful for investigating the expression and function of CD44 in various cancers.

Detection of high CD44 expression in oral cancers using the novel monoclonal antibody, C44Mab-5.

Science.gov (United States)

Yamada, Shinji; Itai, Shunsuke; Nakamura, Takuro; Yanaka, Miyuki; Kaneko, Mika K; Kato, Yukinari

2018-07-01

CD44 is a transmembrane glycoprotein that regulates a variety of genes related to cell-adhesion, migration, proliferation, differentiation, and survival. A large number of alternative splicing isoforms of CD44, containing various combinations of alternative exons, have been reported. CD44 standard (CD44s), which lacks variant exons, is widely expressed on the surface of most tissues and all hematopoietic cells. In contrast, CD44 variant isoforms show tissue-specific expression patterns and have been extensively studied as both prognostic markers and therapeutic targets in cancer and other diseases. In this study, we immunized mice with CHO-K1 cell lines overexpressing CD44v3-10 to obtain novel anti-CD44 mAbs. One of the clones, C 44 Mab-5 (IgG 1 , kappa), recognized both CD44s and CD44v3-10. C 44 Mab-5 also reacted with oral cancer cells such as Ca9-22, HO-1-u-1, SAS, HSC-2, HSC-3, and HSC-4 using flow cytometry. Moreover, immunohistochemical analysis revealed that C 44 Mab-5 detected 166/182 (91.2%) of oral cancers. These results suggest that the C 44 Mab-5 antibody may be useful for investigating the expression and function of CD44 in various cancers.

48 CFR 44.307 - Reports.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Reports. 44.307 Section 44... SUBCONTRACTING POLICIES AND PROCEDURES Contractors' Purchasing Systems Reviews 44.307 Reports. The ACO shall distribute copies of CPSR reports; notifications granting, withholding, or withdrawing system approval; and...

The intensity of non-target site mechanisms influences the level of resistance of sourgrass to glyphosate

Directory of Open Access Journals (Sweden)

Flávia Regina da Costa

2014-02-01

Full Text Available Non-target site mechanisms are involved in the resistance of sourgrass (Digitaria insularis to glyphosate. Studies on the 14C-glyphosate absorption and translocation as well as the detection of glyphosate and its metabolites in sourgrass plants were carried out under controlled conditions to investigate if the differential response of resistant sourgrass biotypes (R1 and R2 is derived from the intensity of non-target site mechanisms involved in the resistance to glyphosate. Different pattern of absorption was observed between S (susceptible and R2 from 12 up to 48 hours after treatment with glyphosate (HAT, and between S and R1 just at 12 HAT. The initial difference in glyphosate absorption among the biotypes did not maintained at 96 HAT and afterwards. Smaller amount of herbicide left the treated leaf into the rest of shoot and roots in R2 (25% than in S (58% and R1 (52%. In addition, slight difference in glyphosate translocation was observed between S and R1. We found high percentage (81% of glyphosate in the S biotype up to 168 HAT, while just 44% and 2% of glyphosate was recovered from R1 and R2 plant tissues. In addition, high percentage of glyphosate metabolites was found in R2 (98% and R1 (56% biotypes, while a very low percentage (11% was found in the S biotype. As previous studies indicated resistant factors of 3.5 and 5.6 for R1 and R2, respectively, we conclude that the differential response of sourgrass biotypes is derived from the intensity of the non-target site mechanisms involved in the resistance to glyphosate.

NCI Think Tank Concerning the Identifiability of Biospecimens and “-Omic” Data

Science.gov (United States)

Weil, Carol J.; Mechanic, Leah E.; Green, Tiffany; Kinsinger, Christopher; Lockhart, Nicole C.; Nelson, Stefanie A.; Rodriguez, Laura L.; Buccini, Laura D.

2014-01-01

On June 11 and 12, 2012, the National Cancer Institute (NCI) hosted a think tank concerning the identifiability of biospecimens and “omic” Data in order to explore challenges surrounding this complex and multifaceted topic. The think tank brought together forty-six leaders from several fields, including cancer genomics, bioinformatics, human subject protection, patient advocacy, and commercial genetics. The first day involved presentations regarding the state of the science of re-identification; current and proposed regulatory frameworks for assessing identifiability; developments in law, industry and biotechnology; and the expectations of patients and research participants. The second day was spent by think tank participants in small break-out groups designed to address specific sub-topics under the umbrella issue of identifiability, including considerations for the development of best practices for data sharing and consent, and targeted opportunities for further empirical research. We describe the outcomes of this two day meeting, including two complimentary themes that emerged from moderated discussions following the presentations on Day 1, and ideas presented for further empirical research to discern the preferences and concerns of research participants about data sharing and individual identifiability. PMID:23579437

Experiències de realitat augmentada en biblioteques : estat de la qüestió

Directory of Open Access Journals (Sweden)

Arroyo Vázquez, Natalia

2016-06-01

Full Text Available Objectiu: donar a conèixer les experiències més significatives d'ús de la realitat augmentada en biblioteques, amb una especial atenció als resultats obtinguts, les aportacions i les limitacions que s'han de tenir en compte. -- Metodologia: revisió bibliogràfica, selecció i anàlisi d'experiències sobre l'ús de realitat augmentada en biblioteques. -- Resultats: tot i ser una tecnologia recent, són diversos els exemples d'ús de la realitat augmentada en biblioteques. No obstant això, es fa necessari donar a conèixer els resultats d'aquestes experiències, de manera que puguin servir no solament com a model, sinó també per conèixer què és el que funciona. Es presenta als professionals un catàleg d'usos de la realitat augmentada en biblioteques, dels quals s'analitzen de forma crítica els possibles beneficis i limitacions, i s'agrupen en set apartats segons la utilitat: geolocalització, contextualització històrica, exposicions i altres activitats, publicacions, enriquiment dels espais físics, alfabetització i ludificació i, finalment, usos professionals.Objetivo: dar a conocer las experiencias más significativas de uso de la realidad aumentada en bibliotecas, con una especial atención a los resultados obtenidos, las aportaciones y las limitaciones que se deben tener en cuenta. -- Metodología: revisión bibliográfica, selección y análisis de experiencias sobre el uso de realidad aumentada en bibliotecas. -- Resultados: a pesar de ser una tecnología reciente, son varios los ejemplos de uso de la realidad aumentada en bibliotecas. Sin embargo, se hace necesario dar a conocer los resultados de dichas experiencias, de forma que puedan servir no solo como modelo, sino también para conocer qué es lo que funciona. Se presenta a los profesionales un catálogo de usos de la realidad aumentada en bibliotecas, analizados de forma crítica sus posibles beneficios y limitaciones, agrupados en siete apartados según la utilidad

Experiències de realitat augmentada en biblioteques : estat de la qüestió

Directory of Open Access Journals (Sweden)

Arroyo Vázquez, Natalia

2016-06-01

Full Text Available Objectiu: donar a conèixer les experiències més significatives d'ús de la realitat augmentada en biblioteques, fent una especial atenció als resultats obtinguts, les aportacions i les limitacions que s'han de tenir en compte. -- Metodologia: revisió bibliogràfica, selecció i anàlisi d'experiències sobre l'ús de la realitat augmentada en biblioteques. -- Resultats: malgrat ser una tecnologia recent, els exemples d'ús de la realitat augmentada en biblioteques són diversos. No obstant això, es fa necessari donar a conèixer els resultats d'aquestes experiències, de manera que puguin servir no solament com a model, sinó també per conèixer què és el que funciona. Es presenta als professionals un catàleg d'usos de la realitat augmentada en biblioteques, dels quals s'analitzen de forma crítica els possibles beneficis i limitacions, i s'agrupen en set apartats segons la utilitat: geolocalització, contextualització històrica, exposicions i altres activitats, publicacions, enriquiment dels espais físics, alfabetització i ludificació i, finalment, usos professionals.Objetivo: dar a conocer las experiencias más significativas de uso de la realidad aumentada en bibliotecas, con una especial atención a los resultados obtenidos, las aportaciones y las limitaciones que se deben tener en cuenta. -- Metodología: revisión bibliográfica, selección y análisis de experiencias sobre el uso de la realidad aumentada en bibliotecas. -- Resultados: a pesar de ser una tecnología reciente, son varios los ejemplos de uso de la realidad aumentada en bibliotecas. Sin embargo, se hace necesario dar a conocer los resultados de dichas experiencias, de forma que puedan servir no solo como modelo, sino también para conocer qué es lo que funciona. Se presenta a los profesionales un catálogo de usos de la realidad aumentada en bibliotecas, analizados de forma crítica sus posibles beneficios y limitaciones, agrupados en siete apartados según la

An ensemble based top performing approach for NCI-DREAM drug sensitivity prediction challenge.

Directory of Open Access Journals (Sweden)

Qian Wan

Full Text Available We consider the problem of predicting sensitivity of cancer cell lines to new drugs based on supervised learning on genomic profiles. The genetic and epigenetic characterization of a cell line provides observations on various aspects of regulation including DNA copy number variations, gene expression, DNA methylation and protein abundance. To extract relevant information from the various data types, we applied a random forest based approach to generate sensitivity predictions from each type of data and combined the predictions in a linear regression model to generate the final drug sensitivity prediction. Our approach when applied to the NCI-DREAM drug sensitivity prediction challenge was a top performer among 47 teams and produced high accuracy predictions. Our results show that the incorporation of multiple genomic characterizations lowered the mean and variance of the estimated bootstrap prediction error. We also applied our approach to the Cancer Cell Line Encyclopedia database for sensitivity prediction and the ability to extract the top targets of an anti-cancer drug. The results illustrate the effectiveness of our approach in predicting drug sensitivity from heterogeneous genomic datasets.

Developing Cancer Informatics Applications and Tools Using the NCI Genomic Data Commons API.

Science.gov (United States)

Wilson, Shane; Fitzsimons, Michael; Ferguson, Martin; Heath, Allison; Jensen, Mark; Miller, Josh; Murphy, Mark W; Porter, James; Sahni, Himanso; Staudt, Louis; Tang, Yajing; Wang, Zhining; Yu, Christine; Zhang, Junjun; Ferretti, Vincent; Grossman, Robert L

2017-11-01

The NCI Genomic Data Commons (GDC) was launched in 2016 and makes available over 4 petabytes (PB) of cancer genomic and associated clinical data to the research community. This dataset continues to grow and currently includes over 14,500 patients. The GDC is an example of a biomedical data commons, which collocates biomedical data with storage and computing infrastructure and commonly used web services, software applications, and tools to create a secure, interoperable, and extensible resource for researchers. The GDC is (i) a data repository for downloading data that have been submitted to it, and also a system that (ii) applies a common set of bioinformatics pipelines to submitted data; (iii) reanalyzes existing data when new pipelines are developed; and (iv) allows users to build their own applications and systems that interoperate with the GDC using the GDC Application Programming Interface (API). We describe the GDC API and how it has been used both by the GDC itself and by third parties. Cancer Res; 77(21); e15-18. ©2017 AACR . ©2017 American Association for Cancer Research.

12 CFR 561.44 - Security.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Security. 561.44 Section 561.44 Banks and... SAVINGS ASSOCIATIONS § 561.44 Security. The term security means any non-withdrawable account, note, stock... commonly known as a security, or any certificate of interest or participation in, temporary or interim...

28 CFR 44.303 - Determination.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Determination. 44.303 Section 44.303... Enforcement Procedures § 44.303 Determination. (a) Within 120 days of the receipt of a charge, the Special... the end of the 120-day period, the Special Counsel shall issue letters of determination by certified...

Functional Differences between Human NKp44(-) and NKp44(+) RORC(+) Innate Lymphoid Cells.

Science.gov (United States)

Hoorweg, Kerim; Peters, Charlotte P; Cornelissen, Ferry; Aparicio-Domingo, Patricia; Papazian, Natalie; Kazemier, Geert; Mjösberg, Jenny M; Spits, Hergen; Cupedo, Tom

2012-01-01

Human RORC(+) lymphoid tissue inducer cells are part of a rapidly expanding family of innate lymphoid cells (ILC) that participate in innate and adaptive immune responses as well as in lymphoid tissue (re) modeling. The assessment of a potential role for innate lymphocyte-derived cytokines in human homeostasis and disease is hampered by a poor characterization of RORC(+) innate cell subsets and a lack of knowledge on the distribution of these cells in adults. Here we show that functionally distinct subsets of human RORC(+) innate lymphoid cells are enriched for secretion of IL-17a or IL-22. Both subsets have an activated phenotype and can be distinguished based on the presence or absence of the natural cytotoxicity receptor NKp44. NKp44(+) IL-22 producing cells are present in tonsils while NKp44(-) IL-17a producing cells are present in fetal developing lymph nodes. Development of human intestinal NKp44(+) ILC is a programmed event that is independent of bacterial colonization and these cells colonize the fetal intestine during the first trimester. In the adult intestine, NKp44(+) ILC are the main ILC subset producing IL-22. NKp44(-) ILC remain present throughout adulthood in peripheral non-inflamed lymph nodes as resting, non-cytokine producing cells. However, upon stimulation lymph node ILC can swiftly initiate cytokine transcription suggesting that secondary human lymphoid organs may function as a reservoir for innate lymphoid cells capable of participating in inflammatory responses.

Regulation of Rac1 GTPase activity by quinine through G-protein and bitter taste receptor T2R4.

Science.gov (United States)

Sidhu, Crystal; Jaggupilli, Appalaraju; Chelikani, Prashen; Bhullar, Rajinder P

2017-02-01

Rac1 belongs to the Rho family of small GTPases and regulates actin cytoskeleton reorganization. T2R4 is a bitter taste receptor belonging to the G protein-coupled receptor family of proteins. In addition to mediating bitter taste perception from the tongue, T2R4s are found in extra-oral tissues, e.g., nasal epithelium, airways, brain, testis suggesting a much broader physiological function for these receptors. Anti-malarial drug and a bitter tasting compound, quinine, is a known agonist for T2R4, whereas BCML (Nα,Nα-Bis(carboxymethyl)-L-lysine) acts as an inverse agonist. Using western blot and Ca ++ mobilization assays, the effects of quinine on Rac1 activity in HEK293T cells stably expressing T2R4/Gα 16/44 , T2R4, or Gα 16/44 and transiently transfected with HA-Rac1 were investigated. Quinine treatment caused a significant reduction in the amount of active Rac1, whereas in the presence of BCML, quinine failed to cause any significant change in active Rac1. No significant change in Rac1 activity was observed in BAPTA-AM plus quinine-treated Gα 16/44 cells, suggesting possibility of a pathway in addition to the canonical Ca ++ -dependent pathway. A noticeable role for Gα 16/44 independent of T2R4 is observed in quinine-mediated Rac1 inactivation. Further, a significant difference in quinine-induced Ca ++ response in T2R4/Gα 16/44 or T2R4 cells was observed validating the partial role of calcium and importance of Gα 16/44 . This study is the first to show an inhibitory downstream action of a T2R4 agonist on Rac1 function. Further investigation will help in better understanding the downstream signal transduction network of T2R4 and its extra-oral physiological roles.

19 CFR 148.44 - Gifts.

Science.gov (United States)

2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Gifts. 148.44 Section 148.44 Customs Duties U.S...) PERSONAL DECLARATIONS AND EXEMPTIONS Exemptions for Nonresidents § 148.44 Gifts. (a) Exemption. An arriving... and are to be disposed of by him as bona fide gifts. See § 148.43(b) for limitations on cigars under...

Resistance mechanisms of linezolid-nonsusceptible enterococci in Korea: low rate of 23S rRNA mutations in Enterococcus faecium.

Science.gov (United States)

Lee, Sae-Mi; Huh, Hee Jae; Song, Dong Joon; Shim, Hyang Jin; Park, Kyung Sun; Kang, Cheol-In; Ki, Chang-Seok; Lee, Nam Yong

2017-12-01

To investigate linezolid-resistance mechanisms in linezolid-nonsusceptible enterococci (LNSE) isolated from a tertiary hospital in Korea. Enterococcal isolates exhibiting linezolid MICs ≥4 mg l -1 that were isolated between December 2011 and May 2016 were investigated by PCR and sequencing for mutations in 23S rRNA or ribosomal proteins (L3, L4 and L22) and for the presence of cfr, cfr(B) and optrA genes.Results/Key findings. Among 135 LNSE (87 Enterococcus faecium and 48 Enterococcus faecalis isolates), 39.1 % (34/87) of E. faecium and 18.8 % (9/48) of E. faecalis isolates were linezolid-resistant. The optrA carriage was the dominant mechanism in E. faecalis: 13 isolates, including 10 E. faecalis [70 % (7/10) linezolid-resistant and 30 % (3/10) linezolid-intermediate] and three E. faecium [33.3 % (1/3) linezolid-resistant and 66.7 % (2/3) linezolid-intermediate], contained the optrA gene. G2576T mutations in the 23S rRNA gene were detected only in E. faecium [14 isolates; 71.4 % (10/14) linezolid-resistant and 28.6 % (4/14) linezolid-intermediate]. One linezolid-intermediate E. faecium harboured a L22 protein alteration (Ser77Thr). No isolates contained cfr or cfr(B) genes and any L3 or L4 protein alterations. No genetic mechanism of resistance was identified for 67.6 % (23/34) of linezolid-resistant E. faecium. A low rate of 23S rRNA mutations and the absence of known linezolid-resistance mechanisms in the majority of E. faecium isolates suggest regional differences in the mechanisms of linezolid resistance and the possibility of additional mechanisms.

R Aqr observing campaign

Science.gov (United States)

Waagen, Elizabeth O.

2016-01-01

Dr. George Wallerstein (University of Washington) has requested AAVSO coverage of the long period/symbiotic variable R Aquarii beginning immediately in support of high resolution spectroscopic observations planned for 2016 January 19 and 21. Several other astronomers, including Drs. Lee Anne Willson (Iowa State University), Ulisse Munari (INAF, Astronomical Observatory of Padua, Italy), and Fred Walter (Stony Brook University) are studying R Aqr closely and additional spectroscopic and other observations are planned for the near future. R Aqr is both a Mira (M) and a symbiotic (ZAND) - it is a close binary system consisting of a hot star and a late-type star (the Mira), both enveloped in nebulosity. As a result, the very interesting light curve shows not only the Mira pulsation but also complex eclipse behavior as the two stars interact. The period of Mira variation is 387.0 days; the eclipse period is 43.6-44 years. The cause of the eclipse is unknown; several theories h! ave been proposed, including a focused accretion stream, a disk or cloud around the secondary, and a triggered mass loss that produces an opaque cloud. Careful investigation of this upcoming event should help to resolve this question. The last eclipse of R Aqr was in 1978. The next eclipse is predicted for 2022, but may be early. The current behavior of R Aqr suggests that the eclipse, which lasts for several years, may either be beginning or its beginning may be imminent. R Aqr was at minimum in early December 2015 at magnitude V=11.4, and is currently at visual magnitude 11.0. During this phase of the approximately 44-year eclipse cycle, at maximum it may be as bright as V 6.0-6.5 but is not expected to become brighter. Beginning immediately, nightly BVRI CCD and DSLR photometry and visual observations are requested. As R Aqr brightens towards maximum and is in range, PEP observations are also requested. Ongoing spectroscopy over the next several years will be interesting to see as the system

Two dimensional untwisted (4,4), twisted (4,4-bar) and chiral supersymmetric non linear σ-models

International Nuclear Information System (INIS)

Lhallabi, T.; Saidi, E.H.

1987-09-01

D=2 N=(4,4) harmonic superspace analysis is developed. The underlying untwisted (4,4) non linear σ-models are studied. A method of deriving chiral (4,0) and (0,4) models is presented. The Lagrange superparameter leading to the constraint specifying the hyperkahler manifold structure is predicted and its relation to the matter superfield is stated in a covariant way. A known construction is recovered. We show also that (4,4) model is not a direct sum of the chiral ones. Finally a twisted (4,4-bar) model is obtained. (author). 28 refs

Can CD44 Be a Mediator of Cell Destruction? The Challenge of Type 1 Diabetes

Science.gov (United States)

Assayag-Asherie, Nathalie; Sever, Dror; Bogdani, Marika; Johnson, Pamela; Weiss, Talya; Ginzberg, Ariel; Perles, Sharon; Weiss, Lola; Sebban, Lora Eshkar; Turley, Eva A.; Okon, Elimelech; Raz, Itamar; Naor, David

2015-01-01

CD44 is a multi-functional receptor with multiple of isoforms engaged in modulation of cell trafficking and transmission of apoptotic signals. We have previously shown that injection of anti-CD44 antibody into NOD mice induced resistance to type 1 diabetes (T1D). In this communication we describe our efforts to understand the mechanism underlying this effect. We found that CD44-deficient NOD mice develop stronger resistance to T1D than wild-type littermates. This effect is not explained by the involvement of CD44 in cell migration, because CD44-deficient inflammatory cells surprisingly had greater invasive potential than the corresponding wild type cells, probably owing to molecular redundancy. We have previously reported and we show here again that CD44 expression and hyaluronic acid (HA, the principal ligand for CD44) accumulation are detected in pancreatic islets of diabetic NOD mice, but not of non-diabetic DBA/1 mice. Expression of CD44 on insulin-secreting β cells renders them susceptible to the autoimmune attack, and is associated with a diminution in β-cells function (e.g., less insulin production and/or insulin secretion) and possibly also with an enhanced apoptosis rate. The diabetes-supportive effect of CD44 expression on β cells was assessed by the TUNEL assay and further strengthened by functional assays exhibiting increased nitric oxide release, reduced insulin secretion after glucose stimulation and decreased insulin content in β cells. All these parameters could not be detected in CD44-deficient islets. We further suggest that HA-binding to CD44-expressing β cells is implicated in β-cell demise. Altogether, these data agree with the concept that CD44 is a receptor capable of modulating cell fate. This finding is important for other pathologies (e.g., cancer, neurodegenerative diseases) in which CD44 and HA appear to be implicated. PMID:26624007

A mechanism for overcoming P-glycoprotein-mediated drug resistance: novel combination therapy that releases stored doxorubicin from lysosomes via lysosomal permeabilization using Dp44mT or DpC.

Science.gov (United States)

Seebacher, Nicole A; Richardson, Des R; Jansson, Patric J

2016-12-01

The intracellular distribution of a drug can cause significant variability in both activity and selectivity. Herein, we investigate the mechanism by which the anti-cancer agents, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) and the clinically trialed, di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC), re-instate the efficacy of doxorubicin (DOX), in drug-resistant P-glycoprotein (Pgp)-expressing cells. Both Dp44mT and DpC potently target and kill Pgp-expressing tumors, while DOX effectively kills non-Pgp-expressing cancers. Thus, the combination of these agents should be considered as an effective rationalized therapy for potently treating advanced and resistant tumors that are often heterogeneous in terms of Pgp-expression. These studies demonstrate that both Dp44mT and DpC are transported into lysosomes via Pgp transport activity, where they induce lysosomal-membrane permeabilization to release DOX trapped within lysosomes. This novel strategy of loading lysosomes with DOX, followed by permeabilization with Dp44mT or DpC, results in the relocalization of stored DOX from its lysosomal 'safe house' to its nuclear targets, markedly enhancing cellular toxicity against resistant tumor cells. Notably, the combination of Dp44mT or DpC with DOX showed a very high level of synergism in multiple Pgp-expressing cell types, for example, cervical, breast and colorectal cancer cells. These studies revealed that the level of drug synergy was proportional to Pgp activity. Interestingly, synergism was ablated by inhibiting Pgp using the pharmacological inhibitor, Elacridar, or by inhibiting Pgp-expression using Pgp-silencing, demonstrating the importance of Pgp in the synergistic interaction. Furthermore, lysosomal-membrane stabilization inhibited the relocalization of DOX from lysosomes to the nucleus upon combination with Dp44mT or DpC, preventing synergism. This latter observation demonstrated the importance of lysosomal

Pharmacokinetics and Safety of Bortezomib in Patients with Advanced Malignancies and Varying Degrees of Liver Dysfunction: Phase 1 NCI Organ Dysfunction Working Group Study NCI-6432

Science.gov (United States)

LoRusso, Patricia M; Venkatakrishnan, Karthik; Ramanathan, Ramesh K; Sarantopoulos, John; Mulkerin, Daniel; Shibata, Stephen I; Hamilton, Anne; Dowlati, Afshin; Mani, Sridhar; Rudek, Michelle A; Takimoto, Chris H; Neuwirth, Rachel; Esseltine, Dixie-Lee; Ivy, Percy

2013-01-01

Purpose The proteasome inhibitor bortezomib undergoes oxidative hepatic metabolism. This study (NCI-6432; NCT00091117) was conducted to evaluate bortezomib pharmacokinetics and safety in patients with varying degrees of hepatic impairment, to inform dosing recommendations in these special populations. Methods Patients received bortezomib on days 1, 4, 8, and 11 of 21-day cycles. Patients were assigned to four hepatic function groups based on the National Cancer Institute Organ Dysfunction Working Group classification. Those with normal function received bortezomib at the 1.3 mg/m2 standard dose. Patients with severe, moderate, and mild impairment received escalating doses from 0.5, 0.7, and 1.0 mg/m2, respectively, up to a 1.3 mg/m2 maximum. Serial blood samples were collected for 24 hours post-dose on days 1 and 8, cycle 1, for bortezomib plasma concentration measurements. Results Sixty-one patients were treated, including 14 with normal hepatic function and 17, 12, and 18 with mild, moderate, and severe impairment, respectively. Mild hepatic impairment did not alter dose-normalized bortezomib exposure (AUC0-tlast) or Cmax compared with patients with normal function. Mean dose-normalized AUC0-tlast was increased by approximately 60% on day 8 in patients with moderate or severe impairment. Conclusions Patients with mild hepatic impairment do not require a starting dose adjustment of bortezomib. Patients with moderate or severe hepatic impairment should be started at a reduced dose of 0.7 mg/m2. PMID:22394984

Disruption of the Putative Vascular Leak Peptide Sequence in the Stabilized Ricin Vaccine Candidate RTA1-33/44-198

Directory of Open Access Journals (Sweden)

Charles B. Millard

2013-01-01

Full Text Available Vitetta and colleagues identified and characterized a putative vascular leak peptide (VLP consensus sequence in recombinant ricin toxin A-chain (RTA that contributed to dose-limiting human toxicity when RTA was administered intravenously in large quantities during chemotherapy. We disrupted this potentially toxic site within the more stable RTA1-33/44-198 vaccine immunogen and determined the impact of these mutations on protein stability, structure and protective immunogenicity using an experimental intranasal ricin challenge model in BALB/c mice to determine if the mutations were compatible. Single amino acid substitutions at the positions corresponding with RTA D75 (to A, or N and V76 (to I, or M had minor effects on the apparent protein melting temperature of RTA1-33/44-198 but all four variants retained greater apparent stability than the parent RTA. Moreover, each VLP(− variant tested provided protection comparable with that of RTA1-33/44-198 against supralethal intranasal ricin challenge as judged by animal survival and several biomarkers. To understand better how VLP substitutions and mutations near the VLP site impact epitope structure, we introduced a previously described thermal stabilizing disulfide bond (R48C/T77C along with the D75N or V76I substitutions in RTA1-33/44-198. The D75N mutation was compatible with the adjacent stabilizing R48C/T77C disulfide bond and the Tm was unaffected, whereas the V76I mutation was less compatible with the adjacent disulfide bond involving C77. A crystal structure of the RTA1-33/44-198 R48C/T77C/D75N variant showed that the structural integrity of the immunogen was largely conserved and that a stable immunogen could be produced from E. coli. We conclude that it is feasible to disrupt the VLP site in RTA1-33/44-198 with little or no impact on apparent protein stability or protective efficacy in mice and such variants can be stabilized further by introduction of a disulfide bond.

Mechanical properties of TiN films deposited by changed-pressure r.f. sputtering

International Nuclear Information System (INIS)

Kubo, Y.; Hashimoto, M.

1991-01-01

TiN was deposited onto glass, stainless steel and cemented carbide by r.f. magnetron sputtering. The mechanical properties of TiN such as hardness, internal stress and adhesion were assessed by the Vickers microhardness test, the bending method and the modified scratch test. It was found that the operating pressure during sputtering deposition strongly affects these mechanical properties. As the operating pressure is increased beyond 0.6-0.7 Pa, the adhesion of TiN films onto the substrate increases enormously, but the hardness decreases owing to the release of the high compressive stress in the film. Therefore changing the pressure from high to low during deposition could be a good way of optimizing both hardness and adhesion. The effectiveness of this changed-pressure process was experimentally verified by cutting tests using TiN-coated cemented carbide tools. This process will be applicable to any other hard coating materials having high compressive stresses. (orig.)

Ab initio R1 mechanism of photostimulated oxygen isotope exchange reaction on a defect TiO{sub 2} surface: The case of terminal oxygen atom exchange

Energy Technology Data Exchange (ETDEWEB)

Kevorkyants, Ruslan, E-mail: ruslan.kevorkyants@gmail.com; Sboev, Mikhail N.; Chizhov, Yuri V.

2017-05-01

Highlights: • DFT R1 mechanism of photostimulated oxygen isotope exchange between {sup 16}O{sup 18}O and terminal oxygen atom of a defect surface of nanocrystalline TiO{sub 2} is proposed. • The mechanism involves four adsorption intermediates and five transition states. • Activation energy of the reaction is 0.24 eV. • G-tensors of O{sub 3}{sup −} intermediates match EPR data on O{sub 2} adsorbed on UV-irradiated TiO{sub 2} surface. - Abstract: Based on density functional theory we propose R1 mechanism of photostimulated oxygen isotope exchange (POIEx) reaction between {sup 16}O{sup 18}O and terminal oxygen atom of a defect TiO{sub 2} surface, which is modeled by amorphous Ti{sub 8}O{sub 16} nanocluster in excited S{sup 1} electronic state. The proposed mechanism involves four adsorption intermediates and five transition states. The computed activation energy of the POIEx equals 0.24 eV. The computed g-tensors of the predicted ozonide O{sub 3}{sup −} chemisorption species match well EPR data on O{sub 2} adsorption on UV-irradiated nanocrystalline TiO{sub 2}. This match serves a mean of justification of the proposed R1 mechanism of the POIEx reaction. In addition, it is found that the proposed R1 POIEx reaction’s mechanism differs from R1 mechanism of thermo-assisted OIEx reaction on a surface of supported vanadium oxide catalyst VO{sub x}/TiO{sub 2} reported earlier.

26 CFR 44.0-1 - Introduction.

Science.gov (United States)

2010-04-01

... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Introduction. 44.0-1 Section 44.0-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES TAXES ON WAGERING; EFFECTIVE JANUARY 1, 1955 Introduction § 44.0-1 Introduction. (a) In general. The...

40 CFR 61.44 - Stack sampling.

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2010-07-01

... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Stack sampling. 61.44 Section 61.44 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL... Firing § 61.44 Stack sampling. (a) Sources subject to § 61.42(b) shall be continuously sampled, during...

7 CFR 930.44 - Quality control.

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2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Quality control. 930.44 Section 930.44 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Control § 930.44 Quality control. (a) Quality standards. The Board may establish, with the approval of the...

18 CFR 420.44 - Cooling water.

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2010-04-01

... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Cooling water. 420.44 Section 420.44 Conservation of Power and Water Resources DELAWARE RIVER BASIN COMMISSION ADMINISTRATIVE MANUAL BASIN REGULATIONS-WATER SUPPLY CHARGES Charges; Exemptions § 420.44 Cooling water. Water used...

27 CFR 44.254 - Shipping containers.

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2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Shipping containers. 44.254 Section 44.254 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU... Requirements § 44.254 Shipping containers. Each shipping case, crate, or other container, in which cigars are...

34 CFR 300.44 - Universal design.

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2010-07-01

... 34 Education 2 2010-07-01 2010-07-01 false Universal design. 300.44 Section 300.44 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND... DISABILITIES General Definitions Used in This Part § 300.44 Universal design. Universal design has the meaning...

29 CFR 44.3 - Election process.

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2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true Election process. 44.3 Section 44.3 Labor Office of the Secretary of Labor PROCESS FOR ELECTING STATE AGENCY EMPLOYMENT STATISTICS REPRESENTATIVES FOR CONSULTATIONS WITH DEPARTMENT OF LABOR § 44.3 Election process. (a) Process. The Commissioner of Labor Statistics of...

27 CFR 478.44 - Original license.

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2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 3 2010-04-01 2010-04-01 false Original license. 478.44 Section 478.44 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND....44 Original license. (a)(1) Any person who intends to engage in business as a firearms or ammunition...

30 CFR 256.44 - Bids disqualified.

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2010-07-01

... by law, regulation, lease or stipulation to lease shall not disqualify an otherwise qualified bid; or... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Bids disqualified. 256.44 Section 256.44... OIL AND GAS IN THE OUTER CONTINENTAL SHELF Issuance of Leases § 256.44 Bids disqualified. The...

Synthesis and characterization of tritium labeled N-((R)-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)-3-sulfamoylbenzamide.

Science.gov (United States)

Hong, Yang; Hynes, John; Tian, Yuan; Balasubramanian, Balu; Bonacorsi, Samuel

2015-08-01

N-((R)-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)-3-sulfamoylbenzamide is a potent C-C chemokine receptor 1 (CCR1) antagonist. The compound, possessing benzamide functionality, successfully underwent tritium/hydrogen (T/H) exchange with an organoiridium catalyst (Crabtree's catalyst). The labeling pattern in the product was studied with liquid chromatography-mass spectrometry, time-of-flight mass spectrometry, and (3) H-NMR. Overall, multiple labeled species were identified. In addition to the anticipated incorporation of tritium in the benzamide moiety, tritium labeling was observed in the valine portion of the molecule including substitution at its chiral carbon. Using authentic standards, liquid chromatography analysis of the labeled compound showed complete retention of stereochemical configuration. Copyright © 2015 John Wiley & Sons, Ltd.

78 FR 52934 - Government-Owned Inventions; Availability for Licensing

Science.gov (United States)

2013-08-27

... low systemic toxicity. Potential Commercial Applications: Pharmaceutical compositions to selectively... (NCI), Rui Sousa (Univ. Texas Health Science Ctr) Publications: 1. Guajardo R, Sousa R. A model for the...

CD44 standard and CD44v10 isoform expression on leukemia cells distinctly influences niche embedding of hematopoietic stem cells.

Science.gov (United States)

Erb, Ulrike; Megaptche, Amelie Pajip; Gu, Xiaoyu; Büchler, Markus W; Zöller, Margot

2014-03-31

A blockade of CD44 is considered a therapeutic option for the elimination of leukemia initiating cells. However, anti-panCD44 can interfere with hematopoiesis. Therefore we explored, whether a CD44 variant isoform (CD44v)-specific antibody can inhibit leukemia growth without attacking hematopoiesis. As a model we used CD44v10 transfected EL4 thymoma cells (EL4-v10). The therapeutic efficacy of anti-panCD44 and anti-CD44v10 was evaluated after intravenous application of EL4/EL4-v10. Ex vivo and in vitro studies evaluated the impact of anti-panCD44 and anti-CD44v10 as well as of EL4 and EL4-v10 on hematopoietic stem cells (HSC) in cocultures with bone marrow stroma cells with a focus on adhesion, migration, cell cycle progression and apoptosis resistance. Intravenously injected EL4-v10 grow in bone marrow and spleen. Anti-panCD44 and, more pronounced anti-CD44v10 prolong the survival time. The higher efficacy of anti-CD44v10 compared to anti-panCD44 does not rely on stronger antibody-dependent cellular cytotoxicity or on promoting EL4-v10 apoptosis. Instead, EL4 compete with HSC niche embedding. This has consequences on quiescence and apoptosis-protecting signals provided by the stroma. Anti-panCD44, too, more efficiently affected embedding of HSC than of EL4 in the bone marrow stroma. EL4-v10, by catching osteopontin, migrated on bone marrow stroma and did not or weakly interfere with HSC adhesion. Anti-CD44v10, too, did not affect the HSC--bone marrow stroma crosstalk. The therapeutic effect of anti-panCD44 and anti-CD44v10 is based on stimulation of antibody-dependent cellular cytotoxicity. The superiority of anti-CD44v10 is partly due to blocking CD44v10-stimulated osteopontin expression that could drive HSC out of the niche. However, the main reason for the superiority of anti-CD44v10 relies on neither EL4-v10 nor anti-CD44v10 severely interfering with HSC--stroma cell interactions that, on the other hand, are affected by EL4 and anti-panCD44. Anti-panCD44

49 CFR 1150.44 - Caption summary.

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2010-10-01

... 49 Transportation 8 2010-10-01 2010-10-01 false Caption summary. 1150.44 Section 1150.44... Exempt Transactions Under 49 U.S.C. 10902 for Class III Rail Carriers § 1150.44 Caption summary. The caption summary must be in the following form. The information symbolized by numbers is identified in the...

Vladimír Vand (1911-1968): Pioneer of computational methods in crystallography

Czech Academy of Sciences Publication Activity Database

Šolcová, A.; Křížek, Michal

2011-01-01

Roč. 33, č. 4 (2011), s. 38-44 ISSN 1058-6180 R&D Projects: GA AV ČR(CZ) IAA100190803 Institutional research plan: CEZ:AV0Z10190503 Keywords : history of computing * Vladimír Vand * crystallography Subject RIV: BA - General Mathematics Impact factor: 0.378, year: 2011 http://www.computer.org/portal/web/csdl/doi/10.1109/MAHC.2011.80

A novel GJA8 mutation (p.V44A causing autosomal dominant congenital cataract.

Directory of Open Access Journals (Sweden)

Yanan Zhu

Full Text Available To examine the mechanism by which a novel connexin 50 (Cx50 mutation, Cx50 V44A, in a Chinese family causes suture-sparing autosomal dominant congenital nuclear cataracts.Family history and clinical data were recorded and direct gene sequencing was used to identify the disease-causing mutation. The Cx50 gene was cloned from a human lens cDNA library. Connexin protein distributions were assessed by fluorescence microscopy. Hemichannel functions were analyzed by dye uptake assay. Formation of functional channels was assessed by dye transfer experiments.Direct sequencing of the candidate GJA8 gene revealed a novel c.131T>C transition in exon 2, which cosegregated with the disease in the family and resulted in the substitution of a valine residue with alanine at codon 44 (p. V44A in the extracellular loop 1 of the Cx50 protein. Both Cx50 and Cx50V44A formed functional gap junctions, as shown by the neurobiotin transfer assay. However, unlike wild-type Cx50, Cx50V44A was unable to form open hemichannels in dye uptake experiments.This work identified a unique congenital cataract in the Chinese population, caused by the novel mutation Cx50V44A, and it showed that the V44A mutation specifically impairs the gating of the hemichannels but not the gap junction channels. The dysfunctional hemichannels resulted in the development of human congenital cataracts.

12 CFR 4.4 - Washington office.

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2010-01-01

... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Washington office. 4.4 Section 4.4 Banks and... EXAMINERS Organization and Functions § 4.4 Washington office. The Washington office of the OCC is the main office and headquarters of the OCC. The Washington office directs OCC policy, oversees OCC operations...

40 CFR 230.44 - Coral reefs.

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2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Coral reefs. 230.44 Section 230.44... Aquatic Sites § 230.44 Coral reefs. (a) Coral reefs consist of the skeletal deposit, usually of calcareous... organisms present in growing portions of the reef. (b) Possible loss of values: The discharge of dredged or...

Kaempferol regulates OPN–CD44 pathway to inhibit the atherogenesis of apolipoprotein E deficient mice

International Nuclear Information System (INIS)

Xiao, Hong-Bo; Lu, Xiang-Yang; Sun, Zhi-Liang; Zhang, Heng-Bo

2011-01-01

Recent studies show that osteopontin (OPN) and its receptor cluster of differentiation 44 (CD44) are two pro-inflammatory cytokines contributing to the development of atherosclerosis. The objective of this study was to explore the inhibitory effect of kaempferol, a naturally occurring flavonoid compound, on atherogenesis and the mechanisms involved. The experiments were performed in aorta and plasma from C57BL/6J control and apolipoprotein E-deficient (ApoE −/− ) mice treated or not with kaempferol (50 or 100 mg/kg, intragastrically) for 4 weeks. Kaempferol treatment decreased atherosclerotic lesion area, improved endothelium-dependent vasorelaxation, and increased the maximal relaxation value concomitantly with decrease in the half-maximum effective concentration, plasma OPN level, aortic OPN expression, and aortic CD44 expression in ApoE −/− mice. In addition, treatment with kaempferol also significantly decreased reactive oxygen species production in mice aorta. The present results suggest that kaempferol regulates OPN–CD44 pathway to inhibit the atherogenesis of ApoE −/− mice. -- Graphical abstract: Kaempferol regulates OPN–CD44 pathway to inhibit the atherogenesis of ApoE −/− mice. Highlights: ► OPN–CD44 pathway plays a critical role in the development of atherosclerosis. ► We examine lesion area, OPN and CD44 changes after kaempferol treatment. ► Kaempferol treatment decreased atherosclerotic lesion area in ApoE −/− mice. ► Kaempferol treatment decreased aortic OPN and CD44 expressions in ApoE −/− mice. ► Kaempferol regulates OPN–CD44 pathway to inhibit the atherogenesis.

Kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis of apolipoprotein E deficient mice

Energy Technology Data Exchange (ETDEWEB)

Xiao, Hong-Bo, E-mail: xhbzhb@yahoo.com [College of Veterinary Medicine, Hunan Agricultural University, Changsha 410128 (China); Lu, Xiang-Yang; Sun, Zhi-Liang [Hunan Agricultural University, Changsha 410128 (China); Zhang, Heng-Bo [Furong District Red Cross Hospital, Changsha 410126 (China)

2011-12-15

Recent studies show that osteopontin (OPN) and its receptor cluster of differentiation 44 (CD44) are two pro-inflammatory cytokines contributing to the development of atherosclerosis. The objective of this study was to explore the inhibitory effect of kaempferol, a naturally occurring flavonoid compound, on atherogenesis and the mechanisms involved. The experiments were performed in aorta and plasma from C57BL/6J control and apolipoprotein E-deficient (ApoE{sup -/-}) mice treated or not with kaempferol (50 or 100 mg/kg, intragastrically) for 4 weeks. Kaempferol treatment decreased atherosclerotic lesion area, improved endothelium-dependent vasorelaxation, and increased the maximal relaxation value concomitantly with decrease in the half-maximum effective concentration, plasma OPN level, aortic OPN expression, and aortic CD44 expression in ApoE{sup -/-} mice. In addition, treatment with kaempferol also significantly decreased reactive oxygen species production in mice aorta. The present results suggest that kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis of ApoE{sup -/-} mice. -- Graphical abstract: Kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis of ApoE{sup -/-} mice. Highlights: Black-Right-Pointing-Pointer OPN-CD44 pathway plays a critical role in the development of atherosclerosis. Black-Right-Pointing-Pointer We examine lesion area, OPN and CD44 changes after kaempferol treatment. Black-Right-Pointing-Pointer Kaempferol treatment decreased atherosclerotic lesion area in ApoE{sup -/-} mice. Black-Right-Pointing-Pointer Kaempferol treatment decreased aortic OPN and CD44 expressions in ApoE{sup -/-} mice. Black-Right-Pointing-Pointer Kaempferol regulates OPN-CD44 pathway to inhibit the atherogenesis.

Usual Intake Distribution of Vitamins and Prevalence of Inadequacy in a Large Sample of Iranian At-Risk Population: Application of NCI Method.

Science.gov (United States)

Heidari, Zahra; Feizi, Awat; Azadbakht, Leila; Sarrafzadegan, Nizal

2016-01-01

This study provides an assessment of usual intake distribution of vitamins and estimating prevalence of inadequacy and excess among a large representative sample of middle-aged and elderly people in central regions of Iran. A cross-sectional study that is a second follow-up to the Isfahan Cohort Study (ICS). The study setting included urban and rural areas from 3 cities (Isfahan, Najafabad, and Arak) in central regions of Iran. Subjects included 1922 people aged 40 years and older, with a mean age of 55.9 ± 10.6; 50.4% were male and the majority (79.3%) were urban. Dietary intakes were collected using a 24-hour recall and 2 food records. Distribution of vitamins intake was estimated using traditional and national cancer institute (NCI) methods. The proportion of subjects at risk of vitamin intake inadequacy or excess was estimated using the estimated average requirement (EAR) cut-point method and the tolerable upper intake levels (UL) index. There were differences between values obtained from traditional and NCI methods, particularly in the lower and upper percentiles of the intake distribution. High prevalence of inadequacies for vitamins A, D, E, B2, B3 (especially among females), and B9 was observed. Significant gender differences were found in terms of inadequate intakes for vitamins A, B1, B2, B3, B6, B9, B12, and C (p vitamin intake was observed in the middle-aged and elderly Iranian population. Nutritional interventions particularly through population-based educational programs in order to improve diet variety and consume nutrient supplements may be necessary.

Competències i factors clau per a l’èxit educatiu des de la perspectiva dels estudiants universitaris fills/es dels immigrants

OpenAIRE

Cano García, Elena

2013-01-01

L’estudi realitzat ha abordat quines són les competències i els factors clau que estudiants universitaris d’origen immigrant consideren que han estat claus per arribar a la universitat, assolint així l’èxit educatiu. S’han escollit estudiants que haguessin fet l’escolaritat obligatòria total o parcialment a Catalunya.Per dur a terme la recerca s’ha treballat amb relats de vida (un total de 13 escrits) i narracions audiovisuals (amb un total de 4 produccions), essent finalment 17 les evidèncie...

Magnetoelectrochemistry of 4,4'-bis(dimethylamino)biphenyl and 4,4'-dinitrobiphenyl azacrown macrocyclic lactams

Energy Technology Data Exchange (ETDEWEB)

Domenech, Antonio [Departament de Quimica Analitica, Universitat de Valencia, Dr. Moliner 50, 46100 Burjassot, Valencia (Spain); Costero, Ana Maria; Banuls, Maria Jose; Aurell, Maria Jose [Departament de Quimica Organica, Universitat de Valencia, Dr. Moliner 50, 46100 Burjassot, Valencia (Spain)

2005-07-25

The voltammetric behaviour at carbon fibre microelectrodes under the application of static magnetic fields of two series of macrolactams containing in their structure 4,4'-bis(dimethylamino)biphenyl or 4,4'-dinitrobiphenyl groups in MeCN solution is described. The response of 4,4'-dinitrobiphenyl receptors is dominated by two successive one-electron reduction processes at -0.9 and -1.6 V versus AgCl/Ag. 4,4'-bis(dimethylamino)biphenyl-containing receptors display two one-electron oxidations above +0.8 and +1.0 V. In both cases, a dihedral/planar interconversion precedes the second electron transfer step. Upon application of moderate (0.05-0.2 T) static magnetic fields to the electrochemical cell, the rate of such dihedral/planar interconversion is lowered for both the reduction of 4,4'-dinitrobiphenyl receptors and the oxidation of 4,4'-bis(dimethylamino)biphenyl lactams. The electrochemical response of N-methylated receptors, for which different cisoid-cisoid, cisoid-transoid, and transoid-transoid forms exist, exhibits a significant peak splitting that can be associated to the presence of such conformational isomers. Application of magnetic fields produces a relative enhancement of some peaks that can be interpreted in terms of differential magnetoconvection involving such conformational isomers. (author)

Dual role of CD44 isoforms in ampullary adenocarcinoma: CD44s predicts poor prognosis in early cancer and CD44ν is an indicator for recurrence in advanced cancer

International Nuclear Information System (INIS)

Wu, Cheng-Lin; Chao, Ying-Jui; Yang, Ta-Ming; Chen, Yi-Ling; Chang, Kung-Chao; Hsu, Hui-Ping; Shan, Yan-Shen; Lai, Ming-Derg

2015-01-01

Although postoperative adjuvant chemoradiotherapies prevent recurrence for some patients with ampullary cancer, the recurrence rate is as high as 29 % in patients with stage I cancer. In an effort to identify predictors of recurrence in patients with ampullary adenocarcinoma, we investigated the clinical value of assessing standard and variant forms of CD44. Immunohistochemistry staining and reverse-transcription polymerase chain reaction (RT-PCR) was used to detect standard and variant forms of CD44 in samples of ampullary adenocarcinoma. The cDNA microarray analysis comparing tumors with or without pancreatic invasion was undertaken and analyzed by Ingenuity Pathway Analysis. The standard CD44 (CD44s) isoform was detected in 76 of 98 patients with ampullary adenocarcinoma, and the negative or weak expression of CD44s was correlated with pancreatic invasion, lymphovascular invasion, advanced stage and bone metastasis. Moderate to dense expression of CD44s was correlated with shorter overall survival in patients with localized cancer (T1 or T2 disease, P = 0.0268). The patients with advanced cancer (T3 or T4 disease) and moderate or dense CD44s expression had a trend toward better survival. Alternative splicing of CD44 was confirmed using RT-PCR, which revealed that the CD44ν3-10 isoform was only expressed in patients with cancer recurrence. Fold change of CD44ν6-10 was also increased. In addition, networks containing CD44, vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), transforming growth factor-β (TGF-β), matrix metalloproteinase 2 (MMP2), AKT, extracellular signal-regulated protein kinase 1 and 2 (ERK1/2), p38 MAPK, activated protein 1 (AP1)‚ and CTNNB1 were constructed after comparing microarray data from patients with and without pancreatic invasion. Whereas CD44s functions as tumor-promoting oncoprotein in early localized ampullary adenocarcinoma, CD44 variants are expressed in advanced cancer and patients with

CD44v6 regulates growth of brain tumor stem cells partially through the AKT-mediated pathway.

Directory of Open Access Journals (Sweden)

Mayumi Jijiwa

Full Text Available Identification of stem cell-like brain tumor cells (brain tumor stem-like cells; BTSC has gained substantial attention by scientists and physicians. However, the mechanism of tumor initiation and proliferation is still poorly understood. CD44 is a cell surface protein linked to tumorigenesis in various cancers. In particular, one of its variant isoforms, CD44v6, is associated with several cancer types. To date its expression and function in BTSC is yet to be identified. Here, we demonstrate the presence and function of the variant form 6 of CD44 (CD44v6 in BTSC of a subset of glioblastoma multiforme (GBM. Patients with CD44(high GBM exhibited significantly poorer prognoses. Among various variant forms, CD44v6 was the only isoform that was detected in BTSC and its knockdown inhibited in vitro growth of BTSC from CD44(high GBM but not from CD44(low GBM. In contrast, this siRNA-mediated growth inhibition was not apparent in the matched GBM sample that does not possess stem-like properties. Stimulation with a CD44v6 ligand, osteopontin (OPN, increased expression of phosphorylated AKT in CD44(high GBM, but not in CD44(low GBM. Lastly, in a mouse spontaneous intracranial tumor model, CD44v6 was abundantly expressed by tumor precursors, in contrast to no detectable CD44v6 expression in normal neural precursors. Furthermore, overexpression of mouse CD44v6 or OPN, but not its dominant negative form, resulted in enhanced growth of the mouse tumor stem-like cells in vitro. Collectively, these data indicate that a subset of GBM expresses high CD44 in BTSC, and its growth may depend on CD44v6/AKT pathway.

Elimination Reactions of (E)-2,4,6-Trinitrobenzaldehyde O-benzoyloximes Promoted by R2NH in MeCN. Change of Reaction Mechanism

International Nuclear Information System (INIS)

Cho, Bong Rae; Pyun, Sang Yong

2010-01-01

We have studied the nitrile-forming elimination reactions from 1 promoted by R 2 NH in MeCN. The reaction proceeded by (E1cb) irr mechanism. Change of the β-aryl group from 2,4-dinitrophenyl to a more strongly electron-withdrawing 2,4,6-trinitrophenyl increased the reaction rate by 470-fold, shifted the transition state toward more reactant-like, and changed the reaction mechanism from E2 to (E1cb) irr . To the best of our knowledge, this is the first example of nitrile-forming elimination reaction that proceeds by the (E1cb) irr mechanism in MeCN. Noteworthy is the carbanion stabilizing ability of the 2,4,6-trinitrophenyl group in aprotic solvent. Nitrile-forming elimination reactions of (E)-benzaldoxime derivatives have been extensively investigated under various conditions. The reactions proceeded by the E2 mechanism in MeCN despite the fact that the reactants have syn stereochemistry, poor leaving, and sp 2 hybridized β-carbon atom, all of which favor E1cb- or E1cb-like transition state. Moreover, the transition state structures were relatively insensitive to the variation of the reactant structures. The results have been attributed to the poor anion solvating ability of MeCN, which favors E2 transition state with maximum charge dispersal. For eliminations from strongly activated (E)-2,4-(NO 2 ) 2 C 6 H 3 CH=NOC(O)C 6 H 4 X, a change in the reaction mechanism from E2 to (E1cb) irr was observed as the base-solvent was changed from R 2 NH in MeCN to R 2 NH/R 2 NH 2 + in 70 mol % MeCN(aq). A combination of a strong electron-withdrawing β-aryl group and anion-solvating protic solvent was required for the mechanistic change

SYNTHESIS AND STRUCTURAL CHARACTERIZATION OF A Zn(II COORDINATION POLYMER BASED ON 4,4’-BIPYRIDINE AND ACETATO

Directory of Open Access Journals (Sweden)

LI-HUA WANG

2015-05-01

Full Text Available A novel Zn(II coordination polymer, [Zn(bpy(acetato2]n (bpy = 4,4’-bipyridine, has been synthesized and characterized by elemental analysis and single-crystal X-ray diffraction. The Zn(II coordination polymer is triclinic, space group P-1 with a = 8.046(3 Å, b = 9.161(3 Å, c = 10.663(3 Å, α = 109.769(4º, β = 99.966(5º, γ = 101.666(5º, V= 699.1(4 Å3, Z = 2, Dc = 1.614 mg·m-3, μ = 1.774 mm-1, F(000 = 348, and final R1 = 0.0541, ωR2 = 0.1605. X-ray diffraction analysis reveals that the Zn(II center is six-coordination with a N2O4 distorted octahedral coordination environment. The Zn(II complex forms 1D chain structure by the bridge of 4,4’-bipyridine and acetato.

Can CD44 Be a Mediator of Cell Destruction? The Challenge of Type 1 Diabetes.

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Nathalie Assayag-Asherie

Full Text Available CD44 is a multi-functional receptor with multiple of isoforms engaged in modulation of cell trafficking and transmission of apoptotic signals. We have previously shown that injection of anti-CD44 antibody into NOD mice induced resistance to type 1 diabetes (T1D. In this communication we describe our efforts to understand the mechanism underlying this effect. We found that CD44-deficient NOD mice develop stronger resistance to T1D than wild-type littermates. This effect is not explained by the involvement of CD44 in cell migration, because CD44-deficient inflammatory cells surprisingly had greater invasive potential than the corresponding wild type cells, probably owing to molecular redundancy. We have previously reported and we show here again that CD44 expression and hyaluronic acid (HA, the principal ligand for CD44 accumulation are detected in pancreatic islets of diabetic NOD mice, but not of non-diabetic DBA/1 mice. Expression of CD44 on insulin-secreting β cells renders them susceptible to the autoimmune attack, and is associated with a diminution in β-cells function (e.g., less insulin production and/or insulin secretion and possibly also with an enhanced apoptosis rate. The diabetes-supportive effect of CD44 expression on β cells was assessed by the TUNEL assay and further strengthened by functional assays exhibiting increased nitric oxide release, reduced insulin secretion after glucose stimulation and decreased insulin content in β cells. All these parameters could not be detected in CD44-deficient islets. We further suggest that HA-binding to CD44-expressing β cells is implicated in β-cell demise. Altogether, these data agree with the concept that CD44 is a receptor capable of modulating cell fate. This finding is important for other pathologies (e.g., cancer, neurodegenerative diseases in which CD44 and HA appear to be implicated.

Transcriptional response of Nautella italica R11 towards its macroalgal host uncovers new mechanisms of host-pathogen interaction.

Science.gov (United States)

Hudson, Jennifer; Gardiner, Melissa; Deshpande, Nandan; Egan, Suhelen

2018-04-01

Macroalgae (seaweeds) are essential for the functioning of temperate marine ecosystems, but there is increasing evidence to suggest that their survival is under threat from anthropogenic stressors and disease. Nautella italica R11 is recognized as an aetiological agent of bleaching disease in the red alga, Delisea pulchra. Yet, there is a lack of knowledge surrounding the molecular mechanisms involved in this model host-pathogen interaction. Here we report that mutations in the gene encoding for a LuxR-type quorum sensing transcriptional regulator, RaiR, render N. italica R11 avirulent, suggesting this gene is important for regulating the expression of virulence phenotypes. Using an RNA sequencing approach, we observed a strong transcriptional response of N. italica R11 towards the presence of D. pulchra. In particular, genes involved in oxidative stress resistance, carbohydrate and central metabolism were upregulated in the presence of the host, suggesting a role for these functions in the opportunistic pathogenicity of N. italica R11. Furthermore, we show that RaiR regulates a subset of genes in N. italica R11, including those involved in metabolism and the expression of phage-related proteins. The outcome of this research reveals new functions important for virulence of N. italica R11 and contributes to our greater understanding of the complex factors mitigating microbial diseases in macroalgae. © 2017 John Wiley & Sons Ltd.

Intense light-elicited upregulation of miR-21 facilitates glycolysis and cardioprotection through Per2-dependent mechanisms.

Directory of Open Access Journals (Sweden)

Colleen Marie Bartman

Full Text Available A wide search for ischemic preconditioning (IPC mechanisms of cardioprotection identified the light elicited circadian rhythm protein Period 2 (Per2 to be cardioprotective. Studies on cardiac metabolism found a key role for light elicited Per2 in mediating metabolic dependence on carbohydrate metabolism. To profile Per2 mediated pathways following IPC of the mouse heart, we performed a genome array and identified 352 abundantly expressed and well-characterized Per2 dependent micro RNAs. One prominent result of our in silico analysis for cardiac Per2 dependent micro RNAs revealed a selective role for miR-21 in the regulation of hypoxia and metabolic pathways. Based on this Per2 dependency, we subsequently found a diurnal expression pattern for miR-21 with higher miR-21 expression levels at Zeitgeber time (ZT 15 compared to ZT3. Gain or loss of function studies for miR-21 using miRNA mimics or miRNA inhibitors and a Seahorse Bioanalyzer uncovered a critical role of miR-21 for cellular glycolysis, glycolytic capacity, and glycolytic reserve. Exposing mice to intense light, a strategy to induce Per2, led to a robust induction of cardiac miR-21 tissue levels and decreased infarct sizes, which was abolished in miR-21-/- mice. Similarly, first translational studies in humans using intense blue light exposure for 5 days in healthy volunteers resulted in increased plasma miR-21 levels which was associated with increased phosphofructokinase activity, the rate-limiting enzyme in glycolysis. Together, we identified miR-21 as cardioprotective downstream target of Per2 and suggest intense light therapy as a potential strategy to enhance miR-21 activity and subsequent carbohydrate metabolism in humans.

CD44 standard and CD44v10 isoform expression on leukemia cells distinctly influences niche embedding of hematopoietic stem cells

OpenAIRE

Erb, Ulrike; Megaptche, Amelie Pajip; Gu, Xiaoyu; Büchler, Markus W; Zöller, Margot

2014-01-01

Background A blockade of CD44 is considered a therapeutic option for the elimination of leukemia initiating cells. However, anti-panCD44 can interfere with hematopoiesis. Therefore we explored, whether a CD44 variant isoform (CD44v)-specific antibody can inhibit leukemia growth without attacking hematopoiesis. As a model we used CD44v10 transfected EL4 thymoma cells (EL4-v10). Methods The therapeutic efficacy of anti-panCD44 and anti-CD44v10 was evaluated after intravenous application of EL4/...

20 CFR 901.44 - Hearings.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Hearings. 901.44 Section 901.44 Employees' Benefits JOINT BOARD FOR THE ENROLLMENT OF ACTUARIES REGULATIONS GOVERNING THE PERFORMANCE OF ACTUARIAL... complaint for the suspension or termination of an enrolled actuary. Hearings shall be stenographically...

Radiosensitive effect of hypoxia-inducible factor 1α inhibitor YC-1 on hypoxic glioma SHG44 cell line

International Nuclear Information System (INIS)

Guo Xinwei; Lu Xueguan; Tong Liumei; Zong Tianzhou; Chen Liesong

2011-01-01

Objective: To investigate the radiosensitive effect of hypoxia-inducible factor 1α (HIF-1α) inhibitor YC-1 on hypoxic glioma SHG44 cell line and its related mechanism. Methods: Glioma SHG44 cell line was cultured in normoxic (20% O 2 ), continuous hypoxia (1% O 2 ) for 12 h and 24 h, continuous hypoxia plus YC-1 was performed for 12 h and 24 h, respectively. The expression of HIF-1α was assessed by Western blot. The radiosensitivity was evaluated by the survival curve, and the sublethal damage repair (SLDR) ability was measured by dose-fraction experiment. Results: HIF-1α protein levels of glioma SHG44 cells were significantly increased after hypoxic cultures for 12 h and 24 h than those of the corresponding cells cultured in normoxic, while the radiosensitivity was lower. The OER (oxygen-enhancement ratio) of SHG44 cells in hypoxia for 12 h and 24 h were 1.22 and 1.37, respectively. By the further statistical analysis it was found that SLDR ability of glioma SHG44 was increased at hypoxia, and when irradiation was carried one at the interval of 8, 10, 12 h it was statistically significant (P<0.05). HIF-1α protein levels of glioma SHG44 cells cultured in hypoxia plus YC-1 for 12 h and 24 h were decreased significantly compared to the corresponding cells cultured in hypoxia only, while the radiosensitivity was significantly increased. the EF (enhancement factor) of YC-1 for glioma SHG44 cells at hypoxia for 12 h and 24 h was 1.27. By the further statistical analysis it was also found that SLDR ability was decreased significantly for hypoxic SHG44 cells which was co-cultured with YC-1, and at the interval of 8, 10, 12 h irradiation was statistically significant (P<0.05). Conclusion: YC-1 can increase the radiosensitivity of hypoxic glioma SHG44 cell line, and its mechanism is related to SLDR inhibited by YC-1. (authors)

Conditional expression of CD44 isoforms in lymphoma cells: influence on hyaluronate binding and tumor growth

Energy Technology Data Exchange (ETDEWEB)

Fu, J.

2002-03-01

CD44 describes a family of surface proteins consisting of many isoforms due to alternative splice of ten 'variant' exons. Members of this family are involved in various processes including hematopoiesis, lymphocyte activation and homing, limb development, wound healing and tumor progression. Clinically, CD44 has been shown to be a prognostic factor for several human cancers. To answer the question which isoform might be relevant for tumor progression and to gain an insight into the mechanism of its function, I established transfectants of the LB lymphoma cell line in which the expression of four CD44 isoforms, namely CD44v3-10, CD44v4-10, CD44v8-10 and CD44s, was controlled by the Tet-off promoter. In the presence of Doxycycline, the expression was repressed. Removal of Doxycycline switched on expression and the maximal CD44 amount was obtained within two days. The transfectants were characterized regarding their ability to bind to the extracellular matrix component hyaluronate (HA). Overexpression of all four CD44 isoforms conferred the ability to bind HA on LB cells. Other glycosaminoglycans (GAGs) were bound in an isotype-specific fashion. CD44v3-10, CD44v4-10 and CD44v8-10 showed high binding affinity to chondroitin A, B and C, and low affinity to heparin, heparan sulfate and keratan sulfate. CD44s could not bind to these GAGs. Among these three variants, the binding ability of CD44v3-10 was the strongest. CD44 clustering seemed to play a crucial role for HA binding. Both CD44s and CD44v8-10 formed reduction-sensitive complexes in LB cells. The complexes are homooligomers or heterooligomers composed of different isoforms. Cys286 in CD44 transmember domain was not responsible for the formation of reduction-sensitive oligomer or for the enhanced HA binding in LB cell line. Using a conditional dimerization system the requirement of CD44 oligomerization for HA binding was directly demonstrated. The induction of oligomerization increased HA binding

Conditional expression of CD44 isoforms in lymphoma cells: influence on hyaluronate binding and tumor growth

International Nuclear Information System (INIS)

Fu, J.

2002-03-01

CD44 describes a family of surface proteins consisting of many isoforms due to alternative splice of ten 'variant' exons. Members of this family are involved in various processes including hematopoiesis, lymphocyte activation and homing, limb development, wound healing and tumor progression. Clinically, CD44 has been shown to be a prognostic factor for several human cancers. To answer the question which isoform might be relevant for tumor progression and to gain an insight into the mechanism of its function, I established transfectants of the LB lymphoma cell line in which the expression of four CD44 isoforms, namely CD44v3-10, CD44v4-10, CD44v8-10 and CD44s, was controlled by the Tet-off promoter. In the presence of Doxycycline, the expression was repressed. Removal of Doxycycline switched on expression and the maximal CD44 amount was obtained within two days. The transfectants were characterized regarding their ability to bind to the extracellular matrix component hyaluronate (HA). Overexpression of all four CD44 isoforms conferred the ability to bind HA on LB cells. Other glycosaminoglycans (GAGs) were bound in an isotype-specific fashion. CD44v3-10, CD44v4-10 and CD44v8-10 showed high binding affinity to chondroitin A, B and C, and low affinity to heparin, heparan sulfate and keratan sulfate. CD44s could not bind to these GAGs. Among these three variants, the binding ability of CD44v3-10 was the strongest. CD44 clustering seemed to play a crucial role for HA binding. Both CD44s and CD44v8-10 formed reduction-sensitive complexes in LB cells. The complexes are homooligomers or heterooligomers composed of different isoforms. Cys286 in CD44 transmember domain was not responsible for the formation of reduction-sensitive oligomer or for the enhanced HA binding in LB cell line. Using a conditional dimerization system the requirement of CD44 oligomerization for HA binding was directly demonstrated. The induction of oligomerization increased HA binding. Finally, I

Setting the anomeric effect against steric effects in simple acyclic acetals. Non-anomeric non-classical conformations. An n.m.r. and molecular mechanics investigation

DEFF Research Database (Denmark)

Anderson, J. Edgar; Heki, Katsuhiko; Hirota, Minoru

1987-01-01

N.m.r. parameters for a series of simple aliphatic acetals indicate that the preferred conformation changes from the anomeric one found in formaldehyde dimethyl acetal (formal), to a new one whose structure is suggested by molecular mechanics calculations.......N.m.r. parameters for a series of simple aliphatic acetals indicate that the preferred conformation changes from the anomeric one found in formaldehyde dimethyl acetal (formal), to a new one whose structure is suggested by molecular mechanics calculations....

7 CFR 906.44 - Safeguards.

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2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Safeguards. 906.44 Section 906.44 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... pursuant to § 906.41 or § 906.42 from entering channels of trade for other than the specific purpose...

30 CFR 44.24 - Discovery.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Discovery. 44.24 Section 44.24 Mineral... Discovery. Parties shall be governed in their conduct of discovery by appropriate provisions of the Federal... discovery. Alternative periods of time for discovery may be prescribed by the presiding administrative law...

Cleavage of Hyaluronan and CD44 Adhesion Molecule Regulate Astrocyte Morphology via Rac1 Signalling.

Directory of Open Access Journals (Sweden)

Anna Konopka

Full Text Available Communication of cells with their extracellular environment is crucial to fulfill their function in physiological and pathophysiological conditions. The literature data provide evidence that such a communication is also important in case of astrocytes. Mechanisms that contribute to the interaction between astrocytes and extracellular matrix (ECM proteins are still poorly understood. Hyaluronan is the main component of ECM in the brain, where its major receptor protein CD44 is expressed by a subset of astrocytes. Considering the fact that functions of astrocytes are tightly coupled with changes in their morphology (e.g.: glutamate clearance in the synaptic cleft, migration, astrogliosis, we investigated the influence of hyaluronan cleavage by hyaluronidase, knockdown of CD44 by specific shRNA and CD44 overexpression on astrocyte morphology. Our results show that hyaluronidase treatment, as well as knockdown of CD44, in astrocytes result in a "stellate"-like morphology, whereas overexpression of CD44 causes an increase in cell body size and changes the shape of astrocytes into flattened cells. Moreover, as a dynamic reorganization of the actin cytoskeleton is supposed to be responsible for morphological changes of cells, and this reorganization is controlled by small GTPases of the Rho family, we hypothesized that GTPase Rac1 acts as a downstream effector for hyaluronan and CD44 in astrocytes. We used FRET-based biosensor and a dominant negative mutant of Rac1 to investigate the involvement of Rac1 activity in hyaluronidase- and CD44-dependent morphological changes of astrocytes. Both, hyaluronidase treatment and knockdown of CD44, enhances Rac1 activity while overexpression of CD44 reduces the activity state in astrocytes. Furthermore, morphological changes were blocked by specific inhibition of Rac1 activity. These findings indicate for the first time that regulation of Rac1 activity is responsible for hyaluronidase and CD44-driven morphological

Cleavage of Hyaluronan and CD44 Adhesion Molecule Regulate Astrocyte Morphology via Rac1 Signalling.

Science.gov (United States)

Konopka, Anna; Zeug, Andre; Skupien, Anna; Kaza, Beata; Mueller, Franziska; Chwedorowicz, Agnieszka; Ponimaskin, Evgeni; Wilczynski, Grzegorz M; Dzwonek, Joanna

2016-01-01

Communication of cells with their extracellular environment is crucial to fulfill their function in physiological and pathophysiological conditions. The literature data provide evidence that such a communication is also important in case of astrocytes. Mechanisms that contribute to the interaction between astrocytes and extracellular matrix (ECM) proteins are still poorly understood. Hyaluronan is the main component of ECM in the brain, where its major receptor protein CD44 is expressed by a subset of astrocytes. Considering the fact that functions of astrocytes are tightly coupled with changes in their morphology (e.g.: glutamate clearance in the synaptic cleft, migration, astrogliosis), we investigated the influence of hyaluronan cleavage by hyaluronidase, knockdown of CD44 by specific shRNA and CD44 overexpression on astrocyte morphology. Our results show that hyaluronidase treatment, as well as knockdown of CD44, in astrocytes result in a "stellate"-like morphology, whereas overexpression of CD44 causes an increase in cell body size and changes the shape of astrocytes into flattened cells. Moreover, as a dynamic reorganization of the actin cytoskeleton is supposed to be responsible for morphological changes of cells, and this reorganization is controlled by small GTPases of the Rho family, we hypothesized that GTPase Rac1 acts as a downstream effector for hyaluronan and CD44 in astrocytes. We used FRET-based biosensor and a dominant negative mutant of Rac1 to investigate the involvement of Rac1 activity in hyaluronidase- and CD44-dependent morphological changes of astrocytes. Both, hyaluronidase treatment and knockdown of CD44, enhances Rac1 activity while overexpression of CD44 reduces the activity state in astrocytes. Furthermore, morphological changes were blocked by specific inhibition of Rac1 activity. These findings indicate for the first time that regulation of Rac1 activity is responsible for hyaluronidase and CD44-driven morphological changes of

Diarachidonoylphosphoethanolamine induces apoptosis of malignant pleural mesothelioma cells through a Trx/ASK1/p38 MAPK pathway

OpenAIRE

Ayako Tsuchiya; Yoshiko Kaku; Takashi Nakano; Tomoyuki Nishizaki

2015-01-01

1,2-Diarachidonoyl-sn-glycero-3-phosphoethanolamine (DAPE) induces both necrosis/necroptosis and apoptosis of NCI-H28 malignant pleural mesothelioma (MPM) cells. The present study was conducted to understand the mechanism for DAPE-induced apoptosis of NCI-H28 cells. DAPE induced caspase-independent apoptosis of NCI-H28 malignant pleural mesothelioma (MPM) cells, and the effect of DAPE was prevented by antioxidants or an inhibitor of NADPH oxidase (NOX). DAPE generated reactive oxygen species ...

Molecular mechanisms of 3,3′4,4′,5-pentachlorobiphenyl-induced epithelial-mesenchymal transition in human hepatocellular carcinoma cells

International Nuclear Information System (INIS)

Song, Li; Guo, Linlin; Li, Zhuoyu

2017-01-01

Polychlorinated biphenyls (PCBs) are classic persistent organic pollutants (POPs). Many studies have found a positive association between the progression of hepatocellular carcinoma (HCC) and PCBs exposure. However, the influence of PCBs on epithelial-mesenchymal transition (EMT) of HCC remains to be unclear. In this study, we explored the effect of PCB126 on EMT in HCC cells and its underlying mechanisms. The data showed that PCB126, exposing both Bel-7402 and SMMC-7721 cells for 48 h, promoted EMT that was demonstrated by E-cadherin repression, up-regulation of N-cadherin and vimentin, and morphological alteration. We found that signal transducer and activator of transcription 3 (STAT3)/Snail1 signaling was activated after PCB126 exposure, and the addition of STAT3 inhibitor WP1066 blocked PCB126-induced down-regulation of E-cadherin as well as up-regulation of N-cadherin and vimentin. Moreover, PCB126 exposure increased pyruvate kinase M2 (PKM2) expression and its nuclear translocation, whereas treatment with PKM2 shRNA suppressed the activation of STAT3/Snail1 signaling and the alternation of EMT-related molecules (E-cadherin, N-cadherin and vimentin). Furthermore, this study indicated estrogen receptor (ER) and aryl hydrocarbon receptor (AhR) were involved in PCB126-induced effects on PKM2, STAT3/Snail1 signaling and EMT by according treatment using ER inhibitor ICI and AhR shRNA. Notably, PCB126-increased reactive oxygen species (ROS) production via AhR is associated with activation of PKM2/STAT3/Snail1 cascades and contributes to EMT. Taken together, these results indicated that PCB126 promotes EMT process of HCC cells via PKM2/STAT3/Snail1 signaling which is mediated by ER and AhR. - Highlights: • PCB126 promotes epithelial-mesenchymal transition of HCC cells. • PCB126 regulates EMT through the activation of STAT3/Snail1 signaling. • PKM2 is responsible for PCB126-induced activation of STAT3/Snail1 signaling. • AhR-induced ROS generation regulates

Molecular mechanisms of 3,3′4,4′,5-pentachlorobiphenyl-induced epithelial-mesenchymal transition in human hepatocellular carcinoma cells

Energy Technology Data Exchange (ETDEWEB)

Song, Li; Guo, Linlin [Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006 (China); Li, Zhuoyu, E-mail: lzy@sxu.edu.cn [Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006 (China); College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053 (China)

2017-05-01

Polychlorinated biphenyls (PCBs) are classic persistent organic pollutants (POPs). Many studies have found a positive association between the progression of hepatocellular carcinoma (HCC) and PCBs exposure. However, the influence of PCBs on epithelial-mesenchymal transition (EMT) of HCC remains to be unclear. In this study, we explored the effect of PCB126 on EMT in HCC cells and its underlying mechanisms. The data showed that PCB126, exposing both Bel-7402 and SMMC-7721 cells for 48 h, promoted EMT that was demonstrated by E-cadherin repression, up-regulation of N-cadherin and vimentin, and morphological alteration. We found that signal transducer and activator of transcription 3 (STAT3)/Snail1 signaling was activated after PCB126 exposure, and the addition of STAT3 inhibitor WP1066 blocked PCB126-induced down-regulation of E-cadherin as well as up-regulation of N-cadherin and vimentin. Moreover, PCB126 exposure increased pyruvate kinase M2 (PKM2) expression and its nuclear translocation, whereas treatment with PKM2 shRNA suppressed the activation of STAT3/Snail1 signaling and the alternation of EMT-related molecules (E-cadherin, N-cadherin and vimentin). Furthermore, this study indicated estrogen receptor (ER) and aryl hydrocarbon receptor (AhR) were involved in PCB126-induced effects on PKM2, STAT3/Snail1 signaling and EMT by according treatment using ER inhibitor ICI and AhR shRNA. Notably, PCB126-increased reactive oxygen species (ROS) production via AhR is associated with activation of PKM2/STAT3/Snail1 cascades and contributes to EMT. Taken together, these results indicated that PCB126 promotes EMT process of HCC cells via PKM2/STAT3/Snail1 signaling which is mediated by ER and AhR. - Highlights: • PCB126 promotes epithelial-mesenchymal transition of HCC cells. • PCB126 regulates EMT through the activation of STAT3/Snail1 signaling. • PKM2 is responsible for PCB126-induced activation of STAT3/Snail1 signaling. • AhR-induced ROS generation regulates

IP and Data Access | Division of Cancer Prevention

Science.gov (United States)

The following outlines the different patent and licensing mechanisms applicable to studies of third-party agents in the PREVENT Program. Please note that the NCI has a variety of agreement mechanisms by which these terms may be applied and will work with the NCI Technology Transfer Center to determine the appropriate agreement for the studies approved by the PREVENT Program. | The section outlines the different patent and licensing mechanisms applicable to studies of third-party agents in the PREVENT Program.

27 CFR 44.144 - Opening.

Science.gov (United States)

2010-04-01

... PAYMENT OF TAX, OR WITH DRAWBACK OF TAX Operations by Export Warehouse Proprietors Inventories § 44.144 Opening. An opening inventory shall be made by the export warehouse proprietor at the time of commencing... permit issued under § 44.93. A similar inventory shall be made by the export warehouse proprietor when he...

The ADOR mechanism for the synthesis of new zeolites

Czech Academy of Sciences Publication Activity Database

Eliášová, Pavla; Opanasenko, Maksym; Wheatley, P. S.; Shamzhy, Mariya; Mazur, Michal; Nachtigall, P.; Roth, Wieslaw Jerzy; Morris, R. E.; Čejka, Jiří

2015-01-01

Roč. 44, č. 20 (2015), s. 7177-7206 ISSN 0306-0012 R&D Projects: GA ČR GBP106/12/G015; GA ČR(CZ) GP14-30898P Institutional support: RVO:61388955 Keywords : STRUCTURE -DIRECTING AGENTS * LARGE-PORE ZEOLITES * PILLARED MOLECULAR-SIEVE Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 34.090, year: 2015

Coupling Effect between Mechanical Loading and Chemical Reactions

Czech Academy of Sciences Publication Activity Database

Klika, Václav; Maršík, František

2009-01-01

Roč. 113, č. 44 (2009), s. 14689-14697 ISSN 1520-6106 R&D Projects: GA ČR(CZ) GA106/08/0557 Institutional research plan: CEZ:AV0Z20760514 Keywords : coupling * dynamic loading * reaction kinetics Subject RIV: FI - Traumatology, Orthopedics Impact factor: 3.471, year: 2009

28 CFR 66.44 - Termination for convenience.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Termination for convenience. 66.44 Section 66.44 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) UNIFORM ADMINISTRATIVE... Reports, Records, Retention, and Enforcement § 66.44 Termination for convenience. Except as provided in...

Clonal deletion: A mechanism of tolerance in mixed bone marrow chimeras

International Nuclear Information System (INIS)

Yu, J.C.; Webster, M.; Fox, I.J.

1990-01-01

The mechanism of antigen-specific immunologic unresponsiveness which results from lethal irradiation and mixed (syngeneic-allogeneic) bone marrow cell (BMC) reconstitution is unknown. To determine whether clonal deletion is the mechanism of tolerance in this model, monoclonal antibody (Mab) RR-4-4, specific for a T-cell receptor (V beta 6) reactive against the minor alloantigen MLsa, was employed. Six-week-old B10 mice (H-2b, Mlsb, Thyl.2) were tolerized to AKR antigens (H-2k, Mlsa, Thyl.1) by whole body irradiation (950 R) and iv infusion of T-cell-depleted (TCD) B10 BMC + non-TCD AKR BMC. Chimerism and antigen-specific tolerance were documented by flow microfluorometry (FMF), skin grafting, mixed lymphocyte reaction, and cell-mediated lympholysis. When tolerant B10 mice (n = 15) had accepted AKR skin grafts for greater than 100 days, these animals were studied for the presence of host V beta 6+ T cells using Mab RR-4-4. FMF revealed that 0-5% of host (B10) lymph node and spleen cells from chimeras were V beta 6+ while 15-20% of lymph node and spleen cells from control B10 mice expressed V beta 6. These data demonstrate that clonal deletion occurs in the lethal irradiation-mixed reconstitution model as evidenced by the near total elimination of Mlsa-reactive V beta 6+ T cells and suggest that it maybe a mechanism responsible for tolerance in adult mice

RFLP for Duchenne muscular dystrophy cDNA clone 44-1

Energy Technology Data Exchange (ETDEWEB)

Laing, N G; Siddique, T; Bartlett, R J; Yamaoka, L H; Chen, J C; Walker, A P; Hung, W Y; Roses, A D [Duke Univ. Medical Center, Durham, NC (USA)

1988-07-25

Clone 44-1 is one of six cDNA clones which comprise the cDNA for the Duchenne muscular dystrophy gene. It is a 0.9kb fragment in the EcoR1 site of Bluescript. Taq1 (TlCGA) identifies two alleles with bands at 6.8 and 5.7kb, as well as four constant bands at 4.8, 3.9, 3.5 and 2.5kb. Its frequency was studied in 62 unrelated individuals. Mendelian inheritance was demonstrated in one three generation and three two generation informative families, 26 individuals. There were no problems on RFLP analysis under normal stringency conditions.

44 CFR 71.2 - Definitions.

Science.gov (United States)

2010-10-01

... as by a private sector insurance company under the Write Your Own Program as authorized by 44 CFR... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Definitions. 71.2 Section 71... LEGISLATION § 71.2 Definitions. (a) Except as otherwise provided in this part, the definitions set forth in...

Sigma models in (4,4) harmonic superspace

International Nuclear Information System (INIS)

Ivanov, E.; Joint Inst. for Nuclear Research, Dubna; Sutulin, A.

1994-04-01

We define basics of (4,4) 2D harmonic superspace with two independent sets of SU(2) harmonic variables and apply it to construct new superfield actions of (4,4) supersymmetric two-dimensional sigma models with torsion and mutually commuting left and right complex structures, as well as of their massive deformations. We show that the generic off-shell sigma model action is the general action of constrained analytic superfields q (1,1) representing twisted N=4 multiplets in (4,4) harmonic superspace. The massive term of q (1,1) is shown to be unique; it generates a scalar potential the form of which is determined by the metric on the target bosonic manifold. We discuss in detail (4,4) supersymmetric group manifold SU(2)xU(1) WZNW sigma model and its Liouville deformation. A deep analogy of the relevant superconformally invariant analytic superfield action to that of the improved tensor N=2 4D multiplet is found. We define (4,4) duality transformation and find new off-shell dual representations of the previously constructed actions via unconstrained analytic (4,4) superfields. The main peculiarities of the (4,4) duality transformation are: (i) It preserves manifest (4,4) supersymmetry; (ii) dual actions reveal a gauge invariance needed for the onshell equivalence to the original description; (iii) in the actions dual to the massive ones 2D supersymmetry is modified off shell by SU(2) tensor central charges. The dual representation suggests some hints of how to describe (4,4) models with non-commuting complex structures in the harmonic superspace. (orig.)

[Dectection of G3BP and CD44v6 in the tissues of laryngeal squamous cell carcinoma and their clinical significance].

Science.gov (United States)

Luo, Dahu; Lou, Weihua

2017-07-01

Objective To study the expressions of RNA-binding Ras-GAP SH3 binding protein (G3BP) and tumor stem cell marker CD44v6 in laryngeal squamous cell carcinoma and their correlations with angiogenesis. Methods We collected the cancer tissues and corresponding paracancerous tissues from 56 patients with laryngeal squamous cell carcinoma. The expressions of G3BP and CD44v6 proteins were detected by Western blotting in cancer tissues and corresponding paracancerous tissues; the expressions of G3BP, CD44v6 and vascular endothelial growth factor A (VEGF-A) were tested by immunohistochemistry. Thereafter, we compared the positive expression rates of G3BP and CD44v6 between in cancer tissues and in normal tissues, analyzed the correlations between the expressions of G3BP, CD44v6 and the laryngeal squamous cell carcinoma features as well as their correlations with microvessel density (MVD) that was determined by FVIIIAg immunohistochemistry. Results Western blotting showed that the expressions of G3BP and CD44v6 proteins in the laryngeal squamous cell carcinoma were higher than those in the paracancerous tissues. Immunohistochemistry showed that compared with the paracancerous tissues, G3BP, CD44v6 and VEGF-A expressions (the positive rates are 58.9%, 53.6%, 46.4%, respectively) were higher in cancer tissues. The positive rates of G3BP and CD44v6 in cancer tissues were related with the clinical stage, recurrence or metastasis, and lymph node metastasis of laryngeal squamous cell carcinoma, but had nothing to do with patients' age and tumor size. Pearson correlation analysis showed the expressions of both G3BP and CD44v6 were positively correlated with VEGF-A (r=0.741, r=0.756). MVD values were significantly higher in the G3BP and CD44v6 positive cases than in paracancerous tissues, but there was no difference in MVD between those without G3BP and CD44v6 positive expressions and the paracancerous tissues. Conclusion The positive expression rates of G3BP and CD44v6 in laryngeal

45 CFR 92.44 - Termination for convenience.

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2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Termination for convenience. 92.44 Section 92.44 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION UNIFORM ADMINISTRATIVE... Requirements Reports, Records Retention, and Enforcement § 92.44 Termination for convenience. Except as...

14 CFR 1273.44 - Termination for convenience.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Termination for convenience. 1273.44 Section 1273.44 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION UNIFORM ADMINISTRATIVE... Reports, Records, Retention, and Enforcement § 1273.44 Termination for convenience. Except as provided in...

13 CFR 143.44 - Termination for convenience.

Science.gov (United States)

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Termination for convenience. 143.44 Section 143.44 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION UNIFORM ADMINISTRATIVE... Reports, Records, Retention, and Enforcement § 143.44 Termination for convenience. Except as provided in...

Anàlisi de la mobilitat de l'estudiant universitari en el marc de l'Europa 2020 per al foment de l'ocupació i les competències genèriques. Un estudi de casos en la Universitat d'Oviedo

Directory of Open Access Journals (Sweden)

Javier Fombona Cadavieco

2012-12-01

Full Text Available Aquesta investigació analitza la percepció de l'estudiant universitari sobre els beneficis de la mobilitat estudiantil en l'Espai Europeu d'Educació Superior. Especialment atenem a l'anàlisi de competències genèriques que puguin atorgar més possibilitats en la recerca d'ocupació. Per això, abordem un estudi de casos a la Universitat d'Oviedo des d'una metodologia quantitativa prenent com a referència els objectius marcats en la iniciativa Europa 2020. Les conclusions donen resultats molt positius en competències interdisciplinars per a la recerca de feina, com ara el domini idiomàtic, el coneixement de noves societats i dels entorns professionals. 

L'urétroplastie par résection anastomose terminoterminale pour ...

African Journals Online (AJOL)

K.H. Sikpa

Résumé. Objectif : évaluer l'uretroplastie par résection anastomose terminoterminale (URAT) au CHU Sylvanus. Olympio de Lomé au Togo. Patients et méthodes : étude descriptive, rétrospective sur 30 mois, portant sur 34 patients qui ont subi une. URAT. Résultats : L'âge moyen des patients était de 44,79+/-15 ans.

20 CFR 437.44 - Termination for convenience.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Termination for convenience. 437.44 Section 437.44 Employees' Benefits SOCIAL SECURITY ADMINISTRATION UNIFORM ADMINISTRATIVE REQUIREMENTS FOR..., Retention, and Enforcement § 437.44 Termination for convenience. Except as provided in § 437.43, awards may...

29 CFR 1470.44 - Termination for convenience.

Science.gov (United States)

2010-07-01

... 29 Labor 4 2010-07-01 2010-07-01 false Termination for convenience. 1470.44 Section 1470.44 Labor Regulations Relating to Labor (Continued) FEDERAL MEDIATION AND CONCILIATION SERVICE UNIFORM ADMINISTRATIVE... Reports, Records Retention, and Enforcement § 1470.44 Termination for convenience. Except as provided in...

Imaging of Protein Synthesis: In Vitro and In Vivo Evaluation of Sc-44-DOTA-Puromycin

Czech Academy of Sciences Publication Activity Database

Eigner, Sebastian; Beckford, Denis R.; Fellner, M.; Loktionova, N.; Piel, M.; Lebeda, Ondřej; Rosch, F.; Ross, T. L.; Eigner-Henke, Kateřina

2013-01-01

Roč. 15, č. 1 (2013), s. 79-86 ISSN 1536-1632 R&D Projects: GA MŠk 2B06165 Institutional support: RVO:61389005 Keywords : protein synthesis * Scandium-44 * DOTA-Pur * therapy control * mu PET * preclinical imaging Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 2.869, year: 2013 http://link.springer.com/content/pdf/10.1007%2Fs11307-012-0561-3

Promoter- and cell-specific epigenetic regulation of CD44, Cyclin D2, GLIPR1 and PTEN by Methyl-CpG binding proteins and histone modifications

International Nuclear Information System (INIS)

Müller, Imke; Wischnewski, Frank; Pantel, Klaus; Schwarzenbach, Heidi

2010-01-01

The aim of the current study was to analyze the involvement of methyl-CpG binding proteins (MBDs) and histone modifications on the regulation of CD44, Cyclin D2, GLIPR1 and PTEN in different cellular contexts such as the prostate cancer cells DU145 and LNCaP, and the breast cancer cells MCF-7. Since global chromatin changes have been shown to occur in tumours and regions of tumour-associated genes are affected by epigenetic modifications, these may constitute important regulatory mechanisms for the pathogenesis of malignant transformation. In DU145, LNCaP and MCF-7 cells mRNA expression levels of CD44, Cyclin D2, GLIPR1 and PTEN were determined by quantitative RT-PCR at the basal status as well as after treatment with demethylating agent 5-aza-2'-deoxycytidine and/or histone deacetylase inhibitor Trichostatin A. Furthermore, genomic DNA was bisulfite-converted and sequenced. Chromatin immunoprecipitation was performed with the stimulated and unstimulated cells using antibodies for MBD1, MBD2 and MeCP2 as well as 17 different histone antibodies. Comparison of the different promoters showed that MeCP2 and MBD2a repressed promoter-specifically Cyclin D2 in all cell lines, whereas in MCF-7 cells MeCP2 repressed cell-specifically all methylated promoters. Chromatin immunoprecipitation showed that all methylated promoters associated with at least one MBD. Treatment of the cells by the demethylating agent 5-aza-2'-deoxycytidine (5-aza-CdR) caused dissociation of the MBDs from the promoters. Only MBD1v1 bound and repressed methylation-independently all promoters. Real-time amplification of DNA immunoprecipitated by 17 different antibodies showed a preferential enrichment for methylated lysine of histone H3 (H3K4me1, H3K4me2 and H3K4me3) at the particular promoters. Notably, the silent promoters were associated with unmodified histones which were acetylated following treatment by 5-aza-CdR. This study is one of the first to reveal the histone code and MBD profile

CD44 Binding to Hyaluronic Acid Is Redox Regulated by a Labile Disulfide Bond in the Hyaluronic Acid Binding Site.

Directory of Open Access Journals (Sweden)

Helena Kellett-Clarke

Full Text Available CD44 is the primary leukocyte cell surface receptor for hyaluronic acid (HA, a component of the extracellular matrix. Enzymatic post translational cleavage of labile disulfide bonds is a mechanism by which proteins are structurally regulated by imparting an allosteric change and altering activity. We have identified one such disulfide bond in CD44 formed by Cys77 and Cys97 that stabilises the HA binding groove. This bond is labile on the surface of leukocytes treated with chemical and enzymatic reducing agents. Analysis of CD44 crystal structures reveal the disulfide bond to be solvent accessible and in the-LH hook configuration characteristic of labile disulfide bonds. Kinetic trapping and binding experiments on CD44-Fc chimeric proteins show the bond is preferentially reduced over the other disulfide bonds in CD44 and reduction inhibits the CD44-HA interaction. Furthermore cells transfected with CD44 no longer adhere to HA coated surfaces after pre-treatment with reducing agents. The implications of CD44 redox regulation are discussed in the context of immune function, disease and therapeutic strategies.

22 CFR 135.44 - Termination for convenience.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Termination for convenience. 135.44 Section 135.44 Foreign Relations DEPARTMENT OF STATE MISCELLANEOUS UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS..., Retention, and Enforcement § 135.44 Termination for convenience. Except as provided in § 135.43 awards may...

15 CFR 24.44 - Termination for convenience.

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2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Termination for convenience. 24.44 Section 24.44 Commerce and Foreign Trade Office of the Secretary of Commerce UNIFORM ADMINISTRATIVE... Reports, Records, Retention, and Enforcement § 24.44 Termination for convenience. Except as provided in...

30 CFR 44.11 - Contents of petition.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Contents of petition. 44.11 Section 44.11... ADMINISTRATIVE REQUIREMENTS RULES OF PRACTICE FOR PETITIONS FOR MODIFICATION OF MANDATORY SAFETY STANDARDS Initial Procedure for Petitions for Modification § 44.11 Contents of petition. (a) A petition for...

7 CFR 868.44 - New original inspection.

Science.gov (United States)

2010-01-01

... 7 Agriculture 7 2010-01-01 2010-01-01 false New original inspection. 868.44 Section 868.44... FOR CERTAIN AGRICULTURAL COMMODITIES Regulations Original Inspection Service § 868.44 New original... applicant may request a new original inspection on any previously inspected lot; except that a new original...

Cyclotron production of {sup 44}Sc for clinical application

Energy Technology Data Exchange (ETDEWEB)

Krajewski, S.; Bilewicz, A. [Institute of Nuclear Chemistry and Technology, Warsaw (Poland); Cydzik, I. [Institute of Nuclear Chemistry and Technology, Warsaw (Poland); European Commission Joint Research Center, Ispra (Italy). Inst. for Health and Consumer Protection; Warsaw Univ. (Poland). Heavy Ion Lab.; Abbas, K. [European Commission Joint Research Center, Ispra (Italy). Institute for Transuranium Elements; Bulgheroni, A.; Simonelli, F.; Holzwarth, U. [European Commission Joint Research Center, Ispra (Italy). Inst. for Health and Consumer Protection

2013-08-01

{sup 44} is a promising {beta}{sup +}-emitter for molecular imaging with intermediate half-life of 4 h. Due to the chemical similarity of Sc{sup 3+} to the Lu{sup 3+} and Y{sup 3+} cations, {sup 44}Sc-DOTA bioconjugates are expected to demonstrate similar properties in vivo as the {sup 177}Lu- and {sup 90}Y-bioconjugates, what is important in planning the radionuclide therapy. {sup 44}Sc can be obtained from the {sup 44}Ti/{sup 44}Sc generator. An alternative method for {sup 44}Sc production can be the irradiation of {sup 44}Ca target at small cyclotrons. The aim of our work was to optimize the parameters of {sup 44}CaCO{sub 3} irradiation and to develop a simple procedure for {sup 44}Sc separation from the calcium target. For optimization study, {sup 44}CaCO{sub 3} targets were irradiated by protons in the energy range of 5.6-17.5 MeV with 9 MeV being found to be the best energy for {sup 44}Ca irradiations. A simple and fast separation procedure of {sup 44}Sc from calcium target was developed using chelating resin Chelex 100. DOTATATE conjugate was successfully radiolabelled with high yield at elevated temperature using the produced {sup 44}Sc. While {sup 44}CaCO{sub 3} is relatively expensive, the cost of {sup 44}Sc-DOTATATE production can be reduced by target recovery. Due to low proton energy required to produce GBq activity level of {sup 44}Sc, the availability of {sup 44}Sc radioisotope could be enhanced to open new opportunities for applications in medical imaging. (orig.)

CD44 isoforms are heterogeneously expressed in breast cancer and correlate with tumor subtypes and cancer stem cell markers

International Nuclear Information System (INIS)

Olsson, Eleonor; Lövgren, Kristina; Fernö, Mårten; Grabau, Dorthe; Borg, Åke; Hegardt, Cecilia; Honeth, Gabriella; Bendahl, Pär-Ola; Saal, Lao H; Gruvberger-Saal, Sofia; Ringnér, Markus; Vallon-Christersson, Johan; Jönsson, Göran; Holm, Karolina

2011-01-01

The CD44 cell adhesion molecule is aberrantly expressed in many breast tumors and has been implicated in the metastatic process as well as in the putative cancer stem cell (CSC) compartment. We aimed to investigate potential associations between alternatively spliced isoforms of CD44 and CSCs as well as to various breast cancer biomarkers and molecular subtypes. We used q-RT-PCR and exon-exon spanning assays to analyze the expression of four alternatively spliced CD44 isoforms as well as the total expression of CD44 in 187 breast tumors and 13 cell lines. ALDH1 protein expression was determined by IHC on TMA. Breast cancer cell lines showed a heterogeneous expression pattern of the CD44 isoforms, which shifted considerably when cells were grown as mammospheres. Tumors characterized as positive for the CD44 + /CD24 - phenotype by immunohistochemistry were associated to all isoforms except the CD44 standard (CD44S) isoform, which lacks all variant exons. Conversely, tumors with strong expression of the CSC marker ALDH1 had elevated expression of CD44S. A high expression of the CD44v2-v10 isoform, which retain all variant exons, was correlated to positive steroid receptor status, low proliferation and luminal A subtype. The CD44v3-v10 isoform showed similar correlations, while high expression of CD44v8-v10 was correlated to positive EGFR, negative/low HER2 status and basal-like subtype. High expression of CD44S was associated with strong HER2 staining and also a subgroup of basal-like tumors. Unsupervised hierarchical cluster analysis of CD44 isoform expression data divided tumors into four main clusters, which showed significant correlations to molecular subtypes and differences in 10-year overall survival. We demonstrate that individual CD44 isoforms can be associated to different breast cancer subtypes and clinical markers such as HER2, ER and PgR, which suggests involvement of CD44 splice variants in specific oncogenic signaling pathways. Efforts to link CD44 to

CD44 isoforms are heterogeneously expressed in breast cancer and correlate with tumor subtypes and cancer stem cell markers

Directory of Open Access Journals (Sweden)

Vallon-Christersson Johan

2011-09-01

Full Text Available Abstract Background The CD44 cell adhesion molecule is aberrantly expressed in many breast tumors and has been implicated in the metastatic process as well as in the putative cancer stem cell (CSC compartment. We aimed to investigate potential associations between alternatively spliced isoforms of CD44 and CSCs as well as to various breast cancer biomarkers and molecular subtypes. Methods We used q-RT-PCR and exon-exon spanning assays to analyze the expression of four alternatively spliced CD44 isoforms as well as the total expression of CD44 in 187 breast tumors and 13 cell lines. ALDH1 protein expression was determined by IHC on TMA. Results Breast cancer cell lines showed a heterogeneous expression pattern of the CD44 isoforms, which shifted considerably when cells were grown as mammospheres. Tumors characterized as positive for the CD44+/CD24- phenotype by immunohistochemistry were associated to all isoforms except the CD44 standard (CD44S isoform, which lacks all variant exons. Conversely, tumors with strong expression of the CSC marker ALDH1 had elevated expression of CD44S. A high expression of the CD44v2-v10 isoform, which retain all variant exons, was correlated to positive steroid receptor status, low proliferation and luminal A subtype. The CD44v3-v10 isoform showed similar correlations, while high expression of CD44v8-v10 was correlated to positive EGFR, negative/low HER2 status and basal-like subtype. High expression of CD44S was associated with strong HER2 staining and also a subgroup of basal-like tumors. Unsupervised hierarchical cluster analysis of CD44 isoform expression data divided tumors into four main clusters, which showed significant correlations to molecular subtypes and differences in 10-year overall survival. Conclusions We demonstrate that individual CD44 isoforms can be associated to different breast cancer subtypes and clinical markers such as HER2, ER and PgR, which suggests involvement of CD44 splice variants in

Influence of Route-R on wrought magnesium AZ61 alloy mechanical properties through equal channel angular pressing

Directory of Open Access Journals (Sweden)

Muralidhar Avvari

2014-06-01

Full Text Available A new fundamental route entitled ‘Route-R’ is introduced to refine the grains in the material through Equal Channel Angular Pressing (ECAP process. In route R, specimen is inverted to the original position in each ECAP pass. In the present work, AZ61 alloy is processed using ECAP process for three different fundamental routes mainly route A, route Bc, and route R. ECAP experiment is carried out on AZ61 alloy at lower temperature of 483 K up to two passes. Microstructural characterization is evaluated on unECAPed and ECAPed specimens for three routes. Average grain size of the alloy is to be reduced from 66 μm to 16 μm, 14.1 μm and 10 μm for route A routes Bc, and route R respectively. Vickers microhardness of the alloy is found to be 60 HV for as received material. This microhardness of the alloy is increased to 71 HV, 72 HV, and 74 HV for route A, route Bc, and route R respectively. Mechanical properties of the AZ61 alloy are observed to be route R is providing maximum YS, UTS, and percentage elongation than other route A and route Bc. Tensile fracture topography of the specimen is analyzed using three different routes for two passes.

Oxidative stress-induced overexpression of miR-25: the mechanism underlying the degeneration of melanocytes in vitiligo

Science.gov (United States)

Shi, Q; Zhang, W; Guo, S; Jian, Z; Li, S; Li, K; Ge, R; Dai, W; Wang, G; Gao, T; Li, C

2016-01-01

Oxidative stress has a critical role in the pathogenesis of vitiligo. However, the specific molecular mechanism involved in oxidative stress-induced melanocyte death is not well characterized. Given the powerful role of microRNAs (miRNAs) in the regulation of cell survival as well as the fact that the generation of miRNAs can be affected by oxidative stress, we hypothesized that miRNAs may participate in vitiligo pathogenesis by modulating the expression of vital genes in melanocytes. In the present study, we initially found that miR-25 was increased in both serum and lesion samples from vitiligo patients, and its serum level was correlated with the activity of vitiligo. Moreover, restoration of miR-25 promoted the H2O2-induced melanocyte destruction and led to the dysfunction of melanocytes. Further experiments proved that MITF, a master regulator in melanocyte survival and function, accounted for the miR-25-caused damaging impact on melanocytes. Notably, other than the direct role on melanocytes, we observed that miR-25 inhibited the production and secretion of SCF and bFGF from keratinocytes, thus impairing their paracrine protective effect on the survival of melanocytes under oxidative stress. At last, we verified that oxidative stress could induce the overexpression of miR-25 in both melanocytes and keratinocytes possibly by demethylating the promoter region of miR-25. Taken together, our study demonstrates that oxidative stress-induced overexpression of miR-25 in vitiligo has a crucial role in promoting the degeneration of melanocytes by not only suppressing MITF in melanocytes but also impairing the paracrine protective effect of keratinocytes. Therefore, it is worthy to investigate the possibility of miR-25 as a potential drug target for anti-oxidative therapy in vitiligo. PMID:26315342

49 CFR 18.44 - Termination for convenience.

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2010-10-01

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34 CFR 80.44 - Termination for convenience.

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2010-07-01

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45 CFR 1157.44 - Termination for convenience.

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2010-10-01

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45 CFR 1183.44 - Termination for convenience.

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2010-10-01

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21 CFR 1403.44 - Termination for convenience.

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2010-04-01

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45 CFR 1174.44 - Termination for convenience.

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2010-10-01

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45 CFR 602.44 - Termination for convenience.

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2010-10-01

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miR-155 Deletion in Mice Overcomes Neuron-Intrinsic and Neuron-Extrinsic Barriers to Spinal Cord Repair.

Science.gov (United States)

Gaudet, Andrew D; Mandrekar-Colucci, Shweta; Hall, Jodie C E; Sweet, David R; Schmitt, Philipp J; Xu, Xinyang; Guan, Zhen; Mo, Xiaokui; Guerau-de-Arellano, Mireia; Popovich, Phillip G

2016-08-10

Axon regeneration after spinal cord injury (SCI) fails due to neuron-intrinsic mechanisms and extracellular barriers including inflammation. microRNA (miR)-155-5p is a small, noncoding RNA that negatively regulates mRNA translation. In macrophages, miR-155-5p is induced by inflammatory stimuli and elicits a response that could be toxic after SCI. miR-155 may also independently alter expression of genes that regulate axon growth in neurons. Here, we hypothesized that miR-155 deletion would simultaneously improve axon growth and reduce neuroinflammation after SCI by acting on both neurons and macrophages. New data show that miR-155 deletion attenuates inflammatory signaling in macrophages, reduces macrophage-mediated neuron toxicity, and increases macrophage-elicited axon growth by ∼40% relative to control conditions. In addition, miR-155 deletion increases spontaneous axon growth from neurons; adult miR-155 KO dorsal root ganglion (DRG) neurons extend 44% longer neurites than WT neurons. In vivo, miR-155 deletion augments conditioning lesion-induced intraneuronal expression of SPRR1A, a regeneration-associated gene; ∼50% more injured KO DRG neurons expressed SPRR1A versus WT neurons. After dorsal column SCI, miR-155 KO mouse spinal cord has reduced neuroinflammation and increased peripheral conditioning-lesion-enhanced axon regeneration beyond the epicenter. Finally, in a model of spinal contusion injury, miR-155 deletion improves locomotor function at postinjury times corresponding with the arrival and maximal appearance of activated intraspinal macrophages. In miR-155 KO mice, improved locomotor function is associated with smaller contusion lesions and decreased accumulation of inflammatory macrophages. Collectively, these data indicate that miR-155 is a novel therapeutic target capable of simultaneously overcoming neuron-intrinsic and neuron-extrinsic barriers to repair after SCI. Axon regeneration after spinal cord injury (SCI) fails due to neuron

miR-155 Deletion in Mice Overcomes Neuron-Intrinsic and Neuron-Extrinsic Barriers to Spinal Cord Repair

Science.gov (United States)

Mandrekar-Colucci, Shweta; Hall, Jodie C.E.; Sweet, David R.; Schmitt, Philipp J.; Xu, Xinyang; Guan, Zhen; Mo, Xiaokui; Guerau-de-Arellano, Mireia

2016-01-01

Axon regeneration after spinal cord injury (SCI) fails due to neuron-intrinsic mechanisms and extracellular barriers including inflammation. microRNA (miR)-155–5p is a small, noncoding RNA that negatively regulates mRNA translation. In macrophages, miR-155-5p is induced by inflammatory stimuli and elicits a response that could be toxic after SCI. miR-155 may also independently alter expression of genes that regulate axon growth in neurons. Here, we hypothesized that miR-155 deletion would simultaneously improve axon growth and reduce neuroinflammation after SCI by acting on both neurons and macrophages. New data show that miR-155 deletion attenuates inflammatory signaling in macrophages, reduces macrophage-mediated neuron toxicity, and increases macrophage-elicited axon growth by ∼40% relative to control conditions. In addition, miR-155 deletion increases spontaneous axon growth from neurons; adult miR-155 KO dorsal root ganglion (DRG) neurons extend 44% longer neurites than WT neurons. In vivo, miR-155 deletion augments conditioning lesion-induced intraneuronal expression of SPRR1A, a regeneration-associated gene; ∼50% more injured KO DRG neurons expressed SPRR1A versus WT neurons. After dorsal column SCI, miR-155 KO mouse spinal cord has reduced neuroinflammation and increased peripheral conditioning-lesion-enhanced axon regeneration beyond the epicenter. Finally, in a model of spinal contusion injury, miR-155 deletion improves locomotor function at postinjury times corresponding with the arrival and maximal appearance of activated intraspinal macrophages. In miR-155 KO mice, improved locomotor function is associated with smaller contusion lesions and decreased accumulation of inflammatory macrophages. Collectively, these data indicate that miR-155 is a novel therapeutic target capable of simultaneously overcoming neuron-intrinsic and neuron-extrinsic barriers to repair after SCI. SIGNIFICANCE STATEMENT Axon regeneration after spinal cord injury (SCI) fails

Insight into the molecular mechanism of yeast acetyl-coenzyme A carboxylase mutants F510I, N485G, I69E, E477R, and K73R resistant to soraphen A

Science.gov (United States)

Gao, Jian; Liang, Li; Chen, Qingqing; Zhang, Ling; Huang, Tonghui

2018-02-01

Acetyl-coenzyme A carboxylases (ACCs) is the first committed enzyme of fatty acid synthesis pathway. The inhibition of ACC is thought to be beneficial not only for diseases related to metabolism, such as type-2 diabetes, but also for infectious disease like bacterial infection disease. Soraphen A, a potent allosteric inhibitor of BC domain of yeast ACC, exhibit lower binding affinities to several yeast ACC mutants and the corresponding drug resistance mechanisms are still unknown. We report here a theoretical study of binding of soraphen A to wild type and yeast ACC mutants (including F510I, N485G, I69E, E477R, and K73R) via molecular dynamic simulation and molecular mechanics/generalized Born surface area free energy calculations methods. The calculated binding free energies of soraphen A to yeast ACC mutants are weaker than to wild type, which is highly consistent with the experimental results. The mutant F510I weakens the binding affinity of soraphen A to yeast ACC mainly by decreasing the van der Waals contributions, while the weaker binding affinities of Soraphen A to other yeast ACC mutants including N485G, I69E, E477R, and K73R are largely attributed to the decreased net electrostatic (ΔE ele + ΔG GB) interactions. Our simulation results could provide important insights for the development of more potent ACC inhibitors.

29 CFR 97.44 - Termination for convenience.

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2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true Termination for convenience. 97.44 Section 97.44 Labor Office of the Secretary of Labor UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND COOPERATIVE... § 97.44 Termination for convenience. Except as provided in § 97.43 awards may be terminated in whole or...

Tumor production in Syrian hamsters following inhalation of PuO2--ZrO2 aerosol

International Nuclear Information System (INIS)

Thomas, R.G.; Smith, D.M.

1978-01-01

Syrian golden hamsters of both sexes were exposed to aerosols of ZrO 2 containing PuO 2 . The starting material in the aerosol generator also had a small amount of 57 Co added as a tracer. The mixture of all three constituents was nebulized and the droplets passed through a heating column at 1000 0 C. Aerosol sampling was accomplished with a cascade impactor and electrostatic precipitator. The median aerodynamic diameters in all inhalation runs were approximately 2 μm with a geometric standard deviation of 2. One exposed group of 60 hamsters had 6-day lung burdens averaging 100 nCi. This group had a lung tumor incidence of 44% with an even distribution of adenomas and carcinomas. Two other groups had average 6-day lung burdens of 80 to 90 nCi plus 55 nCi of intravenously injected spheres localized in the lung. These animals had tumor incidences of approximately 30%

24 CFR 85.44 - Termination for convenience.

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2010-04-01

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30 CFR 44.9 - Posting of petition.

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2010-07-01

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46 CFR 44.01-13 - Heavy weather plan.

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2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Heavy weather plan. 44.01-13 Section 44.01-13 Shipping... VOYAGES Administration § 44.01-13 Heavy weather plan. (a) Each heavy weather plan under § 44.01-12(b) must... Inspection. Approval of a heavy weather plan is limited to the current hurricane season. (b) The cognizant...

Study of the $^{44}$Ti$(\\alpha,p)^{47}$V47 reaction and implications for core collapse supernovae

CERN Document Server

Margerin, V; Davinson, T; Dressler, R; Fallis, J; Kankainen, A; Laird, A M; Lotay, G; Mountford, D J; Murphy, C D; Seiffert, C; Schumann, D; Stowasser, T; Stora, T; Wang, C H -T; Woods, P J

2014-01-01

The underlying physics triggering core collapse supernovae is not fully understood but observations of material ejected during such events helps to solve this puzzle. In particular, several satellite based γ -ray observations of the isotope 44 Ti have been reported recently. Conveniently, the amount of this isotope in stellar ejecta is thought to depend critically on the explosion mechanism. The most influential reaction to the amount of 44 Ti in supernovae is 44 Ti ( α , p ) 47 V. Here we report on a direct study of this reaction conducted at the REX-ISOLDE facility, CERN. The experiment was performed with a 44 Ti beam at E lab = 2 . 16 MeV / u, corresponding to an energy distribution, for reacting α -particles, centred on E cm = 4 . 15 with a 1 σ width of 0.23 MeV. This is, for the first time, well within the Gamow window for core collapse supernovae. The material from which the 44 Ti beam was extracted originates from highly irradiated components of the SINQ spallation neutron source of the Paul Scherr...

Neutron Reference Benchmark Field Specification: ACRR 44 Inch Lead-Boron (LB44) Bucket Environment (ACRR-LB44-CC-32-CL).

Energy Technology Data Exchange (ETDEWEB)

Vega, Richard Manuel [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Parma, Edward J. [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Griffin, Patrick J. [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Vehar, David W. [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States)

2015-07-01

This report was put together to support the International Atomic Energy Agency (IAEA) REAL- 2016 activity to validate the dosimetry community’s ability to use a consistent set of activation data and to derive consistent spectral characterizations. The report captures details of integral measurements taken in the Annular Core Research Reactor (ACRR) central cavity with the 44 inch Lead-Boron (LB44) bucket, reference neutron benchmark field. The field is described and an “a priori” calculated neutron spectrum is reported, based on MCNP6 calculations, and a subject matter expert (SME) based covariance matrix is given for this “a priori” spectrum. The results of 31 integral dosimetry measurements in the neutron field are reported.

The metric approximation property and Lipschitz-free spaces over subsets of R-N

Czech Academy of Sciences Publication Activity Database

Pernecká, Eva; Smith, R.J.

2015-01-01

Roč. 199, November (2015), s. 29-44 ISSN 0021-9045 R&D Projects: GA ČR(CZ) GAP201/11/0345 Institutional support: RVO:67985840 Keywords : Lipschitz-free space * approximation property Subject RIV: BA - General Mathematics Impact factor: 0.921, year: 2015 http://www.sciencedirect.com/science/article/pii/S0021904515000970

Isospin excitation of nucleus in 42,44,48Ca (p,n)42,44,48Sc

International Nuclear Information System (INIS)

Suzuki, Keiji

2002-01-01

To obtain information of (p,n) reaction of heavy nucleus in 100 MeV or less, 42,44,48 Ca(p,n) 42,44,48 Sc was observed on the Cyclotron Radio Isotope Center in Tohoku University. The experimental results showed that 7, 8 and 10 spin parities were determined for 42 Sc, 44 Sc and 48 SC, respectively. It was the first determination of one and two negative parity transition of 42 Sc and 48 Sc,respectively, by (p,n) reaction. The full space wave function made by 0f1p shell effective interaction by Richter,et al is good accuracy and reliability. On the (p,n) reaction at E p =35 MeV, the transition matrix elements of 42 Ca, 44 Ca and 48 Ca were derived. On the experiment of 42 Ca(p,n) 42 Sc at E p 2 on energy was agreed with the calculation results by Franey and Love. The nuclear structure of 42 Ca was thought to show more stronger U(4) symmetry, because strong GT transition at T=1 was not observed, which was expected by j-j bonding shell model calculation. (S.Y.)

Crystal structure of (1S,3R,8R,9R-2,2-dichloro-3,7,7-trimethyl-10-methylenetricyclo[6.4.0.01,3]dodecan-9-ol

Directory of Open Access Journals (Sweden)

Ahmed Benzalim

2016-08-01

Full Text Available The title compound, C16H24Cl2O, was synthesized by treating (1S,3R,8S,9R,10S-2,2-dichloro-3,7,7,10-tetramethyl-9,10-epoxytricyclo[6.4.0.01,3]dodecane with a concentrated solution of hydrobromic acid. It is built up from three fused rings: a cycloheptane ring, a cyclohexyl ring bearing alkene and hydroxy substituents, and a cyclopropane ring bearing two chlorine atoms. The asymmetric unit contains two molecules linked by an O—H...O hydrogen bond. In the crystal, further O—H...O hydrogen bonds build up an R44(8 cyclic tetramer. One of the molecules presents disorder that affects the seven-membered ring. In both molecules, the six-membered rings display a chair conformation, whereas the seven-membered rings display conformations intermediate between boat and twist-boat for the non-disordered molecule and either a chair or boat and twist-boat for the disordered molecule owing to the disorder. The absolute configuration for both molecules is 1S,3R,8R,9R and was deduced from the chemical pathway and further confirmed by the X-ray structural analysis.

Obesity-stimulated aldosterone release is not related to an S1P-dependent mechanism.

Science.gov (United States)

Werth, Stephan; Müller-Fielitz, Helge; Raasch, Walter

2017-12-01

Aldosterone has been identified as an important factor in obesity-associated hypertension. Here, we investigated whether sphingosine-1-phosphate (S1P), which has previously been linked to obesity, increases aldosterone release. S1P-induced aldosterone release was determined in NCI H295R cells in the presence of S1P receptor (S1PR) antagonists. In vivo release of S1P (100-300 µg/kg bw ) was investigated in pithed, lean Sprague Dawley (SD) rats, diet-obese spontaneous hypertensive rats (SHRs), as well as in lean or obese Zucker rats. Aldosterone secretion was increased in NCI H295R cells by S1P, the selective S1PR1 agonist SEW2871 and the selective S1PR2 antagonist JTE013. Treatment with the S1PR1 antagonist W146 or fingolimod and the S1PR1/3 antagonist VPbib2319 decreased baseline and/or S1P-stimulated aldosterone release. Compared to saline-treated SD rats, plasma aldosterone increased by ~50 pg/mL after infusing S1P. Baseline levels of S1P and aldosterone were higher in obese than in lean SHRs. Adrenal S1PR expression did not differ between chow- or CD-fed rats that had the highest S1PR1 and lowest S1PR4 levels. S1P induced a short-lasting increase in plasma aldosterone in obese, but not in lean SHRs. However, 2-ANOVA did not demonstrate any difference between lean and obese rats. S1P-induced aldosterone release was also similar between obese and lean Zucker rats. We conclude that S1P is a local regulator of aldosterone production. S1PR1 agonism induces an increase in aldosterone secretion, while stimulating adrenal S1PR2 receptor suppresses aldosterone production. A significant role of S1P in influencing aldosterone secretion in states of obesity seems unlikely. © 2017 Society for Endocrinology.

High prevalence of plasmid-mediated 16S rRNA methylase gene rmtB among Escherichia coli clinical isolates from a Chinese teaching hospital

Directory of Open Access Journals (Sweden)

Zhang Xue-qing

2010-06-01

Full Text Available Abstract Background Recently, production of 16S rRNA methylases by Gram-negative bacilli has emerged as a novel mechanism for high-level resistance to aminoglycosides by these organisms in a variety of geographic locations. Therefore, the spread of high-level aminoglycoside resistance determinants has become a great concern. Methods Between January 2006 and July 2008, 680 distinct Escherichia coli clinical isolates were collected from a teaching hospital in Wenzhou, China. PCR and DNA sequencing were used to identify 16S rRNA methylase and extended-spectrum β-lactamase (ESBL genes, including armA and rmtB, and in situ hybridization was performed to determine the location of 16S rRNA methylase genes. Conjugation experiments were subsequently performed to determine whether aminoglycoside resistance was transferable from the E. coli isolates via 16S rRNA methylase-bearing plasmids. Homology of the isolates harboring 16S rRNA methylase genes was determined using pulse-field gel electrophoresis (PFGE. Results Among the 680 E. coli isolates, 357 (52.5%, 346 (50.9% and 44 (6.5% isolates were resistant to gentamicin, tobramycin and amikacin, respectively. Thirty-seven of 44 amikacin-resistant isolates harbored 16S rRNA methylase genes, with 36 of 37 harboring the rmtB gene and only one harboring armA. The positive rates of 16S rRNA methylase genes among all isolates and amikacin-resistant isolates were 5.4% (37/680 and 84.1% (37/44, respectively. Thirty-one isolates harboring 16S rRNA methylase genes also produced ESBLs. In addition, high-level aminoglycoside resistance could be transferred by conjugation from four rmtB-positive donors. The plasmids of incompatibility groups IncF, IncK and IncN were detected in 34, 3 and 3 isolates, respectively. Upstream regions of the armA gene contained ISCR1 and tnpU, the latter a putative transposase gene,. Another putative transposase gene, tnpD, was located within a region downstream of armA. Moreover, a

Exosomes Promote Ovarian Cancer Cell Invasion through Transfer of CD44 to Peritoneal Mesothelial Cells.

Science.gov (United States)

Nakamura, Koji; Sawada, Kenjiro; Kinose, Yasuto; Yoshimura, Akihiko; Toda, Aska; Nakatsuka, Erika; Hashimoto, Kae; Mabuchi, Seiji; Morishige, Ken-Ichirou; Kurachi, Hirohisa; Lengyel, Ernst; Kimura, Tadashi

2017-01-01

Epithelial ovarian cancer (EOC) cells metastasize within the peritoneal cavity and directly encounter human peritoneal mesothelial cells (HPMC) as the initial step of metastasis. The contact between ovarian cancer cells and the single layer of mesothelial cells involves direct communications that modulate cancer progression but the mechanisms are unclear. One candidate mediating cell-cell communications is exosomes, 30-100 nm membrane vesicles of endocytic origin, through the cell-cell transfer of proteins, mRNAs, or microRNAs. Therefore, the goal was to mechanistically characterize how EOC-derived exosomes modulate metastasis. Exosomes from ovarian cancer cells were fluorescently labeled and cocultured with HPMCs which internalized the exosomes. Upon exosome uptake, HPMCs underwent a change in cellular morphology to a mesenchymal, spindle phenotype. CD44, a cell surface glycoprotein, was found to be enriched in the cancer cell-derived exosomes, transferred, and internalized to HPMCs, leading to high levels of CD44 in HPMCs. This increased CD44 expression in HPMCs promoted cancer invasion by inducing the HPMCs to secrete MMP9 and by cleaning the mesothelial barrier for improved cancer cell invasion. When CD44 expression was knocked down in cancer cells, exosomes had fewer effects on HPMCs. The inhibition of exosome release from cancer cells blocked CD44 internalization in HPMCs and suppressed ovarian cancer invasion. In ovarian cancer omental metastasis, positive CD44 expression was observed in those mesothelial cells that directly interacted with cancer cells, whereas CD44 expression was negative in the mesothelial cells remote from the invading edge. This study indicates that ovarian cancer-derived exosomes transfer CD44 to HPMCs, facilitating cancer invasion. Mechanistic insight from the current study suggests that therapeutic targeting of exosomes may be beneficial in treating ovarian cancer. Mol Cancer Res; 15(1); 78-92. ©2016 AACR. ©2016 American

Identification of IbeR as a Stationary-Phase Regulator in Meningitic Escherichia coli K1 that Carries a Loss-of-Function Mutation in rpoS

Directory of Open Access Journals (Sweden)

Feng Chi

2009-01-01

Full Text Available IbeR is a regulator present in meningitic Escherichia coli strain E44 that carries a loss-of-function mutation in the stationary-phase (SP regulatory gene rpoS. In order to determine whether IbeR is an SP regulator in E44, two-dimensional gel electrophoresis and LC-MS were used to compare the proteomes of a noninvasive ibeR deletion mutant BR2 and its parent strain E44 in the SP. Four up-regulated (TufB, GapA, OmpA, AhpC and three down-regulated (LpdA, TnaA, OpmC proteins in BR2 were identified when compared to E44. All these proteins contribute to energy metabolism or stress resistance, which is related to SP regulation. One of the down-regulated proteins, tryptophanase (TnaA, which is regulated by RpoS in other E. coli strains, is associated with SP regulation via production of a signal molecule indole. Our studies demonstrated that TnaA was required for E44 invasion, and that indole was able to restore the noninvasive phenotype of the tnaA mutant. The production of indole was significantly reduced in BR2, indicating that ibeR is required for the indole production via tnaA. Survival studies under different stress conditions indicated that IbeR contributed to bacteria stress resistance in the SP. Taken together, IbeR is a novel regulator contributing to the SP regulation.

Operation experience of the UE44 fixed gap APPLE II at SLS

International Nuclear Information System (INIS)

Schmidt, T; Calvi, M; Schmitt, T; Strocov, V N; Zimoch, D

2013-01-01

All soft x-ray beamlines at the Swiss Light Source (SLS) are served with variable polarization from APPLE II [1] type and electromagnetic undulators. Three APPLE II type undulators are used: a twin and a single standard APPLE II (UE56 and UE54) and a fixed gap APPLE II (UE44) which follows the adjustable-phase undulator approach by R. Carr [2], [3]. The demand to rotate the linear polarization vector from 0 – 180° required all four magnet arrays to be shiftable. This opened the possibility to also vary the energy by a suitable shift of the magnet arrays with a simplified support structure lacking in any gap drive system [4], [5]. The current photon beam quality in linear and circular mode and the pros and cons of the operation of the UE44 will be discussed, namely the underestimated influence of gradients in the complex field distribution. As a consequence the spectra are degraded, but can be recovered by use of distributed coils or by a simple change in the operation mode.

Rasch-built Overall Disability Scale for patients with chemotherapy-induced peripheral neuropathy (CIPN-R-ODS).

Science.gov (United States)

Binda, D; Vanhoutte, E K; Cavaletti, G; Cornblath, D R; Postma, T J; Frigeni, B; Alberti, P; Bruna, J; Velasco, R; Argyriou, A A; Kalofonos, H P; Psimaras, D; Ricard, D; Pace, A; Galiè, E; Briani, C; Dalla Torre, C; Lalisang, R I; Boogerd, W; Brandsma, D; Koeppen, S; Hense, J; Storey, D; Kerrigan, S; Schenone, A; Fabbri, S; Rossi, E; Valsecchi, M G; Faber, C G; Merkies, I S J; Galimberti, S; Lanzani, F; Mattavelli, L; Piatti, M L; Bidoli, P; Cazzaniga, M; Cortinovis, D; Lucchetta, M; Campagnolo, M; Bakkers, M; Brouwer, B; Boogerd, W; Grant, R; Reni, L; Piras, B; Pessino, A; Padua, L; Granata, G; Leandri, M; Ghignotti, I; Plasmati, R; Pastorelli, F; Heimans, J J; Eurelings, M; Meijer, R J; Grisold, W; Lindeck Pozza, E; Mazzeo, A; Toscano, A; Russo, M; Tomasello, C; Altavilla, G; Penas Prado, M; Dominguez Gonzalez, C; Dorsey, S G

2013-09-01

Chemotherapy-induced peripheral neuropathy (CIPN) is a common neurological side-effect of cancer treatment and may lead to declines in patients' daily functioning and quality of life. To date, there are no modern clinimetrically well-evaluated outcome measures available to assess disability in CIPN patients. The objective of the study was to develop an interval-weighted scale to capture activity limitations and participation restrictions in CIPN patients using the Rasch methodology and to determine its validity and reliability properties. A preliminary Rasch-built Overall Disability Scale (pre-R-ODS) comprising 146 items was assessed twice (interval: 2-3 weeks; test-retest reliability) in 281 CIPN patients with a stable clinical condition. The obtained data were subjected to Rasch analyses to determine whether model expectations would be met, and if necessarily, adaptations were made to obtain proper model fit (internal validity). External validity was obtained by correlating the CIPN-R-ODS with the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) neuropathy scales and the Pain-Intensity Numeric-Rating-Scale (PI-NRS). The preliminary R-ODS did not meet Rasch model's expectations. Items displaying misfit statistics, disordered thresholds, item bias or local dependency were systematically removed. The final CIPN-R-ODS consisting of 28 items fulfilled all the model's expectations with proper validity and reliability, and was unidimensional. The final CIPN-R-ODS is a Rasch-built disease-specific, interval measure suitable to detect disability in CIPN patients and bypasses the shortcomings of classical test theory ordinal-based measures. Its use is recommended in future clinical trials in CIPN. Copyright © 2013 Elsevier Ltd. All rights reserved.

44Sc-DOTA-BN[2-14]NH2 in comparison to 68Ga-DOTA-BN[2-14]NH2 in pre-clinical investigation. Is 44Sc a potential radionuclide for PET?

International Nuclear Information System (INIS)

Koumarianou, E.; Loktionova, N.S.; Fellner, M.; Roesch, F.; Thews, O.; Pawlak, D.; Archimandritis, S.C.; Mikolajczak, R.

2012-01-01

Aim: In the present study we demonstrate the in vitro and in vivo comparison of the 44 Sc and 68 Ga labeled DOTA-BN[2-14]NH 2 . 44 Sc is a positron emitter with a half life of 3.92 h. Hence it could be used for PET imaging with ligands requiring longer observation time than in the case of 68 Ga. Methods: The binding affinity of nat Sc-DOTA-BN[2-14]NH 2 and nat Ga-DOTA-BN[2-14]NH 2 to GRP receptors was studied in competition to [ 125 I-Tyr 4 ]-Bombesin in the human prostate cancer cell line PC-3. A preliminary biodistribution in normal rats was performed, while first microPET images were assessed in male Copenhagen rats bearing the androgen-independent Dunning R-3327-AT-1 prostate cancer tumor. Results: The affinity to GRP receptors in the PC-3 cell line was higher for nat Ga-DOTA-BN[2-14]NH 2 (IC 50 (nM)=0.85±0.06) than that of nat Sc-DOTA-BN[2-14]NH 2 (IC 50 (nM)=6.49±0.13). The internalization rate of 68 Ga labeled DOTA-BN[2-14]NH 2 was slower than that of 44 Sc, but their final internalization percents were comparable. 68 Ga-DOTA-BN[2-14]NH 2 was externalized faster than 44 Sc-DOTA-BN[2-14]NH 2 . The biodistribution of 44 Sc-DOTA-BN[2-14]NH 2 and 68 Ga-DOTA-BN[2-14]NH 2 in normal rats revealed a higher uptake in target organs and tissues of the first one while both excreted mainly through urinary tract. In microPET images both tracers were accumulated in the tumor with similar uptake patterns. Conclusions: Despite the differences in the receptor affinity both the 68 Ga- and the 44 Sc-labeled DOTA-BN[2-14]NH 2 tracers showed comparable distribution and similar time constants of uptake and elimination. Moreover no differences in tumor accumulation (neither in the overall uptake nor in the dynamics) were observed from the microPet imaging. From that perspective the use of either 44 Sc or 68 Ga for detecting tumors with GRP receptors is equivalent. - Highlights: ► In vitro and in vivo evaluation of 44 Sc- and 68 Ga-DOTA-BN[2-14]NH 2 in reference to published

La història de les ciències en l'ensenyament de la física i la química

OpenAIRE

Traver i Ribes, Manel Josep

1996-01-01

TESI DOCTORAL : “LA HISTÒRIA DE LES CIÈNCIES EN L’ENSENYAMENT DE LA FÍSICA I LA QUÍMICA” RESUM El problema que s’ha investigat en aquest treball consisteix en l’anàlisi del paper que juga actualment la Història de la Ciència en l’ensenyament de la Física i la Química i de la seua influència en la imatge de la ciència i en les actituds dels alumnes. S’hi han investigat dues hipòtesis principals. La primera consisteix en la constatació de l’escàs paper atribuït habitualment a la His...

28 CFR 544.44 - Disciplinary action.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Disciplinary action. 544.44 Section 544... EDUCATION Mandatory English-as-a-Second Language Program (ESL) § 544.44 Disciplinary action. As with any other mandatory programs, such as work assignments, staff may take disciplinary action against an inmate...

SYNTHESIS AND HEMOLYTIC PROPERTIES OF DERIVATIVES OF 4,4'-DIHYDROXYBIPHENYL – 2,2'-[BIPHENYL-4,4'- DIYLBIS(OXY]BIS[N-(METHYLAMINOALKILACETAMIDES

Directory of Open Access Journals (Sweden)

S. O. Zanoza

2016-04-01

Full Text Available The purpose of this work was synthesis of 4,4’-dihydroxybiphenyl derivatives, namely 2,2’-[biphenyl-4,4’-diylbis(oxy]bis[N-(2-aminoalkylacetamide], study of their hemolytic properties and the effect of the side chain structure on hemolytic properties. 2,2’-[Biphenyl-4,4’-diylbis(oxy]diacetic acid was synthesized by alkylation of 4,4’-dihydroxybiphenyl with methylbromoacetate, followed by alkaline hydrolysis. Chloroanhydride was obtained by treatment of this acid with thionyl chloride. 2,2’-[Biphenyl-4,4’-diylbis(oxy]  bis-[N-(2-aminoalkylacetamides] were synthesized in the biphasic media (dichloromethane/ aqueous sodium carbonate. Structures of synthesized compounds were proved by mass-spectrometryand 1Н NMR. Hemolytic properties were studied using healthy donors’ erythrocytes 0(I/Rh+. The absence of hemolytic properties for obtained compounds was shown, unlike similar 4,4’-aminoalkoxybiphenyls for which a significant hemolysis was shown. Thus, replacement of the ethylene group with amide group in the side chain of 4,4’-bissubstituted biphenyls significantly reduces hemolytic properties.

Analysis of neural mechanisms underlying verbal fluency in cytoarchitectonically defined stereotaxic space--the roles of Brodmann areas 44 and 45.

Science.gov (United States)

Amunts, Katrin; Weiss, Peter H; Mohlberg, Hartmut; Pieperhoff, Peter; Eickhoff, Simon; Gurd, Jennifer M; Marshall, John C; Shah, Nadim J; Fink, Gereon R; Zilles, Karl

2004-05-01

We investigated neural activations underlying a verbal fluency task and cytoarchitectonic probabilistic maps of Broca's speech region (Brodmann's areas 44 and 45). To do so, we reanalyzed data from a previous functional magnetic resonance imaging (fMRI) [Brain 125 (2002) 1024] and from a cytoarchitectonic study [J. Comp. Neurol. 412 (1999) 319] and developed a method to combine both data sets. In the fMRI experiment, verbal fluency was investigated in 11 healthy volunteers, who covertly produced words from predefined categories. A factorial design was used with factors verbal class (semantic vs. overlearned fluency) and switching between categories (no vs. yes). fMRI data analysis employed SPM99 (Statistical Parametric Mapping). Cytoarchitectonic maps of areas 44 and 45 were derived from histologic sections of 10 postmortem brains. Both the in vivo fMRI and postmortem MR data were warped to a common reference brain using a new elastic warping tool. Cytoarchitectonic probability maps with stereotaxic information about intersubject variability were calculated for both areas and superimposed on the functional data, which showed the involvement of left hemisphere areas with verbal fluency relative to the baseline. Semantic relative to overlearned fluency showed greater involvement of left area 45 than of 44. Thus, although both areas participate in verbal fluency, they do so differentially. Left area 45 is more involved in semantic aspects of language processing, while area 44 is probably involved in high-level aspects of programming speech production per se. The combination of functional data analysis with a new elastic warping tool and cytoarchitectonic maps opens new perspectives for analyzing the cortical networks involved in language.

38 CFR 4.44 - The bones.

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2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false The bones. 4.44 Section 4... DISABILITIES Disability Ratings The Musculoskeletal System § 4.44 The bones. The osseous abnormalities incident... convalescence, and progress of recovery with development of permanent residuals. With shortening of a long bone...

27 CFR 44.227 - Customs procedure.

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2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Customs procedure. 44.227..., WITHOUT PAYMENT OF TAX, OR WITH DRAWBACK OF TAX Drawback of Tax § 44.227 Customs procedure. The customs... having inspected the articles and supervised the lading thereof on the export carrier, the customs...

16 CFR 1502.44 - Review by the courts.

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2010-01-01

... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Review by the courts. 1502.44 Section 1502.44 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS PROCEDURES FOR FORMAL EVIDENTIARY PUBLIC HEARING Judicial Review § 1502.44 Review by the courts...

Regulation Mechanism of the ald Gene Encoding Alanine Dehydrogenase in Mycobacterium smegmatis and Mycobacterium tuberculosis by the Lrp/AsnC Family Regulator AldR.

Science.gov (United States)

Jeong, Ji-A; Hyun, Jaekyung; Oh, Jeong-Il

2015-10-01

In the presence of alanine, AldR, which belongs to the Lrp/AsnC family of transcriptional regulators and regulates ald encoding alanine dehydrogenase in Mycobacterium smegmatis, changes its quaternary structure from a homodimer to an octamer with an open-ring conformation. Four AldR-binding sites (O2, O1, O4, and O3) with a consensus sequence of GA/T-N2-NWW/WWN-N2-A/TC were identified upstream of the M. smegmatis ald gene by means of DNase I footprinting analysis. O2, O1, and O4 are required for the induction of ald expression by alanine, while O3 is directly involved in the repression of ald expression. In addition to O3, both O1 and O4 are also necessary for full repression of ald expression in the absence of alanine, due to cooperative binding of AldR dimers to O1, O4, and O3. Binding of a molecule of the AldR octamer to the ald control region was demonstrated to require two AldR-binding sites separated by three helical turns between their centers and one additional binding site that is in phase with the two AldR-binding sites. The cooperative binding of AldR dimers to DNA requires three AldR-binding sites that are aligned with a periodicity of three helical turns. The aldR gene is negatively autoregulated independently of alanine. Comparative analysis of ald expression of M. smegmatis and Mycobacterium tuberculosis in conjunction with sequence analysis of both ald control regions led us to suggest that the expression of the ald genes in both mycobacterial species is regulated by the same mechanism. In mycobacteria, alanine dehydrogenase (Ald) is the enzyme required both to utilize alanine as a nitrogen source and to grow under hypoxic conditions by maintaining the redox state of the NADH/NAD(+) pool. Expression of the ald gene was reported to be regulated by the AldR regulator that belongs to the Lrp/AsnC (feast/famine) family, but the underlying mechanism was unknown. This study revealed the regulation mechanism of ald in Mycobacterium smegmatis and

Conceptual design and related R and D on ITER mechanical based primary pumping system

International Nuclear Information System (INIS)

Tanzawa, Sadamitsu; Hiroki, Seiji; Abe, Tetsuya; Shimizu, Katsusuke; Inoue, Masahiko; Watanabe, Mitsunori; Iguchi, Masashi; Sugimoto, Tomoko; Inohara, Takashi; Nakamura, Jun-ichi

2008-12-01

The primary vacuum pumping system of the International Thermonuclear Experimental Reactor (ITER) exhausts a helium (He) ash resulting from the DT-burn with excess DT fueling gas, as well as performing a variety of functions such as pump-down, leak testing and wall conditioning. A mechanical based vacuum pumping system has some merits of a continuous pumping, a much lower tritium inventory, a lower operational cost and easy maintenance, comparing with a cryopump system, although demerits of an indispensable magnetic shield and insufficient performance for hydrogen (H 2 ) pumping is are well recognized. To overcome the demerits, we newly fabricated and tested a helical grooved pump (HGP) unit suitable for H 2 pumping at the ITER divertor pressure of 0.1-10 Pa. Through this R and D, we successfully established many design and manufacturing databases of large HGP units for the lightweight gas pumping. Based on the databases, we conceptually designed the ITER vacuum pumping system mainly comprising the HGP with an optimal pump unit layout and a magnetic shield. We also designed conceptually the reduced cost (RC)-ITER pumping system, where a compound molecular pump combining turbine bladed rotors and helical grooved ones was mainly used. The ITER mechanical based primary pumping system proposed has eventually been a back-up solution, whereas a cryopump based one was formally selected to the ITER for construction. The mechanical pumps are increasingly used in many areas with well sophisticated performance, so we believe that fusion reactors of subsequent prototype ones will select the mechanical based pumping system due to primarily a high operational reliability and a cost melt. (author)

30 CFR 44.10 - Filing of petition; service.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Filing of petition; service. 44.10 Section 44... ADMINISTRATIVE REQUIREMENTS RULES OF PRACTICE FOR PETITIONS FOR MODIFICATION OF MANDATORY SAFETY STANDARDS Initial Procedure for Petitions for Modification § 44.10 Filing of petition; service. A petition for...

44Sc-DOTA-BN[2-14]NH2 in comparison to 68Ga-DOTA-BN[2-14]NH2 in pre-clinical investigation. Is 44Sc a potential radionuclide for PET?

Science.gov (United States)

Koumarianou, E; Loktionova, N S; Fellner, M; Roesch, F; Thews, O; Pawlak, D; Archimandritis, S C; Mikolajczak, R

2012-12-01

In the present study we demonstrate the in vitro and in vivo comparison of the (44)Sc and (68)Ga labeled DOTA-BN[2-14]NH(2). (44)Sc is a positron emitter with a half life of 3.92 h. Hence it could be used for PET imaging with ligands requiring longer observation time than in the case of (68)Ga. The binding affinity of (nat)Sc-DOTA-BN[2-14]NH(2) and (nat)Ga-DOTA-BN[2-14]NH(2) to GRP receptors was studied in competition to [(125)I-Tyr(4)]-Bombesin in the human prostate cancer cell line PC-3. A preliminary biodistribution in normal rats was performed, while first microPET images were assessed in male Copenhagen rats bearing the androgen-independent Dunning R-3327-AT-1 prostate cancer tumor. The affinity to GRP receptors in the PC-3 cell line was higher for (nat)Ga-DOTA-BN[2-14]NH(2) (IC(50)(nM)=0.85 ± 0.06) than that of (nat)Sc-DOTA-BN[2-14]NH(2) (IC(50) (nM)=6.49 ± 0.13). The internalization rate of (68)Ga labeled DOTA-BN[2-14]NH(2) was slower than that of (44)Sc, but their final internalization percents were comparable. (68)Ga-DOTA-BN[2-14]NH(2) was externalized faster than (44)Sc-DOTA-BN[2-14]NH(2). The biodistribution of (44)Sc-DOTA-BN[2-14]NH(2) and (68)Ga-DOTA-BN[2-14]NH(2) in normal rats revealed a higher uptake in target organs and tissues of the first one while both excreted mainly through urinary tract. In microPET images both tracers were accumulated in the tumor with similar uptake patterns. Despite the differences in the receptor affinity both the (68)Ga- and the (44)Sc-labeled DOTA-BN[2-14]NH(2) tracers showed comparable distribution and similar time constants of uptake and elimination. Moreover no differences in tumor accumulation (neither in the overall uptake nor in the dynamics) were observed from the microPet imaging. From that perspective the use of either (44)Sc or (68)Ga for detecting tumors with GRP receptors is equivalent. Copyright © 2012 Elsevier Ltd. All rights reserved.

Neutral coordination polymers based on a metal-mono(dithiolene) complex: synthesis, crystal structure and supramolecular chemistry of [Zn(dmit)(4,4'-bpy)]n, [Zn(dmit)(4,4'-bpe)]n and [Zn(dmit)(bix)]n (4,4'-bpy = 4,4'-bipyridine, 4,4'-bpe = trans-1,2-bis(4-pyridyl)ethene, bix = 1,4-bis(imidazole-1-ylmethyl)-benzene.

Science.gov (United States)

Madhu, Vedichi; Das, Samar K

2011-12-28

This article describes a unique synthetic route that enables a neutral mono(dithiolene)metal unit, {Zn(dmit)}, to link with three different organic molecules, resulting in the isolation of a new class of neutral coordination polymers. The species {Zn(dmit)} coordinates with 4,4'-bipyridine (4,4'-bpy), trans-1,2-bis(4-pyridyl)ethene (4,4'-bpe) and 1,4-bis(imidazole-1-ylmethyl)-benzene (bix) as linkers giving rise to the formation of coordination polymers [Zn(dmit)(4,4'-bpy)](n) (1), [Zn(dmit)(4,4'-bpe)](n) (2) and [Zn(dmit)(bix)](n) (3) respectively. Compounds 1-3 were characterized by elemental analyses, IR, diffuse reflectance and single crystal X-ray diffraction studies. Compounds 1 and 3 crystallize in the monoclinic space group P2(1)/n, whereby compound 2 crystallizes in triclinic space group P1[combining macron]. In the present study, we chose three linkers 4,4'-bpy, 4,4'-bpe and bix (see , respectively, for their structural drawings), that differ in terms of their molecular dimensions. The crystal structures of compounds 1-3 are described here in terms of their supramolecular diversities that include π-π interactions, not only among aromatic stacking (compounds 1 and 3), but also between an aromatic ring and an ethylenic double bond (compound 2). The electronic absorption spectroscopy of compounds 1-3 support these intermolecular π-π interactions. This journal is © The Royal Society of Chemistry 2011

Self-consistent stationary MHD shear flows in the solar atmosphere as electric field generators

Czech Academy of Sciences Publication Activity Database

Nickeler, Dieter Horst; Karlický, Marian; Wiegelmann, T.; Kraus, Michaela

2014-01-01

Roč. 569, September (2014), A44/1-A44/10 ISSN 0004-6361 R&D Projects: GA ČR GA13-24782S; GA ČR GAP209/12/0103 Institutional support: RVO:67985815 Keywords : magnetohydrodynamics * Sum : flares * Sun : corona Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics Impact factor: 4.378, year: 2014

Similarity Theory Based Radial Turbine Performance and Loss Mechanism Comparison between R245fa and Air for Heavy-Duty Diesel Engine Organic Rankine Cycles

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Lei Zhang

2017-01-01

Full Text Available Organic Rankine Cycles using radial turbines as expanders are considered as one of the most efficient technologies to convert heavy-duty diesel engine waste heat into useful work. Turbine similarity design based on the existing air turbine profiles is time saving. Due to totally different thermodynamic properties between organic fluids and air, its influence on turbine performance and loss mechanisms need to be analyzed. This paper numerically simulated a radial turbine under similar conditions between R245fa and air, and compared the differences of the turbine performance and loss mechanisms. Larger specific heat ratio of air leads to air turbine operating at higher pressure ratios. As R245fa gas constant is only about one-fifth of air gas constant, reduced rotating speeds of R245fa turbine are only 0.4-fold of those of air turbine, and reduced mass flow rates are about twice of those of air turbine. When using R245fa as working fluid, the nozzle shock wave losses decrease but rotor suction surface separation vortex losses increase, and eventually leads that isentropic efficiencies of R245fa turbine in the commonly used velocity ratio range from 0.5 to 0.9 are 3%–4% lower than those of air turbine.

6 CFR 13.44 - Right to administrative offset.

Science.gov (United States)

2010-01-01

... 6 Domestic Security 1 2010-01-01 2010-01-01 false Right to administrative offset. 13.44 Section 13.44 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY PROGRAM FRAUD CIVIL REMEDIES § 13.44 Right to administrative offset. The amount of any penalty or assessment that has become...

The mechanism of flow and fabric development in mechanically anisotropic trachyte lava

Czech Academy of Sciences Publication Activity Database

Závada, Prokop; Schulmann, K.; Lexa, O.; Hrouda, F.; Haloda, J.; Týcová, P.

2009-01-01

Roč. 31, č. 11 (2009), s. 1295-1307 ISSN 0191-8141 R&D Projects: GA AV ČR KJB301110703 Grant - others:GA ČR(CZ) GA205/03/0204 Institutional research plan: CEZ:AV0Z30120515 Keywords : trachyte * anisotropy of magnetic susceptibility * fibre-slip mechanism * lava dome * mechanical anisotropy * sanidine Subject RIV: DB - Geology ; Mineralogy Impact factor: 1.732, year: 2009

Studies of killing effect of ionization radiation associated with As2O3 on SHG44 human glioma cells

International Nuclear Information System (INIS)

Huang Hui; Liu Fenju; Chen Jian; Ning Ping

2004-01-01

Objective: To study the effect of ionization radiation combined with As 2 O 3 on the killing of SHG44 human glioma cells. Methods: The survival rates of SHG44 cells treated with different doses of ionization radiation, As 2 O 3 respectively and radiation associated were determined with As 2 O 3 by MTT assay. The change of cell morphology was observed by confocal laser scanning microscopy. Results: (1) The survival rate of the group treated with ionization radiation combined with As 2 O 3 was significantly lower than that of the group treated with radiation or As 2 O 3 only (P 2 O 3 was significantly lower than that of the group treated with 6 Gy radiation (P 0.05); (3) Cells treated with radiation or As 2 O 3 had a morphological change indicating the apoptosis of SHG44 cells. Conclusion: The killing effect of ionization radiation combined with As 2 O 3 on the SHG44 cells is stronger than that of radiation or As 2 O 3 only. Inducing SHG44 cells' apoptosis may be the mechanism of As 2 O 3 killing effects on SHG44 cells. (authors)

Mechanisms underlying aberrant expression of miR-29c in uterine leiomyoma.

Science.gov (United States)

Chuang, Tsai-Der; Khorram, Omid

2016-01-01

To determine the expression of miR-29c and its target genes in leiomyoma and the role of NF-κB, specific protein 1 (SP1), and DNA methylation in its regulation. Experimental study. Academic research laboratory. Women undergoing hysterectomy for leiomyoma. Over- and underexpression of miR-29c; blockade of transcription factors. MiR-29c and its target gene levels in leiomyoma and the effects of blockade of transcription factors on miR-29c expression. Leiomyoma as compared with myometrium expressed significantly lower levels of miR-29c, with an inverse relationship with expression of its targets, COL3A1 and DNMT3A. Gain of function of miR-29c inhibited the expression of COL3A1 and DNMT3A at protein and mRNA levels, secreted COL3A1, and rate of cell proliferation. Loss of function of miR-29c had the opposite effect. E2, P, and their combination inhibited miR-29c in leiomyoma smooth muscle cells (LSMC). Phosphorylated NF-κB (p65) and SP1 protein expression were significantly increased in leiomyoma. SiRNA knockdown of SP1 and DNMT3A or their specific inhibitors significantly increased the expression of miR-29c, accompanied by the inhibition of cellular and secreted COL3A1 in siRNA-treated cells. Knockdown of p65 also induced miR-29c expression but had no effect on COL3A1 expression. MiR-29c expression is suppressed in leiomyoma, resulting in an increase in expression of its targets COL3A1 and DNMT3A. The suppression of miR-29c in LSMC is primarily mediated by SP1, NF-κB signaling, and epigenetic modification. Collectively, these results indicate a significant role for miR-29c in leiomyoma pathogenesis. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

N = (4,4 Supersymmetry and T-Duality

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Malin Göteman

2012-10-01

Full Text Available A sigma model with four-dimensional target space parametrized by chiral and twisted chiral N =(2,2 superfields can be extended to N =(4,4 supersymmetry off-shell, but this is not true for a model of semichiral fields, where the N = (4,4 supersymmetry can only be realized on-shell. The two models can be related to each other by T-duality. In this paper we perform a duality transformation from a chiral and twisted chiral model with off-shell N = (4,4 supersymmetry to a semichiral model. We find that additional non-linear terms must be added to the original transformations to obtain a semichiral model with N =(4,4 supersymmetry, and that the algebra closes on-shell as a direct consequence of the T-duality.

19 CFR 191.44 - Destruction under Customs supervision.

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2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Destruction under Customs supervision. 191.44 Section 191.44 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) DRAWBACK Rejected Merchandise § 191.44 Destruction under Customs supervision. A claimant may destroy merchandise an...

27 CFR 4.4 - Delegations of the Administrator.

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2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Delegations of the Administrator. 4.4 Section 4.4 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF WINE Scope § 4.4 Delegations of the...

Enhancement of radiotherapy efficacy by miR-200c-loaded gelatinase-stimuli PEG-Pep-PCL nanoparticles in gastric cancer cells

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Cui FB

2014-05-01

Full Text Available Fang-bo Cui,1,* Qin Liu,1,* Ru-Tian Li,1 Jie Shen,1 Pu-yuan Wu,1 Li-Xia Yu,1 Wen-jing Hu,1 Feng-lei Wu,2 Chun-Ping Jiang,1 Guo-feng Yue,2 Xiao-Ping Qian,1 Xi-Qun Jiang,3 Bao-Rui Liu11The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, 2Nanjing Medical University, 3Laboratory of Mesoscopic Chemistry and Department of Polymer Science and Engineering, College of Chemistry and Chemical Engineering, Nanjing University, Nanjing, People's Republic of China*These authors contributed equally to this workAbstract: Radiotherapy is the main locoregional control modality for many types of unresectable tumors, including gastric cancer. However, many patients fail radiotherapy due to intrinsic radioresistance of cancer cells, which has been found to be strongly associated with cancer stem cell (CSC-like properties. In this study, we developed a nanoparticle formulation to deliver miR-200c, which is reported to inhibit CSC-like properties, and then evaluated its potential activity as a radiosensitizer. miR-200c nanoparticles significantly augmented radiosensitivity in three gastric cancer cell lines (sensitization enhancement ratio 1.13–1.25, but only slightly in GES-1 cells (1.06. In addition to radioenhancement, miR-200c nanoparticles reduced the expression of CD44, a putative CSC marker, and the percentage of CD44+ BGC823 cells. Meanwhile, other CSC-like properties, including invasiveness and resistance to apoptosis, could be suppressed by miR-200c nanoparticles. CSC-associated radioresistance mechanisms, involving reactive oxygen species levels and DNA repair capacity, were also attenuated. We have demonstrated that miR-200c nanoparticles are an effective radiosensitizer in gastric cancer cells and induce little radiosensitization in normal cells, which suggests that they are as a promising candidate for further preclinical and clinical evaluation

Jaroslav Kolár. Vědec a přítel Zdeněk Horský

Czech Academy of Sciences Publication Activity Database

Hermann, Tomáš; Kolár, J.

2011-01-01

Roč. 44, č. 2 (2011), s. 117-122 ISSN 0300-4414 R&D Projects: GA ČR GPP410/10/P550 Institutional research plan: CEZ:AV0Z80630520 Keywords : Zdeněk Horský * historiography of science * history of astronomy Subject RIV: AB - History

An attempt of application of short lived 44K activity induced in the 44Ca(n,p)44K reaction using 14 MeV neutrons for total body calcium assessment in human subject

International Nuclear Information System (INIS)

Haratym, Z.; Kempisty, T.; Mikolajewski, S.; Rurarz, E.

1999-01-01

The status of in vivo neutron activation analysis techniques for the measurement of total body calcium in human subject is reviewed. Relevant data on the nuclear characteristics of calcium isotopes during interaction with neutrons ranging from slow up to 14 MeV neutrons are presented. Physical aspects of the measurement of in vivo total body calcium (TBCa) using 44 K activity induced in the 44 Ca(n,p) 44 K(T 1/2 =22.3 min) reaction by 14 MeV neutrons are discussed. The measurement of delayed γ-ray emitted during decay of activities induced in enriched 44 Ca, nat Ca, phantom filled with water solution of natural calcium and skeletal arm are considered. Results of measurements on the phantom and skeletal arm indicate a possibility to measure the TBCa using the 44 K activity. (author)

Promoter- and cell-specific epigenetic regulation of CD44, Cyclin D2, GLIPR1 and PTEN by Methyl-CpG binding proteins and histone modifications

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Schwarzenbach Heidi

2010-06-01

Full Text Available Abstract Background The aim of the current study was to analyze the involvement of methyl-CpG binding proteins (MBDs and histone modifications on the regulation of CD44, Cyclin D2, GLIPR1 and PTEN in different cellular contexts such as the prostate cancer cells DU145 and LNCaP, and the breast cancer cells MCF-7. Since global chromatin changes have been shown to occur in tumours and regions of tumour-associated genes are affected by epigenetic modifications, these may constitute important regulatory mechanisms for the pathogenesis of malignant transformation. Methods In DU145, LNCaP and MCF-7 cells mRNA expression levels of CD44, Cyclin D2, GLIPR1 and PTEN were determined by quantitative RT-PCR at the basal status as well as after treatment with demethylating agent 5-aza-2'-deoxycytidine and/or histone deacetylase inhibitor Trichostatin A. Furthermore, genomic DNA was bisulfite-converted and sequenced. Chromatin immunoprecipitation was performed with the stimulated and unstimulated cells using antibodies for MBD1, MBD2 and MeCP2 as well as 17 different histone antibodies. Results Comparison of the different promoters showed that MeCP2 and MBD2a repressed promoter-specifically Cyclin D2 in all cell lines, whereas in MCF-7 cells MeCP2 repressed cell-specifically all methylated promoters. Chromatin immunoprecipitation showed that all methylated promoters associated with at least one MBD. Treatment of the cells by the demethylating agent 5-aza-2'-deoxycytidine (5-aza-CdR caused dissociation of the MBDs from the promoters. Only MBD1v1 bound and repressed methylation-independently all promoters. Real-time amplification of DNA immunoprecipitated by 17 different antibodies showed a preferential enrichment for methylated lysine of histone H3 (H3K4me1, H3K4me2 and H3K4me3 at the particular promoters. Notably, the silent promoters were associated with unmodified histones which were acetylated following treatment by 5-aza-CdR. Conclusions This study is one

Modely pro konstrukci větrných map v ČR

Czech Academy of Sciences Publication Activity Database

Hanslian, David; Chládová, Zuzana; Pop, Lukáš

2012-01-01

Roč. 65, č. 2 (2012), s. 36-44 ISSN 0026-1173 R&D Projects: GA AV ČR KJB300420905 Institutional support: RVO:68378289 Keywords : wind map * average wind speed * Czech Republic * boundary layer model * interpolation method * VAS method * WAsP model * PIAP model * VAS/WAsP model Subject RIV: DG - Athmosphere Sciences, Meteorology http://portal.chmi.cz/files/portal/docs/reditel/SIS/abstrakta/2012_2.pdf

12 CFR 345.44 - Public notice by banks.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Public notice by banks. 345.44 Section 345.44... COMMUNITY REINVESTMENT Records, Reporting, and Disclosure Requirements § 345.44 Public notice by banks. A bank shall provide in the public lobby of its main office and each of its branches the appropriate...

27 CFR 44.102 - Change in trade name.

Science.gov (United States)

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Change in trade name. 44.102 Section 44.102 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU... Warehouse Proprietors Changes in Name § 44.102 Change in trade name. Where there is a change in, or an...

R-spondin1/Wnt-enhanced Ascl2 autoregulation controls the self-renewal of colorectal cancer progenitor cells.

Science.gov (United States)

Ye, Jun; Liu, Shanxi; Shang, Yangyang; Chen, Haoyuan; Wang, Rongquan

2018-06-25

The Wnt signaling pathway controls stem cell identity in the intestinal epithelium and cancer stem cells (CSCs). The transcription factor Ascl2 (Wnt target gene) is fate decider of intestinal cryptic stem cells and colon cancer stem cells. It is unclear how Wnt signaling is translated into Ascl2 expression and keeping the self-renewal of CRC progenitor cells. We showed that the exogenous Ascl2 in colorectal cancer (CRC) cells activated the endogenous Ascl2 expression via a direct autoactivatory loop, including Ascl2 binding to its own promoter and further transcriptional activation. Higher Ascl2 expression in human CRC cancerous tissues led to greater enrichment in Ascl2 immunoprecipitated DNA within the Ascl2 promoter in the CRC cancerous sample than the peri-cancerous mucosa. Ascl2 binding to its own promoter and inducing further transcriptional activation of the Ascl2 gene was predominant in the CD133 + CD44 + CRC population. R-spondin1/Wnt activated Ascl2 expression dose-dependently in the CD133 + CD44 + CRC population, but not in the CD133 - CD44 - CRC population, which was caused by differences in Ascl2 autoregulation under R-spondin1/Wnt activation. R-spondin1/Wnt treatment in the CD133 + CD44 + or CRC CD133 - CD44 - populations exerted a different pattern of stemness maintenance, which was defined by alterations of the mRNA levels of stemness-associated genes, the protein expression levels (Bmi1, C-myc, Oct-4 and Nanog) and tumorsphere formation. The results indicated that Ascl2 autoregulation formed a transcriptional switch that was enhanced by Wnt signaling in the CD133 + CD44 + CRC population, thus conferring their self-renewal.

Grant Application Development, Submission, Review, & Award

Science.gov (United States)

This infographic shows the National Cancer Institute general timeline progression through Grant Application Development, Submission, Review, and Award Infographic. In the first month, Applicant prepares and submits Grant Application to Grants.gov in response to FOA. In month two, The Center for Scientific Review (CSR) assigns applications that fall under the category of R01s, etc. to a Scientific Review Group (SRG) or the CSR assigns applications that fall under the category of Program Projects and Center Grants to NCI Division of Extramural Activities (DEA). Months four through five: First-level review by Scientific Review Group (SRG) for Scientific Merit: SRG assigns Impact Scores. Month five Summary Sstatements are prepared and are available to NCI Program staff and applicants. Month six, second-level review by National Cancer Advisory board (NCAB) for NCI Funding determination begins. NCAB makes recommendation to NCI Director, NCI develops funding plan, Applications selected for Funding, “Paylists” forwarded to Office of Grant Administration (OGA). Month ten, Award Negotiations and Issuance: Award issued, Award received by Institution, and Investigator begins work. www.cancer.gov Icons made by Freepik from http://www.flaticon.com is licensed by CC BY3.0

Molecular Mechanisms of Microbially Facilitated Corrosion

Science.gov (United States)

1986-10-23

destierliaoice Mickels et ill. inl experimne desi 19810c, the efferts ol amipil ’ td grazi gig amiud resoutrce loirtitioli itg gas well dril Ii in i (Morrison...utilized todihlerenti- Gendrean td lakol isms contained all enlarged carliosyl hand tt 1740 cvi 1. This Lijotn co ati osY at group i nch uded Biacillus... Ihq *It mtl’ idi~ o, Chlratvi .44 Alr"It 04’/ ,t44 .4. lh ,,f,, 4 4 l,/. 4 I’m ~ .. 1igI4.ii . -hdC4itS %e.iliti, I I At% S Ir. r,- (Atc-,,n ift 215

7 CFR 1412.44 - Notification of base acres.

Science.gov (United States)

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Notification of base acres. 1412.44 Section 1412.44... through 2012 § 1412.44 Notification of base acres. The operator and owners of record of a farm will be notified in writing of the number of base acres eligible for enrollment in a contract, unless such operator...

Presència, tendències i aspectes diferenciadors de la formació sobre drets d'autor en l'alfabetització informacional en l'àmbit universitari

OpenAIRE

Uribe Tirado, Alejandro

2010-01-01

Objectiu. Analitzar la presència de la temàtica dels drets d'autor, dels aspectes legals de la informació acadèmica i científica, en diferents programes, cursos o programes d'aprenentatge d'alfabetització informacional (ALFIN) de diferents universitats al voltant del món, per identificar les tendències i aspectes diferenciadors que es presenten actualment respecte a la formació en aquestes temàtiques en relació amb la informació digital. També s'analitza com de preparades estan les comunitats...

Optimisation of the magnetic properties of mechanically milled R5.5Fe73.5-xCoxCr3B18 nanocomposites

International Nuclear Information System (INIS)

O'Sullivan, J.F.; Smith, P.A.I.; Coey, J.M.D.

1998-01-01

Mechanical milling and subsequent annealing of R 4.5 R'Fe 73.5-x Co x Cr 3 B 18 (R=Nd,Pr and R'=Tb,Dy) ingots has been found to produce hard magnetic nanocomposites of (R,R') 2 (Fe,Co) 14 B, (Fe,Cr) 2 B and α-(Fe,Co) phases. Here we report on the optimisation of the composition of such nanocomposites. Substituting different rare-earth metals has a significant effect on the magnetic properties. The replacement of Nd with Pr produces higher coercivity and remanence, and better loop squareness. However, the replacement of Tb with Dy produced inferior properties when the main rare-earth component was Nd. Improved properties were obtained with the combination of Pr and Dy or Tb. Substitution of Co for Fe was found to lower coercivity but increase the remanence. The best combination of properties measured was for Pr 4.5 Dy 1 Fe 68.5 Co 5 Cr 3 B 1x , where H c =0.41 MA/m, J r =1 T, and (BH) max for the powder was 100 kJ/m 3 . These results will be discussed in terms of the grain size and the intrinsic properties of the hard and soft magnetic phases identified using X-ray diffraction. (orig.)

Complement component 1, q subcomponent binding protein (C1QBP) in lipid rafts mediates hepatic metastasis of pancreatic cancer by regulating IGF-1/IGF-1R signaling.

Science.gov (United States)

Shi, Haojun; Fang, Winston; Liu, Minda; Fu, Deliang

2017-10-01

Pancreatic cancer shows a remarkable predilection for hepatic metastasis. Complement component 1, q subcomponent binding protein (C1QBP) can mediate growth factor-induced cancer cell chemotaxis and distant metastasis by activation of receptor tyrosine kinases. Coincidentally, insulin-like growth factor-1 (IGF-1) derived from the liver and cancer cells itself has been recognized as a critical inducer of hepatic metastasis. However, the mechanism underlying IGF-1-dependent hepatic metastasis of pancreatic cancer, in which C1QBP may be involved, remains unknown. In the study, we demonstrated a significant association between C1QBP expression and hepatic metastasis in patients with pancreatic cancer. IGF-1 induced the translocation of C1QBP from cytoplasm to lipid rafts and further drove the formation of CD44 variant 6 (CD44v6)/C1QBP complex in pancreatic cancer cells. C1QBP interacting with CD44v6 in lipid rafts promoted phosphorylation of IGF-1R and thus activated downstream PI3K and MAPK signaling pathways which mediated metastatic potential of pancreatic cancer cells including proliferation, apoptosis, invasion, adhesion and energy metabolism. Furthermore, C1QBP knockdown suppressed hepatic metastasis of pancreatic cancer cells in nude mice. We therefore conclude that C1QBP in lipid rafts serves a key regulator of IGF-1/IGF-1R-induced hepatic metastasis from pancreatic cancer. Our findings about C1QBP in lipid rafts provide a novel strategy to block IGF-1/IGF-1R signaling in pancreatic cancer and a reliable premise for more efficient combined modality therapies. © 2017 UICC.

Construct and content validity of the Turkish Birth Satisfaction Scale - Revised (T-BSS-R).

Science.gov (United States)

Göncü Serhatlıoğlu, Seda; Karahan, Nazan; Hollins Martin, Caroline J; Martin, Colin R

2018-03-19

The Birth Satisfaction Scale - Revised (BSS-R) is a valid and reliable scale designed to assess women's experiences of labour and childbirth. To assess factor structure, validity, and reliability of the Turkish Birth Satisfaction Scale - Revised (T-BSS-R) using data collected from a Turkish population. Istanbul Ministry of Health Zeynep Kamil Women's and Children's Training and Research Hospital. A convenience sample of healthy child-bearing women (n = 120) who had experienced a spontaneous vertex delivery at full term. A survey was conducted post backtranslating the T-BSS-R, with survey data analysed using confirmatory factor analysis. Factor modelling found three subscales embedded in the T-BSS-R, which indicated a good model fit, χ 2 = 44.67, CFI = .94; RMSEA = .057; SRMR = .075. A Chi-square value of 1.33 also indicated a good fit. Means for the T-BSS-R subdimensions (1) Stress Experienced (T-BSS-SE-R) = 6.86 ± 3.10, (2) Women's Attributes (T-BSS-WA-R) = 2.84 ± 1.89, (3) Quality of Care (T-BSS-QC-R) = 10.69 ± 3.19 and total scale = 20.39 ± 5.98. The Cronbach alpha coefficient for total scale = 0.71 and for subdimensions T-BSS-SE-R = 0.55, T-BSS-WA-R = 0.44 and T-BSS-QC-R = -0.74. Data analysis determined that the T-BSS-R is a valid and reliable instrument to measure birth satisfaction in a population of Turkish women. The T-BSS-R is available for use from c.hollinsmartin@napier.ac.uk .

Lifetime and g-factor measurements in 44Sc

International Nuclear Information System (INIS)

Chevallier, A.; Chavallier, J.; Gross, J.L.; Haas, B.; Schulz, N.; Styczen, J.; Toulemonde, M.

1975-01-01

The lifetimes of the 235 keV, 2 - state and 350 keV, 4 + state in 44 Sc have been measured via the 44 Ca(p, n) 44 Sc reaction with a pulsed proton beam. The time integral perturbed angular distribution technique with an external field was used to measure the precession angles of the 2 - and 4 + states populated by the 30 Si( 16 O, pnγ) 44 Sc reaction. The following values for the mean-lives and g-factors were obtained: π(2 - ) = 8.83(33) ns, g(2 - ) = 0.30(13) and π(4 + ) = 4.52(27)ns, g(4 + ) = 0.90(12). The results for the 2 - state support a rotational description of the negative parity states in 44 Sc. The magnetic moment of the 4 + state is compared to shell model predictions. (orig.) [de

Electric conduction mechanism of some heterocyclic compounds, 4,4′-bipyridine and indolizine derivatives in thin films

Energy Technology Data Exchange (ETDEWEB)

Danac, Ramona, E-mail: rdanac@uaic.ro [Faculty of Chemistry, Alexandru Ioan Cuza University of Iasi, Bulevardul Carol I, Nr. 11, 700506 Iasi (Romania); Leontie, Liviu, E-mail: lleontie@uaic.ro [Faculty of Physics, Alexandru Ioan Cuza University of Iasi, Bulevardul Carol I, Nr. 11, 700506 Iasi (Romania); Carlescu, Aurelian, E-mail: carlescu_aurelian@yahoo.com [Faculty of Physics, Alexandru Ioan Cuza University of Iasi, Bulevardul Carol I, Nr. 11, 700506 Iasi (Romania); Shova, Sergiu, E-mail: shova@icmpp.ro [Petru Poni Institute of Macromolecular Chemistry, Aleea Grigore Ghica Voda, Nr. 41A, 700487 Iasi (Romania); Tiron, Vasile, E-mail: vasile.tiron@uaic.ro [Faculty of Physics, Alexandru Ioan Cuza University of Iasi, Bulevardul Carol I, Nr. 11, 700506 Iasi (Romania); Rusu, George G., E-mail: rusugxg@uaic.ro [Faculty of Physics, Alexandru Ioan Cuza University of Iasi, Bulevardul Carol I, Nr. 11, 700506 Iasi (Romania); Iacomi, Felicia, E-mail: iacomi@uaic.ro [Faculty of Physics, Alexandru Ioan Cuza University of Iasi, Bulevardul Carol I, Nr. 11, 700506 Iasi (Romania); Gurlui, Silviu, E-mail: sgurlui@uaic.ro [Faculty of Physics, Alexandru Ioan Cuza University of Iasi, Bulevardul Carol I, Nr. 11, 700506 Iasi (Romania); Șușu, Oana, E-mail: oasusu@gmail.com [Faculty of Physics, Alexandru Ioan Cuza University of Iasi, Bulevardul Carol I, Nr. 11, 700506 Iasi (Romania); Rusu, Gheorghe I., E-mail: girusu@uaic.ro [Faculty of Physics, Alexandru Ioan Cuza University of Iasi, Bulevardul Carol I, Nr. 11, 700506 Iasi (Romania)

2016-08-01

Temperature dependence of d. c. electric conductivity of some recently synthesized heterocyclic compounds, 4,4′-bipyridine and indolizine derivatives, in thin films (d = 0.27–0.51 μm) spin-coated from chloroform solutions onto glass, is studied. The investigated compounds are polycrystalline (as shown by X-ray Diffraction analysis) and show typical n-type semiconductor behavior. The activation energy of d. c. electric conduction ranges between 1.55 and 2.33 eV. Some correlations between semiconducting characteristics and essential features of molecular structure of organic compounds have been established. In the higher temperature range (400–520 K), the electronic transport properties in present compounds can be explained in the frame of band gap representation model, while in the lower temperature range (300–350 K), the Mott's variable-range hopping conduction model can be conveniently used. - Highlights: • 4,4′-bipyridine and indolizine derivatives in thin films behave as n-type semiconductors. • The electron transfer is favored by extended conjugation and packing capacity. • The band gap representation is suitable in the higher temperature range. • The Mott's VRH conduction model may be used in the lower temperature range.

HA/CD44 interactions as potential targets for cancer therapy

Science.gov (United States)

Misra, Suniti; Heldin, Paraskevi; Hascall, Vincent C.; Karamanos, Nikos K.; Skandalis, Spyros S.; Markwald, Roger R.; Ghatak, Shibnath

2011-01-01

It is becoming increasingly clear that signals generated in tumor microenvironments are crucial to tumor cell behavior, such as, survival progression, and metastasis. The establishment of these malignant behaviors requires that tumor cells acquire novel adhesion and migration properties to detach from their original sites for localizing into distant organs. CD44, an adhesion/homing molecule is a major receptor for the glycosaminoglycan hyaluronan, which is one of the major components of the tumor extracellular matrix (ECM). CD44, a multi structural and multifunctional molecule, detects changes in ECM components, and thus is well positioned to provide appropriate responses to changes in the microenvironment, i.e. engagement in cell-cell and cell-ECM interactions, cell traffic, lymph node homing, and presentation of growth factors/cytokines/chemokines to co-ordinate signaling events that enable the cell responses that change in the tissue environment. The potential involvement of CD44variants (CD44v), especially CD44v4-v7 and CD44v6-v9 in tumor progression was confirmed for many tumor types in numerous clinical studies. Down regulation of the standard CD44 isoform (CD44s) in colon cancer is postulated to result in increased tumorigenicity. CD44v-specific functions could be due to their higher binding affinity for hyaluronan than CD44s. Alternatively, CD44v-specific functions could be due to differences in associating molecules, which may bind selectively to the CD44v exon. This review summarizes how the interaction between hyaluronan and CD44v can serve as a potential target for cancer therapy, in particular how silencing the CD44v can target multiple metastatic tumors. PMID:21362138

CURVES AND AESTHETIC SURFACES GENERATED BY THE R-R-RTR MECHANISM

Directory of Open Access Journals (Sweden)

Liliana LUCA

2013-05-01

Full Text Available Let’s consider a mechanism having two driving elements with revolving movements and a RTR dyad, with elements of null length and aesthetic tracks of a point are determined on a rod, for various linear movement laws of driving elements. The generated curves revolve around x and y axes and aesthetic surfaces result.

miR-598 acts as a tumor suppressor in human gastric cancer by targeting IGF-1R.

Science.gov (United States)

Liu, Na; Yang, Hua; Wang, Hong

2018-01-01

In recent years, the aberrant expression of miR-598 in tumorigenesis has been demonstrated, as well as the fact that the IGF-1R pathway is also involved in the development of human gastric cancer (GC). The present study aimed to investigate the molecular mechanisms underlying miR-598-regulated IGF-1R expression in human GC. We analyzed the expression of miR-598 and IGF-1R in GC samples and cells, and evaluated the clinical significance of miR-598 and IGF-1R in GC patients. Furthermore, in vitro and in vivo assays were used to investigate the molecular mechanisms of miR-598 and IGF-1R. miR-598 expression was frequently downregulated in GC tissues and cells, and significantly correlated with poor prognosis, vascular invasion, TNM stage, and lymph node metastases as well as IGF-1R expression. The overexpression of miR-598 obviously inhibited cell proliferation, migration, invasion, and induced cell cycle arrest in the G1/S phase, and increased the apoptosis of GC cells. The overexpression of miR-598 also significantly inhibited ERK1/2 and Akt phosphorylation level. In vivo assay validated the inhibitory effect of miR-598 on tumor growth. Further studies showed that miR-598 inhibited IGF-1R protein expression by directly targeting its 3'-UTR. Besides, over-expression of IGF-1R reversed the inhibitory effects of miR-598, while suppression of IGF-1R expression showed inverse effects. miR-598 suppresses GC cell proliferation, migration and invasion by directly targeting IGF-1R expression. Thus, miR-598 may be a useful target for GC patients.

The mechanical design of the BARREL section of the detector CALIFA for R3B-FAIR.

Directory of Open Access Journals (Sweden)

Casarejos E.

2014-03-01

Full Text Available In this work we present the mechanical concept proposed for one of the sections of the detector CALIFA of the R3B experiment for FAIR. The use of an alveolar structure made of carbon-fiber composites allows for a light and robust solution to hold the active elements with an extreme mass ratio below 0.7%. The active core is supported by structural elements designed to make a fully operational assembly, taking care of different configurations and functionality. All the design has been developed using intensive calculation based in finite elements models and physical simulations.

Corrosion mechanisms and behaviour of actinides in the 'R7T7' nuclear glass

International Nuclear Information System (INIS)

Fillet, Sylvie

1987-01-01

This research thesis reports the study of aqueous corrosion of the R7T7 nuclear glass and of the identified corrosion mechanisms in conditions of static lixiviation which are close to that expected during long term storage in a geological environment. More specifically, this work aims at assessing the durability of this glass which has been selected for the vitrification of solutions from pressurized water reactors. The main glass alteration phenomena have been studied. The first part addresses the study of the alteration of the glassy matrix, and aims at identifying corrosion mechanisms in various lixiviation conditions (high temperature, saturation). The second part addresses the action of different materials present in the environment on the glassy matrix by simulating as well as possible a storage case. Based on the obtained results, a mathematical model is developed to predict the glass behaviour on the long term. Finally, the glass confinement power with respect to actinides is studied [fr

Tendències de les publicacions informatives cientificomèdiques en l'era 2.0

Directory of Open Access Journals (Sweden)

González Pacanowski, Antonio

2014-12-01

Full Text Available En els últims anys ha crescut l'audiència que consulta continguts de salut en publicacions i mitjans a Internet, especialment a Europa i als Estats Units. S'ha passat d'un usuari d'Internet unidireccional en la comunicació a un escenari en el qual la multidireccionalitat i la instantaneïtat són constants. Els nous mitjans i la creació de plataformes d'intercanvi d'informació més especialitzada mostren que els recursos multimèdia i la interactivitat també poden donar-se en mitjans especialitzats i distants del públic general com ara informació sobre biomedicina i salut. Simultàniament, el canvi cap a actituds més solidàries i d'ajuda mútua aflora mitjançant les xarxes socials. Amb l'objectiu de traçar un escenari sobre el comportament de les audiències davant els continguts de caràcter científic, especialment els de tipus sanitari, s'analitzen en aquest treball els perfils i costums dels usuaris utilitzant referències estadístiques tant europees com nord-americanes. De la mateixa manera, s'identifica el mapa actual de cibermitjans relacionats amb la informació cientificomèdica segmentada en mitjans de comunicació generals, especialitzats i els propis del web 2.0, com ara blogs i mitjans cocreatius. Aquesta descripció permet orientar sobre les tendències que seguiran els públics diferents i segmentats, però ara interconnectats per les noves tecnologies, i sobre la transformació de l'arquitectura i les funcionalitats dels mitjans a Internet.En los últimos años ha crecido la audiencia que consulta contenidos de salud en publicaciones y medios en Internet, especialmente en Europa y Estados Unidos. Se ha pasado de un usuario de Internet unidireccional en la comunicación a un escenario en el que la multidireccionalidad y la instantaneidad son constantes. Los nuevos medios y la creación de plataformas de intercambio de información más especializada evidencian que los recursos multimedia y la interactividad tambi

Mutation-Induced Population Shift in the MexR Conformational Ensemble Disengages DNA Binding: A Novel Mechanism for MarR Family Derepression.

Science.gov (United States)

Anandapadamanaban, Madhanagopal; Pilstål, Robert; Andresen, Cecilia; Trewhella, Jill; Moche, Martin; Wallner, Björn; Sunnerhagen, Maria

2016-08-02

MexR is a repressor of the MexAB-OprM multidrug efflux pump operon of Pseudomonas aeruginosa, where DNA-binding impairing mutations lead to multidrug resistance (MDR). Surprisingly, the crystal structure of an MDR-conferring MexR mutant R21W (2.19 Å) presented here is closely similar to wild-type MexR. However, our extended analysis, by molecular dynamics and small-angle X-ray scattering, reveals that the mutation stabilizes a ground state that is deficient of DNA binding and is shared by both mutant and wild-type MexR, whereas the DNA-binding state is only transiently reached by the more flexible wild-type MexR. This population shift in the conformational ensemble is effected by mutation-induced allosteric coupling of contact networks that are independent in the wild-type protein. We propose that the MexR-R21W mutant mimics derepression by small-molecule binding to MarR proteins, and that the described allosteric model based on population shifts may also apply to other MarR family members. Copyright © 2016 Elsevier Ltd. All rights reserved.

MDRL lncRNA regulates the processing of miR-484 primary transcript by targeting miR-361.

Directory of Open Access Journals (Sweden)

Kun Wang

2014-07-01

Full Text Available Long noncoding RNAs (lncRNAs are emerging as new players in gene regulation, but whether lncRNAs operate in the processing of miRNA primary transcript is unclear. Also, whether lncRNAs are involved in the regulation of the mitochondrial network remains to be elucidated. Here, we report that a long noncoding RNA, named mitochondrial dynamic related lncRNA (MDRL, affects the processing of miR-484 primary transcript in nucleus and regulates the mitochondrial network by targeting miR-361 and miR-484. The results showed that miR-361 that predominantly located in nucleus can directly bind to primary transcript of miR-484 (pri-miR-484 and prevent its processing by Drosha into pre-miR-484. miR-361 is able to regulate mitochondrial fission and apoptosis by regulating miR-484 levels. In exploring the underlying molecular mechanism by which miR-361 is regulated, we identified MDRL and demonstrated that it could directly bind to miR-361 and downregulate its expression levels, which promotes the processing of pri-miR-484. MDRL inhibits mitochondrial fission and apoptosis by downregulating miR-361, which in turn relieves inhibition of miR-484 processing by miR-361. Our present study reveals a novel regulating model of mitochondrial fission program which is composed of MDRL, miR-361 and miR-484. Our work not only expands the function of the lncRNA pathway in gene regulation but also establishes a new mechanism for controlling miRNA expression.

IX Jornadas de educación emocional. Educación emocional y valores

OpenAIRE

Barredo Gutiérrez, Blanca; Bisquerra Alzina, Rafael; Blanco Cuch, Aida; Giner, Antoni; Pérez Escoda, Núria; Tey, Amèlia

2013-01-01

Barredo Gutierrez, B.; Bisquerra Alzina, R.; Blanco Cuch, A.; Giner Tarrida, A.; Perez Escoda, N.; Tey Teijón, A. (eds.) IX Jornades d’educació emocional. Educació emocional i valors / IX Jornadas de educación emocional. Educación emocional y valores. Barcelona, Universitat de Barcelona (Institut de Ciències de l’Educació), 2013. Document electrònic.valores. Barcelona, Universitat de Barcelona (Institut de Ciències de l’Educació), 2013. Document electrònic

First Annual Ethnic Food Cook-off Offers Tastes from Around the World | Poster

Science.gov (United States)

The Employee Diversity Team (EDT), with the support of the R&W Club Frederick, hosted its first Annual Ethnic Food Cook-off on March 27, in the lobby of Building 549, at NCI at Frederick. The event drew chefs of all nationalities from around the NCI at Frederick community. The goal of the cook-off was to encourage members of the community to embrace various ethnic cultures and backgrounds, according to Andrea Frydl, public affairs specialist, Office of Scientific Operations, and EDT chairperson.

Ternary copper(II) complex: NCI60 screening, toxicity studies, and evaluation of efficacy in xenograft models of nasopharyngeal carcinoma

Science.gov (United States)

Chu, Tai-Lin; Abdul Aziz, Norazlin; Mohd Kornain, Noor-Kaslina; Samiulla, D. S.; Lo, Kwok-Wai; Ng, Chew-Hee

2018-01-01

Copper(II) ternary complex, [Cu(phen)(C-dmg)(H2O)]NO3 was evaluated against a panel of cell lines, tested for in vivo efficacy in nasopharyngeal carcinoma xenograft models as well as for toxicity in NOD scid gamma mice. The Cu(II) complex displayed broad spectrum cytotoxicity against multiple cancer types, including lung, colon, central nervous system, melanoma, ovarian, and prostate cancer cell lines in the NCI-60 panel. The Cu(II) complex did not cause significant induction of cytochrome P450 (CYP) 3A and 1A enzymes but moderately inhibited CYP isoforms 1A2, 2C9, 2C19, 2D6, 2B6, 2C8 and 3A4. The complex significantly inhibited tumor growth in nasopharyngeal carcinoma xenograft bearing mice models at doses which were well tolerated without causing significant or permanent toxic side effects. However, higher doses which resulted in better inhibition of tumor growth also resulted in toxicity. PMID:29329342

miR Profiling Identifies Cyclin-Dependent Kinase 6 Downregulation as a Potential Mechanism of Acquired Cisplatin Resistance in Non-Small-Cell Lung Carcinoma.

Science.gov (United States)

Bar, Jair; Gorn-Hondermann, Ivan; Moretto, Patricia; Perkins, Theodore J; Niknejad, Nima; Stewart, David J; Goss, Glenwood D; Dimitroulakos, Jim

2015-11-01

To identify the mechanisms of cisplatin resistance, global microRNA (miR) expression was tested. The expression of miR-145 was consistently higher in resistant cells. The expression of cyclin-dependent kinase 6 (CDK6), a potential target of miR-145, was lower in resistant cells, and inhibition of CDK4/6 protected cells from cisplatin. Cell cycle inhibition, currently being tested in clinical trials, might be antagonistic to cisplatin and other cytotoxic drugs. Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death. Platinum-based chemotherapeutic drugs are the most active agents in treating advanced disease. Resistance to these drugs is common and multifactorial; insight into the molecular mechanisms involved will likely enhance efficacy. A set of NSCLC platinum-resistant sublines was created from the Calu6 cell line. Cell viability was quantified using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Differentially expressed microRNAs (miRs) in these lines were identified using Affymetrix miR arrays. The potential genes targeted by these miRs were searched using the TargetScan algorithm. The expression levels of miRs and mRNA were tested using real-time polymerase chain reaction. miR-145 was reproducibly elevated in all the resistant sublines tested; however, modulation of miR-145 levels alone in these cells did not affect their response to cisplatin. A potential target of miR-145 is cyclin-dependent kinase 6 (CDK6), an important regulator of cell proliferation. The mRNA and protein levels of CDK6 were both downregulated in the resistant sublines. An inhibitor of CDK4/6 (PD0332991) protected parental NSCLC cells from cisplatin cytotoxicity. In the present study, we identified miRs differentially expressed in cisplatin-resistant cell lines, including miR-145. A predicted target of miR-145 is CDK6, and its expression was found to be downregulated in the resistant sublines, although not directly by miR-145. Inhibition

41 CFR 109-44.702 - Donations to public bodies.

Science.gov (United States)

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Donations to public... AND DISPOSAL 44-DONATION OF PERSONAL PROPERTY 44.7-Donations of Property to Public Bodies § 109-44.702 Donations to public bodies. ...

40 CFR 406.44 - Pretreatment standards for existing sources.