Plasma-sprayed coatings for fusion reactor applications

A series of plasma-sprayed coatings has been given a preliminary evaluation to assess the potential of this class of materials in fusion reactor applications. TiC, TiB/sub 2/, Be and VBe/sub 12/ coatings on copper and stainless steel were tested for coating adherence, ion erosion resistance and susceptability to arc erosion. The coatings, in general, display a good resistance to thermal shock failure. The TiC and TiB/sub 2/ coatings exhibit favorable ion erosion characteristics and the resistance of the coatings to arc erosion was, in general, superior to that of stainless steel

Standard requirements for GCP-compliant data management in multinational clinical trials

<p>Abstract</p> <p>Background</p> <p>A recent survey has shown that data management in clinical trials performed by academic trial units still faces many difficulties (e.g. heterogeneity of software products, deficits in quality management, limited human and financial resources and the complexity of running a local computer centre). Unfortunately, no specific, practical and open standard for both GCP-compliant data management and the underlying IT-infrastructure is available to improve the situation. For that reason the "Working Group on Data Centres" of the European Clinical Research Infrastructures Network (ECRIN) has developed a standard specifying the requirements for high quality GCP-compliant data management in multinational clinical trials.</p> <p>Methods</p> <p>International, European and national regulations and guidelines relevant to GCP, data security and IT infrastructures, as well as ECRIN documents produced previously, were evaluated to provide a starting point for the development of standard requirements. The requirements were produced by expert consensus of the ECRIN Working group on Data Centres, using a structured and standardised process. The requirements were divided into two main parts: an IT part covering standards for the underlying IT infrastructure and computer systems in general, and a Data Management (DM) part covering requirements for data management applications in clinical trials.</p> <p>Results</p> <p>The standard developed includes 115 IT requirements, split into 15 separate sections, 107 DM requirements (in 12 sections) and 13 other requirements (2 sections). Sections IT01 to IT05 deal with the basic IT infrastructure while IT06 and IT07 cover validation and local software development. IT08 to IT015 concern the aspects of IT systems that directly support clinical trial management. Sections DM01 to DM03 cover the implementation of a specific clinical data management application, i.e. for a specific trial, whilst DM04 to DM12 address the data management of trials across the unit. Section IN01 is dedicated to international aspects and ST01 to the competence of a trials unit's staff.</p> <p>Conclusions</p> <p>The standard is intended to provide an open and widely used set of requirements for GCP-compliant data management, particularly in academic trial units. It is the intention that ECRIN will use these requirements as the basis for the certification of ECRIN data centres.</p

Protein Kinase C Iota Regulates Pancreatic Acinar-to-Ductal Metaplasia

Pancreatic acinar-to-ductal metaplasia (ADM) is associated with an increased risk of pancreatic cancer and is considered a precursor of pancreatic ductal adenocarcinoma. Transgenic expression of transforming growth factor alpha (TGF-α) or K-rasG12D in mouse pancreatic epithelium induces ADM in vivo. Protein kinase C iota (PKCι) is highly expressed in human pancreatic cancer and is required for the transformed growth and tumorigenesis of pancreatic cancer cells. In this study, PKCι expression was assessed in a mouse model of K-rasG12D-induced pancreatic ADM and pancreatic cancer. The ability of K-rasG12D to induce pancreatic ADM in explant culture, and the requirement for PKCι, was investigated. PKCι is elevated in human and mouse pancreatic ADM and intraepithelial neoplastic lesions in vivo. We demonstrate that K-rasG12D is sufficient to induce pancreatic ADM in explant culture, exhibiting many of the same morphologic and biochemical alterations observed in TGF-α-induced ADM, including a dependence on Notch activation. PKCι is highly expressed in both TGF-α- and K-rasG12D-induced pancreatic ADM and inhibition of PKCι significantly reduces TGF-α- and K-rasG12D-mediated ADM. Inhibition of PKCι suppresses K-rasG12D–induced MMP-7 expression and Notch activation, and exogenous MMP-7 restores K-rasG12D–mediated ADM in PKCι-depleted cells, implicating a K-rasG12D-PKCι-MMP-7 signaling axis that likely induces ADM through Notch activation. Our results indicate that PKCι is an early marker of pancreatic neoplasia and suggest that PKCι is a potential downstream target of K-rasG12D in pancreatic ductal metaplasia in vivo

Cell cycle and aging, morphogenesis, and response to stimuli genes are individualized biomarkers of glioblastoma progression and survival

<p>Abstract</p> <p>Background</p> <p>Glioblastoma is a complex multifactorial disorder that has swift and devastating consequences. Few genes have been consistently identified as prognostic biomarkers of glioblastoma survival. The goal of this study was to identify general and clinical-dependent biomarker genes and biological processes of three complementary events: lifetime, overall and progression-free glioblastoma survival.</p> <p>Methods</p> <p>A novel analytical strategy was developed to identify general associations between the biomarkers and glioblastoma, and associations that depend on cohort groups, such as race, gender, and therapy. Gene network inference, cross-validation and functional analyses further supported the identified biomarkers.</p> <p>Results</p> <p>A total of 61, 47 and 60 gene expression profiles were significantly associated with lifetime, overall, and progression-free survival, respectively. The vast majority of these genes have been previously reported to be associated with glioblastoma (35, 24, and 35 genes, respectively) or with other cancers (10, 19, and 15 genes, respectively) and the rest (16, 4, and 10 genes, respectively) are novel associations. <it>Pik3r1</it>, <it>E2f3, Akr1c3</it>, <it>Csf1</it>, <it>Jag2</it>, <it>Plcg1</it>, <it>Rpl37a</it>, <it>Sod2</it>, <it>Topors</it>, <it>Hras</it>, <it>Mdm2, Camk2g</it>, <it>Fstl1</it>, <it>Il13ra1</it>, <it>Mtap </it>and <it>Tp53 </it>were associated with multiple survival events.</p> <p>Most genes (from 90 to 96%) were associated with survival in a general or cohort-independent manner and thus the same trend is observed across all clinical levels studied. The most extreme associations between profiles and survival were observed for <it>Syne1</it>, <it>Pdcd4</it>, <it>Ighg1</it>, <it>Tgfa</it>, <it>Pla2g7</it>, and <it>Paics</it>. Several genes were found to have a cohort-dependent association with survival and these associations are the basis for individualized prognostic and gene-based therapies. <it>C2</it>, <it>Egfr</it>, <it>Prkcb</it>, <it>Igf2bp3</it>, and <it>Gdf10 </it>had gender-dependent associations; <it>Sox10</it>, <it>Rps20</it>, <it>Rab31</it>, and <it>Vav3 </it>had race-dependent associations; <it>Chi3l1</it>, <it>Prkcb</it>, <it>Polr2d</it>, and <it>Apool </it>had therapy-dependent associations. Biological processes associated glioblastoma survival included morphogenesis, cell cycle, aging, response to stimuli, and programmed cell death.</p> <p>Conclusions</p> <p>Known biomarkers of glioblastoma survival were confirmed, and new general and clinical-dependent gene profiles were uncovered. The comparison of biomarkers across glioblastoma phases and functional analyses offered insights into the role of genes. These findings support the development of more accurate and personalized prognostic tools and gene-based therapies that improve the survival and quality of life of individuals afflicted by glioblastoma multiforme.</p

Note and Comment

Dean Pound Harvard has honored itself in the appointment of Roscoe POUND to the deanship of its law schoo

Note and Comment

Dean Pound Harvard has honored itself in the appointment of Roscoe POUND to the deanship of its law schoo

Initial testing of coated limiters in ISX-B

Low-Z coatings on graphite substrates have been developed for testing as limiters in the Impurity Study Experiment (ISX-B) tokamak. Laboratory and tokamak testings have been accomplished. The laboratory tests included thermal shock experiments by means of pulsed e-beam irradiation, arcing experiments, and hydrogen and xenon ion erosion experiments. The tokamak testing consisted of ohmically heated plasma exposures with energy depositions up to 10 kJ/discharge on the limiters. The coatings, applied by chemical vapor deposition, consisted of TiB/sub 2/ and TiC deposited on POCO graphite substrates

Development and laboratory testing of low Z refractory coatings for fusion reactor limiters

A materials development program for low Z (Z < 24) coated tokamak limiters is described. A variety of refractory coatings applied by chemical vapor deposition, plasma spraying and chemical conversion to graphite and copper substrates have been evaluated. The results of laboratory testing for low energy hydrogen ion erosion, arc erosion and thermal fatigue by pulsed electron beam heating are reported. The 250 V hydrogen ion erosion data, analysed in terms of the effect of plasma radiation losses from resultant contaminants, indicates near equivalence of the very low Z (B and B/sub 4/C e.g.) and the moderate Z (e.g., TiB/sub 2/) coatings. Thermal fatigue testing has identified several candidate materials which can survice 1000, 3 kJ /cm/sup 2/ pulses of electron beam heating. The development of prototype limiters of TiB/sub 2/, TiC and B coated graphite for testing in the ORNL ISX-B tokamak is described

Note and Comment

Attempt, Assault, and Assault with Intent - The case of State v. Lewis, decided in October, 1915, by the Supreme Court of Iowa, has an interesting bearing upon the law of assault and of criminal attempts. Two men, Tropp and Cox, observed a third, Dunlevy, asleep on a cot with a pocketbook under his pillow. Tropp armed himself with a leather sap and a loaded revolver and moved quietly to the head of the cot, when Dunlevy, feeling the presence of some one in the room, sprang to his feet. Tropp fled from the room with Dunlevy after him, but fell before making his escape. Dunlevy undertook to secure him, but Cox came up from behind with a lead pipe and struck Dunlevy over the head. Tropp and Dunlevy both testified that Tropp did not speak to or touch Dunlevy, but Tropp stated that he made a movement under the pillow. Tropp pleaded guilty to a charge of assault with intent to commit robbery, but one Lewis, who was charged with aiding and abetting in this same crime, contended that there was no evidence that Tropp had committed an assault with intent to rob

Note and Comment

Attempt, Assault, and Assault with Intent - The case of State v. Lewis, decided in October, 1915, by the Supreme Court of Iowa, has an interesting bearing upon the law of assault and of criminal attempts. Two men, Tropp and Cox, observed a third, Dunlevy, asleep on a cot with a pocketbook under his pillow. Tropp armed himself with a leather sap and a loaded revolver and moved quietly to the head of the cot, when Dunlevy, feeling the presence of some one in the room, sprang to his feet. Tropp fled from the room with Dunlevy after him, but fell before making his escape. Dunlevy undertook to secure him, but Cox came up from behind with a lead pipe and struck Dunlevy over the head. Tropp and Dunlevy both testified that Tropp did not speak to or touch Dunlevy, but Tropp stated that he made a movement under the pillow. Tropp pleaded guilty to a charge of assault with intent to commit robbery, but one Lewis, who was charged with aiding and abetting in this same crime, contended that there was no evidence that Tropp had committed an assault with intent to rob