Homozygosity at variant MLH1 can lead to secondary mutation in NF1, neurofibromatosis type I and early onset leukemia

Cataloged from PDF version of article.Heterozygous germ-line variants of DNA mismatch repair (MMR) genes predispose individuals to hereditary non-polyposis colorectal cancer. Several independent reports have shown that individuals constitutionally homozygous for MMR allelic variants develop early onset hematological malignancies often associated to features of neurofibromatosis type 1 (NF1) syndrome. The genetic mechanism of NF1 associated to MMR gene deficiency is not fully known. We report here that a child with this form of NF1 displays a heterozygous NF1 gene mutation (c.3721C > T), in addition to a homozygous MLH1 gene mutation (c.676C > T) leading to a truncated MLH1 protein (p.R226X). The parents did not display NF1 features nor the NF1 mutation. This new NF1 gene mutation is recurrent and predicts a truncated neurofibromin (p.R1241X) lacking its GTPase activating function, as well as all C-terminally located functional domains. Our findings suggest that NF1 disease observed in individuals homozygous for deleterious MMR variants may be due to a concomitant NF1 gene mutation. The presence of both homozygous MLH1 and heterozygous NF1 mutation in the child studied here also provides a mechanistic explanation for early onset malignancies that are observed in affected individuals. It also provides a model for cooperation between genetic alterations in human carcinogenesis. © 2007 Elsevier B.V. All rights reserved

Metalorganic chemical vapor deposition growth and thermal stability of the AllNN/GaN high electron mobility transistor structure

Cataloged from PDF version of article.The AlxIn1-xN barrier high electron mobility transistor (HEMT) structure has been optimized with varied barrier composition and thickness grown by metalorganic chemical vapor deposition. After optimization, a transistor structure comprising a 7 nm thick nearly lattice-matched Al0.83In0.17 N barrier exhibits a sheet electron density of 2.0 x 10(13) cm(-2) with a high electron mobility of 1540 cm(2) V-1 s(-1). AnAl(0.83)In(0.17)N barrier HEMT device with 1 mu m gate length provides a current density of 1.0 A mm(-1) at V-GS = 0 V and an extrinsic transconductance of 242 mS mm(-1), which are remarkably improved compared to that of a conventional Al0.3Ga0.7N barrier HEMT. To investigate the thermal stability of the HEMT epi-structures, post-growth annealing experiments up to 800 degrees C have been applied to Al0.83In0.17N and Al0.3Ga0.7N barrier heterostructures. As expected, the electrical properties of an Al0.83In0.17N barrier HEMT structure showed less stability than that of an Al0.3Ga0.7N barrier HEMT to the thermal annealing. The structural properties of Al0.83In0.17N/GaN also showed more evidence for decomposition than that of the Al0.3Ga0.7N/GaN structure after 800 degrees C post-annealing

Proxemic Flow: Dynamic Peripheral Floor Visualizations for Revealing and Mediating Large Surface Interactions

Interactive large surfaces have recently become commonplace for interactions in public settings. The fact that people can engage with them and the spectrum of possible interactions, however, often remain invisible and can be confusing or ambiguous to passersby. In this paper, we explore the design of dynamic peripheral floor visualizations for revealing and mediating large surface interactions. Extending earlier work on interactive illuminated floors, we introduce a novel approach for leveraging floor displays in a secondary, assisting role to aid users in interacting with the primary display. We illustrate a series of visualizations with the illuminated floor of the Proxemic Flow system. In particular, we contribute a design space for peripheral floor visualizations that (a) provides peripheral information about tracking fidelity with personal halos, (b) makes interaction zones and borders explicit for easy opt-in and opt-out, and (c) gives cues inviting for spatial movement or possible next interaction steps through wave, trail, and footstep animations. We demonstrate our proposed techniques in the context of a large surface application and discuss important design considerations for assistive floor visualizations

Genome-Wide Transcriptional Reorganization Associated with Senescence-to-Immortality Switch during Human Hepatocellular Carcinogenesis

Cataloged from PDF version of article.Senescence is a permanent proliferation arrest in response to cell stress such as DNA damage. It contributes strongly to tissue aging and serves as a major barrier against tumor development. Most tumor cells are believed to bypass the senescence barrier (become "immortal") by inactivating growth control genes such as TP53 and CDKN2A. They also reactivate telomerase reverse transcriptase. Senescence-to-immortality transition is accompanied by major phenotypic and biochemical changes mediated by genome-wide transcriptional modifications. This appears to happen during hepatocellular carcinoma (HCC) development in patients with liver cirrhosis, however, the accompanying transcriptional changes are virtually unknown. We investigated genome-wide transcriptional changes related to the senescence-to-immortality switch during hepatocellular carcinogenesis. Initially, we performed transcriptome analysis of senescent and immortal clones of Huh7 HCC cell line, and identified genes with significant differential expression to establish a senescence-related gene list. Through the analysis of senescence-related gene expression in different liver tissues we showed that cirrhosis and HCC display expression patterns compatible with senescent and immortal phenotypes, respectively; dysplasia being a transitional state. Gene set enrichment analysis revealed that cirrhosis/senescence-associated genes were preferentially expressed in non-tumor tissues, less malignant tumors, and differentiated or senescent cells. In contrast, HCC/immortality genes were up-regulated in tumor tissues, or more malignant tumors and progenitor cells. In HCC tumors and immortal cells genes involved in DNA repair, cell cycle, telomere extension and branched chain amino acid metabolism were up-regulated, whereas genes involved in cell signaling, as well as in drug, lipid, retinoid and glycolytic metabolism were down-regulated. Based on these distinctive gene expression features we developed a 15-gene hepatocellular immortality signature test that discriminated HCC from cirrhosis with high accuracy. Our findings demonstrate that senescence bypass plays a central role in hepatocellular carcinogenesis engendering systematic changes in the transcription of genes regulating DNA repair, proliferation, differentiation and metabolism

Searching for Extraterrestrial Amino Acids in a Contaminated Meteorite: Amino Acid Analyses of the Canakkale L6 Chondrite

Amino acids can serve as important markers of cosmochemistry, as their abundances and isomeric and isotopic compositions have been found to vary predictably with changes in parent body chemistry and alteration processes. Amino acids are also of astrobiological interest because they are essential for life on Earth. Analyses of a range of meteorites, including all groups of carbonaceous chondrites, along with H, R, and LL chondrites, ureilites, and a martian shergottite, have revealed that amino acids of plausible extraterrestrial origin can be formed in and persist after a wide range of parent body conditions. However, amino acid analyses of L6 chondrites to date have not provided evidence for indigenous amino acids. In the present study, we performed amino acid analysis on larger samples of a different L6 chondite, Canakkale, to determine whether or not trace levels of indigenous amino acids could be found. The Canakkale meteor was an observed fall in late July, 1964, near Canakkale, Turkey. The meteorite samples (1.36 and 1.09 g) analyzed in this study were allocated by C. Y. Ornek, along with a soil sample (1.5 g) collected near the Canakkale recovery site

Reservoir Computing Approach to Robust Computation using Unreliable Nanoscale Networks

As we approach the physical limits of CMOS technology, advances in materials science and nanotechnology are making available a variety of unconventional computing substrates that can potentially replace top-down-designed silicon-based computing devices. Inherent stochasticity in the fabrication process and nanometer scale of these substrates inevitably lead to design variations, defects, faults, and noise in the resulting devices. A key challenge is how to harness such devices to perform robust computation. We propose reservoir computing as a solution. In reservoir computing, computation takes place by translating the dynamics of an excited medium, called a reservoir, into a desired output. This approach eliminates the need for external control and redundancy, and the programming is done using a closed-form regression problem on the output, which also allows concurrent programming using a single device. Using a theoretical model, we show that both regular and irregular reservoirs are intrinsically robust to structural noise as they perform computation

Improvement of breakdown characteristics in AlGaN/GaN/Al xGa 1-xN HEMT based on a grading Al xGa 1-xN buffer layer

To improve the breakdown characteristics of an AlGaN/GaN based high electron mobility transistor (HEMT) for high voltage applications, AlGaN/GaN/Al xGa 1-xN double heterostructure (DH-HEMTs) were designed and fabricated by replacing the semi-insulating GaN buffer with content graded Al xGa 1-xN (x=x 1 → x 2, x 1 > x 2), in turn linearly lowering the Al content x from x 1=90% to x 2=5% toward the front side GaN channel on a high temperature AlN buffer layer. The use of a highly resistive Al xGa 1-xN epilayer suppresses the parasitic conduction in the GaN buffer, and the band edge discontinuity limits the channel electrons spillover, thereby reducing leakage current and drain current collapse. In comparison with the conventional HEMT that use a semi-insulating GaN buffer, the fabricated DH-HEMT device with the same size presents a remarkable enhancement of the breakdown voltage. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Illness causal beliefs in Turkish immigrants

<p>Abstract</p> <p>Background</p> <p>People hold a wide variety of beliefs concerning the causes of illness. Such beliefs vary across cultures and, among immigrants, may be influenced by many factors, including level of acculturation, gender, level of education, and experience of illness and treatment. This study examines illness causal beliefs in Turkish-immigrants in Australia.</p> <p>Methods</p> <p>Causal beliefs about somatic and mental illness were examined in a sample of 444 members of the Turkish population of Melbourne. The socio-demographic characteristics of the sample were broadly similar to those of the Melbourne Turkish community. Five issues were examined: the structure of causal beliefs; the relative frequency of natural, supernatural and metaphysical beliefs; ascription of somatic, mental, or both somatic and mental conditions to the various causes; the correlations of belief types with socio-demographic, modernizing and acculturation variables; and the relationship between causal beliefs and current illness.</p> <p>Results</p> <p>Principal components analysis revealed two broad factors, accounting for 58 percent of the variation in scores on illness belief scales, distinctly interpretable as natural and supernatural beliefs. Second, beliefs in natural causes were more frequent than beliefs in supernatural causes. Third, some causal beliefs were commonly linked to both somatic and mental conditions while others were regarded as more specific to either somatic or mental disorders. Last, there was a range of correlations between endorsement of belief types and factors defining heterogeneity within the community, including with demographic factors, indicators of modernizing and acculturative processes, and the current presence of illness.</p> <p>Conclusion</p> <p>Results supported the classification of causal beliefs proposed by Murdock, Wilson & Frederick, with a division into natural and supernatural causes. While belief in natural causes is more common, belief in supernatural causes persists despite modernizing and acculturative influences. Different types of causal beliefs are held in relation to somatic or mental illness, and a variety of apparently logically incompatible beliefs may be concurrently held. Illness causal beliefs are dynamic and are related to demographic, modernizing, and acculturative factors, and to the current presence of illness. Any assumption of uniformity of illness causal beliefs within a community, even one that is relatively culturally homogeneous, is likely to be misleading. A better understanding of the diversity, and determinants, of illness causal beliefs can be of value in improving our understanding of illness experience, the clinical process, and in developing more effective health services and population health strategies.</p

Influence of intensive melt shearing on the microstructure and mechanical properties of an Al-Mg alloy with high added impurity content

The official published version can be accessed from the link below - Copyright @ The Minerals, Metals & Materials Society and ASM International 2011We have investigated the influence of melt conditioning by intensive shearing on the mechanical behavior and microstructure of Al-Mg-Mn-Fe-Cu-Si alloy sheet produced from a small book mold ingot with high added impurity content. The melt conditioned ingot has fine grains throughout its cross section, whereas a conventionally cast ingot, without melt shearing, has coarser grains and shows a wider variation of grain size. Both needle-shaped and coarse Chinese script iron bearing intermetallic particles are found in the microstructure at the center of the conventionally processed ingot, but for the melt conditioned ingot, only fine Chinese script intermetallic particles are observed. In addition to the iron bearing intermetallics, Mg2Si particles are also observed. The ingots were rolled to thin sheet and solution heat treated (SHT). During rolling, the iron-based intermetallics and Mg2Si particles are broken and aligned along the rolling direction. Yield strength (YS), ultimate tensile strength (UTS), and elongation of the intensively melt sheared and processed sheet are all improved compared to the conventionally cast and processed sheet. Fractographic analysis of the tensile fracture surfaces shows that the clustered and coarse iron bearing intermetallic particles are responsible for the observed reduction in mechanical properties of the conventionally cast sheet. We have shown that by refining the initial microstructure of the ingot by intensive shear melt conditioning, it is possible to achieve improved mechanical properties at the final sheet gage of an AlMgMn alloy with a high content of impurities.This study is under the Technology Strategy Board funded REALCAR projec

Mechanical and Thermal Properties of Polyvinyl Chloride Plasticized with Natural Fatty Acid Esters

From an industrial point of view, the use of new nontoxic and biodegradable plasticizers coming from natural resources is an interesting alternative to traditional plasticizers based on phthalates. In this study, two types of epoxidized fatty acids esters (EFAE) with different molecular weights have been used in order to produce flexible PVC with low toxicity. Different amounts of EFAE 201 and 401 have been considered in this study. Mechanical and thermal properties have been determined and morphology of fracture surface has been studied by scanning electron microscopy.This work was supported by the "Ministerio de Ciencia e Innovacion" [Grant number IPT-310000-2010-37] and the "Universitat Politecnica de Valencia" [Grant number PAID 06-10 Ref: 003-300].Fenollar Gimeno, OÁ.; García Sanoguera, D.; Sánchez Nacher, L.; Boronat Vitoria, T.; López Martínez, J.; Balart Gimeno, RA. (2013). Mechanical and Thermal Properties of Polyvinyl Chloride Plasticized with Natural Fatty Acid Esters. 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