Analysis of the singular value decomposition as a tool for processing microarray expression data

We give two informative derivations of a spectral algorithm for clustering and partitioning a bi-partite graph. In the first case we begin with a discrete optimization problem that relaxes into a tractable continuous analogue. In the second case we use the power method to derive an iterative interpretation of the algorithm. Both versions reveal a natural approach for re-scaling the edge weights and help to explain the performance of the algorithm in the presence of outliers. Our motivation for this work is in the analysis of microarray data from bioinformatics, and we give some numerical results for a publicly available acute leukemia data set

Spin recovery in the 25nm gate length InGaAs field effect transistore

We augmented an ensemble Monte-Carlo semiconductor device simulator [3] to incorporate electron spin degrees of freedom using a Bloch equation model to investigate the feasibility of spintronic devices. Results are presented for the steady state polarization and polarization decay due to scattering and spin orbit coupling for a III-V MOSFET device as a function of gate voltages, injection polarization and strain

A study of the effects of exercise on the urinary metabolome using normalisation to individual metabolic output

Aerobic exercise, in spite of its multi-organ benefit and potent effect on the metabolome, has yet to be investigated comprehensively via an untargeted metabolomics technology. We conducted an exploratory untargeted liquid chromatography mass spectrometry study to investigate the effects of a one-h aerobic exercise session in the urine of three physically active males. Individual urine samples were collected over a 37-h protocol (two pre-exercise and eight post-exercise). Raw data were subjected to a variety of normalization techniques, with the most effective measure dividing each metabolite by the sum response of that metabolite for each individual across the 37-h protocol expressed as a percentage. This allowed the metabolite responses to be plotted on a normalised scale. Our results highlight significant metabolites located in the following systems: purine pathway, tryptophan metabolism, carnitine metabolism, cortisol metabolism, androgen metabolism, amino acid oxidation, as well as metabolites from the gastrointestinal microbiome. Many of the significant changes observed in our pilot investigation mirror previous research studies, of various methodological designs, published within the last 15 years, although they have never been reported at the same time in a single study

Comparison of fin-edge roughness and metal grain work function variability in InGaAs and Si FinFETs

The fin-edge roughness (FER) and the TiN metal grain work function (MGW)-induced variability affecting OFF and ON device characteristics are studied and compared between a 10.4 nm gate length In0.53Ga0.47As FinFET and a 10.7 nm gate length Si FinFET. We have analyzed the impact of variability by assessing five figures of merit (threshold voltage, subthreshold slope, OFF-current, drain-induced-barrier-lowering, and ON-current) using the two state-of-the-art in-house-build 3-D simulation tools based on the finite-element method. Quantum-corrected 3-D drift-diffusion simulations are employed for variability studies in the subthreshold region while, in the ON-region, we use quantum-corrected 3-D ensemble Monte Carlo simulations. The In0.53Ga0.47As FinFET is more resilient to the FER and MGW variability in the subthreshold compared with the Si FinFET due to a stronger quantum carrier confinement present in the In0.53Ga0.47As channel. However, the ON-current variability is between 1.1 and 2.2 times larger for the In0.53Ga0.47As FinFET than for the Si counterpart, respectively

Anisotropic Quantum Corrections for 3-D Finite-Element Monte Carlo Simulations of Nanoscale Multigate Transistors

Anisotropic 2-D Schrödinger equation-based quantum corrections dependent on valley orientation are incorporated into a 3-D finite-element Monte Carlo simulation toolbox. The new toolbox is then applied to simulate nanoscale Si Siliconon-Insulator FinFETs with a gate length of 8.1 nm to study the contributions of conduction valleys to the drive current in various FinFET architectures and channel orientations. The 8.1 nm gate length FinFETs are studied for two cross sections: rectangular-like and triangular-like, and for two channel orientations: 〈100〉 and 〈110〉. We have found that quantum anisotropy effects play the strongest role in the triangular-like 〈100〉 channel device increasing the drain current by ~13% and slightly decreasing the current by 2% in the rectangular-like 〈100〉 channel device. The quantum anisotropy has a negligible effect in any device with the 〈110〉 channel orientation

Spin recovery in the 25nm gate length InGaAs field effect transistore

We augmented an ensemble Monte-Carlo semiconductor device simulator [3] to incorporate electron spin degrees of freedom using a Bloch equation model to investigate the feasibility of spintronic devices. Results are presented for the steady state polarization and polarization decay due to scattering and spin orbit coupling for a III-V MOSFET device as a function of gate voltages, injection polarization and strain

P08.36 Radioresistance of glioblastoma stem-like cells is associated with DNA replication stress, which is a promising therapeutic target

Introduction: The inevitability of tumour recurrence in glioblastoma (GBM) patients despite multi-modality treatment consisting of surgery, radiotherapy and chemotherapy, is reflected by a median survival of only 14 months. Tumour recurrence is thought to be driven by a small population of glioblastoma stem-like cells (GSCs) that are resistant to conventional therapies. DNA damage response (DDR) pathways have been shown to be up-regulated in GSCs and implicated in radioresistance and treatment failure. However the precise cause of enhanced DDR signalling in GSCs and the extent to which these signalling networks contribute to therapy resistance remains elusive. The objectives of this study were to investigate the underlying cause of DDR upregulation and treatment resistance in GSCs with a view to identifying novel and promising therapeutic targets. Materials and Methods: A panel of primary patient derived GBM cell lines cultured under conditions to enrich for or deplete the tumour stem cell population (GSC vs bulk respectively) were utilised in order to investigate enhanced GSC DDR under basal conditions and in response to ionising radiation. Confirmatory studies were also performed in cells sorted for the putative GSC marker CD133. The effects of a panel of small molecule DDR inhibitor agents on cell survival in GSC and bulk cells were quantified. Results: GSCs exhibited higher levels of total and activated DDR targets ATR, CHK1, ATM and PARP1 under basal conditions and were radioresistant compared to paired bulk populations. This was not due to increased levels of reactive oxygen species (ROS). Instead, we show that RPA is significantly higher in replicating GSCs and confirm by DNA fibre assays that GSCs and CD133+ cells have increased numbers of stalled replication forks, fewer new origins and slower DNA replication compared to bulk or CD133- populations, demonstrating for the first time that replication stress (RS) is a hallmark of GSCs. We identify increased expression of long neural genes as a likely mechanism for RS and DNA double strand breaks (DSBs) in GSCs and show that their radioresistance is reversed by dual inhibition of key RS and DDR proteins ATR and PARP. Conclusions: This study demonstrates the novel finding that replication stress is a hallmark of GSCs and resonates with recently published studies in neural progenitor cells showing that RS preferentially induces DNA DSB in long neural genes. Taken together, we implicate RS as a driver of enhanced DDR in GSCs and identify novel therapeutics with potential to improve clinical outcomes by overcoming the radioresistance of GB

3-D Finite Element Monte Carlo Simulations of Scaled Si SOI FinFET With Different Cross Sections

Si SOI FinFETs with gate lengths of 12.8 nm and 10.7 nm are modelled using 3D Finite Element Monte Carlo (MC) simulations with 2D Schroedinger equation quantum corrections. These non-planar transistors are studied for two cross-sections: rectangular-like and triangular-like, and for two channel orientations: h100i and h110i. The 10.7 nm gate length rectangular-like FinFET is also simulated using the 3D Non-Equilibrium Green’s Functions (NEGF) technique and the results are compared with MC simulations. The 12.8 nm and 10.7 nm gate length rectangular-like FinFETs give larger drive currents per perimeter by about 25−27% than the triangular-like shaped but are outperformed by the triangular-like ones when normalised by channel area. The devices with a <100> channel orientation deliver a larger drive current by about 11% than their counterparts with a h110i channel when scaled to 12.8 nm and to 10.7 nm gate lengths. ID–VG characteristics at low and high drain biases obtained from the 3D NEGF simulations show a remarkable agreement with the MC results and overestimate the drain current from a gate bias of 0.5 V only due to exclusion of the interface roughness and ionized impurity scatterings

Reversed argininosuccinate lyase activity in fumarate hydratase-deficient cancer cells.

BACKGROUND: Loss of function of fumarate hydratase (FH), the mitochondrial tumor suppressor and tricarboxylic acid (TCA) cycle enzyme, is associated with a highly malignant form of papillary and collecting duct renal cell cancer. The accumulation of fumarate in these cells has been linked to the tumorigenic process. However, little is known about the overall effects of the loss of FH on cellular metabolism. METHODS: We performed comprehensive metabolomic analyses of urine from Fh1-deficient mice and stable isotopologue tracing from human and mouse FH-deficient cell lines to investigate the biochemical signature of the loss of FH. RESULTS: The metabolomics analysis revealed that the urea cycle metabolite argininosuccinate is a common metabolic biomarker of FH deficiency. Argininosuccinate was found to be produced from arginine and fumarate by the reverse activity of the urea cycle enzyme argininosuccinate lyase (ASL), making these cells auxotrophic for arginine. Depleting arginine from the growth media by the addition of pegylated arginine deiminase (ADI-PEG 20) decreased the production of argininosuccinate in FH-deficient cells and reduced cell survival and proliferation. CONCLUSIONS: These results unravel a previously unidentified correlation between fumarate accumulation and the urea cycle enzyme ASL in FH-deficient cells. The finding that FH-deficient cells become auxotrophic for arginine opens a new therapeutic perspective for the cure of hereditary leiomyomatosis and renal cell cancer (HLRCC).RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Dilute magnetic contact for a spin GaN HEMT

Semiconductor CMOS nano-electronics is intensively seeking solutions for future digital applications. One of the most promising solutions to deliver a technological breakthrough is exploring electron spin in metals and semiconductors with applications from spin transistors to quantum sensors, and quantum computing. Spintronic applications rely on magnetic semiconductor materials with suitable properties. In particular, dilute magnetic semiconductors (DMS), such as Mn doped GaN, show the great promise of a high Curie temperature (220K–370K), exceeding room temperature, and a large concentration of holes. These are all the essential pre-requisites for operation of spin transistors in circuits. In this work, we dope an AlGaN/GaN heterostructure consisting of a GaN (2 nm) cap layer, an Al0.25Ga0.75N (25 nm) barrier, and a GaN (2 μm) substrate grown on a 6” Si wafer with Mn by sputtering deposition and thermal annealing to create a dilute magnetic semiconductor material following the process flow. While initial attempts resulted in the formation of a MnO surface layer, the SEM/XDS and XPS data suggest a diffusion of Mn into the GaN layer using thermal annealing at 900◦C for 7h with a concentration of 4.5% which is very close to the desired concentration of 5% needed for a DMS. The annealing temperature has to be below 1000◦ C since temperatures around 1000◦C result in significant damage to the 2DEG and diffusion of Al from the AlGaN layer