Suppression of interdiffusion in GaAs/AlGaAs quantum-well structure capped with dielectric films by deposition of gallium oxide

In this work, different dielectric caps were deposited on the GaAs/AlGaAs quantum well(QW) structures followed by rapid thermal annealing to generate different degrees of interdiffusion. Deposition of a layer of GaxOy on top of these dielectric caps resulted in significant suppression of interdiffusion. In these samples, it was found that although the deposition of GaxOy and subsequent annealing caused additional injection of Ga into the SiO₂ layer, Ga atoms were still able to outdiffuse from the GaAsQW structure during annealing, to generate excess Ga vacancies. The suppression of interdiffusion with the presence of Ga vacancies was explained by the thermal stress effect which suppressed Ga vacancydiffusion during annealing. It suggests that GaxOy may therefore be used as a mask material in conjunction with other dielectric capping layers in order to control and selectively achieve impurity-free vacancy disordering.J. Wong-Leung, P. N. K. Deenapanray, and H. H. Tan acknowledge the fellowships awarded by the Australian Research Council

The SEGUE Stellar Parameter Pipeline. IV. Validation with an Extended Sample of Galactic Globular and Open Clusters

Spectroscopic and photometric data for likely member stars of five Galactic globular clusters (M3, M53, M71, M92, and NGC 5053) and three open clusters (M35, NGC 2158, and NGC 6791) are processed by the current version of the SEGUE Stellar Parameter Pipeline (SSPP), in order to determine estimates of metallicities and radial velocities for the clusters. These results are then compared to values from the literature. We find that the mean metallicity () and mean radial velocity () estimates for each cluster are almost all within 2{\sigma} of the adopted literature values; most are within 1{\sigma}. We also demonstrate that the new version of the SSPP achieves small, but noteworthy, improvements in estimates at the extrema of the cluster metallicity range, as compared to a previous version of the pipeline software. These results provide additional confidence in the application of the SSPP for studies of the abundances and kinematics of stellar populations in the Galaxy.Comment: 98 pages, 31 figures; accepted for publication in A

Sensitivity of Lipid Metabolism and Insulin Signaling to Genetic Alterations in Hepatic Peroxisome Proliferator–Activated Receptor-γ\gamma Coactivator-1α\alpha Expression

Objective: The peroxisome proliferator–activated receptor-$\gamma$ coactivator (PGC)-1 family of transcriptional coactivators controls hepatic function by modulating the expression of key metabolic enzymes. Hepatic gain of function and complete genetic ablation of PGC-1$\alpha$ show that this coactivator is important for activating the programs of gluconeogenesis, fatty acid oxidation, oxidative phosphorylation, and lipid secretion during times of nutrient deprivation. However, how moderate changes in PGC-1$\alpha$ activity affect metabolism and energy homeostasis has yet to be determined. Research Design and Methods: To identify key metabolic pathways that may be physiologically relevant in the context of reduced hepatic PGC-1$\alpha$ levels, we used the Cre/Lox system to create mice heterozygous for PGC-1$\alpha$ specifically within the liver (LH mice). Results: These mice showed fasting hepatic steatosis and diminished ketogenesis associated with decreased expression of genes involved in mitochondrial $\beta$-oxidation. LH mice also exhibited high circulating levels of triglyceride that correlated with increased expression of genes involved in triglyceride-rich lipoprotein assembly. Concomitant with defects in lipid metabolism, hepatic insulin resistance was observed both in LH mice fed a high-fat diet as well as in primary hepatocytes. Results: These data highlight both the dose-dependent and long-term effects of reducing hepatic PGC-1$\alpha$ levels, underlining the importance of tightly regulated PGC-1$\alpha$ expression in the maintenance of lipid homeostasis and glucose metabolism

Can verbal instruction enhance the recall of an everyday task and promote error-monitoring in people with dementia of the Alzheimer-type?

People with dementia of the Alzheimer-type (DAT) have difficulties with performing everyday tasks and error awareness is poor. Here we investigated whether recall of actions and error monitoring in everyday task performance improved when they instructed another person on how to make tea. In this situation, both visual and motor cues are present, and attention sustained by the requirement to keep instructing. The data were drawn from a longitudinal study recording performance in four participants with DAT, filmed regularly for five years in their own homes, completing three tea-making conditions: performed-recall (they made tea themselves); instructed-recall (they instructed the experimenter on how to make tea); and verbal-recall (they described how to make tea). Accomplishment scores (percentage of task they correctly recalled), errors and error-monitoring were coded. Task accomplishment was comparable in the performed-recall and instructed-recall conditions, but both were significantly better than task accomplishment in the verbal-recall condition. Third person instruction did not improve error-monitoring. This study has implications for everyday task rehabilitation for people with DAT

Global use of Haemophilus influenzae type b conjugate vaccine.

Haemophilus influenzae type b (Hib) conjugate vaccines have been underutilized globally. We report progress in global use of Hib vaccines included in national immunization schedules. The number of countries using Hib vaccine increased from 89/193 (46%) in 2004 to 158/193 (82%) by the end of 2009. The increase was greatest among low-income countries eligible for financial support from the GAVI Alliance [13/75 (17%) in 2004, 60/72 (83%) by the end of 2009], and can be attributed to various factors. Additional efforts are still needed to increase vaccine adoption in lower middle income countries [20/31 (65%) by the end of 2009]

Predictive validity of the UK clinical aptitude test in the final years of medical school:a prospective cohort study

Peer reviewedPublisher PD

Efficient, high-throughput transfection of human embryonic stem cells

INTRODUCTION: Genetic manipulation of human embryonic stem cells (hESC) has been limited by their general resistance to common methods used to introduce exogenous DNA or RNA. Efficient and high throughput transfection of nucleic acids into hESC would be a valuable experimental tool to manipulate these cells for research and clinical applications. METHODS: We investigated the ability of two commercially available electroporation systems, the Nucleofection(® )96-well Shuttle(® )System from Lonza and the Neon™ Transfection System from Invitrogen to efficiently transfect hESC. Transfection efficiency was measured by flow cytometry for the expression of the green fluorescent protein and the viability of the transfected cells was determined by an ATP catalyzed luciferase reaction. The transfected cells were also analyzed by flow cytometry for common markers of pluripotency. RESULTS: Both systems are capable of transfecting hESC at high efficiencies with little loss of cell viability. However, the reproducibility and the ease of scaling for high throughput applications led us to perform more comprehensive tests on the Nucleofection(® )96-well Shuttle(® )System. We demonstrate that this method yields a large fraction of transiently transfected cells with minimal loss of cell viability and pluripotency, producing protein expression from plasmid vectors in several different hESC lines. The method scales to a 96-well plate with similar transfection efficiencies at the start and end of the plate. We also investigated the efficiency with which stable transfectants can be generated and recovered under antibiotic selection. Finally, we found that this method is effective in the delivery of short synthetic RNA oligonucleotides (siRNA) into hESC for knockdown of translation activity via RNA interference. CONCLUSIONS: Our results indicate that these electroporation methods provide a reliable, efficient, and high-throughput approach to the genetic manipulation of hESC

Portable prehospital methods to treat near-hypothermic shivering cold casualties

Objectives To compare the effectiveness of a single-layered polyethylene survival bag (P), a single-layered polyethylene survival bag with a hot drink (P+HD), a multi-layered metalized plastic sheeting survival bag (MPS: Blizzard Survival), and a multi-layered MPS survival bag with four large chemical-heat pads (MPS+HP: Blizzard Heat) to treat cold casualties. Methods Portable cold casualty treatment methods were compared by examining core and skin temperature, metabolic heat production and thermal comfort during a 3-h, 0°C cold-air exposure in seven shivering, near-hypothermic men (35.4°C). The hot drink (70°C, ~400ml, ~28kJ) was consumed at 0, 1 and 2 h during the cold-air exposure. Results During the cold-air exposure, core-rewarming and thermal comfort were similar on all trials (P = 0.45 and P = 0.36, respectively). However, skin temperature was higher (10-13%, P 2.7) and metabolic heat production lower (15-39%, P 0.9) on MPS and MPS+HP than P and P+HD. The addition of heat pads further lowered metabolic heat production by 15% (MPS+HP vs. MPS, P = 0.05, large effect size d = 0.9). The addition of the hot drink to polyethylene survival bag did not increase skin temperature or lower metabolic heat production. Conclusions Near-hypothermic cold casualties are rewarmed with less peripheral cold stress and shivering thermogenesis using a multi-layered MPS survival bag compared with a polyethylene survival bag. Prehospital rewarming is further aided by large chemical heat pads but not by hot drinks

Chemical carcinogenicity revisited 3: Risk assessment of carcinogenic potential based on the current state of knowledge of carcinogenesis in humans

Abstract Over 50 years, we have learned a great deal about the biology that underpins cancer but our approach to testing chemicals for carcinogenic potential has not kept up. Only a small number of chemicals has been tested in animal-intensive, time consuming, and expensive long-term bioassays in rodents. We now recommend a transition from the bioassay to a decision-tree matrix that can be applied to a broader range of chemicals, with better predictivity, based on the premise that cancer is the consequence of DNA coding errors that arise either directly from mutagenic events or indirectly from sustained cell proliferation. The first step is in silico and in vitro assessment for mutagenic (DNA reactive) activity. If mutagenic, it is assumed to be carcinogenic unless evidence indicates otherwise. If the chemical does not show mutagenic potential, the next step is assessment of potential human exposure compared to the threshold for toxicological concern (TTC). If potential human exposure exceeds the TTC, then testing is done to look for effects associated with the key characteristics that are precursors to the carcinogenic process, such as increased cell proliferation, immunosuppression, or significant estrogenic activity. Protection of human health is achieved by limiting exposures to below NOEALs for these precursor effects. The decision tree matrix is animal-sparing, cost effective, and in step with our growing knowledge of the process of cancer formation

Chemical carcinogenicity revisited 1: A unified theory of carcinogenicity based on contemporary knowledge

Abstract Developments in the understanding of the etiology of cancer have profound implications for the way the carcinogenicity of chemicals is addressed. This paper proposes a unified theory of carcinogenesis that will illuminate better ways to evaluate and regulate chemicals. In the last four decades, we have come to understand that for a cell and a group of cells to begin the process of unrestrained growth that is defined as cancer, there must be changes in DNA that reprogram the cell from normal to abnormal. Cancer is the consequence of DNA coding errors that arise either directly from mutagenic events or indirectly from cell proliferation especially if sustained. Chemicals that act via direct interaction with DNA can induce cancer because they cause mutations which can be carried forward in dividing cells. Chemicals that act via non-genotoxic mechanisms must be dosed to maintain a proliferative environment so that the steps toward neoplasia have time to occur. Chemicals that induce increased cellular proliferation can be divided into two categories: those which act by a cellular receptor to induce cellular proliferation, and those which act via non-specific mechanisms such as cytotoxicity. This knowledge has implications for testing chemicals for carcinogenic potential and risk management