635 research outputs found

    Back gating of a two-dimensional hole gas in a SiGe quantum well

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    A device comprising a low-resistivity, n-type, Si substrate as a back gate to a p-type (boron), remote-doped, SiGe quantum well has been fabricated and characterized. Reverse and forward voltage biasing of the gate with respect to the two-dimensional hole gas in the quantum well allows the density of holes to be varied from 8 × 1011 cm–2 down to a measurement-limited value of 4 × 1011 cm–2. This device is used to demonstrate the evolution with decreasing carrier density of a re-entrant insulator state between the integer quantum Hall effect states with filling factors 1 and 3

    Pathways to economic well-being among teenage mothers in Great Britain

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    The present study examines pathways to independence from social welfare among 738 teenage mothers, participants of the 1970 British Cohort Study, who were followed up at age 30 years. Using a longitudinal design, a pathway model is tested, examining linkages between family social background, cognitive ability, school motivation, and individual investments in education, as well as work- and family-related roles. The most important factors associated with financial independence by age 30 are continued attachment to the labor market as well as a stable relationship with a partner (not necessarily the father of the child). Pathways to financial independence, in turn, are predicted through own cognitive resources, school motivation, and family cohesion. Implications of findings for policy making are discussed.© 2010 Hogrefe Publishing

    The relative importance of electron-electron interactions compared to disorder in the two-dimensional "metallic" state

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    The effect of substrate bias and surface gate voltage on the low temperature resistivity of a Si-MOSFET is studied for electron concentrations where the resistivity increases with increasing temperature. This technique offers two degrees of freedom for controlling the electron concentration and the device mobility, thereby providing a means to evaluate the relative importance of electron-electron interactions and disorder in this so-called ``metallic'' regime. For temperatures well below the Fermi temperature, the data obey a scaling law where the disorder parameter (kFlk_{\rm{F}}l), and not the concentration, appears explicitly. This suggests that interactions, although present, do not alter the Fermi-liquid properties of the system fundamentally. Furthermore, this experimental observation is reproduced in results of calculations based on temperature-dependent screening, in the context of Drude-Boltzmann theory.Comment: 5 pages, 6 figure

    A high-throughput splinkerette-PCR method for the isolation and sequencing of retroviral insertion sites

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    Insertional mutagens such as viruses and transposons are a useful tool for performing forward genetic screens in mice to discover cancer genes. These screens are most effective when performed using hundreds of mice, however until recently a major limitation to performing screens on this scale has been the cost effective isolation and sequencing of insertion sites. Here we present a method for the high-throughput isolation of insertion sites using a highly efficient splinkerette-PCR method coupled with capillary or 454 sequencing. This protocol includes a description of the procedure for DNA isolation, DNA digestion, linker or splinkerette ligation, primary and secondary PCR amplification, and sequencing. This method, which takes about 1 week to perform, has allowed us to isolate hundreds of thousands of insertion sites from mouse tumours and, unlike other methods, has been specifically optimised for the isolation of insertion sites generated with the murine leukaemia virus (MuLV), and can easily be performed in 96 well plate format for the efficient multiplex isolation of insertion sites

    Living with AIDS in Uganda: a qualitative study of patients' and families' experiences following referral to hospice

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    Background: Globally, the majority of people with HIV/AIDS live in sub-Saharan Africa. While the increasing availability of antiretroviral therapy is improving the outlook for many, its effects are yet to reach all of those in need and patients still present with advanced disease. This paper reports findings from qualitative interviews with patients living with AIDS and their caregivers who were receiving palliative care from Hospice Africa Uganda (HAU). We aimed to understand what motivated patients and their families to seek formal healthcare, whether there were any barriers to help- seeking and how the help and support provided to them by HAU was perceived. Methods: We invited patients with AIDS and their relatives who were newly referred to HAU to participate in qualitative interviews. Patients and carers were interviewed in their homes approximately four weeks after the patient’s enrolment at HAU. Interviews were translated, transcribed and analysed using narrative and thematic approaches. Results: Interviews were completed with 22 patients (10 women and 12 men) and 20 family caregivers, nominated by patients. Interviews revealed the extent of suffering patients endured and the strain that family caregivers experienced before help was sought or accessed. Patients reported a wide range of severe physical symptoms. Patients and their relatives reported worries about the disclosure of the AIDS diagnosis and fear of stigma. Profound poverty framed all accounts. Poverty and stigma were, depending on the patient and family situation, both motivators and barriers to help seeking behaviour. Hospice services were perceived to provide essential relief of pain and symptoms, as well as providing rehabilitative support and a sense of caring. The hospice was perceived relieve utter destitution, although it was unable to meet all the expectations that patients had. Conclusion: Hospice care was highly valued and perceived to effectively manage problems such as pain and other symptoms and to provide rehabilitation. Participants noted a strong sense of being “cared for”. However, poverty and a sense of stigma were widespread. Further research is needed to understand how poverty and stigma can be effectively managed in hospice care for patients for advanced AIDS and their families

    Metal-insulator transition at B=0 in a dilute two dimensional GaAs-AlGaAs hole gas

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    We report the observation of a metal insulator transition at B=0 in a high mobility two dimensional hole gas in a GaAs-AlGaAs heterostructure. A clear critical point separates the insulating phase from the metallic phase, demonstrating the existence of a well defined minimum metallic conductivity sigma(min)=2e/h. The sigma(T) data either side of the transition can be `scaled' on to one curve with a single parameter (To). The application of a parallel magnetic field increases sigma(min) and broadens the transition. We argue that strong electron-electron interactions (rs = 10) destroy phase coherence, removing quantum intereference corrections to the conductivity.Comment: 4 pages RevTex + 4 figures. Submitted to PRL. Originally posted 22 September 1997. Revised 12 October 1997 - minor changes to referencing, figure cations and figure

    Expression of different survivin variants in gastric carcinomas: first clues to a role of survivin-2B in tumour progression

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    Survivin is a novel member of the inhibitor of apoptosis family and determines the susceptibility of tumour cells to pro-apoptotic stimuli. Recently, we identified two novel alternative splice variants of survivin, differing in their anti-apoptotic properties: whereas the anti-apoptotic potential of survivin-ΔEx3 is preserved, survivin-2B has lost its anti-apoptotic potential and may act as a naturally occurring antagonist of survivin. Because the in vivo expression of these alternative splice variants has not been explored so far, we analysed gastric carcinomas of different histological subtypes, grades and stages. Since no antibodies are currently available to determine the novel splice variants, quantitative reverse transcriptase polymerase chain reaction was performed, using RNA samples obtained from 30 different gastric carcinomas. Polymerase chain reactions products were quantified by densitometric evaluation. We found that all gastric carcinomas, irrespective of their histological types, grades or stages, express survivin-ΔEx3, survivin-2B and survivin, the latter being the dominant transcript. Comparing the disease stages I+II with III+IV, expression of survivin and survivin-ΔEx3 remained unchanged. In contrast, a significant (P=0.033) stage-dependent decrease in the expression of survivin-2B became evident. Our study demonstrates for the first time the expression of alternative splice variants in gastric carcinomas and provides a first clue to a role of survivin-2B in tumour progression

    Effects of Glyphosate and its Formulation, Roundup, on Reproduction in Zebrafish (Danio rerio)

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    This is an open access article that is freely available in ORE or from the publisher's web site. Please cite the published version.Copyright © 2014 American Chemical SocietyRoundup and its active ingredient glyphosate are among the most widely used herbicides worldwide and may contaminate surface waters. Research suggests both Roundup and glyphosate induce oxidative stress in fish and may also cause reproductive toxicity in mammalian systems. We aimed to investigate the reproductive effects of Roundup and glyphosate in fish and the potential associated mechanisms of toxicity. To do this, we conducted a 21-day exposure of breeding zebrafish (Danio rerio) to 0.01, 0.5, and 10 mg/L (glyphosate acid equivalent) Roundup and 10 mg/L glyphosate. 10 mg/L glyphosate reduced egg production but not fertilization rate in breeding colonies. Both 10 mg/L Roundup and glyphosate increased early stage embryo mortalities and premature hatching. However, exposure during embryogenesis alone did not increase embryo mortality, suggesting that this effect was caused primarily by exposure during gametogenesis. Transcript profiling of the gonads revealed 10 mg/L Roundup and glyphosate induced changes in the expression of cyp19a1 and esr1 in the ovary and hsd3b2, cat, and sod1 in the testis. Our results demonstrate that these chemicals cause reproductive toxicity in zebrafish, although only at high concentrations unlikely to occur in the environment, and likely mechanisms of toxicity include disruption of the steroidogenic biosynthesis pathway and oxidative stress.Natural Environment Research Counci

    Sigma-2 receptor ligand as a novel method for delivering a SMAC mimetic drug for treating ovarian cancer

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    BACKGROUND: The sigma-2 receptor has been validated as a biomarker for proliferating tumours. Second mitochondria-derived activator of caspase (Smac) is a protein released from mitochondria into the cytosol, leading to apoptosis. In this study, we investigated a sigma-2 ligand as a tumour-targeting drug delivery agent for treating ovarian cancer. METHODS: A sigma-2 ligand, SW 43, was conjugated with a Smac mimetic compound (SMC), SW IV-52s, to form SW III-123. The delivery function of the sigma-2 moiety and cell killing mechanisms of SW III-123 were examined in human ovarian cancer cell lines. RESULTS: SW III-123 internalisation into ovarian cancer cells was mediated by sigma-2 receptors. SW III-123, but not SW IV-52s or SW 43, exhibited potent cytotoxicity in human ovarian cancer cell lines SKOV-3, CaOV-3 and BG-1 after 24-h treatment, suggesting that the sigma-2 ligand successfully delivered SMC into ovarian cancer cells. SW III-123 induced rapid degradation of inhibitor of apoptosis proteins (cIAP1 and cIAP2), accumulation of NF-κB-inducing kinase (NIK) and phosphorylation of NF-κB p65, suggesting that SW III-123 activated both canonical and noncanonical NF-κB pathways in SKOV-3 cells. SW III-123 cleaved caspase-8, -9 and -3. Tumour necrosis factor alpha (TNFα) antibody markedly blocked SW III-123-induced cell death and caspase-3 activity in SKOV-3 cells, indicating that SW III-123 activated both intrinsic and extrinsic apoptotic pathways and induced TNFα-dependent cell death in SKOV-3 cells. CONCLUSION: Sigma-2 ligands are a promising tumour-targeting drug delivery agent. Sigma-2-conjugated SMC exemplifies a novel class of therapeutic drugs for treating ovarian cancer
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