927 research outputs found

    Probing the Role of the Barrier Layer in Magnetic Tunnel Junction Transport

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    Magnetic tunnel junctions with a ferrimagnetic barrier layer have been studied to understand the role of the barrier layer in the tunneling process - a factor that has been largely overlooked until recently. Epitaxial oxide junctions of highly spin polarized La0.7Sr0.3MnO3 and Fe3O4 electrodes with magnetic NiMn2O4 (NMO) insulating barrier layers provide a magnetic tunnel junction system in which we can probe the effect of the barrier by comparing junction behavior above and below the Curie temperature of the barrier layer. When the barrier is paramagnetic, the spin polarized transport is dominated by interface scattering and surface spin waves; however, when the barrier is ferrimagnetic, spin flip scattering due to spin waves within the NMO barrier dominates the transport.Comment: 10 pages, 3 figure

    Zero-order controlled release of ciprofloxacin-HCl from a reservoir-based, bioresorbable and elastomeric device

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    A reservoir-based device constructed of a completely biodegradable elastomer can enable several new implantation and insertion options for localized drug therapy, particularly in the case of urological therapies. We performed an in vitro performance evaluation of an implantable, bio-resorbable device that supplies short-term controlled release of ciprofloxacin-HCl (CIP). The proposed device functions through a combination of osmosis and diffusion mechanisms to release CIP for short-term therapies of a few weeks duration. Poly(glycerol-co-sebacic acid) (PGS) was cast in a tubular geometry with solid drug powder packed into its core and a micro-machined release orifice drilled through its wall. Drug release experiments were performed to determine the effective release rate from a single orifice and the range of orifice sizes in which controlled zero-order release was the main form of drug expulsion from the device. It is demonstrated that PGS is sufficiently permeable to water to allow the design of an elementary osmotic pump for drug delivery. Indeed, PGS's water permeability is several orders of magnitude larger than commonly used cellulose acetate for elementary osmotic pumps.Deshpande Center for Technological InnovationSamsung Scholarship Foundatio

    Stone-Wales Transformation Paths in Fullerene C60

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    The mechanisms of formation of a metastable defect isomer of fullerene C60 due to the Stone-Wales transformation are theoretically studied. It is demonstrated that the paths of the "dynamic" Stone-Wales transformation at a high sufficient for overcoming potential barriers) temperature can differ from the two "adiabatic" transformation paths discussed in the literature. This behavior is due to the presence of a great near-flat segment of the potential-energy surface in the neighborhood of metastable states. Besides, the sequence of rupture and formation of interatomic bonds is other than that in the case of the adiabatictransformation.Comment: 10 pages, 6 figure

    The Caenorhabditis elegans vulva: A post-embryonic gene regulatory network controlling organogenesis

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    The Caenorhabditis elegans vulva is an elegant model for dissecting a gene regulatory network (GRN) that directs postembryonic organogenesis. The mature vulva comprises seven cell types (vulA, vulB1, vulB2, vulC, vulD, vulE, and vulF), each with its own unique pattern of spatial and temporal gene expression. The mechanisms that specify these cell types in a precise spatial pattern are not well understood. Using reverse genetic screens, we identified novel components of the vulval GRN, including nhr-113 in vulA. Several transcription factors (lin-11, lin-29, cog-1, egl-38, and nhr-67) interact with each other and act in concert to regulate target gene expression in the diverse vulval cell types. For example, egl-38 (Pax2/5/8) stabilizes the vulF fate by positively regulating vulF characteristics and by inhibiting characteristics associated with the neighboring vulE cells. nhr-67 and egl-38 regulate cog-1, helping restrict its expression to vulE. Computational approaches have been successfully used to identify functional cis-regulatory motifs in the zmp-1 (zinc metalloproteinase) promoter. These results provide an overview of the regulatory network architecture for each vulval cell type

    A Small Conductance Calcium-Activated K<sup>+</sup> Channel in C. elegans, KCNL-2, Plays a Role in the Regulation of the Rate of Egg-Laying

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    In the nervous system of mice, small conductance calcium-activated potassium (SK) channels function to regulate neuronal excitability through the generation of a component of the medium afterhyperpolarization that follows action potentials. In humans, irregular action potential firing frequency underlies diseases such as ataxia, epilepsy, schizophrenia and Parkinson's disease. Due to the complexity of studying protein function in the mammalian nervous system, we sought to characterize an SK channel homologue, KCNL-2, in C. elegans, a genetically tractable system in which the lineage of individual neurons was mapped from their early developmental stages. Sequence analysis of the KCNL-2 protein reveals that the six transmembrane domains, the potassium-selective pore and the calmodulin binding domain are highly conserved with the mammalian homologues. We used widefield and confocal fluorescent imaging to show that a fusion construct of KCNL-2 with GFP in transgenic lines is expressed in the nervous system of C. elegans. We also show that a KCNL-2 null strain, kcnl-2(tm1885), demonstrates a mild egg-laying defective phenotype, a phenotype that is rescued in a KCNL-2-dependent manner. Conversely, we show that transgenic lines that overexpress KCNL-2 demonstrate a hyperactive egg-laying phenotype. In this study, we show that the vulva of transgenic hermaphrodites is highly innervated by neuronal processes and by the VC4 and VC5 neurons that express GFP-tagged KCNL-2. We propose that KCNL-2 functions in the nervous system of C. elegans to regulate the rate of egg-laying. © 2013 Chotoo et al

    Magnetism of NiMn2O4-Fe3O4 spinel interfaces

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    We investigate the magnetic properties of the isostructural spinel-spinel interface of NiMn{sub 2}O{sub 4}(NMO)-Fe{sub 3}O{sub 4}. Although the magnetic transition temperature of the NMO film is preserved, both bulk and interface sensitive measurements demonstrate that the interface exhibits strong interfacial magnetic coupling up to room temperature. While NMO thin films have a ferrimagnetic transition temperature of 60 K, both NiFe{sub 2}O{sub 4} and MnFe{sub 2}O{sub 4} are ferrimagnetic at room temperature. Our experimental results suggest that these magnetic properties arise from a thin interdiffused region of (Fe,Mn,Ni){sub 3}O{sub 4} at the interface, leading to Mn and Ni magnetic properties similar to those of MnFe{sub 2}O{sub 4} and NiFe{sub 2}O{sub 4}

    Impact of COVID-19 on 1-year survival outcomes in hepatocellular carcinoma: a multicenter cohort study

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    INTRODUCTION: The COVID-19 pandemic has caused severe disruption of healthcare services worldwide and interrupted patients' access to essential services. During the first lockdown, many healthcare services were shut to all but emergencies. In this study, we aimed to determine the immediate and long-term indirect impact of COVID-19 health services utilisation on hepatocellular cancer (HCC) outcomes. METHODS: A prospective cohort study was conducted from 1 March 2020 until 30 June 2020, correlating to the first wave of the COVID-19 pandemic. Patients were enrolled from tertiary hospitals in the UK and Germany with dedicated HCC management services. All patients with current or past HCC who were discussed at a multidisciplinary meeting (MDM) were identified. Any delay to treatment (DTT) and the effect on survival at one year were reported. RESULTS: The median time to receipt of therapy following MDM discussion was 49 days. Patients with Barcelona Clinic Liver Cancer (BCLC) stages-A/B disease were more likely to experience DTT. Significant delays across all treatments for HCC were observed, but delay was most marked for those undergoing curative therapies. Even though severe delays were observed in curative HCC treatments, this did not translate into reduced survival in patients. CONCLUSION: Interruption of routine healthcare services because of the COVID-19 pandemic caused severe delays in HCC treatment. However, DTT did not translate to reduced survival. Longer follow is important given the delay in therapy in those receiving curative therapy

    Improved survival prediction and comparison of prognostic models for patients with hepatocellular carcinoma treated with sorafenib

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    BACKGROUND: The 'Prediction Of Survival in Advanced Sorafenib-treated HCC' (PROSASH) model addressed the heterogeneous survival of patients with hepatocellular carcinoma (HCC) treated with sorafenib in clinical trials, but requires validation in daily clinical practice. This study aimed to validate, compare and optimize this model for survival prediction. METHODS: Patients treated with sorafenib for HCC at 5 tertiary European centres were retrospectively staged according to the PROSASH model. In addition, the optimized PROSASH-II model was developed using the data of 4 centres (training set) and tested in an independent dataset. These models for overall survival (OS) were then compared with existing prognostic models. RESULTS: The PROSASH model was validated in 445 patients, showing clear differences between the 4 risk groups (OS 16.9-4.6 months). A total of 920 patients (n=615 in training set, n=305 in validation set) were available to develop PROSASH-II. This optimized model incorporated fewer and less subjective parameters: the serum albumin, bilirubin and alpha-fetoprotein, and macrovascular invasion, extrahepatic spread and largest tumour size on imaging. Both PROSASH and PROSASH-II showed improved discrimination (C-index 0.62 and 0.63, respectively) compared with existing prognostic scores (C-index ≤0.59). CONCLUSIONS: In HCC patients treated with sorafenib, individualized prediction of survival and risk group stratification using baseline prognostic and predictive parameters with the PROSASH model was validated. The refined PROSASH-II model performed at least as good with fewer and more objective parameters. PROSASH-II can be used as a tool for tailored treatment of HCC in daily practice and to define pre-planned subgroups for future studies
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