472 research outputs found

    Atomic resolution imaging of electrode surfaces in solutions containing reversible redox species

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    Procedures are described for insulating metal scanning tunneling microscope (STM) tips with either glass or polymer coatings. In solutions containing 0.10 M of a reversible redox couple, Fe(CN) - 3/-46 , the faradaic limiting current to polymer coated tips was 200–500 pA and that for glass coated tips was <10 pA. For polymer insulated tips, steady-state currents of 10–100 pA were observed at tip-sample displacements less than 0.3 µm. The suppression of faradaic current achieved by these coating procedures enabled the collection of the first atomic resolution STM images of highly ordered pyrolytic graphite electrodes in contact with redox-active electrolytes. Preliminary data for the in situ electrochemical characterization of these tips are also discussed

    Design of a scanning tunneling microscope for electrochemical applications

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    A design for a scanning tunneling microscope that is well suited for electrochemical investigations is presented. The construction of the microscope ensures that only the tunneling tip and the sample participate in electrochemical reactions. The design also allows rapid replacement of the tip or sample, and enables facile introduction of auxiliary electrodes for use in electrochemical experiments. The microscope utilizes stepper motor driven approach mechanics in order to achieve fully remote operation and to allow reproducible coarse control of tip/sample spacings for electrochemical experiments. Highly ordered pyrolytic graphite images at atomic resolution in air and aqueous solutions can be obtained with this microscope

    Management and outcome of patients with established coronary artery disease: the Euro Heart Survey on coronary revascularization

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    Aims The purpose of the Euro Heart Survey Programme of the European Society of Cardiology is to evaluate to which extent clinical practice endorses existing guidelines as well as to identify differences in population profiles, patient management, and outcome across Europe. The current survey focuses on the invasive diagnosis and treatment of patients with established coronary artery disease (CAD). Methods and results Between November 2001 and March 2002, 7769 consecutive patients undergoing invasive evaluation at 130 hospitals (31 countries) were screened for the presence of one or more coronary stenosis >50% in diameter. Patient demographics and comorbidity, clinical presentation, invasive parameters, treatment options, and procedural techniques were prospectively entered in an electronic database (550 variables+29 per diseased coronary segment). Major adverse cardiac events (MACE) were evaluated at 30 days and 1 year. Out of 5619 patients with angiographically proven coronary stenosis (72% of screened population), 53% presented with stable angina while ST elevation myocardial infarction (STEMI) was the indication for coronary angiography in 16% and non-ST segment elevation myocardial infarction or unstable angina in 30%. Only medical therapy was continued in 21%, whereas mechanical revascularization was performed in the remainder [percutaneous coronary intervention (PCI) in 58% and coronary artery bypass grafting (CABG) in 21%]. Patients referred for PCI were younger, were more active, had a lower risk profile, and had less comorbid conditions. CABG was performed mostly in patients with left main lesions (21%), two- (25%), or three-vessel disease (67%) with 4.1 diseased segments, on average. Single-vessel PCI was performed in 82% of patients with either single- (45%), two- (33%), or three-vessel disease (21%). Stents were used in 75% of attempted lesions, with a large variation between sites. Direct PCI for STEMI was performed in 410 cases, representing 7% of the entire workload in the participating catheterization laboratories. Time delay was within 90 min in 76% of direct PCI cases. In keeping with the recommendations of practice guidelines, the survey identified under-use of adjunctive medication (GP IIb/IIIa receptor blockers, statins, and angiotensin-converting enzyme-inhibitors). Mortality rates at 30 days and 1 year were low in all subgroups. MACE primarily consisted of repeat PCI (12%). Conclusion The current Euro Heart Survey on coronary revascularization was performed in the era of bare metal stenting and provides a global European picture of the invasive approach to patients with CAD. These data will serve as a benchmark for the future evaluation of the impact of drug-eluting stents on the practice of interventional cardiology and bypass surger

    Serum α-Fetoprotein Levels at Time of Recurrence Predict Post-Recurrence Outcomes Following Resection of Hepatocellular Carcinoma

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    Introduction: Although preoperative α-fetoprotein (AFP) has been recognized as an important tumor marker among patients with hepatocellular carcinoma (HCC), the predictive value of AFP levels at the time of recurrence (rAFP) on post-recurrence outcomes has not been well examined. Methods: Patients undergoing curative-intent resection of HCC between 2000 and 2017 were identified using a multi-institutional database. The impact of rAFP on post-recurrence survival, as well as the impact of rAFP relative to the timing and treatment of HCC recurrence were examined. Results: Among 852 patients who underwent resection of HCC, 307 (36.0%) individuals developed a recurrence. The median rAFP level was 8 ng/mL (interquartile range 3-100). Among the 307 patients who developed recurrence, 3-year post-recurrence survival was 48.5%. Patients with rAFP > 10 ng/mL had worse 3-year post-recurrence survival compared with individuals with rAFP 10 vs. 10 vs. 10 ng/mL had a twofold higher hazard of death in the post-recurrence setting (hazard ratio 1.96, 95% confidence interval 1.26-3.04). Conclusion: AFP levels at the time of recurrence following resection of HCC predicted post-recurrence survival independent of the secondary treatment modality used. Evaluating AFP levels at the time of recurrence can help inform post-recurrence risk stratification of patients with recurrent HCC.info:eu-repo/semantics/publishedVersio

    Single-cell and spatial transcriptomics reveal somitogenesis in gastruloids.

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    Gastruloids are three-dimensional aggregates of embryonic stem cells that display key features of mammalian development after implantation, including germ-layer specification and axial organization1-3. To date, the expression pattern of only a small number of genes in gastruloids has been explored with microscopy, and the extent to which genome-wide expression patterns in gastruloids mimic those in embryos is unclear. Here we compare mouse gastruloids with mouse embryos using single-cell RNA sequencing and spatial transcriptomics. We identify various embryonic cell types that were not previously known to be present in gastruloids, and show that key regulators of somitogenesis are expressed similarly between embryos and gastruloids. Using live imaging, we show that the somitogenesis clock is active in gastruloids and has dynamics that resemble those in vivo. Because gastruloids can be grown in large quantities, we performed a small screen that revealed how reduced FGF signalling induces a short-tail phenotype in embryos. Finally, we demonstrate that embedding in Matrigel induces gastruloids to generate somites with the correct rostral-caudal patterning, which appear sequentially in an anterior-to-posterior direction over time. This study thus shows the power of gastruloids as a model system for exploring development and somitogenesis in vitro in a high-throughput manner.This work was supported by an European Research Council Advanced grant (ERC-AdG 742225-IntScOmics), a Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO) TOP award (NWOCW 714.016.001), and the Foundation for Fundamental Research on Matter, financially supported by NWO (FOM-14NOISE01) to S.C.v.d.B., A.A., V.v.B., M.B., J.V. and A.v.O., a BBSRC (No. BB/M023370/1 and BB/P003184/1), Newton Trust (INT16.24b) and MRC (MR/R017190/1) grant to A.M.A., a Newnham College Cambridge Junior Research Fellowship to N.M., and a studentship from the Engineering and Physical Sciences Research Council (EPSRC) to P.B.J.. The Cambridge Stem Cell Institute is supported by core funding from the Wellcome Trust and Medical Research Council; J. N. was funded by the University of Cambridge, and K.F.S. by core funding from the Hubrecht Institute. This work is part of the Oncode Institute which is partly financed by the Dutch Cancer Society

    Fermiology and superconductivity studies on the non-tetrachalcogenafulvalene structured organic superconductor beta-(BDA-TTP)_2SbF_6

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    The quantum oscillatory effect and superconductivity in a non-tetrachalcogenafulvalene (TCF) structure based organic superconductor beta-(BDA-TTP)_2SbF_6 are studied. Here the Shubnikov-de Haas effect (SdH) and angular dependent magnetoresistance oscillations (AMRO) are observed. The oscillation frequency associated with a cylindrical Fermi surface is found to be about 4050 tesla, which is also verified by the tunnel diode oscillator (TDO) measurement. The upper critical field Hc2 measurement in a tilted magnetic field and the TDO measurement in the mixed state reveal a highly anisotropic superconducting nature in this material. We compared physical properties of beta-(BDA-TTP)_2SbF_6 with typical TCF structure based quasi two-dimensional organic conductors. A notable feature of beta-(BDA-TTP)_2SbF_6 superconductor is a large value of effective cyclotron mass m_c^*=12.4+/1.1 m_e, which is the largest yet found in an organic superconductor. A possible origin of the enhanced effective mass and its relation to the superconductivity are briefly discussed.Comment: 8 pages, 10 figure

    HIV Traffics through a Specialized, Surface-Accessible Intracellular Compartment during trans-Infection of T Cells by Mature Dendritic Cells

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    In vitro, dendritic cells (DCs) bind and transfer intact, infectious HIV to CD4 T cells without first becoming infected, a process known as trans-infection. trans-infection is accomplished by recruitment of HIV and its receptors to the site of DC–T cell contact and transfer of virions at a structure known as the infectious synapse. In this study, we used fluorescent microscopy to track individual HIV particles trafficking in DCs during virus uptake and trans-infection. Mature DCs rapidly concentrated HIV into an apparently intracellular compartment that lacked markers characteristic of early endosomes, lysosomes, or antigen-processing vesicles. Live cell microscopy demonstrated that the HIV-containing compartment was rapidly polarized toward the infectious synapse after contact with a T cell; however, the bulk of the concentrated virus remained in the DCs after T cell engagement. Individual virions were observed emerging from the compartment and fusing with the T cell membrane at the infectious synapse. The compartmentalized HIV, although engulfed by the cytoplasm, was fully accessible to HIV envelope-specific inhibitors and other membrane-impermeable probes that were delivered to the cell surface. These results demonstrate that HIV resides in an invaginated domain within DCs that is both contiguous with the plasma membrane and distinct from endocytic vesicles. We conclude that HIV virions are routed through this specialized compartment, which allows individual particles to be delivered to T cells during trans-infection

    The relationship between transmission time and clustering methods in Mycobacterium tuberculosis epidemiology

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    YesBackground: Tracking recent transmission is a vital part of controlling widespread pathogens such as Mycobacterium tuberculosis. Multiple methods with specific performance characteristics exist for detecting recent transmission chains, usually by clustering strains based on genotype similarities. With such a large variety of methods available, informed selection of an appropriate approach for determining transmissions within a given setting/time period is difficult. Methods: This study combines whole genome sequence (WGS) data derived from 324 isolates collected 2005–2010 in Kinshasa, Democratic Republic of Congo (DRC), a high endemic setting, with phylodynamics to unveil the timing of transmission events posited by a variety of standard genotyping methods. Clustering data based on Spoligotyping, 24-loci MIRU-VNTR typing, WGS based SNP (Single Nucleotide Polymorphism) and core genome multi locus sequence typing (cgMLST) typing were evaluated. Findings: Our results suggest that clusters based on Spoligotyping could encompass transmission events that occurred almost 200 years prior to sampling while 24-loci-MIRU-VNTR often represented three decades of transmission. Instead, WGS based genotyping applying low SNP or cgMLST allele thresholds allows for determination of recent transmission events, e.g. in timespans of up to 10 years for a 5 SNP/allele cut-off. Interpretation: With the rapid uptake of WGS methods in surveillance and outbreak tracking, the findings obtained in this study can guide the selection of appropriate clustering methods for uncovering relevant transmission chains within a given time-period. For high resolution cluster analyses, WGS-SNP and cgMLST based analyses have similar clustering/timing characteristics even for data obtained from a high incidence setting.ERC grant [INTERRUPTB; no. 311725] to BdJ, FG and CJM; an ERC grant to TS [PhyPD; no. 335529]; an FWO PhD fellowship to PM [grant number 1141217N]; the Leibniz Science Campus EvolLUNG for MM and SN; the German Centre for Infection Research (DZIF) for TAK, MM, CU, PB and SN; a SNF SystemsX grant (TBX) to JP and TS and a Marie Heim-Vögtlin fellowship granted to DK by the Swiss National Science Foundation. The computational resources and services used in this work were provided by the VSC (Flemish Supercomputer Center), funded by the Research Foundation - Flanders (FWO) and the Flemish Government – department EWI
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