1,282 research outputs found

    Formation and stability of self-assembled coherent islands in highly mismatched heteroepitaxy

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    We study the energetics of island formation in Stranski-Krastanow growth within a parameter-free approach. It is shown that an optimum island size exists for a given coverage and island density if changes in the wetting layer morphology after the 3D transition are properly taken into account. Our approach reproduces well the experimental island size dependence on coverage, and indicates that the critical layer thickness depends on growth conditions. The present study provides a new explanation for the (frequently found) rather narrow size distribution of self-assembled coherent islands.Comment: 4 pages, 5 figures, In print, Phys. Rev. Lett. Other related publications can be found at http://www.fhi-berlin.mpg.de/th/paper.htm

    Mutations of the BRAF gene in human cancer

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    Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma

    Microtesla MRI of the human brain combined with MEG

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    One of the challenges in functional brain imaging is integration of complementary imaging modalities, such as magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI). MEG, which uses highly sensitive superconducting quantum interference devices (SQUIDs) to directly measure magnetic fields of neuronal currents, cannot be combined with conventional high-field MRI in a single instrument. Indirect matching of MEG and MRI data leads to significant co-registration errors. A recently proposed imaging method - SQUID-based microtesla MRI - can be naturally combined with MEG in the same system to directly provide structural maps for MEG-localized sources. It enables easy and accurate integration of MEG and MRI/fMRI, because microtesla MR images can be precisely matched to structural images provided by high-field MRI and other techniques. Here we report the first images of the human brain by microtesla MRI, together with auditory MEG (functional) data, recorded using the same seven-channel SQUID system during the same imaging session. The images were acquired at 46 microtesla measurement field with pre-polarization at 30 mT. We also estimated transverse relaxation times for different tissues at microtesla fields. Our results demonstrate feasibility and potential of human brain imaging by microtesla MRI. They also show that two new types of imaging equipment - low-cost systems for anatomical MRI of the human brain at microtesla fields, and more advanced instruments for combined functional (MEG) and structural (microtesla MRI) brain imaging - are practical.Comment: 8 pages, 5 figures - accepted by JM

    The reductive activation of CO2 across a Ti═Ti double bond: synthetic, structural, and mechanistic studies

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    [Image: see text] The reactivity of the bis(pentalene)dititanium double-sandwich compound Ti(2)Pn(†)(2) (1) (Pn(†) = 1,4-{Si(i)Pr(3)}(2)C(8)H(4)) with CO(2) is investigated in detail using spectroscopic, X-ray crystallographic, and computational studies. When the CO(2) reaction is performed at −78 °C, the 1:1 adduct 4 is formed, and low-temperature spectroscopic measurements are consistent with a CO(2) molecule bound symmetrically to the two Ti centers in a μ:η(2),η(2) binding mode, a structure also indicated by theory. Upon warming to room temperature the coordinated CO(2) is quantitatively reduced over a period of minutes to give the bis(oxo)-bridged dimer 2 and the dicarbonyl complex 3. In situ NMR studies indicated that this decomposition proceeds in a stepwise process via monooxo (5) and monocarbonyl (7) double-sandwich complexes, which have been independently synthesized and structurally characterized. 5 is thermally unstable with respect to a μ-O dimer in which the Ti–Ti bond has been cleaved and one pentalene ligand binds in an η(8) fashion to each of the formally Ti(III) centers. The molecular structure of 7 shows a “side-on” bound carbonyl ligand. Bonding of the double-sandwich species Ti(2)Pn(2) (Pn = C(8)H(6)) to other fragments has been investigated by density functional theory calculations and fragment analysis, providing insight into the CO(2) reaction pathway consistent with the experimentally observed intermediates. A key step in the proposed mechanism is disproportionation of a mono(oxo) di-Ti(III) species to yield di-Ti(II) and di-Ti(IV) products. 1 forms a structurally characterized, thermally stable CS(2) adduct 8 that shows symmetrical binding to the Ti(2) unit and supports the formulation of 4. The reaction of 1 with COS forms a thermally unstable complex 9 that undergoes scission to give mono(μ-S) mono(CO) species 10. Ph(3)PS is an effective sulfur transfer agent for 1, enabling the synthesis of mono(μ-S) complex 11 with a double-sandwich structure and bis(μ-S) dimer 12 in which the Ti–Ti bond has been cleaved

    Competitiveness and communication for effective inoculation byRhizobium, Bradyrhizobium and vesicular-arbuscular mycorrhiza fungi

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    After a short summary on the ecology and rhizosphere biology of symbiotic bacteria and vesicular-arbuscular (VA) mycorrhiza fungi and their application as microbial inocula, results on competitiveness and communication are summarized. Stress factors such as high temperature, low soil pH, aluminium concentrations and phytoalexins produced by the host plants were studied withRhizobium leguminosarum bv.phaseoli andRhizobium tropici onPhaseolus beans. Quantitative data for competitiveness were obtained by usinggus + (glucoronidase) labelled strains, which produce blue-coloured nodules. ForPhaseolus-nodulating rhizobia, a group specific DNA probe was also developed, which did not hybridize with more than 20 other common soil and rhizosphere bacteria. Results from several laboratories contributing to knowledge of signal exchange and communication in theRhizobium/Bradyrhizobium legume system are summarized in a new scheme, including also defense reactions at the early stages of legume nodule initiation. Stimulating effects of flavonoids on germination and growth of VA mycorrhiza fungi were also found. A constitutive antifungal compound in pea roots, -isoxazolinonyl-alanine, was characterized

    Effects of anharmonic strain on phase stability of epitaxial films and superlattices: applications to noble metals

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    Epitaxial strain energies of epitaxial films and bulk superlattices are studied via first-principles total energy calculations using the local-density approximation. Anharmonic effects due to large lattice mismatch, beyond the reach of the harmonic elasticity theory, are found to be very important in Cu/Au (lattice mismatch 12%), Cu/Ag (12%) and Ni/Au (15%). We find that is the elastically soft direction for biaxial expansion of Cu and Ni, but it is for large biaxial compression of Cu, Ag, and Au. The stability of superlattices is discussed in terms of the coherency strain and interfacial energies. We find that in phase-separating systems such as Cu-Ag the superlattice formation energies decrease with superlattice period, and the interfacial energy is positive. Superlattices are formed easiest on (001) and hardest on (111) substrates. For ordering systems, such as Cu-Au and Ag-Au, the formation energy of superlattices increases with period, and interfacial energies are negative. These superlattices are formed easiest on (001) or (110) and hardest on (111) substrates. For Ni-Au we find a hybrid behavior: superlattices along and like in phase-separating systems, while for they behave like in ordering systems. Finally, recent experimental results on epitaxial stabilization of disordered Ni-Au and Cu-Ag alloys, immiscible in the bulk form, are explained in terms of destabilization of the phase separated state due to lattice mismatch between the substrate and constituents.Comment: RevTeX galley format, 16 pages, includes 9 EPS figures, to appear in Physical Review

    Research engagement by British early-career practitioners in nephrology: a multidisciplinary survey

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    Objectives To establish barriers and motivators underlying research engagement among early-career practitioners in nephrology across the UK, in order to guide potential interventions to enhance research involvement in renal units. Design Cross-sectional online survey employing a range of free-text, Likert scale and binomial/multiple-choice responses, distributed via mailing lists and social media. Topics covered research experience, research involvement and barriers, impact of COVID-19 and strategies to improve research engagement. Thematic analysis was used to assess free-text responses. Setting Renal units throughout the UK. Participants Non-consultant healthcare staff self-identifying as working in nephrology were included (n=211), with responses from non-UK respondents or consultant nephrologists excluded (n=12). Results Responses were received from across the multidisciplinary team (physicians (n=83) and nurses (n=83)) and other allied health professionals (n=45). Most were aware of ongoing local research, but under half of them were actively involved. Multivariate analysis indicated employment as a physician, protected time for research activity and provision of appropriate training were associated with greater research experience and output. There was general enthusiasm to undertake research, but perceived barriers included insufficient staffing, lack of time, funding and encouragement. COVID-19 was felt to have further impacted negatively upon opportunities. Among the suggested strategies to promote engagement, mentorship and an online research resource were felt to be of most interest. Conclusions In the first survey of this type in nephrology, we demonstrate differences across the multidisciplinary spectrum in perceived research experience and accessibility, which have been worsened by COVID-19. Our findings will guide strategies to broaden engagement in early-career practitioners and serve as a baseline to assess the impact of these interventions

    Left ventricular T2 distribution in Duchenne Muscular Dystrophy

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    <p>Abstract</p> <p>Background</p> <p>Although previous studies have helped define the natural history of Duchenne Muscular Dystrophy (DMD)-associated cardiomyopathy, the myocardial pathobiology associated with functional impairment in DMD is not yet known.</p> <p>The objective of this study was to assess the distribution of transverse relaxation time (T2) in the left ventricle (LV) of DMD patients, and to determine the association of myocardial T2 heterogeneity to the severity of cardiac dysfunction. DMD patients (n = 26) and normal control subjects (n = 13) were studied by Cardiovascular Magnetic Resonance (CMR). DMD subject data was stratified based on subject age and LV Ejection Fraction (EF) into the following groups: A (<12 years old, n = 12); B (≥12 years old, EF ≤ 55%, n = 8) and C (≥12 years old, EF = 55%, n = 6). Controls were also stratified by age into Groups N1 (<12 years, n = 6) and N2 (>12 years, n = 5). LV mid-slice circumferential myocardial strain (ε<sub>cc</sub>) was calculated using tagged CMR imaging. T2 maps of the LV were generated for all subjects using a black blood dual spin echo method at two echo times. The Full Width at Half Maximum (<it>FWHM</it>) was calculated from a histogram of LV T2 distribution constructed for each subject.</p> <p>Results</p> <p>In DMD subject groups, <it>FWHM </it>of the T2 histogram rose progressively with age and decreasing EF (Group A <it>FWHM</it>= 25.3 ± 3.8 ms; Group B <it>FWHM</it>= 30.9 ± 5.3 ms; Group C <it>FWHM</it>= 33.0 ± 6.4 ms). Further, <it>FWHM </it>was significantly higher in those with reduced circumferential strain (|ε<sub>cc</sub>| ≤ 12%) (Group B, and C) than those with |ε<sub>cc</sub>| > 12% (Group A). Group A <it>FWHM </it>was not different from the two normal groups (N1 <it>FWHM </it>= 25.3 ± 3.5 ms; N2 <it>FWHM</it>= 24.0 ± 7.3 ms).</p> <p>Conclusion</p> <p>Reduced EF and ε<sub>cc </sub>correlates well with increased T2 heterogeneity quantified by <it>FWHM</it>, indicating that subclinical functional impairments could be associated with pre-existing abnormalities in tissue structure in young DMD patients.</p
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