437 research outputs found
Continuum limit of amorphous elastic bodies: A finite-size study of low frequency harmonic vibrations
The approach of the elastic continuum limit in small amorphous bodies formed
by weakly polydisperse Lennard-Jones beads is investigated in a systematic
finite-size study. We show that classical continuum elasticity breaks down when
the wavelength of the sollicitation is smaller than a characteristic length of
approximately 30 molecular sizes. Due to this surprisingly large effect
ensembles containing up to N=40,000 particles have been required in two
dimensions to yield a convincing match with the classical continuum predictions
for the eigenfrequency spectrum of disk-shaped aggregates and periodic bulk
systems. The existence of an effective length scale \xi is confirmed by the
analysis of the (non-gaussian) noisy part of the low frequency vibrational
eigenmodes. Moreover, we relate it to the {\em non-affine} part of the
displacement fields under imposed elongation and shear. Similar correlations
(vortices) are indeed observed on distances up to \xi~30 particle sizes.Comment: 28 pages, 13 figures, 3 table
Nanoantenna-enhanced ultrafast nonlinear spectroscopy of a single gold nanoparticle
Optical nanoantennas are a novel tool to investigate previously unattainable
dimensions in the nanocosmos. Just like their radio-frequency equivalents,
nanoantennas enhance the light-matter interaction in their feed gap. Antenna
enhancement of small signals promises to open a new regime in linear and
nonlinear spectroscopy on the nanoscale. Without antennas especially the
nonlinear spectroscopy of single nanoobjects is very demanding. Here, we
present for the first time antenna-enhanced ultrafast nonlinear optical
spectroscopy. In particular, we utilize the antenna to determine the nonlinear
transient absorption signal of a single gold nanoparticle caused by mechanical
breathing oscillations. We increase the signal amplitude by an order of
magnitude which is in good agreement with our analytical and numerical models.
Our method will find applications in linear and nonlinear spectroscopy of
nanoobjects, ranging from single protein binding events via nonlinear tensor
elements to the limits of continuum mechanics
Mechanism of copper(II)-induced misfolding of Parkinson's disease protein
α-synuclein (aS) is a natively unfolded pre-synaptic protein found in all Parkinson's disease patients as the major component of fibrillar plaques. Metal ions, and especially Cu(II), have been demonstrated to accelerate aggregation of aS into fibrillar plaques, the precursors to Lewy bodies. In this work, copper binding to aS is investigated by a combination of quantum and molecular mechanics simulations. Starting from the experimentally observed attachment site, several optimized structures of Cu-binding geometries are examined. The most energetically favorable attachment results in significant allosteric changes, making aS more susceptible to misfolding. Indeed, an inverse kinematics investigation of the configuration space uncovers a dynamically stable β-sheet conformation of Cu-aS that serves as a nucleation point for a second β-strand. Based on these findings, we propose an atomistic mechanism of copper-induced misfolding of aS as an initial event in the formation of Lewy bodies and thus in PD pathogenesis
Structural and functional characterization of Pseudomonas aeruginosa CupB chaperones
Pseudomonas aeruginosa, an important human pathogen, is estimated to be responsible for,10% of nosocomial infections worldwide. The pathogenesis of P. aeruginosa starts from its colonization in the damaged tissue or medical devices (e. g. catheters, prothesis and implanted heart valve etc.) facilitated by several extracellular adhesive factors including fimbrial pili. Several clusters containing fimbrial genes have been previously identified on the P. aeruginosa chromosome and named cup [1]. The assembly of the CupB pili is thought to be coordinated by two chaperones, CupB2 and CupB4. However, due to the lack of structural and biochemical data, their chaperone activities remain speculative. In this study, we report the 2.5 A crystal structure of P. aeruginosa CupB2. Based on the structure, we further tested the binding specificity of CupB2 and CupB4 towards CupB1 (the presumed major pilus subunit) and CupB6 (the putative adhesin) using limited trypsin digestion and strep-tactin pull-down assay. The structural and biochemical data suggest that CupB2 and CupB4 might play different, but not redundant, roles in CupB secretion. CupB2 is likely to be the chaperone of CupB1, and CupB4 could be the chaperone of CupB4:CupB5:CupB6, in which the interaction of CupB4 and CupB6 might be mediated via CupB5
Polytetrahedral Clusters
By studying the structures of clusters bound by a model potential that
favours polytetrahedral order, we find a previously unknown series of `magic
numbers' (i.e. sizes of special stability) whose polytetrahedral structures are
characterized by disclination networks that are analogous to hydrocarbons.Comment: 4 pages, 4 figure
EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome - Update 2023.
On behalf of the EORTC Cutaneous Lymphoma Tumours Group (EORTC-CLTG) and following up on earlier versions published in 2006 and 2017 this document provides an updated standard for the treatment of mycosis fungoides and Sézary syndrome (MF/SS). It considers recent relevant publications and treatment options introduced into clinical practice after 2017. Consensus was established among the authors through a series of consecutive consultations in writing and a round of discussion. Treatment options are assigned to each disease stage and, whenever possible and clinically useful, separated into first- and second line options annotated with levels of evidence. Major changes to the previous version include the incorporation of chlormethine, brentuximab vedotin, and mogamulizumab, recommendations on the use of pegylated interferon α (after withdrawal of recombinant unpegylated interferons), and the addition of paragraphs on supportive therapy and on the care of older patients. Still, skin-directed therapies are the most appropriate option for early-stage MF and most patients have a normal life expectancy but may suffer morbidity and impaired quality of life. In advanced disease treatment options have expanded recently. Most patients receive multiple consecutive therapies with treatments often having a relatively short duration of response. For those patients prognosis is still poor and only for a highly selected subset long term remission can be achieved with allogeneic stem cell transplantation. Understanding of the disease, its epidemiology and clinical course, and its most appropriate management are gradually advancing, and there is well-founded hope that this will lead to further improvements in the care of patients with MF/SS
The Large Enriched Germanium Experiment for Neutrinoless Double Beta Decay (LEGEND)
The observation of neutrinoless double-beta decay (0)
would show that lepton number is violated, reveal that neutrinos are Majorana
particles, and provide information on neutrino mass. A discovery-capable
experiment covering the inverted ordering region, with effective Majorana
neutrino masses of 15 - 50 meV, will require a tonne-scale experiment with
excellent energy resolution and extremely low backgrounds, at the level of
0.1 count /(FWHMtyr) in the region of the signal. The
current generation Ge experiments GERDA and the MAJORANA DEMONSTRATOR
utilizing high purity Germanium detectors with an intrinsic energy resolution
of 0.12%, have achieved the lowest backgrounds by over an order of magnitude in
the 0 signal region of all 0
experiments. Building on this success, the LEGEND collaboration has been formed
to pursue a tonne-scale Ge experiment. The collaboration aims to develop
a phased 0 experimental program with discovery potential
at a half-life approaching or at years, using existing resources as
appropriate to expedite physics results.Comment: Proceedings of the MEDEX'17 meeting (Prague, May 29 - June 2, 2017
Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma:a paradigm shift to reduce overtreatment of indolent tumors
Although growing evidence points to highly indolent behavior of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), most patients with EFVPTC are treated as having conventional thyroid cancer
IgA Anti-β2-Glycoprotein I Autoantibodies Are Associated with an Increased Risk of Thromboembolic Events in Patients with Systemic Lupus Erythematosus
The clinical utility of testing for antiphospholipid antibodies (aPL) of IgA isotype remains controversial.To address this issue, we reasoned that if IgA aPL contribute to the clinical manifestations of the antiphospholipid syndrome, then an association with thromboembolic events should manifest in patients whose only aPL is of IgA isotype. We performed a retrospective chart review of 56 patients (31 with systemic lupus erythematosus [SLE] and 25 without SLE) whose only positive aPL was IgA anti-beta2-glycoprotein I (isolated IgA anti-beta2GPI) and compared their clinical features with 56 individually matched control patients without any aPL. Patients with isolated IgA anti-beta2GPI had a significantly increased number of thromboembolic events, as compared to controls. When patients were stratified into those with and without SLE, the association between isolated IgA anti-beta2GPI and thromboembolic events persisted for patients with SLE, but was lost for those without SLE. Titers of IgA anti-beta2GPI were significantly higher in SLE patients who suffered a thromboembolic event. Among patients with isolated IgA anti-beta2GPI, there was an increased prevalence of diseases or morbidities involving organs of mucosal immunity (i.e., gastrointestinal system, pulmonary system, and skin).The presence of isolated IgA anti-beta2GPI is associated with an increased risk of thromboembolic events, especially among patients with SLE. IgA anti-beta2GPI is associated with an increased prevalence of morbidities involving organs of mucosal immunity
Multivector Fluorescence Analysis of the xpt Guanine Riboswitch Aptamer Domain and the Conformational Role of Guanine†
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