93 research outputs found
Shot Noise in Mesoscopic Diffusive Andreev Wires
We study shot noise in mesoscopic diffusive wires between a normal and a
superconducting terminal. We particularly focus on the regime, in which the
proximity-induced reentrance effect is important. We will examine the
difference between a simple Boltzmann-Langevin description, which neglects
induced correlations beyond the simple conductivity correction, and a full
quantum calculation. In the latter approach, it turns out that two Andreev
pairs propagating coherently into the normal metal are anti-correlated for
E<E_c, where E_c=D/L^2 is the Thouless energy. In a fork geometry the
flux-sensitive suppression of the effective charge was confirmed
experimentally.Comment: 12 pages, proceedings of the NATO ARW MQO, Bled, Sloveni
Reflectionless tunneling in ballistic normal-metal--superconductor junctions
We investigate the phenomenon of reflectionless tunneling in ballistic
normal-metal--superconductor (NS) structures, using a semiclassical formalism.
It is shown that applied magnetic field and superconducting phase difference
both impair the constructive interference leading to this effect, but in a
qualitatively different way. This is manifested both in the conductance and in
the shot noise properties of the system considered. Unlike diffusive systems,
the features of the conductance are sharp, and enable fine spatial control of
the current, as well as single channel manipulations. We discuss the
possibility of conducting experiments in ballistic semiconductor-superconductor
structures with smooth interfaces and some of the phenomena, specific to such
structures, that could be measured. A general criterion for the barrier at NS
interfaces, though large, to be effectively transparent to pair current is
obtained.Comment: published versio
Safety and Short-term Outcomes of High-Dose Erythropoietin in Preterm Infants With Intraventricular Hemorrhage: The EpoRepair Randomized Clinical Trial
IMPORTANCE
Intraventricular hemorrhage (IVH) is a major cause of neonatal morbidity and mortality in preterm infants without a specific medical treatment to date.
OBJECTIVE
To assess the safety and short-term outcomes of high-dose erythropoietin in preterm infants with IVH.
DESIGN, SETTING, AND PARTICIPANTS
Between April 1, 2014, and August 3, 2018, a randomized double-blind clinical trial enrolled 121 preterm infants (gestational age <32 weeks or birth weight <1500 g) aged 8 or less days with moderate to severe IVH identified by cerebral ultrasonography from 8 Swiss and Austrian tertiary neonatal units. Statistical analyses were performed between October 1, 2019, and September 12, 2022.
INTERVENTIONS
Infants received intravenous high-dose erythropoietin (2000 units/kg body weight) or placebo at 4 time points between weeks 1 and 4 of life.
MAIN OUTCOMES AND MEASURES
Secondary outcomes included (1) mortality and morbidity rates and (2) brain magnetic resonance imaging findings at term-equivalent age (TEA). The primary outcome was the composite intelligence quotient at 5 years of age (not available before 2023).
RESULTS
Sixty infants (48% male [nâ=â29]) were randomly assigned to receive erythropoietin, and 61 infants (61% male [nâ=â37]) were randomly assigned to receive placebo. The median birth weight was 832 g (IQR, 687-990 g) in the erythropoietin group and 870 g (IQR, 680-1110 g) in the placebo group. Median gestation was 26.1 weeks (IQR, 24.8-27.3 weeks) in the erythropoietin group and 27.0 weeks (24.9-28.1 weeks) in the placebo group. The 2 groups had similar baseline characteristics and morbidities. Up to TEA, 10 newborns died (16.7%) in the erythropoietin group, and 5 newborns (8.2%) died in the placebo group (adjusted odds ratio, 2.24 [95% CI, 0.74-7.66]; Pâ=â.15). Infants receiving erythropoietin had higher mean hematocrit levels. Conventional magnetic resonance imaging at TEA for 100 infants showed no significant differences in global or regional brain injury scores.
CONCLUSIONS AND RELEVANCE
This preliminary report of a randomized clinical trial found no evidence that high-dose erythropoietin in preterm infants with IVH affects brain injury scores on conventional magnetic resonance imaging at TEA. Higher mortality in the erythropoietin group was not significant but should be reassessed based on future results from similar trials.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02076373
Metropolis simulations of Met-Enkephalin with solvent-accessible area parameterizations
We investigate the solvent-accessible area method by means of Metropolis
simulations of the brain peptide Met-Enkephalin at 300. For the energy
function ECEPP/2 nine atomic solvation parameter (ASP) sets are studied. The
simulations are compared with one another, with simulations with a distance
dependent electrostatic permittivity , and with vacuum
simulations (). Parallel tempering and the biased Metropolis
techniques RM are employed and their performance is evaluated. The measured
observables include energy and dihedral probability densities (pds), integrated
autocorrelation times, and acceptance rates. Two of the ASP sets turn out to be
unsuitable for these simulations. For all other systems selected configurations
are minimized in search of the global energy minima, which are found for the
vacuum and the system, but for none of the ASP models. Other
observables show a remarkable dependence on the ASPs. In particular, we find
three ASP sets for which the autocorrelations at 300K are considerably
smaller than for vacuum simulations.Comment: 10 pages and 8 figure
Energy dependent counting statistics in diffusive superconducting tunnel junctions
We present an investigation of the energy dependence of the full charge
counting statistics in diffusive
normal-insulating-normal-insulating-superconducting junctions. It is found that
the current in general is transported via a correlated transfer of pairs of
electrons. Only in the case of strongly asymmetric tunnel barriers or energies
much larger than the Thouless energy is the pair transfer uncorrelated. The
second cumulant, the noise, is found to depend strongly on the applied voltage
and temperature. For a junction resistance dominated by the tunnel barrier to
the normal reservoir, the differential shot noise shows a double peak feature
at voltages of the order of the Thouless energy, a signature of an ensemble
averaged electron-hole resonance.Comment: 8 pages, 5 figure
Quasiclassical theory of superconductivity: a multiple interface geometry
The purpose of the paper is to suggest a new method which allows one to study
multiple coherent reflection/transmissions by partially transparent interfaces
(e.g. in multi-layer mesoscopic structures or grain boundaries in high-Tc's) in
the framework of the quasiclassical theory of superconductivity. It is argued
that typically the trajectory of the particle is a simply connected tree (no
loops) with knots, i.e. the points where interface scattering events occur and
ballistic pieces of the trajectory are mixed. A linear boundary condition for
the 2-component trajectory "wave function" which factorizes matrix (retarded)
Green's function, is formulated for an arbitrary interface, specular or
diffusive. To show the usage of the method, the current response to the vector
potential (the total superfluid density rho_s) of a SS' sandwich with the
different signs of the order parameter in S and S', is calculated. In this
model, a few percent of reflection by the SS' interface transforms the
paramagnetic response (rho_s < 0) created by the zero-energy Andreev bound
states near an ideal interface (see Fauchere et al. PRL, 82, 3336 (1999),
cond-mat/9901112), into the usual diamagnetic one (rho_s >0).Comment: Extended abstract submitted to "Electron Transport in Mesoscopic
Systems", Satellite conference to LT22, Goteborg, 12-15 August, 1999. 2 pages
Minor changes + the text height problem fixe
SARS-CoV-2 mRNA vaccinations fail to elicit humoral and cellular immune responses in patients with multiple sclerosis receiving fingolimod
BACKGROUND: SARS-CoV-2 mRNA vaccination of healthy individuals is highly immunogenic and protective against severe COVID-19. However, there are limited data on how disease-modifying therapies (DMTs) alter SARS-CoV-2 mRNA vaccine immunogenicity in patients with autoimmune diseases. METHODS: As part of a prospective cohort study, we investigated the induction, stability and boosting of vaccine-specific antibodies, B cells and T cells in patients with multiple sclerosis (MS) on different DMTs after homologous primary, secondary and booster SARS-CoV-2 mRNA vaccinations. Of 126 patients with MS analysed, 105 received either anti-CD20-based B cell depletion (aCD20-BCD), fingolimod, interferon-ÎČ, dimethyl fumarate, glatiramer acetate, teriflunomide or natalizumab, and 21 were untreated MS patients for comparison. RESULTS: In contrast to all other MS patients, and even after booster, most aCD20-BCD- and fingolimod-treated patients showed no to markedly reduced anti-S1 IgG, serum neutralising activity and a lack of receptor binding domain-specific and S2-specific B cells. Patients receiving fingolimod additionally lacked spike-reactive CD4(+) T cell responses. The duration of fingolimod treatment, rather than peripheral blood B and T cell counts prior to vaccination, determined whether a humoral immune response was elicited. CONCLUSIONS: The lack of immunogenicity under long-term fingolimod treatment demonstrates that functional immune responses require not only immune cells themselves, but also access of these cells to the site of inoculation and their unimpeded movement. The absence of humoral and T cell responses suggests that fingolimod-treated patients with MS are at risk for severe SARS-CoV-2 infections despite booster vaccinations, which is highly relevant for clinical decision-making and adapted protective measures, particularly considering additional recently approved sphingosine-1-phosphate receptor antagonists for MS treatment
Rapid Probing of Biological Surfaces with a Sparse-Matrix Peptide Library
Finding unique peptides to target specific biological surfaces is crucial to basic research and technology development, though methods based on biological arrays or large libraries limit the speed and ease with which these necessary compounds can be found. We reasoned that because biological surfaces, such as cell surfaces, mineralized tissues, and various extracellular matrices have unique molecular compositions, they present unique physicochemical signatures to the surrounding medium which could be probed by peptides with appropriately corresponding physicochemical properties. To test this hypothesis, a naĂŻve pilot library of 36 peptides, varying in their hydrophobicity and charge, was arranged in a two-dimensional matrix and screened against various biological surfaces. While the number of peptides in the matrix library was very small, we obtained âhitsâ against all biological surfaces probed. Sequence refinement of the âhitsâ led to peptides with markedly higher specificity and binding activity against screened biological surfaces. Genetic studies revealed that peptide binding to bacteria was mediated, at least in some cases, by specific cell-surface molecules, while examination of human tooth sections showed that this method can be used to derive peptides with highly specific binding to human tissue
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SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the rapidly unfolding coronavirus disease 2019 (COVID-19) pandemic1,2. Clinical manifestations of COVID-19 vary, ranging from asymptomatic infection to respiratory failure. The mechanisms that determine such variable outcomes remain unresolved. Here we investigated CD4+ T cells that are reactive against the spike glycoprotein of SARS-CoV-2 in the peripheral blood of patients with COVID-19 and SARS-CoV-2-unexposed healthy donors. We detected spike-reactive CD4+ T cells not only in 83% of patients with COVID-19 but also in 35% of healthy donors. Spike-reactive CD4+ T cells in healthy donors were primarily active against C-terminal epitopes in the spike protein, which show a higher homology to spike glycoproteins of human endemic coronaviruses, compared with N-terminal epitopes. Spike-protein-reactive T cell lines generated from SARS-CoV-2-naive healthy donors responded similarly to the C-terminal region of the spike proteins of the human endemic coronaviruses 229E and OC43, as well as that of SARS-CoV-2. This results indicate that spike-protein cross-reactive T cells are present, which were probably generated during previous encounters with endemic coronaviruses. The effect of pre-existing SARS-CoV-2 cross-reactive T cells on clinical outcomes remains to be determined in larger cohorts. However, the presence of spike-protein cross-reactive T cells in a considerable fraction of the general population may affect the dynamics of the current pandemic, and has important implications for the design and analysis of upcoming trials investigating COVID-19 vaccines
Analysis of Peptide-Protein Binding Using Amino Acid Descriptors: Prediction and Experimental Verification for Human Histocompatibility Complex HLA-A*0201
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