501 research outputs found
Toward the First Nonpeptidic Molecular Tong Inhibitor of Wild-Type and Mutated HIV-1 Protease Dimerization
The study of the negative pion production in neutron-proton collisions at beam momenta below 1.8 GeV/c
A detailed investigation of the reaction np -> pp\pi^{-} has been carried out
using the data obtained with the continuous neutron beam produced by charge
exchange scattering of protons off a deuterium target. A partial wave
event-by-event based maximum likelihood analysis was applied to determine
contributions of different partial waves to the pion production process. The
combined analysis of the np -> pp\pi^{-} and pp -> pp\pi^{0} data measured in
the same energy region allows us to determine the contribution of isoscalar
partial waves (I=0) in the momentum range from 1.1 up to 1.8 GeV/c. The decay
of isoscalar partial waves into (^1S_0)_{pp}\pi$ channel provides a good tool
for a determination of the pp S-wave scalar scattering length in the final
state which was found to be a_{pp}=-7.5\pm 0.3 fm.Comment: 6 pages, 6 figure
Observation of strong final-state effects in pi+ production in pp collisions at 400 MeV
Differential cross sections of the reactions and have been measured at MeV by detecting the charged
ejectiles in the angular range . The
deduced total cross sections agree well with those published previously for
neighbouring energies. The invariant mass spectra are observed to be strongly
affected by production and final-state interaction. The data are
well described by Monte Carlo simulations including both these effects. The
ratio of and cross sections also compares
favourably to a recent theoretical prediction which suggests a dominance of
-production in the relative -state.Comment: 17 pages, 5 figure
Single \pi^- production in np collisions for excess energies up to 90 MeV
The quasifree reaction np\to pp\pim was studied in a kinematically complete
experiment by bombarding a liquid hydrogen target with a deuteron beam of
momentum 1.85 GeV/c and analyzing the data along the lines of the spectator
model. In addition to the three charged ejectiles the spectator proton was also
detected in the large-acceptance time-of-flight spectrometer COSY-TOF. It was
identified by its momentum and flight direction thus yielding access to the
Fermi motion of the bound neutron and to the effective neutron 4-momentum
vector which differed from event to event. A range of almost 90
MeV excess energy above threshold was covered. Energy dependent angular
distributions, invariant mass spectra as well as fully covered Dalitz plots
were deduced. Sizeable FSI effects were found as were contributions of
and partial waves. The behavior of the elementary cross section
close to threshold is discussed in view of new cross section
data. In comparison with existing literature data the results provide a
sensitive test of the spectator model.Comment: 21 pages, 9 figures, 4 tables, submitted to EPJ
Processing and adjusting the hydrophilicity of poly(oxymethylene) (co)polymers: nanoparticle preparation and film formation
Handling the insoluble POM: the preparation of organic and aqueous nanoparticle dispersions based on poly(oxymethylene) copolymers and their film formation is described.</p
Controlled assembly of SNAP-PNA-fluorophore systems on DNA templates to produce fluorescence resonance energy transfer
The SNAP protein is a widely used self-labeling tag that can be used for tracking protein localization and trafficking in living systems. A model system providing controlled alignment of SNAP-tag units can provide a new way to study clustering of fusion proteins. In this work, fluorescent SNAP-PNA conjugates were controllably assembled on DNA frameworks forming dimers, trimers, and tetramers. Modification of peptide nucleic acid (PNA) with the O6-benzyl guanine (BG) group allowed the generation of site-selective covalent links between PNA and the SNAP protein. The modified BG-PNAs were labeled with fluorescent Atto dyes and subsequently chemo-selectively conjugated to SNAP protein. Efficient assembly into dimer and oligomer forms was verified via size exclusion chromatography (SEC), electrophoresis (SDS-PAGE), and fluorescence spectroscopy. DNA directed assembly of homo- and hetero-dimers of SNAP-PNA constructs induced homo- and hetero-FRET, respectively. Longer DNA scaffolds controllably aligned similar fluorescent SNAP-PNA constructs into higher oligomers exhibiting homo-FRET. The combined SEC and homo-FRET studies indicated the 1:1 and saturated assemblies of SNAP-PNA-fluorophore:DNA formed preferentially in this system. This suggested a kinetic/stoichiometric model of assembly rather than binomially distributed products. These BG-PNA-fluorophore building blocks allow facile introduction of fluorophores and/or assembly directing moieties onto any protein containing SNAP. Template directed assembly of PNA modified SNAP proteins may be used to investigate clustering behavior both with and without fluorescent labels which may find use in the study of assembly processes in cells
Multifunctional clickable and protein-repellent magnetic silica nanoparticles
Multiple functionalization of magnetic silica particles allows simultaneously their bio-orthogonal modification and less unspecific protein adsorption to occur.</p
Pathogenic p62/SQSTM1 mutations impair energy metabolism through limitation of mitochondrial substrates
Abnormal mitochondrial function has been found in patients with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Mutations in the p62 gene (also known as SQSTM1) which encodes the p62 protein have been reported in both disorders supporting the idea of an ALS/FTD continuum. In this work the role of p62 in energy metabolism was studied in fibroblasts from FTD patients carrying two independent pathogenic mutations in the p62 gene, and in a p62-knock-down (p62 KD) human dopaminergic neuroblastoma cell line (SH-SY5Y). We found that p62 deficiency is associated with inhibited complex I mitochondrial respiration due to lack of NADH for the electron transport chain. This deficiency was also associated with increased levels of NADPH reflecting a higher activation of pentose phosphate pathway as this is accompanied with higher cytosolic reduced glutathione (GSH) levels. Complex I inhibition resulted in lower mitochondrial membrane potential and higher cytosolic ROS production. Pharmacological activation of transcription factor Nrf2 increased mitochondrial NADH levels and restored mitochondrial membrane potential in p62-deficient cells. Our results suggest that the phenotype is caused by a loss-of-function effect, because similar alterations were found both in the mutant fibroblasts and the p62 KD model. These findings highlight the implication of energy metabolism in pathophysiological events associated with p62 deficiency
Modeling interstellar amorphous solid water grains by tight-binding based methods: comparison between GFN-XTB and CCSD(T) results for water clusters
One believed path to Interstellar Complexes Organic Molecules (iCOMs)
formation inside the Interstellar Medium (ISM) is through chemical
recombination at the surface of amorphous solid water (ASW) mantle covering the
silicate-based core of the interstellar grains. The study of these iCOMs
formation and their binding energy to the ASW, using computational chemistry,
depends strongly on the ASW models used, as different models may exhibit sites
with different adsorbing features. ASW extended models are rare in the
literature because large sizes require very large computational resources when
quantum mechanical methods based on DFT are used. To circumvent this problem,
we propose to use the newly developed GFN-xTB Semi-empirical Quantum Mechanical
(SQM) methods from the Grimme's group. These methods are, at least, two orders
of magnitude faster than conventional DFT, only require modest central memory,
and in this paper we aim to benchmark their accuracy against rigorous and
resource hungry quantum mechanical methods. We focused on 38 water structures
studied by MP2 and CCSD(T) approaches comparing energetic and structures with
three levels of GFN-xTB parametrization (GFN0, GFN1, GFN2) methods. The
extremely good results obtained at the very cheap GFN-xTB level for both water
cluster structures and energetic paved the way towards the modeling of very
large AWS models of astrochemical interest.Comment: 9 pages, 4 figures, Submitted to LNCS (Springer) ICCSA202
Impact of discontinuation of antithrombotic therapy after surgery for chronic subdural hematoma [Impact de l'interruption des antithrombotiques après traitement chirurgicale de l'hématome sous dural chronique]
Introduction: The management of antithrombotic therapy (AT) after surgery for chronic subdural hematoma (cSDH) requires taking account of the balance of risk between hemorrhage recurrence (HR) and the prophylactic thromboembolic effect (TE). The goal of the present study was to evaluate the prevalence of vascular events (VE: TE and/or HR) in the first 3 postoperative months after cSDH evacuation in patients previously treated by AT. The impact of AT resumption was also evaluated. Patients and methods: This observational prospective multicenter collaborative study (14 French neurosurgery centers) included patients with cSDH treated by AT and operated on between May 2017 and March 2018. Data collection used an e-CRF, and was principally based on an admission questionnaire and outcome/progression at 3 months. Results: In this cohort of 211 patients, VE occurred in 58 patients (27.5%): HR in 47 (22.3%), TE in 17 (8%), with mixed event in 6 cases (2%). Median overall time to onset of complications 26 days ± 31.5, and specifically 43.5 days ± 29.25 for HR. Non-resumption of AT significantly increased the relative risk of VE [OR: 4.14; 95% CI: 2.08 - 8.56; P < 0.001] and especially of TE [OR: 7.5; 95% CI: 1.2 - 42; P < 0.001]. The relative risk of HR was significantly increased when AT was resumed at less than 30 days (P = 0.015). Conclusion: The occurrence of VE in patients operated on for cSDH and previously treated by AT was statistically significant (27.5%). HR was the most common event (22.3%), whereas TE accounted for only the 8%, although with shorter time to onset. In order to prevent TE risk, AT should be restarted after 30 days, as HR risk is greatly decreased beyond this time
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