949 research outputs found
Unambiguous interpretation of atomically resolved force microscopy images of an insulator
The (111) surface of CaF 2 was imaged with dynamic mode scanning force microscopy and modeled using atomistic simulation. Both experiment and theory showed a clear triangular contrast pattern in images, and theory demonstrated that the contrast pattern is due to the interaction of a positive electrostatic potential tip with fluorine ions in the two topmost surface layers. We find a good agreement of position and relative height of scan line features between theory and experiment and thus establish for the first time an unambiguous identification of sublattices of an insulator imaged by force microscopy
Role of image forces in non-contact scanning force microscope images of ionic surfaces
AbstractWe consider the effect of the image interaction on the force acting between tip and surface in non-contact scanning force microscope experiments. This interaction is relevant when a conducting tip interacts with either a polar bulk sample or with a thick film grown on a conducting substrate. We compare the atomistic contribution due to the interaction between the microscopic tip apex and the sample with the macroscopic van der Waals and image contributions to the force on the tip for several representative NaCl clusters adsorbed on a metal substrate. We show that the microscopic force dominates above the plain (001) terrace sites and is solely responsible for image contrast. However, the image force becomes comparable to the microscopic force above the surface di-vacancy and dominates the interaction above a charged step
Interactive Boundary Element Analysis for Engineering Design
Structural design of mechanical components is an iterative process that involves multiple stress analysis runs; this can be time consuming and expensive. Significant improvements in the eciency of this process can be made by increasing the level of interactivity. One approach is through real-time re-analysis of models with continuously updating geometry. Three primary areas need to be considered to accelerate the re-solution of boundary element problems. These are re-meshing the model, updating the boundary element system of equations and re-solution of the system. Once the initial model has been constructed and solved, the user may apply geometric perturbations to parts of the model. The re-meshing algorithm must accommodate these changes in geometry whilst retaining as much of the existing mesh as possible. This allows the majority of the previous boundary element system of equations to be re-used for the new analysis. For this problem, a GMRES solver has been shown to provide the fastest convergence rate. Further time savings can be made by preconditioning the updated system with the LU decomposition of the original system. Using these techniques, near real-time analysis can be achieved for 3D simulations; for 2D models such real-time performance has already been demonstrated
Short-Term Effects of Gender-Affirming Hormone Therapy on Dysphoria and Quality of Life in Transgender Individuals: A Prospective Controlled Study
Background: Gender affirming hormone therapy (GAHT), whilst considered the standard of care in clinical guidelines for the treatment of many transgender (trans) people is supported by low quality evidence. In this prospective longitudinal controlled study, we aimed to examine the effect of newly commencing GAHT on gender dysphoria and quality of life (QoL) over a 6 month period. Methods: Adult trans (including those with binary and/or non-binary identities) people newly commencing standard full-doses of masculinising (n = 42; 35 = trans masculine, 7 = non-binary) or feminising (n = 35; 33 = trans feminine, 2 = non-binary) GAHT and cisgender participants (n=53 male, n=50 female) were recruited to participate in this longitudinal prospective study. This analysis of gender dysphoria measured by the Gender Preoccupation and Stability Questionnaire and QoL measured by the RAND Short-Form 36 Health survey at baseline, 3 and 6 months after commencement of GAHT was a prespecified secondary outcome. Dysphoria and QoL over time in those starting GAHT compared to cisgender comparison group matched for their presumed sex at birth is reported as the mean difference (95% confidence interval) adjusted for age. Results: In trans people initiating masculinising GAHT, there was a decrease in gender dysphoria with adjusted mean difference -6.80 (-8.68, -4.91), p < 0.001, and a clinically significant improvement in emotional well-being [adjusted mean difference 7.48 (1.32, 13.64), p = 0.018] and social functioning [adjusted mean difference 12.50 (2.84, 22.15), p = 0.011] aspects of QoL over the first 6 months of treatment relative to the cisgender female comparison group. No significant differences were observed in other QoL domains. In trans people initiating feminising GAHT, there was a decrease in gender dysphoria [adjusted mean difference -4.22 (-6.21, -2.24), p < 0.001] but no differences in any aspects of QoL were observed. Conclusions: In the short-term, our findings support the benefit of initiating masculinising or feminising GAHT for gender dysphoria. Masculinising GAHT improves emotional wellbeing and social functioning within 6 months of treatment. Multidisciplinary input with speech pathology and surgery to support trans people seeking feminisation is likely needed. Further longitudinal studies controlled for other confounders (such as the presence of social supports) contributing to QoL are needed.Lucas Foster Skewis, Ingrid Bretherton, Shalem Y. Leemaqz, Jeffrey D. Zajac, and Ada S. Cheun
Response to Tyrosine Kinase Inhibitors in Real-World Patients With Chronic Myeloid Leukemia
Background: Tyrosine kinase inhibitors (TKIs) are the front-line therapy for chronic myeloid leukemia (CML), where phase 3 clinical trials have demonstrated their safety and efficacy. However, trial patients may not be representative of real-world patients (RWPs). Objective: To evaluate RWP clinical factors associated with effectiveness and safety in CML patients treated with TKIs. Methods: Patients with CML treated with at least 30 days of imatinib, dasatinib, nilotinib, or bosutinib between 2014 and 2018 were included. Patients were stratified into categories based on the number of factors that would have precluded enrollment into pivotal TKI phase 3 trials (0, 1, ≥2). End points included complete hematologic response (CHR), early molecular response (EMR), major molecular response (MMR), adverse event (AE)-induced dose decreases, treatment interruptions, and treatment discontinuations. Results: Final analyses included 174 patients. Patients with ≥2 factors had a higher risk of dose decreases (relative risk = 1.54; 95% CI = 1.02-2.34; P = 0.02) and a shorter time to dose decrease (hazard ratio = 2.43; 95% CI = 1.23-4.97; P = 0.006) compared with patients with 0 factors. Significant differences were observed in CHR at 1 month and MMR at 3 months between patients with 0 and ≥2 factors (P = 0.03 and P = 0.04, respectively). Conclusion and Relevance: Approximately 60% of our RWPs would have been excluded from the pivotal phase 3 TKI trials. These data suggest that RWPs require more precise dosing to achieve CML clinical milestones and to mitigate AEs, but findings should be validated prospectively
Master Sculptor at Work: Enteropathogenic Escherichia coli Infection Uniquely Modifies Mitochondrial Proteolysis during Its Control of Human Cell Death
Enteropathogenic Escherichia coli (EPEC) causes severe diarrheal disease
and is present globally. EPEC virulence requires a bacterial type III secretion system
to inject 20 effector proteins into human intestinal cells. Three effectors travel to
mitochondria and modulate apoptosis; however, the mechanisms by which effectors
control apoptosis from within mitochondria are unknown. To identify and quantify
global changes in mitochondrial proteolysis during infection, we applied the mitochondrial terminal proteomics technique mitochondrial stable isotope labeling by
amino acids in cell culture-terminal amine isotopic labeling of substrates (MS-TAILS).
MS-TAILS identified 1,695 amino N-terminal peptides from 1,060 unique proteins
and 390 N-terminal peptides from 215 mitochondrial proteins at a false discovery
rate of 0.01. Infection modified 230 cellular and 40 mitochondrial proteins, generating 27 cleaved mitochondrial neo-N termini, demonstrating altered proteolytic processing within mitochondria. To distinguish proteolytic events specific to EPEC from
those of canonical apoptosis, we compared mitochondrial changes during infection
with those reported from chemically induced apoptosis. During infection, fewer than
half of all mitochondrial cleavages were previously described for canonical apoptosis, and we identified nine mitochondrial proteolytic sites not previously reported,
including several in proteins with an annotated role in apoptosis, although none occurred at canonical Asp-Glu-Val-Asp (DEVD) sites associated with caspase cleavage.
The identification and quantification of novel neo-N termini evidences the involvement of noncaspase human or EPEC protease(s) resulting from mitochondrialtargeting effectors that modulate cell death upon infection. All proteomics data are
available via ProteomeXchange with identifier PXD016994.
IMPORTANCE To our knowledge, this is the first study of the mitochondrial proteome or N-terminome during bacterial infection. Identified cleavage sites that had
not been previously reported in the mitochondrial N-terminome and that were not
generated in canonical apoptosis revealed a pathogen-specific strategy to control
human cell apoptosis. These data inform new mechanisms of virulence factors targeting mitochondria and apoptosis during infection and highlight how enteropathogenic Escherichia coli (EPEC) manipulates human cell death pathways during infection, including candidate substrates of an EPEC protease within mitochondria. This
understanding informs the development of new antivirulence strategies against the
many human pathogens that targe
Measurement of (anti)deuteron and (anti)proton production in DIS at HERA
The first observation of (anti)deuterons in deep inelastic scattering at HERA
has been made with the ZEUS detector at a centre-of-mass energy of 300--318 GeV
using an integrated luminosity of 120 pb-1. The measurement was performed in
the central rapidity region for transverse momentum per unit of mass in the
range 0.3<p_T/M<0.7. The particle rates have been extracted and interpreted in
terms of the coalescence model. The (anti)deuteron production yield is smaller
than the (anti)proton yield by approximately three orders of magnitude,
consistent with the world measurements.Comment: 26 pages, 9 figures, 5 tables, submitted to Nucl. Phys.
D* Production in Deep Inelastic Scattering at HERA
This paper presents measurements of D^{*\pm} production in deep inelastic
scattering from collisions between 27.5 GeV positrons and 820 GeV protons. The
data have been taken with the ZEUS detector at HERA. The decay channel
(+ c.c.) has been used in the study. The
cross section for inclusive D^{*\pm} production with
and is 5.3 \pms 1.0 \pms 0.8 nb in the kinematic region
{ GeV and }. Differential cross
sections as functions of p_T(D^{*\pm}), and are
compared with next-to-leading order QCD calculations based on the photon-gluon
fusion production mechanism. After an extrapolation of the cross section to the
full kinematic region in p_T(D^{*\pm}) and (D^{*\pm}), the charm
contribution to the proton structure function is
determined for Bjorken between 2 10 and 5 10.Comment: 17 pages including 4 figure
Observation of isolated high-E_T photons in deep inelastic scattering
First measurements of cross sections for isolated prompt photon production in
deep inelastic ep scattering have been made using the ZEUS detector at the HERA
electron-proton collider using an integrated luminosity of 121 pb^-1. A signal
for isolated photons in the transverse energy and rapidity ranges 5 < E_T^gamma
< 10 GeV and -0.7 < eta^gamma < 0.9 was observed for virtualities of the
exchanged photon of Q^2 > 35 GeV^2. Cross sections are presented for inclusive
prompt photons and for those accompanied by a single jet in the range E_T^jet
\geq 6 GeV and -1.5 \leq eta^jet < 1.8. Calculations at order alpha^3alpha_s
describe the data reasonably well.Comment: 16 pages, 5 figure
Photoproduction of mesons associated with a leading neutron
The photoproduction of mesons associated with a leading
neutron has been observed with the ZEUS detector in collisions at HERA
using an integrated luminosity of 80 pb. The neutron carries a large
fraction, {}, of the incoming proton beam energy and is detected at
very small production angles, { mrad}, an indication of
peripheral scattering. The meson is centrally produced with
pseudorapidity {
GeV}, which is large compared to the average transverse momentum of the neutron
of 0.22 GeV. The ratio of neutron-tagged to inclusive production is
in the photon-proton
center-of-mass energy range { GeV}. The data suggest that the
presence of a hard scale enhances the fraction of events with a leading neutron
in the final state.Comment: 28 pages, 4 figures, 2 table
- …