Debris development in fretting contacts: debris particles and debris beds

In this study, the formation and destruction of compacted beds of oxidized debris particles are investigated. Fretting tests of steel specimens were conducted, employing a cylinder-on-flat geometry with displacement amplitude being varied. The debris was examined, both in the form of the debris beds and in the form of loose debris; together, these were characterized to better understand the mechanisms of debris bed formation and development throughout the fretting process. XRD was employed to determine the phase makeup of the debris, with SEM imaging and particle size analysis employed to understand the evolution of the debris from nanoparticles into agglomerates and then into sintered bed structures

Overcoming bortezomib resistance in human B cells by anti-CD20/rituximab-mediated complement-dependent cytotoxicity and epoxyketone-based irreversible proteasome inhibitors

UNLABELLED: BACKGROUND: In clinical and experimental settings, antibody-based anti-CD20/rituximab and small molecule proteasome inhibitor (PI) bortezomib (BTZ) treatment proved effective modalities for B cell depletion in lymphoproliferative disorders as well as autoimmune diseases. However, the chronic nature of these diseases requires either prolonged or re-treatment, often with acquired resistance as a consequence. METHODS: Here we studied the molecular basis of acquired resistance to BTZ in JY human B lymphoblastic cells following prolonged exposure to this drug and examined possibilities to overcome resistance by next generation PIs and anti-CD20/rituximab-mediated complement-dependent cytotoxicity (CDC). RESULTS: Characterization of BTZ-resistant JY/BTZ cells compared to parental JY/WT cells revealed the following features: (a) 10-12 fold resistance to BTZ associated with the acquisition of a mutation in the PSMB5 gene (encoding the constitutive $β$5 proteasome subunit) introducing an amino acid substitution (Met45Ile) in the BTZ-binding pocket, (b) a significant 2-4 fold increase in the mRNA and protein levels of the constitutive $β$5 proteasome subunit along with unaltered immunoproteasome expression, (c) full sensitivity to the irreversible epoxyketone-based PIs carfilzomib and (to a lesser extent) the immunoproteasome inhibitor ONX 0914. Finally, in association with impaired ubiquitination and attenuated breakdown of CD20, JY/BTZ cells harbored a net 3-fold increase in CD20 cell surface expression, which was functionally implicated in conferring a significantly increased anti-CD20/rituximab-mediated CDC. CONCLUSIONS: These results demonstrate that acquired resistance to BTZ in B cells can be overcome by next generation PIs and by anti-CD20/rituximab-induced CDC, thereby paving the way for salvage therapy in BTZ-resistant disease

Star and Planet Formation with ALMA: an Overview

Submillimeter observations with ALMA will be the essential next step in our understanding of how stars and planets form. Key projects range from detailed imaging of the collapse of pre-stellar cores and measuring the accretion rate of matter onto deeply embedded protostars, to unravelling the chemistry and dynamics of high-mass star-forming clusters and high-spatial resolution studies of protoplanetary disks down to the 1 AU scale.Comment: Invited review, 8 pages, 5 figures; to appear in the proceedings of "Science with ALMA: a New Era for Astrophysics". Astrophysics & Space Science, in pres

Research Article (New England Journal of Medicine) Severe anemia in Malawian children

Background: Severe anemia is a major cause of sickness and death in African children, yet the causes of anemia in this population have been inadequately studied.Methods: We conducted a case–control study of 381 preschool children with severe anemia (hemoglobin concentration, <5.0 g per deciliter) and 757 preschool children without severe anemia in urban and rural settings in Malawi. Causal factors  previously associated with severe anemia were studied. The data were examined by multivariate analysis and structural equation modeling.Results: Bacteremia (adjusted odds ratio, 5.3; 95% confidence interval [CI], 2.6 to 10.9), malaria (adjusted odds ratio, 2.3; 95% CI, 1.6 to 3.3), hookworm (adjusted odds ratio, 4.8; 95% CI, 2.0 to 11.8), human immunodeficiency virus infection (adjusted odds ratio, 2.0; 95% CI, 1.0 to 3.8), the G6PD−202/−376 genetic disorder (adjusted odds ratio, 2.4; 95% CI, 1.3 to 4.4), vitamin A deficiency (adjusted odds ratio, 2.8; 95% CI, 1.3 to 5.8), and vitamin B12 deficiency (adjusted odds ratio, 2.2; 95% CI, 1.4 to 3.6) were associated with severe anemia. Folate deficiency, sickle cell disease, and laboratory signs of an abnormal  inflammatory response were uncommon. Iron deficiency was not prevalent in case patients (adjusted odds ratio, 0.37; 95% CI, 0.22 to 0.60) and was negatively associated with bacteremia. Malaria was associated with severe anemia in the urban site (with seasonal transmission) but not in the rural site (where malaria was holoendemic). Seventy-six percent of hookworm infections were found in children under 2 years of age.Conclusions: There are multiple causes of severe anemia in Malawian preschool children, but folate and iron deficiencies are not prominent among them. Even in the presence of malaria parasites, additional or alternative causes of severe anemia should be considered

Automated Detection of EUV Polar Coronal Holes During Solar Cycle 23

A new method for automated detection of polar coronal holes is presented. This method, called perimeter tracing, uses a series of 171, 195, and 304 \AA\ full disk images from the Extreme ultraviolet Imaging Telescope (EIT) on SOHO over solar cycle 23 to measure the perimeter of polar coronal holes as they appear on the limbs. Perimeter tracing minimizes line-of-sight obscurations caused by the emitting plasma of the various wavelengths by taking measurements at the solar limb. Perimeter tracing also allows for the polar rotation period to emerge organically from the data as 33 days. We have called this the Harvey rotation rate and count Harvey rotations starting 4 January 1900. From the measured perimeter, we are then able to fit a curve to the data and derive an area within the line of best fit. We observe the area of the northern polar hole area in 1996, at the beginning of solar cycle 23, to be about 4.2% of the total solar surface area and about 3.6% in 2007. The area of the southern polar hole is observed to be about 4.0% in 1996 and about 3.4% in 2007. Thus, both the north and south polar hole areas are no more than 15% smaller now than they were at the beginning of cycle 23. This compares to the polar magnetic field measured to be about 40% less now than it was a cycle ago.Comment: 18 pagers, 7 figures, accepted to Solar Physic

Peeling-ballooning stability of tokamak plasmas with applied 3D magnetic fields

The poloidal harmonics of the toroidal normal modes of an unstable axisymmetric tokamak plasma are employed as basis functions for the minimisation of the 3D energy functional. This approach presents a natural extension of the perturbative method considered in Anastopoulos Tzanis et al (2019 Nucl. Fusion 59 126028). This variational formulation is applied to the stability of tokamak plasmas subject to external non-axisymmetric magnetic fields. A comparison of the variational and perturbative methods shows that for D-shaped, high β N plasmas, the coupling of normal modes becomes strong at experimentally relevant applied 3D fields, leading to violation of the assumptions that justify a perturbative analysis. The variational analysis employed here addresses strong coupling, minimising energy with respect to both toroidal and poloidal Fourier coefficients. In general, it is observed that ballooning unstable modes are further destabilised by the applied 3D fields and field-aligned localisation of the perturbation takes place, as local ballooning theory suggests. For D-shaped high β N plasmas, relevant to experimental cases, it is observed that the existence of intermediate n unstable peeling-ballooning modes, where a maximum in the growth rate spectrum typically occurs, leads to a destabilising synergistic coupling that strongly degrades the stability of the 3D system

Pulsar-wind nebulae and magnetar outflows: observations at radio, X-ray, and gamma-ray wavelengths

We review observations of several classes of neutron-star-powered outflows: pulsar-wind nebulae (PWNe) inside shell supernova remnants (SNRs), PWNe interacting directly with interstellar medium (ISM), and magnetar-powered outflows. We describe radio, X-ray, and gamma-ray observations of PWNe, focusing first on integrated spectral-energy distributions (SEDs) and global spectral properties. High-resolution X-ray imaging of PWNe shows a bewildering array of morphologies, with jets, trails, and other structures. Several of the 23 so far identified magnetars show evidence for continuous or sporadic emission of material, sometimes associated with giant flares, and a few possible "magnetar-wind nebulae" have been recently identified.Comment: 61 pages, 44 figures (reduced in quality for size reasons). Published in Space Science Reviews, "Jets and Winds in Pulsar Wind Nebulae, Gamma-ray Bursts and Blazars: Physics of Extreme Energy Release

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results