1,726 research outputs found
Gate-Controlled Ionization and Screening of Cobalt Adatoms on a Graphene Surface
We describe scanning tunneling spectroscopy (STS) measurements performed on
individual cobalt (Co) atoms deposited onto backgated graphene devices. We find
that Co adatoms on graphene can be ionized by either the application of a
global backgate voltage or by the application of a local electric field from a
scanning tunneling microscope (STM) tip. Large screening clouds are observed to
form around Co adatoms ionized in this way, and we observe that some intrinsic
graphene defects display a similar behavior. Our results provide new insight
into charged impurity scattering in graphene, as well as the possibility of
using graphene devices as chemical sensors.Comment: 19 pages, 4 figure
An evaluation of seasonal variations in footwear worn by adults with inflammatory arthritis: a cross-sectional observational study using a web-based survey
Background: Foot problems are common in adults with inflammatory arthritis and therapeutic footwear can be
effective in managing arthritic foot problems. Accessing appropriate footwear has been identified as a major barrier,
resulting in poor adherence to treatment plans involving footwear. Indeed, previous New Zealand based studies
found that many people with rheumatoid arthritis and gout wore inappropriate footwear. However, these studies
were conducted in a single teaching hospital during the New Zealand summer therefore the findings may not be
representative of footwear styles worn elsewhere in New Zealand, or reflect the potential influence of seasonal
climate changes. The aim of the study was to evaluate seasonal variations in footwear habits of people with
inflammatory arthritic conditions in New Zealand.
Methods: A cross-sectional study design using a web-based survey. The survey questions were designed to elicit
demographic and clinical information, features of importance when choosing footwear and seasonal footwear
habits, including questions related to the provision of therapeutic footwear/orthoses and footwear experiences.
Results: One-hundred and ninety-seven participants responded who were predominantly women of European
descent, aged between 46–65 years old, from the North Island of New Zealand. The majority of participants
identified with having either rheumatoid arthritis (35%) and/or osteoarthritis (57%) and 68% reported established
disease (>5 years duration). 18% of participants had been issued with therapeutic footwear. Walking and athletic
shoes were the most frequently reported footwear type worn regardless of the time of year. In the summer,
42% reported wearing sandals most often. Comfort, fit and support were reported most frequently as the footwear
features of greatest importance. Many participants reported difficulties with footwear (63%), getting hot feet in the
summer (63%) and the need for a sandal which could accommodate a supportive insole (73%).
Conclusions: Athletic and walking shoes were the most popular style of footwear reported regardless of seasonal
variation. During the summer season people with inflammatory arthritis may wear sandals more frequently in
order to accommodate disease-related foot deformity. Healthcare professionals and researchers should consider
seasonal variation when recommending appropriate footwear, or conducting footwear studies in people with
inflammatory arthritis, to reduce non-adherence to prescribed footwear
Direct photon production with effective field theory
The production of hard photons in hadronic collisions is studied using
Soft-Collinear Effective Theory (SCET). This is the first application of SCET
to a physical, observable cross section involving energetic partons in more
than two directions. A factorization formula is derived which involves a
non-trivial interplay of the angular dependence in the hard and soft functions,
both quark and gluon jet functions, and multiple partonic channels. The
relevant hard, jet and soft functions are computed to one loop and their
anomalous dimensions are determined to three loops. The final resummed
inclusive direct photon distribution is valid to next-to-next-to-leading
logarithmic order (NNLL), one order beyond previous work. The result is
improved by including non-logarithmic terms and photon isolation cuts through
matching, and compared to Tevatron data and to fixed order results at the
Tevatron and the LHC. The resummed cross section has a significantly smaller
theoretical uncertainty than the next-to-leading fixed-order result,
particularly at high transverse momentum.Comment: 42 pages, 9 figures; v2: references added, minor changes; v3: typos;
v4: typos, corrections in (16), (47), (72
Theory of Multidimensional Solitons
We review a number of topics germane to higher-dimensional solitons in
Bose-Einstein condensates. For dark solitons, we discuss dark band and planar
solitons; ring dark solitons and spherical shell solitons; solitary waves in
restricted geometries; vortex rings and rarefaction pulses; and multi-component
Bose-Einstein condensates. For bright solitons, we discuss instability,
stability, and metastability; bright soliton engineering, including pulsed atom
lasers; solitons in a thermal bath; soliton-soliton interactions; and bright
ring solitons and quantum vortices. A thorough reference list is included.Comment: review paper, to appear as Chapter 5a in "Emergent Nonlinear
Phenomena in Bose-Einstein Condensates: Theory and Experiment," edited by P.
G. Kevrekidis, D. J. Frantzeskakis, and R. Carretero-Gonzalez
(Springer-Verlag
Impact of efalizumab on patient-reported outcomes in high-need psoriasis patients: results of the international, randomized, placebo-controlled Phase III Clinical Experience Acquired with Raptiva (CLEAR) trial [NCT00256139]
BACKGROUND: Chronic psoriasis can negatively affect patients' lives. Assessing the impact of treatment on different aspects of a patient's health-related quality of life (HRQOL) is therefore important and relevant in trials of anti-psoriasis agents. The recombinant humanized IgG(1 )monoclonal antibody efalizumab targets multiple T-cell-dependent steps in the immunopathogenesis of psoriasis. Efalizumab has demonstrated safety and efficacy in several clinical trials, and improves patients' quality of life. Objective: To evaluate the impact of efalizumab on HRQOL and other patient-reported outcomes in patients with moderate to severe plaque psoriasis, including a large cohort of High-Need patients for whom at least 2 other systemic therapies were unsuitable because of lack of efficacy, intolerance, or contraindication. METHODS: A total of 793 patients were randomized in a 2:1 ratio to receive efalizumab 1 mg/kg/wk (n = 529) or placebo (n = 264) for 12 weeks. The study population included 526 High-Need patients (342 efalizumab, 184 placebo). The treatment was evaluated by patients using the HRQOL assessment tools Short Form-36 (SF-36) and Dermatology Life Quality Index (DLQI). Other patient-reported assessments included the Psoriasis Symptom Assessment (PSA), a visual analog scale (VAS) for itching, and the Patient's Global Psoriasis Assessment (PGPA). RESULTS: Efalizumab was associated with improvements at Week 12 from baseline in patient-reported outcomes, both in the total study population and in the High-Need cohort. Among all efalizumab-treated patients, the DLQI improved by 5.7 points from baseline to Week 12, relative to an improvement of 2.3 points for placebo patients (P < .001). Corresponding improvements in DLQI in the High-Need cohort were 5.4 points for efalizumab compared to 2.3 for placebo (P < .001). Improvements from baseline on the SF-36, PSA, PGPA, and itching VAS at Week 12 were also significantly greater in efalizumab-treated patients than for placebo. CONCLUSION: A 12-week course of efalizumab improved HRQOL and other patient-reported outcomes in patients with moderate to severe plaque psoriasis. The benefits of efalizumab therapy in High-Need patients were similar to those observed in the total study population, indicating that the beneficial impact of efalizumab on QOL is consistent regardless of disease severity, prior therapy, or contraindications to previous therapies
Where the Wild Things Are: Pathogenesis of SIV Infection in African Nonhuman Primate Hosts
African nonhuman primates that are natural hosts of simian immunodeficiency virus (SIV) are generally spared from disease progression. Pathogenic and nonpathogenic SIV infections share some major features: high viral replication, massive acute depletion of mucosal CD4+ T cells, and partial control of the virus by both adaptive and innate immune responses. A key distinction of natural SIV infections is rapid and active control of immune activation and apoptosis of T cells that contributes to the integrity of mucosal barrier and lack of microbial translocation. This allows partial recovery of CD4+ T cells and preservation of the function of other immune cell subsets. A better understanding of the mechanisms underlying the lack of disease in natural hosts for SIV infection will likely provide important clues as to the therapy of HIV-1 infection
Endocytosis of the Anthrax Toxin Is Mediated by Clathrin, Actin and Unconventional Adaptors
The anthrax toxin is a tripartite toxin, where the two enzymatic subunits require the third subunit, the protective antigen (PA), to interact with cells and be escorted to their cytoplasmic targets. PA binds to cells via one of two receptors, TEM8 and CMG2. Interestingly, the toxin times and triggers its own endocytosis, in particular through the heptamerization of PA. Here we show that PA triggers the ubiquitination of its receptors in a β-arrestin-dependent manner and that this step is required for clathrin-mediated endocytosis. In addition, we find that endocytosis is dependent on the heterotetrameric adaptor AP-1 but not the more conventional AP-2. Finally, we show that endocytosis of PA is strongly dependent on actin. Unexpectedly, actin was also found to be essential for efficient heptamerization of PA, but only when bound to one of its 2 receptors, TEM8, due to the active organization of TEM8 into actin-dependent domains. Endocytic pathways are highly modular systems. Here we identify some of the key players that allow efficient heptamerization of PA and subsequent ubiquitin-dependent, clathrin-mediated endocytosis of the anthrax toxin
Bordetella Adenylate Cyclase Toxin Mobilizes Its β2 Integrin Receptor into Lipid Rafts to Accomplish Translocation across Target Cell Membrane in Two Steps
Bordetella adenylate cyclase toxin (CyaA) binds the αMβ2 integrin (CD11b/CD18, Mac-1, or CR3) of myeloid phagocytes and delivers into their cytosol an adenylate cyclase (AC) enzyme that converts ATP into the key signaling molecule cAMP. We show that penetration of the AC domain across cell membrane proceeds in two steps. It starts by membrane insertion of a toxin ‘translocation intermediate’, which can be ‘locked’ in the membrane by the 3D1 antibody blocking AC domain translocation. Insertion of the ‘intermediate’ permeabilizes cells for influx of extracellular calcium ions and thus activates calpain-mediated cleavage of the talin tether. Recruitment of the integrin-CyaA complex into lipid rafts follows and the cholesterol-rich lipid environment promotes translocation of the AC domain across cell membrane. AC translocation into cells was inhibited upon raft disruption by cholesterol depletion, or when CyaA mobilization into rafts was blocked by inhibition of talin processing. Furthermore, CyaA mutants unable to mobilize calcium into cells failed to relocate into lipid rafts, and failed to translocate the AC domain across cell membrane, unless rescued by Ca2+ influx promoted in trans by ionomycin or another CyaA protein. Hence, by mobilizing calcium ions into phagocytes, the ‘translocation intermediate’ promotes toxin piggybacking on integrin into lipid rafts and enables AC enzyme delivery into host cytosol
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