157 research outputs found
Frenkel and charge transfer excitons in C60
We have studied the low energy electronic excitations of C60 using momentum
dependent electron energy-loss spectroscopy in transmission. The momentum
dependent intensity of the gap excitation allows the first direct experimental
determination of the energy of the 1Hg excitation and thus also of the total
width of the multiplet resulting from the gap transition. In addition, we could
elucidate the nature of the following excitations - as either Frenkel or charge
transfer excitons.Comment: RevTEX, 3 Figures, to appear in Phys. Rev.
Structure and magnetism of atomically thin Fe layers on flat and vicinal Pt surfaces
Ultrathin Fe films on Pt substrates have been investigated under ultrahigh vacuum conditions by scanning tunneling microscopy, low energy electron diffraction, magneto-optical Kerr effect, x-ray magnetic circular dichroism measurements, and Kerr microscopy. We present a comparison between Fe films on flat Pt(111) and stepped Pt(997), with particular focus on the magnetic anisotropy in the submonolayer thickness range below 0.2 monolayer coverage, and above the spin reorientation transition at 3 monolayer thickness. The comparison of structure and magnetism suggests that the perpendicular easy axis found for films thinner than three monolayers is due to dominating contributions from both film interfaces to the anisotropy energy. The Fe-Pt interface contribution has its origin in the hybridization of the Fe 3d with the Pt 5d band. The in-plane magnetic anisotropy above 3 atomic layers film thickness can be correlated directly with peculiarities of the film structure
MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 1: Frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin
BACKGROUND: Antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) have been suggested to play a role in a subset of patients with neuromyelitis optica and related disorders. OBJECTIVE: To assess (i) the frequency of MOG-IgG in a large and predominantly Caucasian cohort of patients with optic neuritis (ON) and/or myelitis; (ii) the frequency of MOG-IgG among AQP4-IgG-positive patients and vice versa; (iii) the origin and frequency of MOG-IgG in the cerebrospinal fluid (CSF); (iv) the presence of MOG-IgG at disease onset; and (v) the influence of disease activity and treatment status on MOG-IgG titers. METHODS: 614 serum samples from patients with ON and/or myelitis and from controls, including 92 follow-up samples from 55 subjects, and 18 CSF samples were tested for MOG-IgG using a live cell-based assay (CBA) employing full-length human MOG-transfected HEK293A cells. RESULTS: MOG-IgG was detected in 95 sera from 50 patients with ON and/or myelitis, including 22/54 (40.7 %) patients with a history of both ON and myelitis, 22/103 (21.4 %) with a history of ON but no myelitis and 6/45 (13.3 %) with a history of longitudinally extensive transverse myelitis but no ON, and in 1 control patient with encephalitis and a connective tissue disorder, all of whom were negative for AQP4-IgG. MOG-IgG was absent in 221 further controls, including 83 patients with AQP4-IgG-seropositive neuromyelitis optica spectrum disorders and 85 with multiple sclerosis (MS). MOG-IgG was found in 12/18 (67 %) CSF samples from MOG-IgG-seropositive patients; the MOG-IgG-specific antibody index was negative in all cases, indicating a predominantly peripheral origin of CSF MOG-IgG. Serum and CSF MOG-IgG belonged to the complement-activating IgG1 subclass. MOG-IgG was present already at disease onset. The antibodies remained detectable in 40/45 (89 %) follow-up samples obtained over a median period of 16.5 months (range 0-123). Serum titers were higher during attacks than during remission (p < 0.0001), highest during attacks of simultaneous myelitis and ON, lowest during acute isolated ON, and declined following treatment. CONCLUSIONS: To date, this is the largest cohort studied for IgG to human full-length MOG by means of an up-to-date CBA. MOG-IgG is present in a substantial subset of patients with ON and/or myelitis, but not in classical MS. Co-existence of MOG-IgG and AQP4-IgG is highly uncommon. CSF MOG-IgG is of extrathecal origin. Serum MOG-IgG is present already at disease onset and remains detectable in the long-term course. Serum titers depend on disease activity and treatment status
Autologous haematopoietic stem cell transplantation for multiple sclerosis: a position paper and registry outline
Background:
While substantial progress has been made in the development of disease-modifying medications for multiple sclerosis (MS), a high percentage of treated patients still show progression and persistent inflammatory activity. Autologous haematopoietic stem cell transplantation (AHSCT) aims at eliminating a pathogenic immune repertoire through intense short-term immunosuppression that enables subsequent regeneration of a new and healthy immune system to re-establish immune tolerance for a long period of time. A number of mostly open-label, uncontrolled studies conducted over the past 20 years collected about 4000 cases. They uniformly reported high efficacy of AHSCT in controlling MS inflammatory disease activity, more markedly beneficial in relapsing-remitting MS. Immunological studies provided evidence for qualitative immune resetting following AHSCT. These data and improved safety profiles of transplantation procedures spurred interest in using AHSCT as a treatment option for MS.
Objective:
To develop expert consensus recommendations on AHSCT in Germany and outline a registry study project.
Methods:
An open call among MS neurologists as well as among experts in stem cell transplantation in Germany started in December 2021 to join a series of virtual meetings.
Results:
We provide a consensus-based opinion paper authored by 25 experts on the up-to-date optimal use of AHSCT in managing MS based on the Swiss criteria. Current data indicate that patients who are most likely to benefit from AHSCT have relapsing-remitting MS and are young, ambulatory and have high disease activity. Treatment data with AHSCT will be collected within the German REgistry Cohort of autologous haematopoietic stem CeLl trAnsplantation In MS (RECLAIM).
Conclusion:
Further clinical trials, including registry-based analyses, are urgently needed to better define the patient characteristics, efficacy and safety profile of AHSCT compared with other high-efficacy therapies and to optimally position it as a treatment option in different MS disease stages.
Keywords: Autologous haematopoietic stem cell transplantation (AHSCT), multiple sclerosis, registry study, treatment recommendation
Top-layer superstructures of the reconstructed Pt(100) surface
The structures of the two reconstructed phases of the Pt(100) surface have been studied by high-resolution helium diffraction. In contrast to earlier investigations, we show that for both phases the superstructure in the approximate 〈011〉 direction is not fivefold but much larger. The mean distance between atom rows in the top layer, however, is very close to that of a fivefold superstructure. This supports the description of the surface layer in a model which assumes static oscillations about a flat and equidistant atom arrangement. The results are discussed in comparison with low-energy electron diffraction, scanning-tunneling-microscopy, and x-ray-diffraction results
Disruption of arterial perivascular drainage of amyloid-β from the brains of mice expressing the human APOE ε4 allele
Failure of elimination of amyloid-β (Aβ) from the brain and vasculature appears to be a key factor in the etiology of sporadic Alzheimer’s disease (AD) and cerebral amyloid angiopathy (CAA). In addition to age, possession of an apolipoprotein E (APOE) ε4 allele is a strong risk factor for the development of sporadic AD. The present study tested the hypothesis that possession of the APOE ε4 allele is associated with disruption of perivascular drainage of Aβ from the brain and with changes in cerebrovascular basement membrane protein levels. Targeted replacement (TR) mice expressing the human APOE3 (TRE3) or APOE4 (TRE4) genes and wildtype mice received intracerebral injections of human Aβ40. Aβ40 aggregated in peri-arterial drainage pathways in TRE4 mice, but not in TRE3 or wildtype mice. The number of Aβ deposits was significantly higher in the hippocampi of TRE4 mice than in the TRE3 mice, at both 3- and 16-months of age, suggesting that clearance of Aβ was disrupted in the brains of TRE4 mice. Immunocytochemical and Western blot analysis of vascular basement membrane proteins demonstrated significantly raised levels of collagen IV in 3-month-old TRE4 mice compared with TRE3 and wild type mice. In 16-month-old mice, collagen IV and laminin levels were unchanged between wild type and TRE3 mice, but were lower in TRE4 mice. The results of this study suggest that APOE4 may increase the risk for AD through disruption and impedance of perivascular drainage of soluble Aβ from the brain. This effect may be mediated, in part, by changes in age-related expression of basement membrane proteins in the cerebral vasculature
Characterization of the Metabolic Phenotype of Rapamycin-Treated CD8+ T Cells with Augmented Ability to Generate Long-Lasting Memory Cells
Cellular metabolism plays a critical role in regulating T cell responses and the development of memory T cells with long-term protections. However, the metabolic phenotype of antigen-activated T cells that are responsible for the generation of long-lived memory cells has not been characterized.. than untreated control T cells. In contrast to that control T cells only increased glycolysis, rapamycin-treated T cells upregulated both glycolysis and oxidative phosphorylation (OXPHOS). These rapamycin-treated T cells had greater ability than control T cells to survive withdrawal of either glucose or growth factors. Inhibition of OXPHOS by oligomycin significantly reduced the ability of rapamycin-treated T cells to survive growth factor withdrawal. This effect of OXPHOS inhibition was accompanied with mitochondrial hyperpolarization and elevation of reactive oxygen species that are known to be toxic to cells.Our findings indicate that these rapamycin-treated T cells may represent a unique cell model for identifying nutrients and signals critical to regulating metabolism in both effector and memory T cells, and for the development of new methods to improve the efficacy of adoptive T cell cancer therapy
Modified constraint-induced movement therapy or bimanual occupational therapy following injection of Botulinum toxin-A to improve bimanual performance in young children with hemiplegic cerebral palsy: a randomised controlled trial methods paper
<p>Abstract</p> <p>Background</p> <p>Use of Botulinum toxin-A (BoNT-A) for treatment of upper limb spasticity in children with cerebral palsy has become routine clinical practice in many paediatric treatment centres worldwide. There is now high-level evidence that upper limb BoNT-A injection, in combination with occupational therapy, improves outcomes in children with cerebral palsy at both the body function/structure and activity level domains of the International Classification of Functioning, Disability and Health. Investigation is now required to establish what amount and specific type of occupational therapy will further enhance functional outcomes and prolong the beneficial effects of BoNT-A.</p> <p>Methods/Design</p> <p>A randomised, controlled, evaluator blinded, prospective parallel-group trial. Eligible participants were children aged 18 months to 6 years, diagnosed with spastic hemiplegic cerebral palsy and who were able to demonstrate selective motor control of the affected upper limb. Both groups received upper limb injections of BoNT-A. Children were randomised to either the modified constraint-induced movement therapy group (experimental) or bimanual occupational therapy group (control). Outcome assessments were undertaken at pre-injection and 1, 3 and 6 months following injection of BoNT-A. The primary outcome measure was the Assisting Hand Assessment. Secondary outcomes included: the Quality of Upper Extremity Skills Test; Pediatric Evaluation of Disability Inventory; Canadian Occupational Performance Measure; Goal Attainment Scaling; Pediatric Motor Activity Log; modified Ashworth Scale and; the modified Tardieu Scale.</p> <p>Discussion</p> <p>The aim of this paper is to describe the methodology of a randomised controlled trial comparing the effects of modified constraint-induced movement therapy (a uni-manual therapy) versus bimanual occupational therapy (a bimanual therapy) on improving bimanual upper limb performance of children with hemiplegic cerebral palsy following upper limb injection of BoNT-A. The paper outlines the background to the study, the study hypotheses, outcome measures and trial methodology. It also provides a comprehensive description of the interventions provided.</p> <p>Trial Registration</p> <p>ACTRN12605000002684</p
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