332 research outputs found

    Linking Dynamical and Thermal Models of Ultrarelativistic Nuclear Scattering

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    To analyse ultrarelativistic nuclear interactions, usually either dynamical models like the string model are employed, or a thermal treatment based on hadrons or quarks is applied. String models encounter problems due to high string densities, thermal approaches are too simplistic considering only average distributions, ignoring fluctuations. We propose a completely new approach, providing a link between the two treatments, and avoiding their main shortcomings: based on the string model, connected regions of high energy density are identified for single events, such regions referred to as quark matter droplets. Each individual droplet hadronizes instantaneously according to the available n-body phase space. Due to the huge number of possible hadron configurations, special Monte Carlo techniques have been developed to calculate this disintegration.Comment: Complete paper enclosed as postscript file (uuencoded

    Different neuroinflammatory profile in amyotrophic lateral sclerosis and frontotemporal dementia is linked to the clinical phase

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    Objective To investigate the role of neuroinflammation in asymptomatic and symptomatic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) mutation carriers. Methods The neuroinflammatory markers chitotriosidase 1 (CHIT1), YKL-40 and glial fibrillary acidic protein (GFAP) were measured in cerebrospinal fluid (CSF) and blood samples from asymptomatic and symptomatic ALS/FTD mutation carriers, sporadic cases and controls by ELISA. Results CSF levels of CHIT1, YKL-40 and GFAP were unaffected in asymptomatic mutation carriers (n=16). CHIT1 and YKL-40 were increased in gALS (p<0.001, n=65) whereas GFAP was not affected. Patients with ALS carrying a CHIT1 polymorphism had lower CHIT1 concentrations in CSF (-80%) whereas this polymorphism had no influence on disease severity. In gFTD (n=23), increased YKL-40 and GFAP were observed (p<0.05), whereas CHIT1 was nearly not affected. The same profile as in gALS and gFTD was observed in sALS (n=64/70) and sFTD (n=20/26). CSF and blood concentrations correlated moderately (CHIT1, r=0.51) to weak (YKL-40, r=0.30, GFAP, r=0.39). Blood concentrations of these three markers were not significantly altered in any of the groups except CHIT1 in gALS of the Ulm cohort (p<0.05). Conclusion Our data indicate that neuroinflammation is linked to the symptomatic phase of ALS/FTD and shows a similar pattern in sporadic and genetic cases. ALS and FTD are characterised by a different neuroinflammatory profile, which might be one driver of the diverse presentations of the ALS/FTD syndrome

    BRCA1-regulated RRM2 expression protects glioblastoma cells from endogenous replication stress and promotes tumorigenicity

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    Oncogene-evoked replication stress (RS) fuels genomic instability in diverse cancer types. Here we report that BRCA1, traditionally regarded a tumour suppressor, plays an unexpected tumour-promoting role in glioblastoma (GBM), safeguarding a protective response to supraphysiological RS levels. Higher BRCA1 positivity is associated with shorter survival of glioma patients and the abrogation of BRCA1 function in GBM enhances RS, DNA damage (DD) accumulation and impairs tumour growth. Mechanistically, we identify a novel role of BRCA1 as a transcriptional co-activator of RRM2 (catalytic subunit of ribonucleotide reductase), whereby BRCA1-mediated RRM2 expression protects GBM cells from endogenous RS, DD and apoptosis. Notably, we show that treatment with a RRM2 inhibitor triapine reproduces the BRCA1-depletion GBM-repressive phenotypes and sensitizes GBM cells to PARP inhibition. We propose that GBM cells are addicted to the RS-protective role of the BRCA1-RRM2 axis, targeting of which may represent a novel paradigm for therapeutic intervention in GBM

    Two cases of occupational allergic contact dermatitis from a cycloaliphatic epoxy resin in a neat oil: Case Report

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    BACKGROUND: Metal-working fluids contain complex mixtures of chemicals and metal workers constitute a potential risk group for the development of allergic contact dermatitis. CASE PRESENTATION: Two metal workers developed allergic contact dermatitis on the hands and lower arms from exposure to a neat oil used in metal processing. Patch testing revealed that the relevant contact allergen was a cycloaliphatic epoxy resin, 1,2-cyclohexanedicarboxylic acid, bis(oxiranylmethyl) ester, added to the oil as a stabilizer. None of the patients had positive reactions to the bisphenol A-based epoxy resin in the standard series. CONCLUSIONS: These cases emphasize that well-known contact allergens may show up from unexpected sources of exposure. Further, it can be a long-lasting, laborious process to detect an occupational contact allergen and cooperation from the patient and the manufacturer of the sensitizing product is essential

    Magnetic Catalysis: A Review

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    We give an overview of the magnetic catalysis phenomenon. In the framework of quantum field theory, magnetic catalysis is broadly defined as an enhancement of dynamical symmetry breaking by an external magnetic field. We start from a brief discussion of spontaneous symmetry breaking and the role of a magnetic field in its a dynamics. This is followed by a detailed presentation of the essential features of the phenomenon. In particular, we emphasize that the dimensional reduction plays a profound role in the pairing dynamics in a magnetic field. Using the general nature of underlying physics and its robustness with respect to interaction types and model content, we argue that magnetic catalysis is a universal and model-independent phenomenon. In support of this claim, we show how magnetic catalysis is realized in various models with short-range and long-range interactions. We argue that the general nature of the phenomenon implies a wide range of potential applications: from certain types of solid state systems to models in cosmology, particle and nuclear physics. We finish the review with general remarks about magnetic catalysis and an outlook for future research.Comment: 37 pages, to appear in Lect. Notes Phys. "Strongly interacting matter in magnetic fields" (Springer), edited by D. Kharzeev, K. Landsteiner, A. Schmitt, H.-U. Yee. Version 2: references adde

    Physics with Coherent Matter Waves

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    This review discusses progress in the new field of coherent matter waves, in particular with respect to Bose-Einstein condensates. We give a short introduction to Bose-Einstein condensation and the theoretical description of the condensate wavefunction. We concentrate on the coherence properties of this new type of matter wave as a basis for fundamental physics and applications. The main part of this review treats various measurements and concepts in the physics with coherent matter waves. In particular we present phase manipulation methods, atom lasers, nonlinear atom optics, optical elements, interferometry and physics in optical lattices. We give an overview of the state of the art in the respective fields and discuss achievements and challenges for the future

    Immune-Complex Mimics as a Molecular Platform for Adjuvant-Free Vaccine Delivery

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    Protein-based vaccine development faces the difficult challenge of finding robust yet non-toxic adjuvants suitable for humans. Here, using a molecular engineering approach, we have developed a molecular platform for generating self-adjuvanting immunogens that do not depend on exogenous adjuvants for induction of immune responses. These are based on the concept of Immune Complex Mimics (ICM), structures that are formed between an oligomeric antigen and a monoclonal antibody (mAb) to that antigen. In this way, the roles of antigens and antibodies within the structure of immune complexes are reversed, so that a single monoclonal antibody, rather than polyclonal sera or expensive mAb cocktails can be used. We tested this approach in the context of Mycobacterium tuberculosis (MTB) infection by linking the highly immunogenic and potentially protective Ag85B with the oligomeric Acr (alpha crystallin, HspX) antigen. When combined with an anti-Acr monoclonal antibody, the fusion protein formed ICM which bound to C1q component of the complement system and were readily taken up by antigen-presenting cells in vitro. ICM induced a strong Th1/Th2 mixed type antibody response, which was comparable to cholera toxin adjuvanted antigen, but only moderate levels of T cell proliferation and IFN-γ secretion. Unfortunately, the systemic administration of ICM did not confer statistically significant protection against intranasal MTB challenge, although a small BCG-boosting effect was observed. We conclude that ICM are capable of inducing strong humoral responses to incorporated antigens and may be a suitable vaccination approach for pathogens other than MTB, where antibody-based immunity may play a more protective role

    In vivo percutaneous penetration/absorption : Sponsored by the American Association of Pharmaceutical Scientist, U.S. Food and Drug Administration, American Academy of Dermatology, Skin Pharmacology Society and the U.S. Army Environmental Hygiene Agency May 1-3, 1989, Washington, DC

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    This workshop, `In Vivo Percutaneous Penetration/Absorption' was held in Washington, DC, on May 1-3, 1989. The first workshop in this series, `In Vitro Percutaneous Penetration', took place in November 1986 (the report of this earlier meeting was published in Pharmaceutical Research, 4 (1987) 265-267). The objectives of the workshop were to review the relevant literature and to address in detail: (1) In vivo percutaneous penetration/absorption methodology; (2) The characteristics of dosage forms designed for application to the skin; (3) Critical factors controlling in vivo drug transport into and across the skin; (4) The use of models in the assessment and evaluation of in vivo percutaneous penetration/absorption; and (5) Bioavailability/bioequivalence considerations for topical drug products. Scientific knowledge and technology are rapidly evolving in the topical and transdermal drug products area. This report focuses on the methodologies available for the measurement of percutaneous penetration in vivo; each scientific approach is discussed briefly followed by advantages and disadvantages of the methodology.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29180/1/0000227.pd
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