142 research outputs found
FIRE-the Frankfurt Ion stoRage Experiments
Abstract Existing electrostatic storage rings have proven to be a valuable tool for molecular and atomic physics in the low-energy regime. At the new Stern-Gerlach Center of Frankfurt University a small machine for ion energies up to 50 keV will be build up. It will serve as a tool to analyze the structure and dynamics of many particle systems from atoms to complex organic biomolecules. It will be possible to prepare the particle beams of interest in novel and unique ways. In direct comparison to traditional setups, the luminosity of the measurements will be improved by many orders of magnitude. In combination with the newest reaction microscopes, the F rankfurt Ion stoRage Experiments (FIRE) will allow analysis of many particle fragmentation processes of atoms and molecules with unrivaled resolution and completeness. In contrast to experiments with traps, an electrostatic storage ring has the advantage of being able to record the momenta of all neutral fragments. This paper gives an overview of the design parameters, the optical elements used and the project status.
Nonlinear Cancer Response at Ultralow Dose: A 40800-Animal ED 001 Tumor and Biomarker Study
Assessment of human cancer risk from animal carcinogen studies is severely limited by inadequate experimental data at environmentally relevant exposures, and procedures requiring modeled extrapolations many orders of magnitude below observable data. We used rainbow trout, an animal model well suited to ultra low-dose carcinogenesis research, to explore dose-response down to a targeted 10 excess liver tumors per 10,000 animals (ED001). A total of 40,800 trout were fed 0–225 ppm dibenzo[a,l]pyrene (DBP) for four weeks, sampled for biomarker analyses, and returned to control diet for nine months prior to gross and histologic examination. Suspect tumors were confirmed by pathology, and resulting incidences were modeled and compared to the default EPA LED10 linear extrapolation method. The study provided observed incidence data down to two above-background liver tumors per 10,000 animals at lowest dose (that is, an un-modeled ED0002 measurement). Among nine statistical models explored, three were determined to fit the liver data well - linear probit, quadratic logit, and Ryzin-Rai. None of these fitted models is compatible with the LED10 default assumption, and all fell increasingly below the default extrapolation with decreasing DBP dose. Low-dose tumor response was also not predictable from hepatic DBP-DNA adduct biomarkers, which accumulated as a power function of dose (adducts = 100 * DBP1.31). Two-order extrapolations below the modeled tumor data predicted DBP doses producing one excess cancer per million individuals (ED10−6) that were 500–1500-fold higher than that predicted by the five-order LED10 extrapolation. These results are considered specific to the animal model, carcinogen, and protocol used. They provide the first experimental estimation in any model of the degree of conservatism that may exist for the EPA default linear assumption for a genotoxic carcinogen
Initial Commitment to Pre-Exposure Prophylaxis and Circumcision for HIV Prevention amongst Indian Truck Drivers
Studies of HIV prevention interventions such as pre-exposure prophylaxis (PREP) and circumcision in India are limited. The present study sought to investigate Indian truck-drivers initial commitment to PREP and circumcision utilizing the AIDS Risk Reduction Model. Ninety truck-drivers completed an in-depth qualitative interview and provided a blood sample for HIV and HSV-2 testing. Truck-drivers exhibited low levels of initial commitment towards PREP and even lower for circumcision. However, potential leverage points for increasing commitment were realized in fear of infecting family rather than self, self-perceptions of risk, and for PREP focusing on cultural beliefs towards medication and physicians. Cost was a major barrier to both HIV prevention interventions. Despite these barriers, our findings suggest that the ARRM may be useful in identifying several leverage points that may be used by peers, health care providers and public health field workers to enhance initial commitment to novel HIV prevention interventions in India
Macrocyclic β-Sheet Peptides That Inhibit the Aggregation of a Tau-Protein-Derived Hexapeptide
This paper describes studies of a series of macrocyclic β-sheet peptides 1 that inhibit the aggregation of a tau-protein-derived peptide. The macrocyclic β-sheet peptides comprise a pentapeptide "upper" strand, two δ-linked ornithine turn units, and a "lower" strand comprising two additional residues and the β-sheet peptidomimetic template "Hao". The tau-derived peptide Ac-VQIVYK-NH(2) (AcPHF6) aggregates in solution through β-sheet interactions to form straight and twisted filaments similar to those formed by tau protein in Alzheimer's neurofibrillary tangles. Macrocycles 1 containing the pentapeptide VQIVY in the "upper" strand delay and suppress the onset of aggregation of the AcPHF6 peptide. Inhibition is particularly pronounced in macrocycles 1a, 1d, and 1f, in which the two residues in the "lower" strand provide a pattern of hydrophobicity and hydrophilicity that matches that of the pentapeptide "upper" strand. Inhibition varies strongly with the concentration of these macrocycles, suggesting that it is cooperative. Macrocycle 1b containing the pentapeptide QIVYK shows little inhibition, suggesting the possibility of a preferred direction of growth of AcPHF6 β-sheets. On the basis of these studies, a model is proposed in which the AcPHF6 amyloid grows as a layered pair of β-sheets and in which growth is blocked by a pair of macrocycles that cap the growing paired hydrogen-bonding edges. This model provides a provocative and appealing target for future inhibitor design
Who is accessing public-sector anti-retroviral treatment in the Free State, South Africa? An exploratory study of the first three years of programme implementation
<p>Abstract</p> <p>Background</p> <p>Although South Africa has the largest public-sector anti-retroviral treatment (ART) programme in the world, anti-retroviral coverage in adults was only 40.2% in 2008. However, longitudinal studies of who is accessing the South African public-sector ART programme are scarce. This study therefore had one main research question: who is accessing public-sector ART in the Free State Province, South Africa? The study aimed to extend the current literature by investigating, in a quantitative manner and using a longitudinal study design, the participants enrolled in the public-sector ART programme in the period 2004-2006 in the Free State Province of South Africa.</p> <p>Methods</p> <p>Differences in the demographic (age, sex, population group and marital status) socio-economic (education, income, neo-material indicators), geographic (travel costs, relocation for ART), and medical characteristics (CD4, viral load, time since first diagnosis, treatment status) among 912 patients enrolled in the Free State public-sector ART programme between 2004 and 2006 were assessed with one-way analysis of variance, Bonferroni post-hoc analysis, and cross tabulations with the chi square test.</p> <p>Results</p> <p>The patients accessing treatment tended to be female (71.1%) and unemployed (83.4%). However, although relatively poor, those most likely to access ART services were not the most impoverished patients. The proportion of female patients increased (<it>P </it>< 0.05) and their socio-economic situation improved between 2004 and 2006 (<it>P </it>< 0.05). The increasing mean transport cost (<it>P </it>< 0.05) to visit the facility is worrying, because this cost is an important barrier to ART uptake and adherence. Encouragingly, the study results revealed that the interval between the first HIV-positive diagnosis and ART initiation decreased steadily over time (<it>P </it>< 0.05). This was also reflected in the increasing baseline CD4 cell count at ART initiation (<it>P </it>< 0.05).</p> <p>Conclusions</p> <p>Our analysis showed significant changes in the demographic, socio-economic, geographic, and medical characteristics of the patients during the first three years of the programme. Knowledge of the characteristics of these patients can assist policy makers in developing measures to retain them in care. The information reported here can also be usefully applied to target patient groups that are currently not reached in the implementation of the ART programme.</p
Multizone Paper Platform for 3D Cell Cultures
In vitro 3D culture is an important model for tissues in
vivo. Cells in different locations of 3D tissues are
physiologically different, because they are exposed to different concentrations
of oxygen, nutrients, and signaling molecules, and to other environmental
factors (temperature, mechanical stress, etc). The majority of high-throughput
assays based on 3D cultures, however, can only detect the
average behavior of cells in the whole 3D construct.
Isolation of cells from specific regions of 3D cultures is possible, but relies
on low-throughput techniques such as tissue sectioning and micromanipulation.
Based on a procedure reported previously (“cells-in-gels-in-paper”
or CiGiP), this paper describes a simple method for culture of arrays of thin
planar sections of tissues, either alone or stacked to create more complex 3D
tissue structures. This procedure starts with sheets of paper patterned with
hydrophobic regions that form 96 hydrophilic zones. Serial spotting of cells
suspended in extracellular matrix (ECM) gel onto the patterned paper creates an
array of 200 micron-thick slabs of ECM gel (supported mechanically by cellulose
fibers) containing cells. Stacking the sheets with zones aligned on top of one
another assembles 96 3D multilayer constructs. De-stacking the layers of the 3D
culture, by peeling apart the sheets of paper, “sections” all 96
cultures at once. It is, thus, simple to isolate 200-micron-thick
cell-containing slabs from each 3D culture in the 96-zone array. Because the 3D
cultures are assembled from multiple layers, the number of cells plated
initially in each layer determines the spatial distribution of cells in the
stacked 3D cultures. This capability made it possible to compare the growth of
3D tumor models of different spatial composition, and to examine the migration
of cells in these structures
Description and performance of track and primary-vertex reconstruction with the CMS tracker
A description is provided of the software algorithms developed for the CMS tracker both for reconstructing charged-particle trajectories in proton-proton interactions and for using the resulting tracks to estimate the positions of the LHC luminous region and individual primary-interaction vertices. Despite the very hostile environment at the LHC, the performance obtained with these algorithms is found to be excellent. For tbar t events under typical 2011 pileup conditions, the average track-reconstruction efficiency for promptly-produced charged particles with transverse momenta of pT > 0.9GeV is 94% for pseudorapidities of |η| < 0.9 and 85% for 0.9 < |η| < 2.5. The inefficiency is caused mainly by hadrons that undergo nuclear interactions in the tracker material. For isolated muons, the corresponding efficiencies are essentially 100%. For isolated muons of pT = 100GeV emitted at |η| < 1.4, the resolutions are approximately 2.8% in pT, and respectively, 10μm and 30μm in the transverse and longitudinal impact parameters. The position resolution achieved for reconstructed primary vertices that correspond to interesting pp collisions is 10–12μm in each of the three spatial dimensions. The tracking and vertexing software is fast and flexible, and easily adaptable to other functions, such as fast tracking for the trigger, or dedicated tracking for electrons that takes into account bremsstrahlung
Computational analysis of protein-protein interfaces involving an alpha helix: insights for terphenyl–like molecules binding
Peptide, Peptidomimetic, and Small-molecule Antagonists of the p53–HDM2 Protein–Protein Interaction
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