809 research outputs found
Selective-pivot sampling of radial distribution functions in asymmetric liquid mixtures
We present a Monte Carlo algorithm for selectively sampling radial
distribution functions and effective interaction potentials in asymmetric
liquid mixtures. We demonstrate its efficiency for hard-sphere mixtures, and
for model systems with more general interactions, and compare our simulations
with several analytical approximations. For interaction potentials containing a
hard-sphere contribution, the algorithm yields the contact value of the radial
distribution function.Comment: 5 pages, 5 figure
The photospheric solar oxygen project: III. Investigation of the centre-to-limb variation of the 630nm [OI]-NiI blend
The solar photospheric abundance of oxygen is still a matter of debate. For
about ten years some determinations have favoured a low oxygen abundance which
is at variance with the value inferred by helioseismology. Among the oxygen
abundance indicators, the forbidden line at 630nm has often been considered the
most reliable even though it is blended with a NiI line. In Papers I and Paper
II of this series we reported a discrepancy in the oxygen abundance derived
from the 630nm and the subordinate [OI] line at 636nm in dwarf stars, including
the Sun. Here we analyse several, in part new, solar observations of the the
centre-to-limb variation of the spectral region including the blend at 630nm in
order to separate the individual contributions of oxygen and nickel. We analyse
intensity spectra observed at different limb angles in comparison with line
formation computations performed on a CO5BOLD 3D hydrodynamical simulation of
the solar atmosphere. The oxygen abundances obtained from the forbidden line at
different limb angles are inconsistent if the commonly adopted nickel abundance
of 6.25 is assumed in our local thermodynamic equilibrium computations. With a
slightly lower nickel abundance, A(Ni)~6.1, we obtain consistent fits
indicating an oxygen abundance of A(O)=8.73+/-0.05. At this value the
discrepancy with the subordinate oxygen line remains. The derived value of the
oxygen abundance supports the notion of a rather low oxygen abundance in the
solar hotosphere. However, it is disconcerting that the forbidden oxygen lines
at 630 and 636nm give noticeably different results, and that the nickel
abundance derived here from the 630nm blend is lower than expected from other
nickel lines.Comment: to appear in A&
Preliminary risk assessment of common-use pesticides using PRIMET and PERPEST pesticide risk models in a semi-arid subtropical region
The pesticide risk in agriculture in developing countries has not been adequately studied due to the extent and fate of pesticides in the environment often being unknown. South Africa is a country that has significant pressure on its freshwater and agricultural resources, which increases the possibility of pesticide effects. Thus, the aim of this study was to evaluate the use of the PRIMET (Pesticide Risks in the Tropics to Man, Environment and Trade) and PERPEST (Predicting the Ecological Risk of PESTicides) models to predict pesticide exposure and effects on aquatic ecosystems due to spray drift. Vaalharts Irrigation Scheme is situated in the Northern Cape Province and receives water from the Vaal River for 43 000 ha of agricultural land. Crops in the area mostly consist of wheat, maize and groundnuts. Data gathered through household surveys with farmers were used in PRIMET as a first-tier estimate of the potential risk of the pesticides. The Predicted Effect Concentrations (PEC) calculated for the pesticides indicating a possible to definite risk were then used as input for PERPEST. PERPEST is a higher-tier model that predicts the potential effects of a pesticide on various grouped endpoints in the aquatic environment. The PRIMET results indicated most pesticides posed no risk to the environment, except the pyrethroid, deltamethrin. The ETR for deltamethrin indicated a possible to definite risk to the aquatic environment. The PERPEST results for deltamethrin indicated a high probability of clear effects on insects, micro- and macro-crustacean communities, with a lower probability for rotifers, algae, macrophytes and fish. PRIMET and PERPEST provided valid estimates of risk for pesticides and could be used effectively in South Africa.Keywords: pesticides, PRIMET, PERPEST, Vaalhart
Generalized surgical emphysema as an early complication of facial fracture : a case report
The original publication is available at http://www.samj.org.zaA case of multiple facial fractures complicated by subcutaneous emphysema, pneumomediastinum and pneumoretroperitoneum, in the absence of intra-abdominal, neck or chest injuries, is described.Publishers' versio
P05-10. Sequential Immunization with a Subtype B HIV-1 Envelope Quasispecies Elicits Broader Neutralization than Vaccination with a Single Envelope Clone
Aspekte van die ekologiese toestand van die Mvotirivier in die Stanger-omgewing, KwaZulu-Natal
Aspects of the ecological state of the Mvoti River in the Stanger area, KwaZulu-Natal Water is a scarce resource and if its quantity and quality are insufficient, it cannot provide the necessary goods and services to the various water consumers. Biomonitoring is used to determine the ecological state of water resources through the use of various biotic indices. The initiation of the River Health Programme (RHP) in South Africa has given sufficient momentum to biomonitoring of rivers in South Africa. The RHP has developed and refined various biomonitoring indices to assess the ecological state of ecosystem components. The Mvoti River, in the vicinity of Stanger, is subjected to extensive water abstraction, which is then utilised for irrigation, industrial use, urban water requirements and various domestic uses by informal settlements. Previous studies on the river indicated that it is in a severely degraded state, especially below the confluences of the Nchaweni and Mbozambo rivers. Thus, this assessment of the current ecological status of the Mvoti River was undertaken to possibly identify the main causes of the degraded state. The study was undertaken during the high (February) and low flow (August) periods in 2005. Selected monitoring sites included sites used in previous studies on the Mvoti River as well as sites on the Nchaweni and Mbozambo tributaries. The RHP methods were implemented in this study to determine the ecological state of the macroinvertebrate and fish communities. Habitat indices and water samples were also used to assess the state of the abiotic components. The habitat indices implemented in this study were the Habitat Quality Index (HQI) and Integrated Habitat Assessment System (IHAS). Physicochemical water analyses were done during each sampling period to assess the water quality. The biotic indices used included the South African Scoring System 5 (SASS5) index to assess the macro-invertebrate community and the Fish Assemblage Integrity Index (FAII) to assess the fish community. The lower Mvoti River contains very little habitat of good quality to support the biotic communities. The habitat is generally degraded due to the destruction of the riparian zone and the dominance of alien vegetation in the form of reeds. This, together with land-use and water abstraction activities, has caused high sediment loads in the lower Mvoti River which are continually moving. The results have shown that site MR1 is in an almost natural state with few modifications. The relative reference site, MR2, was, except for the fish community that showed various modifications, in good condition. The condition of the sites downstream decreased as the various activities around Stanger started to impact on the river. Site MR4 located directly below all activities surrounding Stanger was in a poor ecological state. The results of the Nchaweni and Mbozambo tributaries also indicated that the macroinvertebrate and fish communities are in a degraded condition due to the poor water quality in these systems. The main impact on the Mvoti River and its tributaries is the low habitat diversity together with the altered water quality associated with the multitude of activities in the Stanger area. Overall, the Mvoti River is in a seriously degraded state with even the reference site being subjected to impacts that could potentially be harmful to the ecosystem. The ecological state of the river decreases as it moves past Stanger and is subjected to the impacts from the Nchaweni and Mbozambo rivers in the form of nutrients and salinity concentrations. The impacts on the Mvoti River have a multitude of different sources and if the aquatic ecosystem is to improve, only a collective effort will be of any value
Positive allosteric modulation of GABAB receptors ameliorates sensorimotor gating in rodent models
This is the peer reviewed version of the following article: Frau, R., Bini, V., Pillolla, G., Malherbe, P., Pardu, A., Thomas, A. W., Devoto, P. and Bortolato, M. (2014), Positive Allosteric Modulation of GABAB Receptors Ameliorates Sensorimotor Gating in Rodent Models. CNS Neurosci Ther, 20: 679–684. doi:10.1111/cns.12261, which has been published in final form at http://doi.org/10.1111/cns.12261. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.BACKGROUND: Converging evidence points to the involvement of γ-amino-butyric acid B receptors (GABABRs) in the regulation of information processing. We previously showed that GABABR agonists exhibit antipsychotic-like properties in rodent models of sensorimotor gating deficits, as measured by the prepulse inhibition (PPI) of the acoustic startle reflex. The therapeutic potential of these agents, however, is limited by their neuromuscular side effects; thus, in the present study we analyzed whether rac-BHFF, a potent GABABR positive allosteric modulator (PAM), could counter spontaneous and pharmacologically induced PPI deficits across various rodent models. METHODS: We tested the antipsychotic effects of rac-BHFF on the PPI deficits caused by the N-methyl-D-aspartate glutamate receptor antagonist dizocilpine, in Sprague-Dawley rats and C57BL/6 mice. Furthermore, we verified whether rac-BHFF ameliorated the spontaneous PPI impairments in DBA/2J mice. RESULTS: rac-BHFF dose-dependently countered the PPI deficits across all three models, in a fashion akin to the GABABR agonist baclofen and the atypical antipsychotic clozapine; in contrast with these compounds, however, rac-BHFF did not affect startle magnitude. CONCLUSIONS: The present data further support the implication of GABABRs in the modulation of sensorimotor gating, and point to their PAMs as a novel promising tool for antipsychotic treatment, with fewer side effects than GABABR agonists
Insights into GABA receptor signalling in TM3 Leydig cells
gamma-Aminobutyric acid (GABA) is an emerging signalling molecule in endocrine organs, since it is produced by endocrine cells and acts via GABA(A) receptors in a paracrine/autocrine fashion. Testicular Leydig cells are producers and targets for GABA. These cells express GABA(A) receptor subunits and in the murine Leydig cell line TM3 pharmacological activation leads to increased proliferation. The signalling pathway of GABA in these cells is not known in this study. We therefore attempted to elucidate details of GABA(A) signalling in TM3 and adult mouse Leydig cells using several experimental approaches. TM3 cells not only express GABA(A) receptor subunits, but also bind the GABA agonist {[}H-3] muscimol with a binding affinity in the range reported for other endocrine cells (K-d = 2.740 +/- 0.721 nM). However, they exhibit a low B-max value of 28.08 fmol/mg protein. Typical GABA(A) receptor-associated events, including Cl- currents, changes in resting membrane potential, intracellular Ca2+ or cAMP, were not measurable with the methods employed in TM3 cells, or, as studied in part, in primary mouse Leydig cells. GABA or GABA(A) agonist isoguvacine treatment resulted in increased or decreased levels of several mRNAs, including transcription factors (c-fos, hsf-1, egr-1) and cell cycle-associated genes (Cdk2, cyclin D1). In an attempt to verify the cDNA array results and because egr-1 was recently implied in Leydig cell development, we further studied this factor. RT-PCR and Western blotting confirmed a time-dependent regulation of egr-1 in TM3. In the postnatal testis egr-1 was seen in cytoplasmic and nuclear locations of developing Leydig cells, which bear GABA(A) receptors and correspond well to TM3 cells. Thus, GABA acts via an untypical novel signalling pathway in TM3 cells. Further details of this pathway remain to be elucidated. Copyright (c) 2005 S. Karger AG, Base
The HLA class I immunopeptidomes of AAV capsid proteins
IntroductionCellular immune responses against AAV vector capsid represent an obstacle for successful gene therapy. Previous studies have used overlapping peptides spanning the entire capsid sequence to identify T cell epitopes recognized by AAV-specific CD8+ T cells. However, the repertoire of peptides naturally displayed by HLA class I molecules for CD8 T cell recognition is unknown.MethodsUsing mRNA transfected monocyte-derived dendritic cells (MDDCs) and MHC-associated peptide proteomics (MAPPs), we identified the HLA class I immunopeptidomes of AAV2, AAV6 and AAV9 capsids. MDDCs were isolated from a panel of healthy donors that have diverse alleles across the US population. mRNA-transfected MDDCs were lysed, the peptide:HLA complexes immunoprecipitated, and peptides eluted and analyzed by mass spectrometry.ResultsWe identified 65 AAV capsid-derived peptides loaded on HLA class I molecules of mRNA transfected monocyte derived dendritic cells. The HLA class I peptides are distributed along the entire capsid and more than 60% are contained within HLA class II clusters. Most of the peptides are organized as single species, however we identified twelve clusters containing at least 2 peptides of different lengths. Only 9% of the identified peptides have been previously identified as T cell epitopes, demonstrating that the immunogenicity potential for the vast majority of the AAV HLA class I immunopeptidome remains uncharacterized. In contrast, 12 immunogenic epitopes identified before were not found to be naturally processed in our study. Remarkably, 11 naturally presented AAV peptides were highly conserved among the three serotypes analyzed suggesting the possibility of cross-reactive AAV-specific CD8 T cells.DiscussionThis work is the first comprehensive study identifying the naturally displayed HLA class I peptides derived from the capsid of AAVs. The results from this study can be used to generate strategies to assess immunogenicity risk and cross-reactivity among serotypes during gene therapies
- …