Emergence of a highly pathogenic simian/human immunodeficiency virus in a rhesus macaque treated with anti-CD8 mAb during a primary infection with a nonpathogenic virus

Although simian/human immunodeficiency virus (SHIV) strain DH12 replicates to high titers and causes immunodeficiency in pig-tailed macaques, virus loads measured in SHIVDH12-infected rhesus monkeys are consistently 100-fold lower and none of 22 inoculated animals have developed disease. We previously reported that the administration of anti-human CD8 mAb to rhesus macaques at the time of primary SHIVDH12 infection resulted in marked elevations of virus loads. One of the treated animals experienced rapid and profound depletions of circulating CD4+ T lymphocytes. Although the CD4+ T cell number partially recovered, this monkey subsequently suffered significant weight loss and was euthanized. A tissue culture virus stock derived from this animal, designated SHIVDH12R, induced marked and rapid CD4+ cell loss after i.v. inoculation of rhesus monkeys. Retrospective analyses of clinical specimens, collected during the emergence of SHIVDH12R indicated: (i) the input cloned SHIV remained the predominant virus during the first 5–7 months of infection; (ii) variants bearing only a few of the SHIVDH12R consensus changes first appeared 7 months after the administration of anti-CD8 mAb; (iii) high titers of neutralizing antibody directed against the input SHIV were detected by week 10 and persisted throughout the infection; and (iv) no neutralizing antibody against SHIVDH12R ever developed.

Identification and localization of huntingtin in brain and human lymphoblastoid cell lines with anti-fusion protein antibodies.

The Huntington disease (HD) phenotype is associated with expansion of a trinucleotide repeat in the IT15 gene, which is predicted to encode a 348-kDa protein named huntington. We used polyclonal and monoclonal anti-fusion protein antibodies to identify native huntingtin in rat, monkey, and human. Western blots revealed a protein with the expected molecular weight which is present in the soluble fraction of rat and monkey brain tissues and lymphoblastoid cells from control cases. In lymphoblastoid cell lines from juvenile-onset heterozygote HD cases, both normal and mutant huntingtin are expressed, and increasing repeat expansion leads to lower levels of the mutant protein. Immunocytochemistry indicates that huntingtin is located in neurons throughout the brain, with the highest levels evident in larger neurons. In the human striatum, huntingtin is enriched in a patch-like distribution, potentially corresponding to the first areas affected in HD. Subcellular localization of huntingtin is consistent with a cytosolic protein primarily found in somatodendritic regions. Huntingtin appears to particularly associate with microtubules, although some is also associated with synaptic vesicles. On the basis of the localization of huntingtin in association with microtubules, we speculate that the mutation impairs the cytoskeletal anchoring or transport of mitochondria, vesicles, or other organelles or molecules.

Retinal ganglion cell layer change in patients treated with anti-VEGF for neovascular age related macular degeneration.

PURPOSE To evaluate macular retinal ganglion cell thickness in patients with neovascular age-related macular degeneration (AMD) and intravitreal anti-vascular endothelial growth factor (VEGF) therapy. DESIGN Retrospective case series with fellow-eye comparison METHODS: Patients with continuous unilateral anti-VEGF treatment for sub- and juxtafoveal neovascular AMD and a minimum follow-up of 24 months were included. The retinal nerve fiber (RNFL) and retinal ganglion cell layer (RGCL) in the macula were segmented using an ETDRS grid. RNFL and RGCL thickness of the outer ring of the ETDRS grid were quantified at baseline and after repeated anti-VEGF injections, and compared to the patients' untreated fellow eye. Furthermore, best-corrected visual acuity (BCVA), age, and retinal pigment epithelium (RPE) atrophy were recorded and correlated with RNFL and RGCL. RESULTS Sixty eight eyes of 34 patients (23 female and 11 male; mean age 76.7 (SD±8.2) with a mean number of 31.5 (SD ±9.8) anti-VEGF injections and a mean follow-up period of 45.3 months (SD±10.5) were included. Whereas the RGCL thickness decreased significantly compared to the non-injected fellow eye (p=0.01) the decrease of the RNFL was not significant. Visual acuity gain was significantly correlated with RGCL thickness (r=0.52, p<0.05) at follow-up and negatively correlated (r=-0.41, p<0.05) with age. Presence of RPE atrophy correlated negatively with the RGCL thickness at follow-up (r= -0.37, p=0.03). CONCLUSION During the course of long term anti-VEGF therapy there is a significant decrease of the RGCL in patients with neovascular AMD to the fellow (untreated) eye.

Ammonium diuranate precipitation with anhydrous ammonia /

Ammonium diuranate has been precipitated from nitric acid solutions by the addition of anhydrous ammonia on both laboratory and production scales. This process produced more dense and more rapidly filtered precipitates than those formed by the addition of aqueous ammonia or slurried calcium hydroxide. The filtrates from the anhydrous ammonia process were lower in uranium content than those obtained by the addition of the other reagents. Processing equipment and precipitate characteristics are discussed.

Comparison of generalized estimates of probable maximum precipitation with greatest observed rainfalls /

Mar. 1980.

Effect of medications with anti-cholinergic properties on cognitive function, delirium, physical function and mortality:a systematic review

Objectives: to determine the effect of drugs with anti-cholinergic properties on relevant health outcomes.Design: electronic published and unpublished literature/trial registries were systematically reviewed. Studies evaluating medications with anti-cholinergic activity on cognitive function, delirium, physical function or mortality were eligible.Results: forty-six studies including 60,944 participants were included. Seventy-seven percent of included studies evaluating cognitive function (n = 33) reported a significant decline in cognitive ability with increasing anti-cholinergic load (P < 0.05). Four of five included studies reported no association with delirium and increasing anti-cholinergic drug load (P > 0.05). Five of the eight included studies reported a decline in physical function in users of anti-cholinergics (P < 0.05). Three of nine studies evaluating mortality reported that the use of drugs with anti-cholinergic properties was associated with a trend towards increased mortality, but this was not statistically significant. The methodological quality of the evidence-base ranged from poor to very good.Conclusion: medicines with anti-cholinergic properties have a significant adverse effect on cognitive and physical function, but limited evidence exists for delirium or mortality outcomes. © The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved.

Peak -to -average power ratio reduced parallel interference cancellation Multicarrier-Code Division Multiple Access system with anti -interference property

Orthogonal Frequency-Division Multiplexing (OFDM) has been proved to be a promising technology that enables the transmission of higher data rate. Multicarrier Code-Division Multiple Access (MC-CDMA) is a transmission technique which combines the advantages of both OFDM and Code-Division Multiplexing Access (CDMA), so as to allow high transmission rates over severe time-dispersive multi-path channels without the need of a complex receiver implementation. Also MC-CDMA exploits frequency diversity via the different subcarriers, and therefore allows the high code rates systems to achieve good Bit Error Rate (BER) performances. Furthermore, the spreading in the frequency domain makes the time synchronization requirement much lower than traditional direct sequence CDMA schemes. There are still some problems when we use MC-CDMA. One is the high Peak-to-Average Power Ratio (PAPR) of the transmit signal. High PAPR leads to nonlinear distortion of the amplifier and results in inter-carrier self-interference plus out-of-band radiation. On the other hand, suppressing the Multiple Access Interference (MAI) is another crucial problem in the MC-CDMA system. Imperfect cross-correlation characteristics of the spreading codes and the multipath fading destroy the orthogonality among the users, and then cause MAI, which produces serious BER degradation in the system. Moreover, in uplink system the received signals at a base station are always asynchronous. This also destroys the orthogonality among the users, and hence, generates MAI which degrades the system performance. Besides those two problems, the interference should always be considered seriously for any communication system. In this dissertation, we design a novel MC-CDMA system, which has low PAPR and mitigated MAI. The new Semi-blind channel estimation and multi-user data detection based on Parallel Interference Cancellation (PIC) have been applied in the system. The Low Density Parity Codes (LDPC) has also been introduced into the system to improve the performance. Different interference models are analyzed in multi-carrier communication systems and then the effective interference suppression for MC-CDMA systems is employed in this dissertation. The experimental results indicate that our system not only significantly reduces the PAPR and MAI but also effectively suppresses the outside interference with low complexity. Finally, we present a practical cognitive application of the proposed system over the software defined radio platform.

Peak-to-Average Power Ratio Reduced Parallel Interference Cancellation Multicarrier-Code Division Multiple Access System with Anti-Interference Property

Orthogonal Frequency-Division Multiplexing (OFDM) has been proved to be a promising technology that enables the transmission of higher data rate. Multicarrier Code-Division Multiple Access (MC-CDMA) is a transmission technique which combines the advantages of both OFDM and Code-Division Multiplexing Access (CDMA), so as to allow high transmission rates over severe time-dispersive multi-path channels without the need of a complex receiver implementation. Also MC-CDMA exploits frequency diversity via the different subcarriers, and therefore allows the high code rates systems to achieve good Bit Error Rate (BER) performances. Furthermore, the spreading in the frequency domain makes the time synchronization requirement much lower than traditional direct sequence CDMA schemes. There are still some problems when we use MC-CDMA. One is the high Peak-to-Average Power Ratio (PAPR) of the transmit signal. High PAPR leads to nonlinear distortion of the amplifier and results in inter-carrier self-interference plus out-of-band radiation. On the other hand, suppressing the Multiple Access Interference (MAI) is another crucial problem in the MC-CDMA system. Imperfect cross-correlation characteristics of the spreading codes and the multipath fading destroy the orthogonality among the users, and then cause MAI, which produces serious BER degradation in the system. Moreover, in uplink system the received signals at a base station are always asynchronous. This also destroys the orthogonality among the users, and hence, generates MAI which degrades the system performance. Besides those two problems, the interference should always be considered seriously for any communication system. In this dissertation, we design a novel MC-CDMA system, which has low PAPR and mitigated MAI. The new Semi-blind channel estimation and multi-user data detection based on Parallel Interference Cancellation (PIC) have been applied in the system. The Low Density Parity Codes (LDPC) has also been introduced into the system to improve the performance. Different interference models are analyzed in multi-carrier communication systems and then the effective interference suppression for MC-CDMA systems is employed in this dissertation. The experimental results indicate that our system not only significantly reduces the PAPR and MAI but also effectively suppresses the outside interference with low complexity. Finally, we present a practical cognitive application of the proposed system over the software defined radio platform.

Widespread contamination of coastal sediments in the Transmanche Channel with anti-androgenic compounds

This study analysed the levels of androgen receptor antagonist activity in extracts of coastal sediments sampled from estuaries in southern UK and northern France. Anti-androgenic (AA) activity varied between <0.2 and 224.3±38.4μg flutamide equivalents/g dry weight of sediment and was significantly correlated with the total organic carbon and silt content of samples. AA activity was detected in tissues extracts of clams, Scrobicularia plana, sampled from a contaminated estuary, some of which was due to uptake of a series of 4 or 5 ring polycyclic aromatic hydrocarbons (PAHs). Initial studies also indicated that fractionated extracts of male, but not female, clams also contained androgen receptor agonist activity due to the presence of dihydrotestosterone in tissues. This study reveals widespread contamination of coastal sediments of the Transmanche region with anti-androgenic compounds and these contaminants should be investigated for their potential to disrupt sexual differentiation in aquatic organisms.

Widespread contamination of coastal sediments in the Transmanche Channel with anti-androgenic compounds

This study analysed the levels of androgen receptor antagonist activity in extracts of coastal sediments sampled from estuaries in southern UK and northern France. Anti-androgenic (AA) activity varied between <0.2 and 224.3±38.4μg flutamide equivalents/g dry weight of sediment and was significantly correlated with the total organic carbon and silt content of samples. AA activity was detected in tissues extracts of clams, Scrobicularia plana, sampled from a contaminated estuary, some of which was due to uptake of a series of 4 or 5 ring polycyclic aromatic hydrocarbons (PAHs). Initial studies also indicated that fractionated extracts of male, but not female, clams also contained androgen receptor agonist activity due to the presence of dihydrotestosterone in tissues. This study reveals widespread contamination of coastal sediments of the Transmanche region with anti-androgenic compounds and these contaminants should be investigated for their potential to disrupt sexual differentiation in aquatic organisms.

Design of functional hybrid coatings with anti-biofouling, self-cleaning and anti-reflecting applications

263 p.

Development of paclitaxel-loaded liposomal systems with anti-her2 antibody for targeted therapy

Purpose: To develop liposome formulations containing monoclonal antibody anti-HER2 (MabHer2), and Paclitaxel (PTX). Methods: Seven different liposomal systems containing PTX, or MabHer2 or a combination of PTX and MabHer2 were made using lipid film hydration technique and sonication. The effects of liposome preparation conditions and extraction methods on antibody structure were investigated by polyacrylamide gel electrophoresis and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The characteristics of the liposomes were determined by a zetasizer, while drug-loading efficiency was evaluated by high-performance liquid chromatography. The cytotoxic effect of the liposome formulations was evaluated on MDA-MB-453 (HER2+) and MCF-7 (HER2-) breast cancer cell lines by MTT assay. Results: The antibody was not significantly affected by the stress conditions and the method of extraction. The particle size of liposomes was < 200 nm while the amount of incorporated PTX was 97.6 % for liposome without cationic agent and 98.2 % for those with cationic agent. Recovery of MabHer2 was 94.38 % after extraction. Combined PTX/MabHer2 liposome was more toxic on HER2 overexpressing positive MDA-MB-453 cell line than PTX-loaded liposomes and MabHer2. MabHer2 and combined PTX/MabHer2 liposomes showed no toxic effects on HER2 overexpressing negative MCF-7 cells relative to cationic PTX-loaded liposomes. Conclusions: This results obtained show that PTX can be encapsulated successfully into liposoma systems and that owing to Her2 specific antibody, these systems can be delivered directly to the target cell.