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Multiple Routes (multiple + route)
Selected AbstractsCombined exposures to anti-androgenic chemicals: steps towards cumulative risk assessmentINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 2 2010A. Kortenkamp Summary There is widespread exposure to anti-androgens, a group of chemicals able to disrupt androgen action in foetal life, with irreversible de-masculinizing consequences. Substances of concern include certain phthalates, pesticides and chemicals used in cosmetics and personal care products. Although people come into contact with several anti-androgens, chemicals risk assessment normally does not take account of the effects of combined exposures. However, a disregard for combination effects may lead to underestimations of risks and for this reason, we have assessed the feasibility of conducting cumulative risk assessment, where the focus is on considering the effects of exposure to multiple chemicals, via multiple routes and pathways. Following recent recommendations by the US National Research Council, we have, for the first time, included phthalates and other anti-androgenic chemicals, a total of 15 substances. On the basis of exposure estimates for the individual chemicals and reference doses for anti-androgenicity, we have used the hazard index approach. We show that the cumulative risks from anti-androgen exposures exceed acceptable levels for people on the upper end of exposure levels. The value obtained for median exposures to the 15 substances can be judged tolerable. However, significant knowledge gaps exist that prevent us from arriving at definitive conclusions. Of greatest concern is an absence of appropriate in vivo toxicity data about large numbers of in vitro androgen receptor antagonists. Knowledge about the effect profiles of these chemicals will lead to higher risk estimates. Our analysis suggests that risk reductions can be achieved by limiting exposures to the plasticizer diethyl hexyl phthalate, the cosmetic ingredients butyl- and propyl paraben, the pesticides vinclozolin, prochloraz and procymidone and bisphenol A. [source] Parental lung cancer as predictor of cancer risks in offspring: Clues about multiple routes of harmful influence?INTERNATIONAL JOURNAL OF CANCER, Issue 3 2006Kari Hemminki Abstract The carcinogenic effects of active smoking have been demonstrated for many sites, but the effects of passive smoking and exposures during pregnancy and breastfeeding are less well documented. We examined whether 0,70-year-old offspring of parents with lung cancer are at a risk of cancer that cannot be explained by their smoking or familial risk. It was assumed that known target sites for tobacco carcinogenesis would be affected, if any. The nationwide Swedish Family-Cancer Database with cancers recorded from 1958 to 2002 was used to calculate age-specific standardized incidence ratios (SIRs). Among offspring of affected mothers, increased risks were observed for upper aerodigestive (SIR 1.45), nasal (2.93), lung (1.71) and bladder (1.52) cancers and for kidney cancer (6.41) in one age group. The risk of bladder cancer was found in younger age groups than that of lung cancer. Cancers at many of these sites, but not the kidney or the bladder, were in excess in offspring of affected fathers. Nasal cancer was even increased when either parent was diagnosed with lung cancer; the highest risk was for nasal adenoid cystic carcinoma (7.73). The data suggest that passive smoking during childhood is associated with an increase risk of nasal cancer. For bladder and kidney cancers, a contribution by tobacco carcinogens is implicated through breastfeeding and in utero exposure. © 2005 Wiley-Liss, Inc. [source] Error-aware and energy-efficient routing approach in MANETsINTERNATIONAL JOURNAL OF COMMUNICATION SYSTEMS, Issue 1 2009Liansheng Tan Abstract The lifetime of a network is the key design factor of mobile ad hoc networks (MANETs). To prolong the lifetime of MANETs, one is forced to attain a tradeoff of minimizing the energy consumption and load balancing. In MANETs, energy waste resulting from retransmission due to high bit error rate (BER) and high frame error rate (FER) of wireless channel is significant. In this paper, we propose two novel protocols termed multi-threshold routing protocol (MTRP) and enhanced multi-threshold routing protocol (EMTRP). MTRP divides the total energy of a wireless node into multiple ranges. The lower bound of each range corresponds to a threshold. The protocol iterates from the highest threshold to the lowest one and chooses those routes with bottleneck energy being larger than the current threshold during each iteration. This approach thus avoids overusing certain routes and achieves load balancing. If multiple routes satisfy the threshold constraint, MTRP selects a route with the smallest hop count to further attain energy efficiency. Based on MTRP, EMTRP further takes channel condition into consideration and selects routes with better channel condition and consequently reduces the number of retransmissions and saves energy. We analyze the average loss probability (ALP) of the uniform error model and Gilbert error model and give a distributed algorithm to obtain the maximal ALP along a route. Descriptions of MTRP and EMTRP are given in pseudocode form. Simulation results demonstrate that our proposed EMTRP outperforms the representative protocol CMMBCR in terms of total energy consumption and load balancing. Copyright © 2008 John Wiley & Sons, Ltd. [source] A new ferrous iron-uptake transporter, EfeU (YcdN), from Escherichia coliMOLECULAR MICROBIOLOGY, Issue 1 2006Cornelia Große Summary Escherichia coli possesses multiple routes for iron uptake. Here we present EfeU (YcdN), a novel iron acquisition system of E. coli strain Nissle 1917. Laboratory strains of E. coli such as K12 lack a functional (efeU) ycdN gene caused by a frameshift mutation. EfeU, a member of the oxidase-dependent iron transporters (OFeT), is a homologue of the iron permease Ftr1p from yeast. The ycdN gene is part of the ycdNOB tricistronic operon which is expressed in response to iron deprivation in a Fur-dependent manner. Expression of efeU resulted in improved growth of an E. coli mutant lacking all known iron-uptake systems and mediated increased iron uptake into cells. Furthermore, the presence of other divalent metal cations did not impair growth of strains expressing efeU. The EfeU protein functioned as ferrous iron permease in proteoliposomes in vitro. Topology analysis indicated that EfeU is an integral cytoplasmic membrane protein exhibiting seven transmembrane helices. Two REXXE motifs within transmembrane helices of OFeT family members are implicated in iron translocation. Site-directed mutagenesis of each REGLE motif of EfeU diminished iron uptake in vivo and growth yield. In vitro the EfeU variant protein with an altered first REGLE motif was impaired in iron permeation, whereas activity of the EfeU variant with a mutation in the second motif was similar to the wild-type protein. [source] Growth of the vacuoleless mutant of Tetrahymena thermophila NP1 in phytateTHE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 2 2005SAMANTHA WEBB Phytate, the salt form of phytic acid, is the major store of phosphate in seeds and grain. Since non-ruminant farm animals poorly digest phytate, it is also a source of environmental phosphate contamination in agricultural areas. We are using Tetrahymena, a ciliated protist with multiple routes for nutrient assimilation, as a model to investigate the contribution of heterotrophic protists to the environmental cycling of phosphate from phytate. This ciliate has the ability to grow on phytate as the sole phosphate source (Ziemkiewicz, H. T., Johnson, M. D. & Smith-Somerville, H. E. 2002. J. Eukaryot. Microbiol., 49:428). Tetrahymena thermophila NP1, a temperature-sensitive vacuoleless mutant (ATCC #50202), provides a way to separate membrane transport from uptake through phagosomes, and to assess the importance of each mechanism. This cell grows equally well at the permissive and non-permissive temperatures with either phytate or inorganic phosphate as the phosphate source. Our results demonstrate that phagosomes are not required to use the phosphate from phytate. [source] Improvement of low-temperature caseinolytic activity of a thermophilic subtilase by directed evolution and site-directed mutagenesisBIOTECHNOLOGY & BIOENGINEERING, Issue 5 2009Chuan-Qi Zhong Abstract By directed evolution and subsequent site-directed mutagenesis, cold-adapted variants of WF146 protease, a thermophilic subtilase, have been successfully engineered. A four-amino acid substitution variant RTN29 displayed a sixfold increase in caseinolytic activity in the temperature range of 15,25°C, a down-shift of optimum temperature by ,15°C, as well as a decrease in thermostability, indicating it follows the general principle of trade-off between activity and stability. Nevertheless, to some extent RTN29 remained its thermophilic nature, and no loss of activity was observed after heat-treatment at 60°C for 2,h. Notably, RTN29 exhibited a lower hydrolytic activity toward suc-AAPF-pNA, due to an increase in Km and a decrease in kcat, in contrast to other artificially cold-adapted subtilases with increased low-temperature activity toward small synthetic substrates. All mutations (S100P, G108S, D114G, M137T, T153A, and S246N) identified in the cold-adapted variants occurred within or near the substrate-binding region. None of these mutations, however, match the corresponding sites in naturally psychrophilic and other artificially cold-adapted subtilases, implying there are multiple routes to cold adaptation. Homology modeling and structural analysis demonstrated that these mutations led to an increase in mobility of substrate-binding region and a modulation of substrate specificity, which seemed to account for the improvement of the enzyme's catalytic activity toward macromolecular substrates at lower temperatures. Our study may provide valuable information needed to develop enzymes coupling high stability and high low-temperature activity, which are highly desired for industrial use. Biotechnol. Bioeng. 2009; 104: 862,870. © 2009 Wiley Periodicals, Inc. [source] | |||||||||||||