Waterborne exposure to fluorotelomer alcohol 6:2 FTOH alters plasma sex hormone and gene transcription in the hypothalamic-pituitary-gonadal (HPG) axis of zebrafish

Fluorotelomer alcohols (FTOHs) have shown estrogenic activity in vitro and in vivo, but the mechanism of this activity is not known. In this study, 18-week-old zebrafish (Danio rerio) were exposed to 0, 0.03, 0.3 and 3.0 mg/l 1H, 1H, 2H, 2H-perfluorooctan-1-ol (6:2 ETCH) for 7 days, and the effects on plasma sex hormone levels were measured followed by use of real-time PCR to examine selected gene expression in hypothalamic-pituitary-gonadal (HPG) axis and liver. Exposure to 6:2 FTOH significantly increased plasma estradiol (E2) and testosterone (T) levels in both males and females. Furthermore, the ratio of T/E2 was reduced in females while increased in males. In females, the increase of E2 was accompanied by up-regulated hepatic estrogenic receptor alpha (ER alpha) and vitellogenin (VTG1 and VTG3) expression. In males, the elevation of the T level is consistent with the up-regulation of cytochrome P450 c17 alpha-hydroxylase, 17, 20-lase (CYP17) and the down-regulation of cytochrome P450 aromatase A (CYP19A). The present study demonstrated that waterborne exposure to 6:2 FTOH alter plasma sex hormone levels and the ratio of T/E2, as well as the transcriptional profiles of some genes in the HPG axis and liver. The results suggested that FTOHs may disturb fish reproduction through endocrine disrupted activity. (C) 2009 Elsevier B.V. All rights reserved.

Antisense for gonadotropin-releasing hormone reduces gonadotropin synthesis and gonadal development in transgenic common carp (Cyprinus carpio)

Generating transgenic fish with desirable traits (e.g., rapid growth, larger size, etc.) for commercial use has been hampered by concerns for biosafety and competition if these fish are released into the environment. These obstacles may be overcome by producing transgenic fish that are sterile, possibly by inhibiting hormones related to reproduction. In vertebrates, synthesis and release of gonadotropin (GtH) and other reproductive hormones is mediated by gonadotropin-releasing hormone (GnRH). Recently two cDNA sequences encoding salmon-type GnRH (sGnRH) decapeptides were cloned from common carp (Cyprinus carpio). This study analyzed the expression of these two genes using real-time polymerase chain reaction (RT-PCR) in different tissues carp at varying developmental stages. Transcripts of both genes were detected in ovary and testis in mature and regressed, but not in juvenile carp. To evaluate the effects of sGnRH inhibition, the recombinant gene CAsGnRHpc-antisense, expressing antisense sGnRH RNA driven by a carp beta-actin promoter, was constructed. Blocking sGnRH expression using antisense sGnRH significantly decreased GtH in the blood of male transgenic carp. Furthermore, some antisense transgenic fish had no gonadal development and were completely sterile. These data demonstrate that sGnRH is important for GtH synthesis and development of reproductive organs in carp. Also, the antisense sGnRH strategy may prove effective in generating sterile transgenic fish, eliminating environmental concerns these fish may raise. (c) 2007 Published by Elsevier B.V.

Using Warp to Control Network Contention in Mermera

Parallel computing on a network of workstations can saturate the communication network, leading to excessive message delays and consequently poor application performance. We examine empirically the consequences of integrating a flow control protocol, called Warp control [Par93], into Mermera, a software shared memory system that supports parallel computing on distributed systems [HS93]. For an asynchronous iterative program that solves a system of linear equations, our measurements show that Warp succeeds in stabilizing the network's behavior even under high levels of contention. As a result, the application achieves a higher effective communication throughput, and a reduced completion time. In some cases, however, Warp control does not achieve the performance attainable by fixed size buffering when using a statically optimal buffer size. Our use of Warp to regulate the allocation of network bandwidth emphasizes the possibility for integrating it with the allocation of other resources, such as CPU cycles and disk bandwidth, so as to optimize overall system throughput, and enable fully-shared execution of parallel programs.

Identifying sources of global contention in constraint satisfaction search

Much work has been done on learning from failure in search to boost solving of combinatorial problems, such as clause-learning and clause-weighting in boolean satisfiability (SAT), nogood and explanation-based learning, and constraint weighting in constraint satisfaction problems (CSPs). Many of the top solvers in SAT use clause learning to good effect. A similar approach (nogood learning) has not had as large an impact in CSPs. Constraint weighting is a less fine-grained approach where the information learnt gives an approximation as to which variables may be the sources of greatest contention. In this work we present two methods for learning from search using restarts, in order to identify these critical variables prior to solving. Both methods are based on the conflict-directed heuristic (weighted-degree heuristic) introduced by Boussemart et al. and are aimed at producing a better-informed version of the heuristic by gathering information through restarting and probing of the search space prior to solving, while minimizing the overhead of these restarts. We further examine the impact of different sampling strategies and different measurements of contention, and assess different restarting strategies for the heuristic. Finally, two applications for constraint weighting are considered in detail: dynamic constraint satisfaction problems and unary resource scheduling problems.

A k-round Elimination Contention Scheme for WLANs

currently in press. This is the first published attempt to engineer QoS into a contention-based MAC layer protocol. The work was based on a cross-layer approach to providing programmability into wireless LANs. The work arose from an EPSRC grant in the "programmable networks" call, with Philips / STM research in Italy (Dr Melpignano). Subsequent follow-on includes the formation of a spin-out company (TOM) based on the idea.

Query cost estimation through remote system contention states analysis over the Internet

Query processing over the Internet involving autonomous data sources is a major task in data integration. It requires the estimated costs of possible queries in order to select the best one that has the minimum cost. In this context, the cost of a query is affected by three factors: network congestion, server contention state, and complexity of the query. In this paper, we study the effects of both the network congestion and server contention state on the cost of a query. We refer to these two factors together as system contention states. We present a new approach to determining the system contention states by clustering the costs of a sample query. For each system contention state, we construct two cost formulas for unary and join queries respectively using the multiple regression process. When a new query is submitted, its system contention state is estimated first using either the time slides method or the statistical method. The cost of the query is then calculated using the corresponding cost formulas. The estimated cost of the query is further adjusted to improve its accuracy. Our experiments show that our methods can produce quite accurate cost estimates of the submitted queries to remote data sources over the Internet.

A distributed contention-vector division multiple access (D-CVDMA) protocol for wireless networks

Traditional Time Division Multiple Access (TDMA) protocol provides deterministic periodic collision free data transmissions. However, TDMA lacks flexibility and exhibits low efficiency in dynamic environments such as wireless LANs. On the other hand contention-based MAC protocols such as the IEEE 802.11 DCF are adaptive to network dynamics but are generally inefficient in heavily loaded or large networks. To take advantage of the both types of protocols, a D-CVDMA protocol is proposed. It is based on the k-round elimination contention (k-EC) scheme, which provides fast contention resolution for Wireless LANs. D-CVDMA uses a contention mechanism to achieve TDMA-like collision-free data transmissions, which does not need to reserve time slots for forthcoming transmissions. These features make the D-CVDMA robust and adaptive to network dynamics such as node leaving and joining, changes in packet size and arrival rate, which in turn make it suitable for the delivery of hybrid traffic including multimedia and data content. Analyses and simulations demonstrate that D-CVDMA outperforms the IEEE 802.11 DCF and k-EC in terms of network throughput, delay, jitter, and fairness.

Performance models of storage contention in cloud environments

We propose simple models to predict the performance degradation of disk requests due to storage device contention in consolidated virtualized environments. Model parameters can be deduced from measurements obtained inside Virtual Machines (VMs) from a system where a single VM accesses a remote storage server. The parameterized model can then be used to predict the effect of storage contention when multiple VMs are consolidated on the same server. We first propose a trace-driven approach that evaluates a queueing network with fair share scheduling using simulation. The model parameters consider Virtual Machine Monitor level disk access optimizations and rely on a calibration technique. We further present a measurement-based approach that allows a distinct characterization of read/write performance attributes. In particular, we define simple linear prediction models for I/O request mean response times, throughputs and read/write mixes, as well as a simulation model for predicting response time distributions. We found our models to be effective in predicting such quantities across a range of synthetic and emulated application workloads. 

Growth hormone (GH) responsiveness to GHRH in normal adults is not affected by short-term gonadal blockade

The effects of changes in circulating gonadal steroids on GH secretion elicited by GHRH challenge (1µg/kg) in normal adults volunteers (aged 18-24 years), were evaluated in 10 women and 10 men before and after gonadal blockade was achieved by a GnRH agonist (1500 µg/day by nasal spray for 40 days). To see if the effect of testosterone on GH secretion was dependent on its aromatization to estradiol (E), GHRH tests were performed in 7 normal men prior to administration of testosterone enanthate (250 mg im), 8 days after this treatment had began, and again after E receptor blockade with tamoxifen (30 mg for 2 days plus 10 mg on the third day 2 h before the GHRH test, po) administered 8 days after testosterone enanthate. The study of the functional status of the somatotropes at the time of GHRH testing was made according to our previous postulate. Short-term gonadal blockade did not affect the parameters of GH response to GHRH in neither women nor men. Thus, the functional blockade of the gonads may be advisable as an adjunct therapy in the treatment of hypothalamic GH deficiency during the prepubertal stage. In the other group of men, administration of testosterone enanthate significantly increased GHRH-elicited GH release, but this was reverted after E receptor blockade. Since the hypothalamic-somatotrope rhythm was altered by both these farmacological manipulations, it appears that testosterone acts on GH release mainly at the suprapituitary level, and that this action is secondary to its aromatization to E.