Role of β-adrenergic receptors in the anti-obesity and anti-diabetic effects of zinc-α2-glycoprotien (ZAG)

Objectives: The goal of the current study is to determine whether the ß-adrenoreceptor (ß-AR) plays a role in the anti-obesity and anti-diabetic effects of zinc-a2-glycoprotein (ZAG). Material and methods: This has been investigated in CHO-K1 cells transfected with the human ß1-, ß2-, ß3-AR and in ob/ob mice. Cyclic AMP assays were carried out along with binding studies. Ob/ob mice were treated with ZAG and glucose transportation and insulin were examined in the presence or absence of propranolol. Results: ZAG bound to the ß3-AR with higher affinity (Kd 46±1nM) than the ß2-AR (Kd 71±3nM) while there was no binding to the ß1-AR, and this correlated with the increases in cyclic AMP in CHO-K1 cells transfected with the various ß-AR and treated with ZAG. Treatment of ob/ob mice with ZAG increased protein expression of ß3-AR in gastrocnemius muscle, and in white and brown adipose tissues, but had no effect on expression of ß1- and ß2-AR. A reduction of body weight was seen and urinary glucose excretion, increase in body temperature, reduction in maximal plasma glucose and insulin levels in the oral glucose tolerance test, and stimulation of glucose transport into skeletal muscle and adipose tissue, were completely attenuated by the non-specific ß-AR antagonist propranolol. Conclusion: The results suggest that the effects of ZAG on body weight and insulin sensitivity in ob/ob mice are manifested through a ß-3AR, or possibly a ß2-AR.

Role of β-adrenergic receptors in the oral activity of zinc-α2-glycoprotein (ZAG)

Zinc-a2-glycoprotein (ZAG) is an adipokine with the potential as a therapeutic agent in the treatment of obesity and type 2 diabetes. In this study we show that human ZAG, which is a 41-kDa protein, when administered to ob/ob mice at 50 µg/d-1 orally in the drinking water produced a progressive loss of body weight (5 g after 8 d treatment), together with a 0.5 C increase in rectal temperature and a 40% reduction in urinary excretion of glucose. There was also a 33% reduction in the area under the curve during an oral glucose tolerance test and an increased sensitivity to insulin. These results were similar to those after iv administration of ZAG. However, tryptic digestion was shown to inactivate ZAG. There was no evidence of human ZAG in the serum but a 2-fold elevation of murine ZAG, which was also observed in target tissues such as white adipose tissue. To determine whether the effect was due to interaction of the human ZAG with the ß-adrenergic (ß-AR) in the gastrointestinal tract before digestion, ZAG was coadministered to ob/ob mice together with propanolol (40 mg/kg-1), a nonspecific ß-AR antagonist. The effect of ZAG on body weight, rectal temperature, urinary glucose excretion, improvement in glucose disposal, and increased insulin sensitivity were attenuated by propanolol, as was the increase in murine ZAG in the serum. These results suggest that oral administration of ZAG increases serum levels through interaction with a ß-AR in the upper gastrointestinal tract, and gene expression studies showed this to be in the esophagus.

Network lifetime maximization with cross-layer design in wireless sensor networks

This paper investigates a cross-layer design approach for minimizing energy consumption and maximizing network lifetime (NL) of a multiple-source and single-sink (MSSS) WSN with energy constraints. The optimization problem for MSSS WSN can be formulated as a mixed integer convex optimization problem with the adoption of time division multiple access (TDMA) in medium access control (MAC) layer, and it becomes a convex problem by relaxing the integer constraint on time slots. Impacts of data rate, link access and routing are jointly taken into account in the optimization problem formulation. Both linear and planar network topologies are considered for NL maximization (NLM). With linear MSSS and planar single-source and single-sink (SSSS) topologies, we successfully use Karush-Kuhn-Tucker (KKT) optimality conditions to derive analytical expressions of the optimal NL when all nodes are exhausted simultaneously. The problem for planar MSSS topology is more complicated, and a decomposition and combination (D&C) approach is proposed to compute suboptimal solutions. An analytical expression of the suboptimal NL is derived for a small scale planar network. To deal with larger scale planar network, an iterative algorithm is proposed for the D&C approach. Numerical results show that the upper-bounds of the network lifetime obtained by our proposed optimization models are tight. Important insights into the NL and benefits of cross-layer design for WSN NLM are obtained.

2 μm mode-locked thulium doped fiber laser using tilted fiber grating

A nonlinear polarization rotation based all-fiber passively mode-locked Tm3+-doped fiber laser is demonstrated by using a 45° tilted fiber grating (TFG) as an in-line polarizer. Stable soliton pulses centered at 1992.7 nm with 2.02 nm FWHM bandwidth were produced at a repetition rate of 1.902 MHz with pulse duration of 2.2 ps and pulse energy of 74.6 pJ. With the increased pump power, the laser also can operate at noise-like regime with 18.1 nm FWHM bandwidth and pulse energy of up to 250.1 nJ. Using the same 45° TFG, both stable soliton and noise-like mode-locking centered at ∼1970 nm and ∼2050 nm, were also achieved by shortening and extending the length of Tm3+-doped fiber, respectively, exhibiting advantages of broadband and low insertion loss at 2 μm band.

Service differentiation in OFDM-Based IEEE 802.16 networks

IEEE 802.16 network is widely viewed as a strong candidate solution for broadband wireless access systems. Various flexible mechanisms related to QoS provisioning have been specified for uplink traffic at the medium access control (MAC) layer in the standards. Among the mechanisms, bandwidth request scheme can be used to indicate and request bandwidth demands to the base station for different services. Due to the diverse QoS requirements of the applications, service differentiation (SD) is desirable for the bandwidth request scheme. In this paper, we propose several SD approaches. The approaches are based on the contention-based bandwidth request scheme and achieved by the means of assigning different channel access parameters and/or bandwidth allocation priorities to different services. Additionally, we propose effective analytical model to study the impacts of the SD approaches, which can be used for the configuration and optimization of the SD services. It is observed from simulations that the analytical model has high accuracy. Service can be efficiently differentiated with initial backoff window in terms of throughput and channel access delay. Moreover, the service differentiation can be improved if combined with the bandwidth allocation priority approach without adverse impacts on the overall system throughput.

Design and fabrication of fibre Bragg gratings with V-shaped dispersion profile for multi-channel signal processing

We have designed and fabricated a new type of fibre Bragg grating (FBG) with a V-shaped dispersion profile for multi-channel dispersion compensation in communication links.

Soliton transmission at 10 Gbit/s over 2022 km of standard fibre with dispersion compensation

We present experimental results of 10 Gbit/s, 20 ps soliton data transmission over standard fibre, dispersion compensated to 0.5 ps/nm/km. Acceptable Q values were measured to a distance of 2022 km.

Signal power excursion and pump efficiency in quasi-lossless ultra-long Raman laser links

Performance optimisation of ultra-long Raman laser links is studied theoretically and experimentally. We observe that it is possible to reduce signal power excursion by adjusting FBG reflectivity without compromising pump efficiency.

Population pharmacokinetic and pharmacogenetic analysis of 6-mercaptopurine in paediatric patients with acute lymphoblastic leukaemia

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The cytotoxic effects of 6-mercaptopurine (6-MP) were found to be due to drug-derived intracellular metabolites (mainly 6-thioguanine nucleotides and to some extent 6-methylmercaptopurine nucleotides) rather than the drug itself. • Current empirical dosing methods for oral 6-MP result in highly variable drug and metabolite concentrations and hence variability in treatment outcome. WHAT THIS STUDY ADDS • The first population pharmacokinetic model has been developed for 6-MP active metabolites in paediatric patients with acute lymphoblastic leukaemia and the potential demographic and genetically controlled factors that could lead to interpatient pharmacokinetic variability among this population have been assessed. • The model shows a large reduction in interindividual variability of pharmacokinetic parameters when body surface area and thiopurine methyltransferase polymorphism are incorporated into the model as covariates. • The developed model offers a more rational dosing approach for 6-MP than the traditional empirical method (based on body surface area) through combining it with pharmacogenetically guided dosing based on thiopurine methyltransferase genotype. AIMS - To investigate the population pharmacokinetics of 6-mercaptopurine (6-MP) active metabolites in paediatric patients with acute lymphoblastic leukaemia (ALL) and examine the effects of various genetic polymorphisms on the disposition of these metabolites. METHODS - Data were collected prospectively from 19 paediatric patients with ALL (n = 75 samples, 150 concentrations) who received 6-MP maintenance chemotherapy (titrated to a target dose of 75 mg m−2 day−1). All patients were genotyped for polymorphisms in three enzymes involved in 6-MP metabolism. Population pharmacokinetic analysis was performed with the nonlinear mixed effects modelling program (nonmem) to determine the population mean parameter estimate of clearance for the active metabolites. RESULTS - The developed model revealed considerable interindividual variability (IIV) in the clearance of 6-MP active metabolites [6-thioguanine nucleotides (6-TGNs) and 6-methylmercaptopurine nucleotides (6-mMPNs)]. Body surface area explained a significant part of 6-TGNs clearance IIV when incorporated in the model (IIV reduced from 69.9 to 29.3%). The most influential covariate examined, however, was thiopurine methyltransferase (TPMT) genotype, which resulted in the greatest reduction in the model's objective function (P < 0.005) when incorporated as a covariate affecting the fractional metabolic transformation of 6-MP into 6-TGNs. The other genetic covariates tested were not statistically significant and therefore were not included in the final model. CONCLUSIONS - The developed pharmacokinetic model (if successful at external validation) would offer a more rational dosing approach for 6-MP than the traditional empirical method since it combines the current practice of using body surface area in 6-MP dosing with a pharmacogenetically guided dosing based on TPMT genotype.

Ultra-long laser cavities for non-repeated fibre transmission

We propose the use of ultra-long laser cavities for non-repeated fibre communication. We perform a comparison based on nonlinearity management theory between the performance of ultra-long cavities and other amplification schemes for non-repeated transmission.

Experimental comparison of fibre and grating-based dispersion compensation schemes for 40 channel 10Gb/s DWDM systems

We report an experimental comparison between broadband fibre Bragg gratings (FBGs) and conventional dispersion compensating fibre (DCF) for a 40 x 10Gb/s DWDM system over 525km. A performanceoptimised configuration using FBG compensators is presented.

Performance comparison of duobinary modulation formats for 40 Gb/s long-haul WDM transmissions

With their compact spectrum and high tolerance to residual chromatic dispersion, duobinary formats are attractive for the deployment of 40 Gb/s technology on 10 Gb/s WDM Long-Haul transmission infrastructures. Here, we compare the robustness of various duobinary formats when facing 40 Gb/s transmission impairments.

Subjective quality evaluation for voice communication over MANET

Due to the dynamic and mutihop nature of the Mobile Ad-hoc Network (MANET), voice communication over MANET may encounter many challenges. We set up a subjective quality evaluation model using ITU-T E-model with extension. And through simulation in NS-2, we evaluate how the following factors impact voice quality in MANET: the number of hops, the number of route breakages, the number of communication pairs and the background traffic. Using AODV as the underlying routing protocol, and with the MAC layer changed from 802.11 DCF to 802.11e EDCF, we observe that 802.11e is more suitable for implementating voice communication over MANET. © 2005 IEEE.

Polarizing fibre Bragg grating filters and its fibre laser application

Poster