GIP(Lys16PAL) and GIP(Lys37PAL): novel long-acting acylated analogues of glucose-dependent insulinotropic polypeptide with improved antidiabetic potential.

Glucose-dependent insulinotropic polypeptide (GIP) is a physiological insulin releasing peptide. We have developed two novel fatty acid derivatized GIP analogues, which bind to serum albumin and demonstrate enhanced duration of action in vivo. GIP(Lys(16)PAL) and GIP(Lys(37)PAL) were resistant to dipeptidyl peptidase IV (DPP IV) degradation. In vitro studies demonstrated that GIP analogues retained their ability to activate the GIP receptor through production of cAMP and to stimulate insulin secretion. Intraperitoneal administration of GIP analogues to obese diabetic (ob/ob) mice significantly decreased the glycemic excursion and elicited increased and prolonged insulin responses compared to native GIP. A protracted glucose-lowering effect was observed 24 h following GIP(LyS(37)PAL) administration. Once a day injection for 14 days decreased nonfasting glucose, improved glucose tolerance, and enhanced the insulin response to glucose. These data demonstrate that fatty acid derivatized GIP peptides represent a novel class of long-acting stable GIP analogues for therapy of type 2 diabetes.

SOCS3 regulates onset and maintenance of TH2- mediated allergic responses

Members of the suppressor of cytokine signaling (SOCS) family are involved in the pathogenesis of many inflammatory diseases. SOCS-3 is predominantly expressed in T-helper type 2 (TH2) cells, but its role in TH2-related allergic diseases remains to be investigated. In this study we provide a strong correlation between SOCS-3 expression and the pathology of asthma and atopic dermatitis, as well as serum IgE levels in allergic human patients. SOCS-3 transgenic mice showed increased TH2 responses and multiple pathological features characteristic of asthma in an airway hypersensitivity model system. In contrast, dominant-negative mutant SOCS-3 transgenic mice, as well as mice with a heterozygous deletion of Socs3, had decreased TH2 development. These data indicate that SOCS-3 has an important role in regulating the onset and maintenance of TH2-mediated allergic immune disease, and suggest that SOCS-3 may be a new therapeutic target for the development of antiallergic drugs.

Investigation of various growth mechanisms of solid tumour growth within the linear-quadratic model for radiotherapy

The standard linear-quadratic survival model for radiotherapy is used to investigate different schedules of radiation treatment planning to study how these may be affected by different tumour repopulation kinetics between treatments.

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.

Contingency Fit, Institutional Fit, and Firm Performance: A Metafit Approach to Organization–Environment Relationships

In this paper, we attempt to reconcile contingency and institutional fit approaches concerning the organization-environment relationship. While prior scholarly research has examined both theories and compared their impacts on organizational fit and performance, we lay the groundwork for a meta-fit approach by investigating how contingency and institutional fit interact to influence firm performance. We test our theoretical framework using a dataset of 3,259 respondents from 1,904 companies regarding task environmental demands and institutional demands on organizational design across a broad range of industries and firm size classes. Our results show that contingency and institutional fit provide complementary and interdependent explanations of firm performance. Importantly, our findings indicate that for firms under conditions of “quasi-fit” rather than perfect contingency fit or optimal institutional fit, improvements in contingency and/or institutional fit will result in better performance. However, firms with high contingency fit are less vulnerable to deviation from institutional fit in the formation of firm performance, while firms with perfect institutional fit will slightly decrease their performance when they strive to achieve contingency fit.

The chemistry of deuterium in hot molecular cores

This paper presents the results of a model of the chemistry of deuterium-bearing molecules in hot molecular cores. It is found that because hydrogen- and deuterium-bearing molecules are destroyed by the same reactions at about the same rates, the initial fractionation present in ice mantles persists for over 10(4) yr. This is the case for a wide range of physical conditions, so it is safe to infer the fractionation on grain surfaces from observations of deuterated molecules in hot cores. The implications of the observed abundances of deuterium-bearing species in Orion are then discussed.

Climate change and the cost of conserving species in Madagascar

We examined the cost of conserving species as climate changes using Madagascar as an example. We used a Maxent species distribution model to predict the ranges of 74 plant species endemic to the forests of Madagascar from 2000-2080 in three climate scenarios. We set a conservation target of achieving 10,000 hectares of forest cover for each species, and calculated the cost of achieving this target under each climate scenario. We interviewed natural forest restoration project managers and conducted a literature review to obtain the net present cost per hectare of management actions to maintain or establish forest cover. For each species we added hectares of land from lowest to highest cost per additional year of forest cover until the conservation target was achieved throughout the time period. Climate change was predicted to reduce the size of species’ ranges, the overlap between species’ ranges and existing or planned protected areas, and the overlap between species’ ranges and existing forest. As a result, climate change increased the cost of achieving the conservation target by necessitating successively more costly management actions: additional management within existing protected areas (US$0-60/ha), avoidance of forest degradation (loss of biomass) in community-managed areas ($160-576/ha), avoidance of deforestation in unprotected areas ($252-1069/ha), and establishment of forest on non-forested land within protected areas ($802-2710/ha), in community-managed areas ($962-3226/ha), and in unprotected areas ($1054-3719/ha). Our results suggest that though forest restoration may be required for the conservation of some species as climate changes, it is more cost-effective to maintain existing forest wherever possible.

Recent fast electron energy transport experiments relevant to fast ignition inertial fusion

A number of experiments have been undertaken at the Rutherford Appleton Laboratory that were designed to investigate the physics of fast electron transport relevant to fast ignition inertial fusion. The laser, operating at a wavelength of 1054 nm, provided pulses of up to 350 J of energy on target in a duration that varied in the range 0.5-5 ps and a focused intensity of up to 10(21) W cm(-2). A dependence of the divergence of the fast electron beam with intensity on target has been identified for the first time. This dependence is reproduced in two-dimensional particle-in-cell simulations and has been found to be an intrinsic property of the laser-plasma interaction. A number of ideas to control the divergence of the fast electron beam are described. The fractional energy transfer to the fast electron beam has been obtained from calibrated, time-resolved, target rear-surface radiation temperature measurements. It is in the range 15-30%, increasing with incident laser energy on target. The fast electron temperature has been measured to be lower than the ponderomotive potential energy and is well described by Haines' relativistic absorption model.