USP1 deubiquitinase: cellular functions, regulatory mechanisms and emerging potential as target in cancer therapy

12 p.

Blue Crab target setting: final report

We have developed a hierarchy of target levels, designated to address sustainability, efficiency, and recovery scenarios. Targets were derived from: 1) reported catches and effort in the commercial fishery, 2) statistics from fishery-independent surveys, and 3) knowledge of the biology of blue crab. Targets that are recommended include population sizes, catches, and effort levels, as well as reference fishing mortality rates. They are intended to be conservative and risk-averse. (PDF contains 182 pages)

Aquatic insects as target organisms for the study of effects of projected climate change in the British Isles

One of the objectives of the Terrestrial Initiative in Global Environmental Research is to assess the sensitivity of British plant and animal species to climate change. The first phase of the program involved the identification of criteria for selecting species suitable for the study of effects of projected climate change in the British Isles. Apart from shallow ponds, annual temperature ranges of 0 to 25 C in temperate freshwater habitats are narrower than those in most temperate terrestrial habitats. Although freshwater organisms have to exist within a narrower range than their terrestrial equivalents, few species can survive throughout their life cycle over the whole temperature range. Field studies on the effects of natural and artificial thermal discharges into streams and rivers have shown that increases in water temperature affect aquatic insects at both the species and community level. Although field data provide valuable information, a more productive approach is to determine experimentally the requirements of different species. Although there are just over 1850 species of aquatic insects in the British Isles, detailed quantitative information on the relationship between temperature and development of eggs, larvae and pupa is available for relatively few species. One exception is the egg stage of stoneflies (Plecoptera). The range for egg hatching in stoneflies clearly show that some species could be threatened while others could benefit from a defined increase in water temperature as a result of climate change. A critical review of the available data on this group would produce a set of equations that could be used to predict the ecological effects of climate change on this group of indicator species.

Ion cascade acceleration from the interaction of a relativistic femtosecond laser pulse with a narrow thin target

Particle-in-cell simulations are performed to study the acceleration of ions due to the interaction of a relativistic femtosecond laser pulse with a narrow thin target. The numerical results show that ions can be accelerated in a cascade by two electrostatic fields if the width of the target is smaller than the laser beam waist. The first field is formed in front of the target by the central part of the laser beam, which pushes the electron layer inward. The major part of the abaxial laser energy propagates along the edges to the rear side of the target and pulls out some hot electrons from the edges of the target, which form another electrostatic field at the rear side of the target. The ions from the front surface are accelerated stepwise by these two electrostatic fields to high energies at the rear side of the target. The simulations show that the largest ion energy gain for a narrow target is about four times higher than in the case of a wide target. (c) 2006 American Institute of Physics.

Characterization of a multi-keV x-ray source produced by nanosecond laser irradiation of a solid target: The influence of laser focus spot and target thickness

The influence of focus spot and target thickness on multi-keV x-ray sources generated by 2 ns duration laser heated solid targets are investigated on the Shenguang II laser facility. In the case of thick-foil targets, the experimental data and theoretical analysis show that the emission volume of the x-ray sources is sensitive to the laser focus spot and proportional to the 3 power of the focus spot size. The steady x-ray flux is proportional to the 5/3 power of the focus spot size of the given laser beam in our experimental condition. In the case of thin-foil targets, experimental data show that there is an optimal foil thickness corresponding to the given laser parameters. With the given laser beam, the optimal thin-foil thickness is proportional to the -2/3 power of the focus spot size, and the optimal x-ray energy of thin foil is independent of focus spot size. (C) 2008 American Institute of Physics.

Influence of target thickness on the generation of high-density ion bunches by ultrashort circularly polarized laser pulses

Ion acceleration by ultrashort circularly polarized laser pulse in a solid-density target is investigated using two-dimensional particle-in-cell simulation. The ions are accelerated and compressed by the continuously extending space-charge field created by the evacuation and compression of the target electrons by the laser light pressure. For a sufficiently thin target, the accelerated and compressed ions can reach and exit from the rear surface as a high-density high-energy ion bunch. The peak ion energy depends on the target thickness and reaches maximum when the compressed ion layer can just reach the rear target surface. The compressed ion layer exhibits lateral striation which can be suppressed by using a sharp-rising laser pulse. (c) 2008 American Institute of Physics.

Generation of plasma intrinsic oscillation at the front surface of a target irradiated by a circularly polarized laser pulse

In laser-target interaction, the effects of laser intensity on plasma oscillation at the front surface of targets have been investigated by one-dimensional particle in cell simulations. The periodical oscillations of the ion density and electrostatic field at the front surface of the targets are reported for the first time, which is considered as an intrinsic property of the target excited by the laser. The oscillation period depends only on initial plasma density and is irrelevant with laser intensity. Flattop structures with curves in ion phase space are found with a more intense laser pulse due to the larger amplitude variation of the electrostatic field. A simple but valid model is proposed to interpret the curves.

Aquatic insects as target organisms for the study of effects of projected climate change in the British Isles

The chief objectives of this brief review are to collate and synthesise quantitative information on the temperature requirements of aquatic insects, and to identify species, and groups of species, that could be useful indicators of climate change and predictors of the ecological effects of change. It arose from the first phase of the Terrestrial Initiative in Global Environmental Research (TIGER), a five-year, NERC Community Programme on the role of the terrestrial biosphere in the science of global change. This phase involved the identification of criteria for selecting species suitable for the study of effects of projected climate change in the British Isles. Field and laboratory studies are reviewed, and criteria for selection of species for future research are suggested. The literature survey shows that no species of aquatic insect can be found to meet all three criteria, but information on the British stoneflies and their eggs already satisfies two of them.

In vivo analysis of interactions between trans-acting factors and their target genes

The investigations presented in this thesis use various in vivo techniques to understand how trans-acting factors control gene expression. The first part addresses the transcriptional regulation of muscle creatine kinase (MCK). MCK expression is activated during the course of development and is found only in differentiated muscle. Several in vivo footprints are observed at the enhancer of this gene, but all of these interactions are limited to cell types that express MCK. This is interesting because two of the footprints appear to represent muscle specific use of general transcription factors, while the other two correspond to sites that can bind the myogenic regulator, MyoD1, in vitro. MyoD1 and these general factors are present in myoblasts, but can bind to the enhancer only in myocytes. This suggests that either the factors themselves are post-translationally modified (phosphorylation or protein:protein interactions), or the accessibility of the enhancer to the factors is limited (changes in chromatin structure). The in vivo footprinting study of MCK was performed with a new ligation mediated, single-sided PCR (polymerase chain reaction) technique that I have developed.

The second half of the thesis concerns the regulation of mouse metallothionein (MT). Metallothioneins are a family of highly conserved housekeeping genes whose expression can be induced by heavy metals, steroids, and other stresses. By adapting a primer extension method of genomic sequencing to in vivo footprinting, I've observed both metal inducible and noninducible interactions at the promoter of MT-I. From these results I've been able to limit the possible mechanisms by which metal responsive trans-acting factors induce transcription. These interpretations correlate with a second line of experiments involving the stable titration of positive acting factors necessary for induction of MT. I've amplified the promoter of MT to 10^2-10^3 copies per cell by fusing the 5' and 3' ends of the MT gene to the coding region of DHFR and selecting cells for methotrexate resistance. In these cells, there is a metal-specific titration effect, and although it acts at the level of transcription, it appears to be independent of direct DNA binding factors.