Adjustment to inflammatory bowel disease: The relative influence of illness perceptions and coping

Background: The Common Sense Model (CSM) of illness representations was used in the current study to examine the relative contribution of illness perceptions and coping strategies in explaining adjustment to inflammatory bowel disease (IBD). Methods: Participants were 80 adults consecutively attending an outpatients' clinic with a diagnosis of either Crohn's disease or ulcerative colitis. Respondents completed and returned a questionnaire booklet that assessed illness perceptions, coping, and adjustment. Adjustment was measured from the perspectives of psychological distress, quality of life, and functional independence. Results: Illness perceptions (particularly perception of consequences of IBD) were uniformly the most consistent variables explaining adjustment to IBD. Coping did not significantly add to predicting adjustment once illness perceptions were controlled for and therefore did not mediate the relationship between illness perceptions and adjustment, as proposed in the CSM. Conclusions: The results suggest the importance of addressing illness perceptions in developing appropriate psychological interventions for IBD.

Antidepressant specificity of serotonin transporter suggested by three LeuT-SSRI structures.

Sertraline and fluoxetine are selective serotonin re-uptake inhibitors (SSRIs) that are widely prescribed to treat depression. They exert their effects by inhibiting the presynaptic plasma membrane serotonin transporter (SERT). All SSRIs possess halogen atoms at specific positions, which are key determinants for the drugs' specificity for SERT. For the SERT protein, however, the structural basis of its specificity for SSRIs is poorly understood. Here we report the crystal structures of LeuT, a bacterial SERT homolog, in complex with sertraline, R-fluoxetine or S-fluoxetine. The SSRI halogens all bind to exactly the same pocket within LeuT. Mutation at this halogen-binding pocket (HBP) in SERT markedly reduces the transporter's affinity for SSRIs but not for tricyclic antidepressants. Conversely, when the only nonconserved HBP residue in both norepinephrine and dopamine transporters is mutated into that found in SERT, their affinities for all the three SSRIs increase uniformly. Thus, the specificity of SERT for SSRIs is dependent largely on interaction of the drug halogens with the protein's HBP.

Vaginal delivery of the recombinant HIV-1 clade-C trimeric gp140 envelope protein CN54gp140 within novel rheologically structured vehicles elicits specific immune responses

Rheologically structured vehicle (RSV) gels were developed as delivery systems for vaginal mucosal vaccination with an HIV-1 envelope glycoprotein (CN54gp140). RSVs comprised a mucoadhesive matrix forming and vaginal fluid absorbing polymer. The mucoadhesive and rheological properties of the RSVs were evaluated in vitro, and the distribution, antigenicity and release of CN54gp140 were analysed by ELISA. CN54gp140 was uniformly distributed within the RSVs and continuously released in vitro in an antigenically intact form over 24 h. Vaginal administration to rabbits induced specific serum IgG, and IgG and IgA in genital tract secretions. The RSVs are a viable delivery modality for vaginal immunization.

Unconditional constants and polynomial inequalities

If P is a polynomial on Rm of degree at most n then we define the polynomial |P|. Now if B is a convex compact set in Rm, we define the norm ||P||B of P as the maximum of P on B, and then we investigate the inequality || |P| ||B

Convergence of bimodules over maximal abelian selfadjoint algebras

We prove a continuity result for the map sending a masa-bimodule to its support. We characterise the convergence of a net of weakly closed convex hulls of bilattices in terms of the convergence of the corresponding supports, and establish a lower-semicontinuity result for the map sending a support to the corresponding masa-bimodule.

Genetic regulation of the ramA locus and its expression in clinical isolates of Klebsiella pneumoniae

Tigecycline resistance has been attributed to ramA overexpression and subsequent acrA upregulation. The ramA locus, originally identified in Klebsiella pneumoniae, has homologues in Enterobacter and Salmonella spp. In this study, we identify in silico that the ramR binding site is also present in Citrobacter spp. and that Enterobacter, Citrobacter and Klebsiella spp. share key regulatory elements in the control of the romA–ramA locus. RACE (rapid amplification of cDNA ends) mapping indicated that there are two promoters from which romA–ramA expression can be regulated in K. pneumoniae. Correspondingly, electrophoretic binding studies clearly showed that purified RamA and RamR proteins bind to both of these promoters. Hence, there appear to be two RamR binding sites within the Klebsiella romA–ramA locus. Like MarA, RamA binds the promoter region, implying that it might be subject to autoregulation. We have identified changes within ramR in geographically distinct clinical isolates of K. pneumoniae. Intriguingly, levels of romA and ramA expression were not uniformly affected by changes within the ramR gene, thereby supporting the dual promoter finding. Furthermore, a subset of strains sustained no changes within the ramR gene but which still overexpressed the romA–ramA genes, strongly suggesting that a secondary regulator may control ramA expression.

The level sets of the resolvent norm and convexity properties of Banach spaces

We construct a bounded linear operator on a separable, reflexive and strictly convex Banach space whose resolvent norm is constant in a neighbourhood of zero.

RUNX3 protein is overexpressed in human basal cell carcinomas

Basal cell carcinomas (BCC), which are the most common form of skin malignancy, are invariably associated with the deregulation of the Sonic Hedgehog (Shh) signalling pathway. As such, BCC represent a unique model for the study of interactions of the Shh pathway with other genes and pathways. We constructed a tissue microarray (TMA) of 75 paired BCC and normal skin and analysed the expression of beta-catenin and RUNX3, nuclear effectors of the wingless-Int (Wnt) and bone morphogenetic protein/transforming growth factor-beta pathways, respectively. In line with previous reports, we observed varying subcellular expression pattern of beta-catenin in BCC, with 31 cases (41%) showing nuclear accumulation. In contrast, all the BCC cases tested by the TMA showed RUNX3 protein uniformly overexpressed in the nuclei of the cancer cells. Analysis by Western blotting and DNA sequencing indicates that the overexpressed protein is normal and full-length, containing no mutation in the coding region, implicating RUNX3 as an oncogene in certain human cancers. Our results indicate that although the deregulation of Wnt signalling could contribute to the pathogenesis of a subset of BCC, RUNX3 appears to be a universal downstream mediator of a constitutively active Shh pathway in BCC.

On the Capacity of Non-Uniform Phase MIMO Nakagami-m Fading Channels

This letter investigates the ergodic capacity of MIMO Nakagami-m fading channels with both uniformly and non-uniformly distributed phases. We first obtain a tight capacity upper bound for the channel and then derive exact expressions for the low signal-to-noise ratio (SNR) capacity metrics, based on which we examine the impact of fading parameter m on the capacity.

Research intensity and knowledge transfer activity in UK universities

As the innovation process has become more open and networked, Government policy in the UK has sought to promote both research excellence in the university sector and the translation of this into economic benefit through university–business engagement. However, this policy approach has tended to be applied uniformly with little account for organisational differences within the sector. In this paper we consider if differences between universities in their research performance is reflected in their knowledge transfer activity. Specifically, as universities develop a commercialization agenda are the strategic priorities for knowledge transfer, the organisational supports in place to facilitate knowledge transfer and the scale and scope of knowledge transfer activity different for high research intensive (HRI) and low research intensive (LRI) universities? The findings demonstrate that universities’ approach to knowledge transfer is shaped by institutional and organisational resources, in particular their ethos and research quality, rather than the capability to undertake knowledge transfer through a Technology Transfer Office (TTO). Strategic priorities for knowledge transfer are reflected in activity, in terms of the dominance of specific knowledge transfer channels, the partners with which universities engage and the geography of business engagement.

Nonlinear excitations in ferromagnetic chains with nearest and next nearest neighbor exchange interactions

Weakly nonlinear excitations in one-dimensional isotropic Heisenberg ferromagnetic chains with nearest- and next-nearest-neighbor exchange interactions are considered. Based on the properties of modulational stability of corresponding linear spin waves, the existence regions of bright and dark magnetic solitons of the system are discussed in the whole Brillouin zone. The antidark soliton mode which is convex soliton super-imposed with a plane wave component is obtained near the zero-dispersion points of the spin wave frequency spectrum. The analytical results are checked by numerical simulations. [S0163;1829(98)01838-4].

Distribution and abundance of Pale-bellied Brent Geese and Wigeon on Strangford Lough, Northern Ireland

Strangford Lough, County Down holds internationally important numbers of wintering Pale-bellied Brent Geese Branta bernicla hrota with peak counts of up to 16 000. In the past, the Lough was also important for overwintering Wigeon Anas penelope with peak counts up to 20 000 in the early 1970s. However, this population has declined drastically with winter peaks at fewer than 2000 since the mid-1980s. As the overall flyway numbers of Wigeon have not fallen over this period, it has been suggested that the reasons for the decline are intrinsic to Strangford Lough. Wigeon did not decline uniformly throughout Strangford Lough. The greatest fall in numbers occurred on the northern mudflats suggesting a decline in carrying capacity. Factors responsible for this decline may include the reduction of Eelgrass Zostera spp. which is the main food of both species, and increases in human activity near and on the foreshore, especially in the case of Wigeon. Indirect interspecific interactions between Brent Geese and Wigeon are discussed as they may have been significant in reducing the numbers of Wigeon in the system.

NE-LIKE GE SLAB TARGET STUDIES CARRIED OUT AT RAL

The effect of non-uniform target illumination on the soft X-ray lasing output intensity of the J=2-1 Ne-like Ge transitions as a function of length was investigated. As the degree of nonunifonnity increased with length the Ne-like Ge 23.2 and 23.6 nm J=2-1 transitions did not show exponentiation of output intensity. Using an experimentally measured gain-intensity scaling relationship these results were modelled and good qualitative agreement obtained. The model indicates that for Ge targets which are non-uniformly illuminated, even with peak to valley ratios of up to 3 efficient operation can be achieved at between 2-3x threshold intensity. Further studies of the effect of increasing the separation between the two targets of a double target geometry are also presented.

A computational model of cellular response to modulated radiation fields

Purpose:
To develop a model to describe the response of cell populations to spatially modulated radiation exposures of relevance to advanced radiotherapies.

Materials and Methods:
A Monte Carlo model of cellular radiation response was developed. This model incorporated damage from both direct radiation and intercellular communication including bystander signaling. The predictions of this model were compared to previously measured survival curves for a normal human fibroblast line (AGO1522) and prostate tumor cells (DU145) exposed to spatially modulated fields.

Results:
The model was found to be able to accurately reproduce cell survival both in populations which were directly exposed to radiation and those which were outside the primary treatment field. The model predicts that the bystander effect makes a significant contribution to cell killing even in uniformly irradiated cells. The bystander effect contribution varies strongly with dose, falling from a high of 80% at low doses to 25% and 50% at 4 Gy for AGO1522 and DU145 cells, respectively. This was verified using the inducible nitric oxide synthase inhibitor aminoguanidine to inhibit the bystander effect in cells exposed to different doses, which showed significantly larger reductions in cell killing at lower doses.

Conclusions:
The model presented in this work accurately reproduces cell survival following modulated radiation exposures, both in and out of the primary treatment field, by incorporating a bystander component. In addition, the model suggests that the bystander effect is responsible for a significant portion of cell killing in uniformly irradiated cells, 50% and 70% at doses of 2 Gy in AGO1522 and DU145 cells, respectively. This description is a significant departure from accepted radiobiological models and may have a significant impact on optimization of treatment planning approaches if proven to be applicable in vivo.

A Monte Carlo model of DNA double-strand break clustering and rejoining kinetics for the analysis of pulsed-field gel electrophoresis data

In studies of radiation-induced DNA fragmentation and repair, analytical models may provide rapid and easy-to-use methods to test simple hypotheses regarding the breakage and rejoining mechanisms involved. The random breakage model, according to which lesions are distributed uniformly and independently of each other along the DNA, has been the model most used to describe spatial distribution of radiation-induced DNA damage. Recently several mechanistic approaches have been proposed that model clustered damage to DNA. In general, such approaches focus on the study of initial radiation-induced DNA damage and repair, without considering the effects of additional (unwanted and unavoidable) fragmentation that may take place during the experimental procedures. While most approaches, including measurement of total DNA mass below a specified value, allow for the occurrence of background experimental damage by means of simple subtractive procedures, a more detailed analysis of DNA fragmentation necessitates a more accurate treatment. We have developed a new, relatively simple model of DNA breakage and the resulting rejoining kinetics of broken fragments. Initial radiation-induced DNA damage is simulated using a clustered breakage approach, with three free parameters: the number of independently located clusters, each containing several DNA double-strand breaks (DSBs), the average number of DSBs within a cluster (multiplicity of the cluster), and the maximum allowed radius within which DSBs belonging to the same cluster are distributed. Random breakage is simulated as a special case of the DSB clustering procedure. When the model is applied to the analysis of DNA fragmentation as measured with pulsed-field gel electrophoresis (PFGE), the hypothesis that DSBs in proximity rejoin at a different rate from that of sparse isolated breaks can be tested, since the kinetics of rejoining of fragments of varying size may be followed by means of computer simulations. The problem of how to account for background damage from experimental handling is also carefully considered. We have shown that the conventional procedure of subtracting the background damage from the experimental data may lead to erroneous conclusions during the analysis of both initial fragmentation and DSB rejoining. Despite its relative simplicity, the method presented allows both the quantitative and qualitative description of radiation-induced DNA fragmentation and subsequent rejoining of double-stranded DNA fragments. (C) 2004 by Radiation Research Society.