Mechanism of action of 5-arninosalicylic acid

5-Aminosalicylic Acid (5-ASA) has been used for over 50 years in the treatment of inflammatory bowel disease in the pro-drug form sulphasalazine (SASP). SASP is also used to treat rheumatoid arthritis. However whether the therapeutic properties of SASP are due to the intact molecule, the 5-ASA or sulphapyridine components is unknown. Several mechanisms of action have been proposed for 5-ASA and SASP including interference in the metabolism of arachidonic acid to prostaglandins and leukotrienes, scavenging,of reactive oxygen species, effects on leucocyte function and production of cytokines. However, it is unlikely that the anti-inflammatory properties of SASP and 5-ASA are due to several different properties but more likely that a single property of 5-ASA explains the theraapeutic effects of 5-ASA and SASP. Reactive oxygen species (ROS) are involved in the metabolism of prostaglandins and leukotrienes and can act as second messengers, and so the scavenging of ROS may be the single mechanism of action of 5-ASA that gives rise to its antiinflammatory effects in both inflammatory bowel disease and rheumatoid arthritis

Thermonuclear Reaction Rate of 23Mg(p,gamma)24$Al

Updated stellar rates for the reaction 23Mg(p,gamma)24Al are calculated by using all available experimental information on 24Al excitation energies. Proton and gamma-ray partial widths for astrophysically important resonances are derived from shell model calculations. Correspondences of experimentally observed 24Al levels with shell model states are based on application of the isobaric multiplet mass equation. Our new rates suggest that the 23Mg(p,gamma)24Al reaction influences the nucleosynthesis in the mass A>20 region during thermonuclear runaways on massive white dwarfs.Comment: 13 pages (uses Revtex) including 3 postscript figures (uses epsfig.sty), accepted for publication in Phys. Rev.

What’s Worth Talking About? Information Theory Reveals How Children Balance Informativeness and Ease of Production

Of all the things we could say, what determines what is worth saying? Greenfield’s principle of informativeness states that, right from the onset of language, humans selectively comment on whatever they find unexpected. We quantify this tendency using information theoretic measures, and test the counterintuitive prediction that children will produce words that are low frequency given the context because these will be most informative. Using corpora of child directed speech, we identified adjectives that varied in how informative (i.e., unexpected) they were given the noun they modified. Three-year-olds (N=31, replication N=13) heard an experimenter use these adjectives to describe pictures. The children’s task was then to describe the pictures to another person. As the information content of the experimenter’s adjective increased, so did children’s tendency to comment on the feature that adjective had encoded. Furthermore, our analyses suggest that children balance this informativeness with a competing drive to ease production

SCRIB expression is deregulated in human prostate cancer, and its deficiency in mice promotes prostate neoplasia

Loss of cellular polarity is a hallmark of epithelial cancers, raising the possibility that regulators of polarity have a role in suppressing tumorigenesis. The Scribble complex is one of at least three interacting protein complexes that have a critical role in establishing and maintaining epithelial polarity. In human colorectal, breast, and endometrial cancers, expression of the Scribble complex member SCRIB is often mislocalized and deregulated. Here, we report that Scrib is indispensable for prostate homeostasis in mice. Scrib heterozygosity initiated prostate hyperplasia, while targeted biallelic Scrib loss predisposed mice to prostate intraepithelial neoplasia. Mechanistically, Scrib was shown to negatively regulate the MAPK cascade to suppress tumorigenesis. Further analysis revealed that prostate-specific loss of Scrib in mice combined with expression of an oncogenic Kras mutation promoted the progression of prostate cancer that recapitulated the human disease. The clinical significance of the work in mice was highlighted by our observation that SCRIB deregulation strongly correlated with poor survival in human prostate cancer. These data suggest that the polarity network could provide a new avenue for therapeutic intervention

SPRWeb: preserving subjective responses to website colour schemes through automatic recolouring

Colours are an important part of user experiences on the Web. Colour schemes influence the aesthetics, first impressions and long-term engagement with websites. However, five percent of people perceive a subset of all colours because they have colour vision deficiency (CVD), resulting in an unequal and less-rich user experience on the Web. Traditionally, people with CVD have been supported by recolouring tools that improve colour differentiability, but do not consider the subjective properties of colour schemes while recolouring. To address this, we developed SPRWeb, a tool that recolours websites to preserve subjective responses and improve colour differentiability - thus enabling users with CVD to have similar online experiences. To develop SPRWeb, we extended existing models of non-CVD subjective responses to CVD, then used this extended model to steer the recolouring process. In a lab study, we found that SPRWeb did significantly better than a standard recolouring tool at preserving the temperature and naturalness of websites, while achieving similar weight and differentiability preservation. We also found that recolouring did not preserve activity, and hypothesize that visual complexity influences activity more than colour. SPRWeb is the first tool to automatically preserve the subjective and perceptual properties of website colour schemes thereby equalizing the colour-based web experience for people with CVD.Engineering and Applied Science

Linearization of Cohomology-free Vector Fields

We study the cohomological equation for a smooth vector field on a compact manifold. We show that if the vector field is cohomology free, then it can be embedded continuously in a linear flow on an Abelian group

Multi-layer scintillation detector for the MOON double beta decay experiment: Scintillation photon responses studied by a prototype detector MOON-1

An ensemble of multi-layer scintillators is discussed as an option of the high-sensitivity detector Mo Observatory Of Neutrinos (MOON) for spectroscopic measurements of neutrino-less double beta decays. A prototype detector MOON-1, which consists of 6 layer plastic-scintillator plates, was built to study the sensitivity of the MOON-type detector. The scintillation photon collection and the energy resolution, which are key elements for the high-sensitivity experiments, are found to be 1835+/-30 photo-electrons for 976 keV electrons and sigma = 2.9+/-0.1% (dE/E = 6.8+/-0.3 % in FWHM) at the Qbb ~ 3 MeV region, respectively. The multi-layer plastic-scintillator structure with good energy resolution as well as good background suppression of beta-gamma rays is crucial for the MOON-type detector to achieve the inverted hierarchy neutrino mass sensitivity.Comment: 8 pages, 16 figures, submitted to Nucl.Instrum.Met

A four-year, systems-wide intervention promoting interprofessional collaboration

Background: A four-year action research study was conducted across the Australian Capital Territory health system to strengthen interprofessional collaboration (IPC) through multiple intervention activities. Methods: We developed 272 substantial IPC intervention activities involving 2,407 face-to-face encounters with health system personnel. Staff attitudes toward IPC were surveyed yearly using Heinemann et al’s Attitudes toward Health Care Teams and Parsell and Bligh’s Readiness for Interprofessional Learning scales (RIPLS). At study’s end staff assessed whether project goals were achieved. Results: Of the improvement projects, 76 exhibited progress, and 57 made considerable gains in IPC. Educational workshops and feedback sessions were well received and stimulated interprofessional activities. Over time staff scores on Heinemann’s Quality of Interprofessional Care subscale did not change significantly and scores on the Doctor Centrality subscale increased, contrary to predictions. Scores on the RIPLS subscales of Teamwork & Collaboration and Professional Identity did not alter. On average for the assessment items 33% of staff agreed that goals had been achieved, 10% disagreed, and 57% checked ‘neutral’. There was most agreement that the study had resulted in increased sharing of knowledge between professions and improved quality of patient care, and least agreement that between-professional rivalries had lessened and communication and trust between professions improved. Conclusions: Our longitudinal interventional study of IPC involving multiple activities supporting increased IPC achieved many project-specific goals, but improvements in attitudes over time were not demonstrated and neutral assessments predominated, highlighting the difficulties faced by studies targeting change at the systems level and over extended periods

Lifeworld Inc. : and what to do about it

Can we detect changes in the way that the world turns up as they turn up? This paper makes such an attempt. The first part of the paper argues that a wide-ranging change is occurring in the ontological preconditions of Euro-American cultures, based in reworking what and how an event is produced. Driven by the security – entertainment complex, the aim is to mass produce phenomenological encounter: Lifeworld Inc as I call it. Swimming in a sea of data, such an aim requires the construction of just enough authenticity over and over again. In the second part of the paper, I go on to argue that this new world requires a different kind of social science, one that is experimental in its orientation—just as Lifeworld Inc is—but with a mission to provoke awareness in untoward ways in order to produce new means of association. Only thus, or so I argue, can social science add to the world we are now beginning to live in

Conformational Preferences of a 14-Residue Fibrillogenic Peptide from Acetylcholinesterase†

A 14-residue fragment from near the C-terminus of the enzyme acetylcholinesterase (AChE) is believed to have a neurotoxic/neurotrophic effect acting via an unknown pathway. While the peptide is α-helical in the full-length enzyme, the structure and association mechanism of the fragment are unknown. Using multiple molecular dynamics simulations, starting from a tetrameric complex of the association domain of AChE and systematicall disassembled subsets that include the peptide fragment, we show that the fragment is incapable of retaining its helicity in solution. Extensive replica exchange Monte Carlo folding and unfolding simulations in implicit solvent with capped and uncappted termini failed to converge to any consistent cluster of structures, suggesting that the fragment remains largely unstructured in solution under the conditions considered. Furthermore, extended molecular dynamics simulations of two steric zipper models show that the peptide is likely to form a zipper with antiparallel sheets and that peptides with mutations known to prevent fibril formation likely do so by interfering with this packing. The results demonstrate how the local environment of a peptide can stabilize a particular conformation