Analysis of void volumes in proteins and application to stability of the p53 tumour suppressor protein

We have developed a new method for the analysis of voids in proteins (defined as empty cavities not accessible to solvent). This method combines analysis of individual discrete voids with analysis of packing quality. While these are different aspects of the same effect, they have traditionally been analysed using different approaches. The method has been applied to the calculation of total void volume and maximum void size in a non-redundant set of protein domains and has been used to examine correlations between thermal stability and void size. The tumour-suppressor protein p53 has then been compared with the non-redundant data set to determine whether its low thermal stability results from poor packing. We found that p53 has average packing, but the detrimental effects of some previously unexplained mutations to p53 observed in cancer can be explained by the creation of unusually large voids. (C) 2004 Elsevier Ltd. All rights reserved.

A new theory of educational change - punctuated equilibrium: the case of the internationalisation of Higher Education institutions

This article argues for a new theoretical paradigm for the analysis of change in educational institutions that is able to deal with such issues as readiness for change, transformational change and the failure of change strategies. Punctuated equilibrium (Tushman and Romanelli, 1985) is a theory which has wide application. It envisages long-term change as being made up of a succession of long periods of relative stability interspersed by brief periods of rapid profound change. In the periods of stability only relatively small incremental changes are possible. The periods of transformational change may be triggered by external or internal influences. A recent study of the long-term process of internationalisation in higher education institutions shows evidence to support the theory: long periods of incremental change, events precipitating profound change and the failure of externally imposed attempts to change. Also, as the theory predicts, changes in collegial organisations are slower and more uncertain than changes in managed organisations.

The effect of windstress change on future sea level change in the Southern Ocean

AOGCMs of the two latest phases (CMIP3 and CMIP5) of the Coupled Model Intercomparison Project, like earlier AOGCMs, predict large regional variations in future sea level change. The model-mean pattern of change in CMIP3 and CMIP5 is very similar, and its most prominent feature is a zonal dipole in the Southern Ocean: sea level rise is larger than the global mean north of 50°S and smaller than the global mean south of 50°S in most models. The individual models show widely varying patterns, although the inter-model spread in local sea level change is smaller in CMIP5 than in CMIP3. Here we investigate whether changes in windstress can explain the different patterns of projected sea level change, especially the Southern Ocean feature, using two AOGCMs forced by the changes in windstress from the CMIP3 and CMIP5 AOGCMs. We show that the strengthening and poleward shift of westerly windstress accounts for the most of the large spread among models in magnitude of this feature. In the Indian, North Pacific and Arctic Oceans, the windstress change is influential, but does not completely account for the projected sea level change.

Plane wave discontinuous Galerkin methods for the 2D Helmholtz equation: analysis of the $p$-version

Plane wave discontinuous Galerkin (PWDG) methods are a class of Trefftz-type methods for the spatial discretization of boundary value problems for the Helmholtz operator $-\Delta-\omega^2$, $\omega>0$. They include the so-called ultra weak variational formulation from [O. Cessenat and B. Després, SIAM J. Numer. Anal., 35 (1998), pp. 255–299]. This paper is concerned with the a priori convergence analysis of PWDG in the case of $p$-refinement, that is, the study of the asymptotic behavior of relevant error norms as the number of plane wave directions in the local trial spaces is increased. For convex domains in two space dimensions, we derive convergence rates, employing mesh skeleton-based norms, duality techniques from [P. Monk and D. Wang, Comput. Methods Appl. Mech. Engrg., 175 (1999), pp. 121–136], and plane wave approximation theory.

Use of nutritional complete supplements in older adults with dementia: systematic review and meta-analysis of clinical outcomes

Background & Aims: Malnutrition is prevalent in people diagnosed with dementia however ensuring adequate oral intake within this group is often problematic. It is important to determine whether providing nutritionally complete oral nutritional supplements (ONS) drinks is an effective way of improving clinical outcomes for older people with dementia. This paper systematically reviewed clinical, wellbeing and nutritional outcomes in people with long-term cognitive impairment. Methods: The CINAHL, Medline and EMBASE databases were searched from their inception until January 2012. Reference lists of the included papers, foreign language papers and review articles obtained were manually searched. Results: Twelve articles were included in the review containing 1076 people in the supplement groups (intervention) and 748 people in the control groups. Meta-analysis shows there was a significant improvement in weight (p=<0.0001), Body Mass Index (BMI) (p=<0.0001) and cognition at 6.5+/-3.9 month follow up (p=0.002) when supplements were given compared to the control group. Conclusions: Providing ONS drinks has a positive effect on weight gain and cognition at follow up in older people with dementia. Additional research is required in both comparing nutritional supplements to vitamin/mineral tablets and high protein/calorie shots and clinical outcomes relevant to hospitalised people with dementia.

Landscape change in central Latvia since the Iron Age: multi-proxy analysis of the vegetation impact of conflict, colonization and economic expansion during the last 2000 years

This study represents the first detailed multi-proxy palaeoenvironmental investigation associated with a Late Iron Age lake-dwelling site in the eastern Baltic. The main objective was to reconstruct the environmental and vegetation dynamics associated with the establishment of the lake-dwelling and land-use during the last 2,000 years. A lacustrine sediment core located adjacent to a Late Iron Age lake-dwelling, medieval castle and Post-medieval manor was sampled in Lake Āraiši. The core was dated using spheroidal fly-ash particles and radiocarbon dating, and analysed in terms of pollen, non-pollen palynomorphs, diatoms, loss-on-ignition, magnetic susceptibility and element geochemistry. Associations between pollen and other proxies were statistically tested. During ad 1–700, the vicinity of Lake Āraiši was covered by forests and human activities were only small-scale with the first appearance of cereal pollen (Triticum and Secale cereale) after ad 400. The most significant changes in vegetation and environment occurred with the establishment of the lake-dwelling around ad 780 when the immediate surroundings of the lake were cleared for agriculture, and within the lake there were increased nutrient levels. The highest accumulation rates of coprophilous fungi coincide with the occupation of the lake-dwelling from ad 780–1050, indicating that parts of the dwelling functioned as byres for livestock. The conquest of tribal lands during the crusades resulted in changes to the ownership, administration and organisation of the land, but our results indicate that the form and type of agriculture and land-use continued much as it had during the preceding Late Iron Age.

Analysis of the regional pattern of sea level change due to ocean dynamics and density changes for 1993-2099 in observations and CMIP5 AOGCMs

Predictions of twenty-first century sea level change show strong regional variation. Regional sea level change observed by satellite altimetry since 1993 is also not spatially homogenous. By comparison with historical and pre-industrial control simulations using the atmosphere–ocean general circulation models (AOGCMs) of the CMIP5 project, we conclude that the observed pattern is generally dominated by unforced (internal generated) variability, although some regions, especially in the Southern Ocean, may already show an externally forced response. Simulated unforced variability cannot explain the observed trends in the tropical Pacific, but we suggest that this is due to inadequate simulation of variability by CMIP5 AOGCMs, rather than evidence of anthropogenic change. We apply the method of pattern scaling to projections of sea level change and show that it gives accurate estimates of future local sea level change in response to anthropogenic forcing as simulated by the AOGCMs under RCP scenarios, implying that the pattern will remain stable in future decades. We note, however, that use of a single integration to evaluate the performance of the pattern-scaling method tends to exaggerate its accuracy. We find that ocean volume mean temperature is generally a better predictor than global mean surface temperature of the magnitude of sea level change, and that the pattern is very similar under the different RCPs for a given model. We determine that the forced signal will be detectable above the noise of unforced internal variability within the next decade globally and may already be detectable in the tropical Atlantic.