Hawks and Doves on Small-World Networks

We explore the Hawk-Dove game on networks with topologies ranging from regular lattices to random graphs with small-world networks in between. This is done by means of computer simulations using several update rules for the population evolutionary dynamics. We find the overall result that cooperation is sometimes inhibited and sometimes enhanced in those network structures, with respect to the mixing population case. The differences are due to different update rules and depend on the gain-to-cost ratio. We analyse and qualitatively explain this behavior by using local topological arguments.Comment: 12 pages, 8 figure

Mechanics of the Ski-Snow Contact

Two outstanding questions of the ski-snow friction are considered: the deformation mode of the snow and the real contact area. The deformation of hard, well sintered snow in a short time impact has been measured with a special linear friction tester. Four types of deformations have been identified: brittle fracture of bonds, plastic deformation of ice at the contact spots, elastic and delayed elastic deformation of the snow matrix. The latter is the dominant deformation in the ski-snow contact. Based on the measured loading curves the mechanical energy dissipation of snow deformation in skiing on hard snow has been determined and found negligible compared to the thermal energy dissipation. A mechanical model consisting of ice spheres supported by rheological elements (a non-linear spring in series with a Kelvin element) is proposed to model the deformation of snow in the ski-snow contact. The model can describe the delayed elastic behaviour of snow. Coupled with the complete topographical description of the snow surface obtained from X-ray micro computer tomography measurements, the model predicts the number and area of contact spots between ski and snow. An average contact spot size of 110μm, and a relative real contact area of 0.4% has been foun

Low income, community poverty and risk of end stage renal disease

BACKGROUND: The risk of end stage renal disease (ESRD) is increased among individuals with low income and in low income communities. However, few studies have examined the relation of both individual and community socioeconomic status (SES) with incident ESRD. METHODS: Among 23,314 U.S. adults in the population-based Reasons for Geographic and Racial Differences in Stroke study, we assessed participant differences across geospatially-linked categories of county poverty [outlier poverty, extremely high poverty, very high poverty, high poverty, neither (reference), high affluence and outlier affluence]. Multivariable Cox proportional hazards models were used to examine associations of annual household income and geospatially-linked county poverty measures with incident ESRD, while accounting for death as a competing event using the Fine and Gray method. RESULTS: There were 158 ESRD cases during follow-up. Incident ESRD rates were 178.8 per 100,000 person-years (105 py) in high poverty outlier counties and were 76.3 /105 py in affluent outlier counties, p trend = 0.06. In unadjusted competing risk models, persons residing in high poverty outlier counties had higher incidence of ESRD (which was not statistically significant) when compared to those persons residing in counties with neither high poverty nor affluence [hazard ratio (HR) 1.54, 95% Confidence Interval (CI) 0.75-3.20]. This association was markedly attenuated following adjustment for socio-demographic factors (age, sex, race, education, and income); HR 0.96, 95% CI 0.46-2.00. However, in the same adjusted model, income was independently associated with risk of ESRD [HR 3.75, 95% CI 1.62-8.64, comparing the < 20,000 income group to the > 75,000 group]. There were no statistically significant associations of county measures of poverty with incident ESRD, and no evidence of effect modification. CONCLUSIONS: In contrast to annual family income, geospatially-linked measures of county poverty have little relation with risk of ESRD. Efforts to mitigate socioeconomic disparities in kidney disease may be best appropriated at the individual level

Thermal expansion, heat capacity and magnetostriction of RAl3_3 (R = Tm, Yb, Lu) single crystals

We present thermal expansion and longitudinal magnetostriction data for cubic RAl3 (R = Tm, Yb, Lu) single crystals. The thermal expansion coefficient for YbAl3 is consistent with an intermediate valence of the Yb ion, whereas the data for TmAl3 show crystal electric field contributions and have strong magnetic field dependencies. de Haas-van Alphen-like oscillations were observed in the magnetostriction data of YbAl3 and LuAl3, several new extreme orbits were measured and their effective masses were estimated. Zero and 140 kOe specific heat data taken on both LuAl3 and TmAl3 for T < 200 K allow for the determination of a CEF splitting scheme for TmAl3

Decreased Striatal RGS2 Expression Is Neuroprotective in Huntington's Disease (HD) and Exemplifies a Compensatory Aspect of HD-Induced Gene Regulation

The molecular phenotype of Huntington's disease (HD) is known to comprise highly reproducible changes in gene expression involving striatal signaling genes. Here we test whether individual changes in striatal gene expression are capable of mitigating HD-related neurotoxicity.We used protein-encoding and shRNA-expressing lentiviral vectors to evaluate the effects of RGS2, RASD2, STEP and NNAT downregulation in HD. Of these four genes, only RGS2 and RASD2 modified mutant htt fragment toxicity in cultured rat primary striatal neurons. In both cases, disease modulation was in the opposite of the predicted direction: whereas decreased expression of RGS2 and RASD2 was associated with the HD condition, restoring expression enhanced degeneration of striatal cells. Conversely, silencing of RGS2 or RASD2 enhanced disease-related changes in gene expression and resulted in significant neuroprotection. These results indicate that RGS2 and RASD2 downregulation comprises a compensatory response that allows neurons to better tolerate huntingtin toxicity. Assessment of the possible mechanism of RGS2-mediated neuroprotection showed that RGS2 downregulation enhanced ERK activation. These results establish a novel link between the inhibition of RGS2 and neuroprotective modulation of ERK activity.Our findings both identify RGS2 downregulation as a novel compensatory response in HD neurons and suggest that RGS2 inhibition might be considered as an innovative target for neuroprotective drug development

Multipole Ordering and Fluctuations in f-Electron Systems

We investigate effects of multipole moments in f-electron systems both from phenomenological and microscopic viewpoints. First, we discuss significant effects of octupole moment on the magnetic susceptibility in a paramagnetic phase. It is found that even within mean-field approximation, the magnetic susceptibility deviates from the Curie-Weiss law due to interactions between dipole and octupole moments. Next, we proceed to a microscopic theory for multipole ordering on the basis of a j-j coupling scheme. After brief explanation of a method to derive multipole interactions from the $f$-electron model, we discuss several multipole ordered phases depending on lattice structure. Finally, we show our new development of the microscopic approach to the evaluation of multipole response functions. We apply fluctuation exchange approximation to the f-electron model, and evaluate multipole response functions.Comment: 7 pages, 4 figures, Proceedings of ASR-WYP-200

Fully developed turbulence and the multifractal conjecture

We review the Parisi-Frisch MultiFractal formalism for Navier--Stokes turbulence with particular emphasis on the issue of statistical fluctuations of the dissipative scale. We do it for both Eulerian and Lagrangian Turbulence. We also show new results concerning the application of the formalism to the case of Shell Models for turbulence. The latter case will allow us to discuss the issue of Reynolds number dependence and the role played by vorticity and vortex filaments in real turbulent flows.Comment: Special Issue dedicated to E. Brezin and G. Paris

Generation and characterization of antibodies specific for caspase-cleaved neo-epitopes: a novel approach

Apoptosis research has been significantly aided by the generation of antibodies against caspase-cleaved peptide neo-epitopes. However, most of these antibodies recognize the N-terminal fragment and are specific for the protein in question. The aim of this project was to create antibodies, which could identify caspase-cleaved proteins without a priori knowledge of the cleavage sites or even the proteins themselves. We hypothesized that many caspase-cleavage products might have a common antigenic shape, given that they must all fit into the same active site of caspases. Rabbits were immunized with the eight most prevalent exposed C-terminal tetrapeptide sequences following caspase cleavage. After purification of the antibodies we demonstrated (1) their specificity for exposed C-terminal (but not internal) peptides, (2) their ability to detect known caspase-cleaved proteins from apoptotic cell lysates or supernatants from apoptotic cell culture and (3) their ability to detect a caspase-cleaved protein whose tetrapeptide sequence differs from the eight tetrapeptides used to generate the antibodies. These antibodies have the potential to identify novel neo-epitopes produced by caspase cleavage and so can be used to identify pathway-specific caspase cleavage events in a specific cell type. Additionally this methodology may be applied to generate antibodies against products of other proteases, which have a well-defined and non-promiscuous cleavage activity

Regional and cellular gene expression changes in human Huntington's disease brain

Huntington's disease (HD) pathology is well understood at a histological level but a comprehensive molecular analysis of the effect of the disease in the human brain has not previously been available. To elucidate the molecular phenotype of HD on a genome-wide scale, we compared mRNA profiles from 44 human HD brains with those from 36 unaffected controls using microarray analysis. Four brain regions were analyzed: caudate nucleus, cerebellum, prefrontal association cortex [Brodmann's area 9 (BA9)] and motor cortex [Brodmann's area 4 (BA4)]. The greatest number and magnitude of differentially expressed mRNAs were detected in the caudate nucleus, followed by motor cortex, then cerebellum. Thus, the molecular phenotype of HD generally parallels established neuropathology. Surprisingly, no mRNA changes were detected in prefrontal association cortex, thereby revealing subtleties of pathology not previously disclosed by histological methods. To establish that the observed changes were not simply the result of cell loss, we examined mRNA levels in laser-capture microdissected neurons from Grade 1 HD caudate compared to control. These analyses confirmed changes in expression seen in tissue homogenates; we thus conclude that mRNA changes are not attributable to cell loss alone. These data from bona fide HD brains comprise an important reference for hypotheses related to HD and other neurodegenerative disease

A large and accurate collection of peptidase cleavages in the MEROPS database

Peptidases are enzymes that hydrolyse peptide bonds in proteins and peptides. Peptidases are important in pathological conditions such as Alzheimer's disease, tumour and parasite invasion, and for processing viral polyproteins. The MEROPS database is an Internet resource containing information on peptidases, their substrates and inhibitors. The database now includes details of cleavage positions in substrates, both physiological and non-physiological, natural and synthetic. There are 39 118 cleavages in the collection; including 34 606 from a total of 10 513 different proteins and 2677 cleavages in synthetic substrates. The number of cleavages designated as ‘physiological’ is 13 307. The data are derived from 6095 publications. At least one substrate cleavage is known for 45% of the 2415 different peptidases recognized in the MEROPS database. The website now has three new displays: two showing peptidase specificity as a logo and a frequency matrix, the third showing a dynamically generated alignment between each protein substrate and its most closely related homologues. Many of the proteins described in the literature as peptidase substrates have been studied only in vitro. On the assumption that a physiologically relevant cleavage site would be conserved between species, the conservation of every site in terms of peptidase preference has been examined and a number have been identified that are not conserved. There are a number of cogent reasons why a site might not be conserved. Each poorly conserved site has been examined and a reason postulated. Some sites are identified that are very poorly conserved where cleavage is more likely to be fortuitous than of physiological relevance. This data-set is freely available via the Internet and is a useful training set for algorithms to predict substrates for peptidases and cleavage positions within those substrates. The data may also be useful for the design of inhibitors and for engineering novel specificities into peptidases