Computation in Physical Systems: A Normative Mapping Account

The relationship between abstract formal procedures and the activities of actual physical systems has proved to be surprisingly subtle and controversial, and there are a number of competing accounts of when a physical system can be properly said to implement a mathematical formalism and hence perform a computation. I defend an account wherein computational descriptions of physical systems are high-level normative interpretations motivated by our pragmatic concerns. Furthermore, the criteria of utility and success vary according to our diverse purposes and pragmatic goals. Hence there is no independent or uniform fact to the matter, and I advance the ‘anti-realist’ conclusion that computational descriptions of physical systems are not founded upon deep ontological distinctions, but rather upon interest-relative human conventions. Hence physical computation is a ‘conventional’ rather than a ‘natural’ kind

A Characterization of Scale Invariant Responses in Enzymatic Networks

An ubiquitous property of biological sensory systems is adaptation: a step increase in stimulus triggers an initial change in a biochemical or physiological response, followed by a more gradual relaxation toward a basal, pre-stimulus level. Adaptation helps maintain essential variables within acceptable bounds and allows organisms to readjust themselves to an optimum and non-saturating sensitivity range when faced with a prolonged change in their environment. Recently, it was shown theoretically and experimentally that many adapting systems, both at the organism and single-cell level, enjoy a remarkable additional feature: scale invariance, meaning that the initial, transient behavior remains (approximately) the same even when the background signal level is scaled. In this work, we set out to investigate under what conditions a broadly used model of biochemical enzymatic networks will exhibit scale-invariant behavior. An exhaustive computational study led us to discover a new property of surprising simplicity and generality, uniform linearizations with fast output (ULFO), whose validity we show is both necessary and sufficient for scale invariance of enzymatic networks. Based on this study, we go on to develop a mathematical explanation of how ULFO results in scale invariance. Our work provides a surprisingly consistent, simple, and general framework for understanding this phenomenon, and results in concrete experimental predictions

Moderate alcohol consumption is associated with better endothelial function: a cross sectional study

<p>Abstract</p> <p>Background</p> <p>Moderate alcohol consumption is protective against coronary artery disease. Endothelial dysfunction contributes to atherosclerosis and the pathogenesis of cardiovascular disease. The effects of alcohol consumption on endothelial function may be relevant to these cardiovascular outcomes, but very few studies have examined the effect of alcohol consumption on endothelial function assessed by flow-mediated dilation (FMD) of the brachial artery in humans.</p> <p>Methods</p> <p>In the population-based Northern Manhattan Study (NOMAS), we performed a cross-sectional analysis of lifetime alcohol intake and brachial artery FMD during reactive hyperemia using high-resolution B-mode ultrasound images among 884 stroke-free participants (mean age 66.8 years, women 56.6%, Hispanic 67.4%, black 17.4%, and white 15.2%).</p> <p>Results</p> <p>The mean brachial FMD was 5.7% and the median was 5.5%. Compared to non-drinkers, those who drank >1 drink/month to 2 drinks/day were more likely to have FMD above the median FMD (5.5%) (unadjusted OR 1.7, 95% CI 1.2–2.4, p = 0.005). In multivariate analysis, the relationship between moderate alcohol consumption and FMD remained significant after adjusting for multiple traditional cardiovascular risk factors, including sex, race-ethnicity, body mass index, diabetes mellitus, coronary artery disease, Framingham risk score, medication use (adjusted OR 1.8, 95%CI 1.1–3.0, p = 0.03). No beneficial effect on FMD was seen for those who drank more than 2 drinks/day.</p> <p>Conclusion</p> <p>In conclusion, consumption of up to 2 alcoholic beverages per day was independently associated with better FMD compared to no alcohol consumption in this multiethnic population. This effect on FMD may represent an important mechanism in explaining the protective effect of alcohol intake on cardiovascular disease.</p

Small-Scale Fisheries Bycatch Jeopardizes Endangered Pacific Loggerhead Turtles

Background. Although bycatch of industrial-scale fisheries can cause declines in migratory megafauna including seabirds, marine mammals, and sea turtles, the impacts of small-scale fisheries have been largely overlooked. Small-scale fisheries occur in coastal waters worldwide, employing over 99 % of the world’s 51 million fishers. New telemetry data reveal that migratory megafauna frequent coastal habitats well within the range of small-scale fisheries, potentially producing high bycatch. These fisheries occur primarily in developing nations, and their documentation and management are limited or non-existent, precluding evaluation of their impacts on non-target megafauna. Principal Findings/Methodology. 30 North Pacific loggerhead turtles that we satellite-tracked from 1996–2005 ranged oceanwide, but juveniles spent 70 % of their time at a high use area coincident with small-scale fisheries in Baja California Sur, Mexico (BCS). We assessed loggerhead bycatch mortality in this area by partnering with local fishers to 1) observe two small-scale fleets that operated closest to the high use area and 2) through shoreline surveys for discarded carcasses. Minimum annual bycatch mortality in just these two fleets at the high use area exceeded 1000 loggerheads year 21, rivaling that of oceanwide industrial-scale fisheries, and threatening the persistence of this critically endangered population. As a result of fisher participation in this study and a bycatch awareness campaign, a consortium of local fishers and other citizens are working to eliminate their bycatch and to establish a national loggerhea

Reduced Expression of Fumarate Hydratase in Clear Cell Renal Cancer Mediates HIF-2α Accumulation and Promotes Migration and Invasion

Germline mutations of FH, the gene that encodes for the tricarboxylic acid TCA (TCA) cycle enzyme fumarate hydratase, are associated with an inherited form of cancer referred to as Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC). Individuals with HLRCC are predisposed to the development of highly malignant and lethal renal cell carcinoma (RCC). The mechanisms of tumorigenesis proposed have largely focused on the biochemical consequences of loss of FH enzymatic activity. While loss of the tumor suppressor gene von Hippel Lindau (VHL) is thought to be an initiating event for the majority of RCCs, a role for FH in sporadic renal cancer has not been explored. Here we report that FH mRNA and protein expression are reduced in clear cell renal cancer, the most common histologic variant of kidney cancer. Moreover, we demonstrate that reduced FH leads to the accumulation of hypoxia inducible factor- 2α (HIF-2α), a transcription factor known to promote renal carcinogenesis. Finally, we demonstrate that overexpression of FH in renal cancer cells inhibits cellular migration and invasion. These data provide novel insights into the tumor suppressor functions of FH in sporadic kidney cancer

An Information Theory Approach to Hypothesis Testing in Criminological Research

Background: This research demonstrates how the Akaike information criterion (AIC) can be an alternative to null hypothesis significance testing in selecting best fitting models. It presents an example to illustrate how AIC can be used in this way. Methods: Using data from Milwaukee, Wisconsin, we test models of place-based predictor variables on street robbery and commercial robbery. We build models to balance explanatory power and parsimony. Measures include the presence of different kinds of businesses, together with selected age groups and social disadvantage. Results: Models including place-based measures of land use emerged as the best models among the set of tested models. These were superior to models that included measures of age and socioeconomic status. The best models for commercial and street robbery include three measures of ordinary businesses, liquor stores, and spatial lag. Conclusions: Models based on information theory offer a useful alternative to significance testing when a strong theoretical framework guides the selection of model sets. Theoretically relevant ‘ordinary businesses’ have a greater influence on robbery than socioeconomic variables and most measures of discretionary businesses

A unified treatment of single component replacement models

In this paper we discuss a general framework for single component replacement models. This framework is based on the regenerative structure of these models and by using results from renewal theory a unified presentation of the discounted and average finite and infinite horizon cost models is given. Finally, some well-known replacement models are discussed, and making use of the previous results an easy derivation of their cost functions is presented