Modeling of Oxygen Transport and Cellular Energetics Explains Observations on In Vivo Cardiac Energy Metabolism

Observations on the relationship between cardiac work rate and the levels of energy metabolites adenosine triphosphate (ATP), adenosine diphosphate (ADP), and phosphocreatine (CrP) have not been satisfactorily explained by theoretical models of cardiac energy metabolism. Specifically, the in vivo stability of ATP, ADP, and CrP levels in response to changes in work and respiratory rate has eluded explanation. Here a previously developed model of mitochondrial oxidative phosphorylation, which was developed based on data obtained from isolated cardiac mitochondria, is integrated with a spatially distributed model of oxygen transport in the myocardium to analyze data obtained from several laboratories over the past two decades. The model includes the components of the respiratory chain, the F(0)F(1)-ATPase, adenine nucleotide translocase, and the mitochondrial phosphate transporter at the mitochondrial level; adenylate kinase, creatine kinase, and ATP consumption in the cytoplasm; and oxygen transport between capillaries, interstitial fluid, and cardiomyocytes. The integrated model is able to reproduce experimental observations on ATP, ADP, CrP, and inorganic phosphate levels in canine hearts over a range of workload and during coronary hypoperfusion and predicts that cytoplasmic inorganic phosphate level is a key regulator of the rate of mitochondrial respiration at workloads for which the rate of cardiac oxygen consumption is less than or equal to approximately 12 μmol per minute per gram of tissue. At work rates corresponding to oxygen consumption higher than 12 μmol min(−1) g(−1), model predictions deviate from the experimental data, indicating that at high work rates, additional regulatory mechanisms that are not currently incorporated into the model may be important. Nevertheless, the integrated model explains metabolite levels observed at low to moderate workloads and the changes in metabolite levels and tissue oxygenation observed during graded hypoperfusion. These findings suggest that the observed stability of energy metabolites emerges as a property of a properly constructed model of cardiac substrate transport and mitochondrial metabolism. In addition, the validated model provides quantitative predictions of changes in phosphate metabolites during cardiac ischemia

Diphenylchloronitroethane Insecticides

Insecticidal activity of chloronitroalkanes was predicted on the basis of structure-activity relationships. Two series of new bis(substituted-phenyl) chloronitroalkanes were synthesized and evaluated for insecticidal activity. The synthetic pathway proceeded through phenylnitroethanols and diphenylnitroethanes as intermediates. Final products were 1,1-bis (substituted-phenyl)-2-chloro-2-nitroethanes and 1,1-bis(substituted-phenyl)-2,2-dichloro-2-nitroethanes. Aromatic substituents were selected from alkyl, alkoxy, and halogen moieties. Following purifications and confirmation of structures, the compounds were bioassayed against insects. The two series were compared for potency, as were various combinations of X and Y substituents. Adult female house flies (Musca domestica), mosquito larvae (Aedes aegypti), western corn rootworm (Diabrotica virgifera virgifera) and German cockroach (Blattellagermanica) have been tested. In general, the mono-chloro series is more toxic than the di-chloro series. Five of the mono-chloro analogs are 8-10 times more potent than pyrethrins and 6-7 times more toxic than methoxychlor to the house fly

Biodiversity and Ecosystem Informatics: Event and Process Tagging for Information Integration for the International Gulf of Main Watershed

This incubation proposal addresses the issue of integrating large, diverse, and autonomous collections of scientific data within a complex institutional setting. The goal is to convert these autonomous collections into a shareable repository that supports synthesis of data through new metadata structures based on events and processes. The institutional setting is the data and data-gathering activities of over 80 agencies, NGOS, and academic and research institutions operating within the Gulf of Maine watershed. The metadata development will be coordinated by library and spatial information scientists working jointly with domain scientists. An essential task of this incubation effort will be the development of a shared understanding of environmental processes and events that becomes a shareable ontology.Libraries play a vital role in organizing intellectual access to creative works. Scientific data has tended to be outside this traditional purview and has thus lacked the benefits of cataloging and indexing that promote shared access. We are proposing a new metadata structure that exploits common units of analysis in environmental studies: events and processes. Associating scientific data sets with event and process tags, in addition to other metadata elements, can substantially improve the ability to integrate and synthesize diverse scientific collections. The metadata initiative of this proposal will lay the foundation for specifying events and processes through the collaboration of data collections content specialists and information management specialists

Ascaris suum: cDNA microarray analysis of 4th stage larvae (L4) during self-cure from the intestine

There is spontaneous cure of a large portion of Ascaris suum 4th-stage larvae (L4) from the jejunum of infected pigs between 14 and 21 days after inoculation (DAI). Those L4 that remain in the jejunum continue to develop while those that have moved to the ileum are eventually expelled from the intestines. Although increases in intestinal mucosal mast cells and changes in localhost immunity are coincidental with spontaneous cure, the population of L4 that continue to develop in the jejunum may counteract host protective mechanisms by the differential production of factors related to parasitism. To this end, a cDNA library was constructed from L4 isolated from pig jejunum at 21 DAI, and 93% of 1920 original clones containing a single amplicon in the range 400– 1500 bp were verified by gel electrophoresis and printed onto glass slides for microarray analysis. Fluorescent probes were prepared from total RNA isolated from: (1) 3rd stage-larvae from lung at 7 DAI, (L3); (2) L4 from jejunum at 14 DAI (L4-14-J); (3) L4 from jejunum at 21 DAI (L4-21-J); (4) L4 from ileum at 21 DAI (L4-21-I, and; (5) adults (L5). Cy3-labeled L3, L4-14-J, L4-21-I and L5 cDNA, and Cy5-labeled L4-21-J cDNA were simultaneously used to screen the printed arrays containing the L4-21-J-derived cDNA library. Several clones showed consistent differential gene expression over two separate experiments and were grouped into 3 distinct transcription patterns. The data showed that sequences from muscle actin and myosin, ribosomal protein L11, glyceraldehyde-3- phosphate dehydrogenase and the flavoprotein subunit of succinate dehydrogenase were highly expressed in L4-21-J, but not in L4- 21-I; as were a collection of unannotated genes derived from a worm body wall-hypodermis library, and a testes germinal zone tissue library. These results suggest that only actively developing A. suum L4 are destined to parasitize the host and successfully neutralize host protective responses

High Temperature, Wireless Seismometer Sensor for Venus

Space agency mission plans state the need to measure the seismic activity on Venus. Because of the high temperature on Venus (462? C average surface temperature) and the difficulty in placing and wiring multiple sensors using robots, a high temperature, wireless sensor using a wide bandgap semiconductor is an attractive option. This paper presents the description and proof of concept measurements of a high temperature, wireless seismometer sensor for Venus. A variation in inductance of a coil caused by the movement of an aluminum probe held in the coil and attached to a balanced leaf-spring seismometer causes a variation of 700 Hz in the transmitted signal from the oscillator/sensor system at 426? C. This result indicates that the concept may be used on Venus

Iron isotope systematics in estuaries : the case of North River, Massachusetts (USA)

Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Geochimica et Cosmochimica Acta 73 (2009): 4045-4059, doi:10.1016/j.gca.2009.04.026.Recent studies have suggested that rivers may present an isotopically light Fe source to the oceans. Since the input of dissolved iron from river water is generally controlled by flocculation processes that occur during estuarine mixing, it is important to investigate potential fractionation of Fe-isotopes during this process. In this study, we investigate the influence of the flocculation of Fe-rich colloids on the iron isotope composition of pristine estuarine waters and suspended particles. The samples were collected along a salinity gradient from the fresh water to the ocean in the North River estuary (MA, USA). Estuarine samples were filtered at 0.22 μm and the iron isotope composition of the two fractions (dissolved and particles) were analyzed using high resolution MC-ICP-MS after chemical purification. Dissolved iron results show positive δ56Fe values (with an average of 0.43 ± 0.04 ‰) relative to the IRMM-14 standard and do not display any relationships with salinity or with percentage of colloid flocculation. The iron isotopic composition of the particles suspended in fresh water is characterized by more negative δ56Fe values than for dissolved Fe and correlate with the percentage of Fe flocculation. Particulate δ56Fe values vary from -0.09‰ at no flocculation to ~ 0.1‰ at the flocculation maximum, which reflect mixing effects between river-borne particles, lithogenic particles derived from coastal seawaters and newly precipitated colloids. Since the process of flocculation produces minimal Fe-isotope fractionation in the dissolved Fe pool, we suggest that the pristine iron isotope composition of fresh water is preserved during estuarine mixing and that the value of the global riverine source into the ocean can be identified from the fresh water values. However, this study also suggests that δ56Fe composition of rivers can also be characterized by more positive δ56Fe values (up to 0.3 per mil) relative to the crust than previously reported. In order to improve our current understanding of the oceanic iron isotope cycling, further work is now required to determine the processes controlling the fractionation of Fe isotopes during continental run-off.This study was supported by the National Science Foundation (OCE 0550066) to O. Rouxel and Edward Sholkovitz

CellML metadata standards, associated tools and repositories

The development of standards for encoding mathematical models is an important component of model building and model sharing among scientists interested in understanding multi-scale physiological processes. CellML provides such a standard, particularly for models based on biophysical mechanisms, and a substantial number of models are now available in the CellML Model Repository. However, there is an urgent need to extend the current CellML metadata standard to provide biological and biophysical annotation of the models in order to facilitate model sharing, automated model reduction and connection to biological databases. This paper gives a broad overview of a number of new developments on CellML metadata and provides links to further methodological details available from the CellML website

Motivation to reduce alcohol consumption and subsequent attempts at reduction and changes in consumption in increasing and higher-risk drinkers in England:a prospective population survey

AIMS: To assess how far motivation to reduce alcohol consumption in increasing and higher-risk drinkers in England predicts self-reported attempts to reduce alcohol consumption and changes in alcohol intake during the following 6 months. METHODS: This study used self-reported data from 2928 higher-risk drinkers in the Alcohol Toolkit Study (ATS): a series of monthly cross-sectional household surveys of adults aged 16+ years of age in England. Alcohol consumption was measured in an initial survey and in a 6-month telephone follow-up interview using the Alcohol Use Disorders Identification Test (AUDIT)-C questionnaire. Motivation was measured in the initial survey using the Motivation to Reduce Alcohol Consumption (MRAC) scale. Attempts to reduce alcohol consumption during the past 6 months were recorded at follow-up. Data were analysed using repeated-measures difference-in-differences and logistic regression models. RESULTS: Participants with higher initial motivation to reduce alcohol consumption were more likely to report that they had made an attempt to reduce consumption at follow-up [adjusted odds ratio (ORadj ) = 2.39, 95% confidence interval (CI) = 1.75-3.29]. There was an overall reduction in alcohol consumption between initial survey and follow-up (ORadj  = 0.72, 95% CI = 0.65-0.79), but there was insufficient evidence of an additional effect of motivation to reduce consumption on subsequent changes in alcohol consumption, with the difference-in-differences effect instead suggesting an average increase (ORadj  = 1.37, 95% CI = 1.00-1.88). CONCLUSIONS: Increasing and higher-risk drinkers in England who report greater motivation to reduce their consumption are more likely to report making an attempt to reduce during the next 6 months, but this may not be associated with a reduction in alcohol consumption

Ageing, dementia and the social mind: past, present and future perspectives.

Accompanying the ageing of contemporary ageing societies is an increase in age associated morbidity, with dementia having an important impact. Mental frailty in later life is a source of fear for many and a major policy concern to all those concerned with health and welfare services. This introduction to the special issue on 'Ageing, dementia and the social mind' situates the selected papers within the context of debates about dementia and its social relations. In particular it draws attention to the importance of the social imaginary of the fourth age and what this means for the issue of personhood, care, social representations of dementia and its social contextualisation. The papers illuminating these themes draw on a variety of disciplines and approaches; from the social sciences to the humanities and from the theoretical to the empirical in order to help orientate future researchers to the complexities of dementia and the social and cultural matrix in which it exists. This paper provides an introduction to the potential for a more extended sociology of dementia; one which could combine the insights from medical sociology with the concerns of social gerontology