A Cellular, Language Directed Computer Architecture

If a VLSI computer architecture is to influence the field of computing in some major way, it must have attractive properties in all important aspects affecting the design, production, and the use of the resulting computers. A computer architecture that is believed to have such properties is briefly discussed

Potential for adaptation in response to thermal stress in an intertidal macroalga

Understanding responses of marine algae to changing ocean temperatures requires knowledge of the impacts of elevated temperatures and the likelihood of adaptation to thermal stress. The potential for rapid evolution of thermal tolerance is dependent on the levels of heritable genetic variation in response to thermal stress within a population. Here, we use a quantitative genetic breeding design to establish whether there is a heritable variation in thermal sensitivity in two populations of a habitat-forming intertidal macroalga, Hormosira banksii (Turner) Descaisne. Gametes from multiple parents were mixed and growth and photosynthetic performance were measured in the resulting embryos, which were incubated under control and elevated temperature (20°C and 28°C). Embryo growth was reduced at 28°C, but significant interactions between male genotype and temperature in one population indicated the presence of genetic variation in thermal sensitivity. Selection for more tolerant genotypes thus has the ability to result in the evolution of increased thermal tolerance. Furthermore, genetic correlations between embryos grown in the two temperatures were positive, indicating that those genotypes that performed well in elevated temperature also performed well in control temperature. Chlorophyll a fluorescence measurements showed a marked decrease in maximum quantum yield of photosystem II (PSII) under elevated temperature. There was an increase in the proportion of energy directed to photoinhibition (nonregulated nonphotochemical quenching) and a concomitant decrease in energy used to drive photochemistry and xanthophyll cycling (regulated nonphotochemical quenching). However, PSII performance between genotypes was similar, suggesting that thermal sensitivity is related to processes other than photosynthesis. © 2013 Phycological Society of America

The influence of ocean acidification on nitrogen regeneration and nitrous oxide production in the North-West European shelf sea

The assimilation and regeneration of dissolved inorganic nitrogen, and the concentration of N2O, was investigated at stations located in the NW European shelf sea during June/July 2011. These observational measurements within the photic zone demonstrated the simultaneous regeneration and assimilation of NH4+, NO2− and NO3−. NH4+ was assimilated at 1.82–49.12 nmol N L−1 h−1 and regenerated at 3.46–14.60 nmol N L−1 h−1; NO2− was assimilated at 0–2.08 nmol N L−1 h−1 and regenerated at 0.01–1.85 nmol N L−1 h−1; NO3− was assimilated at 0.67–18.75 nmol N L−1 h−1 and regenerated at 0.05–28.97 nmol N L−1 h−1. Observations implied that these processes were closely coupled at the regional scale and nitrogen recycling played an important role in sustaining phytoplankton growth during the summer. The [N2O], measured in water column profiles, was 10.13 ± 1.11 nmol L−1 and did not strongly diverge from atmospheric equilibrium indicating that sampled marine regions where neither a strong source nor sink of N2O to the atmosphere. Multivariate analysis of data describing water column biogeochemistry and its links to N-cycling activity failed to explain the observed variance in rates of N-regeneration and N-assimilation, possibly due to the limited number of process rate observations. In the surface waters of 5 further stations, Ocean Acidification (OA) bioassay experiments were conducted to investigate the response of NH4+ oxidising and regenerating organisms to simulated OA conditions, including the implications for [N2O]. Multivariate analysis was undertaken which considered the complete bioassay dataset of measured variables describing changes in N-regeneration rate, [N2O] and the biogeochemical composition of seawater. While anticipating biogeochemical differences between locations, we aimed to test the hypothesis that the underlying mechanism through which pelagic N-regeneration responded to simulated OA conditions was independent of location and that a mechanistic understanding of how NH4+ oxidation, NH4+ regeneration and N2O production responded to OA could be developed. Results indicated that N-regeneration process responses to OA treatments were location specific; no mechanistic understanding of how N-regeneration processes respond to OA in the surface ocean of the NW European shelf sea could be developed

A Retrospective Cohort Study to Assess Patient and Physician Reported Outcome Measures After Decompressive Hemicraniectomy for Malignant Middle Cerebral Artery Stroke.

INTRODUCTION: Decompressive hemicraniectomy for malignant middle cerebral artery (MCA) infarction is known to reduce mortality. However, there are on-going concerns in terms of the quality of life in survivors. We aimed to examine the correlation between patient and physician reported outcome measures in decompressive hemicraniectomy. PATIENTS AND METHODS: We analyzed outcomes in 21 patients who underwent decompressive hemicraniectomy for malignant MCA infarction between September 2003 and August 2013 within a regional health system. Patient and physician reported outcome measures were collected at follow-up. These were Stroke Impact Scale (SIS) Version 3, modified Rankin Scale (mRS), National Hospital Seizure Severity Scale, Headache Impact Test and Patient Health Questionnaire for depression. RESULTS: There was a good correlation between physician and patient reported outcome measures. The Spearman's rank correlation coefficient between mRS and structured SIS Version 3 was -0.887 (p < 0.001); with unstructured SIS results, the correlation coefficient was -0.663 (p = 0.001). There was no statistically significant correlation between life worth and modified Rankin Scale: r = -0.3383 (p = 0.087). DISCUSSION: Our findings of a statistically significant correlation between mRS and SIS have not previously been reported in patients with this condition. These findings provide further information to inform patient and next of kin discussions regarding outcomes from decompressive hemicraniectomy in malignant MCA infarction

MRAP deficiency impairs adrenal progenitor cell differentiation and gland zonation.

Melanocortin 2 receptor accessory protein (MRAP) is a single transmembrane domain accessory protein and a critical component of the hypothamo-pituitary-adrenal axis. MRAP is highly expressed in the adrenal gland and is essential for adrenocorticotropin hormone (ACTH) receptor expression and function. Human loss-of-function mutations in MRAP cause familial glucocorticoid (GC) deficiency (FGD) type 2 (FGD2), whereby the adrenal gland fails to respond to ACTH and to produce cortisol. In this study, we generated Mrap-null mice to study the function of MRAP in vivo. We found that the vast majority of Mrap-/- mice died at birth but could be rescued by administration of corticosterone to pregnant dams. Surviving Mrap-/- mice developed isolated GC deficiency with normal mineralocorticoid and catecholamine production, recapitulating FGD2. The adrenal glands of adult Mrap-/- mice were small, with grossly impaired adrenal capsular morphology and cortex zonation. Progenitor cell differentiation was significantly impaired, with dysregulation of WNT4/β-catenin and sonic hedgehog pathways. These data demonstrate the roles of MRAP in both steroidogenesis and the regulation of adrenal cortex zonation. This is the first mouse model of isolated GC deficiency and reveals the role of MRAP in adrenal progenitor cell regulation and cortex zonation.-Novoselova, T. V., Hussain, M., King, P. J., Guasti, L., Metherell, L. A., Charalambous, M., Clark, A. J. L., Chan, L. F. MRAP deficiency impairs adrenal progenitor cell differentiation and gland zonation

SCAMP:standardised, concentrated, additional macronutrients, parenteral nutrition in very preterm infants: a phase IV randomised, controlled exploratory study of macronutrient intake, growth and other aspects of neonatal care

<p>Abstract</p> <p>Background</p> <p>Infants born <29 weeks gestation are at high risk of neurocognitive disability. Early postnatal growth failure, particularly head growth, is an important and potentially reversible risk factor for impaired neurodevelopmental outcome. Inadequate nutrition is a major factor in this postnatal growth failure, optimal protein and calorie (macronutrient) intakes are rarely achieved, especially in the first week. Infants <29 weeks are dependent on parenteral nutrition for the bulk of their nutrient needs for the first 2-3 weeks of life to allow gut adaptation to milk digestion. The prescription, formulation and administration of neonatal parenteral nutrition is critical to achieving optimal protein and calorie intake but has received little scientific evaluation. Current neonatal parenteral nutrition regimens often rely on individualised prescription to manage the labile, unpredictable biochemical and metabolic control characteristic of the early neonatal period. Individualised prescription frequently fails to translate into optimal macronutrient delivery. We have previously shown that a standardised, concentrated neonatal parenteral nutrition regimen can optimise macronutrient intake.</p> <p>Methods</p> <p>We propose a single centre, randomised controlled exploratory trial of two standardised, concentrated neonatal parenteral nutrition regimens comparing a standard macronutrient content (maximum protein 2.8 g/kg/day; lipid 2.8 g/kg/day, dextrose 10%) with a higher macronutrient content (maximum protein 3.8 g/kg/day; lipid 3.8 g/kg/day, dextrose 12%) over the first 28 days of life. 150 infants 24-28 completed weeks gestation and birthweight <1200 g will be recruited. The primary outcome will be head growth velocity in the first 28 days of life. Secondary outcomes will include a) auxological data between birth and 36 weeks corrected gestational age b) actual macronutrient intake in first 28 days c) biomarkers of biochemical and metabolic tolerance d) infection biomarkers and other intravascular line complications e) incidence of major complications of prematurity including mortality f) neurodevelopmental outcome at 2 years corrected gestational age</p> <p>Trial registration</p> <p>Current controlled trials: <a href="http://www.controlled-trials.com/ISRCTN76597892">ISRCTN76597892</a>; EudraCT Number: 2008-008899-14</p

A substantial fraction of phytoplankton-derived DON is resistant to degradation by a metabolically versatile, widely distributed marine bacterium

The capacity of bacteria for degrading dissolved organic nitrogen (DON) and remineralising ammonium is of importance for marine ecosystems, as nitrogen availability frequently limits productivity. Here, we assess the capacity of a widely distributed and metabolically versatile marine bacterium to degrade phytoplankton-derived dissolved organic carbon (DOC) and nitrogen. To achieve this, we lysed exponentially growing diatoms and used the derived dissolved organic matter (DOM) to support an axenic culture of Alteromonas sp.. Bacterial biomass (as particulate carbon and nitrogen) was monitored for 70 days while growth dynamics (cell count), DOM (DOC, DON) and dissolved nutrient concentrations were monitored for up to 208 days. Bacterial biomass increased rapidly within the first 7 days prior to a period of growth/death cycles potentially linked to rapid nutrient recycling. We found that ≈75% of the initial DOC and ≈35% of the initial DON were consumed by bacteria within 40 and 4 days respectively, leaving a significant fraction of DOM resilient to degradation by this bacterial species. The different rates and extents to which DOC and DON were accessed resulted in changes in DOM stoichiometry and the iterative relationship between DOM quality and bacterial growth over time influenced bacterial cell C:N molar ratio. C:N values increased to 10 during the growth phase before decreasing to values of ≈5, indicating a change from relative N-limitation/C-sufficiency to relative C-limitation/N-sufficiency. Consequently, despite its reported metabolic versatility, we demonstrate that Alteromonas sp. was unable to access all phytoplankton derived DOM and that a bacterial community is likely to be required. By making the relatively simple assumption that an experimentally derived fraction of DOM remains resilient to bacterial degradation, these experimental results were corroborated by numerical simulations using a previously published model describing the interaction between DOM and bacteria in marine systems, thus supporting our hypothesis