Water diffusion in rat brain in vivo as detected at very large b values is multicompartmental

The diffusion-weighted signal attenuation of water in rat brain was measured with pulsed-field gradient nuclear magnetic resonance methods in a single voxel under in vivo and global ischemic conditions. The diffusion-attenuated water signal was observed in vivo at b values of 300 ms/ mu m/sup 2/ (strength of diffusion weighting) and diffusion times up to 400 ms. A series of constant diffusion time (CT) experiments with varied gradient directions and diffusion times revealed a multiexponential decay with apparent diffusion coefficients (ADC) covering two orders of magnitude from I to 0.01 mu m/sup 2//ms. In a four-exponential fit, the observed changes during global ischemia could be fully explained by changes in the relative volume fractions only with unchanged ADCs. An anisotropy of the ADC, detected at small b values, was not observed for the ADC at large b values, but for the concomitant volume fractions. An inverse Laplace Transform of the CT curves, performed with CONTIN, resulted in continuously distributed diffusion coefficients, for which the term `diffusogram' is proposed. This approach was more appropriate than a discrete exponential model with four to six components, being related to the morphology of brain tissue and its cell size distribution. On the basis of an analytical, quantitative model, it is suggested that the measured ADC at small b values reflects mainly properties of the restricting boundaries, i.e. the relative volume fractions and the extracellular tortuosity, while the intrinsic intracellular diffusion constant and the exchange time are predicted to have minor influence

Spacecraft design sensitivity for a disaster warning satellite system

A disaster warning satellite (DWS) is described for warning the general public of impending natural catastrophes. The concept is responsive to NOAA requirements and maximizes the use of ATS-6 technology. Upon completion of concept development, the study was extended to establishing the sensitivity of the DWSS spacecraft power, weight, and cost to variations in both warning and conventional communications functions. The results of this sensitivity analysis are presented

Water diffusion in rat brain in vivo as detected at very large b values is multicompartmental

The diffusion-weighted signal attenuation of water in rat brain was measured with pulsed-field gradient nuclear magnetic resonance methods in a single voxel under in vivo and global ischemic conditions. The diffusion- attenuated water signal was observed in vivo at b values of 300 ms/μm2 (strength of diffusion weighting) and diffusion times up to 400 ms. A series of constant diffusion time (CT) experiments with varied gradient directions and diffusion times revealed a multiexponential decay with apparent diffusion coefficients (ADC) covering two orders of magnitude from 1 to 0.01 μm2/ms. In a four-exponential fit, the observed changes during global ischemia could be fully explained by changes in the relative volume fractions only with unchanged ADCs. An anisotropy of the ADC, detected at small b values, was not observed for the ADC at large b values, but for the concomitant volume fractions. An inverse Laplace Transform of the CT curves, performed with CONTIN, resulted in continuously distributed diffusion coefficients, for which the term 'diffusogram' is proposed. This approach was more appropriate than a discrete exponential model with four to six components, being related to the morphology of brain tissue and its cell size distribution. On the basis of an analytical, quantitative model, it is suggested that the measured ADC at small b values reflects mainly properties of the restricting boundaries, i.e. the relative volume fractions and the extracellular tortuosity, while the intrinsic intracellular diffusion constant and the exchange time are predicted to have minor influence

Germline TP53 mutational spectrum in French Canadians with breast cancer

Abstract Background Specific germline mutations in the hereditary breast-ovarian cancer susceptibility (HBC/HBOC) genes, BRCA1, BRCA2 and PALB2, have been shown to recur in French Canadians of Quebec, Canada, and this has been attributed to common ancestors. Germline TP53 mutation carriers are known to segregate in Li-Fraumeni syndrome families, which feature young age of onset breast cancer. We have reported rare TP53 mutation carriers in French Canadian HBC families, though none recurred possibly due to the limited number of cancer families investigated. Here we describe TP53 germline mutations found in French Canadian cancer families provided from hereditary cancer clinics; investigate 37 new BRCA1 and BRCA2 mutation-negative HBC/HBOC families for the TP53 mutations; and assess the frequency of TP53 mutations in a 1235 French Canadian breast cancer cases not selected for family history of cancer. Methods TP53 mutation-positive pedigrees from French Canadian cancer families were provided from local hereditary cancer clinics. Bidirectional Sanger sequencing of all protein encoding exons of TP53 was performed using peripheral blood lymphocyte DNA from breast/ovarian cancer probands from 37 HBC/HBOC families of French Canadian descent. Targeted bidirectional Sanger sequencing assay of regions containing the identified TP53 mutations was performed on 1235 French Canadian breast cancer cases not selected for family history cancer. Results Five new TP53 mutations were identified in six pedigrees from hereditary cancer clinics. No deleterious mutations were identified in cancer probands from 37 HBC/HBOC families. A targeted mutation screen of the 1235 breast cancer cases identified a c.844C>T [p.Arg282Trp] mutation carrier. This mutation was also found among the six mutation-positive cancer families provided by the local hereditary cancer clinics. The targeted screen also uncovered a new TP53 mutation, c.685T>C [p.Cys229Arg] that was found in two breast cancer cases. All TP53 mutation carriers were among the 656 women with breast cancer diagnosed less than 50 years of age. Conclusions In all six new TP53 mutations were identified in French Canadians, where two each occurred in independently ascertained cases/families. Although all newly identified breast cancer mutation carriers reported a family history of cancer, none were consistent with features of Li-Fraumeni syndrome families

Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I

Glutaric acidemia type I (GA-I) is an inherited disorder of lysine and tryptophan metabolism presenting with striatal lesions anatomically and symptomatically similar to Huntington disease. Affected children commonly suffer acute brain injury in the context of a catabolic state associated with nonspecific illness. The mechanisms underlying injury and age-dependent susceptibility have been unknown, and lack of a diagnostic marker heralding brain injury has impeded intervention efforts. Using a mouse model of GA-I, we show that pathologic events began in the neuronal compartment while enhanced lysine accumulation in the immature brain allowed increased glutaric acid production resulting in age-dependent injury. Glutamate and GABA depletion correlated with brain glutaric acid accumulation and could be monitored in vivo by proton nuclear magnetic resonance (1H NMR) spectroscopy as a diagnostic marker. Blocking brain lysine uptake reduced glutaric acid levels and brain injury. These findings provide what we believe are new monitoring and treatment strategies that may translate for use in human GA-I

Acute hunger modifies responses on the Three Factor Eating Questionnaire hunger and disinhibition, but not restraint, scales

It is widely assumed that responses on the Three Factor Eating Questionnaire (TFEQ) represent long-term (trait) attitudes to eating behaviour. However, the questionnaire requires agreement with a number of food related statements, and it is possible that some are easier to agree with when assessed hungry than sated. To test this potential state-dependency, participants completed a 100 mm visual analogue scale rating of their current hunger at the time they completed the TFEQ. Data were collected from two cohorts: Cohort 1 (507 women and 119 men) completed both measures on paper, while the hunger rating was computerised in Cohort 2 (179 women). Regression analysis revealed significant effects of rated hunger on scores on the hunger (TFEQ-H) and disinhibition (TFEQ-D) but not restraint (TFEQ-R) subscales, with higher TFEQ-H and TFEQ-D scores when participants were more hungry. In addition, 61 women and two men from Cohort 1 completed the measures on two separate occasions. Here, scores on TFEQ-H were higher on days when these participants were hungrier, but no differences in TFEQ-D or TFEQ-R were found. Overall these data suggest TFEQ-H could be interpreted as an indirect measure of current hunger, that scores on TFEQ-D are partly moderated by hunger but TFEQ-R is a more trait-like measure of restraint

Heritability of Body Mass Index: A comparison between the Netherlands and Spain.

A high body mass index (BMI) is commonly used as an index of overweight and obesity. There is persistent evidence of high heritability for variation in BMI, but the effects of common environment appear inconsistent across different European countries. Our objective was to compare genetic and environmental effects on BMI in a sample of twins from two different European countries with distinct population and cultural backgrounds. We analysed data of adult female twins from the Netherlands Twin Register (222 monozygotic [MZ] and 103 dizygotic [DZ] pairs) and the Murcia Twin Register (Spain; 202 MZ and 235 DZ pairs). BMI was based on self-reported weight and height. Dutch women were taller and heavier, but Spanish women had a significantly higher mean BMI. The age related weight increase was significantly stronger in the Spanish sample. Genetic analyses showed that genetic factors are the main contributors to variation in height, weight, and BMI, within both countries. For height and weight, estimates of genetic variances did not differ, but for height, the estimate for the environmental variance was significantly larger in Spanish women. For BMI, both the genetic and the environmental variance components were larger in Spanish than in Dutch women

Smart SPHERES: A Telerobotic Free-Flyer for Intravehicular Activities in Space

Smart SPHERES is a prototype free-flying space robot based on the SPHERES platform. Smart SPHERES can be remotely operated by astronauts inside a spacecraft, or by mission controllers on the ground. We developed Smart SPHERES to perform a variety of intravehicular activities (IVA), such as operations inside the International Space Station (ISS). These IVA tasks include environmental monitoring surveys (radiation, sound levels, etc.), inventory, and mobile camera work. In this paper, we first discuss the motivation for free-flying space robots. We then describe the development of the Smart SPHERES prototype, including avionics, software, and data communications. Finally, we present results of initial flight tests on-board the ISS

Assessment of Daily Life Physical Activities in Pulmonary Arterial Hypertension

Background: In pulmonary arterial hypertension (PAH), the six-minute walk test (6MWT) is believed to be representative of patient’s daily life physical activities (DLPA). Whether DLPA are decreased in PAH and whether the 6MWT is representative of patient’s DL PA remain unknown. Methods: 15 patients with idiopathic PAH (IPAH) and 10 patients with PAH associated with limited systemic sclerosis (PAH-SSc) were matched with 15 healthy control subjects and 10 patients with limited systemic sclerosis without PAH. Each subject completed a 6MWT. The mean number of daily steps and the mean energy expenditure and duration of physical activities.3 METs were assessed with a physical activity monitor for seven consecutive days and used as markers of DLPA. Results: The mean number of daily steps and the mean daily energy expenditure and duration of physical activities.3 METs were all reduced in PAH patients compared to their controls (all p,0.05). The mean number of daily steps correlated with the 6MWT distance for both IPAH and PAH-SSc patients (r = 0.76, p,0.01 and r = 0.85, p,0.01), respectively. Conclusion: DLPA are decreased in PAH and correlate with the 6MWT distance. Functional exercise capacity may thus be a useful surrogate of DL PA in PAH

A Horizon Scan of research priorities to inform policies aimed at reducing the harm of plastic pollution to biota

Plastic pollution in the oceans is a priority environmental issue. The recent increase in research on the topic, coupled with growing public awareness, has catalyzed policymakers around the world to identify and implement solutions that minimize the harm caused by plastic pollution. To aid and coordinate these efforts, we surveyed experts with scientific experience identified through their peer-reviewed publications. We asked experts about the most pressing research questions relating to how biota interact with plastic pollution that in turn can inform policy decisions and research agendas to best contribute to understanding and reducing the harm of plastic pollution to biota. We used a modified Horizon Scan method that first used a subgroup of experts to generate 46 research questions on aquatic biota and plastics, and then conducted an online survey of researchers globally to prioritize questions in terms of their importance to inform policy development. One hundred and fifteen experts from 29 countries ranked research questions in six themes. The questions were ranked by urgency, indicating which research should be addressed immediately, which can be addressed later, and which are of limited relevance to inform action on plastics as an environmental pollutant. We found that questions relating to the following four themes were the most commonly top-ranked research priorities: (i) sources, circulation and distribution of plastics, (ii) type of harm from plastics, (iii) detection of ingested plastics and the associated problems, and (iv) related economies and policy to ingested plastics. While there are many research questions on the topic of impacts of plastic pollution on biota that could be funded and investigated, our results focus collective priorities in terms of research that experts believe will inform effective policy and on-the-ground conservation.© 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/