No abstract

A large-Schmidt-number asymptotic approximation procedure is employed to derive an equation which represents mass transfer accompanied by a first-order chemical reaction for liquids in fully developed turbulent flow in a circular tube. However, since the concentration boundary layer is very thin, the results obtained should also apply to the parallel-plate and concentric-annulus geometries when proper scaling is employed. A modified Van Driest formula for the eddy diffusivity

Froment, G. F., Ed.; Elsevier: Amsterdam, 1980 p 91. Mlron, S.; Lee, R. J. Dev. 1062, 7, 102. 1964. Process Des. Dev. 1066, 5, 193. Ozawa, Y.; Blschoff, K. Ind. fng. Chem. Process Des. Dev. 1068r, 7 , 72. Ozawa, Y.; Blschoff, K. Ind. Eng. Chem. Process Des. Dev. 1068b, 7, 67. Pachovsky, R. A.; Best, D.; Wojciechowskl, B. W. Ind. fng. Chem. Process Poutsma, M. L.A UNIFAC groupinteraction parameter table especially suited for prediction of liquid-liquid equilibria at temperatures between 10 and 40 O C has been developed. A total of 512 binary parameters representing the interactions between 32 different groups have been determined on the basis of approximately 100 binary and 300 ternary liquid-liquid

Brain-derived neurotrophic factor (BDNF) has an important role in regulating maintenance, growth and survival of neurons. However, the main source of circulating BDNF in response to exercise is unknown. To identify whether the brain is a source of BDNF during exercise, eight volunteers rowed for 4 h while simultaneous blood samples were obtained from the radial artery and the internal jugular vein. To further identify putative cerebral region(s) responsible for BDNF release, mouse brains were dissected and analysed for BDNF mRNA expression following treadmill exercise. In humans, a BDNF release from the brain was observed at rest (P < 0.05), and increased two-to threefold during exercise (P < 0.05). Both at rest and during exercise, the brain contributed 70-80% of circulating BDNF, while that contribution decreased following 1 h of recovery. In mice, exercise induced a three-to fivefold increase in BDNF mRNA expression in the hippocampus and cortex, peaking 2 h after the termination of exercise. These results suggest that the brain is a major but not the sole contributor to circulating BDNF. Moreover, the importance of the cortex and hippocampus as a source for plasma BDNF becomes even more prominent in response to exercise. Brain-derived neurotrophic factor (BDNF) is a key protein in regulating maintenance, growth and even survival of neurons (Mattson et al. 2004). Brain-derived neurotrophic factor also influences learning and memory (Tyler et al. 2002), and brain tissue from patients with Alzheimer's disease and clinical depression exhibit low expression of BDNF (Connor et al. 1997;Karege et al. 2002). Brainderived neurotrophic factor has also been identified as a key component of the hypothalamic pathway that controls body weight and energy homeostasis (Wisse & Schwartz, 2003). Obese phenotypes are found in BDNFheterozygous mice and are associated with hyperphagia, hyperleptinaemia, hyperinsulinaemia and hyperglycaemia (Lyons et al. 1999). In addition, BDNF reduces food intake and lowers blood glucose in diabetic mice (Nakagawa et al. 2000). In humans, similar symptoms are associated with * P. Rasmussen and P. Brassard contributed equally to the manuscript. the functional loss of one copy of the BDNF gene and with a mutation in the BDNF receptor Ntrk2 gene (Yeo et al. 2004;Gray et al. 2006).Physically and socially more complex housing leads to increased neurogenesis, improved learning and less weight gain in rats (Young et al. 1999;Cao et al. 2004) associated with consistent up-regulation of BDNF expression, and a direct role for BDNF has recently been reported (Cao et al. 2009). A better understanding of therapeutic actions aimed at increasing BDNF levels, such as exercise (Neeper et al. 1995), is of clinical relevance. It is well known that BDNF synthesis is centrally mediated and activity dependent (Johnson & Mitchell, 2003) and that exercise enhances BDNF transcription in the brain (Oliff et al. 1998). In addition, exercise induces brain uptake of insulin-like growth factor 1, which is a prerequisite for ...

Aims/hypothesis Decreased levels of brain-derived neurotrophic factor (BDNF) have been implicated in the pathogenesis of Alzheimer's disease and depression. These disorders are associated with type 2 diabetes, and animal models suggest that BDNF plays a role in insulin resistance. We therefore explored whether BDNF plays a role in human glucose metabolism. Subjects and methods We included (Study 1) 233 humans divided into four groups depending on presence or absence of type 2 diabetes and presence or absence of obesity; and (Study 2) seven healthy volunteers who underwent both a hyperglycaemic and a hyperinsulinaemic-euglycaemic clamp.Results Plasma levels of BDNF in Study 1 were decreased in humans with type 2 diabetes independently of obesity. Plasma BDNF was inversely associated with fasting plasma glucose, but not with insulin. No association was found between the BDNF G196A (Val66Met) polymorphism and diabetes or obesity. In Study 2 an output of BDNF from the human brain was detected at basal conditions. This output was inhibited when blood glucose levels were elevated. In contrast, when plasma insulin was increased while maintaining normal blood glucose, the cerebral output of BDNF was not inhibited, indicating that high levels of glucose, but not insulin, inhibit the output of BDNF from the human brain. Conclusions/interpretation Low levels of BDNF accompany impaired glucose metabolism. Decreased BDNF may be a pathogenetic factor involved not only in dementia and depression, but also in type 2 diabetes, potentially explaining the clustering of these conditions in epidemiological studies.

Lactate is a potential energy source for the brain. The aim of this study was to establish whether systemic lactate is a brain energy source. We measured in vivo cerebral lactate kinetics and oxidation rates in 6 healthy individuals at rest with and without 90 mins of intravenous lactate infusion (36 mumol per kg bw per min), and during 30 mins of cycling exercise at 75% of maximal oxygen uptake while the lactate infusion continued to establish arterial lactate concentrations of 0.89+/-0.08, 3.9+/-0.3, and 6.9+/-1.3 mmol/L, respectively. At rest, cerebral lactate utilization changed from a net lactate release of 0.06+/-0.01 to an uptake of 0.16+/-0.07 mmol/min during lactate infusion, with a concomitant decrease in the net glucose uptake. During exercise, the net cerebral lactate uptake was further increased to 0.28+/-0.16 mmol/min. Most (13)C-label from cerebral [1-(13)C]lactate uptake was released as (13)CO(2) with 100%+/-24%, 86%+/-15%, and 87%+/-30% at rest with and without lactate infusion and during exercise, respectively. The contribution of systemic lactate to cerebral energy expenditure was 8%+/-2%, 19%+/-4%, and 27%+/-4% for the respective conditions. In conclusion, systemic lactate is taken up and oxidized by the human brain and is an important substrate for the brain both under basal and hyperlactatemic conditions.

The early secreted antigenic target 6 kDa protein (ESAT-6) is a potent T-cell protein antigen synthesized by Mycobacterium tuberculosis. Its corresponding gene (esat-6) is located in RD1, a 10 kb DNA region deleted in the attenuated tuberculosis vaccine strain Mycobacterium bowis BCG. The promoter region of M. tuberculosis esat-6 was cloned and characterized. A new gene, designated lhp and cotranscribed with esat-6, was identified. Moreover, computer searches in the M. tuberculosis genome identified 13 genes related to the lhplesat-6 operon, defining a novel gene family. The transcription initiation sites of the lhplesat-6 operon were mapped using M. tuberculosis RNA. The corresponding promoter signals were not recognized in Mycobacterium smegmatis, in which transcription of lhplesat-6 is initiated at different locations. The M. tuberculosis lhp gene product was identified as CFP-10, a lowmolecular-mass protein found in the short-term culture filtrate. These results show that the genes encoding CFP-10 and ESAT-6 are transcribed together in M. tuberculosis and that both code for small exported proteins.

Background and Purpose— Remote ischemic preconditioning is neuroprotective in models of acute cerebral ischemia. We tested the effect of prehospital rPerC as an adjunct to treatment with intravenous alteplase in patients with acute ischemic stroke. Methods— Open-label blinded outcome proof-of-concept study of prehospital, paramedic-administered rPerC at a 1:1 ratio in consecutive patients with suspected acute stroke. After neurological examination and MRI, patients with verified stroke receiving alteplase treatment were included and received MRI at 24 hours and 1 month and clinical re-examination after 3 months. The primary end point was penumbral salvage, defined as the volume of the perfusion–diffusion mismatch not progressing to infarction after 1 month. Results— Four hundred forty-three patients were randomized after provisional consent, 247 received rPerC and 196 received standard treatment. Patients with a nonstroke diagnosis (n=105) were excluded from further examinations. The remaining patients had transient ischemic attack (n=58), acute ischemic stroke (n=240), or hemorrhagic stroke (n=37). Transient ischemic attack was more frequent ( P =0.006), and National Institutes of Health Stroke Scale score on admission was lower ( P =0.016) in the intervention group compared with controls. Penumbral salvage, final infarct size at 1 month, infarct growth between baseline and 1 month, and clinical outcome after 3 months did not differ among groups. After adjustment for baseline perfusion and diffusion lesion severity, voxelwise analysis showed that rPerC reduced tissue risk of infarction ( P =0.0003). Conclusions— Although the overall results were neutral, a tissue survival analysis suggests that prehospital rPerC may have immediate neuroprotective effects. Future clinical trials should take such immediate effects, and their duration, into account. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00975962.