Investigation of the effects of inlet shapes on fan noise radiation

The effect of inlet shape on forward radiated fan tone noise directivities was investigated under experimentally simplified zero flow conditions. Simulated fan tone noise was radiated to the far field through various shaped zero flow inlets. Baseline data were collected for the simplest baffled and unbaffled straight pipe inlets. These data compared well with prediction. The more general inlet shapes tested were the conical, circular, and exponential surfaces of revolution and an asymmetric inlet achieved by cutting a straight pipe inlet at an acute angle. Approximate theories were developed for these general shapes and some comparisons with data are presented. The conical and exponential shapes produced directivities that differed considerably from the baseline data while the circular shape produced directivities similar to the baseline data. The asymmetric inlet produced asymmetric directivities with significant reductions over the straight pipe data for some angles

Muscle glycogen recovery after exercise measured by13C-magnetic resonance spectroscopy in humans: effect of nutritional solutions

The rate of glycogen resynthesis in human skeletal muscle after glycogen-depleting exercise is known to depend on carbohydrate intake and is reported to reach a platean after an adequate amount of carbohydrate (CHO) consumption. Efforts to maximize the rate of glycogen storage by changing the type and form of CHO, as well as by adding proteins or lipids have yielded inconsistent results. The objective of this study was to assess whether isocaloric addition of proteins and arginine to a CHO diet in the first 4 h after an endurance exercise would increase the rate of glycogen synthesis. The CHO solution, given twice at a 2 h interval according to earlier optimized protocols, contained 1.7 g CHO kgbody weight. The effects of this solution were compared to those of an isocaloric solution containing 1.2 g CHO/kgbody weight plus 0.5 g protein/kgbody weight (including 5 g arginine). Glycogen was measured in quadriceps muscle in vivo with natural abundance13C-magnetic resonance spectroscopy before exercise and twice after exercise, before and at the end of a 4-h period following the intake of one of the solutions. Eight subjects took part in a randomized cross-over trial separated by at least 1 week. Glycogen synthesis was found to be significantly increased with both regimes compared to a zero-caloric placebo diet, but no significant difference in glycogen resynthesis was found between the CHO-only diet and the one supplemented by proteins and arginine. It is estimated that significance would have been reached for an increase of 34%, while the effectively measured synthesis rates only differed by 5

Correction to:On the Role of a Conserved Methionine in the Na+-Coupling Mechanism of a Neurotransmitter Transporter Homolog (Neurochemical Research, (2022), 47, 1, (163-175), 10.1007/s11064-021-03253-w)

After publication, the authors realized that the version of the supplementary information that was originally submitted was incomplete in that it omitted results examining alternative NBFIX corrections to the force field. Those data have now been added as Supplementary Fig. S3 and they reaffirm the conclusions of the manuscript. In addition, the legend to Fig. 3b should read: “Using the NBFIX correction of Na+- methionine interactions, all Na+ ions and the substrate remain stably bound throughout the trajectory. See also Fig. S3.

On the Role of a Conserved Methionine in the Na+-Coupling Mechanism of a Neurotransmitter Transporter Homolog

Excitatory amino acid transporters (EAAT) play a key role in glutamatergic synaptic communication. Driven by transmembrane cation gradients, these transporters catalyze the reuptake of glutamate from the synaptic cleft once this neurotransmitter has been utilized for signaling. Two decades ago, pioneering studies in the Kanner lab identified a conserved methionine within the transmembrane domain as key for substrate turnover rate and specificity; later structural work, particularly for the prokaryotic homologs Glt(Ph) and Glt(Tk), revealed that this methionine is involved in the coordination of one of the three Na(+) ions that are co-transported with the substrate. Albeit extremely atypical, the existence of this interaction is consistent with biophysical analyses of Glt(Ph) showing that mutations of this methionine diminish the binding cooperativity between substrates and Na(+). It has been unclear, however, whether this intriguing methionine influences the thermodynamics of the transport reaction, i.e., its substrate:ion stoichiometry, or whether it simply fosters a specific kinetics in the binding reaction, which, while influential for the turnover rate, do not fundamentally explain the ion-coupling mechanism of this class of transporters. Here, studies of Glt(Tk) using experimental and computational methods independently arrive at the conclusion that the latter hypothesis is the most plausible, and lay the groundwork for future efforts to uncover the underlying mechanism. SUPPLEMENTARY INFORMATION: The online version of this article (10.1007/s11064-021-03253-w) contains supplementary material, which is available to authorized users

High-speed atomic force microscopy reveals a three-state elevator mechanism in the citrate transporter CitS

The secondary active transporter CitS shuttles citrate across the cytoplasmic membrane of gram-negative bacteria by coupling substrate translocation to the transport of two Na(+) ions. Static crystal structures suggest an elevator type of transport mechanism with two states: up and down. However, no dynamic measurements have been performed to substantiate this assumption. Here, we use high-speed atomic force microscopy for real-time visualization of the transport cycle at the level of single transporters. Unexpectedly, instead of a bimodal height distribution for the up and down states, the experiments reveal movements between three distinguishable states, with protrusions of ∼0.5 nm, ∼1.0 nm, and ∼1.6 nm above the membrane, respectively. Furthermore, the real-time measurements show that the individual protomers of the CitS dimer move up and down independently. A three-state elevator model of independently operating protomers resembles the mechanism proposed for the aspartate transporter Glt(Ph). Since CitS and Glt(Ph) are structurally unrelated, we conclude that the three-state elevators have evolved independently

Noninvasive Assessment of Exercise-Related Intramyocellular Acetylcarnitine in Euglycemia and Hyperglycemia in Patients With Type 1 Diabetes Using 1H Magnetic Resonance Spectroscopy: A randomized single-blind crossover study

Intramyocellular acetylcarnitine (IMAC) is involved in exercise-related fuel metabolism. It is not known whether levels of systemic glucose influence IMAC levels in type 1 diabetes

Dose Reduction in Standard Head CT: First Results from a New Scanner Using Iterative Reconstruction and a New Detector Type in Comparison with Two Previous Generations of Multi-slice CT

Purpose: Computed tomography (CT) accounts for more than half of the total radiation exposure from medical procedures, which makes dose reduction in CT an effective means of reducing radiation exposure. We analysed the dose reduction that can be achieved with a new CT scanner [Somatom Edge (E)] that incorporates new developments in hardware (detector) and software (iterative reconstruction). Methods: We compared weighted volume CT dose index (CTDIvol) and dose length product (DLP) values of 25 consecutive patients studied with non-enhanced standard brain CT with the new scanner and with two previous models each, a 64-slice 64-row multi-detector CT (MDCT) scanner with 64 rows (S64) and a 16-slice 16-row MDCT scanner with 16 rows (S16). We analysed signal-to-noise and contrast-to-noise ratios in images from the three scanners and performed a quality rating by three neuroradiologists to analyse whether dose reduction techniques still yield sufficient diagnostic quality. Results: CTDIVol of scanner E was 41.5 and 36.4 % less than the values of scanners S16 and S64, respectively; the DLP values were 40 and 38.3 % less. All differences were statistically significant (p < 0.0001). Signal-to-noise and contrast-to-noise ratios were best in S64; these differences also reached statistical significance. Image analysis, however, showed "non-inferiority” of scanner E regarding image quality. Conclusions: The first experience with the new scanner shows that new dose reduction techniques allow for up to 40 % dose reduction while still maintaining image quality at a diagnostically usable level

Limited tolerance towards folded elements during secretion of the autotransporter Hbp

Many virulence factors secreted by pathogenic Gram-negative bacteria belong to the autotransporter (AT) family. ATs consist of a passenger domain, which is the actual secreted moiety, and a β-domain that facilitates the transfer of the passenger domain across the outer membrane. Here, we analysed folding and translocation of the AT passenger, using Escherichia coli haemoglobin protease (Hbp) as a model protein. Dual cysteine mutagenesis, instigated by the unique crystal structure of the Hbp passenger, resulted in intramolecular disulphide bond formation dependent on the periplasmic enzyme DsbA. A small loop tied off by a disulphide bond did not interfere with secretion of Hbp. In contrast, a bond between different domains of the Hbp passenger completely blocked secretion resulting in degradation by the periplasmic protease DegP. In the absence of DegP, a translocation intermediate accumulated in the outer membrane. A similar jammed intermediate was formed upon insertion of a calmodulin folding moiety into Hbp. The data suggest that Hbp can fold in the periplasm but must retain a certain degree of flexibility and/or modest width to allow translocation across the outer membrane

Factors that determine penumbral tissue loss in acute ischaemic stroke

The goal of acute stroke treatment with intravenous thrombolysis or endovascular recanalization techniques is to rescue the penumbral tissue. Therefore, knowing the factors that influence the loss of penumbral tissue is of major interest. In this study we aimed to identify factors that determine the evolution of the penumbra in patients with proximal (M1 or M2) middle cerebral artery occlusion. Among these factors collaterals as seen on angiography were of special interest. Forty-four patients were included in this analysis. They had all received endovascular therapy and at least minimal reperfusion was achieved. Their penumbra was assessed with perfusion- and diffusion-weighted imaging. Perfusion-weighted imaging volumes were defined by circular singular value decomposition deconvolution maps (Tmax > 6 s) and results were compared with volumes obtained with non-deconvolved maps (time to peak > 4 s). Loss of penumbral volume was defined as difference of post- minus pretreatment diffusion-weighted imaging volumes and calculated in per cent of pretreatment penumbral volume. Correlations between baseline characteristics, reperfusion, collaterals, time to reperfusion and penumbral volume loss were assessed using analysis of covariance. Collaterals (P = 0.021), reperfusion (P = 0.003) and their interaction (P = 0.031) independently influenced penumbral tissue loss, but not time from magnetic resonance (P = 0.254) or from symptom onset (P = 0.360) to reperfusion. Good collaterals markedly slowed down and reduced the penumbra loss: in patients with thrombolysis in cerebral infarction 2 b-3 reperfusion and without any haemorrhage, 27% of the penumbra was lost with 8.9 ml/h with grade 0 collaterals, whereas 11% with 3.4 ml/h were lost with grade 1 collaterals. With grade 2 collaterals the penumbral volume change was −2% with −1.5 ml/h, indicating an overall diffusion-weighted imaging lesion reversal. We conclude that collaterals and reperfusion are the main factors determining loss of penumbral tissue in patients with middle cerebral artery occlusions. Collaterals markedly reduce and slow down penumbra loss. In patients with good collaterals, time to successful reperfusion accounts only for a minor fraction of penumbra loss. These results support the hypothesis that good collaterals extend the time window for acute stroke treatmen