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Sporadic Alzheimer’s disease (sAD) represents a serious and growing worldwide economic and healthcare burden. Almost 95% of current AD patients are associated with sAD as opposed to patients presenting with well-characterized genetic mutations that lead to AD predisposition, i.e., familial AD (fAD). Presently, the use of transgenic (Tg) animals overexpressing human versions of these causative fAD genes represents the dominant research model for AD therapeutic development. As significant differences in etiology exist between sAD and fAD, it is perhaps more appropriate to develop novel, more sAD-reminiscent experimental models that would expedite the discovery of effective therapies for the majority of AD patients. Here we present the oDGal mouse model, a novel model of sAD that displays a range of AD-like pathologies as well as multiple cognitive deficits reminiscent of AD symptomology. Hippocampal cognitive impairment and pathology were delayed with N-acetyl-cysteine (NaC) treatment, which strongly suggests that reactive oxygen species (ROS) are the drivers of downstream pathologies such as elevated amyloid beta and hyperphosphorylated tau. These features demonstrate a desired pathophenotype that distinguishes our model from current transgenic rodent AD models. A preclinical model that presents a phenotype of non-genetic AD-like pathologies and cognitive deficits would benefit the sAD field, particularly when translating therapeutics from the preclinical to the clinical phase.

Magnetic fields, spontaneously generated around laser heating nonuniformities, have been found to invert and enhance electron pressure perturbations in the conduction zones of laser-produced plasmas without applied magnetic fields. The application of a sufficiently strong magnetic field is predicted to damp this phenomenon, but may instead result in magneto-thermal instability. Two-dimensional Vlasov–Fokker–Planck simulations of the conduction zone of laser-produced plasmas, subject to externally applied magnetic fields of different field strengths, are performed. The effects of non-locality upon extended collisional transport terms and instability thresholds are investigated. It is found that magnetized transport terms Righi–Leduc heat flow and thermoelectric heat flow are strongly enhanced by non-locality (up to twofold), even at the top of the temperature gradient, due to larger magnetization of the mediating hot electrons (relative to their thermal counterparts). Meanwhile, the Nernst effect efficiently advects magnetic field out of the conduction zone before instability (which requires Hall parameters, χ>0.1) can take hold.

Extended-magnetohydrodynamics (MHD) transports magnetic flux and electron energy in high-energy-density experiments, but individual transport effects remain unobserved experimentally. Two factors are responsible in defining the transport: electron temperature and electron current. Each electron energy transport term has a direct analog in magnetic flux transport. To measure the thermally driven transport of magnetic flux and electron energy, a simple experimental configuration is explored computationally using a laser-heated pre-magnetized under-dense plasma. Changes to the laser heating profile precipitate clear diagnostic signatures from the Nernst, cross-gradient-Nernst, anisotropic conduction, and Righi-Leduc heat-flow. With a wide operating parameter range, this configuration can be used in both small and large scale facilities to benchmark MHD and kinetic transport in collisional/semi-collisional, local/non-local, and magnetized/unmagnetized regimes.

This paper discusses the interrelationship between retinal and choroidal blood flow, citing particularly the circulatory changes in light and dark adaptation, and the response vessels to hypoxia. The problems of diabetic retinopathy are also considered.

Copper doped polymer shells can provide a very useful diagnostic for fast ignition experiments currently being performed at various laboratories around the world. The low concentration copper dopant acts as an efficient x-ray source providing information on the physics of fast ignition. We have developed copper doped glow discharge (GDP) coatings suitable for such purposes. Copper acetylacetonate (CuAcAC), a solid at room temperature, was used in a heated jacket as the dopant source. We used this technique to fabricate thin ({approx}5-7 {mu}m) GDP shells doped with {approx}1 at % copper through the depolymerizable mandrel process for fast ignition experiments. The details of the experimental set up and the range and limitations of the technique are discussed.

Inertial Confinement Fusion (ICF) shells are mesoscale objects with nano-scale dimensional and nanosurface finish requirements. Currently, the shell dimensions are measured by white-light interferometry and an image analysis method. These two methods complement each other and give a rather complete data set on a single shell. The process is, however, labor intensive. We have developed an automation routine to fully characterize a shell in one shot and perform unattended batch measurement. The method is useful to the ICF program both for production screening and for full characterization. It also has potential for Inertial Fusion Energy (IFE) power plant where half a million shells need to be processed daily.

Polarization effects have been studied in GaN/AlGaN multiple quantum wells (MQWs) with different c-axis orientation by means of excitation-dependent photoluminescence (PL) analysis. Quantum structures were grown on [0001]-oriented sapphire substrates (C plane) and single-crystalline [1100]-oriented freestanding GaN (M plane) using the metalorganic chemical vapor deposition technique. Strong PL spectrum line blueshifts (up to 140 meV) which are correlated with the excitation intensity have been obtained for C-plane MQWs, whereas no shift has been observed for M-plane MQWs. Theoretical calculations and comparison with the PL data confirm that the built-in electric field for C-plane structures is much stronger than the field present for M-plane MQWs. In the former case, the excitation-induced blueshift of the PL line is due to the screening of the built-in electric field by photoinjected carriers, which is consistent with the field strength of 1.23 MV/cm in the absence of excitation.

We report homoepitaxial GaN growth on freestanding (1100) oriented (M-plane GaN) substrates using low-pressure metalorganic chemical vapor deposition. Scanning electron microscopy, atomic-force microscopy, and photoluminescence were used to study the influence of growth conditions such as the V/III molar ratio and temperature on the surface morphology and optical properties of the epilayers. Optimized growth conditions led to high quality (1100) oriented GaN epilayers with a smooth surface morphology and strong band-edge emission. These layers also exhibited strong room temperature stimulated emission under high intensity pulsed optical pumping. Since for III-N materials the (1100) crystal orientation is free from piezoelectric or spontaneous polarization electric fields, our work forms the basis for developing high performance III-N optoelectronic devices.

Summary Isolates from a presumptive nosocomial outbreak of Clostridium difficile infection at a large teaching hospital were typed by pyrolysis mass spectrometry (PMS) and antibiograms. One isolate, from the putative index case, was dissimilar from the outbreak strain, but 24 isolates from 16 patients were indistinguishable by both methods. The outbreak centred on two wards for the acute care of the elderly, with a few cases elsewhere. Transfer of patients appeared to be the route of transmission between wards. There was a significant fall in the incidence of cases following intervention by the Infection Control Unit. This included ward inspection, advice on antibiotic usage and advice on prevention of faecal-oral transfer, particularly by proper handwashing. Subsequent monitoring of C. difficile infection showed a background of sporadic, dissimilar isolates with occasional apparent cross-infection incidents limited to a few patients. In suspected outbreaks, patterns of antibiotic susceptibility may be useful in initial screening, before referral for more sophisticated typing. There was excellent correlation between PMS results, antibiograms and epidemiological information.

We examined the efficacy of 2 commercially available wipes to effectively remove, kill, and prevent the transfer of both methicillin-resistant and methicillin-susceptible Staphylococcus aureus from contaminated surfaces. Although wipes play a role in decreasing the number of pathogenic bacteria from contaminated surfaces, they can potentially transfer bacteria to other surfaces if they are reused.

This study establishes the age-adjusted tolerance intervals for retinal vascular responses to sustained handgrip contraction (a test of sympathetic nerve function). Forty adult subjects (mean age: 39.7 +/- 14.1 years, range: 20 to 72 years; 19 males) were included in the final analysis. Mean percentage calibre change in response to sustained handgrip contraction in this population was -5.61% with a significant correlation between subject age and percentage retinal vessel calibre change (p less than 0.001). Mean retinal arteriolar calibre change in response to systemic autonomic stimulation varied significantly with age: between -8.48% at age 20 years and -2.06% at age 70 years with a mean of -5.95% at the mean age of 39.7 years. The standard deviation is 3.04% and the 95% confidence intervals were set between +/-6.17%. This autoregulatory reflex appears to be inversely related to age.

International audience; AimThis study aimed to test if investigate whether the anaerobic work capacity is replenished while exercising at critical power intensity. Then, a known exercise duration, which demands high anaerobic energy contribution, was compared to intermittent exercise duration with passive and active (cycling at critical power intensity) rest periods.MethodsNine participants performed five sessions of testing. From the 1st to the 3rd sessions, individuals cycled continuously at different workloads (Phigh, Pintermediate and Plow) in order to estimate the critical power and the anaerobic work capacity. The 4th and 5th sessions were performed in order to determine the influence of anaerobic work capacity replenishment on exercise duration. They consisted of manipulating the resting type (passive or active) between two cycling efforts. The total exercise duration was determined by the sum of the two cycling efforts duration.ResultsThe exercise duration under passive resting condition (408.0 ± 42.0 s) was longer (p < 0.05) than known exercise duration at Pintermediate (Tintermediate = 305.8 ± 30.5 s) and than exercise duration performed under active resting conditions (Tactive = 304.4 ± 30.7 s). However, there was no significant difference between Tintermediate and Tactive.ConclusionThese results demonstrated indirect evidence that the anaerobic work capacity is not replenished while exercising at critical power intensity.; ObjectifL’objectif de cette étude est d’examiner si la capacité de travail anaérobie est restaurée lors d’un exercice réalisé à puissance critique. Pour cela, un exercice de durée connue, qui sollicite à un haut niveau la filière anaérobie a été comparé à un exercice intermittent réalisé soit suivant une modalité de récupération passive, soit suivant une modalité de récupération active (à puissance critique).MéthodesNeuf sujets ont participé à cinq sessions de tests. Lors des sessions un à trois, des exercices continus sur ergocycle étaient réalisés à trois puissances différentes (Pélevée, Pintermdiaire et Pfaible), afin de déterminer la puissance critique et la capacité de travail anaérobie. Les sessions quatre et cinq étaient réalisées dans un ordre aléatoire pour identifier l’influence de la restauration de la capacité de travail anaérobie sur le temps d’exercice. Elles se différenciaient suivant l’intensité de la récupération (passive ou active) et consistaient en un exercice de 150 secondes à Pintermédiare, suivi de 300 secondes de récupération et d’un exercice à Pintermédiare poursuivi jusqu’à épuisement.RésultatsDans de la condition de récupération passive (Tpassive = 408,0 ± 42,0 secondes), la durée d’exercice était plus longue (p < 0,05) que lors de l’exercice à Pintermédiare (Tintermédiare = 305,8 ± 42,0 secondes) et lors de l’exercice réalisé avec une récupération active (Tactive = 304,4 ± 30,5 secondes). Il n’y avait pas de différence significative entre Tintermédiaire et Tactive.ConclusionCes résultats montrent de façon indirecte que la capacité de travail anaérobie n’est pas restaurée lors d’un exercice réalisé à puissance critique.

The retinal vessel calibre responses to systemic sympathetic stimulation, were studied in nine patients (eight male; mean age: 31.7 years; range: 19-58 years) with unilateral disruption of their cervical sympathetic tract. All patients had ipsilateral decreased/absent facial sweating and a Horners syndrome, evidence of unilateral sympathetic denervation. Both eyes of each patient were studied and the results were analysed in two groups: the group of nine sympathectomised eyes and the control group of unaffected fellow eyes. During handgrip contraction there was a significant difference in the mean retinal arteriolar constriction (mean +/- SEM) between the group of sympathectomised eyes (4.6 +/- 0.89%) and control eyes (7.1 +/- 1.13%), p less than 0.01. Similarly, there was a significant difference in mean venule constriction during sustained handgrip contraction between the group of sympathectomised eyes (1.5 +/- 0.67%) and control eyes (4.9 +/- 0.98%), p less than 0.05. There was no significant difference in the mean rise in diastolic blood pressure between the two groups: control eyes +27.9 +/- 2.38 mmHg and sympathectomised eyes +27.8 +/- 2.25 mmHg. There was no correlation between the blood pressure and retinal vessel responses in either group. These results suggest that the sympathetic nervous system plays an integral role in retinal blood flow regulation.

The present study describes the first molecular characterization of environmental and clinical isolates of vancomycin-resistant enterococci (VRE) in Wales. Over a 3-month period (May-July 2000), 134 isolates of VRE (89 Enterococcus faecium and 45 Enterococcus faecalis) were isolated from the patient environment of the University Hospital of Wales (UHW) in Cardiff, Wales, UK. In addition, over the same time-period, 24 clinical isolates of VRE (20 isolates of E. faecium and four isolates of E. faecalis) were obtained from 14 patients. All study isolates were subjected to PFGE typing and their van genotypes were determined by using multiplex PCR. The vanA PCR product (231 bp) was evident in 146 (92 %) of 158 VRE isolates; the remaining 12 isolates (8 %) were positive for the vanB gene. All isolates of E. faecalis were found to be vanA-positive. In total, 16 PFGE banding profiles (pulsotypes) were observed for environmental isolates of E. faecium, whilst eight pulsotypes were found for isolates of E. faecalis. Some of these pulsotypes were isolated from multiple sites, whereas others were more restricted in their distribution. Eleven pulsotypes were evident for clinical isolates and eight of these (representing 11 isolates) were also encountered in environmental isolates. Eleven clinical isolates of E. faecium (55 %) shared an identical pulsotype that was not detected in environmental isolates. These results demonstrate a heterogeneous environmental population of VRE and an association of certain strains with clinical isolates. Predominance of a single pulsotype (not detected in the environment) amongst clinical isolates suggests non-environmental transmission between patients.

(1010) GaN wafers grown on (100) face of γ-LiAlO2 were studied using transmission electron microscopy. Despite good lattice matching in this heteroepitaxial system, high densities of planar structural defects in the form of stacking faults on the basal plane and networks of boundaries located on prism planes inclined to the layer/substrate interface were present in these GaN layers. In addition, significant numbers of threading dislocations were observed. High-resolution electron microscopy indicates that stacking faults present on the basal plane in these layers are of low-energy intrinsic I1 type. This is consistent with diffraction contrast experiments.

Antiphase domains are seen in single crystal gamma lithium aluminate (γ-LiAlO2) with 16.7 nm periodicity in the ⟨110⟩ direction. Alternate domains have a 12 [001] shift. Beta phase lithium aluminate (β-LiAlO2) is seen to form on the surface of the as-received wafers with an epitaxial strain limited relationship with the bulk γ phase. The orthorhombic β phase aligns with the a and b axes (0.528 and 0.630 nm) matching with the tetragonal γ phase’s a and c axes (0.5168 and 0.6268 nm). The γ and β phases are seen to have different etch rates. The β phase converts back to the γ phase above 450 °C.

In this study we elucidate the interaction of physical activity with aging as regards skeletal muscle fiber distribution and size. Thirty-three male athletes and 42 normally active counterparts served as subjects. They were assigned to younger (less than 25.5 years) and older (greater than 25.5 years) subgroups. Serial cross-sections from muscle biopsy samples (musculus vastus lateralis) were stained to distinguish fiber type: fast glycolytic (type IIb), fast oxidative-glycolytic (type IIa), or slow oxidative (type I). We also measured fiber diameters. A greater mean diameter of type I fibers was seen in older as opposed to younger athletes. Older controls had a smaller mean diameter of type IIb fibers than did younger controls. Athletes had a smaller mean percentage of type IIa fibers and a greater mean percentage of type I fibers than did controls. There was a greater mean percentage of type I fibers in older as opposed to younger controls, but this was not the case in athletes. Athletes may have larger fibers and a greater percentage of type I fibers at the expense of type IIa fibers. Atrophy of fibers with aging might be retarded by training, which might also reduce the age-associated rate of type IIb percentage loss and type I percentage gain.

The relationship between microalbuminuria and retinal vessel responses to sustained handgrip contraction was studied in a group of 20 diabetic patients. The diabetics were divided into two groups based on their albumin excretion rates (AER): Group 1 (AER less than or equal to 10 mcg/min) consisted of ten diabetic patients, mean age 55.8 +/- 3.9 years (mean +/- SEM); five IDDM and five NIDDM. Group 2 (AER greater than 10 mcg/min) comprised ten diabetic patients: mean age 56.8 +/- 3.04 years; six IDDM and four NIDDM. Both groups were similar in that there were no significant differences between mean age, type of diabetes, mean duration of diabetes, glycaemic control or mean resting blood pressures. Group 2 diabetics had a higher incidence of autonomic dysfunction than Group 1, based on the results of four standard tests of autonomic nerve function. There were significantly decreased retinal vessel responses to sustained handgrip contraction in Group 2 diabetics (mean arteriolar constriction 0.1 +/- 0.32%, and mean venule constriction 1.0% +/- 0.99%) compared with Group 1 diabetics (mean arteriolar constriction 6.9 +/- 1.69%, and mean venule constriction 4.2 +/- 0.05%). Retinopathy was slightly worse in Group 2. The implications of the association of microalbuminuria (AER greater than 10 mcg/min) and loss of retinal vessel reactivity to sustained handgrip contraction are discussed.

Alterations in retinal vessel calibre on changing posture may indicate an autoregulatory response to changing perfusion pressure. The effect of passive tilting on retinal response in healthy individuals was investigated. Subjects were supported on a specially constructed tilting table. The control measurements were taken with the body in a 30 degrees head up position. Red-free fundus photographs were taken before, during and after a three minute period of 30 degrees head down tilting. Ten subjects were assessed (mean age 29 years: range 18-38). A total of 92 arteriolar and 86 venular sites were measured. On tilting to the head down position arterioles showed an early and significant decrease in calibre: mean -3.1% (p less than 0.001). Venules showed an increase of 3.7% (p less than 0.001). The response was not sustained throughout the period of tilting despite a maintained increase in ocular perfusion pressure, which was estimated in six of the subjects.

Ophthalmic artery perfusion pressures and retinal arteriolar calibres were studied in 10 human subjects when sitting, standing, and lying. Differing responses in perfusion pressure were found; autoregulatory responses were found in 13 of the 18 significant calibre changes on moving from sitting to standing and 13 of 22 significant calibre changes on moving from standing to lying. The remaining significant calibre changes were non-autoregulatory, the arterioles dilating with perfusion pressure increase and constricting with decrease.

The envelope of the bunyavirus La Crosse contains two glycoproteins, G1 (120 000 mol. wt.) and G2 (38 000 mol. wt.). When incubated with trypsin or plasmin, the G1 glycoprotein of virus grown in cell culture was cleaved, leaving two different sized polypeptides in the envelope (67 000 and 95 000 mol. wt.). Chymotrypsin cleaved G1 leaving polypeptides of 70 000 and 100 000 mol. wt. G2, however, was not altered by these enzymes. When used in antibody neutralization studies, these proteolytically modified viruses were neutralized approximately 1 to 2 log10 units in 60 min while control virus was neutralized by over 4 log10 units in 20 min. Because antibody to G1, but not G2, was involved in La Crosse virus neutralization, cleavage of G1 appeared to be directly responsible for these altered kinetics of neutralization. Antibody did bind to the polypeptides remaining associated with the envelope resulting in infectious virus-antibody complexes. This indicated that a critical site in terms of antibody neutralization was removed from G1 by proteolytic enzymes.

The retinal vessel calibre responses to systemic sympathetic stimulation, were studied in 22 randomly selected diabetic patients (mean age +/- SEM: 54.7 +/- 2.59 years, range 25-73; 13 IDDM, 9 NIDDM; 4 females), using sustained isometric muscle contraction as the stimulus. At a different session the integrity of the autonomic nerve function in these diabetic patients was assessed using 3 standard tests of autonomic nerve function, based on cardiovascular reflexes. Diabetic patients with an intact autonomic nervous system: Group 1, (n = 11, mean age: 54.9 +/- 4.55 years, 7 IDDM 4 NIDDM) showed a mean arteriolar constriction of 9.2% (SEM 2.89, p less than 0.01) and a mean venule constriction of 5.1% (SEM 1.73, p less than 0.02), for a mean rise in diastolic blood pressure of 23.7 mmHg (SEM 2.19 range: 13-33). There were no significant mean retinal vessel responses however, in diabetics with autonomic dysfunction (Group 2): mean arteriolar constriction of 1.2% (SEM 1.38 p greater than 0.05) and venule constriction of 2.1% (SEM 1.38, p greater than 0.05); for a mean rise in diastolic blood pressure of 19.8 mmHg (SEM 4.49, range: 2-50). There was no correlation between the rise in diastolic blood pressure and the retinal arteriolar constriction in the 2 groups (Group 1:r = 0.45, p greater than 0.01 and Group 2: r = 0.56, p greater than 0.05). Duration, type and control of diabetes were not significantly different between the 2 groups. The severity of retinopathy was slightly worse in Group 2 compared to Group 1. These results point to an association between autonomic neuropathy and failure of regulation of retinal blood flow.

The retinal microcirculation of anaesthetised normal cats was studied during hyperglycaemia (15 to 55 mmol/l) induced by intravenous infusion of glucose, using high speed cine fluorescence angiography. Saline (0.150 mmol/l) was infused as a control for the volume effect of glucose solution and equiosmolar mannitol was infused as a control for the osmotic effect. The mean retinal arteriolar inflow rate increased from 34 +/- 1 mm/sec to 41 +/- 4 mm/sec during glucose infusion, and from 46 +/- 1 mm/sec to 56 +/- 3 mm/sec during mannitol infusion. The blood pressure similarly increased from 105 +/- 5 mmHg to 125 +/- 2 mmHg during glucose infusion and from 110 +/- 7 mmHg to 129 +/- 1 mmHg during mannitol infusion. During mannitol infusion the increased inflow was accompanied by a reduction in the arteriolar width so that the volume flow remained unchanged. During glucose infusion this constriction did not occur, resulting in a significantly increased volume of retinal blood flow (9 +/- 1 microliter/min to 12 +/- 1 microliter/min).