Size frequency distributions of the florid prion protein aggregates in variant Creutzfeldt-Jakob disease follow a power-law function

The objective was to test the hypothesis that the size frequency distributions of the prion protein (PrP) plaques in cases of variant Creutzfeldt-Jakob disease (vCJD) follow a power-law function. The design was a retrospective neuropathological study. The patients were 11 cases of clinically and neuropathologically verified vCJD. Size distributions of the diffuse and florid-type plaques were measured in several areas of the cerebral cortex and hippocampus from each case and a power-law function fitted to each distribution. The size distributions of the florid and diffuse plaques were fitted successfully by a powerlaw function in 100% and 42% of brain areas investigated respectively. Processes of aggregation/disaggregation may be more important than surface diffusion in the pathogenesis of the florid plaques. By contrast, surface diffusion may be a more significant factor in the development of the diffuse plaques. © Springer-Verlag Italia 2006.

Integration of the Manakov-PMD Equation with Precomputed M(w) Matrices for PMD Simulation

A novel direct integration technique of the Manakov-PMD equation for the simulation of polarisation mode dispersion (PMD) in optical communication systems is demonstrated and shown to be numerically as efficient as the commonly used coarse-step method. The main advantage of using a direct integration of the Manakov-PMD equation over the coarse-step method is a higher accuracy of the PMD model. The new algorithm uses precomputed M(w) matrices to increase the computational speed compared to a full integration without loss of accuracy. The simulation results for the probability distribution function (PDF) of the differential group delay (DGD) and the autocorrelation function (ACF) of the polarisation dispersion vector for varying numbers of precomputed M(w) matrices are compared to analytical models and results from the coarse-step method. It is shown that the coarse-step method achieves a significantly inferior reproduction of the statistical properties of PMD in optical fibres compared to a direct integration of the Manakov-PMD equation.

Cognition, ocular accommodation, and cardiovascular function in emmetropes and late-onset myopes

PURPOSE. To investigate objectively and noninvasively the role of cognitive demand on autonomic control of systemic cardiovascular and ocular accommodative responses in emmetropes and myopes of late-onset. METHODS. Sixteen subjects (10 men, 6 women) aged between 18 and 34 years (mean ± SD: 22.6 ± 4.4 years), eight emmetropes (EMMs; mean spherical equivalent [MSE] refractive error ± SD: 0.05 ± 0.24 D) and eight with late-onset myopia (LOMs; MSE ± SD: -3.66 ± 2.31 D) participated in the study. Subjects viewed stationary numerical digits monocularly within a Badal optical system (at both 0.0 and -3.0 D) while performing a two-alternative, forced-choice paradigm that matched cognitive loading across subjects. Five individually matched cognitive levels of increasing difficulty were used in random order for each subject. Five 20-second, continuous-objective recordings of the accommodative response measured with an open-view infrared autorefractor were obtained for each cognitive level, whereas simultaneous measurement of heart rate was continuously recorded with a finger-mounted piezoelectric pulse transducer for 5 minutes. Fast Fourier transformation of cardiovascular function allowed the relative power of the autonomic components to be assessed in the frequency domain, whereas heart period gave an indication of the time-domain response. RESULTS. Increasing the cognitive demand led to a significant reduction in the accommodative response in all subjects (0.0 D: by -0.35 ± 0.33 D; -3.0 D: by -0.31 ± 0.40 D, P < 0.001). The greater lag of LOMs compared with EMMs was not significant (P = 0.07) at both distance (0.38 ± 0.35 D) and near (0.14 ± 0.42 D). Mean heart period reduced with increasing levels of workload (P < 0.0005). LOMs exhibited a relative elevation in sympathetic system activity compared to EMMs. Within refractive groups, however, accommodative shifts with increasing cognition correlated with parasympathetic activity (r = 0.99, P < 0.001), more than with sympathetic activity (r = 0.62, P > 0.05). CONCLUSIONS. In an equivalent workload paradigm, increasing cognitive demand caused a reduction in accommodative response that was attributable principally to a concurrent reduction in the relative power of the parasympathetic component of the autonomic nervous system (ANS). The disparity in accommodative response between EMMs and LOMs, however, appears to be augmented by changes in the sympathetic nervous component of the systemic ANS. Copyright © Association for Research in Vision and Ophthalmology.

Autonomic correlates of ocular accommodation and cardiovascular function

PURPOSE: To evaluate the hypothesis that objective measures of open- and closed-loop ocular accommodation are related to systemic cardiovascular function, and ipso facto autonomic nervous system activity. METHODS: Sixty subjects (29 male; 31 female) varying in age from 18 to 33 years (average: 20.3 +/- 2.9 years) with a range of refractive errors [mean spherical equivalent (MSE): -7.12 to +1.82 D] participated in the study. Five 20-s continuous objective recordings of the accommodative response, measured with an open-view IR autorefractor (Shin-Nippon SRW-5000), were obtained for a variety of open- and closed-loop accommodative demands while simultaneous continuous measurement of heart rate was recorded with a finger-mounted piezo-electric pulse transducer for 5 min. Fast Fourier Transformation of cardiovascular function allowed the absolute and relative power of the autonomic components to be assessed in the frequency-domain, whereas heart period gave an indication of the time-domain response. RESULTS: Increasing closed-loop accommodative demand led to a concurrent increase in heart rate of approximately 2 beats/min for a 4.0 D increase in accommodative demand. The increase was attributable to a reduction in the absolute (p < 0.05) and normalised (p < 0.001) input of the systemic parasympathetic nervous system, and was unaffected by refractive group. The interaction with refractive group failed to reach significance. CONCLUSIONS: For sustained accommodation effort, the data demonstrate covariation between the oculomotor and cardiovascular systems which implies that a near visual task can significantly influence cardiovascular behaviour. Accommodative effort alone, however, is not a sufficient stimulus to induce autonomic differences between refractive groups. The data suggest that both the oculomotor and cardiovascular systems are predominantly attributable to changes in the systemic parasympathetic nervous system.

Structure and function in primary open angle glaucoma

The study utilised a Normal group, an Ocular Hypertensive (OHT) group and a Primary Open Angle Glaucoma (POAG) group to investigate two aspects. Firstly, the within- and between-visit variability for stereometric measurements of the optic nerve head (ONH) using the Heidelberg Retina Tomograph (HRT); retinal nerve fibre layer (RNFL) thickness using the HRT and using optical coherence tomography with the Optical Coherence Tomography Scanner (OCT); the visual field using white-on-white (W-W), short-wavelength (SWAP) and Frequency Doubling perimetry (FDT); and retinal haemodynamics using the Heidelberg Retinal Flowmeter (HRF). Secondly, the association demonstrated between some of the derived variables. The within- and between-visit variability for stereometric measurements of the entire ONH and the between-visit variability for sectoral measurements were similar for Normals and OHTs but greater for POAGs. The within-visit variability of the visual field pointwise parameters for SWAP were greater than for W-W and FDT particularly with increase in eccentricity and for the OHT group. The between-visit variability increased with increase in defect depth for the POAG group, across all types of perimetry. The MS was greater, the MD and PSD smaller and the examination duration shorter in FDT compared to W-W and SWAP across all groups. The within-visit variability was less than the between-visit variability for the OCT circumferential and sector RNFL thickness using the 1.5R, 2.0R and the fixed 1.73mm circular scan radii, across the three groups. The variability increased with decrease in the RNFL thickness, and was least for the 2.0R scan radius.

Autocrine activity of soluble Flt-1 controls endothelial cell function and angiogenesis

Background - The negative feedback system is an important physiological regulatory mechanism controlling angiogenesis. Soluble vascular endothelial growth factor (VEGF) receptor-1 (sFlt-1), acts as a potent endogenous soluble inhibitor of VEGF- and placenta growth factor (PlGF)-mediated biological function and can also form dominant-negative complexes with competent full-length VEGF receptors. Methods and results - Systemic overexpression of VEGF-A in mice resulted in significantly elevated circulating sFlt-1. In addition, stimulation of human umbilical vein endothelial cells (HUVEC) with VEGF-A, induced a five-fold increase in sFlt-1 mRNA, a time-dependent significant increase in the release of sFlt-1 into the culture medium and activation of the flt-1 gene promoter. This response was dependent on VEGF receptor-2 (VEGFR-2) and phosphoinositide-3'-kinase signalling. siRNA-mediated knockdown of sFlt-1 in HUVEC stimulated the activation of endothelial nitric oxide synthase, increased basal and VEGF-induced cell migration and enhanced endothelial tube formation on growth factor reduced Matrigel. In contrast, adenoviral overexpression of sFlt-1 suppressed phosphorylation of VEGFR-2 at tyrosine 951 and ERK-1/-2 MAPK and reduced HUVEC proliferation. Preeclampsia is associated with elevated placental and systemic sFlt-1. Phosphorylation of VEGFR-2 tyrosine 951 was greatly reduced in placenta from preeclamptic patients compared to gestationally-matched normal placenta. Conclusion - These results show that endothelial sFlt-1 expression is regulated by VEGF and acts as an autocrine regulator of endothelial cell function.

Weight loss strategies, stress, and cognitive function:supervised versus unsupervised dieting

The early stages of dieting to lose weight have been associated with neuro-psychological impairments. Previous work has not elucidated whether these impairments are a function solely of unsupported or supported dieting. Raised cortico-steroid levels have been implicated as a possible causal mechanism. Healthy, overweight, pre-menopausal women were randomised to one of three conditions in which they dieted either as part of a commercially available weight loss group, dieted without any group support or acted as non-dieting controls for 8 weeks. Testing occurred at baseline and at 1, 4 and 8 weeks post baseline. During each session, participants completed measures of simple reaction time, motor speed, vigilance, immediate verbal recall, visuo-spatial processing and (at Week 1 only) executive function. Cortisol levels were gathered at the beginning and 30 min into each test session, via saliva samples. Also, food intake was self-recorded prior to each session and fasting body weight and percentage body fat were measured at each session. Participants in the unsupported diet condition displayed poorer vigilance performance (p=0.001) and impaired executive planning function (p=0.013) (along with a marginally significant trend for poorer visual recall (p=0.089)) after 1 week of dieting. No such impairments were observed in the other two groups. In addition, the unsupported dieters experienced a significant rise in salivary cortisol levels after 1 week of dieting (p<0.001). Both dieting groups lost roughly the same amount of body mass (p=0.011) over the course of the 8 weeks of dieting, although only the unsupported dieters experienced a significant drop in percentage body fat over the course of dieting (p=0.016). The precise causal nature of the relationship between stress, cortisol, unsupported dieting and cognitive function is, however, uncertain and should be the focus of further research. © 2005 Elsevier Ltd. All rights reserved.

Nutritional influences on cognitive function:mechanisms of susceptibility

The impact of nutritional variation, within populations not overtly malnourished, on cognitive function and arousal is considered. The emphasis is on susceptibility to acute effects of meals and glucose loads, and chronic effects of dieting, on mental performance, and effects of cholesterol and vitamin levels on cognitive impairment. New developments in understanding dietary influences on neurohormonal systems, and their implications for cognition and affect, allow reinterpretation of both earlier and recent findings. Evidence for a detrimental effect of omitting a meal on cognitive performance remains equivocal: from the outset, idiosyncrasy has prevailed. Yet, for young and nutritionally vulnerable children, breakfast is more likely to benefit than hinder performance. For nutrient composition, despite inconsistencies, some cautious predictions can be made. Acutely, carbohydrate-rich–protein-poor meals can be sedating and anxiolytic; by comparison, protein-rich meals may be arousing, improving reaction time but also increasing unfocused vigilance. Fat-rich meals can lead to a decline in alertness, especially where they differ from habitual fat intake. These acute effects may vary with time of day and nutritional status. Chronically, protein-rich diets have been associated with decreased positive and increased negative affect relative to carbohydrate-rich diets. Probable mechanisms include diet-induced changes in monoamine, especially serotoninergic neurotransmitter activity, and functioning of the hypothalamic pituitary adrenal axis. Effects are interpreted in the context of individual traits and susceptibility to challenging, even stressful, tests of performance. Preoccupation with dieting may impair cognition by interfering with working memory capacity, independently of nutritional status. The change in cognitive performance after administration of glucose, and other foods, may depend on the level of sympathetic activation, glucocorticoid secretion, and pancreatic β-cell function, rather than simple fuelling of neural activity. Thus, outcomes can be predicted by vulnerability in coping with stressful challenges, interacting with nutritional history and neuroendocrine status. Functioning of such systems may be susceptible to dietary influences on neural membrane fluidity, and vitamin-dependent cerebrovascular health, with cognitive vulnerability increasing with age.

Direct evidence for endothelial vascular endothelial growth factor receptor-1 function in nitric oxide-mediated angiogenesis

Vascular endothelial growth factor-A (VEGF) is critical for angiogenesis but fails to induce neovascularization in ischemic tissue lesions in mice lacking endothelial nitric oxide synthase (eNOS). VEGF receptor-2 (VEGFR-2) is critical for angiogenesis, although little is known about the precise role of endothelial VEGFR-1 and its downstream effectors in this process. Here we have used a chimeric receptor approach in which the extracellular domain of the epidermal growth factor receptor was substituted for that of VEGFR-1 (EGLT) or VEGFR-2 (EGDR) and transduced into primary cultures of human umbilical vein endothelial cells (HUVECs) using a retroviral system. Activation of HUVECs expressing EGLT or EGDR induced rapid phosphorylation of eNOS at Ser1177, release of NO, and formation of capillary networks, similar to VEGF. Activation of eNOS by VEGFR-1 was dependent on Tyr794 and was mediated via phosphatidylinositol 3-kinase, whereas VEGFR-2 Tyr951 was involved in eNOS activation via phospholipase Cgamma1. Consistent with these findings, the VEGFR-1-specific ligand placenta growth factor-1 activated phosphatidylinositol 3-kinase and VEGF-E, which is selective for VEGFR-2-activated phospholipase Cgamma1. Both VEGFR-1 and VEGFR-2 signal pathways converged on Akt, as dominant-negative Akt inhibited the NO release and in vitro tube formation induced following activation of EGLT and EGDR. The identification Tyr794 of VEGFR-1 as a key residue in this process provides direct evidence of endothelial VEGFR-1 in NO-driven in vitro angiogenesis. These studies provide new sites of modulation in VEGF-mediated vascular morphogenesis and highlight new therapeutic targets for management of vascular diseases.

High performance microwave photonic response of superstructured fibre Bragg grating with designed apodisation function

The microwave photonic responses based on the superstructure fibre Bragg gratings with designed apodisation profile are investigated. The rejection level of more than 60 dB for a bandpass filtering response is demonstrated.

Isomorphism Problems for the Baire Function Spaces of Topological Spaces

Let a compact Hausdorff space X contain a non-empty perfect subset. If α < β and β is a countable ordinal, then the Banach space Bα (X) of all bounded real-valued functions of Baire class α on X is a proper subspace of the Banach space Bβ (X). In this paper it is shown that: 1. Bα (X) has a representation as C(bα X), where bα X is a compactification of the space P X – the underlying set of X in the Baire topology generated by the Gδ -sets in X. 2. If 1 ≤ α < β ≤ Ω, where Ω is the first uncountable ordinal number, then Bα (X) is uncomplemented as a closed subspace of Bβ (X). These assertions for X = [0, 1] were proved by W. G. Bade [4] and in the case when X contains an uncountable compact metrizable space – by F.K.Dashiell [9]. Our argumentation is one non-metrizable modification of both Bade’s and Dashiell’s methods.

Body iron is associated with cognitive executive planning function in college women

Evidence of the relationship between altered cognitive function and depleted Fe status is accumulating in women of reproductive age but the degree of Fe deficiency associated with negative neuropsychological outcomes needs to be delineated. Data are limited regarding this relationship in university women in whom optimal cognitive function is critical to academic success. The aim of the present study was to examine the relationship between body Fe, in the absence of Fe-deficiency anaemia, and neuropsychological function in young college women. Healthy, non-Anaemic undergraduate women (n 42) provided a blood sample and completed a standardised cognitive test battery consisting of one manual (Tower of London (TOL), a measure of central executive function) and five computerised (Bakan vigilance task, mental rotation, simple reaction time, immediate word recall and two-finger tapping) tasks. Women's body Fe ranged from - 4·2 to 8·1 mg/kg. General linear model ANOVA revealed a significant effect of body Fe on TOL planning time (P= 0.002). Spearman's correlation coefficients showed a significant inverse relationship between body Fe and TOL planning time for move categories 4 (r - 0.39, P= 0.01) and 5 (r - 0.47, P= 0.002). Performance on the computerised cognitive tasks was not affected by body Fe level. These findings suggest that Fe status in the absence of anaemia is positively associated with central executive function in otherwise healthy college women. Copyright © The Authors 2012.

Are dieting-related cognitive impairments a function of iron status?

The aim of the present study was to investigate whether the impairments in cognitive function observed in unsupported dieting are related to compromised Fe status. During a non-clinical intervention, overweight participants (age: 18-45 years, BMI: 25-30 kg/m2) either participated in a commercially available weight-loss regimen (n 14), dieted without support (n 17) or acted as a non-dieting control group (n 14) for a period of 8 weeks. Measurements of cognitive function and blood chemistry were taken at a pre-diet baseline, after 1 week and 8 weeks of dieting. After 1 week, unsupported dieters displayed impaired verbal memory, executive function and slower reaction speeds than the other two groups, this difference disappearing by the end of the study. There were no significant group-related changes in blood chemistry over the course of the study, although there were group-related changes in a number of self-reported food-related cognitions. In conclusion, impaired cognition among unsupported dieters is not due to compromised Fe status and is most likely to result from psychological variables. © 2012 The Authors.

Estimation of a Regression Function on a Point Process and its Application to Financial Ruin Risk Forecast

2000 Mathematics Subject Classification: Primary 60G55; secondary 60G25.

Effects of irradiance and spectral quality on leaf structure and function in seedlings of two Southeast Asian Hopea species

We studied the development of leaf characters in two Southeast Asian dipterocarp forest trees under different photosynthetic photon flux densities (PFD) and spectral qualities (red to far-red, R:FR). The two species, Hopea helferi and H. odorata, are taxonomically closely related but differ in their ecological requirements; H. helferi is more drought tolerant and H. odorata more shade tolerant. Seedlings were grown in replicated shadehouse treatments of differing PFD and R:FR. We measured or calculated (1) leaf and tissue thicknesses; (2) mesophyll parenchyma, air space, and lignified tissue volumes; (3) mesophyll air volumes (Vmes/Asurf) and surfaces (Ames/Asurf); (4) palisade cell length and width; (5) chlorophyll/cm2 and a/ b; (6) leaf absorption; and (7) attenuance/absorbance at 652 and 550 nm. These characters varied in response to light conditions in both taxa. Characters were predominantly affected by PFD, and R:FR slightly influenced many characters. Leaf characters of H. odorata were more plastic in response to treatment conditions. Characters were correlated with each other in a complex fashion. Variation in leaf anatomy is most likely a consequence of increasing leaf thickness in both taxa, which may increase mechanical strength and defense against herbivory in more exposed environments. Variation in leaf optical properties was most likely affected by pigment photo-bleaching in treatments of more intense PFD and was not correlated with Amax. The greater plasticity of leaf responses in H. odorata helps explain the acclimation over the range of light conditions encountered by this shade-tolerant taxon. The dense layer of scales on the leaf undersurface and other anatomical characters in H. helferi reduced gas exchange and growth in this drought-tolerant tree.