3,946 research outputs found

    Constraining inverse-curvature gravity with supernovae

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    We show that models of generalized modified gravity, with inverse powers of the curvature, can explain the current accelerated expansion of the Universe without resorting to dark energy and without conflicting with solar system experiments. We have solved the Friedmann equations for the full dynamical range of the evolution of the Universe and performed a detailed analysis of supernovae data in the context of such models that results in an excellent fit. If we further include constraints on the current expansion of the Universe and on its age, we obtain that the matter content of the Universe is 0.07 <=omega(m)<= 0.21 (95% C.L.). Hence the inverse-curvature gravity models considered cannot explain the dynamics of the Universe just with a baryonic matter component

    Geoadditive Regression Modeling of Stream Biological Condition

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    Indices of biotic integrity (IBI) have become an established tool to quantify the condition of small non-tidal streams and their watersheds. To investigate the effects of watershed characteristics on stream biological condition, we present a new technique for regressing IBIs on watershed-specific explanatory variables. Since IBIs are typically evaluated on anordinal scale, our method is based on the proportional odds model for ordinal outcomes. To avoid overfitting, we do not use classical maximum likelihood estimation but a component-wise functional gradient boosting approach. Because component-wise gradient boosting has an intrinsic mechanism for variable selection and model choice, determinants of biotic integrity can be identified. In addition, the method offers a relatively simple way to account for spatial correlation in ecological data. An analysis of the Maryland Biological Streams Survey shows that nonlinear effects of predictor variables on stream condition can be quantified while, in addition, accurate predictions of biological condition at unsurveyed locations are obtained

    Convective infux/glymphatic system: tracers injected into the CSF enter and leave the brain along separate periarterial basement membrane pathways

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    Tracers injected into CSF pass into the brain alongside arteries and out again. This has been recently termed the "glymphatic system" that proposes tracers enter the brain along periarterial "spaces" and leave the brain along the walls of veins. The object of the present study is to test the hypothesis that: (1) tracers from the CSF enter the cerebral cortex along pial-glial basement membranes as there are no perivascular "spaces" around cortical arteries, (2) tracers leave the brain along smooth muscle cell basement membranes that form the Intramural Peri-Arterial Drainage (IPAD) pathways for the elimination of interstitial fluid and solutes from the brain. 2 μL of 100 μM soluble, fluorescent fixable amyloid β (Aβ) were injected into the CSF of the cisterna magna of 6-10 and 24-30 month-old male mice and their brains were examined 5 and 30 min later. At 5 min, immunocytochemistry and confocal microscopy revealed Aβ on the outer aspects of cortical arteries colocalized with α-2 laminin in the pial-glial basement membranes. At 30 min, Aβ was colocalised with collagen IV in smooth muscle cell basement membranes in the walls of cortical arteries corresponding to the IPAD pathways. No evidence for drainage along the walls of veins was found. Measurements of the depth of penetration of tracer were taken from 11 regions of the brain. Maximum depths of penetration of tracer into the brain were achieved in the pons and caudoputamen. Conclusions drawn from the present study are that tracers injected into the CSF enter and leave the brain along separate periarterial basement membrane pathways. The exit route is along IPAD pathways in which Aβ accumulates in cerebral amyloid angiopathy (CAA) in Alzheimer's disease. Results from this study suggest that CSF may be a suitable route for delivery of therapies for neurological diseases, including CAA

    Effects of Malting and Fermentation on the amount of reducing Sugars and Soluble Proteins and free Amino Acids in White Macia and Red Tannin Sorghum flour

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    The purpose of this study was to investigate effects of malting and fermentation methods on the amounts of sugars and proteins in food grade Macia and Red tannin sorghum flours. Measurements to determine the amounts of reducing sugars, soluble protein, and free amino acids, in sorghum flour samples were performed. Grain sorghum kernels (5.2kg) from each sorghum variety were cleaned and kernel hardness tested using Tangential Abrasive Decortication Device (TADD).Half of the kernels (2.6kg) were milled to get regular (Rg) flour samples and the other half (2.6kg) were malted and milled to get malted (mal).flour samples. About 300g of both regular (Rg) and malted (mal) flour samples from both sorghum cultivars (in duplicate) were fermented, dried and milled again to get regular and fermented (Rgfe) and malted and fermented (malfe) flour samples. Extracts were prepared for all (8) flour samples by weighing about 0.5g of flour into centrifuge tubes, then 10 ml of water was added, vortexes 3 times, boiled for 15min and then centrifuged at 5250 RCF for 10 min. The reducing sugars in the extracted material of the regular, fermented, malted and malted/fermented flours from both food grade white Macia and the red tannin sorghum samples were determined by the (DNS) colorimetric methods with glucose as the standard and the absorbance values were read at 540 mm (Miller, 1959).The quantitative measurement of free amino acids of the supernatant material from all flour samples from both the food grade white macia and red tannin sorghum samples were performed using the ninhydrin reaction (Plummer, 1978). The amounts of soluble proteins in the supernatant material were measured using the Lowry method (Lowry et al, 1951). Results showed an increase in reducing sugars, soluble proteins and free amino acids in the malted and fermented flour samples compared to the control or regular flour samples, respectively. Malting and fermentation resulted in increased amounts of reducing sugars, soluble proteins and free amino acids in both food grade Macia and Red tannins sorghum flour. Statistical analysis results showed a significant (p < 0.05) difference between malting and fermentation but no significant (p >0.05) difference between the two sorghum varieties (Macia and Red sorghum). Malting and fermentation may be used to improve the nutritional quality of sorghum food products

    Is sunlight good for our heart?

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    Humans evolved being exposed for about half of the day to the light of the sun. Nowadays, exposure to sunlight is actively discouraged for fear of skin cancer, and contemporary lifestyles are associated with long hours spent under artificial light indoors. Besides an increasing appreciation for the adverse effects of these life-style-related behavioural changes on our chronobiology, the balance between the beneficial and harmful effects of sunlight on human health is the subject of considerable debate, in both the scientific and popular press, and the latter is of major public health significance. While there is incontrovertible evidence that ultraviolet radiation (UVR) in the form of sunlight is a significant predisposing factor for non-melanoma and melanoma skin cancers in pale skinned people,1 a growing body of data suggest general health benefits brought about by sunlight.2 These are believed to be mediated either by melatonin or vitamin D. Melatonin is produced from serotonin by the pineal gland located in the centre of the brain during periods of darkness, and its release is suppressed as a function of the visible light intensity sensed through ocular photoreceptors. Vitamin D is formed by ultraviolet B (UVB)-mediated photolysis of 7-dehydrocholesterol in the skin. Both melatonin and vitamin D are pleiotropic hormones that exert a multitude of cellular effects by interacting with membrane and nuclear receptors, and receptor-independent actions. People with more heavily pigmented skin require higher doses of UVB to produce adequate amounts of vitamin D, and this may have been an evolutionary driver to the variation of human skin colour with latitude and intensity of solar irradiation. Our degree of exposure to sunlight is easily modified by behavioural factors such as the use of clothing, sunglasses, and sun-blocking creams, and time spent outdoors. Balancing the carcinogenic risks with the requirement for vitamin D has led to advice on moderating sun exposure, while supplementing food with vitamin D. Guidance on such behaviour is part of the public health campaigns in most countries with Caucasian populations. Following these suggestions, we may, however, be missing out on other health benefits provided by natural sunlight that are less obvious and unrelated to the above classical mediators

    Cerebral amyloid angiopathy in the aetiology and immunotherapy of Alzheimer disease

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    Amyloid is deposited in the walls of arteries and capillaries as cerebral amyloid angiopathy (CAA) in the brains of older individuals and of those with Alzheimer disease (AD). CAA in AD reflects an age-related failure of elimination of amyloid-beta (Aβ) from the brain along perivascular lymphatic drainage pathways. In the absence of conventional lymphatic vessel in the brain, interstitial fluid and solutes drain from the brain to cervical lymph nodes along narrow basement membranes in the walls of capillaries and arteries, a pathway that is largely separate from the cerebrospinal fluid. In this review we focus on the pathology and pathogenesis of CAA, its role in the aetiology of AD and its impact on immunotherapy for AD. The motive force for lymphatic drainage of the brain appears to be generated by arterial pulsations. Failure of elimination of Aβ along perivascular pathways coincides with a reduction in enzymic degradation of Aβ, reduced absorption of Aβ into the blood and age-related stiffening of artery walls that appears to reduce the motive force for lymphatic drainage. Reduced clearances of Aβ and CAA are associated with the accumulation of insoluble and soluble Aβs in the brain in AD and the probable loss of homeostasis of the neuronal environment due to retention of soluble metabolites within the brain. Tau metabolism may also be affected. Immunotherapy has been successful in removing insoluble plaques of Aβ from the brain in AD but with little effect on cognitive decline. One major problem is the increase in CAA in immunised patients that probably prevents the complete removal of Aβ from the brain. Increased knowledge of the physiology and structural and genetic aspects of the lymphatic drainage of Aβ from the brain will stimulate the development of therapeutic strategies for the prevention and treatment of AD

    Validity of the activPAL3 activity monitor in people moderately affected by Multiple Sclerosis

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    Background: Walking is the primary form of physical activity performed by people with Multiple Sclerosis (MS), therefore it is important to ensure the validity of tools employed to measure walking activity. The aim of this study was to assess the criterion validity of the activPAL3 activity monitor during overground walking in people with MS.\ud Methods: Validity of the activPAL3 accelerometer was compared to video observation in 20 people moderately affected by MS. Participants walked 20-30m twice along a straight quiet corridor at a comfortable speed.\ud Results: Inter-rater reliability of video observations was excellent (all intraclass correlations > 0.99). The mean difference (activPAL3- mean of raters) was -4.70 ± 9.09, -4.55 s ± 10.76 and 1.11 s ± 1.11 for steps taken, walking duration and upright duration respectively. These differences represented 8.7, 10.0 and 1.8% of the mean for each measure respectively. The activPAL3 tended to underestimate steps taken and walking duration in those who walked at cadences of ≤ 38 steps/minute by 60% and 47% respectively.\ud Discussion: The activPAL3 is valid for measuring walking activity in people moderately affected by MS. It is accurate for upright duration regardless of cadence. In participants with slow walking cadences, outcomes of steps taken and walking duration should be interpreted with caution

    Cerebrovascular Smooth Muscle Cells as the Drivers of Intramural Periarterial Drainage of the Brain

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    The human brain is the organ with the highest metabolic activity but it lacks a traditional lymphatic system responsible for clearing waste products. We have demonstrated that the basement membranes of cerebral capillaries and arteries represent the lymphatic pathways of the brain along which intramural periarterial drainage (IPAD) of soluble metabolites occurs. Failure of IPAD could explain the vascular deposition of the amyloid-beta protein as cerebral amyloid angiopathy (CAA), which is a key pathological feature of Alzheimer\u27s disease. The underlying mechanisms of IPAD, including its motive force, have not been clarified, delaying successful therapies for CAA. Although arterial pulsations from the heart were initially considered to be the motive force for IPAD, they are not strong enough for efficient IPAD. This study aims to unravel the driving force for IPAD, by shifting the perspective of a heart-driven clearance of soluble metabolites from the brain to an intrinsic mechanism of cerebral arteries (e.g., vasomotion-driven IPAD). We test the hypothesis that the cerebrovascular smooth muscle cells, whose cycles of contraction and relaxation generate vasomotion, are the drivers of IPAD. A novel multiscale model of arteries, in which we treat the basement membrane as a fluid-filled poroelastic medium deformed by the contractile cerebrovascular smooth muscle cells, is used to test the hypothesis. The vasomotion-induced intramural flow rates suggest that vasomotion-driven IPAD is the only mechanism postulated to date capable of explaining the available experimental observations. The cerebrovascular smooth muscle cells could represent valuable drug targets for prevention and early interventions in CAA
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