Effect of diabetes and aging on carboxymethyllysine levels in human urine

Carboxymethyllysine (CML) has been identified as a modified amino acid that accumulates with age in human lens proteins and collagen. CML may be formed by oxidation of fructoselysine (FL), the Amadori adduct formed on nonenzymatic glycosylation of lysine residues in protein, or by reaction of ascorbate with protein under autoxidizing conditions. We proposed that measurements of tissue and urinary CML may be useful as indices of oxidative stress or damage to proteins in vivo. To determine the extent to which oxidation of nonenzymatically glycosylated proteins contributes to urinary CML, we measured the urinary concentrations of FL and CML in diabetic (n = 26) and control (n = 28) patients. The urinary concentration of FL correlated strongly with HbA1 measurements and was significantly higher in diabetic compared with control samples (9.2 +/- 6.5 and 4.0 +/- 2.8 micrograms/mg creatinine, respectively; P less than 0.0001). There was also a strong correlation between the concentrations of CML and FL in both diabetic and control urine (r = 0.67, P less than 0.0001) but only a weakly significant increase in the CML concentration in diabetic compared with control urine (1.2 +/- 0.5 and 1.0 +/- 0.3 micrograms/mg creatinine, respectively; P = 0.05). The molar ratio of CML to FL was significantly lower in diabetic compared with control patients (0.25 +/- 0.12 and 0.43 +/- 0.16, respectively; P less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Strudel: A corpus-based semantic model based on properties and types

Computational models of meaning trained on naturally occurring text successfully model human performance on tasks involving simple similarity measures, but they characterize meaning in terms of undifferentiated bags of words or topical dimensions. This has led some to question their psychological plausibility (Murphy, 2002; Schunn, 1999). We present here a fully automatic method for extracting a structured and comprehensive set of concept descriptions directly from an English part-of-speech-tagged corpus. Concepts are characterized by weighted properties, enriched with concept-property types that approximate classical relations such as hypernymy and function. Our model outperforms comparable algorithms in cognitive tasks pertaining not only to concept-internal structures (discovering properties of concepts, grouping properties by property type) but also to inter-concept relations (clustering into superordinates), suggesting the empirical validity of the property-based approach. Copyright © 2009 Cognitive Science Society, Inc. All rights reserved.

The combined effects of diabetes and ionising radiation on the rat retina: an ultrastructural study

The combined effect of STZ-diabetes and ionising radiation on the rat retina was investigated. Wistar rats, which had been diabetic for 6 months, were irradiated with a single dose of x-rays (1500 cGy) and the ultrastructural effects evaluated at 4-10 mths post-irradiation. At 4 months post-irradiation, the outer nuclear layer of the retina was greatly reduced in thickness and the photoreceptor outer segments were disorganised and reduced in length. In addition, the nerve fibre layer contained many cytoid bodies and there were many redundant basement membrane tubes throughout the inner retina. By 6 months post-irradiation, the photoreceptor cells were virtually absent, bringing the external limiting membrane into close apposition to the RPE. Throughout large areas of the outer retina, RPE cells were hypertrophic and some had proliferated into the inner retina. In many regions, proliferating retinal capillaries were observed within the RPE layer, and at 8 months post-irradiation, some vessels extended into the inner retina accompanied by RPE cells. At 10 months post-irradiation, the RPE was atrophic and degenerative with retinal glial cells coming into contact with Bruch's membrane. In some areas, the glia which had breached Bruch's membrane had invaded the underlying choroid. Where glial cells contacted the choriocapillaries, the vessels assumed the appearance of retinal vessels with plump endothelia and no fenestrations. This study has described a progressive inner retinal ischemia, with cytoid bodies, capillary non-perfusion and general atrophy of the inner retina intensifying markedly with increasing post-irradiation time.(ABSTRACT TRUNCATED AT 250 WORDS)

Screw conveyor device for laboratory tests on conditioned soil for EPB tunneling operations

Earth pressure balanced (EPB) full face tunneling machines have experienced a remarkable increase in the number of applications throughout the world due to both mechanical developments and a more effective use of additives to condition the ground. Conditioning modifies the mechanical and hydraulic properties of a soil by making it suitable for the pressure control in the bulk chamber and extraction with the screw conveyor. The extraction system plays a fundamental role during the EPB operations particularly for a correct application of the face pressure. Despite the extensive use of the EPB technique, little knowledge exists concerning the understanding of the behavior of conditioned soil, particularly for noncohesive ground (sand and gravel). This paper presents and describes a prototype laboratory device, which simulates the extraction of the ground from a pressurized tank with a screw conveyor. The results of a preliminary test program carried out on a medium sized sand show that the prototype device is efficient in verifying the effects of foam for an optimal use in EPB conditioning. © 2007 ASCE.

Low loading platinum nanoparticles on reduced graphene oxide-supported tungsten carbide crystallites as a highly active electrocatalyst for methanol oxidation

In this study, low loading platinum nanoparticles (Pt NPs) have been highly dispersed on reduced graphene oxide-supported WC nanocrystallites (Pt-WC/RGO) via program-controlled reduction-carburization technique and microwave-assisted method. The scanning electron microscopy and transmission electron microscopy results show that WC nanocrystallites are homogeneously decorated on RGO, and Pt NPs with a size of ca. 3 nm are dispersed on both RGO and WC. The prepared Pt-WC/RGO is used as an electrocatalyst for methanol oxidation reaction (MOR). Compared with the Pt/RGO, commercial carbon-supported Pt (Pt/C) and PtRu alloy (PtRu/C) electrocatalysts, the Pt-WC/RGO composites demonstrate higher electrochemical active surface area and excellent electrocatalytic activity toward the methanol oxidation, such as better tolerance toward CO, higher peak current density, lower onset potential and long-term stability, which could be attributed to the characterized RGO support, highly dispersed Pt NPs and WC nanocrystallites and the valid synergistic effect resulted from the increased interface between WC and Pt. The present work proves that Pt-WC/RGO composites could be a promising alternative catalyst for direct methanol fuel cells where WC plays the important role as a functional additive in preparing Pt-based catalysts because of its CO tolerance and lower price. 

Impact of tooth replacement strategies on the nutritional status of partially-dentate elders

OBJECTIVE: To investigate the impact of tooth replacement on the nutritional status of partially dentate older patients, and, to compare two different tooth replacement strategies; conventional treatment using removable partial dentures and functionally orientated treatment based on the shortened dental arch.

BACKGROUND: Amongst older patients, diet plays a key role in disease prevention, as poor diets have been linked to numerous illnesses. Poor oral health and loss of teeth can have very significant negative effects on dietary intake and nutritional status for elderly patients. There is evidence that good oral health generally, has positive effects on the nutritional intake of older adults.

MATERIALS AND METHODS: A randomised, controlled clinical trial was designed to investigate the impact of tooth replacement on the nutritional status of partially dentate elders. Forty-four patients aged over 65 years completed the trial, with 21 allocated to conventional treatment and 23 allocated to functionally orientated treatment. Nutritional status was accessed at baseline and after treatment using the Mini Nutritional Assessment (MNA) and a range of haematological markers.

RESULTS: At baseline, relationships were observed between the number of occluding tooth contacts and some measures of nutritional status. As the number of contacts increased, MNA scores (R = 0.16), in addition to vitamin B12 (R = 0.21), serum folate (R = 0.32) and total lymphocyte count (R = 0.35), also increased. After treatment intervention, the only measure of nutritional status that showed a statistically significant improvement for both treatment groups was MNA score (p = 0.03). No significant between group differences were observed from analysis of the haematological data.

CONCLUSION: In this study, prosthodontic rehabilitation with both conventional treatment and functionally orientated treatment resulted in an improvement in MNA score. Haematological markers did not illustrate a clear picture of improvement in nutritional status for either treatment group.

Ageing and the immune system: focus on macrophages

A fully functioning immune system is essential in order to maintain good health. However, the immune system deteriorates with advancing age, and this contributes to increased susceptibility to infection, autoimmunity, and cancer in the older population. Progress has been made in identifying age-related defects in the adaptive immune system. In contrast, relatively little research has been carried out on the impact of ageing on the innate immune response. This area requires further research as the innate immune system plays a crucial role in protection against infection and represents a first line of defence. Macrophages are central effector cells of the innate immune system and have many diverse functions. As a result, age-related impairments in macrophage function are likely to have important consequences for the health of the older population. It has been reported that ageing in macrophages impacts on many processes including toll-like receptor signalling, polarisation, phagocytosis, and wound repair. A detailed understanding of the impact of ageing on macrophages is required in order to develop therapeutics that will boost immune responses in the older population.

Density functional theory study on the activation of molecular oxygen on a stepped gold surface in an aqueous environment: a new approach for simulating reactions in solution

The activation of oxygen molecules is an important issue in the gold-catalyzed partial oxidation of alcohols in aqueous solution. The complexity of the solution arising from a large number of solvent molecules makes it difficult to study the reaction in the system. In this work, O-2 activation on an Au catalyst is investigated using an effective approach to estimate the reaction barriers in the presence of solvent. Our calculations show that O-2 can be activated, undergoing OOH* in the presence of water molecules. The OOH* can readily be formed on Au(211) via four possible pathways with almost equivalent free energy barriers at the aqueous-solid interface: the direct or indirect activation of O-2 by surface hydrogen or the hydrolysis of O-2 following a Langmuir-Hinshelwood mechanism or an Eley-Rideal mechanism. Among them, the Eley-Rideal mechanism may be slightly more favorable due to the restriction of the low coverage of surface H on Au(211) in the other mechanisms. The results shed light on the importance of water molecules on the activation of oxygen in gold-catalyzed systems. Solvent is found to facilitate the oxygen activation process mainly by offering extra electrons and stabilizing the transition states. A correlation between the energy barrier and the negative charge of the reaction center is found. The activation barrier is substantially reduced by the aqueous environment, in which the first solvation shell plays the most important role in the barrier reduction. Our approach may be useful for estimating the reaction barriers in aqueous systems.

The interaction between adsorbed OH and O-2 on TiO2 surfaces

Reduced TiO2 (110) surfaces usually have OH groups as a result of H2O dissociation at oxygen vacancy defects. Because of excess electrons due to OH adsorption, OH/TiO2. exhibit interesting properties favorable to further O-2 or H2O adsorption. Both O-2 and H2O can adsorb and easily diffuse on the OH/TiO2 surface; such behavior plays a significant role in photocatalysis, heterogeneous catalysis, electronic devices and sensors. Indeed, the processes of H2O dissociation, O-2 and H2O diffusion on Such TiO2 surfaces, in the presence of OH groups, are important issues in their own right. Herein, the most recent experimental and theoretical progresses in understanding the interactions between adsorbed OH groups and O-2, or H2O, over TiO2 (110) surfaces and their implications will be reviewed. (c) 2009 Elsevier Ltd. All rights reserved.

Dup discourses on violence and their impact on the northern ireland peace process

This paper analyses the Democratic Unionist Party's (DUP) discourses about paramilitary violence in Northern Ireland. Drawing on narrative analysis of DUP discourses reported in Northern Ireland's largest unionist newspaper, the News Letter (1998-2006), it explores the relationship between the party's identity, its discourses about republican and loyalist paramilitaries, and the impact of these words on the DUP's electoral success and on the peace process. The paper argues that these discourses may haunt the progress of peace-building, not least because the DUP will find it hard to disentangle itself from a history of scepticism and nay-saying even as it takes a leading role in a devolved Executive designed by an Agreement it longscorned.

Electroless nickel composite (Ni-P/SiC) coating - A study on interface and corrosion characteristic

Surface behaviour is of paramount importance as failure and degradation tend to initiate from the surface. Electroless composite coating (NiP/SiC) was developed using SiC as reinforcing particles. As heat treatment plays a vital role in electroless nickel coating owing to the changes in microstructure, phase structure and mechanical properties, an insight at the interface changes in chemistry and micromechanical behaviour was investigated using scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) and microindentation techniques. Corrosion performance was analysed using electrochemical impedance spectroscopy (EIS). Absence of zinc and migration of copper at the interface was detected. Brittleness and microcracks was seen long the interface when indenting at load of 500 gf (Vickers). Corrosion performance is weaker than particles free coating. However, a thin blanket of NiP could enhance the resistance to corrosive medium.

Effect of monovalent cations on the kinetics of hypoxic conformational change of mitochondrial complex i

Mitochondrial complex I is a large, membrane-bound enzyme central to energy metabolism, and its dysfunction is implicated in cardiovascular and neurodegenerative diseases. An interesting feature of mammalian complex I is the so-called A/D transition, when the idle enzyme spontaneously converts from the active (A) to the de-active, dormant (D) form. The A/D transition plays an important role in tissue response to ischemia and rate of the conversion can be a crucial factor determining outcome of ischemia/reperfusion. Here, we describe the effects of alkali cations on the rate of the D-to-A transition to define whether A/D conversion may be regulated by sodium.At neutral pH (7–7.5) sodium resulted in a clear increase of rates of activation (D-to-A conversion) while other cations had minor effects. The stimulating effect of sodium in this pH range was not caused by an increase in ionic strength. EIPA, an inhibitor of Na+/H+antiporters, decreased the rate of D-to-A conversion and sodium partially eliminated this effect of EIPA. At higher pH (> 8.0), acceleration of the D-to-A conversion by sodium was abolished, and all tested cations decreased the rate of activation, probably due to the effect of ionic strength.The implications of this finding for the mechanism of complex I energy transduction and possible physiological importance of sodium stimulation of the D-to-A conversion at pathophysiological conditions in vivo are discussed.

To fasten words again to visible – and invisible – things

In this extended introductory essay, Catherine Gander and Sarah Garland suggest new ways of looking at the correspondences between visual and verbal practices to consider their material and conceptual connections in a specifically American set of histories, contexts and interpretive traditions. Tracing a lineage of experiential philosophy that is grounded in the overturning of a Cartesian mind/body split, the authors argue for pluralistic perspectives on intermedial innovations that situate embodied and imaginative reader-viewer response as vital to the life of the artwork. Gander and Garland chart two main strands to this approach: the pragmatist strain of American aesthetics and social politics, rooted in the essays of transcendentalist Ralph Waldo Emerson and emanating from the writings of John Dewey and William James; and the conceptualist strain of French-American Marcel Duchamp, whose ground-breaking ideas both positioned the artwork as a phenomenological construction and liberated the artist from established methods of practice and discourse. The ‘imagetext’ (after W. J. T. Mitchell) is therefore, argue Gander and Garland, a site consisting of far more than word and image – but a living assemblage of language, idea, thing, cognition, affect and shared experience.

Effects of LL-37 on Human Gingival Fibroblast Function

Background and Objectives: Gingival fibroblasts play a significant role in the innate immune response of the periodontium to bacterial stimulation. A number of microorganisms and their by-products induce a host response that commonly leads to tissue destruction and periodontal disease progression. LL-37 is an antimicrobial peptide which has multiple roles in host defence including immunomodulation and wound-healing. We have investigated the role of LL-37 on the responsiveness of human gingival fibroblasts to microbial challenge from E. coli lipopolysaccharide (LPS) and P. gingivalis LPS, as well as exploring the direct effects of LL-37 on human gingival fibroblasts. Methods: The effect of LL-37 on bacterial LPS-induced expression of IL-6 and IL-8 by gingival fibroblasts was determined by ELISA. The influence of LL-37 on bacterial LPS-induced IκBα degradation in human gingival fibroblasts was investigated by western blot. The direct effects of LL-37 on modulating gingival fibroblasts gene expression were initially determined by DNA microarray analysis and subsequently confirmed by quantitative polymerase chain reaction (Q-PCR) and ELISA analysis of 9 selected genes. Results: Bacterial LPS-induced IL-8 and IL-6 production by human gingival fibroblasts were significantly reduced in the presence of LL-37 at concentrations in the range of 1-10 µg/ml (p<0.05). The presence of LL-37 at a concentration of 5 µg/ml led to a reduction in LPS-induced IκBα degradation by E. coli LPS (100 ng/ml) and P. gingivalis LPS (10 µg/ml). LL-37 (50 µg/ml) significantly altered the gene expression of 367 genes in human gingival fibroblasts by at least 2-fold. CXCL1, CXCL2, CXCL3, IL-24, IL-8, CCL2, and SOCS3 mRNA were significantly upregulated by LL-37 (p<0.05). LL-37 also significantly stimulated expression of IL-8, hepatocyte growth factor (HGF) and CXCL1 (p<0.05) at the protein level. Discussion: LL-37 plays an important role in the innate immune response due to its broad spectrum antimicrobial and immunomodulatory activity. The ability of LL-37 to directly regulate expression of a range of genes, central to the pathogenesis of periodontitis, identifies multiple roles for the peptide in host homeostasis.

INFLUENCE OF NOX4 NADPH OXIDASE ON GENERATION AND ANGIOGENIC FUNCTION OF INDUCED PLURIPOTENT STEM CELL-DERIVED ENDOTHELIAL CELLS

Human induced pluripotent stem (iPS) cell-derived endothelial cells (ECs) hold clear potential for therapeutic angiogenesis as a novel strategy for ischaemic disease. Recently, we have developed a novel method for direct reprogramming of partial iPS (PiPS) cells, which unlike iPS cells, are generated before pluripotency so do not form tumours, and may be differentiated into ECs with characteristic morphology and pro-angiogenic actions. Our previous work showed that PiPS-derived ECs are capable of forming vascular-like tubes both in vitro and in vivo and promoting re-endothelialisation of ischemic tissue, with greater effectiveness versus mature ECs.

Interestingly, our preliminary data demonstrate that Nox NADPH oxidases, which are reported to influence stem cell function, are progressively induced during PiPs/PiPS-EC differentiation and in response to hypoxia, with Nox4 demonstrating highest expression. As this isoform is an established regulator of angiogenesis, we hypothesize that Nox4 plays a key role in modulating PiPS-EC generation and angiogenic function.

The aim of this project is therefore to investigate: (1) the specific role of Nox4 in direct reprogramming of PiPS cells and differentiation to PiPS-ECs; (2) whether genetic manipulation of Nox4 influences in vitro function of PiPs-ECs and their ability to promote in vivo angiogenesis. This will be achieved by employing established in vitro functional assays and an experimental model of hindlimb ischaemia with assessment of relevant end-points. Identification of a key role for Nox4 in regulating PiPS-EC generation/function may inform selective targeting of this isoform to enhance the efficiency of PiPS-EC differentiation and their capacity to treat ischemic disease.