Glycation, oxidation, and lipoxidation in the development of the complications of diabetes: a carbonyl stress hypothesis

Modifications of extant plasma proteins, structural proteins,and other macromolecules are enhanced in diabetes because of increased glycation (secondary to increased glucose concentrations) and perhaps because of increased oxidative stress, Increased glycation is present from the time of onset of diabetes, but the relation between diabetes and oxidative stress is less clear: increased oxidative stress may occur later in the course of disease, as vascular damage becomes established, or it may be a feature of uncomplicated diabetes, The combined effects of protein modification by glycation and oxidation may contribute to the development of accelerated atherosclerosis in diabetes and to the development of microvascular complications, Thus, even if not increased by diabetes, variations in oxidative stress may modulate the consequences of hyperglycemia in individual diabetic patients, In this review, the close interaction between glycation and oxidative processes is discussed, and the theme is developed that the most significant modifications of proteins are the result of interactions with reactive carbonyl groups, While glucose itself contains a carbonyl group that is involved in the initial glycation reaction, the most important and reactive carbonyls are formed by free radical-oxidation reactions damaging either carbohydrates (including glucose itself) or lipids, The resulting carbonyl-containing intermediate products then modify proteins, yielding "glycoxidation" and "lipoxidation" products, respectively, This common pathway for glucose and lipid-mediated stress, which may contribute to diabetic complications, is the basis for the carbonyl stress hypothesis for the development of diabetic complications.

Serine proteases in bone disease

Serine proteases are active in many physiological and pathological processes within bone tissue. Although essential to adequate maintenance of bone and cartilage, their inappropriate expression can lead to exacerbation of tissue destruction and inflammation. Their effects are exerted through multiple pathways, including interaction with signalling molecules such as transforming growth factor ß (TGFß), binding to protease-activated receptors (PARs), and direct proteolysis of extracellular matrix proteins, in some cases working synergistically with matrix metalloproteases in the remodelling of bone tissue. The overall effect of these interactions is not yet clear, but there are strong links between some serine proteases and arthropathies, in addition to metastatic bone invasion. Understanding the contribution of each of these enzymes to the molecular disease process is crucial to developing effective treatment based on inhibitors or agonists. Serine protease inhibitors have shown promise in reducing the severity of arthritis, but greater specificity is required to avoid undesired systemic effects. © 2009 Bentham Science Publishers Ltd.

Global talent management: exploring talent identification in the multinational enterprise

In recent decades, interest in talent management has continued to grow among practitioners, consultants and academics. Conceptual development and subsequent empirical analysis has been limited and struggled to keep pace with the plethora of management consultancy reports in the area. More recently, global talent management has come to the fore due to the increasing importance and challenges multinational enterprises (MNEs) face in satisfying their talent demands. This paper analyses the operationalisation of the talent identification stage in global talent management. In so doing, we find that the use of talent pool segmentation is becoming a popular means of identifying and managing talent. However, MNEs face a number of challenges in ensuring that it is an effective system.

Changing shape and shifting boundaries - the media portrayal of probation in Ireland

Literature on the media representation of probation highlights that probation as a ‘brand’ and concept is poorly understood and lacks public visibility. This has implications for its legitimacy and credibility. In this article we explore probation’s visibility in one country, the Republic of Ireland, through a critical analysis of print media representations of probationover a 12-year period (2001 to 2012). While our study finds that the majority of the coverage of probation was either positive or neutral in tone, we note a recent shift towards a more negative tone that we argue is reflective of the changing shape of the penal-probation boundaries. These changes are linked to resourcing of the criminal justice system and have implications for the public perception of probation.

Orthogonal space-time block coded rate-adaptive modulation with outdated feedbasck

Abstract-Channel state information (CSI) at the transmitter can be used to adapt transmission rate or antenna gains in multi-antenna systems. We propose a rate-adaptive M-QAM scheme equipped with orthogonal space-time block coding with simple outdated, finite-rate feedback over independent flat fading channels. We obtain closed-form expressions for the average BER and throughput for our scheme, and analyze the effects of possibly delayed feedback on the performance gains. We derive optimal switching thresholds maximizing the average throughput under average and outage BER constraints with outdated feedback. Our numerical results illustrate the immunity of our optimal thresholds to delayed feedback.

Ionizing radiation and the retina

This review considers the effects of ionizing radiation on the retina and examines the relationship between the natural course of radiation retinopathy and the radiobiology of the retinal vascular endothelial cell (RVEC). Radiation retinopathy presents clinically as a progressive pattern of degenerative and proliferative vascular changes, chiefly affecting the macula, and ranging from capillary occlusion, dilation, and microaneurysm formation, to telangiectasia, intraretinal microvascular abnormalities, and neovascularization. The total-radiation dose and fractionation schedule are the major determinants for the time of onset, rate of progression, and severity of retinopathy, although other factors such as concomitant chemotherapy and preexisting diabetes may exaggerate the vasculopathy by intensifying the oxygen-derived free-radical assault on the vascular cells. The differential radiosensitivity of RVECs is attributed to their nuclear chromatin conformation, their antioxidant status, and their environment. We propose pathogenetic mechanisms for radiation retinopathy and suggest that the peculiar latency and unique clinical pattern is related to the life cycle of the RVEC. A rationale is also proposed for the use of radiotherapy in the treatment of subneovascularization and age-related macular degeneration.

Radiation retinopathy--clinical, histopathological, ultrastructural and experimental correlations

Clinical, pathological and experimental studies of radiation retinopathy confirm that the primary vascular event is endothelial cell loss and capillary closure. Pericytes are less susceptible, but typically atrophy as the capillaries become non-functional. The immediate effects of radiation reflect interphase and early mitotic death of injured endothelial cells, whereas later changes may be attributed to delayed mitotic death of compromised endothelial cells as they attempt division in the ordinary course of repair and replacement. Capillary occlusion leads to the formation of dilated capillary collaterals which may remain serviceable and competent for years. Microaneurysms develop in acellular and poorly supported capillaries, predominantly on the arterial side of the circulation and adjacent to regions of poorly perfused retina. Alterations in haemodynamics produce large telangiectatic-like channels which, typically develop a thick collagenous adventitia and may become fenestrated. Limited capillary regeneration occurs, usually evident as recanalisation of arterioles or venules by new capillaries. Vitreo-retinal neovascularisation may occur where retinal ischaemia is widespread. Radiation produces an exaggerated vasculopathy in patients with diabetes mellitus, and five month streptozotocin-induced diabetic rats develop a severe ischaemic retinopathy with vitreoretinal neovascularisation when exposed to 1500 cGy of radiation. Later photocoagulation is useful in containing or reversing microvascular incompetence and vasoproliferation in some patients with advanced radiation retinopathy.

Fasciola hepatica:development of monoclonal antibodies and their use to characterize a glycocalyx antigen in migrating flukes

Using mice harbouring early Fasciola hepatica infections, six monoclonal antibodies were prepared against a tegumental antigen present in T1 granules and glycocalyx of flukes. Blocking tests indicated that all monoclonals bound the same T1 epitope (or epitopes in close proximity on the antigen molecule), but this was not the determinant recognized by sheep and cattle. Localization of antibody binding at light and electron microscope levels showed that T1-type antigen also occurred in metacercarial tegument and in glycocalyx of gut cells and excretory ducts in juvenile and adult flukes. This indicates that the natural host-antibody response to F. hepatica may be to one antigen early in the infection. Protein A-gold labelling of monoclonal treated fluke sections revealed that the epitope was probably a polypeptide, unmodified by glycosylation in Golgi bodies. When isolated by immunoadsorption and separated electrophoretically under reducing conditions T1-type antigen was found to consist of a polypeptide mol. wt. 50 000, possibly linked to smaller entities mol. wt. 25-40 000. Tissue-specific variations in the antigen molecule might be conferred by linkage of different polypeptides or carbohydrate side-chains to an antigenic core polypeptide. A component of T1-type antigen was found to have mol. wt. of 25 000, possibly resembling a polypeptide of mol. wt. 24 000 from Schistosoma mansoni tegument.

Religiosity, Political Orientation, and Consequentialist Moral Thinking

Three studies demonstrated that the moral judgments of religious individuals and political conservatives are highly insensitive to consequentialist (i.e., outcome-based) considerations. In Study 1, both religiosity and political conservatism predicted a resistance toward consequentialist thinking concerning a range of transgressive acts, independent of other relevant dispositional factors (e.g., disgust sensitivity). Study 2 ruled out differences in welfare sensitivity as an explanation for these findings. In Study 3, religiosity and political conservatism predicted a commitment to judging “harmless” taboo violations morally impermissible, rather than discretionary, despite the lack of negative consequences rising from the act. Furthermore, non-consequentialist thinking style was shown to mediate the relationship religiosity/conservatism had with impermissibility judgments, while intuitive thinking style did not. These data provide further evidence for the influence of religious and political commitments in motivating divergent moral judgments, while highlighting a new dispositional factor, non-consequentialist thinking style, as a mediator of these effects.

Distributed Adaptive Learning Framework for Wide Area Monitoring of Power Systems Integrated with Distributed Generations

This paper presents a preliminary study of developing a novel distributed adaptive real-time learning framework for wide area monitoring of power systems integrated with distributed generations using synchrophasor technology. The framework comprises distributed agents (synchrophasors) for autonomous local condition monitoring and fault detection, and a central unit for generating global view for situation awareness and decision making. Key technologies that can be integrated into this hierarchical distributed learning scheme are discussed to enable real-time information extraction and knowledge discovery for decision making, without explicitly accumulating and storing all raw data by the central unit. Based on this, the configuration of a wide area monitoring system of power systems using synchrophasor technology, and the functionalities for locally installed open-phasor-measurement-units (OpenPMUs) and a central unit are presented. Initial results on anti-islanding protection using the proposed approach are given to illustrate the effectiveness.

Next generation femtocells: An enabler for high efficiency multimedia transmission

The first generation of femtocells is evolving to the next generation with many more capabilities in terms of better utilisation of radio resources and support of high data rates. It is thus logical to conjecture that with these abilities and their inherent suitability for home environment, they stand out as an ideal enabler for delivery of high efficiency multimedia services. This paper presents a comprehensive vision towards this objective and extends the concept of femtocells from indoor to outdoor environments, and strongly couples femtocells to emergency and safety services. It also presents and identifies relevant issues and challenges that have to be overcome in realization of this vision.