Advanced glycation end products (AGEs) co-localize with AGE receptors in the retinal vasculature of diabetic and of AGE-infused rats

Advanced glycation end products (AGEs), formed from the nonenzymatic glycation of proteins and lipids with reducing sugars, have been implicated in many diabetic complications; however, their role in diabetic retinopathy remains largely unknown. Recent studies suggest that the cellular actions of AGEs may be mediated by AGE-specific receptors (AGE-R). We have examined the immunolocalization of AGEs and AGE-R components R1 and R2 in the retinal vasculature at 2, 4, and 8 months after STZ-induced diabetes as well as in nondiabetic rats infused with AGE bovine serum albumin for 2 weeks. Using polyclonal or monoclonal anti-AGE antibodies and polyclonal antibodies to recombinant AGE-R1 and AGE-R2, immunoreactivity (IR) was examined in the complete retinal vascular tree after isolation by trypsin digestion. After 2, 4, and 8 months of diabetes, there was a gradual increase in AGE IR in basement membrane. At 8 months, pericytes, smooth muscle cells, and endothelial cells of the retinal vessels showed dense intracellular AGE IR. AGE epitopes stained most intensely within pericytes and smooth muscle cells but less in basement membrane of AGE-infused rats compared with the diabetic group. Retinas from normal or bovine-serum-albumin-infused rats were largely negative for AGE IR. AGE-R1 and -R2 co-localized strongly with AGEs of vascular endothelial cells, pericytes, and smooth muscle cells of either normal, diabetic, or AGE-infused rat retinas, and this distribution did not vary with each condition. The data indicate that AGEs accumulate as a function of diabetes duration first within the basement membrane and then intracellularly, co-localizing with cellular AGE-Rs. Significant AGE deposits appear within the pericytes after long-term diabetes or acute challenge with AGE infusion conditions associated with pericyte damage. Co-localization of AGEs and AGE-Rs in retinal cells points to possible interactions of pathogenic significance.

Normalisers, nest algebras and tensor products

We show that if $\cl A$ is the tensor product of finitely many continuous nest algebras, $\cl B$ is a CDCSL algebra and $\cl A$ and $\cl B$ have the same normaliser semi-group then either $\cl A = \cl B$ or $\cl A^* = \cl B$.

Tensor products of operator systems

The purpose of the present paper is to lay the foundations for a systematic study of tensor products of operator systems. After giving an axiomatic definition of tensor products in this category, we examine in detail several particular examples of tensor products, including a minimal, maximal, maximal commuting, maximal injective and some asymmetric tensor products. We characterize these tensor products in terms of their universal properties and give descriptions of their positive cones. We also characterize the corresponding tensor products of operator spaces induced by a certain canonical inclusion of an operator space into an operator system. We examine notions of nuclearity for our tensor products which, on the category of C*-algebras, reduce to the classical notion. We exhibit an operator system S which is not completely order isomorphic to a C*-algebra yet has the property that for every C*-algebra A, the minimal and maximal tensor product of S and A are equal.

Müller glial dysfunction during diabetic retinopathy in rats is linked to accumulation of advanced glycation end-products and advanced lipoxidation end-products.

Aims/hypothesis: The impact of AGEs and advanced lipoxidation end-products (ALEs) on neuronal and Müller glial dysfunction in the diabetic retina is not well understood. We therefore sought to identify dysfunction of the retinal Müller glia during diabetes and to determine whether inhibition of AGEs/ALEs can prevent it.

Methods: Sprague-Dawley rats were divided into three groups: (1) non-diabetic; (2) untreated streptozotocin-induced diabetic; and (3) diabetic treated with the AGE/ALE inhibitor pyridoxamine for the duration of diabetes. Rats were killed and their retinas were evaluated for neuroglial pathology. Results: AGEs and ALEs accumulated at higher levels in diabetic retinas than in controls (p<0.001). AGE/ALE immunoreactivity was significantly diminished by pyridoxamine treatment of diabetic rats. Diabetes was also associated with the up-regulation of the oxidative stress marker haemoxygenase-1 and the induction of glial fibrillary acidic protein production in Müller glia (p<0.001). Pyridoxamine treatment of diabetic rats had a significant beneficial effect on both variables (p<0.001). Diabetes also significantly altered the normal localisation of the potassium inwardly rectifying channel Kir4.1 and the water channel aquaporin 4 to the Müller glia end-feet interacting with retinal capillaries. These abnormalities were prevented by pyridoxamine treatment.

Conclusions/interpretation: While it is established that AGE/ALE formation in the retina during diabetes is linked to microvascular dysfunction, this study suggests that these pathogenic adducts also play a role in Müller glial dysfunction.

Dynamic pricing models for used products in remanufacturing with lost-sales and uncertain quality

In this paper, we investigate the remanufacturing problem of pricing single-class used products (cores) in the face of random price-dependent returns and random demand. Specifically, we propose a dynamic pricing policy for the cores and then model the problem as a continuous-time Markov decision process. Our models are designed to address three objectives: finite horizon total cost minimization, infinite horizon discounted cost, and average cost minimization. Besides proving optimal policy uniqueness and establishing monotonicity results for the infinite horizon problem, we also characterize the structures of the optimal policies, which can greatly simplify the computational procedure. Finally, we use computational examples to assess the impacts of specific parameters on optimal price and reveal the benefits of a dynamic pricing policy. © 2013 Elsevier B.V. All rights reserved.

Dynamic pricing for used products in remanufacturing with back orders(ABS 3* Journal, Accepted with Revision on 2nd December 2011).

In remanufacturing, the supply of used products and the demand for remanufactured products are usually mismatched because of the great uncertainties on both sides. In this paper, we propose a dynamic pricing policy to balance this uncertain supply and demand. Specifically, we study a remanufacturer’s problem of pricing a single class of cores with random price-dependent returns and random demand for the remanufactured products with backlogs. We model this pricing task as a continuous-time Markov decision process, which addresses both the finite and infinite horizon problems, and provide managerial insights by analyzing the structural properties of the optimal policy. We then use several computational examples to illustrate the impacts of particular system parameters on pricing policy.

A comparative study of qualitative immunochemical screening assays for the combined measurement of T-2/HT-2 in cereals and cereal-based products

Many different immunochemical platforms exist for the screening of naturally occurring contaminants in food from the low cost enzyme linked immunosorbent assays (ELISA) to the expensive instruments such as optical biosensors based on the phenomenon of surface plasmon resonance (SPR). The primary aim of this study was to evaluate and compare a number of these platforms to assess their accuracy and precision when applied to naturally contaminated samples containing HT-2/T-2 mycotoxins. Other important factors considered were the speed of analysis, ease of use (sample preparation techniques and use of the equipment) and ultimately the cost implications. The three screening procedures compared included an SPR biosensor assay, a commercially available ELISA and an enzyme-linked immunomagnetic electrochemical array (ELIME array). The qualitative data for all methods demonstrated very good overall agreements with each other, however on comparison with mass spectrometry confirmatory results, the ELISA and SPR assay performed slightly better than the ELIME array, exhibiting an overall agreement of 95.8% compared to 91.7%. Currently, SPR is more costly than the other two platforms and can only be used in the laboratory whereas in theory both the ELISA and ELIME array are portable and can be used in the field, but ultimately this is dependent on the sample preparation techniques employed. Sample preparative techniques varied for all methods evaluated, the ELISA was the most simple to perform followed by that of the SPR method. The ELIME array involved an additional clean-up step thereby increasing both the time and cost of analysis. Therefore in the current format, field use would not be an option for the ELIME array. In relation to speed of analysis, the ELISA outperformed the other methods.

Controlling the response characteristics of luminescent porphyrin plastic film sensors for oxygen

Two porphyrins, platinum(II) octaethylporphyrin (Pt-OEP) and palladium(II) octaethylporphyrin (Pd-OEP), are incorporated into a wide variety of different encapsulating matricies and tested as oxygen sensors, The excited state lifetimes of the two porphyrins are quite different, 0.091 ms for Pt-OEP and 0.99 ms for Pd-OEP, and Pt-OEP-based oxygen sensors are found to be much less sensitive than Pd-OEP-based ones to quenching by oxygen, Two major response characteristics of an oxygen sensor are (i) its sensitivity toward oxygen and (ii) its response and recovery times when exposed to an alternating atmosphere of nitrogen and air. The response characteristics of a rang of Pt-OEP, and Pd-OEP-based oxygen sensors were determined using cellulose acetate butyrate (CAB), poly(methyl methacrylate) (PMMA), and PMMA/CAB polymer blends as the encapsulating media. Pt-OEP and Pd-OEP oxygen sensors have better response characteristics (i.e., more sensitive and lower response and recovery times) when CAB is used as the encapsulating medium rather than PMMA. For both Pt-OEP- and Pd-OEP-based oxygen sensors, in either polymer, increasing the level of tributyl phosphate plasticizer improves the response characteristics of the final oxygen-sensitive film. Pt-OEP in different unplasticized PMMA/CAB blended films produced a range of oxygen sensors in which the response characteristics improved with increasing level of CAB present.

Fluorescence-based thin plastic film ion-pair sensors for oxygen

A general method of preparation of thin-film sensors for O-2, incorporating the dye ion-pair tris(4,7-diphenyl-1,10-phenanthroline) rutheninm(II) ditetraphenylborate, in a variety of different thin film polymer/plasticizer matrices is described, The sensitivity of the sensor depends upon the nature of the polymer matrix and plasticizer, A detailed study of one of these systems utilising the polymer poly(methyl methacrylate), PMMA, is reported. The sensitivity of this O-2 sensor depends markedly upon the plasticizer concentration and is largely independent of temperature (24,5-52.5 degrees C) and age (up to 30 d), When exposed to an alternating atmosphere of O-2 and N-2, a typical oxygen film sensor in PMMA exhibits a 0-90% response and recovery time of 0.4 and 4.5 s, respectively.

Thin plastic film colorimetric sensors for carbon dioxide: Effect of plasticizer on response

Different plasticizers, including phosphate-, phthalate-and adipate-based types were used in the creation of a range of colorimetric plastic film sensors for CO2, The different types of plasticizer used in the formulation of a colorimetric plastic film sensor for CO2 affect the response and recovery times of the sensor differently, An effective plasticizer was taken as one that decreased the response and recovery times of the final film sensor when exposed to an alternating atmosphere of 0-5% CO2. On this basis, the most efficient plasticizers appeared to be phosphate-based, followed by phthalate- and adipate-based plasticizers, This trend appears to reflect the degree of the polymer-plasticizer compatibility. Increasing the amount of plasticizer in the film formulation decreased the response and recovery times of the sensor dramatically, The sensitivity of the film sensor towards CO2 appears to decrease with increasing plasticizer effectiveness; thus, the general order of film CO2 sensitivity with respect to plasticizer type was found to be adipate > phthalate > phosphate. In general, the response of the optical films towards CO2 was found to be temperature sensitive [typically, Delta H = -(44-55) kJ mol(-1)], The phosphate-based plasticized films appear to be less temperature sensitive than the other plasticized films, and 2-ethylhexyl diphenylphosphate appears particularly effective in this respect (Delta H = -18.5 kJ mol(-1)).

Plastic colorimetric film sensors for gaseous ammonia

The preparation and characterization of three different plastic thin-film colorimetric sensors for gaseous ammonia is described. In the film sensors, the neutral form of a pH-sensitive dye (Bromophenol Blue, Bromocresol Green or Chlorophenol Red) was encapsulated in a plastic medium, either poly(vinyl butyral) or ethylcellulose plasticized with tributyl phosphate. Each of these film optodes gave a reproducible and reversible response towards gaseous ammonia. The sensitivity of the film sensors towards ammonia was found to be strongly dependent upon the pK(a) of the encapsulated dye. Thus, the film with Chlorophenol Red (pK(a) = 6.25), proved to be very insensitive (operating range: 0.29%