A Potent Mimetic of the Siglec-8 Ligand 6’-Sulfo-Sialyl Lewisx

Siglecs are members of the immunoglobulin gene family containing sialic acid binding N-terminal domains. Among them, Siglec-8 is expressed on various cell types of the immune system such as eosinophils, mast cells and weakly on basophils. Cross-linking of Siglec-8 with monoclonal antibodies triggers apoptosis in eosinophils and inhibits degranulation of mast cells, making Siglec-8 a promising target for the treatment of eosinophil- and mast cell-associated diseases such as asthma. The tetrasaccharide 6’-sulfo-sialyl Lewis^x has been identified as a specific Siglec-8 ligand in glycan array screening. Here, we describe an extended study enlightening the pharmacophores of 6’-sulfo-sialyl Lewis^x and the successful development of a high-affinity mimetic. Retaining the neuraminic acid core, the introduction of a carbocyclic mimetic of the Gal moiety and a sulfonamide substituent in the 9-position gave a 20-fold improved binding affinity. Finally, the residence time, which usually is the Achilles tendon of carbohydrate/lectin interactions, could be improved.     

Design,Facile Synthesis and Characterization of Porphyrin-Zirconium-Ferrite@SiO2 Core-Shell and Catalytic Application in Cyclohexane Oxidation

Silicon - In this study, a new magnetic ZrFe2O4@SiO2-TCPP nanocatalyst with high efficiency was used for the oxidation of cyclohexane to cyclohexanone (Ke) and cyclohexanol (Al). The mesoporous...     

A comprehensive decision making structure for partitioning of make-to-order, make-to-stock and hybrid products

Manufacturing systems produce their products by making use of three main strategies: make-to-order, make-to-stock and hybrid (combination of MTO and MTS strategies) systems. Hence, several products must be considered and partitioned in terms of many different conflicting criteria, leading to a large set of subjective or ambiguous data. Thus, an effective evaluation approach is essential to improve decision quality. In this paper a comprehensive decision, making structure is proposed to choose the proper strategy for producing the products. It consists of a novel hybrid methodology, which combines analytical hierarchy process (AHP) and technique for order performance by similarity to ideal solution (TOPSIS) for partitioning of products. In this study, the rating of each alternative regarding different criteria (throughout the TOPSIS technique) is described by means of linguistic variables. Furthermore, fuzzy AHP methodology is applied to determine the weights of evaluation criteria. At the end, the effectiveness of the proposed model is demonstrated through a case study.     

Determination of number of kanbans in a supply chain system via Memetic algorithm

In this research multi-stage supply chain system which is controlled by kanban system, is evaluated. In kanban system, decision making is based on determination of the number of kanbans as well as batch sizes. This paper attempts to model supply chain system with regard to costs under just-in-time (JIT) production philosophy. Since adopted model is of mixed integer non-linear programming (MINLP) type and solving it by exact algorithm such as branch and bound (B&B) takes a lot of time, a heuristic method via Memetic algorithm (MA) is presented. Some problems are solved by our proposed MA to illustrate its performance.     

Restoration of bilinearly distorted images. 3: Constrained least-squares method

A constrained least-squares solution based on a second difference smoothing measure is obtained for images which are distorted by a bilinear (quadratic and with nonzero memory) system in the presence of additive signal-independent noise. Results are applied to a partially coherent diffraction-limited imaging system. It is found that the optimum weight given to the smoothness factor is larger for a coherent (nonlinear) system than for an incoherent (linear) system. However, the restoration quality improves as the imaging system approaches incoherence.     

Solving a bi-objective cell formation problem with stochastic production quantities by a two-phase fuzzy linear programming approach

We propose a bi-objective cell formation problem with demand of products expressed in a number of probabilistic scenarios. To deal with the uncertain demand of products, a framework of two-stage stochastic programming model is presented. The proposed model considers minimizing the sum of the miscellaneous costs (machine constant cost, expected machine variable cost, cell fixed-charge cost, and expected intercell movement cost) and expected total cell loading variation. Because of conflicting objectives, we develop a two-phase fuzzy linear programming approach for solving bi-objective cell formation problem. To show the effectiveness of the proposed approach, numerical examples are solved and the results are compared with the two existing approaches in the literature. The computational results show that the proposed fuzzy method achieves lower objective functions as well as higher satisfaction degrees.     

Preparation, Characterization and Photocatalytic Properties of Ba-Cd-Sr-Ti Doped Fe3O4 Nanohollow Spheres on Removal of Congo Red Under Visible-Light Irradiation

In this study, Ba-Cd-Sr-Ti doped Fe₃O₄ nanohollow spheres were successfully prepared via a simple solvothermal method. The crystal size, structure, morphology and elemental analysis of the as-prepared sample were investigated in detail by X-ray diffraction (XRD), FT-IR, scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) spectroscopy, respectively. Magnetic hysteresis measurement was carried out on a vibrant sample magnetometer (VSM) showing the soft ferromagnetic property at room temperature. The synthesized nanohollow spheres were employed as a photocatalyst to study the photocatalytic degradation of dye contaminations. The UV-Vis results showed that the specimen could well catalyze the decolorizing of congo red (CR) solution and a removal efficiency of 99.5 % was obtained at pH 6. The optical characteristic of the products was studied by estimating the band-gap energy based on diffuse-reflectance spectroscopy (DRS) which represented the doped magnetite with semiconductor metals to be more prone in the visible region as compared to UV region. Some factors such as initial dye concentration, pH, and contact time influencing the decomposition of CR were evaluated.     

Determining parameters of heat exchangers for heat recovery in a Cu–Cl thermochemical hydrogen production cycle

A heat exchanger is a device built for efficient heat transfer from one medium to another. Shell and tube heat exchangers are separated wall heat exchangers and are commonly used in the nuclear and process industry. The CuCl cycle is used to thermally crack water in to H₂ and O₂. The present study presents the heat exchanger thermal design using analysis of variance for heat recovery from oxygen at 500 °C, coming from the molten salt reactor. Polynomial regressions in terms of the amount of chlorine in the oxygen, the mass flow rate on the tube side, and the shell's outlet temperature are estimated for various exchanger parameters and the results are compared with the bell Delaware method. Based on energy and exergy analysis, this study also discusses the best possible path for the recovered heat from oxygen. Optimal heat exchanger parameters are estimated by Design-Expert^® Stat-Ease for most effective heat recovery.     

Sensitivity Analysis to Operational Parameters of the Offset Well During Fast-SAGD Process in Naturally Fractured Reservoir

Few studies were done to investigate performance of the Fast steam-assisted gravity damage (SAGD) recovery method especially in naturally fractured reservoirs (NFR). The authors studied some cyclic steam stimulated operational parameters effects on the Fast-SAGD performance in NFR. A synthetic 2D homogenous model was constructed by Computer Modelling Group's (CMG) and simulated using the STARS module. Comparison between SAGD and Fast-SAGD recovery methods in this model shows great increase in the oil production but small increase of thermal efficiency in the Fast-SAGD recovery method. Simulation outcomes represent 17% increment in ultimate recovery factor but small reduction in steam-oil ratio. Results show that increasing the number of offset cycles and injection period yield increment in the oil production. Increasing the offset injection rate causes growth in the oil production, but has an optimal value. By increasing the distance between the offset well and SAGD well pairs up to a certain value, oil production increases but decreases after that point. This is due to the ability of the fractures in making connection between the steam chambers in higher distances. When production bottom-hole pressure decreases, the heated oil in near well region is subjected to more pressure drop and causes more oil to be produced. More offset wells result in higher production but simultaneously lower recovery factors. Increasing and decreasing soak time as the last investigated parameter did not affect the trend of production anyway.     

Hexokinase-2-Linked Glycolytic Overload and Unscheduled Glycolysis—Driver of Insulin Resistance and Development of Vascular Complications of Diabetes

The recent discovery of the glucose-induced stabilization of hexokinase-2 (HK2) to proteolysis in cell dysfunction in model hyperglycemia has revealed a likely key initiating factor contributing to the development of insulin resistance and vascular complications in diabetes. Consequently, the increased flux of glucose metabolism without a change in the expression and activity of glycolytic enzymes produces a wave of increased glycolytic intermediates driving mitochondrial dysfunction and increased reactive oxygen species (ROS) formation, the activation of hexosamine and protein kinase C pathways, the increased formation of methylglyoxal-producing dicarbonyl stress, and the activation of the unfolded protein response. This is called HK2-linked glycolytic overload and unscheduled glycolysis. The conditions required to sustain this are GLUT1 and/or GLUT3 glucose uptake and the expression of HK2. A metabolic biomarker of its occurrence is the abnormally increased deposition of glycogen, which is produced by metabolic channeling when HK2 becomes detached from mitochondria. These conditions and metabolic consequences are found in the vasculature, kidneys, retina, peripheral nerves, and early-stage embryo development in diabetes and likely sustain the development of diabetic vascular complications and embryopathy. In insulin resistance, HK2-linked unscheduled glycolysis may also be established in skeletal muscle and adipose tissue. This may explain the increased glucose disposal by skeletal uptake in the fasting phase in patients with type 2 diabetes mellitus, compared to healthy controls, and the presence of insulin resistance in patients with type 1 diabetes mellitus. Importantly, glyoxalase 1 inducer—trans-resveratrol and hesperetin in combination (tRES-HESP)—corrected HK2-linked glycolytic overload and unscheduled glycolysis and reversed insulin resistance and improved vascular inflammation in overweight and obese subjects in clinical trial. Further studies are now required to evaluate tRES-HESP for the prevention and reversal of early-stage type 2 diabetes and for the treatment of the vascular complications of diabetes.