Inhibition of Toll-Like Receptor 4 Signaling Mitigates Microvascular Loss but Not Fibrosis in a Model of Ischemic Acute Kidney Injury

The development of chronic kidney disease (CKD) following an episode of acute kidney injury (AKI) is an increasingly recognized clinical problem. Inhibition of toll-like receptor 4 (TLR4) protects renal function in animal models of AKI and has become a viable therapeutic strategy in AKI. However, the impact of TLR4 inhibition on the chronic sequelae of AKI is unknown. Consequently, we examined the chronic effects of TLR4 inhibition in a model of ischemic AKI. Mice with a TLR4-deletion on a C57BL/6 background and wild-type (WT) background control mice (C57BL/6) were subjected to bilateral renal artery clamping for 19 min and reperfusion for up to 6 weeks. Despite the acute protective effect of TLR4 inhibition on renal function (serum creatinine 1.6 ± 0.4 mg/dL TLR4-deletion vs. 2.8 ± 0.3 mg/dL·WT) and rates of tubular apoptosis following ischemic AKI, we found no difference in neutrophil or macrophage infiltration. Furthermore, we observed significant protection from microvascular rarefaction at six weeks following injury with TLR4-deletion, but this did not alter development of fibrosis. In conclusion, we validate the acute protective effect of TLR4 signal inhibition in AKI but demonstrate that this protective effect does not mitigate the sequential fibrogenic response in this model of ischemic AKI.     

Optical and structural properties of highly porous shell structured Fe doped TiO2 thin films

TiO2thin films with 0.2 wt%, 0.4 wt%, 0.6wt%, and 0.8 wt% Fe were prepared on glass and silicon substrates using sol–gel spin coating technique. The optical cut-off points are increasingly red-shifted and the absorption edge is shifted over the higher wavelength region with Fe content increasing. As Fe content increases, the optical band gap decreases from 3.03 to 2.48 eV whereas the tail width increases from 0.26 to 1.43 eV. The X-ray diffraction（XRD） patterns for doped films at 0.2 wt% and0.8 wt% Fe reveal no characteristic peaks, indicating that the film is amorphous whereas undoped TiO2exhibits（101） orientation with anatase phase. Thin films of higher Fe content exhibit a homogeneous, uniform, and nanostructured highly porous shell morphology.     

Development and benchmarking of a mechanical model for GFR plate-type fuel

The reference fuel design currently being considered within the Generation-IV Gas-cooled Fast Reactor (GFR) project is a ceramic plate matrix with a honeycomb inner structure containing small fuel cylinders. The fuel is mixed plutonium–uranium carbide, while the matrix material is silicon carbide. The present paper describes the mechanical part of a thermal–mechanical model being developed for studying the transient behavior of this highly heterogeneous fuel type. Benchmarking has been carried out against detailed finite-elements modeling (FEM).The resultant thermal–mechanical model can provide reliable fuel and cladding (matrix) stress/strain conditions to evaluate temperatures and neutronic feedbacks. As such, it has been integrated into PSI’s coupled code system “FAST”, which aims at the comprehensive safety analysis of advanced fast reactor systems.The detailed FEM analysis of the GFR fuel has been useful not only for benchmarking the new model, but also for obtaining an in-depth understanding of fuel stress/strain characteristics, which cannot be reproduced with simplified models. Thereby, the range of applicability of the new model has clearly been defined. In particular, the 3D FEM analysis has revealed a concentration of stresses at the pellet corners during pellet/matrix contact, which could lead to fuel element failure. This effect is found to be mitigated considerably, if the fuel pellets are shaped in a manner which enhances the contact area.     

Finding rectilinear least cost paths in the presence of convex polygonal congested regions

This paper considers the problem of finding the least cost rectilinear distance path in the presence of convex polygonal congested regions. We demonstrate that there are a finite, though exponential number of potential staircase least cost paths between a specified pair of origin–destination points. An upper bound for the number of entry/exit points of a rectilinear path between two points specified a priori in the presence of a congested region is obtained. Based on this key finding, a “memory-based probing algorithm” is proposed for the problem and computational experience for various problem instances is reported. A special case where polynomial time solutions can be obtained has also been outlined.     

Protein kinases in mammary gland development and cancer

Protein kinases, the enzymes responsible for phosphorylation of a wide variety of proteins, are the largest class of genes known to regulate growth, development, and neoplastic transformation of mammary gland. Mammary gland growth and maturation consist of a series of highly ordered events involving interactions among several distinct cell types that are regulated by complex interactions among many steroid hormones and growth factors. The mammary gland is one of the few organ systems in mammals that complete their morphologic development postnatally during two discrete physiologic states, puberty and pregnancy. Thus, the mammary gland is an excellent model for studying normal development and the early steps of tumor formation. The susceptibility of the mammary gland to tumorigenesis is influenced by its normal development, particularly during stages of puberty and pregnancy. Numerous experimental and epidemiological studies have suggested that specific details in the development of the mammary gland play a critical role in breast cancer risk. Mammary gland development is characterized by dynamic changes in the expression and functions of protein kinases. Perturbations in the regulated expression or function of protein kinases or their associated signaling pathways can lead to malignant transformation of the breast. For example, overexpression of several receptor-tyrosine kinases, including human epidermal growth factor receptor and HER2/Neu, has been shown to contribute to the development of breast cancer. Since receptor-tyrosine kinases regulate several essential processes such as mitogenesis, motility, invasion, cell survival, and angiogenesis, targeting receptor-tyrosine kinases may have important implications in designing strategies against breast cancer.     

Sponsored R&D in India: The project sponsoring pattern and main outcome of projects sponsored by major central departments/agencies

This paper examines the project sponsoring pattern and the outcome of extramural R&D with respect to the projects sponsored by country's eleven central agencies during the Seventh Five-Year Plan period. The outcome considered are: contribution of R&D support to development of R&D facilities at the recipient institutions, creation of employment through project posts, development of new technologies, quantum and quality of research publications and generation of doctoral thesis. The paper concludes that sponsored R&D has largely remained one-way flow of funds to a preferred set of institutions (as perceived by each sponsoring agency) and the outcome of the R&D have also remained unexamined by the respective funding agencies. The paper advocates development of a monitoring system which would help in enhancing the utilisation of sponsored R&D and its overall impact on science, society and economy.     

A multi-standby multi-failure mode system with repair and replacement policy

This paper investigates the mathematical model of a system composed of (m + 1) non identical units—one functioning and m standby. Each unit of the system has three possible states—normal, degraded and failed. We consider two types of repair facilities—overhaul and minor repair. The system breaks down when the (m + 1)th unit after total failure is finally rejected and no standby remains to replace it. Several reliability characteristics of interest to system designers as well as operations managers have been computed. Results obtained earlier are verified as particular cases.     

Studies on β-alkoxypropionitriles as solvents for extractive distillation

Five solvents of the β-alkoxypropionitrile series have been studied by gas-chromatography in order to examine their potential usefulness as solvents for extractive distillation. Four isomers of C₄-olefin and a diene were used as solutes for the determination of activity coefficients at infinite dilution at 30°C. Relative volatilities were calculated for these solvents and compared with those for other commercial solvents used currently. Relative volatilities of seven C₄-hydrocarbons in two solvents were also studied and compared with the existing literature data for β-methoxypropionitrile containing 5% antisolvent. The present g.c. studies show that besides the well-studied β-methoxypropionitrile, the second member of the series, β-ethoxypropionitrile, also has the potential for use as a selective solvent.     

Photodegradation of direct yellow-12 using UV/H2O2/Fe2+

A detailed investigation of photodegradation of direct yellow-12 (DY12) using UV/H(2)O(2)/Fe(2+) has been carried out in a photochemical reactor. Experiments studied degradation as a function of concentration, decolorization and reduction in chemical oxygen demand (COD). The effect of operating parameters, such as UV, pH, amount of Fenton's reagent (H(2)O(2) and FeSO(4)), and amount of DY12 dye has also been determined. It has been observed that simultaneous utilization of UV irradiation with Fenton's reagent increases the degradation rate of DY12 dye. The dye quickly losses its color and there is an appreciable decrease in COD value, indicating that the dissolved organic have been oxidized. The kinetics of degradation of the dye in dilute aqueous solutions follows pseudo-first order kinetics. Final products detected at the end of the reaction include NO(3)(-), NO(2)(-), N(2)O, NO(2), SO(2), CO(2) and CO. Results indicate that dye degradation is dependent upon pH, UV-intensity, concentration of Fenton's reagent and dye. Acidic pH has been found to be more suitable in comparison to neutral and alkaline. The optimum concentration of Fenton's reagent (H(2)O(2)/Fe(2+)) was found as 1500/500 mg l(-1) for 50 mg l(-1) DY12 dye in water at pH 4. The results indicate that the treatment of DY12 dye wastewater with UV/Fe(2+)/H(2)O(2) system is efficient.