Attenuating Effects of Dieckol on Hypertensive Nephropathy in Spontaneously Hypertensive Rats

Hypertension induces renal fibrosis or tubular interstitial fibrosis, which eventually results in end-stage renal disease. Epithelial-to-mesenchymal transition (EMT) is one of the underlying mechanisms of renal fibrosis. Though previous studies showed that Ecklonia cava extracts (ECE) and dieckol (DK) had inhibitory action on angiotensin (Ang) I-converting enzyme, which converts Ang I to Ang II. It is known that Ang II is involved in renal fibrosis; however, it was not evaluated whether ECE or DK attenuated hypertensive nephropathy by decreasing EMT. In this study, the effect of ECE and DK on decreasing Ang II and its down signal pathway of angiotensin type 1 receptor (AT1R)/TGFβ/SMAD, which is related with the EMT and restoring renal function in spontaneously hypertensive rats (SHRs), was investigated. Either ECE or DK significantly decreased the serum level of Ang II in the SHRs. Moreover, the renal expression of AT1R/TGFβ/SMAD was decreased by the administration of either ECE or DK. The mesenchymal cell markers in the kidney of SHRs was significantly decreased by ECE or DK. The fibrotic tissue of the kidney of SHRs was also significantly decreased by ECE or DK. The ratio of urine albumin/creatinine of SHRs was significantly decreased by ECE or DK. Overall, the results of this study indicate that ECE and DK decreased the serum levels of Ang II and expression of AT1R/TGFβ/SMAD, and then decreased the EMT and renal fibrosis in SHRs. Furthermore, the decrease in EMT and renal fibrosis could lead to the restoration of renal function. It seems that ECE or DK could be beneficial for decreasing hypertensive nephropathy by decreasing EMT and renal fibrosis.     

Clinical Significance of Tumor Infiltrating Lymphocytes in Association with Hormone Receptor Expression Patterns in Epithelial Ovarian Cancer

Hormone receptor expression patterns often correlate with infiltration of specific lymphocytes in tumors. Specifically, the presence of specific tumor-infiltrating lymphocytes (TILs) with particular hormone receptor expression is reportedly associated with breast cancer, however, this has not been revealed in epithelial ovarian cancer (EOC). Therefore, we investigated the association between hormone receptor expression and TILs in EOC. Here we found that ERα, AR, and GR expression increased in EOC, while PR was significantly reduced and ERβ expression showed a reduced trend compared to normal epithelium. Cluster analysis indicated poor disease-free survival (DFS) in AR+/GR+/PR+ subgroup (triple dominant group); while the Cox proportional-hazards model highlighted the triple dominant group as an independent prognostic factor for DFS. In addition, significant upregulation of FoxP3+ TILs, PD-1, and PD-L1 was observed in the triple dominant group compared to other groups. NanoString analyses further suggested that tumor necrosis factor (TNF) and/or NF-κB signaling pathways were activated with significant upregulation of RELA, MAP3K5, TNFAIP3, BCL2L1, RIPK1, TRAF2, PARP1, and AKT1 in the triple dominant EOC group. The triple dominant subgroup correlates with poor prognosis in EOC. Moreover, the TNF and/or NF-κB signaling pathways may be responsible for hormone-mediated inhibition of the immune microenvironment.     

Computational-Driven Epitope Verification and Affinity Maturation of TLR4-Targeting Antibodies

Toll-like receptor (TLR) signaling plays a critical role in the induction and progression of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematous, experimental autoimmune encephalitis, type 1 diabetes mellitus and neurodegenerative diseases. Deciphering antigen recognition by antibodies provides insights and defines the mechanism of action into the progression of immune responses. Multiple strategies, including phage display and hybridoma technologies, have been used to enhance the affinity of antibodies for their respective epitopes. Here, we investigate the TLR4 antibody-binding epitope by computational-driven approach. We demonstrate that three important residues, i.e., Y328, N329, and K349 of TLR4 antibody binding epitope identified upon in silico mutagenesis, affect not only the interaction and binding affinity of antibody but also influence the structural integrity of TLR4. Furthermore, we predict a novel epitope at the TLR4-MD2 interface which can be targeted and explored for therapeutic antibodies and small molecules. This technique provides an in-depth insight into antibody–antigen interactions at the resolution and will be beneficial for the development of new monoclonal antibodies. Computational techniques, if coupled with experimental methods, will shorten the duration of rational design and development of antibody therapeutics.     

Facile Deposition of Silver Nanoparticles on Photonic Cellulose Nanocrystals Films: A Study on Solvent Stability and Post Antibacterial Activity

Cellulose nanocrystals (CNCs) incorporated with silver nanoparticles (AgNPs) photonic films have drawn considerable attention due to their plasmonic chiroptical activity. However, the exploitation of some fundamental properties for practical use such as the affinity analysis of metal nanoparticles attached to the surface of photonic films according to the solvent compatibility and antibacterial activity under physical conditions has yet not been studied. Hence, a facile process of in situ deposition of AgNPs into the chiral structure of CNC films is proposed. CNC photonic films, cross-linked by glutaraldehyde are prepared. This interaction generated the solvents-stable photonic film with a considerable amount of unreacted aldehyde functional groups that facilitates the reduction of Ag salt to AgNPs. The formed AgNPs in the photonic films show excellent stability over immersion in various polar and non-polar solvents. The post-solvent treated photonic films display excellent contact-based antibacterial behavior against gram-negative Escherichia coli.     

An experimental evaluation of the effects of ripple current generated by the power conditioning stage on a proton exchange membrane fuel cell stack

In this article, an impedance model of the proton exchange membrane fuel cell stack (PEMFCS) is proposed. The proposed study employs an equivalent circuit of the PEMFCS derived by the frequency response analysis technique. An equivalent circuit for the PEMFCS is developed to evaluate the effects of ripple currents generated by the power-conditioning unit. The calculated results are then verified by means of experiments using a commercially available PEMFCS. The relationship between ripple current and fuel cell performance, such as power loss and fuel consumption, is investigated. Experimental results show that the ripple current can contribute up to a 6% reduction in the available output power. This paper was presented at the Fuel Cells: Materials, Processing, and Manufacturing Technologies Symposium sponsored by the Energy/Utilities Industrial Sector & Ground Transportation Industrial Sector and the Specialty Materials Critical Technologies Sector at the ASM International Materials Solutions Conference, October 13–15, 2003, in Pittsburgh, PA. The symposium was organized by P. Singh, Pacific Northwest National Laboratory, S.C. Deevi, Philip Morris USA, T. Armstrong, Oak Ridge National Laboratory, and T. Dubois, U.S. Army CECOM.     

Shear strength and aging characteristics of 63Sn−37Pb solder bumps with various solder ball and pad sizes

The shear strength and aging characteristics of 63Sn–37Pb solder bumps were characterized with variation in solder ball and UBM pad sizes. The shear strength increased with shorter effective crack size,a _effs which was determined with the solder ball and pad sizes. The shear strength of the solder bumps on Au/Ni/Cu and Ni/Cu did not change significantly with reflow time. Substantial decrease in the shear strength occurred for the solder bumps formed on Au/Ni/Cu with aging treatment, and the shear strength after aging was also related to the bump shape which was determined with the solder ball and pad sizes.     

Development of microstructure and mechanical properties of a Ni-base single-crystal superalloy by hot-isostatic pressing

Effects of the hot-isostatic pressing (HIP) process on microstructures and mechanical properties of Ni-base single crystal superalloy CMSX-4 were investigated. In the overall heat treatment process, the HIP treatment remarkably induced the healing behavior of micropores and decreased the pore size and porosity of superalloy CMSX-4 compared with normally treated specimens. The microstructure of γ′ phase after the HIP process showed rather a coarsening tendency and could be developed by the partially solution and aging treatment. Consequently, the elimination of cast micropores using the HIP step resulted in the inhibition of crack initiation in microstructure and improved the stress-rupture lives of Ni-base single crystal superalloy by 185%.     

SEQUENTIAL LOOP CLOSING IDENTIFICATION OF MULTIVARIABLE PROCESSES USING THE BIASED RELAY FEEDBACK METHOD

Each controller in multiloop control systems for multivariable processes can be tuned sequentially with the ultimate information for the paired input and output while former loops have been closed, and hence, single-input single-output autotuning methods can be applied. In this sequential autotuning for multiloop control systems, several iterations are usually required for better control performances. Especially when pairings are undesirable, the autotuning sequences should be repeated with correct pairings, which result in long field experiments. Here, to avoid this drawback, a simple method to identify process models while loops are being sequentially tuned is proposed. The identified models can be used to correct pairings of multiloop control systems and to improve tuning performances without several field iterations. In addition, they can be used to obtain model-based control systems such as decoupling control systems.     

Preparation and characterization of rubber‐toughened poly(trimethylene terephthalate)/organoclay nanocomposite

Rubber‐toughened poly(trimethylene terephthalate) (PTT)–organoclay nanocomposite (RTPTTCN) was prepared by a melt mixing technique. The rubber‐toughened PTT (RTPTT) was made by blending it with ethylene propylene diene terpolymer (EPDM) and with a small amount of maleated EPDM as a compatibilizer. XRD and TEM analysis indicated that the RTPTTCN forms a partially exfoliated nanocomposite. It was observed from SEM analysis that the clay nanoparticles induced a reduction of rubber particle size in the PTT matrix. Tensile and dynamic mechanical analysis indicated that the clay nanoparticles enhance the stiffness of the RTPTT without adversely affecting its toughness. Melt rheological studies revealed that the nanocomposites exhibited strong shear thinning behavior, and a percolated network of the clay particles was formed. It was also observed from DSC that the clay nanoparticles caused an increase in the nonisothermal crystallization temperature of the PTT. POLYM. ENG. SCI., 47:863–870, 2007. © 2007 Society of Plastics Engineers