Pro-Resolving Lipid Mediator Resolvin E1 Mitigates the Progress of Diethylnitrosamine-Induced Liver Fibrosis in Sprague-Dawley Rats by Attenuating Fibrogenesis and Restricting Proliferation

Liver fibrosis is a complex process associated to most types of chronic liver disease, which is characterized by a disturbance of hepatic tissue architecture and the excessive accumulation of extracellular matrix. Resolvin E1 (RvE1) is a representative member of the eicosapentaenoic omega-3 lipid derivatives, and is a drug candidate of the growing family of endogenous resolvins. Considering the aforementioned, the main objective of this study was to analyze the hepatoprotective effect of RvE1 in a rat model of liver fibrosis. Male Sprague-Dawley rats received diethylnitrosamine (DEN, 70 mg/mg body weight intraperitoneally (i.p)) as an inductor of liver fibrosis once weekly and RvE1(100 ng/body weight i.p) twice weekly for four weeks. RvE1 suppressed the alterations induced by DEN, normalizing the levels of alanine aminotransferase (ALT), albumin, and lactate dehydrogenase (LDH), and ameliorated DEN injury by decreasing the architecture distortion, inflammatory infiltration, necrotic areas, and microsteatosis. RvE1 also limited DEN-induced proliferation through a decrease in Ki67-positive cells and cyclin D1 protein expression, which is related to an increase of the levels of cleaved caspase-3. Interestingly, we found that RvE1 promotes higher nuclear translocation of nuclear factor κB (NF-κB)p65 than DEN. RvE1 also increased the levels of nuclear the nuclear factor erythroid 2–related factor 2 (Nrf2), but with no antioxidant effect, measured as an increase in glutathione disulfide (GSSG) and a decrease in the ratio of glutathione (GSH)/GSSG. Taken together, these results suggest that RvE1 modulates the fibrogenesis, steatosis, and cell proliferation in a model of DEN induced fibrosis.     

Ubiquitin C-Terminal Hydrolase L1: Biochemical and Cellular Characterization of a Covalent Cyanopyrrolidine-Based Inhibitor

The deubiquitinase (DUB) ubiquitin C-terminal hydrolase L1 (UCHL1) is expressed primarily in the central nervous system under normal physiological conditions. However, UCHL1 is overexpressed in various aggressive forms of cancer with strong evidence supporting UCHL1 as an oncogene in lung, glioma, and blood cancers. In particular, the level of UCHL1 expression in these cancers correlates with increased invasiveness and metastatic behavior, as well as poor patient prognosis. Although UCHL1 is considered an oncogene with potential as a therapeutic target, there remains a significant lack of useful small-molecule probes to pharmacologically validate in vivo targeting of the enzyme. Herein, we describe the characterization of a new covalent cyanopyrrolidine-based UCHL1 inhibitory scaffold in biochemical and cellular studies to better understand the utility of this inhibitor in elucidating the role of UCHL1 in cancer biology.     

Investigation of Performance Enhancements for Air Brayton/ORC Combined Cycles for Small (~ 2 MWe) Power Systems and a Moderate Heat Source Temperature

JOM - Attractive power generation cycles from economic and sustainability considerations are highly efficient and require minimal cooling water. Air Brayton cycles (ABCs) require no cooling water;...     

WIRELESS BODY-AREA NETWORKS

The last decade has witnessed the convergence of three giant worlds:electronics,computer science and telecommunications.The next decade should follow this convergence in most of our activities with the generalization of sensor networks.In particular with the progress in medicine,people live longer and the aging of population will push the development of wireless person-     

The Role of Cholesterol on Triterpenoid Saponin-Induced Endolysosomal Escape of a Saporin-Based Immunotoxin

Cholesterol seems to play a central role in the augmentation of saporin-based immunotoxin (IT) cytotoxicity by triterpenoid saponins. Endolysosomal escape has been proposed as one mechanism for the saponin-mediated enhancement of targeted toxins. We investigated the effects of lipid depletion followed by repletion on Saponinum album (SA)-induced endolysosomal escape of Alexa Fluor labelled saporin and the saporin-based immunotoxin OKT10-SAP, directed against CD38, in Daudi lymphoma cells. Lipid deprived cells showed reduced SA-induced endolysosomal escape at two concentrations of SA, as determined by a flow cytometric method. The repletion of membrane cholesterol by low density lipoprotein (LDL) restored SA-induced endolysosomal escape at a concentration of 5 µg/mL SA but not at 1 µg/mL SA. When LDL was used to restore the cholesterol levels in lipid deprived cells, the SA augmentation of OKT10-SAP cytotoxicity was partially restored at 1 µg/mL SA and fully restored at 5 µg/mL SA. These results suggest that different mechanisms of action might be involved for the two different concentrations of SA and that endosomal escape may not be the main mechanism for the augmentation of saporin IT cytotoxicity by SA at the sub-lytic concentration of 1 µg/mL SA.     

Metallocene QACs: The Incorporation of Ferrocene Moieties into monoQAC and bisQAC Structures

Inspired by the incorporation of metallocene functionalities into a variety of bioactive structures, particularly antimicrobial peptides, we endeavored to broaden the structural variety of quaternary ammonium compounds (QACs) by the incorporation of the ferrocene moiety. Accordingly, 23 ferrocene-containing mono- and bisQACs were prepared in high yields and tested for activity against a variety of bacteria, including Gram-negative strains and a panel of clinically isolated MRSA strains. Ferrocene QACs were shown to be effective antiseptics with some displaying single-digit micromolar activity against all bacteria tested, demonstrating yet another step in the expansion of structural variety of antiseptic QACs.     

TESLA: an extended study of an energy-saving agent that leverages schedule flexibility

This paper presents transformative energy-saving schedule-leveraging agent (TESLA), an agent for optimizing energy usage in commercial buildings. TESLA’s key insight is that adding flexibility to event/meeting schedules can lead to significant energy savings. This paper provides four key contributions: (i) online scheduling algorithms, which are at the heart of TESLA, to solve a stochastic mixed integer linear program for energy-efficient scheduling of incrementally/dynamically arriving meetings and events; (ii) an algorithm to effectively identify key meetings that lead to significant energy savings by adjusting their flexibility; (iii) an extensive analysis on energy savings achieved by TESLA; and (iv) surveys of real users which indicate that TESLA’s assumptions of user flexibility hold in practice. TESLA was evaluated on data gathered from over 110,000 meetings held at nine campus buildings during an 8-month period in 2011–2012 at the University of Southern California and Singapore Management University. These results and analysis show that, compared to the current systems, TESLA can substantially reduce overall energy consumption.     

Nutrient budget for Saguling Reservoir,West Java,Indonesia

A preliminary nutrient budget for Saguling Reservoir is reported as a first attempt to quantify the behaviour of nutrients entering this reservoir. This work is part of a larger Indonesia-Australia collaborative research and training project, involving Padjadjaran University and Monash University, established to study nutrient dynamics in Saguling Reservoir. Saguling Reservoir, the first of a chain of three large reservoirs (Saguling, Cirata and Jatilahur), built on the Citarum River in central Java, was completed in 1985. It has already become highly polluted, particularly with domestic and industrial effluent (organic matter, nutrients, heavy metals) from the urban areas of Bandung (population 2 million). The reservoir experiences major water quality problems, including excessive growths of floating plants, toxic cyanobacterial blooms and regular fish-kills. The work reported in this paper shows that Saguling receives a very large nutrient load from the city of Bandung and because of this, is highly eutrophic. It is unlikely that the water quality of Saguling will improve until a substantial part of Bandung is sewered and adequate discharge controls are placed on the many industries in the region upstream of the reservoir.