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.     

Performance investigation in modified and improved augmented power generation Kalina cycle using Python

In the generation of electricity and cogeneration, Kalina cycle is considered as one of the competitors to organic Rankine cycle. With the simplicity and identical components of the binary mixture, Kalina system makes it more prominent to get developed and implemented as well with its environmental friendly associate. This work proposes a new improved Kalina cycle system to convert the natural source from sun to useful work. The proposed system utilizes heat source suitable to medium temperature heat applications. The proposed cycle have 2 units of solar collector, favoring an additional heat recovery and higher performance. Solar hot source temperature and pressure are 190°C and 45 bar with additional flow to the turbine of 1.15 kg/s. Energy and second law analysis have considered in evaluating the performance of the proposed plant. The energy analysis shows minimum value of net power, energy efficiency and plant efficiency as 241 kW, 15.5% and 5.7. The exergy analysis defines that, to the proposed cycle, the exergy efficiency initializes at 77% with more exergy destruction at turbine with 31%. With the parametric analysis, the system is amended to have the maximum values of energy and exergy performances as 18.5%, 7.1% and 85%. The parametric study identifies the optimum value of the inlet temperature and pressure of the pump and turbine.     

Enhancement of the Dynamic Computation-Offloading Service Selection Framework in Mobile Cloud Environment

Wireless Personal Communications - In the era of cloud computing, any mobile device can augment its capabilities by using Cloud computation service. There are different services provided by...     

Renal cell tumours in mice: electron microscopy versus immunohistochemistry

15 renal cell tumours induced in CBA male mice by 1,2-dimethylhydrazine were studied electronmicroscopically (EM). All these tumours earlier were investigated histochemically and immunohistochemically with the use of gamma-glutamyltranspeptidase (GGT) as a marker of the proximal tubules and antigen A6 as a marker of distal tubules and/or collecting ducts. One of the tumours was GGT-positive and antigen A6-negative and ultrastructurally well developed brush border was found. This correlation between immunohistochemistry and EM data allowed to conclude that the site of origin of this tumour were the cells of the proximal tubules. All other tumours were GGT-negative and antigen A6-positive, i.e. the development of these tumours from the distal tubules (and not from the proximal tubules) could be suspected. However in 5 of these neoplasms reduced brush border was found. Microvilli were of a smaller size than in normal proximal tubules and were frequently located not on the apical cell surface but in the narrow spaces between two cells. Invaginations and apical vesicles typical for the normal proximal tubules were also found in some tumour cells. EM and immunohistochemical data combined allow to suggest the origin of these tumours from the common precursor cell capable of differentiation, in the course of tumour progression, into the cells with properties of proximal and/or distal tubules.     

Diagnosis-related groups: a comparative analysis of hospital activity in different countries

Comparative study of hospital activities in the Novgorod district and nine countries of the European Community, carried out within the framework of the International Project CAMISE (Case Mix and Severity) of the European Community on the basis of the classification system for diagnosis-related groups, showed a lower Case Mix Index, a longer hospital stay for all major disease, and a lower surgical activity in the hospitals of the Novgorod district in comparison with other European countries. The detected differences are largely due to specific features in the organization of hospital service in Russia (no special hospitals for acute and chronic patients, no nursing homes) and insufficiently intensive therapeutic and diagnostic process.