Effects of 2-(2,4-dimethylphenyl)indan-1,3-dione on serum lipoprotein and lipid metabolism of rodents

2-(2,4-Dimethylphenyl)indan-1,3-dione was shown to be a potent hypolipidemic agent in rodents, lowering significantly both serum cholesterol and triglyceride levels at 20 mg/kg/day. The agent in vivo inhibited the enzymatic activities of ATP-dependent citrate lyase, acetyl-CoA synthetase, cholesterol-7α-hydroxylase, acyl-CoA cholesterol acyl transferase,sn-glycerol-3-phosphate acyl transferase and phosphatidylate phosphohydrolase. Tissue lipid levels of liver and small intestine also were reduced by the agent. The rat serum lipoprotein lipid content was modulated by the drug, which should be favorable for the removable of cholesterol from peripheral tissue for conduction to the liver for clearance from the body. Low density lipoprotein (LDL) cholesterol levels were reduced after treatment, which suggests that the agent potentially reduces deposition of cholesterol in plaques. If chemotherapy for atherosclerosis is to be successful, then the high density lipoprotein (HDL) cholesterol level needs to be elevated more than 16% to 25%, the level produced by current hypolipidemic agents. 2-(2,4-Dimethylphenyl)-indan-1,3-dione offers a 75% increase in HDL cholesterol levels and a 30% reduction of LDL cholesterol levels with a suppression of de novo synthesis of lipids and a reduction of tissue cholesterol deposition.     

十二星座的吸金大法

乐观进取的火象星座敢于投资股市;然而土象星座更愿意选择稳妥保守的理财产品,十二星座各有各青睐的吸金大法。     

Effects of systematic partial volume errors on the estimation of gray matter cerebral blood flow with arterial spin labeling MRI

Objective

Partial volume (PV) correction is an important step in arterial spin labeling (ASL) MRI that is used to separate perfusion from structural effects when computing the mean gray matter (GM) perfusion. There are three main methods for performing this correction: (1) GM-threshold, which includes only voxels with GM volume above a preset threshold; (2) GM-weighted, which uses voxel-wise GM contribution combined with thresholding; and (3) PVC, which applies a spatial linear regression algorithm to estimate the flow contribution of each tissue at a given voxel. In all cases, GM volume is obtained using PV maps extracted from the segmentation of the T1-weighted (T1w) image. As such, PV maps contain errors due to the difference in readout type and spatial resolution between ASL and T1w images. Here, we estimated these errors and evaluated their effect on the performance of each PV correction method in computing GM cerebral blood flow (CBF).

Materials and methods

Twenty-two volunteers underwent scanning using 2D echo planar imaging (EPI) and 3D spiral ASL. For each PV correction method, GM CBF was computed using PV maps simulated to contain estimated errors due to spatial resolution mismatch and geometric distortions which are caused by the mismatch in readout between ASL and T1w images. Results were analyzed to assess the effect of each error on the estimation of GM CBF from ASL data.

Results

Geometric distortion had the largest effect on the 2D EPI data, whereas the 3D spiral was most affected by the resolution mismatch. The PVC method outperformed the GM-threshold even in the presence of combined errors from resolution mismatch and geometric distortions. The quantitative advantage of PVC was 16% without and 10% with the combined errors for both 2D and 3D ASL. Consistent with theoretical expectations, for error-free PV maps, the PVC method extracted the true GM CBF. In contrast, GM-weighted overestimated GM CBF by 5%, while GM-threshold underestimated it by 16%. The presence of PV map errors decreased the calculated GM CBF for all methods.

Conclusion

The quality of PV maps presents no argument for the preferential use of the GM-threshold method over PVC in the clinical application of ASL.

     

Molecular Insights on the Role of (CTA+)(SiO−) Ion Pair into the Catalytic Activity of [CTA+]–Si–MCM-41

Topics in Catalysis - In this work, a theoretical study in conjunction with a spectroscopic analysis by FTIR were carried out in order to obtain molecular insights on the role of...     

Design,Synthesis, and Characterization of Macrocyclic Inhibitors of the Proprotein Convertase Furin

The activation of viral glycoproteins by the host protease furin is an essential step in the replication of numerous pathogenic viruses. Thus, effective inhibitors of furin could serve as broad-spectrum antiviral drugs. A crystal structure of an inhibitory hexapeptide derivative in complex with furin served as template for the rational design of various types of new cyclic inhibitors. Most of the prepared derivatives are relatively potent furin inhibitors with inhibition constants in the low nanomolar or even sub-nanomolar range. For seven derivatives the crystal structures in complex with furin could be determined. In three complexes, electron density was found for the entire inhibitor. In the other cases the structures could be determined only for the P6/P5-P1 segments, which directly interact with furin. The cyclic derivatives together with two non-cyclic reference compounds were tested as inhibitors of the proteolytic activation and replication of respiratory syncytial virus in cells. Significant antiviral activity was found for both linear reference inhibitors, whereas a negligible efficacy was determined for the cyclic derivatives.     

Technische Möglichkeiten und Akzeptanz mobiler Anwendungen

Mobile data communication applications, referred to in this paper as mobile applications, were one of the technological innovation and investment targets in recent years. From the past it became obvious that mono-disciplinary approaches to investigate mobile applications have shortcomings when it comes to successful innovation and investment decisions as interdependencies are insufficiently addressed. The paper therefore aims at structuring the scientific contributions of computer science, business economics and sociology in the context of mobile applications to approximate a holistic understanding comprising technological feasibility, economic opportunities and human needs.     

Comprehensibility of UML-based software product line specifications

Software Product Line Engineering (SPLE) deals with developing artifacts that capture the common and variable aspects of software product families. Domain models are one kind of such artifacts. Being developed in early stages, domain models need to specify commonality and variability and guide the reuse of the artifacts in particular software products. Although different modeling methods have been proposed to manage and support these activities, the assessment of these methods is still in an inceptive stage. In this work, we examined the comprehensibility of domain models specified in ADOM, a UML-based SPLE method. In particular, we conducted a controlled experiment in which 116 undergraduate students were required to answer comprehension questions regarding a domain model that was equipped with explicit reuse guidance and/or variability specification. We found that explicit specification of reuse guidance within the domain model helped understand the model, whereas explicit specification of variability increased comprehensibility only to a limited extent. Explicit specification of both reuse guidance and variability often provided intermediate results, namely, results that were better than specification of variability without reuse guidance, but worse than specification of reuse guidance without variability. All these results were perceived in different UML diagram types, namely, use case, class, and sequence diagrams and for different commonality-, variability-, and reuse-related aspects.     

DIDS: rapidly prototyping configuration design systems

The domain independent design system (DIDS) provides a set of tools for rapidly constructing new configuration design systems from a library of reusable software elements called mechanisms. A DIDS user begins by creating a model of the problem domain and the task to be automated. This includes describing a library of parts from which new artifacts could be configured, optimization and preference criteria, and functionality constraints. DIDS analyzes this input and automatically builds an operational prototype system by selecting and combining mechanisms. DIDS' ability to automate this process is derived from its model of configuration design, which enables reusable mechanisms to be identified and automatically selected based on a problem's characteristics. The use of DIDS is illustrated by showing how DIDS solved an elevator-configuration problem.