Cholesteryl ester transfer protein (CETP) mediates the transfer of cholesterol esters (CE) from atheroprotective high-density lipoproteins (HDL) to atherogenic low-density lipoproteins (LDL). CETP ...inhibition has been regarded as a promising strategy for increasing HDL levels and subsequently reducing the risk of cardiovascular diseases (CVD). Although the crystal structure of CETP is known, little is known regarding how CETP binds to HDL. Here, we investigated how various HDL-like particles interact with CETP by electron microscopy and molecular dynamics simulations. Results showed that CETP binds to HDL via hydrophobic interactions rather than protein-protein interactions. The HDL surface lipid curvature generates a hydrophobic environment, leading to CETP hydrophobic distal end interaction. This interaction is independent of other HDL components, such as apolipoproteins, cholesteryl esters and triglycerides. Thus, disrupting these hydrophobic interactions could be a new therapeutic strategy for attenuating the interaction of CETP with HDL.
The standard placement of a subpalpebral lavage system may not be feasible in some horses with eyelid disease. We describe placement of a commercially available, indwelling nasolacrimal lavage system ...that circumvents eyelid perforation. This novel approach provided for effective delivery of drugs to 1 horse with periocular and corneal disease.
The authors' goal was to assess dexamethasone for the treatment of depression.
Thirty-seven outpatients (11 men and 26 women) meeting DSM-III-R criteria for major depressive disorder were randomly ...assigned to receive either placebo or 4 mg/day of oral dexamethasone for 4 days. Baseline Hamilton depression scale scores were compared with scores obtained 14 days after the first dose of study medication. Data were analyzed by using two-sample t tests, chi-square methods, and Fisher's exact test.
Seven (37%) of the 19 patients given dexamethasone but only one (6%) of the 18 patients given placebo responded positively. No adverse events or side effects were reported, and all patients who entered the study completed it.
A brief course of oral dexamethasone (4 days) was significantly more effective than placebo within 14 days for the treatment of depression in a randomized, double-blind study of depressed outpatients.
We have measured parity-violating asymmetries in elastic electron-proton scattering over the range of momentum transfers 0.12 < or =Q2 < or =1.0 GeV2. These asymmetries, arising from interference of ...the electromagnetic and neutral weak interactions, are sensitive to strange-quark contributions to the currents of the proton. The measurements were made at Jefferson Laboratory using a toroidal spectrometer to detect the recoiling protons from a liquid hydrogen target. The results indicate nonzero, Q2 dependent, strange-quark contributions and provide new information beyond that obtained in previous experiments.
The authors discuss obstacles and incentives associated with successful community-based public-academic liaison activities and illustrate their conclusions by describing their public-academic liaison ...program, which received the American College of Psychiatrists' first annual Award for Creativity in Psychiatric Education.
The first 8 years of a state/university collaboration are described in which the parties involved first developed a variety of innovative services designed to fill specific gaps in the public service delivery system and subsequently integrated academic research and training components.
The carefully planned and monitored process resulted in the exponential growth of interest in public sector work, the realization of the university's primary goals of developing high quality training and research sites, a substantial increase in the number of graduates accepting positions in the public sector, several projects funded by the National Institute of Mental Health, and two national awards.
These collaborations illustrate the highly complementary relationship of public-academic liaison activities and their potential capacity to improve access to services, substantially improve the quality of these services, generate extramural support for services research, and increase the number of well-trained professionals in the public sector.
Cholesteryl ester transfer protein (CETP) mediates the transfer of cholesterol esters (CE) from atheroprotective high-density lipoproteins (HDL) to atherogenic low-density lipoproteins (LDL). CETP ...inhibition has been regarded as a promising strategy for increasing HDL levels and subsequently reducing the risk of cardiovascular diseases (CVD). Although the crystal structure of CETP is known, little is known regarding how CETP binds to HDL. Here, we investigated how various HDL-like particles interact with CETP by electron microscopy and molecular dynamics simulations. Results showed that CETP binds to HDL via hydrophobic interactions rather than protein-protein interactions. The HDL surface lipid curvature generates a hydrophobic environment, leading to CETP hydrophobic distal end interaction. This interaction is independent of other HDL components, such as apolipoproteins, cholesteryl esters and triglycerides. Thus, disrupting these hydrophobic interactions could be a new therapeutic strategy for attenuating the interaction of CETP with HDL.
Designers of office information systems, which share various features with information systems and software development, need to carefully consider special issues such as document and communication ...flows, user roles, user interfaces, and available technology. The ESPRIT Project, Automatic TOols for Designing Office Information Systems (TODOS), proposes an integrated environment for office design with tools for requirements collection and analysis, conceptual design, rapid prototyping, and architecture selection. Conceptual design is a central phase of office system design: It provides correct and complete functional requirements from which the office prototype will be developed and the final architecture chosen. C-TODOS, the conceptual design support tool developed within TODOS, is presented in this paper. The purpose of C-TODOS is to give the designer tools for supporting conceptual modeling activities with the goal of obtaining correct, consistent, and good quality office-functional specifications. This paper presents C-TODOS within the TODOS development environment and describes the basic features of the tool: the TODOS Conceptual Model, the Specification Database, and the Modeling, Query and Consistency Checking Modules. The use of C-TODOS, through illustration of the development of a test case, and possible future research are discussed.
We report on a 13-yr-old boy with acrodysostosis, a review of 30 cases in the literature, and metacarpophalangeal pattern profile (MCPP) analysis. The prominent manifestations (present in greater ...than 75% of cases) of this condition include nasal and maxillary hypoplasia, peripheral dysostosis, first ray hyperplasia of the foot, acromesomelic brachymelia, decreased interpedicular distance, advanced skeletal maturation and mental retardation. Results of chromosome studies have been normal. An autosomal dominant inheritance pattern was reported in two families. Maternal and paternal ages were 2 and 3 yr, respectively, above the average age of the general parent population, which suggests that advanced parental age may be a factor in the cause of this condition. A characteristically abnormal MCPP was found in our patient and in 16 additional cases studied from the literature. A mean MCPP was developed for the syndrome. MCPP analysis may be useful as a diagnostic tool in patients suspected to have acrodysostosis.