Pharmacological distribution diagrams: a tool for de novo drug design

BACKGROUND: There is no empirical data available on attitudes concerning AIDS and habits towards HIV infected patients of physicians in general or private practice. In this study results of a self-evaluation are presented. METHODS: 178 physicians working with out-patients in different medical fields were randomly selected for a cross sectional study and interviewed using a standardised questionnaire. RESULTS: 89% think that they are sufficiently informed about AIDS (in the USA 20%). They regarded the risk of infection to be lower than the Anglo-American physicians. They believed there is a lack of interchange of information between colleagues regarding the degree of infectiousness of referred patients. A third of the physicians fear that other patients will go elsewhere if they find out that their physician is treating AIDS patients. 54% would hold special clinic sessions for HIV-patients outside the normal schedule for practice times. 89% believed that HIV patients were partly to blame for their illness. CONCLUSIONS: Although the physicians recognise the problem of HIV-infection, they partly deny the real necessities and facts. A reason for this could be the emotions underlying the general attitude to everything pertaining to HIV-disease. Attitudes to HIV-disease and the dealing with it in daily practice must be considered on the basis of individual emotional motives.     

Prostaglandin E receptor subtypes in mouse osteoblastic cell line

PGE2 is one of the key molecules in the osteoblast. It is the major prostanoid in the bone, and its production is under the control of both systemic and local factors. PGE2 has been reported to have multiple actions in the osteoblast, such as growth promotion and cell differentiation. To better understand the action of PGE2 in the osteoblast, we determined the PGE receptor subtypes in MC3T3-E1, an osteoblastic cell line derived from the normal mouse calvaria. Northern blot analysis revealed that EP1 and EP4 subtypes are expressed in MC3T3-E1. In contrast, EP3 subtype was not detected by either Northern blot analysis or RT-PCR. The contribution of each subtype was evaluated by studying the effects of subtype-specific analogs on osteoblastic function at confluency and 5 days after confluency. An EP1 agonist, 17-phenyl-omega-trinor PGE2, increased DNA synthesis and decreased alkaline phosphatase activity. 11-Deoxy-PGE1, and EP2 and EP4 agonist, decreased DNA synthesis and increased alkaline phosphatase activity at both stages. Butaprost, an EP2-selective agonist, showed effects similar to those of 11-deoxy-PGE1 only at confluency. Another and more differentiated osteoblastic marker, osteocalcin production, was detectable and was stimulated by 11-deoxy-PGE1 only 5 days after confluency. The exposure of these cells to EP1 agonist changed the cell shape to a more fibroblastic appearance. These results indicate that EP1, EP4, and probably EP2 are present in MC3T3-E1 cells; EP1 promotes cell growth, and EP2 and EP4 mediate differentiation of the osteoblast. Furthermore, the decreased response to EP2-specific agonist 5 days after confluency suggests that the expression of PGE receptor subtype is dependent on the stage of osteoblastic differentiation. This is the first report to determine PGE receptor subtypes in the bone.     

Improving the performance of microstrip-patch antennas

This paper describes a cavity-backed patch-antenna geometry, which features multiple dielectric layers and shorting posts. These features are exploited to design antennas which retain many of the desirable characteristics of conventional microstrip antennas, yet overcome some of their inherent disadvantages     

Electronic `how things work' articles: two early prototypes

The electronic encyclopedia exploratorium (E³) is a vision of a future computer system-an electronic book describing how thing work. Typical articles in E³ will describe such mechanisms as compression refrigerators, engines, telescopes, and mechanical linkages. Each article will provide simulations, three-dimensional animated graphics that the user can manipulate, laboratory areas that allow a user to modify the device or experiment with related artifacts, and a facility for asking questions and receiving customized, computer-generated English-language explanations. Some of the foundational technology is discussed, focusing on topics in artificial intelligence, graphics, and user interfaces. The initial prototype system and the technical lessons learned from it, as well as the second prototype currently under construction, are described     

Performance of the PAC optical packet network

For multiuser packet communications with unpredictable user demands (e.g., in a local or metropolitan area network), coordination and control of access to the frequency-division multiplexing (FDM) channels are difficult. B. Glance (J. Lightwave Technol., vol.10, pp.1323-1328, Sep 1992) proposed using a simple protection-against-collision (PAC) circuit to solve this media access problem and achieve full optical connectivity. The PAC system has the potential to interconnect hundreds of ports, each transmitting at several gigabits per second. Performance aspects of the PAC optical packet network are discussed here. The delay-throughout performance of this network is analyzed for uniform traffic patterns. The results show that in geographically distributed applications the maximum achievable throughput (normalized to the transmission rate) is typically between 0.4 and 0.5 per channel. In a centralized switch the (normalized) maximum achievable throughput can approach 0.8 per channel     

Planned versus actual duration of drug abuse treatment. Reconciling observational and experimental evidence

The purpose of the study was to evaluate the associations of planned versus actual duration of drug abuse treatment with psychosocial outcomes and drug use at follow-up. A randomized trial was conducted in a modified therapeutic community in which 444 clients were assigned to programs with planned durations of either 3 or 6 months. Outcomes were psychosocial measures assessing changes in mood and in stage of behavior change between admission and exit and return to drug use and patterns of use 2 to 6 months after exit. Planned duration was not associated with any of the outcomes. A longer actual length of stay was, however, associated with greater improvements in the mood variables; lower rates of drug use at follow-up; and, among those using drugs at follow-up, a longer time from exit to first drug use. Intention-to-treat analyses supported these results. Randomized controlled trials are needed to distinguish the effects of planned duration and actual length of stay.     

Spatial retardation of carrier heating in scaled 0.1-μmn-MOSFET's using Monte Carlo simulations

A comprehensive Monte Carlo simulator is employed to investigate nonlocal carrier transport in 0.1 μm n-MOSFET's under low-voltage stress. Specifically, the role of electron-electron (e-e) interactions on hot electron injection is explored for two emerging device designs biased at a drain voltage V_d considerably less than the Si/SiO₂ injection barrier height φ_b. Simulation of both devices reveal that 1) although qV_d<φ_b, carriers can obtain energies greater than φ_b, and 2) the peak for electron injection is displaced approximately 20 nm beyond the peak in the parallel channel electric field. These phenomena constitute a spatial retardation of carrier heating that is strongly influenced by e-e interactions near the drain edge. (Virtually no injection is observed in our simulations when e-e scattering is not considered.) Simulations also show that an aggressive design based on larger dopant atoms, steeper doping gradients, and a self-aligned junction counter-doping process produces a higher peak in the channel electric field, a hotter carrier energy distribution, and a greater total electron injection rate into the oxide when compared to a more conventionally-doped design. The impact of spatially retarded carrier heating on hot-electron-induced device degradation is further examined by coupling an interface state distribution obtained from Monte Carlo simulations with a drift-diffusion simulator. Because of retarded carrier heating, the interface states are mainly generated further over the drain region where interface charge produces minimal degradation. Thus, surprisingly, both 0.1 μm n-MOSFET designs exhibit comparable drain current degradation rates     

Phase I trial of inhaled natural interleukin 2 for treatment of pulmonary malignancy: toxicity, pharmacokinetics, and biological effects

Safety, local and systemic immunomodulation, and tumor response to treatment with aerosolized natural interleukin 2 (nIL-2) applied five times a day were studied in a Phase I trial in 16 patients with pulmonary malignancies refractory to conventional therapy. The toxicity of inhaled nIL-2 was different from that observed after systemic administration. Reversible airway irritation causing a nonproductive cough represented the dose-limiting toxicity. Mild to moderate reduction of the vital capacity and forced expiratory volume (FEV1) with minor effects on relative FEV1, peak expiratory flow, airway resistance, and PaO2 was experienced by individual patients. In 14 patients suffering from pulmonary metastases due to renal cell cancer, one durable complete response, one partial response, and one mixed response were observed. Inhalation of nIL-2 aerosol resulted in a dose-dependent expansion of pulmonary immunocompetent cells in bronchoalveolar lavage fluid. Posttreatment bronchoalveolar lavage showed an activated lymphocyte phenotype with increased HLA-DR expression. The only systemic biological effect detectable in peripheral blood was a marked increase of soluble interleukin 2 receptor serum levels. We conclude that treatment with aerosolized nIL-2 is an effective means for site-specific immunomodulation and deserves further investigation for the treatment of malignant and inflammatory lung disease.     

The greenhouse effect; Impact upon and the role to be played by construction

The authors highlight several possible ways in which the construction industry could lower present emissions of the greenhouse gas, carbon dioxide. It is an excellent discussion document and is recommended reading.