Molecular structures and conformational studies of triarylcyclopropyl and related nonsteroidal antiestrogens

Molecular structures and conformational characteristics of a series of 1,1-dichloro-2,2,3-triarylcyclopropanes (DTACs), which were reported previously to be distinctly antiestrogenic and inhibitors of the estrogen-receptor-positive MCF-7 human breast cancer cells in culture, are reported. In addition, structural and conformational features of the DTACs were compared to the first-known nonsteroidal antiestrogen, MER25, and the clinically useful antiestrogen Tamoxifen. The molecular structures of four DTAC compounds were determined by X-ray diffraction. Crystallographic structures show that the DTAC molecules have nearly the same relative conformation for the three aryl rings which is designated as a "nonpropeller" conformation in contrast to the observed "propeller" conformation for the three rings in all known triarylethylenes. Systematic conformational searches were performed to find the conformational preferences of DTACs, MER25, and Tamoxifen using idealized model compounds built from their respective crystal structure. Energy-minimization and conformational-search studies demonstrated that all DTAC molecules have a common, single global minimum energy conformer for their central core containing the dichlorotriarylcyclopropyl system, which is similar to that found in their crystal structures. Conformational search of MER25 showed that the molecule can assume a number of low-energy conformers of which two, one anti (A1) and one gauche (G1A), have about the same energy. The anti conformation is similar to the one observed in its crystal structure and resembles the estrogenic E-isomer of Tamoxifen, while the lowest energy gauche conformer of MER25 resembles more closely the antiestrogenic Z-isomer of Tamoxifen. NMR spectroscopic analysis of MER25 showed that the molecule exists predominantly in the anti conformation in solution. A comparative review of the structural features and bioactivities of Tamoxifen, DTACs, and MER25 provides a possible explanation for their low estrogen receptor binding affinity which is common to these compounds together with their antiestrogenic activity.     

The necessity of conducting to the end the activities of vector control in the onchocerciasis control program in west Africa: recall of the stakes and proposal of a minimum budget for the period 1998-2002

After a brief presentation of the Onchocerciasis Control Programme in West Africa (OCP), the authors realize the health and socioeconomic consequences that could follow a cessation of larvicide treatment before 2002 in the south-eastern and western extensions of the Programme. Taking into account that OCP activities are theoretically supported until 1997, but aware of financial constraints that will probably increase from now to 2002, this paper proposes an a minima estimation of the residual vector control activities for a "phasing out" spread out for five years (1998-2002). These estimations essentially concern the larvicide coverage, the insecticides used, the entomological surveillance, the logistical support and their financial aspects. As far as 48 U.S. $ million amount for 5 years are concerned, the budget allocated for vector control activities should not exceed the third of the global amount allocated to OCP for the actual fourth financial phase of the Programme (1992-1997).     

Retrospective correction of intensity inhomogeneities in MRI

Medical imaging data sets are often corrupted by multiplicative inhomogeneities, often referred to as nonuniformities or intensity variations, that hamper the use of quantitative analyses. The authors describe an automatic technique that not only improves the worst situations, such as those encountered with magnetic resonance imaging (MRI) surface coils, but also corrects typical inhomogeneities encountered in routine volume data sets, such as MRI head scans, without generating additional artifact. Because the technique uses only the patient data set, the technique can be applied retrospectively to all data sets, and corrects both patient independent effects, such as rf coil design, and patient dependent effects, such as attenuation of overlying tissue experienced both in high field MRI and X-ray computed tomography (CT). The authors show results for several MRI imaging situations including thorax, head, and breast. Following such corrections, region of interest analyses, volume histograms, and thresholding techniques are more meaningful. The value of such correction algorithms may increase dramatically with increased use of high field strength magnets and associated patient-dependent rf attenuation in overlying tissues.     

Can twice weekly hemodialysis expand patient access under resource constraints?

The convention of prescribing hemodialysis on a thrice weekly schedule began empirically when it seemed that this frequency was convenient and likely to treat symptoms for a majority of patients. Later, when urea was identified as the main target and marker of clearance, studies supported the prevailing notion that thrice weekly dialysis provided appropriate clearance of urea. Today, national guidelines on hemodialysis from most countries recommend patients receive at least thrice weekly therapy. However, resource constraints in low‐ and middle‐income countries (LMIC) have resulted in a substantial proportion of patients using less frequent hemodialysis in these settings. Observational studies of patients on twice weekly dialysis show that twice weekly therapy has noninferior survival rates compared with thrice weekly therapy. In fact, models of urea clearance also show that twice weekly therapy can meet urea clearance “targets” if patients have significant residual function or if they follow a protein‐restricted diet, as may be common in LMIC. Greater reliance on twice weekly therapy, at least at the start of hemodialysis, therefore has potential to reduce health care costs and increase access to renal replacement therapy in low‐resource settings; however, randomized control trials are needed to better understand long‐term outcomes of twice versus thrice weekly therapy.     

Spray-Coating of Superhydrophobic Coatings for Advanced Applications

Superhydrophobic coatings are widely applicable, e.g., as self-cleaning surfaces or water–oil separation membranes, yet their wider usage is impeded due to costs of fabrication, size, or substrate limitation. Spray-coating is a versatile coating procedures and might offer a good solution for the fabrication of these superhydrophobic coatings, due to the fact that coatings can be fabricated on various materials in a simple, fast, and inexpensive manner. Most procedures rely on hybrid coatings of hydrophobized nanoparticles and a polymeric matrix, which have several drawbacks including the easy loss of nanoparticles and difficult waste handling. Here, the fabrication of the superhydrophobic material, called Fluoropor, for the first time, by spray-coating on various substrates including metals, tissues, concrete, and glass is presented. It is fabricated by spray-coating a mixture of a highly fluorinated monomer blended with porogens followed by photopolymerization. The superhydrophobicity of the material relies on the porous structure on the micro-/nanoscale across the bulk material and does not require any nanoparticles. Excellent self-cleaning ability of these coatings, resistance against thermal and abrasive impact, and their application as oil–water separation membranes are shown. This versatile applicability is highly promising for real-world application as self-cleaning coatings or oil–water separating membranes.     

Ultralow Expansion Glass as Material for Advanced Micromechanical Systems

Ultralow expansion (ULE) glasses are of special interest for temperature stabilized systems for example in precision metrology. Nowadays, ULE materials are mainly used in macroscopic and less in micromechanical systems. Reasons for this are a lack of technologies for parallel fabricating high-quality released microstructures with a high accuracy. As a result, there is a high demand in transferring these materials into miniaturized application examples, realistic system modeling, and the investigation of microscopic material properties. Herein, a technological base for fabricating released micromechanical structures and systems with a structure height above 100 μm in ULE 7972 glass is established. Herein, the main fabrication parameters that are important for the system design and contribute thus to the introduction of titanium silicate as material for glass-based micromechanical systems are discussed. To study the mechanical properties in combination with respective simulation models, microcantilevers are used as basic mechanical elements to evaluate technological parameters and other impact factors. The implemented models allow to predict the micromechanical system properties with a deviation of only ±5% and can thus effectively support the micromechanical system design in an early stage of development.     

Using Selective Electron Beam Melting to Enhance the High-Temperature Strength and Creep Resistance of NiAl–28Cr–6Mo In Situ Composites

By increasing the density of interfaces in NiAl–CrMo in situ composites, the mechanical properties can be significantly improved compared to conventionally cast material. The refined microstructure is achieved by manufacturing through electron beam powder bed fusion (PBF-EB). By varying the process parameters, an equiaxed or columnar cell morphology can be obtained, exhibiting a plate-like or an interconnected network of the (Cr,Mo) reinforcement phase which is embedded in a NiAl matrix. The microstructure of the different cell morphologies is investigated in detail using scanning electron microscope, transmission electron microscopy, and atom probe tomography. For both morphologies, the mechanical properties at elevated temperatures are analyzed by compression and creep experiments parallel and perpendicular to the building direction. In comparison to cast NiAl and NiAl–(Cr, Mo), the yield strength of the PBF-EB fabricated specimens is significantly improved at temperatures up to 1,027 °C. While the columnar morphology exhibits the best improved mechanical properties at high temperatures, the equiaxial morphology shows nearly ideal isotropic mechanical behavior, which is a substantial advantage over directionally solidified material.     

The smart car seat: personalized monitoring of vital signs in automotive applications

Embedded wireless sensors are important components of mobile distributed computing networks, and one of the target applications areas is health care. The preservation of mobility for senior citizens is one of the key issues in maintaining an independent lifestyle. Thus health technologies inside a car can contribute both to safety issues (supervision of driver fitness) as well as healthcare issues by monitoring vitals signs imperceptibly. In this paper, three embedded measurement techniques for non-contact monitoring of vital signals have been investigated. Specifically, capacitive electrocardiogram (cECG) monitoring, mechanical movement analysis (ballistocardiogram, BCG) using piezo-foils and inductive impedance monitoring were examined regarding their potential for integration into car seats. All three sensing techniques omit the need for electroconductive contact to the human body, but require defined mechanical boundary conditions (stable distances or, in the case of BCG, frictional connection). The physical principles of operation, the specific boundary conditions regarding automotive integration and the results during wireless operation in a running car are presented. All three sensors were equipped with local intelligence by incorporating a microcontroller. To eliminate the need for additional cabling, a wireless Bluetooth communication module was added and used to transmit data to a measurement PC. Finally, preliminary results obtained during test drives on German city roads and highways are discussed.     

A fully integrated 1‐in. AMOLED display using current feedback based on a five‐mask LTPS CMOS process

Abstract— In the past, a five‐mask LTPS CMOS process requiring only one single ion‐doping step was used. Based on that process, all necessary components for the realization of a fully integrated AMOLED display using a 3T1C current‐feedback pixel circuit has recently been developed. The integrated data driver is based on a newly developed LTPS operational amplifier, which does not require any compensation for Vth or mobility variations. Only one operational amplifier per column is used to perform digital‐to‐analog conversion as well as current control. In order to achieve high‐precision analog behavior, the operational amplifier is embedded in a switched capacitor network. In addition to circuit verification by simulation and analytic analysis, a 1‐in. fully integrated AMOLED demonstrator was successfully built. To the best of the authors' knowledge, this is the first implementation of a fully integrated AMOLED display with current feedback.