Comparison of 6-s-cis- and 6-s-trans-locked analogs of 1alpha,25-dihydroxyvitamin D3 indicates that the 6-s-cis conformation is preferred for rapid nongenomic biological responses and that neither 6-s-cis- nor 6-s-trans-locked analogs are preferred for genomic biological responses

The hormone 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] generates biological responses via both genomic and rapid, nongenomic mechanisms. The genomic responses utilize signal transduction pathways linked to a nuclear receptor (VDRnuc) for 1alpha,25(OH)2D3, while the rapid responses are believed to utilize other signal transduction pathways that may be linked to a putative membrane receptor for 1alpha,25(OH)2D3. The natural seco steroid is capable of facile rotation about its 6,7 single carbon bond, which permits generation of a continuum of potential ligand shapes extending from the 6-s-cis (steroid like) to the 6-s-trans (extended). To identify the shape of conformer(s) that can serve as agonists for the genomic and rapid biological responses, we measured multiple known agonist activities of two families of chemically synthesized analogs that were either locked in the 6-s-cis (6C) or 6-s-trans (6T) conformation. We found that 6T locked analogs were inactive or significantly less active than 1alpha,25(OH)2D3 in both rapid responses (transcaltachia in perfused chick intestine, 45Ca2+ influx in ROS 17/2.8 cells) and genomic (osteocalcin induction in MG-63 cells, differentiation of HL-60 cells, growth arrest of MCF-7 cells, promoter transfection in COS-7 cells) assays. In genomic assays, 6C locked analogs bound poorly to the VDRnuc and were significantly less effective than 1alpha,25(OH)2D3 in the same series of assays designed to measure genomic responses. In contrast, the 6C locked analogs were potent agonists of both rapid response pathways and had activities equivalent to the conformationally flexibile 1alpha,25(OH)2D3; this represents the first demonstration that 6-s-cis locked analogs can function as agonists for vitamin D responses.     

Fully differential operational amplifiers with accurate outputbalancing

Design considerations are presented for attaining accurate output balancing in fully differential operational amplifiers over the useful operating frequency of the differential signals. Such output balancing is obtained by merging the common-mode feedback and the differential gain paths as close to the front end of the amplifier as possible, ensuring maximum sharing of circuit components. Two circuit designs implemented in a 5-V, 1.75-μm process are presented, one based on a two-stage topology and one based on a folded cascode topology. Experimental results for both designs are given     

Outcome analysis of vesicoureteral reflux in children with myelodysplasia

PURPOSE: Vesicoureteral reflux in children with myelodysplasia is usually secondary to abnormal bladder storage. The purpose of this study was to assess the outcome of vesicoureteral reflux in children with myelodysplasia. MATERIALS AND METHODS: We retrospectively analyzed the records of 319 children with myelodysplasia who presented to our institution between 1978 and 1985. Of these children 95 presented with or had reflux during followup and they were treated with prophylactic antibiotics. Clean intermittent catheterization and anticholinergic medication were added to the regimen when indicated. RESULTS: Reflux resolved in 63% of these patients with nonsurgical management. Temporary cutaneous vesicostomy was performed in 23 children (24%) with persistent high grade reflux or evidence of upper tract deterioration. Ureteral reimplantation and augmentation cystoplasty were performed in 18 (20%) and 8 (8%) patients, respectively. No patient had progression to chronic renal failure and scars developed in only 14 kidneys (10%). CONCLUSIONS: In the majority of cases (63%) reflux resolved with nonsurgical management. Reflux in these patients should not be treated in isolation. The management of reflux is primarily aimed at improving bladder storage. The combination of aggressive nonsurgical therapy and close observation is recommended. This regimen leads to the satisfactory resolution of reflux with minimal renal morbidity.     

Effect of veno-venous ultrafiltration on myocardial performance immediately after cardiac surgery in children. A prospective randomized study

OBJECTIVES: This study sought to evaluate the effects of veno-venous ultrafiltration on myocardial contractility in children undergoing cardiopulmonary bypass (CPB) for repair of congenital heart defects. BACKGROUND: Ultrafiltration (UF) is currently used to diminish postoperative fluid accumulation following CPB in children. Previous reports indicate improvement in hemodynamics immediately after UF, but the mechanism of its action is unknown. METHODS: Twenty-three patients (ages 2 months to 9.1 years; 13 males, 10 females) underwent UF for 10 min after CPB. Twelve patients underwent UF immediately after CPB (Group A). They were studied: (1) before and (2) after CPB, (3) after UF, and (4) 10 min after UF. Eleven patients underwent UF 10 min after CPB (Group B). They were studied: (1) before and (2) after CPB, (3) after a 10-min delay before UF, and (4) after UF. Contractility was determined by the difference in the observed and predicted velocity of circumferential fiber shortening for the measured wall stress, using transesophageal echocardiography. Left ventricular wall thickness was also measured. RESULTS: There was significant improvement in contractility after UF in both groups (mean+/-SD, Group A: -0.28+/-0.13 to -0.01+/-0.21 circ/s, p < 0.05; Group B: -0.26+/-0.16 to -0.11+/-0.17 circ/s, p < 0.05). Myocardial thickness to cavity dimension decreased in both groups following UF (Group A: 0.19+/-0.04 to 0.14+/-0.03, p < 0.05; Group B: 0.18+/-0.04 to 0.14+/-0.03, p < 0.05). CONCLUSIONS: UF improves hemodynamics by improving contractility and possibly by reducing myocardial edema in children following cardiac surgery. Enhanced patient outcome after ultrafiltration may in part be due to these changes.     

Trends and patterns of mortality associated with birth defects and genetic diseases in the United States, 1979-1992: an analysis of multiple-cause mortality data

Contemporary information on the trends and patterns of mortality associated with birth defects and genetic diseases is lacking in the United States. To study these trends and patterns, we used the Multiple-Cause Mortality Files of the National Center for Health Statistics. From 1979 through 1992, 320,208 deaths in the United States were associated with birth defects and genetic diseases. The age-adjusted mortality rates for people with birth defects declined from about 8.2/100,000 in 1979 to about 6.7/100,000 in 1992, and the mortality rates for people with genetic diseases increased from 2.2/100,000 in 1979 to 2.5/100,000 in 1992. The mortality rate was higher among men than among women and higher among blacks than among whites or other races for both birth defect- and genetic disease-associated deaths. The rate among infants with birth defects was more than 25 times higher than that among other age groups. About half of the children whose deaths were associated with birth defects had cardiovascular system defects, 15% had central nervous system defects, and 12% had chromosomal defects. For deaths associated with genetic diseases, hereditary neurologic or storage disorders were the most common genetic diseases (38%), followed by metabolic disorders (21%), sickle cell and thalassemia (12%). The decline in the rate of mortality from birth defects in the United States probably reflects improvements in medical and surgical care and other factors. Most of the mortality associated with birth defects remains in the pediatric age group (less than 15 years old). The upward trend we detected for the deaths with genetic diseases was most likely related to improved recognition and reporting of some genetic diseases rather than to the increased prevalence.     

Reaction of phenol with nitrite ion: pathways of formation of nitrophenols in environmental waters

When sodium nitrite is spiked into phenolic waters, 2-nitrophenol is produced immediately while 4-nitrophenol forms in minor yield after an induction period. The reaction occurs at ambient temperature under acidic, neutral and alkaline conditions. The reaction also occurs in the dark. The nature and yield of the products formed in the dark are analogous to that obtained under ordinary light. Results show that the formation of 2-nitrophenol is first order in nitrite, however, within a narrow range of concentrations. No such order of reaction could be determined for 4-nitrophenol, the yield of which increases in presence of excess nitrite ions and at high nitrite to phenol ratios. Results of this study indicate that NO(2)(-) is the active species in the reaction, attacking the phenol ring at the ortho position and at the same time undergoing a para-substitution in excess nitrite atmosphere. Neither any photo-induced oxidation nor any nitronium ion, NO(2)(+) formation is involved as active species in the nitration of phenol. Our study indicates that in environmental waters a simple contact of nitrite ion with phenolic wastewaters under ambient conditions may form mononitrophenols, which are toxic to aquatic species.     

Semantic Understanding of General Linguistic Items by Means of Fuzzy Set Theory

Modern statistical techniques used in the field of natural language processing are limited in their applications by the fact they suffer from the loss of most of the semantic information contained in text documents. Fuzzy techniques have been proposed as a way to correct this problem through the modelling of the relationships between words while accommodating the ambiguities of natural languages. However, these techniques are currently either restricted to modelling the effects of simple words or are specialized in a single domain. In this paper, we propose a novel statistical-fuzzy methodology to represent the actions described in a variety of text documents by modelling the relationships between subject-verb-object triplets. The research will focus in the first place on the technique used to accurately extract the triplets from the text, on the necessary equations to compute the statistics of the subject-verb and verb-object pairs, and on the formulas needed to interpolate the fuzzy membership functions from these statistics and on those needed to de fuzzify the membership value of unseen triplets. Taken together, these sets of equations constitute a comprehensive system that allows the quantification and evaluation of the meaning of text documents, while being general enough to be applied to any domain. In the second phase, this paper will proceed to experimentally demonstrate the validity of our new methodology by applying it to the implementation of a fuzzy classifier conceived especially for this research. This classifier is trained using a section of the Brown Corpus, and its efficiency is tested with a corpus of 20 unseen documents drawn from three different domains. The positive results obtained from these experimental tests confirm the soundness of our new approach and show that it is a promising avenue of research.     

Patterned Multipixel Membrane Mirror MEMS Optically Addressed Spatial Light Modulator With Megahertz Response

In this letter, we report the fabrication, modeling and characterization of an all-optically addressed spring patterned silicon-nitride deformable mirror microelectromechanical-systems device. Combinations of high-frequency ac and dc bias voltages are applied across the device. The experimental verified theoretical modeling for this device shows the mirror deflection saturation as a function of light intensity appropriate for the dynamic range compression deconvolution. Frequency response up to 10MHz, practical for correcting very fast turbulences, was measured