Expression studies of delta-globin gene alleles associated with reduced hemoglobin A2 levels in Greek Cypriots

We previously identified five delta-globin gene alleles associated with reduced hemoglobin (Hb) A2 (Trifillis, P., Ioannou, P., Schwartz, E., and Surrey, S. (1991) Blood 78, 3298-3305). We have now evaluated functional consequences of the changes after expression in COS-1 cells to monitor effects on RNA splicing. In addition, variant Hb A2 tetramers were expressed in yeast to assess effects of amino acid changes on oxygen binding and stability to heat and mechanical agitation. The G --> T change at codon 27 and the A --> G change in IVS-2 both affect RNA splicing, whereas the C --> T change at codon 97 and the AT deletion in IVS-2 have no effect. Oxygen equilibrium curves of the Hb A2 variants expressed in yeast were similar to that of wild type Hb A2. None of the three variant Hb A2 tetramers (Thr --> Ile at codon 4 (Hb deltaT4I), Ala --> Ser at codon 27 (Hb deltaA27S), and Arg --> Cys at codon 116 (Hb deltaR116C)) showed decreased heat stability compared with Hb A2, whereas the Hb deltaT4I variant showed highest instability to mechanical agitation. Co-expression in yeast of alpha-globin chain and the delta-chain variant containing a Leu --> Pro change at codon 141 yielded no identifiable tetramers, suggesting lack of assembly or severe tetramer instability. These studies show the probable cause for decreased Hb A2 for two alleles is due to defective splicing, whereas decreased protein stability, increased tetramer association with red cell membranes, increased interdisulfide bond formation of delta-chains, which inhibits assembly with alpha-chains, and/or reduced assembly is suggested for the other three alleles.     

Adverse environmental conditions in the respiratory and medical ICU settings

Sleep deprivation and fragmentation occurring in the hospital setting may have a negative impact on the respiratory system by decreasing respiratory muscle function and ventilatory response to CO2. Sleep deprivation in a patient with respiratory failure may, therefore, impair recovery and weaning from mechanical ventilation. We postulate that light, sound, and interruption levels in a weaning unit are major factors resulting in sleep disorders and possibly circadian rhythm disruption. As an initial test of this hypothesis, we sampled interruption levels and continuously monitored light and sound levels for a minimum of seven consecutive days in a medical ICU, a multiple bed respiratory care unit (RCU) room, a single-bed RCU room, and a private room. Light levels in all areas maintained a day-night rhythm, with peak levels dependent on window orientation and shading. Peak sound levels were extremely high in all areas representing values significantly higher than those recommended by the Environmental Protection Agency as acceptable for a hospital environment. The number of sound peaks greater than 80 decibels, which may result in sleep arousals, was especially high in the intensive and respiratory care areas, but did show a day-night rhythm in all settings. Patient interruptions tended to be erratic, leaving little time for condensed sleep. We conclude that the potential for environmentally induced sleep disruption is high in all areas, but especially high in the intensive and respiratory care areas where the negative consequences may be the most severe.     

Special issue on women, psychoanalysis, and gender: Editors' introduction.

Introduces this special issue of Psychoanalytic Psychology. This special issue on Women, Psychoanalysis, and Gender is a commemoration of the capability, influence, acceptance, and authority of women in the community of psychoanalysis. In this issue, we turn to both new and more established voices in an expanded arena of gender, culture, and psychoanalysis. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reprocessing of Microcrystalline Cellulose Spheres with Low Drug Concentrations

Spherical dosage forms have been reported to be an efficient and effective method for delivering drugs into the body and controlling their dissolution rate. Substantial work has been conducted in these laboratories illustrating the advantages of microcrystalline cellulose-based spheres for these purposes. Through various methodologies, but most routinely the extrusion and marumerization technique, it has been determined by Funck, et al. that not more than 50% drug can be incorporated into a sphere formulation without the addition of other binders.

Because of the nature of the extrusion and marumerization manufacturing process, the type of drug being processed and the resultant particle size requirements of the spheres, the percent of spheres falling outside the desired particle size can range from between 3% and 20%. For this reason and the possibility of operator errors, our objective was to determine the parameters which needed monitoring when reprocessing was necessary.     

Application of multilayer feedforward neural networks toprecipitation cell-top altitude estimation

The use of passive 118-GHz O₂ observations of rain cells for precipitation cell-top altitude estimation is demonstrated by using a multilayer feedforward neural network retrieval system. Rain cell observations at 118 GHz were compared with estimates of the cell-top altitude obtained by optical stereoscopy. The observations were made with 2-4-km horizontal spatial resolution by using the millimeter-wave temperature sounder (MTS) scanning spectrometer aboard the NASA ER-2 research aircraft during the Genesis of Atlantic Lows Experiment (GALE) and the Cooperative Huntsville Meteorological Experiment (COHMEX) in 1986. The neural network estimator applied to MTS spectral differences between clouds, and nearby clear air yielded an rms discrepancy of 1.76 km for a combined cumulus, mature, and dissipating cell set and 1.44 km for the cumulus-only set. An improvement in rms discrepancy to 1.36 km was achieved by including additional MTS information on the absolute atmospheric temperature profile. An incremental method for training neural networks was developed that yielded robust results, despite the use of as few as 56 training spectra. Comparison of these results with a nonlinear statistical estimator shows that superior results can be obtained with a neural network retrieval system. Imagery of estimated cell-top altitudes was created from 118-GHz spectral imagery gathered from CAMEX, September through October 1993, and from cyclone Oliver, February 7, 1993     

The cue-familiarity heuristic in metacognition

Four experiments contrasted the cue-familiarity hypothesis of feeling-of-knowing judgments (FKJs) and tip-of-the-tongue feelings (TOTs) to the target-retrievability hypothesis. Familiarity of the cues was contrasted to memorability of the targets in a paired-associate design (e.g., A-B A-B, A-B A-B', A-B A-D, A-B C-D), in which the number of repetitions of the cue A terms was dissociated from the memorability of the target B terms. Little support was found for the target-retrievability hypothesis, because in none of the 4 experiments were FKJs related to target memorability. In one experiment, an omnibus retrieval hypothesis (which implicates total retrieval rather than just correct retrieval) and the cue-familiarity hypothesis produced isomorphic predictions that were borne out by the FKJ and TOT results. All 4 experiments supported the cue-familiarity hypothesis, because FKJs and TOTs were directly related to the number of presentations (and thereby the familiarity) of the cues.     

Ionoluminescence decay measured with single ions

A new ion beam analysis-based, single ion technique called the time to first photon has been developed to measure the decay of the luminescence signal of phosphors. Such measurements are currently needed to study luminescence decay mechanisms following high-density excitations and to identify strongly luminescent phosphor coatings with short lifetimes for ion photon emission microscopy (IPEM). The samples for this technique consist of thin phosphor layers placed or coated on the surface of PIN diodes. Single ions from an accelerator strike this sample and simultaneously create ion beam induced luminescence (IBIL) from the phosphor that is measured by a single-photon-detector, and an ion beam induced charge collection (IBICC) signal in the PIN diode. In this case, the IBICC signal provides the start pulse and the IBIL signal the stop pulse to a time to amplitude converter. It is straightforward to show that this approach also measures a signal proportional to activity versus time with an accuracy of 5% as long as the number of detected photons per ion is less than 0.1, which usually requires the use of absorbers for the IBIL detector or electronic discrimination for the IBIL signals. Details of the new analysis are given together with examples of luminescence decay measurements of several ceramic phosphors being considered to coat IPEM samples. IPEM is currently being developed at Sandia National Laboratory (SNL), the University of North Texas in Denton, and the Universities and INFN of Padova and Torino.     

Analysis of interfacial failure in a composite microbundle pull-out experiment

Modeling of the failure of polymer-matrix composites requires substantial information about the mechanisms of failure at the interface, and load redistribution around fiber breaks in the composite. Current interface experiments involving the use of ‘microcomposites’ of single embedded fibers in a matrix generally do not include all the key geometric features of the real composite; in particular, they do not include the effects of fiber volume fraction and the higher matrix shear resulting from closely neighboring fibers. A new experiment was recently devised to assess some of these effects: it is referred to as the single-fiber pull-out from microbundle (SFPOM) experiment. It consists of a hexagonal arrat of seven fibers in a matrix where the outer six fibers are restrained and the center fiber is pulled out. Recent experimental data from tests with this geometry are analyzed here using three mechanical models of the failure process, and parametric studies of the data are performed to assess the appropriateness of each model. Two of the models, based on fracture energy considerations as applied earlier to single embedded fibers in a matrix and adapted to our geometry, were found to model data from the SFPOM experiments poorly. The third model assumes the existence of three zones near a fiber break, including elastic, plastic and frictional debond zones, and was found to provide reasonable fit to the data under realistic assumptions.