Mutation-selection balance under genomic imprinting at an autosomal locus

I model the effect of genomic imprinting on the equilibrium allele frequencies at an autosomal diallelic locus subject to viability selection and mutation. The population size is assumed to be very large; male and female mutation rates may be unequal. Different models examine cases of the inactivation of one gene (with both complete and partial penetrance) and of differential expression of genes according to the parent of origin. In the simplest cases the frequency of the deleterious allele is approximately twice that of a dominant nonimprinting mutant, but considerably less than that of a recessive nonimprinting mutant. Under imprinting, selection and unequal mutation rates interact: other things being equal, male-biased mutation leads to lower mutant frequencies under maternal imprinting and higher frequencies under paternal imprinting. I also model cases where just one allele is imprintable (and the other not). These models allow us to predict the frequency of a failure to imprint in a normally imprinting system, as well as the frequency of imprinting at a standard nonimprinting locus.     

Sedation in practice. 4: The use of sedation for the medically compromised patient

Anti-craving compounds have recently been registered for relapse prophylaxis in weaned alcoholics in various European countries (acamprosate), and in the United States (naltrexone). Acamprosate, the Ca(2+)-salt of N-acetyl-homotaurinate, interacts with NMDA receptor-mediated glutamatergic neurotransmission in various brain regions and reduces Ca2+ fluxes through voltage-operated channels. The opioid receptor antagonist naltrexone most likely interferes with alcohol-induced reinforcement via the block of opioid receptors. In this article Rainer Spanagel and Walter Zieglg?nsberger discuss the pivotal role of incremental neuroadaptation to alcohol and alcohol-associated stimuli for craving, and the possible mechanisms of action underlying the anti-craving properties of acamprosate and naltrexone.     

Case–Based Reasoning for Assessing Intelligent Transportation Systems Benefits

Existing transportation planning modeling tools have critical limitations with respect to assessing the benefits of intelligent transportation systems (ITS) deployment. In this article, we present a novel framework for developing modeling tools for quantifying ITS deployments benefits. This approach is based on using case–based reasoning (CBR), an artificial intelligence paradigm, to capture and organize the insights gained from running a dynamic traffic assignment (DTA) model. To demonstrate the feasibility of the approach, the study develops a prototype system for evaluating the benefits of diverting traffic away from incident locations using variable message signs. A real–world network from the Hartford area in Connecticut is used in developing the system. The performance of the prototype is evaluated by comparing its predictions to those obtained using a detailed DTA model. The prototype system is shown to yield solutions comparable to those obtained from the DTA model, thus demonstrating the feasibility of the approach.     

Stability of intact chorionic gonadotropin (hCG) in serum, liquid whole blood, and dried whole-blood filter-paper spots: impact on screening for Down syndrome by measurement of free beta-hCG subunit

The use of multiple maternal serum biochemical markers in screening for Down syndrome is gaining worldwide acceptance. We sought to study the impact of the potential instability of intact human chorionic gonadotropin (hCG) on free beta-hCG subunit, a marker that has recently been used successfully in such screening. We found that, in practice, any changes in free beta-hCG due to the instability of intact hCG do not inhibit the effectiveness of free beta-hCG as a marker for Down syndrome. This was proven by controlled laboratory experiments at various stress temperatures, freeze-thaw studies, and analysis of a large set of screening data with particular reference to time in transit for individual samples. Data from controlled dissociation studies demonstrate that any apparent increase in free beta-hCG due to the instability of intact hCG cannot be attributed simply to the dissociation of intact hCG. Finally, for large-scale mass population screening in areas of the world where transport delays, safety concerns, and high temperatures preclude the shipment of liquid whole blood, dried whole-blood spots in filter paper provide a suitable delivery system with many advantages.     

Immunoblot studies in the differential diagnosis of porcine brucellosis: an immunodominant 62 kDa protein is related to the mycobacterial 65 kDa heat shock protein (HSP-65)

Smooth Brucella spp. share certain lipopolysaccharide antigens with other bacteria, resulting in serological cross-reactions which can prevent the definitive diagnosis of brucellosis. To identify other antigens with serodiagnostic potential, immunoblot studies following sodium dodecyl sulphate-polyacrylamide gel electrophoresis were carried out. Sera from pigs experimentally infected with Brucella suis and naturally infected feral pigs, sera from pigs from a farm with a known history of Yersinia enterocolitica 0:9 infection, Brucella Complement Fixation Test (CFT) reactor pigs (aetiology unknown) and pigs from consistently Brucella CFT negative farms were examined. Although B. suis infected pigs recognized a total of nine B. melitensis antigens, individual pigs rarely recognized more than three antigens in the range. A 62 kDa antigen was recognized by the majority (73%) of the Brucella infected pigs, but only by 10 to 23% of pigs from the other groups. This antigen was shown to be the Brucella homologue of the ubiquitous 65 kDa heat shock protein (HSP-65) family by immunoblot studies with 14 monoclonal antibodies to the Mycobacterium leprae HSP-65. Only four of these monoclones (Y1.2, ML-30, D7C and IIIC8) identified the B. melitensis 62 kDa protein suggesting that unshared, potentially Brucella specific, regions exist. Sera from Y. enterocolitica 0:9 infected pigs, CFT reactor pigs (aetiology unknown), CFT negative pigs and hyperimmune pig serum raised to Y. enterocolitica 0:9 also recognized B. melitensis antigens, most notably a 17 kDa protein. This antigen appears to be a common cross-reactive protein.     

Inhaled nitric oxide, right ventricular efficiency, and pulmonary vascular mechanics: selective vasodilation of small pulmonary vessels during hypoxic pulmonary vasoconstriction

OBJECTIVE: In the setting of acute pulmonary artery hypertension, techniques to reduce right ventricular energy requirements may ameliorate cardiac failure and reduce morbidity and mortality. Inhaled nitric oxide, a selective pulmonary vasodilator, may be effective in the treatment of pulmonary artery hypertension, but its effects on cardiopulmonary interactions are poorly understood. METHODS: We therefore developed a model of hypoxic pulmonary vasoconstriction that mimics the clinical syndrome of acute pulmonary hypertension. Inhaled nitric oxide was administered in concentrations of 20, 40, and 80 ppm. RESULTS: During hypoxic pulmonary vasoconstriction, the administration of nitric oxide resulted in a significant improvement in pulmonary vascular mechanics and a reduction in right ventricular afterload. These improvements were a result of selective vasodilation of small pulmonary vessels and more efficient blood flow through the pulmonary vascular bed (improved transpulmonary vascular efficiency). The right ventricular total power output diminished during the inhalation of nitric oxide, indicating a reduction in right ventricular energy requirements. The net result of nitric oxide administration was an increase in right ventricular efficiency. CONCLUSION: These data suggest that nitric oxide may be beneficial to the failing right ventricle by improving pulmonary vascular mechanics and right ventricular efficiency.     

Regulation of EGF receptor signaling establishes pattern across the developing Drosophila retina

Developing epithelia use a variety of patterning mechanisms to place individual cells into their correct positions. However, the means by which pattern elements are established are poorly understood. Here, we report evidence that regulation of Drosophila EGF receptor (DER) activity plays a central role in propagating the evenly spaced array of ommatidia across the developing Drosophila retina. DER activity is essential for establishing the first ommatidial cell fate, the R8 photoreceptor neuron. R8s in turn appear to signal through Rhomboid and Vein to create a patterned array of 'proneural clusters' which contain high levels of phosphorylated ERKA and the bHLH protein Atonal. Finally, secretion by the proneural clusters of Argos represses DER activity in less mature regions to create a new pattern of R8s. Propagation of this process anteriorly results in a retina with a precise array of maturing ommatidia.     

Autonomy of the renin system in type II diabetes mellitus: dietary sodium and renal hemodynamic responses to ACE inhibition

OBJECTIVE: To characterize the cytomorphologic features of pilomatrixoma. STUDY DESIGN: Aspirate findings in nine cases of PMX were correlated with clinical data and subsequent histology. This relatively large volume of case material afforded an opportunity to test the cytologic criteria that have been proposed as diagnostic of pilomatrixoma in the case reports published previously. RESULTS: Ghost cells, basaloid cells and calcium deposits were the features found to be most characteristic of PMX and were observed in all four cases in which a correct diagnosis was made originally. CONCLUSION: The presence of ghost cells seems to be the key to recognizing PMX. These cells are visible in the majority of air-dried smears but seldom in alcohol-fixed smears. Adequate cytologic sampling and the routine use of both wet-fixed and air-dried smears should preclude an incorrect diagnosis.     

Tradeoffs in the design of a spaceborne scanning pencil beamscatterometer: application to SeaWinds

SeaWinds is a spaceborne wind scatterometer to be flown on the second Japanese Advanced Earth Observing Satellite (ADEOS-II) in 1999. An important international element of NASA's Earth Observing System (EOS), SeaWinds is an advanced follow-on to the NASA scatterometer (NSCAT) on the first ADEOS platform. Unlike previous operational spaceborne scatterometer systems. SeaWinds employs a scanning “pencil-beam” antenna rather than a “fan-beam” antenna, making the instrument more compact and yielding greater ocean coverage. The goals of this paper are twofold. First, the overall SeaWinds functional design and backscatter measurement approach are described, and the relative advantages of the pencil-beam technique are outlined. Second, the unique aspects of measurement accuracy optimization and signal processing for the SeaWinds instrument are discussed. Applying the results of a separate companion paper, ibid., 1997, a technique to significantly improve measurement accuracy by modulating the transmit pulse is described. Trade-offs to optimize the transmit modulation bandwidth are presented