Limitations on wind-tunnel pressure signature extrapolation

Analysis of some recent experimental sonic boom data has revived the hypothesis that there is a closeness limit to the near-field separation distance from which measured wind tunnel pressure signatures can be extrapolated to the ground as though generated by a supersonic-cruise aircraft. Geometric acoustic theory is used to derive an estimate of this distance and the sample data is used to provide a preliminary indication of practical separation distance values

Black-White Disparities in Pain Management among Nursing Home Residents with Cancer

Background: Racial disparities in pain management persist across healthcare settings and likely extend into nursing homes. No studies to-date have thoroughly evaluated racial disparities in cancer pain management in this setting. Methods: Using a cross-sectional study design, we compared reported pain and pharmacological pain management between non-Hispanic White and Black newly admitted nursing home residents with cancer (n=113,765) using the Minimum Data Set version 3.0. Pain management strategies considered included: use of scheduled analgesics, pro re nata analgesics, and non-pharmacological methods. Presence of pain was based on self-report when residents were able to, or by staff. Logistic models provided estimates of odds ratios for pain management strategies adjusted for resident factors. Results: Among nursing home residents with cancer, nearly one-third reported pain with estimates similar in Black (32.4%) and White (32.8%) residents. Estimates of pain frequency and intensity were also similar by race. While most residents received scheduled pharmacologic pain management, Whites had greater odds of receiving it than Blacks (Whites: 72.8%, Blacks: 69.3%, adjusted odds ratio Black vs. White (aOR): 0.92; 95% confidence interval (CI): 0.88-0.96). Pro re nata analgesic use was more common in Whites than Blacks (Whites: 40.1%, Blacks: 38.5%, aOR: 0.78; 95% CI: 0.75-0.81) as were non-pharmacologic approaches (Whites: 33.1%, Blacks: 25.3%, aOR: 0.70; 95 CI%: 0.67-0.73). Conclusions: While reporting of pain was similar for Black and White nursing home residents, White residents received more frequent pain management at admission. The extent to which unequal management of pain persists in nursing homes should be further explored

Frameshift Variant in MFSD12 Explains the Mushroom Coat Color Dilution in Shetland Ponies

Mushroom is a unique coat color phenotype in Shetland Ponies characterized by the dilution of the chestnut coat color to a sepia tone and is hypothesized to be a recessive trait. A genome wide association study (GWAS), utilizing the Affymetrix 670K array (MNEc670k) and a single locus mixed linear model analysis (EMMAX), identified a locus on ECA7 for further investigation (Pcorrected = 2.08 × 10−10). This locus contained a 3 Mb run of homozygosity in the 12 mushroom ponies tested. Analysis of high throughput Illumina sequencing data from one mushroom Shetland pony compared to 87 genomes from horses of various breeds, uncovered a frameshift variant, p.Asp201fs, in the MFSD12 gene encoding the major facilitator superfamily domain containing 12 protein. This variant was perfectly concordant with phenotype in 96 Shetland Ponies (P = 1.15 × 10−22), was identified in the closely related Miniature Horse for which the mushroom phenotype is suspected to occur (fmu = 0.02), and was absent in 252 individuals from seven additional breeds not reported to have the mushroom phenotype. MFSD12 is highly expressed in melanocytes and variants in this gene in humans, mice, and dogs impact pigmentation. Given the role of MFSD12 in melanogenesis, we propose that p.Asp201fs is causal for the dilution observed in mushroom ponies

Design and analysis of low boom concepts at Langley Research Center

The objective of the sonic boom research in the current High Speed Research Program is to ultimately make possible overland supersonic flight by a high speed civil transport. To accomplish this objective, it is felt that results in four areas must demonstrate that such a vehicle would be acceptable by the general public, by the airframers, and by the airlines. It should be demonstrated: (1) that some waveform shape has the possibility of being acceptable to the general public; (2) that the atmosphere would not totally destroy such a waveform during propagation; (3) that a viable airplane could be built which produces such a waveform; and (4) that any performance penalty suffered by a low boom aircraft would be counteracted by the economic benefit of overland supersonic flight. The work being done at LaRC is in support of the third element listed above--the area of configuration design. The initial part of the paper will give a review of the theory being used for configuration designs and discuss two theory validation models which were built and tested within the past two years. Discussion of the wind tunnel and theoretical results (linear theory and higher order methods) and their implications for future designs will be included

Blunted apoptosis of erythrocytes in mice deficient in the heterotrimeric G-protein subunit Gαi2

Putative functions of the heterotrimeric G-protein subunit Gαi2-dependent signaling include ion channel regulation, cell differentiation, proliferation and apoptosis. Erythrocytes may, similar to apoptosis of nucleated cells, undergo eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine (PS) exposure. Eryptosis may be triggered by increased cytosolic Ca2+ activity and ceramide. In the present study, we show that Gαi2 is expressed in both murine and human erythrocytes and further examined the survival of erythrocytes drawn from Gαi2-deficient mice (Gαi2−/−) and corresponding wild-type mice (Gαi2+/+). Our data show that plasma erythropoietin levels, erythrocyte maturation markers, erythrocyte counts, hematocrit and hemoglobin concentration were similar in Gαi2−/− and Gαi2+/+ mice but the mean corpuscular volume was significantly larger in Gαi2−/− mice. Spontaneous PS exposure of circulating Gαi2−/− erythrocytes was significantly lower than that of circulating Gαi2+/+ erythrocytes. PS exposure was significantly lower in Gαi2−/− than in Gαi2+/+ erythrocytes following ex vivo exposure to hyperosmotic shock, bacterial sphingomyelinase or C6 ceramide. Erythrocyte Gαi2 deficiency further attenuated hyperosmotic shock-induced increase of cytosolic Ca2+ activity and cell shrinkage. Moreover, Gαi2−/− erythrocytes were more resistant to osmosensitive hemolysis as compared to Gαi2+/+ erythrocytes. In conclusion, Gαi2 deficiency in erythrocytes confers partial protection against suicidal cell death

Blunted apoptosis of erythrocytes in mice deficient in the heterotrimeric G-protein subunit Gαi2

Putative functions of the heterotrimeric G-protein subunit Gαi2-dependent signaling include ion channel regulation, cell differentiation, proliferation and apoptosis. Erythrocytes may, similar to apoptosis of nucleated cells, undergo eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine (PS) exposure. Eryptosis may be triggered by increased cytosolic Ca2+ activity and ceramide. In the present study, we show that Gαi2 is expressed in both murine and human erythrocytes and further examined the survival of erythrocytes drawn from Gαi2-deficient mice (Gαi2−/−) and corresponding wild-type mice (Gαi2+/+). Our data show that plasma erythropoietin levels, erythrocyte maturation markers, erythrocyte counts, hematocrit and hemoglobin concentration were similar in Gαi2−/− and Gαi2+/+ mice but the mean corpuscular volume was significantly larger in Gαi2−/− mice. Spontaneous PS exposure of circulating Gαi2−/− erythrocytes was significantly lower than that of circulating Gαi2+/+ erythrocytes. PS exposure was significantly lower in Gαi2−/− than in Gαi2+/+ erythrocytes following ex vivo exposure to hyperosmotic shock, bacterial sphingomyelinase or C6 ceramide. Erythrocyte Gαi2 deficiency further attenuated hyperosmotic shock-induced increase of cytosolic Ca2+ activity and cell shrinkage. Moreover, Gαi2−/− erythrocytes were more resistant to osmosensitive hemolysis as compared to Gαi2+/+ erythrocytes. In conclusion, Gαi2 deficiency in erythrocytes confers partial protection against suicidal cell death.Fil: Bissinger, Rosi. Eberhard Karls Universität Tübingen; AlemaniaFil: Lang, Elisabeth. Universitat Dusseldorf; AlemaniaFil: Ghashghaeinia, Mehrdad. Eberhard Karls Universität Tübingen; AlemaniaFil: Singh, Yogesh. Eberhard Karls Universität Tübingen; AlemaniaFil: Zelenak, Christine. Charité Medical University; AlemaniaFil: Fehrenbacher, Birgit. Eberhard Karls Universität Tübingen; AlemaniaFil: Honisch, Sabina. Eberhard Karls Universität Tübingen; AlemaniaFil: Chen, Hong. Eberhard Karls Universität Tübingen; AlemaniaFil: Fakhri, Hajar. Eberhard Karls Universität Tübingen; AlemaniaFil: Umbach, Anja T.. Eberhard Karls Universität Tübingen; AlemaniaFil: Liu, Guilai. Eberhard Karls Universität Tübingen; AlemaniaFil: Rexhepaj, Rexhep. Universitat Bonn; AlemaniaFil: Liu, Guoxing. Eberhard Karls Universität Tübingen; AlemaniaFil: Schaller, Martin. Eberhard Karls Universität Tübingen; AlemaniaFil: Mack, Andreas F.. Eberhard Karls Universität Tübingen; AlemaniaFil: Lupescu, Adrian. Eberhard Karls Universität Tübingen; AlemaniaFil: Birnbaumer, Lutz. National Institutes of Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Lang, Florian. Eberhard Karls Universität Tübingen; AlemaniaFil: Qadri, Syed M.. Eberhard Karls Universität Tübingen; Alemania. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentin

A combined low-radio frequency/X-ray study of galaxy groups I. Giant Metrewave Radio Telescope observations at 235 MHz and 610 MHz

We present new Giant Metrewave Radio Telescope observations at 235 MHz and 610 MHz of 18 X-ray bright galaxy groups. These observations are part of an extended project, presented here and in future papers, which combines low-frequency radio and X-ray data to investigate the interaction between central active galactic nuclei (AGN) and the intra-group medium (IGM). The radio images show a very diverse population of group-central radio sources, varying widely in size, power, morphology and spectral index. Comparison of the radio images with Chandra and XMM-Newton X-ray images shows that groups with significant substructure in the X-ray band and marginal radio emission at >= 1 GHz host low-frequency radio structures that correlate with substructures in IGM. Radio-filled X-ray cavities, the most evident form of AGN/IGM interaction in our sample, are found in half of the systems, and are typically associated with small, low- or mid-power double radio sources. Two systems, NGC5044 and NGC4636, possess multiple cavities, which are isotropically distributed around the group center, possibly due to group weather. In other systems the radio/X-ray correlations are less evident. However, the AGN/IGM interaction can manifest itself through the effects of the high-pressure medium on the morphology, spectral properties and evolution of the radio-emitting plasma. In particular, the IGM can confine fading radio lobes in old/dying radio galaxies and prevent them from dissipating quickly. Evidence for radio emission produced by former outbursts that coexist with current activity is found in six groups of the sample.Comment: Accepted for publication in the Astrophysical Journal Supplement Series, 26 pages, 18 figures. A version with high-quality figures is http://www.astro.umd.edu/~simona/giacintucci_hr.pd

Fetal-derived adrenomedullin mediates the innate immune milieu of the placenta

The remodeling of maternal uterine spiral arteries (SAs) is an essential process for ensuring low-resistance, high-capacitance blood flow to the growing fetus. Failure of SAs to remodel is causally associated with preeclampsia, a common and life-threatening complication of pregnancy that is harmful to both mother and fetus. Here, using both loss-of-function and gain-of-function genetic mouse models, we show that expression of the pregnancy-related peptide adrenomedullin (AM) by fetal trophoblast cells is necessary and sufficient to promote appropriate recruitment and activation of maternal uterine NK (uNK) cells to the placenta and ultimately facilitate remodeling of maternal SAs. Placentas that lacked either AM or its receptor exhibited reduced fetal vessel branching in the labyrinth, failed SA remodeling and reendothelialization, and markedly reduced numbers of maternal uNK cells. In contrast, overexpression of AM caused a reversal of these phenotypes with a concomitant increase in uNK cell content in vivo. Moreover, AM dose-dependently stimulated the secretion of numerous chemokines, cytokines, and MMPs from uNK cells, which in turn induced VSMC apoptosis. These data identify an essential function for fetal-derived factors in the maternal vascular adaptation to pregnancy and underscore the importance of exploring AM as a biomarker and therapeutic agent for preeclampsia