431 research outputs found
Operational Use of GPS Navigation for Space Shuttle Entry
The STS-118 flight of the Space Shuttle Endeavour was the first shuttle mission flown with three Global Positioning System (GPS) receivers in place of the three legacy Tactical Air Navigation (TACAN) units. This marked the conclusion of a 15 year effort involving procurement, missionization, integration, and flight testing of a GPS receiver and a parallel effort to formulate and implement shuttle computer software changes to support GPS. The use of GPS data from a single receiver in parallel with TACAN during entry was successfully demonstrated by the orbiters Discovery and Atlantis during four shuttle missions in 2006 and 2007. This provided the confidence needed before flying the first all GPS, no TACAN flight with Endeavour. A significant number of lessons were learned concerning the integration of a software intensive navigation unit into a legacy avionics system. These lessons have been taken into consideration during vehicle design by other flight programs, including the vehicle that will replace the Space Shuttle, Orion
Nondestructive SEM for surface and subsurface wafer imaging
The scanning electron microscope (SEM) is considered as a tool for both failure analysis as well as device characterization. A survey is made of various operational SEM modes and their applicability to image processing methods on semiconductor devices
Cirrhosis-induced defects in innate pulmonary defenses against Streptococcus pneumoniae
<p>Abstract</p> <p>Background</p> <p>The risk of mortality from pneumonia caused by <it>Streptococcus pneumoniae </it>is increased in patients with cirrhosis. However, the specific pneumococcal virulence factors and host immune defects responsible for this finding have not been clearly established. This study used a cirrhotic rat model of pneumococcal pneumonia to identify defect(s) in innate pulmonary defenses in the cirrhotic host and to determine the impact of the pneumococcal toxin pneumolysin on these defenses in the setting of severe cirrhosis.</p> <p>Results</p> <p>No cirrhosis-associated defects in mucociliary clearance of pneumococci were found in these studies, but early intrapulmonary killing of the organisms before the arrival of neutrophils was significantly impaired. This defect was exacerbated by pneumolysin production in cirrhotic but not in control rats. Neutrophil-mediated killing of a particularly virulent type 3 pneumococcal strain also was significantly diminished within the lungs of cirrhotic rats with ascites. Levels of lysozyme and complement component C3 were both significantly reduced in bronchoalveolar lavage fluid from cirrhotic rats. Finally, complement deposition was reduced on the surface of pneumococci recovered from the lungs of cirrhotic rats in comparison to organisms recovered from the lungs of control animals.</p> <p>Conclusion</p> <p>Increased mortality from pneumococcal pneumonia in this cirrhotic host is related to defects in both early pre-neutrophil- and later neutrophil-mediated pulmonary killing of the organisms. The fact that pneumolysin production impaired pre-neutrophil-mediated pneumococcal killing in cirrhotic but not control rats suggests that pneumolysin may be particularly detrimental to this defense mechanism in the severely cirrhotic host. The decrease in neutrophil-mediated killing of pneumococci within the lungs of the cirrhotic host is related to insufficient deposition of host proteins such as complement C3 on their surfaces. Pneumolysin likely plays a role in complement consumption within the lungs. Our studies, however, were unable to determine whether pneumolysin more negatively impacted this defense mechanism in cirrhotic than in control rats. These findings contribute to our understanding of the defects in innate pulmonary defenses that lead to increased mortality from pneumococcal pneumonia in the severely cirrhotic host. They also suggest that pneumolysin may be a particularly potent pneumococcal virulence factor in the setting of cirrhosis.</p
Data Acquisition and Processing Techniques for Voltage Contrast Measurements
The effects of several data acquisition techniques on the accuracy of voltage contrast measurements are studied. In particular, the effect of using a voltage reference region directly connected to an external voltage source in performing the image intensity-to-voltage mapping of a node whose voltage is to be determined is examined. This is found to allow improved voltage measurement. The actual reference curves were obtained by least squares fitting the measured intensity-voltage reference data alternately to a quadratic and a cubic function. In addition, various mapping algorithms are considered including ones based alternately on the use of unprocessed, subtracted and normalized data. Using these techniques, one should expect voltage errors with means of approximately 25 mV and standard deviations of approximately 160 mV even with an unmodified commercial SEM incorporating no additional hardware to increase precision
Advanced Scanning Electron Microscopy Methods and Applications to Integrated Circuit Failure Analysis
Semiconductor device failure analysis using the scanning electron microscope (SEM) has become a standard component of integrated circuit fabrication. Improvements in SEM capabilities and in digital imaging and processing have advanced standard acquisition modes and have promoted new failure analysis methods. The physical basis of various data acquisition modes, both standard and new, and their implementation on a computer controlled SEM image acquisition/processing system are discussed, emphasizing the advantages of each method. Design considerations for an integrated, online failure analysis system are also described. Recent developments in the integration of the information provided by electron beam analysis, conventional integrated circuit (IC) testing, computer-aided design (CAD), and device parameter testing into a single system promise to provide powerful future tools for failure analysis
Molecular Basis of Rare Aminoglycoside Susceptibility and Pathogenesis of Burkholderia pseudomallei Clinical Isolates from Thailand
Burkholderia pseudomallei is the etiologic agent of melioidosis, an emerging tropical disease. Because of low infectious dose, broad-host-range infectivity, intrinsic antibiotic resistance and historic precedent as a bioweapon, B. pseudomallei was listed in the United States as a Select Agent and Priority Pathogen of biodefense concern by the US Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases. The mechanisms governing antibiotic resistance and/or susceptibility and virulence in this bacterium are not well understood. Most clinical and environmental B. pseudomallei isolates are highly resistant to aminoglycosides, but susceptible variants do exist. The results of our studies with three such variants from Thailand reveal that lack of expression or deletion of an efflux pump is responsible for this susceptibility. The large deletion present in one strain not only removes an efflux pump but also several putative virulence genes, including an entire siderophore gene cluster. Despite this deletion, the strain is fully virulent in an acute mouse melioidosis model. In summary, our findings shed light on mechanisms of antibiotic resistance and pathogenesis. They also validate the previously advocated use of laboratory-constructed, aminoglycoside susceptible efflux pump mutants in genetic manipulation experiments
Catastrophic wildfire and number of populations as factors influencing risk of extinction for Gila trout (Oncorhynchus gilae)
We used the computer program RAMAS to explore the sensitivity of an extinction-risk model for the Gila trout (Oncorhynchus gilae) to management of wildfires and number of populations of the species. The Gila trout is an endangered salmonid presently restricted to very few headwaters of the Gila and San Francisco river tributaries in southwestern New Mexico. Life history data for 10 extant populations were used to examine sensitivity of the species' viability to changes in a variety of factors including population size, fecundity, life stage structure, number of populations, severity and probability of forest fires, and a regulated fishery. The probability and severity of forest fires and number of populations had the greatest effect on viability. Results indicate that successful conservation of Gila trout requires establishment of additional populations and reduction of the severity of forest fires through a program incorporating more frequent, but less severe, fires.Peer reviewedZoolog
Polymorphism of alpha-1-antitrypsin in hematological malignancies
Alpha-1-antitrypsin (AAT) or serine protease inhibitor A1 (SERPINA1) is an important serine protease inhibitor in humans. The main physiological role of AAT is to inhibit neutrophil elastase (NE) released from triggered neutrophils, with an additional lesser role in the defense against damage inflicted by other serine proteases, such as cathepsin G and proteinase 3. Although there is a reported association between AAT polymorphism and different types of cancer, this association with hematological malignancies (HM) is, as yet, unknown. We identified AAT phenotypes by isoelectric focusing (in the pH 4.2-4.9 range) in 151 serum samples from patients with HM (Hodgkins lymphomas, non-Hodgkins lymphomas and malignant monoclonal gammopathies). Healthy blood-donors constituted the control group (n = 272). The evaluated population of patients as well as the control group, were at Hardy-Weinberg equilibrium for the AAT gene (χ2 = 4.42, d.f.11, p = 0.96 and χ2 = 4.71, d.f.11, p = 0.97, respectively). There was no difference in the frequency of deficient AAT alleles (Pi Z and Pi S) between patients and control. However, we found a significantly higher frequency of PiM1M1 homozygote and PiM1 allele in HM patients than in control (for phenotype: f = 0.5166 and 0.4118 respectively, p = 0.037; for allele: f = 0.7020 and 0.6360 respectively, p = 0.05). In addition, PiM homozygotes in HM-patients were more numerous than in controls (59% and 48%, respectively, p = 0.044). PiM1 alleles and PiM1 homozygotes are both associated with hematological malignancies, although this is considered a functionally normal AAT variant
Novel variants in GNAI3 associated with auriculocondylar syndrome strengthen a common dominant negative effect
Auriculocondylar syndrome is a rare craniofacial disorder comprising core features of micrognathia, condyle dysplasia and question mark ear. Causative variants have been identified in PLCB4, GNAI3 and EDN1, which are predicted to function within the EDN1-EDNRA pathway during early pharyngeal arch patterning. To date, two GNAI3 variants in three families have been reported. Here we report three novel GNAI3 variants, one segregating with affected members in a family previously linked to 1p21.1-q23.3 and two de novo variants in simplex cases. Two variants occur in known functional motifs, the G1 and G4 boxes, and the third variant is one amino acid outside of the G1 box. Structural modeling shows that all five altered GNAI3 residues identified to date cluster in a region involved in GDP/GTP binding. We hypothesize that all GNAI3 variants lead to dominant negative effects.CRANIRAREUniversite Paris Descartes-Sorbonne Paris Cite Pole de Recherche et d'Enseignement SuperieurAgence Nationale de la Recherche (project EvoDevoMut)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento CientÃfico e Tecnológico (CNPq)National Health and Medical Research Council of AustraliaUniv São Paulo, Inst Biociencias, Dept Genet & Biol Evolut, Ctr Pesquisas Genoma Humano & Celulas Tronco, BR-05508090 São Paulo, BrazilUniv Paris 05, Sorbonne Paris Cite, INSERM, U1163, Paris, FranceUniv São Paulo, HRCA, Dept Clin Genet, Bauru, BrazilUniv Melbourne, Royal Childrens Hosp, Murdoch Childrens Res Inst, Victorian Clin Genet Serv, Melbourne, Vic, AustraliaUniv Melbourne, Dept Paediat, Melbourne, Vic, AustraliaRoyal Childrens Hosp, Dept Plast & Maxillofacial Surg, Melbourne, Vic, AustraliaHosp Sick Children, Dept Otolaryngol Head & Neck Surg, Toronto, ON M5G 1X8, CanadaUniv São Paulo, Inst Biosci, BR-05508090 São Paulo, BrazilLeiden Univ, Med Ctr, Leiden Genome Technol Ctr, Leiden, NetherlandsUniversidade Federal de São Paulo, Inst Ciencia & Tecnol, Sao Jose Dos Campos, BrazilHop Necker Enfants Malad, AP HP, Dept Genet, Paris, FranceUniversidade Federal de São Paulo, Inst Ciencia & Tecnol, Sao Jose Dos Campos, BrazilUniversite Paris Descartes-Sorbonne Paris Cite Pole de Recherche et d'Enseignement Superieur: SPC/JFG/2013-031National Health and Medical Research Council of Australia: 607431Web of Scienc
Effects of Thioglycolic Acid on Parthenogenetic Activation of Xenopus Oocytes
BACKGROUND: Existing in Permanent-wave solutions (PWS), thioglycolic acid (TGA) is widely used in hairdressing industry for its contribution to hair styling. However, the toxicity of TGA, especially its reproductive toxicity, gradually calls the attention of more and more researchers. METHOD: In this work, xenopus oocytes were pretreated with different concentration of TGA, and then activated by calcium ionophore A23187. During culture, the oocytes activation rates were taken note at different time after adding calcium ionophore A23187. At the end of the culture period, the nuclear status was detected under confocal microscope. In addition, some other samples were collected for Western-Blotting analysis. RESULT: TGA significantly inhibited the oocytes activation rate and pronuclear formation. It may be resulted from the inhibition of the degradation of p-ERK1, Mos and CyclinB2. CONCLUSION: TGA inhibits in vitro parthenogenetic activation of xenopus oocytes with inhibited the degradation of proteins involved in mitogenic-activated protein kinase (MAPK) and maturation-promoting factor (MPF) pathways
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