Green building

"Thinking Green" is the new buzzword of the twenty-first century. There are the green IBM commercials that demonstrate a substantial amount of money saved if a business, "goes green" the Mac commercial with the new energy saving computer that runs on less energy than a quarter of a light bulb; the car commercials competing for the most fuel efficiency. It seems that every individual or business in the twenty-first century is concerned with the environment and what we are putting into it

The Aerostatic Seal: Analysis and Development of a New Dynamic Seal Concept for Steam Turbine Application

This thesis describes the development of a new seal concept for steam turbines called the Aerostatic Seal. The Aerostatic Seal is a dynamic seal, and so can respond to rotor radial movement to maintain a low clearance between the seal and the rotor. As the seal is dynamic, smaller clearances can be achieved without rotor contact compared to conventional static seals such as the labyrinth seal, hence increasing the efficiency of the turbine through reduced leakage. Furthermore, as the seal is dynamic it can tolerate larger radial transients typically found during start up and shut down of the steam turbine, and so also contributes to increasing the flexibility of the turbine plant. In this thesis an analytical design and analysis methodology was developed for the Aerostatic Seal. The methodology was used to generate a number of seal designs which were experimentally tested in a non-rotating test facility using room temperature air. The results confirmed that the seal would operate dynamically, and the experimental campaign provided valuable data on the operation of the seal. The non-rotating rig was also used to test a second generation seal design. The seal was then tested in a rotating test facility, which modelled high speed rotor radial transients with an adjustable eccentric rotor. The Aerostatic Seal demonstrated the ability to respond to high speed transients. A final test campaign was conducted in the high temperature steam rig at TU Braunschweig, Germany, enabling experimental demonstration of the Aerostatic Seal using realistic materials and represented realistic steam turbine conditions. Finally, based on the experimental and analytical work carried out within this thesis, a proposed Aerostatic Seal design for steam turbine implementation is presented

Implementation of the frequency-modulated sideband search method for gravitational waves from low mass X-ray binaries

We describe the practical implementation of the sideband search, a search for periodic gravitational waves from neutron stars in binary systems. The orbital motion of the source in its binary system causes frequency-modulation in the combination of matched filters known as the $\mathcal{F}$-statistic. The sideband search is based on the incoherent summation of these frequency-modulated $\mathcal{F}$-statistic sidebands. It provides a new detection statistic for sources in binary systems, called the $\mathcal{C}$-statistic. The search is well suited to low-mass X-ray binaries, the brightest of which, called Sco X-1, is an ideal target candidate. For sources like Sco X-1, with well constrained orbital parameters, a slight variation on the search is possible. The extra orbital information can be used to approximately demodulate the data from the binary orbital motion in the coherent stage, before incoherently summing the now reduced number of sidebands. We investigate this approach and show that it improves the sensitivity of the standard Sco X-1 directed sideband search. Prior information on the neutron star inclination and gravitational wave polarization can also be used to improve upper limit sensitivity. We estimate the sensitivity of a Sco X-1 directed sideband search on 10 days of LIGO data and show that it can beat previous upper limits in current LIGO data, with a possibility of constraining theoretical upper limits using future advanced instruments.Comment: 20 pages, 5 figure

A Mutational Hotspot in the 2B Domain of Human Hair Basic Keratin 6 (hHb6) in Monilethrix Patients

Monilethrix is an inherited hair dystrophy in which affected, fragile, hairs have an unique beaded morphology. Ultrastructural studies suggest a defect in filament structure in the cortex of the hair, and the hard keratins of hair and nail are thus candidate genes. In several families with autosomal dominant monilethrix, the disorder has been linked to the type II keratin gene cluster at chromosome 12q13. Recently, causative mutations in the critical helix termination motif in the 2B domain of the human hair basic keratin 6 (hHb6) have been identified. We now report the results of sequencing this domain in 13 unrelated families or cases with monilethrix. Five of the 13 had the same mutation as previously found, a G to A transversion leading to a lysine for glutamic acid substitution (E413K) in the 2B domain (residue 117 of the 2B helix) of hHb6. The mutation was confirmed by a restriction fragment length polymorphism assay developed for this purpose, and, as this mutation is evidently a common cause of the syndrome, for use in screening other cases. In eight families or cases, however, including three in whom linkage data are consistent with a defect at the type II keratin locus, no mutation was found in this domain of hHb6

Percutaneous Coronary Intervention and Drug-Eluting Stent Use Among Patients ≥85 Years of Age in the United States

ObjectivesThis study assessed the comparative effectiveness of drug-eluting stents (DES) versus bare-metal stents (BMS) among patients ≥85 years of age.BackgroundDespite an aging population, little is known about the comparative effectiveness of DES versus BMS among patients age ≥85 years undergoing percutaneous coronary intervention (PCI).MethodsWe examined 471,006 PCI patients age ≥65 years at 947 hospitals in the National Cardiovascular Data Registry between 2004 and 2008 and linked to Medicare claims data. Long-term outcomes (median follow-up 640.8 ± 423.5 days) were compared between users of DES and BMS.ResultsPatients age ≥85 years comprise an increasing proportion of PCIs performed among elderly subjects, yet rates of DES use declined the most in this age group. Compared with BMS, use of DES was associated with lower mortality: age ≥85 years, 29% versus 38% (adjusted hazard ratio [HR]: 0.80 [95% confidence interval (CI): 0.77 to 0.83]); age 75 to 84 years, 17% versus 25% (HR: 0.77 [95% CI: 0.75 to 0.79]); and age 65 to 74 years, 10% versus 16% (HR: 0.73 [95% CI: 0.71 to 0.75]). However, the adjusted mortality difference narrowed with increasing age (pinteraction <0.001). In contrast, the adjusted HR for myocardial infarction rehospitalization associated with DES use was significantly lower with increasing age: age ≥85 years, 9% versus 12% (HR: 0.77 [95% CI: 0.71 to 0.83]); age 75 to 84 years, 7% versus 9% (HR: 0.81 [95% CI: 0.77 to 0.84]); and age 65 to 74 years, 7% versus 8% (HR: 0.84 [95% CI: 0.80 to 0.88]) (pinteraction <0.001).ConclusionsIn this national study of older patients undergoing PCI, declines in DES use were most pronounced among those aged ≥85 years, yet lower adverse-event rates associated with DES versus BMS use were observed

Development of peptide-based lineage-specific serology for chronic Chagas disease: geographical and clinical distribution of epitope recognition.

BACKGROUND: Chagas disease, caused by infection with the protozoan Trypanosoma cruzi, remains a serious public health issue in Latin America. Genetically diverse, the species is sub-divided into six lineages, known as TcI-TcVI, which have disparate geographical and ecological distributions. TcII, TcV, and TcVI are associated with severe human disease in the Southern Cone countries, whereas TcI is associated with cardiomyopathy north of the Amazon. T. cruzi persists as a chronic infection, with cardiac and/or gastrointestinal symptoms developing years or decades after initial infection. Identifying an individual's history of T. cruzi lineage infection directly by genotyping of the parasite is complicated by the low parasitaemia and sequestration in the host tissues. METHODOLOGY/PRINCIPAL FINDINGS: We have applied here serology against lineage-specific epitopes of the T. cruzi surface antigen TSSA, as an indirect approach to allow identification of infecting lineage. Chagasic sera from chronic patients from a range of endemic countries were tested by ELISA against synthetic peptides representing lineage-specific TSSA epitopes bound to avidin-coated ELISA plates via a biotin labelled polyethylene glycol-glycine spacer to increase rotation and ensure each amino acid side chain could freely interact with their antibodies. 79/113 (70%) of samples from Brazil, Bolivia, and Argentina recognised the TSSA epitope common to lineages TcII/TcV/TcVI. Comparison with clinical information showed that a higher proportion of Brazilian TSSApep-II/V/VI responders had ECG abnormalities than non-responders (38% vs 17%; p<0.0001). Among northern chagasic sera 4/20 (20%) from Ecuador reacted with this peptide; 1/12 Venezuelan and 1/34 Colombian samples reacted with TSSApep-IV. In addition, a proposed TcI-specific epitope, described elsewhere, was demonstrated here to be highly conserved across lineages and therefore not applicable to lineage-specific serology. CONCLUSIONS/SIGNIFICANCE: These results demonstrate the considerable potential for synthetic peptide serology to investigate the infection history of individuals, geographical and clinical associations of T. cruzi lineages

Emergence of Variability in Isogenic Escherichia coli Populations Infected by a Filamentous Virus

The spread of epidemics not only depends on the average number of parasites produced per host, but also on the existence of highly infectious individuals. It is widely accepted that infectiousness depends on genetic and environmental determinants. However, even in clonal populations of host and viruses growing in homogeneous conditions, high variability can exist. Here we show that Escherichia coli cells commonly display high differentials in viral burst size, and address the kinetics of emergence of such variability with the non-lytic filamentous virus M13. By single-cell imaging of a virally-encoded fluorescent reporter, we monitor the viral charge distribution in infected bacterial populations at different time following infection. A mathematical model assuming autocatalytic virus replication and inheritance of bacterial growth rates quantitatively reproduces the experimental distributions, demonstrating that deterministic amplification of small host inhomogeneities is a mechanism sufficient to explain large and highly skewed distributions. This mechanism of amplification is general and may occur whenever a parasite has an initial phase of exponential growth within its host. Moreover, it naturally reproduces the shift towards higher virulence when the host is experimenting poor conditions, as observed commonly in host-parasite systems

The AIRE-230Y Polymorphism Affects AIRE Transcriptional Activity: Potential Influence on AIRE Function in the Thymus

Background The autoimmune regulator (AIRE) is expressed in the thymus, particularly in thymic medullary epithelial cells (mTECs), and is required for the ectopic expression of a diverse range of peripheral tissue antigens by mTECs, facilitating their ability to perform negative selection of auto-reactive immature T-cells. The expression profile of peripheral tissue antigens is affected not only by AIRE deficiency but also with variation of AIRE activity in the thymus. Method and Results Therefore we screened 591bp upstream of the AIRE transcription start site including AIRE minimal promoter for single nucleotide polymorphism (SNPs) and identified two SNPs -655R (rs117557896) and -230Y (rs751032) respectively. To study the effect of these variations on AIRE promoter activity we generated a Flp-In host cell line which was stably transfected with a single copy of the reporter vector. Relative promoter activity was estimated by comparing the luciferase specific activity for lysates of the different reporter AIRE promoterreporter gene constructs including AIRE-655G AIRE-230C, AIRE-655G AIRE-230T and AIRE-655A AIRE-230C. The analysis showed that the commonest haplotype AIRE-655G AIRE-230C has the highest luciferase specific activity (p<0.001). Whereas AIRE-655G AIRE-230T has a luciferase specific activity value that approaches null. Both AIRE promoter polymorphic sites have one allele that forms a CpG methylation site which we determined can be methylated in methylation assays using the M.SssI CpG methyltransferase. Conclusion AIRE-230Y is in a conserved region of the promoter and is adjacent to a predicted WT1 transcription factor binding site, suggesting that AIRE-230Y affects AIRE expression by influencing the binding of biochemical factors to this region. Our findings show that AIRE655GAIRE-230T haplotype could dramatically alter AIRE transcription and so have an effect on the process of negative selection and affect susceptibility to autoimmune conditions