A single microphone capillary-based system for measuring the complex input impedance of musical wind instruments

Capillary-based systems for measuring the input impedance of musical wind instruments were first developed in the mid-20th century and remain in widespread use today. In this paper, the basic principles and assumptions underpinning the design of such systems are examined. Inexpensive modifications to a capillary-based impedance measurement set-up made possible due to advances in computing and data acquisition technology are discussed. The modified set-up is able to measure both impedance magnitude and impedance phase even though it only contains one microphone. In addition, a method of calibration is described that results in a significant improvement in accuracy when measuring high impedance objects on the modified capillary-based system. The method involves carrying out calibration measurements on two different objects whose impedances are well-known theoretically. The benefits of performing two calibration measurements (as opposed to the one calibration measurement that has been traditionally used) are demonstrated experimentally through input impedance measurements on two test objects and a Boosey and Hawkes oboe. © S. Hirzel Verlag · EAA.

A Variant in LDLR is Associated with Abdominal Aortic Aneurysm

Background—Abdominal aortic aneurysm (AAA) is a common cardiovascular disease among older people and demonstrates significant heritability. In contrast to similar complex diseases, relatively few genetic associations with AAA have been confirmed. We reanalysed our genome-wide study and carried through to replication suggestive discovery associations at a lower level of significance.

Methods and Results—A genome-wide association study was conducted using 1,830 cases from the UK, New Zealand and Australia with infra-renal aorta diameter =30mm or ruptured AAA and 5,435 unscreened controls from the 1958 Birth Cohort and National Blood Service cohort from the Wellcome Trust Case Control Consortium. Eight suggestive associations with P<1x10-4 were carried through to in silico replication in 1,292 AAA cases and 30,503 controls. One SNP associated with P<0.05 after Bonferroni correction in the in silico study underwent further replication (706 AAA cases and 1,063 controls from the UK, 507 AAA cases and 199 controls from Denmark and 885 AAA cases and 1,000 controls from New Zealand). Low density lipoprotein receptor (LDLR) rs6511720 A, was significantly associated overall and in three of five individual replication studies. The full study showed an association that reached genome-wide significance (odds ratio 0.76; 95% confidence interval 0.70 to 0.83; P=2.08x10-10).

Conclusions—LDLR rs6511720 is associated with abdominal aortic aneurysm. This finding is consistent with established effects of this variant on coronary artery disease. Shared aetiological pathways with other cardiovascular diseases may present novel opportunities for preventative and therapeutic strategies for AAA.

Off-Centre Localisation Performance of Ambisonics and HOA For Large and Small Loudspeaker Array Radii

Ambisonics and Higher Order Ambisonics (HOA) are scalable spatial audio techniques that attempt to present a sound scene to listeners over as large an area as possible. A localisation experiment was carried out to investigate the performance of a first and third order system at three listening positions - one in the centre and two off-centre - using a 5 m radius loudspeaker array. The results are briefly presented and compared to those of an earlier experiment on a 2.2 m loudspeaker array. In both experiments the off-centre listeners were placed such that the ratio of distance from the centre to the array radius was constant in both experiments. The test used a reverse target-pointer adjustment method to determine the error, both signed and absolute, for each combination of listening position and system. The results for both arrays were found to be very similar, suggesting that the relative amplitude of the loudspeakers, which were the same in both cases, was more dominant for localisation than the arrival time differences, which differed between array sizes.

A randomized clinical trial of ascorbic acid in open abdominal aortic aneurysm repair

BACKGROUND: Open AAA repair is associated with ischaemia-reperfusion injury where systemic inflammation and endothelial dysfunction can lead to multiple organ injury including acute lung injury. Oxidative stress plays a role that may be inhibited by ascorbic acid.

METHODS: A double blind, allocation concealed, randomized placebo-controlled trial was performed to test the hypothesis that a single bolus dose (2g) of intra-operative parenteral ascorbic acid would attenuate biomarkers of ischaemia-reperfusion injury in patients undergoing elective open AAA repair.

RESULTS: Thirty one patients completed the study; 18 received placebo and 13 ascorbic acid. Groups were comparable demographically. Open AAA repair caused an increase in urinary Albumin:Creatinine Ratio (ACR) as well as plasma IL-6 and IL-8. There was a decrease in exhaled breath pH and oxygenation. Lipid hydroperoxides were significantly higher in the ascorbic acid group following open AAA repair. There were no other differences between the ascorbic acid or placebo groups up to 4 hours after removal of the aortic clamping.

CONCLUSIONS: Open AAA repair caused an increase in markers of systemic endothelial damage and systemic inflammation. Administration of 2g parenteral ascorbic acid did not attenuate this response and with higher levels of lipid hydroperoxides post-operatively a pro-oxidant effect could not be excluded.

TRIAL REGISTRATION: ISRCTN27369400.

Genome wide interactions of wild-type and activator bypass forms of σ54

Enhancer-dependent transcription involving the promoter specificity factor σ54 is widely distributed amongst bacteria and commonly associated with cell envelope function. For transcription initiation, σ54-RNA polymerase yields open promoter complexes through its remodelling by cognate AAA+ ATPase activators. Since activators can be bypassed in vitro, bypass transcription in vivo could be a source of emergent gene expression along evolutionary pathways yielding new control networks and transcription patterns. At a single test promoter in vivo bypass transcription was not observed. We now use genome-wide transcription profiling, genome-wide mutagenesis and gene over-expression strategies in Escherichia coli, to (i) scope the range of bypass transcription in vivo and (ii) identify genes which might alter bypass transcription in vivo. We find little evidence for pervasive bypass transcription in vivo with only a small subset of σ54 promoters functioning without activators. Results also suggest no one gene limits bypass transcription in vivo, arguing bypass transcription is strongly kept in check. Promoter sequences subject to repression by σ54 were evident, indicating loss of rpoN (encoding σ54) rather than creating rpoN bypass alleles would be one evolutionary route for new gene expression patterns. Finally, cold-shock promoters showed unusual σ54-dependence in vivo not readily correlated with conventional σ54 binding-sites.

Abdominal Aortic Aneurysm Genetic Associations: Mostly False? A Systematic Review and Meta-analysis

OBJECTIVE/BACKGROUND: Many associations between abdominal aortic aneurysm (AAA) and genetic polymorphisms have been reported. It is unclear which are genuine and which may be caused by type 1 errors, biases, and flexible study design. The objectives of the study were to identify associations supported by current evidence and to investigate the effect of study design on reporting associations.

METHODS: Data sources were MEDLINE, Embase, and Web of Science. Reports were dual-reviewed for relevance and inclusion against predefined criteria (studies of genetic polymorphisms and AAA risk). Study characteristics and data were extracted using an agreed tool and reports assessed for quality. Heterogeneity was assessed using I(2) and fixed- and random-effects meta-analyses were conducted for variants that were reported at least twice, if any had reported an association. Strength of evidence was assessed using a standard guideline.

RESULTS: Searches identified 467 unique articles, of which 97 were included. Of 97 studies, 63 reported at least one association. Of 92 studies that conducted multiple tests, only 27% corrected their analyses. In total, 263 genes were investigated, and associations were reported in polymorphisms in 87 genes. Associations in CDKN2BAS, SORT1, LRP1, IL6R, MMP3, AGTR1, ACE, and APOA1 were supported by meta-analyses.

CONCLUSION: Uncorrected multiple testing and flexible study design (particularly testing many inheritance models and subgroups, and failure to check for Hardy-Weinberg equilibrium) contributed to apparently false associations being reported. Heterogeneity, possibly due to the case mix, geographical, temporal, and environmental variation between different studies, was evident. Polymorphisms in nine genes had strong or moderate support on the basis of the literature at this time. Suggestions are made for improving AAA genetics study design and conduct.

Address inaccuracy in health registration data: determinants and impacts

Access to demographic data that are complete, accurate and up-to-date is fundamental to many aspects of public health, government and academic work and for accurate interpretation of other databases. Health registration data are the prime source of demographic information for health and social care systems; for example, as an indicator of need, as a source of denominators to convert number of events into rates, or in the case of the residential address information as the basis for generating the call-recall invitation letters that are used for most screening programs (e.g. breast, colo-rectal and AAA screening). However, list inflation (ghosts, duplicates or emigrants) and a degree of address inaccuracy are recognised caveats with the health registration data and a recent NILS-related study on breast screening suggests that improved address accuracy might be a fast and efficient means of increasing screening uptake rates in cities and amongst deprived populations. In NI these data are collated by the BSO who uniquely in the UK also have access to data relating to prescribing, dental registrations and use of A&E services. These can be used to supplement the standard demographic and address information by (i) indicating patients who are alive and resident in NI and (ii) providing an independent source of probably improved address information. This study will use the NI Unique Property Reference Number (UPRN), rather than the addresses per se which are difficult to work with, to compare the addresses registered in the BSO with those addresses in the enumerated 2011 census. Assuming that the census is a more accurate source of address information for individuals, a comparison of the health registration addresses with those recorded at the census, the aim of the proposed study will be to (i) characterise the amount and distributions of these differences, (ii) to see what proportion of those who do not attend for screening did not actually receive an invitation letter because the addresses were incorrect, (iii) to determine how much of the social gradient (and urban/rural differences) in screening uptake are due to address inaccuracies, (iv) a comparison of timing of address changes at the BSO will provide information on the delays in updating of addresses.

Mitochondrial plasticity in pathophysiological conditions

Both skeletal and cardiac muscles daily burn tremendous amounts of ATP to meet the energy requirements for contraction. So, it is not surprising that the maintenance of mitochondrial morphology, number, distribution and functionality in striated muscle are important for muscle homeostasis. In these tissues mitochondria present the added dimension of two populations, the intermyofibrillar (IMF) and the subsarcolemmal (SS) mitochondria, being IMF the most abundant one. In the present thesis, the molecular mechanisms harboured in mitochondria of striated muscles were studied using animal models, to better comprehend the role of mitochondrial plasticity in several pathophysiological conditions such as aging, diabetes mellitus and bladder cancer. The comparative analysis of IMF and SS populations isolated from heart evidenced a higher respiratory chain activity of mitochondria interspersed in the contractile apparatus. The higher susceptible of SS respiratory chain complexes subunits to carbonylation, but not to nitration, seems to justify the lower respiratory chain activity observed in this mitochondrial population. Our results showed that in heart from aged mice there is an accumulation of dysfunctional mitochondria. The age-related decrease of oxidative phosphorylation activity seems to be justified, at least partially, by the increased proneness of mitochondrial proteins as OXPHOS subunits and MnSOD to oxidative modifications. Moreover, a sedentary lifestyle seems to worsen the functional consequences of aging in heart by increasing mitochondrial proteins susceptibility to nitration. In skeletal muscle from rats with type 1 diabetes mellitus induced by streptozotocin administration, we verified the accumulation of dysfunctional mitochondria due, at least in part, to the impairment of PQC system. Indeed, the decreased activity of AAA proteases was accompanied by the accumulation of oxidatively modified mitochondrial proteins with impact in respiratory chain activity. The diminishing of mitochondria activity also underlies cancer-induced muscle wasting. Indeed, using a rat model of chemically induced urothelial carcinoma we verified that the loss of gastrocnemius mass was related to mitochondrial dysfunction due to, at least partially, the down-regulation of PQC system involving the mitochondrial proteases paraplegin and Lon. PQC impairment resulted in the accumulation of oxidatively modified mitochondrial proteins. In overall, regardless the pathophysiological stimuli that promote mitochondrial alterations, there are similarities in the pattern of disease-related mitochondrial plasticity. The diminished capacity for ATP production in striated muscle seems to be due to increased oxidative damage of mitochondrial proteins, namely subunits of respiratory chain complexes, metabolic proteins and MnSOD. Our data highlighted, for the first time, the impact of mitochondrial PQC system impairment in the accumulation of oxidized proteins, exacerbating the dysfunction of this organelle in striated muscle in several pathophysiological conditions.

The contribution of skate blade properties to skating speed

The purpose of the study was to investigate the relative contribution of skate blade properties to on-ice skating speed. Thirty-two male ice hockey players (mean age = 19±2.65 yrs.) representing the Ontario Minor Hockey Association (OMHA; Midget AAA and Junior), Canadian Inter University Sport (CIS: Varsity), Ontario hockey league (OHL) and East Coast Hockey League (ECHL), and the playing positions of forwards (n=18) and defense (n=14) were recruited to participate. Skate related equipment worn by the players for the purpose of the research was documented and revealed that 80% of the players wore Bauer skates, Tuuk blade holders and LS2 skate blades. Subjects completed a battery of eight on-ice skating drills used to measure and compare two aspects of skating speed; acceleration [T1(s)] and total time to complete each drill [TT(s)] while skating on three skate blade conditions. The drills represented skills used in the game of hockey, both in isolation (e.g., forward skating, backward skating, stops and starts, and cornering) and in sequence to simulate the combination of skills used in a shift of game play. The three blade conditions consisted of (i) baseline, represented by the blades worn by the player throughout their current season of play; (ii) experimental blades (EB), represented by brand name experimental blades with manufacturers radius of contour and a standardized radius of hollow; and (iii) customized experimental blades (CEB), represented by the same brand name experimental blades sharpened to the players’ preference as identified in the baseline condition. No significant differences were found in acceleration time [T1(s)] or total time to complete [TT(s)] the isolated drills across blade conditions; however significant differences were revealed in both T1(s) and TT(s) measured during the execution of the sequenced drill across blade conditions. A iii Bonferroni post hoc test revealed that players skated significantly faster when skating on the CEB condition compared to the baseline condition (p≤.05). A questionnaire assessing subjects perceived comfort, confidence and effort expended while skating on the experimental blades revealed that players were significantly more comfortable when skating on the CEB versus the EB condition (p≤.05). Outcomes of the study provide evidence to suggest that the experimental skate blades customized with the players preferred blade sharpening characteristics results in faster skating speed in a combination drill representing skills performed in gameplay.

Requirements for the selective degradation of CD4 receptor molecules by the human immunodeficiency virus type 1 Vpu protein in the endoplasmic reticulum.

BACKGROUND: HIV-1 Vpu targets newly synthesized CD4 receptor for rapid degradation by a process reminiscent of endoplasmic reticulum (ER)-associated protein degradation (ERAD). Vpu is thought to act as an adaptor protein, connecting CD4 to the ubiquitin (Ub)-proteasome degradative system through an interaction with beta-TrCP, a component of the SCFbeta-TrCP E3 Ub ligase complex. RESULTS: Here, we provide direct evidence indicating that Vpu promotes trans-ubiquitination of CD4 through recruitment of SCFbeta-TrCP in human cells. To examine whether Ub conjugation occurs on the cytosolic tail of CD4, we substituted all four Ub acceptor lysine residues for arginines. Replacement of cytosolic lysine residues reduced but did not prevent Vpu-mediated CD4 degradation and ubiquitination, suggesting that Vpu-mediated CD4 degradation is not entirely dependent on the ubiquitination of cytosolic lysines and as such might also involve ubiquitination of other sites. Cell fractionation studies revealed that Vpu enhanced the levels of ubiquitinated forms of CD4 detected in association with not only the ER membrane but also the cytosol. Interestingly, significant amounts of membrane-associated ubiquitinated CD4 appeared to be fully dislocated since they could be recovered following sodium carbonate salt treatment. Finally, expression of a transdominant negative mutant of the AAA ATPase Cdc48/p97 involved in the extraction of ERAD substrates from the ER membrane inhibited Vpu-mediated CD4 degradation. CONCLUSION: Taken together, these results are consistent with a model whereby HIV-1 Vpu targets CD4 for degradation by an ERAD-like process involving most likely poly-ubiquitination of the CD4 cytosolic tail by SCFbeta-TrCP prior to dislocation of receptor molecules across the ER membrane by a process that depends on the AAA ATPase Cdc48/p97.

Revêtement anti-apoptotique à base de chondroïtine sulfate : vers un stent-graft bioactif

La réparation endovasculaire (EVAR) est une technique minimalement invasive permettant de traiter l’anévrisme de l’aorte abdominale (AAA) par l’entremise d’un stent- graft (SG). L’utilisation d’EVAR est actuellement limitée par de fréquentes complications liées à une guérison inadéquate autour de l’implant. Ce manque de guérison est principalement dû au type de recouvrement polymérique des SG, au milieu pro-apoptotique des AAA et à l’accès réduit aux nutriments et à l’oxygène après EVAR. L’objectif de cette thèse consistait à concevoir un revêtement bioactif permettant d’inhiber l’apoptose et stimuler la croissance des cellules musculaires lisses vasculaires (CMLV), pour ainsi favoriser la guérison des tissus vasculaires autour des SG. La chondroïtine-4-sulfate (CS) a d’abord été choisie, car elle a été identifiée comme un médiateur important de la réparation vasculaire. Il a été démontré que la CS en solution influence directement la résistance à l’apoptose des CMLV, en plus de favoriser la différenciation myofibroblastique chez les fibroblastes. Dans le cadre de ce projet, un premier revêtement à base de CS et de collagène a été créé. Bien que le revêtement permettait d’induire une résistance à l’apoptose chez les CMLV, il se désintégrait trop rapidement dans des conditions aqueuses. Une nouvelle méthodologie a donc été adaptée afin de greffer la CS directement sur des surfaces aminées, à l’aide d’un système utilisant un carbodiimide. Dans le but d’accroître la croissance des CMLV à la surface des revêtements, le facteur de croissance de l’épiderme (EGF) a ensuite été sélectionné. En plus de ses propriétés mitogéniques et chimiotactiques, l’EGF stimule la production d’éléments de la matrice extracellulaire, comme le collagène et la fibronectine. De plus, l’activation du récepteur de l’EGF inhibe également l’apoptose des CMLV. L’EGF a donc été greffé sur la CS. Le revêtement de CS+EGF a démontré une bonne uniformité et bioactivité sur des surfaces de verre aminé. iii iv Dans une 3ème étape, afin de permettre de transposer ce revêtement bioactif sur des implants, plusieurs méthodes permettant de créer des groupements d’amines primaires sur les biomatériaux polymériques comme le PET ou le ePTFE ont été étudiées. La polymérisation par plasma a été choisie pour créer le revêtement CS+EGF à la surface de PET. Une fois de plus, celui-ci a permis d’inhiber l’apoptose des CMLV, dans des conditions pro-apoptotiques, et de favoriser la croissance des cellules. Le revêtement de CS et d’EGF, déposé sur des surfaces aminées, possède des caractéristiques biologiques intéressantes et semble donc prometteur pour favoriser une meilleure guérison autour des SG.

Morphologic evaluation of ruptured abdominal aortic aneurysm by 3D modeling

This thesis was created in Word and converted to PDF using Mac OS X 10.7.5 Quartz PDFContext.

Dissecting the dynamic of Noc2p and its partners in pre-60S particles maturation

Plusieurs études ont permis la caractérisation de la structure et de la fonction du ribosome. En ce qui attrait à la biogénèse du ribosome, nombreux aspects restent à être découverts et compris de façon plus dynamique. En effet, cette biogénèse englobe une variété de voies de modifications et d’assemblages requises pour la maturation des ARNr et pour leurs liaisons avec les protéines ribosomales. De ce fait, les protéines Noc ont été caractérisées comme des facteurs d’assemblages et ont permis la découverte d’une des premières indications sur l’ordre spatio-temporel de la maturation du ribosome. Ainsi, en utilisant la levure comme modèle, notre objectif est d’étudier d’avantage l’échange des complexes composés des protéines Noc ainsi que leur localisation intranucléaire. Ainsi, la nature des interactions de Noc2p avec Noc1p et Noc3p et l’influence de l’arrêt du transport intranucléaire ont été étudiés en utilisant des promoteurs inductibles, la microscopie à fluorescence, des immunobuvardages, qRT-PCR et des purifications par affinité.

Abdominal aortic aneurysm follow-up after endovascular repair in a canine model with non-invasive vascular elastography

Le traitement chirurgical des anévrismes de l'aorte abdominale est de plus en plus remplacé par la réparation endovasculaire de l’anévrisme (« endovascular aneurysm repair », EVAR) en utilisant des endoprothèses (« stent-grafts », SGs). Cependant, l'efficacité de cette approche moins invasive est compromise par l'incidence de l'écoulement persistant dans l'anévrisme, appelé endofuites menant à une rupture d'anévrisme si elle n'est pas détectée. Par conséquent, une surveillance de longue durée par tomodensitométrie sur une base annuelle est nécessaire ce qui augmente le coût de la procédure EVAR, exposant le patient à un rayonnement ionisants et un agent de contraste néphrotoxique. Le mécanisme de rupture d'anévrisme secondaire à l'endofuite est lié à une pression du sac de l'anévrisme proche de la pression systémique. Il existe une relation entre la contraction ou l'expansion du sac et la pressurisation du sac. La pressurisation résiduelle de l'anévrisme aortique abdominale va induire une pulsation et une circulation sanguine à l'intérieur du sac empêchant ainsi la thrombose du sac et la guérison de l'anévrisme. L'élastographie vasculaire non-invasive (« non-invasive vascular elastography », NIVE) utilisant le « Lagrangian Speckle Model Estimator » (LSME) peut devenir une technique d'imagerie complémentaire pour le suivi des anévrismes après réparation endovasculaire. NIVE a la capacité de fournir des informations importantes sur l'organisation d'un thrombus dans le sac de l'anévrisme et sur la détection des endofuites. La caractérisation de l'organisation d'un thrombus n'a pas été possible dans une étude NIVE précédente. Une limitation de cette étude était l'absence d'examen tomodensitométrique comme étalon-or pour le diagnostic d'endofuites. Nous avons cherché à appliquer et optimiser la technique NIVE pour le suivi des anévrismes de l'aorte abdominale (AAA) après EVAR avec endoprothèse dans un modèle canin dans le but de détecter et caractériser les endofuites et l'organisation du thrombus. Des SGs ont été implantés dans un groupe de 18 chiens avec un anévrisme créé dans l'aorte abdominale. Des endofuites de type I ont été créés dans 4 anévrismes, de type II dans 13 anévrismes tandis qu’un anévrisme n’avait aucune endofuite. L'échographie Doppler (« Doppler ultrasound », DUS) et les examens NIVE ont été réalisés avant puis à 1 semaine, 1 mois, 3 mois et 6 mois après l’EVAR. Une angiographie, une tomodensitométrie et des coupes macroscopiques ont été réalisées au moment du sacrifice. Les valeurs de contrainte ont été calculées en utilisant l`algorithme LSME. Les régions d'endofuite, de thrombus frais (non organisé) et de thrombus solide (organisé) ont été identifiées et segmentées en comparant les résultats de la tomodensitométrie et de l’étude macroscopique. Les valeurs de contrainte dans les zones avec endofuite, thrombus frais et organisé ont été comparées. Les valeurs de contrainte étaient significativement différentes entre les zones d'endofuites, les zones de thrombus frais ou organisé et entre les zones de thrombus frais et organisé. Toutes les endofuites ont été clairement caractérisées par les examens d'élastographie. Aucune corrélation n'a été trouvée entre les valeurs de contrainte et le type d'endofuite, la pression de sac, la taille des endofuites et la taille de l'anévrisme.