Multilevel oblique corpectomy for cervical spondylotic myelopathy preserves segmental motion.

PURPOSE: To document the neurological outcome, spinal alignment and segmental range of movement after oblique cervical corpectomy (OCC) for cervical compressive myelopathy. METHODS: This retrospective study included 109 patients--93 with cervical spondylotic myelopathy and 16 with ossified posterior longitudinal ligament in whom spinal curvature and range of segmental movements were assessed on neutral and dynamic cervical radiographs. Neurological function was measured by Nurick's grade and modified Japanese Orthopedic Association (JOA) scores. Eighty-eight patients (81%) underwent either a single- or two-level corpectomy; the remaining (19%) undergoing three- or four-level corpectomies. The average duration of follow-up was 30.52 months. RESULTS: The Nurick's grade and the JOA scores showed statistically significant improvements after surgery (p < 0.001). The mean postoperative segmental angle in the neutral position straightened by 4.7 ± 6.5°. The residual segmental range of movement for a single-level corpectomy was 16.7° (59.7% of the preoperative value), for two-level corpectomy it was 20.0° (67.2%) and for three-level corpectomies it was 22.9° (74.3%). 63% of patients with lordotic spines continued to have lordosis postoperatively while only one became kyphotic without clinical worsening. Four patients with preoperative kyphotic spines showed no change in spine curvature. None developed spinal instability. CONCLUSIONS: The OCC preserves segmental motion in the short-term, however, the tendency towards straightening of the spine, albeit without clinical worsening, warrants serial follow-up imaging to determine whether this motion preservation is long lasting.

Computational quest for understanding the role of astrocyte signaling in synaptic transmission and plasticity.

The complexity of the signaling network that underlies astrocyte-synapse interactions may seem discouraging when tackled from a theoretical perspective. Computational modeling is challenged by the fact that many details remain hitherto unknown and conventional approaches to describe synaptic function are unsuitable to explain experimental observations when astrocytic signaling is taken into account. Supported by experimental evidence is the possibility that astrocytes perform genuine information processing by means of their calcium signaling and are players in the physiological setting of the basal tone of synaptic transmission. Here we consider the plausibility of this scenario from a theoretical perspective, focusing on the modulation of synaptic release probability by the astrocyte and its implications on synaptic plasticity. The analysis of the signaling pathways underlying such modulation refines our notion of tripartite synapse and has profound implications on our understanding of brain function.

Production of low phytic acid rice by hairpin RNA- and artificial microRNA-mediated silencing of OsMIK in seeds

To produce agronomically competitive rice with nutritionally superior, environmentally safe phytic acid (PA) levels, hairpin RNA (hpRNA)- and artificial microRNA (amiRNA)-mediated gene silencing approaches were explored to reduce both myo-inositol kinase gene (OsMIK) expression and PA accumulation in rice seeds. hpRNA and amiRNA sequences targeted to OsMIK (hpMIK and amiMIK), under the control of a rice Ole18 promoter, were transformed into the rice cultivar Nippon-bare. Fourteen and 21 independent transgenic events were identified containing the hpMIK and amiMIK constructs, respectively, from which five stable homozygous transgenic lines of each were developed together with their null siblings. Southern blotting demonstrated transgene integration into the genome and quantitative real-time PCR showed that gene silencing was restricted to seeds. OsMIK transcripts were significantly reduced in both transgenic amiMIK and hpMIK seeds, which had PA levels reduced by 14.9-50.2 and 38.1-50.7 %, respectively, compared with their respective null siblings. There were no systematic significant differences in agronomic traits between the transgenic lines and their non-transgenic siblings, and no correlation between seed PA contents and decreased rates of seed germination and seedling emergence. The results of the present study suggest that Ole 18-driven OsMIK silencing via hpRNA and amiRNA could be an effective way to develop agronomically competitive low phytic acid rice.

Functional Characterization of a n NTPase Activity of the Hepatitis C Virus Nonstructural Protein 4B

Background: Nonstructural p rotein 4 B (NS4B) i s the m asterorganizer of hepatitis C virus (HCV) replication complexformation. It is a multispanning membrane protein that has beenreported to p ossess NTPase activity. This enzymatic functionhas been poorly studied so far and its role in the HCV life cycleis u nknown. T he present w ork-in-progress a ims at validatingand functionally c haracterizing this a ctivity a nd its r ole in t heviral life cycle.Methods: B ioinformatic analyses were performed to i dentifykey residues for site-directed mutagenesis, both in t he contextof s ubgenomic r eplicons a s well as recombinant v iruses.Mutants were investigated with respect to R NA replication andinfectious particle p roduction. In p arallel, expression andpurification of recombinant wild-type and mutant NS4B proteinsare being pursued to characterize enzymatic activity in vitro.Results: B ioinformatic a nalyses revealed t hat p redictedNTPase features are conserved only in H CV NS4B b ut n ot i nNS4B from other Flaviviridae f amily m embers. A laninesubstitutions were designed to target predicted key Walker A, Band C motifs. These substitutions affected RNA replication andinfectious virus production to v arying degrees. Optimization ofrecombinant protein production is i n progress both in b acterialas well as mammalian expression systems.Conclusions: These studies should yield new insights into thefunctions of this hitherto poorly characterized viral nonstructuralprotein and may reveal novel targets for antiviral intervention inthe future.

'Good-genes' and 'compatible-genes' effects in an Alpine whitefish and the information content of breeding tubercles over the course of the spawning season.

Some models of sexual selection predict that individuals vary in their genetic quality and reveal some of this variation in their secondary sexual characteristics. Alpine whitefish (Coregonus sp.) develop breeding tubercles shortly before their spawning season. These tubercles are epidermal structures that are distributed regularly along the body sides of both males and females. There is still much unexplained variation in the size of breeding tubercles within both sexes and with much overlap between the sexes. It has been suggested that breeding tubercles function to maintain body contact between the mating partners during spawning, act as weapons for defence of spawning territories, or are sexual signals that reveal aspects of genetic quality. We took two samples of whitefish from their spawning place, one at the beginning and one around the peak of spawning season. We found that females have on average smaller breeding tubercles than males, and that tubercle size partly reveals the stage of gonad maturation. Two independent full-factorial breeding experiments revealed that embryo mortality was significantly influenced by male and female effects. This finding demonstrates that the males differed in their genetic quality (because offspring get nothing but genes from their fathers). Tubercle size was negatively linked to some aspects of embryo mortality in the first breeding experiment but not significantly so in the second. This lack of consistency adds to inconsistent results that were reported before and suggests that (i) some aspects of genetic quality are not revealed in breeding tubercles while others are, or (ii) individuals vary in their signaling strategies and the information content of breeding tubercles is not always reliable. Moreover, the fact that female whitefish have breeding tubercles of significant size while males seem to have few reasons to be choosy suggests that the tubercles might also serve some functions that are not linked to sexual signaling.

The genetic consequences of hatchery-induced sperm competition in a salmonid

Supportive breeding is an important tool in conservation management, but its long-term genetic consequences are not well understood. Among the factors that could affect the genetics of the offspring is sperm competition as a consequence of mixed-milt fertilizations - which is still a common practice in many hatcheries. Here, we measured and combined the relevant factors to predict the genetic consequences of various kinds of hatchery-induced sperm competition. We drew a random sample of male Coregonus zugensis (an Alpine whitefish) from a hatchery program and quantified their in vitro sperm potency by integrating sperm velocity during the first minute after activation, and their in vitro milt potency by multiplying sperm potency with milt volume and sperm cell density. We found that not controlling for sperm density and/or milt volume would, at a constant population size, decrease the variance effective number of male breeders N-em by around 40-50%. This loss would decrease with increasing population growth rates. Partial multifactorial breeding and the separate rearing of in total 799 batches of eggs revealed that neither sperm nor milt potency was significantly linked to egg survival. Sperm and milt potency was also not significantly correlated to other potential quality measures such as breeding tubercles or condition factor. However, sperm potency was correlated to male age and milt potency to male growth rate. Our findings suggest that hatchery-induced sperm competition not only increases the loss of genetic variation but may also induce artificial selection, depending on the fertilization protocol. By not equalizing milt volume in multi-male fertilization hatchery managers lose relatively more genetic variation and give fast-growing males a reproductive advantage, while equalizing milt volume reduces the loss of genetic variation and favors younger males who may have fast sperm to compensate for their subdominance at the spawning place. (c) 2007 Elsevier Ltd. All rights reserved.

Intra- and intersexual selection and their potential consequences on fitness-relevant traits in several fish species

Résumé : Les mécanismes de sélection sexuelle, en particulier la compétition entre mâles (sélection inter-sexuelle) et le choix des femelles (sélection intra-sexuelle), peuvent fortement influencer le succès reproducteur d'un individu, c'est-à-dire son nombre de descendants. On observe ainsi que les mâles dominants et les mâles élaborant des caractères sexuels secondaires marqués ont un succès reproducteur élevé. Toutefois, le succès reproducteur ne suffit pas pour garantir une contribution génétique élevée, parce que la fitness dépend également de la performance des descendants (c'est-à-dire de leur survie et de leur propre succès reproducteur). Si cette performance dépend en partie des gènes paternels, les males ont un avantage certain à signaler leur qualité aux femelles afin d'atteindre des taux de reproduction élevé. Ce mécanisme de signalisation est connu sous le nom de 'good genes hypothesis', toutefois très peu d'études ont clairement démontré le lien entre la qualité génétique des individus et la signalisation. De plus, la performance des descendants peut aussi dépendre des effets génétiques de compatibilité entre mâles et femelles ('compatible genes'). C'est-à-dire que certains allèles paternels n'apporteraient un avantage aux descendants qu'en combinaison avec certains allèles maternels. Nous avons déterminé, durant la période de reproduction, le statut de dominance des mâles pour deux espèces de poissons d'eau douce : la truite (Salmo trotta) et le vairon (Phoxinus phoxinus), puis nous avons évalué la relation entre le succès reproducteur et le statut de dominance et/ou la quantité de signalisation des caractères sexuels secondaires. Nous avons également fécondés artificiellement des oeufs de truites et de corégones (Coregonus palaea), en croisant chaque mâle avec chaque femelle (full-factorial breeding design). Ce type de design autorise la quantification précise des effets génétiques et permet de séparer les effets de 'good genes' et de 'compatible genes'. Cela a été fait sous différentes intensités de stress bactérien, ainsi que dans des conditions naturelles, et nous avons pu ainsi tester si certains indicateurs de qualité génétique des mâles ('good genes') étaient liés a) à la dominance et/ou b) à l'expression des caractères sexuels secondaires des mâles comme l'intensité mélanique ou la taille des tubercules sexuels. En outre, nous cherchons à savoir si la survie des descendants est liée à certaines combinaison des gènes du complexe d'histocompatibilité majeur (MHC) et/ou à la parenté génétique des parents, les deux traits étant soupçonnés d'avoir des influences génétique de compatibilité (`compatible genes') à la performance des descendants. Nous avons constaté que la dominance des mâles est directement liée à la taille et au poids des mâles (truites, vairons), mais également aux caractères sexuels secondaires (tubercules). De plus, les mâles vairons dominant ont eu un succès de fécondation plus élevés que les mâles subordonnés. Nous montrons que les truites et corégones mâles diffèrent dans leur qualité génétique, qui a été mesurée avéc la survie embryonnaire, le temps avant l'éclosion et enfin la croissance juvénile. Contrairement aux prédictions, la dominance (ou les traits indicatifs de dominance) n'était liée à la qualité génétique, dans aucun des traitements, et ne fonctionne donc pas comme indicateur de qualité. Par contre, la qualité génétique était liée aux caractères sexuels secondaires, particulièrement par la teinte mélanique chez les truites. Les embryons de truites issus de pères sombres survivaient mieux que ceux issus de pères clairs dans des environnements difficiles, de plus leur croissance était plus élevée lors de leur première année dans des conditions naturelles. La taille des juvéniles lors de leur première année est un trait important lié au succès dans la compétition pour des ressources telles qu'abri ou nourriture. De plus, les femelles truites peuvent augmenter la survie de leurs descendants en choisissant des mâles selon leur type de MHC ou selon leur degré de parenté. En outre, chez les corégones, la morphologie des tubercules sexuels ne semble pas signaler la qualité génétique. Nous avons également remarqué que l'exposition à des pathogènes non-létaux pouvait influencer la performance des alevins à court et long terme, probablement en affaiblissant leur système immunitaire. Cette thèse montre que les mâles diffèrent dans leur qualité génétique et que différents mécanismes de sélection inter- ou intra-sexuelle (par exemple la préférence pour des mâles sombres, pour des génotypes MHC ou pour des couples avec degré de parenté basse) pouvait avoir un effet positif sur la qualité des descendants, bien que cet effet génétique pouvait changer au cours du temps et entre différents environnements. Contrairement à nos attentes, le résultat de la compétition intra-sexuelle (la hiérarchie de dominance entre mâles) n'était pas lié à la qualité génétique individuelle ('good genes'). Dans ce sens, ce travail permet également de contribuer à l'explication du fait que la sélection sexuelle, de par sa forte sélection directionnelle, ne conduit pas à la diminution de la variance génétique, mais plutôt à la maintenance du polymorphisme génétique. Summary : Sexual selection mechanisms, especially male-male competition (inteasexual selection) and female mate choice (inteasexual selection), can strongly influence individual mating success, often resulting in dominant males and males with elaborate secondary sexual characters having higher fertilisation success. However, siring a high number of offspring alone does not guarantee high individual fitness, as fitness does also strongly depend on offspring performance (i.e. survival, fecundity). If this superiority in offspring performance depends on paternally inherited genes, the fathers are expected to signal this potential indirect benefit to females in order to attain high mating rates. This mechanism is also known as the 'good genes' hypothesis of sexual selection but until now most studies failed to conclusively show the relation of an individual genetic quality and its potential signalling traits. Further, offspring performance could also depend on compatible gene effects. These are alleles that increase offspring performance only in combination with other specific alleles. We first determined male dominance status from intrasexual competition during mating season for brown trout (Salmo trutta) and European minnows (Phoxinus phoxinus). For minnows we additionally checked if dominance and/or secondary sexual traits were linked to fertilisation success. Further, we artificially fertilised brown trout and alpine whitefish (Coregonus palaea) eggs, following full factorial breeding designs, enabling to properly measure `good gene' and `compatible gene' effects on offspring performance. This was done under different intensities of natural stressors, as well as under natural conditions. This procedure allowed us to test if the obtained male genetic quality measures (good genes effects) were indicated by a) dominance or lay traits linked to dominance and/or by b) secondary sexual characteristics such as melanin-based male skin darkness or breeding tubercles. Further, we investigated if offspring survival was linked to the MHC (major histocompatibility complex) gene combinations and/or to the parental genetic relatedness, as both traits were shown to have 'compatible gene' effects that may influence offspring performance. We found that male dominance in intrasexual competition was positively linked to body size, body weight (brown trout, minnows) but also to elaborate secondary sexual characteristics (breeding tubercles in minnows). Further, dominant minnow males did have an increased fertilisation success compared to subordinate ones. We show that brown trout and whitefish males do usually differ in their genetic quality, which was measured as embryo survival, hatching timing and finally as juvenile growth. Contrary to prediction male dominance or dominance indicating traits do not function as a quality signal as they were not linked to genetic quality. This result was constant when measuring genetic quality under different levels of natural stressors and under natural conditions (brown trout). On the other hand genetic quality seemed to be indicated by secondary sexual characteristics, specifically by melanin-based skin darkness in brown trout as brown trout embryos sired by darker fathers had increased survival rates when raised under harsh conditions and. they grew larger as juveniles after one year of growth in a natural stream, which is an important trait influencing success of juveniles in competition for hidings, food and other resources. Furthermore, brown trout females may increase the survival of their embryos when choosing males according to their MHC genotypes or to the general genetic relatedness between themselves and their potential mates. In whitefish on the other hand breeding tubercle morphology did not seem to signal genetic quality. Eventually, we saw that anon-lethal exposure to pathogens might influence short term and long term offspring performance probably by weakening an exposed individual's immune system. This thesis shows that males usually differ in their genetic quality and that different inter- or intrasexual selection mechanisms (e.g. mate selection favouring dark males, preference for MHC genotype combinations or for unrelated mates) may have strong positive effects on genetically dependent offspring performance but that such genetìc effects can change over time and environments. In contrast to our a priori expectations, the outcome of intrasexual selection, namely male dominance hierarchies, with dominant males often having high fertilisation success, was not linked to individual genetic quality (`good genes'). In this sense the present thesis may also be a helpful contribution to understand why sexual selection does not lead to rapid loss of genetic variation by strong directional selection but could even lead to the maintenance of genetic variation in natural populations.

Surface-sampling and analysis of TATP by swabbing and gas chromatography/mass spectrometry

The method of sample recovery for trace detection and identification of explosives plays a critical role in several criminal investigations. After bombing, there can be difficulties in sending big objects to a laboratory for analysis. Traces can also be searched for on large surfaces, on hands of suspects or on surfaces where the explosive was placed during preparatory phases (e.g. places where an IED was assembled, vehicles used for transportation, etc.). In this work, triacetone triperoxide (TATP) was synthesized from commercial precursors following reported methods. Several portions of about 6 mg of TATP were then spread on different surfaces (e.g. floors, tables, etc.) or used in handling tests. Three different swabbing systems were used: a commercial swab, pre-wetted with propan-2-ol (isopropanol) and water (7:3), dry paper swabs, and cotton swabs wetted with propan-2-ol. Paper and commercial swabs were also used to sample a metal plate, where a small charge of about 4 g of TATP was detonated. Swabs were sealed in small glass jars with screw caps and Parafilm® M and sent to the laboratory for analysis. Swabs were extracted and analysed several weeks later by gas chromatography/mass spectrometry. All the three systems gave positive results, but wetted swabs collected higher amounts of TATP. The developed procedure showed its suitability for use in real cases, allowing TATP detection in several simulations, including a situation in which people wash their hands after handling the explosive.

Protocol for the modeling the epidemiologic transition study: a longitudinal observational study of energy balance and change in body weight, diabetes and cardiovascular disease risk.

ABSTRACT: BACKGROUND: The prevalence of obesity has increased in societies of all socio-cultural backgrounds. To date, guidelines set forward to prevent obesity have universally emphasized optimal levels of physical activity. However there are few empirical data to support the assertion that low levels of energy expenditure in activity is a causal factor in the current obesity epidemic are very limited. METHODS: The Modeling the Epidemiologic Transition Study (METS) is a cohort study designed to assess the association between physical activity levels and relative weight, weight gain and diabetes and cardiovascular disease risk in five population-based samples at different stages of economic development. Twenty-five hundred young adults, ages 25-45, were enrolled in the study; 500 from sites in Ghana, South Africa, Seychelles, Jamaica and the United States. At baseline, physical activity levels were assessed using accelerometry and a questionnaire in all participants and by doubly labeled water in a subsample of 75 per site. We assessed dietary intake using two separate 24-h recalls, body composition using bioelectrical impedance analysis, and health history, social and economic indicators by questionnaire. Blood pressure was measured and blood samples collected for measurement of lipids, glucose, insulin and adipokines. Full examination including physical activity using accelerometry, anthropometric data and fasting glucose will take place at 12 and 24 months. The distribution of the main variables and the associations between physical activity, independent of energy intake, glucose metabolism and anthropometric measures will be assessed using cross-section and longitudinal analysis within and between sites. DISCUSSION: METS will provide insight on the relative contribution of physical activity and diet to excess weight, age-related weight gain and incident glucose impairment in five populations' samples of young adults at different stages of economic development. These data should be useful for the development of empirically-based public health policy aimed at the prevention of obesity and associated chronic diseases.

MPI-DING reference glasses for in situ microanalysis: New reference values for element concentrations and isotope ratios

[1] We present new analytical data of major and trace elements for the geological MPI-DING glasses KL2-G, ML3B-G, StHs6/80-G, GOR128-G, GOR132-G, BM90/21-G, T1-G, and ATHO-G. Different analytical methods were used to obtain a large spectrum of major and trace element data, in particular, EPMA, SIMS, LA-ICPMS, and isotope dilution by TIMS and ICPMS. Altogether, more than 60 qualified geochemical laboratories worldwide contributed to the analyses, allowing us to present new reference and information values and their uncertainties ( at 95% confidence level) for up to 74 elements. We complied with the recommendations for the certification of geological reference materials by the International Association of Geoanalysts (IAG). The reference values were derived from the results of 16 independent techniques, including definitive ( isotope dilution) and comparative bulk ( e. g., INAA, ICPMS, SSMS) and microanalytical ( e. g., LA-ICPMS, SIMS, EPMA) methods. Agreement between two or more independent methods and the use of definitive methods provided traceability to the fullest extent possible. We also present new and recently published data for the isotopic compositions of H, B, Li, O, Ca, Sr, Nd, Hf, and Pb. The results were mainly obtained by high-precision bulk techniques, such as TIMS and MC-ICPMS. In addition, LA-ICPMS and SIMS isotope data of B, Li, and Pb are presented.

Tree-based message diffusion for managing replicated data in unreliable and resource-constrained peer-to-peer environment

Abstract This thesis proposes a set of adaptive broadcast solutions and an adaptive data replication solution to support the deployment of P2P applications. P2P applications are an emerging type of distributed applications that are running on top of P2P networks. Typical P2P applications are video streaming, file sharing, etc. While interesting because they are fully distributed, P2P applications suffer from several deployment problems, due to the nature of the environment on which they perform. Indeed, defining an application on top of a P2P network often means defining an application where peers contribute resources in exchange for their ability to use the P2P application. For example, in P2P file sharing application, while the user is downloading some file, the P2P application is in parallel serving that file to other users. Such peers could have limited hardware resources, e.g., CPU, bandwidth and memory or the end-user could decide to limit the resources it dedicates to the P2P application a priori. In addition, a P2P network is typically emerged into an unreliable environment, where communication links and processes are subject to message losses and crashes, respectively. To support P2P applications, this thesis proposes a set of services that address some underlying constraints related to the nature of P2P networks. The proposed services include a set of adaptive broadcast solutions and an adaptive data replication solution that can be used as the basis of several P2P applications. Our data replication solution permits to increase availability and to reduce the communication overhead. The broadcast solutions aim, at providing a communication substrate encapsulating one of the key communication paradigms used by P2P applications: broadcast. Our broadcast solutions typically aim at offering reliability and scalability to some upper layer, be it an end-to-end P2P application or another system-level layer, such as a data replication layer. Our contributions are organized in a protocol stack made of three layers. In each layer, we propose a set of adaptive protocols that address specific constraints imposed by the environment. Each protocol is evaluated through a set of simulations. The adaptiveness aspect of our solutions relies on the fact that they take into account the constraints of the underlying system in a proactive manner. To model these constraints, we define an environment approximation algorithm allowing us to obtain an approximated view about the system or part of it. This approximated view includes the topology and the components reliability expressed in probabilistic terms. To adapt to the underlying system constraints, the proposed broadcast solutions route messages through tree overlays permitting to maximize the broadcast reliability. Here, the broadcast reliability is expressed as a function of the selected paths reliability and of the use of available resources. These resources are modeled in terms of quotas of messages translating the receiving and sending capacities at each node. To allow a deployment in a large-scale system, we take into account the available memory at processes by limiting the view they have to maintain about the system. Using this partial view, we propose three scalable broadcast algorithms, which are based on a propagation overlay that tends to the global tree overlay and adapts to some constraints of the underlying system. At a higher level, this thesis also proposes a data replication solution that is adaptive both in terms of replica placement and in terms of request routing. At the routing level, this solution takes the unreliability of the environment into account, in order to maximize reliable delivery of requests. At the replica placement level, the dynamically changing origin and frequency of read/write requests are analyzed, in order to define a set of replica that minimizes communication cost.