La santé et la fertilité des vaches laitières sont au cœur des préoccupations de la filière professionnelle dans un objectif d’efficience, de quantité et de qualité de la production de lait. La mise en place d’une lactation performante se superpose aux profonds changements hormonaux et métaboliques de la période postpartum, se traduisant par une balance énergétique négative. Les conséquences en sont souvent une altération de la fertilité et une immunodépression qui accroit la susceptibilité aux pathologies. Dans les élevages, il existe encore une grande variabilité d’état général et de performances chez les vaches laitières malgré la sélection génomique. Il est proposé que des modifications de la méthylation de l’ADN puissent contribuer à cette variabilité phénotypique individuelle. En effet, la méthylation de l’ADN, en tant que processus épigénétique, est impliquée dans la régulation transcriptionnelle des gènes, et présente une certaine plasticité face aux contraintes environnementales. Nous avons fait l’hypothèse que des signatures épigénétiques portées par les cellules du sang, pourraient refléter l’état de santé des vaches et pourraient être modifiées en réponse à différents facteurs intrinsèques (parité, stades physiologiques…) et aux contraintes environnementales. Ces signatures ont été recherchées dans une population de cellules du sang particulière : les monocytes. Ces cellules, accessibles par prélèvements sanguins et purification en présence d’un anticorps spécifique, constituent la première ligne de réponse d’immunité innée face aux infections aigües participant à la dégradation de l’état de santé des vaches en postpartum. Pour tester l’hypothèse de signatures épigénétiques monocytaires, une analyse du méthylome par « Reduced Representation Bisulfite Sequencing », (RRBS) dans diverses situations d’élevage a été réalisée. En utilisant des ADN génomiques de vaches incluses dans plusieurs protocoles, 22 banques ont été construites et séquencées. Leur analyse a été réalisée en utilisant un pipeline d’analyses bioinformatique et biostatistique développé au laboratoire.En moyenne 1 250 000 CpG sont pris en considération et permettent l’identification et la localisation de cytosines différentiellement méthylées (DMC) : i) 27143 DMC en comparant les méthylomes de différents types cellulaires (monocytes versus fibroblastes et PBMC) ii) 4788 DMC en réponse à un challenge nutritionnel basé sur la distribution du complément alimentaire GENIAL®, fabriqué et distribué en élevage par nos partenaires PILARDIERE et XR-Repro. iii) 2615 et 4616 DMC en réponse au challenge infectieux pour le groupe de vaches témoins et le groupe en restriction alimentaire respectivement (protocole coordonné par Christine Leroux et José Pires (RUMINFLAME, INRA, Theix) combinant une restriction alimentaire et un challenge immunitaire, par injection de LipoPolySaccharide). iv) 4420 DMC issues de la comparaison entre méthylomes de vaches à génome constant (issues du transfert nucléaire, clones) et de vaches à génome variable mais de même âge et élevées dans les mêmes conditions que les clones. Pour certaines régions différentiellement méthylées (DMR) ciblant le promoteur de gènes, le statut de méthylation a été confirmé par conversion bisulfite et pyroséquençage. L’expression des gènes associés a été étudiée. Une anti corrélation significative est observée entre méthylation et expression signant la fonctionnalité de ces régions.En comparant les 11 méthylomes monocytaires, il est montré que 21% des CpG sont extrêmement stables et ne présentent qu’une faible variation de méthylation entre échantillons ( 20%). L’ensemble de ces informations peut être pris en considération pour la conception d’un outil d’épigénotypage. A l’avenir, il serait aussi possible d’utiliser cet outil en routine afin d’appréhender les variations du méthylome monocytaire dans différentes conditions d’élevage. / In dairy breeding, the health and fertility of cows are the main concern with the aims to maintain milk quantity and quality and to reduce the interval between calving in a high competitive economical context. Postpartum period is marked by major hormonal and metabolic changes that affect productivity, immune responses and fertility. The consequences of immune response deterioration are an increasing susceptibility to diseases (mastitis, metritis, endometritis…). Genomic selection in livestock improves the performance of the population but does not exclude phenotypic variability at the level of livestock and the individual. It is proposed that DNA methylation could contribute to this individual phenotype variability. Indeed, DNA methylation is an epigenetic process involved in transcriptional regulation of genes displaying certain plasticity in front of environmental constraints.We assumed the epigenetic signatures carried by blood cells, could reflect overall health and could be modified in response to intrinsic factors (parity, stages …) and to environmental changes. These signatures were researched in a particular blood cells subpopulation: the monocytes. These cells, obtained by blood sampling and purification with a specific antibody, are the first line of defense against acute infections participating in health status deterioration of postpartum cows.To test the monocyte epigenetic signatures hypothesis, monocyte methylome were analyzed by « Reduced Representation Bisulfite Sequencing » (RRBS), in various breeding conditions. Using genomic DNA form cows included in several protocols, 22 libraries were constructed and sequenced. Their analyses were accomplished using a « homemade » pipeline which integrates bioinformatics and biostatistics analyses. On average, 1 250 000 CpGs were analyzed in order to identify differentially methylated cytosines (DMCs): i) 27143 DMC by comparison between different cells types (monocytes versus fibroblasts and PBMC) ii) 4788 DMCs in response to nutritional challenge based on the dietary supplement, GENIAL®, produced and distributed in breeding by our partner PILARDIERE and XR-Repro (in collaboration with Marion Boutinaud, INRA, Rennes). iii) 2615 and 4616 DMCs in response to infectious challenge with LipoPolySaccharide injection for control cows group fed normal diet and for dietary restriction cows group, respectively (collaboration with Christine Leroux and José Pires, RUMINFLAME, INRA, Theix; and Gilles Foucras (ENVT, Toulouse)). iv) 4420 DMCs from the comparison between constant genomic cow (Somatic cell nuclear transfer, clones) and variable genomic cows but with the same age and raised in the same conditions than clones.From DMCs, we identified differentially methylated regions (DMRs) defined as region with at least 3 DMCs inside 100 bp. For some DMRs targeting gene promoter, the methylation status was validated by bisulfite conversion and pyrosequencing. Gene associated expression were also investigated. A significant negative correlation has been observed between methylation and expression, highlighting the functional relevance of these DMRs in gene transcription control.By comparing the 11 monocyte methylomes, 21% of CpGs present a remarkable constant methylation level with weak variability between samples (20%).Taking together, these data can provide a list of relevant DMCs for an epigenetic tool conception. In the future, it would be possible to use this tool for a routine analysis in order to grasp monocyte methylome variations in different breeding management.

L'interaction entre impulsions lasers ultra-brèves et matériaux diélectriques est un sujet d'étude en constant renouvellement, motivé aussi bien par la naissance d'une multitude d'applications (micro-usinage laser, opérations de la cornée, ...) que par ses aspects fondamentaux (génération d'harmoniques d'ordre élevé, électronique au cycle optique, ...). Pourtant, les mécanismes sous-jacents à cette interaction sont encore mal compris, en particulier d'un point de vue quantitatif. En effet, une bonne partie des phénomènes ont lieu durant le passage de l'impulsion laser, c'est-à-dire pendant quelques dizaines de femtosecondes. De surcroît, les éclairements impliqués dans l'interaction sont élevés : quelques dizaines de TW/cm^2. La compréhension et la quantification des processus élémentaires ayant lieu durant l'interaction requiert donc de concevoir des expériences sur mesure ainsi que d'effectuer un travail approfondi de modélisation. Dans ce manuscrit sont présentées deux techniques expérimentales complémentaires utilisées durant la thèse : l'interférométrie fréquentielle et la spectroscopie d'absorption résolues en temps. Ces deux techniques sont employées pour étudier les processus électroniques d'excitation et de relaxation dans trois matériaux distincts : le quartz, le saphir et l'oxyde de magnésium. La quasi-intégralité des résultats expérimentaux sont analysés à l'aide d'un modèle en équation de taux multiples (MRE) permettant de discriminer l'importance relative de chacun des processus pris en compte. Tout d'abord, une preuve expérimentale directe de l'existence de l'ionisation par impact dans le quartz est présentée. Ces résultats ont été obtenus par l'exposition de l'échantillon à une série de deux impulsions, ce qui permet de moduler indépendamment la densité et la température du plasma. Les résultats expérimentaux sont reproduits avec succès par le modèle MRE intégrant l'ionisation multiphotonique, le chauffage des porteurs photo-excités ainsi que l'ionisation par impact comme processus d'excitation. Nous nous concentrons ensuite sur une seconde série de résultats concernant la relaxation du saphir après excitation induite par laser. Un nouveau mécanisme de relaxation est proposé et testé par la modélisation pour tenter d'expliquer la dynamique de ce processus. Ce mécanisme implique la formation d'excitons auto-piégés puis leur recombinaison. Enfin, le modèle MRE est appliqué à la détection de seuils d'ablation dans les trois solides. Le choix du critère physique déterminant ce seuil, sujet soumis à d'intenses débats dans la littérature, est alors discuté. / The interaction between an ultrashort laser pulse et dielectric materials is a constantly evolving field motivated by the birth of various applications (laser micro-machining, cornea surgery, ...) as well as its fundamental aspects (high-order harmonic generation, electronics at optical-cycle regime, ...). However, the underlying mechanisms of this interaction are still to be understood, especially from a quantitative point of view. Indeed, most phenomena occur during the pulse propagation through the material (i.e. in a few tens of femtoseconds). Moreover, the involved intensities are very high: a few tens of TW/cm^2. These two aspects make it difficult to study this interaction. To push the understanding forward, it is necessary to design new experiments and carry out an extensive work in modelling. Two complementary experimental techniques are presented in this manuscript: time resolved spectral interferometry and absorption spectroscopy. These two techniques are used to study elementary excitation and relaxation electronic processes in three different materials: Quartz, sapphire and magnesium oxide. Almost all experimental results are analyzed using a multiple rate equations (MRE) model allowing us to discriminate the relative importance of each of these processes. Firstly, a direct experimental proof of the existence of impact ionization in quartz is presented. These results have been obtained by exposing the sample to a sequence of two laser pulses, allowing us to tune independently both density and temperature of the plasma. The experimental results are successfully reproduced by the MRE model including multiphoton ionization, inverse bremsstrahlung and impact ionization as excitation processes. We then focus on another series of results on sapphire relaxation after laser-induced excitation. A new relaxation mechanism is proposed and tested by modelling to attempt to explain the dynamic of this process. This mechanism involves the formation of self-trapped excitons and their recombination. Finally, the MRE model is applied to the detection of the laser-induced ablation threshold in all three solids. The choice of the physical criterion defining this threshold, a subject that has caused intense debates over the past years, is discussed.

Des antibiotiques sont introduits de façon chronique dans les sols lors de l’épandage des matières fertilisantes d’origine résiduaire (MAFOR), telles que le fumier ou les boues de station d’épuration. La dissémination de ces polluants dans l’environnement présente un risque à long terme pour la santé en raison notamment de l’apparition de résistances aux antibiotiques. L’origine et les propriétés des MAFOR peuvent influencer le devenir ultérieur des antibiotiques dans les sols. Ce devenir et les effets des antibiotiques sur les organismes vivants dépendent de leur (bio)disponibilité. Peu de données existent sur la (bio)disponibilité des antibiotiques dans les sols car elles sont conditionnées par le développement de méthodes d’extraction et d’analyse des molécules à de faibles teneurs, dans des matrices organo-minérales complexes. Ce travail de recherche se focalise sur les liens entre nature des MAFOR, devenir et biodisponibilité des antibiotiques dans les sols, et impacts sur les micro-organismes du sol. Des méthodes chimiques ont été développées pour estimer la (bio)disponibilité et le devenir de deux antibiotiques (ciprofloxacine et sulfaméthoxazole) et de certains produits de transformation dans les sols amendés par des MAFOR et incubés au laboratoire. Un modèle a été utilisé pour décrire le devenir du sulfaméthoxazole et de son métabolite principal dans les sols en fonction de l’évolution de la matière organique de la MAFOR ; ceci a permis de montrer que le co-métabolisme pouvait être à l’origine de la biodégradation des molécules et de la formation de résidus non-extractibles. Enfin, ces données chimiques ont été confrontées à des mesures biologiques : la (bio)disponibilité des antibiotiques mesurée à l’aide de différentes extractions aqueuses a été reliée à leur biodégradation par des micro-organismes adaptés dans les sols ou à leur toxicité sur les activités nitrifiantes microbiennes des sols. Ce travail a permis d’obtenir des résultats originaux qui pourront être utiles pour une évaluation des risques liés à la dispersion des antibiotiques dans l’environnement. / Antibiotics are chronically introduced in soils through the application of exogenous organic matter (EOM) such as manure or sewage sludge. The environmental dissemination of these pollutants presents a long-term risk for health particularly due to the acquisition of antibiotic resistances. The origin and the properties of EOM can influence the antibiotic behavior in soils. This behavior and the potential impact on living-organisms depends on the antibiotic (bio)availability. Few data about the antibiotic bioavailability in soils exist and increasing knowledge is conditioned by the development of extraction and analytical methods for molecules at low concentrations in complex organomineral matrices. This research work focuses on the link between the MAFOR type, the behavior and the bioavailability of antibiotics in soils, and their impacts on soil microorganisms. Chemical methods were developed to assess the(bio)availability and the behavior of two antibiotics (sulfamethoxazole and ciprofloxacin) and some transformation products in EOM-amended soils incubated in controlled conditions. A modelling approach was used to describe the behavior of sulfamethoxazole and its main metabolite in soils as a function of the organic matter evolution; the modelling results suggest that co-metabolism was responsible for the molecule mineralization and the formation of biogenic non-extractable residues. Finally chemical data were confronted to biological measures: the (bio)availability of antibiotics estimated through different aqueous extractions was related to their biodegradation by adapted soil microorganisms or to their toxicity on soil microbial activities. Original results were obtained in this work and will be useful to assess the risk related to the antibiotic dispersion in the environment.

This thesis presents the design and construction of a micro-scale, air powered, impact testing device for use in Virginia Tech's Biological and Bio-inspired Materials Laboratory. A brief overview of current projectile impact testers is presented along with motivation for the fabrication of a new testing system capable of firing a projectile with a maximum diameter of 0.5 mm at velocities ranging from 20 to 50 m/s. Initial design calculations and analysis were performed to optimize barrel length, projectile size, and air pressure for desired velocity ranges. Computer aided design was then utilized to create a digital model of the entire system before production began on the device. Within the scope of this project was the development of a large-scale projectile impact tester as a proof of concept of the system's design that would later be utilized by other researchers as well as the micro-scale tester which carried over the lessons learned and design improvements from the larger device. The culmination of the project was the testing of biological samples (sea urchin spine cross sections) to prove the viability of the device and highlight its research niche. Future use cases and design improvements of the small-scale impact tester were also investigated as part of this thesis work. / Master of Science / This thesis encompasses the design and fabrication of both a large-scale projectile impact tester as a proof of concept design as well as a micro-scale version that carries over many of the design elements of the large version but is designed to fire projectiles for small scale biological material tests. Also included as part of this thesis is a breakdown of the various impact testers currently available within research to show why this project was necessary. The project culminated in simple impact studies of sea urchin spines to showcase the capabilities of the impact tester in its current form as well as to outline some of the expanded properties that could be determined with simple experimental setup changes. From this impact, study it was determined that sea urchin spines are a leading candidate in the formulation of bio-inspired impact resistant ceramic foams as they have excellent energy absorption properties during dynamic loading. The calcite foam structure of the sea urchin spines proved to have better impact absorption capabilities in comparison to many current engineering materials used for impact resistance. The final part of this thesis is a brief overview of the planned future use cases of the device.

The topic of Impact Investing has been creating waves and generating a lot of interest in the funding ecosystem with the growth of impact startups & because of pressure from the populace in the face of global challenges. At the same time the field has been under-explored by scholars. The exploration of the investment industry is performed by collecting investors' perspective on the self defined concept of Impact investing. The research attempts to portray the perspective of the established Venture Capital regime on Impact Investment and understand whether it is still perceived as philanthropic endeavors investing in an alternative asset class, suggested by previous academic research or an industry wide transition and change of investment practices as portrayed by the industry research. This study is focused on the Swedish & U.S. Venture Capital regimes. Sweden, a country that has been described as the “Impact Capital”, and the U.S. that represents worlds largest VC capital sector. Semi-structured qualitative interviews were used in this study to explore the industry dynamics using a MLP(Multi Level Perspective) framework. The interviews with VCs help understand the current sentiment on the growth in impact investing and why the Swedish market is seeing an industry-wide transition while the U.S. VC’s treat it as a separate asset class.  The authors identified that the U.S. regime is currently in the emergence phase of transition while the Swedish regime has reached the transformation phase. Additionally four key themes that differentiate the perspective of the Swedish and US regimes were identified; Risk, Profitability, Use-Case & Branding. / Impact Investing är ett ämne som har skapat vågor och genererat ett stort intresse för finansieringsekosystemet i samband med tillväxten av nystartade företag och påtryckningar från befolkningen inför de globala utmaningarna. Trots det har ämnet sett begränsad akademisk forskning. Explorationen av investeringsbranschen utförs genom att samla investerarnas perspektiv på det självdefinierade konceptet Impact Investing. Forskningen försöker skildra hur den etablerade riskkapitalregimen ser på Impact Investment och förstå om det fortfarande uppfattas som filantropiska initiativ av att investera i en alternativ tillgångskategori, som föreslås av tidigare akademisk forskning eller en branschomfattande övergång och förändring av investeringspraxis som framställts av industriforskningen.  Denna studie fokuserar på riskkapitalsregiment i Sverige och Amerika. Sverige, ett land som har beskrivits som "Impact Capital", och USA som representerar världens största VC-kapitalsektor. Semistrukturerade kvalitativa intervjuer används i denna studie för att utforska industridynamiken med hjälp av MLP(Multi Level Perspective)-ramverket. Intervjuerna med riskkapitalister hjälper till att förstå den nuvarande uppfattningen om tillväxten av impact investment och varför den svenska marknaden ser en branschomfattande förändringsprocess medan amerikanska VC:s behandlar det som en separat tillgångskategori. Författarna identifierade att den amerikanska regimen för närvarande befinner sig i begynnelsefasen medan den svenska regimen har nått transformationsfasen. Dessutom identifierades fyra nyckelteman som skiljer de svenska och amerikanska regimernas perspektiv; Risk, Lönsamhet, användningsfall & varumärke.

No description available.

El presente trabajo de investigación denominado: “Evaluación del Impacto Financiero y Tributario en la transición de la NIC 17 a la NIIF 16 en el sector minero", tiene como objetivo ilustrar a las empresas del sector, sobre la trascendencia de la nueva norma de arrendamientos en los estados financieros. El estudio se encuentra dividido en seis capítulos principales. En el marco teórico se presentan los constructos fundamentales del estudio, en los cuales se definen los conceptos clave que sitúan al lector en el contexto de la investigación. Acto seguido se expone el plan de investigación, en el cual se identifica el problema, la hipótesis planteada y los objetivos trazados. Más adelante se emplea la metodología mixta para profundizar en la percepción de las empresas del sector y medir su conocimiento sobre la nueva norma. Después se presentan los resultados del estudio y mediante la aplicación de un caso, se pretende ilustrar los principales cambios de la nueva norma. A continuación, se analizan los resultados de la investigación y se pretende evaluar el impacto en la transición hacia una nueva partiendo de los resultados de la investigación mixta y la literatura consultada. Finalmente, se concluye que la nueva norma traerá beneficios que mejoran la transparencia y la comparabilidad de la información, pero tendrá consecuencias en los contratos alquiler y los contratos de operación minera que involucran el arrendamiento de maquinaria y equipos, que pueden afectar las condiciones de los convenios de deuda y la calificación crediticia de las compañías mineras. / This research paper entitled: "Evaluation of Financial Impact and Taxation in the transition from IAS 17 to IFRS 16 in the mining industry", aims to illustrate to companies in the industry, about the importance of the new accounting standard for leases in the financial statements. The study is divided into six main chapters. In the theoretical framework the main constructs of the study are presented, in which the key concepts that put the reader in the context of the investigation are defined. Then is exposed the research plan, in which is identified the problem, the hypothesis and objectives. Later, the mixed methodology is used to deepen the perception of companies in the sector and to measure their knowledge of the new standard. After, the results of the study are presented and by applying a case, are intended to illustrate the main changes in the new standard. Then the research results are analyzed and pretend to assess the impact on the transition to a new standard, on the results of the joint research and the literature. Finally, we conclude that the new standard will bring benefits to improve transparency and comparability of information, but it will have consequences in the contracts rent and contract mining operation involving the leasing of machinery and equipment, which may affect the conditions of debt covenants and the rating credit of mining companies. / Trabajo de Suficiencia Profesional

The objective of this research is to simulate the response of an isolated substructure such that the response of the substructure in isolation would be the same as the substructure within the structure. Generally, the behaviour of an isolated subsystem (substructure) subjected to dynamic loading is different than the behaviour of the same substructure within a system (structure). This is primarily caused by the boundary conditions that are imposed on the substructure from the surrounding subsystem in the entire structure. A new systematic approach (methodology) is developed for performing impact analysis on the isolated substructure. The developed technique is fundamentally based on enforcing the mode shapes around the boundary of the substructure in the full structure to be similar to the mode shapes of the isolated substructure. This is achieved by providing a consistent adjustment to the loading conditions (impact velocity and mass) to account for the loss of restraint at the interface with the full structure. Another important aspect of this research is experimental validation of proposed method. This method allows the experimental testing of an isolated substructure since the testing is performed by impacting the isolated substructure with an appropriate mass and velocity. In the finite element analysis, the structure is analyzed, and then the isolated substructure simulation is performed using the developed technique. The results obtained from the numerical simulations, for both the substructure in situ and the substructure in isolation, are compared and found to be in good agreement. For instance, the effective plastic strains, kinetic and internal energies for the substructure within the structure and the substructure in isolation range from 7% to 12% discrepancies between two analyses. The numerical simulations of a full structure are verified by performing a series of experimental impact tests on the full structure. Finally, the experimental applicability of the technique is studied and its results are validated with FE simulation of substructure in isolation. This problem of experimentally testing an isolated substructure had previously not been addressed. The comparisons of FE simulation and experimental testing are made based on the deformed geometries, out-of-plane deflections and accelerometer readings. For example, the out-of-plane deformations from the FE analysis and the experimental test were determined to be within 7% to 9%. The experimental validation and numerical simulations indicates the technique is reliable, repeatable and can predict dynamic response of the substructures when tested in isolation. / Thesis / Doctor of Philosophy (PhD)

This paper is an investigation into the effect of the bat support conditions on the collision between a baseball and a baseball bat. Bat performance is tested using both machines and human subjects. For the machine tests, a baseball is fired from an air-cannon at a stationary bat, where the bat is either allowed to rotate only or is completely unrestricted after impact. The initial and rebound ball speeds are measured for a range of impact locations. For the human tests, a person swings the bat and hits the ball off of a tee. The bat speed prior to impact and the ball speed after impact are measured. The results for each method of testing are compared, and the final ball speed is found to be independent of the bat support condition.

No description available.