Innate and adaptive effects of inflammasomes on T cell responses.

Inflammasomes are protein complexes that form in response to pathogen-derived or host-derived stress signals. Their activation leads to the production of inflammatory cytokines and promotes a pyrogenic cell death process. The massive release of inflammatory mediators that follows inflammasome activation is a key event in alarming innate immune cells. Growing evidence also highlights the role of inflammasome-dependent cytokines in shaping the adaptive immune response, as exemplified by the capacity of IL-1β to support Th17 responses, or by the finding that IL-18 evokes antigen-independent IFN-γ secretion by memory CD8(+) T cells. A deeper understanding of these mechanisms and on how to manipulate this powerful inflammatory system therefore represents an important step forward in the development of improved vaccine strategies.

Nucleation and growth of metamorphic minerals in contact aureoles

THESIS ABSTRACT Nucleation and growth of metamorphic minerals are the consequence of changing P-T-X-conditions. The thesis presented here focuses on processes governing nucleation and growth of minerals in contact metamorphic environments using a combination of geochemical analytics (chemical-, isotope-, and trace element composition), statistical treatments of spatial data, and numerical models. It is shown, that a combination of textural modeling and stable isotope analysis allows a distinction between several possible reaction paths for olivine growth in a siliceous dolomite contact aureole. It is suggested that olivine forms directly from dolomite and quartz. The formation of olivine from this metastable reaction implies metamorphic crystallization far from equilibrium. As a major consequence, the spatial distribution of metamorphic mineral assemblages in a contact aureole cannot be interpreted as a proxy for the temporal evolution of a single rock specimen, because each rock undergoes a different reaction path, depending on temperature, heating rate, and fluid-infiltration rate. A detailed calcite-dolomite thermometry study was initiated on multiple scales ranging from aureole scale to the size of individual crystals. Quantitative forward models were developed to evaluate the effect of growth zoning, volume diffusion and the formation of submicroscopic exsolution lamellae (<1 µm) on the measured Mg-distribution in individual calcite crystals and compare the modeling results to field data. This study concludes that Mg-distributions in calcite grains of the Ubehebe Peak contact aureole are the consequence of rapid crystal growth in combination with diffusion and exsolution. The crystallization history of a rock is recorded in the chemical composition, the size and the distribution of its minerals. Near the Cima Uzza summit, located in the southern Adamello massif (Italy), contact metamorphic brucite bearing dolomite marbles are exposed as xenoliths surrounded by mafic intrusive rocks. Brucite is formed retrograde pseudomorphing spherical periclase crystals. Crystal size distributions (CSD's) of brucite pseudomorphs are presented for two profiles and combined with geochemistry data and petrological information. Textural analyses are combined with geochemistry data in a qualitative model that describes the formation periclase. As a major outcome, this expands the potential use of CSD's to systems of mineral formation driven by fluid-infiltration. RESUME DE LA THESE La nucléation et la croissance des minéraux métamorphiques sont la conséquence de changements des conditions de pression, température et composition chimique du système (PT-X). Cette thèse s'intéresse aux processus gouvernant la nucléation et la croissance des minéraux au cours d'un épisode de métamorphisme de contact, en utilisant la géochimie analytique (composition chimique, isotopique et en éléments traces), le traitement statistique des données spatiales et la modélisation numérique. Il est montré que la combinaison d'un modèle textural avec des analyses en isotopes stables permet de distinguer plusieurs chemins de réactions possibles conduisant à la croissance de l'olivine dans une auréole de contact riche en Silice et dolomite. Il est suggéré que l'olivine se forme directement à partir de la dolomie et du quartz. Cette réaction métastable de formation de l'olivine implique une cristallisation métamorphique loin de l'équilibre. La principale conséquence est que la distribution spatiale des assemblages de minéraux métamorphiques dans une auréole de contact ne peut pas être considérée comme un témoin de l'évolution temporelle d'un type de roche donné, puisque chaque type de roche suit différents chemins de réactions, en fonction de la température, la vitesse de réchauffement et le taux d'infiltration du fluide. Une étude thermométrique calcite-dolomite détaillée a été réalisée à diverses échelles, depuis l'échelle de l'auréole de contact jusqu'à l'échelle du cristal. Des modèles numériques quantitatifs ont été développés pour évaluer l'effet des zonations de croissance, de la diffusion volumique et de la formation de lamelles d'exsolution submicroscopiques (<1µm) sur la distribution du magnésium mesuré dans des cristaux de calcite individuels. Les résultats de ce modèle ont été comparés ä des échantillons naturels. Cette étude montre que la distribution du Mg dans les grains de calcite de l'auréole de contact de l'Ubehebe Peak (USA) résulte d'une croissance cristalline rapide, associée aux processus de diffusion et d'exsolution. L'histoire de cristallisation d'une roche est enregistrée dans la composition chimique, la taille et la distribution de ses minéraux. Près du sommet Cima Uzza situé au sud du massif d'Adamello (Italie), des marbres dolomitiques à brucite du métamorphisme de contact forment des xénolithes dans une intrusion mafique. La brucite constitue des pseudomorphes rétrogrades du périclase. Les distributions de taille des cristaux (CSD) des pseudomorphes de brucite sont présentées pour deux profiles et sont combinées aux données géochimiques et pétrologiques. Les analyses textorales sont combinées aux données géochimiques dans un modèle qualitatif qui décrit la formation du périclase. Ceci élargit l'utilisation potentielle de la C5D aux systèmes de formation de minéraux controlés par les infiltrations fluides. THESIS ABSTRACT (GENERAL PUBLIC) Rock textures are essentially the result of a complex interaction of nucleation, growth and deformation as a function of changing physical conditions such as pressure and temperature. Igneous and metamorphic textures are especially attractive to study the different mechanisms of texture formation since most of the parameters like pressure-temperature-paths are quite well known for a variety of geological settings. The fact that textures are supposed to record the crystallization history of a rock traditionally allowed them to be used for geothermobarometry or dating. During the last decades the focus of metamorphic petrology changed from a static point of view, i.e. the representation of a texture as one single point in the petrogenetic grid towards a more dynamic view, where multiple metamorphic processes govern the texture formation, including non-equilibrium processes. This thesis tries to advance our understanding on the processes governing nucleation and growth of minerals in contact metamorphic environments and their dynamic interplay by using a combination of geochemical analyses (chemical-, isotope-, and trace element composition), statistical treatments of spatial data and numerical models. In a first part the thesis describes the formation of metamorphic olivine porphyroblast in the Ubehebe Peak contact aureole (USA). It is shown that not the commonly assumed succession of equilibrium reactions along a T-t-path formed the textures present in the rocks today, but rather the presence of a meta-stable reaction is responsible for forming the olivine porphyroblast. Consequently, the spatial distribution of metamorphic minerals within a contact aureole can no longer be regarded as a proxy for the temporal evolution of a single rock sample. Metamorphic peak temperatures for samples of the Ubehebe Peak contact aureole were determined using calcite-dolomite. This geothermometer is based on the temperature-dependent exchange of Mg between calcite and dolomite. The purpose of the second part of this thesis was to explain the interfering systematic scatter of measured Mg-content on different scales and thus to clarify the interpretation of metamorphic temperatures recorded in carbonates. Numerical quantitative forward models are used to evaluate the effect of several processes on the distribution of magnesium in individual calcite crystals and the modeling results were then compared to measured field. Information about the crystallization history is not only recorded in the chemical composition of grains, like isotope composition or mineral zoning. Crystal size distributions (CSD's) provide essential information about the complex interaction of nucleation and growth of minerals. CSD's of brucite pseudomorphs formed retrograde after periclase of the southern Adamello massif (Italy) are presented. A combination of the textural 3D-information with geochemistry data is then used to evaluate reaction kinetics and to constrain the actual reaction mechanism for the formation of periclase. The reaction is shown to be the consequence of the infiltration of a limited amount of a fluid phase at high temperatures. The composition of this fluid phase is in large disequilibrium with the rest of the rock resulting in very fast reaction rates. RESUME DE LA THESE POUR LE GRAND PUBLIC: La texture d'une roche résulte de l'interaction complexe entre les processus de nucléation, croissance et déformation, en fonction des variations de conditions physiques telles que la pression et la température. Les textures ignées et métamorphiques présentent un intérêt particulier pour l'étude des différents mécanismes à l'origine de ces textures, puisque la plupart des paramètres comme les chemin pression-température sont relativement bien contraints dans la plupart des environnements géologiques. Le fait que les textures soient supposées enregistrer l'histoire de cristallisation des roches permet leur utilisation pour la datation et la géothermobarométrie. Durant les dernières décennies, la recherche en pétrologie métamorphique a évolué depuis une visualisation statique, c'est-à-dire qu'une texture donnée correspondait à un point unique de la grille pétrogénétique, jusqu'à une visualisation plus dynamique, où les multiples processus métamorphiques qui gouvernent 1a formation d'une texture incluent des processus hors équilibre. Cette thèse a pour but d'améliorer les connaissances actuelles sur les processus gouvernant la nucléation et la croissance des minéraux lors d'épisodes de métamorphisme de contact et l'interaction dynamique existant entre nucléation et croissance. Pour cela, les analyses géochimiques (compositions chimiques en éléments majeurs et traces et composition isotopique), le traitement statistique des données spatiales et la modélisation numérique ont été combinés. Dans la première partie, cette thèse décrit la formation de porphyroblastes d'olivine métamorphique dans l'auréole de contact de l'Ubehebe Peak (USA). Il est montré que la succession généralement admise des réactions d'équilibre le long d'un chemin T-t ne peut pas expliquer les textures présentes dans les roches aujourd'hui. Cette thèse montre qu'il s'agirait plutôt d'une réaction métastable qui soit responsable de la formation des porphyroblastes d'olivine. En conséquence, la distribution spatiale des minéraux métamorphiques dans l'auréole de contact ne peut plus être interprétée comme le témoin de l'évolution temporelle d'un échantillon unique de roche. Les pics de température des échantillons de l'auréole de contact de l'Ubehebe Peak ont été déterminés grâce au géothermomètre calcite-dolomite. Celui-ci est basé sur l'échange du magnésium entre la calcite et la dolomite, qui est fonction de la température. Le but de la deuxième partie de cette thèse est d'expliquer la dispersion systématique de la composition en magnésium à différentes échelles, et ainsi d'améliorer l'interprétation des températures du métamorphisme enregistrées dans les carbonates. Des modèles numériques quantitatifs ont permis d'évaluer le rôle de différents processus sur la distribution du magnésium dans des cristaux de calcite individuels. Les résultats des modèles ont été comparés aux échantillons naturels. La composition chimique des grains, comme la composition isotopique ou la zonation minérale, n'est pas le seul témoin de l'histoire de la cristallisation. La distribution de la taille des cristaux (CSD) fournit des informations essentielles sur les interactions entre nucléation et croissance des minéraux. La CSD des pseudomorphes de brucite retrograde formés après le périclase dans le sud du massif Adamello (Italie) est présentée dans la troisième partie. La combinaison entre les données textorales en trois dimensions et les données géochimiques a permis d'évaluer les cinétiques de réaction et de contraindre les mécanismes conduisant à la formation du périclase. Cette réaction est présentée comme étant la conséquence de l'infiltration d'une quantité limitée d'une phase fluide à haute température. La composition de cette phase fluide est en grand déséquilibre avec le reste de la roche, ce qui permet des cinétiques de réactions très rapides.

Supermarket key attributes and location decisions: A comparative study between British and Spanish consumers

The Maximum Capture problem (MAXCAP) is a decision model that addresses the issue of location in a competitive environment. This paper presents a new approach to determine which store s attributes (other than distance) should be included in the newMarket Capture Models and how they ought to be reflected using the Multiplicative Competitive Interaction model. The methodology involves the design and development of a survey; and the application of factor analysis and ordinary least squares. Themethodology has been applied to the supermarket sector in two different scenarios: Milton Keynes (Great Britain) and Barcelona (Spain).

Surface swimming behavior of the curculionid Ochetina uniformis Pascoe (Erirhininae, Stenopelmini) and Ludovix fasciatus (Gyllenhal) (Curculioninae, Erodiscini)

The swimming behavior exhibited by specimens of L. fasciatus and O. uniformis was analyzed frame-by-frame with video observation recorded with a digital camera, attached to a stereomicroscope. Adults of O. uniformis, an aquatic insect, swim with all three pairs of legs. During the process of swimming the majority of the abdomen and rostrum remain submerged, part of the fore and hind tibiae remain above the surface, while the mid tibiae remain submerged. The mesothoracic legs, during the power-stroke stage, provide the greatest thrust while the metathoracic legs provide the least forward propulsion. The prothoracic legs, extended forward, help to direct the swimming. The semi-aquatic specie L. fasciatus shows the same swimming style as O. uniformis, that is, with movement of all the three pairs of legs; the mesothoracic legs are responsible for the main propulsion. The insect body remains on the water surface during the process of swimming, while the legs remain submerged. Both species complete a swimming cycle in 0.33 and 0.32 seconds, respectively, with an average speed of 1.38 cm/s and a maximum and minimum swimming duration time of 11.15 and 5.05 minutes, respectively, for L. fasciatus. The swimming behavior exhibited by O. uniformis and L. fasciatus corresponds to the style known as a breast strokelike maneuver. This is the first record of this kind of swimming for both species here observed and increases to seven the number of genera of Curculionidae exhibiting this behavior.

Hypothesis on immigration and welfare

The number of hypothesis trying to explain which are the reasons behind the decision to migrate to work into a developed country are diverse and at the same time, difficult to test due to the multiplicity of factors which affect it. This papers attempts to move forward trying to disentangle which are the socio-economic factors that explain the differences in the figures of immigrants in the OECD countries. We show empirical evidence about the determinants of the migratory flows to 17 OECD countries from 65 countries in the 1980-2000 period. Our results reveal the importance to differentiate the inflows composition by at least income in the origin countries. Thus, regarding inflows from non-high-income countries, the results suggest that there is a pull effect from monetary and not real income, and then, the welfare magnets hypothesis should be rejected. This group reacts more to the migratory policy than the inflows coming from high-income countries, although those policies designed to slow down the inflows have not been able, in the aggregate, to reduce them.

Annual Report of the Iowa Grape and Wine Development Commission for Fiscal Year, 2007

FY2007 was a productive year for the Iowa Grape and Wine Development Commission. Fourteen proposals were recommended for funding totaling over $390,000 in outlays. Included in the approved proposals were funds for the establishment and staffing of a Midwest Grape and Wine Institute at Iowa State University, a newly created viticulturist position at Des Moines Area Community College, funding for the first annual Mid-American Wine Competition, and marketing and promotion of four regional cooperative wine events and one wine trail. Commission funding supported a survey of commercial wine producers and grape growers and a new brochure on Iowa’s vineyards. A committee was formed to provide details for a Scholarship Program to aid vineyard and winery staff with the expenses of accredited coursework. Based on the survey conducted and from other governmental and industry sources, the Iowa grape and wine industry appears to continue to be very viable and growth continues at a strong pace. Wine produced in the state for 2007 was estimated at a market value in excess of $12.3 million. A tabulation of the budget revealed that just over $800,000 in wine gallonage tax appropriations have been received into the Grape and Wine Development Fund from 15 FY2003 through FY2007. Expenditures have totaled just over $607,000 during that same time. Just over 80% of expenditures have gone to “Technical” spending. Over time, funds invested in “Technical” programs will translate into an increasingly educated and institutionally-supported industry. Local, regional, and statewide events also appear to be increasing in popularity and the Commission plans to continue and increase support for these events. It is hoped the Scholarship Program will be up and running and funding will need to be appropriated for that project. The Commission also believes many projects and events will become more and more self sustaining as they develop and mature. As they continue to support Iowa’s grape and wine industry, the members of the Commission look forward to working with individuals, commercial enterprises, state and federal agencies, and industry-sponsored institutions in the upcoming year and in years to come.

Annual Report of the Iowa Grape and Wine Development Commission for Fiscal Year, 2008

FY2008 was a productive year for the Iowa Grape and Wine Development Commission. Sixteen proposals were recommended for funding from FY2008 funds and carryover totaling just over $396,000 in outlays. Included in the approved proposals were staffing and equipment for the Midwest Grape and Wine Industry Institute’s wine diagnostics laboratory at Iowa State University, continued support for the viticulturist position at Des Moines Area Community College, funding for the second annual Mid-American Wine Competition, and assistance for marketing and promotion of Ice coats an Iowa vineyard after a February 2008 ice storm. Photo by Mike White and courtesy of Iowa State University. 16 two wine trail associations and seven festivals and events. Commission funding supported a salaried position within IDALS to manage the Iowa Grape and Wine Development Fund and to serve as the Director of the Iowa Grape and Wine Development Commission. The Commission approved funding for a Scholarship Program. The formally created Scholarship Committee met twice in FY2008 to finalize details for the Program and to approve scholarships to twenty-six applicants to aid with the expenses of accredited coursework. Based on data collected by IDALS, the Iowa Department of Economic Development, the Iowa Alcoholic Beverages Division, and Iowa State University the Iowa grape and wine industry appears to continue to be very viable and growth continues at a strong pace. Presently, Iowa ranks 14th in the nation for the number of wineries, and wine produced in the state for 2008 was estimated at a market value in excess of $14.0 million. A tabulation of the budget revealed that just over $1,080,000 in wine gallonage tax appropriations and legislative appropriations have been deposited into the Grape and Wine Development Fund from FY2003 through FY2008. Removing encumbered funds, expenditures have totaled just over $942,500 during that same time. “Financial” funding – used for fostering public awareness and participation of industry events - increased from 6% of expenditures in FY2007 to 9% in FY2008. Used for support of research, education, and outreach, a little over 80% of expenditures and encumbered funds were earmarked for “Technical” spending. Over time, funds invested in “Technical” programs will translate into an increasingly educated and institutionally-supported industry. Local, regional, and statewide events also appeared to be increasing in popularity. The Commission was encouraged to see increased support for these events. It is hoped, too, that the Scholarship Program will provide needed funding to help meet the educational goals of the industry’s workforce. As they continue to support Iowa’s grape and wine industry, the Commissioners look forward to working with individuals, commercial enterprises, state and federal agencies, and industry-sponsored institutions in FY2009 and in years to come.

Dissociation of thymic positive and negative selection in transgenic mice expressing major histocompatibility complex class I molecules exclusively on thymic cortical epithelial cells.

Thymic positive and negative selection of developing T lymphocytes confronts us with a paradox: How can a T-cell antigen receptor (TCR)-major histocompatibility complex (MHC)/peptide interaction in the former process lead to transduction of signals allowing for cell survival and in the latter induce programmed cell death or a hyporesponsive state known as anergy? One of the hypotheses put forward states that the outcome of a TCR-MHC/peptide interaction depends on the cell type presenting the selecting ligand to the developing thymocyte. Here we describe the development and lack of self-tolerance of CD8(+) T lymphocytes in transgenic mice expressing MHC class I molecules in the thymus exclusively on cortical epithelial cells. Despite the absence of MHC class I expression on professional antigen-presenting cells, normal numbers of CD8(+) cells were observed in the periphery. Upon specific activation, transgenic CD8(+) T cells efficiently lysed syngeneic MHC class I(+) targets in vitro and in vivo, indicating that thymic cortical epithelium (in contrast to medullary epithelium and antigen-presenting cells of hematopoietic origin) is incapable of tolerance induction. Thus, compartmentalization of the antigen-presenting cells involved in thymic positive selection and tolerance induction can (at least in part) explain the positive/negative selection paradox.

Forward, Spring 2009

Newsletter for the Iowa Commission on the Status of Women. Forward is the new quarterly newsletter published by the Iowa Commission on the Status of Women. We are sure that you will continue to find information of use for Iowa’s women and girls.

Forward, Summer 2009

Newsletter for the Iowa Commission on the Status of Women. Forward is the quarterly newsletter published by the Iowa Commission on the Status of Women. We are sure that you will continue to find information of use for Iowa’s women and girls.

Information security and the enforcement of secrecy : the practical application of quantum key distribution

There is no doubt about the necessity of protecting digital communication: Citizens are entrusting their most confidential and sensitive data to digital processing and communication, and so do governments, corporations, and armed forces. Digital communication networks are also an integral component of many critical infrastructures we are seriously depending on in our daily lives. Transportation services, financial services, energy grids, food production and distribution networks are only a few examples of such infrastructures. Protecting digital communication means protecting confidentiality and integrity by encrypting and authenticating its contents. But most digital communication is not secure today. Nevertheless, some of the most ardent problems could be solved with a more stringent use of current cryptographic technologies. Quite surprisingly, a new cryptographic primitive emerges from the ap-plication of quantum mechanics to information and communication theory: Quantum Key Distribution. QKD is difficult to understand, it is complex, technically challenging, and costly-yet it enables two parties to share a secret key for use in any subsequent cryptographic task, with an unprecedented long-term security. It is disputed, whether technically and economically fea-sible applications can be found. Our vision is, that despite technical difficulty and inherent limitations, Quantum Key Distribution has a great potential and fits well with other cryptographic primitives, enabling the development of highly secure new applications and services. In this thesis we take a structured approach to analyze the practical applicability of QKD and display several use cases of different complexity, for which it can be a technology of choice, either because of its unique forward security features, or because of its practicability.

Dipeptidyl-peptidase-IV by cleaving neuropeptide Y induces lipid accumulation and PPAR-γ expression.

We evaluated the effects of dipeptidyl peptidase-IV (DPPIV), and its inhibitor, vildagliptin, on adipogenesis and lipolysis in a pre-adipocyte murine cell line (3T3-L1). The exogenous rDPPIV increased lipid accumulation and PPAR-γ expression, whereas an inhibitor of DPPIV, the anti-diabetic drug vildagliptin, suppresses the stimulatory role of DPPIV on adipogenesis and lipid accumulation, but had no effect on lipolysis. NPY immunoneutralization or NPY Y(2) receptor blockage inhibited DPPIV stimulatory effects on lipid accumulation, collectively, indicating that DPPIV has an adipogenic effect through NPY cleavage and subsequent NPY Y(2) activation. Vildagliptin inhibits PPAR-γ expression and lipid accumulation without changing lipolysis, suggesting that this does not impair the ability of adipose tissue to store triglycerides inside lipid droplets. These data indicate that DPPIV and NPY interact on lipid metabolism to promote adipose tissue depot.

Forward, Fall 2009

Newsletter for the Iowa Commission on the Status of Women. Forward is the quarterly newsletter published by the Iowa Commission on the Status of Women. We are sure that you will continue to find information of use for Iowa’s women and girls.

Forward, Spring 2010

Newsletter for the Iowa Commission on the Status of Women. Forward is the quarterly newsletter published by the Iowa Commission on the Status of Women. We are sure that you will continue to find information of use for Iowa’s women and girls.

The Macrocirculation and Microcirculation of Hypertension.

Changes in vascular structure that accompany hypertension may contribute to hypertensive end-organ damage. Both the macrovascular and microvascular levels should be considered, as interactions between them are believed to be critically important. Regarding the macrocirculation, the article first reviews basic concepts of vascular biomechanics, such as arterial compliance, arterial distensibility, and stress-strain relationships of arterial wall material, and then reviews how hypertension affects the properties of conduit arteries, particularly examining evidence that it accelerates the progressive stiffening that normally occurs with advancing age. High arterial stiffness may increase central systolic and pulse pressure by two different mechanisms: 1) Abnormally high pulse wave velocity may cause pressure waves reflected in the periphery to reach the central aorta in systole, thus augmenting systolic pressure; 2) In the elderly, the interaction of the forward pressure wave with high arterial stiffness is mostly responsible for abnormally high pulse pressure. At the microvascular level, hypertensive disease is characterized by inward eutrophic or hypertrophic arteriolar remodeling and capillary rarefaction. These abnormalities may depend in part on the abnormal transmission of highly pulsatile blood pressure into microvascular networks, especially in highly perfused organs with low vascular resistance, such as the kidney, heart, and brain, where it contributes to hypertensive end-organ damage.