Hybrid process algebra

IV+276hlm.;24c

Study of the Role of Biologically-Relevant, Labile Nickel Pools in the Maturation of Nickel-Dependent Enzymes

Cellular nickel pools, comprised of static and labile pools of nickel complexes, play important roles in maintaining nickel homeostasis in various organisms (microbes, fungi, and plants), which utilize it as a cofactor of one or more nickel enzymes that catalyze specific reactions and are essential for their proper growth and survival in various ecological niches. Like other metals, tight regulation of cellular nickel levels is critical to prevent toxic effects of nickel deprivation, nickel overload, and ‘free’ nickel. While more static nickel pools include nickel tightly bound to nickel-dependent enzymes, nickel in the labile pool is exchangeable and weakly bound to either nickel chaperones or low-molecular-weight (LMW) ligands, as is the case for many other transition metals. The role of nickel chaperones in enzyme maturation and activation is being extensively investigated, but the importance of cellular LMW complexes in the process remains largely unknown. In this work, I investigated the role of labile nickel pools (both non-proteinaceous and proteinaceous ligands) in the maturation of nickel-dependent enzymes - Nickel Superoxide Dismutase (NiSOD) from Streptomyces coelicolor, and urease and Ni, Fe-hydrogenase from Helicobacter pylori. For the maturation of NiSOD, no chaperone has been characterized for nickel delivery to the active site. Using biochemical assays, mass spectrometry, and spectroscopic methods, I provide compelling evidence that biologically relevant, non-proteinaceous, LMW ligand complexes of nickel with L-histidine are inevitable for the proper maturation of the enzyme. In Helicobacter pylori, which is a human pathogen, there are two nickel dependent enzymes – urease and Ni, Fe hydrogenase both of which require a proteinaceous labile nickel ligand (common nickel-chaperone), HypA for maturation. HypA interacts with HypB for the maturation of Ni, Fe-hydrogenase, and with UreE for the maturation of urease, but what factors determine its differential interaction with its downstream partner proteins are unknown. I interrogated the flexibility and dynamics of HypA by glycine mutations to perturb the maturation of the two nickel enzymes in the pathogen and using in vitro assays I show that the glycine mutations differentially affect the maturation of urease and Ni, Fe – hydrogenase in the pathogen

Utilizing topology based domain segmentation for in-situ identification and classification of vortices in simulations of turbulent flows

Fully turbulent flow fields are populated with features such as vortices or eddies. Analysing flow features and their interaction can lead to insight into the physics of turbulence. An enhanced understanding of turbulence benefits, for example, the development of turbulence models, which can help dramatically reducing the computational costs of turbulent flow simulations. The vast abundance of features in fully turbulent flow fields demands an automated identification and analysis process. To address this issue Tracer was developed, an in-situ software framework to extract flow features from data produced by high-fidelity unsteady computational fluid dynamics (CFD) simulations conducted on GPU systems. Unsteady CFD simulations can produce a significant amount of data. The majority of this data cannot be accessed following the classical paradigm of storing the flow field to disk due to the bottleneck of writing the data disk and limitations of available storage capacity. To avoid the restrictions related to moving and storing data, Tracer is able to run concurrently with the simulation, analysing the data while it is still on the GPU's system memory. The intensities of flow features generally span multiple orders of magnitude making their identification a challenging task. Contrary to the classic approach of extracting features by defining a global threshold of a scalar $f$, Tracer identifies an individual threshold for each feature based on the topology of $f$, facilitating the identification of features over a wide range of scales and intensities. The individual thresholds are identified using a join tree, which tracks the topology of superlevel sets of $f$. A performance analysis showed that Tracer requires less system memory than the standalone CFD solver. Adding Tracer in-situ to a CFD simulation hence comes with a reasonable increase in system memory usage. The increase in runtime depends on the number of time steps that the CFD solver takes between two applications of Tracer to the flow field, but is typically within the single-digit percentage range. The advantages of topology based feature identification using Tracer versus the classic approach of using a global threshold are demonstrated qualitatively by visualising vortices in flow around an SD7003 aerofoil. The application of Tracer is demonstrated on the simulation of the turbulent transition of a Taylor-Green vortex with the aim of counting the number of vortices over time. If vortices are extracted based on the topolgy of the $Q$-criterion field a steep increase in the number of vortices can be observed during turbulent breakdown and a decrease during the decay of turbulence. Additionally a feature based analysis of turbulent channel flows up to $Re_\tau = 550$ was conducted examining the topology and the geometry of vortices. While the topological organisation of individual vortices in the near-wall and in the central region are found to be indistinguishable, there is a difference when vortex clusters are extracted. It was also found that vortices less than 70 wall units away from the wall tend to align in the streamwise direction; vortices further away from the wall were found to be geometrically isotropic. These results furthermore support the assumption that the diameter of elongated vortices scales with the Kolmogorov length.Open Acces

The evolution and regulation of DNA-binding by the nickel-dependent transcription factor NikR

Transition metal homeostasis is critical for all cells to balance cellular metal requirements with metal availability. One common homeostatic mechanism in bacteria is metal-dependent transcriptional regulation. The Ni2+-dependent transcription factor NikR is a member of the ribbon-helix-helix: RHH) family of DNA-binding proteins and is widespread among bacteria and archea with vastly different nickel physiologies. The goal of this thesis was to better understand basic aspects of cellular transition metal homeostasis by examining the activity and regulatory properties of NikR family members from different bacterial species. One organism that exhibits a prominent and well-defined nickel physiology is Helicobacter pylori, making it an ideal system with which to examine various aspects of metal homeostasis. Genetic studies demonstrated that NikR activation is controlled by a hierarchy of nickel-trafficking in H. pylori, where nickel is preferentially trafficked to the urease assembly pathway. NikR differentially regulates multiple nickel-related genes in response to distinct extracellular nickel concentrations, functioning to coordinate multiple activities important for metal homeostasis. Differential gene regulation resulted from NikR binding to promoters from different genes with a range of affinities and in distinct conformations, due to a flexible N-terminal arm that makes different DNA contacts at two promoters. In addition, the arm expands the specific DNA interactions by NikR as compared to previously characterized RHH transcription factors. Examination of additional previously uncharacterized NikR family members revealed that the N-terminal arm has been adapted differently in some cases but is also critical for DNA-binding affinity and specificity. This structural feature provides a molecular basis for tuning NikR activity to the physiology of the cell. These studies provide insight into how multiple metal-dependent activities in cells are coordinated and controlled in response to fluctuations in environmental metal. Further, they establish a robust experimental system with which to further investigate the molecular details of the evolution of transcriptional regulation, an integral component of metal homeostasis

Protein Folding by NMR

Protein folding is a highly complex process proceeding through a number of disordered and partially folded nonnative states with various degrees of structural organization. These transiently and sparsely populated species on the protein folding energy landscape play crucial roles in driving folding toward the native conformation, yet some of these nonnative states may also serve as precursors for protein misfolding and aggregation associated with a range of devastating diseases, including neuro-degeneration, diabetes and cancer. Therefore, in vivo protein folding is often reshaped co- and post-translationally through interactions with the ribosome, molecular chaperones and/or other cellular components. Owing to developments in instrumentation and methodology, solution NMR spectroscopy has emerged as the central experimental approach for the detailed characterization of the complex protein folding processes in vitro and in vivo. NMR relaxation dispersion and saturation transfer methods provide the means for a detailed characterization of protein folding kinetics and thermodynamics under native-like conditions, as well as modeling high-resolution structures of weakly populated short-lived conformational states on the protein folding energy landscape. Continuing development of isotope labeling strategies and NMR methods to probe high molecular weight protein assemblies, along with advances of in-cell NMR, have recently allowed protein folding to be studied in the context of ribosome-nascent chain complexes and molecular chaperones, and even inside living cells. Here we review solution NMR approaches to investigate the protein folding energy landscape, and discuss selected applications of NMR methodology to studying protein folding in vitro and in vivo. Together, these examples highlight a vast potential of solution NMR in providing atomistic insights into molecular mechanisms of protein folding and homeostasis in health and disease

Program and Abstracts of the Annual Meeting of the Georgia Academy of Science, 2012

The annual meeting of the Georgia Academy of Science took place March 23-34, 2012, at Kennesaw State University, Kennesaw, Georgia. Presentations were provided by members of the Academy who represented the following sections: I. Biological Sciences II Chemistry III. Earth & Atmospheric Sciences IV. Physics, Mathematics, Computer Science, Engineering & Technology V. Biomedical Sciences VI. Philosophy & History of Science VII. Science Education VIII. Anthropology

Pensioners' subjective economic well-being in European countries : comparisons behind the income satisfaction paradox

The purpose of this doctoral thesis is to expand the relative perspective in the analysis of financial satisfaction in old age, by which is meant the formation of financial satisfaction as part of different types of comparisons. The old-age population is known to be financially more satisfied than other population groups, a paradoxical finding considering their generally lower-than-average income level. This phenomenon is called the satisfaction paradox. With the help of multilevel and longitudinal analyses, this study investigates how income levels in European countries and retirement are associated with subjective economic well-being. Questions of central importance to this study include to what degree satisfaction can be explained by the population group one compares oneself to, and to what degree one's current economic status is compared to one's own previous economic status. The results clarify our understanding of the relationship between objective income and subjective evaluations of economic well-being in the old-age population. The theoretical framework of this thesis consists of Nordic welfare research, quality of life research and economist-driven happiness research. The data consists of results from "The Welfare and Services survey in Finland" from the years 2004, 2006 and 2009 as well as a cross-section of and longitudinal data from EU-SILC (European Union Statistics on Income and Living Conditions) from the time period 2005−2013. Results show income and experience to be linked as presumed. Those with the highest income experienced their income as more adequate in making ends meet than did those with a lower income. This applies to Finnish pensioners as well as more broadly to older people living in Europe. Income growth also increased the sense of ease associated with income adequacy. However, results also showed that the oldest age groups experience a greater ease in making ends meet than might be assumed based on their income. For this reason, we cannot dismiss the existence of the satisfaction paradox. Retirement weakened the perception of income adequacy. However, the effect was not as dramatic as is generally thought. Perceptions of weakened adequacy cannot be explained by the absolute decrease in income, but rather by changes between a person's previous economic status and current status. A European comparison showed weakened perceptions of adequacy at retirement for those transferring directly from working life, but a significant improvement for the unemployed retiring and a slight improvement in the perceptions of those retiring from other statuses. These differences may, for instance, be linked to people's expectations on the sufficiency of their pension. For the unemployed and others, getting a pension means having a stable and continuous source of income. The Finnish study, on the other hand, showed that improved relative income status gained at retirement compared to the population at large increased the experience of income sufficiency. Experiences of income adequacy were weakened, however, when the individual's relative income status became higher in relation to that of other pensioners compared to previous status among active age population while still working. This may indicate that a newly retired person does not immediately consider other pensioners as his or her reference group, or it may be a general indication of weakened future prospects. Pensioners evaluate their income in relation to other pensioners rather than to the population as a whole, or to the population of active age. This applies to both younger and older old-age pensioners in different European countries. Income distribution within a country also does not have any bearing on pensioners' evaluation of income adequacy. What does matter, on the other hand, is the average income level of pensioners in the country, which can also be seen as an indication of the standard of living. In countries with a higher standard of living, pensioners perceived their income adequacy as lesser than in countries with a lower standard of living. This difference may be linked to the expectations on consumption created by different standards of living. All in all, it may be concluded that the financial satisfaction of the aged population is linked to income as well as to what we compare our own economic status. Retirement and the economic context of the country of residence play a role in these comparisons. Key terms: subjective economic well-being, perceived income adequacy, livelihood, retirement, financial satisfaction, reference group, EU-SILCTämän väitöskirjan tarkoitus on laajentaa ikääntyneiden taloudellisen tyytyväisyyden tutkimuksen suhteellista näkökulmaa, jolla tarkoitetaan taloudellisen tyytyväisyyden muodostumista osana erilaisia vertailuja. Ikääntyneiden tiedetään olevan muita väestöryhmiä tyytyväisempiä taloudelliseen tilanteeseensa, mikä on ristiriitainen havainto ottaen huomioon heidän keskimääräistä matalampi tulotasonsa. Ilmiötä on kutsuttu myös tyytyväisyysparadoksiksi. Tässä tutkimuksessa tarkastellaan monitaso- ja pitkittäisanalyysien avulla, millaisia yhteyksiä Euroopan maiden tulotasoilla ja eläkkeelle siirtymisellä on subjektiiviseen taloudelliseen hyvinvointiin. Keskeisiä kysymyksiä ovat missä määrin tyytyväisyys selittyy sillä, mihin väestöryhmään omaa taloudellista tilannetta verrataan ja missä määrin nykyistä tilannetta verrataan omaan aiempaan taloudelliseen tilanteeseen. Tulokset täsmentävät ymmärrystä objektiivisten tulojen ja subjektiivisten toimeentulokokemusten välisestä suhteesta ikääntyneiden väestöryhmässä. Tutkimuksen teoreettiset lähtökohdat ovat pohjoismaisessa hyvinvointitutkimuksessa, elämänlaaduntutkimuksessa ja taloustieteellisessä subjektiivisen hyvinvoinnin tutkimuksessa. Aineistoina on käytetty Suomalaisten Hyvinvointi ja Palvelut -kyselytutkimuksia vuosilta 2004, 2006 ja 2009 sekä Eurooppalaisen tulo- ja elinoloaineisto EU-SILC:n poikkileikkaus- ja pitkittäisaineistoja vuosilta 2005−2013. Tulokset osoittivat tulojen ja kokemusten olevan yhteydessä toisiinsa oletetulla tavalla. Suurituloisimmat kokivat tulojen riittävän paremmin menojen kattamiseen kuin pienituloiset. Tämä koski sekä suomalaisia eläkeläisiä että laajemmin Euroopassa asuvia ikääntyneitä. Tulojen kasvu myös lisäsi koetun toimeentulon helppoutta. Tulokset kuitenkin osoittivat, että vanhimmat ikäryhmät kokevat toimeentulonsa helpommaksi kuin tulojen perusteella voisi olettaa. Tämän vuoksi tyytyväisyysparadoksin olemassaoloa ei voida kumota. Eläkkeelle siirtyminen heikensi koettua toimeentuloa jonkin verran. Vaikutus ei kuitenkaan ole yhtä jyrkkä kuin yleisesti arvellaan. Heikentyneet toimeentulokokemukset eivät selity absoluuttisella tulojen vähenemisellä, vaan pikemminkin aiemman taloudellisen aseman ja nykytilanteen välisillä muutoksilla. Eurooppalainen vertailu osoitti työstä eläkkeelle siirtyneiden toimeentulokokemusten heikkenevän mutta työttömyydestä eläköityvien paranevan selkeästi ja muista asemista eläköityvien paranevan hieman. Erot voivat liittyä esimerkiksi siihen, millaisia odotuksia eläkkeiden riittävyydelle asetetaan. Työttömien ja muiden kohdalla eläketulo lisää myös varmuutta toimeentulon jatkuvuudesta. Suomalainen vertailu puolestaan osoitti, että eläkkeelle siirtymisen myötä kohentunut tuloasema väestön keskuudessa lisää kokemusta toimeentulon riittävyydestä. Kokemuksia sen sijaan heikensi tilanne, jossa uusi tuloasema eläkeläisten keskuudessa oli parempi kuin aiemmin työikäisten keskuudessa. Tämä voi kertoa siitä, että muita eläkeläisiä ei pidetä vertailuryhmänä heti eläkkeelle siirtymisen jälkeen tai yleisemmin heikentyneistä tulevaisuudennäkymistä. Koko väestön tai työikäisten sijaan eläkkeellä olevat arvioivat toimeentuloaan suhteessa toisiin eläkeläisiin. Tämä koskee sekä nuorempia että ikääntyneempiä vanhuuseläkeläisiä eri Euroopan maissa. Maiden sisäisellä tulonjaolla ei ole merkitystä eläkeläisten toimeentulokokemusten kannalta. Sen sijaan maiden keskimääräisellä eläkeläisten tulotasolla, jonka voidaan katsoa kuvaavan myös maiden elintasoa, on merkitystä. Korkeamman tulotason maissa eläkeläiset kokevat toimeentulonsa heikommaksi kuin matalamman tulotason maissa. Ero voi liittyä esimerkiksi maiden erilaisten elintasojen luomiin kulutusta koskeviin odotuksiin. Kaikkiaan ikääntyneiden taloudellisen tyytyväisyyden voidaan todeta olevan yhteydessä sekä tuloihin että siihen, mihin omaa taloudellista asemaa kulloinkin verrataan. Näihin vertailuihin ovat keskeisesti yhteydessä sekä eläkkeelle siirtyminen että asuinmaan taloudellinen konteksti.Alkuperäinen julkaisija: Finnish Centre for Pensions, Eläketurvakeskus. ISBN 978-951-691-291-5, ISBN 978-951-691-292-2 (PDF

Architectures of Emergency. Sentinel operations for a rapidly changing environment

[EN] The declaration of an emergency is given by various protocols that respond to a series of interventions driven by an environmental urgency (Anderson 2017), designed by global networks of experts that mobilize advertising modes of economic development in the face of environmental collapse (Goh 2021). This research proposes a different imaginary of the Emergency. This reflection aims to resignify the Emergency from the embodied experiences of the disruptive events we live, opening the discussion on the frictions between a normative world based on human security and the modalities of militant movements dedicated to redressing social, environmental, and economic inequalities (Whyte 2018). In this sense, we develop the idea of sentinel modes of care that reflect the affective scaffolding of life-related to the environment and potential catastrophe (Wright, Plahe, and Jack 2022). A state of constant alertness characterizes sentinel care within a more-than-human register of the relationship and potentialities of the territory. This text aims to position itself on emergency protocols while exploring other imaginaries and their impact on spatial practices.Mompean Botias, E. (2023). Architectures of Emergency. Sentinel operations for a rapidly changing environment. Editorial Universitat Politècnica de València. 598-611. https://doi.org/10.4995/VIBRArch2022.2022.1527459861

Impact of undesirable plant communities on the carrying capacity and livestock performance in pastoral systems of south-western Uganda

The impact of undesirable plant communities (Cymbopogon afronardus and woody species dominated by Acacia species) on livestock carrying capacity and performance was investigated on 15 farms in an Acacia/Cymbopogon dominated pastoral system of south-western Uganda. Species prevalence based on basal cover for grasses, frequency for forbs and effective canopy cover for trees/shrubs were determined on farms. The PHYGROW model was used to predict forage productivity for computation of carrying capacity. The NIRS/NUTBAL nutritional management system was used to determine cattle dietary CP and DOM through fecal scans and to estimate animal performance. Cymbopogon afronardus had a prevalence of 10.29% among the grasses while Acacia gerrardii (34.37%) and Acacia hockii (33.66%) were the most prevalent woody species. Forage productivity differed significantly among the farms with a mean long-term annual forage yield of 4560(SE+41) kg/ha. Farms infested with Cymbopogon and woody species produced the least amount of forage and therefore had the lowest carrying capacities (0.38 -0.39 AU/ha) while improved farms had comparatively higher forage yields with higher carrying capacities (0.49 - 0.52 AU/ha). A mean carrying capacity for the system was estimated at 0.44 AU/ha using a 25% harvest efficiency for ANPP. All the farms were overstocked, on average by 3.2 times. Livestock BCS, diet CP and DOM were significantly different (P<0.0001) among the different farm types. BCS were highest on improved farms and lowest on Cymbopogon infested farms while dietary CP and DOM values were lowest on improved farms and highest on farms with a high woody component. Farms with a relatively high woody component exhibited intermediate BCS despite the high dietary CP values. Cattle on Cymbopogon infested farms had consistently lower body weights over the months although there were no significant differences in daily live weight gains among farms. Recommendations included need for research into appropriate control measures for both Cymbopogon afronardus and woody species, farmer sensitization about overstocking, research to improve forage quality on improved farms and need for feed supplementation for improved breeds on improved farms. Integration of NIRS/NUTBAL and PHYGROW models into the research and management systems was desirable. The observed increase in Sporobolus spp. required investigation