Investigations into the mechanism of orotidine 5'-monophosphate decarboxylase: Sources of substrate destabilization and transition state stabilization

Orotidine 5′-monophosphate decarboxylase (OMPDC) achieves a rarely paralleled rate acceleration, yet the catalytic basis prompting this enhancement have yet to be fully elucidated. To accomplish decarboxylation, OMPDC must overcome the high energy barrier due to the localized anionic charge of the intermediate. Mechanistic studies employing enzyme mutagenesis and product or intermediate analogues were used to investigate possible transition state stabilization by a carbene resonance structure. Viability of the carbene structure depends upon a key hydrogen bond between O4 of the substrate and the amide backbone of a conserved serine or threonine. Substitution of the conserved residue with Pro resulted in a kcat/KM of 1 M-1s-1; deletion of the FUMP O4 resulted in a product analogue that does not undergo H6 exchange or inhibit decarboxylation. Hence, indirect evidence reveals the O4-backbone interaction plays an important role for binding and catalysis. OMPDC likely has honed multiple mechanisms to attain its remarkable catalysis. The successful crystallizations of OMPDC a decade ago sparked hypotheses that structure and sequence conserved residues induced productive strain on the substrate-enzyme complex. Here, we demonstrate a new source of stress: a hydrophobic pocket adjacent to the OMP carboxylate that exhibits kinetic parameters characteristic of substrate destabilization. Substitution of these residues with hydrophilic side-chains, by providing hydrogen-bonding partners, decreased kcat by 10 to 10^4–fold. The same substitutions display very little change in the rate of product H6 exchange, supporting that this hydrophobic pocket affects the substrate-enzyme complex before the transition state. We also provide evidence that hydrophilic residues can insert water molecules into the pocket with detrimental effects to catalysis.

The role of knowledge management and renewal in building innovation performance

Tämän työn tavoitteena oli selvittää tietojohtamisen eri käytäntöjen vaikutusta oppimiseen, uudistumiseen sekä yrityksen innovaatiokyvykkyyteen. Työssä on keskitytty erityisesti sellaisiin tietojohtamisen käytäntöihin, jotka edistävät oppimista ja uusiutumista yrityksissä. Työssä on käytetty tilastollisia menetelmiä, muun muassa faktorianalyysia, korrelaatioanalyysia sekä regressiota, analysoitaessa 259 suomalaisesta yrityksestä kerättyä kyselydataa niiden tietojohtamisen käytöntöihin ja aineettomaan pääomaan liittyen. Analyysi osoittaa, että useat tietojohtamisen käytännöt vaikuttavat positiivisesti yrityksen uudistumiseen ja sitä kautta innovaatiokyvykkyyteen. Henkilöstön kouluttaminen sekä parhaiden käytäntöjen kerääminen ja soveltaminen yrityksessä ovat positiivisesti yhteydessä innovaatiokyvykkyyteen. Henkilöstön kouluttamisella on merkittävin suora vaikutus innovaatiokyvykkyyteen ja tässä työssä on esitetty, että koulutuksen tarjoamisen suurin vaikutus on oppimismyönteisen kulttuurin kehittyminen yrityksiin sen sijaan, että koulutuksella pyrittäisiin vain parantamaan tehtäväkenttään liittyviä taitoja ja tietoja. Henkilöstön kouluttaminen, parhaat käytännöt sekä sosialisaatiossa tapahtuva tiedon vaihto ja suhteiden solmiminen vaikuttavat positiivisesti uudistumispääomaan. Työn tulosten perusteella uudistumispääomalla on merkittävä rooli innovaatioiden syntymisessä yrityksissä. Uudistumispääoma medioi koulutuksen, parhaiden käytäntöjen ja mahdollisesti myös sosialisaation vaikutusta innovaatiokyvykkyyteen ja on näin merkittävä osa innovaatioiden syntyä yrityksissä. Innovaatiokyvykkyyden osatekijöiden ymmärtäminen voi auttaa johtajia ja esimiehiä keskittämään huomionsa tiettyihin tietojohtamisen käytäntöihin edistääkseen innovaatioiden syntymistä yrityksessä sen sijaan, että he pyrkisivät vain vaikuttamaan innovaatioprosessiin.

Quantum Gate and Quantum State Preparation through Neighboring Optimal Control

Successful implementation of fault-tolerant quantum computation on a system of qubits places severe demands on the hardware used to control the many-qubit state. It is known that an accuracy threshold Pa exists for any quantum gate that is to be used for such a computation to be able to continue for an unlimited number of steps. Specifically, the error probability Pe for such a gate must fall below the accuracy threshold: Pe < Pa. Estimates of Pa vary widely, though Pa ∼ 10−4 has emerged as a challenging target for hardware designers. I present a theoretical framework based on neighboring optimal control that takes as input a good quantum gate and returns a new gate with better performance. I illustrate this approach by applying it to a universal set of quantum gates produced using non-adiabatic rapid passage. Performance improvements are substantial comparing to the original (unimproved) gates, both for ideal and non-ideal controls. Under suitable conditions detailed below, all gate error probabilities fall by 1 to 4 orders of magnitude below the target threshold of 10−4. After applying the neighboring optimal control theory to improve the performance of quantum gates in a universal set, I further apply the general control theory in a two-step procedure for fault-tolerant logical state preparation, and I illustrate this procedure by preparing a logical Bell state fault-tolerantly. The two-step preparation procedure is as follow: Step 1 provides a one-shot procedure using neighboring optimal control theory to prepare a physical qubit state which is a high-fidelity approximation to the Bell state |β01⟩ = 1/√2(|01⟩ + |10⟩). I show that for ideal (non-ideal) control, an approximate |β01⟩ state could be prepared with error probability ϵ ∼ 10−6 (10−5) with one-shot local operations. Step 2 then takes a block of p pairs of physical qubits, each prepared in |β01⟩ state using Step 1, and fault-tolerantly prepares the logical Bell state for the C4 quantum error detection code.

REDUCING TEACHER ATTRITION: THE ROLES AND RESPONSIBILITIES OF BUILDING PRINCIPALS IN A LARGE URBAN DISTRICT TO SUPPORT TEACHER RETENTION

The high rate of teacher attrition in urban schools is well documented. While this does not seem like a problem in Carter County, this equates to hundreds of teachers that need to be replaced annually. Since school year (SY) 2007-08, Carter County has lost over 7,100 teachers, approximately half of (50.1%) of whom resigned, often going to neighboring, higher-paying jurisdictions as suggested by exit survey data (SY2016-2020 Strategic Plan). Included in this study is a range of practices principals use to retain teachers. While the role of the principal is recognized as a critical element in teacher retention, few studies explore the specific practices principals implement to retain teachers and how they use their time to accomplish this task. Through interviews, observations, document analysis and reflective notes, the study identifies the practices four elementary school principals of high and relatively low attrition schools use to support teacher retention. In doing so, the study uses a qualitative cross-case analysis approach. The researcher examined the following leadership practices of the principal and their impact on teacher retention: (a) providing leadership, (b) supporting new teachers, (c) training and mentoring teaching staff, (d) creating opportunities for collaboration, (d) creating a positive school climate, and (e) promoting teacher autonomy. The following research questions served as a foundational guide for the development and implementation of this study: 1. How do principals prioritize addressing teacher attrition or retention relative to all of their other responsibilities? How do they allocate their time to this challenge? 2. What do principals in schools with low attrition rates do to promote retention that principals in high attrition schools do not? What specific practices or interventions are principals in these two types of schools utilizing to retain teachers? Is there evidence to support their use of the practices? The findings that emerge from the data revealed the various practices principals use to influence and support teachers do not differ between the four schools.

Hygiene and biosecurity: the language and politics of risk in an era of emerging infectious diseases

Infectious diseases, such as methicillin-resistant Staphylococcus aureus and avian influenza, have recently been high on the agenda of policy makers and the public. Although hygiene and biosecurity are preferred options for disease management, policy makers have become increasingly aware of the critical role that communication assumes in protecting people during outbreaks and epidemics. This article makes the case for a language-based approach to understanding the public perception of disease. Health language research carried out by the authors, based on metaphor analysis and corpus linguistics, has shown that concepts of journeys, pathways, thresholds, boundaries and barriers have emerged as principal framing devices used by stakeholders to advocate a hygiene based risk and disease management. These framings provide a common ground for debate, but lead to quite different perceptions and practices. This in turn might be a barrier to global disease management in a modern world.

Entropy, chaos, and excited-state quantum phase transitions in the Dicke model

We study nonequilibrium processes in an isolated quantum system-the Dicke model-focusing on the role played by the transition from integrability to chaos and the presence of excited-state quantum phase transitions. We show that both diagonal and entanglement entropies are abruptly increased by the onset of chaos. Also, this increase ends in both cases just after the system crosses the critical energy of the excited-state quantum phase transition. The link between entropy production, the development of chaos, and the excited-state quantum phase transition is more clear for the entanglement entropy.

Employability study of the graduates at the English Language and Literature School

El propósito de este Proyecto fue evaluar los principales factores que influyen en la empleabilidad de los graduados de la escuela de lengua y literatura inglesa de la universidad de cuenca. La población de este estudio fue constituida por titulados que trabajaban en el área educativa y pocos graduados desempleados. El trabajo de campo fue llevado a cabo por medio de una encuesta, la cual fue aplicada a 161 graduados de la carrera de los años 2000 a 2013. La encuesta recogió información personal de los profesionales así como también datos relacionados al conocimiento adquirido en la carrera, situación laboral entre otros. Las técnicas para el análisis de datos fueron: análisis cuantitativo y cualitativo. El estudio también examina los métodos usados por los graduados para obtener un trabajo, los requerimientos de las instituciones educativas y causas para el desempleo de los graduados así aspectos del currículo de inglés para mejorar. Algunosde los descubrimientos más importantes en este estudio fueron que más de la mitad de graduados tienen un alto grado de satisfacción con su empleo. También fue descubierto que 96.3% de los graduados están trabajando en el área de su especialidad consecuentemente un gran porcentaje de licenciados de inglés usan el conocimiento adquirido en la universidad en sus empleos.Se espera, por lo tanto, que la información publicada en esta investigación sea un importante recurso para estudios futuros.

Modern Computational Chemistry Methods for Prediction of Ground- and Excited-State Properties in Open-Shell Systems

The main goal of the research presented in this work is to provide some important insights about computational modeling of open-shell species. Such projects are: the investigation of the size-extensivity error in Equation-of-Motion Coupled Cluster methods, the analysis of the Long-Range corrected scheme in predicting UV-Vis spectra of Cu(II) complexes with the 4-imidazole acetate and its ethylated derivative, and the exploration of the importance of choosing a proper basis set for the description of systems such as the lithium monoxide anion. The most significant findings of this research are: (i) The contribution of the left operator to the size-extensivity error of the CR-EOMCC(2,3) approach, (ii) The cause of d-d shifts when varying the range-separation parameter and the amount of the exact exchange arising from the imbalanced treatment of localized vs. delocalized orbitals via the "tuned" CAM-B3LYP* functional, (iii) The proper acidity trend of the first-row hydrides and their lithiated analogs that may be reversed if the basis sets are not correctly selected.

Switching Patterns and Steady-State Analysis of Grid-Connected and Stand-Alone Single-Stage Boost-Inverters for PV Applications

Renewable or sustainable energy (SE) sources have attracted the attention of many countries because the power generated is environmentally friendly, and the sources are not subject to the instability of price and availability. This dissertation presents new trends in the DC-AC converters (inverters) used in renewable energy sources, particularly for photovoltaic (PV) energy systems. A review of the existing technologies is performed for both single-phase and three-phase systems, and the pros and cons of the best candidates are investigated. In many modern energy conversion systems, a DC voltage, which is provided from a SE source or energy storage device, must be boosted and converted to an AC voltage with a fixed amplitude and frequency. A novel switching pattern based on the concept of the conventional space-vector pulse-width-modulated (SVPWM) technique is developed for single-stage, boost-inverters using the topology of current source inverters (CSI). The six main switching states, and two zeros, with three switches conducting at any given instant in conventional SVPWM techniques are modified herein into three charging states and six discharging states with only two switches conducting at any given instant. The charging states are necessary in order to boost the DC input voltage. It is demonstrated that the CSI topology in conjunction with the developed switching pattern is capable of providing the required residential AC voltage from a low DC voltage of one PV panel at its rated power for both linear and nonlinear loads. In a micro-grid, the active and reactive power control and consequently voltage regulation is one of the main requirements. Therefore, the capability of the single-stage boost-inverter in controlling the active power and providing the reactive power is investigated. It is demonstrated that the injected active and reactive power can be independently controlled through two modulation indices introduced in the proposed switching algorithm. The system is capable of injecting a desirable level of reactive power, while the maximum power point tracking (MPPT) dictates the desirable active power. The developed switching pattern is experimentally verified through a laboratory scaled three-phase 200W boost-inverter for both grid-connected and stand-alone cases and the results are presented.

The Weight of Language and Action: Epistemic Stance, Methodological Action,and Theoretical Perspective in Knowledge Organization

Knowledge organization (KO) research is a field of scholarship concerned with the design, study and critique of the processes of organizing and representing documents that societies see as worthy of preserving (Tennis, 2008). In this context we are concerned with the relationship between language and action.On the one hand, we are concerned with what language can and does do for our knowledge organization systems (KOS). For example, how do the words NEGRO or INDIAN work in historical and contemporary indexing languages? In relation to this, we are also concerned with how we know about knowledge organization (KO) and its languages. On the other hand, we are concerned with how to act given this knowledge. That is, how do we carry out research and how do we design, implement, and evaluate KO systems?It is important to consider these questions in the context of our work because we are delegated by society to disseminate cultural memory. We are endowed with a perspective, prepared by an education, and granted positions whereby society asks us to ensure that documentary material is accessible to future generations. There is a social value in our work, and as such there is a social imperative to our work. We must act with good conscience, and use language judiciously, for the memory of the world is a heavy burden.In this paper, I explore these two weights of language and action that bear down on KO researchers. I first summarize what extant literature says about the knowledge claims we make with regard to KO practices and systems. To make it clear what it is that I think we know, I create a schematic that will link claims (language) to actions in advising, implementing, or evaluating information practices and systems.I will then contrast this with what we do not know, that is, what the unanswered questions might be (Gnoli, 2008 ; Dahlberg, 2011), and I will discuss them in relation to the two weights in our field of KO.Further, I will try to provide a systematic overview of possible ways to address these open questions in KO research. I will draw on the concept of elenchus - the forms of epistemology, theory, and methodology in KO (Tennis, 2008), and framework analysis which are structures, work practice, and discourses of KO systems (Tennis, 2006). In so doing, I will argue for a Neopragmatic stance on the weight of language and action in KO (Rorty, 1982 ; 2000). I will close by addressing the lacuna left in Neopragmatic thought – the ethical imperative to use language and action in a particular good and moral way. That is, I will address the ethical imperative of KO given its weights, epistemologies, theories, and methods. To do this, I will review a sample of relevant work on deontology in both western and eastern philosophical schools (e.g., Harvey, 1995).The perspective I want to communicate in this section is that the good in carrying out KO research may begin with epistemic stances (cf., language), but ultimately stands on ethical actions. I will present an analysis describing the micro and the macro ethical concerns in relation to KO research and its advice on practice. I hope this demonstrates that the direction of epistemology, theory, and methodology in KO, while burdened with the dual weights of language and action, is clear when provided an ethical sounding board. We know how to proceed when we understand how our work can benefit the world.KO is an important, if not always understood, division of labor in a society that values its documentary heritage and memory institutions. Being able to do good requires us to understand how to balance the weights of language and action. We must understand where we stand and be able to chart a path forward, one that does not cause harm, but adds value to the world and those that want to access recorded knowledge.

Between service and loyalty: chancery and chancellors of Portugal in the 14th century

Estudo dos perfis e carreiras dos chancelares que serviram os reis portugueses ao longo do século XIV. Procura-se, com este estudo, reflectir sobre a evolução do papel dos eclesiásticos na construção da realeza e estabelecer tendências para a evolução dos perfis dos protagonistas do serviço régio.

La invención de la diferencia costarricense, 1810-1870

Resumen En este artículo el autor ratrea el proceso de formación de los principales atributos de la nación costarricense y procura determinar cuales eran los sentidos de pertenencia en Costa Rica en el perido de 1810-1870 Abstract In this article the author traces the process of formation of the principal attributes of the Costa Rica nation, and determines which were the meanings of belonging in Costa Rica in the period 1810-1870

La invención de la diferencia costarricense, 1810-1870

Resumen En este artículo el autor ratrea el proceso de formación de los principales atributos de la nación costarricense y procura determinar cuales eran los sentidos de pertenencia en Costa Rica en el perido de 1810-1870 Abstract In this article the author traces the process of formation of the principal attributes of the Costa Rica nation, and determines which were the meanings of belonging in Costa Rica in the period 1810-1870.

Sequential exhaustive extraction of a Mollisol soil, and characterizations of humic components, including humin, by solid and solution state NMR.

A comprehensive sequential extraction procedure was applied to isolate soil organic components using aqueous solvents at different pH values, base plus urea (base-urea), and finally dimethylsulfoxide (DMSO) plus concentrated H2SO4 (DMSO-acid) for the humin-enriched clay separates. The extracts from base-urea and DMSO-acid would be regarded as 'humin' in the classical definitions. The fractions isolated from aqueous base, base-urea and DMSO-acid were characterized by solid and solution state NMR spectroscopy. The base-urea solvent system isolated ca. 10% (by mass) additional humic substances. The combined base-urea and DMSO-acid solvents isolated ca. 93% of total organic carbon from the humin-enriched fine clay fraction (<2 ?m). Characterization of the humic fractions by solid-state NMR spectroscopy showed that oxidized char materials were concentrated in humic acids isolated at pH 7, and in the base-urea extract. Lignin-derived materials were in considerable abundance in the humic acids isolated at pH 12.6. Only very small amounts of char-derived structures were contained in the fulvic acids and fulvic acids-like material isolated from the base-urea solvent. After extraction with base-urea, the 0.5 m NaOH extract from the humin-enriched clay was predominantly composed of aliphatic hydrocarbon groups, and with lesser amounts of aromatic carbon (probably including some char material), and carbohydrates and peptides. From the combination of solid and solution-state NMR spectroscopy, it is clear that the major components of humin materials, from the DMSO-acid solvent, after the exhaustive extraction sequence, were composed of microbial and plant derived components, mainly long-chain aliphatic species (including fatty acids/ester, waxes, lipids and cuticular material), carbohydrate, peptides/proteins, lignin derivatives, lipoprotein and peptidoglycan (major structural components in bacteria cell walls). Black carbon or char materials were enriched in humic acids isolated at pH 7 and humic acids-like material isolated in the base-urea medium, indicating that urea can liberate char-derived material hydrogen bonded or trapped within the humin matrix.