Biosynthesis and mode of action of ribosomally synthesized and post-translationally modified antimicrobial peptides

One of the greatest sources of biologically active compounds is natural products. Often these compounds serve as platforms for the design and development of novel drugs and therapeutics. The overwhelming amount of genomic information acquired in recent years has revealed that ribosomally synthesized and post-translationally modified natural products are much more widespread than originally anticipated. Identified in nearly all forms of life, these natural products display incredible structural diversity and possess a wide range of biological functions that include antimicrobial, antiviral, anti-inflammatory, antitumor, and antiallodynic activities. The unique pathways taken to biosynthesize these compounds offer exciting opportunities for the bioengineering of these complex molecules. The studies described herein focus on both the mode of action and biosynthesis of antimicrobial peptides. In Chapter 2, it is demonstrated that haloduracin, a recently discovered two-peptide lantibiotic, possesses nanomolar antimicrobial activity against a panel of bacteria strains. The potency of haloduracin rivals that of nisin, an economically and therapeutically relevant lantibiotic, which can be attributed to a similar dual mode of action. Moreover, it was demonstrated that this lantibiotic of alkaliphile origin has better stability at physiological pH than nisin. The molecular target of haloduracin was identified as the cell wall peptidoglycan precursor lipid II. Through the in vitro biosynthesis of haloduracin, several analogues of Halα were prepared and evaluated for their ability to inhibit peptidoglycan biosynthesis as well as bacterial cell growth. In an effort to overcome the limitations of in vitro biosynthesis strategies, a novel strategy was developed resulting in a constitutively active lantibiotic synthetase enzyme. This methodology, described in Chapter 3, enabled the production of fully-modified lacticin 481 products with proteinogenic and non-proteinogenic amino acid substitutions. A number of lacticin 481 analogues were prepared and their antimicrobial activity and ability to bind lipid II was assessed. Moreover, site-directed mutagenesis of the constitutively active synthetase resulted in a kinase-like enzyme with the ability to phosphorylate a number of peptide substrates. The hunt for a lantibiotic synthetase enzyme responsible for installing the presumed dehydro amino acids and a thioether ring in the natural product sublancin, led to the identification and characterization of a unique post-translational modification. The studies described in Chapter 4, demonstrate that sublancin is not a lantibiotic, but rather an unusual S-linked glycopeptide. Its structure was revised based on extensive chemical, biochemical, and spectroscopic characterization. In addition to structural investigation, bioinformatic analysis of the sublancin gene cluster led to the identification of an S-glycosyltransferase predicted to be responsible for the post-translational modification of the sublancin precursor peptide. The unprecedented glycosyltransferase was reconstituted in vitro and demonstrated remarkable substrate promiscuity for both the NDP-sugar co-substrate as well as the precursor peptide itself. An in vitro method was developed for the production of sublancin and analogues which were subsequently evaluated in bioactivity assays. Finally, a number of putative biosynthetic gene clusters were identified that appear to harbor the necessary genes for production of an S-glycopeptide. An additional S-glycosyltransferase with more favorable intrinsic properties including better expression, stability, and solubility was reconstituted in vitro and demonstrated robust catalytic abilities.

Governmentality and exclusion in post-disaster spaces : conducting the conduct of the survivors of Typhoon Sendong in Cagayan de Oro, Philippines

Lorsque les aléas naturels se déroulent en catastrophes, les réponses des religieux, de l’Etat, et d’autres acteurs puissants dans une société révèlent à la fois les relations complexes entre ces parties et leur pouvoir dans la production des espaces auxquelles les survivants accèdent. La réponse en cas de catastrophe comprend la création d’espaces post-catastrophes, tels que des centres d’évacuation, des logements de transition et des sites de réinstallation permanente, qui ciblent spécifiquement un sous-ensemble particulier de survivants, et visent à les aider à survivre, à faire face, et à se remettre de la catastrophe. Les acteurs puissants dans une société dirigent les processus de secours, de récupération et de reconstruction sont des acteurs puissants qui cherchent à problématiser et à rendre un problème technique dans des termes qu’ils sont idéalement placés pour aborder à travers une variété d'interventions. Ce projet de recherche vise à répondre à la question: où les survivants d'une catastrophe reconstruisent-ils leurs vies et leurs moyens de subsistance? Il enquête sur un cas spécifique de la migration environnementale dans laquelle des dizaines de milliers d'habitants ont été déplacés de façon permanente et temporaire de leurs résidences habituelles après le typhon Sendong à Cagayan de Oro, Philippines en 2011. La recherche est basée sur des entretiens avec les acteurs puissants et les survivants, des vidéos participatives réalisées par des survivants pauvres urbains, et des activités de cartographie. L’étude se fonde sur la théorie féministe, les études de migration, les études dans la gouvernementalité, la recherche sur les changements de l’environnement planétaire, et les études régionales afin de situer les diverses expériences de la migration dans un contexte géographique et historique. Cette thèse propose une topographie critique dans laquelle les processus et les pratiques de production d’espaces post-catastrophe sont exposés. Parce que l’espace est nécessairement malléable, fluide, et relationnelle en raison de l'évolution constante des activités, des conflits, et des expériences qui se déroulent dans le paysage, une analyse de l'espace doit être formulée en termes de relations sociales qui se produisent dans et au-delà de ses frontières poreuses. En conséquence, cette étude explore comment les relations sociales entre les survivants et les acteurs puissants sont liées à l’exclusion, la gouvernementalité, la mobilité, et la production des espaces, des lieux et des territoires. Il constate que, si les trajectoires de migration de la plupart des survivants ont été confinés à l'intérieur des limites de la ville, les expériences de ces survivants et leur utilisation des espaces urbains sont très différentes. Ces différences peuvent être expliquées par des structures politiques, économiques, et sociales, et par les différences religieuses, économiques, et de genre. En outre, il fait valoir que les espaces post-catastrophe doivent être considérés comme des «espaces d’exclusion» où les fiduciaires exercent une rationalité gouvernementale. C’est-à-dire, les espaces post-catastrophe prétendument inclusives servent à marginaliser davantage les populations vulnérables. Ces espaces offrent aussi des occasions pour les acteurs puissants dans la société philippine d'effectuer des interventions gouvernementales dans lesquelles certaines personnes et les paysages sont simplifiées, rendues lisibles, et améliorés.

Post-neodarwinismo

La conferencia aborda diferentes aspectos de lo que se ha dado en llamar post-neodarwinismo. Entre ellos, el que más repercusión mediática ha tenido ha sido la expansión de la cladística en detrimento de la sistemática de la teoría sintética. Por otra parte, el paradigma adaptativo ha sido sustituido por una visión más plural en la que la historia y los denominados "structural constraints" explican buena parte de la variación fenotípica observada. Para terminar se abordan problemas relacionados con los mecanismos de especiación.

Theory of mind after mild TBI in preschool children : a longitudinal perspective

Les enfants d’âge préscolaire (≤ 5 ans) sont plus à risque de subir un traumatisme crânio-cérébral (TCC) que les enfants plus agés, et 90% de ces TCC sont de sévérité légère (TCCL). De nombreuses études publiées dans les deux dernières décennies démontrent que le TCCL pédiatrique peut engendrer des difficultés cognitives, comportementales et psychiatriques en phase aigüe qui, chez certains enfants, peuvent perdurer à long terme. Il existe une littérature florissante concernant l'impact du TCCL sur le fonctionnement social et sur la cognition sociale (les processus cognitifs qui sous-tendent la socialisation) chez les enfants d'âge scolaire et les adolescents. Or, seulement deux études ont examiné l'impact d'un TCCL à l'âge préscolaire sur le développement social et aucune étude ne s'est penchée sur les répercussions socio-cognitives d'un TCCL précoce (à l’âge préscolaire). L'objectif de la présente thèse était donc d'étudier les conséquences du TCCL en bas âge sur la cognition sociale. Pour ce faire, nous avons examiné un aspect de la cognition sociale qui est en plein essor à cet âge, soit la théorie de l'esprit (TE), qui réfère à la capacité de se mettre à la place d'autrui et de comprendre sa perspective. Le premier article avait pour but d'étudier deux sous-composantes de la TE, soit la compréhension des fausses croyances et le raisonnement des désirs et des émotions d'autrui, six mois post-TCCL. Les résultats indiquent que les enfants d'âge préscolaire (18 à 60 mois) qui subissent un TCCL ont une TE significativement moins bonne 6 mois post-TCCL comparativement à un groupe contrôle d'enfants n'ayant subi aucune blessure. Le deuxième article visait à éclaircir l'origine de la diminution de la TE suite à un TCCL précoce. Cet objectif découle du débat qui existe actuellement dans la littérature. En effet, plusieurs scientifiques sont d'avis que l'on peut conclure à un effet découlant de la blessure au cerveau seulement lorsque les enfants ayant subi un TCCL sont comparés à des enfants ayant subi une blessure n'impliquant pas la tête (p.ex., une blessure orthopédique). Cet argument est fondé sur des études qui démontrent qu'en général, les enfants qui sont plus susceptibles de subir une blessure, peu importe la nature de celle-ci, ont des caractéristiques cognitives pré-existantes (p.ex. impulsivité, difficultés attentionnelles). Il s'avère donc possible que les difficultés que nous croyons attribuables à la blessure cérébrale étaient présentes avant même que l'enfant ne subisse un TCCL. Dans cette deuxième étude, nous avons donc comparé les performances aux tâches de TE d'enfants ayant subi un TCCL à ceux d'enfants appartenant à deux groupes contrôles, soit des enfants n'ayant subi aucune blessure et à des pairs ayant subi une blessure orthopédique. De façon générale, les enfants ayant subi un TCCL ont obtenu des performances significativement plus faibles à la tâche évaluant le raisonnement des désirs et des émotions d'autrui, 6 mois post-blessure, comparativement aux deux groupes contrôles. Cette étude visait également à examiner l'évolution de la TE suite à un TCCL, soit de 6 mois à 18 mois post-blessure. Les résultats démontrent que les moindres performances sont maintenues 18 mois post-TCCL. Enfin, le troisième but de cette étude était d’investiguer s’il existe un lien en la performance aux tâches de TE et les habiletés sociales, telles qu’évaluées à l’aide d’un questionnaire rempli par le parent. De façon intéressante, la TE est associée aux habiletés sociales seulement chez les enfants ayant subi un TCCL. Dans l'ensemble, ces deux études mettent en évidence des répercussions spécifiques du TCCL précoce sur la TE qui persistent à long terme, et une TE amoindrie seraient associée à de moins bonnes habiletés sociales. Cette thèse démontre qu'un TCCL en bas âge peut faire obstacle au développement sociocognitif, par le biais de répercussions sur la TE. Ces résultats appuient la théorie selon laquelle le jeune cerveau immature présente une vulnérabilité accrue aux blessures cérébrales. Enfin, ces études mettent en lumière la nécessité d'étudier ce groupe d'âge, plutôt que d'extrapoler à partir de résultats obtenus avec des enfants plus âgés, puisque les enjeux développementaux s'avèrent différents, et que ceux-ci ont potentiellement une influence majeure sur les répercussions d'une blessure cérébrale sur le fonctionnement sociocognitif.

The antecedents of post-initial adoption behavior in a S-D logic context

Repercussions of innovation adoption and diffusion studies have long been imperative to the success of novel introductions. However, perceptions and deductions of current innovation understandings have been changing over time. The paradigm shift from the goods-dominant (G-D) logic to the service-dominant (S-D) logic potentially makes the distinction between product (goods) innovation and service innovation redundant as the S-D logic lens views all innovations as service innovations (Vargo and Lusch, 2004; 2008; Lusch and Nambisan, 2015). From this perspective, product innovations are in essence service innovations, as goods serve as mere distribution mechanisms to deliver service. Nonetheless, the transition to such a broadened and transcending view of service innovation necessitates concurrently a change in the underlying models used to investigate innovation and its subsequent adoption. The present research addresses this gap by engendering a novel model for the most crucial period of service diffusion within the S-D logic context – the post-initial adoption phase, which demarcates an individual’s behavior after the initial adoption decision of a service. As a wellfounded understanding of service diffusion and the complementary innovation adoption still lingers in its infancy, the current study develops a model based on interdisciplinary domains mapping. Here fore, knowledge of the relatively established viral source domain is mapped to the comparatively undetermined target domain of service innovation adoption. To assess the model and test the importance of the explanatory variables, survey data from 750 respondents of a bank in Northern Germany is scrutinized by means of Structural Equation Modeling (SEM). The findings reveal that the continuance intention of a customer, actual usage of the service and the customer influencer value all constitute important postinitial adoption behavior that have meaningful implications for a successful service adoption. Second, the four constructs customer influencer value, organizational commitment, perceived usefulness and service customization are evidenced to have a differential impact on a iv customer’s post-initial adoption behavior. Third, this study indicates that post-initial adoption behavior further underlies the influence of a user’s age and besides that is also provoked by the internal and external environments of service adoption. Finally, this research amalgamates the broad view of service innovation by Nambisan and Lusch (2015) with the findings ensuing this enquiry’s model to arrive at a framework that it both, generalizable and practically applicable. Implications for academia and practitioners are captured along with avenues for future research.

A multi-sectoral version of the Post-Keynesian growth model

Neste artigo, pretende-se desenvolver uma versão desagregada da abordagem pós-Keynesiana para o crescimento econômico, mostrando que de fato esse modelo pode ser tratado como um caso particular do modelo Pasinettiano de mudança estrutural e crescimento econômico. Utilizando-se o conceito de integração vertical, torna-se possível conduzir a análise iniciada por Kaldor (1956) e Robinson (1956, 1962), e seguido por Dutt (1984), Rowthorn (1982) e, posteriormente, Bhaduri e Marglin (1990) em um modelo multi-sectorial em que há aumentos da demanda e produtividade em ritmos diferentes em cada setor. Ao adotar essa abordagem, é possível mostrar que a dinâmica de mudança estrutural está condicionada não apenas aos padrões de demanda de evolução das preferências e da difusão do progresso tecnológico, mas também com as características distributivas da economia, que podem dar origem a diferentes regimes setoriais de crescimento econômico. Além disso, é possível determinar a taxa natural de lucro que faz com que a taxa de mark-up seja constante ao longo do tempo. _________________________________________________________________________________ ABSTRACT

Double Hybrid Functionals and the Π-System Bond Length Alternation Challenge: Rivaling Accuracy of Post-HF Methods

Predicting accurate bond length alternations (BLAs) in long conjugated oligomers has been a significant challenge for electronic-structure methods for many decades, made particularly important by the close relationships between BLA and the rich optoelectronic properties of π-delocalized systems. Here, we test the accuracy of recently developed, and increasingly popular, double hybrid (DH) functionals, positioned at the top of Jacobs Ladder of DFT methods of increasing sophistication, computational cost, and accuracy, due to incorporation of MP2 correlation energy. Our test systems comprise oligomeric series of polyacetylene, polymethineimine, and polysilaacetylene up to six units long. MP2 calculations reveal a pronounced shift in BLAs between the 6-31G(d) basis set used in many studies of BLA to date and the larger cc-pVTZ basis set, but only modest shifts between cc-pVTZ and aug-cc-pVQZ results. We hence perform new reference CCSD(T)/cc-pVTZ calculations for all three series of oligomers against which we assess the performance of several families of DH functionals based on BLYP, PBE, and TPSS, along with lower-rung relatives including global- and range-separated hybrids. Our results show that DH functionals systematically improve the accuracy of BLAs relative to single hybrid functionals. xDH-PBE0 (N4 scaling using SOS-MP2) emerges as a DH functional rivaling the BLA accuracy of SCS-MP2 (N5 scaling), which was found to offer the best compromise between computational cost and accuracy the last time the BLA accuracy of DFT- and wave function-based methods was systematically investigated. Interestingly, xDH-PBE0 (XYG3), which differs to other DHs in that its MP2 term uses PBE0 (B3LYP) orbitals that are not self-consistent with the DH functional, is an outlier of trends of decreasing average BLA errors with increasing fractions of MP2 correlation and HF exchange.

Post-Revolutionary Post-Modernism: Central American Detective Fiction by the Turn of the 21st Century

Contemporary Central American fiction has become a vital project of revision of the tragic events and the social conditions in the recent history of the countries from which they emerge. The literary projects of Sergio Ramirez (Nicaragua), Dante Liano (Guatemala), Horacio Castellanos Moya (El Salvador), and Ramon Fonseca Mora (Panama), are representative of the latest trends in Central American narrative. These trends conform to a new literary paradigm that consists of an amalgam of styles and discourses, which combine the testimonial, the historical, and the political with the mystery and suspense of noir thrillers. Contemporary Central American noir narrative depicts the persistent war against social injustice, violence, criminal activities, as well as the new technological advances and economic challenges of the post-war neo-liberal order that still prevails throughout the region. Drawing on postmodernism theory proposed by Ihab Hassan, Linda Hutcheon and Brian MacHale, I argued that the new Central American literary paradigm exemplified by Sergio Ramirez’s El cielo llora por mí, Dante Liano’s El hombre de Montserrat, Horacio Castellanos Moya’s El arma en el hombre and La diabla en el espejo, and Ramon Fonseca Mora’s El desenterrador, are highly structured novels that display the characteristic marks of postmodern cultural expression through their ambivalence, which results from the coexistence of multiple styles and conflicting ideologies and narrative trends. The novels analyzed in this dissertation make use of a noir sensitivity in which corruption, decay and disillusionment are at their core to portray the events that shaped the modern history of the countries from which they emerge. The revolutionary armed struggle, the state of terror imposed by military regimes and the fight against drug trafficking and organized crime, are among the major themes of these contemporary works of fiction, which I have categorized as perfect examples of the post-revolutionary post-modernism Central American detective fiction at the turn of the 21st century.

Use of Fiber Reinforced Polymer Composite Cable for Post-tensioning Application

Corrosion of steel tendons is a major problem for post-tensioned concrete, especially because corrosion of the steel strands is often hard to detect inside grouted ducts. Non-metallic tendons can serve as an alternative material to steel for post-tensioning applications. Carbon fiber reinforced polymer (CFRP), given its higher strength and elastic modulus, as well as excellent durability and fatigue strength, is the most practical option for post-tensioning applications. The primary objective of this research project was to assess the feasibility of the use of innovative carbon fiber reinforced polymer (CFRP) tendons and to develop guidelines for CFRP in post-tensioned bridge applications, including segmental bridges and pier caps. An experimental investigation and a numerical simulation were conducted to compare the performance of a scaled segmental bridge model, post-tensioned with two types of carbon fiber strands and steel strands. The model was tested at different prestress levels and at different loading configurations. While the study confirms feasibility of both types of carbon fiber strands for segmental bridge applications, and their similar serviceability behavior, strands with higher elastic modulus could improve structural performance and minimize displacements beyond service loads. As the second component of the project, a side-by-side comparison of two types of carbon fiber strands against steel strands was conducted in a scaled pier cap model. Two different strand arrangements were used for post-tensioning, with eight and six strands, respectively representing an over-design and a slight under-design relative to the factored demand. The model was tested under service and factored loads. The investigation confirmed the feasibility of using carbon fiber strands in unbonded post-tensioning of pier caps. Considering both serviceability and overload conditions, the general performance of the pier cap model was deemed acceptable using either type of carbon fiber strands and quite comparable to that of steel strands. In another component of this research, creep stress tests were conducted with carbon fiber composite cable (CFCC). The anchorages for all the specimens were prepared using a commercially available expansive grout. Specimens withstood 95% of the guaranteed capacity provided by the manufacturer for a period of five months, without any sign of rupture.

Foreign Direct Investment in Central and Eastern Europe:post-crisis perspectives

This book examines how foreign direct investment (FDI) inflows to Central and Eastern Europe have changed after the Great Recession. It argues that beyond their cyclical effects, the economic crisis and the changing competitiveness of Central and Eastern European countries have had structural impacts on FDI in the region. FDI has traditionally been viewed as the key driver of national development, but the apparent structural shift means that focusing on cheap labour as a competitive advantage is no longer a viable strategy for the countries in the region. The authors argue that these countries need to move beyond the narrative of upgrading (attracting FDI inflows with increasingly higher value added), and focus on ensuring greater value capture instead. A potential way for doing this is by developing the conditions in which innovative national companies can emerge, thrive and eventually develop into lead firms of global value chains. The book provides readers with a highly informative account of the reasons why this shift is necessary, as well as diverse perspectives and extensive discussions on the dynamics and structural impacts of FDI in post-crisis Central and Eastern Europe.

Design of products to honor people post mortem

The cemeterial units, are places of social practices of everyday life and worship and the tomb where nostalgia can be externalized and the memory of the deceased revered. In Western societies we can find a category of artifacts meant to evoke the memory or honor the dead. In this paper we we mention three examples of products that enabled a reflection on the concepts that gave rise to their ways, and that risks to fit them into a new "material culture", in that it may have created a break with the traditional system codes and standards shared by companies, and its manifestations in relation to the physical creation of this category of products. This work offers a reflection on the Design Products.What probably makes it special is the field where it is located: the design of products in one post mortem memory. Usually made of granite rock or marble, have the form of plate or tablet, open book or rolled sheet. On one side have a photograph of the person who intend to honor and inscriptions. The thought of inherent design of this work put on one side the intricate set of emotions that this type of product can generate, and other components more affordable, and concerning the form, function and object interactions with users and with use environments. In the definition of the problem it was regarded as mandatory requirements: differentiation, added value and durability as key objectives.The first two should be manifested in the various components / product attributes. The aesthetic and material/structural durability of product necessarily imply the introduction of qualifying terms and quantitative weights, which positively influence the generation and evaluation of concepts based on the set of 10 principles for the project that originated a matrix as a tool to aid designing products. The concrete definition of a target audience was equally important. At this stage, the collaboration of other experts in the fields of psychology and sociology as disciplines with particular ability to understand individuals and social phenomena respectively was crucial. It was concluded that a product design to honor someone post mortem, should abandon the more traditional habits and customs to focus on identifying new audiences. Although at present it can be considered a niche market, it is believed that in the future may grow as well as their interest in this type of products.

A test of basic psychological needs theory in young soccer players: Time-lagged design at the individual and team levels

Within the framework of basic psychological needs theory (Deci & Ryan, 2000), multilevel structural equation modeling (MSEM) with a time-lagged design was used to test a mediation model examining the relationship between perceptions of coaches’ interpersonal styles (autonomy supportive and controlling), athletes’ basic psychological needs (satisfaction and thwarting), and indicators of well-being (subjective vitality) and ill-being (burnout), estimating separately between and within effects. The participants were 597 Spanish male soccer players aged between 11 and 14 years (M = 12.57, SD = 0.54) from 40 teams who completed a questionnaire package at two time points in a competitive season. Results revealed that at the individual level, athletes’ perceptions of autonomy support positively predicted athletes’ need satisfaction (autonomy, competence, and relatedness), whereas athletes’ perceptions of controlling style positively predicted athletes’ need thwarting (autonomy, competence, and relatedness). In turn, all three athletes’ need satisfaction dimensions predicted athletes’ subjective vitality and burnout (positively and negatively, respectively), whereas competence thwarting negatively predicted subjective vitality and competence and relatedness positively predicted burnout. At the team level, team perceptions of autonomy supportive style positively predicted team autonomy and relatedness satisfaction. Mediation effects only appeared at the individual level.

Hilbert Space Valued Signal Plus Noise Models: Analysis of Structural Breaks under High Dimensionality and Temporal Dependence

This thesis is concerned with change point analysis for time series, i.e. with detection of structural breaks in time-ordered, random data. This long-standing research field regained popularity over the last few years and is still undergoing, as statistical analysis in general, a transformation to high-dimensional problems. We focus on the fundamental »change in the mean« problem and provide extensions of the classical non-parametric Darling-Erdős-type cumulative sum (CUSUM) testing and estimation theory within highdimensional Hilbert space settings. In the first part we contribute to (long run) principal component based testing methods for Hilbert space valued time series under a rather broad (abrupt, epidemic, gradual, multiple) change setting and under dependence. For the dependence structure we consider either traditional m-dependence assumptions or more recently developed m-approximability conditions which cover, e.g., MA, AR and ARCH models. We derive Gumbel and Brownian bridge type approximations of the distribution of the test statistic under the null hypothesis of no change and consistency conditions under the alternative. A new formulation of the test statistic using projections on subspaces allows us to simplify the standard proof techniques and to weaken common assumptions on the covariance structure. Furthermore, we propose to adjust the principal components by an implicit estimation of a (possible) change direction. This approach adds flexibility to projection based methods, weakens typical technical conditions and provides better consistency properties under the alternative. In the second part we contribute to estimation methods for common changes in the means of panels of Hilbert space valued time series. We analyze weighted CUSUM estimates within a recently proposed »high-dimensional low sample size (HDLSS)« framework, where the sample size is fixed but the number of panels increases. We derive sharp conditions on »pointwise asymptotic accuracy« or »uniform asymptotic accuracy« of those estimates in terms of the weighting function. Particularly, we prove that a covariance-based correction of Darling-Erdős-type CUSUM estimates is required to guarantee uniform asymptotic accuracy under moderate dependence conditions within panels and that these conditions are fulfilled, e.g., by any MA(1) time series. As a counterexample we show that for AR(1) time series, close to the non-stationary case, the dependence is too strong and uniform asymptotic accuracy cannot be ensured. Finally, we conduct simulations to demonstrate that our results are practically applicable and that our methodological suggestions are advantageous.

Experientialist Epistemology and Classification Theory: Embodied and Dimensional Classification

What theoretical framework can help in building, maintaining and evaluating networked knowledge organization resources? Specifically, what theoretical framework makes sense of the semantic prowess of ontologies and peer-to-peer sys- tems, and by extension aids in their building, maintenance, and evaluation? I posit that a theoretical work that weds both for- mal and associative (structural and interpretive) aspects of knowledge organization systems provides that framework. Here I lay out the terms and the intellectual constructs that serve as the foundation for investigative work into experientialist classifi- cation theory, a theoretical framework of embodied, infrastructural, and reified knowledge organization. I build on the inter- pretive work of scholars in information studies, cognitive semantics, sociology, and science studies. With the terms and the framework in place, I then outline classification theory s critiques of classificatory structures. In order to address these cri- tiques with an experientialist approach an experientialist semantics is offered as a design commitment for an example: metadata in peer-to-peer network knowledge organization structures.