Photoactive yellow protein: A structural prototype for the three-dimensional fold of the PAS domain superfamily

PAS domains are found in diverse proteins throughout all three kingdoms of life, where they apparently function in sensing and signal transduction. Although a wealth of useful sequence and functional information has become recently available, these data have not been integrated into a three-dimensional (3D) framework. The very early evolutionary development and diverse functions of PAS domains have made sequence analysis and modeling of this protein superfamily challenging. Limited sequence similarities between the ∼50-residue PAS repeats and one region of the bacterial blue-light photosensor photoactive yellow protein (PYP), for which ground-state and light-activated crystallographic structures have been determined to high resolution, originally were identified in sequence searches using consensus sequence probes from PAS-containing proteins. Here, we found that by changing a few residues particular to PYP function, the modified PYP sequence probe also could select PAS protein sequences. By mapping a typical ∼150-residue PAS domain sequence onto the entire crystallographic structure of PYP, we show that the PAS sequence similarities and differences are consistent with a shared 3D fold (the PAS/PYP module) with obvious potential for a ligand-binding cavity. Thus, PYP appears to prototypically exhibit all the major structural and functional features characteristic of the PAS domain superfamily: the shared PAS/PYP modular domain fold of ∼125–150 residues, a sensor function often linked to ligand or cofactor (chromophore) binding, and signal transduction capability governed by heterodimeric assembly (to the downstream partner of PYP). This 3D PAS/PYP module provides a structural model to guide experimental testing of hypotheses regarding ligand-binding, dimerization, and signal transduction.

Total chemical synthesis of a ribozyme derived from a group I intron.

We describe the complete chemical synthesis of a ribozyme that catalyzes template-directed oligonucleotide ligation. The specific activity of the synthetic ribozyme is nearly identical to that of the same enzyme generated by in vitro transcription with T7 RNA polymerase. The ribozyme is derived from a group I intron and consists of three RNA fragments of 36, 43, and 59 nt that self-assemble to form a catalytically active complex. We have site-specifically substituted ribonucleotide analogs into this enzyme and have identified two 2'-hydroxyl groups that are required for full catalytic activity. In contrast, neither the 2'-hydroxyl nor the exocyclic amino group of the conserved guanosine in the guanosine binding site is necessary for catalysis. By allowing the ribozyme to be modified as easily as its substrates, this synthetic ribozyme system should be useful for testing specific hypotheses concerning ribozyme-substrate interactions and tertiary interactions within the ribozyme.

A primeira dança : o papel da intersubjectividade na interacção mãe-bebé

Tese de doutoramento, Psicologia (Psicologia Clínica), Universidade de Lisboa, Faculdade de Psicologia, 2016

Assessing US and EU Foreign Targeting Arab Youth: Lessons from Morocco. ACES Working Papers (progress report), August 2009

As stated in the opening sentence of the proposal submitted for the ACES grant in 2009, the research that this seed grant is supporting is ambitious and large in scale. The primary goal is to produce a book-length study that assesses the priorities and impact of European and American foreign aid targeting youth in the Middle East and North Africa (MENA). To date, the research undertaken with the support of the grant has helped in providing some preliminary data for a) testing few hypotheses, b) fine-tuning the research design; and c) pointing to the direction where more conceptual and ethnographic research should be undertaken.

Examining a key aspect of agency-to-business relationships:the effects of regulatory control on the satisfaction of regulated firms

This paper studies an overlooked, but highly important relationship, the relationship that exists between regulatory agencies (e.g., the EPA, OSHA, and the FDA) and the for-profit businesses they attempt to govern. Drawing on business-to-business control and satisfaction research, a framework is developed to understand how regulatory control influences the satisfaction levels of customer firms. Regulatory control is disaggregated into four distinct facets: the controlling agency, the rules and regulations of control, the processes used by the agency to apply the regulations, and sanctions. Each facet is hypothesized to have an effect on satisfaction. A regulator's administration of state food safety regulations provides the empirical context for testing the hypotheses. Results from a survey of 173 restaurants provide empirical support for the conceptual model. Most importantly, the study finds that the informal control process increases customer satisfaction, while the formal control process decreases customer satisfaction. We discuss how these and other findings may contribute to more effective agency-to-business relationships and ongoing research.

When do firms conform? The effect of regulatory control processes on compliance and opportunism

The authors use social control theory to develop a conceptual model that addresses the effectiveness of regulatory agencies’ (e.g., Food and Drug Administration, Occupational Safety and Health Administration) field-level efforts to obtain conformance with product safety laws. Central to the model are the control processes agencies use when monitoring organizations and enforcing the safety rules. These approaches can be labeled formal control (e.g., rigid enforcement) and informal control (e.g., social instruction). The theoretical framework identifies an important antecedent of control and the relative effectiveness of control’s alternative forms in gaining compliance and reducing opportunism. Furthermore, the model predicts that the regulated firms’ level of agreement with the safety rules moderates the relationships between control and firm responses. A local health department’s administration of state food safety regulations provides the empirical context for testing the hypotheses. The results from a survey of 173 restaurants largely support the proposed model. The study findings inform a discussion of effective methods of administering product safety laws. The authors use social control theory to develop a conceptual model that addresses the effectiveness of regulatory agencies’ (e.g., Food and Drug Administration, Occupational Safety and Health Administration) field-level efforts to obtain conformance with product safety laws. Central to the model are the control processes agencies use when monitoring organizations and enforcing the safety rules. These approaches can be labeled formal control (e.g., rigid enforcement) and informal control (e.g., social instruction). The theoretical framework identifies an important antecedent of control and the relative effectiveness of control’s alternative forms in gaining compliance and reducing opportunism. Furthermore, the model predicts that the regulated firms’ level of agreement with the safety rules moderates the relationships between control and firm responses. A local health department’s administration of state food safety regulations provides the empirical context for testing the hypotheses. The results from a survey of 173 restaurants largely support the proposed model. The study findings inform a discussion of effective methods of administering product safety laws.

Agent-based simulation of lock-in dynamics in a duopoly

Lock-in is observed in real world markets of experience goods; experience goods are goods whose characteristics are difficult to determine in advance, but ascertained upon consumption. We create an agent-based simulation of consumers choosing between two experience goods available in a virtual market. We model consumers in a grid representing the spatial network of the consumers. Utilising simple assumptions, including identical distributions of product experience and consumers having a degree of follower tendency, we explore the dynamics of the model through simulations. We conduct simulations to create a lock-in before testing several hypotheses upon how to break an existing lock-in; these include the effect of advertising and free give-away. Our experiments show that the key to successfully breaking a lock-in required the creation of regions in a consumer population. Regions arise due to the degree of local conformity between agents within the regions, which spread throughout the population when a mildly superior competitor was available. These regions may be likened to a niche in a market, which gains in popularity to transition into the mainstream.

Magyar egyetemi hallgatók vállalkozási attitűdjei és az attitűdöket befolyásoló tényezők elemzése a GUESSS-felmérés adatai alapján - Kik is akarnak ténylegesen vállalkozni? (Entrepreneurial attitudes of the Hungarian students and the analysis of the factors influencing attitudes based on the datas of GUESSS survey – Who want to undertake really?)

A vállalkozóvá válás meghatározó tényezőinek kutatása szakmai berkekben leginkább a Szent Grál keresésére emlékeztet: már lassan azt sem tudjuk, hogy egyáltalán léteznek-e ilyen tényezők. A kutatást nehezítik a többnyire önbevallásos kérdésekre adott torzított válaszok, a szóba jöhető tényezők számossága és a vállalkozói motivációk heterogenitása a különböző demográfiai karakterisztikákkal rendelkező népesség körében. Az egyetemi hallgatók körében némileg egyszerűbb a vizsgálat, hiszen ez egy relatíve homogén minta. Ugyanakkor itt a leginkább áttételesek a hatások, és ráadásul nem a tényleges vállalkozóvá válás, hanem többnyire csak a szándékok tesztelhetők. A vállalkozóvá válás szándékát Bandura társadalmi megismerés-elmélete, Shapero elmozduláselmélete és az Ajzen-féle tervezett magatartás elmélet alapján felállított koncepcionális modell keretén belül vizsgálják és elemzik a szerzők. Arra keresik a választ, hogy az egyes vállalkozói tulajdonságok, az egyetemi környezeti tényezők és a családi háttér hogyan hatnak a vállalkozóvá válásra. A teszteléshez a 21 országra kiterjedő 2011-es GUESSS-felmérésből a magyar egyetemi/ főiskolai hallgatók 5224-es erősségű mintáját használták fel. A multimoniális regressziós vizsgálat eredményei megerősítik, hogy a vállalkozói tulajdonságok és a családban levő vállalkozó megléte mellett a vállalkozói oktatás is pozitívan befolyásolják a vállalkozásindítási szándékot. A klaszterelemzés rámutatott arra, hogy a vállalkozói szándékok, az erre ható tényezők, továbbá a választott szak és más demográfiai tényezők szempontjából a hallgatók meglehetősen heterogének. _______ The search for the determining factors to become an entrepreneur is something like searching for the Holy Grail: After many decades we do not even know if these factors exist or not. The research is difficult because the questionnaires are self esteem, the potential influential factors are numerous, and the motivations do vary across the different cohorts of population. It is easier to conduct a survey amongst university students since this sample is relatively homogenous. At the same times, the determining factors to become an entrepreneur cannot be really tested; the authors can examine mostly the attitudes and the intentions. The conceptual model of entrepreneurial intentions, developed in the paper, based on Bandura, Shaper and Ajzen. The paper is testing eight hypotheses about the influential factors of entrepreneurial intentions such as entrepreneurial traits, the university environment, and the family background. For testing the hypothesis they use a sample of 5224 Hungarian students from the GUESSS 2011 survey. According to the multinomial regression, entrepreneurial intentions are positively influenced by certain entrepreneurial traits, entrepreneur in the family, and entrepreneurship courses at the higher education institutions. The cluster analysis results underline the heterogeneity of the students in terms of entrepreneurial intentions, gender, and the major field of studies

Changes in Caribbean paleoproductivity, diversity and benthic foraminiferal test size caused by the Neogene closing of the tropical Atlantic-Pacific ocean gateway

The purpose of this study was to test 3 hypotheses: (a) that late Miocene to early Pliocene constriction and complete closure of the Central American Seaway (CAS), connecting tropical Atlantic and East Equatorial Pacific (EEP) oceans, caused decreased productivity in the Caribbean, due to reduced coastal upwelling and an end to the connection with high-productivity Pacific waters, (b) reduced paleoproductivity resulted in decreased diversity in the Caribbean and, (c) this decreased availability of food (reduced paleoproductivity) was responsible for larger mean test size in the three most common benthic foraminiferal species Epistominella exigua, Oridorsalis umbonatus and Globocassidulina subglobosa. ^ These are tested by applying correlation analysis to 7 groups of paleoceanographic proxies, 3 indices of diversity measures and mean test size data from the Caribbean Ocean Drilling Project Site 999, to 47 core samples for the interval between 8.3-2.5 Ma. Results are compared with published Caribbean and Pacific deep-sea records. ^ The Caribbean, between 8.3-7.9 Ma, experienced reduced current velocity and lower ventilation of bottom waters. Thereafter, until 4.2 Ma, the seasonality of phytodetritus input increased and ventilation further reduced. From 4.2-2.5 Ma, paleoproductivity decreased, current velocity reduced, ventilation improved, and the seasonality of phytodetrital input decreased dramatically. The benthic foraminiferal diversity followed the same trend as paleoproductivity. Individual correlation analysis between mean test size of benthic foraminiferal species Epistominella exigua, Oridorsalis umbonatus and Globocassidulina subglobosa and paleoceanographic proxies yielded a positive and significant relationship with paleoproductivity. However, a combined datasets of all 3 species yielded a negative and significant relationship with species abundance. ^ Thus, the study concludes that (a) the gradual closure of the CAS led Caribbean diversity and paleoproductivity to decrease abruptly at 7.9 Ma, when the nutrient-rich Pacific deep waters were cut off, and then, again with the complete closure of the seaway at 4.2 Ma, (b) diversity and paleoproductivity are positively correlated in the Caribbean and (c) that the availability of food is an overriding factor that influences mean test size; lower availability of food and decreased abundance leads to larger test size. ^

Phylogenetic and ecological significance in the evolution of Cetacean tonal sounds

Cetaceans are aquatic mammals that rely primarily on sound for most daily tasks. A compendium of sounds is emitted for orientation, prey detection, and predator avoidance, and to communicate. Communicative sounds are among the most studied Cetacean signals, particularly those referred to as tonal sounds. Because tonal sounds have been studied especially well in social dolphins, it has been assumed these sounds evolved as a social adaptation. However, whistles have been reported in ‘solitary’ species and have been secondarily lost three times in social lineages. Clearly, therefore, it is necessary to examine closely the association, if any, between whistles and sociality instead of merely assuming it. Several hypotheses have been proposed to explain the evolutionary history of Cetacean tonal sounds. The main goal of this dissertation is to cast light on the evolutionary history of tonal sounds by testing these hypotheses by combining comparative phylogenetic and field methods. This dissertation provides the first species-level phylogeny of Cetacea and phylogenetic tests of evolutionary hypotheses of cetacean communicative signals. Tonal sounds evolution is complex in that has likely been shaped by a combination of factors that may influence different aspects of their acoustical structure. At the inter-specific level, these results suggest that only tonal sound minimum frequency is constrained by body size. Group size also influences tonal sound minimum frequency. Species that live in large groups tend to produce higher frequency tonal sounds. The evolutionary history of tonal sounds and sociality may be intertwined, but in a complex manner rejecting simplistic views such as the hypothesis that tonal sounds evolved ‘for’ social communication in dolphins. Levels of social and tonal sound complexity nevertheless correlate indicating the importance of tonal sounds in social communication. At the intraspecific level, tonal sound variation in frequency and temporal parameters may be product of genetic isolation and local levels of underwater noise. This dissertation provides one of the first insights into the evolution of Cetacean tonal sounds in a phylogenetic context, and points out key species where future studies would be valuable to enrich our understanding of other factors also playing a role in tonal sound evolution. ^

The Transitioning Economic Dynamics of the Military in Communist Regimes: A Comparison of Cuba, China and Vietnam [Student's Paper Series]

Several factors can increase or decrease military-economic involvement in communist regimes. This anomalous form of military behavior, labeled as the Military Business Complex (MBC), emerged in various communist regimes in the 1980s. However, in early 2000s, the communist governments of China and Vietnam began to decrease the number of military-managed industries, while similar industries increased in Cuba. This paper explains why military industries in Cuba have increased over the last two decades, while they decreased in the Chinese and Vietnamese examples. This question is answered by comparatively testing two hypotheses: the Communist Party and the Bureaucratic-Authoritarian (BA) Hypotheses. The Communist Party hypotheses helps explain how the historical and current structures of Party oversight of the military have been lacking in strength and reliability in Cuba, while they traditionally have been more robust in China and Vietnam. The BA hypotheses helps explain how, due to the lack of a strong civilian institutional oversight, the Cuban military has grown into a bureaucratic entity with many political officers holding autonomous positions of power, an outcome that is not prevalent in the Chinese and Vietnamese examples. Thus, with the establishment of a bureaucratic military government and with the absence of a strong party oversight, the Cuban military has been able to protect its economic endeavors while the Chinese and Vietnamese MBC regimes have contracted.

Phylogenetic and Ecological Significance in the Evolution of Cetacean Tonal Sounds

Cetaceans are aquatic mammals that rely primarily on sound for most daily tasks. A compendium of sounds is emitted for orientation, prey detection, and predator avoidance, and to communicate. Communicative sounds are among the most studied Cetacean signals, particularly those referred to as tonal sounds. Because tonal sounds have been studied especially well in social dolphins, it has been assumed these sounds evolved as a social adaptation. However, whistles have been reported in ‘solitary’ species and have been secondarily lost three times in social lineages. Clearly, therefore, it is necessary to examine closely the association, if any, between whistles and sociality instead of merely assuming it. Several hypotheses have been proposed to explain the evolutionary history of Cetacean tonal sounds. The main goal of this dissertation is to cast light on the evolutionary history of tonal sounds by testing these hypotheses by combining comparative phylogenetic and field methods. This dissertation provides the first species-level phylogeny of Cetacea and phylogenetic tests of evolutionary hypotheses of cetacean communicative signals. Tonal sounds evolution is complex in that has likely been shaped by a combination of factors that may influence different aspects of their acoustical structure. At the inter-specific level, these results suggest that only tonal sound minimum frequency is constrained by body size. Group size also influences tonal sound minimum frequency. Species that live in large groups tend to produce higher frequency tonal sounds. The evolutionary history of tonal sounds and sociality may be intertwined, but in a complex manner rejecting simplistic views such as the hypothesis that tonal sounds evolved ‘for’ social communication in dolphins. Levels of social and tonal sound complexity nevertheless correlate indicating the importance of tonal sounds in social communication. At the intraspecific level, tonal sound variation in frequency and temporal parameters may be product of genetic isolation and local levels of underwater noise. This dissertation provides one of the first insights into the evolution of Cetacean tonal sounds in a phylogenetic context, and points out key species where future studies would be valuable to enrich our understanding of other factors also playing a role in tonal sound evolution.

Bayesian nonparametric latent variable models

L’un des problèmes importants en apprentissage automatique est de déterminer la complexité du modèle à apprendre. Une trop grande complexité mène au surapprentissage, ce qui correspond à trouver des structures qui n’existent pas réellement dans les données, tandis qu’une trop faible complexité mène au sous-apprentissage, c’est-à-dire que l’expressivité du modèle est insuffisante pour capturer l’ensemble des structures présentes dans les données. Pour certains modèles probabilistes, la complexité du modèle se traduit par l’introduction d’une ou plusieurs variables cachées dont le rôle est d’expliquer le processus génératif des données. Il existe diverses approches permettant d’identifier le nombre approprié de variables cachées d’un modèle. Cette thèse s’intéresse aux méthodes Bayésiennes nonparamétriques permettant de déterminer le nombre de variables cachées à utiliser ainsi que leur dimensionnalité. La popularisation des statistiques Bayésiennes nonparamétriques au sein de la communauté de l’apprentissage automatique est assez récente. Leur principal attrait vient du fait qu’elles offrent des modèles hautement flexibles et dont la complexité s’ajuste proportionnellement à la quantité de données disponibles. Au cours des dernières années, la recherche sur les méthodes d’apprentissage Bayésiennes nonparamétriques a porté sur trois aspects principaux : la construction de nouveaux modèles, le développement d’algorithmes d’inférence et les applications. Cette thèse présente nos contributions à ces trois sujets de recherches dans le contexte d’apprentissage de modèles à variables cachées. Dans un premier temps, nous introduisons le Pitman-Yor process mixture of Gaussians, un modèle permettant l’apprentissage de mélanges infinis de Gaussiennes. Nous présentons aussi un algorithme d’inférence permettant de découvrir les composantes cachées du modèle que nous évaluons sur deux applications concrètes de robotique. Nos résultats démontrent que l’approche proposée surpasse en performance et en flexibilité les approches classiques d’apprentissage. Dans un deuxième temps, nous proposons l’extended cascading Indian buffet process, un modèle servant de distribution de probabilité a priori sur l’espace des graphes dirigés acycliques. Dans le contexte de réseaux Bayésien, ce prior permet d’identifier à la fois la présence de variables cachées et la structure du réseau parmi celles-ci. Un algorithme d’inférence Monte Carlo par chaîne de Markov est utilisé pour l’évaluation sur des problèmes d’identification de structures et d’estimation de densités. Dans un dernier temps, nous proposons le Indian chefs process, un modèle plus général que l’extended cascading Indian buffet process servant à l’apprentissage de graphes et d’ordres. L’avantage du nouveau modèle est qu’il admet les connections entres les variables observables et qu’il prend en compte l’ordre des variables. Nous présentons un algorithme d’inférence Monte Carlo par chaîne de Markov avec saut réversible permettant l’apprentissage conjoint de graphes et d’ordres. L’évaluation est faite sur des problèmes d’estimations de densité et de test d’indépendance. Ce modèle est le premier modèle Bayésien nonparamétrique permettant d’apprendre des réseaux Bayésiens disposant d’une structure complètement arbitraire.

The value of eutherian-marsupial comparisons for understanding the function of glucocorticoids in female mammal reproduction.

This article is part of a Special Issue "SBN 2014". Chronic stress is known to inhibit female reproductive function. Consequently, it is often assumed that glucocorticoid (GC) concentrations should be negatively correlated with reproductive success because of the role they play in stress physiology. In contrast, a growing body of evidence indicates that GCs play an active role in promoting reproductive function. It is precisely because GCs are so integral to the entire process that disruptions to adrenal activity have negative consequences for reproduction. The goal of this paper is to draw attention to the increasing evidence showing that increases in adrenal activity are important for healthy female reproduction. Furthermore, we outline several hypotheses about the functional role(s) that GCs may play in mediating reproduction and argue that comparative studies between eutherian and marsupial mammals, which exhibit some pronounced differences in reproductive physiology, may be particularly useful for testing different hypotheses about the functional role of GCs in reproduction. Much of our current thinking about GCs and reproduction comes from research involving stress-induced levels of GCs and has led to broad assumptions about the effects of GCs on reproduction. Unfortunately, this has left a gaping hole in our knowledge about basal GC levels and how they may influence reproductive function, thereby preventing a broader understanding of adrenal physiology and obscuring potential solutions for reproductive dysfunction.

Age diversity and firm performance in an emerging economy: Implications for cross-cultural human resource management

This study tests the effect of age diversity on firm performance among international firms. Based on the resource-based view of the firm, it argues that age diversity among employees will influence firm performance. Moreover, it argues that two contextual variables—a firm's level of market diversification and its country of origin—influence the relationship between age diversity and firm performance. By testing relevant hypotheses in a major emerging economy, that is, the People's Republic of China, this study finds a significant and positive effect of age diversity and a significant interactive effect between age diversity and firm strategy on profitability. We also find a significant relationship between age diversity and firm profitability for firms from Western societies, but not for firms from East Asian societies. The paper concludes by discussing the implications of this study's findings. © 2011 Wiley Periodicals, Inc.