Coupling the phosphotransferase system and the methyl-accepting chemotaxis protein-dependent chemotaxis signaling pathways of Escherichia coli.

Chemotactic responses in Escherichia coli are typically mediated by transmembrane receptors that monitor chemoeffector levels with periplasmic binding domains and communicate with the flagellar motors through two cytoplasmic proteins, CheA and CheY. CheA autophosphorylates and then donates its phosphate to CheY, which in turn controls flagellar rotation. E. coli also exhibits chemotactic responses to substrates that are transported by the phosphoenolpyruvate (PEP)-dependent carbohydrate phosphotransferase system (PTS). Unlike conventional chemoreception, PTS substrates are sensed during their uptake and concomitant phosphorylation by the cell. The phosphoryl groups are transferred from PEP to the carbohydrates through two common intermediates, enzyme I (EI) and phosphohistidine carrier protein (HPr), and then to sugar-specific enzymes II. We found that in mutant strains HPr-like proteins could substitute for HPr in transport but did not mediate chemotactic signaling. In in vitro assays, these proteins exhibited reduced phosphotransfer rates from EI, indicating that the phosphorylation state of EI might link the PTS phospho-relay to the flagellar signaling pathway. Tests with purified proteins revealed that unphosphorylated EI inhibited CheA autophosphorylation, whereas phosphorylated EI did not. These findings suggest the following model for signal transduction in PTS-dependent chemotaxis. During uptake of a PTS carbohydrate, EI is dephosphorylated more rapidly by HPr than it is phosphorylated at the expense of PEP. Consequently, unphosphorylated EI builds up and inhibits CheA autophosphorylation. This slows the flow of phosphates to CheY, eliciting an up-gradient swimming response by the cell.

Expression of PTPH1, a rat protein tyrosine phosphatase, is restricted to the derivatives of a specific diencephalic segment.

Studies to date have identified only a few proteins that are expressed in a segment-specific manner within the mammalian brain. Here we report that a nonreceptor protein tyrosine phosphatase, PTPH1, is selectively expressed in the adult thalamus. Expression of PTPH1 mRNA is detected in most, but not all, thalamic nuclei. Nuclei that are derived embryonically from the dorsal thalamus and project to the neocortex express this gene, whereas those derived from the ventral thalamus do not. PTPH1 mRNA expression is also restricted to the dorsal thalamus during development and, thus, can serve as a specific marker for the dorsal thalamic nuclei. Since the subcellular localization of PTPH1 protein is not known, its functional role is not clear. However, the restriction of its expression to the thalamic nuclei that have thalamocortical connections suggests that PTPH1 may play a role in the maintenance of these connections or in determining the physiological properties of thalamic relay nuclei.

Emergent spindle oscillations and intermittent burst firing in a thalamic model: specific neuronal mechanisms.

The rhythmogenesis of 10-Hz sleep spindles is studied in a large-scale thalamic network model with two cell populations: the excitatory thalamocortical (TC) relay neurons and the inhibitory nucleus reticularis thalami (RE) neurons. Spindle-like bursting oscillations emerge naturally from reciprocal interactions between TC and RE neurons. We find that the network oscillations can be synchronized coherently, even though the RE-TC connections are random and sparse, and even though individual neurons fire rebound bursts intermittently in time. When the fast gamma-aminobutyrate type A synaptic inhibition is blocked, synchronous slow oscillations resembling absence seizures are observed. Near-maximal network synchrony is established with even modest convergence in the RE-to-TC projection (as few as 5-10 RE inputs per TC cell suffice). The hyperpolarization-activated cation current (Ih) is found to provide a cellular basis for the intermittency of rebound bursting that is commonly observed in TC neurons during spindles. Such synchronous oscillations with intermittency can be maintained only with a significant degree of convergence for the TC-to-RE projection.

Three-dimensional scroll waves of cAMP could direct cell movement and gene expression in Dictyostelium slugs.

Complex three-dimensional waves of excitation can explain the observed cell movement pattern in Dictyostelium slugs. Here we show that these three-dimensional waves can be produced by a realistic model for the cAMP relay system [Martiel, J. L. & Goldbeter, A. (1987) Biophys J. 52, 807-828]. The conversion of scroll waves in the prestalk zone of the slug into planar wave fronts in the prespore zone can result from a smaller fraction of relaying cells in the prespore zone. Further, we show that the cAMP concentrations to which cells in a slug are exposed over time display a simple pattern, despite the complex spatial geometry of the waves. This cAMP distribution agrees well with observed patterns of cAMP-regulated cell type-specific gene expression. The core of the spiral, which is a region of low cAMP concentration, might direct expression of stalk-specific genes during culmination.

Stathmin interaction with a putative kinase and coiled-coil-forming protein domains.

Stathmin is a ubiquitous, cytosolic 19-kDa protein, which is phosphorylated on up to four sites in response to many regulatory signals within cells. Its molecular characterization indicates a functional organization including an N-terminal regulatory domain that bears the phosphorylation sites, linked to a putative alpha-helical binding domain predicted to participate in coiled-coil, protein-protein interactions. We therefore proposed that stathmin may play the role of a relay integrating diverse intracellular regulatory pathways; its action on various target proteins would be a function of its combined phosphorylation state. To search for such target proteins, we used the two-hybrid screen in yeast, with stathmin as a "bait." We isolated and characterized four cDNAs encoding protein domains that interact with stathmin in vivo. One of the corresponding proteins was identified as BiP, a member of the hsp70 heat-shock protein family. Another is a previously unidentified, putative serine/threonine kinase, KIS, which might be regulated by stathmin or, more likely, be part of the kinases controlling its phosphorylation state. Finally, two clones code for subdomains of two proteins, CC1 and CC2, predicted to form alpha-helices participating in coiled-coil interacting structures. Their isolation by interaction screening further supports our model for the regulatory function of stathmin through coiled-coil interactions with diverse downstream targets via its presumed alpha-helical binding domain. The molecular and biological characterization of KIS, CC1, and CC2 proteins will give further insights into the molecular functions and mechanisms of action of stathmin as a relay of integrated intracellular regulatory pathways.

Ajuste e ensaio de sistemas de proteção de geradores síncronos.

Os sistemas de proteção dos elementos da rede elétrica desempenham um papel de fundamental importância na segurança e confiabilidade dos sistemas de potência. A não atuação ou a atuação incorreta dos relés de proteção durante uma falta localizada em um componente da rede pode transformar-se em um evento sistêmico de grandes proporções (blecaute). Esses eventos trazem riscos e elevados prejuízos econômicos à sociedade. A proteção dos geradores síncronos, apesar do alto custo e complexidade deste tipo de equipamento, não recebe a mesma atenção na literatura que a dedicada à proteção de outros elementos da rede, como, por exemplo, a das linhas de transmissão. Isso decorre do menor número de geradores existentes na rede e também da ideia que as faltas neste tipo de equipamento são menos frequentes. Este trabalho aborda os principais aspectos envolvidos com o projeto de um sistema de proteção para geradores síncronos de grande porte. Incialmente, discutese os principais conceitos associados com os geradores, de interesse para a tarefa de proteção. Particular atenção é dedicada às formas de aterramento e aos critérios adotados para projeto do resistor de aterramento utilizado nesse equipamento. Em seguida, apresentam-se as principais funções de proteção aplicáveis aos geradores, particularmente aquelas voltadas para a detecção de faltas nos enrolamentos do estator. Discute-se também os critérios de ajustes dos parâmetros dessas funções. Descreve-se o uso de uma plataforma laboratorial, baseada em simulador de tempo real (RTDS), para ensaio e análise do sistema de proteção visando validar seu correto desempenho frente às possíveis condições operativas que podem ser encontradas em campo. Finalmente, utilizando os conceitos desenvolvidos ao longo do trabalho, desenvolve-se um estudo de caso, onde é realizado o projeto e implementação do sistema de proteção dos geradores de uma usina hidrelétrica hipotética. Para avaliar e analisar o desempenho do sistema de proteção dessa rede exemplo, parametrizou-se o IED G60 (GE) e realizou-se inúmeras simulações na plataforma de testes proposta.

Contribuições para a implementação de um barramento de processo segundo a norma IEC 61850-9.

Desde seu lançamento, em 2002, a Norma IEC 61850 vem evoluindo para se tornar o padrão adotado nos Sistemas de Automação de Subestações. Dentre seus vários aspectos, destacam- se os serviços de tempo real, que permitem a implementação de funções de automação e de proteção dentro da subestação através da troca de mensagens específicas entre Dispositivos Eletrônicos Inteligentes através de um barramento digital de rede de dados. O objetivo central deste trabalho é explorar algumas das questões que envolvem a implementação de uma classe de serviços de tempo real: a transmissão de valores amostrados através de Serviços SMV, definidos pela Norma IEC 61850-9. Primeiramente, apresenta-se um breve resumo das principais características da Norma IEC 61850 que possibilitam o atendimento dos três requisitos por ela estabelecidos como base: a interoperabilidade entre dispositivos de diferentes fabricantes, a versatilidade na configuração e reconfiguração do Sistema de Automação da Subestação, e a possibilidade de implementação de novas tecnologias. Em seguida, explora-se com maior profundidade todos os aspectos relevantes à implementação dos Serviços SMV. Devido à complexidade deste assunto, o autor propõe abordá-lo sob a ótica de cinco tópicos interdependentes: variações da Norma IEC 61850-9, confiabilidade do barramento de processo, sincronismo de tempo, análise da qualidade da medição e segurança cibernética. Com base nos resultados apresentados neste estudo, propõem-se duas plataformas, um protótipo de Transformador de Potencial Óptico e um protótipo de Relé de Proteção Diferencial para transformadores de potência, com o objetivo de explorar alguns dos aspectos pertinentes à implementação de um barramento de processo de acordo com a Norma IEC 61850-9. Também foram realizados testes de geração e transmissão de mensagens contendo valores de amostras de tensão/corrente do sistema elétrico (denominadas de SV Messages) com a finalidade de implementá-las de fato e avaliar as ferramentas de mercado disponíveis. Por fim foi proposto um modelo para a simulação do sistema de potência em conjunto com a rede de comunicação utilizando o programa Matlab/Simulink. O autor espera que este trabalho contribua para esclarecer os vários conceitos envolvidos na implementação do barramento de processo definido pela Norma IEC 61850-9, auxiliando na pesquisa e no desenvolvimento de novas ferramentas e dispositivos, e no aprimoramento da Norma IEC 61850.

Ethnobotanic importance of plants used in pigeon-breeding in Eastern Spain

Background: The importance that birds of the Columbidae family have had throughout history is visible on the Mediterranean coast. Pigeon fancying is the art of breeding and training carrier pigeons and currently, several breeds exist. The sport of racing pigeons consists in covering a distance at maximum possible speed. However, pigeon breeding has another modality called “sport pigeon”, where several males follow a female. This study focusses on ethnobotanical knowledge of native and exotic plant species that are used for diet, breeding, stimulation, healing illnesses and staining the plumage of pigeons bred in captivity. Methods: Using semi-structured interviews, we gathered information about the different plant species traditionally used for pigeon-breeding in the region of Valencia. Background material on remedies for bird illnesses was gathered from folk botanical references, local books and journals. The plant species were collected in the study area, then identified in the laboratory using dichotomous keys and vouchered in the ABH (Herbarium of Alicante University). We used Excel ® 2003 to perform a simple statistical analysis of the data collected. Results: We collected 56 species of plants (and one variety) that included 29 botanical families. The total number of species was made up of 35 cultivated and 21 wild plants. The most common were Gramineae (14 species), Leguminosae (6 species), and Compositae (4 species). Conclusions: Pigeon breeding is an immensely popular activity in Eastern Spain, and ethnobiological knowledge about breeding pigeons and caring for them is considerable. The names and traditional uses of plants depend on their geographical location, vernacular names serve as an intangible heritage. Feeding, environmental features, and genetic makeup of individuals are relevant aspects in the maintenance of avian health.

Letters from Thomas ap Catesby Jones to William Tudor,

Two letters in which Jones requests that Tudor relay his regrets to José de la Mar for missing the general’s installation as president of Peru, and mentions he is sending Tudor an ensign to be used "at the Palace."

Letter from Robert A. Dobbins to William Tudor,

One letter providing detailed information on the capture of the schooner Shillelah by the Brazilian government and requesting Tudor relay to Dobbins the status of the ship.

Carcinoma renal em doentes com leiomiomatose hereditária e cancro de células renais : a propósito de um caso clínico

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Perceção dos educadores sobre as potencialidades do livro de literatura para a infância

Tese de doutoramento, Educação (Psicologia da Educação), Universidade de Lisboa, Instituto de Educação, 2016

Greater TTIP Ambition in Chemicals: Why and how. CEPS Special Report, 28 July 2015. Paper No. 10 in the CEPS-CTR project ‘TTIP in the Balance’ and CEPS Special Report No. 114/July 2015.

To date, the negotiations over chemicals in the Translatlantic Trade and Investment Partnership (TTIP) have not shown sufficient ambition. The talks have focused too much on the differences in the two ‘systems’, rather than on the actual levels of health and environmental protection for substances regulated by both the US and the EU. Given the accomplishments within the OECD and the UN Globally Harmonised System of Classification and Labelling of Chemicals (GHS), the question is whether TTIP can be any more ambitious in the area of chemicals? We find that there is no detailed or systematic knowledge about how the two levels of protection in chemicals compare, although caricatures and stereotypes abound. This is partly due to an obsessive focus on a single US federal law, the Toxic Subtances Control Act (TSCA), whereas in practice US protection depends on many statutes and regulations, as well as on voluntary withdrawals (under pressure from the Environmental Protection Agency) and severe common law liability. This paper makes the economic case for firmly addressing the regulatory barriers, discusses the EU’s proposals, finds that the European Parliament’s Resolution on TTIP of July 2015 lacks a rationale (for chemicals), argues that both TSCA and REACH ought to be improved (based on ‘better regulation’), discusses the link with a global regime, advocates significant improvement of market access where equivalence of health and environmental objectives is agreed and, finally, proposes to lower the costs for companies selling in both markets by allowing them to opt into the other party’s more stringent rules, thereby avoiding duplication while racing-to-the-top. The ‘living agreement’ on chemicals ought to be led by a new TTIP institution authorised to establish the level of health and environmental protection on both sides of the Atlantic for substances regulated on both sides. These findings will lay the foundation for a highly beneficial lowering of trading costs without in any way affecting the level of protection. Indeed, this is exactly what TTIP is, or should be, all about.This paper is the 10th in a series produced in the context of the “TTIP in the Balance” project, jointly organised by CEPS and the Center for Transatlantic Relations (CTR) in Washington, D.C. It is published simultaneously on the CEPS (www.ceps.eu) and CTR websites (http://transatlantic.sais-jhu.edu).

A Comprehensive Discussion of HMBC Pulse Sequences: 4. Establishing Two-Bond Correlations from HMBC and Related Experiments

The utility of the HMBC experiment for structure elucidation is unquestionable, but the nature of the coupling pathways leading to correlations in an HMBC experiment creates the potential for misinterpretation. This misinterpretation potential is intimately linked to the size of the long-range heteronuclear couplings involved, and may become troublesome in those cases of a particularly strong 2JCH correlation that might be mistaken for a 3JCH correlation or a 4JCH correlation of appreciable strength that could be mistaken for a weaker 3JCH correlation. To address these potential avenues of confusion, work from several laboratories has been focused on the development of what might be considered “coupling pathway edited” long-range heteronuclear correlation experiments that are derived from or related to the HMBC experiment. The first example of an effort to address the problems associated with correlation path length was seen in the heteronucleus-detected XCORFE experiment described by Reynolds and co-workers that predated the development of the HMBC experiment. Proton-detected analogs of the HMBC experiment intended to differentiate 2JCH correlations from nJCH correlations where n = 3, 4, include the 2J,3J-HMBC, HMBC-RELAY, H2BC, edited-HMBC, and HAT H2BC experiments. The principles underlying the critical components of each of these experiments are discussed and experimental verification of the results that can be obtained using model compounds are shown. This contribution concludes with a brief discussion of the 1,1-ADEQUATE experiments that provide an alternative means of identifying adjacent protonated and non-protonated carbon correlations by exploiting 1JCC correlations at natural abundance.

Butch Woolfolk, UM track

{Woolfolk winning relay in UM-Chicago meet]