Gramaticalização da construção 'é claro que': padrões na fala e na escrita.

In this paper, we investigate the grammatical construction “é claro (que)”, which is characterized as a matrix clause. As it is produced, an argumentative clause is added to the matrix clause in subject position. We analyze oral speech and writing data of contemporary Portuguese and show that the grammatical construction undergoes processes of change, which are identified by desentencialization clauses and grammaticalization process. In addition, by analyzing parameters such as the position of grammatical construction, the presence of copulation and the use of a complementizer, we show that the absence of copulation and a complementizer in the matrix leads to a reduced clause, i.e., a monoclause, and a categorical change of the matrix adjective, which plays the role of functioning adverb.

Algumas reflexões sobre a questão da gramaticalização de Marcadores Discursivos

In this paper, we present a discussion on the class of Discourse Markers (DMs), aiming at providing some specific contributions to studies on the grammaticalization of DMs. We highlight the fact that DMs do not constitute a grammatical class, and then we formulate a few insights on the adequacy of the notion of the “grammaticalization of DMs”.

A análise funcionalista e o estabelecimento de quadros categoriais na gramática

Committed to a functionalist view of grammar, this study takes word classes as its object of analysis, aiming to show that categorical rigidity cannot be upheld in linguistic use. The analysis sample presented starts from the solutions of dictionaries in the registration of word classes parts and from the fluidity that these classes show in their use. Aspects of grammaticalization in Portuguese language are taken as evidence. It is argued that the grammatical organization of language has properties that support categorical shift processes, however singular they may seem to examination.

Localizando o pretérito perfecto compuesto na linha do tempo: o estágio da gramaticalização do PPC nas variedades diatópicas argentinas

The aim of this study was to observe Argentine diatopic varieties and to identify in which stage of the evolution of the pretérito perfecto compuesto (PPC) the use of compound tense fits into these variations. Therefore, we assume as assumptions (I) some authors` description of the evolutionary stages of this verb tense in Spanish, (II) the description of the values assigned to the perfecto compuesto in the dialect regions of Argentina and (III) the contributions of studies on grammaticalization for the verb tenses analysis.

As construções verbais paratáticas: gramaticalização em português europeu

This paper aims to analyze the so-called paratactic verbal constructions, or PVCs, in contemporary European Portuguese. The PVCs are built from the cohesion of two inflected verbs, V1 and V2, connected or not by the conjunction e (and), and only the second verb retains its full semantic content. Our analysis follows the grammaticalization and functional linguistics approaches. The process of grammaticalization of the PVCs allowed the verbs ir (go), chegar (arrive), pegar (take) and agarrar (grab), in specific contexts such as the PVCs, to undergo changes in their morphosyntactic and semantic features, what leads its categorial status and its function to change.

Gramaticalização e tradição discursiva: um estudo dos processos constitutivos do texto relacionados a assim

This paper is focused in a qualitative analysis on the item assim in correlation to its topic function in Tradições Discursivas (Discursive Traditions), investigated in the from 18th to 21th centuries. The results point out to a close relation between the investigated texts traditions and the changes that have occured concerning the item mentioned above, from a historical conception of non-linear diachrony.

Um enfoque diacrônico de assim no domínio da junção

This study proposes, based on Halliday (1985) and Raible (1992, 2001), that the interpropositional patterns of assim are distributed in continuum, which is set among the representative usages of different types of interdependency, starting from the examples of domination relations of parataxis up to the examples of hypotatics, passing through the ones that are between the poles of the continuum. We will exemplify this paperwork starting from the functioning of the phrase assim que, describing its syntactic and semantic behavior in the selected corpus and in an evidence analysis of the linguistic changing process through grammaticalization, which infers its functioning as a secular connector in order to indicate its position held by this pattern in the continuum.

Trajetórias de mudança dos predicados acabar, acontecer e começar sob perspectiva discursivo-funcional

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

As construções verbais paratáticas: gramaticalização em italiano

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Um estudo sobre os diferentes valores modais do verbo 'poder' em entrevistas jornalísticas do espanhol

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

A 12-Month Phase 3 Study of Pasireotide in Cushing's Disease

BACKGROUND Cushing's disease is associated with high morbidity and mortality. Pasireotide, a potential therapy, has a unique, broad somatostatin-receptor-binding profile, with high binding affinity for somatostatin-receptor subtype 5. METHODS In this double-blind, phase 3 study, we randomly assigned 162 adults with Cushing's disease and a urinary free cortisol level of at least 1.5 times the upper limit of the normal range to receive subcutaneous pasireotide at a dose of 600 mu g (82 patients) or 900 mu g (80 patients) twice daily. Patients with urinary free cortisol not exceeding 2 times the upper limit of the normal range and not exceeding the baseline level at month 3 continued to receive their randomly assigned dose; all others received an additional 300 mu g twice daily. The primary end point was a urinary free cortisol level at or below the upper limit of the normal range at month 6 without an increased dose. Open-label treatment continued through month 12. RESULTS Twelve of the 82 patients in the 600-mu g group and 21 of the 80 patients in the 900-mu g group met the primary end point. The median urinary free cortisol level decreased by approximately 50% by month 2 and remained stable in both groups. A normal urinary free cortisol level was achieved more frequently in patients with baseline levels not exceeding 5 times the upper limit of the normal range than in patients with higher baseline levels. Serum and salivary cortisol and plasma corticotropin levels decreased, and clinical signs and symptoms of Cushing's disease diminished. Pasireotide was associated with hyperglycemia-related adverse events in 118 of 162 patients; other adverse events were similar to those associated with other somatostatin analogues. Despite declines in cortisol levels, blood glucose and glycated hemoglobin levels increased soon after treatment initiation and then stabilized; treatment with a glucose- lowering medication was initiated in 74 of 162 patients. CONCLUSIONS The significant decrease in cortisol levels in patients with Cushing's disease who received pasireotide supports its potential use as a targeted treatment for corticotropinsecreting pituitary adenomas. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT00434148.)

Distribution of major elements in Atlantic surface sediments (36 degrees N-49 degrees S): Imprint of terrigenous input and continental weathering

Numerous studies use major element concentrations measured on continental margin sediments to reconstruct terrestrial climate variations. The choice and interpretation of climate proxies however differ from site to site. Here we map the concentrations of major elements (Ca, Fe, Al, Si, Ti, K) in Atlantic surface sediments (36 degrees N-49 degrees S) to assess the factors influencing the geochemistry of Atlantic hemipelagic sediments and the potential of elemental ratios to reconstruct different terrestrial climate regimes. High concentrations of terrigenous elements and low Ca concentrations along the African and South American margins reflect the dominance of terrigenous input in these regions. Single element concentrations and elemental ratios including Ca (e. g., Fe/Ca) are too sensitive to dilution effects (enhanced biological productivity, carbonate dissolution) to allow reliable reconstructions of terrestrial climate. Other elemental ratios reflect the composition of terrigenous material and mirror the climatic conditions within the continental catchment areas. The Atlantic distribution of Ti/Al supports its use as a proxy for eolian versus fluvial input in regions of dust deposition that are not affected by the input of mafic rock material. The spatial distributions of Al/Si and Fe/K reflect the relative input of intensively weathered material from humid regions versus slightly weathered particles from drier areas. High biogenic opal input however influences the Al/Si ratio. Fe/K is sensitive to the input of mafic material and the topography of Andean river drainage basins. Both ratios are suitable to reconstruct African and South American climatic zones characterized by different intensities of chemical weathering in well-understood environmental settings.

Duplications of BHLHA9 are associated with ectrodactyly and tibia hemimelia inherited in non-Mendelian fashion

Background Split-hand/foot malformation (SHFM)-also known as ectrodactyly-is a congenital disorder characterised by severe malformations of the distal limbs affecting the central rays of hands and/or feet. A distinct entity termed SHFLD presents with SHFM and long bone deficiency. Mouse models suggest that a defect of the central apical ectodermal ridge leads to the phenotype. Although six different loci/mutations (SHFM1-6) have been associated with SHFM, the underlying cause in a large number of cases is still unresolved. Methods High resolution array comparative genomic hybridisation (CGH) was performed in patients with SHFLD to detect copy number changes. Candidate genes were further evaluated for expression and function during limb development by whole mount in situ hybridisation and morpholino knock-down experiments. Results Array CGH showed microduplications on chromosome 17p13.3, a locus previously associated with SHFLD. Detailed analysis of 17 families revealed that this copy number variation serves as a susceptibility factor for a highly variable phenotype with reduced penetrance, particularly in females. Compared to other known causes for SHFLD 17p duplications appear to be the most frequent cause of SHFLD. A similar to 11.8 kb minimal critical region was identified encompassing a single gene, BHLHA9, a putative basic loop helix transcription factor. Whole mount in situ hybridisation showed expression restricted to the limb bud mesenchyme underlying the apical ectodermal ridge in mouse and zebrafish embryos. Knock down of bhlha9 in zebrafish resulted in shortening of the pectoral fins. Conclusions Genomic duplications encompassing BHLHA9 are associated with SHFLD and non-Mendelian inheritance characterised by a high degree of non-penetrance with sex bias. Knock-down of bhlha9 in zebrafish causes severe reduction defects of the pectoral fin, indicating a role for this gene in limb development.

Regulation und Funktion von hunchback in Neuroblasten-Zellstammbäumen von Drosophila melanogaster

In Drosophila melanogaster wird das Nervensystem von neuralen Vorläuferzellen, den Neuroblasten (NB) gebildet. Diese teilen sich im Stammzellmodus und bringen bei jeder Teilung eine Ganglienmutterzelle (GMZ) hervor. GMZ teilen sich einmal und generieren zwei Zellen, die ein neuronales und/oder gliales Schicksal annehmen. Die Reihenfolge in der ein NB GMZ generiert, ist vermutlich ein zellautonomer Prozess, der an die transiente und sequenzielle Expression der Transkriptionsfaktoren Hunchback (Hb), Krüppel (Kr), Pdm, Castor (Cas) und Grainy head (Grh) gekoppelt ist. Hb ist der erste Faktor dieser Genkaskade. Damit der NB zur nächsten zeitlichen Identität übergehen kann, die in der Regel von Kr bestimmt wird, muss die Hb-Expression im NB beendet werden. Das Abschalten wird transkriptionell reguliert und ist von einer vorhergehenden Mitose abhängig. Im Gegensatz zum NB wird in der GMZ, die bei dieser Teilung entsteht, die Hb-Expression beibehalten. In der vorliegenden Arbeit wurde der Mitose-abhängige Mechanismus aufgeklärt, durch den eine selektive Abschaltung von hb im NB erfolgt, nicht aber in der GMZ. Der Transkriptionsfaktor Seven-up (Svp) beendet die hb-Expression im NB. svp wird vor der entscheidenden Zellteilung im NB transkribiert, aber kaum translatiert. Nach erfolgter Zellteilung wird Svp verstärkt translatiert und sowohl im NB als auch in der neu entstandenen GMZ exprimiert. Im NB führt die Svp-Funktion zur Abschaltung von Hb. In der ebenfalls Svp-positiven GMZ verhindert jedoch Prospero (Pros), das während der Teilung in diese Zelle segregiert ist, die Aktivität von Svp. Um zu überprüfen, ob Svp und Pros die Transkription von Hb entweder direkt oder indirekt regulieren, wurde eine Enhancerfragment-Analyse durchgeführt. Durch diese Unter-suchungen sollten relevante regulatorische Bereiche des hb-Gens identifiziert werden. Zusätzlich zu den bereits bekannten Regionen im 5´-Bereich von hb, konnten 3´ des transkribierten Bereiches weitere nervensystemspezifische Enhancerelemente gefunden werden. Neben der Spezifizierung von früh geborenen Nachkommen von NB hat Hb im Nervensystem die Funktion, den multipotenten Zustand junger NB aufrecht zu erhalten. Um den Beitrag einzelner Domänen des Hb-Proteins an diesen Aufgaben zu bestimmen, wurden verschiedene hb-Varianten, in denen spezifische Domänen deletiert bzw. mutiert waren, im NB7-1 überexprimiert und auf die Induktion von „frühem“ Schicksal getestet. In einem zweiten Ansatz wurden mutante hb-Allele analysiert. Es stellte sich heraus, dass der D-Box eine entscheidende Rolle bei der Spezifizierung von „frühem“ Schicksal zukommt. Die terminalen Zinkfinger sind vermutlich in die Aufrechterhaltung der Kompetenz von NB involviert. Eine Deletion der A-Box erhöht möglicherweise die Aktivität des Hb-Proteins.