The Trouble with "Articulatory" Pauses

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.The historical provenance of a minimum cut-off point (of about 0.25 sec) for pauses in temporal analyses of speech production is associated with Goldman-Eisler's usage. Her rationale was the predominance of articulatory pauses at lengths shorter than 0.25 sec. Both phonotactic facts and empirical analysis of several corpora of readings disconfirm this predominance with respect to pauses 0.13-0.25 sec in length. The vast majority of these pauses are found to be psychological; they are determined by syntax, punctuation, rhetorical and expressive emphasis, poetic format, and stylistic pecularities

Perforated tunnel exit regions and micro-pressure waves:geometrical influence

ACKNOWLEDGEMENTS The authors are grateful to the following bodies that provided financial support for the project: (i) China Scholarship Council, (ii) National Natural Science Foundation of China (Grant No. U1334201 and (iii) UK Engineering and Physical Sciences Research Council (Grant No. EP/G069441/1).Peer reviewedPublisher PD

Communication in refugee and migrant mental healthcare:A systematic rapid review on the needs, barriers and strategies of seekers and providers of mental health services

BackgroundMigrants and refugees may not access mental health services due to linguistic and cultural discordance between them and health and social care professionals (HSCPs). The aim of this review is to identify the communication needs and barriers experienced by third-country nationals (TCNs), their carers, and HSCPs, as well as the strategies they use and their preferences when accessing/providing mental health services and language barriers are present.MethodsWe undertook a rapid systematic review of the literature (01/01/2011 – 09/03/2022) on seeking and/or providing mental health services in linguistically discordant settings. Quality appraisal was performed, data was extracted, and evidence was reviewed and synthesised qualitatively.Results58/5,650 papers met the inclusion criteria. Both TCNs (and their carers) and HSCPs experience difficulties when seeking or providing mental health services and language barriers are present. TCNs and HSCPs prefer linguistically and culturally concordant provision of mental health services but professional interpreters are often required. However, their use is not always preferred, nor is it without problems.ConclusionsLanguage barriers impede TCNs’ access to mental health services. Improving language support options and cultural competency in mental health services is crucial to ensure that individuals from diverse linguistic and cultural backgrounds can access and/or provide high-quality mental health services

Presenilin Is the Molecular Target of Acidic γ-Secretase Modulators in Living Cells

The intramembrane-cleaving protease γ-secretase catalyzes the last step in the generation of toxic amyloid-β (Aβ) peptides and is a principal therapeutic target in Alzheimer's disease. Both preclinical and clinical studies have demonstrated that inhibition of γ-secretase is associated with prohibitive side effects due to suppression of Notch processing and signaling. Potentially safer are γ-secretase modulators (GSMs), which are small molecules that selectively lower generation of the highly amyloidogenic Aβ42 peptides but spare Notch processing. GSMs with nanomolar potency and favorable pharmacological properties have been described, but the molecular mechanism of GSMs remains uncertain and both the substrate amyloid precursor protein (APP) and subunits of the γ-secretase complex have been proposed as the molecular target of GSMs. We have generated a potent photo-probe based on an acidic GSM that lowers Aβ42 generation with an IC50 of 290 nM in cellular assays. By combining in vivo photo-crosslinking with affinity purification, we demonstrated that this probe binds the N-terminal fragment of presenilin (PSEN), the catalytic subunit of the γ-secretase complex, in living cells. Labeling was not observed for APP or any of the other γ-secretase subunits. Binding was readily competed by structurally divergent acidic and non-acidic GSMs suggesting a shared mode of action. These findings indicate that potent acidic GSMs target presenilin to modulate the enzymatic activity of the γ-secretase complex

Desenvolvimento do fruto da lichieira (Litchi chinensis Sonn.) 'Bengal'

Estudou-se o desenvolvimento do fruto da lichieira (Litchi chinensis Sonn.) 'Bengal'. Realizaram-se amostragens semanais, com início aos 35 dias após a antese e término no início da senescência dos frutos. A partir do 77º dia após a antese, os frutos foram decompostos em pericarpo, semente e arilo. A antese ocorreu na primeira semana de setembro. Foram ajustados modelos sigmoidais simples para acúmulo de matéria seca, comprimento e diâmetro. Para o acúmulo de matéria seca, uma fase inicial, de crescimento lento, prolongou-se até o 63º dia após a antese e coincidiu com um período de intensa queda natural de frutos. Do 63º ao 98º dia após a antese, houve uma fase de rápido acúmulo de matéria seca. Até o 77º dia, pericarpo e semente foram os principais responsáveis pelo acúmulo de matéria seca. Oitenta e oito por cento do comprimento e 65% do diâmetro máximos foram atingidos nesse período. Do 84º ao 98º dia após a antese, o desenvolvimento do fruto foi determinado basicamente pelo arilo. As dimensões e a matéria seca do fruto estabilizaram-se a partir do 98º dia após a antese. O ponto de colheita comercial dos frutos, caracterizado pela coloração avermelhada do pericarpo, ocorreu a partir do 112º dia após a antese. Verificou-se um quadro senescente nos frutos a partir do 119º dia após a antese.It was studied the fruit development in 'Bengal' litchi (Litchi chinensis Sonn.). The samples were taken weekly 35 days after anthesis until the beginning of fruit senescence. From the 77th day after anthesis, fruits were decomposed in pericarp, aril and seed. Anthesis occurred in the first week of September. The fruit dry matter, length and diameter followed a single-sigmoid pattern. For dry matter accumulation, an initial phase, of slow growth, ended the 63rd day after anthesis and was coincident with a period of intense fruit drop. The next phase occurred from the 63rd to the 98th day and showed a rapid dry matter accumulation. Until the 77th day, the main increment in fruit dry matter was due to pericarp and seed growth. Eighty eight percent of the maximum length and 65% of the maximum diameter were reached at the end of this phase. From the 84th until the 98th day after anthesis, fruit growth was determined, basically, by aril. Fruit dimensions and dry matter were stabilized after the 98th day. The commercial harvest of the fruits, characterized by the reddish color of the pericarp, occurred at the 112th day after anthesis. Fruits at the 119th day after anthesis were senescent

DOGS: Reaction-Driven de novo Design of Bioactive Compounds

We present a computational method for the reaction-based de novo design of drug-like molecules. The software DOGS (Design of Genuine Structures) features a ligand-based strategy for automated ‘in silico’ assembly of potentially novel bioactive compounds. The quality of the designed compounds is assessed by a graph kernel method measuring their similarity to known bioactive reference ligands in terms of structural and pharmacophoric features. We implemented a deterministic compound construction procedure that explicitly considers compound synthesizability, based on a compilation of 25'144 readily available synthetic building blocks and 58 established reaction principles. This enables the software to suggest a synthesis route for each designed compound. Two prospective case studies are presented together with details on the algorithm and its implementation. De novo designed ligand candidates for the human histamine H4 receptor and γ-secretase were synthesized as suggested by the software. The computational approach proved to be suitable for scaffold-hopping from known ligands to novel chemotypes, and for generating bioactive molecules with drug-like properties

The Reading Palaeofire Database : an expanded global resource to document changes in fire regimes from sedimentary charcoal records

Sedimentary charcoal records are widely used to reconstruct regional changes in fire regimes through time in the geological past. Existing global compilations are not geographically comprehensive and do not provide consistent metadata for all sites. Furthermore, the age models provided for these records are not harmonised and many are based on older calibrations of the radiocarbon ages. These issues limit the use of existing compilations for research into past fire regimes. Here, we present an expanded database of charcoal records, accompanied by new age models based on recalibration of radiocarbon ages using IntCal20 and Bayesian age-modelling software. We document the structure and contents of the database, the construction of the age models, and the quality control measures applied. We also record the expansion of geographical coverage relative to previous charcoal compilations and the expansion of metadata that can be used to inform analyses. This first version of the Reading Palaeofire Database contains 1676 records (entities) from 1480 sites worldwide. The database (RPDv1b - Harrison et al., 2021) is available at https://doi.org/10.17864/1947.000345.Peer reviewe

Identifying moderators of brand attachment for driving customer purchase intention of original vs counterfeits of luxury brands

Few studies have examined the relationships between brands and consumers in the context of counterfeiting. In this context, this research aims to explore how the attachment of a consumer with a luxury brand can affect her/his decision to buy counterfeits, and how this relates to her/his public self-consciousness. Two survey based studies were conducted among potential counterfeit buyers in Brazil. Innovatively, this research provides convincing implications for the need to differentiate counterfeiting theory between emerging and developed economies. Evidence of the positive impact of actual self-congruence and ideal self-congruence on brand attachment to luxury brands in emerging economies is provided. Interestingly, the results demonstrate that the purchase of counterfeits is a more hedonic process compared to the purchase of originals (study 1). Moreover, the effect of brand attachment on the willingness to buy counterfeits may vary according to how attachment is measured (study 2). Producing increments in the emotional brand attachment level can reduce the behavioral intentions of purchasing counterfeits. Hence, the findings suggest that the creation of emotional links with brands can be an appropriate strategy to reduce counterfeiting