Translational Scheme Research Articles

A Modal Translational Semantics in Prior’s “Symbolism and Analogy”

This paper explores a modal semantics Arthur Prior developed in his 1957 lecture, “Symbolism and Analogy.” Prior’s semantics employs a translational scheme where certain modal axioms are translated as sentences in an easily understood language. Using Prior’s semantics, we show that one can distinguish between modal logics like D, M, T, S4, and S5 without recourse to possible worlds. Finally, given the current conception of what a semantics ought to be, we consider whether Prior’s modal semantics is indeed a semantics.

Effectiveness and co-benefits of a telephone-based intervention in reducing obesity risk of children aged 2–4 years: findings from a pragmatic randomised controlled trial during the COVID-19 pandemic in Australia

BackgroundEvidence of effective early childhood obesity prevention is scarce and mainly derived from face-to-face interventions. However, the COVID-19 pandemic drastically reduced face-to-face health programmes globally. This study assessed effectiveness of a telephone-based intervention in reducing obesity risk of young children. MethodsWe adapted a study protocol (developed before the pandemic) and conducted a pragmatic randomised controlled trial of 662 women with children aged 2 years (mean age 24·06 months [SD 0·69]) during March, 2019, and October, 2021, extending the original planned intervention of 12 months to 24 months. The adapted intervention comprised five telephone-based support sessions plus text messages over a 24-month period (at child ages 24–26 months, 28–30 months, 32–34 months, 36–38 months, and 42–44 months). The intervention group (n=331) received staged telephone plus SMS support regarding healthy eating, physical activity, and information about COVID-19. The control group (n=331) received four staged mail-outs on information not related to the obesity prevention intervention, such as toilet training, language development, and sibling relationships, as a retention strategy. The intervention effects on BMI (primary outcome) and eating habits (secondary outcome), and perceived co-benefits, were evaluated using surveys and qualitative telephone interviews at 12 months and 24 months after baseline (age 2 years). The trial is registered with the Australian Clinical Trial Registry, ACTRN12618001571268. FindingsOf 662 mothers, 537 (81%) completed the follow-up assessments at 3 years, and 491 (74%) completed the follow-up assessment at 4 years. Multiple imputation analysis showed no significant difference in mean BMI between the groups. Among low-income families (ie, annual household income <AU$80 000) at age 3 years, the intervention was significantly associated with a lower mean BMI (16·26 kg/m2 [SD 2·22]) in the intervention group than in the control group (16·84 kg/m2 [2·37]; p=0·040), a difference of –0·59 (95% CI –1·15 to –0·03; p=0·040). Children in the intervention group were more likely not to eat in front of the television than the control group, with an adjusted odds ratio (aOR) of 2·00 (95% CI 1·33 to 2·99) at 3 years and an aOR of 2·50 (1·63 to 3·83) at 4 years. Qualitative interviews with 28 mothers revealed that the intervention increased their awareness, confidence, and motivation to implement healthy feeding practices, particularly for families from culturally diverse backgrounds (ie, speaking a language other than English at home). InterpretationA telephone-based intervention was well received by the mothers who participated in the study. The intervention could reduce children's BMI from low-income families. Telephone-based support targeted at low-income families and families from culturally diverse backgrounds could reduce current inequalities in childhood obesity. FundingThe trial was funded under the NSW Health Translational Research Grant Scheme 2016 (number TRGS 200) and also by a National Health and Medical Research Council Partnership grant (number 1169823).

Drug discovery and development scheme for liver-targeting bridged nucleic acid antisense oligonucleotides

Antisense oligonucleotides (ASOs) containing bridged nucleic acids (BNAs) have been proven to be very powerful. However, ensuring a reliable discovery and translational development scheme for this class of ASOs with wider therapeutic windows remains a fundamental challenge. We here demonstrate the robustness of our scheme in the context of the selection of ASOs having two different BNA chemistries (2,′4′-BNA/locked nucleic acid [LNA] and amido-bridged nucleic acid [AmNA]) targeting human proprotein convertase subtilisin/kexin type 9 (PCSK9). The scheme features a two-step process, including (1) a unique and sensitive in vitro screening approach, called Ca2+ enrichment of medium (CEM) transfection, and (2) a ligand-targeted drug delivery approach to better reach target tissues, averting unintended accumulation of ASOs. Using CEM screening, we identified a candidate ASO that shows >70% cholesterol-lowering action in monkeys. An N-acetylgalactosamine (GalNAc) ligand then was appended to the candidate ASO to further broaden the therapeutic margin by altering the molecule’s pharmacokinetics. The GalNAc conjugate, HsPCSK9-1811-LNA, was found to be at least ten times more potent in non-human primates (compared with the unconjugated counterpart), with reduced nephrotoxicity in rats. Overall, we successfully showed that our drug development scheme is better suited for selecting clinically relevant BNA-based ASOs, especially for the treatment of liver-associated diseases.

New Orleans'da Bir Don Quijote Romanı: A Confederacy of Dunces

Don Quijote romanı dünya edebiyatında kendisinden sonra gelen birçok eseri çeşitli yönlerden etkilemiştir. Özellikle yarattığı kahraman prototipiyle birçok edebi kahramana örnek olmuştur. Kendi hayallerinin peşinde koşan, idealist, içinde yaşadığı toplumla çelişen bir kahraman örneğidir bu. Don Quijote’den yüzyıllar sonra, bambaşka bir coğrafyada basılan bir roman da birçok açıdan bu ilk örnek ile benzerlikler taşır. 1980 yılında New Orleans’da geçen A Confederacy of Dunces romanı barındırdığı pikaresk, karnavalesk ve grotetesk ögelerle bu romanla benzerlikler taşır. Ignatius’da aynı Don Quijote gibi bir pikarodur. Ancak o da kendi ideal dünyasında yaşamaktadır, çevresindeki herkesin, yani “alıkların” ona karşı olduğunu sanır. Her iki romanda da ikili karşıtlıklar romanların karnavalesk tarafını ortaya çıkarır. Hayal, gerçek, delilik, akıl…gibi zıt durumlar eleştirilir. Son olarak da her iki roman da birer grotesk realizm örneğidir. Topluma uymayan dış görünüşleri, beden faaliyetleri ve başarısızlıkla geçen maceralarıyla A Confederacy of Dunces romanı adeta yirminci yüzyılda, New Orleans’da yaşayan bir Don Quijote’yi anlatır.

CHild and Adolescent Health Pathways study: a pragmatic implementation study

Childhood obesity remains one the most important public health challenges globally, potentially affecting 60 million children by 2020. Increasingly, children are becoming overweight at a relatively young age, which affects metabolic health, both in childhood and later life. In New South Wales NSW, Australia, one in four school-aged children and adolescents are overweight or have obesity. Noticeably, the prevalence of severe obesity continues to increase in this age group. Despite this prevalence, weight issues are rarely recognised or managed when patients attend clinical services and there are few appropriate clinical services available. Several Local Health Districts LHDs, across socio-economic and culturally diverse populations, are implementing a new service aiming to deliver integrated weight management services for children and adolescents. This presents a unique opportunity to research the implementation and integration of these new services alongside established services to determine the clinical effectiveness and impact of the services. No such research has been undertaken previously in Australia. Methods: This study will ascertain what factors affect acceptability, reach, and participation and retention rates and measure clinical effectiveness through changes in child weight outcomes. The study aims to: Audit existing tertiary and secondary care models for managing children above a healthy weight. Evaluate the newly established secondary care clinics, models of care and healthcare pathways. Determine what factors, including acceptability, reach, participation and retention rates, effectiveness and sustainability, are important for different models of care through focus groups and stakeholder interviews. Undertake economic analysis to determine cost of services. A range of process and economic cost measures will be collected from: i routinely collected data; ii document review; and iii surveys, key informant interviews and focus groups with clinical staff, health service managers, and patients and families. For the clinical effectiveness component, the primary outcome will be change in body mass index, adjusted for age and sex, at 6 months from baseline. The secondary outcomes will be change in key food and physical activity behaviours at 6 months from baseline. The study has successfully secured funding through the NSW Health Translational Research Grant Scheme. Outcomes: The findings will provide an understanding of the most effective design and delivery of local services, enhancing the accessibility, acceptability, reach and impact of paediatric weight management services. This will enable recommendations to be made for future services planning to optimise scalability and sustainability of integrated, responsive and effective care of paediatric patients with overweight or obesity.

Simulation of Translational Data Acquisition Scheme of X-Ray Computed Tomography for Application in NDT

The invention of computed tomography some few decades ago, coupled with its applications in the field of non-destructive testing for industrial objects inspection has revolutionized the way inspections were formerly done. Despite the conventional data acquisition scheme which is integrated with a rotational stage in between the source and the detector works perfectly for small and lighter objects, hence, it seems impossible to investigate complicated, bulky objects with interconnected unbalanced composites. Moreover, it will be very expensive to harnessed technologies into the rotational stage which can be incorporated into this conventional technique with an optimum degree of accuracy. Therefore, this paper will consider the translational data acquisition scheme which is proven mathematically as an alternative method to the conventional technique [1]. This translational scheme takes into account the variations and the magnification of both the source x-ray and the detector around the object and then proceeded by scans from different focal distances. Python packages with necessary plugins were used in implementing the reconstructive algorithm generated in simulating and modelling a suitable image of inspected object.

Translational Research Grants Scheme (TRGS): a new approach to strengthening health system research capacity.

Bridging the 'gap' between research evidence and the complexities of policy and practice is central to health improvement. The Translational Research Grants Scheme (TRGS) in New South Wales (NSW), Australia, is a funding scheme aimed at reducing the time between research generation and translation to policy and practice. The TRGS is also an important part of NSW Health's efforts to harness and strengthen research capacity to improve health service delivery. A document review and interviews (n = 12) with key stakeholders were undertaken following the first round of TRGS funding in November 2016. The communications from continuing quality improvement processes over the three funding rounds have provided further insight. A total of 53 projects have been funded under the scheme, with recipients across many NSW Health organisations. NSW Health has committed more than $24 million to date. Round one of the TRGS was received well by the policy makers, Local Health Districts and research stakeholders interviewed. Of particular note were: the requirement for Chief Executives to demonstrate strong support for the implementation of findings; requirements to partner with state-wide policy leads and clinical networks; and capacity-building outcomes of the scheme. The ongoing quality improvement processes indicate that the program continues to be well received, with improvements to partnership arrangements, and an acknowledgement of the challenge that arises because the scheme, by nature of its capacity-building aim, attracts proposals from a range of research experience. The TRGS is filling an important gap in the research funding landscape in NSW and is well regarded by stakeholders. To ensure that the TRGS is achieving its intended aims, an evaluation of the impact of the scheme will take place during 2018-19.

Trajectory Tracking Control For Underactuated Thrust-Propelled Aerial Vehicles

We present a trajectory tracking control scheme for a class of underactuated thrust propelled aerial vehicles. The class of aerial vehicles is modeled as a rigid body with a constant thrust direction in the body frame. The attitude of the rigid is fully actuated while only one translational degree of freedom is actuated. Thus, the combined translational and rotational motion is underactuated. The tracking control problem is solved in a two-step approach. First, a translational control scheme that tracks the desired position trajectory is constructed assuming the translational dynamics to be fully actuated. The magnitude of the translational control input is used as the magnitude of the control thrust. Second, the unit vector representing the direction of the translational control input is used as the desired thrust direction. An asymptotically stable attitude control scheme is developed in S2, such that the body fixed thrust direction tracks the desired thrust direction. The overall closed-loop system is analytically shown to be asymptotically tracking the desired position trajectory. The results are validated by numerical simulations.

Ribosome Elongation Stall Directs Gene-specific Translation in the Integrated Stress Response

Upon exposure to environmental stress, phosphorylation of the α subunit of eIF2 (eIF2α-P) represses global protein synthesis, coincident with preferential translation of gene transcripts that mitigate stress damage or alternatively trigger apoptosis. Because there are multiple mammalian eIF2 kinases, each responding to different stress arrangements, this translational control scheme is referred to as the integrated stress response (ISR). Included among the preferentially translated mRNAs induced by eIF2α-P is that encoding the transcription factor CHOP (DDIT3/GADD153). Enhanced levels of CHOP promote cell death when ISR signaling is insufficient to restore cell homeostasis. Preferential translation of CHOP mRNA occurs by a mechanism involving ribosome bypass of an inhibitory upstream ORF (uORF) situated in the 5'-leader of the CHOP mRNA. In this study, we used biochemical and genetic approaches to define the inhibitory features of the CHOP uORF and the biological consequences of loss of the CHOP uORF on CHOP expression during stress. We discovered that specific sequences within the CHOP uORF serve to stall elongating ribosomes and prevent ribosome reinitiation at the downstream CHOP coding sequence. As a consequence, deletion of the CHOP uORF substantially increases the levels and modifies the pattern of induction of CHOP expression in the ISR. Enhanced CHOP expression leads to increased expression of key CHOP target genes, culminating in increased cell death in response to stress.

The Circumscribed Infinites Scheme (CIS)

The purpose of this paper is twofold: on the one hand, it seeks to introduce and explain the CIS (Circumscribed Infinites Scheme), a deconstructive scheme for translating poetry; and, on the other, it aims at analyzing the scheme’s impact on the translation into English of a variety of poems by Jorge Luis Borges. Devised by the present author, who is also responsible for the translations analyzed, the CIS is a translational scheme whereby meaning is understood as an inexhaustible textual effect, and which, in its theoretical elucidation, seeks to raise the practicing translator’s awareness of the control he or she might have over the degree of infinite exegetic circumscription—and subsequent infinite exegetic recreation—during the translation process.

The Dependence of the Circumnuclear Coma Structure on the Properties of the Nucleus: III. First Modeling of a CO-Dominated Coma, with Application to Comets 46 P/Wirtanen and 29 P/Schwassmann–Wachmann I

We present the first gasdynamic simulations of the coma formed by the diffusion from a comet nucleus interior of a volatile molecule at large heliocentic distance. The method used is a generalization of that described in J. F. Crifoet al.(1995,Icarus116, 77–112). The molecule is assumed to be CO. Threehomogeneousnuclei with the same mass, butdifferent shapes, are considered. Molecular production rates and nucleus sizes appropriate for Comets 46 P/Wirtanen at 3 AU from the Sun and 29 P Schwassmann–Wachmann I at 6 AU are considered in alternance. The main results are: (1) a fluid region surrounds the whole nucleus (not only the sunward hemisphere) even for production rates in the 1025molecule per second range; (2) the densest part of the near-nucleus coma is not necessarily the sunward hemisphere; (3) strong day-to-night asymmetries in the CO velocity are predicted, which are due to the surfacetemperaturedistribution,notto differences in surface gas production rate from point to point; (4) even in the case of a near-uniform production of CO over the surface, weak shock structures appear in the coma at the terminator, due to the surface temperature gradient (thus, even a uniform gas production over a spherical nucleus doesnotproduce a uniform coma!); (5) shock structures are also formed in the vicinity of surface concavities, even if the gas production is uniform; (6) the ejection of dust grains up to at least millimeter sizes is possible from both the sunward and the anti-sunward side of the nucleus; (7) the terminal dust grain velocities are comparable to those computed for a H2O-dominated coma at a similar gas production rate. The reasons why we believe that CO is the best candidate for forming the distant comas of comets are discussed at length, but we also indicate why the present results are not critically affected if CO is replaced by another candidate volatile molecule (e.g., CO2, HCN, H2CO…), or by a mixture of such molecules. The CO velocities we derive for 29 P Schwassmann–Wachmann I are shown to be in excellent agreement with those experimentally derived for this comet (J. Crovisieret al.1995,Icarus115, 213–216; N. Biveret al.1997,Science275, 1915–1918); as regards the experimentally derived temperatures, we show that their interpretation is very complicated and will require, in particular, the incorporation in the present model of a gas translational relaxation scheme.

Expression of Aleutian mink disease parvovirus proteins in a baculovirus vector system

We have previously published a detailed transcription map of Aleutian mink disease parvovirus (ADV) and proposed a model for the translation of the two virion structural proteins (VP1 and VP2) and three nonstructural proteins (NS-1, NS-2, and NS-3) (S. Alexandersen, M. E. Bloom, and S. Perryman, J. Virol. 62:3684-3994, 1988). To verify and further characterize this model, we cloned the predicted open reading frames for NS-1, NS-2, NS-3, VP1-VP2, and VP2 alone into a recombinant baculovirus and expressed them in Sf9 insect cells. Expression of VP1-VP2 or VP2 alone in cDNA and in the genomic form was achieved. The expressed proteins had molecular weights similar to those of the corresponding proteins of wild-type ADV-G, although the ratio of VP1 to VP2 was altered. The recombinant baculovirus-expressed ADV VP1 and VP2 showed nuclear localization in Sf9 cells and were able to form particles indistinguishable, by electron microscopy, from wild-type virus. The large nonstructural protein, NS-1, showed predominantly nuclear localization in Sf9 cells when analyzed by immunofluorescence and had a molecular weight similar to that of wild-type ADV NS-1. Moreover, expression of NS-1 in Sf9 cells caused a change in morphology of the cells and resulted in 10-times-lower titers of recombinant baculovirus during infection, suggesting a cytostatic or cytotoxic action of this protein. The smaller NS-2 gene product seems to be located in the cytoplasm. When analyzed by Western immunoblotting, NS-2 comigrated with an approximately 16-kDa band seen in lysates of ADV-infected feline kidney cells. The putative NS-3 gene product exhibited a diffuse distribution in Sf9 cells and had a molecular weight of approximately 10,000. All of the expressed ADV-encoded proteins were recognized by sera from ADV-infected mink. Thus, expression of ADV cDNAs allowed assignment of the different mRNAs to the viral proteins observed during ADV infection in cell culture and supported our previously proposed ADV transcriptional and translational scheme. Moreover, the production of structural proteins from a full-length NS-2 mRNA may add to the repertoire of parvovirus gene expression.