1,802 research outputs found

    The Maritime Basis of American Security in East Asia

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    East Asia is the one part of the world where great-power war remains thinkable. That is because it is the only region where the Cold War left a residue of unresolved great-power strategic tensions. The United States must engage itself, and maintain a balance of power, in the western Pacific. To do so, it still needs large resources of maritime power, and nuclear weapons

    Compound C inhibits nonsense-mediated RNA decay independently of AMPK

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    The nonsense mediated RNA decay (NMD) pathway safeguards the integrity of the transcriptome by targeting mRNAs with premature translation termination codons (PTCs) for degradation. It also regulates gene expression by degrading a large number of non-mutant RNAs (including mRNAs and noncoding RNAs) that bear NMD-inducing features. Consequently, NMD has been shown to influence development, cellular response to stress, and clinical outcome of many genetic diseases. Small molecules that can modulate NMD activity provide critical tools for understanding the mechanism and physiological functions of NMD, and they also offer potential means for treating certain genetic diseases and cancer. Therefore, there is an intense interest in identifying small-molecule NMD inhibitors or enhancers. It was previously reported that both inhibition of NMD and treatment with the AMPK-selective inhibitor Compound C (CC) induce autophagy in human cells, raising the possibility that CC may be capable of inhibiting NMD. Here we show that CC indeed has a NMD-inhibitory activity. Inhibition of NMD by CC is, however, independent of AMPK activity. As a competitive ATP analog, CC does not affect the kinase activity of SMG1, an essential NMD factor and the only known kinase in the NMD pathway. However, CC treatment down-regulates the protein levels of several NMD factors. The induction of autophagy by CC treatment is independent of ATF4, a NMD target that has been shown to promote autophagy in response to NMD inhibition. Our results reveal a new activity of CC as a NMD inhibitor, which has implications for its use in basic research and drug development

    Phylogenetic placement and generic re-circumscriptions of the multilocular genera Arenifera, Octopoma and Schlechteranthus (Aizoaceae: Ruschieae): Evidence from anatomical, morphological and plastid DNA data

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    "Ruschieae is the largest tribe in the highly speciose subfamily Ruschioideae (Aizoaceae). A generic-level phylogeny for the tribe was recently produced, providing new insights into relationships between the taxa. Octopoma and Arenifera are woody shrubs with multilocular capsules and are distributed across the Succulent Karoo. Octopoma was shown to be polyphyletic in the tribal phylogeny, but comprehensive sampling is required to confirm its polyphyly. Arenifera has not previously been sampled and therefore its phylogenetic placement in the tribe is uncertain. In this study, phylogenetic sampling for nine plastid regions (atpB-rbcL, matK, psbJ-petA, rpl16, rps16, trnD-trnT, trnL-F, trnQUUG-rps16, trnS-trnG) was expanded to include all species of Octopoma and Arenifera, to assess phylogenetic placement and relationships of these genera. Three phylogenetic analyses were carried out, maximum parsimony, maximum likelihood and Bayesian inference. Leaf anatomical sections were studied to further inform generic circumscriptions. The phylogenies showed Octopoma to be polyphyletic, with the type, O. octojuge, and the related O. nanum, resolved as sister to Zeuktophyllum and Smicrostigma, while the other species were placed in the Conophytum-clade. Arenifera was also shown to be polyphyletic, with the type, A. pillansii, placed in the xeromorphic-clade, and the remainder of the species recovered among the Octopoma species in the Conophytum-clade (forming the Octopoma subglobosum-Arenifera spinescens subclade). Generic affinities of the O. subglobosum-A. spinescens subclade were assessed in relation to the sister taxon Schlechteranthus. The leaf anatomy was found to be informative within the study group. Bladder cells were observed in Arenifera pillansii, a hypodermis in Little Karoo Octopoma (O. octojuge, O. nanum, O. quadrisepalum) and epidermal cells forming blunt papillae in Schlechteranthus and the O. subglobosum-A. spinescens subclade. Upon assessment of the anatomical, morphological and phylogenetic data, Schlechteranthus is here expanded to include the species in the O. subglobosum-A. spinescens subclade. Eight new combinations are made in Schlechteranthus. As a result, Arenifera is again monotypic and the circumscription of Octopoma is refined to include three species restricted to the Little Karoo. Two subgenera within Schlechteranthus s.l. (subg. Schlechteranthus, subg. Microphyllus) are erected to accommodate differences in leaf size, capsule size, closing body size and locule number."Web of Scienc

    Automated requirements analysis for a molecular watchdog timer

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    Dynamic systems in DNA nanotechnology are often programmed using a chemical reaction network (CRN) model as an intermediate level of abstraction. In this paper, we design and analyze a CRN model of a watchdog timer, a device commonly used to monitor the health of a safety critical system. Our process uses incremental design practices with goal-oriented requirements engineering, software verification tools, and custom software to help automate the software engineering process. The watchdog timer is comprised of three components: an absence detector, a threshold filter, and a signal amplifier. These components are separately designed and verified, and only then composed to create the molecular watchdog timer. During the requirements-design iterations, simulation, model checking, and analysis are used to verify the system. Using this methodology several incomplete requirements and design flaws were found, and the final verified model helped determine specific parameters for biological experiments

    Four Corners: Reflections of Trans and Nonbinary (TNB) Communities Navigating The COVID-19 Pandemic

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    This report is part of a rapid response research project designed to better understand some of the experiences of trans and nonbinary (TNB) people during the COVID-19 pandemic. This preliminary report is based on our initial stages of analysis. The process of reducing abundant and dynamic narratives into a research report is difficult and always partial. We start with who we are, how we did our research, what we found, and what curiosities we have moving forward with our TNB-led health research. We honor each and every person that took the time to share their stories with us and feel deeply interconnected to each participant. There are many ways to interpret and tell these stories, and this is one of them

    Food and mood:how do diet and nutrition affect mental wellbeing?

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    Poor nutrition may be a causal factor in the experience of low mood, and improving diet may help to protect not only the physical health but also the mental health of the population. Depression and anxiety are the most common mental health conditions worldwide, making them a leading cause of disability.1 Even beyond diagnosed conditions, subclinical symptoms of depression and anxiety affect the wellbeing and functioning of a large proportion of the population.2 Therefore, new approaches to managing both clinically diagnosed and subclinical depression and anxiety are needed

    Recommendations for measuring tennis racket parameters

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    Tennis rackets have advanced significantly since the invention of the game in 1874, including innovations in both shape and materials. Advances in these design parameters have implications for racket performance, especially swing speed. This study tested one hundred rackets, spanning brands and eras, using simple, portable instruments in order to pilot protocols and make recommendations for streamlining testing procedures for tennis rackets. A wide range of properties were measured and documented for each racket. We suggest that since Transverse and Lateral Moment of Inertia are well correlated, measuring both is not necessary when processing a large number of rackets. In addition, it is also possible to predict the Transverse Moment of Inertia well from models that use simple dimension and mass measurements, which may be preferable in larger studies. Exploring the use of more complex modelling will allow us to better understand the impact of tennis racket design on performance in the future

    Four Corners: Health Research Priorities Among TNB Communities

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    Transgender and nonbinary (TNB) people experience striking inequities in health and healthcare. In the United States, these inequities are amplified among TNB Black, Indigenous people of color (BIPOC) and TNB people with disabilities, highlighting the need for all TNB health equity initiatives to recognize racism, ableism, and other intersecting forms of oppression. Despite a recent increase in TNB health research, there is a lack of peer-reviewed literature that considers priority issues and accountable research practices from the perspectives of TNB people, and particularly TNB BIPOC and people with disabilities.In 2018, four federally qualified health centers (FQHCs) specializing in LGBTQ care across the United States: Howard Brown Health in Chicago, Whitman-Walker Institute in the District of Columbia, Los Angeles LGBT Center in Los Angeles, and Legacy Community Health in Houston, partnered to form the Four Corners: TNB Health Research Advisory Network. Four Corners is a 16-member network consisting of one researcher, one clinician, and two TNB community members from each FQHC, all of which reside in a geographically distinct region and serve a highly diverse TNB patient panel. Four Corners envisions a world where all TNB people have access to safe, relevant, and equitable healthcare and aims to advance health research by involving TNB community members, researchers, and clinicians as equal partners in the research process.In the summer of 2019, Four Corners conducted eight focus groups, two in each city of participating sites, in order to explore health and research priorities, participants' prior experiences with research, and preferences for research dissemination. Focus groups were facilitated by two TNB project staff and included 65 participants, all of whom were at least eighteen years of age and selfidentified as transgender, nonbinary, or gender nonconforming. Participants were recruited via flyers posted at the four FQHCs and social media advertisements. Focus groups were audio recorded and transcribed
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