Neuromorphic computers could overcome efficiency bottlenecks inherent to conventional computing through parallel programming and readout of artificial neural network weights in a crossbar memory ...array. However, selective and linear weight updates and <10-nanoampere read currents are required for learning that surpasses conventional computing efficiency. We introduce an ionic floating-gate memory array based on a polymer redox transistor connected to a conductive-bridge memory (CBM). Selective and linear programming of a redox transistor array is executed in parallel by overcoming the bridging threshold voltage of the CBMs. Synaptic weight readout with currents <10 nanoamperes is achieved by diluting the conductive polymer with an insulator to decrease the conductance. The redox transistors endure >1 billion write-read operations and support >1-megahertz write-read frequencies.
Abstract A growing body of evidence links type-2 diabetes (T2D) with dementia and neurodegenerative diseases such as Alzheimer's disease (AD). AD is the most common form of dementia and is ...characterised neuropathologically by the accumulation of extracellular beta amyloid (Aβ) peptide aggregates and intracellular hyper-phosphorylated tau protein, which are thought to drive and/or accelerate inflammatory and oxidative stress processes leading to neurodegeneration. Although the precise mechanism remains unclear, T2D can exacerbate these neurodegenerative processes. Brain atrophy, reduced cerebral glucose metabolism and CNS insulin resistance are features of both AD and T2D. Cell culture and animal studies have indicated that the early accumulation of Aβ may play a role in CNS insulin resistance and impaired insulin signalling. From the viewpoint of insulin resistance and impaired insulin signalling in the brain, these are also believed to initiate other aspects of brain injury, including inflammatory and oxidative stress processes. Here we review the clinical and experimental pieces of evidence that link these two chronic diseases of ageing, and discuss underlying mechanisms. The evaluation of treatments for the management of diabetes in preclinical, and clinical studies and trials for AD will also be discussed.
Granulosa cell tumors of the ovary (GCT) comprise a distinct subset of ovarian cancers that account for approximately 5% of all ovarian malignancies. They are thought to arise from normal ...proliferating granulosa cells of the late preovulatory follicle and exhibit many morphological and biochemical features of these cells. GCT are distinct from other ovarian carcinomas in their hormonal activity; their ability to secrete estrogen, inhibin, and Müllerian inhibiting substance accounts for some of the clinical manifestations of the disease and also provides useful tumor markers for disease surveillance. Although considered to be of low malignant potential, GCT are commonly associated with slow, indolent disease progression, and frequent yet long delays to tumor recurrence are characteristic of this disease. Unlike the more intensely investigated epithelial ovarian tumors, relatively little is known about the molecular and genetic changes that give rise to GCT. To date, many investigations have centered around pathways known to be involved in normal granulosa cell proliferation, including those activated by FSH receptor stimulation. Most recently, the finding that approximately 97% of adult GCT harbor a somatic missense mutation in the FOXL2 gene (c.402C→G; p.C134W) represents an exciting advancement in the field of GCT research. The high frequency with which the mutation occurs in adult GCT, along with its absence from juvenile GCT and other human malignancies is suggestive of an oncogenic or gain-of-function mutation and, indeed, that the mutation is pathognomonic for adult GCT. In this review, we explore the implications of this finding and the most recent work characterizing molecular pathways of potential pathogenetic significance in GCT.
Despite concerns regarding the environmental impacts of microplastics, knowledge of the incidence and levels of synthetic particles in large marine vertebrates is lacking. Here, we utilize an ...optimized enzymatic digestion methodology, previously developed for zooplankton, to explore whether synthetic particles could be isolated from marine turtle ingesta. We report the presence of synthetic particles in every turtle subjected to investigation (n = 102) which included individuals from all seven species of marine turtle, sampled from three ocean basins (Atlantic ATL: n = 30, four species; Mediterranean (MED): n = 56, two species; Pacific (PAC): n = 16, five species). Most particles (n = 811) were fibres (ATL: 77.1% MED: 85.3% PAC: 64.8%) with blue and black being the dominant colours. In lesser quantities were fragments (ATL: 22.9%: MED: 14.7% PAC: 20.2%) and microbeads (4.8%; PAC only; to our knowledge the first isolation of microbeads from marine megavertebrates). Fourier transform infrared spectroscopy (FT‐IR) of a subsample of particles (n = 169) showed a range of synthetic materials such as elastomers (MED: 61.2%; PAC: 3.4%), thermoplastics (ATL: 36.8%: MED: 20.7% PAC: 27.7%) and synthetic regenerated cellulosic fibres (SRCF; ATL: 63.2%: MED: 5.8% PAC: 68.9%). Synthetic particles being isolated from species occupying different trophic levels suggest the possibility of multiple ingestion pathways. These include exposure from polluted seawater and sediments and/or additional trophic transfer from contaminated prey/forage items. We assess the likelihood that microplastic ingestion presents a significant conservation problem at current levels compared to other anthropogenic threats.
Knowledge of the incidence and levels of synthetic particles in large marine vertebrates is lacking. Here, we explore whether synthetic particles could be isolated from marine turtle ingesta and report the presence in every turtle subjected to investigation including individuals from all the seven species of marine turtle, sampled from three ocean basins. Most particles were fibres in lesser quantities were fragments/microbeads and were a range of synthetic materials. Synthetic particles isolated from species occupying different trophic levels suggest the possibility of multiple ingestion pathways. We assess the likelihood this presents a significant conservation problem at current levels.
Immune checkpoint inhibitors, including those targeting programmed cell death protein 1 (PD-1), are reshaping cancer therapeutic strategies. Evidence suggests, however, that tumor response and ...patient survival are determined by tumor programmed death ligand 1 (PD-L1) expression. We hypothesized that preconditioning of the tumor immune microenvironment using targeted, virus-mediated interferon (IFN) stimulation would up-regulate tumor PD-L1 protein expression and increase cytotoxic T cell infiltration, improving the efficacy of subsequent checkpoint blockade. Oncolytic viruses (OVs) represent a promising form of cancer immunotherapy. For brain tumors, almost all studies to date have used direct intralesional injection of OV, because of the largely untested belief that intravenous administration will not deliver virus to this site. We show, in a window-of-opportunity clinical study, that intravenous infusion of oncolytic human
(referred to herein as reovirus) leads to infection of tumor cells subsequently resected as part of standard clinical care, both in high-grade glioma and in brain metastases, and increases cytotoxic T cell tumor infiltration relative to patients not treated with virus. We further show that reovirus up-regulates IFN-regulated gene expression, as well as the PD-1/PD-L1 axis in tumors, via an IFN-mediated mechanism. Finally, we show that addition of PD-1 blockade to reovirus enhances systemic therapy in a preclinical glioma model. These results support the development of combined systemic immunovirotherapy strategies for the treatment of both primary and secondary tumors in the brain.
Composite materials usage is limited by linear elasticity and the sudden, brittle failure they often exhibit. It is possible to mitigate this inherent limitation and enlarge the design space by using ...thin plies. This paper presents an experimental study, using a spread tow thin ply carbon–epoxy prepreg material with a cured ply thickness of 0.03mm, which shows that highly non-linear stress–strain behaviour can be achieved with angle-ply laminates, whilst suppressing the damage mechanisms that normally cause their premature failure. Several angles between 15° and 45° are investigated in a ±θ5s layup. It is shown that for all angles delaminations are suppressed, allowing considerable pseudo-ductile strains to develop. Significant fibre rotations take place, permitted by matrix plasticity, leading to a post-yield stiffening of the laminate, as the fibres reorient towards the direction of loading.
Tidally trapped pulsations in binary stars Fuller, J; Kurtz, D W; Handler, G ...
Monthly notices of the Royal Astronomical Society,
11/2020, Letnik:
498, Številka:
4
Journal Article
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ABSTRACT
A new class of pulsating binary stars was recently discovered, whose pulsation amplitudes are strongly modulated with orbital phase. Stars in close binaries are tidally distorted, so we ...examine how a star’s tidally induced asphericity affects its oscillation mode frequencies and eigenfunctions. We explain the pulsation amplitude modulation via tidal mode coupling such that the pulsations are effectively confined to certain regions of the star, e.g. the tidal pole or the tidal equator. In addition to a rigorous mathematical formalism to compute this coupling, we provide a more intuitive semi-analytic description of the process. We discuss three resulting effects: (1) Tidal alignment, i.e. the alignment of oscillation modes about the tidal axis rather than the rotation axis; (2) Tidal trapping, e.g. the confinement of oscillations near the tidal poles or the tidal equator; (3) Tidal amplification, i.e. increased flux perturbations near the tidal poles where acoustic modes can propagate closer to the surface of the star. Together, these phenomena can account for the pulsation amplitude and phase modulation of the recently discovered class of ‘tidally tilted pulsators.’ We compare our theory to the three tidally tilted pulsators HD 74423, CO Cam, and TIC 63328020, finding that tidally trapped modes that are axisymmetric about the tidal axis can largely explain the first two, while a non-axisymmetric tidally aligned mode is present in the latter. Finally, we discuss implications and limitations of the theory, and we make predictions for the many new tidally tilted pulsators likely to be discovered in the near future.
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