Zobrazení zdroje stránky Mcdougallcamacho1188

This antenna can open new routes to highly integrated spiral sound emitters that are critical for practical acoustic functional devices.A widely regarded model for glucocorticoid receptor (GR) action postulates that dimeric binding to DNA regulates unfavorable metabolic pathways while monomeric receptor binding promotes repressive gene responses related to its anti-inflammatory effects. This model has been built upon the characterization of the GRdim mutant, reported to be incapable of DNA binding and dimerization. Although quantitative live-cell imaging data shows GRdim as mostly dimeric, genomic studies based on recovery of enriched half-site response elements suggest monomeric engagement on DNA. Here, we perform genome-wide studies on GRdim and a constitutively monomeric mutant. Our results show that impairing dimerization affects binding even to open chromatin. We also find that GRdim does not exclusively bind half-response elements. Our results do not support a physiological role for monomeric GR and are consistent with a common mode of receptor binding via higher order structures that drives both the activating and repressive actions of glucocorticoids.Understanding how activity of visual neurons represents distinct components of attention and their dynamics that account for improved visual performance remains elusive because single-unit experiments have not isolated the intensive aspect of attention from attentional selectivity. We isolated attentional intensity and its single trial dynamics as determined by spatially non-selective attentional performance in an orientation discrimination task while recording from neurons in monkey visual area V4. We found that attentional intensity is a distinct cognitive signal that can be distinguished from spatial selectivity, reward expectations and motor actions. V4 spiking on single trials encodes a combination of sensory and cognitive signals on different time scales. Attentional intensity and the detection of behaviorally relevant sensory signals are well represented, but immediate reward expectation and behavioral choices are poorly represented in V4 spiking. These results provide a detailed representation of perceptual and cognitive signals in V4 that are crucial for attentional performance.The medial prefrontal cortex (mPFC) steers goal-directed actions and withholds inappropriate behavior. Dorsal and ventral mPFC (dmPFC/vmPFC) circuits have distinct roles in cognitive control, but underlying mechanisms are poorly understood. Here we use neuroanatomical tracing techniques, in vitro electrophysiology, chemogenetics and fiber photometry in rats engaged in a 5-choice serial reaction time task to characterize dmPFC and vmPFC outputs to distinct thalamic and striatal subdomains. We identify four spatially segregated projection neuron populations in the mPFC. Using fiber photometry we show that these projections distinctly encode behavior. Postsynaptic striatal and thalamic neurons differentially process synaptic inputs from dmPFC and vmPFC, highlighting mechanisms that potentially amplify distinct pathways underlying cognitive control of behavior. Chemogenetic silencing of dmPFC and vmPFC projections to lateral and medial mediodorsal thalamus subregions oppositely regulate cognitive control. In addition, dmPFC neurons projecting to striatum and thalamus divergently regulate cognitive control. Collectively, we show that mPFC output pathways targeting anatomically and functionally distinct striatal and thalamic subregions encode bi-directional command of cognitive control.The value assessment of job skills is important for companies to select and retain the right talent. However, there are few quantitative ways available for this assessment. Therefore, we propose a data-driven solution to assess skill value from a market-oriented perspective. Specifically, we formulate the task of job skill value assessment as a Salary-Skill Value Composition Problem, where each job position is regarded as the composition of a set of required skills attached with the contextual information of jobs, and the job salary is assumed to be jointly influenced by the context-aware value of these skills. Then, we propose an enhanced neural network with cooperative structure, namely Salary-Skill Composition Network (SSCN), to separate the job skills and measure their value based on the massive job postings. Experiments show that SSCN can not only assign meaningful value to job skills, but also outperforms benchmark models for job salary prediction.Venous thromboembolism (VTE) is a multifactorial disease. Because low-frequency variants and rare mutations have been found to predispose carriers toward VTE, there is a need for variant discovery in clinical settings. Therefore, we used a whole-exome approach for a young VTE patient with a positive family history. We identified in the proband and his affected mother a rare, functional missense variant of prothrombin, p.Arg541Trp, which contributes to the clinical picture of VTE.Polymer memristors with light weight and mechanical flexibility are preeminent candidates for low-power edge computing paradigms. However, the structural inhomogeneity of most polymers usually leads to random resistive switching characteristics, which lowers the production yield and reliability of nanoscale devices. In this contribution, we report that by adopting the two-dimensional conjugation strategy, a record high 90% production yield of polymer memristors has been achieved with miniaturization and low power potentials. By constructing coplanar macromolecules with 2D conjugated thiophene derivatives to enhance the π-π stacking and crystallinity of the thin film, homogeneous switching takes place across the entire polymer layer, with fast responses in 32 ns, D2D variation down to 3.16% ~ 8.29%, production yield approaching 90%, and scalability into 100 nm scale with tiny power consumption of ~ 10-15 J/bit. The polymer memristor array is capable of acting as both the arithmetic-logic element and multiply-accumulate accelerator for neuromorphic computing tasks.Intratumoral immunotherapy is an emerging modality for the treatment of solid tumors. Toll-like receptor (TLR) agonists have shown promise for eliciting immune responses, but systemic administration often results in the development of adverse side effects. Herein, we investigate whether localized delivery of the TLR agonist, resiquimod (R848), via platelet membrane-coated nanoparticles (PNP-R848) elicits antitumor responses. The membrane coating provides a means of enhancing interactions with the tumor microenvironment, thereby maximizing the activity of R848. Intratumoral administration of PNP-R848 strongly enhances local immune activation and leads to complete tumor regression in a colorectal tumor model, while providing protection against repeated tumor re-challenges. [https://www.selleckchem.com/products/dmx-5084.html this website] Moreover, treatment of an aggressive breast cancer model with intratumoral PNP-R848 delays tumor growth and inhibits lung metastasis. Our findings highlight the promise of locally delivering immunostimulatory payloads using biomimetic nanocarriers, which possess advantages such as enhanced biocompatibility and natural targeting affinities.