Abstract
Classical molecular dynamics (MD) plays a central role in understanding structural and dynamical phenomena across all disciplines of physical chemistry. These models can be used to interpret ...experimental data, or as a method of study in their own right. Their legitimacy however rests solely on the accuracy of the underlying force-field, and so the parameterisation of these force-fields is the most crucial aspect of any study. The typical methods of parameterisation are structural or thermodynamic in nature, however this perspective article will examine a little used metric of parametersation; that of neutron spectroscopy, and in particular quasi-elastic neutron spectroscopy (QENS). QENS data contains self-correlation information for the hydrogen atoms of a system, over a wide range of distances and time-scales. These scales are relevant for local and global diffusion and rotation, thus pairing very well to the scales of molecular dynamics for organic systems. This article focuses in particular on the parameterisation of models of porous and surface catalysts. This area is a particularly rich field for the application of QENS, however there is a distinct lack of accurate classical force-fields currently.
Explore Amazon Connect, from implementing call flows and creating AI bots to integrating artificial intelligence solutions and analyzing critical customer sentimentKey FeaturesDiscover how to ...integrate chat with Connect to allow organizations to reduce operations costsLeverage machine learning to perform natural language processing (NLP) for analyzing customer feedback and trendsLearn how to integrate your enterprise application with Amazon ConnectBook DescriptionAmazon Connect is a pay-as-you-go cloud contact center solution that powers Amazon's customer contact system and provides an impressive user experience while reducing costs. Connect's scalability has been especially helpful during COVID-19, helping customers with research, remote work, and other solutions, and has driven adoption rates higher. Amazon Connect: Up and Running will help you develop a foundational understanding of Connect's capabilities and how businesses can effectively estimate the costs and risks associated with migration.Complete with hands-on tutorials, costing profiles, and real-world use cases relating to improving business operations, this easy-to-follow guide will teach you everything you need to get your call center online, interface with critical business systems, and take your customer experience to the next level. As you advance, you'll understand the benefits of using Amazon Connect and cost estimation guidelines for migration and new deployments. Later, the book guides you through creating AI bots, implementing interfaces, and leveraging machine learning for business analytics.By the end of this book, you'll be able to bring a Connect call center online with all its major components and interfaces to significantly reduce personnel overhead and provide your customers with an enhanced user experience (UX).What you will learnBecome well-versed with the capabilities and benefits of Amazon ConnectDetermine cost-effective solutions by integrating Connect with AWSCreate, modify, and connect contact flows to improve efficiencyBuild a conversational interface with Amazon LexFind out how to transfer contact records out of Connect via KinesisGather user insights and improve business operations with Amazon QuickSightAnalyze customer-agent conversations with ML speech analytics capabilitiesDiscover ways to provide superior customer service at a lower costWho this book is forThis Amazon Connect book is for anyone looking to save costs and improve their customer experience through a more advanced call center using Amazon Connect and other AWS capabilities. A technical understanding of Amazon Web Services (AWS) and beginner-level business administration experience are necessary to address cost concerns and risks.
Metabolic syndrome (MetS) was developed by the National Cholesterol Education Program Adult Treatment Panel III, identifying adults with at least 3 of 5 cardiometabolic risk factors (hyperglycemia, ...increased central adiposity, elevated triglycerides, decreased high-density lipoprotein cholesterol, and elevated blood pressure) who are at increased risk of diabetes and cardiovascular disease. The constellation of MetS component risk factors has a shared pathophysiology and many common treatment approaches grounded in lifestyle modification. Several attempts have been made to define MetS in the pediatric population. However, in children, the construct is difficult to define and has unclear implications for clinical care. In this Clinical Report, we focus on the importance of screening for and treating the individual risk factor components of MetS. Focusing attention on children with cardiometabolic risk factor clustering is emphasized over the need to define a pediatric MetS.
Epistasis is recognized ubiquitous in the genetic architecture of complex traits such as disease susceptibility. Experimental studies in model organisms have revealed extensive evidence of biological ...interactions among genes. Meanwhile, statistical and computational studies in human populations have suggested non-additive effects of genetic variation on complex traits. Although these studies form a baseline for understanding the genetic architecture of complex traits, to date they have only considered interactions among a small number of genetic variants. Our goal here is to use network science to determine the extent to which non-additive interactions exist beyond small subsets of genetic variants. We infer statistical epistasis networks to characterize the global space of pairwise interactions among approximately 1500 Single Nucleotide Polymorphisms (SNPs) spanning nearly 500 cancer susceptibility genes in a large population-based study of bladder cancer.
The statistical epistasis network was built by linking pairs of SNPs if their pairwise interactions were stronger than a systematically derived threshold. Its topology clearly differentiated this real-data network from networks obtained from permutations of the same data under the null hypothesis that no association exists between genotype and phenotype. The network had a significantly higher number of hub SNPs and, interestingly, these hub SNPs were not necessarily with high main effects. The network had a largest connected component of 39 SNPs that was absent in any other permuted-data networks. In addition, the vertex degrees of this network were distinctively found following an approximate power-law distribution and its topology appeared scale-free.
In contrast to many existing techniques focusing on high main-effect SNPs or models of several interacting SNPs, our network approach characterized a global picture of gene-gene interactions in a population-based genetic data. The network was built using pairwise interactions, and its distinctive network topology and large connected components indicated joint effects in a large set of SNPs. Our observations suggested that this particular statistical epistasis network captured important features of the genetic architecture of bladder cancer that have not been described previously.
Commercializing knowledge involves transfer from discovering scientists to those who will develop it commercially. New codes and formulae describing discoveries develop slowly-with little incentive ...if value is low and many competing opportunities if high. Hence new knowledge remains naturally excludable and appropriable. Team production allows more knowledge capture of tacit, complex discoveries by firm scientists. A robust indicator of a firm's tacit knowledge capture (and strong predictor of its success) is the number of research articles written jointly by firm scientists and discovering, "star" scientists, nearly all working at top universities. An operationally attractive generalization of our star measure-collaborative research articles between firm scientists and top research university scientists-replicates the impact on firm success. In panel analyses, publications by firm scientists with stars and/or top 112 university scientists increase the number and citation rate for firm patents. Further, star articles increase these rates significantly more than other top 112 university scientists' articles. Cross-sectional analyses of products and employment show a similar pattern of positive effects on firms' success of collaborations with stars or top university scientists, but estimates of differential effects are nonrobust due to multicollinearity. Venture capital funding has significant, usually positive effects on firm success.
Molecular vibrations play a critical role in the charge transport properties of weakly van der Waals bonded organic semiconductors. To understand which specific phonon modes contribute most strongly ...to the electron–phonon coupling and ensuing thermal energetic disorder in some of the most widely studied high‐mobility molecular semiconductors, state‐of‐the‐art quantum mechanical simulations of the vibrational modes and the ensuing electron–phonon coupling constants are combined with experimental measurements of the low‐frequency vibrations using inelastic neutron scattering and terahertz time‐domain spectroscopy. In this way, the long‐axis sliding motion is identified as a “killer” phonon mode, which in some molecules contributes more than 80% to the total thermal disorder. Based on this insight, a way to rationalize mobility trends between different materials and derive important molecular design guidelines for new high‐mobility molecular semiconductors is suggested.
Molecular vibrations strongly impact the charge transport properties of weakly van der Waals bonded organic semiconductors. Quantum mechanical simulations, combined with low‐frequency vibrational spectroscopy, enable resolution of vibrational modes and ensuing electron–phonon coupling constants. The long‐axis sliding motion of molecular subunits is identified as a “killer” phonon mode, which in some materials contributes more than 80% to the total thermal disorder.
Following significant instrument upgrades and parallel methodological developments over the past decade, the TOSCA neutron spectrometer at the ISIS Pulsed Neutron & Muon Source in the United Kingdom ...has developed a rich and growing scientific community spanning a broad range of non-traditional areas of neutron science, including chemical catalysis, gas adsorption & storage, and new materials for energy and sustainability. High-pressure science, however, has seen little to no representation to date owing to previous limitations in capability. Herein, we explore for the first time the viability of rapid high-pressure measurements in the gigapascal regime, capitalizing from the orders-of-magnitude increase in incident flux afforded by a recent upgrade of the primary-beam path. In particular, we show that spectroscopic measurements up to pressures of ∼2 GPa over an unprecedented energy-transfer range are now possible within the hour timescale. In addition, we have designed and commissioned a dedicated set of high-pressure vessels, with a view to foster and support the further growth and development of an entirely new user community on TOSCA.
Phase 3 Trials of Tapinarof Cream for Plaque Psoriasis Lebwohl, Mark G; Stein Gold, Linda; Strober, Bruce ...
New England journal of medicine/The New England journal of medicine,
12/2021, Letnik:
385, Številka:
24
Journal Article
Recenzirano
Odprti dostop
Tapinarof cream is a topical aryl hydrocarbon receptor-modulating agent under investigation for the treatment of psoriasis. Tapinarof modulates the expression of interleukin-17 and the skin-barrier ...proteins filaggrin and loricrin.
We conducted two identical phase 3 randomized trials of tapinarof in patients with mild-to-severe plaque psoriasis. Adults with a baseline Physician's Global Assessment (PGA) score of 2 (mild) to 4 (severe) (on a scale from 0 to 4, with higher scores indicating more severe psoriasis) and a percent of total body-surface area affected of 3 to 20% were randomly assigned in a 2:1 ratio to use tapinarof 1% cream or vehicle cream once daily for 12 weeks. The primary end point, PGA response, was a PGA score of 0 (clear) or 1 (almost clear) and a decrease from baseline of at least 2 points at week 12. Secondary efficacy end points at week 12 were a reduction of at least 75% in the Psoriasis Area and Severity Index (PASI) score, a PGA score of 0 or 1, the mean change from baseline in the percent of body-surface area affected, and a reduction of at least 90% in the PASI score. Patient-reported outcomes were the mean changes from baseline to week 12 in the proportion of patients who had a decrease of at least 4 points in the Peak Pruritus Numeric Rating Scale (PP-NRS) score (range, 0 no itch to 10 worst imaginable itch), the PP-NRS total score, the Dermatology Life Quality Index total score, and the Psoriasis Symptom Diary score.
In trials 1 and 2, a total of 692 and 674 patients, respectively, were screened, with 510 and 515 patients being enrolled. A PGA response occurred in 35.4% of the patients in the tapinarof group and in 6.0% of those in the vehicle group in trial 1 and in 40.2% and 6.3%, respectively, in trial 2 (P<0.001 for both comparisons). Results for secondary end points and patient-reported outcomes were generally in the same direction as those for the primary end point. Adverse events with tapinarof cream included folliculitis, nasopharyngitis, contact dermatitis, headache, upper respiratory tract infection, and pruritus.
Tapinarof 1% cream once daily was superior to vehicle control in reducing the severity of plaque psoriasis over a period of 12 weeks but was associated with local adverse events and headache. Larger and longer trials are needed to evaluate the efficacy and safety of tapinarof cream as compared with existing treatments for psoriasis. (Funded by Dermavant Sciences; PSOARING 1 and 2 ClinicalTrials.gov numbers, NCT03956355 and NCT03983980, respectively.).
Ideology is widely considered to be an important factor in shaping policy outcomes and in influencing election outcomes. We propose a theory of the coalition-directed vote. The argument suggests that ...voters anticipate the postelection bargains negotiated among potential members of the governing coalition and that these anticipated policy agreements inform their vote choice. Our analysis, based on 86 voter preference surveys from 23 countries and over a 25-year period, confirms that coalition-directed voting occurs with considerable frequency in contexts with multiparty coalition governments.
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