Tangles, Generalized Reidemeister Moves, and Three-Dimensional Mirror Symmetry

Three-dimensional N=2 superconformal field theories are constructed by compactifying M5-branes on three-manifolds. In the infrared the branes recombine, and the physics is captured by a single M5-brane on a branched cover of the original ultraviolet geometry. The branch locus is a tangle, a one-dimensional knotted submanifold of the ultraviolet geometry. A choice of branch sheet for this cover yields a Lagrangian for the theory, and varying the branch sheet provides dual descriptions. Massless matter arises from vanishing size M2-branes and appears as singularities of the tangle where branch lines collide. Massive deformations of the field theory correspond to resolutions of singularities resulting in distinct smooth manifolds connected by geometric transitions. A generalization of Reidemeister moves for singular tangles captures mirror symmetries of the underlying theory yielding a geometric framework where dualities are manifest.Comment: 80 pages, 48 figure

A Semiparametric Bayesian Model for Detecting Synchrony Among Multiple Neurons

We propose a scalable semiparametric Bayesian model to capture dependencies among multiple neurons by detecting their co-firing (possibly with some lag time) patterns over time. After discretizing time so there is at most one spike at each interval, the resulting sequence of 1's (spike) and 0's (silence) for each neuron is modeled using the logistic function of a continuous latent variable with a Gaussian process prior. For multiple neurons, the corresponding marginal distributions are coupled to their joint probability distribution using a parametric copula model. The advantages of our approach are as follows: the nonparametric component (i.e., the Gaussian process model) provides a flexible framework for modeling the underlying firing rates; the parametric component (i.e., the copula model) allows us to make inference regarding both contemporaneous and lagged relationships among neurons; using the copula model, we construct multivariate probabilistic models by separating the modeling of univariate marginal distributions from the modeling of dependence structure among variables; our method is easy to implement using a computationally efficient sampling algorithm that can be easily extended to high dimensional problems. Using simulated data, we show that our approach could correctly capture temporal dependencies in firing rates and identify synchronous neurons. We also apply our model to spike train data obtained from prefrontal cortical areas in rat's brain

Identifying Birds' Collision Risk with Wind Turbines Using a Multidimensional Utilization Distribution Method

Renewable energy plays a key role in reducing greenhouse gas emissions. However, the expansion of wind farms has raised concerns about risks for bird collisions. We tested different methods used to understand whether birds' flight occurs over wind turbines and found kernel density estimators outperform other methods. Previous studies using kernel utilization distribution (KUD) have considered only the 2 horizontal dimensions (2D). However, if altitude is ignored, an unrealistic depiction of the situation may result because birds move in 3 dimensions (3D). We quantified the 3D space use of the Griffon vulture (Gyps fulvus) in El Estrecho natural park in Tarifa (southern Spain, on the northern shore of the Strait of Gibraltar) during 2012-2013, and, for the first time, their risk of collision with wind turbines in an area in the south of Spain. The 2D KUD showed a substantial overlap of the birds' flight paths with the wind turbines in the study area, whereas the 3D kernel estimate did not show such overlap. Our aim was to develop a new approach using 3D kernel estimation to understand the space use of soaring birds; these are killed by collision with wind turbines more often than any other bird types in southern Spain. We determined the probability of bird collision with an obstacle within its range. Other potential application areas include airfields, plane flight paths, and tall buildings. (c) 2020 The Authors. Wildlife Society Bulletin published by Wiley Periodicals, Inc. on behalf of The Wildlife Society.Peer reviewe

A Dual-Purpose Reconfigurable Negative Group Delay Circuit Based on Distributed Amplifiers

In this letter, a novel reconfigurable negative group delay distributed amplifier (NGD-DA) circuit is proposed. This NGD-DA offers a new method to realize negative group delay. By properly choosing the gain coefficient of each tap for the DA, we can synthesize the negative group delay at the reverse port of the DA in the frequency band of interest, while maintaining a flat gain at the forward port; this results in a dual-purpose DA. Moreover, the proposed NGD-DA is reconfigurable; the phase response at the reverse port can be simply controlled by adjusting the tap gain coefficients, and therefore the bandwidth as well as the amount of negative group delay can be manipulated. The proposed active NGD circuit is validated through theoretical explanation and experimental results. © 2013 IEEE

Obesity and insulin sensitivity effects on cardiovascular risk factors: Comparisons of obese dysglycemic youth and adults

Background: Obesity and pubertal insulin resistance worsen cardiovascular (CV) risk factors in youth. It is unclear how the relationships of obesity and insulin resistance with CV risk compare to adults. Subjects and Methods: We evaluated 66 pubertal youth (mean ± SD: age 14.2 ± 2.0 years, body mass index [BMI] 36.6 ± 6.0 kg/m2, hemoglobin A1c [HbA1c] 38.5 ± 6.1 mmol/mol) and 355 adults with comparable BMI (age 52.7 ± 9.4 years, BMI 35.1 ± 5.1 kg/m2, HbA1c 39.8 ± 4.2 mmol/mol) participating in a multicenter study. Insulin sensitivity was quantified using hyperglycemic clamps. Assessment of CV risk factors was standardized across sites. Regression analyses compared the impact of insulin sensitivity and CV risk factors between youth and adults. Results: Obese pubertal youth were more insulin resistant than comparably obese adults (P \u3c.001), but with similar slopes for the inverse relationship between insulin sensitivity and obesity. The impact of obesity on CV risk factors was explained by insulin sensitivity (P = NS after adjustment for sensitivity). The two age groups did not differ in relationships between insulin sensitivity and diastolic blood pressure, total cholesterol, and low-density lipoprotein (LDL) cholesterol, after adjusting for obesity. However, while systolic blood pressure (SBP) and high-density lipoprotein (HDL) cholesterol exhibited the expected direct and inverse relationships, respectively with insulin sensitivity in adults, these slopes were flat in youth across the range of insulin sensitivity (P ≤.05 for group differences). Conclusions: Effects of obesity on CV risk factors were attributable to insulin sensitivity in both groups. The relationships between insulin sensitivity and CV risk factors were similar in obese youth and adult groups except for SBP and HDL cholesterol. Clinical Trial Registration: The RISE consortium studies are registered through Clinicaltrials.gov as NCT01779362 (Adult Medication Study); NCT01763346 (Adult Surgery Study); and NCT01779375 (Pediatric Medication Study). Clinical trial registration numbers: NCT01779362, NCT01779375 and NCT01763346 at clinicaltrials.gov

The effect of LRRK2 loss-of-function variants in humans

Analysis of large genomic datasets, including gnomAD, reveals that partial LRRK2 loss of function is not strongly associated with diseases, serving as an example of how human genetics can be leveraged for target validation in drug discovery. Human genetic variants predicted to cause loss-of-function of protein-coding genes (pLoF variants) provide natural in vivo models of human gene inactivation and can be valuable indicators of gene function and the potential toxicity of therapeutic inhibitors targeting these genes(1,2). Gain-of-kinase-function variants in LRRK2 are known to significantly increase the risk of Parkinson's disease(3,4), suggesting that inhibition of LRRK2 kinase activity is a promising therapeutic strategy. While preclinical studies in model organisms have raised some on-target toxicity concerns(5-8), the biological consequences of LRRK2 inhibition have not been well characterized in humans. Here, we systematically analyze pLoF variants in LRRK2 observed across 141,456 individuals sequenced in the Genome Aggregation Database (gnomAD)(9), 49,960 exome-sequenced individuals from the UK Biobank and over 4 million participants in the 23andMe genotyped dataset. After stringent variant curation, we identify 1,455 individuals with high-confidence pLoF variants in LRRK2. Experimental validation of three variants, combined with previous work(10), confirmed reduced protein levels in 82.5% of our cohort. We show that heterozygous pLoF variants in LRRK2 reduce LRRK2 protein levels but that these are not strongly associated with any specific phenotype or disease state. Our results demonstrate the value of large-scale genomic databases and phenotyping of human loss-of-function carriers for target validation in drug discovery.Peer reviewe

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI