Goodwillie's Calculus of Functors and Higher Topos Theory

We develop an approach to Goodwillie's calculus of functors using the techniques of higher topos theory. Central to our method is the introduction of the notion of fiberwise orthogonality, a strengthening of ordinary orthogonality which allows us to give a number of useful characterizations of the class of $n$-excisive maps. We use these results to show that the pushout product of a $P_n$-equivalence with a $P_m$-equivalence is a $P_{m+n+1}$-equivalence. Then, building on our previous work, we prove a Blakers-Massey type theorem for the Goodwillie tower. We show how to use the resulting techniques to rederive some foundational theorems in the subject, such as delooping of homogeneous functors.Comment: 40 pages, (a slightly modified version of) this paper is accepted for publication by the Journal of Topolog

Higher Sheaves and Left-Exact Localizations of ∞\infty-Topoi

We propose a definition of higher sheaf with respect to an arbitrary set of maps $\Sigma$ in an $\infty$-topos $\mathcal{E}$. We then show that the associated reflection $\mathcal{E} \to {\rm Sh}(\mathcal{E},\Sigma)$ is left-exact so that the subcategory of sheaves with respect to $\Sigma$ is itself an $\infty$-topos. Furthermore, we show that the reflection $\mathcal{E} \to {\rm Sh}(\mathcal{E},\Sigma)$ may be characterized as the left-exact localization generated by $\Sigma$. In the course of the proof, we study the interaction of various types of factorization systems, and make essential use of the notion of a \emph{modality}, that is, a factorization system whose left class is stable by base change.Comment: 44 page

Decoupled Associative and Dissociative Processes in Strong yet Highly Dynamic Host-Guest Complexes.

Kinetics and thermodynamics in supramolecular systems are intimately linked, yet both are independently important for application in sensing assays and stimuli-responsive switching/self-healing of materials. Host-guest interactions are of particular interest in many water-based materials, sensing, and drug delivery applications. Herein we investigate the binding dynamics of a variety of electron-rich aromatic moieties forming hetero-ternary complexes with the macrocycle cucurbit[8]uril (CB[8]) and an auxiliary guest, dimethyl viologen, with high selectivity and equilibrium binding constants (Keq up to 1014 M-2). Using stopped-flow spectrofluorimetry, association rate constants were observed to approach the diffusion limit and were found to be insensitive to the structure of the guest. Conversely, the dissociation rate constants of the ternary complexes varied dramatically with the guest structure and were correlated with the thermodynamic binding selectivity. Hence differing molecular features were found to contribute to the associative and dissociative processes, mimicking naturally occurring reactions and giving rise to a decoupling of these kinetic parameters. Moreover, we demonstrate the ability to exploit these phenomena and selectively perturb the associative process with external stimuli (e.g., viscosity and pressure). Significantly, these complexes exhibit increased binding equilibria with increasing pressure, with important implications for the application of the CB[8] ternary complex for the formation of hydrogels, as these gels exhibit unprecedented pressure-insensitive rheological properties. A high degree of flexibility therefore exists in the design of host-guest systems with tunable kinetic and thermodynamic parameters for tailor-made applications across a broad range of fields

Process Compensated Resonance Testing Modeling for Damage Evolution and Uncertainty Quantification

Process Compensated Resonance Testing (PCRT) is a nondestructive evaluation method that measures and analyzes the resonance frequencies of a component for material state characterization, defect detection and process monitoring. PCRT inspections of gas turbine engine components have demonstrated the sensitivity of resonance frequencies to manufacturing defects and in-service thermal and mechanical damage. Prior work on PCRT modeling has developed forward modeling and model inversion techniques that simulate the effects of geometry variation, material property variation, and damage on Mar-M-247 nickel-based superalloy samples. Finite element method (FEM) forward model simulations predicted the effects of variation in geometry, material properties and damage on resonance frequencies. Model inversion used measured resonance frequencies to characterize the material state of components. Parallel work developed a process for uncertainty quantification (UQ) in PCRT models and measurements. The UQ process evaluated the propagation of uncertainty from various sources, identified the most significant uncertainty sources, and enabled uncertainty mitigation to improve model and measurement accuracy. Current efforts have expanded on those developments in several areas. One-factor-at-a-time (OFAT) forward model simulations were conducted on cylindrical dog bone coupons made from Mar-M-247. The simulations predicted the resonance frequency response to variation in geometry, elastic properties, crystallographic orientation, creep strain and cracking. The OFAT studies were followed by forward model Monte Carlo simulations that predicted the effects of multiple, concurrent sources of variation and damage on resonance frequencies, allowing characterization of virtual populations and quantification of uncertainty propagation. The Monte Carlo simulation design points were used to demonstrate the generation of a virtual database of components for training PCRT inspection applications, or “sorting modules.” Virtual database training sets can potentially overcome the limitations imposed by the availability of components and material states for training sets based on physical examples. Forward modeling tools and techniques were applied to titanium to simulate the effects of material variation, damage, and crystallographic texture. Forward modeling was also applied to more complex geometries, including a notional turbine blade, to demonstrate the application of modeling tools to shapes representative of gas turbine engine components. Model inversion tools and techniques have also advanced under the current effort. Prior inversion methods relied on iterative fitting to polynomial expressions for simple geometries and bulk material properties. Current efforts have demonstrated FEM-based model inversion which allows characterization of complex shapes and material states. FEM-based design spaces were generated, model inversion was carried out for surrogate modeled resonance spectra, and inversion performance was evaluated. Analysis of PCRT modeling results led to the development of automated resonance mode matching tools based on the calculation of modal assurance criteria (MAC) values, mode shape displacement metrics and Hungarian Algorithm sorting methods

Molecular imaging of inflammation and intraplaque vasa vasorum: A step forward to identification of vulnerable plaques?

Current developments in cardiovascular biology and imaging enable the noninvasive molecular evaluation of atherosclerotic vascular disease. Intraplaque neovascularization sprouting from the adventitial vasa vasorum has been identified as an independent predictor of intraplaque hemorrhage and plaque rupture. These intraplaque vasa vasorum result from angiogenesis, most likely under influence of hypoxic and inflammatory stimuli. Several molecular imaging techniques are currently available. Most experience has been obtained with molecular imaging using positron emission tomography and single photon emission computed tomography. Recently, the development of targeted contrast agents has allowed molecular imaging with magnetic resonance imaging, ultrasound and computed tomography. The present review discusses the use of these molecular imaging techniques to identify inflammation and intraplaque vasa vasorum to identify vulnerable atherosclerotic plaques at risk of rupture and thrombosis. The available literature on molecular imaging techniques and molecular targets associated with inflammation and angiogenesis is discussed, and the clinical applications of molecular cardiovascular imaging and the use of molecular techniques for local drug delivery are addressed

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe