cssi/SciSciGPT-SciSciNet huggingface dataset:
Proangiogenic interactions of vascular endothelial MMP14 With VEGF receptor 1 in VEGFA-mediated corneal angiogenesis

Purpose Matrix metalloproteinase 14 (MMP14) has been shown to be required for corneal angiogenesis. We hypothesized that the proangiogenic activity of MMP14 may be based on its selective binding to, and cleaving of, vascular endothelial growth factor receptor 1 (VEGFR1), but not VEGFR2 or VEGFR3. Methods Recombinant human (rh)VEGFR1, R2, and R3 were incubated with human MMP14, and the reaction mixtures were analyzed by SDS-PAGE and Coomassie blue staining. Surface plasmon resonance was used to determine the equilibrium constants (KD) for binding between MMP14 and VEGFA versus rhVEGFR1, R2, and R3. Extracellular signal-regulated kinase (ERK) phosphorylation was assayed in vascular endothelial cells after incubation with VEGF and various concentrations of MMP14. Ex vivo aortic ring tube formation assays and VEGFA micropocket corneal neovascularization assays were performed using Flk1Cre/Flk1mCherry/MMP14lox and Flk1mCherry/MMP14lox control mice. Results Maxtrix metalloproteinase 14 increased VEGFA-induced ERK phosphorylation in a time- and concentration-dependent manner in vascular endothelial cells. Aortic ring assays showed diminished vessel sprouting in vitro in response to VEGFA, but not to basic fibroblast growth factor, in mice with conditional deletion of vascular MMP14 (Flk1creMMP14lox) compared with that in MMP14lox control mice. In addition, diminished VEGFA-induced corneal angiogenesis was seen in flk1creMMP14lox mice compared with MMP14lox mice in vivo. Conclusions Our findings indicate that VEGFR1 interaction with MMP14 and the enzymatic activity of MMP14 are necessary for VEGFA-induced angiogenesis. Additionally, selective cleavage of VEGFR1 by MMP14 may play an important role in VEGFA-induced corneal angiogenesis.
Moral Motivation as a Dynamic Developmental Process: Toward an Integrative Synthesis

The real-life complexity of moral motivation can be examined and explained by reintegrating time and development into moral inquiry. This article is one of the possible integrative steps in this direction. A dynamic developmental conception of moral motivation can be a useful bridge toward such integration. A comprehensive view of moral motivation is presented. Moral motivation is reconceptualized as a developmental process of self-organization and self-regulation out of which moral judgment and action emerge through the interplay of dynamically intertwined cognitive and emotional components. Moral identity is proposed to emerge from long-term self-organization of moral motivation. In turn, as a higher-order construct, moral identity has a top-down influence on real-time self-organization. The article includes an account of short-term changes in moral motivation, and an account that connects real-time moral functioning with long-term changes. Moral motivation is qualified as a dynamic developmental process on the basis of self-organization, multicausality, nonlinearity, interconnectedness of time scales and substantial intrapersonal variability through motivational pluralism.
Making sense of genetic estimates of effective population size

The last decade has seen an explosion of interest in use of genetic markers to estimate effective population size, Ne . Effective population size is important both theoretically (Ne is a key parameter in almost every aspect of evolutionary biology) and for practical application (Ne determines rates of genetic drift and loss of genetic variability and modulates the effectiveness of selection, so it is crucial to consider in conservation). As documented by Palstra & Fraser (), most of the recent growth in Ne estimation can be attributed to development or refinement of methods that can use a single sample of individuals (the older temporal method requires at least two samples separated in time). As with other population genetic methods, performance of new Ne estimators is typically evaluated with simulated data for a few scenarios selected by the author(s). Inevitably, these initial evaluations fail to fully consider the consequences of violating simplifying assumptions, such as discrete generations, closed populations of constant size and selective neutrality. Subsequently, many researchers studying natural or captive populations have reported estimates of Ne for multiple methods; often these estimates are congruent, but that is not always the case. Because true Ne is rarely known in these empirical studies, it is difficult to make sense of the results when estimates differ substantially among methods. What is needed is a rigorous, comparative analysis under realistic scenarios for which true Ne is known. Recently, Gilbert & Whitlock () did just that for both single-sample and temporal methods under a wide range of migration schemes. In the current issue of Molecular Ecology, Wang () uses simulations to evaluate performance of four single-sample Ne estimators. In addition to assessing effects of true Ne , sample size, and number of loci, Wang also evaluated performance under changing abundance, physical linkage and genotyping errors, as well as for some alternative life histories (high rates of selfing; haplodiploids). Wang showed that the sibship frequency (SF) and linkage disequilibrium (LD) methods perform dramatically better than the heterozygote excess and molecular coancestry methods under most scenarios (see Fig. 1, modified from figure 2 in Wang ), and he also concluded that SF is generally more versatile than LD. This article represents a truly Herculean effort, and results should be of considerable value to researchers interested in applying these methods to real-world situations.
Dual-band moiré metasurface patches for multifunctional biomedical applications

There has been strong interest in developing multi-band plasmonic metasurfaces for multiple optical functions on single platforms. Herein, we developed Au moire metasurface patches (AMMP), which leverage the tunable multi-band responses of Au moire metasurfaces and the additional field enhancements of the metal–insulator–metal configuration to achieve dual-band plasmon resonance modes in near-infrared and mid-infrared regimes with high field enhancement. Furthermore, we demonstrate the multifunctional applications of AMMP, including surface-enhanced infrared spectroscopy, optical capture and patterning of bacteria, and photothermal denaturation of proteins. With their multiple functions of high performance, in combination with cost-effective fabrication using moire nanosphere lithography, the AMMP will enable the development of highly integrated biophotonic platforms for a wide range of applications in disease theranostics, sterilization, and the study of microbiomes.
The Good Immigrant Worker: 2013 US Senate Bill 744, Color-Blind Nativism and the Struggle for Comprehensive Immigration Reform

We explore immigration politics in the contemporary USA through analysis of the political framing of 2013 US Senate Bill 744, especially among its supporters. SB 744 is a bipartisan comprehensive immigration reform proposal that called for the largest overhaul of the immigration system in more than 25 years; it was passed in June 2013 by the US Senate but blocked in the House. Through analysis of the 2012–2013 textual content of the official websites and blogs of six US immigration lobby organizations from across the political spectrum, we offer a typology of political framings of comprehensive immigration reform. Drawing on popular anti-immigrant rhetoric, organizations with an agenda of immigration restriction and deterrence battled against the bill. On the other side, supporters of the bill ranged from business coalitions to immigrant rights groups, an assortment of interests that was reflected in the variety of arguments advanced in favor of the bill. Despite the far more fragmented character of pro-SB 744 discourse in comparison to that advanced by the opposition, our investigation suggests the ongoing and contested formation of a strategic pro-SB 744 framing that centered on the “good immigrant worker,” a “race-blind” trope that melds US nationalist narratives of immigration with an ethos of neoliberalism that upholds individual merit and market value to create a notion of “deservingness” that affirms the worth of immigrants as diligent workers.
Recent developments in accuracy and stability improvement of nonlinear filter methods for DNS and LES of compressible flows

Abstract Recent progress in the improvement of numerical stability and accuracy of the Yee and Sjogreen [49] high order nonlinear filter schemes is described. The Yee & Sjogreen adaptive nonlinear filter method consists of a high order non-dissipative spatial base scheme and a nonlinear filter step. The nonlinear filter step consists of a flow sensor and the dissipative portion of a high resolution nonlinear high order shock-capturing method to guide the application of the shock-capturing dissipation where needed. The nonlinear filter idea was first initiated by Yee et al. [54] using an artificial compression method (ACM) of Harten [12] as the flow sensor. The nonlinear filter step was developed to replace high order linear filters so that the same scheme can be used for long time integration of direct numerical simulations (DNS) and large eddy simulations (LES) for both shock-free turbulence and turbulence-shock waves interactions. The improvement includes four major new developments: (a) Smart flow sensors were developed to replace the global ACM flow sensor [21,22,50]. The smart flow sensor provides the locations and the estimated strength of the necessary numerical dissipation needed at these locations and leaves the rest of the flow field free of shock-capturing dissipation. (b) Skew-symmetric splittings were developed for compressible gas dynamics and magnetohydrodynamics (MHD) equations [35,36] to improve numerical stability for long time integration. (c) High order entropy stable numerical fluxes were developed as the spatial base schemes for both the compressible gas dynamics and MHD [37,38]. (d) Several dispersion relation-preserving (DRP) central spatial schemes were included as spatial base schemes in the framework of our nonlinear filter method approach [40]. With these new scheme constructions the nonlinear filter schemes are applicable to a wider class of accurate and stable DNS and LES applications, including forced turbulence simulations where the time evolution of flows might start with low speed shock-free turbulence and develop into supersonic speeds with shocks. Representative test cases for both smooth flows and problems containing discontinuities for compressible flows are included.
Publisher Correction: Feeling stressed? It might be your T cells

In the version of this article initially published, the author surname citing the linked article (Miyama) was incorrect in the seventh and eighth paragraphs. The correct name is Miyajima.
A Perturbation Method for Inverse Scattering in Three-Dimensions Based on the Exact Inverse Scattering Equations

The detection and characterization of macroscopic flaws, such as cracks in solids are fundamental goals of nondestructive evaluation. Many inspection methods use scattered electromagnetic or ultrasonic waves. These methods rely explicitly on the development of inverse scattering theory. This theory seeks to determine the geometrical and material properties of flaws from scattering data.
Computing connection coefficients of compactly supported wavelets on bounded intervals

Daubechies wavelet basis functions have many properties that make them desirable as a basis for a Galerkin approach to solving PDEs: they are orthogonal, with compact support, and their connection coefficients can be computed. The method developed by Latto et al. to compute connection coefficients does not provide the correct inner product near the endpoints of a bounded interval, making the implementation of boundary conditions problematic. Moreover, the highly oscillatory nature of the wavelet basis functions makes standard numerical quadrature of integrals near the boundary impractical. The authors extend the method of Latto et al. to construct and solve a linear system of equations whose solution provides the exact computation of the integrals at the boundaries. As a consequence, they provide the correct inner product for wavelet basis functions on a bounded interval.
Resurgence of Polio? Modern day Epidemic (P2.320)

Objective: Acute flaccid myelitis (AFM) related to Enterovirus seroforms has no cure and reflects the same clinical course as noted previously by Polio, which happens to be a species of the same viral family. No consensus exists on the treatment modality for this disease process. Here we present two of the first cases in Columbia, South Carolina and their clinical course, approach and outcomes. Background: AFM has become an epidemic in the US notably in California, Colorado, and most recently in Philadelphia. The affected population is typically pediatric. The disease course usually starts off with febrile URI symptoms and weakness, progresses rapidly to extensive lateralizing weakness over a few days. Cranial nerve involvement is possible, abnormal studies include LP with normal or elevated protein with pleocytosis and normal glucose, MRI with brain stem and/or ventral grey matter spinal cord hyperintensities +/− nerve root enhancement. Viral PCR may reveal enterovirus positivity with possibly EV D68/C105. Treatment modalities include steroids/PLEX/IVIG. Design/Methods: Two pediatric patients presented to our PICU in 8/2016 within weeks of each other with limb weakness and altered level of awareness, both were intubated, both with reported febrile illnesses within the week. One child 8 years of age had bilateral lower extremity weakness and the other 6 years with left hemiparesis. Both were positive for Enterovirus PCR, MRI was positive for ventral cord myelitis in both, with one of the cases having midbrain involvement.Treatment with steroids and IVIG was pursued in both cases. PLEX was further tried in one case after lack of response. Results: Despite multiple modalities no recovery of dense hemiplegia and paraparesis was noted, comparable to what has been noted by the CDC in the literature. Conclusions: Further studies and discussion are needed on this front, and the development of a vaccine is prudent before this becomes a pandemic as was Polio. Disclosure: Dr. Swamy has nothing to disclose. Dr. Morgan has nothing to disclose.
Race, Xenophobia, and Punitiveness Among the American Public

We outline four connections between xenophobia and punitiveness toward criminals in a national sample of Americans. First, among self-identified whites xenophobia is more predictive of punitiveness...
Monolithic, 3D-Printed Microfluidic Platform for Recapitulation of Dynamic Tumor Microenvironments

We report the development of an entirely 3D-printed, monolithic microfluidic platform that provides a dynamic microenvironment for perfusing and sustaining tumor fragments from a biopsy sample. The finely featured, non-cytotoxic, and transparent tumor trap is integrated with threaded connectors for rapid, leak-proof fluid interfacing, an in-line trap for removal of bubbles arising from oxygenated media flow or tumor loading procedures, and a network of microchannels for supplying media (and potentially immune cells) to the trapped tumor fragment. The devices were additively manufactured in Pro3dure GR-10–a relatively new, high-resolution stereolithographic resin with properties suitable for biomedical applications requiring interrogation via fluorescence microscopy. Overlaid bright-field and fluorescence microscopy images demonstrate trapping of human tumor fragments by the printed microfluidic device, as well as visualization of individual cells within the fragment. A multi-day trapping experiment evidences the ability to sustain a live tumor fragment under dynamic perfusion within the device–a configuration capable of modeling of interactions between tumors and various drug treatments in the presence of circulating immune cells, e.g., for assessment of the efficacy of chemotherapy and immunotherapy treatments. [2018-0048]
Impaired inhibition as an intermediate phenotype for PTSD risk and treatment response.

Abstract Inhibition of fear involves learning and then appropriately responding to safety signals, and has been shown to be impaired in PTSD patients. Response inhibition refers to cognitive control and likely uses the same prefrontal cortex circuits as fear inhibition, and has also been implicated in PTSD. Impaired inhibition can serve as an intermediate phenotype for PTSD and can be measured with neuroimaging and psychophysiological tools. We first review the neurobiological mechanisms of fear and response inhibition. Next, we summarize the functional magnetic resonance imaging (fMRI) and psychophysiological studies using fear and response inhibition paradigms in PTSD patients. Finally, we evaluate the theranostic role of impaired inhibition in PTSD risk and treatment response.
Controlling Selectivity in the Hydroboration of Carbon Dioxide to the Formic Acid, Formaldehyde, and Methanol Oxidation Levels

The factors that influence the selectivity of pincer supported group 10 transition metal hydride catalysts for CO2 hydroboration are investigated. We demonstrate that selective CO2 reduction to eit...
Reduction of vibration and mechanical shocks in MEMS gyroscopes for space application

Novel approach of reducing effect of vibration and mechanical shocks is proposed. It is particularly suitable for existing tuning fork MEMS gyroscopes. The idea is based on the O-factor reduction of those modes which could be actuated by external forces. It is demonstrated that when the adjustment is done selectively only non-operational modes are affected or the change of operation modes does not deteriorate the performance. The entire approach of selective adjustment of damping is first introduced with the help of analytical expression. The extent of achievable damping is experimentally verified by comparing damping of cantilevers before and after adjustment. The estimated damping is used in finite element analysis to demonstrate entire concept on tuning fork MEMS gyroscope. This approach could be used in harsh environments similar to those found in aerospace and defense segments.
Synergistic Effects of Imidazolium-Functionalization on fac-Mn(CO)3 Bipyridine Catalyst Platforms for Electrocatalytic Carbon Dioxide Reduction.

The electrocatalytic reduction of carbon dioxide (CO2) could be a powerful tool for generating chemical fuels and feedstock molecules relevant to the chemical industry. One of the major challenges for molecular catalysts remains the necessity of high overpotentials, which can be overcome by identifying novel routes that improve the energetic reaction trajectory of critical intermediates during catalysis. In this combined experimental and computational study, we show that imidazolium functionalization of molecular fac-Mn(CO)3 bipyridine complexes results in CO2 reduction at mild electrochemical potentials in the presence of H2O. Importantly, our studies suggest that imidazolium groups in the secondary coordination sphere promote the formation of a local hydration shell that facilitates the protonation of CO2 reduction intermediates. As such, we propose a synergistic relationship between the functionalized catalyst and H2O, which stands in contrast to other systems in which the presence of H2O frequently ha...
Laminar-Turbulent Transition Upstream of the Entropy-Layer Swallowing Location in Hypersonic Boundary Layers

Numerical and experimental studies have demonstrated that modal growth of planar Mack modes is responsible for laminar-turbulent transition on sharp cones at hypersonic speeds. However, the physical mechanisms that lead to transition onset upstream of the entropy-layer swallowing location over sufficiently blunt geometries are not well understood as yet. Modal amplification is too weak or nonexistent to initiate transition at moderate-to-large bluntness values. Nonmodal analysis shows that, with increasing nose bluntness, both planar and oblique traveling disturbances that peak within the entropy layer experience appreciable energy amplification. However, because of the relatively weak signature of the nonmodal traveling disturbances within the boundary-layer region, the route to transition onset subsequent to the nonmodal growth remains unclear. Thus, nonlinear parabolized stability equations (NPSE) and direct numerical simulations (DNS) have been used to investigate the potential transition mechanisms over a 7-degree blunt cone that was tested in the AFRL Mach-6 high-Reynoldsnumber facility. Computations are performed to separately follow the nonlinear development of two classes of inflow disturbances, namely, a pair of oblique traveling waves with equal but opposite angles with respect to the mean flow direction and a planar traveling wave. Results in both cases show an excellent agreement between the NPSE and DNS predictions, establishing that the NPSE is an accurate and efficient technique for predicting the nonlinear development for these particular nonmodal traveling disturbances. Computations reveal that the oblique mode interactions lead to the generation of stationary streaks inside the boundary layer that, in turn, facilitate the growth of a subharmonic sinuous disturbance. For relatively modest amplitudes of the inflow disturbance, the oblique-mode breakdown can lead to transition at the measured location of transition onset during the experiment. On the other hand, the nonlinear development of a planar traveling wave leads to the formation of inclined structures just above the boundary-layer edge and these structures are strongly reminiscent of the transitional events observed during blunt cone experiments by using schlieren flow visualizations.
Impact of exposure to counterstereotypic causality of obesity on beliefs about weight controllability and obesity bias.

Individuals with obesity often report experiencing prejudice and discrimination due to their weight. Past research on obesity bias reduction strategies have yielded mixed results. The present study...
Development of Downscaled Climate Projections: A Case Study of the Red River Basin, South-Central U.S.

Climate models provide information that resource managers, policy makers, and researchers can use when planning for the future. While this information is valuable in the broad sense, the low spatial-resolution often lacks local details that resource managers and decision makers need to plan for their communities. Therefore, statistically downscaled climate projections provide a high-resolution output and offer local information that is more beneficial than coarse-resolution global climate model output. In the Red River Basin, located in the south-central U.S., this detailed information is used to develop long-term water plans. This area is prone to drought conditions and heavy precipitation events, and studies have consistently estimated that this will continue in the future. This paper introduces a dataset of statistically downscaled climate projections of daily minimum and maximum temperature and daily precipitation that is a useful tool for studies regarding climatological and hydrological aspects in the region. The dataset was created using two quantile mapping techniques to downscale the CCSM4, MPI-ESM-LR, and MIROC5 model outputs to a 0.1-degree spatial resolution. Furthermore, we describe the added value of coproduction of knowledge between climate scientists and end users, or in this case impacts modelers and decision makers, for creating climate projections that can be used for climate risk assessments. A case study of the data’s development and application is provided, detecting the mean daily changes in temperature and precipitation through the end of the century in the Red River Basin for two representative concentration pathways. After applying the users’ inputs to develop the datasets, results for this example estimate an increase in mean daily precipitation in the eastern portion of the basin and as much as a 15% decline in the west by the end of the century. Furthermore, mean daily temperature is expected to rise across the entire basin in all scenarios by up to 6–7°C.
Acute Postoperative Hypocalcemia After Neck Surgery

Acute hypocalcemia can be a true medical emergency. Symptoms of acute hypocalcemia include paresthesias, carpopedal spasm, broncho- or laryngospasm, tetany, seizures, mental status changes, positive Chvostek’s or Trousseau’s signs, bradycardia, impaired cardiac contractility, and prolongation of the QT interval. We present a case of a 49-year-old woman with acute postoperative hypocalcemia following thyroid and parathyroid surgery and review the management of acute hypocalcemia in adults.
Reconstitution of a Minimal Small Ribosomal Subunit

It is appropriate that at a meeting dedicated to H. G. Wittmann we should emphasize comparative studies of the three-dimensional structure of the ribosome since he and his collaborators have made such important contributions to this field. In this paper we present data detailing the first isolation of small mitochondrial ribosomal subunits from the hemoflagellate Leishmania tarentolae. Their structure is interesting because these are the smallest ribosomes yet found (their small subunit rRNA sediments at 9S and is only 610 nucleotides long). We also show that particles similar in structure to these small subunits can be reconstituted from in vitro transcribed mitochondrial 9S rRNA and E. coli proteins.
Investment, value, and the making of entrepreneurship in India

In recent years, a new class of entrepreneurs and investors has emerged in India. In this article, based on fourteen months of ethnographic fieldwork with start‐ups in Delhi, I examine how entrepreneurs are valued by investors and the sociocultural implications of this process. I make two arguments. First, the criteria used to judge creditworthiness, including personal networks, technological capability, and ability to undertake speculative risk, serve as signals of an entrepreneur's value to prospective investors. Second, as investors acknowledge, the investment is made in the specific personhood of the entrepreneur rather than the business plan. Therefore the process of seeking investment capital, far from being simply a means of scaling one's business, is an act of cultural construction. The entrepreneur's value as wealth‐in‐people is not judged objectively; rather, it is created through the process of pitching and securing investment commitments. One of the contributions of this research is to center the real and perceived relationship between entrepreneurs and investors in studying start‐up spaces in India. Examining this relationship reveals the forms of economic, sociocultural, and moral value that are interwoven with each other. The multiple, often contradictory meanings attached to entrepreneurship are negotiated through the prism of investment, which emerges as a dynamic site for constructing and contesting entrepreneurial identities.
Nano-topology optimization for materials design with atom-by-atom control.

Atoms are the building blocks of matter that make up the world. To create new materials to meet some of civilization’s greatest needs, it is crucial to develop a technology to design materials on the atomic and molecular scales. However, there is currently no computational approach capable of designing materials atom-by-atom. In this study, we consider the possibility of direct manipulation of individual atoms to design materials at the nanoscale using a proposed method coined “Nano-Topology Optimization”. Here, we apply the proposed method to design nanostructured materials to maximize elastic properties. Results show that the performance of our optimized designs not only surpasses that of the gyroid and other triply periodic minimal surface structures, but also exceeds the theoretical maximum (Hashin–Shtrikman upper bound). The significance of the proposed method lies in a platform that allows computers to design novel materials atom-by-atom without the need of a predetermined design. The ability to design materials manipulating individual atoms with the best possible atom distributions for target properties is currently a challenge. Here the authors introduce Nano-TO, a topological based computational approach with an atom-by-atom control for materials design with desired properties.
Static to inducibly dynamic stereocontrol: The convergent use of racemic β-substituted ketones

The synthesis of stereochemically complex molecules in the pharmaceutical and agrochemical industries requires precise control over each distinct stereocenter, a feat that can be challenging and time consuming using traditional asymmetric synthesis. Although stereoconvergent processes have the potential to streamline and simplify synthetic routes, they are currently limited by a narrow scope of inducibly dynamic stereocenters that can be readily epimerized. Here, we report the use of photoredox catalysis to enable the racemization of traditionally static, unreactive stereocenters through the intermediacy of prochiral radical species. This technology was applied in conjunction with biocatalysts such as ketoreductases and aminotransferases to realize stereoconvergent syntheses of stereodefined γ-substituted alcohols and amines from β-substituted ketones.
Optical Tuning of Second-Order Optical Nonlinearity in Transition Metal Dichalcogenides

We show that the optical depopulation of conduction band electrons, close to high-symmetry K/K' points, modulates the contribution of interband electronic transitions in the second-order dielectric susceptibility of transition metal dichalcogenides, enabling ultrafast tuning of nonlinear processes.
An Engineered Contact Lens for Passive and Sustained Release of Lifitegrast, an Anti-Dry Eye Syndrome Drug

Lifitegrast is an FDA-approved drug that inhibits T-cell mediated inflammation associated with dry eye syndrome (DES). Lifitegrast is a potent inhibitor of the interaction between LFA-1 on T-cells and ICAM-1 on endothelial cells at the ocular surface. While effective in treating DES, 5% (81.2 mM) lifitegrast has low drug utilization and elicits off-target effects. Here we engineer contact lenses to release therapeutically-relevant doses of lifitegrast to every tear film for up to 10-hours. Lifitegrast is coupled to the polymer of the soft hydrogel lens via a photolabile (caged) crosslinker. Exposures of the lens to the 400-430 nm wavelengths of indoor daylight excite the caged crosslinker molecules and trigger a bond-cleavage reaction that releases authentic lifitegrast passively to the tear film. The photoproduct of the reaction remains chemically-linked to the polymer of the single-use lens. Our studies show that passive exposures of the lens to indoor light would generate an average of 990 nM lifitegrast to every tear film in a zero-order reaction for up to 10-hours. This concentration exceeds the Kd for the interaction between ICAM-1 and LFA-1 by [~]330-fold and would sustain inhibition of inflammatory responses at the ocular surface. The amount of lifitegrast released from the lens increases during exposures to outdoor sunlight. Over a 10-hour exposure to indoor light, a single lens would release 0.44% of the lifitegrast present in two drops of commercial 5% lifitegrast. Compared to tear-drop approaches, our engineered lenses would sustain the passive delivery of therapeutically-relevant doses of lifitegrast over a longer period, and exhibit improved drug utilization at a lower cost. Our technology could easily be integrated into daily-use contact lenses in order to prevent inflammation at the ocular surface, dry-eye and contact lens-mediated discomfort. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=198 HEIGHT=200 SRC="FIGDIR/small/439289v1_ufig1.gif" ALT="Figure 1"> View larger version (75K): org.highwire.dtl.DTLVardef@1049076org.highwire.dtl.DTLVardef@a83fceorg.highwire.dtl.DTLVardef@1f52c4borg.highwire.dtl.DTLVardef@12f0ead_HPS_FORMAT_FIGEXP M_FIG C_FIG
Law Enforcement and Suicide Calls for Service: A Mixed-Methods Study of Suicide Attempts and Deaths:

IntroductionSuicide is a major public health issue, however, little is known about the characteristics/circumstances of suicide events. Data from law enforcement (LE) call reports are an important ...
Neoclassical Concepts

Linguistic theories of lexical semantics support a Neoclassical Theory of concepts, where entities like CAUSE, STATE, and MANNER serve as necessary conditions for the possession of individual event concepts. Not all concepts have a neoclassical structure, and whether or not words participate in regular linguistic patterns such as verbal alternations will be proposed as a probe for identifying whether their corresponding concepts do indeed have such structure. I show how the Neoclassical Theory supplements existing theories of concepts and supports a version of analyticity and conceptual analysis.
Concerned others’ help utilization and patients’ alcohol treatment outcomes

Abstract Background This study of dyads composed of patients in treatment for alcohol use disorders (AUDs) and their Concerned Others (COs) examined (1) COs’ attendance at three types of help (educational sessions, treatment sessions with the patient, and treatment sessions without the patient) during a 3-month period after patients’ admission, and (2) whether COs’ use of help was associated with better treatment outcomes reported by COs about patients, and patients about themselves. Methods Dyads (n = 277) were assessed when patients entered AUD treatment and 3 months later (80 %). COs rated their patient’s AUD, and patients rated their own AUD, on the Brief Addiction Monitor. At 3-month follow-up, COs answered three items about help (education, treatment with patient, treatment without patient) from their patient’s treatment program. Main analyses were analyses of covariance to examine associations between COs’ help use and patients’ outcomes. Results At 3-month follow-up, COs who had obtained one type of help were significantly more likely to have also obtained the other two types of help. However, relatively few COs (39 %) obtained any type of help. COs who obtained help rated their patient as having more protection against future substance use. And, when COs had obtained help, patients rated themselves as having less risk of future substance use, and had attended a greater number of AA meetings, than when COs had not obtained help. Conclusions Findings suggest that COs’ use of help can benefit patients in AUD treatment. Clinicians and researchers should increase the availability and use of help among COs.
Does a Change in the TED Spread Impact Bank Stock Returns

During the economic crisis of 2008, the global economic system came under tremendous stress due to unusually high activity in the risk spread and volatility in the financial asset valuation. The spread between the US Treasury Bill Rate and the London Interbank Offer Rate (LIBOR), a proxy for perceived counterparty credit risk called the “TED spread,” also increased during the crisis period and impacted other economic variables. This study examines the impact of credit risk, as represented by the TED spread, on the daily returns of the ABAQ index, which represents community banks, and the KBW index, which represents the money center and other major banks. The findings based on daily data from 2010–2020, are as follows: an increase in credit risk led to a decrease in returns for both community banks and money center banks. However, the significance of credit risk and its impact on the stock returns of community banks and money center banks diminished when controlled for other stock market movements. TOPICS:Financial crises and financial market history, credit risk management, performance measurement Key Findings ▪ The TED Spread is critical to investment valuation since it is an indicator of the price of money in the global banking system. ▪ As an indicator of the solvency of financial institutions, monetary liquidity, and perceived risk of the financial system, an increase in the TED spread impacts the daily returns of banks (community banks, money center and other major banks) negatively. ▪ An increase in TED spread leads to the drying up of market liquidity that increases cost of funding and generates a negative reaction in the stock market. The study shows that stocks for both larger banks and community banks, while affected by TED spread, are more impacted by general market movements.
Diagnosis and management of infected arthroplasty

Periprosthetic joint infection (PJI) is one of the most dreadful complications after THA and TKA. Though prevention is of utmost importance in PJI management, the last decade has seen many remarkable developments in PJI diagnosis, including the introduction of several standardized PJI diagnostic definitions and biomarkers. Depending on the specific clinical situation, a myriad of treatment options for PJI are offered. Our review aims to summarize the pertinent information on PJI diagnosis and synthesize literature on the different treatment methods currently used in clinical practice. One of the most accepted PJI diagnostic definitions was developed by the Musculoskeletal Infection Society (MSIS) in 2011, later modified in the 2013 International Consensus Meeting (ICM). After promising results from studies, alpha-defensins and D-dimer were recently incorporated into the 2018 ICM PJI definition. The management choices for PJI include irrigation and debridement (DAIR), one-stage exchange arthroplasty, or two-stage exchange arthroplasty, to name a few. While two-stage revision has traditionally been the treatment of choice in the United States, there has been a growing body of evidence framing one-stage revision as a comparable choice. One-stage revision should be offered in patients meeting strict selection criteria: no sinus tract, proper soft tissue available for wound closure, appropriate bone stock, a favorable identifiable organism with encouraging antibiotic sensitivities (for cement and oral suppression later), and robust immunological status. DAIR can be considered in case of early infections with sensitive infecting organisms. Patients with multiple unsuccessful revisions or those who refuse further surgical intervention for PJI can be offered antibiotic suppression. If nothing seems to work, salvage procedures (resection arthroplasty and arthrodesis) are available as a last resort. Further research is encouraged to improve on diagnostic capabilities and develop evidence on the best treatment of choice for PJI.
Sequence-Disorder Effects on DNA Entropic Elasticity

DNA stretching experiments are usually interpreted using the worm-like chain model; the persistence length A appearing in the model is then interpreted as the elastic stiffness of the double helix. In fact the persistence length obtained by this method is a combination of bend stiffness and intrinsic bend effects reflecting sequence information, just as at zero stretching force. This observation resolves the discrepancy between the value of A measured in these experiments and the larger ``dynamic persistence length'' measured by other means. On the other hand, the twist persistence length deduced from torsionally-constrained stretching experiments suffers no such correction. Our calculation is very simple and analytic; it applies to DNA and other polymers with weak intrinsic disorder.
Learning to Satisfy Conjunctive Goals

Abstract In earlier work (Hammond et al., 1988; Hammond, 1989b) we argued for an execution-time method for constructing useful plans for conjunctive goals. In domains complex enough to preclude complete preplanning for active goals, some goals must be satisfied opportunistically, while in the pursuit of other goals. The recognition of such an opportunity can indicate that an optimized version of the conjoined plan may be worth constructing and saving, with one indication of the utility simply being that the goals were active at the same time and the opportunity was encountered. The utility of learning such a conjoined plan is not completely clear, particularly for action systems that are flexible enough to use multiple plans at once and interleave them at run time. In this paper we attempt to refine the answer to the question of when this sort of plan should be learned.
Isolation ofAspergillus nidulansMutants That OvercomebrlA-Induced Growth Arrest

Abstract TheAspergillus nidulans brlAgene is a primary regulator of development-specific gene expression during conidiation. Forced activation ofbrlAin vegetative cells leads to inappropriate induction of conidiophore formation and causes growth to stop. In fact, when conidia containing a nutritionally induciblebrlAgene fusion are placed on inducing medium, they fail to germinate. We used this phenotype to select 174 mutants that continue growing following such forcedbrlAactivation. Forty-six of these mutants also produced abnormal developmental structures during air-induced conidiation as expected if the mutations resulted in an altered response to BrlA (designatedsbrmutants for suppressors ofbrlAresponse). The predominant mutant class identified was defective in a known developmental regulatory gene,abaA.We also identified mutants with defects in the previously characterized early acting developmental regulatory genesflbBandflbDand in four previously undescribed loci designatedsbrA–D. sbrAmutants represent the second largest group and are characterized by production of conidiophore stalks that lack a normal vesicle and form branching sterigmata that rarely make spores. BecauseabaAexpression could not be detected insbrAmutants followingbrlAactivation we propose thatsbrAfunctions as a developmental modifier, participating inbrlA-dependent activation of other developmental regulators.
The biology of melanoma brain metastasis

Brain metastases are clinically diagnosed in the majority of patients with metastatic melanoma. The prognosis for patients with melanoma brain metastasis is poor with a median survival time of 6 months after diagnosis. Development of better therapies requires a better understanding of the biology of melanoma brain metastasis. The development of a relevant in vivo model offers this possibility. The intracarotid injection of different murine or human melanoma cells into syngeneic or nude mice produces metastases in different regions of the brain. This site-specific metastasis is not due to patterns of initial cell arrest, motility, or invasiveness, but rather to the ability of melanoma cells to proliferate in the brain parenchyma or the meninges. The blood-brain barrier is intact in metastases that are smaller than 0.25 mm in diameter. Although in larger metastases the blood-brain barrier is leaky, the lesions are resistant to many chemotherapeutic drugs. We have also analyzed the malignant behavior of several melanoma cell lines isolated from brain or visceral metastases of patients. The cells from brain metastases showed a slower growth rate and exhibited lower metastatic potential than cells from visceral metastases, indicating that brain metastases do not necessarily represent the end stage in the metastatic cascade. Rather, brain metastases are likely to originate from a unique subpopulation of cells within the primary neoplasm.
Greedy Algorithms for the On-Line Steiner Tree and Generalized Steiner Problems

We study the on-line Steiner tree problem on a general metric space. We show that a class of greedy on-line algorithms are O(log(d/zs))-competitive and no deterministic algorithm is better than Ω(log(d/zs))-competitive, where s is the number of regular nodes, d the maximum metric distance between any two revealed nodes and z the optimal off-line cost. Our results refine the previous known bound [8] and show that Algorithm SB of Bartal et al. [4] for the on-line File Allocation problem is O(log log N)-competitive on an N-node hypercube or butterfly network.
Decoupled Energies in Two Time Scale Linear Systems

This paper presents a technique for simultaneous block diagonalization of linear systems having the two time-scale property to facilitate the decomposition of energy functions into slow and fast components. Mass-spring systems are considered where the spring stiffness matrix K can be either symmetric or nonsymmetric. A linearized large scale power system has a similar structure and results are illustrated for this case.
Wheat From Chaff: Meta-Analysis As Quantitative Literature Review

Abstract This paper presents and develops a quantitative method of literature reviewing and evaluating empirical research, meta-regression analysis or MRA. Economics is theory-driven. Yet, we must learn empirically if economics is to advance. MRA offers a more objective statistical method to summarize our empirical knowledge and to explain the wide study-to-study variation in economic research. MRA is used to assess the evidence for Ricardian equivalence, and its findings are contrasted to those of conventional narrative review. Furthermore, MRA establishes a platform from which to distinguish genuine empirical effect from the exploitable specification error that infests applied econometrics.
On the ring current energy injection rate

Abstract Assuming that the formation of the ring current belt is a direct consequence of an enhanced crosstail electric field and hence of an enhanced convection, we calculate the total ring current kinetic energy (KR) and the ring current energy injection rate (UR) as a function of the cross-tail electric field (ECT); the cross-tail electric field is assumed to have a step function-like increase. The loss of ring current particles due to recombination and charge-exchange is assumed to be distributed over the whole ring current region. It is found that: (1) the steady-state ring current energy KR is approximately linearly proportional to ECT; (2) the characteristic time tc for KR to reach the saturation level is 3–4 h; (3) the injection rate UR is proportional to ECTβ where β ≅ 1.33−1.52; and (4) the characteristic time tp for UR to reach the peak value is 1–2 h and the peak UR value is 50% higher than the steady-state value. Since β is now determined specifically for an enhanced convection, an observational determination of the relationship between ECT(or φCT) and UR is essential to a better understanding of ring current formation processes. If the observed β is greater than 1.5, additional processes (e.g. an injection of heavy ions from the ionosphere to the plasma sheet and subsequently to the ring current region) may be required.
A computer analysis of drug-protein binding data

Abstract This paper describes a computer program for analyzing drug binding data when more than one set of sites on the macromolecule are involved in the interaction. The mainline calculates the concentrations of unbound and bound ligand from absorbance values obtained in equilibrium dialysis experiments. The analysis and program are based on the assumption that two sets of sites are involved in the binding process. Subroutine GAR computes the association constants and binding capacities for each set of sites. The values are used to calculate the amount of ligand bound to each of the sites. These values are then used to calculate the concentration of the unbound ligand which can be compared with the experimental value. The amounts of unbound and bound ligand are added together at each concentration and compared with the experimental values as a check. Subroutine TEN computes dissociation constants and binding capacities, providing a check on the association constants and binding capacities obtained in GAR.
Enhancing availability in distributed real-time databases

One of the issues in distributed databases is to maintain the data consistency when a database is replicated for higher availability. In a real-time database system, availability may be more important than consistency since a result must be produced before a deadline. We propose techniques to increase the availability in a partitioned real-time database. We also suggest that a transaction may execute even when the most up-to-date information is not available or when a serializable execution cannot be guaranteed. As long as data integrity is maintained, serializable execution may not be necessary.