cssi/SciSciGPT-SciSciNet huggingface dataset:
Hepatic cannabinoid-1 receptors mediate diet-induced insulin resistance by increasing de novo synthesis of long-chain ceramides.

Obesity is associated with increased activity of two lipid signaling systems (endocannabinoids [ECs] and ceramides), with both being implicated in insulin resistance. Cannabinoid-1 receptor (CB1R) antagonists reverse obesity and insulin resistance, but have psychiatric side effects. Here we analyzed the role of ceramide in CB1R-mediated insulin resistance in C57Bl6/J mice with high-fat diet-induced obesity (DIO), using JD5037, a peripherally restricted CB1R inverse agonist. Chronic JD5037 treatment of DIO mice reduced body weight and steatosis and improved glucose tolerance and insulin sensitivity. Peripheral CB1R blockade also attenuated the diet-induced increase in C14:0, C16:0, C18:0, and C20:0 ceramide species with either C16 or C18 sphingosine-base in the liver. Decreased ceramide levels reflected their reduced de novo synthesis, due to inhibition of the activity of serine-palmitoyl transferase (SPT) and the expression of its SPTLC3 catalytic subunit, as well as reduced ceramide synthase (CerS) activity related to reduced expression of CerS1 and CerS6. JD5037 treatment also increased ceramide degradation due to increased expression of ceramidases. In primary cultured mouse hepatocytes and HepG2 cells, the EC anandamide increased ceramide synthesis in an eIF2α-dependent manner, and inhibited insulin-induced akt phosphorylation by increased serine phosphorylation of IRS1 and increased expression of the serine/threonine phosphatase Phlpp1. These effects were abrogated by JD5037 or the SPT inhibitor myriocin. Chronic treatment of DIO mice with myriocin or JD5037 similarly reversed hepatic insulin resistance, as verified using a euglycemic/hyperinsulinemic clamp. Conclusion: ECs induce CB1R-mediated, endoplasmic reticulum stress-dependent synthesis of specific ceramide subspecies in the liver, which plays a key role in obesity-related hepatic insulin resistance. (Hepatology 2014;58:143–153)
Precomputed search trees: planning for interactive goal-driven animation

We present a novel approach for interactively synthesizing motions for characters navigating in complex environments. We focus on the runtime efficiency for motion generation, thereby enabling the interactive animation of a large number of characters simultaneously. The key idea is to precompute search trees of motion clips that can be applied to arbitrary environments. Given a navigation goal relative to a current body position, the best available solution paths and motion sequences can be efficiently extracted during runtime through a series of table lookups. For distant start and goal positions, we first use a fast coarse-level planner to generate a rough path of intermediate sub-goals to guide each iteration of the runtime lookup phase.We demonstrate the efficiency of our technique across a range of examples in an interactive application with multiple autonomous characters navigating in dynamic environments. Each character responds in real-time to arbitrary user changes to the environment obstacles or navigation goals. The runtime phase is more than two orders of magnitude faster than existing planning methods or traditional motion synthesis techniques. Our technique is not only useful for autonomous motion generation in games, virtual reality, and interactive simulations, but also for animating massive crowds of characters offline for special effects in movies.
Niches of Saproxylic Weevils (Coleoptera: Curculionidae) in French Guiana

The loss of tropical forests has a direct effect on saproxylic beetles through the loss of larval feeding substrates and an indirect effect through microclimate change in forest fragments. Impacts will be exacerbated by climate change, and species with narrow niches will be particularly vulnerable. This study presents baseline data on niches (seasonality, host plant, stratum, and branch diameter) of saproxylic weevils in a minimally disturbed moist forest of French Guiana. Weevils (excluding bark beetles) were expected to be host specialists and more abundant in moist microhabitats. Bait branches from three species in the Brazil nut family (Lecythidaceae) were exposed during the dry and rainy season at ground and canopy stratum. They yielded 1,262 weevils in 24 species; 95% belonged to the subfamily Conoderinae. Weevils emerged in greatest abundance from Eschweilera coriacea (A. P. de Candolle) S. A. Mori and from branches in the coolest, moistest microhabitat: ground stratum during the rainy season. Shifts towards warmer, drier climatic conditions would probably have a negative impact on most saproxylic weevil species currently associated with the Brazil nut family. Although this family is expected to suffer under biotic homogenization, the favored host species is hyperdominant throughout Amazonia; climate permitting, E. coriacea could provide a refuge.
Comparison of the Reliability of the Orthoranger and the Standard Goniometer for Assessing Active Lower Extremity Range of Motion

The purposes of this study were to determine 1) the reliability of the Orthoranger for assessing active lower extremity joint range of motion, 2) specific methods for applying the Orthoranger, and 3) whether a correlation exists between the measurements obtained with the Orthoranger and those obtained with a standard goniometer. Ten men and 10 women, mean ages 28.3 ± 5.1 and 30.0 ± 10.1 years, respectively, participated in the study. Random selection was used to determine testing sequences. The Orthoranger and the goniometer were used to measure each joint three times during the five sessions. Results indicated that both instruments were reliable for assessing active lower extremity joint ROM. The goniometer showed greater intraclass correlations and confidence levels for all movements except hip lateral rotation, which demonstrated a higher intraclass correlation for the Orthoranger. In addition, all motions except hip adduction and knee extension demonstrated a positive relationship between instruments. Compared with a manual goniometer, the added costs for purchase and use of the Orthoranger appear to be unnecessary until such time that factors enhancing its inherent reliability are identified.
An architectural leakage power simulator for VHDL structural datapaths

We present a fast RTL leakage power simulator for datapaths described hierarchically in VHDL. Only the leafcells such as full adder NAND gate etc., are characterized for leakage power At the bit-slice level, exhaustive characterization can be performed in reasonable time. We observed that in the transient state, the leakage power is dependent on the previous input as well. This dependence is also incorporated into the leakage model. Using the characterized bit-slice cell library and a given set of inputs, the total leakage energy dissipated in a given datapath is estimated. Compared to HSPICE estimates, the average percentage error for three datapath-intensive designs is 1.38%. The estimation times are reduced by 4-5 orders of magnitude.
Evidence of functional selection pressure for alternative splicing events that accelerate evolution of protein subsequences.

Recently, it was proposed that alternative splicing may act as a mechanism for opening accelerated paths of evolution, by reducing negative selection pressure, but there has been little evidence so far that this mechanism could produce adaptive benefit. Here, we use metrics of very different types of selection pressures [e.g., against amino acid mutations (Ka/Ks), against mutations at synonymous sites (Ks), and for protein reading-frame preservation] to address this question by genomewide analyses of human, chimpanzee, mouse, and rat. These data show that alternative splicing relaxes Ka/Ks selection pressure up to 7-fold, but intriguingly this effect is accompanied by a strong increase in selection pressure against synonymous mutations, which propagates into the adjacent intron, and correlates strongly with the alternative splicing level observed for each exon. These effects are highly local to the alternatively spliced exon. Comparisons of these four genomes consistently show an increase in the density of amino acid mutations (Ka) in alternatively spliced exons and a decrease in the density of synonymous mutations (Ks). This selection pressure against synonymous mutations in alternatively spliced exons was accompanied in all four genomes by a striking increase in selection pressure for protein reading-frame preservation, and both increased markedly with increasing evolutionary age. Restricting our analysis to a subset of exons with strong evidence for biologically functional alternative splicing produced identical results. Thus alternative splicing apparently can create evolutionary “hotspots” within a protein sequence, and these events have evidently been selected for during mammalian evolution.
Benchmark Levels of Operational Safety

The remainder of the book deals with operational safety. That is the prevention of collisions and derailments. This chapter discusses how much safety should be provided. It also introduces five possible market failures which may result in railroads providing non-optimal levels of safety. Subsequent chapters will investigate whether railroads are susceptible to these failures, and the possible public policy responses to the failures.
An IP-level analysis of usage statistics for electronic journals in chemistry: Making inferences about user-behavior.

This study reports an analysis of American Chemical Society electronic journal downloads at Cornell University by individual IP addresses. While the majority of users (IPs) limited themselves to a small number of both journals and article downloads, a small minority of heavy users had a large effect on total journal downloads. There was a very strong relationship between the number of article downloads and the number of users, implying that a user-population can be estimated by just knowing the total use of a journal. Aggregate users (i.e. Library Proxy Server and public library computers) can be regarded as a sample of the entire user population. Analysis of article downloads by format (PDF versus HTML) suggests that individuals are using the system like a networked photocopier, for the purposes of creating print-on-demand copies of articles.
Performance Evaluation of Multicast Cost Sharing Mechanisms

In this paper we investigate experimentally the performance of marginal cost (MC) and Shapley value (SH) mechanisms for sharing the cost of multicast transmissions. We implement and deploy the MC and SH mechanisms on PlanetLab and study their properties. We compare the execution time of MC and SH mechanisms for the tamper-proof and autonomous node models. We also study the convergence and scalability of the mechanisms by varying the number of nodes and the number of users per node. We show that the MC mechanisms generate a smaller revenue compared to the SH mechanisms and thus they are not favorable for the content provider. From the computational point of view as well as economic considerations, increasing the number of users per node is beneficial for the system implementing these mechanisms.
Protein-coated nanoparticles are internalized by the epithelial cells of the female reproductive tract and induce systemic and mucosal immune responses.

The female reproductive tract (FRT) includes the oviducts (fallopian tubes), uterus, cervix and vagina. A layer of columnar epithelium separates the endocervix and uterus from the outside environment, while the vagina is lined with stratified squamous epithelium. The mucosa of the FRT is exposed to antigens originating from microflora, and occasionally from infectious microorganisms. Whether epithelial cells (ECs) of the FRT take up (sample) the lumen antigens is not known. To address this question, we examined the uptake of 20–40 nm nanoparticles (NPs) applied vaginally to mice which were not treated with hormones, epithelial disruptors, or adjuvants. We found that 20 and 40 nm NPs are quickly internalized by ECs of the upper FRT and within one hour could be observed in the lymphatic ducts that drain the FRT, as well as in the ileac lymph nodes (ILNs) and the mesenteric lymph nodes (MLNs). Chicken ovalbumin (Ova) conjugated to 20 nm NPs (NP-Ova) when administered vaginally reaches the internal milieu in an immunologically relevant form; thus vaginal immunization of mice with NP-Ova induces systemic IgG to Ova antigen. Most importantly, vaginal immunization primes the intestinal mucosa for secretion of sIgA. Sub-cutaneous (s.c) boosting immunization with Ova in complete Freund's adjuvant (CFA) further elevates the systemic (IgG1 and IgG2c) as well as mucosal (IgG1 and sIgA) antibody titers. These findings suggest that the modes of antigen uptake at mucosal surfaces and pathways of antigen transport are more complex than previously appreciated.
Phosphorylation-Dependent and Phosphorylation-Independent Modes of Modulation of Shaker Family Voltage-Gated Potassium Channels by Src Family Protein Tyrosine Kinases

Modulation of voltage-gated potassium (Kv) channels by protein phosphorylation plays an essential role in the regulation of the membrane properties of cells. Protein-protein binding domains, such as Src homology 3 (SH3) domains, direct ion channel modulation by coupling the channels with intracellular signaling enzymes. The conventional view is that protein kinase binding to ion channels leads to modulation by bringing the channel substrate into physical proximity to the enzyme, thereby fostering covalent modification of the channel. The SH3 domain binding-dependent functional suppression of Kv1.5 currents by Src family protein tyrosine kinases (PTKs) is considered a canonical example of this type of mechanism. In the present study we address whether the SH3-dependent binding of Src family PTKs to Shaker family Kvs mediates modulatory events that are independent of and/or dependent on Src-catalyzed tyrosine phosphorylation of the channel. We find that Src binding and tyrosine phosphorylation are each able to modulate Kv1 family macroscopic channel currents independently. SH3-dependent binding of Src leads to the suppression of both Kv1.5 and Kv1.4 (modified to contain proline-rich SH3 domain binding sites) macroscopic currents even in the absence of Src-catalyzed tyrosine phosphorylation, whereas binding-independent tyrosine phosphorylation by Src leads to the suppression of Kv1.5 macroscopic currents and the modulation of Kv1.4 inactivation kinetics.
The Optimal Inflation Rate in New Keynesian Models: Should Central Banks Raise Their Inflation Targets in Light of the Zero Lower Bound?

We study the effects of positive steady-state inflation in New Keynesian models subject to the zero bound on interest rates. We derive the utility-based welfare loss function taking into account the effects of positive steady-state inflation and solve for the optimal level of inflation in the model. For plausible calibrations with costly but infrequent episodes at the zero-lower bound, the optimal inflation rate is low, typically less than two percent, even after considering a variety of extensions, including optimal stabilization policy, price indexation, endogenous and statedependent price stickiness, capital formation, model-uncertainty, and downward nominal wage rigidities. On the normative side, price level targeting delivers large welfare gains and a very low optimal inflation rate consistent with price stability. These results suggest that raising the inflation target is too blunt an instrument to efficiently reduce the severe costs of zero-bound episodes.
Predication of motor recovery using kinematic and kinetic measures

The objective of this study was to characterize the time-course of changes in motor impairment after stroke, and to use the kinematic and kinetic measures of elbow voluntary movement at 1 month to predict the ensuing recovery patterns over 1 year. The arm motor impairment was assessed using the Fugl-Meyer Assessment (FMA) of the upper extremity at 1, 2, 3, 6, and 12 months after stroke. Several kinematic features of voluntary rapid elbow extension were quantified by measuring the movement trajectory and its derivatives. The "growth mixture” and "logistic regression" models were used to characterize recovery patterns of FMA over 1 year and to predict these patterns, based on the kinematic and kinetic measures at 1 month. We observed two major distinct recovery classes. Class 1 subjects started with low-level FMA score and then increased significantly before tapering off gradually. Conversely, class 2 subjects started with a high-level FMA score but remained invariant or increased slightly. Our results showed that the kinematic and kinetic measures at 1 month were a significant predictor of the motor recovery. These findings demonstrate that the logistical regression class membership may enable us to accurately predict arm impairment recovery during the first year using kinematic and kinetic measures at the early stage of stroke.
A wireless handheld system for interactive multimedia-enhanced instruction

This paper introduces a new wireless handheld computer System (hardware and software) for interactive multimedia-enhanced instruction. This versatile system provides all the multimedia and communication functionality of a traditional desktop computer in a portable device. The system allows the instructor to manage a lecture presentation, access web pages, and control the classroom environment. To encourage classroom interaction, the system includes a web-server where students can anonymously pose questions and voice opinions via their computer In our experience, over 90% of students respond to instructor questions in this fashion, which is considerably higher than in a traditional classroom setting. Furthermore, this system has a relatively small cost in comparison to conventional multimedia based systems.
Dual mode model for mixed gas permeation of CO2, H2, and N2 through a dry chitosan membrane

Dry chitosan is an excellent candidate for facilitated transport membranes that can be utilized in industrial applications, such as fuel cell operations and other purification processes. This article is the first to report temperature effects on transport properties of CO 2 , H 2 , and N 2 in a gas mixture typical of such applications. At a feed pressure of 1.5 atm, CO 2 permeabilities increased (0.381-26.1 barrers) at temperatures of 20-150 °C with decreasing CO 2 /N 2 (19.7-4.55) and CO 2 /H 2 (3.14-1.71) separation factors. The pressure effect on solubilities and permeabilities were fitted to the extended dual mode model and its corresponding mixed gas permeation model. The dual mode and transport parameters, the sorption heats and the activation energies of Henry's and Langmuir's regimes and their pre-exponential parameters were determined. The Langmuir's capacity constants were utilized to estimate chitosan's glass transition temperature (CO 2 : 172 °C, N 2 : 175 °C, and H 2 : 171 °C). The activation energies of diffusion in the Henry's law and Langmuir regimes were dependent on th collision diameter of the gases.
Design and optimization of compatible, segmented thermoelectric generators

The thermoelectric compatibility factor is used to rationally select materials for a segmented thermoelectric generator. The thermoelectric potential is used for the exact analytic expressions for materials with temperature dependent thermoelectric properties. This calculation does not assume constant or averaged thermoelectric properties as is often done for analytic results. The calculations use the relative current density as the intensive independent variable. A method of optimizing the system configuration is outlined that allows a separation of the system level and thermoelectric level with only three interface parameters: thermoelectric hot side temperature, cold side temperature and the heat flux. The calculation of performance under non-optimal conditions is described.
Evolution of upper jaw protrusion mechanisms in elasmobranchs

SYNOPSIS. Upper jaw protrusion is a prominent component of the feeding mechanism in most elasmobranchs and has received considerable attention over the years. In this paper, we review what is known of muscle activity during prey capture in elasmobranchs, particularly that of upper jaw protrusion, and evaluate the extent to which functional modifications have evolved through changes in anatomy or patterns of muscle activity. To date, motor activity during feeding has been documented in only four species of elasmobranchs, although they represent the three major elasmobranch groups: Galea (typical sharks); Squalea (dogfish sharks); and Batoidea (skates and rays). Our efforts show that while muscles involved in cranial elevation and lower jaw depression and elevation show a conserved pattern of motor activity and function across species, other muscles show a more variable history. Our observations of elasmobranch upper jaw protrusion mechanisms suggest a mosaic of character changes over the course of evolution that involve anatomical changes in all cases and modifications of muscle activation patterns in some cases. During the evolution of feeding mechanisms of elasmobranchs, there have been two structural changes incorporating a pre-existing motor pattern to yield an unmodified kinematic profile, the original preorbitalis and the descendent preorbitalis. One additional instance of structural modification is accompanied by an alteration in the motor pattern leading to a change in movement pattern, the levator palatoquadrati.
Rett syndrome: habilitation and management reviewed.

Experience over the past 10 years in the diagnosis and comprehensive management of females with Rett syndrome has given us a better understanding of the potential skills and abilities which need to be identified. This condition is unique in that after a period of early regression of development there appears to be stabilization with some improvement. The potential for these girls to achieve some functional skills and maintain them presents a challenge, but one that needs to be addressed. Medical management should include stabilization of uncontrolled seizures. Developing a comprehensive plan for feeding disorders is required so that resulting nutritional problems and constipation can be corrected. Recognition of gastroesophageal reflux and its proper management may prevent respiratory complications. Appropriate intervention strategies using different therapeutic techniques are described which have been effective in facilitating communication, maintaining hand function and ambulation, and preventing deformities. Progression of scoliosis can be managed with intensive physical therapy. Management encompasses a comprehensive medical, therapeutic, educational, and psychosocial approach, which is best provided by a team in collaboration with community agencies that serve children with special needs and their families. Language: en
Investigation of Photo-Imageable Thick Film Metallization on Low Temperature Cofired Ceramics (LTCC) for Improved Packaging Density

With the increasing electronics demand on complexity and functionality, low temperature cofired ceramic (LTCC) shows its advantages for cost efficiency under high volume, multilayer high packaging density, and compatibility of passive components integration. However, compared with thin film technology, the minimum thick film line width and spacing on LTCC is 4mil, which limits the packaging of fine pitch devices. In this study, one of DuPont™ photoimageable thick film gold (Au) conductors has been selected to fabricate on DuPont 951PX substrate, with the patterns as small as 1mil. Surface insulation resistance (SIR) and serpentine resistance patterns with a series of line width and spacing was printed and post fired on LTCC to investigate the capabilities and limits of the feature size. Feature dimensions were measured to compare with the design value. Metal adhesion and stud bump patterns are also included in the test substrate. After initial testing, the substrates are undergoing 300°C aging. Post aging...
Max Data Report Jet Stability versus Inlet Geometry

This document describes experiments investigating the effect of inlet geometry on the flow field within a glass tank where two jets mix and impinge upon the lid. The setup mimics the outlet plenum of a fast reactor where core exit flows of different temperatures can mix in ways that induce thermal cycling in neighboring structures.
Two new computer based results in game theory related to combinatorial games and nash equilibria

This thesis consists of two chapters. The first chapter is about the new version of NIM recently introduced by Gurvich together with a generalization of the minimal excludant function (mex). This game NIM(a, b) is played with two piles of matches. Two players alternate turns. By one move, each player can take either "almost the same" number of matches from each pile (the difference of the two numbers is strictly less than a) or any number of matches from one pile and strictly less than b from the other. This game further extends Fraenkel's NIM = NIM(a, 1), which, in its turn, is a generalization of the classic Wythoff NIM = NIM(1, 1). Gurvich introduced a generalization mexb of the standard minimum excludant mex = mex1 defining mex b(S ⊂ Z+ ) = min{n : ∀s ∈ S s ≤ n ⇒ s + b ≤ n}. He also showed that P-positions (the kernel) of NIM(a, b) are given by the following recursion: xn=mexb xi,yiv 0≤i 1 is the Perron root of the polynomial Pz=zb+1-z-1 -i=1 a-1 z ib/a, whenever a and b are coprime; furthermore, it is known that e(ka, kb) = ke(a, b). In particular, e(a, 1) = αa = ½(2 − a + a2+4 ). In 1982, Fraenkel introduced the game NIM(a) = NIM(a, 1), obtained the above recursion and solved it explicitly getting xn = faanf , yn = xn + an = faa+a nf . Here we provide a polynomial time algorithm based on the Perron-Frobenius theory solving game NIM(a, b), although we have no explicit formula for its kernel. The second chapter of the thesis is about the existence of Nash equilibria (NE) in pure stationary strategies in n-person positional games with no moves of chance, with perfect information, and with the mean or total effective cost function. We construct a NE-free three-person game with positive local costs, disproving the conjecture suggested by Boros and Gurvich in Math. Soc. Sci. 46 (2003) 207-241. Still, the following four problems remain open: Whether NE exist in all two-person games with total effective costs such that (I) all local costs are strictly positive or (II) without directed cycles of the cost zero? If NE exist in all n-person games with the terminal (transition-free) cost functions, provided all directed cycles form a unique outcome c and (III) assuming that c is worse than any terminal outcome or (IV) without this assumption? For n = 3 cases (I) and (II) are answered in the negative, while for n = 2 cases (III) and (IV) are proven. We briefly survey other negative and positive results on Nash-solvability in pure stationary strategies for the games under consideration.
Disease Heterogeneity in Na+/Citrate Cotransporter Deficiency

We report a novel mutation found in two siblings, a male and a female aged 8 and 5 years, respectively. Both patients presented with developmental delay and intractable seizures consistent with previous reports of SLC13A5 transporter deficiency. Both had two mutations in the SLC13A5 gene, c.655G>A (G219R) and the novel mutation c.245A>G (Y82C). However, the phenotypes were not identical as the female had focal cortical dysplasia that led to brain surgery. This is another example of the heterogeneity in disease expression even when the genotype is identical in the affected individuals.
Prostate cancer chemoprevention agents exhibit selective activity against early stage prostate cancer cells.

Prostate cancer chemoprevention agents exhibit selective activity against early stage prostate cancer cells
Free flap lower extremity reconstruction in the obese population: does weight matter?

The obesity epidemic continues to grow, and we have observed greater numbers of obese individuals among patients seeking lower extremity reconstruction at our institution. These patients may present a greater reconstructive challenge, thus we sought to identify risk factors and differences in outcomes among patients undergoing lower extremity reconstruction. In this study we have performed a retrospective cohort analysis of patients undergoing lower extremity reconstruction with free tissue transfer at our institution from 2005 to 2012. Patients were classified using the World Health Organization criteria for obesity. Records were reviewed for patient characteristics, mechanism of injury, indications for reconstruction, and surgical technique, with a focus on intraoperative and early postoperative complications and outcomes. A total of 43 out of the 119 patients undergoing lower extremity reconstruction were obese (body mass index ≥ 30). Mechanism of injury, wound location, and the indications for reconstruction were similar in both cohorts. No significant differences were found in operative characteristics and techniques, including the type of flap utilized, operative time, or thrombotic events. No significant differences were seen in complication rates overall, however, obese patients more frequently needed second flaps (11.6 vs. 0%, p = 0.005). This study concludes that successful lower extremity reconstruction can be performed in the obese population, with few differences in complication rates and outcomes relative to healthy weight patients.
A fast method for computing eigenvalues of a structural matrix with interval parameters

In order to increase computational efficiency of interval eigenvalues,the monotone property of design parameters of a structural matrix was studied firstly.Then a fast methodology for calculating the eigenvalues of the structural matrix with interval parameters was put forward,which was based on the Rayleigh quotient and the theories of the interval mathematics.It is shown that as the deviation of the interval factors of the design parameters are similar and close to unity,the computational error of the fast methodology are determined by the dispersion between the interval factors;and the error comes up to zero if all the interval factors are equal.Finally,two numerical examples were given,they proved that the presented method is more feasible and efficient than the global optimization algorithm and the interval stepped dividing method.
MS Forum/MS Over the Past 17 Years

At its final meeting, the MS Forum Executive Committee reviewed highlights of where things stood prior to the immunomodulatory era, and how things have evolved subsequently. What the future might hold was discussed in a second session. Prior to 1990: Genetic predisposition to multiple sclerosis (MS), as determined by human leukocyte antigen expression, was established and an environmental trigger (Epstein-Barr virus?) was suspected, as was lack of sunshine. Substantial evidence for activated T-cells as relapse initiators had accumulated. Defective regulatory cell function that correlated with disease activity was shown. Adrenocorticotropic hormone lessened relapse severity as did its steroid replacement. A trial of cyclosporine, a T-cell inhibitor, in progressive MS failed. The drug, not the patients chosen, was blamed. 1990-2010: Approval of interferon-beta (IFNB)-1b was followed promptly by IFNB-1a, glatiramer acetate, mitoxantrone and then by natalizumab and fingolimod. All reduce MS attack frequency and new lesion accumulation. None have reduced disability progression in progressive MS. Brain atrophy, cognitive loss and axonal interruption in progressive MS depend on innate immune system activation rather than on T-cells. New strategies are needed.
Stat5a Is Epigenetically Silenced by Oncogenic Tyrosine Kinase NPM/ALK and Acts as Tumor Suppressor by Reciprocally Inhibiting Expression of NPM/ALK.

Abstract Although Stat5a and Stat5b exhibit some non-redundant functional properties, their distinct contributions to carcinogenesis are not clearly defined. Here we report that Stat5a expression is selectively inhibited by DNA methylation of the Stat5a gene promoter region in cells expressing an oncogenic tyrosine kinase NPM/ALK. The DNA methylation is induced by NPM/ALK itself by employing its key effector Stat3, and is associated with binding to the promoter of MeCP2 capping protein and lack of binding of the Stat5a transcription activator Sp-1. Reversal of the methylation by DNA methyltransferase inhibitor, 5′-aza-2-deoxycytidine, restores the Sp-1 binding and Stat5a expression. Strikingly, the induced or exogenously expressed Stat5a binds to enhancer and exon 14 of the NPM/ALK gene and triggers selective suppression of NPM/ALK expression. These results demonstrate that NPM/ALK induces epigenetic silencing of Stat5a and that Stat5a can act as key tumor suppressor by reciprocally inhibiting expression of NPM/ALK.
A Qualitative Exploration of Why Faith Matters in African American Marriages and Families

Researchers have found recurring connections between shared marital religious involvement and improved marital stability functioning. However, researchers know little about the processes at work be...
To Your Health: The Relationship between Health Insurance and Self-Employment Exit

Drawing on a sample of 5,941 individuals taken from the Health and Retirement Study, we examined what, if any, relationship exists between health insurance and self-employment exit. Interestingly, our results indicate that individuals who are self-insured are more likely to exit self-employment. We further find that females are less likely to exit self-employment, and that gender, age, and the presence of pre-existing medical conditions all moderate the relationship between health insurance and self-employment exit. We conclude by discussing the implications that these findings have on the self-employment literature as well as on policy scholars and policy makers themselves.
Universal Dynamics of Molecular Reorientation in Hybrid Lead Iodide Perovskites

The role of organic molecular cations in the high-performance perovskite photovoltaic absorbers, methylammonium lead iodide (MAPbI3) and formamidinium lead iodide (FAPbI3), has been an enigmatic subject of great interest. Beyond aiding in the ease of processing of thin films for photovoltaic devices, there have been suggestions that many of the remarkable properties of the halide perovskites can be attributed to the dipolar nature and the dynamic behavior of these cations. Here, we establish the dynamics of the molecular cations in FAPbI3 between 4 K and 340 K and the nature of their interaction with the surrounding inorganic cage using a combination of solid state nuclear magnetic resonance and dielectric spectroscopies, neutron scattering, calorimetry, and ab initio calculations. Detailed comparisons with the reported temperature dependence of the dynamics of MAPbI3 are then carried out which reveal the molecular ions in the two different compounds to exhibit very similar rotation rates (≈8 ps) at room ...
Lithium Therapy for Bipolar Disorder

Abstract The management of bipolar disorder (BD) may be challenging because of the disease state itself. In addition, the maintenance of the drug level of lithium plays a vital role in preventing acute manic or mixed episodes. This article reviews the drug properties of lithium, the current treatment guidelines for BD, and best practices in monitoring lithium therapy, as well as the characteristics and classification of BD.
Centralized path planning for multiple robots: Optimal decoupling into sequential plans

We develop an algorithm to decouple a multi-robot path planning problem into subproblems whose solutions can be executed sequentially. Given an external path planner for general configuration spaces, our algorithm finds an execution sequence that minimizes the dimension of the highest-dimensional subproblem over all possible execution sequences. If the external planner is complete (at least up to this minimum dimension), then our algorithm is complete because it invokes the external planner only for spaces of dimension at most this minimum. Our algorithm can decouple and solve path planning problems with many robots, even with incomplete external planners. We show scenarios involving 16 to 65 robots, where our algorithm solves planning problems of dimension 32 to 130 using a PRM planner for at most eight dimensions. 1
Identification of hemopoietic cells responsive to colony-stimulating factor by autoradiography

Binding of radiolabeled L-cell colony-stimulating factor (CSF) was studied using murine bone marrow and fetal liver cells. With 10(7) cells, saturation of binding was seen with approximately 500,000 cpm of 125I-CSF. Minimal binding was detected after one hour incubation with tracer at 37 degrees C; however, marked cellular uptake of radioactivity was noted after 24-hr exposure to CSF. As judged by autoradiographs, small numbers of myeloblasts, promyelocytes, and large mononuclear cells were labeled with 1-hr exposure to tracer. By 6 hr of incubation, 50%-70% of myeloblasts and promyelocytes and small numbers of late granulocytic cells were labeled. Virtually all myeloblasts and promyelocytes and approximately 50% of myelocytes, metamyelocytes, polymorphonuclear granulocytes, and monocytes were labeled after 24-hr exposure to the radioiodinated CSF. Label was not detected on erythroblasts, eosinophils, or megakaryocytes. Suspensions of fetal liver cells had lower uptake of radioactivity than bone marrow cells. This appeared to result from a lesser concentration of granulocytic cells in fetal liver, as labeling of individual cells was similar with both tissues. In additional experiments, CSF binding to marrow cells was assessed after 30-min exposure to tracer at 0 degrees C. Uptake of 125I-CSF exceeded that observed after 24-hr incubation at 37 degrees C. With this technique, cellular label was also confined to granulocytic and monocytic cells. These findings suggest that purified CSF reacts with and may stimulate immature and mature cells of the granulocytic and monocytic lineages.
Intra-patient heterogeneity in urothelial cancer (UC) circulating tumor cells (CTC) and PDL1 expression to identify biomarkers of response and new therapeutic targets: A pilot study.

4537Background: Recent use of immune checkpoint inhibitors (CI) has improved overall survival (OS) in a subset of patients (pts) with metastatic UC. Intra-patient tumoral heterogeneity and epitheli...
Cyber-ARGUS - A mission assurance framework

Abstract The use of cyberspace as a platform for military operations has been growing at impressive rates. Yet, it is still a relatively new area that poses considerable research challenges. Security techniques are not sufficiently effective to protect IT systems and most fail to address the correlation between actions and effects across multiple domains. In other words, identifying how actions performed in the cyber domain affect the mission goals is yet an unsolved problem. This research presents a potential solution and proposes a framework that links the cyber and the operations domains, evaluating how actions in the first impact the effectiveness of missions in the latter. The framework, Cyber-ARGUS, is a Command and Control (C2) support system comprised of a set of tools that provides coherent and consistent mapping between the two domains. Relevant information about the nodes of a cyber infrastructure supporting an operation is stored in a knowledge base, and then used to build a Bayesian Network that provides impact assessment. The technique is illustrated through the simulation of an air transportation scenario in which the C2 infrastructure is subjected to various cyber-attacks, and Cyber-ARGUS is used to assess their associated impact to the air operations. The main contribution of this research is the methodology that enables assessing the cyber impact to ongoing missions. One major advantage of the technique is that it achieves this by calculating the combined effects produced by the attackers and defenders plans, without the requirement of knowing the hard-to-assess enemy's individual actions.
Crystal engineering with DNA

This Review chronicles over two decades of research into creating a genetic code for crystal engineering. Rather than directing biological processes, this code uses synthetic forms of DNA to programme the assembly of nanoparticles and microparticles into 1D, 2D and 3D crystalline architectures, in which almost every aspect of the resultant structures can be systematically controlled. Within this conceptual framework, the structural and functional advances are described in an effort to define the present level of sophistication and to predict future directions of the platform. These advances include exotic structures with programmable lattice symmetries and well-defined crystal habits, responsive materials that leverage the intrinsic properties of nucleic acids to manipulate structures on demand, nanoparticle superlattices grown epitaxially from surfaces and colloidal crystals that offer insights into light–matter interactions. Looking forward, we challenge the community to leverage the extraordinary structural control afforded by crystal engineering with DNA to synthesize classes of functional materials that push beyond what has been possible with naturally occurring crystalline materials or those made by more conventional strategies. This Review outlines the ability of DNA to direct the organization of particle-based building blocks into crystalline architectures. These advancements permit programmable control of each structural element of colloidal crystalline materials and enable the design of functional and responsive behaviours.
Estimating Uterine Fibroid SNP-Based Heritability in European American Women with Imaging-Confirmed Fibroids.

BACKGROUND Heritability estimates (including twin and single nucleotide polymorphism [SNP]-based heritability studies) for fibroids have been inconsistent across prior studies ranging between 9 and 69%. These inconsistencies are due to variations in study design and included populations. A major design issue has been lack of imaging confirmation to identify controls, where asymptomatic women without imaging confirmation may be misclassified as controls leading to an attenuation of heritability estimates. To reconcile the differences in prior heritability estimates and the impact of misclassification of controls on heritability, we determined SNP-based heritability and characterized the genetic architecture of pelvic image-confirmed fibroid cases and controls. METHODS Analyses were performed among women of European American descent using genome-wide SNP data from BioVU, a clinical database composed of DNA linked to de-identified electronic health records. We estimated the genetic variance explained by all SNPs using Genome-Wide Complex Trait Analysis on imputed data. Fibroid cases and controls were identified using a previously reported phenotyping algorithm that required pelvic imaging confirmation. RESULTS In total, we used 1,067 image-confirmed fibroid cases and 1,042 image-confirmed fibroid controls. The SNP-based heritability estimate for fibroid risk was h2 = 0.33 ± 0.18 (p = 0.040). We investigated the relationship between heritability per chromosome and chromosome length (r2 < 1%), with chromosome 8 explaining the highest proportion of variance for fibroid risk. There was no enrichment for intergenic or genic SNPs for the fibroid SNP-based heritability. Excluding loci previously associated with fibroid risk from genome-wide association study did not attenuate fibroid heritability suggesting that loci associating with fibroid risk are yet to be discovered. CONCLUSIONS We observed that fibroid SNP-based heritability was higher than the previous estimate using genome-wide SNP data that relied on self-reported outcomes, but within the range of prior twin pair studies. Furthermore, these data support that imprecise phenotyping can significantly affect the ability to estimate heritability using genotype data.
Elongate hemlock scale, an exotic scale insect pest of Christmas trees and other conifers

Elongate hemlock scale, Fiorinia externa Ferris (Hemiptera: Diaspididae), is an armored scale insect native to Japan and eastern Asia. This insect was first documented in the United States in 1908 in Queens, NY, and has since spread throughout most of the eastern United States. Though the primary hosts of the pest, hemlocks and firs, do not occur in Florida, there are concerns that elongate hemlock scale coming into the region on cut Christmas trees may disperse and establish on conifers that do occur in Florida. Of specific interest are two endangered species, Florida torreya (Torreya taxiflora) and Florida yew (Taxus floridana), which are native to a small region in northwestern Florida. Also of concern are Florida forestry species, Florida Christmas tree species, and species used for ornamental plantings in Florida. What can Florida do to protect its native conifers and farmed trees from the elongate hemlock scale? Find out in this 5-page fact sheet written by Adam Dale, Travis Birdsell, and Jill Sidebottom and published by the UF/IFAS Entomology and Nematology Department. http://edis.ifas.ufl.edu/in1253
Green Fashion Purchase Behavior of Hispanic Consumers in US: Role of Fashion Consciousness, Health Consciousness and Personal Norms

Hispanics are the most rapidly growing ethnic segment in US estimated to reach 21.1% in 2030 and 27.5% in 2060 (Vespa, Armstrong, &Medina, 2018). Due to their strong fashion focus and interest in shopping, they are an important target segment for apparel and fashion retailers. Some recent evidence indicates that Hispanic consumers are also buying more organic products and supporting social conscious brands. This research aims to address gap in the literature and investigate factors that influence green fashion purchase behavior of young Hispanic consumers in US. Using a thorough literature review,eight hypotheses are proposed and tested on a sample of 181 Hispanic college students. Based on the results of structural equation modeling, we find that knowledge of organic apparel and textile products is the strongest driver of purchase behavior towards these products followed by personal norms. Fashion consciousness of Hispanics plays an important role in driving behavior by influencing knowledge. In other words, more fashion-conscious Hispanic consumers tend to have a stronger knowledge of organic apparel and textile products.
Silvicultural options for open forest management in eastern North America

Abstract Fire-sustained open oak and pine forests were once widespread across eastern North America, but are now comparatively scarce. To regain the goods and services of these open forests, managers are increasingly looking to restore them with the silvicultural systems and tools best suited to meet their objectives. Hence, we synthesized a number of research efforts and case studies from open pine, mixedwood, and oak-dominated forests in eastern North America to demonstrate the silvicultural options available and recognized knowledge gaps. The silvicultural treatment options and tools available are very similar to those applied in closed-canopy forests, even if the objectives are fundamentally different. For instance, while conventional practices in naturally regenerated forests concentrate on managing closed tree canopies to increase periodic yields and encourage new tree recruitment, open forest silviculture focuses on the maintenance of a vertically simple and understocked canopy to facilitate a robust herbaceous groundflora and limit woody plant regeneration. To achieve and sustain this understocked condition, open forest management applies multiple tools (e.g., prescribed fire, periodic harvests or deadenings, and herbicide use and planting if and when needed) along with other understory enhancement and maintenance treatments. This review demonstrates that while we have learned much about open forest silviculture over the decades, many information gaps and challenges for managers remain.