cssi/SciSciGPT-SciSciNet huggingface dataset:
Theoretical model for quantifying the operative benefit of unruptured cerebral aneurysms by location, age and size

Aim: The indications for surgery on unruptured asymptomatic cerebral aneurysms are still unclear. Previous mathematical models that have addressed this issue group all aneurysm sizes and locations into one category and report one average rupture and surgical complication rate. In this report the authors used a comprehensive review of the literature and mathematical models to create an online open-access program to quantify the benefit of surgery on unruptured aneurysms according to age, size and location. Materials and methods: Using 5-year prospective International Study of Unruptured Intracranial Aneurysms data and a literature search of 30 additional studies (10,545 patients), we calculated annual rupture rates and operative complication rates for aneurysms by size (5–25 mm), patient age (40–70 years) and 14 common locations. Using this location-, size- and age-specific data, a mathematical model was created by solving differential equations measuring the survival rate of a patient with and without an ...
Estimating Reference Intervals

As indicated in the thought-provoking article in this issue of the Journal by Katayev and colleagues,1 there are few things more important than the reference intervals we report along with our laboratory measurements. Unfortunately, we laboratory professionals give them far too little attention, adopting manufacturers’ recommended intervals, often without even verifying them ourselves and, rarely, if ever, establishing our own values. Thus, the article “Establishing Reference Intervals for Clinical Laboratory Test Results: Is There a Better Way?” is certain to attract much attention. Katayev and colleagues1 make several assertions that bear comment. They claim that there is no clear guideline as to which technique to use, but the recommendations of the International Federation of Clinical Chemistry and Laboratory Medicine2 and the CLSI3 are quite clear. If one collects samples carefully from 120 vetted healthy people, then the technique of choice is nonparametric analysis. The reason for this is that the nonparametric technique requires no knowledge of, and makes no assumptions about, the nature of the data distribution. In other words, the reference interval values obtained are valid no matter what the underlying distribution is. If one has fewer samples, again from carefully screened, apparently healthy people, one can use a parametric technique with as few as 40 points, so long as the original data (or some transformed version of the data) exhibit a gaussian distribution. And with even fewer than 40 data points, one can use robust techniques to get an estimate of the reference interval.3,4 Notwithstanding the assertions by Katayev and colleagues,1 the reference intervals obtained from properly collected and analyzed data do not vary depending on the technique used.3 Katayev and colleagues1 also make the point that it becomes prohibitively difficult to collect sufficient data for all the …
The biologic relevance of daily dose variations in adaptive treatment planning.

Purpose: To explore the biologic relevance of deviations from the intended uniform fractionation scheme. Methods and Materials: We study the effect of the variance of the dose per fraction on the normalized total dose (NTD), which incorporates the linear-quadratic model of radiation effects. In regions of steep dose gradients, we determine the shift between NTD isodose lines and physical isodose lines. We also look at ways to compensate for dose-variation effects through dose adjustments, without changing the number of fractions. Results: Simple equations quantify effects of dose variation on the NTD. If the standard deviation of the dose is 10% of the daily dose fraction, the effects on the NTD for a given point in the irradiated area are always less than 1%, independent of the biologic parameters. In adaptive dose-correction schemes, the dose correction should be applied uniformly over the remaining fractions, to minimize the variance. Incomplete repair leads to a coupling of doses delivered on different days, which complicates the issue. Repopulation appears to be insignificant in the context of this study (constant overall treatment time). Conclusions: A variation of the dose between fractions always leads to a larger biologic effect than does the same total dose delivered with standard uniform fractionation. The increase in NTD is negligible if the standard deviation of the dose is less than 10% of the dose per fraction.
The Lunar Orbiter Laser Altimeter (LOLA) laser transmitter

We present the final configuration of the space flight laser transmitter as delivered to the Lunar Orbiter Laser Altimeter (LOLA) instrument. The instrument was launched in 2009 and has been in operation for close to two years and accumulated over 1.3 billion laser shots in space.
Stability and selectivity of a chronic, multi-contact cuff electrode for sensory stimulation in human amputees

Objective. Stability and selectivity are important when restoring long-term, functional sensory feedback in individuals with limb-loss. Our objective is to demonstrate a chronic, clinical neural stimulation system for providing selective sensory response in two upper-limb amputees. Approach. Multi-contact cuff electrodes were implanted in the median, ulnar, and radial nerves of the upper-limb. Main results. Nerve stimulation produced a selective sensory response on 19 of 20 contacts and 16 of 16 contacts in subjects 1 and 2, respectively. Stimulation elicited multiple, distinct percept areas on the phantom and residual limb. Consistent threshold, impedance, and percept areas have demonstrated that the neural interface is stable for the duration of this on-going, chronic study. Significance. We have achieved selective nerve response from multi-contact cuff electrodes by demonstrating characteristic percept areas and thresholds for each contact. Selective sensory response remains consistent in two upper-limb amputees for 1 and 2 years, the longest multi-contact sensory feedback system to date. Our approach demonstrates selectivity and stability can be achieved through an extraneural interface, which can provide sensory feedback to amputees.
Kinetic coefficient for hard-sphere crystal growth from the melt.

Using molecular-dynamics simulation, we determine the magnitude and anisotropy of the kinetic coefficient ($\ensuremath{\mu}$) for the crystal growth from the melt for the hard-sphere system through an analysis of equilibrium capillary fluctuations in interfacial height. We find ${\ensuremath{\mu}}_{100}=1.44(7)$, ${\ensuremath{\mu}}_{110}=1.10(5)$, and ${\ensuremath{\mu}}_{111}=0.64(3)$ in units of $\sqrt{{k}_{B}/(m{T}_{m})}$, where ${k}_{B}$ is Boltzmann's constant, $m$ is the particle mass, and ${T}_{m}$ is the melting temperature. These values are shown to be consistent, with some exceptions, with those obtained in recent simulation results a variety of fcc metals, when expressed in hard-sphere units. This suggests that the kinetic coefficient for fcc metals can be roughly estimated from $C\sqrt{R/(M{T}_{m})}$, where $R$ is the gas constant, $M$ is the molar mass, and $C$ is a constant that varies with interfacial orientation.
A cooperative game theoretical replica placement technique

Creating replicas of frequently accessed data objects across a read intensive network can lead to reduced communication cost and end-user response time. On the contrary, data replication in the presence of writes incurs extra cost due to multiple updates. The selection of data objects and servers requires solving a constraint optimization problem, which is NP-complete in general. A majority of the current state-of-the-art replica placement techniques suffer from high computational complexity issues. To circumvent such issues, we propose a cooperative game theoretical technique in which the servers (players) in the system collectively deliberate to converge at a replica schema that is beneficial to the system as a whole. In particular we make use of the Aumann-Shapley mechanism of cooperative game theory to propose an effective replica placement technique that yields good solutions when the system is very heavily loaded. Experimental comparisons are made against: (1) branch and bound, (2) greedy, (3) genetic, (4) Dutch auction, and (5) English auction. As demonstrated by the experimental results, the proposed technique maintains superior solution quality in terms of lower communication cost and reduced execution time.
Psychosocial and Contextual Predictors of Educational and Occupational Self-Efficacy among Hispanic Inner-City Adolescents:

This study investigated psychosocial and contextual predictors of self-efficacy beliefs about educational and occupational attainment among Hispanic adolescents living in the inner-city. Participan...
Starry night: a texture devoid of depth cues.

From a modern Bayesian point of view, the classic Julesz random-dot stereogram is a cue-conflict stimulus: Texture cues specify an unbroken, unslanted surface, in conflict with any variation in depth specified by binocular disparity. We introduce a new visual texture—the starry night texture (SNT)—that is incapable of conveying slant, depth edges, or texture boundaries, in a single view. For SNT, changing density is equivalent to changing intensity, so an instance of the texture is characterized (up to the random locations of the texture elements) by what we call its densintensity. We consider deviations from the ideal that are needed to realize the texture in practice. In three experiments with computer-generated stimuli we examined human perception of SNT to show that (1) the deviations from the ideal that were needed to realize SNT do not affect the invariance of its appearance across changes in distance of several orders of magnitude; (2) as predicted, observers match SNT across changes in distance better than other textures; and (3) the use of SNT in a slant perception experiment did not reliably increase observers’ reliance on stereoscopic slant cues, as compared with the sparse random-dot displays that have been commonly employed to study human perception of shape from binocular disparity and motion. © 2004 Optical Society of America OCIS codes: 330.5000, 330.1400.
The Meaning of Self-in-Role: A Modified Measure of Role-Identity

The Burke-Tully technique for the measurement of role-identity offers a theoretically sophisticated quantitative measure of self-in-role. Since its development it has been used to explain a wide range of behaviors from a symbolic interactionist perspective. Three general problem areas, however, challenge its reliability and validity: (1) the identification of counteridentities, (2) the use of adjectives to assess meaning, and (3) cumbersome and lengthy implementation and construction procedures. In this study a modified measure of self-in-role is developed that avoids these three areas. An empirical application of the modified measure demonstrates relatively strong construct validity and a predictive power equal to that of the Burke-Tully technique. The self has long been a central concept in the social sciences. This is especially true in sociology because the self and related ideas of role and identity have been used to establish a link between the individual and the social structure. The importance of the concept of self is articulated in a rich theoretical tradition that begins with the work of James (1890), Cooley (1902), and Mead (1934) and extends to the more recent work of Blumer (1969), Goffman (1959), Turner (1976), Rosenberg (1979), and Stryker (1980), among others (cf. Gecas 1982). Yet, while the concept has undergone extensive theoretical development and elaboration over the years, parallel advances in measurement have not kept pace. Sociologists attempting to measure the self for use in empirical analyses have generally adopted one of two strategies (Burke & Tully 1977). The most common approach has been to focus on global self-esteem - a general
Cosigned vs. group loans

We analyze lending contracts when social sanctions are used to enforce repayments and borrowers differ in their abilities to impose sanctions. Symmetric group loans are preferred to cosigned loans when sanctioning abilities are similar; that is, when the power relation between borrowers is relatively equal. Conversely, cosigned loans are preferred when the power relation is unequal. We analyze why group lending arrangements offering different loan terms to members of the same group are difficult to implement. We also show that our comparison between symmetric group loans and cosigned loans is robust to endogenous matching.
Epilepsy Five New Things

Approximately 30% of patients with epilepsy are medically refractory despite multiple antiepileptic drug (AED) trials due to continued seizures or intolerable side effects. Novel AEDs and other therapies are needed that are more effective with improved tolerability. New treatments and new insights into management of comorbidities are discussed, with a focus on adult patients with epilepsy. The Food and Drug Administration (FDA) recently approved 3 new AEDs, and a fourth AED may be near approval. Lacosamide (LCS) is approved by the FDA for adjunctive treatment for partial-onset seizures. It has novel mechanisms of action, enhancing the slow inactivation of voltage-gated sodium channels and binding collapsing response mediator protein 2. LCS has a low potential for drug–drug interactions, is renally excreted, and is dosed twice daily. It does not affect plasma concentrations of concomitant AEDs. The most common adverse effects were dizziness, headache, diplopia, nausea, and vomiting, which were mild or moderate. Small increases in the PR interval were observed, but were not of clinical consequence. In a recent randomized, double-blinded, placebo-controlled trial of adjunctive treatment with LCS for medically refractory partial-onset seizures at doses of 400 to 600 mg daily, median reductions in seizure frequency were 37.3% for the 400 mg/day and 37.8% for the 600 mg/day groups. For secondarily generalized tonic-clonic seizures, median reductions in seizure frequency were more robust at 59.4% for the 400 mg/day group and 93.0% for the 600 mg/day groups. In addition, 8% of the patients in the 600 mg/day group became seizure-free.1 Rufinamide (RUF) is FDA-approved for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS). This new AED adds to the AEDs already used for LGS including valproic acid, lamotrigine, felbamate, and topiramate. Its mechanism of action includes limiting the excessive firing of sodium-dependent action potentials, but RUF also exhibits a broad …
Semantic similarity analysis of XML schema using grid computing

A growing number of e-businesses have been using XML schemas in recent years. Schema mapping now plays a crucial role in integrating heterogeneous e-business applications. Since large-scale XML schema mapping using complex and hybrid similarity measures requires significant amount of processing time, a sophisticated similarity analysis algorithm is needed to handle its complexity and performance. In this paper, we focus on designing a service-oriented architecture (SoA) for schema mapping, based on a grid computing technology in order to enhance the effectiveness of the mapping algorithm. After comparing three different grid computing technologies (MPJ, Hadoop, and Globus), we explain why MPJ is the most suitable. We propose SoA XML schema mapping based on MPJ, and demonstrate its performance.
Numeric Modeling of Water Mains Filling Considering Air Pressurization

The filling of water mains represents a type of unsteady, two phase flow that normally follows maintenance procedures which require emptying the mains. This is…
Characterization of leaf surface, wax composition, and control of redvine and trumpetcreeper with glyphosate

Abstract Laboratory and greenhouse studies were conducted on redvine and trumpetcreeper to characterize leaf surface and wax composition, determine responses of these weeds to glyphosate, characterize the nature of interactions between glyphosate and several selective postemergence herbicides (e.g., acifluorfen, bentazon, chlorimuron, imazaquin, and pyrithiobac) used in soybean and cotton, and determine the effects of various adjuvants on glyphosate activity on both species. Trumpetcreeper was consistently more susceptible to glyphosate than redvine. Glyphosate spray solution droplets had lower contact angle in trumpetcreeper than in redvine. Micro-roughness of the trumpetcreeper adaxial leaf surface was greater due to trichomes and glands compared to that of redvine, which had no trichomes or glands. Stomata or crystal wax deposition on the adaxial leaf surface were not observed in either species. The wax mass per unit area (22 to 37 µg cm−2) was similar regardless of the leaf age in both species. Epicut...
Credit Spreads in General Equilibrium

We study default risk in an incomplete markets general equilibrium setting. We show some interesting properties of default and recovery rates in equilibrium, and derive CAPM-type equilibrium bounds on credit spreads. We are able to price aggregate components of credit risk, summarized in our model by 'credit quality.' Finally we argue that states with the possibility of 'rolling default' exist when defaultable assets are traded, and because of this possibility, there can be flight to quality and a marketwide increase in credit spreads. When these rolling default states exist, and negative shocks to receivables are anticipated, this ‘contagion risk’ is priced.
Participation in Counseling: Does Family Matter? An Analysis of a Community Population

Premature termination from counseling is a significant problem for the field of counseling. In contrast to previous research on counseling dropout, in this study, the authors examined the impact of family participation and constellation as possible mediators.Archival data were collected from 113 client files at a non-profit community mental health agency in North Texas and chi square analyses were conducted. Results indicated that family participation was an important factor in counseling continuation. Implications for clinical practice, research, training, and public policy are discussed.
Impact of Right-Sided-Catheter-Based Valve Implantation on Decision-Making in Congenital Heart Disease

There is a growing appreciation for the adverse long-term impact of right-sided valvular dysfunction in patients with congenital heart disease. Although right-sided valvular stenosis and/or regurgitation is often better tolerated than left-sided valvular dysfunction in the short and intermediate term, the long-term consequences are numerous and include, but are not limited to, arrhythmias, heart failure, and multi-organ dysfunction. Surgical right-sided valve interventions have been performed for many decades, but the comorbidities associated with multiple surgeries are a concern. Transcatheter right-sided valve replacement is safe and effective and is being performed at an increasing number of centers around the world. It offers an alternative to traditional surgical techniques and may potentially alter the decision making process whereby valvular replacement is performed prior to the development of long-term sequelae of right-sided valvular dysfunction.
Disulfide Cross-linking of a Multidrug and Toxic Compound Extrusion Transporter Impacts Multidrug Efflux

Multidrug and toxic compound extrusion (MATE) transporters contribute to multidrug resistance by extruding different drugs across cell membranes. The MATE transporters alternate between their extracellular and intracellular facing conformations to propel drug export, but how these structural changes occur is unclear. Here we combine site-specific cross-linking and functional studies to probe the movement of transmembrane helices in NorM from Neiserria gonorrheae (NorM-NG), a MATE transporter with known extracellular facing structure. We generated an active, cysteine-less NorM-NG and conducted pairwise cysteine mutagenesis on this variant. We found that copper phenanthroline catalyzed disulfide bond formation within five cysteine pairs and increased the electrophoretic mobility of the corresponding mutants. Furthermore, copper phenanthroline abolished the activity of the five paired cysteine mutants, suggesting that these substituted amino acids come in spatial proximity during transport, and the proximity changes are functionally indispensable. Our data also implied that the substrate-binding transmembrane helices move up to 10 A in NorM-NG during transport and afforded distance restraints for modeling the intracellular facing transporter, thereby casting new light on the underlying mechanism.
A new role for cofilin in retinal neovascularization

Pak1 plays an important role in several cellular processes, including cell migration, but its role in pathological angiogenesis is not known. Here, we have determined its role in pathological retinal angiogenesis using an oxygen-induced retinopathy (OIR) model. VEGFA induced phosphorylation of Pak1 and its effector cofilin in a manner that was dependent on time as well as p38MAPKβ (also known as MAPK11) in human retinal microvascular endothelial cells (HRMVECs). Depletion of the levels of any of these molecules inhibited VEGFA-induced HRMVEC F-actin stress fiber formation, migration, proliferation, sprouting and tube formation. In accordance with these observations, hypoxia induced Pak1 and cofilin phosphorylation with p38MAPKβ being downstream to Pak1 and upstream to cofilin in mouse retina. Furthermore, Pak1 deficiency abolished hypoxia-induced p38MAPKβ and cofilin phosphorylation and abrogated retinal endothelial cell proliferation, tip cell formation and neovascularization. In addition, small interfering RNA (siRNA)-mediated downregulation of p38MAPKβ or cofilin levels in the wild-type mouse retina also diminished endothelial cell proliferation, tip cell formation and neovascularization. Taken together, these observations suggest that, although the p38MAPKβ-Pak1-cofilin axis is required for HRMVEC migration, proliferation, sprouting and tubulogenesis, Pak1-p38MAPKβ-cofilin signaling is also essential for hypoxia-induced mouse retinal endothelial cell proliferation, tip cell formation and neovascularization.
Sheep Ked Control with Pour-On Applications of Organophosphorus Insecticides

Pour-on applications of diazinon at 42.2 mg/kg to lambs and shorn ewes eradicated infestations of Melophagus ovinus (L.). Substantial reductions of ked populations were provided by coumaphos at 14.4 mg/kg, crufomate at 40.0 and 80.0 mg/kg, diazinon at 31.6, 21.0, 10.5, and 5.3 mg/kg, and ronnel at 31.6 mg/kg. All insecticides that were used had an established residue tolerance in sheep, and all formulations were available commercially in the United States.
Looking at spillover from both sides: an examination of work and home flexibility and permeability

ABSTRACTThis study examined how flexibility and permeability in the boundaries surrounding the work and home domains affect the spillover from work to home and home to work. We looked at both flexibility and permeability in each of the two domains using directional and dichotomous measures of both negative and positive spillovers. Multivariate analyses and hierarchical regression showed that for 362 survey respondents, boundary flexibility reduced time- and strain-based spillover from work to home and home to work. Flexibility also was positively related to positive spillover from home to work. Permeability, on the other hand, was positively related to time-based spillover from work to home and from home to work. The results also showed support for the notion of asymmetric permeability, such that the relationships between work boundary permeability and the W→H spillovers were stronger than those between home boundary permeability and the H→W spillovers.
Study of Computing Method to Physical Property Parameters of Steam during the Process of Steam Injection

Transmission of heat will appear from heating steam to well bore and subterranean formation,and physical property parameters of steam will change during the process of steam injection when heavy oil are produced by steam drive or steam stimulation method.In this paper,heat migration theory has been used,and based on the principia of energy conservation,momentum conservation and mass conservation,calculation model of steam pressure gradient,mass dryness fraction gradient and heat transmission during the process of steam injection have been established.The models have been computed by four step Rungekutta method,and with the man-made software,physical property parameters of steam in a well of Liaohe oil field have been predicted.Each error is under 4.11% between the measured data and computed data,this method can be used in working site.
Relations among measures of body composition, age, and sex in the common marmoset monkey (Callithrix jacchus).

Few studies of body composition have been done in New World primates. In the study reported here, four methods of assessing body composition (body weight, anthropometry, labeled-water dilution, and total body electroconductivity) were compared in 20 marmosets, aged 0.96 to 7.97 years. Males and females did not differ in any measure (P > 0.05). Body weight ranged from 272 to 466 g, and body fat estimates varied from 1.6 to 19.5%. Strong positive correlations were observed between total body water and total body electroconductivity (R2 = 0.77), body weight and fat-free mass (males R2 = 0.95; females R2 = 0.91), and body weight and fat mass (males R2 = 0.86; females R2 = 0.85; P 0.05) for the regressions of fat and fat-free mass against body weight. Positive correlations also were observed between girth measures and fat-free mass (R2 = 0.48 to 0.78) and fat mass (R2 = 0.60 to 0.74; P < 0.01). A good second- order polynomial relationship was observed between age and fat-free mass for the combined sample (R2 = 0.64). Results indicated that: subjects were lean; there was no sexual dimorphism relative to measures; body weight provided a reliable estimate of fat and fat-free mass; and within-subject body weight changes reflected a similar relationship between body weight and fat-free mass as did that across subjects.
CPU issues in the representation of the molecular structure of petroleum resid through characterization, reaction, and Monte Carlo modelling

Today it is possible to stimulate molecular structure of petroleum resid with the Monte Carlo method. In this paper, the authors optimize the structural parameters using the reaction simulation. However, time simulation increase and the new model does not prove useful for a results optimization
Chapter 35 Clinical observations on the emotional motor system

Publisher Summary This chapter describes clinical observations on non-verbal aspects of motor control relevant to the emotional motor system. Although motor activity is usually considered, at least at first glance, in terms of its voluntary aspects there are other motor activities that occur spontaneously and are not easily or accurately mimicked on a voluntary basis or in response to verbal instruction. These motor activities are mediated, in large part, by an emotional or non-verbal motor system. There are three relatively independent operations of several anatomically distinct motor systems in man: (1) controlling distal appendicular musculature that can be activated volitionally in a highly fractionated manner, (2) involving more proximal axial musculature involved in whole body activities such as maintenance of posture, body steering, and orientation, and (3) a third motor system innervates the facial and bulbar musculature involved in emotional expression and other affective displays. These three systems for motor control utilize relatively independent, descending pathways. Although neuroanatomic studies have provided much of the basis for the understanding of multiple motor systems in primates, the existence of these parallel systems can also be inferred from clinical observation.
GVHD: ferocity affects feracitas.

In this issue of Blood, Shimoji et al demonstrate for the first time that female mice that develop acute graft-versus-host disease (GVHD) have reduced fertility and that donor CD8+ T lymphocytes are critical for the destruction of granulosa cells and the eventual loss of ovarian function. Importantly, GVHD prophylaxis preserved fertility in their model.1
A New Lens on High School Dropout: Use of Correspondence Analysis and the Statewide Longitudinal Data System

The combination of log-linear models and correspondence analysis have long been used to decompose contingency tables and aid in their interpretation. Until now, this approach has not been applied t...
In Silico Prediction of Ligand Binding Energies in Multiple Therapeutic Targets and Diverse Ligand Sets-A Case Study on BACE1, TYK2, HSP90, and PERK Proteins.

We present here the use of QM/MM LIE (linear interaction energy) based binding free energy calculations that greatly improve the precision and accuracy of predicting experimental binding affinities, in comparison to most current binding free energy methodologies, while maintaining reasonable computational times. Calculations are done for four sets of ligand–protein complexes, chosen on the basis of diversity of protein types and availability of experimental data, totaling 140 ligands binding to therapeutic protein targets BACE1, TYK2, HSP90, and PERK. This method allows calculations for a diverse set of ligands and multiple protein targets without the need for parametrization or extra calculations. The accuracy achieved with this method can be used to guide small molecule computational drug design programs.
Re-characterization of the Glomerulopathy in CD2AP Deficient Mice by High-Resolution Helium Ion Scanning Microscopy

Helium ion scanning microscopy (HIM) is a novel technology that directly visualizes the cell surface ultrastructure without surface coating. Despite its very high resolution, it has not been applied extensively to study biological or pathology samples. Here we report the application of this powerful technology to examine the three-dimensional ultrastructural characteristics of proteinuric glomerulopathy in mice with CD2-associated protein (CD2AP) deficiency. HIM revealed the serial alteration of glomerular features including effacement and disorganization of the slit diaphragm, followed by foot process disappearance, flattening and fusion of major processes, and eventual transformation into a podocyte sheet as the disease progressed. The number and size of the filtration slit pores decreased. Strikingly, numerous “bleb” shaped microprojections were observed extending from podocyte processes and cell body, indicating significant membrane dynamics accompanying CD2AP deficiency. Visualizing the glomerular endothelium and podocyte-endothelium interface revealed the presence of endothelial damage, and disrupted podocyte and endothelial integrity in 6 week-old Cd2ap-KO mice. We used the HIM technology to investigate at nanometer scale resolution the ultrastructural alterations of the glomerular filtration apparatus in mice lacking the critical slit diaphragm-associated protein CD2AP, highlighting the great potential of HIM to provide new insights into the biology and (patho)physiology of glomerular diseases.
Data Mining with Markowitz Portfolio Optimization in Higher Dimensions

In the spirit of financial analytics, this is an applied statistical approach to the data mining of equities price trends in order to gain insight into selecting the most desireable portfolios on the basis of return, volatility, and intersecurity time series correlation. It expands the Markowitz Portfolio Theory approach, which depends upon a multivariate normal distribution of log returns, in finding optimal security portfolios to higher dimensions (N~p). Results are reported for hundreds of candidate securities using data adjustments followed by quadratic programming in the R language.
SHARPIN, a novel regulator of the NLRP3 inflammasome (INM6P.334)

NLRP3 recruits adaptor ASC and protease caspase-1 to assemble the inflammasome, which is critical for maturation of IL-1β and IL-18. Although, NLRP3 is one of the most-studied inflammasome, the direct ligand or the mechanisms that govern activation of NLRP3 inflammasome remains obscure. Recent study with Hoil1 -/- mice demonstrated that HOIL1 is required for NLRP3 inflammasome activation. It was further proposed that HOIL1 was required for linear ubiquitination of ASC to regulate NLRP3 inflammasome assembly. HOIL1 along with HOIP and SHARPIN form linear ubiquitin assembly complex (LUBAC) that is essential for linear ubiquitination of target proteins. Herein, we wanted to determine whether SHARPIN is also involved in the activation of NLRP3 inflammasome. Using Sharpin cpdm mice (spontaneous mutation that results in SHARPIN deficiency), we demonstrated that SHARPIN is critically required for activation of both canonical and non-canonical NLRP3 inflammasome, but dispensable for activation of NLRC4 and AIM2 inflammasome. Interestingly, our studies further show that unlike HOIL1, SHARPIN regulates NLRP3 inflammasome by controlling priming events. To this end, we demonstrated that Sharpin cpdm BMDMs have dramatically reduced NFkB, ERK, p38 MAP kinase activation and pro- Il1b expression. Thus, our study for the first time demonstrates SHARPIN as a novel regulator of NLRP3 inflammasome adding to the complexity of our understanding of NLRP3 inflammasome.
Optimal Blood Pressure After Intracerebral Hemorrhage: Still a Moving Target

See related article, p 348 If you have been following the literature in recent years and feel confused about how to manage acute hypertension in patients with intracerebral hemorrhage (ICH), you are not alone. Two similar randomized controlled trials reaching seemingly different conclusions can confuse anybody.1,2 However, as always, the devil is in the details. It is not just about the blood pressure (BP) target, but also about how and when you reach it. The INTERACT-2 trial (The Second Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial) evaluated nearly 2800 patients with acute hypertension within 6 hours of ICH onset randomized to target systolic BP <140 or <180 mm Hg.1 Hypertension could be treated with any drugs available, and patients were treated to remain below their BP target for 7 days. Death and moderate or severe disability at 90 days (modified Rankin score of 3–6) did not differ significant between the 2 arms (odds ratio, 0.87 with systolic BP <140 mm Hg; 95% confidence interval, 0.75–1.01; P =0.06), but functional outcomes were better in the intensive treatment arm on a prespecified ordinal shift analysis of the modified Rankin score. Serious adverse events were similar in the 2 groups. On the basis of these results, the …
On a linear programming approach to the optimal seeding of cascading failures

We consider the threshold model of cascading behavior in networks, in which a node fails if at least a certain fraction of its neighbors have failed in the previous time step. Our goal is to solve the optimal cascade seeding problem: For a given network and specified time horizon, find the set of nodes whose failure at time zero maximizes the failure amplification ratio — the ratio between the number of final and initial failures. The optimal cascade seeding problem is combinatorial and thus intractable for large networks. We propose an approximation of the threshold model that lends itself to the application of tools from dynamical systems theory and convex optimization. Through a sequence of relaxations we write the approximate optimal cascade seeding problem as a linear program, which has the benefit of scaling gracefully in network size. Our approach retains the original network topology and accommodates the specification of a wide range of additional constraints on the initialization and propagation of failures, such as which nodes are immune from initial failure and which are required to be in failed state by the end of the time horizon.
Pharmacological Characterization of IW-1973, a Novel Soluble Guanylate Cyclase Stimulator with Extensive Tissue Distribution, Antihypertensive, Anti-Inflammatory, and Antifibrotic Effects in Preclinical Models of Disease

Soluble guanylate cyclase (sGC), a key signal-transduction enzyme, increases the conversion of guanosine-5'-triphosphate to cGMP upon binding of nitric oxide (NO). Endothelial dysfunction and/or reduced NO signaling have been implicated in cardiovascular disease pathogenesis and complications of diabetes and have been associated with other disease states and aging. Soluble guanylate cyclase (sGC) stimulators are small-molecule drugs that bind sGC and enhance NO-mediated cGMP signaling. The pharmacological characterization of IW-1973 [1,1,1,3,3,3-hexafluoro-2-(((5-fluoro-2-(1-(2-fluorobenzyl)-5-(isoxazol-3-yl)-1H-pyrazol-3-yl) pyrimidin-4-yl)amino)methyl)propan-2-ol], a novel clinical-stage sGC stimulator under clinical investigation for treatment of heart failure with preserved ejection fraction and diabetic nephropathy, is described. In the presence of NO, IW-1973 stimulated sGC in a human purified enzyme assay and a HEK-293 whole cell assay. sGC stimulation by IW-1973 in cells was associated with increased phosphorylation of vasodilator-stimulated phosphoprotein. IW-1973, at doses of 1-10 mg/kg, significantly lowered blood pressure in normotensive and spontaneously hypertensive rats. In a Dahl salt-sensitive hypertension model, IW-1973 significantly reduced blood pressure, inflammatory cytokine levels, and renal disease markers, including proteinuria and renal fibrotic gene expression. The results were affirmed in mouse lipopolysaccharide-induced inflammation and rat unilateral ureteral obstruction renal fibrosis models. A quantitative whole-body autoradiography study of IW-1973 revealed extensive tissue distribution and pharmacokinetic studies showed a large volume of distribution and a profile consistent with predicted once-a-day dosing in humans. In summary, IW-1973 is a potent, orally available sGC stimulator that exhibits renoprotective, anti-inflammatory, and antifibrotic effects in nonclinical models.
Timely, granular, and actionable: Informatics in the public health 3.0 era

Ensuring the conditions for all people to be healthy, though always the core mission of public health, has evolved in approaches in response to the changing epidemiology and challenges. In the Public Health 3.0 era, multisectorial efforts are essential in addressing not only infectious or noncommunicable diseases but also upstream social determinants of health. In this article, we argue that actionable, geographically granular, and timely intelligence is an essential infrastructure for the protection of our health today. Even though local and state efforts are key, there are substantial federal roles in accelerating data access, connecting existing data systems, providing guidance, incentivizing nonproprietary analytic tools, and coordinating measures that matter most.
Rhizobium Meliloti Lon Protease Plays an Essential Role in the Alfalfa Symbiosis

Screening Rhizobium meliloti strain 104A14 transposon mutants for constitutive expression of phosphatases resulted in the isolation of a mutant exhibiting increased acid phosphatase activity during growth on media containing high phosphorous. The transposon and flanking DNA were cloned in pBluescript and DNA adjacent to the insertion site was sequenced. The inferred peptide sequence of the interrupted gene had high homology with Lon protease from a number of organisms. Unlike Lon mutants in Eschenichia coli, the R. meliloti mutant showed no increase in UV sensitivity. The ion mutant formed pseudonodules on alfalfa plants. These pseudonodules fixed little nitrogen and contained few bacteroids relative to the wild type strain, indicating some aspect of infection is negatively affected in this mutant. A cosmid subclone containing the wild-type Ion allele restored normal symbiotic function.
Nuclear Organization, Chromatin Structure, and Gene Silencing

The nucleus is a specialized compartment within a cell that is surrounded by a nuclear envelope and contains the genomic DNA in the form of chromosomes. Inside the nucleus, chromosomes are confined to specific three-dimensional regions, termed territories. In general, the periphery of the nucleus is a zone of gene silencing; heterochromatin, a condensed form of chromatin possessing little transcriptional activity, resides near the nuclear envelope. In contrast, chromosomes rich in gene activity reside within the interior of the nucleus. Within the nucleus, genes assume specific radial positions that can change with transcriptional activity and in disease states.
Carbon Partitioning, Cost, and Metabolism of Arbuscular Mycorrhizas

Colonization of roots by arbuscular mycorrhizal [AM] fungi results in many changes in the carbon partitioning and metabolism of the host plant. The rate of carbon assimilation, the export of photosynthates from leaves, and the sink strength of roots may be increased relative to that in uncolonized plants. Hexose is taken up by the obligately symbiotic fungus for its growth, maintenance, and reproduction. This can represent a significant cost to the host, most notably under conditions in which the fungus offers little nutritive benefit. The components of the carbon partitioning and cost of arbuscular mycorrhizas, as well as current knowledge of the carbon metabolism of germinating spores and infra- and extraradical hyphae of AM fungi are reviewed in this chapter.
A novel approach for evaluating programs designed to serve military veterans: Using an adapted common components analysis.

Abstract Evaluators are challenged to keep pace with the vast array of Veteran support programs operating in the United States, resulting in a situation in which many programs lack any evidence of impact. Due to this lack of evidence, there is no efficient way to suggest which programs are most effective in helping Veterans in need of support. One potential solution to this dilemma is to reconceptualize program evaluation, by moving away from evaluating programs individually to evaluating what is common across programs. The Common Components Analysis (CCA) is one such technique that aggregates findings from programs that have undergone rigorous evaluation at the level of program components (e.g., content, process, barrier reduction). Given that many Veteran programs lack outcome evidence from rigorous studies, an adaptation to CCA is needed. This report examines cross-sectional data from a pilot study using an adapted CCA across five domains of well-being (i.e., employment, education, legal/financial/housing, mental/physical health, and social/personal relationships). The purpose of this preliminary study is to determine the feasibility of eliciting program nominations and program components from Veterans via an online survey. When coupled with a longitudinal research design, this adaptation to CCA will allow for stronger causal claims about the expected impact of different program components within and across a variety of domains.
OPREVENT (Obesity Prevention and Evaluation of InterVention Effectiveness in NaTive North Americans): Design of a Multilevel, Multicomponent Obesity Intervention for Native American Adults and Households.

Obesity prevalence is high in Native American (NA) adults, and there is a critical need to establish and implement evidence-based social, behavioral, and policy interventions that are theoretically informed. The use of multilevel, multicomponent (MLMC) interventions has been shown to be an effective strategy for comprehensive health behavior change; however, there is little guidance available in the literature to facilitate implementation in this underserved and understudied population. To decrease obesity and related comorbidities in NA adults, an MLMC intervention called OPREVENT (Obesity Prevention and Evaluation of InterVention Effectiveness in NaTive North Americans) was implemented in 5 rural NA communities to modify the food-purchasing environment, improve diet, and increase physical activity (PA). Five NA communities across the Upper Midwest and Southwest United States were randomly assigned to Immediate (n = 3) or Delayed (n = 2) Intervention. OPREVENT was implemented in Immediate Intervention community food stores, worksites, schools, and media over 1 y. A community-randomized controlled trial was used to evaluate intervention impact in adults at the individual and institutional levels, with individual-level data being collected on diet, PA, and psychosocial variables at baseline and follow-up; and institutional-level data being collected on food stores, worksites, and schools, media, and process measures. The OPREVENT intervention was one of the first MLMC obesity interventions in this population and provides evidence-based practices for future program development. The purpose of this article is to describe the design, implementation, and evaluation of OPREVENT. This trial was registered at isrctn.com as ISRCTN76144389.
A Bottom-Up, Top-Down Approach to Formal Control Synthesis for Multi-agent Systems

This paper develops an approach for synthesizing the cooperative control of multiple agents. Typically, the design of the control for this type of system requires a high level of complexity and is based on heuristics. To avoid the use of heuristics, formal supervisory control theory is applied to generate control logic that is correct-by-construction. This paper combines the bottom-up approach of [1] with a novel top-down refinement step to further reduce the complexity of the control synthesis process. The method of this paper is validated using the example of [1] and is shown to provide significant further reduction in computation time.
Remote patient monitoring using smart phone derived patient reported outcomes and Fitbit data to enable longitudinal predictive modeling in prostate cancer: Feasibility results and lessons on platform development.

e18068Background: Wearable activity trackers and frequent interrogation of remote patient reported outcomes (PROs) have the potential to revolutionize oncology clinical trial design, therapeutic se...
CREEP OF TEXTURED TI-3AL-2.5V TUBING UNDER BIAXIAL LOADING

ABSTRACT Creep behavior of stress relieved Ti-3A1-2.5V tubing has been studied under biaxial stress conditions at 673 K using internal pressurization combined with axial loading. Comparison of the experimental creep locus constructed at a constant value of the dissipative work function with isotropic locus showed that the material is highly anisotropic. Crystallographic textures were characterized using both the inverse and direct pole figures from which c rystallite orientation d istribution functions [CODF] were developed. Transmission electron microscopy (TEM) of the stress relieved alloy before and after creep deformation revealed that the observed anisotropy is due to a severe distortion in the microstructure, in addition to preferred grain orientations, as a result of cold work which has not been fully recovered.
Extramedullary Plasmacytoma Involving the Trachea: A Case Report and Literature Review

Abstract Background Extramedullary plasmacytoma is an uncommon type of plasma cell neoplasm that occurs outside of the bone marrow. Very rarely, extramedullary plasmacytomas can involve the trachea, causing significant respiratory distress. Case Report We describe a patient with a history of multiple myeloma who presented with voice hoarseness and dyspnea and was found to have airway obstruction due to an extramedullary plasmacytoma near the larynx. Why Should an Emergency Physician Be Aware of This? It is important to investigate the possibility of upper airway obstruction in cancer patients presenting with hoarseness and dyspnea to prevent incorrect management, which can lead to fatal results. In particular, wheezing and dyspnea in patients with a history of asthma may not always be due to asthma exacerbation. Computed tomography scans and emergency laryngoscopy have been shown to be useful in aiding with correct diagnosis of upper airway obstruction, ensuring appropriate treatment.