cssi/SciSciGPT-SciSciNet huggingface dataset:
Preventing adolescent health-risk behaviors by strengthening protection during childhood.

Objective: To examine the long-term effects of an intervention combining teacher training, parent education, and social competence training for children during the elementary grades on adolescent health-risk behaviors at age 18 years. Design: Nonrandomized controlled trial with follow-up 6 years after intervention. Setting: Public elementary schools serving high-crime areas in Seattle, Wash. Participants: Of the fifth-grade students enrolled in participating schools, 643 (76%) were given written parental consent for the longitudinal study and 598 (93%) were followed up and interviewed at age 18 years. Interventions: A full intervention provided in grades 1 through 6 of 5 days of in-service training for teachers each intervention year, developmentally appropriate parenting classes offered to parents when children were in grades 1 through 3 and 5 through 6, and developmentally adjusted social competence training for children in grades 1 and 6. A late intervention, provided in grades 5 and 6 only, paralleled the full intervention at these grades.
Dynamic optimization of micro-operations

Inherent within complex instruction set architectures such as /spl times/86 are inefficiencies that do not exist in a simpler ISA. Modern /spl times/86 implementations decode instructions into one or more micro-operations in order to deal with the complexity of the ISA. Since these micro-operations are not visible to the compiler the stream of micro-operations can contain redundancies even in statically optimized /spl times/86 code. Within a processor implementation, however barriers at the ISA level do not apply, and these redundancies can be removed by optimizing the micro-operation stream. In this paper we explore the opportunities to optimize code at the micro-operation granularity. We execute these micro-operation optimizations using the rePLay Framework as a microarchitectural substrate. Using a simple set of seven optimizations, including two that aggressively and speculatively attempt to remove redundant load instructions, we examine the effects of dynamic optimization of micro-operations using a trace-driven simulation environment. Simulation reveals that across a sampling of SPECint 2000 and real /spl times/86 applications, rePLay is able to reduce micro-operation count by 21% and, in particular load micro-operation count by 22%. These reductions correspond to a boost in observed instruction-level parallelism on an 8-wide optimizing rePLay processor by 17% over a non-optimizing configuration.
Role of astroglial extracellular matrix in the formation of rat olfactory bulb glomeruli.

Abstract We describe the development of the olfactory bulb (OB) glomeruli, focusing on the role of purported astroglial-associated boundary molecules. as potential guidance factors in glomeruli formation. Glomeruli are unusual structures within the OB formed by extremely tight bundles of afferent fibers that fail to grow deeply into the brain. Using olfactory marker protein antibodies, we found that olfactory axons of stage E17-E18 rat embryos were organized into long strands at the outermost edge of the bulb. By E20-E21 the axons clustered and formed small spheres and by PD1 they gathered into distinct glomeruli. Prior to and during the transformation of olfactory afferents into glomeruli, there was an enhanced expression of cytotactin/tenascin (CT) and chondroitin sulfate-containing proteoglycan (CSPG) associated with VIM/GFAP-positive astroglial cell processes at the base of the glomeruli. During later stages of development (PD3-PD9), the GFAP-positive astroglial processes beneath and within the base of the glomeruli showed intensified GFAP staining while maintaining expression of CT and CS-PG. Some astroglial processes had extended and others went even further peripherally into the olfactory nerve layer (ONL) to encapsulate and fully infiltrate the glomeruli. By PD9, CS-PG and CT levels increased inside and outside the glomeruli. However, by PD15 both molecules had decreased inside the glomeruli but remained highly concentrated around the glomeruli to form rings. Thus, at later stages, axon/glia interactions which result in astroglial rearrangement and matrix alterations in relation to the glomeruli occur. Western blots of stage E20 bulb proteins revealed the presence of three proteoglycan core proteins each containing chondroitin-6-sulfate moieties. In addition, a type of keratan sulfate (KS) glycosaminoglycan was present in a core protein not associated with chondroitin-6-sulfate. Our data suggest that astroglial-associated ECM molecules CT and CSPG, and perhaps KS-PG, present in the core of the early developing OB, could form a molecular "wall" that helps confine ingrowing olfactory axons within the ONL at the outer edge of the astroglial territory. We suggest that the astroglia do not precisely regulate the specific shape of the glomeruli, but rather play a fundamental role in directing the gross position at which formation of the synaptic glomeruli will occur.
Theory of polychromatic microwave photons

In this paper, the possibility of superluminal speed of polychromatic microwave photons is analytically shown. The analytical results are correlated with previous experimental data. In this theoretical analysis, a generic-wave equation is used as the basis and the Maxwellian phase-velocity concept of monochromatic microwave photons is applied to microwave spectra of polychromatic photons. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 41: 213–218, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20097
Sequence Information Encoded in DNA that May Influence Long-Range Chromatin Structure Correlates with Human Chromosome Functions

Little is known about the possible function of the bulk of the human genome. We have recently shown that long-range regular oscillation in the motif non-T, A/T, G (VWG) existing at ten-nucleotide multiples influences large-scale nucleosome array formation. In this work, we have determined the locations of all 100 kb regions that are predicted to form distinctive chromatin structures throughout each human chromosome (except Y). Using these data, we found that a significantly greater fraction of 300 kb sequences lacked annotated transcripts in genomic DNA regions $300 kb that contained nearly continuous chromatin organizing signals than in control regions. We also found a relationship between the meiotic recombination frequency and the presence of strong VWG chromatin organizing signals. Large ($300 kb) genomic DNA regions having low average recombination frequency are enriched in chromatin organizing signals. As additional controls, we show using chromosome 1 that the VWG motif signals are not enriched in randomly selected DNA regions having the mean size of the recombination coldspots, and that non-VWG motif sets do not generate signals that are enriched in recombination coldspots. We also show that tandemly repeated alpha satellite DNA contains strong VWG signals for the formation of distinctive nucleosome arrays, consistent with the low recombination activity of centromeres. Our correlations cannot be explained simply by variations in the GC content. Our findings suggest that a specific set of periodic DNA motifs encoded in genomic DNA, which provide signals for chromatin organization, influence human chromosome function.
Principles of engineering: A national initiative

The author describes New York State's New Compact for Learning educational reform project and specifically discusses the work of the MST (mathematics, science, and technology) curriculum and assessment committee. The design and content of a new introductory high school engineering course will be presented as an exemplary program for helping students to achieve the new integrated MST learning outcomes. Finally, a national teacher enhancement and leadership network program that is supported by the National Science Foundation is described. >
Thermochemistry of nanoparticles on a substrate: Zinc oxide on amorphous silica

Crystalline samples of zinc oxide on a mesoporous amorphous silica substrate were prepared by 5 to 15 atomic layer deposition cycles with diethyl zinc and water at 150 °C. Samples were characterized by x-ray diffraction, thermogravimetry, and nitrogen adsorption–desorption isotherms. High-temperature oxide melt solution calorimetry and water adsorption calorimetry experiments were performed to measure surface enthalpy for crystalline ZnO particles supported on the substrate. The measured enthalpies 1.23 ± 0.35 and 2.07 ± 0.59 J/m2 for hydrous and anhydrous surfaces, respectively, are in agreement with previously reported measurements for unsupported ZnO nanoparticles. Feasibility of thermochemical characterization of complex system of atomic layer deposition (ALD) prepared particles on a substrate was demonstrated.
Characterizing the Human Wrist for Improved Haptic Interaction

Haptic displays provide the user with a sense of touch in both simulation of virtual environments and teleoperation of remote robots. The instantaneous impedance of the user’s hand affects this force interaction, changing the transients experienced during activities such as exploratory tapping. This research characterizes the behavior of the human wrist joint while holding a stylus in a three-fingered grasp. Nonparametric identification methods, evaluating frequency-and time-responses, support a second-order system model. Further analysis shows a positive linear correlation between grip force and wrist impedance for all subjects, though each individual’s trend is unique. These findings suggest that a quick calibration procedure and a realtime grip force measurement could enable a haptic display to predict user response characteristics throughout an interaction. Such knowledge would enable haptic control algorithms to adapt continuously to the user’s instantaneous state for improved performance.Copyright © 2003 by ASME
Effects of carbidopa and entacapone on the metabolic fate of the norepinephrine prodrug L-DOPS.

Background: L-threo-3,4-dihydroxyphenylserine (L-DOPS), a norepinephrine (NE) prodrug, is investigational for orthostatic hypotension, which occurs commonly in Parkinson's disease. Adjunctive anti-parkinsonian drugs might interact with L-DOPS. We tested whether L-aromatic amino-acid decarboxylase inhibition by carbidopa (CAR) attenuates L-DOPS conversion to NE and blocks the pressor effect of L-DOPS, whereas catechol-O-methyltransferase inhibition by entacapone (ENT) interferes with L-DOPS metabolism and augments the pressor effect. Methods: Twelve patients with autonomic failure took 400 mg of L-DOPS with 200 mg of placebo (PLA), CAR, or ENT on different days. Plasma L-DOPS, NE, and deaminated NE metabolites (dihydroxyphenylglycol [DHPG], dihydroxymandelic acid [DHMA]) were measured. Results: L-DOPS+PLA and L-DOPS+ENT increased systolic pressure similarly (by 27 ± 8 and 24 ± 9 mm Hg at 3 hours). L-DOPS+CAR did not increase pressure. The peak increase in plasma NE (0.57 ± 0.11 nmol/L) averaged less than 1/15000th that in L-DOPS and less than 1/35th that in DHPG+DHMA. CAR prevented and ENT augmented responses of plasma DHPG and DHMA to L-DOPS. Conclusions: After L-DOPS administration plasma, NE levels do not increase sufficiently to increase blood pressure. Pressor responses to L-DOPS seem to reflect NE produced extraneuronally that escapes extensive enzymatic deamination and O-methylation and evokes vasoconstriction before reaching the systemic circulation.
PanM, an Acetyl-Coenzyme A Sensor Required for Maturation of l-Aspartate Decarboxylase (PanD)

Coenzyme A (CoA) is essential for cellular chemistry in all forms of life. The pantothenate moiety of CoA is generated from the condensation of pantoate and -alanine.-Alanine is formed by decarboxylation of L-aspartate catalyzed by PanD, a pyruvoyl enzyme that is synthesized by the cell as an inactive precursor (pro-PanD). Maturation of pro-PanD into PanD occurs via a self-cleavage event at residue Ser25, which forms the catalytic pyruvoyl moiety. We recently reported that Salmonella en- terica PanM was necessary for pro-PanD maturation, both in vitro and in vivo. Notably, PanM is annotated as a Gcn5-like N-acetyltransferase (GNAT), which suggested that lysine acetylation might be part of the mechanism of maturation. Here we show that PanM lacks acetyltransferase activity and that acetyl-CoA stimulates its activity. Results of experiments with nonhy- drolyzable ethyl-CoA and genetically encoded acetyl-lysine-containing PanD support the conclusion that PanM-dependent pro- PanD maturation does not involve an acetyl transfer event. We also show that CoA binding to PanM is needed for in vivo activity and that disruption of CoA binding prevents PanM from interacting with PanD. We conclude that PanM is a GNAT homologue that lost its acetyltransferase activity and evolved a new function as an acetyl-CoA sensor that can trigger the maturation of pro- PanD. IMPORTANCE N-lysine acetylation is increasingly being recognized as a widespread and important form of posttranslational regulation in bacteria. The acetyltransferases that catalyze these reactions are poorly characterized in bacteria. Based on annota- tion, most bacterial genomes contain several acetyltransferases, but the physiological roles of only a handful have been deter- mined. Notably, a subset of putative acetyltransferases lack residues that are critical for activity in most biochemically character- ized acetyltransferases. We show that one such putative acetyltransferase, PanM (formerly YhhK), lacks acetyltransferase activity but functions instead as an acetyl-coenzyme A (CoA) sensor. This work establishes the possibility that, like PanM, other putative acetyltransferases may have evolved new functions while retaining the ability to sense acetyl-CoA.
On the generalized von Neumann inequality

for any contraction T on a Hilbert space H and any (scalar) polynomial p. We prove a generalized von Neumann inequality for a special class of commuting multi-contractions T = (Tl, ... , TN) on H and for any polynomial p of N independent complex variables, such that the coefficients of p are operators on H that doubly commute with each Ti , i = 1, N. This is made by means of a construction of a kind of partially doubly commuting isometric dilation for our class of multi-contractions. For similar generalizations of the von Neumann inequality, in the commutative context, we refer to [11] (for the case N = 1) and to [14] (for N = 2).
A New Area Sampling Frame and Its Uses

A REA sampling for agriculture's uses in the United States has been identified with the master sample materials prepared at Iowa State University in the early 1940's. The area method of sampling involves subdividing the entire area to be sampled in each state into sampling units. Sampling based on the master sample frame refers to the use of areas of land as sampling units. In the preparation of this frame, three types of land areas were identified based on incorporation and density of population. The county highway maps were used for this purpose. Thus, three strata, (1) open country, (2) urban places, and (3) rural places, were identified in the sampling material. Also, the open country was divided into units which were called "count units." The word "count" was used to convey the fact that a count of farms and dwellings on the maps was made for each unit. For each count unit, a number of sampling units, or segments, was assigned, based on the farm count. While these three strata plus geographic stratification were adequate for the relatively homogeneous agriculture of the early 1940's because of the general or diversified nature of the family farm, rapid changes have occurred which make the degree of stratification inadequate, especially in the western states. This inadequacy was recognized early by the designers of the master sample materials and efforts were started in the late 1940's to stratify those states west of the 100th meridian. However, this project was never completed because of diversified interests and lack of funds.
Investigation of Parameters Influencing Hunting Performance of a Railway Vehicle With Three-Piece Trucks

This study uses a nonlinear multibody dynamics model of a railway vehicle with three-piece trucks to perform a parametric study on a wide range of parameters influencing the performance of the truck on tangent track. One of the major disadvantages of the three-piece truck is that its performance can be greatly influenced due to worn parts or contaminants on friction surfaces, such as the friction wedge. The influence of worn parts is modeled as increased gap between bodies, using dead-band springs. The influence of environmental contamination is modeled as change in coefficients of friction. Lateral accelerations, measured at the center of gravity of the leading axle of the leading truck (Axle 1) are used for the hunting performance of the vehicle. For the baseline case, an eigenvalue analysis of a linearized model is used to evaluate the effect of speed on damping ratio and lateral motion frequency. A comparison of the linear model and non-linear time series analysis show that the linear model is less conservative, in that it predicts that the onset of hunting occurs at higher speeds.The results indicate a direct relationship between various coefficients of friction and hunting velocity of the rail vehicle. Increasing the gap between the pedestal legs and bearing housing does not influence hunting velocity, but reduces lateral acceleration magnitudes during hunting. The weights of the carbody and cargo also has a direct relationships with hunting velocity, meaning that hunting occurs at lower speeds for unloaded car and at higher speeds for a loaded car.Copyright © 2015 by ASME
Lithium therapy of canine cyclic hematopoiesis

Treatment of cyclic hematopoiesis in the grey collie dog with lithium carbonate eliminated the recurrent neutropenia and normalized the other blood cell counts. These findings suggest that human cyclic hematopoiesis may be successfully treated with lithium. The effects of lithium on the monocytes, platelets, and reticulocytes, as well as the neutrophils, suggest that lithium operates on basic regulatory mechanisms affecting the most primitive hematopoietic precursor cells.
Initial experience with the New York State breast density inform law at a community-based breast center.

Objectives The purpose of this study was to review our initial experience with the New York State breast density inform law (New York public health law, S2404-C) at our outpatient breast center. We sought to review the findings in patients returning for screening breast sonography after a screening mammogram revealed heterogeneously dense or extremely dense breast tissue. Methods From January 1, 2013, through May 31, 2014, 102,841 patients who underwent screening mammography were seen at our institution. Of these, 35,153 were determined to have heterogeneously dense breast tissue, and 11,864 were determined to have extremely dense breast tissue. Due to the New York State breast density inform law, these 47,017 patients were notified of their breast density, with 935 patients (2%) returning for 971 screening breast sonographic examinations. Results Heterogeneously dense breast tissue was noted in 66% of the patients (619), and extremely dense breast tissue was noted in 34% (316). Thirty-one percent of the patients (290) reported no additional risk factors; 68% (635) presented with 1 or more additional risk factors; and 1% (10) were adopted, and the risk status could not be assessed. Twenty-five procedures (2.6%) were performed after screening breast sonography, resulting in 22 benign findings, 1 atypical finding, and 2 malignancies. The overall positive predictive value was 8% (2 of 25), and the overall cancer detection rate was 2.1 per 1000 (2 of 935). Conclusions Handheld screening breast sonography performed in women with dense breast tissue can aid in the detection of otherwise occult breast cancer, as we found 2 cancers in the study population, with an overall positive predictive value of 8%. The addition of screening sonography in this cohort did lead to an increase in minimally invasive procedures in 2.6%.
A qualitative study of factors related to cardiometabolic risk in rural men

Rural men are known to have poor health behaviors, which contribute to their elevated burden of cardiometabolic disorders in the United States. Although regular physical activity, healthy eating, and avoiding tobacco can reduce cardiometabolic risk, little is known about how to engage rural men in health promotion programs. To bridge this gap in evidence, we investigate knowledge of modifiable cardiometabolic risk factors among rural men in the western United States, identify their concerns related to heart health and motivation to reduce risk, and explore individual, social, and community-level influences on heart-healthy behaviors, specifically diet, physical activity, and tobacco use. We conducted seven focus groups with 54 sedentary, overweight/obese men (mean body mass index [BMI] = 31.3 ± 4.6) aged 43–88 residing in government-designated “medically underserved” rural Montana towns in September and October 2014. All sessions were audio-recorded and transcribed verbatim. Transcripts were coded and analyzed thematically using Nvivo software. Participants also completed a brief questionnaire about personal characteristics and health behaviors. These data were explored descriptively. Despite being classified as overweight/obese and sedentary, no participants reported to be in poor health. Many men described health relative to self-reliance and the ability to participate in outdoor recreation; concern with health appeared to be related to age. Participants were generally knowledgeable of heart-healthy behaviors, but many felt fatalistic about their own risk. Catalysts for behavior change included a serious medical event in the household and desire to reduce aging-associated functional decline. Barriers to adopting and maintaining healthy eating and physical activity habits and abstaining from tobacco included normative beliefs around masculinity and individual liberty, the limited social universe of small towns, winter weather, time constraints, and preferences for unhealthy foods. Facilitators included behavioral self-monitoring, exercising with a partner, and opportunities for preferred activities, such as hunting and team sports. These findings provide important insight about influences on rural men’s health behaviors and provide guidance for possible intervention strategies to promote cardiometabolic health. ClinicalTrials.gov NCT02499731 . Registered 1 July 2015.
Cradle to farm gate life cycle assessment of strawberry production in the United States

Abstract The goal of this study was to develop a cradle to farm gate life cycle inventory and assess the environmental impacts of strawberry production in four major strawberry producing states of the United States: California, Florida, North Carolina and Oregon, representing 99% of the United States strawberry production. Life cycle environmental impacts depend strongly on geographic location and production practices. Data for California and North Carolina strawberry production were collected in collaboration with agricultural economists from those states using the “LCA Extended Enterprise Budget” Excel sheet (version 4.11). Data for Florida strawberry production were collected from the state's existing enterprise budget (a detailed accounting of production costs and returns which estimates profitability of an enterprise). Data related to Oregon strawberry production were obtained through interviews with strawberry producers. OpenLCA software was used to conduct life cycle assessment for strawberry production. Missing unit processes for production of agricultural machinery, pesticides, fertilizers and materials were modeled based on existing literature. In order to better assess the sustainability of strawberry production, three metrics encompassing nitrogen productivity, phosphorous productivity and fossil energy productivity were introduced. Global warming potential for California, Florida, North Carolina and Oregon strawberry production was estimated to be 1.75, 2.50, 5.48 and 2.21 kg CO2-eq per 1 kg of strawberry, respectively. The difference between LCA results was due to variation in yield and management practices which depend on geographic location. Plastics, fuels and fertilizers were the inputs with the highest contribution to environmental impact categories. California strawberry production scored the highest on three sustainability metrics mainly due to having the highest strawberry yield.
A Systematic Review of the Energy Cost and Metabolic Intensity of Yoga.

ABSTRACTPurposeWith the increasing popularity of Hatha yoga, it is important to understand the energy cost and METs of yoga practice within the context of the American College of Sports Medicine (ACSM) and the American Heart Association (AHA) physical activity guidelines.MethodsThis systematic revie
Hemigossypol, a constituent in developing glanded cottonseed (Gossypium hirsutum).

Gossypol is a dimeric sesquiterpenoid first identified in cottonseed, but found in various tissues in the cotton plant including the seed. From its first discovery, it was assumed that hemigossypol...
Steady-State Photoconductivity in Undoped Amorphous Silicon

An analytical expression for the thermal activation energy of the steady-state photoconductivity is shown to agree with experimental data in a range of temperature and generation rate for undoped hydrogenated amorphous silicon (a-Si:H). This agreement supports our suggestion that the commonly observed small activation energy of the photoconductivity in undoped a-Si:H originates in the strong temperature dependence of the quasi-Fermi level for electrons.
Molecular Characterization of the sdhB Gene and Baseline Sensitivity to Penthiopyrad, Fluopyram, and Benzovindiflupyr in Venturia inaequalis

The succinate dehydrogenase inhibiting (SDHI) fungicides are a class of single-site fungicides that are increasingly important in the management of Venturia inaequalis. In this study, the baseline sensitivity of V. inaequalis to penthiopyrad, fluopyram, and benzovindiflupyr was investigated. In all, 35 to 70 isolates with no prior exposure to single-site fungicides were used to determine the effective concentration at which growth was inhibited by 50% (EC50). Mean EC50 values for the conidial germ tube growth stage for penthiopyrad, fluopyram, and benzovindiflupyr were 0.086, 0.176, and 0.0016 μg ml-1, respectively. Linear correlation analysis revealed a significant and positive correlation between fluopyram and penthiopyrad (P ≤ 0.0001, r = 0.66) and fluopyram and benzovindiflupyr (P = 0.0014, r = 0.52). Baseline sensitivities of V. inaequalis during the mycelial growth stage were also determined for fluopyram and benzovindiflupyr. EC50 values were higher for fluopyram and benzovindiflupyr during this stage compared with the conidial germ tube growth stage, with means of 0.043 and 2.02 μg ml-1, respectively. In addition, the sdhB gene was characterized for three isolates of V. inaequalis collected from a research, baseline, and commercial orchard population. No common mutation sites associated with SDHI resistance in other phytopathogenic fungi were discovered in these isolates or isolates that were recovered following field applications of SDHI fungicides. The results of this study suggest that SDHI fungicides have a high level of activity during the conidial germ tube elongation stage in V. inaequalis and provide a basis for phenotypic and genotypic monitoring of shifts toward resistance of V. inaequalis populations to the SDHI fungicide class.
Exploring the Intersection of Schooling and Prevention Science

Although educators and prevention scientists are grounded in different disciplines and paradigms, both groups of professionals have a common interest in the growth and development of young people. While educators have a focus on the academic success of their students, there is a recognition that risk factors such as alcohol, tobacco or other drug use, mental health issues, an abusive home environment, peer pressure and others can contribute to academic difficulties and influence later success in life. By working together, educators can better understand the influence of risk factors and minimize their effect on academic performance, and prevention scientists can provide evidence-based programs and strategies that will result in the development of a positive school climate conducive to academic success.
Rescuing the N-cadherin knockout by cardiac-specific expression of N- or E-cadherin

Cell-cell adhesion mediated by some members of the cadherin family is essential for embryonic survival. The N-cadherin-null embryo dies during mid-gestation, with multiple developmental defects. We show that N-cadherin-null embryos expressing cadherins using muscle-specific promoters, alpha- or beta-myosin heavy chain, are partially rescued. Somewhat surprisingly, either N-cadherin or E-cadherin was effective in rescuing the embryos. The rescued embryos exhibited an increased number of somites, branchial arches and the presence of forelimb buds; however, in contrast, brain development was severely impaired. In rescued animals, the aberrant yolk sac morphology seen in N-cadherin-null embryos was corrected, demonstrating that this phenotype was secondary to the cardiac defect. Dye injection studies and analysis of chimeric animals that have both wild-type and N-cadherin-null cells support the conclusion that obstruction of the cardiac outflow tract represents a major defect that is likely to be the primary cause of pericardial swelling seen in null embryos. Although rescued embryos were more developed than null embryos, they were smaller than wild-type embryos, even though the integrity of the cardiovascular system appeared normal. The smaller size of rescued embryos may be due, at least in part, to increased apoptosis observed in tissues not rescued by transgene expression, indicating that N-cadherin-mediated cell adhesion provides an essential survival signal for embryonic cells. Our data provide in vivo evidence that cadherin adhesion is essential for cell survival and for normal heart development. Our data also show that E-cadherin can functionally substitute for N-cadherin during cardiogenesis, suggesting a critical role for cadherin-mediated cell-cell adhesion, but not cadherin family member-specific signaling, at the looping stage of heart development.
An analysis of the robustness and fragility of the coagulation system

The coagulation system (CS) is a complex, inter-connected biological system with major physiological and pathological roles. Adaptive mechanisms such as ubiquitous feedback and feedforward loops create non-linear relationships among its individual components and render the study of this biology at a molecular and cellular level nearly impossible. Computational modeling aims to overcome limitations of current analytical methods through in silico simulation of these complex interplays. We present herein an Agent Based Modeling and Simulation (ABMS) approach for simulating these complex interactions. Our ABMS approach utilizes a subset of 48 rules to define the interactions among 24 enzymes and factors of the CS. These rules simulate the interaction of each “agent”, such as substrates, enzymes, and cofactors, on a two-dimensional grid of ~3,000 cells and ~500,000 agents. Our ABMS method demonstrates the robustness of the physiologic CS system over large ranges of tissue factor (TF) concentrations. The system also demonstrates fragility as complete coagulation occurs at sufficiently high concentrations of TF. Removal of individual coagulation inhibitors from the physiologic system results in system fragility at relatively lower TF concentrations. The complete removal of coagulation inhibitors leads to a system that is incapable of controlling coagulation at all TF concentrations. The synergistic effects of the inhibitory pathways create an intricate regulatory mechanism that allows sufficient clot formation while preventing system wide activation of the CS; a robust system emerges. Introduction
Humanitarian Outreach in Cardiothoracic Surgery: From Setup to Sustainability

Noncommunicable diseases account for 38 million deaths each year, and approximately 75% of these deaths occur in the developing world. The most common causes include cardiovascular diseases, cancer, respiratory diseases, and diabetes mellitus. Many adults with acquired cardiothoracic disease around the world have limited access to health care. In addition, congenital heart disease is present in approximately 1% of live births and is therefore the most common congenital abnormality. More than one million children in the world are born with congenital heart disease each year, and approximately 90% of these children receive suboptimal care or have no access to care. Furthermore, many children affected by noncongenital cardiac conditions also require prevention, diagnosis, and treatment. Medical and surgical volunteerism can help facilitate improvement in cardiothoracic health care in developing countries. As we move into the future, it is essential for physicians and surgeons to be actively involved in political, economic, and social aspects of society to serve health care interests of the underprivileged around the world. Consequently, in developing countries, a critical need exists to establish an increased number of reputable cardiothoracic programs and to enhance many of the programs that already exist. The optimal strategy is usually based on a long-term educational and technical model of support so that as case volumes increase, quality improves and mortality and morbidity decrease. Humanitarian outreach activities should focus on education and sustainability, and surgical tourism should be limited to those countries that will never have the capability to have free-standing cardiothoracic programs.
Diisopropylethylamine/hexafluoroisopropanol-mediated ion-pairing ultra-high-performance liquid chromatography/mass spectrometry for phosphate and carboxylate metabolite analysis: utility for studying cellular metabolism

Rationale Mass spectrometric (MS) analysis of low molecular weight polar metabolites can be challenging because of poor chromatographic resolution of isomers and insufficient ionization efficiency. These metabolites include intermediates in key metabolic pathways, such as glycolysis, the pentose phosphate pathway, and the Krebs cycle. Therefore, sensitive, specific, and comprehensive quantitative analysis of these metabolites in biological fluids or cell culture models can provide insight into multiple disease states where perturbed metabolism plays a role. Methods An ion-pairing reversed-phase ultra-high-performance liquid chromatography (IP-RP-UHPLC)/MS approach to separate and analyze biochemically relevant phosphate- and carboxylic acid-containing metabolites was developed. Diisopropylethylamine (DIPEA) was used as an IP reagent in combination with reversed-phase liquid chromatography (RP-LC) and a triple quadrupole mass spectrometer using selected reaction monitoring (SRM) and negative electrospray ionization (NESI). An additional reagent, hexafluoroisopropanol (HFIP), which has been previously used to improve sensitivity of nucleotide analysis by UHPLC/MS, was used to enhance sensitivity. Results HFIP versus acetic acid, when added with the IP base, increased the sensitivity of IP-RP-UHPLC/NESI-MS up to 10-fold for certain analytes including fructose-1,6-bisphosphate, phosphoenolpyruvate, and 6-phosphogluconate. It also improved the retention of the metabolites on a C18 reversed-phase column, and allowed the chromatographic separation of important isomeric metabolites. This methodology was amenable to quantification of key metabolites in cell culture experiments. The applicability of the method was demonstrated by monitoring the metabolic adaptations resulting from rapamycin treatment of DB-1 human melanoma cells. Conclusions A rapid, sensitive, and specific IP-RP-UHPLC/NESI-MS method was used to quantify metabolites from several biochemical pathways. IP with DIPEA and HFIP increased the sensitivity and improved chromatographic separation when used with reversed-phase UHPLC.
Bayesian Decision Based Estimation and Predictive Inference

Shrinkage estimation is a traditional research topic in Bayesian analysis. The three sections in this chapter convincingly argue that this venerable topic remains a current research frontier with many open problems. The chapter starts with a review of the current state of research and concludes with an insightful discussion of a very specific form of shrinkage estimation arising in recent work on inference in gene-environment interaction studies.
PNA-Assisted Rolling Circle Amplification for Detection of DNA Marker Sequences in Human Cells

Presented here are the methods used for detection of short, single-copy DNA sequences within human cells. These methods rely on (1) peptide nucleic acid (PNA) invasion of the target double-stranded DNA site to locally open a small single-stranded region within long DNA duplex, (2) site-specific formation of padlock probe, and (3) its rolling circle amplification for signal magnification. The signal detection is accomplished via either fluorescent in situ hybridization (FISH), flow cytometry (fluorescence-activated cell sorting, FACS), or droplet-based microfluidics. This methodology allows for sensitive and specific detection of DNA marker sequences without the need for DNA extraction and purification, making it possible to identify small genomic variations within individual human cells.
Embryonic origin of primary colon cancer predicts survival in patients undergoing ablation for colorectal liver metastases.

Abstract Background In patients with primary colorectal cancer (CRC) or unresectable metastatic CRC, midgut embryonic origin is associated with worse prognosis. The impact of embryonic origin on survival after ablation of colorectal liver metastases (CLM) is unclear. Methods We identified 74 patients with CLM who underwent percutaneous ablation during 2004–2015. Survival and recurrence after ablation of CLM from midgut origin (n = 18) and hindgut origin (n = 56) were analyzed. Prognostic value of embryonic origin was evaluated. Results Recurrence-free survival (RFS) and overall survival (OS) after percutaneous ablation were worse in patients from midgut origin (3-year RFS: 5.6% vs. 24%, P = 0.004; 3-year OS: 25% vs. 70%, P 0.001). In multivariable analysis, factors associated with worse OS were midgut origin (hazard ratio [HR] 4.87, 95% CI 2.14–10.9, P 0.001), multiple CLM (HR 2.35, 95% CI 1.02–5.39, P = 0.044), and RAS mutation (HR 2.78, 95% CI 1.25–6.36, P = 0.013). At a median follow-up of 25 months, 56 patients (76%) had developed recurrence, 16 (89%) with midgut origin and 40 (71%) with hindgut origin ( P = 0.133). Recurrent disease was treated with local therapy in 20 patients (36%), 2 (13%) with midgut origin and 18 (45%) with hindgut origin ( P = 0.022). Conclusion Compared to CLM from hindgut origin tumors, CLM from midgut origin tumors were associated with worse survival after ablation, which was partly attributable to the fact that patients with hindgut origin were more frequently candidates for local therapy at recurrence.
Salivary gland lymphocyte response to murine cytomegalovirus (INC1P.344)

The β-herpes virus MCMV, a homologue of HCMV, is a well-characterized animal model of viral infection that results in a non-replicative, chronic infection of an immune-competent animal. In most organs, MCMV is cleared within days by cytotoxic lymphocytes. However, the virus persists in the submandibular salivary glands (SMG) for several weeks, before establishing latency for the life of the host. NK cells are crucial for the early containment of MCMV before T cells can mount an effector response. Recent work from our laboratory has shown that SMG NK cells are hyporesponsive during MCMV infection. Here we show that SMG NK cells regain normal effector functions against MCMV when adoptively transferred into different tissue environments. This indicates that the hyporesponsive phenotype observed is tissue specific, and not cell-intrinsic. In addition, using E4BP4 deficient animals, we determined that two CD3 - NK1.1 + subsets reside within the salivary glands. One subset is derived from the conventional NK cell population and relies on E4BP4 for development, while the other is E4BP4 independent. When the E4BP4 independent NK cells are transferred into different tissue environments, they produce IFN-γ in response to MCMV infection. The SMGs of E4BP4 -/- mice also contain a novel population of CD3 + NK1.1 + NKp46 + cells that produce IFN-γ during MCMV infection. Altogether, our data show that the SMG tissue environment shapes a unique repertoire of NK1.1 + cells with distinctive phenotypes.
Applying Optimization Algorithms to Tuberculosis Antibiotic Treatment Regimens

Tuberculosis (TB), one of the most common infectious diseases, requires treatment with multiple antibiotics taken over at least 6 months. This long treatment often results in poor patient-adherence, which can lead to the emergence of multi-drug resistant TB. New antibiotic treatment strategies are sorely needed. New antibiotics are being developed or repurposed to treat TB, but as there are numerous potential antibiotics, dosing sizes and potential schedules, the regimen design space for new treatments is too large to search exhaustively. Here we propose a method that combines an agent-based multi-scale model capturing TB granuloma formation with algorithms for mathematical optimization to identify optimal TB treatment regimens. We define two different single-antibiotic treatments to compare the efficiency and accuracy in predicting optimal treatment regimens of two optimization algorithms: genetic algorithms (GA) and surrogate-assisted optimization through radial basis function (RBF) networks. We also illustrate the use of RBF networks to optimize double-antibiotic treatments. We found that while GAs can locate optimal treatment regimens more accurately, RBF networks provide a more practical strategy to TB treatment optimization with fewer simulations, and successfully estimated optimal double-antibiotic treatment regimens. Our results indicate surrogate-assisted optimization can locate optimal TB treatment regimens from a larger set of antibiotics, doses and schedules, and could be applied to solve optimization problems in other areas of research using systems biology approaches. Our findings have important implications for the treatment of diseases like TB that have lengthy protocols or for any disease that requires multiple drugs.
Atherosclerosis and Gender-Related Differences

Coronary artery disease (CAD) remains the leading cause of mortality and morbidity world wide. Despite significant advances in our understanding of the atherogenesis, gender related differences in CAD remain unclear. It is generally assumed that the estrogens play a protective role in women in the premenopausal age group; however, hormone replacement therapy in postmenopausal women has not led to a significant decrease in cardiovascular events. Nonetheless, subtle differences at cellular level and in the plaque morphology have been identified in women as compared with men. Recent studies have shown a different pattern of atherosclerotic changes in the distribution of vessels, morphology of lesions and microvasculature between men and women. New markers of atherosclerosis such as G protein coupled estrogen receptors, Toll-like receptors and lipoprotein(a) also exhibit different patterns in men and women. Other studies have shown that women as compared to men have poorer prognosis after STEMI and CABG. An improved understanding the gender related pathophysiology will help in improved management of CAD in women.
MEASURING DISTANCE IN TWO DIMENSIONS

Weakly electric fish produce an electric field with an organ in their tails; sensing distortions of that field gives the fish information about their environment. It was thought that distance could not be judged with this system, but some cunning behavioural experiments show that this is not so. The feat is unusual because most other animals can gauge distance only by using a pair of sense organs, such as two eyes.
Stereochemical Studies at the Herman F. Mark Polymer Research Institute

Although stereochemistry plays a key role in the structure and function of biological polymers it was not until the discovery of isotactic polypropylene, now about 60 years ago, that the role of stereochemistry was seen to be of importance in synthetic polymers. Staudinger had predicted that although the nature of the bonding in small molecules and in macromolecules was identical, polymers would have special properties associated with the size of macromolecules. This article outlines how stereochemical studies demonstrate Staudinger’s prescience in many ways. The story takes us from the tactic nature of vinyl polymers and their unrecognized and recognized chirality, to helicity, a characteristic shared by biological and certain synthetic polymers. There is an advantage to studying stereochemistry in synthetic polymers: their chiral characteristics can be manipulated in ways not possible in biological polymers, allowing discovery of new phenomena that cross boundaries outside of the polymer realm.
Controversies in the management of common duct calculi

Laparoscopic cholecystectomy altered the treatment of suspected common bile duct calculi. Preoperative endoscopic retrograde cholangiopancreatography and endoscopic sphincterotomy supplanted operative common bile duct exploration. The emergence of techniques of laparoscopic common bile duct exploration through the cystic duct or through choledochotomy has decreased preoperative reliance on endoscopic sphincterotomy.
Dipolar susceptibility of protein hydration shells

Abstract We present a formalism for the calculation of interfacial dielectric constant of hydration shells of proteins from configurations produced by atomistic numerical simulations. The theoretical approach is applied to classical molecular dynamics simulations of hydrated cytochrome c protein in the range of temperatures from 280 to 330 K. The interfacial dielectric constant was found to be equal to 2–4 depending on temperature. This dielectric constant reflects constraints imposed by the protein on the hydration waters and their low ability to polarize in response to an external field.
Us against them

If there is a single buzzword that sums up American politics in the present era, it is "polarization." But why has polarization become such a prominent feature of American political life? In Uncivil Agreement , Lilliana Mason provides a novel and compelling answer.