cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 1595: Functional genomic analysis of 18q21.1 locus identifies potential functional variants and genes for colorectal cancer

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers in the world. Genome-wide association studies have identified approximately 50 genetic risk loci for CRC. We have previously identified SNP rs7229639, located in the second intronic region of the SMAD7 gene at locus 18q21.1, in relation to CRC risk in Asians. In this study, we performed functional genomic analysis to identify potential functional variants and target genes for this association. Functional annotation analysis using epigenetic data from ENCODE and Roadmap projects showed functional evidence of promoter and/or enhancer activities for four highly correlated potential functional SNPs, including rs7229639, rs77544449, rs112540150 and rs57668004. Using in vitro luciferase reporter assays in colon cancer HCT116 and PKO cells, we showed that the risk alleles of rs7229639 and rs77544449 increase promoter or enhancer activities, compared to reference alleles. The risk alleles of both SNPs also affect the ability of interacting with nuclear proteins in the electrophoretic mobility shift assays, compared to reference alleles. To identify candidate target genes for this risk locus, we performed cis-expression quantitative trait loci (eQTL) analysis using transcriptome data from the Genotype-Tissue Expression (GTEx) project, The Cancer Genome Atlas (TCGA) and Colonmics. We identified putative target gene LIPG, located 500 kb downstream of rs7229639, in all three datasets. No associations were observed for SMAD7, or eight other genes in the region, via eQTL analysis. To investigate the biological functions of LIPG gene in colorectal cancer, we knock-downed LIPG gene expression using siRNA in HCT116 and PKO cells, which resulted in a significant decrease in cell proliferation, colony formation, migration and invasion in both HCT116 and PKO cells. These results suggest that LIPG gene plays a significant role in colorectal tumorigenesis via disruption of cell behaviors. Taken together, results from our study suggest that the association between the rs7229639/18q21.1 locus and CRC risk may be mediated through SNPs that regulate expression of the LIPG gene. Citation Format: Jifeng Wang, Xingyi Guo, Shimian Qu, Joshua A. Bauer, Jirong Long, Wei Zheng, Qiuyin Cai. Functional genomic analysis of 18q21.1 locus identifies potential functional variants and genes for colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1595.
Dysregulated insulin in pancreatic insufficient cystic fibrosis with post-prandial hypoglycemia.

Abstract Background Post-prandial and oral glucose tolerance test-related hypoglycemia is common in cystic fibrosis (CF); however, the underlying mechanisms are unclear. Methods To understand the relationship of hypoglycemia with meal-related glucose excursion and insulin secretion, we analyzed plasma glucose, insulin, C-peptide, glucagon and incretins obtained during standardized mixed-meal tolerance tests (MMTT) in non-diabetic adolescents and young adults with pancreatic insufficient CF (PI-CF). Results Hypoglycemia, defined as glucose Conclusion Hypoglycemia is common in PI-CF following MMTT and is associated with early glucose dysregulation (higher peak glucose), more impaired early-phase insulin secretion (lower ISR-AUC30min), and possibly late compensatory hyperinsulinemia. Further study is required to understand whether absence of glucagon difference in the hypoglycemia[+] individuals signals counterregulatory impairment, to delineate the role of incretins in hypoglycemia, and to determine the relationship of hypoglycemia to emergence of CFRD.
[Rickets/Osteomalacia. Consensus on Vitamin D Deficiency and Insufficiency in Children]

Vitamin D deficiency is usually manifested as rickets in children. Since vitamin D deficiency/insufficiency is common worldwide, global consensus has been formulated on prevention, diagnosis and treatment of nutritional rickets represented by vitamin D-deficient rickets. This consensus has defined vitamin D insufficiency as the status with serum 25-hydroxyvitamin D(25OHD)level between 12 and 20 ng/mL and vitamin D deficiency as the status with serum 25OHD level below 12 ng/mL. Generally low dietary calcium(Ca)intake coexists with vitamin D deficiency/insufficiency in patients with rickets, and it is important to ensure sufficient Ca intake ensure in the management of nutritional rickets.
Transfusion-Related Acute Lung Injury Resulting From Designated Blood Transfusion Between Mother and Child

Transfusion-related acute lung injury (TRALI) is an underdiagnosed serious complication of blood transfusion characterized by the rapid onset of respiratory distress, hypoxia, and noncardiogenic pulmonary edema during or soon after blood transfusion. The presence of anti-HLA and/or antigranulocyte antibodies in the plasma of donors is implicated in the pathogenesis of TRALI. We report 2 cases of TRALI that were caused by designated blood transfusion between mothers and their daughters; one in a 4-month-old girl who received designated packed RBCs donated by her mother and the second in a 78-year-old mother who received blood from her daughter. In both cases, examination of mother’s serum revealed panel-reactive cytotoxic HLA antibodies. It is most likely that the mothers were sensitized from earlier pregnancy and produced HLA antibodies against the daughters’ paternally derived HLA antigens. Designated blood transfusion between multiparous mothers and children might add an additional transfusion-related risk owing to the higher likelihood of the HLA antibody-antigen specificity between mother and child.
Life-course trajectories of employment quality and health in the U.S.: A multichannel sequence analysis.

Abstract The organization of employment in the U.S. has changed dramatically since the 1970s, causing decreased power and security for workers across many dimensions of the employment relationship. Multidimensional employment-quality (EQ) measures can be used to capture these changes and test their association with health. However, most public-health EQ studies have used cross-sectional, unidimensional data. We addressed these limitations using a longitudinal, multidimensional EQ measure and data on 2779 1985–2017 Panel Study of Income Dynamics respondents. First, using a multichannel sequence-analysis approach, we identified gender-specific clusters of mid-career (ages 29–50) EQ trajectories based on respondents’ employment stability, material rewards, working-time arrangements, collective organization, and power relations. Next, we examined cross-cluster variation in respondent characteristics. Finally, we estimated the gender-specific associations between cluster-membership and post-sequence-analysis-period prevalence of poor/fair self-rated health (SRH) and moderate mental illness (Kessler-K6≥5). We identified five clusters among women and seven among men. Respondents in poor-EQ clusters were disproportionately people of color and less-educated; they also tended to report worse health. For example, among women, the prevalence of poor/fair SRH and moderate mental illness was lowest among standard-employment-relationship-like-non-union workers and the becoming self-employed, and greatest among minimally-attached, returning-to-the-labor-force, and precariously-employed workers. Meanwhile, among men, the prevalence of the outcomes was lowest among stably-high-wage workers and the wealthy self-employed, and greatest among exiting-the-labor-force and precariously-employed workers. Given the potential role of EQ in health inequities, researchers and practitioners should consider EQ in their work.
Abstract 945: Advancing cancer immunotherapeutics: A focus on characterization of anti-CTLA-4 mAbs for better anti-tumor immunity and less toxicity

Anti-CTLA-4 monoclonal antibodies confer a cancer immunotherapeutic effect (CITE) but cause severe immunotherapy-related adverse events (irAEs). How to uncouple the undesired irAEs from the beneficial CITE seen in cancer patients treated with anti-CTLA-4 and/or other checkpoints inhibitors has proven to be a daunting challenge, partially due to the lack of the understanding of the real MOA(mechanism of Action) of CITE and irAEs. Meanwhile, an animal model, which recapitulates clinical irAE and CITE, would be valuable for developing safer CTLA-4-targeting reagents. We not only discovered that the immunotherapy of current anti-CTLA-4 mAbs were dependent on Fc/Fc receptor mediated intra-tumor Treg depletion rather than the widely held mechanism of checkpoint blockade, which raised the reappraisal of CTLA-4 checkpoint blockade in cancer immunotherapy, we also establish one realistic irAEs model and find one mechanism of irAEs. In this model, the clinically used drug Ipilimumab (or TremeIgG1) induced severe irAEs especially when combined with an anti-PD-1 antibody; whereas another mAb L3D10 induced comparable CITE with very mild irAE under the same conditions. Humanization (HL12/HL32) of L3D10, which led to the loss of blocking activity, further increased safety without affecting the therapeutic effect. Furthermore, we report that while irAE-prone Ipilimumab and TremeIgG1 rapidly direct cell surface CTLA-4 for lysosomal degradation, the non-irAE-prone antibodies we generated, HL12 or HL32, dissociate from CTLA-4 after endocytosis and allow CTLA-4 recycling to cell surface, increasing the pH sensitivity of TremeIgG1 by introducing designed tyrosine-to-histidine mutations prevents antibody-triggered lysosomal CTLA-4 downregulation and dramatically attenuates irAE. Our data establish a new paradigm for cancer research that allows for abrogating irAE while increasing CITE of anti-CTLA-4 antibodies. Citation Format: Xuexiang Du, Mingyue Liu, Yan Zhang, Fei Tang, Chunxia Ai, Peng Zhang, Pan Zheng, Yang Liu. Advancing cancer immunotherapeutics: A focus on characterization of anti-CTLA-4 mAbs for better anti-tumor immunity and less toxicity [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 945.
Simultaneous Measurement of Sex Steroid Hormones in Largemouth Bass (Micropterus salmoides) Plasma by Application of Liquid Chromatography-Tandem Mass Spectrometry.

Sex steroid hormones are potential biomarkers of reproductive function in teleost fish, but their measurement continues to rely on antibody-based assays. The objective of this study was to optimize a robust and simultaneous liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for measurement of eight steroid hormones (cortisol, 11-ketotestosterone, estradiol, 17α-ethynyl estradiol, estrone, estriol, progesterone and testosterone) in fish plasma. The extraction was followed by liquid-liquid extraction with tert-butyl methyl ether and time scheduled multi-reaction monitoring (sMRM) was used for quantitation of steroids. Validation of method performance using charcoal-stripped human plasma showed extraction recoveries for eight steroids ranged from 85.5 to 108.2% with matrix effects > 80%. The limits of quantitation were 0.01 pg/μL for testosterone, 0.05 pg/μL for cortisol and progesterone, 0.1 pg/μL for 11-ketotestosterone, estradiol and estrone, 0.125 pg/μL for estriol and 0.25 pg/μL for 17α-ethynyl estradiol. The proposed method was applied to plasma samples of largemouth bass (Micropterus salmoides) collected from contaminated (Lake Apopka) and reference sites (Wildcate Lake) in Florida. Concentrations of testosterone, cortisol, estradiol and estrone were significantly different in female fish, but plasma concentration of cortisol was only statistically different in male fish between two sites (P < 0.05). This study demonstrates the application of a robust LC-MS/MS analysis for a range of sex steroid hormones representative of endocrine function in a top predator, largemouth bass.
Explorations into the Mechanics of Hairy Nanoparticle Assemblies with Molecular Dynamics

This chapter summarizes recent investigations into the mechanical behavior of matrix-free hairy nanoparticles using molecular simulation techniques. Generic as well as systematic coarse-graining techniques are presented, highlighting emerging methods for chemistry-specific modeling of polymeric materials. Applications of coarse-graining to study assembled hairy nanoparticle systems are overviewed, with an emphasis on quantitative structure–property relationships obtained from these investigations. Comparisons of simulations with theoretical scaling relationships such as the Daoud-Cotton theory and experimental data are provided. Methods to accelerate the design space through upscaling techniques and metamodel development are briefly overviewed. Key physical insights obtained from these studies on the effects of grafting density, grafting length, and polymer chain chemistry are mentioned throughout the chapter to illustrate the importance of modeling contributions. A brief outlook into the prospects of using novel mesoscopic approaches such as those based on potentials of mean force is noted. The chapter concludes with a summary and outlook on the state of the art of the computational design of assembled hairy nanoparticles.
Overcoming barriers to outpatient management of emergency department patients with acute pulmonary embolism.

We commend Westafer and colleagues for their study of home discharge of adults with acute pulmonary embolism (PE) from emergency departments (EDs) across 740 diverse U.S. acute care hospitals.1 They found that outpatient management of ED patients with acute PE in the United States in 2016-2018 was uncommon (4.1%). Among 568 hospitals in the study with 20 PE cases or more, the median proportion of home discharge from the ED was only 3.1% and ranged broadly from 0% to 13.0% at 10th and 90th percentiles.
Finding Safety, Building Community, and Providing Hope: The Creation of Pride Healing Center

Pride Healing Center (PHC), a trauma-informed specialty clinic for the LGBTQ+ community, opened its doors at Long Island University Post on January 22, 2017. Following the tragic shooting in Orlando at Pulse nightclub and the shift in our political climate, many LGBTQ+ community members were left scared to be themselves and feeling unsafe in their communities. This is when members of the nationally recognized Trauma Response and Research Team at Post decided to act. With the help of local and national experts on trauma and LGBTQ+ cultural competency, student leaders worked to create a space where members of the LGBTQ+ community would feel welcome and their voices would be heard. Each decision from the name to the marketing materials, treatment modalities, and training of clinicians was carefully considered in an effort to ensure both cultural competency and a high level of trauma services. Now in its infancy, Pride Healing Center continues to grow in clientele, community partnerships, and recognition. The PHC continually hears how safe it feels for clients to be themselves in this space. Readers will benefit from a conversation about the creation and development of this clinic, the benefits of trauma-informed treatment for the LGBTQ+ community, and how to take steps toward cultural competency in their own practices.
Using Deep Learning to Understand Travel Demands in Different Urban Districts

Travel demand forecast plays an important role in transportation planning. Classic models often predict people’s travel behavior based on the physical built environment in a linear fashion. Many sc...
Extradural lumbar nerve root and ganglion capillary hemangioma: case report.

INTRODUCTION Extradural spinal hemangiomas without vertebral body or intradural involvement are rare and often misdiagnosed. When present in the lumbar spine, they typically present with radiculopathy and weakness. CT imaging is helpful in assessing for bony involvement and temporal involvement while MRI imaging can be helpful in distinguishing hemangiomas from other mass lesions, however current reports on imaging features are limited. Diagnosis remains primarily dependent on tissue pathology with surgery as the mainstay of treatment. CASE PRESENTATION We present a unique case report in which we obtain additional DSA imaging to not only visualize the vascular anatomy associated with a L4-5 neuroforaminal capillary hemangioma involving the L4 nerve root and ganglion, but to also embolize the feeding artery prior to surgical resection. Patient initially underwent a CT-guided biopsy that was suspicious for a hemangioma and confirmed on final pathology to be the capillary subtype. DISCUSSION When diagnosed appropriately, patients avoid unnecessary additional testing and avoid erroneous treatment of this rare lesion. Based on our experience, we propose initial MRI imaging to characterize the hemangioma and evaluate for intradural involvement, DSA to assess vascularity followed by embolization of the lesion when able in order to minimize intra-operative hemorrhage risk, and ultimately surgery to achieve a gross total resection.
Notch Sensitivity and Stacking Sequence of Laminated Composites

The effect of laminate stacking sequence and lamination angle on the notched strength of 6-ply graphite/epoxy laminates is investigated. Data is presented for the three different stacking sequences'of a 6-ply laminate comprised of two unidirectional plies and two pairs of angled plies: [′θ/0] s , [0/′θ] s , and [+θ/0/-θ] s for θ equal to 15°, 30°, 45°, 60°, 75°, and 90°. Notch geometry is limited to circular holes of which four different diameters were used: 3.175 mm, 6.35 mm, 9.525 mm, and 12.7 mm. Five specimens of each type (hole diameter and laminate) were tested monotonically to failure in tension. In addition, five unnotched specimens of each laminate were also tested. The fracture stresses of the notched specimens are correlated using the method proposed by Mar and Lin and a modified version of the point stress criterion of Whitney and Nuismer. The data shows that there is a distinct stacking sequence effect on notched fracture stress. The fracture stresses of the notched [+%/0/-θ] s laminates differ significantly from those of the [′θ/0] s and [0/′θ] s laminates that are generally the same for a given laminate and hole diameter. It is suggested that these differences are caused by out-of-plane effects of interlaminar stresses (delamination) or the elastic constraint of neighboring plies or both. These factors change as the stacking sequence and lamination angle are varied.
How Does a Divided Population Respond to Change

Most studies on the response of socioeconomic systems to a sudden shift focus on long-term equilibria or end points. Such narrow focus forgoes many valuable insights. Here we examine the transient dynamics of regime shift on a divided population, exemplified by societies divided ideologically, politically, economically, or technologically. Replicator dynamics is used to investigate the complex transient dynamics of the population response. Though simple, our modeling approach exhibits a surprisingly rich and diverse array of dynamics. Our results highlight the critical roles played by diversity in strategies and the magnitude of the shift. Importantly, it allows for a variety of strategies to arise organically as an integral part of the transient dynamics--as opposed to an independent process--of population response to a regime shift, providing a link between the population's past and future diversity patterns. Several combinations of different populations' strategy distributions and shifts were systematically investigated. Such rich dynamics highlight the challenges of anticipating the response of a divided population to a change. The findings in this paper can potentially improve our understanding of a wide range of socio-ecological and technological transitions.
Controller Design for Robust Stability and Performance

The closed loop system property (A+BG) ≪ 0 is important for robust stability and performance to errors in model parameters. This paper defines the set of all G such that (A+BG) ≪ 0 for a given A and B, and develops a strategy for choosing a particular gain from this set that satisfies the following objectives: (i) The root-mean squared (rms) value for each system state of the nominal system is less than or equal to some prespecified values for a given disturbance environment. (ii) The rms value for each state of the uncertain system is less than or equal to the same prespecified values in (i) for an a posteriori determined set of perturbations.
Rectosigmoid Localization of Radiopaque Markers Does Not Correlate with Prolonged Balloon Expulsion in Chronic Constipation: Results from a Multicenter Cohort

Rectosigmoid Localization of Radiopaque Markers Does Not Correlate with Prolonged Balloon Expulsion in Chronic Constipation: Results from a Multicenter Cohort
Robust Parameter Adjustment

Motivated by uncertainty characterizations often appearing in robust control literature, we treat parameter identification in the presence of nonparametric weighted-ball-in-H? unmodelled dynamics, as well as induced-L2-norm-bounded unmodelled dynamics. A deterministic notion of information is presented and utilized. A robust parameter adjustment law is stated, and monotonic parameter error reduction is proven, with strict monotonicity whenever the information is strictly positive.
Characterization of Glucose Dependent Gel-Sol Phase Transition of the Polymeric Glucose-Concanavalin A Hydrogel System

Purpose. The main goal of this study was to synthesize and characterize hydrogels which undergo reversible gel-sol phase transformation in response to changes in glucose concentration in the surrounding environment. Methods. The glucose-sensitive hydrogels were made by mixing the appropriate concentrations of acrylamide-allyl glucose copolymer and concanavalin A (Con A). To examine their phase reversibility, hydrogels in dialysis membranes were cycled between glucose-free and glucose-containing buffers. The binding affinity of allyl glucose (AG) to Con A was examined by using an equilibrium dialysis technique. Results. The synthesized hydrogels underwent phase transition to sol in the presence of free glucose in the environment. The concentration of external free glucose (Cf) had to be at least 4 times that of polymer-bound glucose (Cp) to induce phase transition from gel to sol. The binding affinity study showed that binding of AG to Con A was four times stronger than that of free glucose. When Cp in the gel was 0.42 mg/ml or higher, Cf had to be much higher than 4 times Cp to induce phase transition. Conclusions. The synthesized hydrogels underwent phase transition in the presence of free glucose in the environment, but the phase transition was not linearly dependent on the concentration of free glucose. This non-linear dependence was explained by the increased binding affinity of AG over native glucose to Con A, and the cooperative interactions between polymer-bound glucose and Con A.
The duration of medium-chain triglyceride feeding determines brush border membrane lipid composition and hydrolase activity in newly weaned rats

To better understand the effect of dietary fat on intestinal brush border (BB) membranes in the young animal, we compared the effect of dietary medium-chain triglycerides (MCT) with that of monounsaturated and saturated long-chain triglycerides (LCT) on jejunal brush border membrane lipid composition and hydrolase activity in newly weaned rats. Twenty-day-old rat pups were divided into three groups and were weaned to diets containing 14% MCT + 6% soybean oil, 18% olive oil + 2% soybean oil, or 14% tallow + 6% soybean oil, and fed for 40 h or for 33 d. The diets were isonitrogenous and contained similar amounts of cholesterol and polyunsaturated fatty acids. Within 40 h, the fatty acid compositions of the brush border membranes were significantly different among treatment groups. These differences were maintained in rats fed for 33 d. No medium-chain fatty acids, but significantly greater amounts of polyunsaturated fatty acids, especially 18:2(n-6) and 20:4(n-6), were found in the brush border membranes of rats fed the medium-chain triglyceride diet. The cholesterol and phospholipid concentrations in the membranes were highest in rats fed the medium-chain triglyceride diet for 33 d. Rats fed that diet for 40 h had generally higher leucine aminopeptidase, sucrase and maltase activities compared with rats fed the olive oil or tallow diets. However, after 33 d of feeding, the differences between dietary treatment groups disappeared. This study demonstrates that, in the newly weaned rat pup, dietary medium-chain triglycerides and long-chain triglycerides rapidly affect the fatty acid composition of the brush border membrane. However, the changes in the hydrolase activities associated with the changes in the lipid composition of the membranes are transient.
Major Unsolved Problems in Space Plasma Physics

There are many space plasma physics problems that are both major and unsolved, there are other problems for which the categorization of solved or unsolved depends on one’s point of view, and there are still other problems that are well understood but unsolved in the sense that quantitative predictions cannot be made although the basic physics is known. The following discussion will, of necessity, be limited and selective. The nature of the Alfvenic turbulence in the solar wind remains a major unsolved mystery: Why is the power spectrum of this anisotropic, compressible, magnetofluid often Kolmogoroff-like, with a power spectral index close to the −5/3 value characteristic of normal fluids? What is the three-dimensional symmetry of the turbulence? Are the magnetic fields quasi-two-dimensional and stochastic, or have they been highly refracted by small velocity shears? What is the origin of the — 1 slope of the energy containing scales? What is the relationship between the turbulent fields and the diffusion coefficients for energetic particle transport parallel and perpendicular to the ambient magnetic field? A general problem in turbulence research is the relationship between the fluid approximation and the kinetic physics that describes the dissipation and damping of fluctuations. There is still much to learn about solar flares, coronal mass ejections and magnetospheric substorms. Another major puzzle is how to quantitatively describe the interaction of the solar wind with the interstellar medium; a problem probably not amenable to solution using fluid equations.
Atypical form of transient reactive papulotranslucent acrokeratoderma in a cystic fibrosis carrier

We report the first documented case of an atypical form of transient reactive papulotranslucent acrokeratoderma (TRPA) in a patient heterozygous for the ΔF508 CFTR(cystic fibrosis transmembrane conductance regulator) mutation. TRPA represents a condition that classically presents with translucent to white plaques that become evident after water exposure. An atypical form with persistent lesions has also been described. Our patient is a 16-year-old girl with small, white papules coalescing into pebbly plaques on the palms. This condition is exacerbated after 5-10 min of water exposure and is associated with discomfort. The skin biopsy showed expanded stratum corneum, orthohyperkeratosis and dilation of eccrine ducts consisting with TRPA. A cystic fibrosis carrier state, barrier function defect, hyperhidrosis and the intake of cyclooxygenase inhibitors may have been pathogenic factors in our patient.
Physiological assessment of complex cardiac phenotypes in genetically engineered mice

The recent development of techniques for surgical manipulation and for the assessment of cardiac physiology in genetically engineered mice has allowed scientists to address some of the most fundamental questions related to congenital and acquired forms of human heart disease. This review discusses recent advances in the techniques for studying cardiac disease using the mouse as a model system. Because cardiac overload is one of the most important stimuli for development of hypertrophy and heart failure in humans, various models of cardiac pressure and volume overload, as well as myocardial ischemia, have been developed and characterized. Moreover, it is possible to reliably examine murine cardiac physiology in vivo with microtransducers, echocardiography, and other miniaturized techniques. Sophisticated methods have also been developed to enable an examination of single-cell phenotypes of isolated cardiomyocytes derived from genetically engineered mice. These physiological assessments, coupled with conventional histology and molecular markers, have allowed the characterization of several gene-targeted and transgenic mouse models of hypertrophy and dilated cardiomyopathy, as well as mouse models of cardiac developmental defects. Such mouse models of heart disease will ultimately allow the molecular dissection of the interplay between the various factors leading to heart disease, and they may serve as a guide to appropriate therapeutic strategies for human heart disease.
The Relaxation Response

When Dr. Herbert Benson introduced this simple, effective, mind/body approach to relieving stress twenty-five years ag, his book became an instant national bestseller. Since that time, millions of people have learned the secret--without high-priced lectures or prescription medicines. The Relaxation Response has become the classic reference recommended by most health care professionals and authorities to treat the harmful effects of stress.Discovered by Dr. Benson and his colleagues in the laboratories of Harvard Medical School and its teaching hospitals, this revitalizing, therapeutic approach is now routinely recommended to treat patients suffering from heart conditions, high blood pressure, chronic pain, insomnia, and many other physical ailments. It requires only minutes to learn, and just ten to twenty minutes of practice twice a day.
Protein synthesis in amphibian oocytes and early embryos.

Abstract Kinetics of amino acid incorporation have been studied in oocytes of Rana pipiens at all stages from the full-grown ovarian oocyte, through the period of pituitary-induced maturation and several hours beyond fertilization or artificial activation. Also, amino acid pool sizes in oocytes have been measured at all these stages. Pool sizes are subject to considerable natural variation in the eggs taken from different animals. However, the rate of flow of amino acid through the pool and, thus, the rate of protein synthesis, are relatively constant in eggs at the same stage, even when taken from different animals. The rate of protein synthesis is very low in the ovarian oocyte from an unstimulated female and in oocytes up to about 20 hours after pituitary stimulation. At this time the rate rises rapidly, reaches a maximum level of about 0.5 μg per oocyte per hour and remains essentially constant thereafter. Neither fertilization nor artificial activation have any observable quantitative effect on protein synthesis.
The effects of vicarious exposure to the recent massacre at Virginia Tech.

The authors examined whether exposure to the April 2007 Virginia Tech school shootings would increase symptoms of acute stress in students at another university who were not personally involved, but who followed the case vicariously through news media. The authors ran a series of regression analyses using multinomial logit (MNL) models, a methodology which can be used for dealing with categorical outcome variables. The authors found that as TV viewing of the Virginia Tech case increased, the probability that a student would respond with moderate or acute stress symptoms also increased. The authors were able to describe the magnitude of the relationship between vicarious exposure to the Virginia Tech case and acute stress symptomatology.
The Impact of GWAS Findings on Cancer Etiology and Prevention

Genome-wide association studies (GWAS) of common genetic variation have contributed immensely to our understanding of inherited susceptibility to cancer. To date, over 400 susceptibility loci have been identified across all cancers. These loci implicate novel as well as established genes and biological pathways, and have reinforced the significance and functionality of non-protein-coding DNA sequence. While the genetic associations for each variant are deemed modest, for some cancers, risk stratification based on aggregate effects may be of value for targeted screening and prevention strategies. Several questions still remain to be answered in order to fully assess the significance of these findings, including a better understanding of the source of the missing heritability. Here we discuss, from studies of common cancers, the impact of GWAS findings on illuminating disease etiology, the potential future utility of polygenic models for screening and prevention, and the future of association studies in the post-genomic era.
Metabolic repair of radiation-induced chromosomal damage

Abstract Chromosomal aberrations of the exchange types induced in the microspores of Tradescantia with 400 r of X-radiation delivered at 50 r/min in a helium atmosphere are used as a measure of radiation damage. Materials treated with potassium gluconate, ATP and glutathione either before or after irradiation showed approximately 40 per cent fewer aberrations than the irradiated controls. Neither doubling the concentrations of chemicals nor increasing the time of treatment gave any further reduction in aberrations. Three experimental temperatures were used with each chemical. The lowest, 0·2°C, when used alone, reduced aberrations to the same extent as the chemicals at 30°C. Any two of the four variables gave some synergistic effect, which was not increased by using all four at one time. In addition to these chemicals, glucose 6-phosphate, 6-phosphogluconate, TPNH, DPNH and others also proved effective, indicating that the energy for recovery was being obtained through the hexose monophosphate shunt.
EMERGENT FEATURES IN A GENERAL FOOD WEB SIMULATION: LOTKA–VOLTERRA, GAUSE'S LAW, AND THE PARADOX OF ENRICHMENT

Computer simulations of complex food-webs are important tools for deepening our understanding of these systems. Yet most computer models assume, rather than generate, key system-level patterns, or use mathematical modeling approaches that make it difficult to fully account for nonlinear dynamics. In this paper, we present a computer simulation model that addresses these concerns by focusing on assumptions of agent attributes rather than agent outcomes. Our model utilizes the techniques of complex adaptive systems and agent-based modeling so that system level patterns of a marine ecosystem emerge from the interactions of thousands of individual computer agents. This methodology is validated by using this general simulation model to replicate fundamental properties of a marine ecosystem, including: (i) the predator–prey oscillations found in Lotka–Volterra; (ii) the stepped pattern of biomass accrual from resource enrichment; (iii) the Paradox of Enrichment; and (iv) Gause's Law.
Elucidating connectivity and metal-binding structures of unlabeled paramagnetic complexes by 13C and 1H solid-state NMR under fast magic angle spinning.

Characterizing paramagnetic complexes in solids is an essential step toward understanding their molecular functions. However, methodologies to characterize chemical and electronic structures of paramagnetic systems at the molecular level have been notably limited, particularly for noncrystalline solids. We present an approach to obtain connectivities of chemical groups and metal-binding structures for unlabeled paramagnetic complexes by 13C and 1H high-resolution solid-state NMR (SSNMR) using very fast magic angle spinning (VFMAS, spinning speed ≥20 kHz). It is experimentally shown for unlabeled Cu(II)(Ala-Thr) that 2D 13C/1H correlation SSNMR under VFMAS provides the connectivity of chemical groups and assignments for the characterization of unlabeled paramagnetic systems in solids. We demonstrate that on the basis of the assignments provided by the VFMAS approach multiple 13C−metal distances can be simultaneously elucidated by a combination of measurements of 13C anisotropic hyperfine shifts and 13C T1 ...
How Well Do You Know Your Personae Non Gratae

Imagine that you're building a software system that collects healthcare data and financial information from its users. It might seem obvious that this personal information should be protected from prying eyes through access control mechanisms, audit trails, transaction controls, transmission encryption, and so on--in fact, perhaps so obvious that in many cases people perform only a cursory security analysis and produce rather generic security requirements. But is this the right way to build secure software? Are security requirements so similar across projects that we simply don't need to invest the time to explore product-level needs or to document requirements at an individual level for each project? The Web extra at http://youtu.be/qoocRI-7yRQ is an audio podcast in which author Jane Cleland-Huang discusses the importance of making informed decisions about how much time and effort to invest in analyzing security needs and specifying product-level security requirements.
Human Sex Trafficking: The Global Becomes Local

Human trafficking is a significant global problem that impacts hundreds of thousands of people each year who are coerced into forced labor, domestic servitude, or the commercial sex industry. Although the international community is becoming more aware of the scope of the trafficking problem, it is not sufficient for governments to enact anti-trafficking legislation. Trafficking victims are difficult to identify and assist, since these victims are often stigmatized or treated as criminal offenders. Greater efforts need to be made at the local level to develop social services properly trained to assist in facilitating victim cooperation with law enforcement and to handle the particular mental and emotional needs of trafficking victims.
Language after dominant hemispherectomy: Are plasticity of function and equipotentiality viable concepts?

Abstract Based on research with brain damaged children, developmental neurolinguists postulated that: (1) at birth both cerebral hemispheres were equipotential with regard to the establishment of language, (2) that specialization of the left cerebral hemisphere for language occurred over development, and (3) that interhemispheric plasticity existed such that with severe left hemisphere damage, the unimpaired cerebral hemisphere could assume linguistic competence. The technique of hemispherectomy provided an optimal means to test these theoretical notions. While early studies provided basic support, more recent and better controlled efforts provide increasing support for a genetically predetermined linguistic system and an age-independent model of recovery from brain damage. Thus, in reviewing this literature, it seems that nearly any early damage affecting the central speech zones will have a variable but nonetheless important impact on linguistic development in the majority of infants and children.
932-86 Importance of Collagen in Myocardial Ischemia and Remodeling of Abnormal Intramural Coronary Arteries (“Small Vessel Disease”) in Young Patients with Hypertrophic Cardiomyopathy and Sudden Cardiac Death

Impaired coronary blood flow reserve and myocardial ischemia in the absence of epicardial coronary artery disease is a frequent and important pathophysiologic feature of hypertrophic cardiomyopathy (HCM). To provide the morphologic basis for such findings, we studied the hearts of 16 pts with HCM (ages 11–31 yrs; mean 20) who had died suddenly. Transmural sections of ventricular septum were studied (area 5.2 ± 2 cm2) after staining with picrosirius-red; 9 ± 2 abnormal intramural coronary arteries (IMCAs)were analyzed per section. Compared to 16 structurally normal control hearts, IMCAs in HCM had substantially greater (12-fold) collagen volume fraction in media (2.5 ± 2-vs-0.2 ± 0.3%, p < 0.01), as well as larger outer diameter (120 ± 46-vs-82 ± 22 JLm,p < 0.01), luminal diameter (88 ± 33-vs-62 ± 19 JLm,p < 0.05), medial thickness (32 ± 20-vs-20 ± 6 JLm,p < 0.05) and also perivascular collagen area (41 ± 37-vs-18 ± 10 /!mZ, p < 0.05). The amount of perivascular collagen correlated directly with medial thickness (r = 0.88, P < 0.01) and volume of medial collagen (r = 0.57, p < 0.05). Thus, IMCAs in HCM are encased in perivascular collagen and also show greatly thickened media due in part to increased collagen. This substantial perivascular and medial collagen potentially impairs vasoreactivity, in turn resulting in diminished coronary blood flow and cell death. The findings provide a morphologic explanation for myocardial ischemia, mediated by “small vessel disease”, in pts with HCM.
A new electrode design for en passant recording, stimulation and intracellular dye infusion.

Abstract 1. 1. A recording technique, using in combination a metal wire and mineral oil, is described. 2. 2. Two methods for construction of this type of electrode are suggested. 3. 3. The advantages of this technique for extracellular en passant recording, stimulation and dye infusion are described.
A model for the prediction of velocity and void fraction profiles in two‐phase flow

An experimental study of velocity and void-fraction profiles has been carried out for the cocurrent two-phase flow of both air and water, and air and glycerine-water systems. The investigation was restricted to flow in a horizontal, 1 in. diam. tube with primary emphasis on the bubble flow regime. The assumptions which must be made to reduce the general equations of continuity, momentum, and energy to the forms appropriate for two-phase flow are presented and the equations simplified for the case of no local slip. A model is proposed which allows the determination, by trial, of the two-phase velocity and void-fraction profiles. The profiles generated by the use of the model in conjunction with experimental sampling data are presented, the profile shapes are discussed, and their variations with Reynolds and Froude numbers and gas volumetric flow fraction are shown to be self-consistent. The horizontal profiles are found to be in fair agreement with those predicted from Levy's mixing length theory. A correlation scheme is outlined which, supplemented by data over wider ranges of operating conditions, would serve as a method for estimating pressure drops in two-phase flow.
Development of a Synthesis For a Long-Term Oxazolidinone Antibacterial

Linezolid, compound 1, is a member of the oxazolidinone class of antibacterials and has had recent clinical interest due to its potential use as a long-term treatment for bacterial infection. Detailed herein are improvements to the original synthesis to enable phase I clinical trials. Of particular interest is the preparation of a key oxindole subunit utilizing a Pd-mediated cyclization. Optimization of the synthesis of the oxindole included the use of trifluorotoluene as the solvent.
An ab initio study of the geometry and energy of six planar conformers of β‐hydroxyacrolein

Ab initio calculations with full geometry optimization have been carried out on the planar cCc, cTc, tTc, tCt, tTt, and cCt conformers of β-hydroxyacrolein using the 4-21G basis set, and on the cCc and cCt conformers using the 4-31G basis set. The hydrogen-bonded cCc conformer is the most stable and the cCt conformer the least stable, with the other conformers following the above sequence. β-Hydroxy substitution has scarcely any influence on the geometry of the trans-acrolein structure, whereas the geometry of the cis-acrolein structure shows significant changes which depend on whether the OH group is cis or trans with respect to the CHO group about the CC bond. The ΔET values for cis → trans isomerization about the CC bond in cCt and cTc support the hypothesis that these changes in geometry are the result of a destabilizing interaction in cCt and a stabilizing interaction in cTc. The geometry of the hydrogen-bonded structure cCc sets it apart from all the other conformers: it has by far the longest CC, the longest CO, the longest OH, the shortest CC, and the shortest CO. Its formation from cCt involves a lengthening of CC, CO, and OH and a shortening of CC and CO, indicating a delocalization of charge within the ring. 4-21G calculations have also been made for a distorted cCt structure that has the same bond lengths and angles as the equilibrium cCc structure, and the distortion energy, cCt (equm. geom.) → cCt (distorted geom.), is found to be +13.1 kJ mole−1. Taking the energy of this distorted cCt structure as the baseline, the hydrogen-bonding energy in cCc is found to be —80.3 kJ mole−1.
Temporal change as an aspect of biogenic shell utilization and damage, Pleistocene of North Carolina, U.S.A

Abstract Sediments and fossils of the Smith Gut and Beard Creek members, middle Pleistocene Flanner Beach Formation, record the development of an interglacial, predominantly softbottom, estuarine basin that consisted first of open bay, then more restricted bay, closed lagoonal, and finally open lagoonal settings as barrier islands formed to the east and partitioned this segment of the North Carolina coast. Within this series of beds were found the remains of a sequence of benthic paleocommunities that changed through time in step with gradually changing properties of the surrounding environments, such as salinity levels, seasonality, water depth and substrate textures. As such, this faunal transition is an example of community replacement, the gradual to abrupt substitution of one community for another owing to directional habitat alterations. This long-term, subevolutionary pattern of faunal change also was resolvable in a study of macroscopic epi- and endozoans, and signs of predation, in autochthonous fossil shells. Open bay fossil associations contained a rich variety of encrusters, borers, and evidences of predator—prey interactions. The suceeding restricted bay associations contained fewer types of epi- and endozoans. At slightly higher stratigraphy levels, bay associations were replaced by comparatively species-poor, high-dominance, closed lagoonal associations containing still fewer encrusters and no boring organisms. And in the highest fossiliferous levels of the Flanner Beach, open lagoonal associations became enriched in epi- and endozoans but never reattained the diversity of forms seen at lower levels in open bay associations. Predation signs vary throughout the sequence in frequency of occurrence, not in kind. The sequential change in shell utilization by encrusters and borers described here does not resemble succession-like sequences observed over short time spans involving hard-substrates faunas, but rather is a conformational transition controlled by long-term environmental changes.
Discrete nebulization using aerosol deposition in electrothermal vaporization for inductively coupled plasma-atomic emission spectrometry

Abstract Discrete nebulization using aerosol deposition is examined as a procedure for sample introduction in electrothermal vaporization for ICP-AES. Small volumes of solution (
Lewy's operator and its ramifications

Soit L l'operateur de Lewy. On donne deux nouvelles demonstrations de l'inesolubilite de L. Chaque demonstration place L dans un nouveau cadre et conduit a une theorie interessante