cssi/SciSciGPT-SciSciNet huggingface dataset:
Identification of a mechanogenetic link between substrate stiffness and chemotherapeutic response in breast cancer

Mechanical feedback from the tumor microenvironment regulates an array of processes underlying cancer biology. For example, increased stiffness of mammary extracellular matrix (ECM) drives malignancy and alters the phenotypes of breast cancer cells. Despite this link, the role of substrate stiffness in chemotherapeutic response in breast cancer remains unclear. This is complicated by routine culture and adaptation of cancer cell lines to unnaturally rigid plastic or glass substrates, leading to profound changes in their growth, metastatic potential and, as we show here, chemotherapeutic response. We demonstrate that primary breast cancer cells undergo dramatic phenotypic changes when removed from the host microenvironment and cultured on rigid surfaces, and that drug responses are profoundly altered by the mechanical feedback cells receive from the culture substrate. Conversely, primary breast cancer cells cultured on substrates mimicking the mechanics of their host tumor ECM have a similar genetic profile to the in situ cells with respect to drug activity and resistance pathways. These results suggest substrate stiffness plays a significant role in susceptibility of breast cancer to clinically-approved chemotherapeutics, and presents an opportunity to improve drug discovery efforts by integrating mechanical rigidity as a parameter in screening campaigns.
Effect of Wall Elasticity on Hemodynamics and Wall Shear Stress in Patient-Specific Simulations in the Coronary Arteries

Wall shear stress (WSS) has been shown to be associated with myocardial infarction (MI) and progression of atherosclerosis. Wall elasticity is an important feature of hemodynamic modeling affecting WSS calculations. The objective of this study was to investigate the role of wall elasticity on WSS, and justify use of either rigid or elastic models in future studies. Digital anatomic models of the aorta and coronaries were created based on coronary computed tomography angiography (CCTA) in four patients. Hemodynamics was computed in rigid and elastic models using a finite element flow solver. WSS in five timepoints in the cardiac cycle and time averaged wall shear stress (TAWSS) were compared between the models at each 3 mm subsegment and 4 arcs in cross sections along the centerlines of coronaries. In the left main (LM), proximal left anterior descending (LAD), left circumflex (LCX), and proximal right coronary artery (RCA) of the elastic model, the mean percent radial increase 5.95 ± 1.25, 4.02 ± 0.97, 4.08 ± 0.94, and 4.84 ± 1.05%, respectively. WSS at each timepoint in the cardiac cycle had slightly different values; however, when averaged over the cardiac cycle, there were negligible differences between the models. In both the subsegments (n = 704) and subarc analysis, TAWSS in the two models were highly correlated (r = 0.99). In investigation on the effect of coronary wall elasticity on WSS in CCTA-based models, the results of this study show no significant differences in TAWSS justifying using rigid wall models for future larger studies.
An Application of Group Theory to Change Ringing

After providing some background on change ringing, this paper introduces a question that arises in the systematic ringing of church bells and uses group theory to solve it.
Chapter 14 – Responsible Management of Biotechnologies

This chapter considers the scientific aspects of the previous chapters from the standpoint of risk management. Biotechnologies are part of the solution to environmental problems as well as being contributors to pollution, e.g., when materials are released during bioprocessing. Practitioner codes of ethics and conduct are discussed. The chapter introduces ways to analyze decisions regarding biotechnology and synthetic biology, including risk and reliability analyses. Offsetting behavior, risk homeostasis, and other social science concepts are applied to biotechnological safety and risk analysis.
LABOR MANAGEMENT ON DAIRY FARMS

Dairy farm managers accomplish their profitability, growth and excellence goals through people. Success with people on dairy farms depends primarily on the dairy manager's effectiveness in the five major components of labor management, to include hiring, orientation, training, communication and motivation of employees. Dairy managers who make labor management one of their important strengths master these five components plus several others. Successful labor management is a combination of positive attitude toward people in the business, carefully honed individual skills and human resource procedures designed to fit the business. This article provides an overview of each of the five major components of labor management.
Cortical Bone Derived Stem Cells Modulate Cardiac Fibroblast Response via miR-18a in the Heart After Injury.

The adult heart following injury such as a myocardial infarction forms a fibrotic scar associated with transformation of resident cardiac fibroblasts into myofibroblast, accelerating cardiac remodeling and dysfunction. Cell therapies provide a novel direction for the enhancement of cardiac structure and function but remain poorly described in terms of the effect on resident cardiac fibroblasts. We have shown cortical bone derived stem cells (CBSCs) exhibit an ability to repair the heart after myocardial injury together with reduced scar formation. Nevertheless, whether CBSCs possess ability to modulate resident fibroblast response after myocardial injury remains untested. Objective; To determine the effect of secreted factors from CSBCs to attenuate myofibroblast formation in the heart after injury. Methods and Results; CBSCs were injected in mice after myocardial infarction which demonstrated reduced fibrosis as determined by Masson’s trichrome and Picro-Sirius red staining. In parallel, decreased expression of myofibroblast markers such as Acta2 was observed compared to PBS injected mice. To determine the effect of CBSCs on cardiac fibrosis, adult mouse cardiac fibroblasts were isolated from C57BL/6 mice, primed with CBSC pre-conditioned media for 12 hours, and treated with 10ng TGF-β for 48 hours to mimic cardiac injury. Decreased expression of Acta2, periostin and CTGF was observed in adult cardiac fibroblasts cultured in CBSC medium compared to control cells. Additionally, analysis of myofibroblast markers such as vimentin and pSMAD/SMAD was also decreased compared to control cells. To determine the mechanism, we looked for enriched miRNA in CBSCs that can mediate anti fibrotic response after injury. Results showed significantly increased expression of miR-18a in CBSCs. The upregulation of miR-18a was also validated in adult fibroblasts treated with CBSCs compared to control cells. Adult fibroblasts treated with mimic for miR-18a followed by TGF-β showed significant decrease in myofibroblast formation while miR-18a inhibitor completely inhibited the effect of CBSC medium. Conclusion; CBSCs reduce fibroblast to myofibroblast transition and differentiation in adult cardiac fibroblasts via miR-18a-5p. This finding reveals a new avenue for cell therapies to target myocardial scar modulation and provides a resolution for the cardiac repair response after injury in the adult myocardium.
Evolutionary Alternatives in the Physiological Ecology of Bats

Bats are often thought to have poor temperature regulation, to feed on insects, and to enter hibernation. This combination of characteristics is typical only of temperate species. In the last two decades intensive work in the tropics, especially in the New World, has shown the great ecological diversity existing among bats, which in turn permits us to place temperate species in their appropriate ecological and evolutionary perspective and to examine some of the physiological and ecological alternatives available to bats when living in a physically benign environment.
N-k interdiction modeling for natural gas networks

Abstract Although electricity transmission systems are typically very robust, the impacts that arise when they are disrupted motivate methods for analyzing outage risk. For example, N-k interdiction models were developed to characterize disruptions by identifying the sets of k power system components whose failure results in “worst case” outages. While such models have advanced considerably, they generally neglect how failures outside the power system can cause large-scale outages. Specifically, failures in natural gas pipeline networks that provide fuel for gas-fired generators can affect the function of the power grid. In this study, we extend N-k interdiction modeling to gas pipeline networks. We use recently developed convex relaxations for natural gas flow equations to yield tractable formulations for identifying sets of k components whose failure can cause curtailment of natural gas delivery. We then present a novel cutting-plane algorithm to solve these problems. Finally, we use test instances to analyze the performance of the approach in conjunction with simulations of outage effects on electrical power grids.
Screen media use and sleep disturbance symptom severity in children.

Abstract Objectives Few studies have sought to evaluate how screen media use relates to symptoms of sleep-wake disturbances. To extend these prior studies in a large sample of children, this study examined associations of different types of screen media with symptom severity of different classes of sleep-wake disturbances. This study was preregistered here. Design This study utilized the baseline cross-sectional survey administered within the Adolescent Brain Cognitive Development Study (ABCD; Release 2.0). Participants ABCD recruited over 11,000 U.S. children age 9–10 across 21 study sites using an epidemiologically-informed school-based recruitment strategy. Measurements Children reported typical weekend and weekday use of TV, video, video game, social media, texting, and video chat, and parents completed reports of the child's symptom severity of sleep-wake disturbances via the Sleep Disturbance Scale for Children. Results Greater screen media use, TV, video, and video game use, was associated with decreased sleep duration, increased sleep onset latency as well as greater excessive sleepiness, insomnia, and overall sleep disturbance symptom severity. Use of these screen medias were also associated with clinically relevant sleep problems. Ethnoracial differences emerged in screen use and sleep, but did not moderate the association between screen use and sleep. Conclusions Greater use of screen medias was not just associated with longer sleep onset latency and shorter sleep duration, but also increased severity of multiple types of sleep-wake disturbances. Future research should use longitudinal designs to determine the direction of these associations in adolescent populations.
The Discovery and Characterization of Targeted Perikaryal-Specific Brain Lesions With Excitotoxins

The neurotoxic action of glutamic acid was first described by Lucas and Newhouse, who demonstrated neural degeneration in the inner layers of the neonatal mouse retina after systemic treatment with L-glutamate. Olney extended these findings by showing that neuronal degeneration affected other brain structures including neurons within the arcuate nucleus of the hypothalamus and the area postrema, that the lesion spared axons passing through these areas, and that the neurotoxic potency of glutamate analogs correlated with their excitatory potency, resulting in the designation "excitotoxins." As this method affected only a small number of brain regions, it was not suitable for targeted brain lesions. The Coyle laboratory showed that direct injection of the potent glutamate receptor agonist, kainic acid, into the rat striatum caused a rapid degeneration of intrinsic neurons while sparing axons of passage or termination including the unmyelinated dopaminergic terminals. Kainic acid also exhibited this perikaryal-specific and axon-sparing profile when injected into the cerebellum, hippocampus and eye. However, neuronal vulnerability was highly variable, with hippocampal CA3, pyriform cortex and amygdala neurons exhibiting great sensitivity due to kainate's high convulsive activity. In a comparison study, ibotenic acid, a potent glutamatergic agonist isolated from the amanita muscaria mushroom, was found to have excitotoxic potency comparable to kainate but was far less epileptogenic. Ibotenate produced spherical, perikaryal-specific lesions regardless of the site of injection, and experiments with specific glutamate receptor antagonists showed that its effects were mediated by the N-methyl-D-aspartate receptor. Because of this uniform neurotoxicity and near ubiquitous efficacy, ibotenic acid became the excitotoxic lesioning agent of choice. The discovery of the excitotoxic properties of the tryptophan metabolite quinolinic acid and of the anti-excitotoxic, neuroprotective effects of the related metabolite kynurenic acid in the Schwarcz laboratory then gave rise to the concept that these endogenous compounds may play causative roles in the neuropathology of a wide range of neurological and psychiatric disorders.
The association between statewide vaping prevalence and COVID-19.

Existing literature indicated electronic cigarette users (vapers) have impaired immune response that might increase vulnerability to coronavirus disease 2019 (COVID-19) infection and death. However, whether vapers are more susceptible to COVID-19 is unknown. Using integrated data in each US state from the 2018 Behavioral Risk Factor Surveillance System (BRFSS), United States Census Bureau and the 1Point3Acres.com website, generalized estimating equation (GEE) models with negative binomial distribution assumption and log link functions were used to examine the association of statewide e-cigarette use prevalence with number of COVID-19 cases and deaths in the US on a state level from January 21, 2020 to April 25, 2020. The weighted proportion of vapers who used e-cigarettes every day or some days ranged from 2.86% to 6.42% for US states. Statistically significant associations were observed between the weighted proportion of vapers and number of COVID-19 cases as well as COVID-19 deaths in the US after adjusting for the weighted proportion of smokers and other significant covariates in the GEE models. With every one percent increase in weighted proportion of vapers in each state, the number of COVID-19 cases increase by 0.3139 (95% CI: 0.0554-0.5723) and the number of COVID-19 deaths increase by 0.3730 (95% CI: 0.0815-0.6646) in log scale in each US state. The positive associations between the proportion of vapers and the number of COVID-19 cases and deaths in each US state in this ecological study suggest an increased susceptibility of vapers to COVID-19 on a state level and warrants further investigation.
Are Single Women Promoted into Leadership Positions in Business? Evidence of Incongruity Penalties of Single Women with Masculine Talents

We advance scholarship on gender inequality in leadership by drawing attention to a growing but less studied group: single women (non-mother) professionals. Our thesis is that single, non-mother status is perceived as incongruent with societal and role expectations of leadership for women, stunting their early career advancement in the workplace relative to other gender and marital status groups. In line with role expectations theory, we expect this incongruity with leadership to be penalizing under conditions that make singlehood status salient for women in the workplace, namely having gender inconsistent (stereotypically masculine) talents. Using a multi-method approach, we investigate the early career promotions of men and women MBAs and present evidence that supports our thesis. In Study 1, an experiment with MBA students, we observe a negative promotion bias against analytically-talented (masculine) single women MBAs whom participants assess as inferior leaders compared to otherwise identical analytically-talented single men, married men, and married women candidates. Study 2 provides external validity by analyzing the actual early career mobility outcomes of two cohorts of MBA graduates and shows consistent evidence of an incongruity penalty toward analytically-talented (masculine) single women. The combined studies unveil a discrimination-based penalty where singlehood status conflicts with the role of leadership ascribed to women when they excel in a masculine talent.
Does M1 More Accurately Define the Extent to Which Crowd Out Can Be Modified Than Total Loanable Funds

This chapter examines the effect of M1 and both endogenous and exogenous loanable funds availability on GDP an concludes FR purchases have the stronger positive effect.
Is There Such a Thing as Genuinely Moral Disgust

In this paper, I defend a novel skeptical view about moral disgust. I argue that much recent discussion of moral disgust neglects an important ontological question: is there a distinctive psychological state of moral disgust that is differentiable from generic disgust, and from other psychological states? I investigate the ontological question and propose two conditions that any aspiring account of moral disgust must satisfy: (1) it must be a genuine form of disgust, and (2) it must be genuinely moral. Next, I examine two prominent accounts of moral disgust by John Kekes and Victor Kumar and argue that neither successfully establishes the existence of genuinely moral disgust: Kekes’ account does not satisfy condition (2), and Kumar’s view does not meet condition (1). I claim that an important general lesson can be drawn from my critiques of Kekes’ and Kumar’s accounts: to establish the existence of moral disgust, one must provide unequivocal evidence that genuinely moral disgust, not generic disgust or anger, is being elicited in response to relevant moral violations. I conclude by considering why we ought to be skeptical about the general prospect of giving a positive answer to the ontological question, given the available evidence.
Unfinished Business: Advancing Workplace Gender Equity Through Complex Systems Strategies Supporting Work/Family Dynamics

The whole world endorses women’s equal rights in workplace, family, and society (Pew Global 2020). Researchers find gender inclusion benefits workers and companies through enhanced worker and customer satisfaction, increased profits, and worker well-being. Why does gender workplace equity remain a “stalled revolution”? We suggest work/family dynamics supporting challenges of care for the most vulnerable—children, elders, the disabled, adults experiencing ill health—need to be “re-visioned” as “wicked problems” within applied complexity/developmental systems sciences. Complexity sciences argue gendered inequalities maintain stability through entangled forces at multiple levels yet can be transformed through problem-and-setting specific ecological analysis, identifying leverage points for maximum impact toward achieving valued outcomes. We apply transdisciplinary cultural/developmental systems perspectives on the gendered, interdependent life course, highlighting shared individual, family/kin, business, and public responsibilities toward supporting work and caretaking (Brandth, Halrynjo, & Kvande, 2017). These approaches help map multi-systemic factors offering impactful leverage points catalyzing measurable change. Global comparative literatures identify three transformative leverage points: (1) Gender-neutral paid family/kinship care leave when meeting life course challenges of childbearing/adoption and infant care; (2) Public/private partnerships providing flexible, predictable employment and institutional supports for early childhood care, schooling, and dependent caretaking needs for workers at all income levels (Thebaud & Halcomb, 2018); (3) Systems-minded organizational interventions addressing gender stereotyping of work/family decisions in Human Resources administration and in leadership training for both managers and workers.
High-Frequency Oscillations in the Pallidum: A Pathophysiological Biomarker in Parkinson's Disease?

Background Abnormal oscillatory neural activity in the beta-frequency band (13-35 Hz) is thought to play a role in Parkinson's disease (PD); however, increasing evidence points to alterations in high-frequency ranges (>100 Hz) also having pathophysiological relevance. Objectives Studies have found that power in subthalamic nucleus (STN) high-frequency oscillations is increased with dopaminergic medication and during voluntary movements, implicating these brain rhythms in normal basal ganglia function. The objective of this study was to investigate whether similar signaling occurs in the internal globus pallidus (GPi), a nucleus increasingly used as a target for deep brain stimulation (DBS) for PD. Methods Spontaneous and movement-related GPi field potentials were recorded from DBS leads in 5 externalized PD patients on and off dopaminergic medication, as well as from 3 rhesus monkeys before and after the induction of parkinsonism with the neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine. Results In the parkinsonian condition, we identified a prominent oscillatory peak centered at 200-300 Hz that increased during movement. In patients the magnitude of high-frequency oscillation modulation was negatively correlated with bradykinesia. In monkeys, high-frequency oscillations were mostly absent in the naive condition but emerged after the neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine. In patients, spontaneous high-frequency oscillations were significantly attenuated on-medication. Conclusions Our findings provide evidence in support of the hypothesis that exaggerated, movement-modulated high-frequency oscillations in the GPi are pathophysiological features of PD. These findings suggest that the functional role(s) of high-frequency oscillations may differ between the STN and GPi and motivate additional investigations into their relationship to motor control in normal and diseased states.
A Novel Report of Vasculitis Secondary to Mycophenolate Mofetil.

Many drugs have been implicated as a cause of vasculitis. Although the overall prevalence of drug-induced vasculitis has not been established at a population level, certain medications carry a high risk, such as the 6.5% incidence with propylthiouracil.1 With the accelerated pace of therapeutic development, including biologics, the number of these agents will surely continue to rise. Here we report a novel case of mycophenolate mofetil (MMF)–induced vasculitis. We have obtained patient consent for publication of this deidentified case, and this study has been reviewed by the Dartmouth-Hitchcock Medical Center institutional review board (STUDY02000740). A 34-year-old man with a history of renal transplant for membranous glomerulonephritis (MGN) was admitted to the hospital with unilateral wrist/hand inflammation. His immunosuppressive regimen comprised MMF 750 mg twice daily, tacrolimus 3 mg twice daily, and prednisone 5 mg daily (Figure 1). Four months prior to admission, his course was complicated by posttransplant recurrent MGN, which improved with an 8-week course of weekly rituximab (RTX). On admission, vital signs were normal and physical exam revealed a red, warm, and swollen left wrist, and a painful, nodular rash on …
Graves, Melissa. Nixon’s FBI: Hoover, Watergate, and a Bureau in Crisis: Boulder, CO: Lynne Rienner Publishers, 2020. 247 Pages. $85 (Hardcover)

The Federal Bureau of Investigation (FBI) is ripe for political manipulation. It happened during the Nixon years, more recently when Trump occupied the White House, and it is possible again in the ...
Two-Photon Spectroscopy by Elliptical Polarization State Alteration

Two-photon spectroscopy is now widely accepted as a useful tool in atomic and molecular spectroscopy. The fact that its selection rules complement the selection rules of one-photon spectroscopy make it useful for finding transitions that are “hidden” in one-photon spectra.
Protein-disulfide Isomerase-mediated Reduction of the A Subunit of Cholera Toxin in a Human Intestinal Cell Line

A key step in the action of cholera toxin (CT) is the reduction of its A subunit to the A1 peptide. The latter is an ADP-ribosyltransferase, which activates the alpha-subunit of the stimulatory G protein of adenylyl cyclase. In this study, the enzymatic reduction of membrane-bound CT in CaCo-2 human intestinal epithelial cells was characterized. Whereas diphtheria toxin was found to be reduced by a cell surface population of protein-disulfide isomerase (PDI) and its cytotoxicity was inhibited by p-chloromercuribenzenesulfonic acid, bacitracin, or anti-PDI antibodies, these inhibitors had no effect on CT reduction or activity in intact cells. In contrast, the reduction of CT in vitro by either postnuclear supernatants (PNS) or microsomal membranes in the presence of Triton X-100 was significantly inhibited by p-chloromercuribenzenesulfonic acid and bacitracin. Anti-PDI monoclonal antibodies likewise inhibited the in vitro reduction of CT and also were effective in depleting reductase activity from PNS. Since inhibition and depletion were not observed in the absence of detergent, these results suggested that the reductase activity was a soluble component localized to the lumen of microsomal vesicles and correlated with the presence of protein-disulfide isomerase. This was further confirmed by showing a corresponding depletion of reductase activity and PDI in alkali-treated microsomes. This activity was restored when purified bovine PDI was added back to alkali-treated microsomes in a redox buffer that reflected conditions found in the lumen of the endoplasmic reticulum (ER). When the CT-related reductase activity was assayed in subcellular fractions of PNS-derived membranes isolated on a 9-30% Iodixanol gradient, the activity, as measured by CT-A1 peptide formation localized to those fractions containing PDI. Likewise CT-A1 peptide formed in intact cells co-localized to those membrane fractions containing the majority of cellular PDI. Furthermore, the banding density corresponded to a region of the gradient containing ER-derived membranes. These results indicated that CT was a substrate for PDI-catalyzed reduction in intact cells and supported the hypothesis that CT reduction and activation occurs in the ER.
Reconceiving the Family: A City without Duty, Fault, or Shame

The American Law Institute's 'Principles of the Law of Family Dissolution' seek in important respects to avoid taking account of fault. This extends a trend of the past several decades towards the development of the no-fault marriage, the no-fault family, and the no-fault legal system. There have been tendencies towards the emergence of a no-fault public culture, a no-fault system of social morality, and even perhaps towards a normative psychology which encourages the individual to maintain an attitude of continuous self-approbation. This chapter deplores these tendencies, presenting the thesis that the recognition of fault - its ascription to others and its acknowledgment in oneself - is in one way and another actually a good thing, or at least that it is involved in an intimate and inextricable way with the remedial side of certain basic personal and social goods, and has a special place in regards to marriage and the family.
Vapor pressure prediction for stacked-chip packages in reflow by convection-diffusion model

Moisture plays a critical role in the reliability of electronic devices, especially in the desorption process at reflow temperatures (around 270° C) when severe damages may occur due to high-pressure vapor concerted from condensed moisture. Such pressure-driven vapor flow, however, could not be described by conventional Fick's Law. Furthermore, using conventional Fick's Law for multi-materials always encounters interface discontinuity issues. Therefore, this paper adopts a Convection-Diffusion Model that is able to describe complex desorption behavior in a multi-material media without the discontinuity issue. Both pressure gradient-driven (convection) and concentration-gradient driven (diffusion) moisture transports are considered in the model. To achieve this, absorbed moisture is partitioned into vapor phase and liquid phase (condensed water), with the vapor flux governed by Darcy's Law and the water flux by Fick's Law. Henry's Law is also implemented so that the Fickian term is converted to pressure, resulting in a unified vapor pressure model. The model is applied to analyze a stacked-chip package by two numerical cases: desorption under 2 typical reflow temperature profiles. Numerical validations are also performed to show that the Convection-Diffusion Model can be reduced to traditional Fickian Model and Convection-Only Model as special cases. The numerical results show that the concentration desorption rate is much faster than that of the traditional Fickian diffusion, and somewhat faster than the Convection Model, this results in a much lower pressure in the material. However, the desorption profile with time and the pressures at low temperatures of the different models— the Convection-Only, Diffusion-only and the Convection-Diffusion Model are indistinguishable which can be seen in both reflow profiles. The sensitivity of the CD Model to the gas permeability k and the reflow temperature profiles governs the maximum pressure that is predicted as well as the concentration content.
The Social Cost of Electricity: Scenarios and Policy Implications

This is a review of The Social Cost of Electricity: Scenarios and Policy Imperatives (Edward Elgar, 2010), which summarizes the results of a European Commission funded research project. The contributions in this volume stands out for their ambitious effort to model and quantify the external costs of electric power generation, as well as their initial assessment of various policy instruments designed to address climate change and promote renewable energy. While a broad range of social cost issues presented by electricity production are incorporated into the project’s modeling, it does not study or attempt to quantify conservation and demand response approaches. Much more complete data will likely be necessary to for policymakers to seriously the assess which instruments are most effective at advancing energy policy goals. Without doubt, however, the data and careful analysis presented in this volume will challenge future decisionmakers to look beyond the private or market cost of energy in their policy decisions.
Implications of the VHE gamma-ray detection of the Quasar 3C279

The MAGIC collaboration recently reported the detection of the quasar 3C279 at > 100 GeV gamma-ray energies. Here we present simultaneous optical (BVRI) and X-ray (RXTE PCA) data from the day of the VHE detection and discuss the implications of the snap-shot spectral energy distribution for jet models of blazars. A one-zone synchrotron-self-Compton origin of the entire SED, including the VHE gamma-ray emission can be ruled out. The VHE emission could, in principle, be interpreted as Compton upscattering of external radiation (e.g., from the broad-line regions). However, such an interpretation would require either an unusually low magnetic field of B ~ 0.03 G or an unrealistically high Doppler factor of Gamma ~ 140. In addition, such a model fails to reproduce the observed X-ray flux. This as well as the lack of correlated variability in the optical with the VHE gamma-ray emission and the substantial gamma-gamma opacity of the BLR radiation field to VHE gamma-rays suggests a multi-zone model. In particular, an SSC model with an emission region far outside the BLR reproduces the simultaneous X-ray -- VHE gamma-ray spectrum of 3C279. Alternatively, a hadronic model is capable of reproducing the observed SED of 3C279 reasonably well. However, the hadronic model requires a rather extreme jet power of L_j ~ 10^{49} erg s^{-1}, compared to a requirement of L_j ~ 2 X 10^{47} erg s^{-1} for a multi-zone leptonic model.
Expanding the indications for pulmonary valve replacement after repair of tetralogy of fallot

Abstract Background Insertion of a competent pulmonary valve has been advocated to reduce right ventricular volume overload associated with pulmonary regurgitation (PR) after repair of tetralogy of Fallot. However the indications, proper timing, and long-term benefits of restoring pulmonary valve function remain controversial. Methods Thirty-six patients (aged 15.2 ± 9.2 years) underwent pulmonary valve implantation (31 homografts, 5 heterografts) 12.2 ± 6.9 years after tetralogy repair. Additional surgical procedures included pulmonary artery augmentation (n = 14), closure of septal defects (n = 10), and cryoablation and endocardial resection of ventricular tachycardia (n = 2). Results All patients have had clinical improvement in their exercise capacity. Preoperative and postoperative bicycle ergometry tests in 6 patients demonstrated significant improvement in the percent of predicted peak workload (68.5% ± 19.8% to 80.7% ± 17.4%, p 2 , p Conclusions Timely insertion of a competent pulmonary valve in children, adolescents, and young adults with significant PR after tetralogy of Fallot repair results in subjective and objective improvement in exercise capacity and is associated with reduction in right ventricle size.
Apurinic acid endonuclease implicated in DNA breakage in Escherichia coli subjected to mild heat.

Summary Alkaline sucrose gradient sedimentation studies reveal that mild heat of 50–60°C triggers DNA strand breakage in E. coli cells. DNA breakage is substantially reduced by enzyme inhibitors, p-chloromercuribenzoate or HgCl2 added before heating. This suggests that DNA breakage is due to enzyme action rather than to direct action of heat itself. Under identical conditions of heating, a mutant of E. coli deficient in apurinic acid endonuclease (BW 2001) yields substantially fewer DNA breaks than wild type cells or ligase deficient strain ts7. These results are consistent with involvement of endonuclease in production of DNA single strand breaks in E. coli subjected to mild thermal stress. The important recognition from this study concerning the role of the cell's endonuclease in thermal damage is that mild heating (50–60°C) is able to trigger endonucleolytic DNA breakage which seems to be the initial event in heat injury.
The preparation of immobilized stationary phase fused silica capillary columns with OV-1701-vinyl deactivation

A new simplified method was developed for the preparation of immobilized stationary phase fused silica capillary columns coated with OV-1-vinyl, SE-54, and OV-1701-vinyl. This methodology includes the application of the moderately polar stationary phase OV-1701-vinyl as a surface deactivation agent that may also participate in the dicumyl peroxide initiated free radical immobilization process. Practical details of the procedure are presented and applications of the laboratory-produced columns are illustrated with capillary gas chromatographic separations of standard mixtures. Possible contributions of the OV-1701-vinyl deactivation layer to both crosslinking and surface bonding in the immobilization process are discussed.
Amplification of stromelysin-3 transcripts from carcinomas of the colon

Stromelysin-3 has been recently described in association with the stroma of different types of cancer including colorectal carcinomas. This article reports the detection of transcripts for stromelysin-3 (matrix metalloproteinase-11 [MMP-11]) in extracts of tissue from colorectal carcinomas using the technique of reverse transcription-polymerase chain reaction (RT-PCR). In 12 cases of primary colon carcinoma, stromelysin-3 messenger RNA (mRNA) was detected after 25 cycles, whereas this procedure did not reveal stromelysin-3 mRNA expression in one rectal carcinoma micrometastasis to the liver or in normal colon tissue (controls) after 30 cycles of PCR. However, stromelysin-3 mRNA was detected in normal colon specimens after 45 cycles. The high sensitivity of this technique allows application for the investigation of the expression of stromelysin-3 in small amounts of tissue.
Abstract 3340: Stapled helix peptides as probes to evaluate targeted disruption of protein-protein interactions mediated by RPA70N.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Replication Protein A (RPA) is a major regulator of checkpoint activation and enhanced DNA repair in cancer cells. In response to genotoxic stress, the RPA complex binds to and protects ssDNA while serving as a scaffold to recruit critical checkpoint and DNA-damage response proteins through the N-terminal region of the 70 kDa subunit of RPA (RPA70N). Specific disruption of the RPA protein-protein interactions mediated by the RPA70N domain has the potential to produce selective killing of cancer cells without the risk of cytotoxicity due to interference in the ssDNA-binding function. Stapled helix peptides are an emerging technology for the inhibition of protein-protein interactions. Incorporation of a hydrocarbon “staple” has the potential to increase the potency, stability, and cell permeability of peptides. Here, we report the development of a potent stapled helix peptide probe, derived from the endogenous RPA binding partner ATRIP (ATR-interacting protein), that binds to and inhibits the RPA70N protein-protein interaction surface. An initial alanine scan of the native ATRIP-derived sequence identified residues critical for peptide binding to RPA70N. In addition, the scan revealed residue positions that were dispensable and therefore suitable as sites for incorporation of a staple. Introduction of a conserved WFA motif derived from analysis of the p53-binding sequence produced a 10-fold gain in potency over the native ATRIP peptide. To facilitate entry into cells, negatively charged residues were replaced by alanines or by neutral, polar residues. In most instances, residues that improved the net charge had a deleterious effect on binding affinity. The resulting peptide, chosen for stapling, represented a balance between net charge and potency and was intended to offer the best chance of cell penetration while still maintaining affinity. Based on the alanine scan data, two positions were chosen for incorporation of a hydrocarbon staple; however, only one of these stapled peptides maintained binding affinity for RPA70N. The optimized peptide was cell penetrant, able to enter the nucleus, and co-localized with RPA in the nucleus at sites of DNA damage. In this study, we further examine the functional consequences of RPA70N disruption by ATRIP-derived hydrocarbon stapled peptides and discuss the use of them as tools to probe the therapeutic relevance of RPA inhibition in breast and other cancers. Citation Format: Bhavatarini Vangamudi, Andreas O. Frank, Elaine M. Souza-Fagundes, Michael D. Feldkamp, Edward T. Olejniczak, Olivia W. Rossanese, Stephen W. Fesik. Stapled helix peptides as probes to evaluate targeted disruption of protein-protein interactions mediated by RPA70N. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3340. doi:10.1158/1538-7445.AM2013-3340
Distribution of endorphins (peptides with morphine-like pharmacological activity) in pituitary

Summary Endorphin was found in the pituitary gland of rat, sheep, pig, cow and man. In bovine pituitary, highest concentrations have been found in that part of the posterior lobe containing the pars intermedia, although endorphin was also present in the pars distalis. Analysis by gel filtration and adsorption chromatography suggested that the major endorphins from rat, pig and cow pituitary were similar, with apparent molecular weights in the range 3000–3500 daltons.
A data-focused perspective on SOA and cloud computing: The utility of patterns in redevelopment

Cloud, SOA, Client-Server, mini computers, NoSQL, Hadoop … the list can appear endless. What these various silver bullets have in common is that they promise to help solve business problems and that as IT solutions they often fail to deliver on initial promises. This talk takes a long-term perspective, examining first the original promise of these two complementary technologies and second, relative track records to date. With this background, it is now possible to understand their strengths and weaknesses in context. Two important concepts emerge: (1) in what contexts do these technologies excel, and (2) how can we use this information to make existing SOA and cloud applications more useful — through maintenance — to their respective applications. The talk closes with some open research challenges as well as general architectural guidelines to help guide future maintenance efforts.
Exploring Component Stability Using Life-Stage Concordance In Sabethine Mosquitoes (Diptera: Culicidae)☆

Abstract Morphological characters from sabethine mosquitoes were coded from larvae, pupae and adults, and life-stage partitions were evaluated to determine the contribution of each to the topology of a combined cladogram. Initial tests failed to find congruence between characters partitioned by life stage. However, when components from the combined analysis were tested using reduced taxon sets, a high degree of concordance between partitions was observed. A procedure for assessing individual life-stage contribution is employed, in which exhaustive searches are used to explore all possible arrangements for each of the selected components. Seven of the 10 components examined were able to recover the combined topology with a reduced taxon set. Congruent arrangements of taxa were typically observed for two or more life stages, although partitioned data were less resolved and frequently included aberrant topologies (those not supported by other partitioned or combined reduced taxon tree sets). In addition, none of the partitioned data sets gave robust results for all tests, suggesting that studies which emphasize character data from single life stages may support misleading arrangements of taxa. One component on the combined cladogram was not supported by any of the life-stage partitions when analysed separately. These results are complementary to “total evidence” approach, and demonstrate that partitions of data are useful for examining suits of characters which may cause some components of the “total
Impact of mandated workplace health insurance on industry costs and prices

(1982). Impact of mandated workplace health insurance on industry costs and prices. Applied Economics: Vol. 14, No. 3, pp. 315-326.
Does the Degree of Campus "Wiredness" Matter?

Responses to the College Student Experience Questionnaire 4th Edition from 18,844 students at 71 colleges and universities were analyzed to determine if the presence of computing and information technology influenced the frequency of use of various forms of technology and other educational resources and the exposure to good educational practices. Undergraduates attending "more wired" campuses as determined by the 1998 and 1999 Yahoo! Most Wired Campus survey more frequently used computing and information technology and reported higher levels of engagement in good educational practices than their counterparts at less wired institutions. Non-traditional students benefited less than traditional students, but both women and men students benefited comparably from campus "wiredness."
Powwows as Identity Markers: Traditional or Pan-Indian ?

This article examines powwows and Indian identity among the Waccamaw Sioux of North Carolina. Data are drawn from structured interviews. The results of our analyses suggest that the salience of powwows to Indian identity rests not in the authenticity of a powwow regarding local history and culture, but rather in the relationship of the activity to popular community participation. Local powwow participation ranks relatively high in importance to Indian identity and is closely associated with more "traditional" community-level identity markers. On the other hand, regional powwow activities rank relatively low in importance to Indian identity and are associated with regional political and administrative aspects of Indian identity. The findings suggest that local powwows have become an important part of traditional Indian identity among the Waccamaw Sioux.
Nativity Status and Sources of Care Assistance Among Elderly Mexican-Origin Adults

Much like other racial/ethnic groups, Latinos are facing challenges to provide needed care to aging adults. Older Latinos underutilize nursing homes and home health care services and primarily rely on their families for assistance. While this general trend has been established, little attention has been paid to nativity differentials in patterns of caregiving for this segment of the aging population. The analyses are based on the latest wave (Wave 7) of the Hispanic Established Population for Epidemiologic Studies of the Elderly or H-EPESE (2010/2011) a sample of older Mexican-origin adults and their family caregivers living in the southwestern U.S. We examine 629 child caregiver/parent care recipient dyads using bivariate statistics and multinomial logistic regression analyses. The results reveal that while grown children of Mexican-origin elders play a critical role in providing instrumental and financial supports to their aging parents, the burden that the children of foreign-born parents bear is greater. Despite higher rates of disability, Mexican-born elders are more dependent on a child for help and far less likely to call upon other family members, relatives and community based-providers for help than the U.S. born. Given the recent and future growth of older Latinos, intervention strategies will need to focus on nativity status and acculturative processes in the context of caregiving and caregiver burden.
Quality enhancement of low-resolution image by using natural images

In this paper, we propose a new algorithm to estimate a super-resolution image from a given low-resolution image, by adding high-frequency information that is extracted from natural high-resolution images in the training dataset. The selection of the high-frequency information from the training dataset is accomplished in two steps: a nearest-neighbor search algorithm is used to select the closest images from the training dataset, which can be implemented in the GPU, and a sparse-representation algorithm is used to estimate a weight parameter to combine the high-frequency information of selected images. This simple but very powerful super-resolution algorithm can produce state-of-the-art results. Qualitatively and quantitatively, we demonstrate that the proposed algorithm outperforms existing common practices.