cssi/SciSciGPT-SciSciNet huggingface dataset:
ATF1 phosphorylation by the ERK MAPK pathway is required for epidermal growth factor-induced c-jun expression.

Epidermal growth factor induction of c-jun expression requires ATF1 and MEF2 sites in the c-jun promoter. We find that activation of the c-jun promoter through the ATF1 site requires phosphorylation of ATF1 at serine 63. A serine 63 to alanine mutation of ATF1 acts to block epidermal growth factor (EGF) induction of a transfected c-jun gene. ATF1 can be phosphorylated by mitogen- and stress-activated protein kinase 1 (MSK1), which is activated by EGF and ERK1/2. Kinase-dead MSK1 mutants blocked EGF induction of a transfected c-jun gene suggesting that MSK1 or a similar family member is required for induced c-junexpression. Use of the MEK1 inhibitor U0126 and dominant negative MEK1 further showed that MSK1 activation and c-jun induction require the ERK pathway. In contrast, a JNK inhibitor blocked EGF induction of c-jun expression but not ATF1 phosphorylation. These results show that the two MAPK pathways, ERK and JNK, are required for EGF-induced c-jun expression and that the ERK pathway acts through downstream phosphorylation of ATF1.
Biotic homogenization: a new research agenda for conservation biogeography

Aim Biotic homogenization describes the process by which species invasions and extinctions increase the genetic, taxonomic or functional similarity of two or more biotas over a specified time interval. The study of biotic homogenization is a young and rapidly emerging research area in the budding field of conservation biogeography, and this paper aims to synthesize our current knowledge of this process and advocate a more systematic approach to its investigation. Methods Based on a comprehensive examination of the primary literature this paper reviews the process of biotic homogenization, including its definition, quantification, underlying ecological mechanisms, environmental drivers, the empirical evidence for different taxonomic groups, and the potential ecological and evolutionary implications. Important gaps in our knowledge are then identified, and areas of new research that show the greatest promise for advancing our current thinking on biotic homogenization are highlighted. Results Current knowledge of the patterns, mechanisms and implications of biotic homogenization is highly variable across taxonomic groups, but in general is incomplete. Quantitative estimates are almost exclusively limited to freshwater fishes and plants in the United States, and the principal mechanisms and drivers of homogenization remain elusive. To date research has focused on taxonomic homogenization, and genetic and functional homogenization has received inadequate attention. Trends over the past decade, however, suggest that biotic homogenization is emerging as a topic of greater research interest. Main conclusions My investigation revealed a number of important knowledge gaps and priority research needs in the science of biotic homogenization. Future studies should examine the homogenization process for different community properties (species occurrence and abundance) at multiple spatial and temporal scales, with careful attention paid to the various biological mechanisms (invasions vs. extinctions) and environmental drivers (environmental alteration vs. biotic interactions) involved. Perhaps most importantly, this research should recognize that there are multiple possible outcomes resulting from the accumulation of species invasions and extinctions, including biotic differentiation whereby genetic, taxonomic or functional similarity of biotas decreases over time.
How connectedness contributes to experimental smoking among rural youth: developmental and ecological analyses.

The influences of peer, sibling, and parents’ smoking on adolescents’ initiation of tobacco use have been explained as a function of peer pressure, genetics, and social learning processes, but rarely in combination or with assessments of the quality of these relationships. This study examined the additional contributions of connectedness to friends, siblings, parents, and teachers beyond the effects of friend, sibling, and parental smoking using logistic regression analyses with a cross-sectional middle and high school sample of 303 rural adolescents. Friends’ and siblings’ smoking, and connectedness to friends, were the strongest predictors of experimental smoking. Parental smoking and connectedness to parents and to teachers were significant predictors of experimental smoking when considered independently, but not after accounting for friend and sibling factors. Connectedness to parents and teachers decreased the odds of experimental smoking, while connectedness to friends increased the odds.
Flexible TIP4P model for molecular dynamics simulation of liquid water

Abstract We have developed a flexible version of the TIP4P model for molecular dynamics simulations. The model does a reasonable job of reproducing the experimental peak frequencies and widths of the bend and stretch peaks in the infrared spectra for both liquid H 2 O and D 2 O .
Adapting the eBlock Platform for Middle School STEM Projects: Initial Platform Usability Testing

The benefits of project-based learning environments are well documented; however, setting up and maintaining these environments can be challenging due to the high cost and expertise associated with these platforms. To alleviate some of these roadblocks, the existing eBlock platform which is composed of fixed function building blocks targeted to enable nonexperts users to easily build a variety of interactive electronic systems is expanded to incorporate newly defined integer-based building blocks to enable a wider range of project possibilities for middle school STEM projects. We discuss various interface possibilities, including initial usability experiments, and summarize our overall experiences and observations in working with local middles school students utilizing the eBlock platform.
Expanding the indications for the David V aortic root replacement: Early results

Objective To examine the early results of the David V valve-sparing aortic root replacement procedure in expanded, higher risk clinical scenarios with appropriately selected patients. Methods From 2005 to 2011, 150 David V valve-sparing aortic root replacements were performed within Emory Healthcare. A total of 78 patients (expanded group) had undergone the David V in expanded, difficult clinical settings such as emergent type A dissection (n = 29), grade 3+ or greater aortic insufficiency (AI) (n = 53), or reoperative cardiac surgery (n = 14). These patients were evaluated and compared with a group of 72 patients (traditional group) with less than grade 3+ AI who underwent a David V in a traditional, elective setting. The mean follow-up was 19 months (range, 1–72), and the follow-up data were 88% complete. Results There were 3 operative deaths (2.2%), all occurring in the expanded group. The overall patient survival at 6 years was 95%. Three patients required aortic valve replacement: two for severe AI and one for fungal endocarditis. Both groups had concomitant cusp repairs performed in conjunction with the David V (traditional, n = 10; and expanded, n = 16; P = .27). At follow-up, freedom from moderate AI was 93%, and the freedom from aortic valve replacement was 98%. No significant difference was observed in the freedom from moderate AI between the expanded and traditional groups (91% vs 95%, respectively; P = .16). Conclusions In selected patients possessing appropriate aortic cusp anatomy, the David V can be safely and effectively performed for the expanded indications of aortic dissection, severe AI, and reoperative cardiac surgery with low operative risk. Valve function has remained excellent in the short term, providing evidence of durability and a low rate of valve-related complications.
Simultaneous laser and radar altimeter measurements over land and sea ice

Elevation data derived from space-based altimeter measurements over landand sea-ice are key to understanding the Earth's ice mass balance. This importance is recognized by both NASA, as expressed in the laser altimeter GLAS on ICESat, and ESA, as expressed in the radar altimeter SIRAL on CryoSat. The JHU/APL Delay-Doppler Phase-monopulse (D2P) radar altimeter has shown its value as a scientific/calibration/validation instrument, and has participated in two airborne field campaigns sponsored by NASA and ESA to collect simultaneous radar and laser altimeter measurements over land and sea ice. These measurements are unique; they provide colocated, cross-calibrated, and high-precision altimetry data over a variety of geophysical ice conditions in two very different frequency regimes. In this paper, we give an overview of the CryoVEx field campaign in 2003 including basic system parameters, flight tracks, and sample waveforms from the airborne experiment.
Effect of Heat Treatment on the Flow Properties of Aqueous Guar Gum and Sodium Carboxymethylcellulose (CMC) Solutions

Prolonged heat treatment of 1% (w/v) guar gum and sodium carboxymethylcellulose (CMC) solutions resulted in a permanent loss of their apparent viscosity. The consistency index (K) of the power law model: τ= K γn, indicated well the loss of viscosity. The reduction in K due to heat treatment could be characterized by D and z parameters. The D250 and z values for guar gum were 32 min and 62°F, respectively; the magnitudes for CMC were 7.9 min and 48°F, respectively. These values were obtained from experiments in which the solutions were placed in sealed cans (201 × 304) and subjected to temperatures between 210–260°F. Because the solutions were viscous, corrections were made for heating and cooling lags during heat treatment. Dilutee solution viscosity data showed that heat treatment resulted in lower magnitudes of intrinsic viscosities and interaction coefficients. The activation energy of flow of the heat-treated solutions was not affected significantly due to heat treatment.
Moving Beyond NDE to Proactive Management of Materials Degradation

There is growing interest in life extensions to enable longer term operation (LTO) for both existing nuclear power plants (NPPs) and proposed new NPPs. In order to justify an initial license extension for the 40–60 year period, new non-destructive examination (NDE) approaches have been developed and deployed by NPP operators in their Aging Management Programs (AMPs). However, to achieve the goals of even longer term operation, and specifically for the USA in looking at methodologies to support subsequent license renewal periods (i.e., 60–80 years, and beyond), it is necessary to understand the capabilities of current NDE methods to detect, monitor and trend degradation and hence enable timely implementation of appropriate corrective actions. This paper discusses insights from past experience, the state-of-the-art, and current activities in the move towards providing a capacity for proactive management of materials degradation (PMMD) to support NPP LTO.© 2010 ASME
Cigarette smoke induces cell motility via platelet-activating factor accumulation in breast cancer cells: a potential mechanism for metastatic disease.

Most cancer deaths are a result of metastasis rather than the primary tumor. Although cigarette smoking has been determined as a risk factor for several cancers, its role in metastasis has not been studied in detail. We propose that cigarette smoking contributes to metastatic disease via inhibition of breast cancer cell platelet-activating factor acetylhydrolase (PAF-AH), resulting in PAF accumulation and a subsequent increase in cell motility. We studied several breast cell lines, including immortalized mammary epithelial cells (MCF-10A), luminal A hormone positive MCF-7, basal-like triple negative MDA-MB-468, and claudin-low triple-negative highly metastatic MDA-MB-231 breast tumor cells. We exposed cells to cigarette smoke extract (CSE) for up to 48 h. CSE inhibited PAF-AH activity, increased PAF accumulation, and increased cell motility in MDA-MB-231 metastatic triple negative breast cancer cells. The calcium-independent phospholipase A2 (iPLA2) inhibitor, (S) bromoenol lactone ((S)-BEL) was used to prevent the accumulation of PAF and further prevented the increase in cell motility seen previously when cells were exposed to CSE. Thus, iPLA2 or PAF may represent a therapeutic target to manage metastatic disease, particularly in triple-negative breast cancer patients who smoke.
Genetic fuzzy tracking controllers for autonomous ground vehicles

Genetic algorithm (CA) based fuzzy logic controller (FLC) design methods are presented for the step-lane-change maneuver of an autonomous ground vehicle. Fuzzy logic allows us to incorporate expert knowledge in the controller design. However, the fine-tuning process of a fuzzy logic controller may be very tedious and time consuming. If the information, regarding the controller operation, derived from the expert knowledge is incomplete, then an appropriately designed genetic algorithm is employed to complete the rule base specifying the desired functioning of the controller.
Arguments Against Mammography Screening Continue to be Based on Faulty Science

Each year there are now more than 30% fewer deaths from breast cancer than there would have been had screening not been initiated. Therapy has improved, but treatment saves lives when breast cancer is found earlier. Analysts who have claimed that excess cancer detection is indicative of overdiagnosis have ignored the fundamentals.
Retrospective evaluation of health event data recording on 50 dairies using Dairy Comp 305.

Abstract The purpose of this study was to characterize health data recording in herds using Dairy Comp 305 (Valley Agricultural Software, Tulare, CA), focused on the most common diseases of dairy cattle: mastitis, uterine infection (metritis), and diseases causing lameness. Herds using Dairy Comp 305 were chosen for the study because it was the most commonly used program in the United States (35% of operations using computer records/60% of cows on operations using computer records), the authors were familiar with the program, and there was convenient access to herds using the program. Specific objectives were to (1) determine the percentage of herds recording mastitis, metritis, and diseases causing lameness and the number of user-defined events used to record those diseases, (2) identify the information recorded in the remarks about the event used for each disease, and (3) evaluate the consistency of health event remarks recorded. A convenience sample of 50 Dairy Comp 305 compressed cow files was obtained directly from dairies that the authors had contact with or files obtained from industry consultants. The 50 herds included in the study were from 9 different states: California (n=3), Colorado (n=2), Iowa (n=2), Idaho (n=8), Minnesota (n=2), New Mexico (n=9), Oregon (n=2), Texas (n=2), Utah (n=1), and Washington (n=19). The average number of milking cows of the herds was 3,053 (median=2,217), ranging from 310 to 12,490 cows. The majority of dairies in this study were recording health events associated with mastitis, metritis, and diseases causing lameness. However, as reported previously, most health records observed in the current study lacked the accuracy and consistency needed to be useful for evaluating and informing herd-level health management decisions. This situation likely reflects the intended use of those records by farm personnel and the user-defined nature of health records in the absence of accepted industry standards or recommendations for health data-recording practices.
Correlation of cell migration, cell invasion, receptor number, proteinase production, and basic fibroblast growth factor levels in endothelial cells

The levels of endogenous basic fibroblast growth factor (bFGF) in seven clones of cultured bovine capillary endothelial (BCE) cells were assayed, and their relation to cell morphology, bFGF receptor number, cell migration, amniotic membrane invasivity, and proteinase levels were studied. Immunoblotting experiments with anti-bFGF IgG demonstrated that cells from these clones contained different amounts of bFGF. The cells containing high levels of bFGF had a spindle or elongated appearance at confluence and a low number of high affinity receptors for bFGF. The cells containing low levels of bFGF had a cobblestone-like appearance and a higher number of high affinity receptors. When exposed to 10 ng/ml bFGF, cells containing a low level of bFGF took on an elongated appearance with a crisscross pattern similar to that seen with the high producer bFGF cells. The endogenous bFGF levels of the BCE cell clones correlated with the extent of cell migration after wounding of a monolayer and the degree of invasion of the human amniotic membrane. Cells from the clone with the highest endogenous bFGF level migrated well, invaded the amnion membrane without the addition of exogenous bFGF, and were relatively unaffected by the addition of bFGF. Cells from the clone containing the lowest level of bFGF did not migrate or invade under normal conditions. However, the addition of bFGF to the culture medium strongly enhanced both of these processes. The inclusion of anti-bFGF IgG in the media suppressed cell migration and invasion. The plasminogen activator (PA) activities of cell lysates of the clones, assayed by the 125I-fibrin plate technique, indicated that the PA levels did not correlate with the bFGF levels. Metalloproteinase activities in the conditioned medium, assayed by gelatin zymography, correlated with the endogenous bFGF levels, suggesting that the degree of expression of metalloproteinases might be critical for cell migration and invasion. These data suggest that endogenous bFGF may have an important role for migration and invasion of BCE cells during neovascularization via the induction and/or activation of specific metalloproteinases.
Disturbance, life history, and optimal management for biodiversity

Both frequency and intensity of disturbances in many ecosystems have been greatly enhanced by increasing human activities. As a consequence, the short-lived plant species including many exotics might have been dramatically increased in terms of both richness and abundance on our planet, while many long-lived species might have been lost. Such conclusions can be drawn from broadly observed successional cycles in both theoretical and empirical studies. This article discusses 2 major issues that have been largely overlooked in current ecosystem management policies and conservation efforts: i) life history constraints; and ii) future global warming trends. It also addresses the importance of these 2 factors in balancing disturbance frequency and intensity for optimal biodiversity maintenance and ecosystem management.
Development of All-Plastic Microvalve Array for Multiplexed Immunoassay

There is a need for low-cost immunoassays that measure the presence and concentration of multiple harmful agents in one device. Currently, comparable immunoassays employ a one-analyte-per-test format that is time consuming and not cost effective for the requirement of detecting multiple analytes in a single sample. For instance, if a spectrum of harmful agents, including E. coli O157, cholera toxin, and Salmonella typhimurium, should be simultaneously monitored in foods and drinking water, then a one-analyte-per-test would be inefficient. This work demonstrates a platform capable of simultaneous detection of multiple analytes in a single, low-cost, microvalve array-enabled multiplexed immunoassay. This multiplexed immunoassay platform is demonstrated in a prototype COC (cyclic olefin copolymer) device with a 2×3 array in which 6 analytes can be detected simultaneously. In order to contain and regulate the flow of reagents in the multichannel device, an array of microfluidic valves actuated by a thermally expandable material and microfabricated resistors have been developed to direct the flow to the necessary assay sites. The microvalve-based immunoassay is shown to be reliable, easy to operate, and compatible with large-scale integration. The all-plastic microvalves use paraffin wax as the thermally sensitive material which drastically reduces power consumption by latching upon closing so that pulsed power is required only to close and latch the microvalve until it is necessary to re-open the valve. The multiplexed detection scheme has been demonstrated by using three proteins, C reactive protein (CRP) and transferrin, both of which are biomarkers associated with traumatic brain injury (TBI) as well as bovine serum albumin (BSA) as the negative control. Since there are no external bulky pneumatic accessories required to operate/latch the microvalves in the device, this compact, thermally actuated and latching microvalve-enabled multiplexed immunoassay has the potential to realize a portable, low power, battery operated microfluidic device for biological assays.Copyright © 2014 by ASME
Bargaining in Supply Chains

We study experimentally bargaining in a multiple-tier supply chain with horizontal competition and sequential bargaining between tiers. Our treatments vary the cost differences between firms in tiers 1 and 2. We measure how these underlying costs influence the efficiency, negotiated prices, and profit distribution across the supply chain, as well as the consistency of these outcomes with existing theory. We find that the structural issue of cost differentials dominates personal characteristics in explaining outcomes, with profits in a tier generally increasing with decreased competition in the tier and increasing with decreased competition in alternate tiers. The balanced principal model of supply chain bargaining does a good job explaining our data, and it outperforms the common assumption of leader-follower negotiations. We find a significant anchoring effect from a firm's first bid but no effect of the sequence of those bids, no evidence of failure to close via escalation of commitment, and mixed results for a deadline effect. We also find an interesting asymmetry between the buy and sell sides in employed bidding strategy. All firms make predominantly concessionary offers after the initial anchor; however, sell-side firms that engage in aggressive anticoncessionary bidding successfully increase prices while not compromising closure rates. Buy-side firms achieve much smaller price changes from anticoncessionary tactics and risk reduced closure, yielding no net benefit. This paper was accepted by Yossi Aviv, operations management.
Abstract 4: Lymphatic Vessels Mediate the Mobilization of Cardiac Progenitor Cells after Myocardial Infarction

The delivery of adult cardiac progenitor cells (CPCs) or their activation in situ constitute an evolving approach for the treatment of heart failure. CPCs are endowed with regenerative capacity, producing differentiating myocytes and vascular structures in the course of homeostasis and upon injury. The regenerative function of CPCs is contingent to their ability to migrate to and engraft within the wounded area. Yet, the mechanisms governing CPC trafficking in the diseased myocardium are largely unknown. The lymphatic system is vital for tissue repair, and the role of the lymphatic vasculature in the trafficking of hematopoietic and cancer cells is well documented. We examined whether cardiac lymphatic vessels mediate the translocation of CPCs in the infarcted myocardium. By imaging of the heart from transgenic c-kit-GFP reporter mice, we found that as early as 4 hours after myocardial infarction (MI), uncommitted lineage-negative progenitors accumulated in the vicinity of the lymphatic vessels located in the region bordering the necrotic area. Histologically, extensive lymphangiogenesis was documented in the mouse heart in the acute (8-48 hours) and chronic (15-35 days) phases of infarct healing and scar formation. CPCs were detected traversing the wall of lymphatic vessels at different stages after MI, indicative of the functional role of the lymphatic circulation in the recruitment of primitive cells to the site of injury. Furthermore, isolated human CPCs exhibited chemotaxis and specific binding to the human lymphatic endothelial cells (LECs) in steady-state conditions and, increasingly, after exposure to an inflammatory cytokine, TNFα. CPCs performed trans-endothelial migration in vitro, and actively intravasated into the lumen of microvessels formed by LECs in three-dimensional matrices. Finally, our data suggest that sphingosine-1-phosphate (S1P)-stimulated signaling governs the interactions of CPCs with LECs. These findings on the direct role of lymphatic vasculature in CPC trafficking may contribute to the development of novel therapeutic modalities to increase mobilization of endogenous or transplanted CPCs, promoting myocardial repair in patients with ischemic heart diseases.
Cauda equina syndrome as a complication of free epidural fat-grafting. A report of two cases and a review of the literature.

On rapporte une complication encore non decrite, la hernie de la greffe dans le canal rachidien avec compression de la moelle epiniere
Numerical Simulation on Pressure Characteristic of Boiler after Flameout

Acording to a 600 MW boiler,three-dimensional model on whole boiler is established in the paper,and validated by test results in Ref ,the values between the test and simulation is well meeted,which proves the model is corrected.Based on the model,the changes characteristic of temperature,gas content,pressure,air or gas mass are researched to discover the reason of furnace implosion.The conclusions show: after flameout,temperature decreasing,volume H2O gas decreasing,gas mass decreasing induced by volume CO2 decreasing,shortage of air,all of them lead to a big negative pressure in boiler.While temperature decreases most quickly and gas content changes most intensively,those lead to that furnace negative pressure is biggest among whole boiler system.ramp shutting fuel is an available way to decrease negative pressure of furnace.
Water Rights during the California Gold Rush: Conflicts over Economic Points of View

he availability of water proved critical as the American West was settled and its natural resources were developed. Under Spanish and Mexican rule, and later when the first Americans moved west, settlers dealt with inadequate rainfall by locating near the few streams and springs. While this settlement pattern accommodated dispersed farming and ranching activities, it precluded the exploitation of mineral resources distant from water sources. The 1848 California discovery of gold caused an upheaval in the pattern of isolated communities separated by vast tracts of arid and semiarid lands. Led by miners lusting for gold, westerners began to settle away from naturally existing water supplies. Major conflicts resulted that ultimately forced California to develop entirely new systems of water use and regulation. California's experience, in turn, influenced other western states as they confronted their own water problems. Much has been written about early water conflicts in the West, and most commentators believe those controversies led to a major departure from the legal treatment of water in the eastern United States. Most of these writings examine the challenge to the common law principle of riparian rights by the western custom of prior appropriation. Riparian and appropriative rights differ significantly. Riparian rights are held by those owning land next to a stream and entitle them to an undiminished flow of water past their property. Generally speaking, riparian owners may divert a stream temporarily (such as to power a mill) but must return it to its bed unchanged in quantity and quality so that downstream riparian owners also may have its use. This common law doctrine assumes that regular rainfall provides adequate water for the crops and domestic needs of those not fortunate enough to live next to a stream.
The Role of Community-Based Longitudinal Studies in Evaluating Treatment Effects Example: Benign Prostatic Hyperplasia

To determine the appropriateness and effectiveness of medical interventions, it is necessary to understand both the natural history of the conditions the interventions are intended to treat or prevent, and the normal reference ranges of tests used in diagnosis and management. The acquisition of this information through clinic-based studies can yield misleading conclusions owing to selection bias. What appears to be intervention-related variation in outcomes may be variation in the magnitude and form of selection bias. To minimize selection bias, population-based studies are required. Results from the Olmsted County Study of Urinary Symptoms and Health Status Among Men were used to show how a population-based longitudinal study of the natural history of benign prostatic hyperplasia (BPH) can complement research programs of the BPH Patient Outcomes Research Team. Population-based studies of disease natural history are a necessary part of medical outcomes research, and deserve greater emphasis in the medical treatment effectiveness research initiative of the Agency for Health Care Policy and Research.
Non-precious Mn1.5Co1.5O4–FeNx/C nanocomposite as a synergistic catalyst for oxygen reduction in alkaline media

In this study we show a method of preparing a high performing catalyst by designing functional nano boundaries in a nanocomposite material. A non-precious nanocomposite material composed of spinel Mn1.5Co1.5O4 nano crystals and FeNx-functioned graphene nano platelets (FeNx/C) was synthesized by an ultrasonic process. The crystal structure and elemental composition of the bimetal oxide were determined by X-ray diffraction (XRD) and energy dispersive X-ray spectroscopy (EDS). The surface morphology of the Mn1.5Co1.5O4–FeNx/C nanocomposite was characterized with transmission electron microscopy (TEM) and scanning transmission electron microscopy (STEM). The catalytic activity for the oxygen reduction reaction (ORR) was analyzed by an electrochemical method. The enhancement of activity for the ORR at the nanocomposite material is attributed to double synergistic effects from the bimetal particles and the FeNx/C nano sheets. The nanocomposite material is able to catalyze 4-electron oxygen reduction to generate water in alkaline media with a high kinetic rate constant (7.6 × 10−2 cm s−1 at 0.7 V vs. reversible hydrogen electrode, RHE). Finally, the activity and stability of the nanocomposite material were compared with that of 40% Pt supported on active carbon (40% Pt/C), which reaches 95% activity and a comparable stability of 40% Pt/C at 0.7 V (vs. RHE).
Abstract A14: Canonical WNT/β-catenin pathway activation suppresses embryonal rhabdomyosarcoma growth and self-renewal

Embryonal rhabdomyosarcoma (ERMS) is a common pediatric malignancy of muscle with relapse being the major clinical challenge. Self-renewing tumor-propagating cells (TPCs) drive cancer relapse and are confined to a molecularly definable subset of ERMS cells. To identify drugs that suppress TPC function, a large-scale chemical screen comprising of ~40,000 compounds including 47% FDA-approved drugs was completed, identifying GSK3-inhibitors as potent suppressors of ERMS growth through inducing terminal differentiation of TPCs into myosin-expressing cells. In support of GSK3 inhibitors functioning through activation of the canonical WNT pathway, recombinant WNT3A and a stabilized β-catenin enhanced differentiation and reduced self-renewal in human ERMS cell lines. Moreover, treatment of tumor-bearing zebrafish with a GSK3 inhibitor activated the WNT/β-catenin pathway, resulting in suppressed ERMS growth, depleted TPCs, and diminished self-renewal capacity in vivo. As canonical WNT signaling is essential for transition from muscle stem cell proliferation to myogenic differentiation during regeneration, our findings suggest that the same developmental pathways that regulate muscle stem cell self-renewal also contribute to tumorigenesis in ERMS. GSK3 inhibitors are being assessed for their efficacy in inhibiting growth as well as inducing differentiation of human ERMS in xenograft mouse models. Our work has identified the vital role of canonical WNT pathway in regulating differentiation and self-renewal of ERMS and demonstrated the effective application of small molecule inhibitors to target differentiation of TPCs in ERMS. Citation Format: Eleanor Chen, Michael DeRan, Katherine Brooke Grandinetti, Myron Ignatius, Ryan Clagg, Karin McCarthy, Riadh Lobbardi, Xu Wu, David Langenau. Canonical WNT/β-catenin pathway activation suppresses embryonal rhabdomyosarcoma growth and self-renewal. [abstract]. In: Proceedings of the AACR Special Conference: The Translational Impact of Model Organisms in Cancer; Nov 5-8, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(11 Suppl):Abstract nr A14.
Customizing haptic and visual feedback for assistive humanrobot interface and the effects on performance improvement

This paper presents an approach to developing an assistive interface for humanrobot interaction that provides users with customized haptic and visual feedback. The developed interface targets to improve users task performance by customizing assistance policy and level based on users performance and control strategy. To achieve this, the users control strategy was modeled based on inverse optimal control technique. Then, features describing the geometric and behavioral characteristics of user control are derived. Finally, an expert whose features most closely matched each user was identified. The identified expert was assigned to the user to define and provide customized assistance via a virtual fixturing. In human subject experiments, control strategies of twenty-three users were identified and featured; their performance was measured with four assistance types(no-assist, haptic assistance, visual zooming assistance, haptic assistance + visual zooming assistance) two parameterization types(customized, non-customized). By analyzing the experimental data, we found an optimal combination of assistance type parameterization type that results in the most improvement of performance. The results showed that the users task completion time and mean required effort yielded the best improvements when haptic assistance (with no visual zooming assistance) customized parameterization were provided for mobile robot driving tasks. We propose a novel approach to customizing haptic and visual feedback.Geometric/behavioral characteristics of user control were extracted from user data.Using the virtual fixturing, we customized haptic and visual assistances.Human subject experiments were conducted to verify the proposed approach.The users performance significantly enhanced with the customized haptic assistance.
PIM2 Upregulation Leads to Physiological Buffering of Metformin-Induced Cell Death Mediated by ER Stress/UPR in Acute Lymphoblastic Leukemia,

Abstract 3496 Acute Lymphoblastic Leukemia (ALL) is the most common malignancy in children and adolescents. Despite significant overall improvements in cure rates, outcome remains dismal for patients with resistant phenotypes or after relapse. Therefore, novel treatment strategies are warranted. Recently, we identified the AMP activated protein kinase (AMPK), a regulator of energy homeostasis in eukaryotic cells, as a potential target for ALL therapy due to its effects on cell growth, proliferation, and cell cycle regulation, as well as its crosstalk with critical metabolic and oncogenic pathways. We showed that activation of AMPK using metformin (1-5 mM) induced significant cell growth inhibition and apoptosis in CCRF-CEM (T-ALL) and NALM6 (Bp-ALL) cell line models. Western blot analysis revealed that metformin led to activation of p-AMPK (Thr172) and its downstream target p-ACC (Ser79), the cell proliferation regulator p-Akt (Ser473), and the protein translation regulator p-4EBP1 (Thr70), suggesting that protein translation may be an important determinant in the mechanism of metformin-induced cell death. Indeed, we demonstrated that blocking protein translation with the mTOR inhibitor rapamycin (1 μg/ml) rescued ALL cells from metformin-induced cell death ( p 10 :437, 2011). To further investigate the relationship between protein translation and ER stress/UPR, we examined the role of PIM1/2 kinases, particularly PIM2 known to regulate CAP protein translation, in metformin-induced ALL cell death. Our results indicate that expression of PIM2 is significantly increased in NALM6 cells treated with metformin (5–10 mM) for 72 h. We also observed concomitant decrease in the expression of the UPR markers IRE1α, ATF6, and CHOP, raising the possibility that PIM2 upregulation may be a compensatory survival mechanism to regulate protein translation and suppress metformin-induced ER stress/UPR. To test this hypothesis, we co-treated NALM6 cells with the small molecule PIM1/2 kinase inhibitor V (80 μM) and metformin (5 mM) and found that inhibition of PIM2 in metformin-treated NALM6 cells induced synergistic cell death (CI = 0.28). Taken together, our data indicate that PIM2 plays a role in buffering cell death in metformin treated cells, and that regulation of protein translation modulates ER stress/UPR induced apoptosis in ALL cells. Consequently, our data support strategies that exploit synthetic lethality by combining activators of AMPK such as metformin and compounds that target regulation of protein translation or protein degradation as suitable for clinical translation in patients with ALL. Disclosures: No relevant conflicts of interest to declare.
Staphylococcal Food Poisoning-A Review. I. Characteristics and Isolation of Staphylococci, Properties of Enterotoxins, and Epidemiology of Staphylococcal Intoxications

Each year, millions of people throughout the world are victims of a foodborne disease which results when an enterotoxin produced by the bacterium Staphylococcus aureus is ingested. This review describes these intoxications, the causative organism, the enterotoxins and describes some outbreaks of staphylococcal food poisoning. After considering the taxonomy and general characteristics of these gram-positive, facultative-anaerobic, mainly parasitic cocci; characteristics suggested as indices of enterotoxigenicity are discussed. The coagulase test is the most widely used of these indices; but, production of hemolysin, phosphatase, urease, deoxyribonuclease, and protein A; hydrolysis of gelatin; pigmentation; and mannitol fermentation also have been suggested. Virtually all selective and diiferential media used to isolate staphylococci, which include those employing tellurite, egg yolk, pyruvate, glycine, fibrinogen, sodium chloride, mannitol, polymyxin and sodium azide are somewhat inhibitory to growth of these organisms. Some studies are cited which compare the relative recovery efficiencies of these media. Staphylococcal food poisoning is strictly an intoxication which is caused by a water-soluble protein called enterotoxin that is secreted by staphylococcal cells, i. e. an exotoxin. After a general discussion of the properties of the enterotoxins, methods and media employed for producing high toxin yields are detailed. Mechanisms whereby these toxins are secreted differ in that enterotoxin A behaves as a primary metabolite and enterotoxin B acts as a secondary metabolite. Some explanations for the synthesis of enterotoxins are presented. Assay methods for these toxins that are discussed include bioassay techniques and serological procedures. Finally, some general aspects of the epidemiology of staphylococcal intoxications are described and some outbreaks of staphylococcal food poisoning are discussed.
Extracting knowledge from expert systems

Our understanding of how to use large amounts of knowledge to enhance the problem solving capabilities of computer programs is quite limited. Over the past several years a number of knowledge based systems have been developed, and this experience has provided us with a handfull of techniques we can apply in a few domains. What we don't have yet is much of an appreciation of why these techniques work or of the limits of their usefulness In order to take this next step, we need more data. Unfoitunately, the analyses of the expert systems currently being built tend to ignore questions that could provide precisely the data needed. This paper proposes a few questions that it might be worth asking and shows how answers to those questions could begin to give us the understanding we lack.
Metallosis in a Dog as a Long-Term Complication Following Total Hip Arthroplasty.

Metallosis is the accumulation of metallic debris in soft tissues resulting from wear following total joint replacement. A dog was evaluated for lameness 4 years after total hip arthroplasty using ...
Larrea tridentata : A novel source for anti-parasitic agents active against Entamoeba histolytica , Giardia lamblia and Naegleria fowleri

Protozoan parasites infect and kill millions of people worldwide every year, particularly in developing countries where access to clean fresh water is limited. Among the most common are intestinal parasites, including Giardia lamblia and Entamoeba histolytica. These parasites wreak havoc on the epithelium lining the small intestines (G. lamblia) and colon (E. histolytica) causing giardiasis and amebiasis, respectively. In addition, there are less common but far more deadly pathogens such as Naegleria fowleri that thrive in warm waters and infect the central nervous systems of their victims via the nasal passages. Despite their prevalence and associated high mortality rates, there remains an unmet need to identify more effective therapeutics for people infected with these opportunistic parasites. To address this unmet need, we have surveyed plants and traditional herbal medicines known throughout the world to identify novel antiparasitic agents with activity against G. lamblia, E. histolytica, and N. fowleri. Herein, we report Larrea tridentata, known as creosote bush, as a novel source for secondary metabolites that display antiparasitic activity against all three pathogens. This report also characterizes the lignan compound classes, nordihydroguairetic acid and demethoxyisoguaiacin, as novel antiparasitic lead agents to further develop more effective drug therapy options for millions of people worldwide.
Second‐hand clothing consumption: A generational cohort analysis of the Chinese market

China's rapidly growing economy and consumption are creating serious environmental problems in the country. The throwaway trend credited to fast fashion changes and short-lived styles made textiles and clothing a new body of solid wastes, resulting in a negative environmental consequence in China. While minimizing consumption of textiles and apparel cannot be the primary solution to environmental problems, it is important to enhance consumer awareness of the impact of their daily consumption on the environment and to promote environmentally sustainable apparel consumption and disposal behaviors. From a generational cohort perspective, this study aims to gain an insight of Chinese consumers' behaviors toward second-hand clothing, in terms of their consumption intentions and the influence of consumers' perceived values, perceived concerns, and descriptive norms on their purchase intentions. Data for this study were collected through a survey of 350 Chinese consumers across the four generational cohorts in China, including the Post-60s, Post-70s, Post-80s, and Post-90s. It was observed that Chinese consumers, in general, had a strong resistance toward second-hand clothing consumption, with the Post-70s having the strongest resistance. Significant differences were identified among the four cohorts. The younger generations perceived higher values and held higher purchase intentions than their older counterparts. Different motivations were also identified among the four cohorts in their second-hand clothing consumption. This article is protected by copyright. All rights reserved.
The HEXACO Model of Personality and Dark Triad In Relational Aggression

Abstract Relational aggression has been linked to many forms of psychological maladjustment. Identifying the personality traits associated with the perpetration of relational aggression offers promise in improving our ability to understand, prevent, and treat relationally aggressive behaviors. Much of the research to date has utilized the Five Factor Model; however, the HEXACO model of personality (Ashton et al., 2004) may offer some advantages in studying aggression. Moreover, the manipulative and often covert nature of relational aggression suggests that the Dark Triad personality traits are likely to be relevant. This study explored the utility of the HEXACO model and Dark Triad in predicting relational aggression in college students' (N = 442) peer relationships. Honesty-Humility, Agreeableness, Conscientiousness, and Openness predicted proactive and reactive relational aggression, and Emotionality also predicted reactive relational aggression. Pathological narcissism and psychopathy predicted proactive and reactive relational aggression while taking respondent gender and the full HEXACO model into account, with vulnerable narcissism and psychopathy serving as positive predictors and grandiose narcissism serving as a negative predictor. Findings support the utility of both the HEXACO and Dark Triad models in understanding peer relational aggression among emerging adults.
Recent Progress in the Pharmacotherapy of Alzheimer’s Disease

Alzheimer's disease is the most common major neurocognitive disorder with substantial social and economic impacts. This article is an update on current pharmacotherapy, advancements in biomarker use, and drugs in the pipeline for this disease. To date, no new drug has qualified to be added to the current therapeutic arsenal comprising cholinesterase inhibitors and the NMDA receptor antagonist memantine. Drugs in the pipeline include symptomatic therapies that are neurotransmitter-based, but mostly disease-modifying therapies. The latter have yielded disappointing results by focusing mainly on the two pathophysiological hallmarks of Alzheimer's disease: Aβ amyloid deposits and tau protein aggregates forming neurofibrillary tangles. These unsuccessful trials may have resulted from studying these drugs 'too late' relative to Alzheimer's disease onset, in addition to focusing only on the amyloid cascade. In fact, Alzheimer's disease is a complex multifactorial disease. Combining different biomarkers might enhance our ability to identify those patients most at risk of developing the disease, and better predict their conversion rates. Furthermore, adopting an integrative treatment approach by targeting additional pathophysiological pathways in Alzheimer's disease such as inflammation and oxidative stress could be the key to better outcomes in Alzheimer's disease pharmacotherapy research.
In Pursuit of Fellowship: Results From a 2016 Survey of US Trainees.

Abstract Purpose The purpose of this study was to gauge radiology trainee perceptions regarding the fellowship selection process and survey their perceived level of preparedness and desire for a fellowship-oriented lecture. Methods A survey, approved by Association of Program Coordinators in Radiology (APCR) was distributed via e-mail to all APCR members for distribution to their residents. Results A total of 98.6% (n = 261) of residents plan to pursue a fellowship. The most popular fellowships are interventional radiology, body, musculoskeletal, and Neuro. For fellowship information, residents believe that fellowship directors in their field of intent were the most reliable (76%), followed by fellows (65%). Only approximately 50% of residents felt somewhat strongly that they were preparing for their fellowship application correctly. Lastly, 44% of residents (n = 94) replied extremely likely to attend a lecture series given by fellowship directors, and 36% (n = 77) said somewhat likely. Conclusion This survey demonstrates that most trainees plan to pursue fellowship training. Residents ranked certain resources as more important in fellowship selection, such as fellowship directors and fellows. Lastly, there is a high interest in a lecture series that would bring together fellowship directors and residents that are interested in that particular fellowship.
Vote misreporting and black turnout studies in the U.S.

ABSTRACTVote misreporting is a major concern for studies of electoral participation. Concern over nonvoters in surveys who claim to vote is especially relevant for black turnout studies in the U.S....