bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fluorescent biosensors for high throughput screening of protein kinase inhibitors
Authors: Prével Camille , Pellerano Morgan , Van Thi Nhu Ngoc , Morris May C. 
Published: December 2013

AbstractHigh throughput screening assays aim to identify small molecules that interfere with protein function, activity, or conformation, which can serve as effective tools for chemical biology studies of targets involved in physiological processes or pathways of interest or disease models, as well as templates for development of therapeutics in medicinal chemistry. Fluorescent biosensors constitute attractive and powerful tools for drug discovery programs, from high throughput screening assays, to postscreen characterization of hits, optimization of lead compounds, and preclinical evaluation of candidate drugs. They provide a means of screening for inhibitors that selectively target enzymatic activity, conformation, and/or function in vitro. Moreover, fluorescent biosensors constitute useful tools for cell‐ and image‐based, multiplex and multiparametric, high‐content screening. Application of fluorescence‐based sensors to screen large and complex libraries of compounds in vitro, in cell‐based formats or whole organisms requires several levels of optimization to establish robust and reproducible assays. In this review, we describe the different fluorescent biosensor technologies which have been applied to high throughput screens, and discuss the prerequisite criteria underlying their successful application. Special emphasis is placed on protein kinase biosensors, since these enzymes constitute one of the most important classes of therapeutic targets in drug discovery.
Mucus trail tracking in a predatory snail: olfactory processing retooled to serve a novel sensory modality
Authors: Patel Kinjal , Shaheen Nagma , Witherspoon Jessica , Robinson Natallia , Harrington Melissa A. 
Published: December 2013

AbstractIntroductionThe rosy wolfsnail (Euglandina rosea), a predatory land snail, finds prey snails and potential mates by following their mucus trails. Euglandina have evolved unique, mobile lip extensions that detect mucus and aid in following trails. Currently, little is known of the neural substrates of the trail‐following behavior.MethodsTo investigate the neural correlates of trail following we used tract‐tracing experiments in which nerves were backfilled with either nickel‐lysine or Lucifer yellow, extracellular recording of spiking neurons in snail procerebra using a multielectrode array, and behavioral assays of trail following and movement toward the source of a conditioned odor.ResultsThe tract‐tracing experiments demonstrate that in Euglandina, the nerves carrying mucus signals innervate the same region of the central ganglia as the olfactory nerves, while the electrophysiology studies show that mucus stimulation of the sensory epithelium on the lip extensions alters the frequency and pattern of neural activity in the procerebrum in a manner similar to odor stimulation of the olfactory epithelium on the optic tentacles of another land snail species, Cantareus aspersa (previously known as Helix aspersa). While Euglandina learn to follow trails of novel chemicals that they contact with their lip extensions in one to three trials, these snails proved remarkably resistant to associative learning in the olfactory modality. Even after seven to nine pairings of odorant molecules with food, they showed no orientation toward the conditioned odor. This is in marked contrast to Cantareus snails, which reliably oriented toward conditioned odors after two to three trials.ConclusionsThe apparent inability of Euglandina to learn to associate food with odors and use odor cues to drive behavior suggests that the capability for sophisticated neural processing of nonvolatile mucus cues detected by the lip extensions has evolved at the expense of processing of odorant molecules detected by the olfactory system.
I'm buying, Jack! Fooling around an ambiguous brand
Authors: Brown Stephen 
Published: December 2013

ABSTRACTWithin consumer research, ambiguity is often regarded as something to be avoided or eliminated. This article argues that ambiguity should be embraced, appreciated and understood as a multifaceted phenomenon found in manifold forms. An empirical study of one of the world's biggest brands, RMSTitanic, reveals that one of ambiguity's most characteristic forms, humour, is everywhere apparent.Titanicbrand culture is comedic to the core, absurd though this seems on the surface. Three categories of ambiguous brand amusement are identified in the vast cultural complex surroundingTitanicand the oceanic implications for branding's received wisdom are considered. The article concludes with the contention that ambiguity strengthens rather than weakens unfathomable brands such asTitanic. Copyright © 2013 John Wiley & Sons, Ltd.
Analysis of Hospital Production: An Output Index Approach
Authors: Gaynor Martin S. , Kleiner Samuel A. , Vogt William B. 
Published: December 2013

SummaryIn this study, we develop and implement an output index approach to the estimation of hospital cost functions that reflects the differentiated nature of hospital care. The approach combines the estimation of an output index within a flexible functional form. We find, in an application to California hospitals, evidence of scope economies across specialties within primary care, and diseconomies of scope within secondary and tertiary care. Minimum efficient scale is reached at larger levels of output than would be estimated by conventional techniques. These results indicate the importance of accounting for firm output heterogeneity when estimating cost functions. Copyright © 2014 John Wiley & Sons, Ltd.
Fish Cholinesterases as Biomarkers of Sublethal Effects of Organophosphorus and Carbamates in Tissues of Labeo Rohita
Authors: Ghazala  , Mahboob Shahid , Ahmad L. , Sultana S. , AlGhanim K. , Al‐Misned F. , Ahmad Z. 
Published: December 2013

ABSTRACTOrganophosphates and carbamates are major agrochemicals that strongly affect different neuroenzymes and the growth of various fish species. Here, we study the effect of sublethal concentrations of profenofos and carbofuran on the activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) and the associated health risk in fish. Labeo rohita fingerlings were exposed to three sublethal concentrations of profenofos and carbofuran. The minimum cholinesterase activities in the brain, gills, muscle, kidney, liver, and blood were after exposure to profenofos (0.06 mg/L). The minimum AChE and BuChE activities in the brain, gills, muscle, kidney, liver, and blood were after exposure to carbofuran (0.28 and 0.198 mg/L). Exposure to both types of pesticides affected the functions of these organs, including metabolism and neurotransmission, to various extents at different exposure concentrations. These findings suggest that they are required to be properly monitored in the environment, to reduce their toxic effects on nontarget organisms
Heparan Sulfate Proteoglycans and Human Breast Cancer Epithelial Cell Tumorigenicity
Authors: Okolicsanyi Rachel K. , van Wijnen Andre J. , Cool Simon M. , Stein Gary S. , Griffiths Lyn R. , Haupt Larisa M. 
Published: December 2013

ABSTRACTHeparan sulfate proteoglycans (HSPGs) are key components of the extracellular matrix that mediate cell proliferation, invasion, and cellular signaling. The biological functions of HSPGs are linked to their co‐stimulatory effects on extracellular ligands (e.g., WNTs) and the resulting activation of transcription factors that control mammalian development but also associated with tumorigenesis. We examined the expression profile of HSPG core protein syndecans (SDC1–4) and glypicans (GPC1–6) along with the enzymes that initiate or modify their glycosaminoglycan chains in human breast cancer (HBC) epithelial cells. Gene expression in relation to cell proliferation was examined in the HBC cell lines MCF‐7 and MDA‐MB‐231 following treatment with the HS agonist heparin. Heparin increased gene expression of chain initiation and modification enzymes including EXT1 and NDST1, as well as core proteins SDC2 and GPC6. With HS/Wnt interactions established, we next investigated WNT pathway components and observed that increased proliferation of the more invasive MDA‐MB‐231 cells is associated with activation of the Wnt signaling pathway. Specifically, there was substantial upregulation (>5‐fold) of AXIN1, WNT4A, and MYC in MDA‐MB‐231 but not in MCF‐7 cells. The changes in gene expression observed for HSPG core proteins and related enzymes along with the associated Wnt signaling components suggest coordinated interactions. The influence of HSPGs on cellular proliferation and invasive potential of breast cancer epithelial cells are cell and niche specific. Further studies on the interactions between HSPGs and WNT ligands may yield clinically relevant molecular targets, as well as new biomarkers for characterization of breast cancer progression. J. Cell. Biochem. 115: 967–976, 2014. © 2013 Wiley Periodicals, Inc.
Estimating the Probability of Meeting Financial Commitments: A Behavioral Finance Perspective Based on Business Simulations
Authors: Conine Thomas E. 
Published: December 2013

AbstractIn an enterprise risk management environment, managers regularly can expect to be called upon to assess the probability that they will meet financial commitments. The ability to do so makes planning easier and enables the prudent risk taking that is crucial to driving growth. But even highly experienced managers are prone to overconfidence—one of the well‐known behavioral biases that can negatively affect their ability to form an accurate assessment. Estimating probability is, in fact, no simple task, and careers have been made and lost over met or missed commitments. Over the decades, a central theme of TRI Corporation's business simulations has been the issue of meeting commitments and managing risk. Now, a study of these simulations has shed light on the challenges inherent in the estimation process. Among the findings: Greater divergence in opinion among team members early in the estimating process can result in more accurate assessments, while divergence later in the process can weaken the team environment and lead to an inability to deliver on commitments. © 2014 Wiley Periodicals, Inc
Prevalence of cancer in Parkinson's disease related to R1441G and G2019S mutations in LRRK2
Authors: Ruiz‐Martínez Javier , de la Riva Patricia , Rodríguez‐Oroz Maria C. , Mondragón Rezola Elisabet , Bergareche Alberto , Gorostidi Ana , Gago Belen , Estanga Ainara , Larrañaga Nerea , Sarasqueta Cristina , López de Munain Adolfo , Martí Massó José F. 
Published: December 2013

ABSTRACTAn inverse relationship between Parkinson's disease (PD) and cancer has been described. However, the association between cancers and genetic forms of PD, in particular the R1441G mutation in the LRRK2 gene, is not well known. The objective of this work was to analyze cancer prevalence in PD patients with R1441G or G2019S mutations in LRRK2, and in idiopathic PD (iPD). A total of 732 patients with PD (70 and 25 carriers of R1441G or G2019S mutations, respectively), and 177 controls, were linked using a population‐based cancer registry of the Spanish province of Gipuzkoa. Cancer prevalence was not significantly higher in PD‐G2019S carriers (20%) than in PD‐R1441G carriers (14.3%), iPD (13.8%), or controls (12.5%). With the exception of a high prevalence of hematological cancers (crude odds ratio of 7.1) in the R1441G group, specific cancer types were not increased in PD mutation carriers. In both the carrier and iPD groups, cancers were diagnosed after the onset of PD. PD patients had a similar prevalence of cancer to control subjects. There was no increased association between G2019S or R1441G mutations and any type of cancer. Although there was a higher prevalence of hematological cancers in the R1441G group, the low number of such cancers overall makes this finding of uncertain significance. There was a slightly higher but not statistically significant prevalence of non‐skin cancers in the G2019S group, suggesting that further study to evaluate the association should be undertaken prior to ascribing an increased cancer risk to this population. © 2013 International Parkinson and Movement Disorder Society
Interaction proteome of human Hippo signaling: modular control of the co‐activator YAP1
Authors: Hauri Simon , Wepf Alexander , van Drogen Audrey , Varjosalo Markku , Tapon Nic , Aebersold Ruedi , Gstaiger Matthias 
Published: December 2013

AbstractTissue homeostasis is controlled by signaling systems that coordinate cell proliferation, cell growth and cell shape upon changes in the cellular environment. Deregulation of these processes is associated with human cancer and can occur at multiple levels of the underlying signaling systems. To gain an integrated view on signaling modules controlling tissue growth, we analyzed the interaction proteome of the human Hippo pathway, an established growth regulatory signaling system. The resulting high‐resolution network model of 480 protein‐protein interactions among 270 network components suggests participation of Hippo pathway components in three distinct modules that all converge on the transcriptional co‐activator YAP1. One of the modules corresponds to the canonical Hippo kinase cassette whereas the other two both contain Hippo components in complexes with cell polarity proteins. Quantitative proteomic data suggests that complex formation with cell polarity proteins is dynamic and depends on the integrity of cell‐cell contacts. Collectively, our systematic analysis greatly enhances our insights into the biochemical landscape underlying human Hippo signaling and emphasizes multifaceted roles of cell polarity complexes in Hippo‐mediated tissue growth control.
An improved return‐map stress update algorithm for finite deformation analysis of general isotropic elastoplastic geomaterials
Authors: Huang Junjie , Peng Qi , Chen Ming‐Xiang 
Published: December 2013

SUMMARYThis paper develops a novel return mapping algorithm for the numerical integration of general isotropic finite strain elastoplastic constitutive models for geomaterials. The constitutive formulation is founded on multiplicative decomposition of the deformation gradient. The logarithmic strain measure as well as the exponential approximation of the plastic flow rule is utilized to restore the standard infinitesimal format return mapping algorithm. Central to the algorithm is the exploitation of a set of three mutually orthogonal unit base tensors for the representation of constitutive relations and the corresponding integration of the rate form of the constitutive equations. The base tensors constitute a local cylindrical coordinate system in the principal space, which allows to formulate the return mapping algorithm in the three‐dimensional space and reduce the dimension of the problem to be analyzed from six down to three. With the proposed approach, direct determination of the principal axes and the transformation procedure between the general space and the principal space, as required in traditional spectral decomposition, are avoided. Furthermore, the matrices that are involved in the inversion evaluation take simple forms, leading to extremely easy inverse computation. As a result, the consistent tangent operator can be streamlined into a form simpler and more compact than those by conventional integration methods. Following the formulation of the integration procedure, a numerical experiment is performed to assess the accuracy and efficiency of the proposed algorithm. Copyright © 2014 John Wiley & Sons, Ltd.
Exploring Sources of Variation in Studies of Knowledge Structure Coherence: Comparing Force Meanings and Force Meaning Consistency Across Two Turkish Cities
Authors: CLARK DOUGLAS B. , MENEKSE MUHSIN , OZDEMIR GOKHAN , D'ANGELO CYNTHIA M. , PRICE SCHLEIGH SHARON 
Published: December 2013

ABSTRACTSubstantial variation has been observed across an international series of studies examining the consistency of students’ explanations of force and the most common meanings of force apparent in those explanations. On the surface, the variations among studies might be attributed to differences at the national level, but the studies also demonstrate differences among students from different schools in the United States. To what degree, therefore, can these variations be attributed to differences in educational systems as opposed to demographic differences or random variation? The current study compares student interviews across two cities in Turkey to provide insight into this question because Turkey, unlike the United States, has a strongly standardized national educational system. The results demonstrate no significant differences in students' consistency or meanings of force between cities. The results, however, demonstrate the expected differences across ages and majors, which suggest that the study has sufficient power. Thus, while differences have been observed between every city and country in the previous studies, and differences are observed in the current study in terms of grade level and academic majors, no differences are observed between the cities in Turkey. The implications of these findings are discussed in terms of ongoing conceptual change research.
Exploring mediating effect of metacognitive awareness on comprehension of science texts through structural equation modeling analysis
Authors: Wang Jing‐Ru , Chen Shin‐Feng 
Published: December 2013

AbstractThis study used a Chinese‐language version of the Index of Science Reading Awareness (ISRA) to investigate metacognitive awareness and the Reading Comprehension of Science Test (RCST) to explore comprehension of science text by Taiwanese students. Structural equation modeling (SEM) results confirmed the validity of the underlying models of metacognitive awareness and comprehension of science text. First, the Interactive‐Constructivist Model of Reading (ICMR) comprises three clusters of knowledge, in which the comprehension of science text was affected by metacognitive awareness and prior knowledge about language and science; second, the effect of prior knowledge on the RCST was mediated by metacognitive awareness of science reading. The implications of these findings for science curriculum aiming to activate students' prior knowledge and raise students' metacognitive awareness on science reading are discussed; as well, directions for future research are provided. © 2013 Wiley Periodicals, Inc. J Res Sci Teach 51: 175–191, 2014
Optimal risk assessment of small‐for‐gestational‐age fetuses using 31–34‐week biometry in a low‐risk population
Authors: Stirnemann J. J. , Benoist G. , Salomon L. J. , Bernard J.‐P. , Ville Y. 
Published: December 2013

ABSTRACTObjectiveTo compare the performance of traditional growth charts for estimated fetal weight (EFW) and a validated pragmatic probabilistic approach using biometry at 31–34 weeks' gestation to screen for late pregnancy small‐for‐gestational age (SGA) fetuses in a low‐risk population.MethodsRecords of ultrasound biometry at 31–34 weeks were reviewed in 7755 consecutive low‐risk women between 2002 and 2011. Fetal malformations, Doppler anomalies and preterm delivery before 37 weeks were excluded. SGA was defined by various percentile cut‐offs of birth weight. The probability of SGA was modeled as a function of Z‐scores of femur length, abdominal circumference and head circumference. The model was validated on a second independent dataset of 1725 pregnancies from a different screening unit. The screening performance of this probabilistic approach was compared with those of traditional EFW growth charts. The additional value of factoring in maternal characteristics was also ascertained.ResultsUsing national birth‐weight charts, the proportions of newborns at 37–42 weeks with birth weight < 3rd, < 5th and < 10th centiles were 3%, 6% and 12%, respectively, and there was a 2% rate of birth weight < 2500 g. For a 10% false‐positive rate, a direct probabilistic approach yielded a 51% detection rate of neonates with birth weight < 10th centile, compared to the 32% and 48% detection rates given by the 10th centile cut‐off of two reference charts for EFW. Adding maternal characteristics significantly improved detection rate by 2% to 53%.ConclusionsThe suggested validated approach to screening for late SGA fetuses outperforms traditional approaches using growth charts. By adding maternal characteristics, this screening method offers a favorable alternative to customized charts. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd
Transumbilical Single‐Incision Laparoscopic Distal Pancreatectomy: Primary Experience and Review of the English Literature
Authors: Yao Dianbo , Wu Shuodong , Tian Yu , Fan Ying , Kong Jing , Li Yongnan 
Published: December 2013

AbstractBackgroundSingle‐incision laparoscopic surgery (SILS) may represent an improvement over conventional laparoscopic surgery, and has been applied in many surgical procedures. However, for pancreatic surgery, experience is rather limited.MethodsThe clinical records of 11 cases in which transumbilical single‐incision laparoscopic distal pancreatectomy (TUSI‐LDP) was performed at our institution since June 2009 were retrospectively analyzed, and all the literatures concerning TUSI‐LDP were retrospectively reviewed.ResultsAll the 11 patients were female. The ages ranged from 20 to 73 years, with an average age of 38.0 years. The average body mass index (BMI) was 22.67 (18.6–26.2). Most TUSI‐LDPs were successfully performed, with only one conversion to multi‐incision surgery. Splenic preservation was performed in six cases. The mean operation time was 163.18 ± 63.18 minutes (range 95–300), and the mean intraoperative blood loss was 159.09 ± 181.02 ml (range 10–500 ml). The surgical wounds healed well, with good cosmetic wound healing, and the patients were discharged from hospital in a mean of 7.45 ± 1.44 days (range 5–10). Only one patient developed pancreatic leakage, which ceased spontaneously with only a drain for 61 days. The parameters were comparable with those found in the English literature.ConclusionsThese recent experiences suggest that SILS in pancreatic surgery is feasible for a select group of patients with relatively small lesions and low BMI, and that, with the gradual accumulation of surgeons’ experience with SILS and improvement of laparoscopic instruments, it might become a safe option for some patients.