bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toca-1 is suppressed by p53 to limit breast cancer cell invasion and tumor metastasis
Authors: Chander Harish , Brien Colin D , Truesdell Peter , Watt Kathleen , Meens Jalna , Schick Colleen , Germain Doris , Craig Andrew WB 
Published: December 2014

Abstract
Introduction
Transducer of Cdc42-dependent actin assembly-1 (Toca-1) recruits actin regulatory proteins to invadopodia, and promotes breast tumor metastasis. Since metastatic breast tumors frequently harbor mutations in the tumor suppressor p53, we tested whether p53 regulates Toca-1 expression.

Methods
Normal mammary epithelial cells (HBL-100, MCF10A) and breast cancer cell lines expressing wild-type (WT) p53 (DU4475, MTLn3) were treated with camptothecin or Nutlin-3 to stabilize p53 to test effects on Toca-1 mRNA and protein levels. Chromatin immunoprecipitation (ChIP) assays were performed to identify p53 binding site in Toca-1 gene. Stable silencing of p53 and Toca-1 were performed in MTLn3 cells to test effects on invadopodia and cell invasion in vitro, and tumor metastasis in vivo.

Results
We observed that breast cancer cell lines with mutant p53 have high levels of Toca-1 compared to those with WT p53. Stabilization of WT p53 led to further reduction in Toca-1 mRNA and protein levels in normal breast epithelial cells and breast cancer cells. ChIP assays revealed p53 binding within intron 2 of toca1, and reduced histone acetylation within its promoter region upon p53 upregulation or activation. Stable silencing of WT p53 in MTLn3 cells led to increased extracellular matrix degradation and cell invasion compared to control cells. Interestingly, the combined silencing of p53 and Toca-1 led to a partial rescue of these effects of p53 silencing in vitro and reduced lung metastases in mice. In human breast tumors, Toca-1 levels were high in subtypes with frequent p53 mutations, and high Toca-1 transcript levels correlated with increased risk of relapse.

Conclusions
Based on these findings, we conclude that loss of p53 tumor suppressor function in breast cancers leads to upregulation of Toca-1, and results in enhanced risk of developing metastatic disease.
Prioritizing causal disease genes using unbiased genomic features
Authors: Deo Rahul C , Musso Gabriel , Tasan Murat , Tang Paul , Poon Annie , Yuan Christiana , Felix Janine F , Vasan Ramachandran S , Beroukhim Rameen , De Marco Teresa , Kwok Pui-Yan , MacRae Calum A , Roth Frederick P 
Published: December 2014

Abstract
Background
Cardiovascular disease (CVD) is the leading cause of death in the developed world. Human genetic studies, including genome-wide sequencing and SNP-array approaches, promise to reveal disease genes and mechanisms representing new therapeutic targets. In practice, however, identification of the actual genes contributing to disease pathogenesis has lagged behind identification of associated loci, thus limiting the clinical benefits.

Results
To aid in localizing causal genes, we develop a machine learning approach, Objective Prioritization for Enhanced Novelty (OPEN), which quantitatively prioritizes gene-disease associations based on a diverse group of genomic features. This approach uses only unbiased predictive features and thus is not hampered by a preference towards previously well-characterized genes. We demonstrate success in identifying genetic determinants for CVD-related traits, including cholesterol levels, blood pressure, and conduction system and cardiomyopathy phenotypes. Using OPEN, we prioritize genes, including FLNC, for association with increased left ventricular diameter, which is a defining feature of a prevalent cardiovascular disorder, dilated cardiomyopathy or DCM. Using a zebrafish model, we experimentally validate FLNC and identify a novel FLNC splice-site mutation in a patient with severe DCM.

Conclusion
Our approach stands to assist interpretation of large-scale genetic studies without compromising their fundamentally unbiased nature.
Thermogravimetric investigation of sol–gel microspheres doped with aqueous glycerol
Authors: Ciriminna Rosaria , Pantaleo Giuseppe , La Mattina Rosa , Pagliaro Mario 
Published: December 2014

Abstract

Background
Silica-based microspheres encapsulating aqueous glycerol are promising curing agents affording the formation of better one-component polyurethane foams, namely thermoset polymers cured by atmospheric moisture that are widely and increasingly utilized in the construction industry. The use of renewable, non toxic glycerol from biodiesel and oleochemicals industry to cure PU foams in place of traditionally employed oil-derived mono and diethylene glycols is both technically and environmentally beneficial. The higher amount of hydroxyl groups in glycerol compared to both mono- and diethylene glycol results in considerably lower percentage of free monomeric methylene diphenyl diisocyanate (MDI) and higher crosslinking density of the cured foam.

Results
We investigate by thermogravimetric analysis the nature and amount of the microencapsulated species in sol–gel silica and organosilica microspheres encapsulating aqueous glycerol. Along with a percentage of glycerol in weight up to 35%, the microspheres contain about 5 wt% water and 4 wt% entrapped surfactant.

Conclusions
The investigation shows the efficacy of the surfactant-assisted sol–gel microencapsulation aqueous glycerol in silica as well as in methyl-silica particles at least until 10% degree of methylation. The results are relevant to the practical development of functional materials that can be used to cure better and greener polyurethane foams largely employed as coatings, adhesives and sealants in many industrial sectors.
Rock properties of smectite- and ooze-rich claystones
Authors: Øygarden Bente , Løseth Helge , Njerve Sigurd 
Published: December 2014

Parameters measured by well logs define rock properties and seismic reflections at lithology interfaces. Parameters from standard embedding claystones are normally used when calculating the top sand amplitude variation with offset (AVO) response, but this might give erroneous results when the real claystone rock properties deviate from the standard. Using cuttings and high-quality wireline logs from well 34/8-A-33 H above the Visund field in the northern North Sea, we evaluated rock properties of the Pleistocene glaciomarine claystones, Lower Miocene and Upper Oligocene oozy claystones, Lower Oligocene and Eocene smectite-rich claystones, and two interbedded sands. Glaciomarine claystones fit best with the Greenberg-Castagna equation and have the highest measured velocities even though they are the shallowest buried sediments. Environmental scanning electron microscope analysis proves the Lower Miocene and Upper Oligocene claystones to be oozy. The amount of low-density oozy material causes significant shifts in the log curves and makes the ooze-rich claystones plot far off the trend given by the Greenberg-Castagna equation. We, therefore, developed a new equation for S-wave velocity prediction for ooze-rich claystones with average densities between [Formula: see text] and [Formula: see text]. The [Formula: see text] ratios increase with depth in the Lower Oligocene and Eocene claystones of the Hordaland Group, and we interpreted this to reflect a downward increase in the amount of smectite, which existence was proven by X-ray diffraction analysis. We modeled how the seismic response at the top of a sand changes with embedding claystone type, saturation fluid, and offset. In glaciomarine claystones, the top of a brine-saturated sand corresponds to a negative trough reflection, in ooze-rich claystones to a positive peak reflection, and in smectite-rich claystones the reflection amplitude is close to zero. The predicted AVO response of sands in oozy claystones is highly dependent on whether the measured or calculated S-wave velocity has been used in the modeling.
Using Mass Spectrometry to Detect, Differentiate, and Semiquantitate Closely Related Peptide Hormones in Complex Milieu: Measurement of IGF-II and Vesiculin
Authors: Lee Kate L. , Middleditch Martin J. , Williams Geoffrey M. , Brimble Margaret A. , Cooper Garth J. S. 
Published: December 2014

Abstract
The search for an islet β-cell growth factor has been a key objective in recent diabetes research, because the ability to regenerate and/or protect the functioning β-cell population in patients could result in a great advancement for diabetes treatment. IGF-I and IGF-II are known to play crucial roles in fetal growth and prenatal development, and there is growing evidence that IGF-II increases β-cell proliferation and survival in vitro and in vivo. A search for the source of IGF-II–like immunoreactivity in isolated β-cell secretory granules from the murine cell line βTC6-F7 revealed a novel 2-chain IGF-II–derived peptide, which we named vesiculin and which has been shown to be a full insulin agonist. Here, we present a liquid chromatography–tandem mass spectrometry method that enables selective detection and semiquantitation of the highly related IGF-II and vesiculin molecules. We have used this method to measure these 2 peptides in conditioned media from 2 β-cell lines, produced under increasing glucose concentrations. This technique detected both IGF-II and vesiculin in media conditioned by MIN6 and βTC6-F7 cells at levels in the range of 0 to 6 μM (total insulin, 80–450 μM) and revealed a glucose-stimulated increase in insulin, IGF-II, and vesiculin. IGF-II was detected in adult human and neonatal mouse serum in high levels, but vesiculin was not present. The methodology we present herein has utility for detecting and differentiating active peptides that are highly related and of low abundance.
Exposure of Female Macaques to Western-Style Diet With or Without Chronic T In Vivo Alters Secondary Follicle Function During Encapsulated 3-Dimensional Culture
Authors: Xu Jing , McGee Whitney K. , Bishop Cecily V. , Park Byung S. , Cameron Judy L. , Zelinski Mary B. , Stouffer Richard L. 
Published: December 2014

AbstractIncreased adiposity and hyperandrogenemia alter reproductive parameters in both animal models and women, but their effects on preantral follicles in the ovary remain unknown. We recently reported that Western-style diet (WSD) consumption over 1 year, with or without chronic exposure to elevated circulating T, increased the body fat percentage, elicited insulin resistance, suppressed estradiol and progesterone production, as well as altered the numbers, size, and dynamics of antral follicles in the ovary during the menstrual cycle in female macaques. Therefore, experiments were designed to compare the WSD and WSD+T effects to age-matched controls on the survival, growth, and function of isolated secondary follicles during 5 weeks of encapsulated 3-dimensional culture. Follicle survival significantly declined in the WSD and WSD+T groups compared with the control (CTRL) group. Although media progesterone levels were comparable among groups, androstenedione and estradiol levels were markedly reduced in the WSD and WSD+T groups compared with the CTRL group at week 5. Anti-Müllerian hormone levels peaked at week 3 and were lower in the WSD+T group compared with the WSD or CTRL group. Vascular endothelial growth factor levels also decreased at week 5 in the WSD+T group compared with the WSD or CTRL group. After human chorionic gonadotropin exposure, only antral follicles developed from the CTRL group yielded metaphase II oocytes. Thus, WSD with or without T exposure affects the cohort of secondary follicles in vivo, suppressing their subsequent survival, production of steroid hormones and local factors, as well as oocyte maturation in vitro.
Pituitary and Brain Dopamine D2 Receptors Regulate Liver Gene Sexual Dimorphism
Authors: Ramirez Maria Cecilia , Ornstein Ana Maria , Luque Guillermina Maria , Perez Millan Maria Ines , Garcia-Tornadu Isabel , Rubinstein Marcelo , Becu-Villalobos Damasia 
Published: December 2014

Abstract
Liver sexual gene dimorphism, which depends mainly on specific patterns of GH secretion, may underlie differential susceptibility to some liver diseases. Because GH and prolactin secretion are regulated by dopaminergic pathways, we studied the participation of brain and lactotrope dopamine 2 receptors (D2Rs) on liver gene sexual dimorphism, to explore a link between the brain and liver gene expression. We used global D2R knockout mice (Drd2−/−) and conducted a functional dissection strategy based on cell-specific Drd2 inactivation in neurons (neuroDrd2KO) or pituitary lactotropes. Disruption of neuronal D2Rs (which impaired the GH axis) decreased most of male or female-predominant class I liver genes and increased female–predominant class II genes in males, consistent with the positive (class I) or negative (class II) regulation of these genes by GH. Notably, sexual dimorphism was lost for class I and II genes in neuroDrd2KO mice. Disruption of lactotrope D2Rs did not modify class I or II genes in either sex, because GH axis was preserved. But surprisingly, 1 class II gene (Prlr) and female-predominant class I genes were markedly up-regulated in lacDrd2KO females, pointing to direct or indirect effects of prolactin in the regulation of selected female-predominant liver genes. This suggestion was strengthened in the hyperprolactinemic Drd2−/− female mouse, in which increased expression of the same 4 liver genes was observed, despite a decreased GH axis. We hereby demonstrate endocrine-mediated D2R actions on sexual dimorphic liver gene expression, which may be relevant during chronic dopaminergic medications in psychiatric disease.
Functions of Indirect Utterances and Interpretation in the Course of the English Language Studies
Authors: Shirokikh Anna 
Published: December 2014

The article looks upon communicative functions of utterances. In the author’s
point of view, rules of speech are dependent on the aim of communication,
situation of speech, communicants’ statuses, properties of speech
channel and supposition. These aspects of communication are reflected in
the context of English language studies. Using the theory of dictema and
factors of speech regulation as the basis for research the author analyses
indirect utterances in publicistic texts read at English language lessons.
Interpretation activities of students help to discover implicit properties of
the indirect utterances and notional components of texts. The aims of utterances
and communicative intention are seen as the basis of post suppositional
research in reading and listening of English language texts. The
author singles out the following functions of indirect utterances: linking and
compression of information, escalation of information, communicative emphasis,
expressing emotions and assessments, confirmation, imperative
function, starter in a conversation, informational and emphatic assertion
function, duality of opinion function and providing background knowledge.
Studies on Civilizational Variability of the Lexical Meaning of Words
Authors: Oganesyan Sergey 
Published: December 2014

The article is a case study showing how words and expressions
of Russian language bear the imprint of mental civilizations quite
remote from our day. It is also being tracked how these changed their lexical
meaning according to mentality peculiarities and lifestyle specifics of
people, which have a great impact on adequate perception of any verbal
information. And it is being proven that the civilizational mentality allows
for tracking and explanation not only of the retrospection of changes in the
lingual system, but of the development prospect of the whole language
as well.
The Strategy of Professional Training of Students-orientalists in West European Languages
Authors: Vorontsova M. , Klyukina E. 
Published: December 2014

The article dwells upon a strategy of professional training of students – Orientalists
in European languages, defines specifics of teaching a European
language to students-orientalists, as well as works out new approaches
meeting new requirements, new methodological aims and objectives. A new
educational complex, aiming at developing communication in all language
spheres, serves as an example of applying new strategies.
Interdisciplinary Research Context of the Pupils’ Ability to Multilingual Communication Forming in the Process of Schooling
Authors: Pershukova Oksana 
Published: December 2014

The article deals with multilingualism analysis as compound and multidimensional
phenomena, which is the subject of scientific interest a number of
disciplines of social, humanitarian and natural science areas. Special attention
is paid to clarify terms. Through the lens of research in different fields of
knowledge the author demonstrates the evolution of ideas about the ability
to multilingual communication forming in the process of schooling. A brief
review of innovative approaches to the formation of multilingualism is given.
The conclusion is made that availability of close contacts between several
scientific directions is a necessary component of multilingualism research
and the solution of practical problems of multilingual competence formation
in the educational process is possible if based on the findings of the
separate sciences and interdisciplinary approach application. An important
role is also played by the constant rethinking and interpretation of existing
in European countries language teaching experience. For multilingual
education as a fundamental method of artificial multilingualism forming is
characteristic an integrated approach, taking into account the knowledge,
skills and experience and, above all, a profound command of student’s native
language as the basis of thinking, and on this foundation the gradual
deepening and understanding the essence of linguistic phenomena, their
laws, inner connections, awareness of different systems of concepts existence,
through which it is possible to perceive the reality and mastering the
different ways of ideas design.
Standardization and the Effectiveness of Online Advertising
Authors: Goldfarb Avi , Tucker Catherine E. 
Published: December 2014

The technological transformation and automation of digital content delivery has revolutionized the media industry. Increased reliance on automation has also led to requirements for standardization of content-delivery formats. This paper examines how the memorability of banner advertising changed with the introduction of new standards regularizing its format. Using data from randomized field tests, we find evidence that for most ads, ad effectiveness falls as the use of standard formats rises. The decline is smaller when a standardized ad appears to be more original (such as ads created by an ad agency). Therefore, a likely explanation is that increased use of a standard format makes it harder for basic ads to distinguish themselves from their competition because the ad format commands less attention. This paper was accepted by Pradeep Chintagunta, marketing.
Measurement of microelectric potentials in a bioelectrically-active wound care device in the presence of bacteria
Authors: Park S.S. , Kim H. , Makin I.R.S. , Skiba J.B. , Izadjoo M.J. 
Published: December 2014

Objective: Wound healing is enhanced in the presence of an external electrical field. The purpose of this study was first to investigate whether microelectric potentials (EPs) can be generated when the innovative design of a silver (Ag)- and zinc (Zn)-printed wound care device was exposed to saline solution which is commonly used to clean wound sites; and second to measure the generated EPs while the device was exposed to bacterial culture suspensions to mimic infection. Method: An Ag/Zn-printed test specimen as a wound care device was designed to accommodate Ag and Zn half-cell potentials by alternatively printing them on a woven polyester material in a well-characterised dot matrix pattern. A well-calibrated high impedance EPs measuring system was used to measure any EPs generated. Ultrasensitive inductively coupled plasma analysis was performed to determine whether the device induced any increase in trace metals in rabbit blood following implantation for 2–4 weeks. Results: EPs were consistently generated under various conductive solutions at the levels of 120.4±26.3mV (average±standard deviation) on Ag dots and -506.5±76.3mV over Zn dots to form microcircuits with EPs of 626.7±86.3mV between the Ag and Zn metallic elements of the dressing. Interestingly, the patterns of EPs generated with stable polarities were consistent when the device was exposed to bacterial suspensions for mimicking wound infection. Implantation of the device did not cause any increase in Ag or Zn in rabbit blood. Conclusion: The Ag/Zn-printed wound device generated sustained EPs successfully in the presence of various conductive fluids without changing EPs including polarities. Consistently generated EPs at each battery couple with Ag/Zn-based wound device would restore disrupted physiologic bioelectric signals on wound sites, which could lead to improved wound healing. Declaration of interest: The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the US Department of the Army, the US Department of Defense, the Department of Veterans Affairs, or the Henry M. Jackson Foundation for Advancement of Military Medicine. The research was supported by the US Air Force medical support agency (AFMSA), office of the Air Force Surgeon General, USA.
Communicational efforts for the construction of relationships in contemporary society: mediations and technology
Authors: Guedes Éllida Neiva , Silva Marcelo da , Santos Protásio Cézar dos 
Published: December 2014

This article aims to discuss the necessary alignment of communication efforts to build longlasting relationships between a organization and it public facing the ephemerality of the contemporary society. It begins with the historical and conceptual evolution of Public Relations activity, highlighting, afterwards, the social and technological context in which we live, which features lead to a discussion about the integration of professionals’ skills from various fields of communication. Such integration enhances the construction of relational process, since it is an absolute necessity that translates changes and challenges over which we shed light with this article.
The urban landscape and fashion advertising: the case of the DKNY brand
Authors: Pires Helena 
Published: December 2014

Investment in strategic communication, and especially in advertising, in the fash- ion design industry remains a prerequisite for promoting the brand value. The effectiveness of brand visibility and awareness depends mostly on advertising, both in the context of fash- ion magazines and the new media, and in the context of the outdoors medium, which is si- multaneously one of the most traditional and modern means of mass communication. This paper aims to analyse and discuss both dimensions. Firstly, it aims to provide an un- derstanding of how the urban landscape is built into fashion advertising, and especially to investigate the extent to which the collective imagination contributes to that process. This research therefore seeks to identify the main landscape referents represented and search for the respective association with various cultural and artistic universes, such as literature, pho- tography or cinema. Underlying this critical reflection is an understanding that landscape is not just a simple decor, but conversely an extremely important visual and discursive re- source for the advertising message. Secondly, this paper attempts to challenge the implica- tions of fashion brands outdoor advertising specifically in relation to the urban landscape and to the everyday life experience. Therefore, it is also an important aim of this article to dis- cuss outdoor advertising within the scope of the more recent cultural and aesthetic trends. In order to achieve the stated objectives and engage in a scientific discussion of the topic, the case of the fashion brand Donna Karan New York – DKNY was selected, as it is considered to be paradigmatic of the main operational principles and hypotheses researched.