bluuebunny/crossref_metadata_2025_split huggingface dataset:
The importance of mother–infant communication for social bond formation in mammals
Authors: OKABE Shota , NAGASAWA Miho , MOGI Kazutaka , KIKUSUI Takefumi 
Published: April 2012

ABSTRACTMother–infant bonding is a universal relationship of all mammalian species. Here, we describe the role of reciprocal communication between mother and infant in the formation of bonding for several mammalian species. Mother–infant bond formation is reinforced by various social cues or stimuli, including communicative signals, such as odor and vocalizations, or tactile stimuli. The mother also develops cross‐modal sensory recognition of the infant, during bond formation. Many studies have indicated that the oxytocin neural system plays a pivotal role in bond formation by the mother; however, the underlying neural mechanisms for infants have not yet been clarified. The comparative understanding of cognitive functions of mother and infants may help us understand the biological significance of mother–infant communication in mammalian species.
How does the Hubble sphere limit our view of the Universe?
Authors: Lewis Geraint F. , van Oirschot Pim 
Published: April 2012

ABSTRACT
It has recently been claimed that the Hubble sphere represents a previously unknown limit to our view of the universe, with light we detect today coming from a proper distance less than this ‘cosmic horizon’ at the present time. By considering the paths of light rays in several cosmologies, we show that this claim is not generally true. In particular, in cosmologies dominated by phantom energy (with an equation of state of ω &lt; −1) the proper distance to the Hubble sphere decreases, and light rays can cross it more than once in both directions; such behaviour further diminishes the claim that the Hubble sphere is a fundamental, but unrecognized, horizon in the universe.
Differentiated swine airway epithelial cell cultures for the investigation of influenza A virus infection and replication
Authors: Bateman Allen C. , Karasin Alexander I. , Olsen Christopher W. 
Published: April 2012

Please cite this paper as: Bateman et al. (2013) Differentiated swine airway epithelial cell cultures for the investigation of influenza A virus infection and replication. Influenza and Other Respiratory Viruses 7(2) 139–150.Background  Differentiated human airway epithelial cell cultures have been utilized to investigate cystic fibrosis, wound healing, and characteristics of viral infections. These cultures, grown at an air–liquid interface (ALI) in media with defined hormones and growth factors, recapitulate many aspects of the in vivo respiratory tract and allow for experimental studies at the cellular level.Objectives  To optimize growth conditions for differentiated swine airway epithelial cultures and to use these cultures to examine influenza virus infection and replication.Methods  Primary swine respiratory epithelial cells were grown at an air–liquid interface with varying amounts of retinoic acid and epidermal growth factor. Cells grown with optimized concentrations of these factors for 4 weeks differentiated into multilayer epithelial cell cultures resembling the lining of the swine respiratory tract. Influenza virus infection and replication were examined in these cultures.Results/Conclusions  Retinoic acid promoted ciliogenesis, whereas epidermal growth factor controlled the thickness of the pseudoepithelium. The optimal concentrations for differentiated swine cell cultures were 1·5 ng/ml epidermal growth factor and 100 nm retinoic acid. Influenza A viruses infected and productively replicated in these cultures in the absence of exogenous trypsin, suggesting that the cultures express a protease capable of activating influenza virus hemagglutinin. Differences in virus infection and replication characteristics found previously in pigs in vivo were recapitulated in the swine cultures. This system could be a useful tool for a range of applications, including investigating influenza virus species specificity, defining cell tropism of influenza viruses in the swine respiratory epithelium, and studying other swine respiratory diseases.
The value of repetitive sequences in chloroplast DNA for phylogeographic inference: A comment on Vachon & Freeland 2011
Authors: SALTONSTALL KRISTIN , LAMBERTINI CARLA 
Published: April 2012

AbstractIn a recent Technical Advance article, Vachon and Freeland (2011, Molecular Ecology Resources, 11, 279‐285.) evaluate the utility of repetitive and non‐repetitive variation in the chloroplast genome for phylogeographic inference, using variation in Phragmites australis as an example. While we agree that repetitive and nonrepetitive regions evolve at different rates and homoplasy can impact results, we disagree with the conclusion that repetitive regions are inappropriate for large‐scale phylogeographic studies. Here we describe limitations to the study dataset and analysis, and provide an alternative viewpoint on the utility of repetitive regions for phylogeographic studies.
Resveratrol Enhances the Antitumor Effects of Temozolomide in Glioblastoma via ROS‐dependent AMPK‐TSC‐mTOR Signaling Pathway
Authors: Yuan Yuan , Xue Xue , Guo Ruo‐Bing , Sun Xiu‐Lan , Hu Gang 
Published: April 2012

SUMMARY Background and purposeResveratrol has been regarded as a promising candidate for cancer prevention and treatment. The present study was to investigate the impact of resveratrol on the antitumor effects of temozolomide (TMZ), a standard treatment regiment of glioblastoma (GBM), in vitro and in vivo.Methods and resultsWe found that the combination of resveratrol and TMZ significantly resulted in G2/M cell cycle arrest by flow cytometry, triggered a robust increase in expression of astrocyte differentiation marker glial fibrillary acid protein (GFAP), downregulated the expression of matrix metalloproteinase‐9 (MMP‐9) by immunohistochemistry and western blot analysis as well as inhibited cell migration by scratch wound assay. Further study revealed that TMZ in combination with resveratrol remarkably increased reactive oxygen species (ROS) production, which serves as an upstream signal for AMP‐activated protein kinase (AMPK) activation. Subsequently, activated AMPK inhibited mTOR signaling and downregulated antiapoptosis protein Bcl‐2, which was contributed to the additive antiproliferation effects of combination treatment. In an orthotopic xenograft model of GBM, TMZ plus resveratrol treatment significantly reduced the volume of tumor, which was confirmed by decreased expression of Ki‐67, a marker of proliferation index.ConclusionsOur findings demonstrate for the first time that resveratrol can enhance TMZ‐mediated antitumor effects in GBM in vitro and in vivo, via ROS‐dependent AMPK‐TSC‐mTOR signaling pathway.
The Internationalization of Corporate R&D and the Automotive Industry R&D of East‐Central Europe
Authors: Pavlínek Petr 
Published: April 2012

abstractThis article examines the development of corporate research and development (R&D) in the automotive industry of East‐Central Europe (ECE) in the context of the internationalization of corporate R&D generally and the automotive industry R&D specifically. Driven by large inflows of foreign direct investment since the early 1990s, vehicle assembly and the production of automotive components grew significantly in ECE. In my study I investigated the extent to which these increases in production have also led to the development of automotive R&D as an example of a higher value‐added function of the automotive value chain. I conducted a more detailed analysis of Czech automotive R&D because of its prominent position in ECE. Despite modest growth, my analysis uncovered inherent weaknesses of automotive R&D in ECE and strong barriers to its future development related to its peripheral position in the European and global automotive production networks.
A sequential analysis of classroom discourse in Italian primary schools: The many faces of the IRF pattern
Authors: Molinari Luisa , Mameli Consuelo , Gnisci Augusto 
Published: April 2012

Background. A sequential analysis of classroom discourse is needed to investigate the conditions under which the triadic initiation‐response‐feedback (IRF) pattern may host different teaching orientations.Aim. The purpose of the study is twofold: first, to describe the characteristics of classroom discourse and, second, to identify and explore the different interactive sequences that can be captured with a sequential statistical analysis.Method. Twelve whole‐class activities were video recorded in three Italian primary schools. We observed classroom interaction as it occurs naturally on an everyday basis. In total, we collected 587 min of video recordings. Subsequently, 828 triadic IRF patterns were extracted from this material and analysed with the programme Generalized Sequential Query (GSEQ).Results. The results indicate that classroom discourse may unfold in different ways. In particular, we identified and described four types of sequences. Dialogic sequences were triggered by authentic questions, and continued through further relaunches. Monologic sequences were directed to fulfil the teachers' pre‐determined didactic purposes. Co‐constructive sequences fostered deduction, reasoning, and thinking. Scaffolding sequences helped and sustained children with difficulties.Conclusions. The application of sequential analyses allowed us to show that interactive sequences may account for a variety of meanings, thus making a significant contribution to the literature and research practice in classroom discourse.
TOWARD A HOLISTIC SIX-PERIOD RADICAL INNOVATION LIFE CYCLE MODEL
Authors: DISMUKES JOHN P. , BERS JOHN A. , SEKHAR JAI A. 
Published: April 2012

In-depth historical assessment of innovation over the past several hundred years shows that the incremental innovation and cost reduction emphasized in the late 20th century will prove inadequate and even counterproductive in the 21st century for achieving sustained, global competitive advantage requiring radical innovation. Accordingly, a comprehensive, holistic innovation life cycle model is needed.Ongoing research since the PICMET'07 Conference has confirmed this need for a viable model, and developed an Accelerated Radical Innovation (ARI) methodology as part of the life cycle framework for a viable model. A significant contribution of the ARI methodology has been to develop improved techniques for measuring and guiding innovation progress, based on focused assessment of 10 innovation attributes at each of the 10 ARI steps in the first two phases of a six-phase life cycle envisioned to describe any radical innovation life cycle.This paper first summarizes systematically the most prominent radical innovation approaches, including quantitative assessment of the dynamics of four major radical innovations over the past 100 years by retrospective application of the ARI theory and its associated four types of challenges and hurdles inherent in commercializing breakthrough innovations. It then proposes future research on a six-period innovation life cycle model as the basis for analysis of breakthrough innovations of all types.
An NQO1 Substrate with Potent Antitumor Activity That Selectively Kills by PARP1-Induced Programmed Necrosis
Authors: Huang Xiumei , Dong Ying , Bey Erik A. , Kilgore Jessica A. , Bair Joseph S. , Li Long-Shan , Patel Malina , Parkinson Elizabeth I. , Wang Yiguang , Williams Noelle S. , Gao Jinming , Hergenrother Paul J. , Boothman David A. 
Published: April 2012

Abstract
Agents, such as β-lapachone, that target the redox enzyme, NAD(P)H:quinone oxidoreductase 1 (NQO1), to induce programmed necrosis in solid tumors have shown great promise, but more potent tumor-selective compounds are needed. Here, we report that deoxynyboquinone kills a wide spectrum of cancer cells in an NQO1-dependent manner with greater potency than β-lapachone. Deoxynyboquinone lethality relies on NQO1-dependent futile redox cycling that consumes oxygen and generates extensive reactive oxygen species (ROS). Elevated ROS levels cause extensive DNA lesions, PARP1 hyperactivation, and severe NAD+/ATP depletion that stimulate Ca2+–dependent programmed necrosis, unique to this new class of NQO1 “bioactivated” drugs. Short-term exposure of NQO1+ cells to deoxynyboquinone was sufficient to trigger cell death, although genetically matched NQO1− cells were unaffected. Moreover, siRNA-mediated NQO1 or PARP1 knockdown spared NQO1+ cells from short-term lethality. Pretreatment of cells with BAPTA-AM (a cytosolic Ca2+ chelator) or catalase (enzymatic H2O2 scavenger) was sufficient to rescue deoxynyboquinone-induced lethality, as noted with β-lapachone. Investigations in vivo showed equivalent antitumor efficacy of deoxynyboquinone to β-lapachone, but at a 6-fold greater potency. PARP1 hyperactivation and dramatic ATP loss were noted in the tumor, but not in the associated normal lung tissue. Our findings offer preclinical proof-of-concept for deoxynyboquinone as a potent chemotherapeutic agent for treatment of a wide spectrum of therapeutically challenging solid tumors, such as pancreatic and lung cancers. Cancer Res; 72(12); 3038–47. ©2012 AACR.
STAT3 Inhibition Overcomes Temozolomide Resistance in Glioblastoma by Downregulating MGMT Expression
Authors: Kohsaka Shinji , Wang Lei , Yachi Kazuhiro , Mahabir Roshan , Narita Takuhito , Itoh Tamio , Tanino Mishie , Kimura Taichi , Nishihara Hiroshi , Tanaka Shinya 
Published: April 2012

Abstract
Glioblastoma multiforme (GBM) is one of the most aggressive human tumors with a poor prognosis. Current standard treatment includes chemotherapy with the DNA-alkylating agent temozolomide concomitant with surgical resection and/or irradiation. However, a number of cases are resistant to temozolomide-induced DNA damage due to elevated expression of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT). Here, we show that upregulation of both MGMT and STAT3 was accompanied with acquisition of temozolomide resistance in the GBM cell line U87. Inactivation of STAT3 by inhibitor or short hairpin RNA (shRNA) downregulated MGMT expression in GBM cell lines. MGMT upregulation was not observed by the treatment of interleukin (IL)-6 which is a strong activator of STAT3. Contrarily, forced expressed MGMT could be downregulated by STAT3 inhibitor which was partially rescued by the proteasome inhibitor, MG132, suggesting the STAT3-mediated posttranscriptional regulation of the protein levels of MGMT. Immunohistochemical analysis of 44 malignant glioma specimens showed significant positive correlation between expression levels of MGMT and phosphorylated STAT3 (p-STAT3; P &lt; 0.001, r = 0.58). Importantly, the levels of both MGMT and p-STAT3 were increased in the recurrence compared with the primary lesion in paired identical tumors of 12 cases. Finally, we showed that STAT3 inhibitor or STAT3 knockdown potentiated temozolomide efficacy in temozolomide-resistant GBM cell lines. Therefore, STAT3 inhibitor might be one of the candidate reagents for combination therapy with temozolomide for patients with temozolomide-resistant GBM. Mol Cancer Ther; 11(6); 1289–99. ©2012 AACR.
The Effect of Climate Change on the Variability of the Northern Hemisphere Stratospheric Polar Vortex
Authors: Mitchell Daniel M. , Osprey Scott M. , Gray Lesley J. , Butchart Neal , Hardiman Steven C. , Charlton-Perez Andrew J. , Watson Peter 
Published: April 2012

Abstract
With extreme variability of the Arctic polar vortex being a key link for stratosphere–troposphere influences, its evolution into the twenty-first century is important for projections of changing surface climate in response to greenhouse gases. Variability of the stratospheric vortex is examined using a state-of-the-art climate model and a suite of specifically developed vortex diagnostics. The model has a fully coupled ocean and a fully resolved stratosphere. Analysis of the standard stratospheric zonal mean wind diagnostic shows no significant increase over the twenty-first century in the number of major sudden stratospheric warmings (SSWs) from its historical value of 0.7 events per decade, although the monthly distribution of SSWs does vary, with events becoming more evenly dispersed throughout the winter. However, further analyses using geometric-based vortex diagnostics show that the vortex mean state becomes weaker, and the vortex centroid is climatologically more equatorward by up to 2.5°, especially during early winter. The results using these diagnostics not only characterize the vortex structure and evolution but also emphasize the need for vortex-centric diagnostics over zonally averaged measures. Finally, vortex variability is subdivided into wave-1 (displaced) and -2 (split) components, and it is implied that vortex displacement events increase in frequency under climate change, whereas little change is observed in splitting events.
Diagnostic Value of Only 18F‐fluorodeocyglucose Positron Emission Tomography/Computed Tomography–Positive Lymph Nodes in Head and Neck Squamous Cell Carcinoma
Authors: Lee Sang‐Hyuk , Huh Se‐Hyung , Jin Sung‐Min , Rho Young‐Soo , Yoon Dae‐Young , Park Chan‐Hee 
Published: April 2012

ObjectiveThe role of 18F‐fluorodeocyglucose positron emission tomography (PET)/computed tomography (CT) in only PET/CT–positive lymph nodes (LNs) is not well elucidated yet. This study was conducted to evaluate the diagnostic value of only PET/CT–positive LNs without correlating positive findings on conventional imaging modalities (CT, magnetic resonance imaging [MRI], and ultrasound [US]) in patients with head and neck squamous cell carcinoma (HNSCC).Study DesignCase series with chart review.SettingHallym University School of Medicine.Subjects and MethodsFrom January 2006 to September 2009, 114 patients with HNSCC who underwent CT, MRI, US, and PET/CT before definitive surgery with neck dissection were reviewed. All imaging tests were interpreted on imaging‐based nodal classification and were compared with histopathological findings.ResultsOnly PET/CT–positive LNs were found at 48 nodal levels in 33 patients. Thirteen of 48 (27%) nodal levels were true‐positive (TP), and 35 of 48 (73%) were false‐positive (FP). Fourteen nodal levels were included on N+ necks, and 34 were included on N0 necks. In N0 necks, the FP rate was significantly higher than the TP rate (28 vs 6, P =. 034). Eleven only PET/CT–positive nodal levels in 10 patients were found on the contralateral neck side, and FP was significantly more prevalent than TP (8 vs 3, P =. 041). No significant difference was observed for mean standardized uptake value and LN sizes between TP and FP.ConclusionOnly PET/CT–positive LNs can frequently be found and do not predict LN metastasis, because a high percentage of results were FP. Our results suggest that only PET/CT–positive LNs should be considered negative, especially in N0 and contralateral necks.
Modifying three-dimensional scaffolds from novel nanocomposite materials using dissolvable porogen particles for use in liver tissue engineering
Authors: Adwan Hussamuddin , Fuller Barry , Seldon Clare , Davidson Brian , Seifalian Alexander 
Published: April 2012

Background: Although hepatocytes have a remarkable regenerative power, the rapidity of acute liver failure makes liver transplantation the only definitive treatment. Attempts to incorporate engineered three-dimensional liver tissue in bioartificial liver devices or in implantable tissue constructs, to treat or bridge patients to self-recovery, were met with many challenges, amongst which is to find suitable polymeric matrices. We studied the feasibility of utilising nanocomposite polymers in three-dimensional scaffolds for hepatocytes. Materials and methods: Hepatocytes (HepG2) were seeded on a flat sheet and in three-dimensional scaffolds made of a nanocomposite polymer (Polyhedral Oligomeric Silsesquioxane [POSS]-modified polycaprolactone urea urethane) alone as well as with porogen particles, i.e. glucose, sodium bicarbonate and sodium chloride. The scaffold architecture, cell attachment and morphology were studied with scanning electron microscopy, and we assessed cell viability and functionality. Results: Cell attachment to the scaffolds was demonstrated. The scaffold made with glucose particles as porogen showed a narrower range of pore size with higher porosity and better inter-pore communications and seemed to encourage near normal cell morphology. There was a steady increase of albumin secretion throughout the experiment while the control (monolayer cell culture) showed a steep decrease after day 7. At the end of the experiment, there was no significant difference in viability and functionality between the scaffolds and the control. Conclusion: In this initial study, porogen particles were used to modify the scaffolds produced from the novel polymer. Although there was no significance against the control in functionality and viability, the demonstrable attachment on scanning electron microscopy suggest potential roles for this polymer and in particular for scaffolds made with glucose particles in liver tissue engineering.
EnzML: multi-label prediction of enzyme classes using InterPro signatures
Authors: De Ferrari Luna , Aitken Stuart , van Hemert Jano , Goryanin Igor 
Published: April 2012

Abstract

Background
Manual annotation of enzymatic functions cannot keep up with automatic genome sequencing. In this work we explore the capacity of InterPro sequence signatures to automatically predict enzymatic function.

Results
We present EnzML, a multi-label classification method that can efficiently account also for proteins with multiple enzymatic functions: 50,000 in UniProt. EnzML was evaluated using a standard set of 300,747 proteins for which the manually curated Swiss-Prot and KEGG databases have agreeing Enzyme Commission (EC) annotations. EnzML achieved more than 98% subset accuracy (exact match of all correct Enzyme Commission classes of a protein) for the entire dataset and between 87 and 97% subset accuracy in reannotating eight entire proteomes: human, mouse, rat, mouse-ear cress, fruit fly, the S. pombe yeast, the E. coli bacterium and the M. jannaschii archaebacterium. To understand the role played by the dataset size, we compared the cross-evaluation results of smaller datasets, either constructed at random or from specific taxonomic domains such as archaea, bacteria, fungi, invertebrates, plants and vertebrates. The results were confirmed even when the redundancy in the dataset was reduced using UniRef100, UniRef90 or UniRef50 clusters.

Conclusions
InterPro signatures are a compact and powerful attribute space for the prediction of enzymatic function. This representation makes multi-label machine learning feasible in reasonable time (30 minutes to train on 300,747 instances with 10,852 attributes and 2,201 class values) using the Mulan Binary Relevance Nearest Neighbours algorithm implementation (BR-kNN).