bluuebunny/crossref_metadata_2025_split huggingface dataset:
Y-box Binding Protein-1 Contributes to Both HER2/ErbB2 Expression and Lapatinib Sensitivity in Human Gastric Cancer Cells
Authors: Shibata Tomohiro , Kan Hitoshi , Murakami Yuichi , Ureshino Hiroki , Watari Kosuke , Kawahara Akihiko , Kage Masayoshi , Hattori Satoshi , Ono Mayumi , Kuwano Michihiko 
Published: February 2013

AbstractGene amplification of HER2/ErbB2 occurs in gastric cancer and the therapeutic efficacy of the HER2-targeted antibody, trastuzumab, has recently been improved against HER2-positive advanced stomach cancer. Here, we examined whether Y-box-binding protein-1 (YB-1) could selectively control HER2 gene expression and cellular sensitivity to EGF receptor (EGFR) family protein-targeted drugs in human gastric cancer cells. HER2 expression was specifically downregulated by YB-1 silencing using its cognate siRNA, whereas there was less change in the expression of EGFR and HER3. A chromatin immunoprecipitation assay revealed the specific binding of YB-1 to its consensus sequence on the 5′-regulatory region of HER2. YB-1 knockdown induced drug resistance to lapatinib, a dual EGFR and HER2 kinase inhibitor, and also to erlotinib, an EGFR kinase inhibitor. Moreover, phosphorylation of protein kinase B (Akt) was not markedly affected by lapatinib or erlotinib when YB-1 was silenced. Nuclear YB-1 expression was significantly (P = 0.026) associated with HER2 expression, but not with EGFR or HER3, in patients with gastric cancer (n = 111). The YB-1-HER2 axis may therefore be useful for the further development of personalized therapeutics against gastric cancer by HER2-targeted drugs. Mol Cancer Ther; 12(5); 737–46. ©2013 AACR.
The Role of Estrogen Receptor β in Transplacental Cancer Prevention by Indole-3-Carbinol
Authors: Benninghoff Abby D. , Williams David E. 
Published: February 2013

AbstractIn the present study, the efficacy of indole-3-carbinol (I3C), a key bioactive component of cruciferous vegetables, for prevention of cancer in offspring exposed in utero to the environmental carcinogen dibenzo[def,p]chrysene (DBC) was evaluated using an estrogen receptor β (ERβ) knockout mouse model. I3C was provided either through the maternal diet coincident with carcinogen exposure during pregnancy or directly to offspring postinitiation with DBC. I3C was effective at reducing T-cell acute lymphoblastic lymphoma/leukemia (T-ALL)–related mortality in offspring only if provided via the maternal diet, although a gender difference in the role of ERβ in mediating this response was evident. In female offspring, chemoprevention of T-ALL by maternal dietary I3C required expression of ERβ; survival in Esr2 wild-type and heterozygous female offspring was more than 90% compared with 66% in Esr2 null females. Alternatively, ERβ status did not significantly impact the transplacental chemoprevention by I3C in males. The possible role of ERβ in mediating lung carcinogenesis or chemoprevention by I3C was similarly complicated. Lung tumor incidence was unaltered by either dietary intervention, whereas lung tumor multiplicity was substantially reduced in Esr2 null females on the control diet and marginally lower in Esr2 null males exposed to I3C via the maternal diet compared with their wild-type and heterozygous counterparts. These findings suggest that I3C may act via ERβ to prevent or suppress DBC-initiated transplacental carcinogenesis but that the involvement of this receptor seems to differ depending on the cancer type and gender of the offspring. Cancer Prev Res; 6(4); 339–48. ©2013 AACR.
Chemoprevention Activity of Dipyridamole in the MMTV-PyMT Transgenic Mouse Model of Breast Cancer
Authors: Wang Chunmei , Schwab Luciana P. , Fan Meiyun , Seagroves Tiffany N. , Buolamwini John K. 
Published: February 2013

AbstractDipyridamole (DPM) is widely used to prevent strokes and vascular thrombosis. Combination therapy of DPM and antimetabolites has shown synergistic anticancer activity. This study investigated the chemopreventive effects of DPM in the mouse mammary tumor virus promoter-driven polyoma middle T oncoprotein metastatic breast cancer model. We also investigated the effects of DPM on gene and miRNA expression. Chemopreventive activity was assessed by comparing the time to onset of palpable lesions, primary tumor growth kinetics, and the number of lung metastases in transgenic mice treated with DPM or vehicle. Gene expression and miRNA expression profiles of mammary tumor tissues were then analyzed using the Affymetrix GeneChip or miRNA 2.0 arrays. Real-time quantitative PCR was used to confirm changes in gene expression. Treatment with DPM beginning at the age of 4 weeks delayed the onset of palpable lesions, delayed tumor progression, and suppressed lung metastasis. Microarray gene expression analysis identified 253 genes differentially expressed between DPM-treated and control mammary tumors. miRNA expression analysis revealed that 53 miRNAs were altered by DPM treatment. The results indicate that DPM has chemoprevention activity against breast cancer tumorigenesis and metastasis in mice. The array analyses provide insights into potential mechanisms of DPM's chemopreventive effects, involving upregulation of several genes and miRNAs known to suppress cancer growth and/or metastasis and downregulation of genes known to promote cancer. Some of these genes have not been previously studied in breast cancer and may serve as novel molecular targets for breast cancer chemoprevention. Cancer Prev Res; 6(5); 437–47. ©2013 AACR.
Prognostic value of post-procedural aPTT in patients with ST-elevation myocardial infarction treated with primary PCI
Authors: Kikkert Wouter J. , van Nes Sophie H. , Lieve Krystien V. V. , Dangas George D. , van Straalen Jan , Vis Marije M. , Baan Jan , Koch Karel T. , de Winter Robbert J. , Piek Jan J. , Tijssen Jan G. P. , Henriques Jose P. 
Published: February 2013

SummaryUnfractionated heparin is the most commonly used anticoagulant in ST-elevation myocardial infarction (STEMI) and its effect can be monitored with activated partial thromboplastin time (aPTT). However, the optimal aPTT range during heparin therapy after primary percutaneous coronary intervention (PCI) is yet to be defined. A mean aPTT was calculated of all aPTT measurements in the first 24 hours after pPCI in a total of 1,876 STEMI patients. Mean aPTT measurements were stratified into four categories; < 1.5 times the upper limit of normal (ULN), 1.5 – 2.0 times ULN (the therapeutic group), 2.01 – 3.99 times ULN, and ≥ 4 times ULN. Compared to patients with a therapeutic aPTT, patients with aPTTs < 1.5 times ULN had no increase in recurrent ischaemic events and had similar rates of bleeding complications. Patients with a mean aPTT ≥ 4 times ULN had higher rates recurrent ischaemic and haemorrhagic complications. After multivariable analyses, aPTT ratios ≥ 4 times ULN were no longer associated with recurrent ischaemic events, but remained a strong predictor of severe and moderate bleeding (hazard ratio [HR] 4.64, p = 0.016 and HR 2.27, p = 0.052). In conclusion, in 1,876 STEMI patients treated with pPCI, low aPTTs in the first 24 hours after PCI were not associated with an increase in ischaemic events, whereas high aPTT values were associated with more frequent bleeding complications. These results indicate no clear benefit as well as a safety concern with heparin treatment after primary PCI.
General mechanisms of coagulation and targets of anticoagulants (Section I)
Authors: Husted Steen , Wallentin Lars , Andreotti Felicita , Arnesen Harald , Bachmann Fedor , Baigent Colin , Huber Kurt , Jespersen Jørgen , Kristensen Steen , Lip Gregory Y. H. , Morais João , Rasmussen Lars , Siegbahn Agneta , Verheugt Freek W. A. , Weitz Jeffrey I. , De Caterina Raffaele 
Published: February 2013

SummaryContrary to previous models based on plasma, coagulation processes are currently believed to be mostly cell surface-based, including three overlapping phases: initiation, when tissue factor-expressing cells and microparticles are exposed to plasma; amplification, whereby small amounts of thrombin induce platelet activation and aggregation, and promote activation of factors (F)V, FVIII and FXI on platelet surfaces; and propagation, in which the Xase (tenase) and prothrombinase complexes are formed, producing a burst of thrombin and the cleavage of fibrinogen to fibrin. Thrombin exerts a number of additional biological actions, including platelet activation, amplification and self-inhibition of coagulation, clot stabilisation and anti-fibrinolysis, in processes occurring in the proximity of vessel injury, tightly regulated by a series of inhibitory mechanisms. ″Classical″ anticoagulants, including heparin and vitamin K antagonists, typically target multiple coagulation steps. A number of new anticoagulants, already developed or under development, target specific steps in the process, inhibiting a single coagulation factor or mimicking natural coagulation inhibitors.
C2362F mutation gives rise to an ADAMTS13-resistant von Willebrand factor
Authors: Pontara Elena , Battiston Monica , Morpurgo Margherita , Cattini Maria , Casarin Elisabetta , Saga Giorgia , Daidone Viviana , De Marco Luigi , Casonato Alessandra 
Published: February 2013

Summaryvon Willebrand factor (VWF) multimers result from proteolysis by the metalloprotease ADAMTS13. Since C2362F-VWF features abnormally large multimers with their triplet oligomer structure replaced by a diffuse smear, we explored the susceptibility of C2362F-VWF to ADAMTS13. VWF-enriched blood samples, obtained by cryoethanol precipitation of plasma from a patient with von Willebrand disease (VWD) homozygous for the C2362F mutation and a normal subject, were submitted to cleavage by recombinant ADAMTS13 under static conditions in the presence of urea. C2362F-VWF proved completely ADAMTS13-resistant in vitro. At any concentration of recombinant ADAMTS13 (from 0.1 μM to 1 μM), there was no evidence of the abnormally large VWF multimers of C2362F-VWF disappearing, nor any increased representation of triplet multimer bands, unlike the situation seen in normal VWF. This is due partly to a defective ADAMTS13 binding to C2362F-VWF under static conditions, as seen in both the patient’s and recombinant mutated VWF proteins. These findings were associated with a significantly shorter than normal survival of C2362F-VWF after DDAVP, demonstrating that proteolysis and VWF survival may be independent phenomena. Our findings clearly demonstrate that the loss of cysteine 2362 makes VWF resistant to proteolysis by ADAMTS13, at least partly due to an impaired ADAMTS13 binding to VWF. This suggests that the B2 domain of VWF is involved in modulating ADAMTS13 binding to VWF and the consequent proteolytic process. The C2362F-VWF mutation also enables a new abnormality to be identified in the VWF-ADAMTS13 relationship, i.e. an ADAMTS13-resistant VWF.
Regulation of kallikrein-related peptidases in the skin – from physiology to diseases to therapeutic options
Authors: Fischer Jan , Meyer-Hoffert Ulf 
Published: February 2013

SummaryKallikrein-related peptidases (KLKs) constitute a family of 15 highly conserved serine proteases, which show a tissue-specific expression profile. This made them valuable tumour expression markers. It became evident that KLKs are involved in many physiological processes like semen liquefaction and skin desquamation. More recently, we have learnt that they are involved in many pathophysiological conditions and diseases making them promising target of therapeutic intervention. Therefore, regulation of KLKs raised the interest of numerous reports. Herein, we summarise the current knowledge on KLKs regulation with an emphasis on skin-relevant KLKs regulation processes. Regulation of KLKs takes place on the level of transcription, on protease activation and on protease inactivation. A variety of protease inhibitors has been described to interact with KLKs including the irreversible serine protease inhibitors (SERPINs) and the reversible serine protease inhibitors of Kazal-type (SPINKs). In an attempt to integrate current knowledge, we propose that KLK regulation has credentials as targets for therapeutic intervention.
Hemispheric Asymmetry in Perception: A Differential Encoding Account
Authors: Hsiao Janet H. , Cipollini Ben , Cottrell Garrison W. 
Published: February 2013

Abstract
Hemispheric asymmetry in the processing of local and global features has been argued to originate from differences in frequency filtering in the two hemispheres, with little neurophysiological support. Here we test the hypothesis that this asymmetry takes place at an encoding stage beyond the sensory level, due to asymmetries in anatomical connections within each hemisphere. We use two simple encoding networks with differential connection structures as models of differential encoding in the two hemispheres based on a hypothesized generalization of neuroanatomical evidence from the auditory modality to the visual modality: The connection structure between columns is more distal in the language areas of the left hemisphere and more local in the homotopic regions in the right hemisphere. We show that both processing differences and differential frequency filtering can arise naturally in this neurocomputational model with neuroanatomically inspired differences in connection structures within the two model hemispheres, suggesting that hemispheric asymmetry in the processing of local and global features may be due to hemispheric asymmetry in connection structure rather than in frequency tuning.
Coadaptive Aiding and Automation Enhance Operator Performance
Authors: Christensen James C. , Estepp Justin R. 
Published: February 2013

Objective: In this work, we expand on the theory of adaptive aiding by measuring the effectiveness of coadaptive aiding, wherein we explicitly allow for both system and user to adapt to each other. Background: Adaptive aiding driven by psycho- physiological monitoring has been demonstrated to be a highly effective means of controlling task allocation and system functioning. Psychophysiological monitoring is uniquely well suited for coadaptation, as malleable brain activity may be used as a continuous input to the adaptive system. Method: To establish the efficacy of the coadaptive system, physiological activation of adaptation was directly compared with manual activation or no activation of the same automation and cuing systems. We used interface adaptations and automation that are plausible for real-world operations, presented in the context of a multi–remotely piloted aircraft control simulation. Each participant completed 3 days of testing during 1 week. Performance was assessed via proportion of targets successfully engaged. Results: In the first 2 days of testing, there were no significant differences in performance between the conditions. However, in the third session, physiological adaptation produced the highest performance. Conclusion: By extending the data collection across multiple days, we offered enough time and repeated experience for user adaptation as well as online system adaptation, hence demonstrating coadaptive aiding. Application: The results of this work may be employed to implement more effective adaptive works-tations in a variety of work domains.
Magnetic resonance imaging outcomes from a phase III trial of teriflunomide
Authors: Wolinsky Jerry S , Narayana Ponnada A , Nelson Flavia , Datta Sushmita , O’Connor Paul , Confavreux Christian , Comi Giancarlo , Kappos Ludwig , Olsson Tomas P , Truffinet Philippe , Wang Lin , Miller Aaron , Freedman Mark S ,   for the Teriflunomide Multiple Sclerosis Oral (TEMSO) Trial Group
Published: February 2013

Objective: The purpose of this study was to determine the effects of oral teriflunomide on multiple sclerosis (MS) pathology inferred by magnetic resonance imaging (MRI). Methods: Patients ( n=1088) with relapsing MS were randomized to once-daily teriflunomide 7 mg or 14 mg, or placebo, for 108 weeks. MRI was recorded at baseline, 24, 48, 72 and 108 weeks. Annualized relapse rate and confirmed progression of disability (sustained ≥12 weeks) were the primary and key secondary outcomes. The principal MRI outcome was change in total lesion volume. Results: After 108 weeks, increase in total lesion volume was 67.4% ( p=0.0003) and 39.4% ( p=0.0317) lower in the 14 and 7 mg dose groups versus placebo. Other measures favoring teriflunomide were accumulated enhanced lesions, combined unique activity, T2-hyperintense and T1-hypointense component lesion volumes, white matter volume, and a composite MRI score; all were significant for teriflunomide 14 mg and most significant for 7 mg versus placebo. Conclusions: Teriflunomide provided benefits on brain MRI activity across multiple measures, with a dose effect evident on several markers. These effects were also consistent across selected subgroups of the study population. These findings complement clinical data showing significant teriflunomide-related reductions in relapse rate and disease progression, and demonstrate containment of MRI-defined disease progression.
Some results on parallel iterative algorithms for strictly pseudocontractive mappings
Authors: Yang Xiaoye , Qing Yuan , Zhang Mingliang 
Published: February 2013

Abstract
In this paper, a parallel iterative algorithm with mixed errors is investigated. Strong and weak convergence theorems of common fixed points of a finite family of strictly pseudocontractive mappings are established in a real Banach space.

AMS Subject Classification:47H05, 47H09, 47J25.
Collaborative routing and data delivery architecture for commercial wireless sensor networks
Authors: Hasani Bilal , Zafar Saima , Akbar Ali Hammad , Magsi Babar Ali 
Published: February 2013

Abstract
Lately, wireless sensor network applications have emerged for provision of commercial services to end users. This results in commercial deployment of sensor networks which is as an important research area due to a number of design and quality of service challenges. An important technical challenge for sensor service provision to end users is managing dynamic network conditions such as unreliability of sensor nodes and network links which results in frequent service outages. This research is aimed at addressing this challenge. It presents a novel architecture which utilizes the availability of multiple sensor networks under different administrative domains, deployed in an area such that maximum network connectivity and high service availability are ensured. The architecture incorporates modifications and enhancements at the medium access control and the routing layers of sensor nodes for the collaborative operation of sensor networks. The design is based on IEEE 802.15.4 standard and ad hoc on demand distance vector routing protocol. The proposed architecture is mathematically analyzed with regards to overheads associated with the design such as routing and communication, and techniques to minimize these overheads are recommended. Through simulations using OMNET++, we show that the proposed architecture effectively provides connectivity for disconnected nodes achieving an overall increase in throughput for all the cooperating networks.
Ethno-ornithology and conservation of wild birds in the semi-arid Caatinga of northeastern Brazil
Authors: Alves Rômulo Romeu Nóbrega , Leite Railson Cidennys Lourenço , Souto Wedson Medeiros Silva , Bezerra Dandara M M , Loures-Ribeiro Alan 
Published: February 2013

AbstractThe utilization of birds as pets has been recognized as one of the principal threats to global avifauna. Most of the information about the use and sale of birds as pets has been limited to areas of high biodiversity and whose impacts of anthropic actions have been widely broadcast internationally, for example for the Amazon Forest and forest remnants of Southeast Asia. The Caatinga predominates in the semi-arid region of Brazil, and is one of the semi-arid biomes with the greatest biological diversity in the world, where 511 species of birds exist. Many of these birds are used as pets, a common practice in the region, which has important conservationist implications but has been little studied. Therefore, the aim of the present study was to detail aspects of the use of birds as pets in a locality in the semi-arid region of Northeast Brazil. Information on the use of avifauna was obtained through interviews and visits to the homes of 78 wild bird keepers. A total of 41 species of birds were recorded, mostly of the families Emberizidae (n = 9 species), Columbidae (n = 7 species), Icteridae (n = 6 species) and Psittacidae (n = 3 species). The birds that were most often recorded wereParoaria dominicana(n = 79 especimens),Sporophila albogularis(n = 67),Aratinga cactorum(n = 49),Sporophila lineola(n = 36),Sicalis flaveola(n = 29) andSporophila nigricollis(n = 27). The use of wild birds in the area studied, as an example of what occurs in other places in the semi-arid Northeast, demonstrates that such activities persist in the region, in spite of being illegal, and have been happening in clandestine or semi-clandestine manner. No statistically significant correlation were found between socioeconomic factors and keeping birds as pets reflects the cultural importance of this practice of rearing wild birds for pets in the region, which is widespread among the local population, independent of socioeconomic factors. Obviously, human pressure on the avifauna exploited has ecological implications and makes it clear that conservationist measures should consider the cultural, economic and social aspects of these practices. These measures should be carried out by both directly combating the illegal traffic of animals and promoting educational campaigns aimed at all the players involved, from the collectors up to the consumer and wild bird keepers.
The many faces of HMGB1: molecular structure-functional activity in inflammation, apoptosis, and chemotaxis
Authors: Yang Huan , Antoine Daniel J , Andersson Ulf , Tracey Kevin J 
Published: February 2013

Abstract
Review of recent advances on post-translational modifications that determine the role of HMGB1 as a cytokine mediator.
HMGB1 is a ubiquitous nuclear protein present in almost all cell types. In addition to its intracellular functions, HMGB1 can be extracellularly released, where it mediates activation of innate immune responses, including chemotaxis and cytokine release. HMGB1 contains three conserved redox-sensitive cysteines (C23, C45, and C106); modification of these cysteines determines the bioactivity of extracellular HMGB1. Firstly, the cytokine-stimulating activity of HMGB1 requires C23 and C45 to be in a disulfide linkage, at the same time that C106 must remain in its reduced form as a thiol. This distinctive molecular conformation enables HMGB1 to bind and signal via the TLR4/MD-2 complex to induce cytokine release in macrophages. Secondly, for HMGB1 to act as a chemotactic mediator, all three cysteines must be in the reduced form. This all-thiol HMGB1 exerts its chemotactic activity to initiate inflammation by forming a heterocomplex with CXCL12; that complex binds exclusively to CXCR4 to initiate chemotaxis. Thirdly, binding of the HMGB1 to CXCR4 or to TLR4 is completely prevented by all-cysteine oxidation. Also, the initial post-translational redox modifications of HMGB1 are reversible processes, enabling HMGB1 to shift from acting as a chemotactic factor to acting as a cytokine and vice versa. Lastly, post-translational acetylation of key lysine residues within NLSs of HMGB1 affects HMGB1 to promote inflammation; hyperacetylation of HMGB1 shifts its equilibrium from a predominant nuclear location toward a cytosolic and subsequent extracellular presence. Hence, post-translational modifications of HMGB1 determine its role in inflammation and immunity.