bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different mechanisms for resistance to trastuzumab versus lapatinib in HER2- positive breast cancers - role of estrogen receptor and HER2 reactivation
Authors: Wang Yen-Chao , Morrison Gladys , Gillihan Ryan , Guo Jun , Ward Robin M , Fu Xiaoyong , Botero Maria F , Healy Nuala A , Hilsenbeck Susan G , Phillips Gail Lewis , Chamness Gary C , Rimawi Mothaffar F , Osborne C Kent , Schiff Rachel 
Published: November 2011

Abstract
Introduction
The human epidermal growth factor receptor 2 (HER2)-targeted therapies trastuzumab (T) and lapatinib (L) show high efficacy in patients with HER2-positive breast cancer, but resistance is prevalent. Here we investigate resistance mechanisms to each drug alone, or to their combination using a large panel of HER2-positive cell lines made resistant to these drugs.

Methods
Response to L + T treatment was characterized in a panel of 13 HER2-positive cell lines to identify lines that were de novo resistant. Acquired resistant lines were then established by long-term exposure to increasing drug concentrations. Levels and activity of HER2 and estrogen receptor (ER) pathways were determined by qRT-PCR, immunohistochemistry, and immunoblotting assays. Cell growth, proliferation, and apoptosis in parental cells and resistant derivatives were assessed in response to inhibition of HER or ER pathways, either pharmacologically (L, T, L + T, or fulvestrant) or by using siRNAs. Efficacy of combined endocrine and anti-HER2 therapies was studied in vivo using UACC-812 xenografts.

Results
ER or its downstream products increased in four out of the five ER+/HER2+ lines, and was evident in one of the two intrinsically resistant lines. In UACC-812 and BT474 parental and resistant derivatives, HER2 inhibition by T reactivated HER network activity to promote resistance. T-resistant lines remained sensitive to HER2 inhibition by either L or HER2 siRNA. With more complete HER2 blockade, resistance to L-containing regimens required the activation of a redundant survival pathway, ER, which was up-regulated and promoted survival via various Bcl2 family members. These L- and L + T-resistant lines were responsive to fulvestrant and to ER siRNA. However, after prolonged treatment with L, but not L + T, BT474 cells switched from depending on ER as a survival pathway, to relying again on the HER network (increased HER2, HER3, and receptor ligands) to overcome L's effects. The combination of endocrine and L + T HER2-targeted therapies achieved complete tumor regression and prevented development of resistance in UACC-812 xenografts.

Conclusions
Combined L + T treatment provides a more complete and stable inhibition of the HER network. With sustained HER2 inhibition, ER functions as a key escape/survival pathway in ER-positive/HER2-positive cells. Complete blockade of the HER network, together with ER inhibition, may provide optimal therapy in selected patients.
Molecular Detection of Tumor Cells in Regional Lymph Nodes Is Associated With Disease Recurrence and Poor Survival in Node-Negative Colorectal Cancer: A Systematic Review and Meta-Analysis
Authors: Rahbari Nuh N. , Bork Ulrich , Motschall Edith , Thorlund Kristian , Büchler Markus W. , Koch Moritz , Weitz Jürgen 
Published: November 2011

Purpose Up to 25% of patients with node-negative colorectal cancer (CRC) on conventional histopathologic analysis ultimately die of recurrent disease. We performed a systematic review with meta-analyses to clarify whether molecular detection of isolated tumor cells or micrometastases in regional lymph nodes indicates high risk of disease recurrence and poor survival in node-negative CRC. Methods The following databases were searched in August 2011 to identify studies on the prognostic significance of molecular tumor-cell detection in regional lymph nodes of node-negative CRC: MEDLINE, BIOSIS, Science Citation Index, EMBASE, CCMed, and publisher databases. We extracted hazard ratios (HRs) and associated 95% CIs from the identified studies and performed random-effects model meta-analyses on overall survival, disease-specific survival, and disease-free survival. Results A total of 39 studies with a cumulative sample size of 4,087 patients were included. Immunohistochemistry, reverse transcriptase polymerase chain reaction, and both techniques were applied in 30, seven, and two studies, respectively. Thirteen studies were graded with low risk of bias. Meta-analyses revealed that molecular tumor-cell detection in regional lymph nodes was associated with poor overall survival (HR, 2.20; 95% CI, 1.43 to 3.40), disease-specific survival (HR, 3.37; 95% CI, 2.31 to 4.93), and disease-free survival (HR, 2.24; 95% CI, 1.57-3.20). Subgroup analyses showed the prognostic significance of molecular tumor-cell detection of being independent of the applied detection method, molecular target, and number of retrieved lymph nodes. Conclusion Molecular detection of occult disease in regional lymph nodes is associated with an increased risk of disease recurrence and poor survival in patients with node-negative CRC.
Midlife and Aging Parents of Adults With Intellectual and Developmental Disabilities: Impacts of Lifelong Parenting
Authors: Seltzer Marsha Mailick , Floyd Frank , Song Jieun , Greenberg Jan , Hong Jinkuk 
Published: November 2011

Abstract
Using population data, this study included parents of individuals with intellectual and developmental disabilities (n  =  220) and parents of individuals without disabilities (n  =  1,042). Parents of individuals with intellectual and developmental disabilities were further divided into those who co-resided with their adult child and those whose adult child lived elsewhere, and the 3 groups were compared regarding parental patterns of attainment, social participation, psychological functioning, and health in midlife and early old age. In midlife, parents of individuals with intellectual and developmental disabilities were similar in general to comparison parents. However, by early old age, these parents had poorer health and mental health. Co-residence between the adult with intellectual and developmental disabilities and the parent was prevalent during midlife (51.4%) and in the early years of old age (38.6%), and there were different patterns of parental outcomes, depending on the residential status of the adult with intellectual and developmental disabilities.
Cyberbullying and adolescent mental health
Authors: Suzuki Keita , Asaga Reiko , Sourander Andre , Hoven Christina W. , Mandell Donald 
Published: November 2011

Abstract
The rapid growth of electronic and computer-based communication and information sharing during the past decade has dramatically changed social interactions, especially among teenagers. Cyberbullying has emerged as a new form of bullying and harassment, and it has been shown to possess different ramifications from traditional schoolyard bullying. This problem has emerged in nations worldwide. Cybervictims have reported various emotional and behavioral symptoms, along with school-related problems. This paper reviews international cross-sectional studies relating to the definition, prevalence, age, and gender differences inherent in cyberbullying. Psychosocial and risk factors associated with cyberbullying are also addressed. Prevention and intervention strategies for school officials and parents are suggested. Healthcare providers, policy makers, and families must be ever-mindful of the grave dangers cyberbullying poses to youths. Longitudinal studies are warranted to assess the psychological risk factors of cyberbullying.
Effect of maropitant, a neurokinin 1 receptor antagonist, on anesthetic requirements during noxious visceral stimulation of the ovary in dogs
Authors: Boscan Pedro , Monnet Eric , Mama Khursheed , Twedt David C. , Congdon Jonathan , Steffey Eugene P. 
Published: November 2011

Abstract
Objective—To determine the anesthetic-sparing effect of maropitant, a neurokinin 1 receptor antagonist, during noxious visceral stimulation of the ovary and ovarian ligament in dogs.
Animals—Eight 1-year-old female dogs.
Procedures—Dogs were anesthetized with sevoflurane. Following instrumentation and stabilization, the right ovary and ovarian ligament were accessed by use of laparoscopy. The ovary was stimulated with a traction force of 6.61 N. The minimum alveolar concentration (MAC) was determined before and after 2 doses of maropitant.
Results—The sevoflurane MAC value was 2.12 ± 0.4% during stimulation without treatment (control). Administration of maropitant (1 mg/kg, IV, followed by 30 μg/kg/h, IV) decreased the sevoflurane MAC to 1.61 ± 0.4% (24% decrease). A higher maropitant dose (5 mg/kg, IV, followed by 150 μg/kg/h, IV) decreased the MAC to 1.48 ± 0.4% (30% decrease).
Conclusions and Clinical Relevance—Maropitant decreased the anesthetic requirements during visceral stimulation of the ovary and ovarian ligament in dogs. Results suggest the potential role for neurokinin 1 receptor antagonists to manage ovarian and visceral pain.
Arthritogenic Self-Reactive CD4+ T Cells Acquire an FR4hiCD73hi Anergic State in the Presence of Foxp3+ Regulatory T Cells
Authors: Martinez Ryan J. , Zhang Na , Thomas Stephanie R. , Nandiwada Sarada L. , Jenkins Marc K. , Binstadt Bryce A. , Mueller Daniel L. 
Published: November 2011

AbstractRheumatoid arthritis develops in association with a defect in peripheral CD4+ T cell homeostasis. T cell lymphopenia has also been shown to be a barrier to CD4+ T cell clonal anergy induction. We therefore explored the relationship between clonal anergy induction and the avoidance of autoimmune arthritis by tracking the fate of glucose-6-phosphate isomerase (GPI)-reactive CD4+ T cells in the setting of selective T cell lymphopenia. CD4+ T cell recognition of self-GPI peptide/MHC class II complexes in normal murine hosts did not lead to arthritis and instead caused those T cells to develop a Folate receptor 4hiCD73hi anergic phenotype. In contrast, hosts selectively depleted of polyclonal Foxp3+CD4+ regulatory T cells could not make GPI-specific CD4+ T cells anergic and failed to control arthritis. This suggests that autoimmune arthritis develops in the setting of lymphopenia when Foxp3+CD4+ regulatory T cells are insufficient to functionally inactivate all autoreactive CD4+ T cells that encounter self-Ag.
An Antitumor Cellular Vaccine Based on a Mini-Membrane IgE
Authors: Nigro Elisa A. , Soprana Elisa , Brini Anna T. , Ambrosi Alessandro , Yenagi Vijay A. , Dombrowicz David , Siccardi Antonio G. , Vangelista Luca 
Published: November 2011

Abstract
The IgE-mediated immune system activation can be redirected to combat tumors. Mouse and human IgE have been shown to provide a potent adjuvant effect in antitumor vaccination, with a crucial role played by FcεRI. This effect results from T cell-mediated adaptive immune response. Modified vaccinia virus Ankara (MVA) has been used to infect IgE-loaded tumor cells. These results led to a shift toward a highly safe protocol employing membrane IgE (mIgE), thus eliminating any possible anaphylactogenicity caused by circulating IgE. Evidence that human mIgE and a truncated version lacking IgE Fabs (tmIgE) bind and activate FcεRI has been fundamental and forms the core of this report. Human tmIgE has been engineered into a recombinant MVA (rMVA-tmIgE), and the expression of tmIgE and its transport to the surface of rMVA-tmIgE–infected cells has been detected by Western blot and cytofluorimetry, respectively. FcεRI activation by tmIgE has been confirmed by the release of β-hexosaminidase in a cell-to-cell contact assay using human FcεRI-transfected RBL-SX38 cells. The rMVA-tmIgE antitumor vaccination strategy has been investigated in FcεRIα−/− human FcεRIα+ mice, with results indicating a level of protection comparable to that obtained using soluble human IgE tumor cell loading. The rMVA-tmIgE vector represents a device that suits safe IgE-based antitumor vaccines, harboring the possibility to couple tmIgE with other gene insertions that might enhance the antitumor effect, thus bringing the field closer to the clinics.
Haemophilus influenzae Uses the Surface Protein E To Acquire Human Plasminogen and To Evade Innate Immunity
Authors: Barthel Diana , Singh Birendra , Riesbeck Kristian , Zipfel Peter F. 
Published: November 2011

Abstract
Pathogenic microbes acquire the human plasma protein plasminogen to their surface. In this article, we characterize binding of this important coagulation regulator to the respiratory pathogen nontypeable Haemophilus influenzae and identify the Haemophilus surface protein E (PE) as a new plasminogen-binding protein. Plasminogen binds dose dependently to intact bacteria and to purified PE. The plasminogen–PE interaction is mediated by lysine residues and is also affected by ionic strength. The H. influenzae PE knockout strain (nontypeable H. influenzae 3655Δpe) bound plasminogen with ∼65% lower intensity as compared with the wild-type, PE-expressing strain. In addition, PE expressed ectopically on the surface of Escherichia coli also bound plasminogen. Plasminogen, either attached to intact H. influenzae or bound to PE, was accessible for urokinase plasminogen activator. The converted active plasmin cleaved the synthetic substrate S-2251, and the natural substrates fibrinogen and C3b. Using synthetic peptides that cover the complete sequence of the PE protein, the major plasminogen-binding region was localized to a linear 28-aa-long N-terminal peptide, which represents aa 41–68. PE binds plasminogen and also vitronectin, and the two human plasma proteins compete for PE binding. Thus, PE is a major plasminogen-binding protein of the Gram-negative bacterium H. influenzae, and when converted to plasmin, PE-bound plasmin aids in immune evasion and contributes to bacterial virulence.
The Family in the Soviet System
Authors: Juviler Peter H. 
Published: November 2011

The Soviet Government after Khrushchev has confronted crucial issues of refonn in family law and family-oriented demographic policy. The central question of policy has been how "to hanoonize the interests of society" in a rcore stable arrl fertile family than now exists, with "the interests of the family" in freer marital and reproductive choice.
White Intelligence and Counter-Intelligence during the Russian Civil War
Authors: Bortnevski Viktor 
Published: November 2011

The activity of various intelligence and security institutions during the Russian Civil War is a complex and understudied topic. It is difficult to fmd any other period in modem Russian history before 1992, in which so many independent or autonomous authorities engaged in espionage and counter-intelligence. The Red and White Armies each organized and operated large counter-intelligence operations during the civil war. Yet the history of intelligence and counter-intelligence during the Russian Civil War has not yet been written. For many years, Soviet historians were not interested in presenting or allowed to present a balanced evaluation picture of such White activities. A favorite subject in novels and movies was the victory of honest and gentle "Chekists" over "White bandits," who never even came close to victory. Since the opening of the relevant archives, other issues and interests have taken priority causing this topic to remain under-researched.
Effective and Appropriate Communication with Children in Legal Proceedings According to Lawyers and Intermediaries
Authors: Krähenbühl Sarah 
Published: November 2011

Following the Government's commitment to improve protection for child witnesses in the Criminal Justice Act 1991, interviewing protocols have been developed to provide guidance on effective interviewing. Additionally, the Youth Justice and Criminal Evidence Act 1999 intermediary special measure was provided in order to facilitate communication between child witnesses and ‘interviewers’ during the entire legal process. This article presents findings from a study that aimed to establish whether, over a decade later, there is accordance between intermediaries and lawyers about perceptions of appropriate communication in the context of investigative interviews and cross‐examination of children. Participants (19 intermediaries and 12 lawyers) examined transcripts of a mock investigative interview and cross‐examination of a child and noted which, if any, questions or phrases they perceived to be inappropriate, to state what was inappropriate and to suggest how these could be amended. Qualitative analysis showed that both groups demonstrated awareness of the emotional and developmental needs of the child but there was a lack of understanding of some aspects of the interviewing guidance, particularly in respect to the definition of leading questions, the use of recommended question formats and procedural aspects. Copyright © 2011 John Wiley & Sons, Ltd.‘From a study that aimed to establish whether, over a decade later, there is accordance between intermediaries and lawyers’
Highly Enantioselective Lewis Base Organocatalyzed Hydrosilylation of γ‐Imino Esters
Authors: Xue Zhou‐Yang , Liu Li‐Xin , Jiang Yan , Yuan Wei‐Cheng , Zhang Xiao‐Mei 
Published: November 2011

AbstractHighly enantioselective hydrosilylation of γ‐imino esters with trichlorosilane promoted by a chiral Lewis base proceeded smoothly to provide various optically active γ‐amino esters in good yields (up to 96 %) with excellent enantioselectivities (up to 99 % ee) at –10 °C in Cl2CHCHCl2. The side reactions were successfully reduced by rational modification of the substrate. The absolute configuration of one of the γ‐amino esters was determined. Finally, two pharmaceutically interesting enantioenriched γ‐lactams were synthesized from two γ‐amino esters.
Built‐in field control in nitride nanostructures operating in the UV
Authors: Caro Miguel A. , Schulz Stefan , Healy Sorcha B. , O'Reilly Eoin P. 
Published: November 2011

AbstractIn this work we apply the concept of polarization‐matching to calculate the reduction of the built‐in field in nitride‐based nanostructures operating predominantly in the UV part of the spectrum. In order to realistically describe these systems, our calculations take into account strain limits set by the epitaxial growth of nitride structures as well as alloy miscibility problems.Complete polarization‐matching can be achieved around and beyond 3.4 eV in the case of quantum wells pseudo‐morphically grown on GaN. For lower band gap regions, we find that a complete suppression of the built‐in field is not possible due to the mentioned constraints. However, the choice of band gap bowing parameter for the AlInN alloy strongly influences the results, particularly in the case of quantum dots. The extent of this effect is studied in detail. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Experiments with different discretizations for the shallow‐water equations on a sphere
Authors: Qaddouri Abdessamad , Pudykiewicz Janusz , Tanguay Monique , Girard Claude , Côté Jean 
Published: November 2011

AbstractThree models with different discretizations for the shallow‐water equations on a sphere are presented and compared using selected test cases. The first model is based on the global latitude–longitude grid system with a uniform Arakawa C grid and a two‐time‐level Crank–Nicolson iterative semi‐Lagrangian method with an advecting wind interpolated in time. The second model uses the overset Yin–Yang grid, which is singularity‐free and has quasi‐uniform resolution. The local solver on each of the two component grids is based on the same time and space discretizations as in the first model. The positive‐definite Helmholtz problem in the second model is solved using an optimized Schwarz‐type domain‐decomposition method with specific Robin or higher‐order transmission conditions. The first and second models are obtained through the barotropic option incorporated into the Global Environmental Multiscale model used operationally at the Canadian Meteorological Center. The third model is discretized using the finite‐volume methodology on a geodesic icosahedral grid. The time integration is performed with a fourth‐order Runge–Kutta scheme. The tests employed to compare the three models are passive advection of a cosine bell, steady‐state geostrophic flow, flow over an idealized mountain, a Rossby–Haurwitz wave, real‐case 500 mb flow and evolution of a growing barotropic wave. When no analytic solution is available for a specific test, we compare the results with a high‐resolution solution obtained from the first model in which all horizontal operations are evaluated in spectral space. © 2011 Crown in the right of Canada. Published by JohnWiley & Sons Ltd.
Byzantine History and the Discourse of the Russian Political/Intellectual Underground
Authors: Shlapentokh Dmitry 
Published: November 2011

Historical subjects often seem to be unrelated to current political discourse still could be often politicized in present-day Russia. And Internet discussions on these historical subjects could well provide insight into the views of the various segments of the country's population. These Internet discussions become especially important sources when one tries to look into the minds of the Russian underground, those who have practically no legal outlet for presenting their views. For this reason, the movie The Death of the Byzantine Empire, shown in the very end of the Putin presidency, is especially important. The movie, created the Orthodox priest Tikhon Shevkunov, (presumably Putin's confessor) made clear references to contemporary Russia. In the view of the producer, the Byzantine Empire was strong when it followed its autocratic tradition and was attached to Orthodoxy. The movie generated extensive discussions, including among those who belong to Russia's political and intellectual fringe. Quite a few of them were neo-pagans; for them, Christianity, including Orthodox Christianity, was Russia's curse. For them, it was an Asian creed foreign to Aryan Russians. The fact that it was accepted by Russians implied that Russians had been subjugated by an alien, Asiatic, force. Many of these neo-pagans were quite pessimistic in regard to the country's future; and, indeed, their response indicates the deep alienation of quite a few Russians, which hardly bodes well for the country's future.
The Potter Petrecvs and his Connexions
Authors: Dannell G. B. 
Published: November 2011

The work of Petrecvs has been discussed by Déchelette and Oswald, both of whom ascribed it to the early Central Gaulish workshops at Lezoux.A bowl at Guildhall Museum, stamped by this potter and seen by Stanfield (fig. 2), clearly the work of a South Gaulish artist, came to the notice of Oswald too late for publication. However, his manuscript notes, on the basis of Stanfield's rubbings, leave no doubt that he realized that the vase recorded by Déchelette from Lezoux was not made at that site. L'Abbé Cérès noted the stamp PETR from La Graufesenque.
The Design of the Roman Mosaic at Hinton St. Mary
Authors: Painter K. S. 
Published: November 2011

SummaryTwo problems in the design of the Hinton St. Mary mosaic are (1) that the elements of the design are placed the wrong way round if the mosaic was planned to be seen like a carpet; and (2) whether the bust of Christ is an original design or whether it is based on a formal set of rules. There is evidence to suggest (1) that the design of the mosaic as a whole may have been conceived as the decoration of a ceiling, and (2) that rules to which the bust of Christ conforms were still in use in the eighteenth century in Byzantine church-painting, and that there is a genuine continuity between the two points in time.