bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peptide Aptamers with Binding Specificity for the Intracellular Domain of the ErbB2 Receptor Interfere with AKT Signaling and Sensitize Breast Cancer Cells to Taxol
Authors: Kunz Christian , Borghouts Corina , Buerger Claudia , Groner Bernd 
Published: December 2006

Abstract
The ErbB2 receptor tyrosine kinase is overexpressed in ∼30% of breast tumor cases and its overexpression correlates with an unfavorable prognosis. A major contributor for this course of the disease is the insensitivity of these tumors toward chemotherapy. Monoclonal antibodies, inhibiting the ligand-induced activation of the receptor and tyrosine kinase inhibitors acting on the intrinsic enzymatic activity of the intracellular domain, have been developed as targeted drugs. Both have been shown to be beneficial for breast cancer patients. We targeted a third aspect of receptor function: its association with intracellular signaling components. For this purpose, we selected peptide aptamers, which specifically interact with defined domains of the intracellular part of the receptor. The peptide aptamers were selected from a random peptide library using a yeast two-hybrid system with the intracellular tyrosine kinase domain of ErbB2 as a bait construct. The peptide aptamer AII-7 interacts with high specificity with the ErbB2 receptor in vitro and in vivo. The aptamers colocalized with the intracellular domain of ErbB2 within cells. We investigated the functional consequences of the aptamer interaction with the ErbB2 receptor within tumor cells. The aptamer sequences were either expressed intracellularly or introduced into the cells as recombinant aptamer proteins. The phosphorylation of p42/44 mitogen-activated protein kinase was nearly unaffected and the activation of signal transducers and activators of transcription-3 was only modestly reduced. In contrast, they strongly inhibited the induction of AKT kinase in MCF7 breast cancer cells treated with heregulin, whereas AKT activation downstream of insulin-like growth factor I or epidermal growth factor receptor was not or only slightly affected. High AKT activity is responsible for the enhanced resistance of ErbB2-overexpressing cancer cells toward chemotherapeutic agents. Peptide aptamer interference with AKT activation resulted in the restoration of regular sensitivity of breast cancer cells toward Taxol. (Mol Cancer Res 2006;4(12):983–98)
Use of an Aggressive MCF-7 Cell Line Variant, TMX2-28, to Study Cell Invasion in Breast Cancer
Authors: Gozgit Joseph M. , Pentecost Brian T. , Marconi Sharon A. , Otis Christopher N. , Wu Chuanyue , Arcaro Kathleen F. 
Published: December 2006

Abstract
An estrogen receptor–negative variant of the MCF-7 breast cancer cell line, TMX2-28, was used as a model in which to study breast cancer cell invasion. Using a reconstituted basement membrane (Matrigel) assay to evaluate cell invasion, we determined that TMX2-28 cells are more invasive than MCF-7 cells and that the invasiveness of TMX2-28 is similar to that of the aggressive MDA-MB-231 breast cancer cell line. TMX2-28 cells displayed a rounded, epithelial cell–like morphology, suggesting an amoeboid mode of cell invasion, in contrast to the mesenchymal mode of invasion characteristic of spindle-shaped, fibroblast-like MDA-MB-231 cells. Using real-time reverse transcription-PCR, we found that mitogen-inducible gene 2 (MIG2) is expressed at a 17-fold higher level in TMX2-28 cells than in nonaggressive MCF-7 cells and that MIG2 mRNA levels are low in the nontumorigenic human mammary epithelial cell line, 184. We determined that MIG2 plays a role in cell invasion by using small interfering RNA (siRNA) to suppress the expression of MIG2 mRNA levels in TMX2-28 cells. TMX2-28 cell invasion was reduced by 48% when the cells were transfected with siRNAs targeting MIG2, relative to cells transfected with siRNAs against glyceraldehyde-3-phosphate dehydrogenase. Finally, MIG2 expression was evaluated in reductive mammoplasty and breast tumor tissue. Although all 21 normal tissues from reduction mammoplasty showed immunoreactivity for MIG2, ranging from weak (62%) to strong (24%), only half of the 34 formalin-fixed breast tumors showed immunoreactivity for MIG2. Of these 17 positive cases, 10 were considered to overexpress MIG2 (moderate to strong staining). Examination of 30 frozen breast tumors supported the finding that MIG2 is overexpressed in a subset of breast cancers. We suggest that MIG2's normal regulation and function are disrupted in breast cancer. (Mol Cancer Res 2006;4(12):905–13)
Ubiquitin Hubs in Oncogenic Networks
Authors: Crosetto Nicola , Bienko Marzena , Dikic Ivan 
Published: December 2006

Abstract
Ubiquitin is an important regulator of diverse biological functions including cell cycle progression, apoptosis, cell proliferation, and DNA damage responses. Crucial proteins involved in the control of such diverse functions are modified by ubiquitin and are frequently altered during oncogenesis. Here, we define such proteins as key-nodes regulated by ubiquitin, discuss examples of their oncogenic aberrations, and indicate how pharmacologic manipulation of such molecular hubs might improve anticancer therapy. (Mol Cancer Res 2006;4(12):899–904)
CBFB-MYH11 hinders early T-cell development and induces massive cell death in the thymus
Authors: Zhao Ling , Cannons Jennifer L. , Anderson Stacie , Kirby Martha , Xu Liping , Castilla Lucio H. , Schwartzberg Pamela L. , Bosselut Rémy , Liu P. Paul 
Published: December 2006

AbstractRecent studies suggest that the chromosome 16 inversion, associated with acute myeloid leukemia M4Eo, takes place in hematopoietic stem cells. If this is the case, it is of interest to know the effects of the resulting fusion gene, CBFB-MYH11, on other lineages. Here we studied T-cell development in mice expressing Cbfb-MYH11 and compared them with mice compound-heterozygous for a Cbfb null and a hypomorphic GFP knock-in allele (Cbfb−/GFP), which had severe Cbfb deficiency. We found a differentiation block at the DN1 stage of thymocyte development in Cbfb-MYH11 knock-in chimeras. In a conditional knock-in model in which Cbfb-MYH11 expression was activated by Lck-Cre, there was a 10-fold reduction in thymocyte numbers in adult thymus, resulting mainly from impaired survival of CD4+CD8+ thymocytes. Although Cbfb-MYH11 derepressed CD4 expression efficiently in reporter assays, such derepression was less pronounced in vivo. On the other hand, CD4 expression was derepressed and thymocyte development was blocked at DN1 and DN2 stages in E17.5 Cbfb−/GFP thymus, with a 20-fold reduction of total thymocyte numbers. Our data suggest that Cbfb-MYH11 suppressed Cbfb in several stages of T-cell development and provide a mechanism for CBFB-MYH11 association with myeloid but not lymphoid leukemia.
Organ procurement organizations Internet enrollment for organ donation: Abandoning informed consent
Authors: Woien Sandra , Rady Mohamed Y , Verheijde Joseph L , McGregor Joan 
Published: December 2006

Abstract

Background
Requirements for organ donation after cardiac or imminent death have been introduced to address the transplantable organs shortage in the United States. Organ procurement organizations (OPOs) increasingly use the Internet for organ donation consent.

Methods
An analysis of OPO Web sites available to the public for enrollment and consent for organ donation. The Web sites and consent forms were examined for the minimal information recommended by the United States Department of Health and Human Services for informed consent. Content scores were calculated as percentages of data elements in four information categories: donor knowledge, donor consent reinforcement, donation promotion, and informed consent.

Results
There were 60 Web sites for organ donation enrollment serving the 52 states. The median percent (10 percentile-90 percentile) content scores of the Web sites for donor knowledge, donor consent reinforcement, and donation promotion were 33% (20–47), 79% (57–86), and 75% (50–100), respectively. The informed consent score was 0% (0–33). The content scores for donor knowledge and informed consent were significantly lower than donor consent reinforcement and donation promotion for all Web sites (P < .05). The content scores for the four categories were similar among the 11 regions of the United Network for Organ Sharing.

Conclusion
The Web sites and consent forms for public enrollment in organ donation do not fulfill the necessary requirements for informed consent. The Web sites predominantly provide positive reinforcement and promotional information rather than the transparent disclosure of organ donation process. Independent regulatory oversight is essential to ensure that Internet enrollment for organ donation complies with legal and ethical standards for informed consent.
Impact of Adjustment for Quality on Results of Metaanalyses of Diagnostic Accuracy
Authors: Leeflang Mariska , Reitsma Johannes , Scholten Rob , Rutjes Anne , Di Nisio Marcello , Deeks Jon , Bossuyt Patrick 
Published: December 2006

Abstract
Background: We examined whether and to what extent different strategies of defining and incorporating quality of included studies affect the results of metaanalyses of diagnostic accuracy.
Methods: We evaluated the methodological quality of 487 diagnostic-accuracy studies in 30 systematic reviews with the QUADAS (Quality Assessment of Diagnostic-Accuracy Studies) checklist. We applied 3 strategies that varied both in the definition of quality and in the statistical approach to incorporate the quality-assessment results into metaanalyses. We compared magnitudes of diagnostic odds ratios, widths of their confidence intervals, and changes in a hypothetical clinical decision between strategies.
Results: Following 2 definitions of quality, we concluded that only 70 or 72 of 487 studies were of “high quality”. This small number was partly due to poor reporting of quality items. None of the strategies for accounting for differences in quality led systematically to accuracy estimates that were less optimistic than ignoring quality in metaanalyses. Limiting the review to high-quality studies considerably reduced the number of studies in all reviews, with wider confidence intervals as a result. In 18 reviews, the quality adjustment would have resulted in a different decision about the usefulness of the test.
Conclusions: Although reporting the results of quality assessment of individual studies is necessary in systematic reviews, reader wariness is warranted regarding claims that differences in methodological quality have been accounted for. Obstacles for adjusting for quality in metaanalyses are poor reporting of design features and patient characteristics and the relatively low number of studies in most diagnostic reviews.
Novel Biosensor–Based Analytic Device for the Detection of Anti–Double-Stranded DNA Antibodies
Authors: Buhl Alexander , Metzger Jochen H , Heegaard Niels H H , von Landenberg Philipp , Fleck Martin , Luppa Peter B 
Published: December 2006

AbstractBackground: Patients with systemic lupus erythematosus (SLE) develop a wide variety of serologic manifestations, including double-stranded DNA autoantibodies (anti-dsDNA). The determination of the potentially pathogenic autoantibodies is diagnostically relevant.Methods: We developed a novel surface plasmon resonance (SPR) biosensor chip for studies of dsDNA and anti-dsDNA binding. A synthetic oligonucleotide was coupled to biotinylated human transferrin, hybridized with the complementary antistrand, and ligated with a human recombinant dsDNA fragment 233 bp in length. After surface immobilization of this antigenic construct, diluted sera from SLE patients and healthy donors were analyzed with the resulting SPR biosensor system.Results: This SPR biosensor allowed specific detection of anti-dsDNA. In pilot experiments, sera from SLE patients were distinguished from control sera. We also confirmed the specificity of this biosensor by supplementing anti-dsDNA–positive sera with salmon sperm DNA, which blocked the surface binding of anti-dsDNA in a concentration-dependent manner.Conclusions: An SPR biosensor monitors interactions in real time under homogeneous conditions, providing information about binding kinetics and affinities. Its applicability critically depends on the design of the solid-state surface of the sensor chips. Covalently immobilizing dsDNA as the antigen to the surface in a flow-through cell assured maximal stability for multiple serum injections and regeneration cycles. This technique, which adds a new analytic quality to existing methods, may be beneficial in the diagnosis and clinical monitoring of SLE.
Heterozygous parkin point mutations are as common in control subjects as in Parkinson's patients
Authors: Kay Denise M. , Moran Dawn , Moses Lina , Poorkaj Parvoneh , Zabetian Cyrus P. , Nutt John , Factor Stewart A. , Yu Chang‐En , Montimurro Jennifer S. , Keefe Robert G. , Schellenberg Gerard D. , Payami Haydeh 
Published: December 2006

AbstractObjectiveHomozygous or compound heterozygous parkin mutations cause juvenile parkinsonism. Heterozygous parkin mutations are also found in patients with typical Parkinson's disease (PD), but it is unclear whether a single “mutation” in a patient is related to disease or is coincidental, because the mutation frequency in control subjects is unknown. We present a comprehensive sequence analysis of parkin in control subjects.MethodsA total of 302 patients and 301 control subjects were sequenced, and findings were replicated in 1,260 additional patients and 1,657 control subjects.ResultsThirty‐four variants were detected, of which 21 were novel; 12 were polymorphisms and 22 were rare variants. Patients and control subjects did not differ in the frequency, type, or functional location of the variants. Even P437L, a common mutation thought to be pathogenic, was present in unaffected control subjects.Interpretationparkin point mutations are not exclusive to PD. The mere presence of a single point mutation in a patient, in the absence of a second mutation, should not be taken as a cause of disease unless corroborated by family data and functional studies. This study does not support the notion that heterozygous parkin sequence variants (mutations or polymorphisms) are risk factors for PD. Whether heterozygous dosage anomalies are associated with PD remains to be determined. Ann Neurol 2006
How to tweak a beak: molecular techniques for studying the evolution of size and shape in Darwin's finches and other birds
Authors: Schneider Richard A. 
Published: December 2006

AbstractA flurry of technological advances in molecular, cellular and developmental biology during the past decade has provided a clearer understanding of mechanisms underlying phenotypic diversification. Building upon such momentum, a recent paper tackles one of the foremost topics in evolution, that is the origin of species‐specific beak morphology in Darwin's finches.1 Previous work involving both domesticated and wild birds implicated a well‐known signaling pathway (i.e. bone morphogenetic proteins) and one population of progenitor cells in particular (i.e. cranial neural crest), as primary factors for establishing beak size and shape. But these results were limited in their ability to explain fully the morphogenetic bases of patterned outgrowth. So in a quest to identify novel genes whose expression correlated with differences in beak anatomy among Darwin's finches, a DNA microarray approach was undertaken using tissues harvested from the Galápagos Islands. The results are striking and point to a protein called calmodulin, which is a mediator of cellular calcium signaling, as a key determinant of beak length. BioEssays 29: 1–6, 2007. © 2006 Wiley Periodicals, Inc.
Application of Residence Time Distribution for Measuring the Fluid Velocity and Dispersion Coefficient
Authors: Zhang T. W. , Wang T. F. , Wang J. F. 
Published: December 2006

AbstractMost studies on residence time distribution (RTD) have focused on the tail of the RTD curve, and very little attention has been paid to the effect of white noise on the measured results. The aim of this work is to study the effect of white noise on the calculated parameters with different data processing methods. The anti‐disturbance abilities of the moment method and the least squares method are compared. The results show that the anti‐disturbance ability of the least squares method was better than that of the moment method. As a result of peak overlapping in the RTD curve of a loop reactor, the moment method cannot be used to calculate the fluid velocity and dispersion coefficient. Experiments show that the least squares method is still applicable in a loop reactor.
Thermodynamic Equilibrium Calculations for the Reforming of Coke Oven Gas with Gasification Gas
Authors: Li Y. B. , Xiao R. , Jin B. S. 
Published: December 2006

AbstractThermodynamic analyses of the reforming of coke oven gas with gasification gas for syngas were investigated as a function of coke oven gas‐to‐gasification gas ratio (1–3), oxygen‐to‐methane ratio (0–1.56), pressure (25–35 bar) and temperature (700–1100 °C). Thermodynamic equilibrium results indicate that the operating temperature should be approximately 1100 °C and the oxygen‐to‐methane ratio should be approximately 0.39, where about 80 % CH4and CO2can be converted at 30 bar. Increasing the operating pressure shifts the equilibrium toward the reactants (CH4and CO2); increasing the pressure from 25 to 35 bar decreases the conversion of CO2from 73.7 % to 67.8 %. The conversion ratio of CO2is less than that in the absence of O2. For a constant feed gas composition (7 % O2, 31 % gasification gas, and 62 % coke oven gas), a H2/CO ratio of about 2 occurs at temperatures of 950 °C and above. Pressure effects on the H2/CO ratio are negligible for temperatures greater than 750 °C. The steam produced has an effect on the hydrogen selectivity, but its mole fraction decreases with temperature; trace amounts of other secondary products are observed.
Residence Time Distribution in Tubular Joule Effect Heaters with and without Geometric Modifications
Authors: André C. , Boissier B. , Fillaudeau L. 
Published: December 2006

AbstractIn the food industry, heat treatment of highly viscous fluids in continuous processes is becoming more and more common, and the process should perform as a homogenous thermal treatment, in order to ensure quality and safety of the final product. To improve treatment homogeneity, geometric modifications can be used even in the laminar regime, to induce flow perturbation and mixing. The objectives of this work include: (i) Investigation of the residence time distribution (RTD) for industrial indirect Joule effect heaters (JEH), with smooth (ST) and modified (MT) tubes, (ii) Demonstration and quantification of the efficiency of the geometrical modifications, and (iii) Proposition of a single semi‐empirical model including the flow regime (10 < Re < 2000) and tube diameters (18 and 23 mm). The results obtained confirm that the simple Dispersed Plug Flow (DPF) model is not adaptable to small Reynolds numbers. Further analysis demonstrates that certain geometrical modifications improve the treatment homogeneity by increasing the plug flow contribution and reducing the value of the reduced variance. These beneficial effects increase when the Reynolds number is increased, the nominal diameter is reduced, and modified tubes are used. The proposed model enables the prediction of the RTD in JEH with an accurate degree of confidence.
Dimethylzinc‐Mediated, Enantioselective Synthesis of Propargylic Amines
Authors: Zani Lorenzo , Eichhorn Torsten , Bolm Carsten 
Published: December 2006

AbstractA one‐pot, enantioselective synthesis of N‐aryl propargylic amines, using alkynylation reagents obtained from dimethylzinc and terminal acetylenes in combination with various aldehydes and o‐methoxyaniline as starting materials, has been developed. Enantiopure β‐amino alcohols derived from norephedrine were used as non‐covalent chiral auxiliaries, both in stoichiometric or substoichiometric amount. After optimization, propargylic amines were obtained in good to high yields (up to 93 %) and with moderate to high enantiomeric excesses (up to 97 % ee). The possibility to recover the chiral auxiliary after the reaction was demonstrated.
Analysis of color symbology from the perspective of cultural semiotics focused on Korean costume colors according to the cultural changes
Authors: Lee Jee Hyun , Kim Young‐In 
Published: December 2006

AbstractThe purpose of this study was to analyze the symbolization of colors as cultural codes, based on costume colors. In order to study the significance of colors in cultural changes, we carried out a quantitative analysis and interpreted it from the perspective of cultural semiotics. The range of this study was focused on Korean costume colors, over diverse diachronic stages of Korean culture. For this study 1535 color samples were collected, measured with a spectrophotometer, and analyzed quantitatively according their diachronic stages of origin. As a result, red, blue, and yellow were found to be the most frequently used colors during the Chosun Dynasty, a period based on Confucianism. These colors acted as cultural codes with cultural significance. During the Modern times pink, light blue, and black increased in frequency and represented the reception of western culture, the changing sex role of women in society, and utilitarianism. In these days, neutral colors and grayish tones of all colors are the most significant colors of high frequency. The use of such colors is closely related to industrialization, mechanization, functionalism, and the changes of women's sex roles in the societies. They are used as cultural codes, especially to emphasize a rational and masculine image rather than a feminine image. © 2006 Wiley Periodicals, Inc. Col Res Appl, 32, 71–79, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/col.20290
Protein crystal nucleation: Recent notions
Authors: Nanev Christo N. 
Published: December 2006

AbstractThe nucleation of protein crystals is reconsidered taking into account the specificity of the protein molecules. In contrast to the homogeneous surface properties of small molecules, the protein molecule surface is highly inhomogeneous. Over their surfaces proteins exhibit high anisotropic distribution of patches, which are able to form crystalline bonds, the crystallization patch representing only a small fraction of the total surface of the protein molecule. Therefore, an appropriate spatial orientation of the colliding protein molecules is required in order to create a crystalline cluster. This scenario decreases considerably the success ratio of the attempt frequency for crystal nucleation. On the other hand a heterogeneous nucleation of (protein) crystals may be accelerated due to the arrival on some support of under‐critical clusters that are formed in bulk solution; when arriving there they may acquire the property of critical nuclei. Thus, a plausible explanation of important peculiarities of protein crystal nucleation, as inferred from the experimental data, is suggested. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)