bluuebunny/crossref_metadata_2025 huggingface dataset:
Low dose interleukin‐2 following intensification therapy with high dose cytarabine for acute myelogenous leukemia in first complete remission
Authors: Stone Richard M. , DeAngelo Daniel J. , Janosova Anna , Galinsky Ilene , Canning Christine , Ritz Jerome , Soiffer Robert J.
Published: July 2008

The most important problem in the therapy of patients with acute myeloid leukemia (AML) is relapse after intensive therapy. We sought to determine if interleukin‐2 (low‐dose with intermittent boluses) administration could be feasibly administered after standard therapy to potentiate anti‐tumor immunity in a fashion analogous to the post‐allogeneic stem cell transplant “graft‐vs‐leukemic” effect. Adults with de novo AML received daunorubicin and cytosine arabinoside induction therapy. Patients achieving complete remission received high dose ara‐C (HIDAC) for three courses followed by low dose rIL‐2 (Amgen), administered by continuous infusion (450,000 U/m2/day) for 10 weeks with intermittent boluses (500,000/U/m2 over 2 hr) given in weekly intervals starting on Week 4. Of the 32 enrolled patients, 27 achieved CR; 8/11 who received rIL‐2 completed therapy. 6/11 are long term survivors (median follow‐up, 139 months). rIL‐2 was well tolerated and associated with a 5‐fold increase in circulating NK‐lymphocytes and a 3‐fold increase in circulating T‐cells. Mononuclear cells from patients receiving rIL‐2 exhibited enhanced cytolytic activity in vitro against cryopreserved autologous leukemia cells. This study supports further investigation of immunotherapy in the post‐intensive chemotherapy setting in the management of patients with AML. Am. J. Hematol., 2008. © 2008 Wiley‐Liss, Inc.
Haplotype analysis at the FRAXA locus in an Indian population
Authors: Chakraborty S. Saha , Mondal Bama Charan , Das S. , Das K. , Dasgupta U.B.
Published: July 2008

The FRAXA locus is flanked by three polymorphic STR markers DXS548, FRAXAC1, and FRAXAC2. Allele frequencies of these markers were determined on a population representing the eastern part of India comprising of 69 normal controls and 69 unrelated subjects with mental retardation, among whom 21 were fragile X patients. These frequencies were compared with published data on other Indian population and the major populations of the world. The allele and haplotype distribution of the studied population were significantly different in some respects from the major populations of the world. The increase of heterozygosities in fragile X samples (DXS548 67.5%, FRAXAC1 63.5%, FRAXAC2 68.5%) relative to the controls (DXS548 63.3%, FRAXAC1 51.0%, FRAXAC2 67.2%) suggests a multimodal distribution of fragile X associated alleles. Haplotype analyses with DXS548 and FRAXAC1 markers revealed that haplotype distribution in the normal controls and fragile X groups were significantly different, suggesting a weak founder effect. © 2008 Wiley‐Liss, Inc.
A 3 Mb deletion in 14q12 causes severe mental retardation, mild facial dysmorphisms and Rett‐like features
Authors: Papa Filomena Tiziana , Mencarelli Maria Antonietta , Caselli Rossella , Katzaki Eleni , Sampieri Katia , Meloni Ilaria , Ariani Francesca , Longo Ilaria , Maggio Angela , Balestri Paolo , Grosso Salvatore , Farnetani Maria Angela , Berardi Rosario , Mari Francesca , Renieri Alessandra
Published: July 2008

The present report describes a 7‐year‐old girl with a de novo 3 Mb interstitial deletion of chromosome 14q12, identified by oligo array‐CGH. The region is gene poor and contains only five genes two of them, FOXG1B and PRKD1 being deleted also in a previously reported case with a very similar phenotype. Both patients present prominent metopic suture, epicanthic folds, bulbous nasal tip, tented upper lip, everted lower lip and large ears and a clinical course like Rett syndrome, including normal perinatal period, postnatal microcephaly, seizures, and severe mental retardation. FOXG1B (forkhead box G1B) is a very intriguing candidate gene since it is known to promote neuronal progenitor proliferation and to suppress premature neurogenesis and its disruption is reported in a patient with postnatal microcephaly, corpus callosum agenesis, seizures, and severe mental retardation. © 2008 Wiley‐Liss, Inc.
Constitutional H19 hypermethylation in a patient with isolated cardiac tumor
Authors: Descartes Maria , Romp Robb , Franklin Judy , Biggio Joseph R. , Zehnbauer Barbara
Published: July 2008

Beckwith–Wiedemann syndrome (BWS) is clinically and molecularly very heterogenous. Molecular findings characteristic of BWS have been reported in individuals with no or few associated features. We report on a child with isolated cardiac tumor and a constitutional H19 hypermethylation with none of the features of BWS. © 2008 Wiley‐Liss, Inc.
CPR honored by mediation organization
Authors: Bleemer Russ
Published: July 2008

In the biggest summer rundown of CPR events ever in Alternatives, details are provided on an honor for CPR, training, meetings, and committees. Also: a recap of Business Mediation Congress, which was held in Vienna
Antibacterial activity of cationically modified cotton fabric with carboxymethyl chitosan
Authors: El‐Shafei Amira M. , Fouda Moustafa M.G. , Knittel Dierk , Schollmeyer Eckhard
Published: July 2008

A water‐soluble carboxymethyl chitosan was prepared with a view to develop a multifunctional finish on cotton. Carboxymethyl chitosan (CMCTS) was synthesized by chemical reaction of chitosan with monochloroacetic acid under alkaline condition. The water soluble CMCTS was applied to cationized cotton with different concentrations. The treated fabrics were characterized through monitoring the textile physical properties and for the antibacterial activity against Escherichia coli DSMZ 498 and Micrococcus luteus ATCC 9341. The results obtained show that the physical properties of the treated fabrics are improved by increasing the CMCTS concentration, as well as the antibacterial activity. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Characterization and solution properties of a partially hydrolyzed graft copolymer of polyacrylamide and dextran
Authors: Krishnamoorthi S. , Mal D. , Singh R. P.
Published: July 2008

Graft copolymers of dextran (Dx) and polyacrylamide (PAM) were synthesized through the grafting of PAM chains onto a Dx backbone with a ceric‐ion‐induced solution polymerization technique. By the variation of the amount of the initiator (ceric ammonium nitrate), four different grades of graft copolymers were synthesized. The partial alkaline hydrolysis of Dx‐g‐PAM was carried out in an alkaline medium. Three grades of partially hydrolyzed products were synthesized through the variation of the amount of alkali. These hydrolyzed graft copolymers were characterized with elemental analysis, infrared spectroscopy, neutralization equivalent measurements, a rheological technique, scanning electron microscopy, thermal analysis, viscometry, and X‐ray diffraction. The flocculation efficiency and viscosifying characteristics of the graft copolymers were enhanced upon their alkaline hydrolysis. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008.
Synthesis and properties of novel phosphorus‐containing poly(ether ether ketone ketone)s
Authors: Chen Xiao‐Ting , Sun Hao , Tang Xu‐Dong , Wang Chun‐Ying
Published: July 2008

A novel monomer, bis[4‐(4‐fluorobenzoyl)phenyl]phenylphosphine oxide, was synthesized through the reaction of bis(4‐chloroformylphenyl) phenyl phosphine oxide with fluorobenzene. Three poly(ether ether ketone ketone)s derived from bis[4‐(4‐fluorobenzoyl)phenyl]phenylphosphine oxide and different aromatic bisphenols were prepared by aromatic nucleophilic substitution reactions. The resulting polymers had inherent viscosities in the range of 0.55–0.73 dL/g. The structures of the poly(ether ether ketone ketone)s were characterized with Fourier transform infrared and 1H‐NMR. Thermal analysis indicated that the glass‐transition temperatures of the poly(ether ether ketone ketone)s were higher than 200°C, and the 5% weight loss temperatures in nitrogen were higher than 463°C. All the polymers showed excellent solubility in polar solvents such as N‐methyl‐2‐pyrrolidone, dimethylformamide, and dimethylacetamide and could also be dissolved in chlorinated methane. The polymers afforded transparent and flexible films by solvent casting. Organic phosphorous moieties also imparted good flame‐retardancy to the polymers. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Synergetic toughness and morphology of poly(propylene)/nylon 11/maleated ethylene‐propylene diene copolymer blends
Authors: Wang Biao‐Bing , Wei Li‐Xia , Hu Guo‐Sheng
Published: July 2008

Polypropylene (PP)/nylon 11/maleated ethylene‐propylene‐diene rubber (EPDM‐g‐MAH) ternary polymer blends were prepared via melt blending in a corotating twin‐screw extruder. The effect of nylon 11 and EPDM‐g‐MAH on the phase morphology and mechanical properties was investigated. Scanning electron microscopy observation revealed that there was apparent phase separation for PP/EPDM‐g‐MAH binary blends at the level of 10 wt % maleated elastomer. For the PP/nylon 11/EPDM‐g‐MAH ternary blends, the dispersed phase morphology of the maleated elastomer was hardly affected by the addition of nylon 11, whereas the reduced dispersed phase domains of nylon 11 were observed with the increasing maleated elastomer loading. Furthermore, a core‐shell structure, in which nylon 11 as a rigid core was surrounded by a soft EPDM‐g‐MAH shell, was formed in the case of 10 wt % nylon 11 and higher EPDM‐g‐MAH concentration. In general, the results of mechanical property measurement showed that the ternary blends exhibited inferior tensile strength in comparison with the PP matrix, but superior toughness. Especially low‐temperature impact strength was obtained. The toughening mechanism was discussed with reference to the phase morphology. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Synthesis and characterization of waterborne polyurethane adhesive from MDI and HDI
Authors: Du Hui , Zhao Yuhua , Li Qifeng , Wang Junwei , Kang Maoqing , Wang Xinkui , Xiang Hongwei
Published: July 2008

A series of waterborne polyurethane adhesives (WPUAs) were prepared from diphenylmethane‐4,4′‐diisocyanate (MDI), 1,6‐hexamethylene diisocyanate (HDI), poly(1,4‐butanediol adipate) diol (PBA), 1,4‐butanediol (BDO), and internal‐emulsifying agents by the prepolymer mixing method. The viscosity, mechanical properties, thermal properties, and adhesion strength of the samples were measured. The structure–property relationship was discussed primarily. The results indicated that the MDI/HDI and PBA/BDO molar ratio influenced these properties. The WPUA exhibited excellent T‐peel strength and mechanical properties at a suitable MDI/HDI (or PBA/BDO) molar ratio. Moreover, higher MDI/HDI (or PBA/BDO) molar ratio resulted in higher thermal stability. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Evolution of research activities and intellectual influences in information science 1996–2005: Introducing author bibliographic‐coupling analysis
Authors: Zhao Dangzhi , Strotmann Andreas
Published: July 2008

Author cocitation analysis (ACA) has frequently been applied over the last two decades for mapping the intellectual structure of a research field as represented by its authors. However, what is mapped in ACA is actually the structure of intellectual influences on a research field as perceived by its active authors. In this exploratory paper, by contrast, we introduce author bibliographic‐coupling analysis (ABCA) as a method to map the research activities of active authors themselves for a more realistic picture of the current state of research in a field. We choose the information science (IS) field and study its intellectual structure both in terms of current research activities as seen from ABCA and in terms of intellectual influences on its research as shown from ACA. We examine how these two aspects of the intellectual structure of the IS field are related, and how they both developed during the “first decade of the Web,” 1996–2005. We find that these two citation‐based author‐mapping methods complement each other, and that, in combination, they provide a more comprehensive view of the intellectual structure of the IS field than either of them can provide on its own.
Undergraduate students' mental models of the Web as an information retrieval system
Authors: Zhang Yan
Published: July 2008

This study explored undergraduate students' mental models of the Web as an information retrieval system. Mental models play an important role in people's interaction with information systems. Better understanding of people's mental models could inspire better interface design and user instruction. Multiple data‐collection methods, including questionnaire, semistructured interview, drawing, and participant observation, were used to elicit students' mental models of the Web from different perspectives, though only data from interviews and drawing descriptions are reported in this article. Content analysis of the transcripts showed that students had utilitarian rather than structural mental models of the Web. The majority of participants saw the Web as a huge information resource where everything can be found rather than an infrastructure consisting of hardware and computer applications. Students had different mental models of how information is organized on the Web, and the models varied in correctness and complexity. Students' mental models of search on the Web were illustrated from three points of view: avenues of getting information, understanding of search engines' working mechanisms, and search tactics. The research results suggest that there are mainly three sources contributing to the construction of mental models: personal observation, communication with others, and class instruction. In addition to structural and functional aspects, mental models have an emotional dimension.
Linguistic politeness and face‐work in computer‐mediated communication, Part 1: A theoretical framework
Authors: Park Jung‐ran
Published: July 2008

Our daily social interaction is anchored in interpersonal discourse; accordingly, the phenomenon of linguistic politeness is prevalent in daily social interaction. Such linguistic behavior underscores the fact that linguistic politeness is a critical component of human communication. Speech participants utilize linguistic politeness to avoid and reduce social friction and enhance each other's face, or public self‐image, during social interaction. It is face‐work that underlies the interpersonal function of language use and encompasses all verbal and nonverbal realizations that bring forth one's positive social value, namely, face. Face‐work is founded in and built into dynamic social relations; these social and cultural relations and context directly affect the enactment of face‐work. Analysis and a subsequent understanding of sociointerpersonal communication are critical to the fostering of successful interaction and collaboration. Linguistic politeness theory is well positioned to provide a framework for an analysis of social interaction and interpersonal variables among discourse participants inasmuch as it is applicable not only to face‐to‐face social interactions but also to those interactions undertaken through online communication.
Assessing the impact of disciplinary research on teaching: An automatic analysis of online syllabuses
Authors: Kousha Kayvan , Thelwall Mike
Published: July 2008

The impact of published academic research in the sciences and social sciences, when measured, is commonly estimated by counting citations from journal articles. The Web has now introduced new potential sources of quantitative data online that could be used to measure aspects of research impact. In this article we assess the extent to which citations from online syllabuses could be a valuable source of evidence about the educational utility of research. An analysis of online syllabus citations to 70,700 articles published in 2003 in the journals of 12 subjects indicates that online syllabus citations were sufficiently numerous to be a useful impact indictor in some social sciences, including political science and information and library science, but not in others, nor in any sciences. This result was consistent with current social science research having, in general, more educational value than current science research. Moreover, articles frequently cited in online syllabuses were not necessarily highly cited by other articles. Hence it seems that online syllabus citations provide a valuable additional source of evidence about the impact of journals, scholars, and research articles in some social sciences.
Using importance flooding to identify interesting networks of criminal activity
Authors: Marshall Byron , Chen Hsinchun , Kaza Siddharth
Published: July 2008

Effectively harnessing available data to support homeland‐security‐related applications is a major focus in the emerging science of intelligence and security informatics (ISI). Many studies have focused on criminal‐network analysis as a major challenge within the ISI domain. Though various methodologies have been proposed, none have been tested for usefulness in creating link charts. This study compares manually created link charts to suggestions made by the proposed importance‐flooding algorithm. Mirroring manual investigational processes, our iterative computation employs association‐strength metrics, incorporates path‐based node importance heuristics, allows for case‐specific notions of importance, and adjusts based on the accuracy of previous suggestions. Interesting items are identified by leveraging both node attributes and network structure in a single computation. Our data set was systematically constructed from heterogeneous sources and omits many privacy‐sensitive data elements such as case narratives and phone numbers. The flooding algorithm improved on both manual and link‐weight‐only computations, and our results suggest that the approach is robust across different interpretations of the user‐provided heuristics. This study demonstrates an interesting methodology for including user‐provided heuristics in network‐based analysis, and can help guide the development of ISI‐related analysis tools.
Linguistic politeness and face‐work in computer mediated communication, Part 2: An application of the theoretical framework
Authors: Park Jung‐ran
Published: July 2008

Analysis of sociointerpersonal communication patterns among discourse participants is essential to understand the manifestation of and the interpersonal‐communication features realized in online social interaction. The linguistic politeness theory provides an effective framework for such an analysis of sociointerpersonal communication features employed by online language users to maintain and enhance their public self‐image, or face. The qualitative data analysis of this study, drawn from the real‐time, online discussions of K–12 students, makes evident that interpersonal‐communication features appear in the form of politeness tactics. The results of the study show that there is decreased use of deferential linguistic forms; on the contrary, a variety of verbal and nonverbal devices that denote positive politeness and bald‐on‐record (i.e., direct speech acts) frequently occur. The commonality of positive politeness and bald‐on‐record lies in the fact that both tactics are grounded in the nature of the close interpersonal relationships between participants. Such a communication pattern in the real‐time, online discourse of K–12 students signifies that cognitive assessment of sociointerpersonal and contextual variables undertaken by speech participants underlies the realization of linguistic politeness. Employment of such politeness tactics indicates that effective and fully realized interpersonal communication plays a vital role in the development of online social interaction.
Iron‐ and Ruthenium‐Lewis Acid Catalyzed Asymmetric 1,3‐Dipolar Cycloaddition Reactions between Enals and Diaryl Nitrones
Authors: Bădoiu Andrei , Bernardinelli Gerald , Mareda Jiri , Kündig E. Peter , Viton Florian
Published: July 2008

The highly tuned, one‐point binding cationic cyclopentadienyl‐iron and ‐ruthenium complexes 1 and 2 that incorporate chiral bidentate pentafluoroaryl‐phosphinite ligands selectively coordinate and activate α,β‐unsaturated carbonyl compounds towards asymmetric catalytic cycloaddition reactions with diaryl nitrones. The reaction gives isoxazolidine products in good yields, with complete endo selectivity and high enantioselectivity. The products are obtained as a mixture of regioisomers in ratios varying from 96:4 to 15:85. The regioselectivity correlates directly with the electronic properties of the nitrone. This is shown by the experimental and computational data.
Folding at the rhythm of the rare codon beat
Authors: Marin Monica
Published: July 2008

The persistent difficulties in the production of protein at high levels in heterologous systems, as well as the inability to understand pathologies associated with protein aggregation, highlight our limited knowledge on the mechanisms of protein folding in vivo. Attempts to improve yield and quality of recombinant proteins are diverse, frequently involving optimization of the cell growth temperature, the use of synonymous codons and/or the co‐expression of tRNAs, chaperones and folding catalysts among others. Although protein secondary structure can be determined largely by the amino acid sequence, protein folding within the cell is affected by a range of factors beyond amino acid sequence. The folding pathway of a nascent polypeptide can be affected by transient interactions with other proteins and ligands, the ribosome, translocation through a pore membrane, redox conditions, among others. The translation rate as well as the translation machinery itself can dramatically affect protein folding, and thus the structure and function of the protein product. This review addresses current efforts to better understand how the use of synonymous codons in the mRNA and the availability of tRNAs can modulate translation kinetics, affecting the folding, the structure and the biological activity of proteins.
Time‐series integrated “omic” analyses to elucidate short‐term stress‐induced responses in plant liquid cultures
Authors: Dutta Bhaskar , Kanani Harin , Quackenbush John , Klapa Maria I.
Published: July 2008

The research that aims at furthering our understanding of plant primary metabolism has intensified during the last decade. The presented study validated a systems biology methodological framework for the analysis of stress‐induced molecular interaction networks in the context of plant primary metabolism, as these are expressed during the first hours of the stress treatment. The framework involves the application of time‐series integrated full‐genome transcriptomic and polar metabolomic analyses on plant liquid cultures. The latter were selected as the model system for this type of analysis, because they provide a well‐controlled growth environment, ensuring that the observed plant response is due only to the applied perturbation. An enhanced gas chromatography–mass spectrometry (GC–MS) metabolomic data correction strategy and a new algorithm for the significance analysis of time‐series “omic” data are used to extract information about the plant's transcriptional and metabolic response to the applied stress from the acquired datasets; in this article, it is the first time that these are applied for the analysis of a large biological dataset from a complex eukaryotic system. The case‐study involved Arabidopsis thaliana liquid cultures subjected for 30 h to elevated (1%) CO2 stress. The advantages and validity of the methodological framework are discussed in the context of the known A. thaliana or plant, in general, physiology under the particular stress. Of note, the ability of the methodology to capture dynamic aspects of the observed molecular response allowed for 9 and 24 h of treatment to be indicated as corresponding to shifts in both the transcriptional and metabolic activity; analysis of the pathways through which these activity changes are manifested provides insight to regulatory processes. Biotechnol. Bioeng. 2009;102: 264–279. © 2008 Wiley Periodicals, Inc.
Anion exchange chromatography provides a robust, predictable process to ensure viral safety of biotechnology products
Authors: Strauss Daniel M. , Gorrell Jeffrey , Plancarte Magdalena , Blank Gregory S. , Chen Qi , Yang Bin
Published: July 2008

The mammalian cell‐lines used to produce biopharmaceutical products are known to produce endogenous retrovirus‐like particles and have the potential to foster adventitious viruses as well. To ensure product safety and regulatory compliance, recovery processes must be capable of removing or inactivating any viral impurities or contaminants which may be present. Anion exchange chromatography (AEX) is a common process in the recovery of monoclonal antibody products and has been shown to be effective for viral removal. To further characterize the robustness of viral clearance by AEX with respect to process variations, we have investigated the ability of an AEX process to remove three model viruses using various combinations of mAb products, feedstock conductivities and compositions, equilibration buffers, and pooling criteria. Our data indicate that AEX provides complete or near‐complete removal of all three model viruses over a wide range of process conditions, including those typically used in manufacturing processes. Furthermore, this process provides effective viral clearance for different mAb products, using a variety of feedstocks, equilibration buffers, and different pooling criteria. Viral clearance is observed to decrease when feedstocks with sufficiently high conductivities are used, and the limit at which the decrease occurs is dependent on the salt composition of the feedstock. These data illustrate the robust nature of the AEX recovery process for removal of viruses, and they indicate that proper design of AEX processes can ensure viral safety of mAb products. Biotechnol. Bioeng. 2009;102: 168–175. © 2008 Wiley Periodicals, Inc.
A standardized protocol for needle placement in suboccipital muscles
Authors: Hallgren Richard C. , Andary Michael T. , Wyman Andrew J. , Rowan Jacob J.
Published: July 2008

The objective of this study was to assess the safety and accuracy of using common anatomic landmarks to guide the placement of needle electrodes into suboccipital muscles. Atrophic changes in suboccipital muscles have been reported in some patients who have tension‐type headaches, and in some patients who have headaches resulting from whiplash‐type injuries. These atrophic changes most likely result from disuse or denervation. Needle electromyography is a definitive technique for determining the cause of muscle atrophy, but requires that needle electrodes be inserted into the muscle. Suboccipital muscles present a challenge to the electromyographer in that they are physically small and are located in close proximity to one another. Atrophied muscles with fatty replacement and the presence of critical structures such as the vertebral artery further complicate the procedure. Using a standardized protocol, three investigators attempted blind needle insertions into each of the suboccipital muscles of eight embalmed cadavers. A dissector then assessed targeted muscle penetrations, final resting positions of the wires, and their proximity to critical structures. Eighty‐one percent of 181 attempted insertions penetrated the targeted muscles: 83% for the rectus capitis posterior minor, 83% for the rectus capitis posterior major, 94% for the obliquus capitis superior, and 63% for the obliquus capitis inferior muscles, respectively. It was concluded that readily palpable external landmarks can be used to safely and reliably guide the insertion of needle electrodes into three of the four pairs of suboccipital muscles. Clin. Anat. 21:501–508, 2008. © 2008 Wiley‐Liss, Inc.
‘You've got to grow up when you've got a kid’: Marginalized young women's accounts of motherhood
Authors: Rolfe Alison
Published: July 2008

Teenage motherhood has been a source of considerable debate in policy and media circles in recent years. This paper explores the meanings of teenage motherhood for young women who were mothers before the age of 21, who were living in economically deprived areas of England and most of whom had been in residential or foster care. Qualitative interviews were carried out at several sites across England, with a total of 33 young women taking part in group interviews and one‐to‐one interviews. The accounts of the young women suggest that they talk about motherhood in three main ways: as ‘hardship and reward’, ‘growing up and responsibility’ and ‘doing things differently’. It is argued that these ways of talking about motherhood present a different picture of teenage motherhood from that of dominant discourses. Furthermore, the young women are active in negotiating and constructing their own identities as mothers, carers and women. Copyright © 2008 John Wiley & Sons, Ltd.
Identity, practice and dialogue
Authors: Hopkins Nick
Published: July 2008

Identities are constructed and contested. This means they may be re‐worked to support more inclusive visions of who belongs and on what basis. However, identity construction does not take place in a vacuum, and social psychological analyses of change need to address the contextual dynamics that shape the processes and outcomes of dialogue. This requires attention to processes of power. Furthermore, we need to consider minority group members' understandings of these processes. From the perspective of the disadvantaged, dialogue may be experienced as disempowering because it is viewed as compromising group members' capacities to organize themselves to pursue strategies of social change. Copyright © 2008 John Wiley & Sons, Ltd.
Molecular Design of Specific Metal‐Binding Peptide Sequences from Protein Fragments: Theory and Experiment
Authors: Kožíšek Milan , Svatoš Aleš , Buděšínský Miloš , Muck Alexander , Bauer Mikael C. , Kotrba Pavel , Ruml Tomáš , Havlas Zdeněk , Linse Sara , Rulíšek Lubomír
Published: July 2008

A novel strategy is presented for designing peptides with specific metal‐ion chelation sites, based on linking computationally predicted ion‐specific combinations of amino acid side chains coordinated at the vertices of the desired coordination polyhedron into a single polypeptide chain. With this aim, a series of computer programs have been written that 1) creates a structural combinatorial library containing Zi–(X)n–Zj sequences (n=0–14; Z: amino acid that binds the metal through the side chain; X: any amino acid) from the existing protein structures in the non‐redundant Protein Data Bank; 2) merges these fragments into a single Z1–(X)–Z2–(X)–Z3–(X)–⋅⋅⋅–Zj polypeptide chain; and 3) automatically performs two simple molecular mechanics calculations that make it possible to estimate the internal strain in the newly designed peptide. The application of this procedure for the most M2+‐specific combinations of amino acid side chains (M: metal; see L. Rulíšek, Z. Havlas J. Phys. Chem. B 2003, 107, 2376–2385) yielded several peptide sequences (with lengths of 6–20 amino acids) with the potential for specific binding with six metal ions (Co2+, Ni2+, Cu2+, Zn2+, Cd2+ and Hg2+). The gas‐phase association constants of the studied metal ions with these de novo designed peptides were experimentally determined by MALDI mass spectrometry by using 3,4,5‐trihydroxyacetophenone as a matrix, whereas the thermodynamic parameters of the metal‐ion coordination in the condensed phase were measured by isothermal titration calorimetry (ITC), chelatometry and NMR spectroscopy methods. The data indicate that some of the computationally predicted peptides are potential M2+‐specific metal‐ion chelators.
Steric Effects in RNA Interference: Probing the Influence of Nucleobase Size and Shape
Authors: Somoza Alvaro , Silverman Adam P. , Miller Rand M. , Chelliserrykattil Jijumon , Kool Eric T.
Published: July 2008

Nonpolar nucleosides with varying size and shape have been used to study the hydrogen‐bonding stabilization and steric effects on RNA interference. The uracil and adenine residues of siRNA guide strands have been replaced by nonpolar isosteres of uracil and adenine and by steric variants. RNAi experiments targeting Renilla luciferase mRNA have shown close correlation between siRNA thermal stability and gene suppression. Interestingly, siRNA modified at position 7 on the guide strand does not follow this correlation, having substantial RNAi activity despite low thermal stability. Sequence‐selectivity studies were carried out at this position with mutated target mRNAs and nucleobase analogues with varied size (2,4‐difluoro‐ and 2,4‐dichlorobenzene) and different shape (2,3‐dichlorobenzene, 4‐methylbenzimidazole). The results point out the importance of nucleobase shape and steric effects in RNA interference.
Advanced bladder cancer: Status of first‐line chemotherapy and the search for active agents in the second‐line setting
Authors: Gallagher David J. , Milowsky Matthew I. , Bajorin Dean F.
Published: July 2008

Urothelial carcinoma (UC) remains a significant health problem affecting an estimated 68,810 people in 2008 alone in the US. The majority of patients with metastatic disease develop disease recurrence, and long‐term survival rates are poor. There is no standard of care for the treatment of patients with UC after the failure of cisplatin‐based regimens in the first‐line setting. Efforts to improve second‐line treatment have led to the evaluation of single agents such as vinflunine and pemetrexed, and multidrug combinations with cytotoxic and targeted agents, including trastuzumab and bevacizumab. The authors reviewed the activity of several single agents and combination regimens in patients with UC. Emerging strategies for the measurement of response in clinical trials were also outlined. Cancer 2008. © 2008 American Cancer Society.
Anatomical and functional characterization of neuropil in the gracile fasciculus
Authors: Ramer Matt S.
Published: July 2008

A fundamental organizational principle of the central nervous system is that gray matter is the province of neuronal somata, white matter their processes. However, the rat and primate dorsal columns (archetypal spinal “white matter” tracts) are actually of intermediate character, insofar as they contain a surprisingly prominent neuropil of unknown function. Here I report on the morphology, inputs, projections, and functional properties of these neurons. Small fusiform and larger lentiform neurons are most abundant in the gracile fasciculus of the cervical and lumbar enlargements and are absent from the cuneate fasciculus and corticospinal tract. Many have dendrites that run along the dorsal pia, and, although in transverse sections these neurons appear isolated from the gray matter, they are also connected to area X by varicose and sometimes loosely fasciculated dendrites. These neurons receive neurochemically diverse, compartmentalized synaptic inputs (primary afferent, intrinsic and descending), half express the substance P receptor, and some project supraspinally. Unlike substantia gelatinosa neurons, they do not express protein kinase C gamma. Functionally, they have small receptive fields, which are somatotopically appropriate with respect to their anterior‐posterior position along the neuraxis. They respond to innocuous and/or noxious mechanical stimulation of the distal extremities, and some are prone to central sensitization or “windup.” Morphologically, neurochemically, and functionally, therefore, these cells most closely resemble neurons in laminae III–VI in the dorsal horn. The proximity of their dorsal dendrites to the pia mater may also reflect an ability to integrate internal (e.g., changes in cerebrospinal fluid compostition) and external (e.g., somatic) stimuli. J. Comp. Neurol. 510:283–296, 2008. © 2008 Wiley‐Liss, Inc.
Connections and synaptic function in the posteroventral cochlear nucleus of deaf jerker mice
Authors: Cao Xiao‐Jie , McGinley Matthew J. , Oertel Donata
Published: July 2008

Mutations in the gene that encodes espins can cause deafness and vestibular disorders; mice that are homozygous for the autosomal recessive jerker mutation in the espin gene never hear. Extracellular injections of biocytin into the anteroventral cochlear nucleus (AVCN) revealed that although the cochlear nuclei are smaller in je/je mice, the topography in its innervation resembles that in wild‐type mice. Auditory nerve fibers innervate narrow, topographically organized, “isofrequency” bands in deaf animals over the ages examined, P18–P70. The projection of tuberculoventral cells was topographic in je/je as in wild‐type mice. Terminals of auditory nerve fibers in the multipolar cell area included both large and small endings, whereas in the octopus cell area they were exclusively small boutons in je/je as in wild‐type mice, but end bulbs near the nerve root of je/je animals were smaller than in hearing animals. In whole‐cell recordings from targets of auditory nerve fibers, octopus and T stellate cells, miniature excitatory postsynaptic currents (mEPSCs) had similar shapes as in +/+, indicating that the properties of AMPA receptors were not affected by the mutation. In je/je animals the frequency of spontaneous mEPSCs was elevated, and synaptic depression in responses to trains of shocks delivered at between 100 and 333 Hz was greater than in wild‐type mice, indicating that the probability of neurotransmitter release was increased. The frequency of spontaneous mEPSCs and extent of synaptic depression were greater in octopus than in T stellate cells, in both wild‐type and in je/je mice. J. Comp. Neurol. 510:297–308, 2008. © 2008 Wiley‐Liss, Inc.
Photodissociation of Dibromobenzenes at 266 nm by the Velocity Imaging Technique
Authors: Zhang Xiao‐Peng , Wei Zheng‐Rong , Lee Wei‐Bin , Chao Ting‐Jung , Lin King‐Chuen
Published: July 2008

A velocity imaging technique combined with (2+1) resonance‐enhanced multiphoton ionization (REMPI) is used to detect the primary Br(2P3/2) fragment in the photodissociation of o‐, m‐, and p‐dibromobenzene at 266 nm. The obtained translational energy distributions suggest that the Br fragments are produced via two dissociation channels. For o‐ and m‐dibromobenzene, the slow channel that yields an anisotropy parameter close to zero is proposed to stem from excitation of the lowest excited singlet (π,π*) state followed by predissociation along a repulsive triplet (n,σ*) state localized on the CBr bond. The fast channel that gives rise to an anisotropy parameter of 0.53–0.73 is attributed to a bound triplet state with smaller dissociation barrier. For p‐dibromobenzene, the dissociation rates are reversed, because the barrier for the bound triplet state becomes higher than the singlet–triplet crossing energy. The fractions of translational energy release are determined to be 6–8 and 29–40 % for the slow and fast channels, respectively; the quantum yields are 0.2 and 0.8, and are insensitive to the position of the substituent. The Br fragmentation from bromobenzene and bromofluorobenzenes at the same photolyzing wavelength is also compared to understand the effect of the number of halogen atoms on the phenyl ring.
Heparan sulfate proteoglycans: A GAGgle of skeletal‐hematopoietic regulators
Authors: Rodgers Kathryn D. , San Antonio James D. , Jacenko Olena
Published: July 2008

This review summarizes our current understanding of the presence and function of heparan sulfate proteoglycans (HSPGs) in skeletal development and hematopoiesis. Although proteoglycans (PGs) comprise a large and diverse group of cell surface and matrix molecules, we chose to focus on HSPGs owing to their many proposed functions in skeletogenesis and hematopoiesis. Specifically, we discuss how HSPGs play predominant roles in establishing and regulating niches during skeleto‐hematopoietic development by participating in distinct developmental processes such as patterning, compartmentalization, growth, differentiation, and maintenance of tissues. Special emphasis is placed on our novel hypothesis that mechanistically links endochondral skeletogenesis to the establishment of the hematopoietic stem cell (HSC) niche in the marrow. HSPGs may contribute to these developmental processes through their unique abilities to establish and mediate morphogen, growth factor, and cytokine gradients; facilitate signaling; provide structural stability to tissues; and act as molecular filters and barriers. Developmental Dynamics 237:2622–2642, 2008. © 2008 Wiley‐Liss, Inc.
Altered endochondral ossification in collagen X mouse models leads to impaired immune responses
Authors: Sweeney E. , Campbell M. , Watkins K. , Hunter C.A. , Jacenko O.
Published: July 2008

Disruption of collagen X function in hypertrophic cartilage undergoing endochondral ossification was previously linked to altered hematopoiesis in collagen X transgenic (Tg) and null (KO) mice (Jacenko et al., [2002] Am J Pathol 160:2019–2034). Mice displayed altered growth plates, diminished trabecular bone, and marrow hypoplasia with an aberrant lymphocyte profile throughout life. This study identifies altered B220+, CD4+, and CD8+ lymphocyte numbers, as well as CD4+/fox3P+ T regulatory cells in the collagen X mice. Additionally, diminished in vitro splenocyte responses to mitogens and an inability of mice to survive a challenge with Toxoplasma gondii, confirm impaired immune responses. In concert, ELISA and protein arrays identify aberrant levels of inflammatory, chemo‐attractant, and matrix binding cytokines in collagen X mouse sera. These data link the disruption of collagen X function in the chondro‐osseous junction to an altered hematopoietic stem cell niche in the marrow, resulting in impaired immune function. Developmental Dynamics 237:2693–2704, 2008. © 2008 Wiley‐Liss, Inc.
Human primary corneal fibroblasts synthesize and deposit proteoglycans in long‐term 3‐D cultures
Authors: Ren R. , Hutcheon A.E.K. , Guo X.Q. , Saeidi N. , Melotti S.A. , Ruberti J.W. , Zieske J.D. , Trinkaus‐Randall V.
Published: July 2008

Our goal was to develop a 3‐D multi‐cellular construct using primary human corneal fibroblasts cultured on a disorganized collagen substrate in a scaffold‐free environment and to use it to determine the regulation of proteoglycans over an extended period of time (11 weeks). Electron micrographs revealed multi‐layered constructs with cells present in between alternating parallel and perpendicular arrays of fibrils. Type I collagen increased 2–4‐fold. Stromal proteoglycans including lumican, syndecan4, decorin, biglycan, mimecan, and perlecan were expressed. The presence of glycosaminoglycan chains was demonstrated for a subset of the core proteins (lumican, biglycan, and decorin) using lyase digestion. Cuprolinic blue–stained cultures showed that sulfated proteoglycans were present throughout the construct and most prominent in its mid‐region. The size of the Cuprolinic‐positive filaments resembled those previously reported in a human corneal stroma. Under the current culture conditions, the cells mimic a development or nonfibrotic repair phenotype. Developmental Dynamics 237:2705–2715, 2008. © 2008 Wiley‐Liss, Inc.
Maintenance of undifferentiated mouse embryonic stem cells in suspension by the serum‐ and feeder‐free defined culture condition
Authors: Tsuji Yukiiko , Yoshimura Naoko , Aoki Hitomi , Sharov Alexei A. , Ko Minoru S.H. , Motohashi Tsutomu , Kunisada Takahiro
Published: July 2008

The proven pluripotency of ES cells is expected to allow their therapeutic use for regenerative medicine. We present here a novel suspension culture method that facilitates the proliferation of pluripotent ES cells without feeder cells. The culture medium contains polyvinyl alcohol (PVA), free of either animal‐derived or synthetic serum, and contains very low amounts of peptidic or proteinaceous materials, which are favorable for therapeutic use. ES cells showed sustained proliferation in the suspension culture, and their undifferentiated state and pluripotency were experimentally verified. DNA microarray analyses showed a close relationship between the elevated expression of genes related to cell adhesions. We suggest that this suspension culture condition provides a better alternative to the conventional attached cell culture condition, especially for possible therapeutic use, by limiting the exposure of ES cells to feeder cells and animal products. Developmental Dynamics 237:2129–2138, 2008. © 2008 Wiley‐Liss, Inc.
Notch‐regulated oligodendrocyte specification from radial glia in the spinal cord of zebrafish embryos
Authors: Kim Ho , Shin Jimann , Kim Suhyun , Poling Justin , Park Hae‐Chul , Appel Bruce
Published: July 2008

During vertebrate neural development, many dividing neuroepithelial precursors adopt features of radial glia, which are now known to also serve as neural precursors. In mammals, most radial glia do not persist past early postnatal stages, whereas zebrafish maintain large numbers of radial glia into adulthood. The mechanisms that maintain and specify radial glia for different fates are still poorly understood. We investigated formation of radial glia in the spinal cord of zebrafish and the role of Notch signaling in their maintenance and specification. We found that spinal cord precursors begin to express gfap+, a marker of radial glia, during neurogenesis and that gfap cells give rise to both neurons and oligodendrocytes. We also determined that Notch signaling is continuously required during embryogenesis to maintain radial glia, limit motor neuron formation and permit oligodendrocyte development, but that radial glia seem to be refractory to changes in Notch activity in postembryonic animals. Developmental Dynamics 237:2081–2089, 2008. © 2008 Wiley‐Liss, Inc.
Endogenous presentation of a nuclear antigen on MHC class II by autophagy in the absence of CRM1‐mediated nuclear export
Authors: Riedel Alexander , Nimmerjahn Falk , Burdach Stefan , Behrends Uta , Bornkamm Georg W. , Mautner Josef
Published: July 2008

Accumulating evidence suggests that intracellular antigens are endogenously presented on MHC class II, but it is still unknown whether antigens within different subcellular compartments are presented with similar efficiency, and via the same or different pathways. We have previously shown that endogenous MHC class II presentation of the cytosolic bacterial antigen neomycin phosphotransferase II (NeoR) is mediated by autophagy. Here, we addressed whether secluding NeoR from this cytoplasmic pathway by directing the protein into the cell nucleus (NucNeoR) would affect antigen presentation. Unexpectedly, NucNeoR was presented at least as efficiently as the cytosolic version of the antigen. Furthermore, presentation of NucNeoR was also dependent on autophagocytosis and lysosomal processing, indicating that both antigens were presented via the same pathway. Inhibition of CRM1‐mediated nuclear export did not impede antigen presentation, indicating that NucNeoR gained access to this autophagy‐dependent MHC class II presentation pathway by a CRM1‐independent route. Thus, this endogenous presentation pathway broadens the spectrum of intracellular antigens surveyed by CD4+ T cells by efficiently sampling cytoplasmic as well as nuclear antigens.