bluuebunny/crossref_metadata_2025 huggingface dataset:
Racial Ideological Beliefs and Racial Discrimination Experiences as Predictors of Academic Engagement Among African American Adolescents
Authors: Smalls Ciara , White Rhonda , Chavous Tabbye , Sellers Robert
Published: August 2007

Adolescents' understandings of their social identities and related personal experiences influence their adaptations and responses within domains in which those identities are salient. The authors explore associations of racial identity beliefs regarding how Blacks should act, think, and behave (racial ideologies) and racial discrimination experiences with academic engagement outcomes among 390 African American adolescents in Grades 7 to 10. Results indicate that youths' endorsement of ideological beliefs emphasizing being more like Whites (assimilation ideology) related to more fears of being viewed as high achievers by peers (public oppositional academic identification), lower academic persistence and curiosity, and more school behavioral problems. Emphasizing commonalties with Blacks and other oppressed groups (minority ideology) related to positive engagement outcomes. Youths reporting more racial discrimination showed lower school engagement. Finally, racial ideologies moderated the relationship between discrimination and academic outcomes, such that youths holding stronger assimilation views showed lower academic identification when reporting racial discrimination, relative to youth who endorsed those views less. Findings are discussed relative to their potential impact on ethnic minority achievement research and educational practice.
Family Influences on Racial Identity Among African American Youth
Authors: Townsend Tiffany , Lanphier Erin
Published: August 2007

The purpose of this study was to examine the influence of parental efficacy, family coping, and adaptive family functioning on the development of racial identity among African American youth. Fifty-two African American parent-child dyads were participants. Results of a hierarchical regression revealed family adaptability and family cognitive reframing to be significant predictors of racial identity. Findings suggest that intervention programs targeting the racial identity of African American youth should include a parenting/family component that facilitates adaptive family functioning and that helps parents model culturally specific coping strategies for their children.
Significance of Individuation in Adult Child–Parent Relationships
Authors: Buhl Heike M.
Published: August 2007

This study investigates the significance of adult children's individuation for the adult child—parent relationship. Following Youniss, individuation was assessed via its dimensions of both connectedness and individuality. A sample of 349 participants between 20 and 47 years of age were given questionnaires containing scales from the Network of Relationships Inventory among others. Individuation predicted satisfaction, intimacy, and conflict. The combination of connectedness and individuality did not have any impact on relationship quality. The significance of children's individuation did not differ between young and middle-aged adults.
Qualitative insights into the use of expressive body movement in solo piano performance: a case study approach
Authors: Davidson Jane W.
Published: August 2007

This article is a contribution to the psychology of performance, investigating the role of body movements both globally and locally in expressive musical performance. A case study of a single pianist is used to explore qualitative similarities and differences within and across different performances of a Beethoven bagatelle. Using observational analyses of the performance movements, the results reveal that the performer uses particular movement shapes that are specific and identifiable `expressive locations' within the context of a whole performance. These movement shapes cannot simply be categorized as being either intention specific or musical structure specific, for there are movement shapes common to locations across different performances and different locations within a performance. These expressive movements have some consistency over time, with the locations of the expression being common, but the movements being used flexibly within and across manner and time. The results are theorized in terms of how these movements may be produced.
Singers' recall for the words and melody of a new, unaccompanied song
Authors: Ginsborg Jane , Sloboda John A.
Published: August 2007

The nature of the relationship between words and music in memory has been studied in a variety of ways, from investigations of listeners' recall for the words of songs stored in long-term memory to recall for novel information set to unfamiliar melodies. We asked singers to perform an unaccompanied song from memory following deliberate learning and memorization of the words and melody separately and together. Participants with high levels of musical expertise gave more accurate and fluent performances than those with lower levels of musical expertise, but only when they had memorized the words and melody together. While some errors were conjoint, such that erroneous recall of one component — words or melody — affected recall for the other, a higher proportion were separate, such that participants were able to preserve one component when they recalled the other erroneously. Words and melody are thus recalled in association with one another, so that retrieving one enables retrieval of the other, but are not integrated to the extent that failure to recall one accurately invariably results in failure to recall the other. Finally, more hesitations were made at the ends of phrases than at the start or mid-phrase, suggesting that the formal structure of a song provides a framework for recall. In conclusion, memorizing words and melody together is an effective strategy, but perhaps only for singers with high levels of musical expertise.
Lifestyle correlates of musical preference: 3. Travel, money, education, employment and health
Authors: North Adrian C. , Hargreaves David J.
Published: August 2007

Several studies indicate that musical preferences provide a means of discriminating between social groups, and suggest indirectly that musical preferences should correlate with a variety of different lifestyle choices. In this study, 2532 participants responded to a questionnaire asking them to state their musical preference and also to provide data on various social class-related aspects of their lifestyle (namely travel, personal finances, education, employment, health, and drinking and smoking). Numerous associations existed between musical preference and these aspects of participants' lifestyle. The nature of these associations indicated that liking for `high-art' music was indicative of a lifestyle of the upper-middle and upper classes, whereas liking for `low-art' music was indicative of a lifestyle of the lower-middle and lower classes. Issues concerning causality are discussed with reference to the likely complex interaction of numerous factors.
The influence of emotion, locus of emotion and familiarity upon preference in music
Authors: Schubert Emery
Published: August 2007

This study reports an empirical investigation of the influence of felt (internal locus — IL) emotion versus expressed (external locus — EL) emotion upon preference in music. Sixty-fve participants rated IL and EL of emotions for fve pieces of romantic western art music. For each locus task `emotional strength', `valence', `arousal' and `dominance' were rated and converted into magnitude scores. Ratings of familiarity and preference were also collected. Gap across emotion loci (GAEL) was calculated overall — which combined GAEL scores in polar-coordinate emotion-space, and for each dimension. Familiarity, felt emotional strength and overall GAEL explained 46.9 percent of the variance in preference. Both IL and EL negative valence were correlated with preference suggesting enjoyment of negative emotion in music through dissociation. The study suggests that the way music makes the listener feel is more important in determining enjoyment than noticing the emotion the music is trying to convey. Also, matching of IL and EL emotions (i.e. minimizing GAEL) is more preferred than when IL emotions are lower in magnitude than EL. Hence two principles of enjoyment are identifed in this study: (1) dissociation and (2) GAEL.
Distinguishing Juvenile Homicide From Violent Juvenile Offending
Authors: DiCataldo Frank , Everett Meghan
Published: August 2007

Juvenile homicide is a social problem that has remained a central focus within juvenile justice research in recent years. The term juvenile murderer describes a legal category, but it is purported to have significant scientific meaning. Research has attempted to conceptualize adolescent murderers as a clinical category that can be reliably distinguished from their nonhomicidal counterparts. This study examined 33 adolescents adjudicated delinquent or awaiting trial for murder and 38 adolescents who committed violent, nonhomicidal offenses to determine whether the two groups differed significantly on family history, early development, delinquency history, mental health, and weapon possession variables. The nonhomicide group proved more problematic on many of these measures. Two key factors did distinguish the homicide group: These adolescents endorsed the greater availability of guns and substance abuse at the time of their commitment offenses. The significance of this finding is discussed, and the implications for risk management and policy are reviewed.
Eliciting Cognitions of Strategizing Using Advanced Repertory Grids in a World Constructed and Reconstructed
Authors: Wright Robert P.
Published: August 2007

Previous application of the repertory grid technique in the strategy field has been noteworthy. However, all have been imprisoned by their adherence to strict element choice based on grid protocol. Elements in past studies have either focused on all competitor companies, or all strategic decisions, or all decision makers, or all strategic issues, inter alia, in an effort to learn more about how strategists see, interpret, and make sense of their strategy experiences. This research note outlines how current strategy research can be advanced by the use of more heterogeneous elements for grid applications, hence allowing researchers to go deeper into eliciting more complex strategic cognitions on how strategy is crafted and recrafted in a world constructed and reconstructed.
Electrical sliding wear property of Al2O3 particle reinforced Cu–Cr–Zr matrix composite
Authors: Zhan Y. Z. , Wang Y. , Yu Z. W. , Xu Y. F. , Xie H. F. , Shi X. B.
Published: August 2007

Al2O3 particle reinforced Cu–Cr–Zr matrix composite was fabricated through a powder metallurgy plus hot extrusion route, with water atomised Cu–Cr–Zr powder as the starting materials. The electrical sliding wear property was investigated using a pin on disc type wear apparatus in air at room temperature (20°C) compared with the matrix alloy. The results show that arc erosion and mechanical wear were the dominant wear mechanism when sliding under the electrical field. The wear rates increased gradually with increasing electrical current, owing to the augment of electrical erosive degree. Incorporation of Al2O3 reinforcement increased the mechanical properties and then effectively decreased the materials loss induced by both electric arc discharge and adhesion wear. As a result, the Al2O3/Cu–Cr–Zr composite has high electrical sliding wear resistance and would be a promising candidate for the electrical sliding contact fields.
Quantitative metallography of deformed grains
Authors: Zhu Q. , Sellars C. M. , Bhadeshia H. K. D. H.
Published: August 2007

The effect of plastic deformation on the grain boundary surface area per unit volume and edge length per unit volume is examined using two methods. The first by applying homogeneous deformations to tetrakaidecahedra in a variety of orientations and the second by using the principles of stereology. It is shown that the methods produce essentially identical results. It is now possible to calculate changes in the grain parameters as a function of a variety of deformations, for combinations of deformations, for complex deformations and for cases where it is not necessary to assume an idealised grain microstructure.
Microstructure and phase constitution near interface of Cu/Al vacuum brazing
Authors: Xia C. Z. , Li Y. J. , Wang J. , Ma H. J.
Published: August 2007

Dissimilar metals of copper (T2) and aluminium (1035) were brazed by vacuum brazing technology. Microstructure and phase constitution for the Cu/Al vacuum brazing were studied by means of metallography, electron probe microanalyser and X-ray diffraction. Experiment results indicated that an obvious transition layer of copper based solution was formed near the interface of copper and braze metal. The brazing seam zone mainly consists of various solid solutions between many elements and a few intermetallic compounds which are hard and brittle. This is favourable to the enhancing of service performance of the Cu/Al brazed joint. Process parameters of vacuum brazing are: brazing temperature T=425°C, vacuum level=10−3 Pa, holding time t=15 min.
Melt flow velocity in high pressure die casting: Its effect on microstructure and mechanical properties in an Al–Si alloy
Authors: Gunasegaram D. R. , Finnin B. R. , Polivka F. B.
Published: August 2007

Analysis of as cast tensile specimens of Australian alloy CA313 (an equivalent of A380) made using the high pressure die casting process at three different melt flow velocities has revealed that increasing melt velocity resulted in a finer microstructure and a reduced pore volume fraction and, consequently, better mechanical properties. Mechanical properties are shown to increase more than proportionately with reducing pore volume fraction and the reason for this is demonstrated to be the contribution from the more refined microstructure. The gate used in the investigation was unusual in that its geometry encouraged and prolonged the shearing of the melt. It is proposed that the microstructure was refined by flow shear, the rate of which increased with melt velocity and consequently enhanced the fragmentation of the externally solidified α-Al grains and inclusions such as oxides, cold flakes and gas bubbles.
Mechanical strength of chip scale package with various underfills under accelerated thermal condition
Authors: Noh B.-I. , Lee B.-Y. , Jung S.-B.
Published: August 2007

The bending strength of chip scale package (CSP) with various underfills was evaluated under thermal shock condition. The maximum bending strength and deflection of package decreased with increasing number of thermal shock cycles. The bending strength of package increased with increasing glass transition temperature Tg and damping property of the underfill, while the bending deflection decreased with increasing Tg and damping property of the underfill.
CDDO induces granulocytic differentiation of myeloid leukemic blasts through translational up-regulation of p42 CCAAT enhancer–binding protein alpha
Authors: Koschmieder Steffen , D'Alò Francesco , Radomska Hanna , Schöneich Christine , Chang Ji Suk , Konopleva Marina , Kobayashi Susumu , Levantini Elena , Suh Nanjoo , Di Ruscio Annalisa , Voso Maria Teresa , Watt Julie C. , Santhanam Ramasamy , Sargin Bülent , Kantarjian Hagop , Andreeff Michael , Sporn Michael B. , Perrotti Danilo , Berdel Wolfgang E. , Müller-Tidow Carsten , Serve Hubert , Tenen Daniel G.
Published: August 2007

2-Cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) induces differentiation and apoptosis of tumor cells in vitro and in vivo. Here we assessed the effects of CDDO on CCAAT enhancer–binding protein alpha (CEBPA), a transcription factor critical for granulocytic differentiation. In HL60 acute myeloid leukemia (AML) cells, CDDO (0.01 to 2 μM) induces apoptosis in a dose-dependent manner. Conversely, subapoptotic doses of CDDO promote phagocytic activity and granulocytic-monocytic differentiation of HL60 cells through increased de novo synthesis of p42 CEBPA protein. CEBPA translational up-regulation is required for CDDO-induced granulocytic differentiation and depends on the integrity of the CEBPA upstream open reading frame (uORF). Moreover, CDDO increases the ratio of transcriptionally active p42 and the inactive p30 CEBPA isoform, which, in turn, leads to transcriptional activation of CEBPA-regulated genes (eg, GSCFR) and is associated with dephosphorylation of eIF2α and phosphorylation of eIF4E. In concordance with these results, CDDO induces a CEBPA ratio change and differentiation of primary blasts from patients with acute myeloid leukemia (AML). Because AML is characterized by arrested differentiation, our data suggest the inclusion of CDDO in the therapy of AML characterized by dysfunctional CEBPA expression.
C/EBPα binds and activates the PU.1 distal enhancer to induce monocyte lineage commitment
Authors: Yeamans Christine , Wang Dehua , Paz-Priel Ido , Torbett Bruce E. , Tenen Daniel G. , Friedman Alan D.
Published: August 2007

The PU.1 gene contains a 237–base pair distal enhancer located 14 kilobases upstream of its promoter. We have identified 2 sites within the PU.1 enhancer that strongly bind C/EBPα in a gel shift assay, and interaction with endogenous C/EBPα was confirmed by chromatin immunoprecipitation. Mutation of these DNA elements reduced activity of a distal enhancer-promoter construct 2- or 5-fold in a myeloid cell line, while mutation of a weaker C/EBPα-binding site located in the promoter minimally reduced activity in this context. These findings strengthen the link between C/EBPα and PU.1 expression. Reduction of C/EBPα activity in cases of acute myeloid leukemia may therefore contribute to transformation by reducing PU.1 levels. In addition, induction of PU.1 by C/EBPα during normal hematopoiesis may contribute to stem cell commitment to the myeloid lineages and further commitment to monopoiesis. Consistent with a requirement for C/EBPα induction of PU.1 during myeloid development, we demonstrate that C/EBPα induces monocytic development when expressed in PU.1+/+, PU.1+/−, or PU.1+/kd marrow myeloid progenitors but induces granulocyte lineage commitment in PU.1kd/kd cells lacking the PU.1 distal enhancer and does not induce either lineage in PU.1−/− cells.
Delayed immune reconstitution after cord blood transplantation is characterized by impaired thymopoiesis and late memory T-cell skewing
Authors: Komanduri Krishna V. , St. John Lisa S. , de Lima Marcos , McMannis John , Rosinski Steven , McNiece Ian , Bryan Susan G. , Kaur Indreshpal , Martin Sean , Wieder Eric D. , Worth Laura , Cooper Laurence J. N. , Petropoulos Demetrios , Molldrem Jeffrey J. , Champlin Richard E. , Shpall Elizabeth J.
Published: August 2007

Advances in immune assessment, including the development of T-cell receptor excision circle (TREC) assays of thymopoiesis, cytokine-flow cytometry assays of T-cell function, and higher-order phenotyping of T-cell maturation subsets have improved our understanding of T-cell homeostasis. Limited data exist using these methods to characterize immune recovery in adult cord blood (CB) transplant recipients, in whom infection is a leading cause of mortality. We now report the results of a single-center prospective study of T-cell immune recovery after cord blood transplantation (CBT) in a predominantly adult population. Our primary findings include the following: (1) Prolonged T lymphopenia and compensatory expansion of B and natural killer (NK) cells was evident; (2) CB transplant recipients had impaired functional recovery, although we did observe posttransplantation de novo T-cell responses to cytomegalovirus (CMV) in a subset of patients; (3) Thymopoietic failure characterized post-CBT immune reconstitution, in marked contrast to results in other transplant recipients; and (4) Thymopoietic failure was associated with late memory T-cell skewing. Our data suggest that efforts to improve outcomes in adult CB transplant recipients should be aimed at optimizing T-cell immune recovery. Strategies that improve the engraftment of lymphoid precursors, protect the thymus during pretransplant conditioning, and/or augment the recovery of thymopoiesis may improve outcomes after CBT.
Time-dependent changes in pulmonary surfactant function and composition in acute respiratory distress syndrome due to pneumonia or aspiration
Authors: Schmidt Reinhold , Markart Philipp , Ruppert Clemens , Wygrecka Malgorzata , Kuchenbuch Tim , Walmrath Dieter , Seeger Werner , Guenther Andreas
Published: August 2007

Background

Alterations to pulmonary surfactant composition have been encountered in the Acute Respiratory Distress Syndrome (ARDS). However, only few data are available regarding the time-course and duration of surfactant changes in ARDS patients, although this information may largely influence the optimum design of clinical trials addressing surfactant replacement therapy. We therefore examined the time-course of surfactant changes in 15 patients with direct ARDS (pneumonia, aspiration) over the first 8 days after onset of mechanical ventilation.

Methods

Three consecutive bronchoalveolar lavages (BAL) were performed shortly after intubation (T0), and four days (T1) and eight days (T2) after intubation. Fifteen healthy volunteers served as controls. Phospholipid-to-protein ratio in BAL fluids, phospholipid class profiles, phosphatidylcholine (PC) molecular species, surfactant proteins (SP)-A, -B, -C, -D, and relative content and surface tension properties of large surfactant aggregates (LA) were assessed.

Results

At T0, a severe and highly significant reduction in SP-A, SP-B and SP-C, the LA fraction, PC and phosphatidylglycerol (PG) percentages, and dipalmitoylation of PC (DPPC) was encountered. Surface activity of the LA fraction was greatly impaired. Over time, significant improvements were encountered especially in view of LA content, DPPC, PG and SP-A, but minimum surface tension of LA was not fully restored (15 mN/m at T2). A highly significant correlation was observed between PaO2/FiO2and minimum surface tension (r = -0.83; p < 0.001), SP-C (r = 0.64; p < 0.001), and DPPC (r = 0.59; p = 0.003). Outcome analysis revealed that non-survivors had even more unfavourable surfactant properties as compared to survivors.

Conclusion

We concluded that a profound impairment of pulmonary surfactant composition and function occurs in the very early stage of the disease and only gradually resolves over time. These observations may explain why former surfactant replacement studies with a short treatment duration failed to improve outcome and may help to establish optimal composition and duration of surfactant administration in future surfactant replacement studies in acute lung injury.
Maternal allergic contact dermatitis causes increased asthma risk in offspring
Authors: Lim Robert H , Arredouani Mohamed S , Fedulov Alexey , Kobzik Lester , Hubeau Cedric
Published: August 2007

Background

Offspring of asthmatic mothers have increased risk of developing asthma, based on human epidemiologic data and experimental animal models. The objective of this study was to determine whether maternal allergy at non-pulmonary sites can increase asthma risk in offspring.

Methods

BALB/c female mice received 2 topical applications of vehicle, dinitrochlorobenzene, or toluene diisocyanate before mating with untreated males. Dinitrochlorobenzene is a skin-sensitizer only and known to induce a Th1 response, while toluene diisocyanate is both a skin and respiratory sensitizer that causes a Th2 response. Both cause allergic contact dermatitis. Offspring underwent an intentionally suboptimal protocol of allergen sensitization and aerosol challenge, followed by evaluation of airway hyperresponsiveness, allergic airway inflammation, and cytokine production. Mothers were tested for allergic airway disease, evidence of dermatitis, cellularity of the draining lymph nodes, and systemic cytokine levels. The role of interleukin-4 was also explored using interleukin-4 deficient mice.

Results

Offspring of toluene diisocyanate but not dinitrochlorobenzene-treated mothers developed an asthmatic phenotype following allergen sensitization and challenge, seen as increased Penh values, airway inflammation, bronchoalveolar lavage total cell counts and eosinophilia, and Th2 cytokine imbalance in the lung. Toluene diisocyanate treated interleukin-4 deficient mothers were able to transfer asthma risk to offspring. Mothers in both experimental groups developed allergic contact dermatitis, but not allergic airway disease.

Conclusion

Maternal non-respiratory allergy (Th2-skewed dermatitis caused by toluene diisocyanate) can result in the maternal transmission of asthma risk in mice.
Automating document classification for the Immune Epitope Database
Authors: Wang Peng , Morgan Alexander A , Zhang Qing , Sette Alessandro , Peters Bjoern
Published: August 2007

Background

The Immune Epitope Database contains information on immune epitopes curated manually from the scientific literature. Like similar projects in other knowledge domains, significant effort is spent on identifying which articles are relevant for this purpose.

Results

We here report our experience in automating this process using Naïve Bayes classifiers trained on 20,910 abstracts classified by domain experts. Improvements on the basic classifier performance were made by a) utilizing information stored in PubMed beyond the abstract itself b) applying standard feature selection criteria and c) extracting domain specific feature patterns that e.g. identify peptides sequences. We have implemented the classifier into the curation process determining if abstracts are clearly relevant, clearly irrelevant, or if no certain classification can be made, in which case the abstracts are manually classified. Testing this classification scheme on an independent dataset, we achieve 95% sensitivity and specificity in the 51.1% of abstracts that were automatically classified.

Conclusion

By implementing text classification, we have sped up the reference selection process without sacrificing sensitivity or specificity of the human expert classification. This study provides both practical recommendations for users of text classification tools, as well as a large dataset which can serve as a benchmark for tool developers.
The utility of MAS5 expression summary and detection call algorithms
Authors: Pepper Stuart D , Saunders Emma K , Edwards Laura E , Wilson Claire L , Miller Crispin J
Published: August 2007

Background

Used alone, the MAS5.0 algorithm for generating expression summaries has been criticized for high False Positive rates resulting from exaggerated variance at low intensities.

Results

Here we show, with replicated cell line data, that, when used alongside detection calls, MAS5 can be both selective and sensitive. A set of differentially expressed transcripts were identified that were found to be changing by MAS5, but unchanging by RMA and GCRMA. Subsequent analysis by real time PCR confirmed these changes. In addition, with the Latin square datasets often used to assess expression summary algorithms, filtered MAS5.0 was found to have performance approaching that of its peers.

Conclusion

When used alongside detection calls, MAS5 is a sensitive and selective algorithm for identifying differentially expressed genes.
Specification of germ layer identity in the chick gastrula
Authors: Chapman Susan C , Matsumoto Kiyoshi , Cai Qin , Schoenwolf Gary C
Published: August 2007

Background

Chick definitive endoderm is an important source of signals that pattern the early embryo forming a central structure around which the body plan is constructed. Although the origin of definitive endoderm has been mapped in the chick, arising principally from rostral streak at elongating streak stages, it is not known when this layer first becomes fully committed to its germ layer fate, an important issue to resolve in light of its critical role in subsequent patterning of the early embryo.

Results

Through gene expression screening of chick gastrula, we identified molecular markers of definitive endoderm restricted to rostral (Sox17) and caudal (Gata5/6) regions, suggesting that at least two subpopulations of definitive endodermal cells exist during ingression. We show (1) that presumptive mesoderm cells migrate to the middle layer and remain mesenchymal when transplanted to rostral primitive streak, and prospective endoderm cells enter the lower layer and become epithelial when transplanted to caudal primitive streak; and (2) that presumptive endoderm cells and mesoderm cells lose normal gene expression (Sox17 and Wnt8c, respectively) when transplanted outside of their normal position of origin. Moreover, when rostral or caudal primitive streak segments are transplanted into rostral blastoderm isolates (RBIs), both types of transplants express Sox17 4–6 hours later–consistent with their new position, regardless of their presumptive germ layer origin–and prospective mesoderm transplants, which normally express Wnt8c, turn off expression, suggesting that signals within the rostral blastoderm induce endoderm gene expression, and repress mesoderm gene expression, during gastrulation.

Conclusion

Our results demonstrate that germ layer identity is fixed at the time populations of endoderm and mesoderm cells ingress through the primitive streak, whereas their gene expression patterns remain labile. In addition, our results show that inductive and repressive signals are present, and that these signals regulate gene expression of both ingressed endoderm and mesoderm cells. Thus, gastrula cells display elements of both pre-patterning and plasticity, with endoderm the first germ layer becoming committed to its fate during early gastrulation stages.
EGFR associated expression profiles vary with breast tumor subtype
Authors: Hoadley Katherine A , Weigman Victor J , Fan Cheng , Sawyer Lynda R , He Xiaping , Troester Melissa A , Sartor Carolyn I , Rieger-House Thais , Bernard Philip S , Carey Lisa A , Perou Charles M
Published: August 2007

Background

The epidermal growth factor receptor (EGFR/HER1) and its downstream signaling events are important for regulating cell growth and behavior in many epithelial tumors types. In breast cancer, the role of EGFR is complex and appears to vary relative to important clinical features including estrogen receptor (ER) status. To investigate EGFR-signaling using a genomics approach, several breast basal-like and luminal epithelial cell lines were examined for sensitivity to EGFR inhibitors. An EGFR-associated gene expression signature was identified in the basal-like SUM102 cell line and was used to classify a diverse set of sporadic breast tumors.

Results

In vitro, breast basal-like cell lines were more sensitive to EGFR inhibitors compared to luminal cell lines. The basal-like tumor derived lines were also the most sensitive to carboplatin, which acted synergistically with cetuximab. An EGFR-associated signature was developed in vitro, evaluated on 241 primary breast tumors; three distinct clusters of genes were evident in vivo, two of which were predictive of poor patient outcomes. These EGFR-associated poor prognostic signatures were highly expressed in almost all basal-like tumors and many of the HER2+/ER- and Luminal B tumors.

Conclusion

These results suggest that breast basal-like cell lines are sensitive to EGFR inhibitors and carboplatin, and this combination may also be synergistic. In vivo, the EGFR-signatures were of prognostic value, were associated with tumor subtype, and were uniquely associated with the high expression of distinct EGFR-RAS-MEK pathway genes.
New pleiotropic effects of eliminating a rare tRNA from Streptomyces coelicolor, revealed by combined proteomic and transcriptomic analysis of liquid cultures
Authors: Hesketh Andy , Bucca Giselda , Laing Emma , Flett Fiona , Hotchkiss Graham , Smith Colin P , Chater Keith F
Published: August 2007

Background

InStreptomyces coelicolor,bldAencodes the only tRNA for a rare leucine codon, UUA. This tRNA is unnecessary for growth, but is required for some aspects of secondary metabolism and morphological development. We describe a transcriptomic and proteomic analysis of the effects of deletingbldAon cellular processes during submerged culture: conditions relevant to the industrial production of antibiotics.

Results

At the end of rapid growth, a co-ordinated transient up-regulation of about 100 genes, including many for ribosomal proteins, was seen in the parent strain but not the ΔbldAmutant. Increased basal levels of the signal molecule ppGpp in the mutant strain may be responsible for this difference. Transcripts or proteins from a further 147 genes classified asbldA-influenced were mostly expressed late in culture in the wild-type, though others were significantly transcribed during exponential growth. Some were involved in the biosynthesis of seven secondary metabolites; and some have probable roles in reorganising metabolism after rapid growth. Many of the 147 genes were "function unknown", and may represent unknown aspects ofStreptomycesbiology. Only two of the 147 genes contain a TTA codon, but some effects ofbldAcould be traced to TTA codons in regulatory genes or polycistronic operons. Several proteins were affected post-translationally by thebldAdeletion. There was a statistically significant but weak positive global correlation between transcript and corresponding protein levels. Different technical limitations of the two approaches were a major cause of discrepancies in the results obtained with them.

Conclusion

Although deletion ofbldAhas very conspicuous effects on the gross phenotype, thebldAmolecular phenotype revealed by the "dualomic" approach has shown that only about 2% of the genome is affected; but this includes many previously unknown effects at a variety of different levels, including post-translational changes in proteins and global cellular physiology.
CD8α is expressed by human monocytes and enhances FcγR-dependent responses
Authors: Gibbings Derrick J , Marcet-Palacios Marcelo , Sekar Yokananth , Ng Marcus CY , Befus A Dean
Published: August 2007

Background

CD8α enhances the responses of antigen-specific CTL activated through TCR through binding MHC class I, favoring lipid raft partitioning of TCR, and inducing intracellular signaling. CD8α is also found on dendritic cells and rat macrophages, but whether CD8α enhances responses of a partner receptor, like TCR, to activate these cells is not known. TCR and FcR, use analogous or occasionally interchangeable signaling mechanisms suggesting the possibility that CD8α co-activates FcR responses. Interestingly, CD8α+ monocytes are often associated with rat models of disease involving immune-complex deposition and FcR-mediated pathology, such as arthritis, glomerulonephritis, ischaemia, and tumors. While rat macrophages have been shown to express CD8α evidence for CD8α expression by mouse or human monocytes or macrophages was incomplete.

Results

We detected CD8α, but not CD8β on human monocytes and the monocytic cell line THP-1 by flow cytometry. Reactivity of anti-CD8α mAb with monocytes is at least partly independent of FcR as anti-CD8α mAb detect CD8α by western blot and inhibit binding of MHC class I tetramers. CD8α mRNA is also found in monocytes and THP-1 suggesting CD8α is synthesized by monocytes and not acquired from other CD8α+ cell types. Interestingly, CD8α from monocytes and blood T cells presented distinguishable patterns by 2-D electrophoresis. Anti-CD8α mAb alone did not activate monocyte TNF release. In comparison, TNF release by human monocytes stimulated in a FcR-dependent manner with immune-complexes was enhanced by inclusion of anti-CD8α mAb in immune-complexes.

Conclusion

Human monocytes express CD8α. Co-engagement of CD8α and FcR enhances monocyte TNF release, suggesting FcR may be a novel partner receptor for CD8α on innate immune cells.
The Pseudomonas putida Lon protease is involved in N-acyl homoserine lactone quorum sensing regulation
Authors: Bertani Iris , Rampioni Giordano , Leoni Livia , Venturi Vittorio
Published: August 2007

Background

In Pseudomonas putida and Pseduomonas aeruginosa, the similar PpuR/RsaL/PpuI and LasR/RsaL/LasI acyl homoserine lactones (AHLs) quorum sensing (QS) systems have been shown to be under considerable regulation by other global regulators. A major regulator is the RsaL protein which strongly directly represses the transcription of the P. putida ppuI and P. aeruginosa lasI AHL synthases. In this study we screened a transposon mutant bank of P. putida in order to identify if any other regulators were involved in negative regulation of AHL QS.

Results

In our screen we identified three Tn5 mutants which displayed overproduction of AHLs in P. putida strain WCS358. Two of the mutants had a Tn5 located in the rsaL gene, whereas in one mutant the transposon was located in the lon protease gene. Lon proteases play important roles in protein quality control via degradation of misfolded proteins. It was determined that in the P. putida lon mutant, AHL levels, PpuR levels and ppuI promoter activity all increased significantly; we therefore postulated that PpuR is a target for Lon. The Lon protease had no effect on AHL production in P. aeruginosa.

Conclusion

The Lon protease is a negative regulator of AHL production in P. putida WCS358. The Lon protease has also been shown by others to influence AHL QS in Vibrio fischeri and Agrobacterium tumefaciens and can thus become an important regulator of AHL QS timing and regulation in bacteria.
Rapid clonal analysis of recurrent tuberculosis by direct MIRU-VNTR typing on stored isolates
Authors: Martín Ana , Herránz Marta , Serrano María Jesús Ruiz , Bouza Emilio , de Viedma Darío García
Published: August 2007

Background

The application of molecular tools to the analysis of tuberculosis has revealed examples of clonal complexity, such as exogenous reinfection, coinfection, microevolution or compartmentalization. The detection of clonal heterogeneity by standard genotyping approaches is laborious and often requires expertise. This restricts the rapid availability of Mycobacterium tuberculosis (MTB) genotypes for clinical or therapeutic decision-making. A new PCR-based technique, MIRU-VNTR, has made it possible to genotype MTB in a time frame close to real-time fingerprinting. Our purpose was to evaluate the capacity of this technique to provide clinicians with a rapid discrimination between reactivation and exogenous reinfection and whether MIRU-VNTR makes it possible to obtain data directly from stored MTB isolates from recurrent episodes.

Results

We detected differences, between the MIRUtypes of recurrent isolates in 38.5% (5/13) of the cases studied. These included cases of i) exogenous reinfection, often with more resistant strains, ii) likely examples of microevolution, leading to the appearance of new clonal variants and iii) a combination of microevolution, coinfection and competition.

Conclusion

MIRU-VNTR rapidly obtained clinically useful genotyping data in a challenging situation, directly from stored MTB isolates without subculturing them or purifying their DNA. Our results also mean that MIRU-VNTR could be applied for easy, rapid and affordable massive screening of collections of stored MTB isolates, which could establish the real dimension of clonal heterogeneity in MTB infection.
Peer support in type 2 diabetes: a randomised controlled trial in primary care with parallel economic and qualitative analyses: pilot study and protocol
Authors: Paul Gillian M , Smith Susan M , Whitford David L , O'Shea Eamon , O'Kelly Fergus , O'Dowd Tom
Published: August 2007

Background

Diabetes is a chronic illness, which requires the individual to assume responsibility for their own care with the aim of maintaining glucose and blood pressure levels as close to normal as possible. Traditionally self-management training for diabetes has been delivered in a didactic manner. In recent times alternatives to the traditional delivery of diabetes care have been investigated, for example, the concept of peer support which emphasises patient rather than professional domination. This paper describes the pilot study and protocol for a study that aims to evaluate the effectiveness of a peer support intervention for people with type 2 diabetes in a primary care setting.

Methods/Design

A pilot study was conducted to access the feasibility of a randomized controlled trial of a peer support intervention. We used the MRC Framework for the evaluation of complex interventions. Elements of the intervention were defined and the study protocol was finalized. In this cluster randomised controlled trial twenty general practices are assigned to control and intervention groups. Each practice compiles a diabetes register and randomly selects 21 patients. All practices implement a standardised diabetes care system. In the intervention group all practices recruit three peer supporters. The peer supporters are trained to conduct nine group meetings in their general practice over a period of two years. Each meeting has a structured component. The primary outcomes are blood pressure, total cholesterol, HBA1c and the Diabetes Well-being score. In addition to biophysical, psychosocial, economic and health service utilization data peer supporter activity and qualitative data are collected.

Discussion

Peer support is a complex intervention and evaluating such an intervention presents challenges to researchers. This study will evaluate whether a peer support programme for patients with type 2 diabetes improves biophysical and psychosocial outcomes and whether it is an acceptable, cost effective intervention in the primary care setting.

Trial registration

Current Controlled Trials ISRCTN42541690
Systematic review of information and support interventions for caregivers of people with dementia
Authors: Thompson Carl A , Spilsbury Karen , Hall Jill , Birks Yvonne , Barnes Colin , Adamson Joy
Published: August 2007

Background

Dementia is an important health and social care problem and is one of the main causes of disability in later life. The number of families affected by dementia will dramatically increase over the next five decades. Despite the implications for health and social care services in the future, the overwhelming majority of care for people with dementia takes place away from health care settings. Providing informal care for someone with dementia can be psychologically, physically and financially expensive and a range of health service interventions aimed at supporting and providing information to these carers has developed to help carers meet these demands. This review examines whether information and support interventions improve the quality of life of people caring for someone with dementia.

Methods

A systematic review examining evidence from randomised controlled trials in which technology, individualised or group-based interventions built around the provision of support and/or information were evaluated.

Results

Forty-four studies were included in the review. Controlling for the quality of the evidence, we found statistically significant evidence that group-based supportive interventions impact positively on psychological morbidity. However, whilst the improvement was unlikely to be due to chance, the clinical significance of this finding should be interpreted tentatively, due to the difficulties in interpreting the standardised mean difference as a measure of effect and the complex aetiology of depression. No evidence was found for the effectiveness of any other form of intervention on a range of physical and psychological health outcomes.

Conclusion

There is little evidence that interventions aimed at supporting and/or providing information to carers of people with dementia are uniformly effective. There is a pressing need to ensure that supportive interventions at the development stage are accompanied by good quality randomised evaluations in which outcomes that are important to clinicians and carers are measured.
Synthesis of two potential NK1-receptor ligands using [1-11C]ethyl iodide and [1-11C]propyl iodide and initial PET-imaging
Authors: Syvänen Stina , Eriksson Jonas , Genchel Tove , Lindhe Örjan , Antoni Gunnar , Långström Bengt
Published: August 2007

Background

The previously validated NK1-receptor ligand [O-methyl-11C]GR205171 binds with a high affinity to the NK1-receptor and displays a slow dissociation from the receptor. Hence, it cannot be used in vivo for detecting concentration changes in substance P, the endogenous ligand for the NK1-receptor. A radioligand used for monitoring these changes has to enable displacement by the endogenous ligand and thus bind reversibly to the receptor. Small changes in the structure of a receptor ligand can lead to changes in binding characteristics and also in the ability to penetrate the blood-brain barrier. The aim of this study was to use carbon-11 labelled ethyl and propyl iodide with high specific radioactivity in the synthesis of two new and potentially reversible NK1-receptor ligands with chemical structures based on [O-methyl-11C]GR205171.

Methods

[1-11C]Ethyl and [1-11C]propyl iodide with specific radioactivities of 90 GBq/μmol and 270 GBq/μmol, respectively, were used in the synthesis of [O-methyl-11C]GR205171 analogues by alkylation of O-desmethyl GR205171. The brain uptake of the obtained (2S,3S)-N-(1-(2- [1-11C]ethoxy-5-(3-(trifluoromethyl)-4H-1,2,4-triazol-4-yl)phenyl)ethyl)-2-phenylpiperidin-3-amine (I) and (2S,3S)-2-phenyl-N-(1-(2- [1-11C]propoxy-5-(3-(trifluoromethyl)-4H-1,2,4-triazol-4-yl)phenyl)ethyl)piperidin-3-amine (II) was studied with PET in guinea pigs and rhesus monkeys and compared to the uptake of [O-methyl-11C]GR205171.

Results

All ligands had similar uptake distribution in the guinea pig brain. The PET-studies in rhesus monkeys showed that (II) had no specific binding in striatum. Ligand (I) had moderate specific binding compared to the [O-methyl-11C]GR205171. The ethyl analogue (I) displayed reversible binding characteristics contrary to the slow dissociation rate shown by [O-methyl-11C]GR205171.

Conclusion

The propyl-analogue (II) cannot be used for detecting changes in NK1-ligand levels, while further studies should be performed with the ethyl-analogue (I).