bluuebunny/crossref_metadata_2025 huggingface dataset:
Design and Ballistic Testing of Ti—6Al—4V Matrix Composites
Authors: Yabei Gu  , Nesterenko Vitali F.
Published: July 2007

Ti—6Al—4V matrix composites enhanced by alumina tubes filled with boron carbide, alumina rods, and alumina plate is termed high gradient composite because of the big density differences among Ti—6Al—4V, alumina, and boron carbide materials. This high gradient composite has been developed for a theoretical study to help determine the best configuration for armor protection. This is the first attempt where materials are prepared using a powder processing method with the specific goal to address the ballistic performance. Hot isostatic pressing (HIP) was first used to manufacture ballistic grade Ti—6Al—4V alloy and high gradient composites incorporating Al2O3 rods, plates, and tubes filled with B4C powders. Processing parameters were investigated and optimized based on materials properties. An important feature of powder-based materials is the lack of texture in comparison with traditional material. Several configurations of this high gradient composite were designed and tested by long rod penetration tests. High gradient composite materials demonstrated new damage patterning features during the long rod projectile penetration process. These features include projectile deflection, self-sealing of the hole, and forced shear localization in the direction of 45° to the impact line caused by fracture of Al2O3 tubes on the initial stage of penetration process. Powder filled voids and rods induced volume distributed, highly heterogeneous pattern of damage initiated by cavities and their interactions. The test results are shown and analyzed in depth in this paper. The results prove that the powder-based approach can be used for processing of materials suitable for ballistic applications.
Everyday memory deficits in ecstasy-polydrug users
Authors: Montgomery Catharine , Fisk John E.
Published: July 2007

Recent research suggests that not only does the use of recreational drugs impact on working memory functioning, but more `everyday' aspects of memory (e.g. remembering to do something in the future) are also affected. Forty-three ecstasy-polydrug users and 51 non-ecstasy users were recruited from a university population. Each participant completed the Cognitive Failures Questionnaire (CFQ) and Everyday Memory Questionnaire (EMQ). Of these, 28 ecstasy-polydrug users and 35 non-ecstasy users completed the Prospective Memory Questionnaire (PMQ). In addition, an objective measure of cognitive failures (the CFQ-for-others) was completed by friends of participants. With the exception of the CFQ-for-others, in each regression equation, cannabis emerged as the only significant predictor of everyday and prospective memory deficits. Significant correlations were found between the different indicators of everyday memory and various measures of illicit drug use. Cannabis featured prominently in this respect. The present study provides further support for cannabis related deficits in aspects of everyday memory functioning. Ecstasy may aLso be associated with cognitive slips, but not to the same extent as cannabis.
Rehabilitation of Scapular Muscle Balance
Authors: Cools Ann M. , Dewitte Vincent , Lanszweert Frederick , Notebaert Dries , Roets Arne , Soetens Barbara , Cagnie Barbara , Witvrouw Erik E.
Published: July 2007

Background

Strengthening exercises for the scapular muscles are used in the treatment of scapulothoracic dysfunction related to shoulder injury. In view of the intermuscular and intramuscular imbalances often established in these patients, exercises promoting lower trapezius (LT), middle trapezius (MT), and serratus anterior (SA) activation with minimal activity in the upper trapezius (UT) are recommended.

Hypothesis

Of 12 commonly used trapezius strengthening exercises, a selection can be performed for muscle balance rehabilitation, based on a low UT/LT, UT/MT, or UT/SA muscle ratio.

Study Design

Controlled laboratory study.

Methods

Electromyographic activity of the 3 trapezius parts and the SA was measured in 45 healthy subjects performing 12 commonly described scapular exercises, using surface electromyography.

Results

For each intramuscular trapezius ratio (UT/LT, UT/MT), 3 exercises were selected for restoration of muscle balance. The exercises side-lying external rotation, side-lying forward flexion, prone horizontal abduction with external rotation, and prone extension were found to be the most appropriate for intramuscular trapezius muscle balance rehabilitation. For the UT/SA ratio, none of the exercises met the criteria for optimal intermuscular balance restoration.

Conclusion

In cases of trapezius muscle imbalance, some exercises are preferable over others because of their low UT/LT and UT/MT ratios.

Clinical Relevance

In the selection of rehabilitation exercises, the clinician should have a preference for exercises with high activation of the LT and MT and low activity of the UT.
Building Social Capital Through an `Active Community Club'
Authors: Burnett Cora
Published: July 2007

The building of social capital at community level is explored by assessing the impact of the Australia Africa 2006 Sport Development Programme's Active Community Clubs Initiative as a catalyst of developing networks and active citizenship in the impoverished rural village of Tshabo, in the Easter Cape Province of South Africa. Main paradigms of neo-classical capital theory (Bourdieu), Coleman's rational choice theory, network theory, Putnam's framework of civil engagement and Verweel's multi-level analysis inform the conceptual framework for analysis. Pre- and post-impact assessments utilized interviews (18 major stakeholders) and focus group sessions during three intervals over a 13-month period which included a representative sample of community leaders ( n = 13), households ( n = 47), volunteer coaches and administrators ( n = 28) and participants who participated in the programme ( n = 121). Participation in the Active Community Club's programmes interfaced with other normative social institutional spheres to generate social capital at an individual and community level.
The Lightness Of Being `Gaie'
Authors: Ravel Barbara , Rail Geneviève
Published: July 2007

In this article, we explore the narratives of 14 young Francophone women from Montreal (Quebec, Canada) competing in team sports and identifying as `gay', `lesbian', `bisexual' or refusing labels altogether. We seek to gain a better understanding of these young women's discursive constructions of gender and sexuality as well as of their performative acts in sport and in other milieus. We submitted their narratives to a thematic analysis which was followed by a critical discourse analysis inspired by poststructuralism. Our findings suggest that the participants generally positioned themselves as ` gaie' (as opposed to lesbian or queer), which seems specific to Quebec. By emphasizing the lightness of being gaie in sport, the participants relied on an alternative discourse that tends to be positive towards gaie sexuality. Moreover, by constructing gaie sexuality as a more `feminine', less visible and consequently less disturbing version of lesbian sexuality, these sportswomen also articulated dominant discourses that reproduce lesbo/butch-phobic ideas. We also show the participants' unstable and changing subjectivity as we highlight the contradictions in their discursive constructions of gender and sexuality.
Health as Balance for the Sto:lo Coast Salish
Authors: Labun Evelyn R. , Emblen Julia
Published: July 2007

The purpose of this study was to examine the concept of health for the Sto:lo Coast Salish of the Pacific Northwest and describe their ways of being healthy within their specific context, considering the climate, the resources of their natural environment, and their spiritual heritage. This study, using a grounded theory approach, focused on the meaning of health for the Sto:lo. A sample of 18 participants and two cultural experts, using the constant comparison method and dimensional analysis, yielded three themes. Health as “balance,” spirituality as “it's an ongoing thing,” and transitions as “those times of change” were the resulting themes. Nurses, who take the themes into account when providing care, will be more culturally competent.
The State of Measurement of Self-Esteem of African American Women
Authors: Hatcher Jennifer
Published: July 2007

This article critically reviews the state of measurement of self-esteem in African American women. The Rosenberg Self-Esteem Scale, the Tennessee Self-Concept Scale, and the Coopersmith Self-Esteem Inventory are three commonly used measures. However, their validity for African American women has not been adequately tested. Given the unique nature of the self-esteem of this group, related to experiences of racism and sexism, the accurate measurement of this construct is important. This review provided support for the internal consistency of each measure with alpha coefficients ranging from .74 to .87. However, the validity of the measures was not fully supported. Suggestions for further research specific to the unique needs of this population are discussed.
Nursing Care of AIDS Patients in Uganda
Authors: Fournier Bonnie , Kipp Walter , Mill Judy , Walusimbi Mariam
Published: July 2007

This article reports the findings from a participatory action research study concerning the experience of Ugandan nurses caring for individuals with HIV illness. Six key informants from government and non-governmental organizations were interviewed using a semistructured format. Six nurses from a large national referral hospital in Kampala, Uganda, participated in 10 focus group meetings during a period of 11 months. In-depth interviews, focus groups, and photovoice were used to collect the data. Findings indicate that nurses faced many challenges in their daily care, including poverty, insufficient resources, fear of contagion, and lack of ongoing education. Nurses experienced moral distress due to the many challenges they faced during the care of their patients. Moral distress may lead nurses to quit their jobs, which would exacerbate the acute shortage of nurses in Uganda. This study provides important knowledge for guiding clinical practice and nursing education in resource-constrained countries like Uganda.
Who gets it?
Authors: Weiler Jim
Published: July 2007

A tension exists between institutional requirements of reflective thinking among teachers and the realities of the classroom. The former is often ambiguous, complex, and difficult. Without laying much groundwork, there is little incentive for student teachers to take on such a challenge. This article offers four vignettes of student teachers' attempts at conducting action research in a Zimbabwean context. With minimal familiarity, preparation, and support, each student's success varied: one student completed the task without a deeper understanding; a second did not conduct much of the research; another was able to integrate the research process with his teaching practice; and the last student already possessed the skills and disposition needed to be successful. This article helps name some of the common enablers and obstacles to promoting reflexive thinking among student teachers. It starts first and foremost by establishing issues that need to be part of any dialogue on the meanings and ideals of action research in support of teaching in a development context.
Participatory action research and the culture of fear
Authors: Pyrch Timothy
Published: July 2007

There is much fear in the world and we must attend to it directly if we are to be relevant to the human condition. Participatory action research (PAR) is equipped to take up the challenge presented by this fear by drawing upon a rich liberatory tradition in the adult education movement, a passionate commitment to equality and justice, and the practical skills to investigate reality in order to transform it. As an adult educator, I have found a natural fit between PAR and my understanding of the community development concept as a guide for creating community as a space for mutuality and freedom; an inclusive and safe place, as a sanctuary in times of alienation and fear. For me, PAR is a form of resistance to all forms of control limiting ourfreedom to pursue a reasoned, compassionate, committed and democratic knowledge base. It can be an antidote to oppressive forces. This is in keeping with our liberatory tradition in the adult education movement which provided fertile ground for PAR. How do these radical variations play out in the notoriously conservative province of Alberta? How can a practitioner acquire the confidence and courage to act upon the hope of PAR?
Pedagogy and Performance in Black Popular Culture
Authors: Dimitriadis Greg
Published: July 2007

Rap artists, in the wake of rap's popular crossover success in the early 1980s, explicitly defined rap as a pedagogical idiom. Lyrics became more complex while epithets of poet and artist proliferated. All of this came as a parallel phenomenon to the emergence of a discourse about rap and its his tories and traditions—a discourse that would have seemed anomalous early on. Drawing on theory and research in performance studies, this arti cle critiques efforts to place rap into ready-made historical trajectories (e.g., Afrocentric or postmodern ones), and focuses on the discourse that rap artists themselves created or performed about rap music and its history at this critical juncture. In redefining notions of "the popular," rap estab lished itself as a kind of alternative curriculum, raising key questions about who needs to be educating whom, and why.
My Tuesdays With Morrie
Authors: Weems Mary E.
Published: July 2007

Mitch Albom's book, Tuesdays with Morrie: An Old Man, A Young Man and Life's Greatest Lesson (1997), entered the poet's life during a time when death and terminal illness were affecting her immediate family and one of her closest friends. This life-affirming case study, the result of a series of taped conversations between Albom and his beloved undergraduate professor, the late Morrie Schwartz, represents good art in the Deweyian sense because it flows from everyday life experience. It inspired the poet to interact with the book through her own hybrid African American cultural lens and create new work.
Critical Ethnography in the Time of Globalization: Toward a New Concept of Site
Authors: Gille Zsuzsa
Published: July 2007

The purpose of this article is to provide one possible answer to the question of how ethnography can remain useful in the age of globalization in which the assumption of a well-bounded site is harder to maintain than ever. The author bases the answer on the example of research, a historical study of the concept of waste involving the case study of a siting controversy around a planned waste incinerator in Hungary. The author argues that George Marcus's solution to the problem above is limited and instead suggests to redefine the concept of ethnographic site by adopting Doreen Massey's global sense of place. The article tackles two political implications of this choice: the subject position of the ethnographer in multiple fields and the consequences for a critical environmental sociology.
Consumed With the Past: Nostalgia, Memory, and Ghostly Encounters at the Picture Palace
Authors: Jones Janna
Published: July 2007

A preserved movie theater in Tampa, Florida, provides an interpretive site for investigating and untangling the meanings of popular memory, nostal gia, and ghosts. By making sense of interviews with theater employees and patrons, chasing a ghost, and investigating personal experiences in the the ater, the author discovers that the past that is located within the auditorium is the collision of both sanctioned, fixed histories and individual, wander ing meanings. Although nostalgia may help to guide consumption of the past, the storied particulars of individuals also help create the meanings of history. Ghost stories become a metaphor for the intersection between these fixed and wandering meanings. The author argues that this metaphor helps us make sense of the many contradictions that we confront as we consume the past.
A Summer of Double Super Secrecy
Authors: Bratich Jack Z.
Published: July 2007

This article examines the news events of summer 2005, focusing on the Valerie Plame leak investigation, the revealing of the identity of Watergate's Deep Throat, and various stories pertaining to the Terror/War. In analyzing the ways evidence is deployed rhetorically, it begins to question an oppositional strategy that relies on publicity and exposure. The article instead calls for a refocus on the "secret sphere" of politics (especially within journalism), which is not the same as eliminating secrecy in the name of the public sphere. Finally, cultural studies' strategic capacities are assessed with regard to evidence, secrecy, and revelation.
Activation of plasminogen into plasmin at the surface of endothelial microparticles: a mechanism that modulates angiogenic properties of endothelial progenitor cells in vitro
Authors: Lacroix Romaric , Sabatier Florence , Mialhe Agnès , Basire Agnès , Pannell Ralph , Borghi Hélène , Robert Stephane , Lamy Edouard , Plawinski Laurent , Camoin-Jau Laurence , Gurewich Victor , Angles-Cano Eduardo , Dignat-George Françoise
Published: July 2007

The regulation of plasmin generation on cell surfaces is of critical importance in the control of vascular homeostasis. Cell-derived microparticles participate in the dissemination of biological activities. However, their capacity to promote plasmin generation has not been documented. In this study, we show that endothelial microparticles (EMPs) from tumor necrosis factor α (TNFα)–stimulated endothelial cells served as a surface for the generation of plasmin. The generation of plasmin involved expression of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) at the surface of EMPs and was further increased by their ability to bind exogenous uPA on uPAR. Plasminogen was activated at the surface of EMPs in a dose-dependent, saturable, and specific manner as indicated by the inhibition of plasmin formation by ϵ-amino-caproic acid (ϵ-ACA) and carboxypeptidase B. EMP-induced plasmin generation affects tube formation mediated by endothelial progenitor cells. However, low amounts of EMPs increased tube formation, whereas higher concentrations inhibited it. Prevention of these effects by inhibitors of either uPA or plasmin underscore the key role of EMP-induced plasmin generation. In conclusion, we demonstrated that EMPs act as vectors supporting efficient plasmin generation and dissemination, a new pathway in the regulation of endothelial proteolytic activities with potential involvement in inflammation, angiogenesis, and atherosclerosis.
Prognostic and oncogenic relevance of TLX1/HOX11 expression level in T-ALLs
Authors: Bergeron Julie , Clappier Emmanuelle , Radford Isabelle , Buzyn Agnès , Millien Corinne , Soler Gwendoline , Ballerini Paola , Thomas Xavier , Soulier Jean , Dombret Hervé , Macintyre Elizabeth A. , Asnafi Vahid
Published: July 2007

TLX1 is a homeodomain transcription factor generally associated with a favorable outcome in T-cell acute lymphoblastic leukemia (T-ALL). However, the molecular mechanisms of TLX1 deregulation remain unclear and various transcript levels in the absence of 10q24 abnormalities have been reported. A reproducible and accurate delineation of TLX1+ T-ALL will be necessary for proper therapeutic stratification. We have studied 264 unselected T-ALLs (171 adults and 93 children) and show that T-ALLs expressing high levels of TLX1 (n = 35, 13%), defined as a real-time quantitative polymerase chain reaction (RQ-PCR) level of TLX1 greater than 1.00 ABL, form a homogeneous oncogenic group, based on their uniform stage of maturation arrest and oncogenetic and transcriptional profiles. Furthermore, TLX1-high T-ALLs harbor molecular TLX1 locus abnormalities in the majority (31/33), a proportion largely underestimated by standard karyotypic screening. T-ALLs expressing TLX1 at lower levels (n = 57, 22%) do not share these characteristics. Prognostic analysis within the adult LALA94 and GRAALL03 prospective protocols demonstrate a better event-free survival (P = .035) and a marked trend for longer overall survival (P = .059) for TLX1-high T-ALLs, while the expression of lower levels of TLX1 does not impact on prognosis. We propose that TLX1+ T-ALLs be defined as cases expressing TLX1/ABL ratios greater than 1 and/or demonstrating TLX1 rearrangement. Therapeutic modification should be considered for those patients.
AIDS patients have increased surfactant protein D but normal mannose binding lectin levels in lung fluid
Authors: Jambo Kondwani C , French Neil , Zijlstra Ed , Gordon Stephen B
Published: July 2007

Background

Surfactant protein D (SP-D) and Mannose Binding Lectin (MBL) are collectins that have opsonic and immunoregulatory functions, are found in lung fluid and interact with the human immunodeficiency virus (HIV). We compared collectin levels in lung fluid and serum from HIV infected and normal subjects to determine if alterations in lung collectin levels were associated with HIV infection and might result in increased susceptibility to other pulmonary infections.

Methods

Blood and bronchoalveolar lavage samples were collected from 19 HIV-infected individuals and 17 HIV-uninfected individuals, all with normal chest X ray at time of study. HIV viral loads and peripheral blood CD4+ T cell counts were measured in all subjects. SP-D was measured in lung fluid, and MBL in both lung fluid and serum.

Results

SP-D levels were not significantly different in lung fluid from HIV-uninfected (median 406.72 ng/ml) and HIV-infected individuals with high CD4 count (CD4 >200) (median 382.60 ng/ml) but were elevated in HIV-infected individuals with low CD4 count (median 577.79 ng/ml; Kruskall Wallis p < 0.05). MBL levels in serum were not significantly different between HIV-uninfected and HIV-infected individuals (median 1782.70 ng/ml vs 2639.73 ng/ml) and were not detectable in lung fluid.

Conclusion

SP-D levels are increased in lung fluid from AIDS patients but not in patients with early HIV infection. MBL levels are not altered by HIV infection or AIDS. There is no evidence that altered pulmonary collectin levels result in susceptibility to infection in these patients.
MASPECTRAS: a platform for management and analysis of proteomics LC-MS/MS data
Authors: Hartler Jürgen , Thallinger Gerhard G , Stocker Gernot , Sturn Alexander , Burkard Thomas R , Körner Erik , Rader Robert , Schmidt Andreas , Mechtler Karl , Trajanoski Zlatko
Published: July 2007

Background

The advancements of proteomics technologies have led to a rapid increase in the number, size and rate at which datasets are generated. Managing and extracting valuable information from such datasets requires the use of data management platforms and computational approaches.

Results

We have developed the MAss SPECTRometry Analysis System (MASPECTRAS), a platform for management and analysis of proteomics LC-MS/MS data. MASPECTRAS is based on the Proteome Experimental Data Repository (PEDRo) relational database schema and follows the guidelines of the Proteomics Standards Initiative (PSI). Analysis modules include: 1) import and parsing of the results from the search engines SEQUEST, Mascot, Spectrum Mill, X! Tandem, and OMSSA; 2) peptide validation, 3) clustering of proteins based on Markov Clustering and multiple alignments; and 4) quantification using the Automated Statistical Analysis of Protein Abundance Ratios algorithm (ASAPRatio). The system provides customizable data retrieval and visualization tools, as well as export to PRoteomics IDEntifications public repository (PRIDE). MASPECTRAS is freely available at http://genome.tugraz.at/maspectras

Conclusion

Given the unique features and the flexibility due to the use of standard software technology, our platform represents significant advance and could be of great interest to the proteomics community.
Absence of glaucoma in DBA/2J mice homozygous for wild-type versions of Gpnmb and Tyrp1
Authors: Howell Gareth R , Libby Richard T , Marchant Jeffrey K , Wilson Lawriston A , Cosma Ioan M , Smith Richard S , Anderson Michael G , John Simon WM
Published: July 2007

Background

The glaucomas are a common but incompletely understood group of diseases. DBA/2J mice develop a pigment liberating iris disease that ultimately causes elevated intraocular pressure (IOP) and glaucoma. We have shown previously that mutations in two genes, Gpnmb and Tyrp1, initiate the iris disease. However, mechanisms involved in the subsequent IOP elevation and optic nerve degeneration remain unclear.

Results

Here we present new mouse strains with Gpnmb and/or Tyrp1 genes of normal function and with a DBA/2J genetic background. These strains do not develop elevated IOP or glaucoma with age.

Conclusion

These strains provide much needed controls for studying pathogenic mechanisms of glaucoma using DBA/2J mice. Given the involvement of Gpnmb and/or Tyrp1 in areas such as immunology and tumor development and progression, these strains are also important in other research fields.
Differential gene expression in femoral bone from red junglefowl and domestic chicken, differing for bone phenotypic traits
Authors: Rubin Carl-Johan , Lindberg Johan , Fitzsimmons Carolyn , Savolainen Peter , Jensen Per , Lundeberg Joakim , Andersson Leif , Kindmark Andreas
Published: July 2007

Background

Osteoporosis is frequently observed among aging hens from egg-producing strains (layers) of domestic chicken. White Leghorn (WL) has been intensively selected for egg production and it manifests striking phenotypic differences for a number of traits including several bone phenotypes in comparison with the wild ancestor of chicken, the red junglefowl (RJ). Previously, we have identified four Quantitative Trait Loci (QTL) affecting bone mineral density and bone strength in an intercross between RJ and WL. With the aim of further elucidating the genetic basis of bone traits in chicken, we have now utilized cDNA-microarray technology in order to compare global RNA-expression in femoral bone from adult RJ and WL (five of each sex and population).

Results

When contrasting microarray data for all WL-individuals to that of all RJ-individuals we observed differential expression (False discovery rate adjusted p-values < 0.015) for 604 microarray probes. In corresponding male and female contrasts, differential expression was observed for 410 and 270 probes, respectively. Altogether, the three contrasts between WL and RJ revealed differential expression of 779 unique transcripts, 57 of which are located to previously identified QTL-regions for bone traits. Some differentially expressed genes have previously been attributed roles in bone metabolism and these were: WNT inhibitory factor 1 (WIF1), WD repeat-containing protein 5 (WDR5) and Syndecan 3 (SDC3). Among differentially expressed transcripts, those encoding structural ribosomal proteins were highly enriched and all 15 had lower expression in WL.

Conclusion

We report the identification of 779 differentially expressed transcripts, several residing within QTL-regions for bone traits. Among differentially expressed transcripts, those encoding structural ribosomal proteins were highly enriched and all had lower expression levels in WL. In addition, transcripts encoding four translation initiation and translation elongation factor proteins also had lower expression levels in WL, possibly indicating perturbation of protein biosynthesis pathways between the two populations. Information derived from this study could be relevant to the bone research field and may also aid in further inference of genetic changes accompanying animal domestication.
Variability in SCC mecN1 spreading among injection drug users in Zurich, Switzerland
Authors: Ender Miriam , Berger-Bächi Brigitte , McCallum Nadine
Published: July 2007

Background

An extremely low level methicillin resistant Staphylococcus aureus (MRSA) belonging to ST45, circulates among intravenous drug users in the Zurich area. This clone can be misinterpreted as an MSSA by phenotypic oxacillin resistance tests, although it carries a staphylococcal cassette chromosome mec (SCCmec) element encoding a functional mecA gene and it produces PBP2a.

Results

This clone carried a new 45.7-kb element, termed SCCmec
N1, containing a class B mec complex (mecA- ΔmecR1::IS1272), a truncated Tn4003 harbouring the dfrA gene, and a fusB1 gene, conferring methicillin, trimethoprim and low level fusidic acid resistance, respectively. In addition to the two insertion site sequences (ISS) framing the SCCmec, a third ISS (ISS*) was identified within the element. SCCmec
N1 also harboured two distinct ccrAB complexes belonging to the class 4 subtype, both of which were shown to be active and to be able to excise the SCCmec
N1 or parts thereof. Slight variations in the SmaI-PFGE pattern of the clinical MRSA isolates belonging to this clone were traced back to differences in the sizes of the SCCmec J2 regions and/or to a 6.4-kb deletion extending from ISS* to the right end ISS. This latter deletion led to a variant right SCCmec-chromosomal junction site. MRSA clones carrying the shorter SCCmec with the 6.4-kb deletion were usually ciprofloxacin resistant, while strains with the complete SCCmec
N1 were co-trimoxazole resistant or had no additional resistances. This suggested that the genetic backbone of the host S. aureus, although identical by PFGE pattern, had at some stage diverged with one branch acquiring a sulfonomide resistance mutation and the other ciprofloxacin resistance.

Conclusion

This description of the structure and variations of SCCmec
N1 will allow for quicker and easier molecular detection of this clone and monitoring of its spread.
Antisense RNA decreases AP33 gene expression and cytoadherence by T. vaginalis
Authors: Mundodi V , Kucknoor AS , Alderete JF
Published: July 2007

Background

Host parasitism by Trichomonas vaginalis is complex. Adherence to vaginal epithelial cells (VECs) is mediated by surface proteins. We showed before that antisense down-regulation of expression of adhesin AP65 decreased amounts of protein, which lowered levels of T. vaginalis adherence to VECs. We now perform antisense down-regulation of expression of the ap33 gene to evaluate and confirm a role for AP33 in adherence by T. vaginalis. We also used an established transfection system for heterologous expression of AP33 in T. foetus as an additional confirmatory approach.

Results

We successfully select stable trichomonads with sense (S) and antisense (AS) plasmids. RT-PCR confirmed decreased amounts of ap33 mRNA in AS-transfected parasites, and decreased amounts of AP33 had no effect on growth and viability when compared to wild-type (wt) trichomonads. Immunoblots of proteins from AS-transfectants gave significant decreased amounts of functional AP33 capable of binding to host cells compared to wt- and S-transfected trichomonads. As expected, AS-transfectants had lower levels of adherence to VECs, which was related to reduction in surface expression of AP33. Stable expression of T. vaginalis AP33::HA fusion in T. foetus was confirmed by immunoblots and fluorescence. The episomally-expressed surface AP33::HA fusion increased adherence of trichomonads to human VECs, which was abrogated with anti-AP33 serum.

Conclusion

These results using both antisense inhibition of gene expression and AP33 synthesis and the heterologous expression of AP33 in T. foetus confirms a role for this protein as an adhesin in T. vaginalis.
Regions important for the adhesin activity of Moraxella catarrhalis Hag
Authors: Bullard Brian , Lipski Serena , Lafontaine Eric R
Published: July 2007

Background

TheMoraxella catarrhalisHag protein, an Oca autotransporter adhesin, has previously been shown to be important for adherence of this respiratory tract pathogen to human middle ear and A549 lung cells.

Results

The present study demonstrates that adherence ofM. catarrhalisisogenichagmutant strains to the human epithelial cell lines Chang (conjunctival) and NCIH292 (lung) is reduced by 50–93%. Furthermore, expressing Hag in a heterologousEscherichia colibackground substantially increased the adherence of recombinant bacteria to NCIH292 cells and murine type IV collagen. Hag did not, however, increase the attachment ofE. colito Chang cells. These results indicate that Hag directly mediates adherence to NCIH292 lung cells and collagen, but is not sufficient to confer binding to conjunctival monolayers. Several in-frame deletions were engineered within thehaggene ofM. catarrhalisstrain O35E and the resulting proteins were tested for their ability to mediate binding to NCIH292 monolayers, middle ear cells, and type IV collagen. These experiments revealed that epithelial cell and collagen binding properties are separable, and that residues 385–705 of this ~2,000 amino acid protein are important for adherence to middle ear and NCIH292 cells. The region of O35E-Hag encompassing aa 706 to 1194 was also found to be required for adherence to collagen. In contrast, β-roll repeats present in Hag, which are structural features conserved in several Oca adhesins and responsible for the adhesive properties ofYersinia enterocoliticaYadA, are not important for Hag-mediated adherence.

Conclusion

Hag is a major adherence factor for human cells derived from various anatomical sites relevant to pathogenesis byM. catarrhalisand its structure-function relationships differ from those of other, closely-related autotransporter proteins.
Tyrosine phosphatases such as SHP-2 act in a balance with Src-family kinases in stabilization of postsynaptic clusters of acetylcholine receptors
Authors: Camilleri Alain A , Willmann Raffaella , Sadasivam Gayathri , Lin Shuo , Rüegg Markus A , Gesemann Matthias , Fuhrer Christian
Published: July 2007

Background

Development of neural networks requires that synapses are formed, eliminated and stabilized. At the neuromuscular junction (NMJ), agrin/MuSK signaling, by triggering downstream pathways, causes clustering and phosphorylation of postsynaptic acetylcholine receptors (AChRs). Postnatally, AChR aggregates are stabilized by molecular pathways that are poorly characterized. Gain or loss of function of Src-family kinases (SFKs) disassembles AChR clusters at adult NMJs in vivo, whereas AChR aggregates disperse rapidly upon withdrawal of agrin from cultured src
-/-;fyn
-/- myotubes. This suggests that a balance between protein tyrosine phosphatases (PTPs) and protein tyrosine kinases (PTKs) such as those of the Src-family may be essential in stabilizing clusters of AChRs.

Results

We have analyzed the role of PTPs in maintenance of AChR aggregates, by adding and then withdrawing agrin from cultured myotubes in the presence of PTP or PTK inhibitors and quantitating remaining AChR clusters. In wild-type myotubes, blocking PTPs with pervanadate caused enhanced disassembly of AChR clusters after agrin withdrawal. When added at the time of agrin withdrawal, SFK inhibitors destabilized AChR aggregates but concomitant addition of pervanadate rescued cluster stability. Likewise in src
-/-;fyn
-/- myotubes, in which agrin-induced AChR clusters form normally but rapidly disintegrate after agrin withdrawal, pervanadate addition stabilized AChR clusters. The PTP SHP-2, known to be enriched at the NMJ, associated and colocalized with MuSK, and agrin increased this interaction. Specific SHP-2 knockdown by RNA interference reduced the stability of AChR clusters in wild-type myotubes. Similarly, knockdown of SHP-2 in adult mouse soleus muscle by electroporation of RNA interference constructs caused disassembly of pretzel-shaped AChR-rich areas in vivo. Finally, we found that src
-/-;fyn
-/- myotubes contained elevated levels of SHP-2 protein.

Conclusion

Our data are the first to show that the fine balance between PTPs and SFKs is a key aspect in stabilization of postsynaptic AChR clusters. One phosphatase that acts in this equilibrium is SHP-2. Thus, PTPs such as SHP-2 stabilize AChR clusters under normal circumstances, but when these PTPs are not balanced by SFKs, they render clusters unstable.
Isolation and characterization of mutated alcohol oxidases from the yeast Hansenula polymorpha with decreased affinity toward substrates and their use as selective elements of an amperometric biosensor
Authors: Dmytruk Kostyantyn V , Smutok Oleh V , Ryabova Olena B , Gayda Galyna Z , Sibirny Volodymyr A , Schuhmann Wolfgang , Gonchar Mykhailo V , Sibirny Andriy A
Published: July 2007

Background

Accurate, rapid, and economic on-line analysis of ethanol is very desirable. However, available biosensors achieve saturation at very low ethanol concentrations and thus demand the time and labour consuming procedure of sample dilution.

Results

Hansenula polymorpha (Pichia angusta) mutant strains resistant to allyl alcohol in methanol medium were selected. Such strains possessed decreased affinity of alcohol oxidase (AOX) towards methanol: the KM values for AOX of wild type and mutant strains CA2 and CA4 are shown to be 0.62, 2.48 and 1.10 mM, respectively, whereas Vmax values are increased or remain unaffected. The mutant AOX alleles from H. polymorpha mutants CA2 and CA4 were isolated and sequenced. Several point mutations in the AOX gene, mostly different between the two mutant alleles, have been identified. Mutant AOX forms were isolated and purified, and some of their biochemical properties were studied. An amperometric biosensor based on the mutated form of AOX from the strain CA2 was constructed and revealed an extended linear response to the target analytes, ethanol and formaldehyde, as compared to the sensor based on the native AOX.

Conclusion

The described selection methodology opens up the possibility of isolating modified forms of AOX with further decreased affinity toward substrates without reduction of the maximal velocity of reaction. It can help in creation of improved ethanol biosensors with a prolonged linear response towards ethanol in real samples of wines, beers or fermentation liquids.
Crystal structure of vaccinia virus uracil-DNA glycosylase reveals dimeric assembly
Authors: Schormann Norbert , Grigorian Alexei , Samal Alexandra , Krishnan Raman , DeLucas Lawrence , Chattopadhyay Debasish
Published: July 2007

Background

Uracil-DNA glycosylases (UDGs) catalyze excision of uracil from DNA. Vaccinia virus, which is the prototype of poxviruses, encodes a UDG (vvUDG) that is significantly different from the UDGs of other organisms in primary, secondary and tertiary structure and characteristic motifs. It adopted a novel catalysis-independent role in DNA replication that involves interaction with a viral protein, A20, to form the processivity factor. UDG:A20 association is essential for assembling of the processive DNA polymerase complex. The structure of the protein must have provisions for such interactions with A20. This paper provides the first glimpse into the structure of a poxvirus UDG.

Results

Results of dynamic light scattering experiments and native size exclusion chromatography showed that vvUDG is a dimer in solution. The dimeric assembly is also maintained in two crystal forms. The core of vvUDG is reasonably well conserved but the structure contains one additional β-sheet at each terminus. A glycerol molecule is found in the active site of the enzyme in both crystal forms. Interaction of this glycerol molecule with the protein possibly mimics the enzyme-substrate (uracil) interactions.

Conclusion

The crystal structures reveal several distinctive features of vvUDG. The new structural features may have evolved for adopting novel functions in the replication machinery of poxviruses. The mode of interaction between the subunits in the dimers suggests a possible model for binding to its partner and the nature of the processivity factor in the polymerase complex.
Spatio-temporal expression of MMP-2, MMP-9 and tissue kallikrein in uteroplacental units of the pregnant guinea-pig (Cavia porcellus)
Authors: Corthorn Jenny , Rey Sergio , Chacón Cecilia , Valdés Gloria
Published: July 2007

Background

In humans trophoblast invasion and vascular remodeling are critical to determine the fate of pregnancy. Since guinea-pigs share with women an extensive migration of the trophoblasts through the decidua and uterine arteries, and a haemomonochorial placenta, this species was used to evaluate the spatio-temporal expression of three enzymes that have been associated to trophoblast invasion, MMP-2, MMP-9 and tissue kallikrein (K1).

Methods

Uteroplacental units were collected from early to term pregnancy. MMP-2, MMP-9 and K1 were analysed by immunohistochemistry and Western blot. The activities of MMP-2 and MMP-9 were assessed by gelatin zymography.

Results

Immunoreactive MMP-2, MMP-9 and K1 were detected in the subplacenta, interlobar and labyrinthine placenta, syncytial sprouts and syncytial streamers throughout pregnancy. In late pregnancy, perivascular or intramural trophoblasts expressed the three enzymes. The intensity of the signal in syncytial streamers was increased in mid and late pregnancy for MMP-2, decreased in late pregnancy for MMP-9, and remained stable for K1. Western blots of placental homogenates at days 20, 40 and 60 of pregnancy identified bands with the molecular weights of MMP-2, MMP-9 and K1. MMP-2 expression remained constant throughout gestation. In contrast, MMP-9 and K1 attained their highest expression during midgestation. Placental homogenates of 20, 40 and 60 days yielded bands of gelatinase activity that were compatible with MMP-2 and MMP-9 activities. ProMMP-2 and MMP-9 activities did not vary along pregnancy, while MMP-2 and MMP-9 increased at 40 and 40–60 days respectively.

Conclusion

The spatio-temporal expression of MMPs and K1 supports a relevant role of these proteins in trophoblast invasion, vascular remodeling and placental angiogenesis, and suggests a functional association between K1 and MMP-9 activation.
Regulation of HTLV-1 Gag budding by Vps4A, Vps4B, and AIP1/Alix
Authors: Urata Shuzo , Yokosawa Hideyoshi , Yasuda Jiro
Published: July 2007

Background

HTLV-1 Gag protein is a matrix protein that contains the PTAP and PPPY sequences as L-domain motifs and which can be released from mammalian cells in the form of virus-like particles (VLPs). The cellular factors Tsg101 and Nedd4.1 interact with PTAP and PPPY, respectively, within the HTLV-1 Gag polyprotein. Tsg101 forms a complex with Vps28 and Vps37 (ESCRT-I complex) and plays an important role in the class E Vps pathway, which mediates protein sorting and invagination of vesicles into multivesicular bodies. Nedd4.1 is an E3 ubiquitin ligase that binds to the PPPY motif through its WW motif, but its function is still unknown. In the present study, to investigate the mechanism of HTLV-1 budding in detail, we analyzed HTLV-1 budding using dominant negative (DN) forms of the class E proteins.

Results

Here, we report that DN forms of Vps4A, Vps4B, and AIP1 inhibit HTLV-1 budding.

Conclusion

These findings suggest that HTLV-1 budding utilizes the MVB pathway and that these class E proteins may be targets for prevention of mother-to-infant vertical transmission of the virus.
Efficacy and Safety of Ixabepilone (BMS-247550) in a Phase II Study of Patients With Advanced Breast Cancer Resistant to an Anthracycline, a Taxane, and Capecitabine
Authors: Perez Edith A. , Lerzo Guillermo , Pivot Xavier , Thomas Eva , Vahdat Linda , Bosserman Linda , Viens Patrice , Cai Can , Mullaney Brian , Peck Ronald , Hortobagyi Gabriel N.
Published: July 2007

Purpose

To evaluate the efficacy and safety of ixabepilone in patients with metastatic breast cancer (MBC) resistant to anthracycline, taxane, and capecitabine, in this multicenter, phase II study.

Patients and Methods

Patients with measurable disease who had tumor progression while receiving prior anthracycline, taxane, and capecitabine were enrolled. Ixabepilone 40 mg/m2 monotherapy was administered as a 3-hour intravenous infusion on day 1 of a 21-day cycle. The primary end point was objective response rate (ORR), assessed by an independent radiology facility (IRF).

Results

A total of 126 patients were treated and 113 were assessable for response. Patients were heavily pretreated: 88% had received at least two lines of prior chemotherapy in the metastatic setting. IRF-assessed ORR was 11.5% (95% CI, 6.3% to 18.9%) for response-assessable patients. Investigator-assessed ORR for all treated patients was 18.3% (95% CI, 11.9% to 26.1%). Fifty percent of patients achieved stable disease (SD); 14.3% achieved SD ≥ 6 months. Median duration of response and progression-free survival were 5.7 and 3.1 months, respectively. Median overall survival was 8.6 months. Patients received a median of 4.0 treatment cycles (range, one to 16 cycles), and 25% of patients received ≥ eight cycles. Grade 3/4 treatment-related events included peripheral sensory neuropathy (14%), fatigue/asthenia (13%), myalgia (8%), and stomatitis/mucositis (6%). Resolution of grade 3/4 peripheral sensory neuropathy occurred after a median period of 5.4 weeks.

Conclusion

Ixabepilone demonstrated clear activity and a manageable safety profile in patients with MBC resistant to anthracycline, taxane, and capecitabine. Responses were durable and notable in patients who had not previously responded to multiple prior therapies.
Triangular finite elements of variable thickness and their application to plate and shell problems
Authors: Dungar R , Severn R T
Published: July 2007

Stiffness and mass matrices are discussed for a plane triangle whose thickness is allowed to vary linearly between the nodes. In-plane and bending actions are considered separately, and the formulation makes use of the ‘hybrid’ approach, in which the from of the stresses is assumed inside, and on the boundary of, the triangle, and displacements additionally assumed on the boundary only. In Appendix 1 the hybrid approach is developed in detail for a simple beam element.

The allowance of variable thickness carries with it a greater reliance on efficient use of computers, and an opportunity is taken in the paper to reorganize the hybrid approach to achieve this.

The accuracy attainable with this new element is assessed by comparison with results obtained by other methods for a flat plate of variable thickness, simply supported along its edges. A similar plate supported at its corners, and containing holes, is also considered, and the finite-element calculations are compared with moiré fringe and other experimental tests. A simple vibration problem is also discussed.

Finally, the problem of a free-edge boundary is considered. In previous studies spurious stresses were calculable on such boundaries. By employing special elements in these regions the required stresses are made indentically zero.
Stresses in compact end closures for cylindrical pressure vessels
Authors: Preater R W T
Published: July 2007

Three different assumptions are made for the behaviour of the junction between the cylindrical shell and the end closure.

Comparisons of analytical and experimental results show that the inclusion of a ‘rigid’ annular ring beam at the junction of the cylider and the closure best represents the shell behaviour for a ratio of cylinder mean radius to thickness of 3–7, and enables a prediction of an optimum vessel configuration to be made.

Experimental verification of this optimum design confirms the predictions.

(The special use of the term ‘rigid’ is taken in this context to refer to a ring beam for which deformations of the cross-section are ignored but rigid body motion is permitted.)