bluuebunny/crossref_metadata_2025 huggingface dataset:
Shear Bond Strength to Dentin and Ni‐Cr‐Be Alloy with the All‐Bond Universal Adhesive System
Authors: Barbuda Wayne W. , Suh Byouna I. , Cooley Robert L.
Published: July 2007

The shear bond strength of the All‐Bond system to dentin and a nonpreeious alloy was evaluated. Eighty human molar teeth (10 per group) were used in the dentin bonding phase of the study. A bond site was prepared in dentin, and both the succinic anhydride modified HEMA and 10 percent phosphoric acid dentin conditioning techniques were evaluated under both wet and dry conditions. Eighty Rexillium III specimens were used in the metal bonding phase of the study. All‐BQnd primer and opaquer were applied to the metal surface, followed by a visible light‐cured composite restorative material. Dentin bond strengths were determined at 24 hours, while metal bond strengths were evaluated both at 24 hours and after thermocycling (2,500 cycles). Separate groups were established for adhesion to both dentin and metal with the composite placed in a plastic matrix or a gelatin capsule. The highest mean shear bond values to dentin were obtained in the groups with the gelatin capsule bonding procedure, where the dentin was treated with 10 percent phosphoric acid and then blotted dry (wet technique) before the bonding procedure (39.99 MPa). These values were higher than the succinic anhydride modified HEMA‐treated group with gentle air drying (wet technique‐29.56 MPa). There was essentially no difference In mean shear bond strengths to dentin when a succinic anhydride modified HEMA dentin conditioner was used with aggressive (dry technique) or gentle air drying (wet technique) [29.56 versus 29.08 MPa], High bond strengths to Rexillium III were obtained when the All‐Bond adhesive system was used in combination with a dual‐care opaquer and a composite restorative material. The adhesive bond values to metal in this study ranged from 23.63 to 25.38 MPa.
The Anxiety of Daughterhood, or Using Bloom to Read Women Writers: The Cases of Louisa May Alcott and Virginia Woolf
Authors: Jensen Meg
Published: July 2007

‘The process of literary influence is a battle between strong equals, father and sons.’ So wrote Harold Bloom in The Anxiety of Influence. But what of literary daughters? Can Bloom's work offer insights into the dynamics of literary influence for daughters as well as sons? Louisa May Alcott and Virginia Woolf were writer‐daughters of writer‐fathers who anxiously negotiated familial patriarchy and patriarchal literary history in their texts. In examinations of the power of fathers over the words of daughters, moreover, critics of Alcott and Woolf allude explicitly or otherwise to the theories of Bloom, the ‘father’ of influence studies. What happens when we apply Bloom's ideas to women's writing? Alcott's Little Women and the so‐called ‘Thrillers’ that she published anonymously offer very different images of daughterhood. When read alongside Bloom, these contradictions suggest Alcott's anxious relation to the influence of her father Bronson, the education reformer and leading member of the Transcendentalist movement. Like Louisa Alcott, Virginia Woolf negotiated her father's personal and public legacy in complex ways. In her writing from ‘A Sketch of the Past’, to To the Lighthouse, Sir Leslie Stephen's characteristic academic and mountaineering tropes may be seen to surface repeatedly. Bloom's model of literary influence as an anxiety towards a father figure that is ‘achieved’ within the writing offers new insights into the works of both women: in their writing Alcott and Woolf confronted their fathers’ legacies. That the personal and public battleground for these confrontations between father and daughter was writing suggests both the usefulness and limitations of Bloom's model for understanding the dynamics of literary influence upon women writers, and points to a new area of study for scholars of writing women.
The loss of tryptophan 194 in antichymotrypsin lowers the kinetic barrier to misfolding
Authors: Pearce Mary C. , Cabrita Lisa D. , Ellisdon Andrew M. , Bottomley Stephen P.
Published: July 2007

Antichymotrypsin, a member of the serpin superfamily, has been shown to form inactive polymers in vivo, leading to chronic obstructive pulmonary disease. At present, however, the molecular determinants underlying the polymerization transition are unclear. Within a serpin, the breach position is implicated in conformational change, as it is the first point of contact for the reactive center loop and the body of the molecule. W194, situated within the breach, represents one of the most highly conserved residues within the serpin architecture. Using a range of equilibrium and kinetic experiments, the contribution of W194 to proteinase inhibition, stability and polymerization was studied for antichymotrypsin. Replacement of W194 with phenylalanine resulted in a fully active inhibitor that was destabilized relative to the wild‐type protein. The aggregation kinetics were significantly altered; wild‐type antichymotrypsin exhibits a lag phase followed by chain elongation. The loss of W194 almost entirely removed the lag phase and accelerated the elongation phase. On the basis of our data, we propose that one of the main roles of W194 in antichymotrypsin is in preventing polymerization.
An audit of patient satisfaction with uro‐oncology nurse specialists – a questionnaire study
Authors: Masood Junaid , Forristal Helen , Cornes Robert , Vandal Mohammed T. , Gujral Sandeep S.
Published: July 2007

Specialist nurses have an established role in the management of urological cancer in helping patients to understand their disease and treatment options and in offering counselling and emotional support. There is evidence to suggest that patients who see the nurse specialist express more satisfaction and have less anxiety than those who see junior doctors. Other studies have found that the specialist nurses’ clinical expertise compared favourably with that of other clinicians. This audit aimed to assess the patient satisfaction with uro‐oncology nurse specialists and their nurse‐led clinics. One hundred, 15‐point patient satisfaction questionnaires were sent to new and existing patients with urological cancer who had been randomly identified by the uro‐oncology nurse specialist. The questions were concerned with the provision of information to patients and with the satisfaction of the nurse specialist service. The results showed that patients found contact with the uro‐oncology nurse specialist supportive, informative and beneficial to their treatment. The authors felt that raising the profile of the uro‐oncology nurse specialist would be beneficial to patient treatment and care.
Hot Deformation Behavior of Bearing Steels
Authors: Moon Ho Keun , Lee Jae Seong , Yoo Sun Joon , Joun Man Soo , Lee June Key
Published: July 2007

The material behaviors of two types of bearing steels at hot working conditions are investigated. Stress-strain curves at various temperatures (900–1300°C) and strain rates (1–50/s) are obtained by compression tests with a computer controlled servo-hydraulic Gleeble 3800 testing machine. Elongation and reduction of the area are also obtained by tensile tests with the Gleeble 1500 testing machine. Flow stresses are calculated from the experiments and are used to predict the temperature distribution and the metal flow of a workpiece during a multistage hot forging process of a bearing race. A rigid-thermoviscoplastic finite element method is applied. The experimental and numerical results are summarized to reveal the reasons for internal crack formation.
Stress-Based Springback Reduction of a Channel Shaped Auto-Body Part With High-Strength Steel Using Response Surface Methodology
Authors: Song Jung-Han , Huh Hoon , Kim Se-Ho
Published: July 2007

In this paper, an optimum design is carried out with finite element analysis to determine process parameters which reduce the amount of springback and improve shape accuracy of a deep drawn product with the channel shape. Without springback simulation usually performed with an implicit solving scheme, the study uses the amount of stress deviation through the sheet thickness direction in the deep drawn product as an indicator of springback. The simulation incorporates the explicit elasto-plastic finite element method for calculation of the final shape and the stress deviation of the final product. The optimization method adopts the response surface methodology in order to seek the optimum condition of process parameters such as the blank holding force and the draw-bead force. The present optimization scheme is applied to the design of the variable blank holding force in the U-draw bending process and the application is further extended to the design of draw-bead force in a front side member formed with advanced high-strength steel (AHSS) sheets made of DP600. Results demonstrate that the optimum design of process parameters decreases the stress deviation throughout the thickness of the sheet and reduces the amount of springback of the channel shaped part. The present analysis provides a guideline in the tool design stage for controlling the evolution of springback based on the finite element simulation of complicated parts.
Determination of Lower-Bound Ductility for AZ31 Magnesium Alloy by Use of the Bulge Specimens
Authors: Lapovok Rimma , Hodgson Peter D.
Published: July 2007

Despite the high demand for industrial applications of magnesium, the forming technology for wrought magnesium alloys is not fully developed due to the limited ductility and high sensitivity to the processing parameters. The processing window for magnesium alloys could be significantly widened if the lower-bound ductility (LBD) for a range of stresses, temperature, and strain rates was known. LBD is the critical strain at the moment of fracture as a function of stress state and temperature. Measurements of LBD are normally performed by testing in a hyperbaric chamber, which is highly specialized, complex, and rare equipment. In this paper an alternative approach to determine LBD is demonstrated using wrought magnesium alloy AZ31 as an example. A series of compression tests of bulge specimens combined with finite element simulation of the tests were performed. The LBD diagram was then deduced by backward calculation.
Mechanical Performance Evaluation of Cast Magnesium Alloys for Automotive and Aeronautical Applications
Authors: Pantelakis Sp. G. , Alexopoulos N. D. , Chamos A. N.
Published: July 2007

The potential of cast magnesium alloys for being used as structural materials in lightweight applications is assessed. The ability of the alloys for mechanical performance is evaluated and compared against the ability of widely used structural aircraft cast aluminum alloys. The specific quality index QDS, devised for evaluating both cast and wrought aluminum alloys, will be exploited to evaluate the ability of a number of cast magnesium alloys for mechanical performance. The exploited quality index QDS involves the material’s yield strength Rp to account for strength, the strain energy density W to account for both tensile ductility and toughness, and the material’s density ρ. The effects of differences in chemical composition and heat treatment conditions on the mechanical performance of cast magnesium alloys have been assessed. The use of the quality index QDS has been proved to appreciably facilitate the evaluation of the mechanical performance of cast magnesium alloys and also the comparison between alloys of different base materials. The results quantify the gap to be closed such as to involve cast magnesium alloys in aircraft structural applications.
An Equivalent Orthotropic Representation of the Nonlinear Elastic Behavior of Multiwalled Carbon Nanotubes
Authors: Garg M. , Pantano A. , Boyce M. C.
Published: July 2007

An equivalent orthotropic representation (EOR) of the nonlinear elastic behavior of multiwalled carbon nanotubes (MWCNTs) was developed based on a nested shell structural representation of MWCNTs. The EOR model was used together with the finite element method to simulate the large deformation of MWCNTs under bending, axial compression and radial compression. Results were compared with those of the nested shell model for four-, eight-, nine-, 14-, and 19-walled carbon nanotubes. The EOR model provides a dramatic improvement in computational efficiency and successfully quantitatively replicates the overall deformation behavior including the initial linear elastic behavior, the onset of local buckling, and the post-buckling compliance. The proposed EOR model together with the finite element method offers a computationally efficient method for simulating large and complex systems of MWCNTs.
Development and Characterization of Ductile Mg∕Y2O3 Nanocomposites
Authors: Hassan S. F. , Gupta M.
Published: July 2007

Nano-Y2O3 particulates containing ductile magnesium nanocomposites were synthesized using blend-press-sinter powder metallurgy technique followed by hot extrusion. Microstructural characterization of the nanocomposite samples showed fairly uniform reinforcement distribution, good reinforcement-matrix interfacial integrity, significant grain refinement of magnesium matrix with increasing presence of reinforcement, and the presence of minimal porosity. Mechanical properties characterization revealed that the presence of nano-Y2O3 reinforcement leads to marginal increases in hardness, 0.2% yield strength and ultimate tensile strength, but a significant increase in ductility and work of fracture of magnesium. The fracture mode was changed from brittle for pure Mg to mix ductile and intergranular in the case of nanocomposites.
A Human Anti-Pseudomonas aeruginosaSerotype O6ad Immunoglobulin G1 Expressed in Transgenic Tobacco Is Capable of Recruiting Immune System Effector Function In Vitro
Authors: McLean Michael D. , Almquist Kurt C. , Niu Yongfing , Kimmel Rhonda , Lai Zengzu , Schreiber John R. , Hall J. Christopher
Published: July 2007

The production of a recombinant human IgG1 in transgenic tobacco was examined to determine whether a plant-derived antibody could recruit immune system effector function against a bacterial pathogen. A plant transformation vector was engineered to contain genes for a human kappa light chain and a human gamma-1 heavy chain with VHand VLsequences from a previously identified human IgG2 monoclonal antibody (MAb) that specifically binds to and opsonizesPseudomonas aeruginosaserotype O6ad. Unique NcoI and NotI restriction sites were incorporated to flank these variable sequences, resulting in a plant transformation vector that could be engineered for expression of any other human IgG1 antibody, requiring only the substitution of other VHand VLantigen-binding coding sequences. The plant-produced IgG1 was determined to have high-mannose glycan content and to be capable of mediating opsonophagocytosis ofP. aeruginosaserotype O6ad in vitro using human complement and human polymorphonuclear leukocytes. Thus, MAbs produced in plants from this vector could provide human IgG1 MAbs for targeting other pathogens that require the recruitment of immune system effector functions.
Pharmacokinetics of Single- and Multiple-Dose Oral Clarithromycin in Soft Tissues Determined by Microdialysis
Authors: Traunmüller Friederike , Zeitlinger Markus , Zeleny Petra , Müller Markus , Joukhadar Christian
Published: July 2007

The antimicrobial spectrum of clarithromycin renders this antibiotic a frequently used option in the treatment of skin and soft-tissue infections. In most cases, these infections are caused by extracellularly proliferating microorganisms. Thus, clarithromycin concentrations achieved in the interstitial space are considered particularly important for clinical efficacy. In the present study, clarithromycin concentrations in plasma and interstitial-space fluid of subcutaneous adipose tissue and skeletal muscle of six healthy male volunteers were assessed by means of the microdialysis technique after oral single-dose administration of 250 mg and multiple doses of 500 mg of clarithromycin twice a day (b.i.d.). The ratios of the area under the concentration-time curve of free clarithromycin from 0 to 24 h calculated for a single dose of 250 mg (
f
AUC
0-24
) in interstitial-space fluid to the
f
AUC
0-24
in plasma were 0.29 ± 0.17 and 0.42 ± 0.18 for subcutis and skeletal muscle, respectively. For 500 mg of clarithromycin at the steady state (3 to 5 days of intake twice daily), the
f
AUC
0-24(b.i.d.)
ratios at the steady state were 0.39 ± 0.04 and 0.41 ± 0.19 for subcutis and skeletal muscle, respectively. The half-life was around 2 h after a single dose but increased to approximately 4 h in plasma and tissues after repetitive clarithromycin administration. Based on subsequently performed pharmacokinetic-pharmacodynamic calculations, a dosing regimen of 500 mg b.i.d. may be ineffective in the treatment of soft-tissue infections caused by pathogens with a drug MIC higher than 0.125 mg/liter.
An Anti-β-Glucan Monoclonal Antibody Inhibits Growth and Capsule Formation of
Cryptococcus neoformans
In Vitro and Exerts Therapeutic, Anticryptococcal Activity In Vivo
Authors: Rachini Anna , Pietrella Donatella , Lupo Patrizia , Torosantucci Antonella , Chiani Paola , Bromuro Carla , Proietti Carla , Bistoni Francesco , Cassone Antonio , Vecchiarelli Anna
Published: July 2007

In this study we tested the in vitro and in vivo anti-
Cryptococcus neoformans
activity of an antilaminarin (anti-β-glucan) monoclonal antibody (MAb 2G8) (immunoglobulin G2b) which was previously shown to inhibit the growth of β-glucan-exposing
Candida albicans
cells. Here we show that MAb 2G8 binds to the cell wall of
C. neoformans
and inhibits its growth to an extent comparable to that observed for
C. albicans
. Binding and growth inhibition were detected almost equally for encapsulated and acapsular
C. neoformans
strains. In addition, at subinhibitory concentrations, MAb 2G8 reduced the capsule thickness without affecting protease or phospholipase production. Acapsular fungal cells, but not encapsulated fungal cells, were opsonized by the antibody and more efficiently phagocytosed and killed by human monocytes and by murine peritoneal macrophages. A single administration of MAb 2G8 resulted in a reduction in the fungal burden in the brains and livers of mice systemically infected with a highly virulent, encapsulated
C. neoformans
strain. This protective effect was also detected in neutropenic mice. Overall, these findings demonstrate that cell wall β-glucan of encapsulated
C. neoformans
is accessible to antibodies which can exert remarkable anticryptococcal activities in vitro and in vivo.
Heligmosomoides polygyrusPromotes Regulatory T-Cell Cytokine Production in the Murine Normal Distal Intestine
Authors: Setiawan Tommy , Metwali Ahmed , Blum Arthur M. , Ince M. Nedim , Urban Joseph F. , Elliott David E. , Weinstock Joel V.
Published: July 2007

Helminths down-regulate inflammation and may prevent development of several autoimmune illnesses, such as inflammatory bowel disease. We determined if exposure to the duodenal helminthHeligmosomoides polygyrusestablishes cytokine pathways in the distal intestine that may protect from intestinal inflammation. Mice received 200H. polygyruslarvae and were studied 2 weeks later. Lamina propria mononuclear cells (LPMC) were isolated from the terminal ileum for analysis and in vitro experiments. Mice withH. polygyruswere resistant to trinitrobenzenesulfonic acid (TNBS)-induced colitis, a Th1 cytokine-dependent inflammation.Heligmosomoides polygyrusdid not change the normal microscopic appearance of the terminal ileum and colon and minimally affected LPMC composition. However, colonization altered LPMC cytokine profiles, blocking gamma interferon (IFN-γ) and interleukin 12 (IL-12) p40 release but promoting IL-4, IL-5, IL-13, and IL-10 secretion. IL-10 blockade in vitro with anti-IL-10 receptor (IL-10R) monoclonal antibody restored LPMC IFN-γ and IL-12 p40 secretion. IL-10 blockade in vivo worsened TNBS colitis inH. polygyrus-colonized mice. Lamina propria CD4+T cells isolated from colonized mice inhibited IFN-γ production by splenic T cells from worm-free mice. This inhibition did not require cell contact and was dependent on IL-10.Heligmosomoides polygyruscolonization inhibits Th1 and promotes Th2 and regulatory cytokine production in distant intestinal regions without changing histology or LPMC composition. IL-10 is particularly important for limiting the Th1 response. The T-cell origin of these cytokines demonstrates mucosal regulatory T-cell induction.
MicroRNAs in the Human Heart
Authors: Thum Thomas , Galuppo Paolo , Wolf Christian , Fiedler Jan , Kneitz Susanne , van Laake Linda W. , Doevendans Pieter A. , Mummery Christine L. , Borlak Jürgen , Haverich Axel , Gross Carina , Engelhardt Stefan , Ertl Georg , Bauersachs Johann
Published: July 2007

Background—

Chronic heart failure is characterized by left ventricular remodeling and reactivation of a fetal gene program; the underlying mechanisms are only partly understood. Here we provide evidence that cardiac microRNAs, recently discovered key regulators of gene expression, contribute to the transcriptional changes observed in heart failure.

Methods and Results—

Cardiac transcriptome analyses revealed striking similarities between fetal and failing human heart tissue. Using microRNA arrays, we discovered profound alterations of microRNA expression in failing hearts. These changes closely mimicked the microRNA expression pattern observed in fetal cardiac tissue. Bioinformatic analysis demonstrated a striking concordance between regulated messenger RNA expression in heart failure and the presence of microRNA binding sites in the respective 3′ untranslated regions. Messenger RNAs upregulated in the failing heart contained preferentially binding sites for downregulated microRNAs and vice versa. Mechanistically, transfection of cardiomyocytes with a set of fetal microRNAs induced cellular hypertrophy as well as changes in gene expression comparable to the failing heart.

Conclusions—

Our data support a novel mode of regulation for the transcriptional changes in cardiac failure. Reactivation of a fetal microRNA program substantially contributes to alterations of gene expression in the failing human heart.
Psychological Types of Academically Gifted Adolescents
Authors: Cross Tracy L. , Speirs Neumeister Kristie L. , Cassady Jerrell C.
Published: July 2007

This study provides descriptive information about the psychological types of a sample of 931 gifted adolescents who attended a public residential academy. Psychological types are assessed with the Myers-Briggs Type Indicator (MBTI). The MBTI reports on four pairs of personality types: Extraversion/Introversion (E/I), Sensing/Intuition (S/N), Thinking/Feeling (T/F), and Judging/Perceiving (J/P). Overall, the most common types reported by this sample were INTJ, INTP, INFP, ENFP, and ENTP. Comparisons between gifted and norming samples are reported. Gender differences for the gifted sample were found on E/I, with males orienting toward I and females orienting toward E. Gender-specific comparisons between gifted and norming samples reveal that gifted females had a greater tendency toward I and T, and gifted males had a greater tendency for I. Overall, both genders in the gifted sample tended to be NP types.
Global Regimes, Local Agendas
Authors: Falcous Mark , Silk Michael
Published: July 2007

Rearticulating Chen (1992, 1994; see also Silk and Andrews, 2005), this article argues for the need to establish an agenda of `internationalist localism' to analyse the place of sport within unfolding socio-political agendas of neoliberal globalization. In doing so, it constitutes a response to calls within the academy to register critical, reflective responses to ongoing international crises (Martin and Shohat, 2002; Denzin and Lincoln, 2003). We thus extend recent calls to interrogate sport as a site through which various socio-political discourses are mobilized in the organization and discipline of daily life in the service of particular political agendas (Andrews, 1995). We do so by illustrating both the global extent of these agendas and the locally conjunctural nature of such processes. We centre upon the case of Aboriginal Muslim-Australian boxer Anthony Mundine, and the response to his post-9/11 criticism of Australian involvement in the US-led `War on Terror'. Mundine was vilified and demonized within the Australian corporate media, and sanctioned by world boxing bodies. Critically, the dominant media discourse of the moment revealed that inherently local agendas contour the connection of the national with the global. Specifically, the contested nature of Australian identities in and through the framing and rebuttal of dissent are writ large in responses to global events. Thus, the intimate, yet nuanced connection between local and global power dynamics is revealed.
Sociogenesis of a Social Field
Authors: Hoibian Olivier
Published: July 2007

The realm where sports are played has often been perceived either as a no-man's land, neutral, and independent from social or political stakes as viewed by Pierre de Coubertin; or, on the contrary, as an example of capitalist domination according to Marxist terminology. Work inspired from Pierre Bourdieu's social theory has remained faithful to the concept of `a degree of self-sufficiency' with regards to these particular social practices, taking into account the cultural background at that time. Research conducted in France around this perspective has essentially dealt with the 1960s and 1970s and the advent of novel sports or new ways of practicing traditional ones considering the Cultural Revolution context of 1968. This approach however may also be explained by examining how modern sports in France were structured at the end of the 19th century. Using the theory of Social Fields to study how the world of mountaineering came to be and how it was further institutionalized, especially with regards to the `Club Alpin Français' appears to explain the previously mentioned shortcomings while at the same time renewing the debate. Originally founded upon a wide range of mountaineering practices derived from a nationalist sentiment, the cultural world of mountaineering has, since the beginning of the 21st century, witnessed a progressive autonomization revealed by the appearance of debate and controversy surrounding the rightful practice, the ranking of members, and the organization of the mountaineering certified guides as a profession.
Cultural Studies as Performative Politics
Authors: Giroux Henry A.
Published: July 2007

This article addresses the role public intellectuals and cultural workers might play in challenging the pervasive institutional and ideological influ ence of neoliberalism as it continues to attack all public spaces and social services not governed by the logic of the market. The author takes up this challenge by articulating a relationship between the political and peda gogical that is central to any notion of cultural politics. In doing so, he attempts to foreground how the diverse forms of critical pedagogy and cul tural studies can engage in progressive cultural politics through the interre lated registers of insurgent citizenship, a performative critical pedagogy, and a contextualized notion of political agency. The interconnected con cepts of discourse, context, power, and theory are used to critique notions of textuality that refuse to link the symbolic to material relations of power and to engage the limits of dystopian performative work that fails in spite of its appeal to the transgressive to address urgent social issues. The author concludes by pointing to a number of cultural activists whose work embod ies a radical intersection of the performative and the political.
Functional interplay between endothelial nitric oxide synthase and membrane type 1–matrix metalloproteinase in migrating endothelial cells
Authors: Genís Laura , Gonzalo Pilar , Tutor Antonio S. , Gálvez Beatriz G. , Martínez-Ruiz Antonio , Zaragoza Carlos , Lamas Santiago , Tryggvason Karl , Apte Suneel S. , Arroyo Alicia G.
Published: July 2007

Nitric oxide (NO) is essential for vascular homeostasis and is also a critical modulator of angiogenesis; however, the molecular mechanisms of NO action during angiogenesis remain elusive. We have investigated the potential relationship between NO and membrane type 1–matrix metalloproteinase (MT1-MMP) during endothelial migration and capillary tube formation. Endothelial NO synthase (eNOS) colocalizes with MT1-MMP at motility-associated structures in migratory human endothelial cells (ECs); moreover, NO is produced at these structures and is released into the medium during EC migration. We have therefore addressed 2 questions: (1) the putative regulation of MT1-MMP by NO in migratory ECs; and (2) the requirement for MT1-MMP in NO-induced EC migration and tube formation. NO upregulates MT1-MMP membrane clustering on migratory human ECs, and this is accompanied by increased degradation of type I collagen substrate. MT1-MMP membrane expression and localization are impaired in lung ECs from eNOS-deficient mice, and these cells also show impaired migration and tube formation in vitro. Inhibition of MT1-MMP with a neutralizing antibody impairs NOinduced tube formation by human ECs, and NO-induced endothelial migration and tube formation are impaired in lung ECs from mice deficient in MT1-MMP. MT1-MMP thus appears to be a key molecular effector of NO during the EC migration and angiogenic processes, and is a potential therapeutic target for NO-associated vascular disorders.
Gene mapping and expression analysis of 16q loss of heterozygosity identifies WWOX and CYLD as being important in determining clinical outcome in multiple myeloma
Authors: Jenner Matthew W. , Leone Paola E. , Walker Brian A. , Ross Fiona M. , Johnson David C. , Gonzalez David , Chiecchio Laura , Dachs Cabanas Elisabet , Paolo Dagrada Gian , Nightingale Mathew , Protheroe Rebecca K. M. , Stockley David , Else Monica , Dickens Nicholas J. , Cross Nicholas C. P. , Davies Faith E. , Morgan Gareth J.
Published: July 2007

We performed fluorescent in situ hybridization (FISH) for 16q23 abnormalities in 861 patients with newly diagnosed multiple myeloma and identified deletion of 16q [del(16q)] in 19.5%. In 467 cases in which demographic and survival data were available, del(16q) was associated with a worse overall survival (OS). It was an independent prognostic marker and conferred additional adverse survival impact in cases with the known poor-risk cytogenetic factors t(4;14) and del(17p). Gene expression profiling and gene mapping using 500K single-nucleotide polymorphism (SNP) mapping arrays revealed loss of heterozygosity (LOH) involving 3 regions: the whole of 16q, a region centered on 16q12 (the location of CYLD), and a region centered on 16q23 (the location of the WW domain-containing oxidoreductase gene WWOX). CYLD is a negative regulator of the NF-κB pathway, and cases with low expression of CYLD were used to define a “low-CYLD signature.” Cases with 16q LOH or t(14;16) had significantly reduced WWOX expression. WWOX, the site of the translocation breakpoint in t(14;16) cases, is a known tumor suppressor gene involved in apoptosis, and we were able to generate a “low-WWOX signature” defined by WWOX expression. These 2 genes and their corresponding pathways provide an important insight into the potential mechanisms by which 16q LOH confers poor prognosis.
Modulation of tolerance to the transgene product in a nonhuman primate model of AAV-mediated gene transfer to liver
Authors: Mingozzi Federico , Hasbrouck Nicole C. , Basner-Tschakarjan Etiena , Edmonson Shyrie A. , Hui Daniel J. , Sabatino Denise E. , Zhou Shangzhen , Wright J. Fraser , Jiang Haiyan , Pierce Glenn F. , Arruda Valder R. , High Katherine A.
Published: July 2007

Adeno-associated virus (AAV)–mediated gene transfer of factor IX (F.IX) to the liver results in long-term expression of transgene in experimental animals, but only short-term expression in humans. Loss of F.IX expression is likely due to a cytotoxic immune response to the AAV capsid, which results in clearance of transduced hepatocytes. We used a nonhuman primate model to assess the safety of AAV gene transfer coupled with an anti–T-cell regimen designed to block this immune response. Administration of a 3-drug regimen consisting of mycophenolate mofetil (MMF), sirolimus, and the anti–IL-2 receptor antibody daclizumab consistently resulted in formation of inhibitory antibodies to human F.IX following hepatic artery administration of an AAV-hF.IX vector, whereas a 2-drug regimen consisting only of MMF and sirolimus did not. Administration of daclizumab was accompanied by a dramatic drop in the population of CD4+CD25+FoxP3+ regulatory T cells (Tregs). We conclude that choice of immunosuppression (IS) regimen can modulate immune responses to the transgene product upon hepatic gene transfer in subjects not fully tolerant; and that induction of transgene tolerance may depend on a population of antigen-specific Tregs.
Improved classification accuracy in 1- and 2-dimensional NMR metabolomics data using the variance stabilising generalised logarithm transformation
Authors: Parsons Helen M , Ludwig Christian , Günther Ulrich L , Viant Mark R
Published: July 2007

Background

Classifying nuclear magnetic resonance (NMR) spectra is a crucial step in many metabolomics experiments. Since several multivariate classification techniques depend upon the variance of the data, it is important to first minimise any contribution from unwanted technical variance arising from sample preparation and analytical measurements, and thereby maximise any contribution from wanted biological variance between different classes. The generalised logarithm (glog) transform was developed to stabilise the variance in DNA microarray datasets, but has rarely been applied to metabolomics data. In particular, it has not been rigorously evaluated against other scaling techniques used in metabolomics, nor tested on all forms of NMR spectra including 1-dimensional (1D) 1H, projections of 2D 1H, 1H J-resolved (pJRES), and intact 2D J-resolved (JRES).

Results

Here, the effects of the glog transform are compared against two commonly used variance stabilising techniques, autoscaling and Pareto scaling, as well as unscaled data. The four methods are evaluated in terms of the effects on the variance of NMR metabolomics data and on the classification accuracy following multivariate analysis, the latter achieved using principal component analysis followed by linear discriminant analysis. For two of three datasets analysed, classification accuracies were highest following glog transformation: 100% accuracy for discriminating 1D NMR spectra of hypoxic and normoxic invertebrate muscle, and 100% accuracy for discriminating 2D JRES spectra of fish livers sampled from two rivers. For the third dataset, pJRES spectra of urine from two breeds of dog, the glog transform and autoscaling achieved equal highest accuracies. Additionally we extended the glog algorithm to effectively suppress noise, which proved critical for the analysis of 2D JRES spectra.

Conclusion

We have demonstrated that the glog and extended glog transforms stabilise the technical variance in NMR metabolomics datasets. This significantly improves the discrimination between sample classes and has resulted in higher classification accuracies compared to unscaled, autoscaled or Pareto scaled data. Additionally we have confirmed the broad applicability of the glog approach using three disparate datasets from different biological samples using 1D NMR spectra, 1D projections of 2D JRES spectra, and intact 2D JRES spectra.
Analysis of septins across kingdoms reveals orthology and new motifs
Authors: Pan Fangfang , Malmberg Russell L , Momany Michelle
Published: July 2007

Background

Septins are cytoskeletal GTPase proteins first discovered in the fungus Saccharomyces cerevisiae where they organize the septum and link nuclear division with cell division. More recently septins have been found in animals where they are important in processes ranging from actin and microtubule organization to embryonic patterning and where defects in septins have been implicated in human disease. Previous studies suggested that many animal septins fell into independent evolutionary groups, confounding cross-kingdom comparison.

Results

In the current work, we identified 162 septins from fungi, microsporidia and animals and analyzed their phylogenetic relationships. There was support for five groups of septins with orthology between kingdoms. Group 1 (which includes S. cerevisiae Cdc10p and human Sept9) and Group 2 (which includes S. cerevisiae Cdc3p and human Sept7) contain sequences from fungi and animals. Group 3 (which includes S. cerevisiae Cdc11p) and Group 4 (which includes S. cerevisiae Cdc12p) contain sequences from fungi and microsporidia. Group 5 (which includes Aspergillus nidulans AspE) contains sequences from filamentous fungi. We suggest a modified nomenclature based on these phylogenetic relationships. Comparative sequence alignments revealed septin derivatives of already known G1, G3 and G4 GTPase motifs, four new motifs from two to twelve amino acids long and six conserved single amino acid positions. One of these new motifs is septin-specific and several are group specific.

Conclusion

Our studies provide an evolutionary history for this important family of proteins and a framework and consistent nomenclature for comparison of septin orthologs across kingdoms.
A genetic association analysis of cognitive ability and cognitive ageing using 325 markers for 109 genes associated with oxidative stress or cognition
Authors: Harris Sarah E , Fox Helen , Wright Alan F , Hayward Caroline , Starr John M , Whalley Lawrence J , Deary Ian J
Published: July 2007

Background

Non-pathological cognitive ageing is a distressing condition affecting an increasing number of people in our 'ageing society'. Oxidative stress is hypothesised to have a major role in cellular ageing, including brain ageing.

Results

Associations between cognitive ageing and 325 single nucleotide polymorphisms (SNPs), located in 109 genes implicated in oxidative stress and/or cognition, were examined in a unique cohort of relatively healthy older people, on whom we have cognitive ability scores at ages 11 and 79 years (LBC1921). SNPs showing a significant positive association were then genotyped in a second cohort for whom we have cognitive ability scores at the ages of 11 and 64 years (ABC1936). An intronic SNP in the APP gene (rs2830102) was significantly associated with cognitive ageing in both LBC1921 and a combined LBC1921/ABC1936 analysis (p < 0.01), but not in ABC1936 alone.

Conclusion

This study suggests a possible role for APP in normal cognitive ageing, in addition to its role in Alzheimer's disease.
Toxicology evaluation of radiotracer doses of 3'-deoxy-3'-[18F]fluorothymidine (18F-FLT) for human PET imaging: Laboratory analysis of serial blood samples and comparison to previously investigated therapeutic FLT doses
Authors: Turcotte Eric , Wiens Linda W , Grierson John R , Peterson Lanell M , Wener Mark H , Vesselle Hubert
Published: July 2007

Background

18F-FLT is a novel PET radiotracer which has demonstrated a strong potential utility for imaging cellular proliferation in human tumors in vivo. To facilitate future regulatory approval of 18F-FLT for clinical use, we wished to demonstrate the safety of radiotracer doses of 18F-FLT administered to human subjects, by: 1) performing an evaluation of the toxicity of 18F-FLT administered in radiotracer amounts for PET imaging, 2) comparing a radiotracer dose of FLT to clinical trial doses of FLT.

Methods

Twenty patients gave consent to a 18F-FLT injection, subsequent PET imaging, and blood draws. For each patient, blood samples were collected at multiple times before and after 18F-FLT PET. These samples were assayed for a comprehensive metabolic panel, total bilirubin, complete blood and platelet counts. 18F-FLT doses of 2.59 MBq/Kg with a maximal dose of 185 MBq (5 mCi) were used. Blood time-activity curves were generated for each patient from dynamic PET data, providing a measure of the area under the FLT concentration curve for 12 hours (AUC12).

Results

No side effects were reported. Only albumin, red blood cell count, hematocrit and hemoglobin showed a statistically significant decrease over time. These changes are attributed to IV hydration during PET imaging and to subsequent blood loss at surgery. The AUC12 values estimated from imaging data are not significantly different from those found from serial measures of FLT blood concentrations (p = 0.66). The blood samples-derived AUC12 values range from 0.232 ng*h/mL to 1.339 ng*h/mL with a mean of 0.802 ± 0.303 ng*h/mL. This corresponds to 0.46% to 2.68% of the lowest and least toxic clinical trial AUC12 of 50 ng*h/mL reported by Flexner et al (1994). This single injection also corresponds to a nearly 3,000-fold lower cumulative dose than in Flexner's twice daily trial.

Conclusion

This study shows no evidence of toxicity or complications attributable to 18F-FLT injected intravenously.
Association of diminished expression of RASSF1A with promoter methylation in primary gastric cancer from patients of central China
Authors: Ye Mei , Xia Bing , Guo Qiusha , Zhou Feng , Zhang Xiaolian
Published: July 2007

Background

Although methylation-mediated inactivation of expression of RASSF1A, a candidate tumor suppressor gene, has been observed in several human cancers, the data concerning alteration of RASSF1A expression and methylation in Chinese primary gastric cancer are scarce. Moreover, direct evidence showing the association between protein expression of RASSF1A and primary human cancers is lacking. The aim of this study was to investigate RASSF1A expression in tissue of primary gastric cancer (GC) at mRNA and protein levels, and to establish the possible relationship between DNA methylation status and protein expression of RASSF1A in Chinese.

Methods

Fifty-four patients with primary gastric cancers were included in the study of RASSF1A mRNA expression and methylation status between the cancer tissue and the corresponding adjacent normal tissue. 20 out of 54 patients were included for study of RASSF1A protein expression. The expression of RASSF1A at mRNA and protein levels was determined by RT-PCR and Western-blotting, respectively. The RASSF1A promoter methylation was detected by methylation-specific PCR.

Results

RASSF1A mRNA and protein expressions in GC were reduced significantly with comparison to the corresponding normal tissues (OD value: 0.2589 ± 0.2407 vs 0.5448 ± 0.2971,P< 0.0001; 0.1874 ± 0.0737 vs 0.6654 ± 0.2201,P< 0.0001, respectively). Methylation frequency of RASSF1A in primary GC is higher than that in the corresponding normal tissues (66.7% vs. 14.8%,P< 0.0001). Furthermore, RASSF1A mRNA expression in methylation group of GC was further reduced when compared to the unmethylation group of GC (0.1384 ± 0.1142 vs. 0.5018 ± 0.2463,P< 0.0001).

Conclusion

Expression of RASSF1A was reduced in tissue of GC at mRNA and protein levels. Diminished expression of RASSF1A was associated with the promoter methylation.
Reincentivizing – a new theory of work and work absence
Authors: Thulesius Hans O , Grahn Birgitta E
Published: July 2007

Background

Work capacity correlates weakly to disease concepts, which in turn are insufficient to explain sick leave behavior. With data mainly from Sweden, a welfare state with high sickness absence rates, our aim was to develop an explanatory theory of how to understand and deal with work absence and sick leave.

Methods

We used classic grounded theory for analyzing data from >130 interviews with people working or on sick leave, physicians, social security officers, and literature. Several hundreds of typed and handwritten memos were the basis for writing up the theory.

Results

In this paper we present a theory of work incentives and how to deal with work absence. We suggest that work disability can be seen as hurt work drivers or people caught in mode traps. Work drivers are specified as work capacities + work incentives, monetary and non-monetary. Also, people can get trapped in certain modes of behavior through changed capacities or incentives, or by inertia. Different modes have different drivers and these can trap the individual from reincentivizing, ie from going back to work or go on working. Hurt drivers and mode traps are recognized by driver assessments done on several different levels. Mode driver calculations are done by the worker. Then follows employer, physician, and social insurance officer assessments. Also, driver assessments are done on the macro level by legislators and other stakeholders. Reincentivizing is done by different repair strategies for hurt work drivers such as body repair, self repair, work-place repair, rehumanizing, controlling sick leave insurance, and strengthening monetary work incentives. Combinations of these driver repair strategies also do release people from mode traps.

Conclusion

Reincentivizing is about recognizing hurt work drivers and mode traps followed by repairing and releasing the same drivers and traps. Reincentivizing aims at explaining what is going on when work absence is dealt with and the theory may add to social psychological research on work and work absence, and possibly inform sick leave policies.
4D treatment planning for scanned ion beams
Authors: Bert Christoph , Rietzel Eike
Published: July 2007

At Gesellschaft für Schwerionenforschung (GSI) more than 330 patients have been treated with scanned carbon ion beams in a pilot project. To date, only stationary tumors have been treated. In the presence of motion, scanned ion beam therapy is not yet possible because of interplay effects between scanned beam and target motion which can cause severe mis-dosage. We have started a project to treat tumors that are subject to respiratory motion. A prototype beam application system for target tracking with the scanned pencil beam has been developed and commissioned.

To facilitate treatment planning for tumors that are subject to organ motion, we have extended our standard treatment planning system TRiP to full 4D functionality. The 4D version of TRiP allows to calculate dose distributions in the presence of motion. Furthermore, for motion mitigation techniques tracking, gating, rescanning, and internal margins optimization of treatment parameters has been implemented. 4D calculations are based on 4D computed tomography data, deformable registration maps, organ motion traces, and beam scanning parameters.

We describe the methods of our 4D treatment planning approach and demonstrate functionality of the system for phantom as well as patient data.
Stress distribution in a tension specimen notched on one edge
Authors: Dixon J R , Strannigan J S , McGregor J
Published: July 2007

The stress distribution in a tension specimen notched on one edge was obtained photoelastically for several ratios of notch depth to specimen width. The stress-concentration factors agreed well with corresponding values derived from Neuber's theory of notch stresses. It was also shown that the stress-intensity factor for a tension specimen with a single crack on one edge, obtained by the collocation method, agreed well with that deduced from Neuber's theory.
Finite-element analysis of axi-symmetric rotors
Authors: Stordahl H , Christensen H
Published: July 2007

The finite-element method (1) (2)∗ is increasingly used in the stress analysis of mechanical-engineering problems. It is the purpose of this paper to described how the finite-element method can be used as an effective tool in the design of rotors. Up to the present time this method has mainly been used in the analysis of two-dimensional problems. However, a special class of three-dimensional problems, namely axi-symmetric rotors, can be treated as a nearly two-dimensional problem.

This paper summarizes the development of the finite-element method as applied to the analysis of the axi-symmetric rotor. A computer programme is then briefly described, and the application of the method to the solution of three examples taken from practical engineering experience are presented.