4,883 research outputs found
A study of a patient with chronic lymphocytic leukemia (CLL) which demonstrates that proliferation of the lymphocytic clone in CLL does not include T lymphocytes
No full textOn the AJ Conjecture for Knots
No full textWe confirm the AJ conjecture [Ga2] that relates the A-polynomial and the colored Jones polynomial for hyperbolic knots satisfying certain conditions. In particular, we show that the conjecture holds true for some classes of two-bridge knots and pretzel knots. This extends the result of the first author in [Le2], who established the AJ conjecture for a large class of two-bridge knots, including all twist knots. Along the way, we explicitly calculate the universal SL₂(C)-character ring of the knot group of the (−2, 3, 2n + 1)-pretzel knot, and show it is reduced for all integers n
Structure-Based Virtual Screening and Biological Evaluation of Mycobacterium tuberculosis Adenosine 5 '-Phosphosulfate Reductase Inhibitors
No full textTuberculosis is among the world's deadliest infectious diseases. APS reductase catalyzes the first committed step in bacterial sulfate reduction and is a validated drug target against latent tuberculosis infection. We performed a virtual screening to identify APSR inhibitors. These inhibitors represent the first non-phosphate-based molecules to inhibit APSR. Common chemical features lay the foundation for the development of agents that could shorten the duration of chemotherapy by targeting the latent stage of TB infection. © 2008 American Chemical Society
Gene Expression Profiling in Down Syndrome Acute Lymphoblastic Leukemia Identifies Distinct Profiles Associated with CRLF2 Expression Status
No full textChildren with Down syndrome (DS) have a 10 to 20-fold increased risk of developing acute lymphoblastic leukemia (ALL), and they have experienced poorer outcomes on recent major protocols worldwide. The cytogenetic abnormalities which are generally common in childhood ALL and contribute to risk-based treatment assignment are markedly less frequent in children with DS-ALL. Recently, activating mutations in Janus kinase 2 (JAK2) have been identified in approximately 20% of DS-ALL, and interstitial deletions involving cytokine receptor-like factor 2 (CRLF2) in approximately 50% of DS-ALL. Global gene expression profiling may provide insights into the biologic consequences of these molecular lesions. We performed microarray analysis of RNA from diagnostic bone marrow samples in 23 DS-ALL and 26 non-DS ALL cases using the Affymetrix Human Genome U133 Plus 2.0 array. CRLF2 expression was high in 10 of the 23 DS-ALL cases, 3 of which also bore JAK2 mutations, and in a single non-DS ALL case. Unsupervised hierarchical clustering analysis demonstrated clustering of non-DS ALL cases belonging to known cytogenetic subgroups such as E2A-PBX1, MLL rearrangement, and high hyperdiploidy. In contrast, neither DS-ALL cases overall nor the JAK2-mutated or high CRLF2 expressing cases formed a cohesive cluster. Supervised analysis identified 43 genes that were differentially expressed between CRLF2 high versus low cases with a false discovery rate <10%. Several of the most highly differentially expressed genes were validated by quantitative real-time PCR. These included three genes with high expression in CRLF2-high cases: chemokine (C-C motif) ligand 17 (CCL17) (p=0.01), V-yes-1 Yamaguchi sarcoma viral oncogene homolog 1 (YES1) (p=0.007), and Iroquois homeobox 2 (IRX2) (p=0.008); and one gene with expression inversely correlated with CRLF2 expression: dual specificity phosphatase 6 (DUSP6) (p=0.0015). Our findings suggest that DS-ALL does not form a single distinct biologic subgroup, but nearly half of DS-ALL cases are defined by high CRLF2 expression, a substantial enrichment for this lesion compared to its prevalence in non-DS ALL. Identification of downstream pathways may identify opportunities for targeted intervention, including interactions with other cytokines and activation of the JAK-STAT pathwa
Discovery of a single faint AGN in a large sample of z > 5 Lyman break galaxies
No full textAs part of a large spectroscopic survey of z > 5 Lyman break galaxies (LBGs), we have identified a single source which is clearly hosting an active galactic nucleus (AGN). Out of a sample of more than 50 spectroscopically confirmed R-band dropout galaxies at z∼ 5 and above, only J104048.6−115550.2 at z= 5.44 shows evidence for a high ionization potential emission line indicating the presence of a hard ionizing continuum from an AGN. Like most objects in our sample the rest-frame-UV spectrum shows the UV continuum breaking across a Lyα line. Uniquely within this sample of LBGs, emission from N V is also detected, a clear signature of AGN photoionization. The object is spatially resolved in Hubble Space Telescope (HST) imaging. This, and the comparatively high Lyα/N V flux ratio indicates that the majority of the Lyα (and the UV continuum longward of it) originates from stellar photoionization, a product of the ongoing starburst in the LBG. Even without the AGN emission, this object would have been photometrically selected and spectroscopically confirmed as a Lyman break in our survey. The measured optical flux (IAB= 26.1) is therefore an upper limit to that from the AGN and is of order 100 times fainter than the majority of known quasars at these redshifts. The detection of a single object in our survey volume is consistent with the best current models of high redshift AGN luminosity function, providing a substantial fraction of such AGN is found within luminous starbursting galaxies. We discuss the cosmological implications of this discovery
The author, the text, and the (post)critic: notes on the encounter between postcritique and postcolonial criticism
No full textThe article confronts postcolonial criticism with postcritique, a proposal by Rita Felski for a hermeneutic strategy aiming to overcome the limits of critique. Because of its self-reflexivity, its liaison with poststructuralism, and the societal categories it mobilizes, postcritics often see postcolonial criticism as a quintessential example of critique. However, postcolonial authors share similar concerns as postcritics, particularly when warning against any hasty conflation between intellectual work and political commitment. This article argues that the postcritical understanding of critique eschews the connection between critique and the realm of culture, thereby running the risk of doing away with context altogether. In order to account for the frameworks or contexts in which cultural objects are produced, without falling into some of the pitfalls of critique that postcritique aims to counter, the article proposes to look at the figure of the author as a bridge between the individual and the collective, as Edward Said suggests. The article closes with an analysis of several (critical and postcritical) readings of J. M. Coetzee’s The Childhood of Jesus to provide an example of how authorship can enter the interpretive scene through the figure of ‘late style’
Exploring the roles, effectiveness and impact of health information professionals within evidence based practice
No full textThis is the thesis (critical appraisal) component of a PhD by Published Works. The overall submission was a portfolio of ten published papers supported by a critical appraisal focusing on two key areas: an exploration of the roles that Health Information Professionals (HIPs) can play within evidence based practice (EBP) and an exploration of the effectiveness and impact of the traditional supportive role played by HIPs within EBP. The published papers are listed and referenced within this document but not contained within it. The majority are available elsewhere within the University of Salford Institutional Repository.Drawing on a model developed from the library literature, the thesis highlights a wide range of supportive and active roles that HIPs can potentially play within EBP. This model is informed and illuminated by the studies within the portfolio that demonstrate how the author has fulfilled a wide range of these roles in practice, and identified a new role within systematic reviews in health and social care. This demonstrates that HIPs can transfer their skills outside their traditional library and information practice domain, thus extending theirrole and offering a range of professional opportunities.Using a varied range of research methodologies, the thesis also explores the effectiveness and impact of the contribution made by HIPs when using traditional skills to support EBP. Two models are used to illustrate the outcomes to which HIPs contribute. These include improving search skills and providing evidence which can, over the longer term, contribute to policy making and patient care. At present the weight of the evidence presented tosupport these links is weak. Methodological issues and future research that needs to be addressed to improve the strength of the evidence base are therefore highlighted and discussed
The XMM-Newton long look of NGC 1365: uncovering of the obscured X-ray source
No full textWe present an analysis of the extreme obscuration variability observed during an XMM–Newton 5-d continuous monitoring of the active galactic nuclei (AGN) in NGC 1365. The source was in a reflection-dominated state in the first ∼1.5 d, then a strong increase in the 7–10 keV emission was observed in ∼10 h, followed by a symmetric decrease. The spectral analysis of the different states clearly shows that this variation is due to an uncovering of the X-ray source. From this observation, we estimate a size of the X-ray source DS < 1013 cm, a distance of the obscuring clouds R∼ 1016 cm and a density n∼ 1011 cm−3. These values suggest that the X-ray absorption/reflection originates from the broad-line region clouds. This is also supported by the resolved width of the iron narrow Kα emission line, consistent with the width of the broad Hβ line
Goals and reputations amongst young children - The validation of the importance of goals and reputation enhancement scales
No full textThe aim of the present research was to provide school psychologists with valid instruments with which to assess the goals and reputations of young children. This was achieved by ascertaining whether the factor structures and the second-order factor models of the high school versions of the Importance of Goals (Carroll, et al., 1997) and Reputation Enhancement Scales (Carroll, et al., 1999) could be replicated with a primary school sample. Eight hundred and eighty-six 10 to 12 year old children were administered modified versions of the two scales, which were combined and renamed the Children's Activity Questionnaire. For the two scales, the factor structure proved replicable and reliable with the primary school sample. A comparison between the factor loadings of the primary school and the high school samples using the coefficient of congruence procedure demonstrated similarity indicating that the scales are replicable and able to be used with a younger primary school sample. Structural equation modelling indicated that the second-order factor structure of the Importance of Goals Scale was acceptable but this was not the case for the second-order factor structure of the Reputation Enhancement Scale
An altered 11-kilobase transcript in leukemic cell lines with the t(4;11)(q21;q23) chromosome translocation.
No full textThe 11q23 chromosome band is frequently associated with chromosomal aberrations in human leukemias. We have previously cloned a DNA fragment derived from chromosome 11 which could be used as a probe to detect rearrangements in DNAs from the leukemic cells of patients with the t(4;11), t(9;11), and t(11;19) translocations. In this study we now show that the same probe detects DNA rearrangements in malignant cells from patients with the t(1;11), t(6;11), t(10;11), and del (11q23) chromosomal abnormalities. A second probe obtained from a region located centrometric to the breakpoint cluster detects major and minor transcripts of 12.5 and 11.5 kilobases, respectively, in all cell lines examined. The same probe identifies an altered 11-kilobase RNA in all three independent cell lines with the t(4;11)(q21;q23) chromosome translocatio
- …
