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Search Results: 1 - 10 of 210911 matches for " Amanda L Cleaver "
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Gene-based outcome prediction in multiple cohorts of pediatric T-cell acute lymphoblastic leukemia: a Children's Oncology Group study
Amanda L Cleaver, Alex H Beesley, Martin J Firth, Nina C Sturges, Rebecca A O'Leary, Stephen P Hunger, David L Baker, Ursula R Kees
Molecular Cancer , 2010, DOI: 10.1186/1476-4598-9-105
Abstract: Using HG-U133Plus2 microarrays we modeled a five-gene classifier (5-GC) that accurately predicted clinical outcome in a cohort of 50 T-ALL patients. The 5-GC was further tested against three independent cohorts of T-ALL patients, using either qRT-PCR or microarray gene expression, and could predict patients with significantly adverse clinical outcome in each. The 5-GC featured the interleukin-7 receptor (IL-7R), low-expression of which was independently predictive of relapse in T-ALL patients. In T-ALL cell lines, low IL-7R expression was correlated with diminished growth response to IL-7 and enhanced glucocorticoid resistance. Analysis of biological pathways identified the NF-κB and Wnt pathways, and the cell adhesion receptor family (particularly integrins) as being predictive of relapse. Outcome modeling using genes from these pathways identified patients with significantly worse relapse-free survival in each T-ALL cohort.We have used two different approaches to identify, for the first time, robust gene signatures that can successfully discriminate relapse and CCR patients at the time of diagnosis across multiple patient cohorts and platforms. Such genes and pathways represent markers for improved patient risk stratification and potential targets for novel T-ALL therapies.T-cell acute lymphoblastic leukemia (T-ALL) affects approximately 15% of newly diagnosed pediatric ALL patients. Continuous complete clinical remission (CCR) in T-ALL patients is now approaching 80% due to the implementation of aggressive chemotherapy protocols [1-6]. However, patients that relapse (R) have poor prognosis and aggressive therapy can lead to long-term side effects in those that achieve CCR [7]. In the clinical setting, age and white blood cell count (WBC) at diagnosis are used to stratify B-lineage ALL patients as either standard or high risk, significantly impacting on the type and intensity of post-induction therapy used. However these NCI-defined criteria have been shown to hav
Cyclophosphamide Chemotherapy Sensitizes Tumor Cells to TRAIL-Dependent CD8 T Cell-Mediated Immune Attack Resulting in Suppression of Tumor Growth
Robbert G. van der Most, Andrew J. Currie, Amanda L. Cleaver, Joanne Salmons, Anna K. Nowak, Sathish Mahendran, Irma Larma, Amy Prosser, Bruce W. S. Robinson, Mark J. Smyth, Anthony A. Scalzo, Mariapia A. Degli-Esposti, Richard A. Lake
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0006982
Abstract: Background Anti-cancer chemotherapy can be simultaneously lymphodepleting and immunostimulatory. Pre-clinical models clearly demonstrate that chemotherapy can synergize with immunotherapy, raising the question how the immune system can be mobilized to generate anti-tumor immune responses in the context of chemotherapy. Methods and Findings We used a mouse model of malignant mesothelioma, AB1-HA, to investigate T cell-dependent tumor resolution after chemotherapy. Established AB1-HA tumors were cured by a single dose of cyclophosphamide in a CD8 T cell- and NK cell-dependent manner. This treatment was associated with an IFN-α/β response and a profound negative impact on the anti-tumor and total CD8 T cell responses. Despite this negative effect, CD8 T cells were essential for curative responses. The important effector molecules used by the anti-tumor immune response included IFN-γ and TRAIL. The importance of TRAIL was supported by experiments in nude mice where the lack of functional T cells could be compensated by agonistic anti-TRAIL-receptor (DR5) antibodies. Conclusion The data support a model in which chemotherapy sensitizes tumor cells for T cell-, and possibly NK cell-, mediated apoptosis. A key role of tumor cell sensitization to immune attack is supported by the role of TRAIL in tumor resolution and explains the paradox of successful CD8 T cell-dependent anti-tumor responses in the absence of CD8 T cell expansion.
Effects of Neurokinin-1 Receptor Inhibition on Anxiety Behavior in Neonatal Rats Selectively Bred for an Infantile Affective Trait  [PDF]
Amanda L. Schott, Betty Zimmerberg
Pharmacology & Pharmacy (PP) , 2014, DOI: 10.4236/pp.2014.59096

Interest in understanding the etiology and developing new treatments for anxiety disorders in children and adolescents has led to recent studies of neurotransmitters not traditionally associated with neural pathways for fear and anxiety. The binding of the neurotransmitter substance P (SP) to its neurokinin-1 (NK1) receptor may be a crucial component in mediating the anxiety response. While previous studies using rodent models have documented the anxiolytic effects of SP antagonists, the role of individual differences in affective temperament has not yet been examined in studies of drug response. This study used intracerebroventricular injections of the NK1 antagonist Spantide II at concentrations of 10 and 100 pmol to examine the consequences of blocking the SP-NK1 pathway in high and low line rats selectively bred for high or low levels of ultrasonic distress calls after a brief maternal separation. Affective temperament was a significant factor in determining drug response. Spantide II resulted in a significant reduction of distress calls in subjects in the high anxiety line, while low line subjects with low anxiety were resistant to the drug. These data indicate that the SP-NK1 pathway could be an important therapeutic target for the treatment of various stress disorders, but drug response might be influenced by the individual’s state anxiety or history of chronic stress.

The phytosociology of the Vermaaks, Marnewicks and Buffelsklip valleys of the Kammanassie Nature Reserve, Western Cape
G. Cleaver,L.R. Brown,G.J. Bredenkamp
Koedoe : African Protected Area Conservation and Science , 2005, DOI: 10.4102/koedoe.v48i1.162
Abstract: Long-term conservation ecosystems require a broader understanding of the ecological processes involved. Because ecosystems react differently to different management practices, it is important that a description and classification of the vegetation of an area are completed. A vegetation survey of the valley areas of the Kammanassie Nature Reserve was undertaken as part of a larger research project to assess the environmental impacts of large-scale groundwater abstraction from Table Mountain Group aquifers on ecosystems in the reserve. From a TWFNSPAN classification, refined by Braun-Blanquet procedures, 21 plant communities, which can be grouped into 13 major groups, were identified. A classification and description of these communities, as well as a vegetation map of the different areas are presented. Associated gradients in habitat w ere identified by using an ordination algorithm (DECORANA). The diagnostic species as well as the prominent and less conspicuous species of the tree, shrub, forb and grass strata are outlined. The study also resulted in a total number of 481 species being identified and the discovery of a new Erica species. These vegetation surveys and descriptions provide baseline information for management purposes and that allows monitoring as well as similar surveys to be conducted in future.
A vegetation description and floristic analyses of the springs on the Kammanassie Mountain, Western Cape
G. Cleaver,L.R. Brown,G.J. Bredenkamp
Koedoe : African Protected Area Conservation and Science , 2004, DOI: 10.4102/koedoe.v47i2.78
Abstract: The Kammanassie Mountain is a declared mountain catchment area and a Cape mountain zebra Equus zebra zebra population is preserved on the mountain. The high number of springs on the mountain not only provides water for the animal species but also contributes to overall ecosystem functioning. Long-term conservation of viable ecosystems requires a broader understanding of the ecological processes involved. It was therefore decided that a classification, description and mapping of the spring vegetation of the Kammanassie Mountain be undertaken. A TWINSPAN classification, refined by Braun-Blanquet procedures, revealed 11 major plant communities that could be related to geological origin. Habitat factors associated with differences in vegetation include topography, soil type and grazing. Descriptions of the plant communities include diagnostic species as well as prominent and less conspicuous species of the tree, shrub and herbaceous layers. The results also indicate a high species richness compared to similar regions and the difference between plant communities of wet and dry springs. This data is important for long-term monitoring of the spring ecosystems as well as for the compilation of management plans.
Knight’s Tours on 3 x n Chessboards with a Single Square Removed  [PDF]
Amanda M. Miller, David L. Farnsworth
Open Journal of Discrete Mathematics (OJDM) , 2013, DOI: 10.4236/ojdm.2013.31012
Abstract: The following theorem is proved: A knights tour exists on all 3 x n chessboards with one square removed unless: n is even, the removed square is (i, j) with i + j odd, n = 3 when any square other than the center square is removed, n = 5, n = 7 when any square other than square (2, 2) or (2, 6) is removed, n = 9 when square (1, 3), (3, 3), (1, 7), (3, 7), (2, 4), (2, 6), (2, 2), or (2, 8) is removed, or when square (1, 3), (2, 4), (3, 3), (1, n – 2), (2, n – 3), or (3, n – 2) is removed.
Counting the Number of Squares Reachable in k Knight’s Moves  [PDF]
Amanda M. Miller, David L. Farnsworth
Open Journal of Discrete Mathematics (OJDM) , 2013, DOI: 10.4236/ojdm.2013.33027

Using geometric techniques, formulas for the number of squares that require k moves in order to be reached by a sole knight from its initial position on an infinite chessboard are derived. The number of squares reachable in exactly k moves are 1, 8, 32, 68, and 96 for k = 0, 1, 2, 3, and 4, respectively, and 28k – 20 for k ≥ 5. The cumulative number of squares reachable in k or fever moves are 1, 9, 41, and 109 for k = 0, 1, 2, and 3, respectively, and 14k2 6k + 5 for k ≥ 4. Although these formulas are known, the proofs that are presented are new and more mathematically accessible then preceding proofs.

The Zapatista Effect: The internet and the rise of an alternativa political fabric
Harry Cleaver
Ciberlegenda , 2001,
Abstract: n o disponível
Phenomenological Survey of a Minimal Superstring Standard Model
Gerald Cleaver
Physics , 2000,
Abstract: We discuss a heterotic-string solution in which the observable sector effective field theory just below the string scale reduces to that of the MSSM, with the standard observable gauge group being just SU(3)_C x SU(2)_L x U(1)_Y and the SU(3)_C x SU(2)_L x U(1)_Y-charged spectrum of the observable sector consisting solely of the MSSM spectrum. Associated with this model is a set of distinct flat directions of vacuum expectation values (VEVs) of fields that all produce solely the MSSM spectrum. Some of these directions only involve VEVs of non-Abelian singlet fields while others also contain VEVs of non-Abelian charged fields.
String Cosmology: A Review
Gerald Cleaver
Physics , 2003, DOI: 10.1016/j.asr.2003.08.046
Abstract: The second string revolution, which begin around 1995, has led to a drastic alteration in our perception of the universe, perhaps even more so then did the first string revolution of 1984. That is, extending 10-dimensional string theory to 11-dimensional M-theory has had more profound implications than did the original extension of 4-dimensional quantum mechanics and relativity to 10-dimensional string theory. After a brief review of M-theory, I discuss some implications of large extra dimensions. I then consider astronomical evidence for, and constraints on, large compactified dimensions. I conclude with a possible resolution to the apparent inconsistency between the MSSM scale and string scale in the weak coupling limit. Talk presented at COSPAR '02, Houston, Texas, October 2002.
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