Transitions

Transitions developed after experiencing one of the largest transitions of my life from an autonomous being and business owner to a pregnant woman to a mother, all during my three year Masters of Fine Art program at Southern Illinois University Carbondale. The first section of the show follows my emotional progression throughout pregnancy, as well as physical form, highlighting inner conflict. An emotional conflict and progression is illustrated through the use of emotional landscapes on the exterior walls of the space. Each emotional landscape is created from 25 canvas prints that I photographed on my mobile devices. The interior walls showcase my growing pregnant torso and separated oversized heads. The second section of Transitions deals with the issues of motherhood, specifically the working mother. As a working mother and graduate student, I have had to spend a large amount of time away from my daughter, and because of this I have felt a large amount of guilt and sadness. To illustrate these feelings I created installations from empty rocking chairs and all of the milk storage bags that have been used to feed my daughter in my absence. These two sculptures bookend a 10 minute long projection of my drive home taken on my iPhone. Around the exterior walls of this space, images of my daughter sleeping, and personal affects of her room are shown on large 36 x24 digital inkjet prints

GPS constraints on interplate locking within the Makran subduction zone

The Makran subduction zone is one of the last convergent margins to be investigated using space-based geodesy. While there is a lack of historical and modern instrumentation in the region, a sparse sampling of continuous and campaign measurements over the past decade has allowed us to make the first estimates of convergence rates. We combine GPS measurements from 20 stations located in Iran, Pakistan and Oman along with hypocentral locations from the International Seismological Centre to create a preliminary 3-D estimate of the geometry of the megathrust, along with a preliminary fault-coupling model for the Makran subduction zone. Using a convergence rate which is strongly constrained by measurements from the incoming Arabia plate along with the backslip method of Savage, we find the Makran subduction zone appears to be locked to a depth of at least 38 km and accumulating strain.We also find evidence for a segmentation of plate coupling, with a 300 km long section of reduced plate coupling. The range of acceptable locking depths from our modelling and the 900 km along-strike length for the megathrust, makes the Makran subduction zone capable of earthquakes up to Mw = 8.8. In addition, we find evidence for slow-slip-like transient deformation events on two GPS stations. These observations are suggestive of transient deformation events observed in Cascadia, Japan and elsewhere

Deterioration of railway track due to dynamic vehicle loading and spatially varying track stiffness

Please read the abstract in the section 00front of this documentThesis (PhD)--University of Pretoria, 2009.Civil Engineeringunrestricte

Cdx4 Dysregulates Hox Gene Expression and Generates Acute Myeloid Leukemia Alone and in Cooperation with Meis1a in a Murine Model

HOX genes have emerged as critical effectors of leukemogenesis, but the mechanisms that regulate their expression in leukemia are not well understood. Recent data suggest that the caudal homeobox transcription factors CDX1, CDX2, and CDX4, developmental regulators of HOX gene expression, may contribute to HOX gene dysregulation in leukemia. We report here that CDX4 is expressed normally in early hematopoietic progenitors and is expressed aberrantly in approximately 25% of acute myeloid leukemia (AML) patient samples. Cdx4 regulates Hox gene expression in the adult murine hematopoietic system and dysregulates Hox genes that are implicated in leukemogenesis. Furthermore, bone marrow progenitors that are retrovirally engineered to express Cdx4 serially replate in methylcellulose cultures, grow in liquid culture, and generate a partially penetrant, long-latency AML in bone marrow transplant recipients. Coexpression of the Hox cofactor Meis1a accelerates the Cdx4 AML phenotype and renders it fully penetrant. Structure-function analysis demonstrates that leukemic transformation requires intact Cdx4 transactivation and DNA-binding domains but not the putative Pbx cofactor interaction motif. Together, these data indicate that Cdx4 regulates Hox gene expression in adult hematopoiesis and may serve as an upstream regulator of Hox gene expression in the induction of acute leukemia. Inasmuch as many human leukemias show dysregulated expression of a spectrum of HOX family members, these collective findings also suggest a central role for CDX4 expression in the genesis of acute leukemia

Experimental characterisation of railway wheel squeal occurring in large-radius curves

Tonal squeal noise (i.e. the high amplitude singing of a railway wheel with pure tone components) is emitted by some trailing inner wagon wheels on heavy haul trains in 1000m radius curves on the iron ore export line in South Africa. Field measurements have shown that the trailing inner wheels that squeal are subject to predominantly longitudinal creepage with little to no lateral creepage. The longitudinal creepage acting at the contact of the squealing wheels exceeds 1%, which supports the likelihood of creep saturation and subsequently squeal due to unsteady longitudinal creepage in the large radius curves. Experimental modal analysis of the wheel types identified to be relevant to squeal has revealed that for each unstable frequency, two eigenmodes are likely to be important: one which has a large mode shape component at the wheel-rail contact in the circumferential direction and another which has a large mode shape component at the wheel-rail contact in the radial direction. A frictional self-excitation mechanism based on mode-coupling is favoured as being responsible for squeal excited in large radius curves.http://pif.sagepub.comhb2017Mechanical and Aeronautical Engineerin

Heterogeneity within AML with CEBPA mutations; only CEBPA double mutations, but not single CEBPA mutations are associated with favourable prognosis

CCAAT/enhancer binding protein alpha (CEBPA) mutations in AML are associated with favourable prognosis and are divided into N- and C-terminal mutations. The majority of AML patients have both types of mutations. We assessed the prognostic significance of single (n=7) and double (n=12) CEBPA mutations among 224 AML patients. Double CEBPA mutations conferred a decisively favourable overall (P=0.006) and disease-free survival (P=0.013). However, clinical outcome of patients with single CEBPA mutations was not different from CEBPA wild-type patients. In a multivariable analysis, only double – but not single – CEBPA mutations were identified as independent prognostic factors. These findings indicate heterogeneity within AML patients with CEBPA mutations

Synthetic Lethal Interaction between Oncogenic KRAS Dependency and STK33 Suppression in Human Cancer Cells

An alternative to therapeutic targeting of oncogenes is to perform “synthetic lethality” screens for genes that are essential only in the context of specific cancer-causing mutations. We used high-throughput RNA interference (RNAi) to identify synthetic lethal interactions in cancer cells harboring mutant KRAS, the most commonly mutated human oncogene. We find that cells that are dependent on mutant KRAS exhibit sensitivity to suppression of the serine/threonine kinase STK33 irrespective of tissue origin, whereas STK33 is not required by KRAS-independent cells. STK33 promotes cancer cell viability in a kinase activity-dependent manner by regulating the suppression of mitochondrial apoptosis mediated through S6K1-induced inactivation of the death agonist BAD selectively in mutant KRAS-dependent cells. These observations identify STK33 as a target for treatment of mutant KRAS-driven cancers and demonstrate the potential of RNAi screens for discovering functional dependencies created by oncogenic mutations that may enable therapeutic intervention for cancers with “undruggable” genetic alterations.National Institutes of Health (U.S.) (grant R33 CA128625)National Institutes of Health (U.S.) (grant NIH U54 CA112962)National Institutes of Health (U.S.) (grant P01 CA095616)National Institutes of Health (U.S.) (grant P01 CA66996)Starr Cancer ConsortiumDoris Duke Charitable FoundationMPN Research FoundationDeutsche Forschungsgemeinschaft (grant SCHO 1215/1-1)Deutsche Forschungsgemeinschaft (grant FR 2113/1-1)Brain Science FoundationLeukemia & Lymphoma Society of Americ