Construction of an alternating gradient magnetometer

A magnetometer is described which was constructed to facilitate the study and characterization of the magnetic properties of high transition temperature superconductors. This instrument was used to measure the dc magnetic susceptibility of several superconducting compounds as a function of temperature. The construction of the magnetometer and the operating parameters are discussed in detail

Adaptive structures for the control of cellular separation

This work describes the research undertaken on the development of adaptive structures to reduce turbulent boundary layer separation from a wing. Separation control is a safety critical function that is currently filled by the application of static vortex generators to the wings on most modern aircraft. These devices generate vorticity which produces a downstream mixing effect, energising the boundary layer and postponing separation. The mixing of the boundary layer also increases the drag of the aircraft, reducing efficiency. As static devices, the mixing effect is also permanent, regardless of the current likelihood of separation. Adaptive structures allow the development of beneficial geometry from the body’s surface without the use of breaks or mechanisms in the structure surface. This allows geometry modification without sources of parasitic drag or turbulent transition. The first subject of this work is the development of an adaptive surface to provide the desired momentum transfer through the boundary layer when required, and which can be retracted when not needed, reducing drag and increasing efficiency. Adaptive structures inhabit a complex design space due to the coupling between bending and in-plane stretching of the surface. In previous morphing studies, design optimisation has frequently been used to identify the ideal design parameters. Initially, the design methodology is developed on a test case transferring momentum within a zero-pressure gradient boundary layer. The resulting geometry is then tested experimentally and the structural and fluidic response is found to compare well to simulations. Once the design approach is validated, it must be applied to an efficient location on an aerofoil. The second area of research is therefore the complex, three-dimensional, separation from a 2D aerofoil. This is investigated experimentally with both mean and time-dependent data. The naturally occurring, three-dimensional and spanwise periodic topology of the separated flow, termed a `stall cell', is investigated to determine a suitable location for the application of targeted control at a critical point. Fourier analysis and Proper Orthogonal Decomposition are applied to the time-dependent data gathered to extract coherent, periodic, fluctuations in the separated flow field. The variation of the relative strengths of these features, distinct in frequency, is isolated to regions within the stall cell. Knowledge of the flow field gained during this work is applied to stall cell reduction and a single vortex generator is applied to the wing upstream of an identified critical point within the flow field. The separated area is seen to reduce significantly with this actuation. The design methodology developed previously is applied to the initially curved surface of an aerofoil. The final structure is manufactured and tested experimentally and found to be effective in reducing the separation extent. The control is found to be less effective than the static vortex generators. However, unlike the static device, the adaptive version is fully elastic, in both deployment and reaction, and thus shows none of the detrimental effects associated with traditional devices.Open Acces

DNMT3A Haploinsufficiency Provokes Hematologic Malignancy of B-Lymphoid, T-Lymphoid, and Myeloid Lineage in Mice

DNA methyltransferase 3A (DNMT3A) is a master epigenetic regulator of benign and malignant hematopoiesis. To dissect the biological consequences of homozygous and heterozygous Dnmt3a inactivation in malignant hematopoiesis, we generated Dnmt3a homozygous null (Dnmt3aΔ/Δ) and Dnmt3a heterozygous (Dnmt3a+/–) mice and compared the presentations of hematologic malignancies between cohorts. Bi-allelic inactivation of Dnmt3a results in the presentation of mature lymphoid neoplasms resembling chronic lymphocytic leukemia (CLL; B220+CD19+CD5+; 88% penetrance (37/42)) and CD8+ peripheral T-cell lymphoma (PTCL; TCRβ+CD3+CD8+CD4—; 40% penetrance (17/42)). In contrast, mono-allelic inactivation of Dnmt3a results in the presentation of CLL and PTCL at reduced penetrance (47% (14/30) & 10% (3/30), respectively) and, rarely, a mature myeloproliferative neoplasm (MPN; CD11b+Gr-1+; 10% penetrance (3/30)). Molecular interrogation of PTCLs revealed genome-wide deregulation of DNA methylation, characterized by 10-fold greater hypomethylation than hypermethylation of promoters and enhancers. Transcription factor binding sites for AML1, NF-κB, and OCT1 were enriched in hypomethylated promoters, implicating these transcription factors in tumor pathogenesis or DNMT3A-associated DNA methylation. Whereas 71 hypomethylated genes showed an increased expression in PTCL, only 3 hypermethylated genes were silenced, suggesting cancer-specific hypomethylation more frequently affects the transcriptome than hypermethylation in lymphoma. Importantly, we observed in Dnmt3a-deficient PTCLs the downregulation of p53 protein by western blot and p53 target genes by gene set enrichment analysis. Decreased p53 protein expression occurred in pre-tumor thymocytes of 9 months old, but not 6 weeks old, Dnmt3a+/– disease-free mice, demonstrating that p53 downregulation occurs an intermediate event in tumorigenesis. Analysis of Dnmt3a+/– tumors revealed that PTCL develops without mutation or silencing of the remaining wild-type Dnmt3a allele. These data demonstrate that Dnmt3a is a haploinsufficient tumor suppressor in murine mature CD8+ PTCL and loss of p53 protein occurs as an intermediate event in tumorigenesis. To better understand the dysregulated epigenetic events favoring the development of CLL and PTCL from B-1a and CD8+ cells in Dnmt3aΔ/Δ mice, we compared the methylomes and transcriptomes of normal B-1a and CD8+ T-cells in addition to comparison of malignant CLL and PTCL cells. We observe that whereas patterns of methylation and transcription in normal B-1a cells and CD8+ T cells are similar, methylomes and transcriptomes in malignant B-1a and CD8+ T cells are remarkably distinct, suggesting a cell-type specific function for Dnmt3a in cellular transformation

Multi-stress proteomics: The global protein response to multiple environmental stressors in the porcelain crab Petrolisthes cinctipes

Global climate change is increasing the number of hot days along the California coast as well as increasing the incidence of off-shore upwelling events that lower the pH of intertidal seawater; thus, intertidal organisms are experiencing an increase in more than one stress simultaneously. This study seeks to characterize the global protein response of the eurythermal porcelain crab Petrolisthes cinctipes to changes in thermal, pH, and tidal regime treatments, either combined or individually. The first experiment examined temperature stress alone and sought to determine the effect of chronic temperature acclimation on the acute heat shock response. We compared the proteomic response of cheliped muscle tissue following a month-long acclimation to either (1) constant 10°C, (2) daily fluctuation from 10-20°C, or (3) daily fluctuation from 10-30°C, all followed by either a 30°C acute heat shock or 10°C control. We found that ATP supply via the phosphagen system, changes in glycolytic enzymes, muscle fiber restructuring, respiratory protein fragmentation, and immunity were primarily affected by acclimation and subsequent heat shock. Acclimation to the “extreme” regimes (10°C and 10-30°C) resulted in the greatest proteomic changes, while acclimation to the moderate regime (10-20°C) resulted in a more mild response to heat shock (i.e., fewer adjustments to relative protein abundance). The second experiment sought to determine the proteomic response of gill tissue following a 17 d acclimation to daily changes in pH (ambient pH 8.1 vs low pH 7.6), tidal regime (constant immersion vs 6 h emersion), and temperature (ambient 11°C vs 22-31°C heat shock during emersion). Low pH alone reduced expression of molecular chaperones of the endoplasmic reticulum, lectins, and serine proteases involved in activating the prophenoloxidase cascade. It also increased the abundance of Na+/K+-ATPase, nitrogen metabolism enzymes, and induced changes in tubulin expression, all suggesting an increase in ammonium excretion. Addition of emersion during low pH reduced the abundance of several metabolic proteins including those involved in the proposed ammonium excretion mechanism, suggesting a decrease in metabolic function in part to prevent toxic accumulation of ammonium in the branchial chambers. Combined pH, emersion, and thermal stress increased the abundance of proteins involved in cuticle binding and crosslinking. These results indicate that the responses to pH, tidal cycle, and temperature are highly dependent on one another and that changes in ER protein maturation, ion transport, immunity, and cuticle structure are the primary biochemical systems impacted by these environmental stressors in crustacean gill

A computer control system for the alternating gradient magnetometer

An alternating gradient magnetometer was interfaced to a computer for the automation of data taking. Using a fast Fourier transform analysis system data can be acquired and processed in real time. Data are stored on disk and can be recalled for plotting and further analysis. With the addition of a simple liquid nitrogen cryostat, magnetization measurements can be performed in the range from 300 to 77 K. Results are reported on three different types of piezoelectric transducers