Pulsed laser deposition for growth of high quality epitaxial garnet films for low threshold waveguide lasers

Pulsed laser deposition (PLD) is a mature technique capable of producing extremely high quality epitaxial single crystalline films. We have grown Nd:doped garnet films of GGG (Gd The talk will summarise our progress using conventional (single beam) PLD in thin-film and waveguide growth, using both nanosecond and femtosecond lasers, and also introduce our new directions in tri-beam PLD (three targets, three lasers) for growth of some interesting, complex and perhaps impossible structures, such as Gaussian doping, internal voids and even helically doped structures

Primary culture and mRNA analysis of human ovarian cells

Established cell lines are invaluable for studying cell and molecular biological questions. A variety of human ovarian cancer (OC) cell lines exist, however, most have acquired significant genetic alterations from their cells of origin, including deletion of important cell cycle regulatory genes. In order to analyze signaling events related to cell cycle control in human OC, we have modified existing protocols for isolating and culturing OC cells from patient ascites fluid and normal ovarian surface epithelial (OSE) cells from benign ovarian tissue sections. These cells maintain an epithelial phenotype and can be manipulated experimentally for several passages before cellular senescence. An example using TGFb1 treatment of OC cells to examine signaling and target gene activation is presented

The appendage role of insect disco genes and possible implications on the evolution of the maggot larval form

AbstractThough initially identified as necessary for neural migration, Disconnected and its partially redundant paralog, Disco-related, are required for proper head segment identity during Drosophila embryogenesis. Here, we present evidence that these genes are also required for proper ventral appendage development during development of the adult fly, where they specify medial to distal appendage development. Cells lacking the disco genes cannot contribute to the medial and distal portions of ventral appendages. Further, ectopic disco transforms dorsal appendages toward ventral fates; in wing discs, the medial and distal leg development pathways are activated. Interestingly, this appendage role is conserved in the red flour beetle, Tribolium (where legs develop during embryogenesis), yet in the beetle we found no evidence for a head segmentation role. The lack of an embryonic head specification role in Tribolium could be interpreted as a loss of the head segmentation function in Tribolium or gain of this function during evolution of flies. However, we suggest an alternative explanation. We propose that the disco genes always function as appendage factors, but their appendage nature is masked during Drosophila embryogenesis due to the reduction of limb fields in the maggot style Drosophila larva

Testing for Network and Spatial Autocorrelation

Testing for dependence has been a well-established component of spatial statistical analyses for decades. In particular, several popular test statistics have desirable properties for testing for the presence of spatial autocorrelation in continuous variables. In this paper we propose two contributions to the literature on tests for autocorrelation. First, we propose a new test for autocorrelation in categorical variables. While some methods currently exist for assessing spatial autocorrelation in categorical variables, the most popular method is unwieldy, somewhat ad hoc, and fails to provide grounds for a single omnibus test. Second, we discuss the importance of testing for autocorrelation in network, rather than spatial, data, motivated by applications in social network data. We demonstrate that existing tests for autocorrelation in spatial data for continuous variables and our new test for categorical variables can both be used in the network setting

The common p.R114W <i>HNF4A </i>mutation causes a distinct clinical subtype of monogenic diabetes

HNF4A mutations cause increased birth weight, transient neonatal hypoglycaemia and maturity onset diabetes of the young (MODY). The most frequently reported HNF4A mutation is p.R114W (previously p.R127W) but functional studies have shown inconsistent results, there is lack of co-segregation in some pedigrees and an unexpectedly high frequency in public variant databases. We confirm that p.R114W is a pathogenic mutation with an odds ratio of 30.4 (95% CI: 9.79 - 125, P=2x10(-21)) for diabetes in our MODY cohort compared to controls. p.R114W heterozygotes do not have the increased birth weight of patients with other HNF4A mutations (3476g vs. 4147g, P=0.0004) and fewer patients responded to sulfonylurea treatment (48% vs. 73%, P=0.038). p.R114W has reduced penetrance; only 54% of heterozygotes developed diabetes by age 30 compared to 71% for other HNF4A mutations. We re-define p.R114W as a pathogenic mutation causing a distinct clinical subtype of HNF4A MODY with reduced penetrance, reduced sensitivity to sulfonylurea treatment and no effect on birth weight. This has implications for diabetes treatment, management of pregnancy and predictive testing of at-risk relatives. The increasing availability of large-scale sequence data is likely to reveal similar examples of rare, low-penetrance MODY mutations.</p

Monitoring Glucocorticoid Receptor in Plasma-derived Extracellular Vesicles as a Marker of Resistance to Androgen Receptor Signaling Inhibition in Prostate Cancer

Disease progression following androgen ablation was shown to be associated with upregulation of the glucocorticoid receptor (GR). Longitudinal monitoring of GR expression in circulating extracellular vesicles (EV) may reflect changes in the tumor cell and facilitates detection of acquired resistance. We utilized LNCaP, LREX cells and a patient-derived xenograft, MDA PDX 322-2-6a, for in vitro and in vivo experiments. Plasma-derived EVs were isolated from patients with localized high-risk prostate cancer undergoing androgen ablation. The mRNA levels of GR in EVs and their responsive genes were detected by transcriptome analysis, qRT-PCR and the protein levels by Western blot analysis. We detected changes in GR expression at mRNA and protein levels in EVs derived from LNCaP and LREX cells in in vitro studies. In in vivo experiments, LNCaP and the PDX MDA 322-2-6a–bearing mice were treated with enzalutamide. GR levels in plasma-derived EVs were increased only in those tumors that did not respond to enzalutamide. Treatment of mice bearing enzalutamide-resistant tumors with a GR inhibitor in combination with enzalutamide led to a transient pause in tumor growth in a subset of tumors and decreased GR levels intracellular and in plasma-derived EVs. In a subgroup of patients with high-risk localized prostate cancer treated with androgen signaling inhibition, GR was found upregulated in matching tissue and plasma EVs. These analyses showed that GR levels in plasma-derived EVs may be used for monitoring the transition of GR expression allowing for early detection of resistance to androgen ablation treatment