Some aspects of steroidal epoxide rearrangements

The reactions of 5,6α-epoxy-3β-hydroxy-5α-cholestane, 5,6β-epoxy-3β-hydroxy-5β-cholestane, and 5,6α-epoxy-3β-methoxy-5α-cholestane with boron trifluoride etherate in benzene give largely products of rearrangement via C(5)-O cleavage. These results contrast with the known reactions of the corresponding 3β-acetoxy-epoxides which give high yields of fluorohydrins. [Continues.

Exploring teachers’ professional development with Twitter: A sociomaterial analysis

“BEST. PD. EVER!” Some teachers make bold claims for the way that Twitter supports their professional development, yet research into this area is rather limited. This study sought to gain a better understanding of the practices involved and the part that Twitter plays. It uses a sociomaterial sensibility informed by actor-network theory (ANT) to unravel the complex webs of relations which form, break apart and reform when knowledge practices are enacted in the mediated arena of Twitter. To explore this rich but messy environment, I evoke the spirit of the Parisian flâneur to develop an ethnographic approach I refer to as ‘flânography.’ Characterised by purposeful wandering, the approach coupled participant observation and interviews, with emerging methods involving a bot and a 'walkie-talkie' app. Adopting the sensibility of the flâneur consistently through data collection, analysis and presentation resulted in traversals which render pathways of experience. This led to me presenting the findings in three ‘Gatherings’ (Law, 2004a), each taking a tweet or other data snippet as a point of departure. Through the Gatherings I present the activities of both human and nonhuman participants, establish how they came together (or didn’t) and gain a better appreciation of the outcomes of those interrelationships. In reading across the Gatherings, two interlocking dimensions emerged through which teachers' learning practices on Twitter might be conceptualised. ‘Compound learning’ describes how practices can be understood through three meanings of compound: framed chemically (through formation of bonds and associations), financially (like interest which grows cumulatively) and as a mixture (an assortment of actors engaged in activities). The second dimension describes how compound learning can be enacted across three ‘scales:’ acts, activities and practices. By extending previous research, this thesis contributes a richer and deeper understanding of what ‘Twitter Professional Development’ involves, thereby helping to legitimise it within broader professional development discourse. Adding to the current literature on teachers’ professional learning, this thesis reveals how significant personal-isation is in two senses: that teachers can exercise choice in what, when and how they learn; and secondly, the importance of being able to forge socio-professional connections with fellow educators in different ways. The flânographic approach and the new methods which arose within it offer wider contributions for studies exploring activities which range across online and offline spaces, and through time

Digital video moving object segmentation using tensor voting: A non-causal, accurate approach

Motion based video segmentation is important in many video processing applications such as MPEG4. This thesis presents an exhaustive, non-causal method to estimate boundaries between moving objects in a video clip. It make use of tensor voting principles. The tensor voting is adapted to allow image structure to manifest in the tangential plane of the saliency map. The technique allows direct estimation of motion vectors from second-order tensor analysis. The tensors make maximal and direct use of the available information by encoding it into the dimensionality of the tensor. The tensor voting methodology introduces a non-symmetrical voting kernel to allow a measure of voting skewness to be inferred. Skewness is found in the third-order tensor in the direction of the tangential first eigenvector. This new concept is introduced as the Tensor Skewness Map or TS map. The TS map gives further information about whether an object is occluding or disoccluding another object. The information can be used to infer the layering order of the moving objects in the video clip. Matched filtering and detection are applied to reduce the TS map into occluding and disoccluding detections. The technique is computationally exhaustive, but may find use in off-line video object segmentation processes. The use of commercial-off-the-shelf Graphic Processor Units is demonstrated to scale well to the tensor voting framework, providing the computational speed improvement required to make the framework realisable on a larger scale and to handle tensor dimensionalities higher than before

Networks of intergenic long-range enhancers and snpRNAs drive castration-resistant phenotype of prostate cancer and contribute to pathogenesis of multiple common human disorders

Biological and mechanistic relevance of intergenic disease-associated genetic loci (IDAGL) containing highly statistically significant disease-linked SNPs remains unknown. Here we present the experimental and clinical evidence revealing important role of IDAGL in human diseases. Targeted RT-PCR screen coupled with sequencing of purified PCR products detects widespread transcription at multiple intergenic disease-associated genomic loci (IDAGL) and identifies 96 small non-coding trans-regulatory RNAs of ~ 100-300 nt in length containing SNPs associated with 21 common human disorders (snpRNAs). Functionality of snpRNAs is supported by multiple independent lines of experimental evidence demonstrating their cell-type-specific expression and evolutionary conservation of sequences, genomic coordinates, and biological effects. Analysis of chromatin state signatures, expression profiling experiments using microarray and Q-PCR technologies, and luciferase reporter assays indicate that many IDAGL are Polycomb-regulated long-range enhancers. Expression of snpRNAs in human and mouse cells markedly affects cellular behavior and induces allele-specific clinically-relevant phenotypic changes: NLRP1-locus snpRNAs exert regulatory effects on monocyte/macrophage trans-differentiation, induce prostate cancer (PC) susceptibility snpRNAs, and transform low-malignancy hormone-dependent human PC cells into highly malignant androgen-independent PC. Q-PCR analysis and luciferase reporter assays demonstrate that snpRNA sequences represent allele-specific “decoy” targets of microRNAs which function as SNP-allele-specific modifiers of microRNA expression and activity. We demonstrate that trans-acting RNA molecules facilitating androgen depletion-independent growth (ADIG) in vitro and castration-resistant (CR) phenotype in vivo of PC contain intergenic 8q24-locus SNP variants which were recently linked with increased risk of developing PC. Expression level of 8q24-locus PC susceptibility snpRNAs is regulated by NLRP1-locus snpRNAs, which are transcribed from the intergenic long-range enhancer sequence located in 17p13 region at ~ 30 kb distance from the NLRP1 gene. Q-PCR analysis of clinical PC samples reveals markedly increased snpRNA expression levels in tumor tissues compared to the adjacent normal prostate [122-fold and 45-fold in Gleason 7 tumors (p = 0.03); 370-fold and 127-fold in Gleason 8 tumors (p = 0.0001); for NLRP1-locus and 8q24-locus SnpRNAs, respectively]. Highly concordant expression profiles of the NLRP1-locus snpRNAs and 8q24 CR-locus snpRNAs (r = 0.896; p < 0.0001) in clinical PC samples and experimental evidence of trans-regulatory effects of NLRP1-locus snpRNAs on expression of 8q24-locus SnpRNAs indicate that ADIG and CR phenotype of human PC cells can be triggered by RNA molecules transcribed from the NLRP1-locus intergenic enhancer and down-stream activation of the 8q24-locus snpRNAs. Our results define the intergenic NLRP1 and 8q24 regions as regulatory loci of ADIG and CR phenotype of human PC, reveal previously unknown molecular links between the innate immunity/inflammasome system and development of hormone-independent PC, and identify novel diagnostic and therapeutic targets exploration of which should be highly beneficial for clinical management of PC

A new sighting study for the fixed concentration procedure to allow for gender differences

The fixed concentration procedure (FCP) has been proposed as an alternative to the median lethal concentration (LC50) test (organisation for economic co-operation and development (OECD) test guideline [TG] 403) for the assessment of acute inhalation toxicity. The FCP tests animals of a single gender (usually females) at a number of fixed concentration levels in a sequential fashion. It begins with a sighting study that precedes the main FCP study and is used to determine the main study starting concentration. In this paper, we propose a modification to the sighting study and suggest that it should be conducted using both male and female animals, rather than just animals of a single gender. Statistical analysis demonstrates that, when females are more sensitive, the new procedure is likely to give the same classification as the original FCP, whereas, if males are more sensitive, the new procedure is much less likely to lead to incorrect classification into a less toxic category. If there is no difference in the LC50 for females and males, the new procedure is slightly more likely to classify into a more stringent class than the original FCP. Overall, these results show that the revised sighting study ensures gender differences in sensitivity do not significantly impact on the performance of the FCP, supporting its use as an alternative test method for assessing acute inhalation toxicity

A statistical evaluation of the effects of gender differences in assessment of acute inhalation toxicity

Acute inhalation toxicity of chemicals has conventionally been assessed by the median lethal concentration (LC50) test (organisation for economic co-operation and development (OECD) TG 403). Two new methods, the recently adopted acute toxic class method (ATC; OECD TG 436) and a proposed fixed concentration procedure (FCP), have recently been considered, but statistical evaluations of these methods did not investigate the influence of differential sensitivity between male and female rats on the outcomes. This paper presents an analysis of data from the assessment of acute inhalation toxicity for 56 substances. Statistically significant differences between the LC50 for males and females were found for 16 substances, with greater than 10-fold differences in the LC50 for two substances. The paper also reports a statistical evaluation of the three test methods in the presence of unanticipated gender differences. With TG 403, a gender difference leads to a slightly greater chance of under-classification. This is also the case for the ATC method, but more pronounced than for TG 403, with misclassification of nearly all substances from Globally Harmonised System (GHS) class 3 into class 4. As the FCP uses females only, if females are more sensitive, the classification is unchanged. If males are more sensitive, the procedure may lead to under-classification. Additional research on modification of the FCP is thus proposed

Personnel management: defence, retrenchment, advance?

It has recently been argued that the use of external consultants is indicative of a crisis in personnel management. However, the use of consultants, of whatever type, has not been adequately explained for a number of reasons. The reasons underlying the increasing usage of external consultants by personnel is a form of defence, allowing it to shed some activities thereby strengthening its position within the organisation. To illustrate this argument the reasons for the growth in the use of a particular type of consultant by personnel – executive recruitment consultancies – are considered. The results reported draw on two major surveys. The first was directed at executive consultancies whereas the second was directed at corporate personnel directors in the Times 100 companies. Response rates of 42 per cent and 55 per cent were achieved