Singular values of some modular functions

We study the properties of special values of the modular functions obtained from Weierstrass P-function at imaginary quadratic points.Comment: 19 pages,corrected typo

Development of systems and techniques for landing an aircraft using onboard television

A flight program was conducted to develop a landing technique with which a pilot could consistently and safely land a remotely piloted research vehicle (RPRV) without outside visual reference except through television. Otherwise, instrumentation was standard. Such factors as the selection of video parameters, the pilot's understanding of the television presentation, the pilot's ground cockpit environment, and the operational procedures for landing were considered. About 30 landings were necessary for a pilot to become sufficiently familiar and competent with the test aircraft to make powered approaches and landings with outside visual references only through television. When steep approaches and landings were made by remote control, the pilot's workload was extremely high. The test aircraft was used as a simulator for the F-15 RPRV, and as such was considered to be essential to the success of landing the F-15 RPRV

Identification of presumed pathogenic KRT3 and KRT12 gene mutations associated with Meesmann corneal dystrophy.

PurposeTo report potentially pathogenic mutations in the keratin 3 (KRT3) and keratin 12 (KRT12) genes in two individuals with clinically diagnosed Meesmann corneal dystrophy (MECD).MethodsSlit-lamp examination was performed on the probands and available family members to identify characteristic features of MECD. After informed consent was obtained, saliva samples were obtained as a source of genomic DNA, and screening of KRT3 and KRT12 was performed. Potentially pathogenic variants were screened for in 200 control chromosomes. PolyPhen-2, SIFT, and PANTHER were used to predict the functional impact of identified variants. Short tandem repeat genotyping was performed to confirm paternity.ResultsSlit-lamp examination of the first proband demonstrated bilateral, diffusely distributed, clear epithelial microcysts, consistent with MECD. Screening of KRT3 revealed a heterozygous missense variant in exon 1, c.250C>T (p.(Arg84Trp)), which has a minor allele frequency of 0.0076 and was not identified in 200 control chromosomes. In silico analysis with PolyPhen-2 and PANTHER predicted the variant to be damaging to protein function; however, SIFT analysis predicted tolerance of the variant. The second proband demonstrated bilateral, diffusely distributed epithelial opacities that appeared gray-white on direct illumination and translucent on retroillumination. Neither parent demonstrated corneal opacities. Screening of KRT12 revealed a novel heterozygous insertion/deletion variant in exon 6, c.1288_1293delinsAGCCCT (p.(Arg430_Arg431delinsSerPro)). This variant was not present in either of the proband's parents or in 200 control chromosomes and was predicted to be damaging by PolyPhen-2, PANTHER, and SIFT. Haplotype analysis confirmed paternity of the second proband, indicating that the variant arose de novo.ConclusionsWe present a novel KRT12 mutation, representing the first de novo mutation and the first indel in KRT12 associated with MECD. In addition, we report a variant of uncertain significance in KRT3 in an individual with MECD. Although the potential pathogenicity of this variant is unknown, it is the first variant affecting the head domain of K3 to be reported in an individual with MECD and suggests that disease-causing variants associated with MECD may not be restricted to primary sequence alterations of either the helix-initiation or helix-termination motifs of K3 and K12

A discourse analysis of trainee teacher identity in online discussion forums

Teacher education involves an identity transformation for trainees from being a student to being a teacher. This discourse analysis examined the online discussion board communications of a cohort of trainee teachers to better understand the situated identities of the trainees and how they were presented online. Their discussion board posts were the primary method of communication during placement periods and, as such, provided insight into how the trainees situated their identities in terms of being a student or being a teacher. During the analysis, the community boundaries, language and culture were explored along with the tutor's power and role in the identity transformation process. This involved looking at the lexis used by the students, the use of pronouns to refer to themselves and others such as teachers and pupils, the types of messages allowed in the community and the effect of the tutor's messages on their communication. The research found that the trainees felt comfortable with teaching but did not feel like teachers during the course. Tutors and school teachers need to develop an awareness of the dual nature of trainees' identities and help promote the transition from student to teacher. In the beginning of the course, trainees should be familiarised with teacher vocabulary and practical concepts in addition to pedagogical theory. Towards the end of the course, trainee identity as teachers could be promoted through the use of authentic assessments that mirror real teacher tasks and requirements

Implant Combinations and Reimplanting Strategies for Yearling Steers Fed High Concentrate Diets

Crossbred yearling steers were used to determine the relative efficacy of specific anabolic implant combinations and sequences on feedlot performance and carcass traits. Steers were fed a high concentrate finishing diet for 112 days. lmplanting was done on days 1 and 42 of the feeding period. lmplanting improved (P \u3c .05) average daily gain (ADG) 22% and feed efficiency 15%. Implant treatment generally increased dry matter intake. Lmplanting increased (P\u3c.05) the rib eye area of carcasses 6.5% and tended to cause a reduction in percentage choice carcasses. The percentage of abscessed implants ranged from \u3c 1 % to 10%, depending on the type of implant used even though implant needles were disinfected between each use

Anti-oestrogen therapy switches off tumour suppressors and proapoptotic genes in breast cancer and reveals a new therapeutic opportunity

Background Previous studies in the Tenovus Centre have demonstrated that the development of antioestrogen resistance in vitro is accompanied by unfavourable changes in the breast cancer phenotype leading to increase tumour cell growth rate. Here evidence is presented to suggest that this is in part due to antihormones causing the epigenetic silencing of oestrogen-induced genes involved in the negative regulation of cell growth. Importantly, we show that reversal of this process using the demethylation agent 5-azacytidine (5AZA) allows oestrogen-induced cell kill by a previously unrecognised mechanism. Methods The breast cancer cell lines used in this study were MCF7, MCF7-derived tamoxifen-resistant variant (TamR) and TamR sublines that had been withdrawn from tamoxifen (TamRwd) for up to 6 months. Cells were challenged by oestradiol (E2), antihormones and 5AZA. Cell growth responses were assessed by anchorage-dependent growth assays and alterations in expression/activity of oestrogen receptor (ER) and ER-regulated genes were analysed by real-time PCR, western blotting and/or immunocytochemistry. Results Compared with the parental MCF7 cells, TamR cells showed a significant upregulated basal rate of growth that was maintained on tamoxifen withdrawal for 6 months. Following the tamoxifen withdrawal, the cells remained ER-positive and showed a slight growth response to E2. In contrast, they showed no growth inhibitory response to tamoxifen. Examination of the methylation status of the promoters of two classically ER-regulated genes switched off in TamR and TamRwd cells, pS2 and progesterone receptor (PR), confirmed their increased methylation and that 5AZA was able to reverse this process, allowing the re-expression of pS2 and PR on E2 treatment. Although pS2 and PR are not thought to play a role in the regulation of cell growth, these data provide proof of principal that gene silencing occurs in TamR cells and that it can be reinstated by 5AZA plus E2. To determine whether tamoxifen was capable of inducing the methylation of ER-regulated genes involved in cell growth, TamRwd cells pretreated with 5AZA were subject to an E2 dose–response challenge. In contrast to TamRwd cells treated with E2, which promoted a growth response, E2 in combination with 5AZA was strongly inhibitory at physiological doses of the steroid (10-9 M), with this action being reversed by tamoxifen. An Affymetrix analysis of the TamR cells has revealed multiple E2-regulated genes that are switched off in the resistant cells whose ontology indicates tumour suppressor/proapoptotic functions. Conclusion Our data suggest that antihormone resistance may be associated with the epigenetic silencing of growth inhibitory genes leading to enhanced growth rates. We propose that reinstatement of the expression of such genes using demethylation agents in combination with E2 may provide a previously unrecognised therapeutic opportunity in breast cancer

Lowering Effects of Onion Intake on Oxidative Stress Biomarkers in Streptozotocin-Induced Diabetic Rats

The protective effect of onion against oxidative stress in streptozotosin-induced diabetic rats was investigated in comparison with that of quercetin aglycone. We measured oxidative stress biomarkers involving the susceptibility of the plasma against copper ion-induced lipid peroxidation, which was estimated by the amounts of thiobarbituric acid-reactive substances (TBARS) and cholesteryl ester hydroperoxides, and urine TBARS and 8-hydroxydeoxyguanosine contents. After the 12-week feeding period, plasma glucose levels and these biomarkers increased in diabetic rats compared to normal rats. In diabetic rats fed a 6.0% onion diet (quercetin equivalent: 0.023%), quercetin metabolites accumulated in the plasma at concentrations of approximately 35 µM. Onion intake decreased plasma glucose levels and lowered the oxidative stress biomarkers. On the other hand, quercetin metabolites in the plasma of rats fed a diet with 0.023% quercetin aglycone were found at lower concentrations (14.2 µM) than the rats fed the onion diet. Furthermore, oxidative stress biomarkers were higher in the quercetin diet group compared to the onion diet group. These results strongly suggest that onion intake suppresses diabetes-induced oxidative stress more effectively than the intake of the same amount of quercetin aglycone alone

Loss of oestrogen receptor alpha in long-term antioestrogen-resistant cells: reversal by a c-src inhibitor

Background Tamoxifen still remains the most frequently used antioestrogen for the treatment of breast cancer. However, its efficacy is often limited by the emergence of acquired resistance and it has been suggested that, in some instances, this may involve oestrogen receptor (ER) loss. This study addresses this issue by examining long-term tamoxifen treatment of breast cancer cells and identifies that progressive ER loss does occur, leading to greatly increased aggressive tumour cell behaviour. Encouragingly, even after 30 months treatment, ER loss is reversible by a c-src inhibitor. Our data therefore provide a new model to study the cellular mechanisms associated with antihormone promoted ER loss and its possible prevention/reversal by signal transduction inhibitors. Methods Using quantitative PCR based on SYBR Green fluorescence, the expression of total ERα mRNA and its constituent mRNA variants were quantified in MCF7 cells and in our in vitro developed tamoxifen-resistant breast cancer cells (TamR), which have been cultured in the presence of tamoxifen for 30 months. Specific PCR amplification of all ERα mRNA variants was possible using forward primers designed to bind specifically to the 5' untranslated regions of ERα mRNA and used separately with a common reverse primer that anneals to the 5' end of the protein encoding region of exon 1 of ERα cDNA. Expression of ERα protein was assessed by western blot and immunohistochemistry. Results In MCF7 cells, the ERα mRNA isoforms A, B and C were detected as the most predominant variants, with C ERα mRNA showing the highest expression level. In TamR cells, about a 40% fall in total ERα mRNA was observed in comparison with MCF7 cells and was most apparent for the C variant. Extension of the tamoxifen treatment period to 30 months produced a further dramatic decrease in ERα mRNA (all variants) and protein levels, resulting in ER negativity being recorded in >90% of the cells by immunohistochemistry. These cells show increased levels of phosphorylated Erk 1&2, AKT, PKCα and src, and are highly aggressive in their growth behaviour, with increased cell motility and invasiveness. Treatment of the cells with the demethylating agent 5-azacytidine did not restore ERα expression, suggesting that epigenetic alterations are unlikely to be responsible for the reduced ER levels. However, Affymetrix data in the TamR cells showed that some positive regulators of ER expression, such as p53 and Foxo3A, are downregulated during the development of the resistant phenotype and their continued absence may contribute to the progressive ER loss. Significantly, pathway inhibitor studies revealed c-src to be an important regulator of ER loss, since its inhibition rapidly restored ER levels. Conclusion Our data indicate that considerable ER loss can occur during antihormonal treatment of breast cancer cells and that this can lead to a more aggressive phenotype. Encouragingly, however, even after 30 months exposure to tamoxifen, the process is reversible by inhibition of c-src. These data suggest that combinations of antihormones with signal transduction inhibitors could retain ER functions in treated cells and prevent a drift towards more aggressive cancer cell behaviour

Reading Videogames as (authorless) Literature

This article presents the outcomes of research, funded by the Arts and Humanities Research Council in England and informed by work in the fields of new literacy research, gaming studies and the socio-cultural framing of education, for which the videogame L.A. Noire (Rockstar Games, 2011) was studied within the orthodox framing of the English Literature curriculum at A Level (pre-University) and Undergraduate (degree level). There is a plethora of published research into the kinds of literacy practices evident in videogame play, virtual world engagement and related forms of digital reading and writing (Gee, 2003; Juul, 2005; Merchant, Gillen, Marsh and Davies, 2012; Apperley and Walsh, 2012; Bazalgette and Buckingham, 2012) as well as the implications of such for home / school learning (Dowdall, 2006; Jenkins, 2006; Potter, 2012) and for teachers’ own digital lives (Graham, 2012). Such studies have tended to focus on younger children and this research is also distinct from such work in the field in its exploration of the potential for certain kinds of videogame to be understood as 'digital transformations' of conventional ‘schooled’ literature. The outcomes of this project raise implications of such a conception for a further implementation of a ‘reframed’ literacy (Marsh, 2007) within the contemporary curriculum of a traditional and conservative ‘subject’. A mixed methods approach was adopted. Firstly, students contributing to a gamplay blog requiring them to discuss their in-game experience through the ‘language game’ of English Literature, culminating in answering a question constructed with the idioms of the subject’s set text ‘final examination’. Secondly, students taught their teachers to play L.A. Noire, with free choice over the context for this collaboration. Thirdly, participants returned to traditional roles in order to work through a set of study materials provided, designed to reproduce the conventions of the ‘study guide’ for literature education. Interviews were conducted after each phase and the outcomes informed a redrafting of the study materials which are now available online for teachers – this being the ‘practical’ outcome of the research (Berger and McDougall, 2012). In the act of inserting the study of L.A. Noire into the English Literature curriculum as currently framed, this research moves, through a practical ‘implementation’ beyond longstanding debates around narratology and ludology (Frasca, 2003; Juul, 2005) in the field of game studies (Leaning, 2012) through a direct connection to new literacy studies and raises epistemological questions about ‘subject identity’, informed by Bernstein (1996) and Bourdieu (1986) and the implications for digital transformations of texts for both ideas about cultural value in schooled literacy (Kendall and McDougall, 2011) and the politics of ‘expertise’ in pedagogic relations (Ranciere, 2009, Bennett, Kendall and McDougall, 2012a)

Stick-Slip Motion and Phase Transition in a Block-Spring System

We study numerically stick slip motions in a model of blocks and springs being pulled slowly. The sliding friction is assumed to change dynamically with a state variable. The transition from steady sliding to stick-slip is subcritical in a single block and spring system. However, we find that the transition is continuous in a long chain of blocks and springs. The size distribution of stick-slip motions exhibits a power law at the critical point.Comment: 8 figure