Ovarian preservation techniques for female pelvic radiotherapy techniques: a critical review

AbstractIntroductionAdvances in treatment over recent years have increased the long-term survival of young, female cancer patients; unfortunately these treatments bring a significant risk of ovarian failure and infertility. This literature review aimed to determine the optimal technique for ovarian preservation in pre-menopausal women receiving pelvic radiotherapy (IMRT). The traditional method comprises surgical transposition; IMRT and other emerging techniques may offer alternative non-invasive means of sparing ovaries and minimising dose.MethodsA critical review of the evidence pertaining to pelvic radiotherapy and ovarian sparing was performed. Evidence was subjected to critical appraisal using the Critical Appraisal Skills Programme tool and thematic analysis of the findings identified key issues.ResultsSurgical transposition appears to be a successful method of preserving ovarian function depending on the position of the ovaries outside of the radiation field, the age of the patient and the total dose received by the ovaries. There is limited modern evidence concerning its usage in relation to emerging techniques and technology. The use of IMRT is certainly widespread in the treatment of female pelvic cancers, however, there is no evidence supporting its use for reduction of ovarian dose. Several other studies have attempted to demonstrate new techniques to preserve ovarian function, but no functional outcome measures have reinforced their results.ConclusionsOvarian transposition has a proven track record for preservation of ovarian function, but the potential value of IMRT as a viable alternative to date remains unexplored. New work should be encouraged to determine the potential value of IMRT as a non-surgical alternative.</jats:sec

Non-bisphosphonate inhibitors of isoprenoid biosynthesis identified via computer-aided drug design.

The relaxed complex scheme, a virtual-screening methodology that accounts for protein receptor flexibility, was used to identify a low-micromolar, non-bisphosphonate inhibitor of farnesyl diphosphate synthase. Serendipitously, we also found that several predicted farnesyl diphosphate synthase inhibitors were low-micromolar inhibitors of undecaprenyl diphosphate synthase. These results are of interest because farnesyl diphosphate synthase inhibitors are being pursued as both anti-infective and anticancer agents, and undecaprenyl diphosphate synthase inhibitors are antibacterial drug leads

Evaluation of Surface State Mediated Charge Recombination in Anatase and Rutile TiO2

In nanostructured thin films, photogenerated charge carriers can access the surface more easily than in dense films and thus react more readily. However, the high surface area of these films has also been associated with enhanced recombination losses via surface states. We herein use transient absorption spectroscopy to compare the ultrafast charge carrier kinetics in dense and nanostructured TiO2 films for its two most widely used polymorphs: anatase and rutile. We find that nanostructuring does not enhance recombination rates on ultrafast timescales, indicating that surface state mediated recombination is not a key loss pathway for either TiO2 polymorph. Rutile shows faster, and less intensity-dependent recombination than anatase, which we assign to its higher doping density. For both polymorphs, we conclude that bulk rather than surface recombination is the primary determinant of charge carrier lifetime

Schema-conformant memories are preferentially consolidated during REM sleep

Memory consolidation is most commonly described by the standard model, which proposes an initial binding role for the hippocampus which diminishes over time as intracortical connections are strengthened. Recent evidence suggests that slow wave sleep (SWS) plays an essential role in this process. Existing animal and human studies have suggested that memories which fit tightly into an existing knowledge framework or schema might use an alternative consolidation route in which the medial prefrontal cortex takes on the binding role. In this study we sought to investigate the role of sleep in this process using a novel melodic memory task. Participants were asked to remember 32 melodies, half of which conformed to a tonal schema present in all enculturated listeners, and half of which did not fit with this schema. After a 24-h consolidation interval, participants were asked to remember a further 32 melodies, before being given a recognition test in which melodies from both sessions were presented alongside some previously unheard foils. Participants remembered schema-conformant melodies better than non-conformant ones. This was much more strongly the case for consolidated melodies, suggesting that consolidation over a 24-h period preferentially consolidated schema-conformant items. Overnight sleep was monitored between the sessions, and the extent of the consolidation benefit for schema-conformant items was associated with both the amount of REM sleep obtained and EEG theta power in frontal and central regions during REM sleep. Overall our data suggest that REM sleep plays a crucial role in the rapid consolidation of schema-conformant items. This finding is consistent with previous results from animal studies and the SLIMM model of Van Kesteren, Ruiter, Fernández, and Henson (2012), and suggest that REM sleep, rather than SWS, may be involved in an alternative pathway of consolidation for schema-conformant memories. Copyright © 2015. Published by Elsevier Inc

Gene expression in Leishmania is regulated predominantly by gene dosage

ABSTRACT Leishmania tropica, a unicellular eukaryotic parasite present in North and East Africa, the Middle East, and the Indian subcontinent, has been linked to large outbreaks of cutaneous leishmaniasis in displaced populations in Iraq, Jordan, and Syria. Here, we report the genome sequence of this pathogen and 7,863 identified protein-coding genes, and we show that the majority of clinical isolates possess high levels of allelic diversity, genetic admixture, heterozygosity, and extensive aneuploidy. By utilizing paired genome-wide high-throughput DNA sequencing (DNA-seq) with RNA-seq, we found that gene dosage, at the level of individual genes or chromosomal “somy” (a general term covering disomy, trisomy, tetrasomy, etc.), accounted for greater than 85% of total gene expression variation in genes with a 2-fold or greater change in expression. High gene copy number variation (CNV) among membrane-bound transporters, a class of proteins previously implicated in drug resistance, was found for the most highly differentially expressed genes. Our results suggest that gene dosage is an adaptive trait that confers phenotypic plasticity among natural Leishmania populations by rapid down- or upregulation of transporter proteins to limit the effects of environmental stresses, such as drug selection. IMPORTANCE Leishmania is a genus of unicellular eukaryotic parasites that is responsible for a spectrum of human diseases that range from cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL) to life-threatening visceral leishmaniasis (VL). Developmental and strain-specific gene expression is largely thought to be due to mRNA message stability or posttranscriptional regulatory networks for this species, whose genome is organized into polycistronic gene clusters in the absence of promoter-mediated regulation of transcription initiation of nuclear genes. Genetic hybridization has been demonstrated to yield dramatic structural genomic variation, but whether such changes in gene dosage impact gene expression has not been formally investigated. Here we show that the predominant mechanism determining transcript abundance differences (>85%) in Leishmania tropica is that of gene dosage at the level of individual genes or chromosomal somy

Gypsum-DL: an open-source program for preparing small-molecule libraries for structure-based virtual screening

Computational techniques such as structure-based virtual screening require carefully prepared 3D models of potential small-molecule ligands. Though powerful, existing commercial programs for virtual-library preparation have restrictive and/or expensive licenses. Freely available alternatives, though often effective, do not fully account for all possible ionization, tautomeric, and ring-conformational variants. We here present Gypsum-DL, a free, robust open-source program that addresses these challenges. As input, Gypsum-DL accepts virtual compound libraries in SMILES or flat SDF formats. For each molecule in the virtual library, it enumerates appropriate ionization, tautomeric, chiral, cis/trans isomeric, and ring-conformational forms. As output, Gypsum-DL produces an SDF file containing each molecular form, with 3D coordinates assigned. To demonstrate its utility, we processed 1558 molecules taken from the NCI Diversity Set VI and 56,608 molecules taken from a Distributed Drug Discovery (D3) combinatorial virtual library. We also used 4463 high-quality protein-ligand complexes from the PDBBind database to show that Gypsum-DL processing can improve virtual-screening pose prediction. Gypsum-DL is available free of charge under the terms of the Apache License, Version 2.0

Inverse problem of photoelastic fringe mapping using neural networks

This paper presents an enhanced technique for inverse analysis of photoelastic fringes using neural networks to determine the applied load. The technique may be useful in whole-field analysis of photoelastic images obtained due to external loading, which may find application in a variety of specialized areas including robotics and biomedical engineering. The presented technique is easy to implement, does not require much computation and can cope well within slight experimental variations. The technique requires image acquisition, filtering and data extraction, which is then fed to the neural network to provide load as output. This technique can be efficiently implemented for determining the applied load in applications where repeated loading is one of the main considerations. The results presented in this paper demonstrate the novelty of this technique to solve the inverse problem from direct image data. It has been shown that the presented technique offers better result for the inverse photoelastic problems than previously published works

Evaluating the Potential of Using 5-Azacytidine as an Epimutagen

A number of early flowering lines were induced when 5-azacytidine was applied to germinating flax (Linum usitatissimum L.) seed. The genetics of these lines indicate that the induced changes are epigenetic and probably result from demethylation of the genomic DNA at loci that affect flowering age. Although the growth and development of three stable early flowering lines are altered and the percentage of filled seed was reduced in all three lines compared with controls, measures of seed productivity demonstrated that harvest index was unaffected in two of the lines. In the third, harvest index was lower than normal and both seed set per capsule and seed mass per 100 seed were reduced. Furthermore, six generations after induction this line began to display relatively high levels of polyembryony. The late appearance of this twinning and other aspects related to working with lines induced by 5-azacytidine and using 5-azacytidine as an epimutagen are discussed

Electron transport in the dye sensitized nanocrystalline cell

Dye sensitised nanocrystalline solar cells (Gr\"{a}tzel cells) have achieved solar-to-electrical energy conversion efficiencies of 12% in diffuse daylight. The cell is based on a thin film of dye-sensitised nanocrystalline TiO$_2$ interpenetrated by a redox electrolyte. The high surface area of the TiO$_2$ and the spectral characteristics of the dye allow the device to harvest 46% of the solar energy flux. One of the puzzling features of dye-sensitised nano-crystalline solar cells is the slow electron transport in the titanium dioxide phase. The available experimental evidence as well as theoretical considerations suggest that the driving force for electron collection at the substrate contact arises primarily from the concentration gradient, ie the contribution of drift is negligible. The transport of electrons has been characterised by small amplitude pulse or intensity modulated illumination. Here, we show how the transport of electrons in the Gr\"{a}tzel cell can be described quantitatively using trap distributions obtained from a novel charge extraction method with a one-dimensional model based on solving the continuity equation for the electron density. For the first time in such a model, a back reaction with the I$_3^-$ ions in the electrolyte that is second order in the electron density has been included.Comment: 6 pages, 5 figures, invited talk at the workshop 'Nanostructures in Photovoltaics' to appear in Physica