An International Ultraviolet Explorer Archival Study of Dwarf Novae in Outburst

We present a synthetic spectral analysis of nearly the entire far ultraviolet International Ultraviolet Explorer (IUE) archive of spectra of dwarf novae in or near outburst. The study includes 46 systems of all dwarf nova subtypes both above and below the period gap. The spectra were uniformly analyzed using synthetic spectral codes for optically thick accretion disks and stellar photospheres along with the best-available distance measurements or estimates. We present newly estimated accretion rates and discuss the implications of our study for disk accretion physics and CV evolution.Comment: Accepted for publication in the ApJ, Part

Sexually dimorphic control of gene expression in sensory neurons regulates decision-making behavior in

Animal behavior is directed by the integration of sensory information from internal states and the environment. Neuroendocrine regulation of diverse behaviors of Caenorhabditis elegans is under the control of the DAF-7/TGF-β ligand that is secreted from sensory neurons. Here, we show that C. elegans males exhibit an altered, male-specific expression pattern of daf-7 in the ASJ sensory neuron pair with the onset of reproductive maturity, which functions to promote male-specific mate-searching behavior. Molecular genetic analysis of the switch-like regulation of daf-7 expression in the ASJ neuron pair reveals a hierarchy of regulation among multiple inputs—sex, age, nutritional status, and microbial environment—which function in the modulation of behavior. Our results suggest that regulation of gene expression in sensory neurons can function in the integration of a wide array of sensory information and facilitate decision-making behaviors in C. elegans.United States. National Institutes of Health (GM084477

Pulse of inflammatory proteins in the pregnant uterus of European polecats (Mustela putorius) leading to the time of implantation

Uterine secretory proteins protect the uterus and conceptuses against infection, facilitate implantation, control cellular damage resulting from implantation, and supply pre-implantation embryos with nutrients. Unlike in humans, the early conceptus of the European polecat (Mustela putorius; ferret) grows and develops free in the uterus until implanting at about 12 days after mating. We found that the proteins appearing in polecat uteri changed dramatically with time leading to implantation. Several of these proteins have also been found in pregnant uteri of other eutherian mammals. However, we found a combination of two increasingly abundant proteins that have not been recorded before in pre-placentation uteri. First, the broad-spectrum proteinase inhibitor α2-macroglobulin rose to dominate the protein profile by the time of implantation. Its functions may be to limit damage caused by the release of proteinases during implantation or infection, and to control other processes around sites of implantation. Second, lipocalin-1 (also known as tear lipocalin) also increased substantially in concentration. This protein has not previously been recorded as a uterine secretion in pregnancy in any species. If polecat lipocalin-1 has similar biological properties to that of humans, then it may have a combined function in antimicrobial protection and transporting or scavenging lipids. The changes in the uterine secretory protein repertoire of European polecats is therefore unusual, and may be representative of pre-placentation supportive uterine secretions in mustelids (otters, weasels, badgers, mink, wolverines) in general

Temporal Difference Learning in Complex Domains

PhDThis thesis adapts and improves on the methods of TD(k) (Sutton 1988) that were successfully used for backgammon (Tesauro 1994) and applies them to other complex games that are less amenable to simple pattem-matching approaches. The games investigated are chess and shogi, both of which (unlike backgammon) require significant amounts of computational effort to be expended on search in order to achieve expert play. The improved methods are also tested in a non-game domain. In the chess domain, the adapted TD(k) method is shown to successfully learn the relative values of the pieces, and matches using these learnt piece values indicate that they perform at least as well as piece values widely quoted in elementary chess books. The adapted TD(X) method is also shown to work well in shogi, considered by many researchers to be the next challenge for computer game-playing, and for which there is no standardised set of piece values. An original method to automatically set and adjust the major control parameters used by TD(k) is presented. The main performance advantage comes from the learning rate adjustment, which is based on a new concept called temporal coherence. Experiments in both chess and a random-walk domain show that the temporal coherence algorithm produces both faster learning and more stable values than both human-chosen parameters and an earlier method for learning rate adjustment. The methods presented in this thesis allow programs to learn with as little input of external knowledge as possible, exploring the domain on their own rather than by being taught. Further experiments show that the method is capable of handling many hundreds of weights, and that it is not necessary to perform deep searches during the leaming phase in order to learn effective weight

High-Throughput Chronological Lifespan Screening of the Fission Yeast Deletion Library Using Barcode Sequencing

Ageing is associated with the development of several chronic illnesses, including cardiovascular diseases, diabetes and cancer. To understand the genetic components driving cellular ageing in higher organisms, like ourselves, we study simple eukaryotic model systems which are more accessible and easier to manipulate than higher eukaryotes. This is possible due to the remarkably conserved ageing mechanisms that occurs between species. Here, we employ fission yeast one of the simplest eukaryotic model organisms to study cellular ageing. In this work, we de- coded the fission yeast deletion collection using our in-house developed pipeline, developed an improved version of Bar-seq along with a custom-developed analysis pipeline, determined a method for high-quality RNA extraction and RNA-seq from long-term quiescent yeast cells, and finally, performed a high-throughput Bar-seq screen to profile the chronological lifespan of our decoded strains. We describe bar- code decoding of 94% of the gene deletions; validation of our Bar-seq developed method; identification of ncRNAs as elements important for the cellular quiescence maintenance; Bar-seq screening of the competitively grown decoded strains which identified several long-lived and short-lived mutants following glucose-starvation and cellular culture re-growth; and also, validation of the top hits using isogenic cell cultures revealing eight novel gene deletions important for the early life maintenance, as well as ten novel gene deletion mutants with pro-ageing effects. Overall, in addition to providing rich datasets, we describe several high-throughput methods that can be used for future genome-wide studies, whereby the complementarity of genomics and transcriptomics can be coupled together to further advance our understanding of the genetic factors underpinning cellular ageing in humans

Temoral Difference Learning in Complex Domains

Submitted to the University of London for the Degree of Doctor of Philosophy in Computer Scienc

Toxic love:Evolutionary genomics of the enigmatic Sex Peptide

Living organisms compete for survival and reproduction, whereupon the fittest live and thrive and the weakest fail and some cases even die. This battle for life acts on different levels, causing individuals of distinct species as well as individuals of the same species to compete over a variety of limiting resources such as food, breeding sites and mates. An important form of competition is driven by sexual conflict and often occurs when reproductive strategies between males and female diverge. These occur because there are differences in the evolutionary interests of the sexes over, for example, optimal reproductive rate, gamete size and parental investments. This has led to the evolution of different strategies to alter or overcome the manipulation of one sex by other, while maintaining a base line level of cooperation sufficient to ensure successful reproduction. This sexual conflict is an important evolutionary process as it can drive rapid evolutionary change. The manipulation of one sex by the other through molecular interactions has been illuminated in studies using the fruit fly Drosophila melanogaster. Males tend to maximize their chances at fatherhood by releasing both sperm and semen inside the female’s body during mating. The effects of semen proteins can benefit both sperm and eggs, but intriguingly they can also favour the interests of males whilst generating costs in females, resulting in sexual conflict. In Drosophila melanogaster, the female body has been the battlefield of sexual conflict, as semen proteins exert their effects in females after mating. This manipulation by males through molecular interactions can inflict substantial physical and physiological costs of mating in females. One enigmatic seminal fluid protein the ‘Sex Peptide’, generates strikingly diverse changes in female physiological and reproductive behaviour. Sex Peptide triggers remarkable female post mating responses including altered fertility, immunity, libido, eating and sleep patterns, by the activation of diverse sets of genes. In many studies of the molecular mechanisms of female manipulation via the effects of Sex Peptide, genetic variation is minimised in order to clearly delineate biological functions. However, to understand the evolutionary processes and dynamics that characterise Sex Peptide mediated interactions between males and females, it is important to study this genetic variation. With high-throughput sequencing technologies that have provided resources such as >200 fully sequenced DGRP lines (Drosophila Genome Reference Panel), we traced the impact of the enigmatic Sex Peptide on the fruitfly genome. In this thesis I performed an in-depth investigation of the phenotypic and genomic differences among 30-32 DGRP lines, with respect to male release of, and female responses to, Sex Peptide. I measured phenotypic variation for Sex Peptide release in males; and in females the phenotypic variation in immune responses, egg laying, receptivity and longevity in response to Sex Peptide receipt. I compared these phenotypic post-mating responses to those of females that mated to males with a null-allele for Sex Peptide, to distinguish the specific response to Sex Pepetide. I mapped these phenotypes to genomic variation using Genome Wide Association Studies and conducted functional characterizations on the genomic variation identified