Therapeutic Antisense Targeting of Huntingtin

Antisense oligonucleotides (ASOs) are a relatively new therapeutic entity that utilizes short chemically modified strands of DNA in targeted interactions with RNA to modulate the type or amount of resultant protein. This brief review summarizes the preclinical, translational, and early clinical development of an ASO designed to reduce the production of the disease-causing protein in Huntington's disease, an inherited neurodegenerative disease

Teaching Stand Management Using Virtual Alfalfa Plants

A ‘virtual’ alfalfa plant model was developed at the University of Manitoba in Canada as part of a comprehensive grazing research project. This model shows an alfalfa plant ‘growing’ on a computer screen and the plant’s response to grazing (similar to time-lapse photography). The original model was designed and constructed by Av Singh to show the research potential of visually modeling alfalfa plant growth. The ability to visually ‘grow’ a plant on a computer screen also provides an excellent teaching and extension tool

Regularity of solutions to higher-order integrals of the calculus of variations

We obtain new regularity conditions for problems of calculus of variations with higher-order derivatives. As a corollary, we get non-occurrence of the Lavrentiev phenomenon. Our main regularity result asserts that autonomous integral functionals with a Lagrangian having coercive partial derivatives with respect to the higher-order derivatives admit only minimizers with essentially bounded derivatives

Reconstituting typeset Marriage Registers using simple software tools

In a world of fully integrated software applications, which can seem daunting to develop and to maintain, it is sometimes useful to recall that a system of loosely-linked software components can provide surprisingly powerful and flexible methods for software development. This paper describes a project which aims to retypeset a series of volumes from the Phillimore Marriage Registers, first published in England around the turn of the last century. The source material is plain text derived from running Optical Character Recognition (OCR) on a set of page scans taken from the original printed volumes. The regular, tabular, structure of the Register pages allows us to automate the re-typesetting process. The UNIX troff software and its tbl preprocessor are used for the typesetting itself, but a series of simple awk-based software tools, all of them parsers and code generators of one sort or another, is used to bring about the OCR-to-troff transformation. By re-parsing the generated troff codes it is possible to produce a surname index as a supplement to the retypeset volume. Moreover, this second-stage parsing has been invaluable in discovering subtle ‘typos’ in the automatically generated material. With small adjustments to this parser it would be possible to output the complete marriage entries in standard XML or GEDCOM notations

A Caenorhabditis elegans model of Yersinia infection: biofilm formation on a biotic surface.

To investigate Yersinia pathogenicity and the evolutionary divergence of the genus, the effect of pathogenic yersiniae on the model organism Caenorhabditis elegans was studied. Three strains of Yersinia pestis, including a strain lacking pMT1, caused blockage and death of C. elegans; one strain, lacking the haemin storage (hms) locus, caused no effect. Similarly, 15 strains of Yersinia enterocolitica caused no effect. Strains of Yersinia pseudotuberculosis showed different levels of pathogenicity. The majority of strains (76 %) caused no discernible effect; 5 % caused a weak infection, 9.5 % an intermediate infection, and 9.5 % a severe infection. There was no consistent relationship between serotype and severity of infection; nor was there any relationship between strains causing infection of C. elegans and those able to form a biofilm on an abiotic surface. Electron microscope and cytochemical examination of infected worms indicated that the infection phenotype is a result of biofilm formation on the head of the worm. Seven transposon mutants of Y. pseudotuberculosis strain YPIII pIB1 were completely or partially attenuated; mutated genes included genes encoding proteins involved in haemin storage and lipopolysaccharide biosynthesis. A screen of 15 defined C. elegans mutants identified four where mutation caused (complete) resistance to infection by Y. pseudotuberculosis YPIII pIB1. These mutants, srf-2, srf-3, srf-5 and the dauer pathway gene daf-1, also exhibit altered binding of lectins to the nematode surface. This suggests that biofilm formation on a biotic surface is an interactive process involving both bacterial and invertebrate control mechanisms

Interacting Supernovae: Types IIn and Ibn

Supernovae (SNe) that show evidence of strong shock interaction between their ejecta and pre-existing, slower circumstellar material (CSM) constitute an interesting, diverse, and still poorly understood category of explosive transients. The chief reason that they are extremely interesting is because they tell us that in a subset of stellar deaths, the progenitor star may become wildly unstable in the years, decades, or centuries before explosion. This is something that has not been included in standard stellar evolution models, but may significantly change the end product and yield of that evolution, and complicates our attempts to map SNe to their progenitors. Another reason they are interesting is because CSM interaction is an efficient engine for making bright transients, allowing super-luminous transients to arise from normal SN explosion energies, and allowing transients of normal SN luminosities to arise from sub-energetic explosions or low radioactivity yield. CSM interaction shrouds the fast ejecta in bright shock emission, obscuring our normal view of the underlying explosion, and the radiation hydrodynamics of the interaction is challenging to model. The CSM interaction may also be highly non-spherical, perhaps linked to binary interaction in the progenitor system. In some cases, these complications make it difficult to definitively tell the difference between a core-collapse or thermonuclear explosion, or to discern between a non-terminal eruption, failed SN, or weak SN. Efforts to uncover the physical parameters of individual events and connections to possible progenitor stars make this a rapidly evolving topic that continues to challenge paradigms of stellar evolution.Comment: Final draft of a chapter in the "SN Handbook". Accepted. 25 pages, 3 fig

A tutorial on the implementations of linear image filters in CPU and GPU

This article presents an overview of the implementation of linear image filters in CPU and GPU. The main goal is to present a self contained discussion of different implementations and their background using tools from digital signal processing. First, using signal processing tools, we discuss different algorithms and estimate their computational cost. Then, we discuss the implementation of these filters in CPU and GPU. It is very common to find in the literature that GPUs can easity reduce computational times in many algorithms (straightforward implementations). In this work we show that GPU implementations not always reduce the computational time but also not all algorithms are suited for GPUs. We beleive this is a review that can help researchers and students working in this area. Although the experimental results are not meant to show which is the best implementation (in terms of running time), the main results can be extrapolated to CPUs and GPUs of different capabilities.XV Workshop de Computación Gráfica, Imágenes y Visualización (WCGIV).Red de Universidades con Carreras en Informática (RedUNCI

Noncommutative generalizations of theorems of Cohen and Kaplansky

This paper investigates situations where a property of a ring can be tested on a set of "prime right ideals." Generalizing theorems of Cohen and Kaplansky, we show that every right ideal of a ring is finitely generated (resp. principal) iff every "prime right ideal" is finitely generated (resp. principal), where the phrase "prime right ideal" can be interpreted in one of many different ways. We also use our methods to show that other properties can be tested on special sets of right ideals, such as the right artinian property and various homological properties. Applying these methods, we prove the following noncommutative generalization of a result of Kaplansky: a (left and right) noetherian ring is a principal right ideal ring iff all of its maximal right ideals are principal. A counterexample shows that the left noetherian hypothesis cannot be dropped. Finally, we compare our results to earlier generalizations of Cohen's and Kaplansky's theorems in the literature.Comment: 41 pages. To appear in Algebras and Representation Theory. Minor changes were made to the numbering system, in order to remain consistent with the published versio

An approach to computing downward closures

The downward closure of a word language is the set of all (not necessarily contiguous) subwords of its members. It is well-known that the downward closure of any language is regular. While the downward closure appears to be a powerful abstraction, algorithms for computing a finite automaton for the downward closure of a given language have been established only for few language classes. This work presents a simple general method for computing downward closures. For language classes that are closed under rational transductions, it is shown that the computation of downward closures can be reduced to checking a certain unboundedness property. This result is used to prove that downward closures are computable for (i) every language class with effectively semilinear Parikh images that are closed under rational transductions, (ii) matrix languages, and (iii) indexed languages (equivalently, languages accepted by higher-order pushdown automata of order 2).Comment: Full version of contribution to ICALP 2015. Comments welcom