A common distributed language approach to software integration

An important objective in software integration is the development of techniques to allow programs written in different languages to function together. Several approaches are discussed toward achieving this objective and the Common Distributed Language Approach is presented as the approach of choice

Non-coding regulatory elements: potential roles in disease and the case of epilepsy

Non-coding DNA (ncDNA) refers to the portion of the genome that does not code for proteins and accounts for the greatest physical proportion of the human genome. ncDNA includes sequences that are transcribed into RNA molecules, such as ribosomal RNAs (rRNAs), microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and un-transcribed sequences that have regulatory functions, including gene promoters and enhancers. Variation in non-coding regions of the genome have an established role in human disease, with growing evidence from many areas, including several cancers, Parkinson's disease and autism. Here, we review the features and functions of the regulatory elements that are present in the non-coding genome and the role that these regions have in human disease. We then review the existing research in epilepsy and emphasise the potential value of further exploring non-coding regulatory elements in epilepsy. In addition, we outline the most widely used techniques for recognising regulatory elements throughout the genome, current methodologies for investigating variation and the main challenges associated with research in the field of non-coding DNA

Lithium and fluoxetine regulate the rate of phosphoinositide synthesis in neurons: a new view of their mechanisms of action in bipolar disorder

Lithium is widely used to treat bipolar disorder, but its primary mechanism of action is uncertain. One proposal has been that lithium's ability to inhibit the enzyme inositol monophosphatase (IMPase) reduces the supply of recycled inositol used for membrane phosphoinositide (PIns) synthesis. This 28-year-old hypothesis is still widely debated, however, largely because total levels of PIns in brain or in cultured neurons do not decrease after lithium treatment. Here we use mature cultured cortical neurons to show that, although lithium has little effect on steady-state levels of either inositol or PIns, it markedly inhibits the rate of PIns synthesis. Moreover, we show that rapid synthesis of membrane PIns preferentially uses inositol newly imported from the extracellular space. Unexpectedly, we also find that the antidepressant drug fluoxetine (FLUO: Prozac) stimulates the rate of PIns synthesis. The convergence of both lithium and FLUO in regulating the rate of synthesis of PIns in opposite ways highlights PIns turnover in neurons as a potential new drug target, as well as for understanding mood control in BD. Our results also indicate new avenues for investigation of how neurons regulate their supply of inositol

Redistribution of cytoplasmic VEGF to the basolateral aspect of renal tubular cells in ischemia-reperfusion injury

Redistribution of cytoplasmic VEGF to the basolateral aspect of renal tubular cells in ischemia-reperfusion injury.BackgroundVascular endothelial growth factor (VEGF) mRNA and protein expression are increased by hypoxia in a variety of cell types and organs. In the kidney, however, chronic hypoxia does not up-regulate VEGF mRNA. This suggests that VEGF may be regulated by unique mechanisms in the kidney.MethodsUnilateral ischemia was induced in rats by vascular cross-clamping (40 min) followed by reperfusion (0, 20, 40, and 80 min). The distribution of VEGF protein was determined by immunohistochemical staining and Western blotting. mRNA was detected by Northern blotting and semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemical staining for VEGF was verified using two VEGF antibodies. To further substantiate the immunohistochemical findings, laser scanning confocal fluorescence microscopy was used to demonstrate the distribution of VEGF protein in rat renal tubular epithelial cells (NRK52-E) subjected to hypoxia (40 min) and re-oxygenation (0, 5, 20, 40 and 80 min).ResultsNormal kidneys showed diffuse immunohistochemical staining for VEGF in all tubules of the renal cortex and medulla. Following ischemia, staining demonstrated a prominent shift of cytoplasmic VEGF to the basolateral aspect of tubular cells with both VEGF antibodies. The distribution of cytoplasmic VEGF returned to normal following 40 and 80 minutes of reperfusion. Western blots of cytoplasmic samples from ischemic kidneys reperfused for 0 and 20 minutes showed decreased levels of VEGF164 compared with normal (P < 0.01). VEGF164 and VEGF188 levels in the membrane fraction showed no change. Northern blots and semiquantitative RT-PCR showed no significant up-regulation of VEGF mRNA or change in the splice pattern. NRK52-E cells subjected to hypoxia and re-oxygenation for 0 and 5 minutes showed increased staining for VEGF compared with normal, with prominent VEGF staining at the periphery of the cell, similar to the appearance in ischemic kidneys. VEGF staining became more diffuse with further re-oxygenation.ConclusionAlthough synthesis of VEGF mRNA and protein is not increased during ischemia reperfusion injury, pre-existing VEGF in the tubular cell cytoplasm redistributes to the basolateral aspect of the cells. These data suggest that the kidney may have evolved unique patterns of VEGF regulation to cope with acute hypoxia

Development of ultrasonic guided wave techniques for examination of non-cylindrical components

AbstractIn the past ten years ultrasonic guided wave systems have become widely used for the rapid large-scale examination of pipes and pipelines in pressure containing systems, for the detection of corrosion and other degradation in service. As a result, the characteristics of the guided wave modes existing in pipes have been studied extensively and are well understood. Advantage is taken of the fact that a pipe is essentially a one-dimensional object and that guided waves travelling along it will return to the sensor location for detection. Guided waves may also be applied to other components which are non-cylindrical, either those of constant cross-section such as railway rails or structural I beams, or constructions consisting of plates. However, in both cases the guided wave systems are more complex than in simple cylinders and successful application of this technique for large scale examination of these constructions requires further development of the understanding of the properties of the waves propagating and regularities of their generation. This paper describes work carried out under the EU-funded LRUCM project to develop techniques for detection of corrosion and cracking in railway rails and structural sheet piles used to retain earth embankments, river banks etc. The work described involved identification of wave modes present, derivation of dispersion curves to describe propagation behaviour and evaluation of experimental data to explain mode conversions and interactions with interfaces observed in the results

Real-time, label-free, intraoperative visualization of peripheral nerves and microvasculatures using multimodal optical imaging techniques

Accurate, real-time identification and display of critical anatomic structures, such as the nerve and vasculature structures, are critical for reducing complications and improving surgical outcomes. Human vision is frequently limited in clearly distinguishing and contrasting these structures. We present a novel imaging system, which enables noninvasive visualization of critical anatomic structures during surgical dissection. Peripheral nerves are visualized by a snapshot polarimetry that calculates the anisotropic optical properties. Vascular structures, both venous and arterial, are identified and monitored in real-time using a near-infrared laser-speckle-contrast imaging. We evaluate the system by performing in vivo animal studies with qualitative comparison by contrast-agent-aided fluorescence imaging

Hierarchical gate-array routing on a hypercube multiprocessor

Gate-arrays are the most common design style for semicustom VLSI integrated circuits. An important part of the gate-array design process is the routing of wires between the logic elements, which is an extremely compute-intensive operation. This paper presents an algorithm for routing gate-arrays that uses a hypercube connected parallel processor to provide the necessary computation power. In order to make optimal use of the hypercube, the routing algorithm is organized so that interprocessor communication is kept to minimum. It occurs only during the global routing and crossing placement phases of the algorithm, which constitute less than 15% of the total running time of the algorithm. On the basis of the results of executing the algorithm on two gate-array benchmarks the case is made for using hypercube multiprocessors as accelerators for compute-intensive CAD operations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28650/1/0000466.pd

Improving GENCODE reference gene annotation using a high-stringency proteogenomics workflow.

Complete annotation of the human genome is indispensable for medical research. The GENCODE consortium strives to provide this, augmenting computational and experimental evidence with manual annotation. The rapidly developing field of proteogenomics provides evidence for the translation of genes into proteins and can be used to discover and refine gene models. However, for both the proteomics and annotation groups, there is a lack of guidelines for integrating this data. Here we report a stringent workflow for the interpretation of proteogenomic data that could be used by the annotation community to interpret novel proteogenomic evidence. Based on reprocessing of three large-scale publicly available human data sets, we show that a conservative approach, using stringent filtering is required to generate valid identifications. Evidence has been found supporting 16 novel protein-coding genes being added to GENCODE. Despite this many peptide identifications in pseudogenes cannot be annotated due to the absence of orthogonal supporting evidence

Use of Guided Wave Inspections to Monitor the Integrity of Nuclear Power Station Boilers

This paper describes a ground-breaking application of guided wave testing for the nuclear power industry. Hartlepool and Heysham 1 power stations in the UK contain boilers of a unique ‘pod’ design in which the spiral boiler tubes are supported from above by a central vertical ‘spine’, which is a tubular component approximately 520mm in diameter and 21m long with complex changes in cross-section and attachments along its length. There are 32 boilers in the two stations. The gas which has passed through the reactor core flows down over the boiler tubes, heating the water inside. Only the top 2m of each spine is accessible above the top of the boiler pod. Plant Integrity Ltd was engaged by to inspect these ‘spine’ supports in 2003 using its Teletest guided wave system at statutory outages, which occur on a 3-year interval for each reactor. The Teletest tool was positioned in the only accessible place, just below the inlet header which protrudes approximately 2m from the top of the boiler. A procedure was developed to enable the full 21m length of the spine inside the boiler pod itself to be examined. During one of the regular Teletest inspections, at Heysham 1 power station in September 2013, a significant change in response was detected from the central part of one of the boiler spines. As a result, two of the eight boilers at Heysham 1 Reactor 1 were shut down pending further investigations. The indication was confirmed to be a structurally significant crack in the spine concerned. The crack detected was at the exact position and of the approximate extent reported by Teletest, which had detected the flaw from some 10m away. All four reactors at Hartlepool and Heysham 1 power stations were shut down in the latter part of 2014 while a new safety case for return to service of the remaining boilers was made. There is currently no viable alternative to guided wave inspection for monitoring the integrity of these boiler spines and a significant programme of work has been carried out to demonstrate the performance of Teletest for detection of flaws in these components under a variety of circumstances in order to support the safety case for operation. This has involved theoretical modelling, review of information contained in historical inspection data, practical tests on a full scale mock-up component, development of high temperature Teletest tooling to allow in- service tests and production of automated Teletest data collection equipment to allow real time in-service monitoring of the spines. TWI’s and Plant Integrity’s support enabled all four reactors to be returned to service before the end of 2014