Magnetic resonance imaging of lung cancer in the presence of respiratory motion: Dynamic keyhole and audio visual biofeedback

Breath-to-breath variations in breathing can cause image artefacts. Day-to-day variations can cause a disagreement of position and volume between planning and treatment throughout radiotherapy procedures, requiring a larger treatment margin and longer treatment time. An advanced radiotherapy system requires: (1) a fast imaging technique for the compensation of breathing variations and/or (2) a respiratory motion management technique for the control of breathing variations. A novel MRI reconstruction method called “Dynamic keyhole” was proposed as a fast imaging technique. This thesis investigated (1) the concept of this method in terms of the improvement in temporal resolution with healthy volunteer MRI datasets and (2) the applicability of real-time lung tumour localization in terms of the accuracy of tumour motion and shape with lung cancer patient MRI datasets. The dynamic keyhole method achieved an increase in imaging frequency by up to a factor of five when compared with full k-space methods whilst achieving sub-millimetre tumour motion accuracy and preserving tumour shape within 98%. AV biofeedback respiratory guidance was used for healthy volunteers and lung cancer patients. This thesis investigated the impact of AV biofeedback on (1) intra- and inter-fraction lung tumour motion using cine-MRI, (2) inter-fraction lung tumour position and intra-fraction tumour volume using breath-hold MRI and (3) the improvement in image quality and the reduction in scan time using respiratory-gated MRI. AV biofeedback respiratory guidance improved intra- and inter-fraction tumour motion and position reproducibility, and intra-fraction tumour volume consistency. In addition, it was found to improve image quality and reduce scan time. The performance of the dynamic keyhole method and AV biofeedback respiratory guidance shown in this thesis illustrates potential advantages of real-time tumour imaging and tumour motion management in the course of lung cancer radiotherapy

Noise Peddler: An exploration of the 21st century pedalboard

Noise Peddler is a practice-based research project exploring the 21st century guitar pedalboard as composition and performance interface. Recent growth in the guitar pedal industry has seen a notable increase in popularity of the pedal platform, expansion in the number of manufacturers, the scope of effects available, and solidification of the concept of the pedalboard. The widespread adoption of MIDI/CV control, alongside the packaging of increasingly experimental and complex processing into stompbox formats has expanded the pedalboardʼs potential as a flexible canvas for the creation of unconventional guitar sounds. Performers such as Sarah Lipstate, Nels Cline and Ed OʼBrien have popularised the use of unconventional processing techniques to produce soundscapes where the guitar itself, arguably, no longer occupies the main role, acting as signal generator at the start of a chain. Noise Peddler takes this development to a possible conclusion, removing the guitar to create no-input pedalboard performance systems. This paper gives an overview of the Noise Peddler project, the contexts in which it operates and the opportunities it offers for reconsidering the pedalboard as a performative and compositional tool. It reflects on the research undertaken to date and engages with a series of questions: what is the role of the pedalboard in the performance ecosystem of the contemporary guitarist? How do the affordances of the pedalboard as a performance system, and guitar pedal technology more broadly, shape composition and performance practice? What is revealed of the ghost of the guitar when the guitar itself is removed and all that remains are the pedals? Ultimately, Noise Peddler explores guitar-based music created beyond the fretboard, in the circuits, systems and processes of the pedalboard, informed by the researchersʼ practices that unite unconventional approaches to contemporary instrumental and electroacoustic composition with musical journeys founded on being guitarists

LINE-1 Based Insertional Mutagenesis Screens to Identify Genes Involved in Embryonic Stem Cell Differentiation

Background: Knowledge of the intrinsic properties of embryonic stem cells is essential before the possibility of using these cells for therapeutic purposes becomes a reality. Insertional mutagenesis screens are widely used to identify genes sufficient to confer a particular phenotype; however, applications of such approaches are limited to mouse models. Thus, there is a need to develop a new DNA transposon system that allows gene discovery approaches in stem cells. Methods: This study was performed to explore the possibility of using the long interspersed nuclear element 1 (LINE -1) retrotransposon as a gene trap vector to identify genes involved in the maintenance and differentiation of mouse embryonic stem cells. Results: We developed an episomal, nonviral LINE-1 retrotransposon system using the scaffold/matrix attachment regions in the backbone of our vector. This gene trap vector harbors a GFP marker whose expression occurs only after successful insertional mutagenesis. By utilizing this vector, coupled with GFP expression, we have successfully isolated four individual embryonic stem cell clones that display disrupted genes, including two known genes. We then confirmed the identity of these genes using an inverse PCR approach and verified their function in cell differentiation using shRNAs and undifferentiated markers of embryonic stem cells. Conclusions: The ease of using this insertional mutagen and the simplicity of identifying the cells with disrupted genes by GFP expression make this LINE-1 vector a promising tool for embryonic stem cell and cancer stem cell gene discovery

An Overview of Testosterone Therapy

Millions of men, as a result of the natural aging process, injury, illness, and medical therapies, experience a decline in testosterone levels that necessitate a need for testosterone supplementation therapy (TST). The signs and symptoms of testosterone decline may occur gradually, and low testosterone levels may be misdiagnosed as other medical conditions. Over the past two decades, there has been an increase in testing of testosterone levels and the use of TST. With so many men now on TST, it is essential for health care professionals to know the signs and symptoms, the causes of testosterone decline, how testosterone deficiency is diagnosed, what pathological changes are associated with testosterone decline, and the benefits and risks of TST. In addition, health care providers need to be aware of the various forms of testosterone available as well as the advantages and disadvantages of each. This article provides a brief overview of testosterone deficiency, TST treatment options and guidelines, and the risks and benefits associated with of TST

Control of chicken CR1 retrotransposons is independent of Dicer-mediated RNA interference pathway

BACKGROUND: Dicer is an RNase III-ribonuclease that initiates the formation of small interfering RNAs as a defence against genomic parasites such as retrotransposons. Despite intensive characterization in mammalian species, the biological functions of Dicer in controlling retrotransposable elements of the non-mammalian vertebrate are poorly understood. In this report, we examine the role of chicken Dicer in controlling the activity of chicken CR1 retrotransposable elements in a chicken-human hybrid DT40 cell line employing a conditional lossof- Dicer function. RESULTS: Retrotransposition is detrimental to host genome stability and thus eukaryotic cells have developed mechanisms to limit the expansion of retrotransposons by Dicer-mediated RNAi silencing pathways. However, the mechanisms that control the activity and copy numbers of transposable elements in chicken remain unclear. Here, we describe how the loss of Dicer in chicken cells does not reactivate endogenous chicken CR1 retrotransposons with impaired RNAi machinery, suggesting that the control of chicken CR1 is independent of Dicer-induced RNAi silencing. In contrast, upon introduction of a functionally active human L1 retrotransposable element that contains an active 5' UTR promoter, the Dicer-deficient chicken cells show a strong increase in the accumulation of human L1 transcripts and retrotransposition activity, highlighting a major difference between chicken CR1 and other mammalian L1 retrotransposons. CONCLUSION: Our data provide evidence that chicken CR1 retrotransposons, unlike their mammalian L1 counterparts, do not undergo retrotransposition because most CR1 retrotransposons are truncated or mutated at their 5'UTR promoters and thus are not subjected to Dicer-mediated RNAi-silencing control

Combler le « vide institutionnel » : Le comportement social et les performances des entreprises familiales comparés à ceux des autres entreprises des marchés émergents dans le secteur des hautes technologies.

Les entreprises familiales (EF) sont réputées prendre un soin particulier de leurs employés, avec l’objectif de créer une « communauté » interne très soudée. Leurs relations et contacts avec leurs partenaires extérieurs seraient aussi plus approfondis et personnels. Ces deux attitudes favoriseraient la viabilité d’une entreprise qui doit faire vivre la famille propriétaire, ainsi que les générations suivantes. Ces liens sociaux nous paraissent pouvoir compenser le manque de capital, de produits et d’infrastructure propre aux économies émergentes dynamiques. Cette étude, menée dans un secteur très compétitif de marché émergent, les entreprises de haute technologie en Corée, examine trois points majeurs :(1) Les relations internes et les liens avec l’extérieur sont plus développés dans les EF que dans les autres. (2) Ces relations améliorent la performance des secteurs de haute technologie dans les marchés émergents, pour lesquels il est indispensable, du fait de leur nature compétitive complexe et évolutive, de disposer d’une expertise pointue et d’un capital social à l’intérieur comme à l’extérieur de l’entreprise. (3) Les performances des EF sont plus dépendantes de ces relations communautaires et de ces liens avec l’extérieur que celles des autres entreprises, parce que dans ce cadre personnel et intime, les employés et les partenaires extérieurs ont généralement tendance à récompenser la générosité, ou au contraire à punir l’égoïsme, d’une famille propriétaire qu’ils voient à l’oeuvre de leurs propres yeux. Nos observations empiriques confirment la plupart de ces hypothèses de façon significative.We argue that family businesses (FBs) will tend to treat their employees with unusual consideration to form a cohesive internal “community”. They are also expected to develop deeper, more extensive “connections” or relationships with outside stakeholders. Both behaviors should increase the viability of a business intended to support an owning family and its later generations. Such social linkages, we believe, may compensate for the lack of capital, product and labor institutional infrastructures in dynamic emerging economies. This survey study of a most challenging emerging market sector, namely, Korean high technology businesses, largely supports these expectations