Hydrogen peroxide induced genomic instability in nucleotide excision repair-deficient lymphoblastoid cells

Copyright @ 2010 Gopalakrishnan et al; licensee BioMed Central Ltd.Background The Nucleotide Excision Repair (NER) pathway specialises in UV-induced DNA damage repair. Inherited defects in the NER can predispose individuals to Xeroderma Pigmentosum (XP). UV-induced DNA damage cannot account for the manifestation of XP in organ systems not directly exposed to sunlight. While the NER has recently been implicated in the repair of oxidative DNA lesions, it is not well characterised. Therefore we sought to investigate the role of NER factors Xeroderma Pigmentosum A (XPA), XPB and XPD in oxidative DNA damage-repair by subjecting lymphoblastoid cells from patients suffering from XP-A, XP-D and XP-B with Cockayne Syndrome to hydrogen peroxide (H2O2). Results Loss of functional XPB or XPD but not XPA led to enhanced sensitivity towards H2O2-induced cell death. XP-deficient lymphoblastoid cells exhibited increased susceptibility to H2O2-induced DNA damage with XPD showing the highest susceptibility and lowest repair capacity. Furthermore, XPB- and XPD-deficient lymphoblastoid cells displayed enhanced DNA damage at the telomeres. XPA- and XPB-deficient lymphoblastoid cells also showed differential regulation of XPD following H2O2 treatment. Conclusions Taken together, our data implicate a role for the NER in H2O2-induced oxidative stress management and further corroborates that oxidative stress is a significant contributing factor in XP symptoms. Resistance of XPA-deficient lymphoblastoid cells to H2O2-induced cell death while harbouring DNA damage poses a potential cancer risk factor for XPA patients. Our data implicate XPB and XPD in the protection against oxidative stress-induced DNA damage and telomere shortening, and thus premature senescence.This research is supported by the Defence Innovative Research Programme, Defence Science and Technology Agency, Singapore (POD: 0613592) and the Academic Research Fund, Ministry of Education, Singapore (T206B3108). Supported in part by a grant from British Council, PMI2 Connect (Grant Number: RC134)

Inter-disciplinary service learning - housing for the community

2014-2015 > Academic research: refereed > Refereed conference paperVersion of RecordPublishe

Persistence of magnetic field driven by relativistic electrons in a plasma

The onset and evolution of magnetic fields in laboratory and astrophysical plasmas is determined by several mechanisms, including instabilities, dynamo effects and ultra-high energy particle flows through gas, plasma and interstellar-media. These processes are relevant over a wide range of conditions, from cosmic ray acceleration and gamma ray bursts to nuclear fusion in stars. The disparate temporal and spatial scales where each operates can be reconciled by scaling parameters that enable to recreate astrophysical conditions in the laboratory. Here we unveil a new mechanism by which the flow of ultra-energetic particles can strongly magnetize the boundary between the plasma and the non-ionized gas to magnetic fields up to 10-100 Tesla (micro Tesla in astrophysical conditions). The physics is observed from the first time-resolved large scale magnetic field measurements obtained in a laser wakefield accelerator. Particle-in-cell simulations capturing the global plasma and field dynamics over the full plasma length confirm the experimental measurements. These results open new paths for the exploration and modelling of ultra high energy particle driven magnetic field generation in the laboratory

A Survey on Continuous Time Computations

We provide an overview of theories of continuous time computation. These theories allow us to understand both the hardness of questions related to continuous time dynamical systems and the computational power of continuous time analog models. We survey the existing models, summarizing results, and point to relevant references in the literature

Micron-scale mapping of megagauss magnetic fields using optical polarimetry to probe hot electron transport in petawatt-class laser-solid interactions

The transport of hot, relativistic electrons produced by the interaction of an intense petawatt laser pulse with a solid has garnered interest due to its potential application in the development of innovative x-ray sources and ion-acceleration schemes. We report on spatially and temporally resolved measurements of megagauss magnetic fields at the rear of a 50-μm thick plastic target, irradiated by a multi-picosecond petawatt laser pulse at an incident intensity of ~1020 W/cm2. The pump-probe polarimetric measurements with micron-scale spatial resolution reveal the dynamics of the magnetic fields generated by the hot electron distribution at the target rear. An annular magnetic field profile was observed ~5 ps after the interaction, indicating a relatively smooth hot electron distribution at the rear-side of the plastic target. This is contrary to previous time-integrated measurements, which infer that such targets will produce highly structured hot electron transport. We measured large-scale filamentation of the hot electron distribution at the target rear only at later time-scales of ~10 ps, resulting in a commensurate large-scale filamentation of the magnetic field profile. Three-dimensional hybrid simulations corroborate our experimental observations and demonstrate a beam-like hot electron transport at initial time-scales that may be attributed to the local resistivity profile at the target rear

Die sicherheitspolitischen Dimensionen der G-20

Meine Diplomarbeit handelt von den sicherheitspolitischen Dimensionen der G-20. Dabei habe ich das Konzept der Kopenhagener Schule teilweise übernommen, da ich die Politiken der Gruppe der 20 größten und wichtigsten Wirtschaftsnationen des angebrochenen 21. Jahrhundert nach den Dimensionen der ökonomischen, politischen, militärischen und ökologischen Sicherheit aufgliedere. Zudem adaptiere ich das Analysekonzept der „Prismatic Security“ das von Zwitter und de Wilde entworfen wurde, um die Kopenhagener Schule auf lokaler Ebene zu transferieren. Durch dieses neuartige Problemfeld werden lokale Sicherheitsbereiche wie Nahrungs- und Gesundheitssicherheit sowie die physische Sicherheit der einzelnen Personen integriert. Um ein Analysekonzept zu entwickeln, dass den aktuellen Anforderungen gerecht wird, erachte ich es als unabdingbar zu jenen Sicherheitsbereichen den Aspekt der Informationssicherheit in eine umfassende Sicherheitsanalyse mit einzubeziehen. Darüber hinaus, und nicht zu letzt durch die aktuelle Revolutionswelle in Nordafrika abermals aufgezeigt, werde ich den Aspekt der Rechtssicherheit ebenfalls beleuchten. Abschließend strukturiere ich die zuvor nachgezeichneten Sicherheitsdimensionen im Kapitel zur Ressourcensicherheit, welches die generelle Installierung von Infrastrukturen in diversen Gesellschaftsbereichen thematisiert.My diploma thesis, I’ve dedicated to “the security dimensions of the G-20”. It uses an amplified concept of the security terminus. It embraces, aside from the traditional military security realm, the Copenhagen security sectors, to wit the economical, political and environmental security dimension. Furthermore, I’ve adopted the concept of Prismatic Security by Zwitter and de Wilde who expanded the Copenhagen School on a local level and therefore, introduced local security areas such as food, health and personal security (the last reflects the bottom up perspective of the military security dimension). To mirror the current aspect of globalisation issues, I’ve also included the realm of informational security. Finally, I illuminate the importance of judical and ressource security. The G-20 have been declared their group as the premier forum for international economic cooperation at the Summit in Pittsburgh (Pittsburgh 2009:Pkt.50). Hence the focus of my research lies in the economic security dimension of the post-Washtington G-20 (where the G-20 started to assemble in form of Leaders Summit in addition to the usual meetings of G-20 Finance Ministers and Centralbank Govornors). This chapter encompasses the reform of the international finance institutions, the new regulation regime with strengthend supervision and better risk management, globally unified high-level standards targeting transperancy and accountability, monetary and exchange rate policies as well as the concept for sustainable and balanced growth. Within the political security dimension, I explore the commitments pledged by the G-20 in their development policy like ressource mobilization for low income or developing countries, their principles regarding financial inclusion, and plans of fiscal consilidation as basis for a health surrounding and functional political system. I will include the counteractions of the G-20 against corruption and financing of terrorism in the military security dimension. Their instruments to address tax haevens and non-cooperative jurisdictions I’ll deal with in the realm of juridical security. In the environmental security dimension I scrutinize the emphased issues affirmed or discussed by the G-20 with regard to curbing the use of fuel fossils, energy security and protection of the environment. Based on the Multi-Year Action Plan of Seoul I scrutinize the measures of the G-20 concerning achieving food and health security, and compare them with the facts provided by the FAO. Finally, I outline the sustainable impact and considerations of the G-20 within the field of resource security

Performance of [(18)F]flutemetamol amyloid imaging against the neuritic plaque component of CERAD and the current (2012) NIA-AA recommendations for the neuropathologic diagnosis of Alzheimer's disease

INTRODUCTION: Performance of the amyloid tracer [(18)F]flutemetamol was evaluated against three pathology standard of truth (SoT) measures including neuritic plaques (CERAD "original" and "modified" and the amyloid component of the 2012 NIA-AA guidelines). METHODS: After [(18)F]flutemetamol imaging, 106 end-of-life patients who died underwent postmortem brain examination for amyloid plaque load. Blinded positron emission tomography scan interpretations by five independent electronically trained readers were compared with pathology measures. RESULTS: By SoT, sensitivity and specificity of majority image interpretations were, respectively, 91.9% and 87.5% with "original CERAD," 90.8% and 90.0% with "modified CERAD," and 85.7% and 100% with the 2012 NIA-AA criteria. DISCUSSION: The high accuracy of either CERAD criteria suggests that [(18)F]flutemetamol predominantly reflects neuritic amyloid plaque density. However, the use of CERAD criteria as the SoT can result in some false-positive results because of the presence of diffuse plaques, which are accounted for when the positron emission tomography read is compared with the 2012 NIA-AA criteria

Letter from P. D. Carey to Mr Hickey

Manuscript letter dated 22 January 1939, to Mr Hickey from P. D. Carey, about League's forthcoming demo in Glasgo