Pivotal Role of Inosine Triphosphate Pyrophosphatase in Maintaining Genome Stability and the Prevention of Apoptosis in Human Cells

Pure nucleotide precursor pools are a prerequisite for high-fidelity DNA replication and the suppression of mutagenesis and carcinogenesis. ITPases are nucleoside triphosphate pyrophosphatases that clean the precursor pools of the non-canonical triphosphates of inosine and xanthine. The precise role of the human ITPase, encoded by the ITPA gene, is not clearly defined. ITPA is clinically important because a widespread polymorphism, 94C>A, leads to null ITPase activity in erythrocytes and is associated with an adverse reaction to thiopurine drugs. We studied the cellular function of ITPA in HeLa cells using the purine analog 6-N hydroxylaminopurine (HAP), whose triphosphate is also a substrate for ITPA. In this study, we demonstrate that ITPA knockdown sensitizes HeLa cells to HAP-induced DNA breaks and apoptosis. The HAP-induced DNA damage and cytotoxicity observed in ITPA knockdown cells are rescued by an overexpression of the yeast ITPase encoded by the HAM1 gene. We further show that ITPA knockdown results in elevated mutagenesis in response to HAP treatment. Our studies reveal the significance of ITPA in preventing base analog-induced apoptosis, DNA damage and mutagenesis in human cells. This implies that individuals with defective ITPase are predisposed to genome damage by impurities in nucleotide pools, which is drastically augmented by therapy with purine analogs. They are also at an elevated risk for degenerative diseases and cancer

Search for the standard model Higgs boson in the diphoton decay channel with 4.9fb -1 of pp collision data at √s=7TeV with atlas

A search for the standard model Higgs boson is performed in the diphoton decay channel. The data used correspond to an integrated luminosity of 4.9  fb-1 collected with the ATLAS detector at the Large Hadron Collider in proton-proton collisions at a center-of-mass energy of √s=7  TeV. In the diphoton mass range 110–150 GeV, the largest excess with respect to the background-only hypothesis is observed at 126.5 GeV, with a local significance of 2.8 standard deviations. Taking the look-elsewhere effect into account in the range 110–150 GeV, this significance becomes 1.5 standard deviations. The standard model Higgs boson is excluded at 95% confidence level in the mass ranges of 113–115 GeV and 134.5–136 GeV

Search for the standard model Higgs boson in the diphoton decay channel with 4.9fb -1 of pp collision data at √s=7TeV with atlas

A search for the standard model Higgs boson is performed in the diphoton decay channel. The data used correspond to an integrated luminosity of 4.9  fb-1 collected with the ATLAS detector at the Large Hadron Collider in proton-proton collisions at a center-of-mass energy of √s=7  TeV. In the diphoton mass range 110–150 GeV, the largest excess with respect to the background-only hypothesis is observed at 126.5 GeV, with a local significance of 2.8 standard deviations. Taking the look-elsewhere effect into account in the range 110–150 GeV, this significance becomes 1.5 standard deviations. The standard model Higgs boson is excluded at 95% confidence level in the mass ranges of 113–115 GeV and 134.5–136 GeV

HealthAgents: distributed multi-agent brain tumor diagnosis and prognosis

We present an agent-based distributed decision support system for the diagnosis and prognosis of brain tumors developed by the HEALTHAGENTS project. HEALTHAGENTS is a European Union funded research project, which aims to enhance the classification of brain tumours using such a decision support system based on intelligent agents to securely connect a network of clinical centres. The HEALTHAGENTS system is implementing novel pattern recognition discrimination methods, in order to analyse in vivo Magnetic Resonance Spectroscopy (MRS) and ex vivo/in vitro High Resolution Magic Angle Spinning Nuclear Magnetic Resonance (HR-MAS) and DNA micro-array data. HEALTHAGENTS intends not only to apply forefront agent technology to the biomedical field, but also develop the HEALTHAGENTS network, a globally distributed information and knowledge repository for brain tumour diagnosis and prognosis

Compound effect of EHD and surface roughness in pool boiling and CHF with R-123

This article is a post-print version of the fianl published article which may be accessed at the link below.Saturated pool boiling of R-123 at 1 bar, including the critical heat flux (CHF), was enhanced by modifying the surface characteristics and applying a high intensity electrostatic field, the latter termed electrohydrodynamic (and abbreviated EHD) enhancement. The heat flux was varied from very low values in the natural convection regime up to CHF. Experiments were performed with increasing and decreasing heat flux to study boiling hysteresis without and with EHD. Boiling occurred on the sand blasted surface of a cylindrical copper block with embedded electrical heating elements, with standardized surface parameter Pa = 3.5 μm. The electric field was generated by a potential of 5 kV to 25 kV, applied through a 40 mm diameter circular electrode of ss-304 wire mesh, aperture size 5.1 mm, located at distances of 5 - 60 mm from the surface, with most of the data obtained for 20 mm. The data for the rough surface were compared with earlier data for a smooth surface and indicated a significant increase in the heat transfer rates. EHD produced a further increase in the heat transfer rates, particularly at low heat flux values and near the CHF. Boiling hysteresis was reduced progressively by EHD and eliminated at high field strength.This work was supported by Government of Pakistan under a scholarship programme