The effect of radio-adaptive doses on HT29 and GM637 cells

<p>Abstract</p> <p>Background</p> <p>The shape of the dose-response curve at low doses differs from the linear quadratic model. The effect of a radio-adaptive response is the centre of many studies and well known inspite that the clinical applications are still rarely considered.</p> <p>Methods</p> <p>We studied the effect of a low-dose pre-irradiation (0.03 Gy – 0.1 Gy) alone or followed by a 2.0 Gy challenging dose 4 h later on the survival of the HT29 cell line (human colorectal cancer cells) and on the GM637 cell line (human fibroblasts).</p> <p>Results</p> <p>0.03 Gy given alone did not have a significant effect on both cell lines, the other low doses alone significantly reduced the cell survival. Applied 4 h before the 2.0 Gy fraction, 0.03 Gy led to a significant induced radioresistance in GM637 cells, but not in HT29 cells, and 0.05 Gy led to a significant hyperradiosensitivity in HT29 cells, but not in GM637 cells.</p> <p>Conclusion</p> <p>A pre-irradiation with 0.03 Gy can protect normal fibroblasts, but not colorectal cancer cells, from damage induced by an irradiation of 2.0 Gy and the application of 0.05 Gy prior to the 2.0 Gy fraction can enhance the cell killing of colorectal cancer cells while not additionally damaging normal fibroblasts. If these findings prove to be true in vivo as well this may optimize the balance between local tumour control and injury to normal tissue in modern radiotherapy.</p

A Role in Immunity for Arabidopsis Cysteine Protease RD21, the Ortholog of the Tomato Immune Protease C14

Secreted papain-like Cys proteases are important players in plant immunity. We previously reported that the C14 protease of tomato is targeted by cystatin-like EPIC proteins that are secreted by the oomycete pathogen Phytophthora infestans (Pinf) during infection. C14 has been under diversifying selection in wild potato species coevolving with Pinf and reduced C14 levels result in enhanced susceptibility for Pinf. Here, we investigated the role C14-EPIC-like interactions in the natural pathosystem of Arabidopsis with the oomycete pathogen Hyaloperonospora arabidopsidis (Hpa). In contrast to the Pinf-solanaceae pathosystem, the C14 orthologous protease of Arabidopsis, RD21, does not evolve under diversifying selection in Arabidopsis, and rd21 null mutants do not show phenotypes upon compatible and incompatible Hpa interactions, despite the evident lack of a major leaf protease. Hpa isolates express highly conserved EPIC-like proteins during infections, but it is unknown if these HpaEPICs can inhibit RD21 and one of these HpaEPICs even lacks the canonical cystatin motifs. The rd21 mutants are unaffected in compatible and incompatible interactions with Pseudomonas syringae pv. tomato, but are significantly more susceptible for the necrotrophic fungal pathogen Botrytis cinerea, demonstrating that RD21 provides immunity to a necrotrophic pathogen

GenCLiP: a software program for clustering gene lists by literature profiling and constructing gene co-occurrence networks related to custom keywords

<p>Abstract</p> <p>Background</p> <p>Biomedical researchers often want to explore pathogenesis and pathways regulated by abnormally expressed genes, such as those identified by microarray analyses. Literature mining is an important way to assist in this task. Many literature mining tools are now available. However, few of them allows the user to make manual adjustments to zero in on what he/she wants to know in particular.</p> <p>Results</p> <p>We present our software program, GenCLiP (Gene Cluster with Literature Profiles), which is based on the methods presented by Chaussabel and Sher (<it>Genome Biol </it>2002, 3(10):RESEARCH0055) that search gene lists to identify functional clusters of genes based on up-to-date literature profiling. Four features were added to this previously described method: the ability to 1) manually curate keywords extracted from the literature, 2) search genes and gene co-occurrence networks related to custom keywords, 3) compare analyzed gene results with negative and positive controls generated by GenCLiP, and 4) calculate probabilities that the resulting genes and gene networks are randomly related. In this paper, we show with a set of differentially expressed genes between keloids and normal control, how implementation of functions in GenCLiP successfully identified keywords related to the pathogenesis of keloids and unknown gene pathways involved in the pathogenesis of keloids.</p> <p>Conclusion</p> <p>With regard to the identification of disease-susceptibility genes, GenCLiP allows one to quickly acquire a primary pathogenesis profile and identify pathways involving abnormally expressed genes not previously associated with the disease.</p

California Men's Health Study (CMHS): a multiethnic cohort in a managed care setting

BACKGROUND: We established a male, multiethnic cohort primarily to study prostate cancer etiology and secondarily to study the etiologies of other cancer and non-cancer conditions. METHODS/DESIGN: Eligible participants were 45-to-69 year old males who were members of a large, prepaid health plan in California. Participants completed two surveys on-line or on paper in 2002 – 2003. Survey content included demographics; family, medical, and cancer screening history; sexuality and sexual development; lifestyle (diet, physical activity, and smoking); prescription and non-prescription drugs; and herbal supplements. We linked study data with clinical data, including laboratory, hospitalization, and cancer data, from electronic health plan files. We recruited 84,170 participants, approximately 40% from minority populations and over 5,000 who identified themselves as other than heterosexual. We observed a wide range of education (53% completed less than college) and income. PSA testing rates (75% overall) were highest among black participants. Body mass index (BMI) (median 27.2) was highest for blacks and Latinos and lowest for Asians, and showed 80.6% agreement with BMI from clinical data sources. The sensitivity and specificity can be assessed by comparing self-reported data, such as PSA testing, diabetes, and history of cancer, to health plan data. We anticipate that nearly 1,500 prostate cancer diagnoses will occur within five years of cohort inception. DISCUSSION: A wide variety of epidemiologic, health services, and outcomes research utilizing a rich array of electronic, biological, and clinical resources is possible within this multiethnic cohort. The California Men's Health Study and other cohorts nested within comprehensive health delivery systems can make important contributions in the area of men's health

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal