BMP7 Gene Transfer via Gold Nanoparticles into Stroma Inhibits Corneal Fibrosis In Vivo

This study examined the effects of BMP7 gene transfer on corneal wound healing and fibrosis inhibition in vivo using a rabbit model. Corneal haze in rabbits was produced with the excimer laser performing -9 diopters photorefractive keratectomy. BMP7 gene was introduced into rabbit keratocytes by polyethylimine-conjugated gold nanoparticles (PEI2-GNPs) transfection solution single 5-minute topical application on the eye. Corneal haze and ocular health in live animals was gauged with stereo- and slit-lamp biomicroscopy. The levels of fibrosis [α-smooth muscle actin (αSMA), F-actin and fibronectin], immune reaction (CD11b and F4/80), keratocyte apoptosis (TUNEL), calcification (alizarin red, vonKossa and osteocalcin), and delivered-BMP7 gene expression in corneal tissues were quantified with immunofluorescence, western blotting and/or real-time PCR. Human corneal fibroblasts (HCF) and in vitro experiments were used to characterize the molecular mechanism mediating BMP7’s anti-fibrosis effects. PEI2-GNPs showed substantial BMP7 gene delivery into rabbit keratocytes in vivo (2×10[superscript 4] gene copies/ug DNA). Localized BMP7 gene therapy showed a significant corneal haze decrease (1.68±0.31 compared to 3.2±0.43 in control corneas; p88%; p<0.0001), and immunoblotting of BMP7-transefected HCFs grown in the presence of TGFβ demonstrated significantly enhanced pSmad-1/5/8 (95%; p<0.001) and Smad6 (53%, p<0.001), and decreased αSMA (78%; p<0.001) protein levels. These results suggest that localized BMP7 gene delivery in rabbit cornea modulates wound healing and inhibits fibrosis in vivo by counter balancing TGFβ1-mediated profibrotic Smad signaling.National Institutes of Health (U.S.) (RO1EB000244)Mason Eye Institute (Research to Prevent Blindness Unrestricted Grant

BMP7 Gene Transfer via Gold Nanoparticles into Stroma Inhibits Corneal Fibrosis \u3cem\u3ein vivo\u3c/em\u3e

This study examined the effects of BMP7 gene transfer on corneal wound healing and fibrosis inhibition in vivo using a rabbit model. Corneal haze in rabbits was produced with the excimer laser performing -9 diopters photorefractive keratectomy. BMP7 gene was introduced into rabbit keratocytes by polyethylimine-conjugated gold nanoparticles (PEI2- GNPs) transfection solution single 5-minute topical application on the eye. Corneal haze and ocular health in live animals was gauged with stereo- and slit-lamp biomicroscopy. The levels of fibrosis [a-smooth muscle actin (aSMA), F-actin and fibronectin], immune reaction (CD11b and F4/80), keratocyte apoptosis (TUNEL), calcification (alizarin red, vonKossa and osteocalcin), and delivered-BMP7 gene expression in corneal tissues were quantified with immunofluorescence, western blotting and/or real-time PCR. Human corneal fibroblasts (HCF) and in vitro experiments were used to characterize the molecular mechanism mediating BMP7’s anti-fibrosis effects. PEI2-GNPs showed substantial BMP7 gene delivery into rabbit keratocytes in vivo (26104 gene copies/ug DNA). Localized BMP7 gene therapy showed a significant corneal haze decrease (1.6860.31 compared to 3.260.43 in control corneas; p,0.05) in Fantes grading scale. Immunostaining and immunoblot analyses detected significantly reduced levels of aSMA (4665% p,0.001) and fibronectin proteins (4865% p,0.01). TUNEL, CD11b, and F4/80 assays revealed that BMP7 gene therapy is nonimmunogenic and nontoxic for the cornea. Furthermore, alizarin red, vonKossa and osteocalcin analyses revealed that localized PEI2-GNP-mediated BMP7 gene transfer in rabbit cornea does not cause calcification or osteoblast recruitment. Immunofluorescence of BMP7-transefected HCFs showed significantly increased pSmad-1/5/8 nuclear localization (.88%; p,0.0001), and immunoblotting of BMP7-transefected HCFs grown in the presence of TGFb demonstrated significantly enhanced pSmad-1/5/8 (95%; p,0.001) and Smad6 (53%, p,0.001), and decreased aSMA (78%; p,0.001) protein levels. These results suggest that localized BMP7 gene delivery in rabbit cornea modulates wound healing and inhibits fibrosis in vivo by counter balancing TGFb1-mediated profibrotic Smad signaling

Hair Manganese and Hyperactive Behaviors: Pilot Study of School-Age Children Exposed through Tap Water

BACKGROUND: Neurotoxic effects are known to occur with inhalation of manganese particulates, but very few data are available on exposure to Mn in water. We undertook a pilot study in a community in Québec (Canada) where naturally occurring high Mn levels were present in the public water system. Our objective was to test the hypothesis that greater exposure to Mn via drinking water would be reflected in higher Mn content in hair which, in turn, would be associated with increased level of hyperactive behaviors. METHODS: Forty-six children participated in the study, 24 boys and 22 girls, 6–15 years of age (median, 11 years). Their homes received water from one of two wells (W) with different Mn concentrations: W1: mean 610 μg/L; W2: mean 160 μg/L. The Revised Conners’ Rating Scale for parents (CPRS-R) and for teachers (CTRS-R) were administered, providing T-scores on the following subscales: Oppositional, Hyperactivity, Cognitive Problems/Inattention, and ADHD Index. RESULTS: Children whose houses were supplied by W1 had higher hair Mn (MnH) than those supplied by W2 (mean 6.2 ± 4.7 μg/g vs. 3.3 ± 3.0 μg/g, p = 0.025). MnH was significantly associated with T-scores on the CTRS-R Oppositional (p = 0.020) and Hyperactivity (p = 0.002) subscales, after adjustment for age, sex, and income. All children with Oppositional and Hyperactivity T-scores ≥ 65 had MnH > 3.0 μg/g. CONCLUSIONS: The findings of this pilot study are sufficiently compelling to warrant more extensive investigations into the risks of Mn exposure in drinking water

Rumors of disease in the global village: outbreak verification.

Emerging infectious diseases and the growth of information technology have produced new demands and possibilities for disease surveillance and response. Increasing numbers of outbreak reports must be assessed rapidly so that control efforts can be initiated and unsubstantiated reports can be identified to protect countries from unnecessary economic damage. The World Health Organization has set up a process for timely outbreak verification to convert large amounts of data into accurate information for suitable action. We describe the context and processes of outbreak verification and information dissemination

Therapeutic targeting of replicative immortality

One of the hallmarks of malignant cell populations is the ability to undergo continuous proliferation. This property allows clonal lineages to acquire sequential aberrations that can fuel increasingly autonomous growth, invasiveness, and therapeutic resistance. Innate cellular mechanisms have evolved to regulate replicative potential as a hedge against malignant progression. When activated in the absence of normal terminal differentiation cues, these mechanisms can result in a state of persistent cytostasis. This state, termed “senescence,” can be triggered by intrinsic cellular processes such as telomere dysfunction and oncogene expression, and by exogenous factors such as DNA damaging agents or oxidative environments. Despite differences in upstream signaling, senescence often involves convergent interdependent activation of tumor suppressors p53 and p16/pRB, but can be induced, albeit with reduced sensitivity, when these suppressors are compromised. Doses of conventional genotoxic drugs required to achieve cancer cell senescence are often much lower than doses required to achieve outright cell death. Additional therapies, such as those targeting cyclin dependent kinases or components of the PI3K signaling pathway, may induce senescence specifically in cancer cells by circumventing defects in tumor suppressor pathways or exploiting cancer cells’ heightened requirements for telomerase. Such treatments sufficient to induce cancer cell senescence could provide increased patient survival with fewer and less severe side effects than conventional cytotoxic regimens. This positive aspect is countered by important caveats regarding senescence reversibility, genomic instability, and paracrine effects that may increase heterogeneity and adaptive resistance of surviving cancer cells. Nevertheless, agents that effectively disrupt replicative immortality will likely be valuable components of new combinatorial approaches to cancer therapy

Measurement of the top quark pair production cross section in pp collisions at √s=7TeV in dilepton final states with ATLAS

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAMA measurement of the production cross section of top quark pairs (t¯t) in proton–proton collisions at a center-of-mass energy of 7 TeV recorded with the ATLAS detector at the Large Hadron Collider is reported. Candidate events are selected in the dilepton topology with large missing transverse energy and at least two jets. Using a data sample corresponding to an integrated luminosity of 35 pb−1, a t¯t production cross section σt¯t = 177±20(stat.)±14(syst.)±7(lum.) pb is measured for an assumed top quark mass of mt = 172.5 GeV. A second measurement requiring at least one jet identified as coming from a b quark yields a comparable result, demonstrating that the dilepton final states are consistent with being accompanied by b-quark jets. These measurements are in good agreement with Standard Model predictionsWe thank CERN for the very successful operation of the LHC, as well as the support staff from our institutions without whom ATLAS could not be operated efficiently. We acknowledge the support of ANPCyT, Argentina; YerPhI, Armenia; ARC, Australia; BMWF, Austria; ANAS, Azerbaijan; SSTC, Belarus; CNPq and FAPESP, Brazil; NSERC, NRC and CFI, Canada; CERN; CONICYT, Chile; CAS, MOST and NSFC, China; COLCIENCIAS, Colombia; MSMT CR, MPO CR and VSC CR, Czech Republic; DNRF, DNSRC and Lundbeck Foundation, Denmark; ARTEMIS, European Union; IN2P3-CNRS, CEA-DSM/IRFU, France; GNAS, Georgia; BMBF, DFG, HGF, MPG and AvH Foundation, Germany; GSRT, Greece; ISF, MINERVA, GIF, DIP and Benoziyo Center, Israel; INFN, Italy; MEXT and JSPS, Japan; CNRST, Morocco; FOM and NWO, Netherlands; RCN, Norway; MNiSW, Poland; GRICES and FCT, Portugal; MERYS (MECTS), Romania; MES of Russia and ROSATOM, Russian Federation; JINR; MSTD, Serbia; MSSR, Slovakia; ARRS and MVZT, Slovenia; DST/NRF, South Africa; MICINN, Spain; SRC and Wallenberg Foundation, Sweden; SER, SNSF and Cantons of Bern and Geneva, Switzerland; NSC, Taiwan; TAEK, Turkey; STFC, the Royal Society and Leverhulme Trust, United Kingdom; DOE and NSF, United States of America. The crucial computing support from all WLCG partners is acknowledged gratefully, in particular from CERN and the ATLAS Tier-1 facilities at TRIUMF (Canada), NDGF (Denmark, Norway, Sweden), CC-IN2P3 (France), KIT/GridKA (Germany), INFN-CNAF (Italy), NL-T1 (Netherlands), PIC (Spain), ASGC (Taiwan), RAL (UK) and BNL (USA) and in the Tier-2 facilities worldwid

Search for diphoton events with large missing transverse momentum in 1 fb-1 of 7 TeV proton-proton collision data with the ATLAS detector

Artículo escrito por muchos autores, sólo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración y los autores que firman como pertenecientes a la UAMA search for diphoton events with large missing transverse momentum has been performed using 1.07 fb−1 of proton–proton collision data at √ s = 7 TeV recorded with the ATLAS detector. No excess of events was observed above the Standard Model prediction and 95% Confidence Level (CL) upper limits are set on the production cross section for new physics. The limits depend on each model parameter space and vary as follows: σ < (22–129) fb in the context of a generalised model of gauge-mediated supersymmetry breaking (GGM) with a bino-like lightest neutralino, σ < (27–91) fb in the context of a minimal model of gauge-mediated supersymmetry breaking (SPS8), and σ < (15–27) fb in the context of a specific model with one universal extra dimension (UED). A 95% CL lower limit of 805 GeV, for bino masses above 50 GeV, is set on the GGM gluino mass. Lower limits of 145 TeV and 1.23 TeV are set on the SPS8 breaking scale Λ and on the UED compactification scale 1/R, respectively. These limits provide the most stringent tests of these models to dateWe thank CERN for the very successful operation of the LHC, as well as the support staff from our institutions without whom ATLAS could not be operated efficiently. We acknowledge the support of ANPCyT, Argentina; YerPhI, Armenia; ARC, Australia; BMWF, Austria; ANAS, Azerbaijan; SSTC, Belarus; CNPq and FAPESP, Brazil; NSERC, NRC and CFI, Canada; CERN; CONICYT, Chile; CAS, MOST and NSFC, China; COLCIENCIAS, Colombia; MSMT CR, MPO CR and VSC CR, Czech Republic; DNRF, DNSRC and Lundbeck Foundation, Denmark; ARTEMIS, European Union; IN2P3-CNRS, CEA-DSM/IRFU, France; GNAS, Georgia; BMBF, DFG, HGF, MPG and AvH Foundation, Germany; GSRT, Greece; ISF, MINERVA, GIF, DIP and Benoziyo Center, Israel; INFN, Italy; MEXT and JSPS, Japan; CNRST, Morocco; FOM and NWO, Netherlands; RCN, Norway; MNiSW, Poland; GRICES and FCT, Portugal; MERYS (MECTS), Romania; MES of Russia and ROSATOM, Russian Federation; JINR; MSTD, Serbia; MSSR, Slovakia; ARRS and MVZT, Slovenia; DST/NRF, South Africa; MICINN, Spain; SRC and Wallenberg Foundation, Sweden; SER, SNSF and Cantons of Bern and Geneva, Switzerland; NSC, Taiwan; TAEK, Turkey; STFC, the Royal Society and Leverhulme Trust, United Kingdom; DOE and NSF, United States of America. The crucial computing support from all WLCG partners is acknowledged gratefully, in particular from CERN and the ATLAS Tier- 1 facilities at TRIUMF (Canada), NDGF (Denmark, Norway, Sweden), CC-IN2P3 (France), KIT/GridKA (Germany), INFN-CNAF (Italy), NLT1 (Netherlands), PIC (Spain), ASGC (Taiwan), RAL (UK) and BNL (USA) and in the Tier-2 facilities worldwid

Measurement of the W ±Z production cross section and limits on anomalous triple gauge couplings in proton-proton collisions at s=7 TeV with the ATLAS detector

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAMThis Letter presents a measurement of W± Z production in 1.02 fb−1 of pp collision data at √ s = 7 TeV collected by the ATLAS experiment in 2011. Doubly leptonic decay events are selected with electrons, muons and missing transverse momentum in the final state. In total 71 candidates are observed, with a background expectation of 12.1 ± 1.4(stat.) +4.1 −2.0(syst.) events. The total cross section for W± Z production for Z/γ ∗ masses within the range 66 GeV to 116 GeV is determined to be σtot WZ = 20.5+3.1 −2.8(stat.) +1.4 −1.3(syst.) +0.9 −0.8(lumi.) pb, which is consistent with the Standard Model expectation of 17.3+1.3 0.8 pb. Limits on anomalous triple gauge boson couplings are extractedWe thank CERN for the very successful operation of the LHC, as well as the support staff from our institutions without whom ATLAS could not be operated efficiently. We acknowledge the support of ANPCyT, Argentina; YerPhI, Armenia; ARC, Australia; BMWF, Austria; ANAS, Azerbaijan; SSTC, Belarus; CNPq and FAPESP, Brazil; NSERC, NRC and CFI, Canada; CERN; CONICYT, Chile; CAS, MOST and NSFC, China; COLCIENCIAS, Colombia; MSMT CR, MPO CR and VSC CR, Czech Republic; DNRF, DNSRC and Lundbeck Foundation, Denmark; ARTEMIS, European Union; IN2P3-CNRS, CEA-DSM/IRFU, France; GNAS, Georgia; BMBF, DFG, HGF, MPG and AvH Foundation, Germany; GSRT, Greece; ISF,MINERVA, GIF, DIP and Benoziyo Center, Israel; INFN, Italy; MEXT and JSPS, Japan; CNRST, Morocco; FOM and NWO, Netherlands; RCN, Norway; MNiSW, Poland; GRICES and FCT, Portugal; MERYS (MECTS), Romania; MES of Russia and ROSATOM, Russian Federation; JINR; MSTD, Serbia; MSSR, Slovakia; ARRS and MVZT, Slovenia; DST/NRF, South Africa; MICINN, Spain; SRC and Wallenberg Foundation, Sweden; SER, SNSF and Cantons of Bern and Geneva, Switzerland; NSC, Taiwan; TAEK, Turkey; STF, the Royal Society and Leverhulme Trust, United Kingdom; DOE and NSF, United States of America. The crucial computing support from all WLCG partners is acknowledged gratefully, in particular from CERN and the ATLAS Tier-1 facilities at TRIUMF (Canada), NDGF (Denmark, Norway, Sweden), CC-IN2P3 (France), KIT/GridKA (Germany), INFN-CNAF (Italy), NL-T1 (Netherlands), PIC (Spain), ASGC (Taiwan), RAL (UK) and BNL (USA) and in the Tier-2 facilities worldwid

Search for a heavy Standard Model Higgs boson in the channel H→ZZ→ℓ+ℓ-qq̄ using the ATLAS detector

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAMA search for a heavy Standard Model Higgs boson decaying via H → Z Z →ℓ+ℓ−qq, where ℓ= e,μ, is presented. The search is performed using a data set of pp collisions at √ s = 7 TeV, corresponding to an integrated luminosity of 1.04 fb−1 collected in 2011 by the ATLAS detector at the CERN LHC collider. No significant excess of events above the estimated background is found. Upper limits at 95% confidence level on the production cross section (relative to that expected from the Standard Model) of a Higgs boson with a mass in the range between 200 and 600 GeV are derived. Within this mass range, there is at present insufficient sensitivity to exclude a Standard Model Higgs boson. For a Higgs boson with a mass of 360 GeV, where the sensitivity is maximal, the observed and expected cross section upper limits are factors of 1.7 and 2.7, respectively, larger than the Standard Model predictionWe thank CERN for the very successful operation of the LHC, as well as the support staff from our institutions without whom ATLAS could not be operated efficiently. We acknowledge the support of ANPCyT, Argentina; YerPhI, Armenia; ARC, Australia; BMWF, Austria; ANAS, Azerbaijan; SSTC, Belarus; CNPq and FAPESP, Brazil; NSERC, NRC and CFI, Canada; CERN; CONICYT, Chile; CAS, MOST and NSFC, China; COLCIENCIAS, Colombia; MSMT CR, MPO CR and VSC CR, Czech Republic; DNRF, DNSRC and Lundbeck Foundation, Denmark; ARTEMIS, European Union; IN2P3-CNRS, CEA-DSM/IRFU, France; GNAS, Georgia; BMBF, DFG, HGF, MPG and AvH Foundation, Germany; GSRT, Greece; ISF, MINERVA, GIF, DIP and Benoziyo Center, Israel; INFN, Italy; MEXT and JSPS, Japan; CNRST, Morocco; FOM and NWO, Netherlands; RCN, Norway; MNiSW, Poland; GRICES and FCT, Portugal; MERYS (MECTS), Romania; MES of Russia and ROSATOM, Russian Federation; JINR; MSTD, Serbia; MSSR, Slovakia; ARRS and MVZT, Slovenia; DST/NRF, South Africa; MICINN, Spain; SRC and Wallenberg Foundation, Sweden; SER, SNSF and Cantons of Bern and Geneva, Switzerland; NSC, Taiwan; TAEK, Turkey; STFC, the Royal Society and Leverhulme Trust, United Kingdom; DOE and NSF, United States. The crucial computing support from all WLCG partners is acknowledged gratefully, in particular from CERN and the ATLAS Tier- 1 facilities at TRIUMF (Canada), NDGF (Denmark, Norway, Sweden), CC-IN2P3 (France), KIT/GridKA (Germany), INFN-CNAF (Italy), NLT1 (Netherlands), PIC (Spain), ASGC (Taiwan), RAL (UK) and BNL (USA) and in the Tier-2 facilities worldwid