236 research outputs found

    Performance of the reconstruction algorithms of the FIRST experiment pixel sensors vertex detector

    Get PDF
    Hadrontherapy treatments use charged particles (e.g. protons and carbon ions) to treat tumors. During a therapeutic treatment with carbon ions, the beam undergoes nuclear fragmentation processes giving rise to significant yields of secondary charged particles. An accurate prediction of these production rates is necessary to estimate precisely the dose deposited into the tumours and the surrounding healthy tissues. Nowadays, a limited set of double differential carbon fragmentation cross-section is available. Experimental data are necessary to benchmark Monte Carlo simulations for their use in hadrontherapy. The purpose of the FIRST experiment is to study nuclear fragmentation processes of ions with kinetic energy in the range from 100 to 1000 MeV/u. Tracks are reconstructed using information from a pixel silicon detector based on the CMOS technology. The performances achieved using this device for hadrontherapy purpose are discussed. For each reconstruction step (clustering, tracking and vertexing), different methods are implemented. The algorithm performances and the accuracy on reconstructed observables are evaluated on the basis of simulated and experimental data

    Novel dual single sided silicon strip detector chip for radiotherapy verification

    Get PDF
    A novel dual single sided silicon strip detector (SSSSD) chip was designed to meet clinical requirements in radiotherapy verification. An available design from Micron Semiconductor Ltd. (BB7, 500 µ m thick) was the base of a two-dimensional detector adapted into a special configuration with the aim of uniforming and minimizing foreing materials around the active area (64 × 64 mm2). With this purpose, two independent BB7 SSSSDs were mounted in a perpendicular configuration, separated by a 500 µ m kapton dielectric film with the same dimensions as the silicon wafers, thus minimizing air gaps in between. This new configuration, called the dual SSSSD chip design, was mounted on kapton printed circuit board (PCB). Both silicon wafers were divided into 32 strips, 2 mm width each. The aim of developing this detector was to allow 2D dose measurements, improve spatial resolution and perform radiotherapy treatment verification faster than with a previous prototype. Characteristics and performance of the novel detector are presented

    Performance of upstream interaction region detectors for the FIRST experiment at GSI

    Get PDF
    The FIRST (Fragmentation of Ions Relevant for Space and Therapy) experiment at GSI has been designed to study carbon fragmentation, measuring 12C double differential cross sections (∂2σ/ ∂θ∂E) for different beam energies between 100 and 1000 MeV/u. The experimental setup integrates newly designed detectors in the, so called, Interaction Region around the graphite target. The Interaction Region upstream detectors are a 250 μm thick scintillator and a drift chamber optimized for a precise measurement of the ions interaction time and position on the target. In this article we review the design of the upstream detectors along with the preliminary results of the data taking performed on August 2011 with 400 MeV/u fully stripped carbon ion beam at GSI. Detectors performances will be reviewed and compared to those obtained during preliminary tests, performed with 500 MeV electrons (at the BTF facility in the INFN Frascati Laboratories) and 80 MeV/u protons and carbon ions (at the INFN LNS Laboratories in Catania)

    Expression of a barley cystatin gene in maize enhances resistance against phytophagous mites by altering their cysteine-proteases

    Get PDF
    Phytocystatins are inhibitors of cysteine-proteases from plants putatively involved in plant defence based on their capability of inhibit heterologous enzymes. We have previously characterised the whole cystatin gene family members from barley (HvCPI-1 to HvCPI-13). The aim of this study was to assess the effects of barley cystatins on two phytophagous spider mites, Tetranychus urticae and Brevipalpus chilensis. The determination of proteolytic activity profile in both mite species showed the presence of the cysteine-proteases, putative targets of cystatins, among other enzymatic activities. All barley cystatins, except HvCPI-1 and HvCPI-7, inhibited in vitro mite cathepsin L- and/or cathepsin B-like activities, HvCPI-6 being the strongest inhibitor for both mite species. Transgenic maize plants expressing HvCPI-6 protein were generated and the functional integrity of the cystatin transgene was confirmed by in vitro inhibitory effect observed against T. urticae and B. chilensis protein extracts. Feeding experiments impaired on transgenic lines performed with T. urticae impaired mite development and reproductive performance. Besides, a significant reduction of cathepsin L-like and/or cathepsin B-like activities was observed when the spider mite fed on maize plants expressing HvCPI-6 cystatin. These findings reveal the potential of barley cystatins as acaricide proteins to protect plants against two important mite pests

    Implementation and first results of the KM3NeT real-time core-collapse supernova neutrino search

    Get PDF
    [EN] The KM3NeT research infrastructure is uncon- struction in the Mediterranean Sea. KM3NeT will study atmospheric and astrophysical neutrinos with two multi- purpose neutrino detectors, ARCA and ORCA, primar-ily aimed at GeV¿PeV neutrinos. Thanks to the multi-photomultiplier tube design of the digital optical modules, KM3NeT is capable of detecting the neutrino burst from a Galactic or near-Galactic core-collapse supernova. This potential is already exploitable with the first detection units deployed in the sea. This paper describes the real-time imple- mentation of the supernova neutrino search, operating on the two KM3NeT detectors since the first months of 2019. A quasi-online astronomy analysis is introduced to study the time profile of the detected neutrinos for especially signifi- cant events. The mechanism of generation and distribution of alerts, as well as the integration into the SNEWS and SNEWS 2.0 global alert systems, are described. The approach for the follow-up of external alerts with a search for a neutrino excess in the archival data is defined. Finally, an overview of the cur-rent detector capabilities and a report after the first two years of operation are given.The authors acknowledge the financial support of the funding agencies: Agence Nationale de la Recherche (contract ANR-15-CE31-0020), Centre National de la Recherche Scientifique (CNRS), Commission Europeenne (FEDER fund and Marie Curie Program), Institut Universitaire de France (IUF), LabEx UnivEarthS (ANR-10-LABX-0023 and ANR-18-IDEX-0001), Paris ile-de-France Region, France; Shota Rustaveli National Science Foundation of Georgia (SRNSFG, FR-18-1268), Georgia; Deutsche Forschungsgemeinschaft (DFG), Germany; The General Secretariat of Research and Technology (GSRT), Greece; Istituto Nazionale di Fisica Nucleare (INFN), Ministero dell'Universita e della Ricerca (MIUR), PRIN 2017 program (Grant NAT-NET 2017W4HA7S) Italy; Ministry of Higher Education Scientific Research and Professional Training, ICTP through Grant AF-13, Morocco; Nederlandse organisatie voor Wetenschappelijk Onderzoek (NWO), the Netherlands; The National Science Centre, Poland (2015/18/E/ST2/00758); National Authority for Scientific Research (ANCS), Romania; Ministerio de Ciencia, Innovacion, Investigacion y Universidades (MCIU): Programa Estatal de Generacion de Conocimiento (refs. PGC2018-096663-B-C41, -A-C42, -B-C43, -B-C44) (MCIU/FEDER), Generalitat Valenciana: Prometeo (PROMETEO/2020/019), Grisolia (ref. GRISOLIA/2018/119) and GenT (refs. CIDEGENT/2018/034, /2019/043, /2020/049) programs, Junta de Andalucia (ref. A-FQM-053-UGR18), La Caixa Foundation (ref. LCF/BQ/IN17/11620019), EU: MSC program (ref. 101025085), Spain.Aiello, S.; Albert, A.; Alshamsi, M.; Alves Garre, S.; Aly, Z.; Ambrosone, A.; Ameli, F.... (2022). Implementation and first results of the KM3NeT real-time core-collapse supernova neutrino search. The European Physical Journal C. 82(4):1-16. https://doi.org/10.1140/epjc/s10052-022-10137-y11682

    Silicon particles as trojan horses for potential cancer therapy

    Get PDF
    [EN] Background: Porous silicon particles (PSiPs) have been used extensively as drug delivery systems, loaded with chemical species for disease treatment. It is well known from silicon producers that silicon is characterized by a low reduction potential, which in the case of PSiPs promotes explosive oxidation reactions with energy yields exceeding that of trinitrotoluene (TNT). The functionalization of the silica layer with sugars prevents its solubilization, while further functionalization with an appropriate antibody enables increased bioaccumulation inside selected cells. Results: We present here an immunotherapy approach for potential cancer treatment. Our platform comprises the use of engineered silicon particles conjugated with a selective antibody. The conceptual advantage of our system is that after reaction, the particles are degraded into soluble and excretable biocomponents. Conclusions: In our study, we demonstrate in particular, specific targeting and destruction of cancer cells in vitro. The fact that the LD50 value of PSiPs-HER-2 for tumor cells was 15-fold lower than the LD50 value for control cells demonstrates very high in vitro specificity. This is the first important step on a long road towards the design and development of novel chemotherapeutic agents against cancer in general, and breast cancer in particular.The authors acknowledge financial support from the following projects FIS2009-07812, MAT2012-35040, PROMETEO/2010/043, CTQ2011-23167, CrossSERS, FP7 MC-IEF 329131, and HSFP (project RGP0052/2012) and Medcom Tech SA. Xiang Yu acknowledges support by the Chinese government (CSC, Nr. 2010691036).Fenollosa Esteve, R.; Garcia-Rico, E.; Alvarez, S.; Alvarez, R.; Yu, X.; Rodriguez, I.; Carregal-Romero, S.... (2014). Silicon particles as trojan horses for potential cancer therapy. Journal of Nanobiotechnology. 12:1-10. https://doi.org/10.1186/s12951-014-0035-7S11012Prasad PN: Introduction to Nanomedicine and Nanobioengineering. Wiley, New York, 2012.Randall CL, Leong TG, Bassik N, Gracias DH: 3D lithographically fabricated nanoliter containers for drug delivery. Adv Drug Del Rev. 2007, 59: 1547-1561. 10.1016/j.addr.2007.08.024.Reibetanz U, Chen MHA, Mutukumaraswamy S, Liaw ZY, Oh BHL, Venkatraman S, Donath E, Neu BR: Colloidal DNA carriers for direct localization in cell compartments by pH sensoring. Biogeosciences. 2010, 11: 1779-1784.Tasciotti E, Liu X, Bhavane R, Plant K, Leonard AD, Price BK, Cheng MM-C, Decuzzi P, Tour JM, Robertson F, Ferrari M: Mesoporous silicon particles as a multistage delivery system for imaging and therapeutic applications. Nat Nano. 2008, 3: 151-157. 10.1038/nnano.2008.34.Park J-H, Gu L, von Maltzahn G, Ruoslahti E, Bhatia SN, Sailor MJ: Biodegradable luminescent porous silicon nanoparticles for in vivo applications. Nat Mater. 2009, 8: 331-336. 10.1038/nmat2398.Hong C, Lee J, Son M, Hong SS, Lee C: In-vivo cancer cell destruction using porous silicon nanoparticles. Anti-Cancer Drugs. 2011, 22: 971-977. 910.1097/CAD.1090b1013e32834b32859cCanham LT: Device Comprising Resorbable Silicon for Boron Capture Neutron Therapy. UK Patent Nr. 0302283.7. Book Device Comprising Resorbable Silicon for Boron Capture Neutron Therapy. UK Patent Nr. 0302283.7 (Editor ed.^eds.). 2003, UK Patent Nr. 0302283.7, CityXiao L, Gu L, Howell SB, Sailor MJ: Porous silicon nanoparticle photosensitizers for singlet oxygen and their phototoxicity against cancer cells. ACS Nano. 2011, 5: 3651-3659. 10.1021/nn1035262.Gil PR, Parak WJ: Composite nanoparticles take Aim at cancer. ACS Nano. 2008, 2: 2200-2205. 10.1021/nn800716j.Gomella LG: Is interstitial hyperthermia a safe and efficacious adjunct to radiotherapy for localized prostate cancer?. Nat Clin Pract Urol. 2004, 1: 72-73. 10.1038/ncpuro0041.Maier-Hauff K, Ulrich F, Nestler D, Niehoff H, Wust P, Thiesen B, Orawa H, Budach V, Jordan A: Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme. J Neuro-Oncol. 2011, 103: 317-324. 10.1007/s11060-010-0389-0.Lal S, Clare SE, Halas NJ: Nanoshell-enabled photothermal cancer therapy: Impending clinical impact. Acc Chem Res. 2008, 41: 1842-1851. 10.1021/ar800150g.Lee C, Kim H, Hong C, Kim M, Hong SS, Lee DH, Lee WI: Porous silicon as an agent for cancer thermotherapy based on near-infrared light irradiation. J Mater Chem. 2008, 18: 4790-4795. 10.1039/b808500e.Osminkina LA, Gongalsky MB, Motuzuk AV, Timoshenko VY, Kudryavtsev AA: Silicon nanocrystals as photo- and sono-sensitizers for biomedical applications. Appl Phys B. 2011, 105: 665-668. 10.1007/s00340-011-4562-8.Jain PK, Huang X, El-Sayed IH, El-Sayed MA: Noble metals on the nanoscale: optical and photothermal properties and some applications in imaging, sensing, biology, and medicine. Acc Chem Res. 2008, 41: 1578-1586. 10.1021/ar7002804.Serda RE, Godin B, Blanco E, Chiappini C, Ferrari M: Multi-stage delivery nano-particle systems for therapeutic applications. Biochim Biophys Acta. 1810, 2011: 317-329.Xu R, Huang Y, Mai J, Zhang G, Guo X, Xia X, Koay EJ, Qin G, Erm DR, Li Q, Liu X, Ferrari M, Shen H: Multistage vectored siRNA targeting ataxia-telangiectasia mutated for breast cancer therapy. Small. 2013, 9: 1799-1808. 10.1002/smll.201201510.Park JS, Kinsella JM, Jandial DD, Howell SB, Sailor MJ: Cisplatin-loaded porous Si microparticles capped by electroless deposition of platinum. Small. 2011, 7: 2061-2069. 10.1002/smll.201100438.Xue M, Zhong X, Shaposhnik Z, Qu Y, Tamanoi F, Duan X, Zink JI: pH-operated mechanized porous silicon nanoparticles. J Am Chem Soc. 2011, 133: 8798-8801. 10.1021/ja201252e.Canham LT: Bioactive silicon structure fabrication through nanoetching techniques. Adv Mater. 1995, 7: 1033-1037. 10.1002/adma.19950071215.Popplewell JF, King SJ, Day JP, Ackrill P, Fifield LK, Cresswell RG, Di Tada ML, Liu K: Kinetics of uptake and elimination of silicic acid by a human subject: a novel application of 32Si and accelerator mass spectrometry. J Inorganic Biochem. 1998, 69: 177-180. 10.1016/S0162-0134(97)10016-2.Shabir Q, Pokale A, Loni A, Johnson DR, Canham LT, Fenollosa R, Tymczenko M, Rodr guez I, Meseguer F, Cros A, Cantarero A: Medically biodegradable hydrogenated amorphous silicon microspheres. Silicon. 2011, 3: 173-176. 10.1007/s12633-011-9097-4.Chen Y, Wan Y, Wang Y, Zhang H, Jiao Z: Anticancer efficacy enhancement and attenuation of side effects of doxorubicin with titanium dioxide nanoparticles. Int J Nanomed. 2011, 6: 2321-2326.Mackowiak SA, Schmidt A, Weiss V, Argyo C, von Schirnding C, Bein T, Bräuchle C: Targeted drug delivery in cancer cells with Red-light photoactivated mesoporous silica nanoparticles. Nano Lett. 2013, 13: 2576-2583. 10.1021/nl400681f.Li Z, Barnes JC, Bosoy A, Stoddart JF, Zink JI: Mesoporous silica nanoparticles in biomedical applications. Chem Soc Rev. 2012, 41: 2590-2605. 10.1039/c1cs15246g.O Mara WC, Herring B, Hunt P: Handbook of Semiconductor Silicon Technology. Noyes Publication, New Jersey, 1990.Mikulec FV, Kirtland JD, Sailor MJ: Explosive nanocrystalline porous silicon and its Use in atomic emission spectroscopy. Adv Mater. 2002, 14: 38-41. 10.1002/1521-4095(20020104)14:13.0.CO;2-Z.Clement D, Diener J, Gross E, Kunzner N, Timoshenko VY, Kovalev D: Highly explosive nanosilicon-based composite materials. Phys Stat Sol A. 2005, 202: 1357-1359. 10.1002/pssa.200461102.Canham LT: Silicon quantum wire array fabrication by electrochemical and chemical dissolution of wafers. Appl Phys Lett. 1990, 57: 1046-1049. 10.1063/1.103561.Canham LT: Properties of Porous Silicon. INSPEC, United Kindom, 1997.Heinrich JL, Curtis CL, Credo GM, Sailor MJ, Kavanagh KL: Luminescent colloidal silicon suspensions from porous silicon. Science. 1992, 255: 66-68. 10.1126/science.255.5040.66.Littau KA, Szajowski PJ, Muller AJ, Kortan AR, Brus LE: A luminescent silicon nanocrystal colloid via a high-temperature aerosol reaction. J Phys Chem. 1993, 97: 1224-1230. 10.1021/j100108a019.Menz WJ, Shekar S, Brownbridge GPE, Mosbach S, Kōrmer R, Peukert W, Kraft M: Synthesis of silicon nanoparticles with a narrow size distribution: a theoretical study. J Aerosol Sci. 2012, 44: 46-61. 10.1016/j.jaerosci.2011.10.005.Swihart MT, Girshick SL: Thermochemistry and kinetics of silicon hydride cluster formation during thermal decomposition of silane. J Phys Chem B. 1998, 103: 64-76. 10.1021/jp983358e.Fenollosa R, Ramiro-Manzano F, Tymczenko M, Meseguer F: Porous silicon microspheres: synthesis, characterization and application to photonic microcavities. J Mater Chem. 2010, 20: 5210-5214. 10.1039/c0jm00079e.Ramiro-Manzano F, Fenollosa R, Xifré-Pérez E, Garín M, Meseguer F: Porous silicon microcavities based photonic barcodes. Adv Mater. 2011, 23: 3022-3025. 10.1002/adma.201100986.Kastl L, Sasse D, Wulf V, Hartmann R, Mircheski J, Ranke C, Carregal-Romero S, Martínez-López JA, Fernández-Chacón R, Parak WJ, Elsasser HP, Rivera-Gil P: Multiple internalization pathways of polyelectrolyte multilayer capsules into mammalian cells. ACS Nano. 2013, 7: 6605-6618. 10.1021/nn306032k.Schweiger C, Hartmann R, Zhang F, Parak W, Kissel T, Rivera_Gil P: Quantification of the internalization patterns of superparamagnetic iron oxide nanoparticles with opposite charge. J Nanobiotech. 2012, 10: 28-10.1186/1477-3155-10-28.Sanles-Sobrido M, Exner W, Rodr guez-Lorenzo L, Rodríguez-Gonzílez B, Correa-Duarte MA, Álvarez-Puebla RA, Liz-Marzán LM: Design of SERS-encoded, submicron, hollow particles through confined growth of encapsulated metal nanoparticles. J Am Chem Soc. 2009, 131: 2699-2705. 10.1021/ja8088444.Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A, Crown J: Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011, 365: 1273-1283. 10.1056/NEJMoa0910383.Agus DB, Gordon MS, Taylor C, Natale RB, Karlan B, Mendelson DS, Press MF, Allison DE, Sliwkowski MX, Lieberman G, Kelsey SM, Fyfe G: Phase I clinical study of pertuzumab, a novel HER dimerization inhibitor, in patients with advanced cancer. J Clin Oncol. 2005, 23: 2534-2543. 10.1200/JCO.2005.03.184.Colombo M, Mazzucchelli S, Montenegro JM, Galbiati E, Corsi F, Parak WJ, Prosperi D: Protein oriented ligation on nanoparticles exploiting O6-alkylguanine-DNA transferase (SNAP) genetically encoded fusion. Small. 2012, 8: 1492-1497. 10.1002/smll.201102284.Franklin MC, Carey KD, Vajdos FF, Leahy DJ, de Vos AM, Sliwkowski MX: Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell. 2004, 5: 317-328. 10.1016/S1535-6108(04)00083-2.Paris L, Cecchetti S, Spadaro F, Abalsamo L, Lugini L, Pisanu ME, Lorio E, Natali PG, Ramoni C, Podo F: Inhibition of phosphatidylcholine-specific phospholipase C downregulates HER2 overexpression on plasma membrane of breast cancer cells. Breast Cancer Res. 2010, 12: R27-10.1186/bcr2575.Fenollosa R, Meseguer F, Tymczenko M: Silicon colloids: from microcavities to photonic sponges. Adv Mater. 2008, 20: 95-98. 10.1002/adma.200701589.Jasinski JM, Gates SM: Silicon chemical vapor deposition one step at a time: fundamental studies of silicon hydride chemistry. Acc Chem Res. 1991, 24: 9-15. 10.1021/ar00001a002.Xiao Q, Liu Y, Qiu Y, Zhou G, Mao C, Li Z, Yao Z-J, Jiang S: Potent antitumor mimetics of annonaceous acetogenins embedded with an aromatic moiety in the left hydrocarbon chain part. J Med Chem. 2010, 54: 525-533. 10.1021/jm101053k.Allman SA, Jensen HH, Vijayakrishnan B, Garnett JA, Leon E, Liu Y, Anthony DC, Sibson NR, Feizi T, Matthews S, Davis BG: Potent fluoro-oligosaccharide probes of adhesion in toxoplasmosis. ChemBioChem. 2009, 10: 2522-2529. 10.1002/cbic.200900425.Chambers DJ, Evans GR, Fairbanks AJ: Elimination reactions of glycosyl selenoxides. Tetrahedron. 2004, 60: 8411-8419. 10.1016/j.tet.2004.07.005.Tomabechi Y, Suzuki R, Haneda K, Inazu T: Chemo-enzymatic synthesis of glycosylated insulin using a GlcNAc tag. Bioorg Med Chem. 2010, 18: 1259-1264. 10.1016/j.bmc.2009.12.031.Pastoriza-Santos I, Gomez D, Perez-Juste J, Liz-Marzan LM, Mulvaney P: Optical properties of metal nanoparticle coated silica spheres: a simple effective medium approach. Phys Chem Chem Phys. 2004, 6: 5056-5060. 10.1039/b405157b

    Quantum numbers of the X(3872)X(3872) state and orbital angular momentum in its ρ0Jψ\rho^0 J\psi decay

    Get PDF
    Angular correlations in B+X(3872)K+B^+\to X(3872) K^+ decays, with X(3872)ρ0J/ψX(3872)\to \rho^0 J/\psi, ρ0π+π\rho^0\to\pi^+\pi^- and J/ψμ+μJ/\psi \to\mu^+\mu^-, are used to measure orbital angular momentum contributions and to determine the JPCJ^{PC} value of the X(3872)X(3872) meson. The data correspond to an integrated luminosity of 3.0 fb1^{-1} of proton-proton collisions collected with the LHCb detector. This determination, for the first time performed without assuming a value for the orbital angular momentum, confirms the quantum numbers to be JPC=1++J^{PC}=1^{++}. The X(3872)X(3872) is found to decay predominantly through S wave and an upper limit of 4%4\% at 95%95\% C.L. is set on the fraction of D wave.Comment: 16 pages, 4 figure

    The Interplay between NF-kappaB and E2F1 Coordinately Regulates Inflammation and Metabolism in Human Cardiac Cells

    Get PDF
    Pyruvate dehydrogenase kinase 4 (PDK4) inhibition by nuclear factor-κB (NF-κB) is related to a shift towards increased glycolysis during cardiac pathological processes such as cardiac hypertrophy and heart failure. The transcription factors estrogen-related receptor-α (ERRα) and peroxisome proliferator-activated receptor (PPAR) regulate PDK4 expression through the potent transcriptional coactivator PPARγ coactivator-1α (PGC-1α). NF-κB activation in AC16 cardiac cells inhibit ERRα and PPARβ/δ transcriptional activity, resulting in reduced PGC-1α and PDK4 expression, and an enhanced glucose oxidation rate. However, addition of the NF-κB inhibitor parthenolide to these cells prevents the downregulation of PDK4 expression but not ERRα and PPARβ/δ DNA binding activity, thus suggesting that additional transcription factors are regulating PDK4. Interestingly, a recent study has demonstrated that the transcription factor E2F1, which is crucial for cell cycle control, may regulate PDK4 expression. Given that NF-κB may antagonize the transcriptional activity of E2F1 in cardiac myocytes, we sought to study whether inflammatory processes driven by NF-κB can downregulate PDK4 expression in human cardiac AC16 cells through E2F1 inhibition. Protein coimmunoprecipitation indicated that PDK4 downregulation entailed enhanced physical interaction between the p65 subunit of NF-κB and E2F1. Chromatin immunoprecipitation analyses demonstrated that p65 translocation into the nucleus prevented the recruitment of E2F1 to the PDK4 promoter and its subsequent E2F1-dependent gene transcription. Interestingly, the NF-κB inhibitor parthenolide prevented the inhibition of E2F1, while E2F1 overexpression reduced interleukin expression in stimulated cardiac cells. Based on these findings, we propose that NF-κB acts as a molecular switch that regulates E2F1-dependent PDK4 gene transcription

    Hypoxia Inducible Factor 1-Alpha (HIF-1 Alpha) Is Induced during Reperfusion after Renal Ischemia and Is Critical for Proximal Tubule Cell Survival

    Get PDF
    Acute tubular necrosis (ATN) caused by ischemia/reperfusion (I/R) during renal transplantation delays allograft function. Identification of factors that mediate protection and/or epithelium recovery could help to improve graft outcome. We studied the expression, regulation and role of hypoxia inducible factor 1-alpha (HIF-1 α), using in vitro and in vivo experimental models of I/R as well as human post-transplant renal biopsies. We found that HIF-1 α is stabilized in proximal tubule cells during ischemia and unexpectedly in late reperfusion, when oxygen tension is normal. Both inductions lead to gene expression in vitro and in vivo. In vitro interference of HIF-1 α promoted cell death and in vivo interference exacerbated tissue damage and renal dysfunction. In pos-transplant human biopsies, HIF-1 α was expressed only in proximal tubules which exhibited normal renal structure with a significant negative correlation with ATN grade. In summary, using experimental models and human biopsies, we identified a novel HIF-1 α induction during reperfusion with a potential critical role in renal transplant

    QCD and strongly coupled gauge theories : challenges and perspectives

    Get PDF
    We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe
    corecore