The effect of basic fibroblast growth factor on the blood flow and morphologic features of a latissimus dorsi cardiomyoplasty

AbstractPrevious studies designed to determine whether latissimus cardiomyoplasty could be used to revascularize ischemic myocardium showed that after operation the latissimus was ischemic and had severely deteriorated. This study was undertaken to determine whether basic fibroblast growth factor, a potent angiogenic peptide, would improve the vascularity of the latissimus and enhance collateral formation between the muscle of the cardiomyoplasty and ischemic myocardium. In goats, myocardial ischemia was induced with an ameroid constrictor and cardiomyoplasty performed. The latissimus was continuously stimulated electrically at 2 Hz for 6 weeks and given four weekly bolus injections of human recombinant basic fibroblast growth factor (80 μg infused into the left subclavian artery). In eight animals, rates of regional blood flow were measured and both the heart and latissimus were evaluated histochemically. The latissimus blood flow rate was 0.114 ± 0.029 ml/gm per minute, which was three times greater than that of historical controls (chronically stimulated latissimus cardiomyoplasty without basic fibroblast growth factor treatment; 0.042 ± 0.007 ml/gm per minute, p < 0.05). Associated with the improved blood flow, there was significantly less evidence of skeletal muscle fiber dropout and muscle fibrosis in the animals treated with basic fibroblast growth factor. Latissimus-derived collateral flow to ischemic myocardium developed in five of the eight goats and averaged 0.288 ± 0.075 ml/gm per minute. This flow was 42.8% ± 15.7% ( n = 5) of the flow required by normal myocardium (which was 0.728 ± 0.095 ml/gm per minute). This value for latissimus-derived collateral blood flow was almost twice that of the historical controls (24.0% ± 3.9%), but the increase did not achieve statistical significance ( p = 0.08). These results hold the promise that basic fibroblast growth factor treatment might enhance the formation of extramyocardial collaterals to the heart and improve skeletal muscle function. (J THORAC CARDIOVASC SURG 1996;111:19-28

LEP1 operation, 1989-1995

In October 1995, the last run foreseen for dedicated Z production at CERN was performed in LEP, thereby bringing to a close the first phase of operation of the machine. A total luminosity of 200 pb-1 has been delivered to each of the four experiments, which together have recorded the decays of over 20 millions Zs. Machine performance has increased to the extent that a good weekend in 1995 saw as much luminosity delivered as in the whole of 1989. This improvement has been made possible by a combination of several things. Over and above general operational expertise, special care went into the treatment and stabilisation of the closed orbit in order to obtain reproducible high performances with vertical beam-beam tune shifts exceeding values of xy = 0.04. Both Pretzel and Bunch Train schemes have been introduced to double the number of bunches, and high-tune optics have been developed to produce low transverse emittances which allow operation at the beam-beam limit throughout physics runs. Included in the integrated luminosity are data taken off the peak of the Z resonance, to allow precise determination of the mass and width of this particle. Accurate measurements of the beam energy during these runs have brought to the fore some unusual effects

Dynamic Effects and their Control at the LHC

Tune, chromaticity and orbit of the LHC beams have to be precisely controlled by synchronising the magnetic field of quadrupole, sextupole and corrector magnets.This is a challenging task for an accelerator using superconducting magnets, whose field and field errors will have large dynamic effects.The accelerator physics requirements are tight due to the limited dynamic aperture and the large energy stored in the beams.The power converters need to be programmed in order to generate the magnetic functions with defined tolerances. During the injection process and the energy ramp the magnetic performance cannot be predicted with sufficient accuracy, and therefore real-time feedback systems based on magnetic measurements and beam observations are proposed. Beam measurements are used to determine a correction factor for some of the power converters. From magnetic measurements the excitation of small magnets to compensate the sextupolar (b3) and decapolar (b5) field components in the dipole magnets will be derived. To meet these requirements a deterministic control system is envisaged

Antigenic Characterization of H3 Subtypes of Avian Influenza A Viruses from North America

Besides humans, H3 subtypes of influenza A viruses (IAVs) can infect various animal hosts, including avian, swine, equine, canine, and sea mammal species. These H3 viruses are both antigenically and genetically diverse. Here, we characterized the antigenic diversity of contemporary H3 avian IAVs recovered from migratory birds in North America. Hemagglutination inhibition (HI) assays were performed on 37 H3 isolates of avian IAVs recovered from 2007 to 2011 using generated reference chicken sera. These isolates were recovered from samples taken in the Atlantic, Mississippi, Central, and Pacific waterfowl migration flyways. Antisera to all the tested H3 isolates cross-reacted with each other and, to a lesser extent, with those to H3 canine and H3 equine IAVs. Antigenic cartography showed that the largest antigenic distance among the 37 avian IAVs is about four units, and each unit corresponds to a 2 log 2 difference in the HI titer. However, none of the tested H3 IAVs cross-reacted with ferret sera derived from contemporary swine and human IAVs. Our results showed that the H3 avian IAVs we tested lacked significant antigenic diversity, and these viruses were antigenically different from those circulating in swine and human populations. This suggests that H3 avian IAVs in North American waterfowl are antigenically relatively stable. Además de infectar a los seres humanos, los subtipos H3 del virus de la influenza A (IAVs) pueden infectar a varios huéspedes animales, incluyendo aves, porcinos, equinos, caninos, y especies de mamíferos marinos. Estos virus H3 son tanto antigénica y genéticamente diversos. En este estudio, se caracterizó la diversidad antigénica de virus H3 contemporáneos recuperados de aves migratorias en América del Norte. Se realizaron pruebas de inhibición de la hemaglutinación (HI) en 37 H3 aislamientos de origen aviar recuperados de 2007 a 2011 usando sueros de pollo de referencia. Estos aislamientos fueron recuperados de las muestras tomadas de las rutas migratorias de aves acuáticas del Atlántico, Mississippi, Centro y del Pacífico. Los antisueros de todos los aislamientos H3 analizados mostraron reacciones cruzadas entre sí y en menor medida, con aquellos virus H3 de origen canino y equino. La cartografía antigénica demostró que la mayor distancia antigénica entre los 37 virus de este tipo de aves es de aproximadamente cuatro unidades, y cada unidad corresponde a una diferencia de dos logaritmos en el título de inhibición de la hemaglutinación. Sin embargo, ninguno de los virus H3 de este tipo mostró reacción cruzada con sueros de hurón específicos para virus de cerdos y humanos contemporáneos. Estos resultados mostraron que los virus H3 de origen aviar que se analizaron carecían de diversidad antigénica significativa y estos virus fueron antigénicamente diferentes de las que circulan en poblaciones de cerdos y de humanos. Esto sugiere que los virus H3 de aves acuáticas de América del Norte son relativamente estables antigénicamente

Mass Determination and Detection of the Onset of Chromospheric Activity for the Sub-Stellar Object in EF Eridani

EF Eri is a magnetic cataclysmic variable that has been in a low accretion state for the past nine years. Low state optical spectra reveal the underlying Zeeman-split white dwarf absorption lines. These features are used to determine a value of 13-14 MG as the white dwarf field strength. Recently, 5-7 years into the low state, Balmer and other emission lines have appeared in the optical. An analysis of the H$\alpha$ emission line yields the first radial velocity solution for EF Eri, leading to a spectroscopic ephemeris for the binary and, using the best available white dwarf mass of 0.6M${\odot}$, a mass estimate for the secondary of 0.055M${\odot}$. For a white dwarf mass of 0.95M${\odot}$, the average for magnetic white dwarfs, the secondary mass increases to 0.087M${\odot}$. At EF Eri's orbital period of 81 minutes, this higher mass secondary could not be a normal star and still fit within the Roche lobe. The source of the Balmer and other emission lines is confirmed to be from the sub-stellar secondary and we argue that it is due to stellar activity. We compare EF Eri's emission line spectrum and activity behavior to that recently observed in AM Her and VV Pup and attributed to stellar activity. We explore observations and models originally developed for V471 Tau, for the RS CVn binaries, and for extra-solar planets. We conclude that irradiation of the secondary in EF Eri and similar systems is unlikely and, in polars, the magnetic field interaction between the two stars (with a possible tidal component) is a probable mechanism which would concentrate chromospheric activity on the secondary near the sub-stellar point of the white dwarf.Comment: 49 pages, 12 figures Accepted to ApJ (Main journal

A cancer drug atlas enables synergistic targeting of independent drug vulnerabilities.

Personalized cancer treatments using combinations of drugs with a synergistic effect is attractive but proves to be highly challenging. Here we present an approach to uncover the efficacy of drug combinations based on the analysis of mono-drug effects. For this we used dose-response data from pharmacogenomic encyclopedias and represent these as a drug atlas. The drug atlas represents the relations between drug effects and allows to identify independent processes for which the tumor might be particularly vulnerable when attacked by two drugs. Our approach enables the prediction of combination-therapy which can be linked to tumor-driving mutations. By using this strategy, we can uncover potential effective drug combinations on a pan-cancer scale. Predicted synergies are provided and have been validated in glioblastoma, breast cancer, melanoma and leukemia mouse-models, resulting in therapeutic synergy in 75% of the tested models. This indicates that we can accurately predict effective drug combinations with translational value

The Ninth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the SDSS-III Baryon Oscillation Spectroscopic Survey

The Sloan Digital Sky Survey III (SDSS-III) presents the first spectroscopic data from the Baryon Oscillation Spectroscopic Survey (BOSS). This ninth data release (DR9) of the SDSS project includes 535,995 new galaxy spectra (median z=0.52), 102,100 new quasar spectra (median z=2.32), and 90,897 new stellar spectra, along with the data presented in previous data releases. These spectra were obtained with the new BOSS spectrograph and were taken between 2009 December and 2011 July. In addition, the stellar parameters pipeline, which determines radial velocities, surface temperatures, surface gravities, and metallicities of stars, has been updated and refined with improvements in temperature estimates for stars with T_eff<5000 K and in metallicity estimates for stars with [Fe/H]>-0.5. DR9 includes new stellar parameters for all stars presented in DR8, including stars from SDSS-I and II, as well as those observed as part of the SDSS-III Sloan Extension for Galactic Understanding and Exploration-2 (SEGUE-2). The astrometry error introduced in the DR8 imaging catalogs has been corrected in the DR9 data products. The next data release for SDSS-III will be in Summer 2013, which will present the first data from the Apache Point Observatory Galactic Evolution Experiment (APOGEE) along with another year of data from BOSS, followed by the final SDSS-III data release in December 2014.Comment: 9 figures; 2 tables. Submitted to ApJS. DR9 is available at http://www.sdss3.org/dr

Transcription restores DNA repair to heterochromatin, determining regional mutation rates in cancer genomes

SummarySomatic mutations in cancer are more frequent in heterochromatic and late-replicating regions of the genome. We report that regional disparities in mutation density are virtually abolished within transcriptionally silent genomic regions of cutaneous squamous cell carcinomas (cSCCs) arising in an XPC−/− background. XPC−/− cells lack global genome nucleotide excision repair (GG-NER), thus establishing differential access of DNA repair machinery within chromatin-rich regions of the genome as the primary cause for the regional disparity. Strikingly, we find that increasing levels of transcription reduce mutation prevalence on both strands of gene bodies embedded within H3K9me3-dense regions, and only to those levels observed in H3K9me3-sparse regions, also in an XPC-dependent manner. Therefore, transcription appears to reduce mutation prevalence specifically by relieving the constraints imposed by chromatin structure on DNA repair. We model this relationship among transcription, chromatin state, and DNA repair, revealing a new, personalized determinant of cancer risk