Enhanced efficiency of genetic programming toward cardiomyocyte creation through topographical cues

AbstractGeneration of de novo cardiomyocytes through viral over-expression of key transcription factors represents a highly promising strategy for cardiac muscle tissue regeneration. Although the feasibility of cell reprogramming has been proven possible both in vitro and in vivo, the efficiency of the process remains extremely low. Here, we report a chemical-free technique in which topographical cues, more specifically parallel microgrooves, enhance the directed differentiation of cardiac progenitors into cardiomyocyte-like cells. Using a lentivirus-mediated direct reprogramming strategy for expression of Myocardin, Tbx5, and Mef2c, we showed that the microgrooved substrate provokes an increase in histone H3 acetylation (AcH3), known to be a permissive environment for reprogramming by “stemness” factors, as well as stimulation of myocardin sumoylation, a post-translational modification essential to the transcriptional function of this key co-activator. These biochemical effects mimicked those of a pharmacological histone deacetylase inhibitor, valproic acid (VPA), and like VPA markedly augmented the expression of cardiomyocyte-specific proteins by the genetically engineered cells. No instructive effect was seen in cells unresponsive to VPA. In addition, the anisotropy resulting from parallel microgrooves induced cellular alignment, mimicking the native ventricular myocardium and augmenting sarcomere organization

The global response of relativistic radiation belt electrons to the January 1997 magnetic cloud

In January 1997 a large fleet of NASA and US military satellites provided the most complete observations to date of the changes in \u3e2 MeV electrons during a geomagnetic storm. Observations at geosynchronous orbit revealed a somewhat unusual two-peaked enhancement in relativistic electron fluxes [ Reeves et al., 1998]. In the heart of the radiation belts at L ≈ 4, however, there was a single enhancement followed by a gradual decay. Radial profiles from the POLAR and GPS satellites revealed three distinct phases. (1) In the acceleration phase electron fluxes increased simultaneously at L ≈ 4–6. (2) During the passage of the cloud the radiation belts were shifted radially outward and then relaxed earthward. (3) For several days after the passage of the cloud the radial gradient of the fluxes flattened, increasing the fluxes at higher L-shells. These observations provide evidence that the acceleration of relativistic electrons takes place within the radiation belts and is rapid. Both magnetospheric compression and radial diffusion can cause a redistribution of electron fluxes within the magnetosphere that make the event profiles appear quite different when viewed at different L-shells

The proton and electron radiation belts at geosynchronous orbit: Statistics and behavior during high‐speed stream‐driven storms

The outer proton radiation belt (OPRB) and outer electron radiation belt (OERB) at geosynchronous orbit are investigated using a reanalysis of the LANL CPA (Charged Particle Analyzer) 8‐satellite 2‐solar cycle energetic particle data set from 1976 to 1995. Statistics of the OPRB and the OERB are calculated, including local time and solar cycle trends. The number density of the OPRB is about 10 times higher than the OERB, but the 1 MeV proton flux is about 1000 times less than the 1 MeV electron flux because the proton energy spectrum is softer than the electron spectrum. Using a collection of 94 high‐speed stream‐driven storms in 1976–1995, the storm time evolutions of the OPRB and OERB are studied via superposed epoch analysis. The evolution of the OERB shows the familiar sequence (1) prestorm decay of density and flux, (2) early‐storm dropout of density and flux, (3) sudden recovery of density, and (4) steady storm time heating to high fluxes. The evolution of the OPRB shows a sudden enhancement of density and flux early in the storm. The absence of a proton dropout when there is an electron dropout is noted. The sudden recovery of the density of the OERB and the sudden density enhancement of the OPRB are both associated with the occurrence of a substorm during the early stage of the storm when the superdense plasma sheet produces a “strong stretching phase” of the storm. These storm time substorms are seen to inject electrons to 1 MeV and protons to beyond 1 MeV into geosynchronous orbit, directly producing a suddenly enhanced radiation belt population.Key PointsDuring high‐speed stream‐driven storms, the electron and proton radiation belts are directly enhanced by a single substormThe enhancing substorm occurs during the “strong stretching” phase of the storm caused by the superdense plasma sheetProton and electron injection to 1 MeV is seen for these strong stretching phase substormsPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/133567/1/jgra52702.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/133567/2/jgra52702_am.pd

Recurrent geomagnetic storms and relativistic electron enhancements in the outer magnetosphere: ISTP coordinated measurements

New, coordinated measurements from the International Solar-Terrestrial Physics (ISTP) constellation of spacecraft are presented to show the causes and effects of recurrent geomagnetic activity during recent solar minimum conditions. It is found using WIND and POLAR data that even for modest geomagnetic storms, relativistic electron fluxes are strongly and rapidly enhanced within the outer radiation zone of the Earth\u27s magnetosphere. Solar wind data are utilized to identify the drivers of magnetospheric acceleration processes. Yohkoh solar soft X-ray data are also used to identify the solar coronal holes that produce the high-speed solar wind streams which, in turn, cause the recurrent geomagnetic activity. It is concluded that even during extremely quiet solar conditions (sunspot minimum) there are discernible coronal holes and resultant solar wind streams which can produce intense magnetospheric particle acceleration. As a practical consequence of this Sun-Earth connection, it is noted that a long-lasting E\u3e1MeV electron event in late March 1996 appears to have contributed significantly to a major spacecraft (Anik E1) operational failure

Results of X-ray and optical monitoring of SCO X-1

Sco X-1 was monitored at optical and X-ray wavelengths from 1970 April 26 to 1970 May 21. The optical observations were made at six observatories around the world and the X-ray observations were made by the Vela satellites. There was a tendency for the object to show greater variability in X-ray when the object is optically bright. A discussion of the intensity histograms is presented for both the optical and X-ray observations. No evidence for optical or X-ray periodicity was detected

A density-temperature description of the outer electron radiation belt during geomagnetic storms

Bi-Maxwellian fits are made to energetic-electron flux measurements from seven satellites in geosynchronous orbit, yielding a number density (n) and temperature (T) description of the outer electron radiation belt. For 54.5 spacecraft years of measurements the median value of n is 3.7 × 10−4 cm−3, and the median value of T is 148 keV. General statistical properties of n, T, and the 1.1–1.5 MeV flux F are investigated, including local-time and solar-cycle dependencies. Using superposed-epoch analysis where the zero epoch is convection onset, the evolution of the outer electron radiation belt through high-speed-stream-driven storms is investigated. The number-density decay during the calm before the storm, relativistic-electron dropouts and recoveries, and the heating of the outer electron radiation belt during storms are analyzed. Using four different “triggers” (sudden storm commencement (SSC), southward interplanetary magnetic field (IMF) portions of coronal mass ejection (CME) sheaths, southward-IMF portions of magnetic clouds, and minimum Dst) a selection of CME-driven storms are analyzed with superposed-epoch techniques. For CME-driven storms, only a very modest density decay prior to storm onset is found. In addition, the compression of the outer electron radiation belt at the time of SSC is analyzed, the number-density increase and temperature decrease during storm main phase are characterized, and the increase in density and temperature during storm recovery phase is determined. During the different phases of storms, changes in the flux are sometimes in response to changes in the temperature, sometimes to changes in the number density, and sometimes to changes in both. Differences are found between the density-temperature and flux descriptions, and it is concluded that more information is available using the density-temperature description

Relativistic electrons in the outer-zone: An 11 year cycle, their relation to the solar wind

We examine Los Alamos energetic electron data from 1979 through the present to show long term trends in the trapped relativistic electron populations at geosynchronous-earth-orbit (GEO). Data is examined from several CPA and SOPA instruments to cover the interval from 1979 through June 1994. It is shown that the higher energy electrons fluxes (E > 300 keV) displayed a cycle of {approx}11 years. In agreement with other investigators, we also show that the relativistic electron cycle is out of phase with the sunspot cycle. We compare the occurrences of relativistic electrons and solar wind high speed streams and determine that on the time scale of 15 years the two do not correlate well. The long-term data set we provide here shows a systematic change of the electron energy spectrum during the course of the solar cycle. This information should be useful to magnetospheric scientists, model designers and space flight planners

Recurrent Geomagnetic Storms and Relativistic Electron Enhancements in the Outer Magnetosphere: ISTP Coordinated Measurements

New, coordinated measurements from the International Solar-Terrestrial Physics (ISTP) constellation of spacecraft are presented to show the causes and effects of recurrent geomagnetic activity during recent solar minimum conditions. It is found using WIND and POLAR data that even for modest geomagnetic storms, relativistic electron fluxes are strongly and rapidly enhanced within the outer radiation zone of the Earth\u27s magnetosphere. Solar wind data are utilized to identify the drivers of magnetospheric acceleration processes. Yohkoh solar soft X-ray data are also used to identify the solar coronal holes that produce the high-speed solar wind streams which, in turn, cause the recurrent geomagnetic activity. It is concluded that even during extremely quiet solar conditions (sunspot minimum) there are discernible coronal holes and resultant solar wind streams which can produce intense magnetospheric particle acceleration. As a practical consequence of this Sun-Earth connection, it is noted that a long-lasting E\u3e1MeV electron event in late March 1996 appears to have contributed significantly to a major spacecraft (Anik E1) operational failure

Entropy mapping of the outer electron radiation belt between the magnetotail and geosynchronous orbit

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94614/1/jgra21264.pd