Intravascular cell delivery device for therapeutic VEGF-induced angiogenesis in chronic vascular occlusion

AbstractSite specific targeting remains elusive for gene and stem cell therapies in the cardiovascular field. One promising option involves use of devices that deliver larger and more sustained cell/gene payloads to specific disease sites using the versatility of percutaneous vascular access technology. Smooth muscle cells (SMCs) engineered to deliver high local concentrations of an angiogenic molecule (VEGF) were placed in an intravascular cell delivery device (ICDD) in a porcine model of chronic total occlusion (CTO) involving ameroid placement on the proximal left circumflex (LCx) artery. Implanted SMC were retained within the ICDD and were competent for VEGF production in vitro and in vivo. Following implantation, micro-CT analyses revealed that ICDD-VEGF significantly enhanced vasa vasora microvessel density with a concomitant increase in tissue VEGF protein levels and formation of endothelial cell colonies suggesting increased angiogenic potential. ICDD-VEGF markedly enhanced regional blood flow determined by microsphere and contrast CT analysis translating to a functional improvement in regional wall motion and global left ventricular (LV) systolic and diastolic function. Our data indicate robust, clinically relevant angiogenesis can be achieved in a human scale porcine chronic vascular occlusion model following ICDD-VEGF-based delivery of angiogenic cells. This may have implications for percutaneous delivery of numerous therapeutic factors promoting creation of microvascular bypass networks in chronic vaso-occlusive diseases

Energy-Dependent Timing of Thermal Emission in Solar Flares

We report solar flare plasma to be multi-thermal in nature based on the theoretical model and study of the energy-dependent timing of thermal emission in ten M-class flares. We employ high-resolution X-ray spectra observed by the Si detector of the "Solar X-ray Spectrometer" (SOXS). The SOXS onboard the Indian GSAT-2 spacecraft was launched by the GSLV-D2 rocket on 8 May 2003. Firstly we model the spectral evolution of the X-ray line and continuum emission flux F(\epsilon) from the flare by integrating a series of isothermal plasma flux. We find that multi-temperature integrated flux F(\epsilon) is a power-law function of \epsilon with a spectral index (\gamma) \approx -4.65. Next, based on spectral-temporal evolution of the flares we find that the emission in the energy range E= 4 - 15 keV is dominated by temperatures of T= 12 - 50 MK, while the multi-thermal power-law DEM index (\gamma) varies in the range of -4.4 and -5.7. The temporal evolution of the X-ray flux F(\epsilon,t) assuming a multi-temperature plasma governed by thermal conduction cooling reveals that the temperature-dependent cooling time varies between 296 and 4640 s and the electron density (n_e) varies in the range of n_e= (1.77-29.3)*10^10 cm-3. Employing temporal evolution technique in the current study as an alternative method for separating thermal from non-thermal components in the energy spectra, we measure the break-energy point ranging between 14 and 21\pm1.0 keV.Comment: Solar Physics, in pres

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe

Search for new physics in events with opposite-sign leptons, jets, and missing transverse energy in pp collisions at sqrt(s) = 7 TeV

A search is presented for physics beyond the standard model (BSM) in final states with a pair of opposite-sign isolated leptons accompanied by jets and missing transverse energy. The search uses LHC data recorded at a center-of-mass energy sqrt(s) = 7 TeV with the CMS detector, corresponding to an integrated luminosity of approximately 5 inverse femtobarns. Two complementary search strategies are employed. The first probes models with a specific dilepton production mechanism that leads to a characteristic kinematic edge in the dilepton mass distribution. The second strategy probes models of dilepton production with heavy, colored objects that decay to final states including invisible particles, leading to very large hadronic activity and missing transverse energy. No evidence for an event yield in excess of the standard model expectations is found. Upper limits on the BSM contributions to the signal regions are deduced from the results, which are used to exclude a region of the parameter space of the constrained minimal supersymmetric extension of the standard model. Additional information related to detector efficiencies and response is provided to allow testing specific models of BSM physics not considered in this paper.Comment: Replaced with published version. Added journal reference and DO

Search for leptophobic Z ' bosons decaying into four-lepton final states in proton-proton collisions at root s=8 TeV

Peer reviewe

Search for heavy resonances decaying into a vector boson and a Higgs boson in final states with charged leptons, neutrinos, and b quarks

Peer reviewe

Search for high-mass diphoton resonances in proton-proton collisions at 13 TeV and combination with 8 TeV search

Peer reviewe

Search for black holes and other new phenomena in high-multiplicity final states in proton-proton collisions at root s=13 TeV

Peer reviewe

Measurement of the mass difference between top quark and antiquark in pp collisions at root s=8 TeV

Peer reviewe

Erratum: "A Gravitational-wave Measurement of the Hubble Constant Following the Second Observing Run of Advanced LIGO and Virgo" (2021, ApJ, 909, 218)

[no abstract available