Reprogramming and transdifferentiation for cardiovascular development and regenerative medicine: where do we stand?

Heart disease remains a leading cause of mortality and a major worldwide healthcare burden. Recent advances in stem cell biology have made it feasible to derive large quantities of cardiomyocytes for disease modeling, drug development, and regenerative medicine. The discoveries of reprogramming and transdifferentiation as novel biological processes have significantly contributed to this paradigm. This review surveys the means by which reprogramming and transdifferentiation can be employed to generate induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and induced cardiomyocytes (iCMs). The application of these patient-specific cardiomyocytes for both in vitro disease modeling and in vivo therapies for various cardiovascular diseases will also be discussed. We propose that, with additional refinement, human disease-specific cardiomyocytes will allow us to significantly advance the understanding of cardiovascular disease mechanisms and accelerate the development of novel therapeutic options

Quantum Hall activation gaps in bilayer graphene

We have measured the quantum Hall activation gaps in bilayer graphene at filling factors $\nu=\pm4$ and $\nu=\pm8$ in high magnetic fields up to 30 T. We find that energy levels can be described by a 4-band relativistic hyperbolic dispersion. The Landau level width is found to contain a field independent background due to an intrinsic level broadening and a component which increases linearly with magnetic field.Comment: 4 pages, accepted version (just removed a few typos), will appear as Fast Track Communication in Solid State Commu

Analysis of Two-Body Decays of Charmed Baryons Using the Quark-Diagram Scheme

We give a general formulation of the quark-diagram scheme for the nonleptonic weak decays of baryons. We apply it to all the decays of the antitriplet and sextet charmed baryons and express their decay amplitudes in terms of the quark-diagram amplitudes. We have also given parametrizations for the effects of final-state interactions. For SU(3) violation effects, we only parametrize those in the horizontal $W$-loop quark diagrams whose contributions are solely due to SU(3)-violation effects. In the absence of all these effects, there are many relations among various decay modes. Some of the relations are valid even in the presence of final-state interactions when each decay amplitude in the relation contains only a single phase shift. All these relations provide useful frameworks to compare with future experiments and to find out the effects of final-state interactions and SU(3) symmetry violations.Comment: 28 pages, 20 Tables in landscape form, 4 figures. Main changes are: (i) some errors in the Tables and in the relations between the quark-diagram amplitudes of this paper and those of Ref.[10] are corrected, (ii) improvements are made in the presentation so that comparisons with previous works and what have been done to include SU(3) breaking and final-state interactions are more clearly stated; to appear in the Physical Review

Novel codon-optimized mini-intronic plasmid for efficient, inexpensive, and xeno-free induction of pluripotency

The development of human induced pluripotent stem cell (iPSC) technology has revolutionized the regenerative medicine field. This technology provides a powerful tool for disease modeling and drug screening approaches. To circumvent the risk of random integration into the host genome caused by retroviruses, non-integrating reprogramming methods have been developed. However, these techniques are relatively inefficient or expensive. The mini-intronic plasmid (MIP) is an alternative, robust transgene expression vector for reprogramming. Here we developed a single plasmid reprogramming system which carries codon-optimized (Co) sequences of the canonical reprogramming factors (Oct4, Klf4, Sox2, and c-Myc) and short hairpin RNA against p53 ("4-in-1 CoMiP"). We have derived human and mouse iPSC lines from fibroblasts by performing a single transfection. Either independently or together with an additional vector encoding for LIN28, NANOG, and GFP, we were also able to reprogram blood-derived peripheral blood mononuclear cells (PBMCs) into iPSCs. Taken together, the CoMiP system offers a new highly efficient, integration-free, easy to use, and inexpensive methodology for reprogramming. Furthermore, the CoMIP construct is color-labeled, free of any antibiotic selection cassettes, and independent of the requirement for expression of the Epstein-Barr Virus nuclear antigen (EBNA), making it particularly beneficial for future applications in regenerative medicine

Propagation and Structure of Planar Streamer Fronts

Streamers often constitute the first stage of dielectric breakdown in strong electric fields: a nonlinear ionization wave transforms a non-ionized medium into a weakly ionized nonequilibrium plasma. New understanding of this old phenomenon can be gained through modern concepts of (interfacial) pattern formation. As a first step towards an effective interface description, we determine the front width, solve the selection problem for planar fronts and calculate their properties. Our results are in good agreement with many features of recent three-dimensional numerical simulations. In the present long paper, you find the physics of the model and the interfacial approach further explained. As a first ingredient of this approach, we here analyze planar fronts, their profile and velocity. We encounter a selection problem, recall some knowledge about such problems and apply it to planar streamer fronts. We make analytical predictions on the selected front profile and velocity and confirm them numerically. (abbreviated abstract)Comment: 23 pages, revtex, 14 ps file

Measurement of Masses and Widths of Excited Charm Mesons D2∗D_2^* and Evidence for Broad States

Using data from the FOCUS experiment we analyze the $D^+\pi^-$ and $D^0\pi^+$ invariant mass distributions. We measure the $D_2^{*0}$ mass M_{D_2^{*0}} = (2464.5 \pm 1.1 \pm 1.9) \mev and width \Gamma_{D_2^{*0}} = (38.7 \pm 5.3 \pm 2.9) \mev, and the $D_2^{*+}$ mass M_{D_2^{*+}} = (2467.6 \pm 1.5 \pm 0.76) \mev and width \Gamma_{D_2^{*+}} = (34.1 \pm 6.5 \pm 4.2) \mev. We find evidence for broad structures over background in both the neutral and charged final state. If each is interpreted as evidence for a single L=1, $j_q=1/2$ excited charm meson resonance, the masses and widths are M_{1/2}^0 =(2407 \pm 21 \pm 35) \mev, \Gamma_{1/2}^0 = (240 \pm 55 \pm 59) \mev, and M_{1/2}^+ = (2403 \pm 14 \pm 35) \mev \Gamma_{1/2}^+ = (283 \pm 24 \pm 34) \mev, respectively.Comment: 15 pages, 4 figures. Submitted to Phys. Lett. B. Added preprint number

Magnetism in Dense Quark Matter

We review the mechanisms via which an external magnetic field can affect the ground state of cold and dense quark matter. In the absence of a magnetic field, at asymptotically high densities, cold quark matter is in the Color-Flavor-Locked (CFL) phase of color superconductivity characterized by three scales: the superconducting gap, the gluon Meissner mass, and the baryonic chemical potential. When an applied magnetic field becomes comparable with each of these scales, new phases and/or condensates may emerge. They include the magnetic CFL (MCFL) phase that becomes relevant for fields of the order of the gap scale; the paramagnetic CFL, important when the field is of the order of the Meissner mass, and a spin-one condensate associated to the magnetic moment of the Cooper pairs, significant at fields of the order of the chemical potential. We discuss the equation of state (EoS) of MCFL matter for a large range of field values and consider possible applications of the magnetic effects on dense quark matter to the astrophysics of compact stars.Comment: To appear in Lect. Notes Phys. "Strongly interacting matter in magnetic fields" (Springer), edited by D. Kharzeev, K. Landsteiner, A. Schmitt, H.-U. Ye

Gene-centric functional dissection of human genetic variation uncovers regulators of hematopoiesis

Genome-wide association studies (GWAS) have identified thousands of variants associated with human diseases and traits. However, the majority of GWAS-implicated variants are in non-coding regions of the genome and require in depth follow-up to identify target genes and decipher biological mechanisms. Here, rather than focusing on causal variants, we have undertaken a pooled loss-of-function screen in primary hematopoietic cells to interrogate 389 candidate genes contained in 75 loci associated with red blood cell traits. Using this approach, we identify 77 genes at 38 GWAS loci, with most loci harboring 1-2 candidate genes. Importantly, the hit set was strongly enriched for genes validated through orthogonal genetic approaches. Genes identified by this approach are enriched in specific and relevant biological pathways, allowing regulators of human erythropoiesis and modifiers of blood diseases to be defined. More generally, this functional screen provides a paradigm for gene-centric follow up of GWAS for a variety of human diseases and traits

Low Q^2 Jet Production at HERA and Virtual Photon Structure

The transition between photoproduction and deep-inelastic scattering is investigated in jet production at the HERA ep collider, using data collected by the H1 experiment. Measurements of the differential inclusive jet cross-sections dsigep/dEt* and dsigmep/deta*, where Et* and eta* are the transverse energy and the pseudorapidity of the jets in the virtual photon-proton centre of mass frame, are presented for 0 < Q2 < 49 GeV2 and 0.3 < y < 0.6. The interpretation of the results in terms of the structure of the virtual photon is discussed. The data are best described by QCD calculations which include a partonic structure of the virtual photon that evolves with Q2.Comment: 20 pages, 5 Figure