An engineered cardiac reporter cell line identifies human embryonic stem cell-derived myocardial precursors.

Unlike some organs, the heart is unable to repair itself after injury. Human embryonic stem cells (hESCs) grow and divide indefinitely while maintaining the potential to develop into many tissues of the body. As such, they provide an unprecedented opportunity to treat human diseases characterized by tissue loss. We have identified early myocardial precursors derived from hESCs (hMPs) using an α-myosin heavy chain (αMHC)-GFP reporter line. We have demonstrated by immunocytochemistry and quantitative real-time PCR (qPCR) that reporter activation is restricted to hESC-derived cardiomyocytes (CMs) differentiated in vitro, and that hMPs give rise exclusively to muscle in an in vivo teratoma formation assay. We also demonstrate that the reporter does not interfere with hESC genomic stability. Importantly, we show that hMPs give rise to atrial, ventricular and specialized conduction CM subtypes by qPCR and microelectrode array analysis. Expression profiling of hMPs over the course of differentiation implicate Wnt and transforming growth factor-β signaling pathways in CM development. The identification of hMPs using this αMHC-GFP reporter line will provide important insight into the pathways regulating human myocardial development, and may provide a novel therapeutic reagent for the treatment of cardiac disease

Probe Brane Dynamics and the Cosmological Constant

Recently a brane world perspective on the cosmological constant and the hierarchy problems was presented. Here, we elaborate on some aspects of that particular scenario and discuss the stability of the stationary brane solution and the dynamics of a probe brane. Even though the brane is unstable under a small perturbation from its stationary position, such instability is harmless when the 4-D cosmological constant is very small, as is the case of our universe. One may also introduce radion stabilizing potentials in a more realistic scenario.Comment: 13 pages, 1 figure, REVTE

Implementation of case management to reduce cardiovascular disease risk in the Stanford and San Mateo Heart to Heart randomized controlled trial: study protocol and baseline characteristics

BACKGROUND: Case management has emerged as a promising alternative approach to supplement traditional one-on-one sessions between patients and doctors for improving the quality of care in chronic diseases such as coronary heart disease (CHD). However, data are lacking in terms of its efficacy and cost-effectiveness when implemented in ethnic and low-income populations. METHODS: The Stanford and San Mateo Heart to Heart (HTH) project is a randomized controlled clinical trial designed to rigorously evaluate the efficacy and cost-effectiveness of a multi-risk cardiovascular case management program in low-income, primarily ethnic minority patients served by a local county health care system in California. Randomization occurred at the patient level. The primary outcome measure is the absolute CHD risk over 10 years. Secondary outcome measures include adherence to guidelines on CHD prevention practice. We documented the study design, methodology, and baseline sociodemographic, clinical and lifestyle characteristics of 419 participants. RESULTS: We achieved equal distributions of the sociodemographic, biophysical and lifestyle characteristics between the two randomization groups. HTH participants had a mean age of 56 years, 63% were Latinos/Hispanics, 65% female, 61% less educated, and 62% were not employed. Twenty percent of participants reported having a prior cardiovascular event. 10-year CHD risk averaged 18% in men and 13% in women despite a modest low-density lipoprotein cholesterol level and a high on-treatment percentage at baseline. Sixty-three percent of participants were diagnosed with diabetes and an additional 22% had metabolic syndrome. In addition, many participants had depressed high-density lipoprotein (HDL) cholesterol levels and elevated values of total cholesterol-to-HDL ratio, triglycerides, triglyceride-to-HDL ratio, and blood pressure. Furthermore, nearly 70% of participants were obese, 45% had a family history of CHD or stroke, and 16% were current smokers. CONCLUSION: We have recruited an ethnically diverse, low-income cohort in which to implement a case management approach and test its efficacy and cost-effectiveness. HTH will advance the scientific understanding of better strategies for CHD prevention among these priority subpopulations and aid in guiding future practice that will reduce health disparities

Gravitating Yang-Mills vortices in 4+1 spacetime dimensions

The coupling to gravity in D=5 spacetime dimensions is considered for the particle-like and vortex-type solutions obtained by uplifting the D=4 Yang-Mills instantons and D=3 Yang-Mills-Higgs monopoles. It turns out that the particles become completely destroyed by gravity, while the vortices admit a rich spectrum of gravitating generalizations. Such vortex defects may be interesting in view of the AdS/CFT correspondence or in the context of the brane world scenario.Comment: 1 figure and 1 formula added; to appear in PL

Phenomenology of the 1/Nf_f Expansion for Field Theories in Extra Dimensions

In this paper we review the properties of the 1/$N_f$ expansion in multidimensional theories. Contrary to the usual perturbative expansion it is renormalizable and contains only logarithmic divergencies. The price for it is the presence of ghost states which, however, in certain cases do not contribute to physical amplitudes. In this case the theory is unitary and one can calculate the cross-sections. As an example we consider the differential cross section of elastic $eq \to eq$ scattering in $D=7,11,...$-dimensional world. We look also for the unification of the gauge couplings in multidimensional Standard Model and its SUSY extension which takes place at energies lower than in 4 dimensions.Comment: Submitted for the SUSY07 proceedings, 4 pages, LaTeX, 4 eps figures + 3 axodraw figure

Targeted in vivo extracellular matrix formation promotes neovascularization in a rodent model of myocardial infarction.

BackgroundThe extracellular matrix plays an important role in tissue regeneration. We investigated whether extracellular matrix protein fragments could be targeted with antibodies to ischemically injured myocardium to promote angiogenesis and myocardial repair.Methodology/principal findingsFour peptides, 2 derived from fibronectin and 2 derived from Type IV Collagen, were assessed for in vitro and in vivo tendencies for angiogenesis. Three of the four peptides--Hep I, Hep III, RGD--were identified and shown to increase endothelial cell attachment, proliferation, migration and cell activation in vitro. By chemically conjugating these peptides to an anti-myosin heavy chain antibody, the peptides could be administered intravenously and specifically targeted to the site of the myocardial infarction. When administered into Sprague-Dawley rats that underwent ischemia-reperfusion myocardial infarction, these peptides produced statistically significantly higher levels of angiogenesis and arteriogenesis 6 weeks post treatment.Conclusions/significanceWe demonstrated that antibody-targeted ECM-derived peptides alone can be used to sufficiently alter the extracellular matrix microenvironment to induce a dramatic angiogenic response in the myocardial infarct area. Our results indicate a potentially new non-invasive strategy for repairing damaged tissue, as well as a novel tool for investigating in vivo cell biology

Towards 5D Grand Unification without SUSY Flavor Problem

We consider the renormalization group approach to the SUSY flavor problem in the supersymmetric SU(5) model with one extra dimension. In higher dimensional SUSY gauge theories, it has been recently shown that power corrections due to the Kaluza-Klein states of gauge fields run the soft masses generated at the orbifold fixed point to flavor conserving values in the infra-red limit. In models with GUT breaking at the brane where the GUT scale can be larger than the compactification scale, we show that the addition of a bulk Higgs multiplet, which is necessary for the successful unification, is compatible with the flavor universality achieved at the compactification scale.Comment: JHEP style file of 35 pages with 3 figures, Version to appear in JHE

Locality in Theory Space

Locality is a guiding principle for constructing realistic quantum field theories. Compactified theories offer an interesting context in which to think about locality, since interactions can be nonlocal in the compact directions while still being local in the extended ones. In this paper, we study locality in "theory space", four-dimensional Lagrangians which are dimensional deconstructions of five-dimensional Yang-Mills. In explicit ultraviolet (UV) completions, one can understand the origin of theory space locality by the irrelevance of nonlocal operators. From an infrared (IR) point of view, though, theory space locality does not appear to be a special property, since the lowest-lying Kaluza-Klein (KK) modes are simply described by a gauged nonlinear sigma model, and locality imposes seemingly arbitrary constraints on the KK spectrum and interactions. We argue that these constraints are nevertheless important from an IR perspective, since they affect the four-dimensional cutoff of the theory where high energy scattering hits strong coupling. Intriguingly, we find that maximizing this cutoff scale implies five-dimensional locality. In this way, theory space locality is correlated with weak coupling in the IR, independent of UV considerations. We briefly comment on other scenarios where maximizing the cutoff scale yields interesting physics, including theory space descriptions of QCD and deconstructions of anti-de Sitter space.Comment: 40 pages, 11 figures; v2: references and clarifications added; v3: version accepted by JHE