Heterotic Action in SUGRA-SYM Background

We consider the generalization of the heterotic action considered by Cherkis and Schwarz where the chiral bosons are introduced in a manifestly covariant way using an auxiliary field. In particular, we construct the kappa-symmetric heterotic action in ten-dimensional supergravity background coupled to super Yang-Mills theory and prove its kappa-symmetry. The usual Bianchi identity of Type I supergravity with super Yang-Mills dH_3= -\tr F\wedge F is crucially used. For technical reason, the Yang-Mills field is restricted to be abelian.Comment: 12 pages, no figures, added comments in the acknowledgmen

Systems Level Approach Reveals the Correlation of Endoderm Differentiation of Mouse Embryonic Stem Cells with Specific Microstructural Cues of Fibrin Gels.

Stem cells receive numerous cues from their associated substrate that help to govern their behaviour. However, identification of influential substrate characteristics poses difficulties because of their complex nature. In this study, we developed an integrated experimental and systems level modelling approach to investigate and identify specific substrate features influencing differentiation of mouse embryonic stem cells (mESCs) on a model fibrous substrate, fibrin. We synthesized a range of fibrin gels by varying fibrinogen and thrombin concentrations, which led to a range of substrate stiffness and microstructure. mESCs were cultured on each of these gels, and characterization of the differentiated cells revealed a strong influence of substrate modulation on gene expression patterning. To identify specific substrate features influencing differentiation, the substrate microstructure was quantified by image analysis and correlated with stem cell gene expression patterns using a statistical model. Significant correlations were observed between differentiation and microstructure features, specifically fibre alignment. Furthermore, this relationship occurred in a lineage-specific manner towards endoderm. This systems level approach allows for identification of specific substrate features from a complex material which are influential to cellular behaviour. Such analysis may be effective in guiding the design of scaffolds with specific properties for tissue engineering applications

Early differentiation patterning of mouse embryonic stem cells in response to variations in alginate substrate stiffness

Background: Embryonic stem cells (ESCs) have been implicated to have tremendous impact in regenerative therapeutics of various diseases, including Type 1 Diabetes. Upon generation of functionally mature ESC derived islet-like cells, they need to be implanted into diabetic patients to restore the loss of islet activity. Encapsulation in alginate microcapsules is a promising route of implantation, which can protect the cells from the recipient's immune system. While there has been a significant investigation into islet encapsulation over the past decade, the feasibility of encapsulation and differentiation of ESCs has been less explored. Research over the past few years has identified the cellular mechanical microenvironment to play a central role in phenotype commitment of stem cells. Therefore it will be important to design the encapsulation material to be supportive to cellular functionality and maturation.Results: This work investigated the effect of stiffness of alginate substrate on initial differentiation and phenotype commitment of murine ESCs. ESCs grown on alginate substrates tuned to similar biomechanical properties of native pancreatic tissue elicited both an enhanced and incrementally responsive differentiation towards endodermal lineage traits.Conclusions: The insight into these biophysical phenomena found in this study can be used along with other cues to enhance the differentiation of embryonic stem cells toward a specific lineage fate. © 2013 Candiello et al.; licensee BioMed Central Ltd

Covariant Action for the Super-Five-Brane of M-Theory

We propose a complete, d=6 covariant and kappa-symmetric, action for an M-theory five-brane propagating in D=11 supergravity background.Comment: LaTeX file, 5 pages, misprints corrected, comments and references adde

Potential for pancreatic maturation of differentiating human embryonic stem cells is sensitive to the specific pathway of definitive endoderm commitment

This study provides a detailed experimental and mathematical analysis of the impact of the initial pathway of definitive endoderm (DE) induction on later stages of pancreatic maturation. Human embryonic stem cells (hESCs) were induced to insulin-producing cells following a directed-differentiation approach. DE was induced following four alternative pathway modulations. DE derivatives obtained from these alternate pathways were subjected to pancreatic progenitor (PP) induction and maturation and analyzed at each stage. Results indicate that late stage maturation is influenced by the initial pathway of DE commitment. Detailed quantitative analysis revealed WNT3A and FGF2 induced DE cells showed highest expression of insulin, are closely aligned in gene expression patterning and have a closer resemblance to pancreatic organogenesis. Conversely, BMP4 at DE induction gave most divergent differentiation dynamics with lowest insulin upregulation, but highest glucagon upregulation. Additionally, we have concluded that early analysis of PP markers is indicative of its potential for pancreatic maturation. © 2014 Jaramillo et al

A Variational Deduction of Second Gradient Poroelasticity Part I: General Theory

Second gradient theories have to be used to capture how local micro heterogeneities macroscopically affect the behavior of a continuum. In this paper a configurational space for a solid matrix filled by an unknown amount of fluid is introduced. The Euler-Lagrange equations valid for second gradient poromechanics, generalizing those due to Biot, are deduced by means of a Lagrangian variational formulation. Starting from a generalized Clausius-Duhem inequality, valid in the framework of second gradient theories, the existence of a macroscopic solid skeleton Lagrangian deformation energy, depending on the solid strain and the Lagrangian fluid mass density as well as on their Lagrangian gradients, is proven.Comment: 20 page

Duality Symmetric Quantization of Superstring

A general covariant quantization of superparticle, Green-Schwarz superstring and a supermembrane with manifest supersymmetry and duality symmetry is proposed. This quantization provides a natural quantum mechanical description of curved BPS-type backgrounds related to the ultra-short supersymmetry multiplets. Half-size commuting and anticommuting Killing spinors admitted by such backgrounds in quantum theory become truncated $\kappa$-symmetry ghosts. The symmetry of Killing spinors under dualities transfers to the symmetry of the spectrum of states. GS superstring in the generalized semi-light-cone gauge can be quantized consistently in the background of ten-dimensional supersymmetric gravitational waves. Upon compactification they become supersymmetric electrically charged black holes, either massive or massless. However, the generalized light-cone gauge breaks S-duality. We propose a new family of gauges, which we call black hole gauges. These gauges are suitable for quantization both in flat Minkowski space and in the black hole background, and they are duality symmetric. As an example, a manifestly S-duality symmetric black hole gauge is constructed in terms of the axion-dilaton-electric-magnetic black hole hair. We also suggest the U-duality covariant class of gauges for type II superstrings.Comment: 49 pages, LaTe

Matrix Rigidity Induces Osteolytic Gene Expression of Metastatic Breast Cancer Cells

Nearly 70% of breast cancer patients with advanced disease will develop bone metastases. Once established in bone, tumor cells produce factors that cause changes in normal bone remodeling, such as parathyroid hormone-related protein (PTHrP). While enhanced expression of PTHrP is known to stimulate osteoclasts to resorb bone, the environmental factors driving tumor cells to express PTHrP in the early stages of development of metastatic bone disease are unknown. In this study, we have shown that tumor cells known to metastasize to bone respond to 2D substrates with rigidities comparable to that of the bone microenvironment by increasing expression and production of PTHrP. The cellular response is regulated by Rho-dependent actomyosin contractility mediated by TGF-ß signaling. Inhibition of Rho-associated kinase (ROCK) using both pharmacological and genetic approaches decreased PTHrP expression. Furthermore, cells expressing a dominant negative form of the TGF-ß receptor did not respond to substrate rigidity, and inhibition of ROCK decreased PTHrP expression induced by exogenous TGF-ß. These observations suggest a role for the differential rigidity of the mineralized bone microenvironment in early stages of tumor-induced osteolysis, which is especially important in metastatic cancer since many cancers (such as those of the breast and lung) preferentially metastasize to bone

The cerebrovascular basement membrane: Role in the clearance of β-amyloid and cerebral amyloid angiopathy

Cerebral amyloid angiopathy (CAA), the accumulation of β-amyloid (Aβ) peptides in the walls of cerebral blood vessels, is observed in the majority of Alzheimer’s disease (AD) brains and is thought to be due to a failure of the aging brain to clear Aβ. Perivascular drainage of Aβ along cerebrovascular basement membranes (CVBMs) is one of the mechanisms by which Aβ is removed from the brain. CVBMs are specialized sheets of extracellular matrix that provide structural and functional support for cerebral blood vessels. Changes in CVBM composition and structure are observed in the aged and AD brain and may contribute to the development and progression of CAA. This review summarizes the properties of the CVBM, its role in mediating clearance of interstitial fluids and solutes from the brain, and evidence supporting a role for CVBM in the etiology of CAA