Numerical study of surface-induced reorientation and smectic layering in a nematic liquid crystal

Surface-induced profiles of both nematic and smectic order parameters in a nematic liquid crystal, ranging from an orienting substrate to "infinity", were evaluated numerically on base of an extended Landau theory. In order to obtain a smooth behavior of the solutions at "infinity" a boundary energy functional was derived by linearizing the Landau energy around its equilibrium solutions. We find that the intrinsic wave number of the smectic structure, which plays the role of a coupling between nematic and smectic order, strongly influences the director reorientation. Whereas the smectic order is rapidly decaying when moving away from the surface, the uniaxial nematic order parameter shows an oscillatory behavior close to the substrate, accompanied by a non-zero local biaxiality.Comment: LaTeX, 17 pages, with 4 postscript figure

Engineering human cell-based, functionally integrated osteochondral grafts by biological bonding of engineered cartilage tissues to bony scaffolds

In this study, we aimed at developing and validating a technique for the engineering of osteochondral grafts based on the biological bonding of a chondral layer with a bony scaffold by cell-laid extracellular matrix. Osteochondral composites were generated by combining collagen-based matrices (Chondro-Gide) containing human chondrocytes with devitalized spongiosa cylinders (Tutobone) using a fibrin gel (Tisseel). We demonstrate that separate pre-culture of the chondral layer for 3 days prior to the generation of the composite allows for (i) more efficient cartilaginous matrix accumulation than no pre-culture, as assessed histologically and biochemically, and (ii) superior biological bonding to the bony scaffold than 14 days of pre-culture, as assessed using a peel-off mechanical test, developed to measure integration of bilayered materials. The presence of the bony scaffold induced an upregulation in the infiltrated cells of the osteoblast-related gene bone sialoprotein, indicative of the establishment of a gradient of cell phenotypes, but did not affect per se the quality of the cartilaginous matrix in the chondral layer. The described strategy to generate osteochondral plugs is simple to be implemented and--since it is based on clinically compliant cells and materials--is amenable to be readily tested in the clinic

SWI/SNF regulates a transcriptional programme that induces senescence to prevent liver cancer

Oncogene-induced senescence (OIS) is a potent tumour suppressor mechanism. To identify senescence regulators relevant to cancer, we screened an shRNA library targeting genes deleted in hepatocellular carcinoma (HCC). Here, we describe how knockdown of the SWI/SNF component ARID1B prevents OIS and cooperates with RAS to induce liver tumours. ARID1B controls p16INK4a and p21CIP1a transcription but also regulates DNA damage, oxidative stress and p53 induction, suggesting that SWI/SNF uses additional mechanisms to regulate senescence. To systematically identify SWI/SNF targets regulating senescence, we carried out a focused shRNA screen. We discovered several new senescence regulators including ENTPD7, an enzyme that hydrolyses nucleotides. ENTPD7 affects oxidative stress, DNA damage and senescence. Importantly, expression of ENTPD7 or inhibition of nucleotide synthesis in ARID1B-depleted cells results in re-establishment of senescence. Our results identify novel mechanisms by which epigenetic regulators can affect tumor progression and suggest that pro-senescence therapies could be employed against SWI/SNF-mutated cancers

Structural Properties of Thermoresponsive Poly(N-isopropylacrylamide)-poly(ethyleneglycol) Microgels

The application of RNA interference to treat disease is an important yet challenging concept in modern medicine. In particular, small interfering RNA (siRNA) have shown tremendous promise in the treatment of cancer. However, siRNA show poor pharmacological properties, which presents a major hurdle for effective disease treatment especially through intravenous delivery routes. In response to these shortcomings, a variety of nanoparticle carriers have emerged, which are designed to encapsulate, protect, and transport siRNA into diseased cells. To be effective as carrier vehicles, nanoparticles must overcome a series of biological hurdles throughout the course of delivery. As a result, one promising approach to siRNA carriers is dynamic versatile nanoparticles that can perform several in vivo functions. Over the last several years, our research group has investigated hydrogel nanoparticles (nanogels) as candidate delivery vehicles for therapeutics, including siRNA. Throughout the course of our research, we have developed higher order architectures composed entirely of hydrogel components, where several different hydrogel chemistries may be isolated in unique compartments of a single construct. In this Account, we summarize a subset of our experiences in the design and application of nanogels in the context of drug delivery, summarizing the relevant characteristics for these materials as delivery vehicles for siRNA. Through the layering of multiple, orthogonal chemistries in a nanogel structure, we can impart multiple functions to the materials. We consider nanogels as a platform technology, where each functional element of the particle may be independently tuned to optimize the particle for the desired application. For instance, we can modify the shell compartment of a vehicle for cell-specific targeting or evasion of the innate immune system, whereas other compartments may incorporate fluorescent probes or regulate the encapsulation and release of macromolecular therapeutics. Proof-of-principle experiments have demonstrated the utility of multifunctional nanogels. For example, using a simple core/shell nanogel architecture, we have recently reported the delivery of siRNA to chemosensitize drug resistant ovarian cancer cells. Ongoing efforts have resulted in several advanced hydrogel structures, including biodegradable nanogels and multicompartment spheres. In parallel, our research group has studied other properties of the nanogels, including their behavior in confined environments and their ability to translocate through small pores

Loop Quantum Cosmology II: Volume Operators

Volume operators measuring the total volume of space in a loop quantum theory of cosmological models are constructed. In the case of models with rotational symmetry an investigation of the Higgs constraint imposed on the reduced connection variables is necessary, a complete solution of which is given for isotropic models; in this case the volume spectrum can be calculated explicitly. It is observed that the stronger the symmetry conditions are the smaller is the volume spectrum, which can be interpreted as level splitting due to broken symmetries. Some implications for quantum cosmology are presented.Comment: 21 page

Using Plasma Etching to Access the Polymer Density Distribution and Diffusivity of Gel Particles

In this paper we examine the polymer density distribution of gel particles and its effect on solvent diffusivity through the polymer network. In order to access the inner particle regions, external polymer layers were removed by plasma etching, thus reducing them from the outside. Higher polymer densities after erosion showed internal heterogeneity, with the density increasing towards the center of the particles. An exponential decay polymer density model is proposed, and the spatial relaxation length measured. The diffusion of solvent through the particles, before and after the plasma oxidation, revealed a correlation between the diffusion coefficient and the internal density

Loop Quantum Cosmology III: Wheeler-DeWitt Operators

In the framework of loop quantum cosmology anomaly free quantizations of the Hamiltonian constraint for Bianchi class A, locally rotationally symmetric and isotropic models are given. Basic ideas of the construction in (non-symmetric) loop quantum gravity can be used, but there are also further inputs because the special structure of symmetric models has to be respected by operators. In particular, the basic building blocks of the homogeneous models are point holonomies rather than holonomies necessitating a new regularization procedure. In this respect, our construction is applicable also for other (non-homogeneous) symmetric models, e.g. the spherically symmetric one.Comment: 19 page

Renormalization Group Analysis of a Quivering String Model of Posture Control

Scaling concepts and renormalization group (RG) methods are applied to a simple linear model of human posture control consisting of a trembling or quivering string subject to damping and restoring forces. The string is driven by uncorrelated white Gaussian noise intended to model the corrections of the physiological control system. We find that adding a weak quadratic nonlinearity to the posture control model opens up a rich and complicated phase space (representing the dynamics) with various non-trivial fixed points and basins of attraction. The transition from diffusive to saturated regimes of the linear model is understood as a crossover phenomenon, and the robustness of the linear model with respect to weak non-linearities is confirmed. Correlations in posture fluctuations are obtained in both the time and space domain. There is an attractive fixed point identified with falling. The scaling of the correlations in the front-back displacement, which can be measured in the laboratory, is predicted for both the large-separation (along the string) and long-time regimes of posture control.Comment: 20 pages, 13 figures, RevTeX, accepted for publication in PR

Consistent canonical quantization of general relativity in the space of Vassiliev knot invariants

We present a quantization of the Hamiltonian and diffeomorphism constraint of canonical quantum gravity in the spin network representation. The novelty consists in considering a space of wavefunctions based on the Vassiliev knot invariants. The constraints are finite, well defined, and reproduce at the level of quantum commutators the Poisson algebra of constraints of the classical theory. A similar construction can be carried out in 2+1 dimensions leading to the correct quantum theory.Comment: 4 pages, RevTex, one figur

Homogeneous Loop Quantum Cosmology

Loop quantum cosmological methods are extended to homogeneous models in diagonalized form. It is shown that the diagonalization leads to a simplification of the volume operator such that its spectrum can be determined explicitly. This allows the calculation of composite operators, most importantly the Hamiltonian constraint. As an application the dynamics of the Bianchi I model is studied and it is shown that its loop quantization is free of singularities.Comment: 25 pages, 3 figure