An investigation into the structure of genomes within an evolution that uses embryogenesis

Evolutionary algorithms that use embryogenesis in the creation of individuals have several desirable qualities. Such algorithms are able to create complex, modular designs which can scale well to large problems. However, the inner workings of developmental algorithms have not been investigated as thoroughly as their direct-encoding counterparts. More precisely, it would be beneficial to look at how the rules used during embryogenesis evolve alongside the phenotypes they produced. This paper reports on such an investigation into the evolution of a rule set for the growth of an artificial neural network, and identifies several aspects that are desirable for the genomes of a developmental evolutionary algorithm

Laplacian Growth, Elliptic Growth, and Singularities of the Schwarz Potential

The Schwarz function has played an elegant role in understanding and in generating new examples of exact solutions to the Laplacian growth (or "Hele- Shaw") problem in the plane. The guiding principle in this connection is the fact that "non-physical" singularities in the "oil domain" of the Schwarz function are stationary, and the "physical" singularities obey simple dynamics. We give an elementary proof that the same holds in any number of dimensions for the Schwarz potential, introduced by D. Khavinson and H. S. Shapiro [17] (1989). A generalization is also given for the so-called "elliptic growth" problem by defining a generalized Schwarz potential. New exact solutions are constructed, and we solve inverse problems of describing the driving singularities of a given flow. We demonstrate, by example, how \mathbb{C}^n - techniques can be used to locate the singularity set of the Schwarz potential. One of our methods is to prolong available local extension theorems by constructing "globalizing families". We make three conjectures in potential theory relating to our investigation

Tracking Neural Progenitor Cell Migration in the Rodent Brain Using Magnetic Resonance Imaging

The study of neurogenesis and neural progenitor cells (NPCs) is important across the biomedical spectrum, from learning about normal brain development and studying disease to engineering new strategies in regenerative medicine. In adult mammals, NPCs proliferate in two main areas of the brain, the subventricular zone (SVZ) and the subgranular zone, and continue to migrate even after neurogenesis has ceased within the rest of the brain. In healthy animals, NPCs migrate along the rostral migratory stream (RMS) from the SVZ to the olfactory bulb, and in diseased animals, NPCs migrate toward lesions such as stroke and tumors. Here we review how MRI-based cell tracking using iron oxide particles can be used to monitor and quantify NPC migration in the intact rodent brain, in a serial and relatively non-invasive fashion. NPCs can either be labeled directly in situ by injecting particles into the lateral ventricle or RMS, where NPCs can take up particles, or cells can be harvested and labeled in vitro, then injected into the brain. For in situ labeling experiments, the particle type, injection site, and image analysis methods have been optimized and cell migration toward stroke and multiple sclerosis lesions has been investigated. Delivery of labeled exogenous NPCs has allowed imaging of cell migration toward more sites of neuropathology, which may enable new diagnostic and therapeutic opportunities for as-of-yet untreatable neurological diseases

An investigation into the structure of genomes within an evolution that uses embryogenesis

Evolutionary algorithms that use embryogenesis in the creation of individuals have several desirable qualities. Such algorithms are able to create complex, modular designs which can scale well to large problems. However, the inner workings of developmental algorithms have not been investigated as thoroughly as their direct-encoding counterparts. More precisely, it would be beneficial to look at how the rules used during embryogenesis evolve alongside the phenotypes they produced. This paper reports on such an investigation into the evolution of a rule set for the growth of an artificial neural network, and identifies several aspects that are desirable for the genomes of a developmental evolutionary algorithm

Dual-modality, fluorescent, PLGA encapsulated bismuth nanoparticles for molecular and cellular fluorescence imaging and computed tomography

Reports of molecular and cellular imaging using computed tomography (CT) are rapidly increasing. Many of these reports use gold nanoparticles. Bismuth has similar CT contrast properties to gold while being approximately 1000-fold less expensive. Herein we report the design, fabrication, characterization, and CT and fluorescence imaging properties of a novel, dual modality, fluorescent, polymer encapsulated bismuth nanoparticle construct for computed tomography and fluorescence imaging. We also report on cellular internalization and preliminary in vitro and in vivo toxicity effects of these constructs. 40 nm bismuth(0) nanocrystals were synthesized and encapsulated within 120 nm Poly(DL-lactic-co-glycolic acid) (PLGA) nanoparticles by oil-in-water emulsion methodologies. Coumarin-6 was co-encapsulated to impart fluorescence. High encapsulation efficiency was achieved ∼ 70% bismuth w/w. Particles were shown to internalize within cells following incubation in culture. Bismuth nanocrystals and PLGA encapsulated bismuth nanoparticles exhibited >90% and >70% degradation, respectively, within 24 hours in acidic, lysosomal environment mimicking media and both remained nearly 100% stable in cytosolic/extracellular fluid mimicking media. μCT and clinical CT imaging was performed at multiple X-ray tube voltages to measure concentration dependent attenuation rates as well as to establish the ability to detect the nanoparticles in an ex vivo biological sample. Dual fluorescence and CT imaging is demonstrated as well. In vivo toxicity studies in rats revealed neither clinically apparent side effects nor major alterations in serum chemistry and hematology parameters. Calculations on minimal detection requirements for in vivo targeted imaging using these nanoparticles are presented. Indeed, our results indicate that these nanoparticles may serve as a platform for sensitive and specific targeted molecular CT and fluorescence imaging

Human Ovarian Cancer Tumor Formation in Severe Combined Immunodeficient (SCID) Pigs

Ovarian cancer (OvCa) is the most lethal gynecologic malignancy, with two-thirds of patients having late-stage disease (II-IV) at diagnosis. Improved diagnosis and therapies are needed, yet preclinical animal models for ovarian cancer research have primarily been restricted to rodents, for data on which can fail to translate to the clinic. Thus, there is currently a need for a large animal OvCa model. Therefore, we sought to determine if pigs, being more similar to humans in terms of anatomy and physiology, would be a viable preclinical animal model for OvCa. We injected human OSPC-ARK1 cells, a chemotherapy-resistant primary ovarian serous papillary carcinoma cell line, into the neck muscle and ear tissue of four severe combined immune deficient (SCID) and two non-SCID pigs housed in novel biocontainment facilities to study the ability of human OvCa cells to form tumors in a xenotransplantation model. Tumors developed in ear tissue of three SCID pigs, while two SCID pigs developed tumors in neck tissue; no tumors were detected in non-SCID control pigs. All tumor masses were confirmed microscopically as ovarian carcinomas. The carcinomas in SCID pigs were morphologically similar to the original ovarian carcinoma and had the same immunohistochemical phenotype based on expression of Claudin 3, Claudin 4, Cytokeratin 7, p16, and EMA. Confirmation that OSPC-ARK1 cells form carcinomas in SCID pigs substantiates further development of orthotopic models of OvCa in pigs

Degenerate Stars and Gravitational Collapse in AdS/CFT

We construct composite CFT operators from a large number of fermionic primary fields corresponding to states that are holographically dual to a zero temperature Fermi gas in AdS space. We identify a large N regime in which the fermions behave as free particles. In the hydrodynamic limit the Fermi gas forms a degenerate star with a radius determined by the Fermi level, and a mass and angular momentum that exactly matches the boundary calculations. Next we consider an interacting regime, and calculate the effect of the gravitational back-reaction on the radius and the mass of the star using the Tolman-Oppenheimer-Volkoff equations. Ignoring other interactions, we determine the "Chandrasekhar limit" beyond which the degenerate star (presumably) undergoes gravitational collapse towards a black hole. This is interpreted on the boundary as a high density phase transition from a cold baryonic phase to a hot deconfined phase.Comment: 75 page

The absence of an auditory-visual attentional blink is not due to echoic memory.

Als binnen een halve seconde twee visuele items in een serieel aangeboden stroom moeten worden geselecteerd, is de prestatie voor het tweede item vaak relatief slecht (er treedt een “attentional blink” op); wanneer het eerste echter item auditief wordt aangeboden, verdwijnt de blink meestal. We hebben aangetoond dat dit laatste niet wordt veroorzaakt doordat proefpersonen hun echoïsch geheugen gebruiken om de verwerking van het auditieve item uit te stellen tot na het einde van de visuele stroom

p21 produces a bioactive secretome that places stressed cells under immunosurveillance

Immune cells identify and destroy damaged cells to prevent them from causing cancer or other pathologies by mechanisms that remain poorly understood. Here, we report that the cell-cycle inhibitor p21 places cells under immunosurveillance to establish a biological timer mechanism that controls cell fate. p21 activates retinoblastoma protein (Rb)-dependent transcription at select gene promoters to generate a complex bioactive secretome, termed p21-activated secretory phenotype (PASP). The PASP includes the chemokine CXCL14, which promptly attracts macrophages. These macrophages disengage if cells normalize p21 within 4 days, but if p21 induction persists, they polarize toward an M1 phenotype and lymphocytes mount a cytotoxic T cell response to eliminate target cells, including preneoplastic cells. Thus, p21 concurrently induces proliferative arrest and immunosurveillance of cells under duress