Open Bar - a Brouwerian Intuitionistic Logic with a Pinch of Excluded Middle

One of the differences between Brouwerian intuitionistic logic and classical logic is their treatment of time. In classical logic truth is atemporal, whereas in intuitionistic logic it is time-relative. Thus, in intuitionistic logic it is possible to acquire new knowledge as time progresses, whereas the classical Law of Excluded Middle (LEM) is essentially flattening the notion of time stating that it is possible to decide whether or not some knowledge will ever be acquired. This paper demonstrates that, nonetheless, the two approaches are not necessarily incompatible by introducing an intuitionistic type theory along with a Beth-like model for it that provide some middle ground. On one hand they incorporate a notion of progressing time and include evolving mathematical entities in the form of choice sequences, and on the other hand they are consistent with a variant of the classical LEM. Accordingly, this new type theory provides the basis for a more classically inclined Brouwerian intuitionistic type theory

Aging display's effect on interpretation of digital pathology slides

It is our conjecture that the variability of colors in a pathology image effects the interpretation of pathology cases, whether it is diagnostic accuracy, diagnostic confidence, or workflow efficiency. In this paper, digital pathology images are analyzed to quantify the perceived difference in color that occurs due to display aging, in particular a change in the maximum luminance, white point, and color gamut. The digital pathology images studied include diagnostically important features, such as the conspicuity of nuclei. Three different display aging models are applied to images: aging of luminance & chrominance, aging of chrominance only, and a stabilized luminance & chrominance (i.e., no aging). These display models and images are then used to compare conspicuity of nuclei using CIE deltaE2000, a perceptual color difference metric. The effect of display aging using these display models and images is further analyzed through a human reader study designed to quantify the effects from a clinical perspective. Results from our reader study indicate significant impact of aged displays on workflow as well as diagnosis as follow. As compared to the originals (no-aging), slides with the effect of aging simulated were significantly more difficult to read (p-value of 0.0005) and took longer to score (p-value of 0.02). Moreover, luminance+chrominance aging significantly reduced inter-session percent agreement of diagnostic scores (p-value of 0.0418)

SH2D1A Regulates T-dependent Humoral Autoimmunity

The signaling lymphocytic activation molecule (SLAM)/CD150 family includes a family of chromosome 1–encoded cell surface molecules with costimulatory functions mediated in part by the adaptor protein SH2D1A (SLAM-associated protein, SAP). Deficiency in SH2D1A protects mice from an experimental model of lupus, including the development of hypergammaglobulinemia, autoantibodies including anti–double stranded DNA, and renal disease. This protection did not reflect grossly defective T or B cell function per se because SH2D1A-deficient mice were susceptible to experimental autoimmune encephalomyelitis, a T cell–dependent disease, and they were capable of mounting normal T-independent antigen-specific immunoglobulin responses. Instead, T-dependent antibody responses were impaired in SH2D1A-deficient mice, reflecting defective germinal center formation. These findings demonstrate a specific role for the SLAM–SH2D1A system in the regulation of T-dependent humoral immune responses, implicating members of the CD150–SH2D1A family as targets in the pathogenesis and therapy of antibody-mediated autoimmune and allergic diseases

Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids

The mTORC1 kinase promotes growth in response to growth factors, energy levels, and amino acids, and its activity is often deregulated in disease. The Rag GTPases interact with mTORC1 and are proposed to activate it in response to amino acids by promoting mTORC1 translocation to a membrane-bound compartment that contains the mTORC1 activator, Rheb. We show that amino acids induce the movement of mTORC1 to lysosomal membranes, where the Rag proteins reside. A complex encoded by the MAPKSP1, ROBLD3, and c11orf59 genes, which we term Ragulator, interacts with the Rag GTPases, recruits them to lysosomes, and is essential for mTORC1 activation. Constitutive targeting of mTORC1 to the lysosomal surface is sufficient to render the mTORC1 pathway amino acid insensitive and independent of Rag and Ragulator, but not Rheb, function. Thus, Rag-Ragulator-mediated translocation of mTORC1 to lysosomal membranes is the key event in amino acid signaling to mTORC1.National Institutes of Health (U.S.) (Grant CA103866)National Institutes of Health (U.S.) (Grant AI47389)United States. Dept. of Defense (W81XWH-07-0448)W. M. Keck FoundationJane Coffin Childs Memorial Fund for Medical ResearchLAM Foundation (Fellowship

Discrete cilia modelling with singularity distributions

We discuss in detail techniques for modelling flows due to finite and infinite arrays of beating cilia. An efficient technique, based on concepts from previous ‘singularity models’ is described, that is accurate in both near and far-fields. Cilia are modelled as curved slender ellipsoidal bodies by distributing Stokeslet and potential source dipole singularities along their centrelines, leading to an integral equation that can be solved using a simple and efficient discretisation. The computed velocity on the cilium surface is found to compare favourably with the boundary condition. We then present results for two topics of current interest in biology. 1) We present the first theoretical results showing the mechanism by which rotating embryonic nodal cilia produce a leftward flow by a ‘posterior tilt,’ and track particle motion in an array of three simulated nodal cilia. We find that, contrary to recent suggestions, there is no continuous layer of negative fluid transport close to the ciliated boundary. The mean leftward particle transport is found to be just over 1 μm/s, within experimentally measured ranges. We also discuss the accuracy of models that represent the action of cilia by steady rotlet arrays, in particular, confirming the importance of image systems in the boundary in establishing the far-field fluid transport. Future modelling may lead to understanding of the mechanisms by which morphogen gradients or mechanosensing cilia convert a directional flow to asymmetric gene expression. 2) We develop a more complex and detailed model of flow patterns in the periciliary layer of the airway surface liquid. Our results confirm that shear flow of the mucous layer drives a significant volume of periciliary liquid in the direction of mucus transport even during the recovery stroke of the cilia. Finally, we discuss the advantages and disadvantages of the singularity technique and outline future theoretical and experimental developments required to apply this technique to various other biological problems, particularly in the reproductive system

Herpes zoster risk factors in a national cohort of veterans with rheumatoid arthritis

BACKGROUND: Herpes zoster occurs more commonly in patients taking immunosuppressive medications, though the risk associated with different medications is poorly understood. METHODS: Retrospective cohort study including 20,357 patients who were followed in the Veterans Affairs healthcare system and treated for rheumatoid arthritis from October 1998 through June 2005. Cox proportional hazards regression was used to determine risk factors for herpes zoster, and herpes zoster-free survival. Chart review was performed to validate the diagnosis of herpes zoster. RESULTS: The incidence of herpes zoster was 9.96 per 1000 patient-years. In time-to-event analysis, patients receiving medications used to treat mild rheumatoid arthritis were less likely to have an episode of herpes zoster than patients receiving medications used to treat moderate and severe rheumatoid arthritis (p<0.001). Independent risk factors for herpes zoster included older age, prednisone use, medications used to treat moderate and severe rheumatoid arthritis, malignancy, chronic lung disease, renal failure, and liver disease. Among patients receiving tumor necrosis factor-alpha antagonists, etanercept (HR 0.62) and adalimumab (HR 0.53) were associated with lower risk of herpes zoster. There was excellent agreement between ICD-9-CM diagnosis of herpes zoster and diagnosis by chart review (kappa = 0.92). CONCLUSIONS: Risk factors for herpes zoster included older age, prednisone use, medications used to treat moderate and severe rheumatoid arthritis, and several comorbid medical conditions. These results demonstrate that the Department of Veterans Affairs’ national administrative databases can be used to study rare adverse drug events

Hydrodynamic Coupling of Two Brownian Spheres to a Planar Surface

We describe direct imaging measurements of the collective and relative diffusion of two colloidal spheres near a flat plate. The bounding surface modifies the spheres' dynamics, even at separations of tens of radii. This behavior is captured by a stokeslet analysis of fluid flow driven by the spheres' and wall's no-slip boundary conditions. In particular, this analysis reveals surprising asymmetry in the normal modes for pair diffusion near a flat surface.Comment: 4 pages, 4 figure

Evaluation of six single nucleotide polymorphisms for bovine traceability in the context of the argentine-chinese beef trade

Genetic traceability refers to methods associated with the identification of animals and their products through DNA characterization of individuals, breeds or species. To trace breeds, it is necessary to define the breed groups to analyze, and the most appropriate molecular marker set. The selection of genetic markers depends on the gene frequency distribution, the genetic distance among breeds and the presence of private alleles. In this study, we assessed six single nucleotide polymorphisms (SNPs) located in the DGAT1, TG, LEP, GH, FABP4 and GnRHR genes, as potential genetic markers to be included into a panel for genetic traceability for the identification of breed origin associated with the bovine beef trade. The results of the genetic characterization of four of the main Chinese cattle populations and of the principal breeds raised in Argentina and in the world (five Bos taurus and two B. indicus) suggest that these SNP markers can be successfully used as a part of an effective traceability system for the identification of cattle breed origin in the context of the Chinese meat imports, and in particular in the Argentine-Chinese beef trade.La trazabilidad genética, la cual se basa en la identificación de animales y sus productos, permite la identificación individual, racial o de especie. Esta metodología es útil para detectar fraudes y valorizar producciones locales. Para llevar a cabo la trazabilidad es necesario definir los grupos raciales a analizar y el panel de marcadores más apropiados a utilizar. La selección de marcadores depende de la distribución de las frecuencias génicas, de la distancia genética entre las razas y de la presencia de alelos privativos. El objetivo de este trabajo consistió en evaluar seis polimorfismos de nucleótido simple (SNPs) ubicados en los genes DGAT1, TG, LEP, GH, FABP4 y GnRHR como posibles marcadores genéticos apropiados para ser incluidos en un panel de trazabilidad para la identificación de la raza de origen en el contexto de la comercialización de carne bovina. Los resultados de la caracterización genética de cuatro de las principales poblaciones bovinas chinas y de las razas más importantes de nuestro país (cinco Bos taurus y dos B. indicus) sugieren que los marcadores estudiados pueden ser utilizados exitosamente como parte de un sistema de trazabilidad efectivo para identificar el origen de la carne bovina en el contexto de la importación de carne en el mercado chino y en particular en el comercio entre Argentina y China.Fil: Ripoli, María Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Genética Veterinaria "Ingeniero Fernando Noel Dulout"; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Wei, S.. Chinese Academy of Agricultural Sciences; ChinaFil: Rogberg Muñoz, Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Genética Veterinaria "Ingeniero Fernando Noel Dulout"; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Guo, B. L.. Chinese Academy of Agricultural Sciences; ChinaFil: Goszczynski, Daniel Estanislao. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Genética Veterinaria "Ingeniero Fernando Noel Dulout"; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Fernandez, María Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Genética Veterinaria "Ingeniero Fernando Noel Dulout"; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Melucci, L.. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires. Estación Experimental Agropecuaria Balcarce; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; ArgentinaFil: Liron, Juan Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Genética Veterinaria "Ingeniero Fernando Noel Dulout"; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Villarreal, E.. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires. Estación Experimental Agropecuaria Balcarce; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; ArgentinaFil: Wei, Y. M.. Chinese Academy of Agricultural Sciences; ChinaFil: Giovambattista, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Genética Veterinaria "Ingeniero Fernando Noel Dulout"; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentin

Screening by symmetry of long-range hydrodynamic interactions of polymers confined in sheets

Hydrodynamic forces may significantly affect the motion of polymers. In sheet-like cavities, such as the cell's cytoplasm and microfluidic channels, the hydrodynamic forces are long-range. It is therefore expected that that hydrodynamic interactions will dominate the motion of polymers in sheets and will be manifested by Zimm-like scaling. Quite the opposite, we note here that although the hydrodynamic forces are long-range their overall effect on the motion of polymers vanishes due to the symmetry of the two-dimensional flow. As a result, the predicted scaling of experimental observables such as the diffusion coefficient or the rotational diffusion time is Rouse-like, in accord with recent experiments. The effective screening validates the use of the non-interacting blobs picture for polymers confined in a sheet.Comment: http://www.weizmann.ac.il/complex/tlusty/papers/Macromolecules2006.pdf http://pubs.acs.org/doi/abs/10.1021/ma060251