70 research outputs found

    Absolutely stable proton and lowering the gauge unification scale

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    A unified model is constructed, based on flipped SU(5) in which the proton is absolutely stable. The model requires the existence of new leptons with masses of order the weak scale. The possibility that the unification scale could be extremely low is discussed

    Genetic association of CDC2 with cerebrospinal fluid tau in Alzheimer's disease

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    We have recently reported that a polymorphism in the cell division cycle (CDC2) gene, designated Ex6 + 7I/D, is associated with Alzheimer's disease (AD). The CDC2 gene is located on chromosome 10q21.1 close to the marker D10S1225 linked to AD. Active cdc2 accumulates in neurons containing neurofibrillary tangles (NFT), a process that can precede the formation of NFT. Therefore, CDC2 is a promising candidate susceptibility gene for AD. We investigated the possible effects of the CDC2 polymorphism on cerebrospinal fluid (CSF) biomarkers in AD patients. CDC2 genotypes were evaluated in relation to CSF protein levels of total tau, phospho-tau and beta-amyloid (1-42) in AD patients and control individuals, and in relation to the amount of senile plaques and NFT in the frontal cortex and in the hippocampus in patients with autopsy-proven AD and controls. The CDC2 Ex6 + 7I allele was associated with a gene dose-dependent increase of CSF total tau levels (F-2,F- 626 = 7.0, p = 0.001) and the homozygous CDC2Ex6 +7II genotype was significantly more frequent among AD patients compared to controls (p = 0.006, OR = 1.57, 95% CI 1.13-2.17). Our results provide further evidence for an involvement of cdc2 in the pathogenesis of AD. Copyright (C) 2005 S. Karger AG, Basel

    SU(7) Unification of SU(3)_C*SU(4)_W* U(1)_{B-L}

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    We propose the SUSY SU(7) unification of the SU(3)_C* SU(4)_W* U(1)_{B-L} model. Such unification scenario has rich symmetry breaking chains in a five-dimensional orbifold. We study in detail the SUSY SU(7) symmetry breaking into SU(3)_C* SU(4)_W* U(1)_{B-L} by boundary conditions in a Randall-Sundrum background and its AdS/CFT interpretation. We find that successful gauge coupling unification can be achieved in our scenario. Gauge unification favors low left-right and unification scales with tree-level \sin^2\theta_W=0.15. We use the AdS/CFT dual of the conformal supersymmetry breaking scenario to break the remaining N=1 supersymmetry. We employ AdS/CFT to reproduce the NSVZ formula and obtain the structure of the Seiberg duality in the strong coupling region for 3/2N_c<N_F<3N_C. We show that supersymmetry is indeed broken in the conformal supersymmetry breaking scenario with a vanishing singlet vacuum expectation value.Comment: 25 pages, 1 figure

    The Cosmology of Composite Inelastic Dark Matter

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    Composite dark matter is a natural setting for implementing inelastic dark matter - the O(100 keV) mass splitting arises from spin-spin interactions of constituent fermions. In models where the constituents are charged under an axial U(1) gauge symmetry that also couples to the Standard Model quarks, dark matter scatters inelastically off Standard Model nuclei and can explain the DAMA/LIBRA annual modulation signal. This article describes the early Universe cosmology of a minimal implementation of a composite inelastic dark matter model where the dark matter is a meson composed of a light and a heavy quark. The synthesis of the constituent quarks into dark mesons and baryons results in several qualitatively different configurations of the resulting dark matter hadrons depending on the relative mass scales in the system.Comment: 31 pages, 4 figures; references added, typos correcte

    Sparticle mass spectra from SU(5) SUSY GUT models with bτb-\tau Yukawa coupling unification

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    Supersymmetric grand unified models based on the gauge group SU(5) often require in addition to gauge coupling unification, the unification of b-quark and τ\tau-lepton Yukawa couplings. We examine SU(5) SUSY GUT parameter space under the condition of bτb-\tau Yukawa coupling unification using 2-loop MSSM RGEs including full 1-loop threshold effects. The Yukawa-unified solutions break down into two classes. Solutions with low tan\beta ~3-11 are characterized by gluino mass ~1-4 TeV and squark mass ~1-5 TeV. Many of these solutions would be beyond LHC reach, although they contain a light Higgs scalar with mass <123 GeV and so may be excluded should the LHC Higgs hint persist. The second class of solutions occurs at large tan\beta ~35-60, and are a subset of tbτt-b-\tau unified solutions. Constraining only bτb-\tau unification to ~5% favors a rather light gluino with mass ~0.5-2 TeV, which should ultimately be accessible to LHC searches. While our bτb-\tau unified solutions can be consistent with a picture of neutralino-only cold dark matter, invoking additional moduli or Peccei-Quinn superfields can allow for all of our Yukawa-unified solutions to be consistent with the measured dark matter abundance.Comment: 19 pages, 5 figures, 1 table, PDFLate

    miRNeye: a microRNA expression atlas of the mouse eye

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    <p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) are key regulators of biological processes. To define miRNA function in the eye, it is essential to determine a high-resolution profile of their spatial and temporal distribution.</p> <p>Results</p> <p>In this report, we present the first comprehensive survey of miRNA expression in ocular tissues, using both microarray and RNA <it>in situ </it>hybridization (ISH) procedures. We initially determined the expression profiles of miRNAs in the retina, lens, cornea and retinal pigment epithelium of the adult mouse eye by microarray. Each tissue exhibited notably distinct miRNA enrichment patterns and cluster analysis identified groups of miRNAs that showed predominant expression in specific ocular tissues or combinations of them. Next, we performed RNA ISH for over 220 miRNAs, including those showing the highest expression levels by microarray, and generated a high-resolution expression atlas of miRNAs in the developing and adult wild-type mouse eye, which is accessible in the form of a publicly available web database. We found that 122 miRNAs displayed restricted expression domains in the eye at different developmental stages, with the majority of them expressed in one or more cell layers of the neural retina.</p> <p>Conclusions</p> <p>This analysis revealed miRNAs with differential expression in ocular tissues and provided a detailed atlas of their tissue-specific distribution during development of the murine eye. The combination of the two approaches offers a valuable resource to decipher the contributions of specific miRNAs and miRNA clusters to the development of distinct ocular structures.</p

    Cytosolic NADPH balancing in Penicillium chrysogenum cultivated on mixtures of glucose and ethanol

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    The in vivo flux through the oxidative branch of the pentose phosphate pathway (oxPPP) in Penicillium chrysogenum was determined during growth in glucose/ethanol carbon-limited chemostat cultures, at the same growth rate. Non-stationary 13C flux analysis was used to measure the oxPPP flux. A nearly constant oxPPP flux was found for all glucose/ethanol ratios studied. This indicates that the cytosolic NADPH supply is independent of the amount of assimilated ethanol. The cofactor assignment in the model of van Gulik et al. (Biotechnol Bioeng 68(6):602–618, 2000) was supported using the published genome annotation of P. chrysogenum. Metabolic flux analysis showed that NADPH requirements in the cytosol remain nearly the same in these experiments due to constant biomass growth. Based on the cytosolic NADPH balance, it is known that the cytosolic aldehyde dehydrogenase in P. chrysogenum is NAD +  dependent. Metabolic modeling shows that changing the NAD + -aldehyde dehydrogenase to NADP + -aldehyde dehydrogenase can increase the penicillin yield on substrate

    Systems Biology by the Rules: Hybrid Intelligent Systems for Pathway Modeling and Discovery

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    Background: Expert knowledge in journal articles is an important source of data for reconstructing biological pathways and creating new hypotheses. An important need for medical research is to integrate this data with high throughput sources to build useful models that span several scales. Researchers traditionally use mental models of pathways to integrate information and development new hypotheses. Unfortunately, the amount of information is often overwhelming and these are inadequate for predicting the dynamic response of complex pathways. Hierarchical computational models that allow exploration of semi-quantitative dynamics are useful systems biology tools for theoreticians, experimentalists and clinicians and may provide a means for cross-communication. Results: A novel approach for biological pathway modeling based on hybrid intelligent systems or soft computing technologies is presented here. Intelligent hybrid systems, which refers to several related computing methods such as fuzzy logic, neural nets, genetic algorithms, and statistical analysis, has become ubiquitous in engineering applications for complex control system modeling and design. Biological pathways may be considered to be complex control systems, which medicine tries to manipulate to achieve desired results. Thus, hybrid intelligent systems may provide a useful tool for modeling biological system dynamics and computational exploration of new drug targets. A new modeling approach based on these methods is presented in the context of hedgehog regulation of the cell cycle in granule cells. Code and input files can be found at the Bionet website: www.chip.ord/~wbosl/Software/Bionet. Conclusion: This paper presents the algorithmic methods needed for modeling complicated biochemical dynamics using rule-based models to represent expert knowledge in the context of cell cycle regulation and tumor growth. A notable feature of this modeling approach is that it allows biologists to build complex models from their knowledge base without the need to translate that knowledge into mathematical form. Dynamics on several levels, from molecular pathways to tissue growth, are seamlessly integrated. A number of common network motifs are examined and used to build a model of hedgehog regulation of the cell cycle in cerebellar neurons, which is believed to play a key role in the etiology of medulloblastoma, a devastating childhood brain cancer
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