189 research outputs found

    Flavor Structure in F-theory Compactifications

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    F-theory is one of frameworks in string theory where supersymmetric grand unification is accommodated, and all the Yukawa couplings and Majorana masses of right-handed neutrinos are generated. Yukawa couplings of charged fermions are generated at codimension-3 singularities, and a contribution from a given singularity point is known to be approximately rank 1. Thus, the approximate rank of Yukawa matrices in low-energy effective theory of generic F-theory compactifications are minimum of either the number of generations N_gen = 3 or the number of singularity points of certain types. If there is a geometry with only one E_6 type point and one D_6 type point over the entire 7-brane for SU(5) gauge fields, F-theory compactified on such a geometry would reproduce approximately rank-1 Yukawa matrices in the real world. We found, however, that there is no such geometry. Thus, it is a problem how to generate hierarchical Yukawa eigenvalues in F-theory compactifications. A solution in the literature so far is to take an appropriate factorization limit. In this article, we propose an alternative solution to the hierarchical structure problem (which requires to tune some parameters) by studying how zero mode wavefunctions depend on complex structure moduli. In this solution, the N_gen x N_gen CKM matrix is predicted to have only N_gen entries of order unity without an extra tuning of parameters, and the lepton flavor anarchy is predicted for the lepton mixing matrix. We also obtained a precise description of zero mode wavefunctions near the E_6 type singularity points, where the up-type Yukawa couplings are generated.Comment: 148 page

    Expression of Drosophila Adenosine Deaminase in Immune Cells during Inflammatory Response

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    Extra-cellular adenosine is an important regulator of inflammatory responses. It is generated from released ATP by a cascade of ectoenzymes and degraded by adenosine deaminase (ADA). There are two types of enzymes with ADA activity: ADA1 and ADGF/ADA2. ADA2 activity originates from macrophages and dendritic cells and is associated with inflammatory responses in humans and rats. Drosophila possesses a family of six ADGF proteins with ADGF-A being the main regulator of extra-cellular adenosine during larval stages. Herein we present the generation of a GFP reporter for ADGF-A expression by a precise replacement of the ADGF-A coding sequence with GFP using homologous recombination. We show that the reporter is specifically expressed in aggregating hemocytes (Drosophila immune cells) forming melanotic capsules; a characteristic of inflammatory response. Our vital reporter thus confirms ADA expression in sites of inflammation in vivo and demonstrates that the requirement for ADA activity during inflammatory response is evolutionary conserved from insects to vertebrates. Our results also suggest that ADA activity is achieved specifically within sites of inflammation by an uncharacterized post-transcriptional regulation based mechanism. Utilizing various mutants that induce melanotic capsule formation and also a real immune challenge provided by parasitic wasps, we show that the acute expression of the ADGF-A protein is not driven by one specific signaling cascade but is rather associated with the behavior of immune cells during the general inflammatory response. Connecting the exclusive expression of ADGF-A within sites of inflammation, as presented here, with the release of energy stores when the ADGF-A activity is absent, suggests that extra-cellular adenosine may function as a signal for energy allocation during immune response and that ADGF-A/ADA2 expression in such sites of inflammation may regulate this role

    Endocytosis of plasma-derived factor V by megakaryocytes occurs via a clathrin-dependent, specific membrane binding event

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    Megakaryocytes were analyzed for their ability to endocytose factor V to define the cellular mechanisms regulating this process. In contrast to fibrinogen, factor V was endocytosed by megakaryocytes derived from CD34 + cells or megakaryocyte-like cell lines, but not by platelets. CD41 + ex vivo -derived megakaryocytes endocytosed factor V, as did subpopulations of the megakaryocyte-like cells MEG-01, and CMK. Similar observations were made for fibrinogen. Phorbol diester-induced megakaryocytic differentiation of the cell lines resulted in a substantial increase in endocytosis of both proteins as compared to untreated cells that did not merely reflect their disparate plasma concentrations. Factor IX, which does not associate with platelets or megakaryocytes, was not endocytosed by any of the cells examined. Endocytosis of factor V by megakaryocytes proceeds through a specific and independent mechanism as CHRF-288 cells endocytosed fibrinogen but not factor V, and the presence of other plasma proteins had no effect on the endocytosis of factor V by MEG-01 cells. Furthermore, as the endocytosis of factor V was also demonstrated to occur through a clathrin-dependent mechanism, these combined data demonstrate that endocytosis of factor V by megakaryocytes occurs via a specific, independent, and most probably receptor-mediated, event.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75473/1/j.1538-7836.2005.01190.x.pd

    Emergent Dark Matter, Baryon, and Lepton Numbers

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    We present a new mechanism for transferring a pre-existing lepton or baryon asymmetry to a dark matter asymmetry that relies on mass mixing which is dynamically induced in the early universe. Such mixing can succeed with only generic scales and operators and can give rise to distinctive relationships between the asymmetries in the two sectors. The mixing eliminates the need for the type of additional higher-dimensional operators that are inherent to many current asymmetric dark matter models. We consider several implementations of this idea. In one model, mass mixing is temporarily induced during a two-stage electroweak phase transition in a two Higgs doublet model. In the other class of models, mass mixing is induced by large field vacuum expectation values at high temperatures - either moduli fields or even more generic kinetic terms. Mass mixing models of this type can readily accommodate asymmetric dark matter masses ranging from 1 GeV to 100 TeV and expand the scope of possible relationships between the dark and visible sectors in such models.Comment: 36 pages, 5 figure

    Rapid Enzymatic Response to Compensate UV Radiation in Copepods

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    Ultraviolet radiation (UVR) causes physical damage to DNA, carboxylation of proteins and peroxidation of lipids in copepod crustaceans, ubiquitous and abundant secondary producers in most aquatic ecosystems. Copepod adaptations for long duration exposures include changes in behaviour, changes in pigmentation and ultimately changes in morphology. Adaptations to short-term exposures are little studied. Here we show that short-duration exposure to UVR causes the freshwater calanoid copepod, Eudiaptomus gracilis, to rapidly activate production of enzymes that prevent widespread collateral peroxidation (glutathione S-transferase, GST), that regulate apoptosis cell death (Caspase-3, Casp-3), and that facilitate neurotransmissions (cholinesterase-ChE). None of these enzyme systems is alone sufficient, but they act in concert to reduce the stress level of the organism. The interplay among enzymatic responses provides useful information on how organisms respond to environmental stressors acting on short time scales

    Computational analyses of eukaryotic promoters

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    Computational analysis of eukaryotic promoters is one of the most difficult problems in computational genomics and is essential for understanding gene expression profiles and reverse-engineering gene regulation network circuits. Here I give a basic introduction of the problem and recent update on both experimental and computational approaches. More details may be found in the extended references. This review is based on a summer lecture given at Max Planck Institute at Berlin in 2005

    Atypical Balance between Occipital and Fronto-Parietal Activation for Visual Shape Extraction in Dyslexia

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    Reading requires the extraction of letter shapes from a complex background of text, and an impairment in visual shape extraction would cause difficulty in reading. To investigate the neural mechanisms of visual shape extraction in dyslexia, we used functional magnetic resonance imaging (fMRI) to examine brain activation while adults with or without dyslexia responded to the change of an arrow’s direction in a complex, relative to a simple, visual background. In comparison to adults with typical reading ability, adults with dyslexia exhibited opposite patterns of atypical activation: decreased activation in occipital visual areas associated with visual perception, and increased activation in frontal and parietal regions associated with visual attention. These findings indicate that dyslexia involves atypical brain organization for fundamental processes of visual shape extraction even when reading is not involved. Overengagement in higher-order association cortices, required to compensate for underengagment in lower-order visual cortices, may result in competition for top-down attentional resources helpful for fluent reading.Ellison Medical FoundationMartin Richmond Memorial FundNational Institutes of Health (U.S.). (Grant UL1RR025758)National Institutes of Health (U.S.). (Grant F32EY014750-01)MIT Class of 1976 (Funds for Dyslexia Research

    On the Importance of Complaint Handling Design : A Multi-Level Analysis of the Impact in Specific Complaint Situations

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    Given the large investments required for high-quality complaint handling design, managers need practical guidance in understanding its actual importance for their particular company. However, while prior research emphasizes the general relevance of complaint handling design, it fails to provide a more differentiated perspective on this interesting issue. This study, which is based on an integrative multi-level framework and a dyadic dataset, addresses this important gap in research. Results indicate that the impact of a company’s complaint handling design varies significantly depending on the characteristics of the complaining customers with which the firm has to deal. Further, this paper shows that, contingent on these characteristics, a company’s complaint handling design can shape complainants’ fairness perceptions either considerably or only slightly. Overall, findings suggest that companies should apply an adaptive approach to complaint handling to avoid misallocation of attention, energy, and resources

    Neoadjuvant treatment of pancreatic adenocarcinoma: a systematic review and meta-analysis of 5520 patients

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