300 research outputs found

    Terminal Antenna Design

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    This paper introduces first some general considerations about antenna miniaturization and multi-band terminal antenna design. These general design principles are then illustrated on some practical applications

    Entropy, Dynamics and Instantaneous Normal Modes in a Random Energy Model

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    It is shown that the fraction f of imaginary frequency instantaneous normal modes (INM) may be defined and calculated in a random energy model(REM) of liquids. The configurational entropy S and the averaged hopping rate among the states R are also obtained and related to f, with the results R~f and S=a+b*ln(f). The proportionality between R and f is the basis of existing INM theories of diffusion, so the REM further confirms their validity. A link to S opens new avenues for introducing INM into dynamical theories. Liquid 'states' are usually defined by assigning a configuration to the minimum to which it will drain, but the REM naturally treats saddle-barriers on the same footing as minima, which may be a better mapping of the continuum of configurations to discrete states. Requirements of a detailed REM description of liquids are discussed

    A severe case of refractory esophageal stenosis induced by nivolumab and responding to tocilizumab therapy.

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    The prevalence of esophageal stenosis caused by immune checkpoint inhibitors in the context of induced immune mucositis and esophagitis is extremely rare. We report the case of a patient with stage IV pulmonary adenocarcinoma treated for 6 months with nivolumab who developed bilateral sterile conjunctivitis followed by oropharyngeal mucositis and esophagitis complicated by a severe esophageal stenosis. The laryngeal margin and hypopharyngeal mucosa appeared highly inflammatory with fibrinous deposits. Esophagogastroduodenoscopy revealed mucositis with a scar-like structure immediately below the upper esophageal sphincter with nonulcerative mucosa and an inflammatory aspect of the entire esophagus. No involvement of the stomach was observed. Oropharynx biopsies displayed marked lymphocytic T cell-infiltration with several foci of monocellular necrosis in the squamous epithelium. No morphologic evidence of adenocarcinoma and no signs of mycotic, bacterial or viral infection were noted. A blood sample revealed a discrete increase in the erythrocyte sedimentation rate (ESR) with no eosinophilia or leukocytosis. Liver and kidney function panel tests were normal. A thoracoabdominal CT scan reported no evidence of disease recurrence. Despite multiple boluses of methylprednisolone and high doses of prednisone continued for several months, the patient experienced very rapid symptomatological reappearance during three steroid tapering attempts and aggravation of his esophageal stenosis to an aphagic stage, requiring a nasogastric tube. This long course of high-dose corticosteroid treatment was complicated with osteoporosis-induced fractures with several spontaneous compressions of thoracolumbar vertebrae requiring an enlarged T10 to L5 cementoplasty. Anti-IL-6 blockade therapy with tocilizumab resulted in excellent clinical response, allowing the total resolution of the immune-related adverse events (irAEs) and leading to successful steroid tapering. Herein, we describe the first case of a patient who developed autoimmune mucositis and esophagitis complicated by a severe refractory esophageal stenosis induced during treatment by nivolumab, which completely resolved after personalized treatment with tocilizumab, suggesting a role of IL-6 blockade in the management of severe steroid refractory esophageal stenosis and more broadly in refractory immune-related adverse events

    APC1638T: a mouse model delineating critical domains of the adenomatous polyposis coli protein involved in tumorigenesis and development

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    This is the publisher's version, also available electronically from "http://genesdev.cshlp.org".The adenomatous polyposis coli (APC) gene is considered as the true gatekeeper of colonic epithelial proliferation: It is mutated in the majority of colorectal tumors, and mutations occur at early stages of tumor development in mouse and man. These mutant proteins lack most of the seven 20-amino-acid repeats and all SAMP motifs that have been associated with down-regulation of intracellular β-catenin levels. In addition, they lack the carboxy-terminal domains that bind to DLG, EB1, and microtubulin. APC also appears to be essential in development because homozygosity for mouse Apcmutations invariably results in early embryonic lethality. Here, we describe the generation of a mouse model carrying a targeted mutation at codon 1638 of the mouse Apc gene, Apc1638T, resulting in a truncated Apc protein encompassing three of the seven 20 amino acid repeats and one SAMP motif, but missing all of the carboxy-terminal domains thought to be associated with tumorigenesis. Surprisingly, homozygosity for the Apc1638T mutation is compatible with postnatal life. However, homozygous mutant animals are characterized by growth retardation, a reduced postnatal viability on the B6 genetic background, the absence of preputial glands, and the formation of nipple-associated cysts. Most importantly,Apc 1638T/1638T animals that survive to adulthood are tumor free. Although the full complement of Apc1638T is sufficient for proper β-catenin signaling, dosage reductions of the truncated protein result in increasingly severe defects in β-catenin regulation. The SAMP motif retained in Apc1638T also appears to be important for this function as shown by analysis of the Apc1572T protein in which its targeted deletion results in a further reduction in the ability of properly controlling β-catenin/Tcf signaling. These results indicate that the association with DLG, EB1, and microtubulin is less critical for the maintenance of homeostasis by APC than has been suggested previously, and that proper β-catenin regulation by APC appears to be required for normal embryonic development and tumor suppression

    Phenotypic and molecular assessment of seven patients with 6p25 deletion syndrome: Relevance to ocular dysgenesis and hearing impairment

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    BACKGROUND: Thirty-nine patients have been described with deletions involving chromosome 6p25. However, relatively few of these deletions have had molecular characterization. Common phenotypes of 6p25 deletion syndrome patients include hydrocephalus, hearing loss, and ocular, craniofacial, skeletal, cardiac, and renal malformations. Molecular characterization of deletions can identify genes that are responsible for these phenotypes. METHODS: We report the clinical phenotype of seven patients with terminal deletions of chromosome 6p25 and compare them to previously reported patients. Molecular characterization of the deletions was performed using polymorphic marker analysis to determine the extents of the deletions in these seven 6p25 deletion syndrome patients. RESULTS: Our results, and previous data, show that ocular dysgenesis and hearing impairment are the two most highly penetrant phenotypes of the 6p25 deletion syndrome. While deletion of the forkhead box C1 gene (FOXC1) probably underlies the ocular dysgenesis, no gene in this region is known to be involved in hearing impairment. CONCLUSIONS: Ocular dysgenesis and hearing impairment are the two most common phenotypes of 6p25 deletion syndrome. We conclude that a locus for dominant hearing loss is present at 6p25 and that this locus is restricted to a region distal to D6S1617. Molecular characterization of more 6p25 deletion patients will aid in refinement of this locus and the identification of a gene involved in dominant hearing loss

    Mean-atom-trajectory model for the velocity autocorrelation function of monatomic liquids

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    We present a model for the motion of an average atom in a liquid or supercooled liquid state and apply it to calculations of the velocity autocorrelation function Z(t)Z(t) and diffusion coefficient DD. The model trajectory consists of oscillations at a distribution of frequencies characteristic of the normal modes of a single potential valley, interspersed with position- and velocity-conserving transits to similar adjacent valleys. The resulting predictions for Z(t)Z(t) and DD agree remarkably well with MD simulations of Na at up to almost three times its melting temperature. Two independent processes in the model relax velocity autocorrelations: (a) dephasing due to the presence of many frequency components, which operates at all temperatures but which produces no diffusion, and (b) the transit process, which increases with increasing temperature and which produces diffusion. Because the model provides a single-atom trajectory in real space and time, including transits, it may be used to calculate all single-atom correlation functions.Comment: LaTeX, 8 figs. This is an updated version of cond-mat/0002057 and cond-mat/0002058 combined Minor changes made to coincide with published versio

    Fragmented in space: the oral history narrative of an Arab Christian from Antioch, Turkey

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    This study uses the case of Can Kılçıksız, an Arab Christian refugee youth from Antioch, Turkey, to argue that globalization may result in fragmented families and subjectivities and can also accelerate processes initiated by modernity and the construction of national identities. Can Kılçıksız and his siblings now live in Turkey, Germany, France and Finland. His life story suggests that males of Arab Christian origin from Antioch who had access to schooling are more likely to be involved in politics whereas females tend to be drawn to evangelical Christian organizations. The case also suggests that sibling ties might prove more durable in the course of transnational migration than conjugal ties. The case of Can Kılçıksız shows that the time/space linked to childhood through memory can play an important role in identity construction of subjects circulating in transnational space

    Cohesin complex-associated holoprosencephaly

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    Marked by incomplete division of the embryonic forebrain, holoprosencephaly is one of the most common human developmental disorders. Despite decades of phenotype-driven research, 80–90% of aneuploidy-negative holoprosencephaly individuals with a probable genetic aetiology do not have a genetic diagnosis. Here we report holoprosencephaly associated with variants in the two X-linked cohesin complex genes, STAG2 and SMC1A, with loss-of-function variants in 10 individuals and a missense variant in one. Additionally, we report four individuals with variants in the cohesin complex genes that are not X-linked, SMC3 and RAD21. Using whole mount in situ hybridization, we show that STAG2 and SMC1A are expressed in the prosencephalic neural folds during primary neurulation in the mouse, consistent with forebrain morphogenesis and holoprosencephaly pathogenesis. Finally, we found that shRNA knockdown of STAG2 and SMC1A causes aberrant expression of HPE-associated genes ZIC2, GLI2, SMAD3 and FGFR1 in human neural stem cells. These findings show the cohesin complex as an important regulator of median forebrain development and X-linked inheritance patterns in holoprosencephaly

    Assessing road effects on bats: the role of landscape, road features, and bat activity on road-kills

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    Recent studies suggest that roads can significantly impact bat populations. Though bats are one of the most threatened groups of European vertebrates, studies aiming to quantify bat mortality and determine the main factors driving it remain scarce. Between March 16 and October 31 of 2009, we surveyed road-killed bats daily along a 51-km-long transect that incorporates different types of roads in southern Portugal. We found 154 road-killed bats of 11 species. The two most common species in the study area, Pipistrellus kuhlii and P. pygmaeus, were also the most commonly identified road-kill, representing 72 % of the total specimens collected. About two-thirds of the total mortality occurred between mid July and late September, peaking in the second half of August. We also recorded casualties of threatened and rare species, including Miniopterus schreibersii, Rhinolophus ferrumequinum, R. hipposideros, Barbastella barbastellus, and Nyctalus leisleri. These species were found mostly in early autumn, corresponding to the mating and swarming periods. Landscape features were the most important variable subset for explaining bat casualties. Road stretches crossing or in the vicinity of high-quality habitats for bats—including dense Mediterranean woodland (‘‘montado’’) areas, water courses with riparian gallery, and water reservoirs—yielded a significantly higher number of casualties. Additionally, more roadkilled bats were recorded on high-traffic road stretches with viaducts, in areas of higher bat activity and near known roosts

    The Cytoplasmic Location of Chicken Mx Is Not the Determining Factor for Its Lack of Antiviral Activity

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    Chicken Mx belongs to the Mx family of interferon-induced dynamin-like GTPases, which in some species possess potent antiviral properties. Conflicting data exist for the antiviral capability of chicken Mx. Reports of anti-influenza activity of alleles encoding an Asn631 polymorphism have not been supported by subsequent studies. The normal cytoplasmic localisation of chicken Mx may influence its antiviral capacity. Here we report further studies to determine the antiviral potential of chicken Mx against Newcastle disease virus (NDV), an economically important cytoplasmic RNA virus of chickens, and Thogoto virus, an orthomyxovirus known to be exquisitely sensitive to the cytoplasmic MxA protein from humans. We also report the consequences of re-locating chicken Mx to the nucleus.Chicken Mx was tested in virus infection assays using NDV. Neither the Asn631 nor Ser631 Mx alleles (when transfected into 293T cells) showed inhibition of virus-directed gene expression when the cells were subsequently infected with NDV. Human MxA however did show significant inhibition of NDV-directed gene expression. Chicken Mx failed to inhibit a Thogoto virus (THOV) minireplicon system in which the cytoplasmic human MxA protein showed potent and specific inhibition. Relocalisation of chicken Mx to the nucleus was achieved by inserting the Simian Virus 40 large T antigen nuclear localisation sequence (SV40 NLS) at the N-terminus of chicken Mx. Nuclear re-localised chicken Mx did not inhibit influenza (A/PR/8/34) gene expression during virus infection in cell culture or influenza polymerase activity in A/PR/8/34 or A/Turkey/50-92/91 minireplicon systems.The chicken Mx protein (Asn631) lacks inhibitory effects against THOV and NDV, and is unable to suppress influenza replication when artificially re-localised to the cell nucleus. Thus, the natural cytoplasmic localisation of the chicken Mx protein does not account for its lack of antiviral activity
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