2,157 research outputs found

    Binding of Integrin α6β4 to Plectin Prevents Plectin Association with F-Actin but Does Not Interfere with Intermediate Filament Binding

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    Hemidesmosomes are stable adhesion complexes in basal epithelial cells that provide a link between the intermediate filament network and the extracellular matrix. We have investigated the recruitment of plectin into hemidesmosomes by the α6β4 integrin and have shown that the cytoplasmic domain of the β4 subunit associates with an NH2-terminal fragment of plectin that contains the actin-binding domain (ABD). When expressed in immortalized plectin-deficient keratinocytes from human patients with epidermol- ysis bullosa (EB) simplex with muscular dystrophy (MD-EBS), this fragment is colocalized with α6β4 in basal hemidesmosome-like clusters or associated with F-actin in stress fibers or focal contacts. We used a yeast two-hybrid binding assay in combination with an in vitro dot blot overlay assay to demonstrate that β4 interacts directly with plectin, and identified a major plectin-binding site on the second fibronectin type III repeat of the β4 cytoplasmic domain. Mapping of the β4 and actin-binding sites on plectin showed that the binding sites overlap and are both located in the plectin ABD. Using an in vitro competition assay, we could show that β4 can compete out the plectin ABD fragment from its association with F-actin. The ability of β4 to prevent binding of F-actin to plectin explains why F-actin has never been found in association with hemidesmosomes, and provides a molecular mechanism for a switch in plectin localization from actin filaments to basal intermediate filament–anchoring hemidesmosomes when β4 is expressed. Finally, by mapping of the COOH-terminally located binding site for several different intermediate filament proteins on plectin using yeast two-hybrid assays and cell transfection experiments with MD-EBS keratinocytes, we confirm that plectin interacts with different cytoskeletal networks

    Entropic uncertainty relations for electromagnetic beams

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    The symplectic tomograms of 2D Hermite--Gauss beams are found and expressed in terms of the Hermite polynomials squared. It is shown that measurements of optical-field intensities may be used to determine the tomograms of electromagnetic-radiation modes. Furthermore, entropic uncertainty relations associated with these tomograms are found and applied to establish the compatibility conditions of the the field profile properties with Hermite--Gauss beam description. Numerical evaluations for some Hermite--Gauss modes illustrating the corresponding entropic uncertainty relations are finally given.Comment: Invited talk at the XV Central European Workshop on Quantum Optics (Belgrade, Serbia, 30 May -- 3 June 2008), to appear in Physica Scripta

    Stochastic collective dynamics of charged--particle beams in the stability regime

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    We introduce a description of the collective transverse dynamics of charged (proton) beams in the stability regime by suitable classical stochastic fluctuations. In this scheme, the collective beam dynamics is described by time--reversal invariant diffusion processes deduced by stochastic variational principles (Nelson processes). By general arguments, we show that the diffusion coefficient, expressed in units of length, is given by λcN\lambda_c\sqrt{N}, where NN is the number of particles in the beam and λc\lambda_c the Compton wavelength of a single constituent. This diffusion coefficient represents an effective unit of beam emittance. The hydrodynamic equations of the stochastic dynamics can be easily recast in the form of a Schr\"odinger equation, with the unit of emittance replacing the Planck action constant. This fact provides a natural connection to the so--called ``quantum--like approaches'' to beam dynamics. The transition probabilities associated to Nelson processes can be exploited to model evolutions suitable to control the transverse beam dynamics. In particular we show how to control, in the quadrupole approximation to the beam--field interaction, both the focusing and the transverse oscillations of the beam, either together or independently.Comment: 15 pages, 9 figure

    Angiographic assessment of reperfusion in acute myocardial infarction by myocardial blush grade

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    Background-Angiographic successful reperfusion in acute myocardial infarction has been defined as TIMI 3 flow. However, TIMI 3 flow does not always result in effective myocardial reperfusion. Myocardial blush grade (MBG) is an angiographic measure of myocardial perfusion. We hypothesized that optimal angiographic reperfusion is defined by TIMI 3 flow and MBG 2 or 3. Methods and Results-In 924 consecutive patients with TIMI 3 flow after angioplasty for acute myocardial infarction, we prospectively studied the value of MBG. End points were death, MACE, enzymatic infarct size, and residual left ventricular ejection fraction. Follow-up was 16+/-11 months. Of the 924 patients, 101 (11%) patients had MBG 0 or 1. Mortality was significantly higher in patients with MBG 0 or 1 compared with patients with MBG 2 or 3 (relative risk, 4.7; 95% CI, 2.3 to 9.5; P Conclusions -MBG is a strong angiographic predictor of mortality in patients with TIMI 3 flow after primary angioplasty. Enzymatic infarct size is larger and residual left ventricular ejection fraction is lower in patients with MBG 0 or 1 compared with MBG 2 or 3. Angiographic definition of successful reperfusion should include both TIMI 3 flow as well as MBG 2 or 3

    How character limit affects language usage in tweets

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    In November 2017 Twitter doubled the available character space from 140 to 280 characters. This provided an opportunity for researchers to investigate the linguistic effects of length constraints in online communication. We asked whether the character limit change (CLC) affected language usage in Dutch tweets and hypothesized that there would be a reduction in the need for character-conserving writing styles. Pre-CLC tweets were compared with post-CLC tweets. Three separate analyses were performed: (I) general analysis: the number of characters, words, and sentences per tweet, as well as the average word and sentence length. (II) Token analysis: the relative frequency of tokens and bigrams; (III) part-of-speech analysis: the grammatical structure of the sentences in tweets (i.e., adjectives, adverbs, articles, conjunctives, interjections, nouns, prepositions, pronouns, and verbs); pre-CLC tweets showed relatively more textisms, which are used to abbreviate and conserve character space. Consequently, they represent more informal language usage (e.g., internet slang); in turn, post-CLC tweets contained relatively more articles, conjunctions, and prepositions. The results show that online language producers adapt their texts to overcome limit constraints

    PerR controls oxidative stress defence and aerotolerance but not motility-associated phenotypes of Campylobacter jejuni

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    The foodborne bacterial pathogen Campylobacter jejuni is an obligate microaerophile, which is exposed to atmospheric oxygen during transmission through the food chain. Survival under aerobic conditions requires the concerted control of oxidative stress systems, which in C. jejuni are intimately connected with iron metabolism via the PerR and Fur regulatory proteins. Here we have characterised the roles of C. jejuni PerR in oxidative stress- and motility phenotypes, and its regulon at the level of transcription, protein expression and promoter interactions. Insertional inactivation of perR in the C. jejuni reference strains NCTC 11168, 81-176 and 81116 did not result in any growth deficiencies, but strongly increased survival in atmospheric oxygen conditions, and allowed growth around filter discs infused with up to 30% H2O2 (8.8 M). Expression of catalase, alkyl hydroperoxide reductase, thioredoxin reductase and the Rrc desulforubrerythrin were increased in the perR mutant, and this was mediated at the transcriptional level as shown by electrophoretic mobility shift assays of the katA, ahpC and trxB promoters using purified PerR. Differential RNA-seq analysis of a fur perR mutant allowed the identification of eight previously unknown transcription start sites of genes controlled by either Fur and/or PerR. Finally, inactivation of perR in C. jejuni did not result in reduced motility, and did not reduce killing of Galleria melonella wax moth larvae. In conclusion, PerR plays an important role in controlling oxidative stress resistance and aerobic survival of C. jejuni, but this role does not extend into control of motility and associated phenotypes

    Innovative treatment modalities for urinary incontinence: a European survey identifying experience and attitude of healthcare providers

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    Introduction and hypothesis Urinary incontinence is a common condition in women, with a reported prevalence ranging from 25% to 51%. Of these women, an estimated 38% suffer from stress urinary incontinence (SUI). A European research consortium is investigating an innovative system based on information and communication technology for the conservative treatment of women with SUI. When introducing a new intervention, implementation barriers arise and need to be identified. Therefore, we investigated healthcare providers’ experience with and attitude towards innovative care options. Methods We performed an online survey to assess (1) the characteristics and practice of healthcare providers, (2) current protocols for SUI, (3) current use of biofeedback, and (4) knowledge about serious gaming. The survey was sent to members of professional societies in Europe (EUGA), UK (BSUG) and The Netherlands (DPFS). Results Of 341 questionnaires analyzed (response rate between 18% and 30%), 64% of the respondents had access to a protocol for the treatment of SUI, and 31% used biofeedback when treating patients with SUI. However, 92% considered that biofeedback has a clear or probable added value, and 97% of those who did not use biofeedback would change their practice if research evidence supported its use. Finally, 89% of respondents indicated that they had no experience of serious gaming, but 92% considered that it could be useful. Conclusions Although inexperienced, European urogynecologists and physical therapists welcome innovative treatment options for the conservative treatment of SUI such as portable wireless biofeedback and serious gaming. Scientific evidence is considered a prerequisite to incorporate such innovations into clinical practice.Peer ReviewedPostprint (published version
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