205 research outputs found

    Domain walls and instantons in N=1, d=4 supergravity

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    We study the supersymmetric sources of (multi-) domain-wall and (multi-) instanton solutions of generic N=1, d=4 supergravities, that is: the worldvolume effective actions for said supersymmetric topological defects. The domain-wall solutions naturally couple to the two 3-forms recently found as part of the N=1, d=4 tensor hierarchy (i.e. they have two charges in general) and their tension is the absolute value of the superpotential section L. The introduction of sources (we study sources with finite and vanishing thickness) is equivalent to the introduction of local coupling constants and results in dramatic changes of the solutions. Our results call for a democratic reformulation of N=1,d=4 supergravity in which coupling constants are, off-shell, scalar fields. The effective actions for the instantons are always proportional to the coordinate orthogonal to the twist-free embedding of the null-geodesic (in the Wick-rotated scalar manifold) describing the instanton. We show their supersymmetry and find the associated supersymmetric (multi-) instanton solutions.Comment: 34 pages, 4 figures, references adde

    Hybrid Equation/Agent-Based Model of Ischemia-Induced Hyperemia and Pressure Ulcer Formation Predicts Greater Propensity to Ulcerate in Subjects with Spinal Cord Injury

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    Pressure ulcers are costly and life-threatening complications for people with spinal cord injury (SCI). People with SCI also exhibit differential blood flow properties in non-ulcerated skin. We hypothesized that a computer simulation of the pressure ulcer formation process, informed by data regarding skin blood flow and reactive hyperemia in response to pressure, could provide insights into the pathogenesis and effective treatment of post-SCI pressure ulcers. Agent-Based Models (ABM) are useful in settings such as pressure ulcers, in which spatial realism is important. Ordinary Differential Equation-based (ODE) models are useful when modeling physiological phenomena such as reactive hyperemia. Accordingly, we constructed a hybrid model that combines ODEs related to blood flow along with an ABM of skin injury, inflammation, and ulcer formation. The relationship between pressure and the course of ulcer formation, as well as several other important characteristic patterns of pressure ulcer formation, was demonstrated in this model. The ODE portion of this model was calibrated to data related to blood flow following experimental pressure responses in non-injured human subjects or to data from people with SCI. This model predicted a higher propensity to form ulcers in response to pressure in people with SCI vs. non-injured control subjects, and thus may serve as novel diagnostic platform for post-SCI ulcer formation. © 2013 Solovyev et al

    Rapid methods to detect organic mercury and total selenium in biological samples

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    <p>Abstract</p> <p>Background</p> <p>Organic mercury (Hg) is a global pollutant of concern and selenium is believed to afford protection against mercury risk though few approaches exist to rapidly assess both chemicals in biological samples. Here, micro-scale and rapid methods to detect organic mercury (< 1.5 ml total sample volume, < 1.5 hour) and total selenium (Se; < 3.0 ml total volume, < 3 hour) from a range of biological samples (10-50 mg) are described.</p> <p>Results</p> <p>For organic Hg, samples are digested using Tris-HCl buffer (with sequential additions of protease, NaOH, cysteine, CuSO<sub>4</sub>, acidic NaBr) followed by extraction with toluene and Na<sub>2</sub>S<sub>2</sub>O<sub>3</sub>. The final product is analyzed via commercially available direct/total mercury analyzers. For Se, a fluorometric assay has been developed for microplate readers that involves digestion (HNO<sub>3</sub>-HClO<sub>4 </sub>and HCl), conjugation (2,3-diaminonaphthalene), and cyclohexane extraction. Recovery of organic Hg (86-107%) and Se (85-121%) were determined through use of Standard Reference Materials and lemon shark kidney tissues.</p> <p>Conclusions</p> <p>The approaches outlined provide an easy, rapid, reproducible, and cost-effective platform for monitoring organic Hg and total Se in biological samples. Owing to the importance of organic Hg and Se in the pathophysiology of Hg, integration of such methods into established research monitoring efforts (that largely focus on screening total Hg only) will help increase understanding of Hg's true risks.</p

    Maharam-type kernel representation for operators with a trigonometric domination

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    [EN] Consider a linear and continuous operator T between Banach function spaces. We prove that under certain requirements an integral inequality for T is equivalent to a factorization of T through a specific kernel operator: in other words, the operator T has what we call a Maharam-type kernel representation. In the case that the inequality provides a domination involving trigonometric functions, a special factorization through the Fourier operator is given. We apply this result to study the problem that motivates the paper: the approximation of functions in L2[0, 1] by means of trigonometric series whose Fourier coefficients are given by weighted trigonometric integrals.This research has been supported by MTM2016-77054-C2-1-P (Ministerio de Economia, Industria y Competitividad, Spain).Sánchez Pérez, EA. (2017). Maharam-type kernel representation for operators with a trigonometric domination. Aequationes Mathematicae. 91(6):1073-1091. https://doi.org/10.1007/s00010-017-0507-6S10731091916Calabuig, J.M., Delgado, O., Sánchez Pérez, E.A.: Generalized perfect spaces. Indag. Math. 19(3), 359–378 (2008)Calabuig, J.M., Delgado, O., Sánchez Pérez, E.A.: Factorizing operators on Banach function spaces through spaces of multiplication operators. J. Math. Anal. Appl. 364, 88–103 (2010)Delgado, O., Sánchez Pérez, E.A.: Strong factorizations between couples of operators on Banach function spaces. J. Convex Anal. 20(3), 599–616 (2013)Dodds, P.G., Huijsmans, C.B., de Pagter, B.: Characterizations of conditional expectation type operators. Pacific J. Math. 141(1), 55–77 (1990)Flores, J., Hernández, F.L., Tradacete, P.: Domination problems for strictly singular operators and other related classes. Positivity 15(4), 595–616 (2011). 2011Fremlin, D.H.: Tensor products of Banach lattices. Math. Ann. 211, 87–106 (1974)Hu, G.: Weighted norm inequalities for bilinear Fourier multiplier operators. Math. Ineq. Appl. 18(4), 1409–1425 (2015)Halmos, P., Sunder, V.: Bounded Integral Operators on L2 L^2 L 2 Spaces. Springer, Berlin (1978)Kantorovitch, L., Vulich, B.: Sur la représentation des opérations linéaires. Compositio Math. 5, 119–165 (1938)Kolwicz, P., Leśnik, K., Maligranda, L.: Pointwise multipliers of Calderón- Lozanovskii spaces. Math. Nachr. 286, 876–907 (2013)Kolwicz, P., Leśnik, K., Maligranda, L.: Pointwise products of some Banach function spaces and factorization. J. Funct. Anal. 266(2), 616–659 (2014)Kuo, W.-C., Labuschagne, C.C.A., Watson, B.A.: Conditional expectations on Riesz spaces. J. Math. Anal. Appl. 303, 509–521 (2005)Lindenstrauss, J., Tzafriri, L.: Classical Banach Spaces II. Springer, Berlin (1979)Maharam, D.: The representation of abstract integrals. Trans. Am. Math. Soc. 75, 154–184 (1953)Maharam, D.: On kernel representation of linear operators. Trans. Am. Math. Soc. 79, 229–255 (1955)Maligranda, L., Persson, L.E.: Generalized duality of some Banach function spaces. Indag. Math. 51, 323–338 (1989)Neugebauer, C.J.: Weighted norm inequalities for averaging operators of monotone functions. Publ. Mat. 35, 429–447 (1991)Okada, S., Ricker, W.J., Sánchez Pérez, E.A.: Optimal Domain and Integral Extension of Operators Acting in Function Spaces. Operator Theory: Adv. Appl., vol. 180. Birkhäuser, Basel (2008)Rota, G.C.: On the representation of averaging operators. Rend. Sem. Mat. Univ. Padova. 30, 52–64 (1960)Sánchez Pérez, E.A.: Factorization theorems for multiplication operators on Banach function spaces. Integr. Equ. Oper. Theory 80(1), 117–135 (2014)Schep, A.R.: Factorization of positive multilinear maps. Ill. J. Math. 28(4), 579–591 (1984)Schep, A.R.: Products and factors of Banach function spaces. Positivity 14(2), 301–319 (2010

    In vitro culturing of porcine tracheal mucosa as an ideal model for investigating the influence of drugs on human respiratory mucosa

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    It has been previously shown that fresh mucosa from different mammals could serve as raw material for in vitro culturing with the differentiation of cilia, which are the most important morphological structures for the function of the mucociliary system. Increasing legal restrictions on the removal of human tissue and changing surgical techniques have led to a lack of fresh human mucosa for culturing. Most of the animals that have been used as donors up to now are genetically not very close to human beings and must all be sacrificed for such studies. We, therefore, established a modified system of culturing mucosa cells from the trachea of pigs, which is available as a regular by-product after slaughtering. With respect to the possibility of developing “beating” cilia, it could be shown that the speed of cell proliferation until adhesion to the coated culture dishes, the formation of conjunctions of cell clusters and the proliferation of cilia were comparable for porcine and human mucosa. Moreover, it could be demonstrated that the porcine cilia beat frequency of 7.57 ± 1.39 Hz was comparable to the human mucosa cells beat frequency of 7.3 ± 1.4 Hz and that this beat frequency was absolutely constant over the investigation time of 360 min. In order to prove whether the reaction to different drugs is comparable between the porcine and human cilia, we initially tested benzalkonium chloride, which is known to be toxic for human cells, followed by naphazoline, which we found in previous studies on human mucosa to be non-toxic. The results clearly showed that the functional and morphological reactions of the porcine ciliated cells to these substances were similar to the reaction we found in the in vitro cultured human mucosa

    Large introns in relation to alternative splicing and gene evolution: a case study of Drosophila bruno-3

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    Background: Alternative splicing (AS) of maturing mRNA can generate structurally and functionally distinct transcripts from the same gene. Recent bioinformatic analyses of available genome databases inferred a positive correlation between intron length and AS. To study the interplay between intron length and AS empirically and in more detail, we analyzed the diversity of alternatively spliced transcripts (ASTs) in the Drosophila RNA-binding Bruno-3 (Bru-3) gene. This gene was known to encode thirteen exons separated by introns of diverse sizes, ranging from 71 to 41,973 nucleotides in D. melanogaster. Although Bru-3's structure is expected to be conducive to AS, only two ASTs of this gene were previously described. Results: Cloning of RT-PCR products of the entire ORF from four species representing three diverged Drosophila lineages provided an evolutionary perspective, high sensitivity, and long-range contiguity of splice choices currently unattainable by high-throughput methods. Consequently, we identified three new exons, a new exon fragment and thirty-three previously unknown ASTs of Bru-3. All exon-skipping events in the gene were mapped to the exons surrounded by introns of at least 800 nucleotides, whereas exons split by introns of less than 250 nucleotides were always spliced contiguously in mRNA. Cases of exon loss and creation during Bru-3 evolution in Drosophila were also localized within large introns. Notably, we identified a true de novo exon gain: exon 8 was created along the lineage of the obscura group from intronic sequence between cryptic splice sites conserved among all Drosophila species surveyed. Exon 8 was included in mature mRNA by the species representing all the major branches of the obscura group. To our knowledge, the origin of exon 8 is the first documented case of exonization of intronic sequence outside vertebrates. Conclusion: We found that large introns can promote AS via exon-skipping and exon turnover during evolution likely due to frequent errors in their removal from maturing mRNA. Large introns could be a reservoir of genetic diversity, because they have a greater number of mutable sites than short introns. Taken together, gene structure can constrain and/or promote gene evolution

    Perceptions of surgical specialists in general surgery, orthopaedic surgery, urology and gynaecology on teaching endoscopic surgery in The Netherlands

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    BACKGROUND: Specific training in endoscopic skills and procedures has become a necessity for profession with embedded endoscopic techniques in their surgical palette. Previous research indicates endoscopic skills training to be inadequate, both from subjective (resident interviews) and objective (skills measurement) viewpoint. Surprisingly, possible shortcomings in endoscopic resident education have never been measured from the perspective of those individuals responsible for resident training, e.g. the program directors. Therefore, a nation-wide survey was conducted to inventory current endoscopic training initiatives and its possible shortcomings among all program directors of the surgical specialties in the Netherlands. METHODS: Program directors for general surgery, orthopaedic surgery, gynaecology and urology were surveyed using a validated 25-item questionnaire. RESULTS: A total of 113 program directors responded (79%). The respective response percentages were 73.6% for general surgeons, 75% for orthopaedic surgeon, 90.9% for urologists and 68.2% for gynaecologists. According to the findings, 35% of general surgeons were concerned about whether residents are properly skilled endoscopically upon completion of training. Among the respondents, 34.6% were unaware of endoscopic training initiatives. The general and orthopaedic surgeons who were aware of these initiatives estimated the number of training hours to be satisfactory, whereas the urologists and gynaecologists estimated training time to be unsatisfactory. Type and duration of endoscopic skill training appears to be heterogeneous, both within and between the specialties. Program directors all perceive virtual reality simulation to be a highly effective training method, and a multimodality training approach to be key. Respondents agree that endoscopic skills education should ideally be coordinated according to national consensus and guidelines. CONCLUSIONS: A delicate balance exists between training hours and clinical working hours during residency. Primarily, a re-allocation of available training hours, aimed at core-endoscopic basic and advanced procedures, tailored to the needs of the resident and his or her phase of training is in place. The professions need to define which basic and advanced endoscopic procedures are to be trained, by whom, and by what outcome standards. According to the majority of program directors, virtual reality (VR) training needs to be integrated in procedural endoscopic training course

    Surface topography regulates wnt signaling through control of primary cilia structure in mesenchymal stem cells

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    The primary cilium regulates cellular signalling including influencing wnt sensitivity by sequestering β-catenin within the ciliary compartment. Topographic regulation of intracellular actin-myosin tension can control stem cell fate of which wnt is an important mediator. We hypothesized that topography influences mesenchymal stem cell (MSC) wnt signaling through the regulation of primary cilia structure and function. MSCs cultured on grooves expressed elongated primary cilia, through reduced actin organization. siRNA inhibition of anterograde intraflagellar transport (IFT88) reduced cilia length and increased active nuclear β-catenin. Conversely, increased primary cilia assembly in MSCs cultured on the grooves was associated with decreased levels of nuclear active β-catenin, axin-2 induction and proliferation, in response to wnt3a. This negative regulation, on grooved topography, was reversed by siRNA to IFT88. This indicates that subtle regulation of IFT and associated cilia structure, tunes the wnt response controlling stem cell differentiation.We acknowledge funding from an EPSRC Platform grant which supported McMurray and a Wellcome Trust project grant which supported Wann and McMurray. Wann is now supported on an ARUK project grant. Thompson was funded by a BBSRC PhD studentshi
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