julilili42/papers huggingface dataset:
Junctional Adhesion Molecule A Expressed on Human CD34 + Cells Promotes Adhesion on Vascular Wall and Differentiation Into Endothelial Progenitor Cells
2010-04-09

Objective— To investigate the role of junctional adhesion molecule A (JAM-A) on adhesion and differentiation of human CD34 + cells into endothelial progenitor cells. Methods and Results— Tissue healing and vascular regeneration is a multistep process requiring firm adhesion of circulating progenitor cells to the vascular wall and their further differentiation into endothelial cells. The role of JAM-A in platelet-mediated adhesion of progenitor cells was investigated by adhesion assays in vitro and with the help of intravital fluorescence microscopy in mice. Preincubation of human CD34 + progenitor cells with soluble JAM-A-Fc (sJAM-A-Fc) resulted in significantly decreased adhesion over immobilized platelets or inflammatory endothelium under high shear stress in vitro and after carotid ligation in vivo or ischemia/reperfusion injury in the microcirculation of mice. Human CD34 + cells express JAM-A, as defined by flow cytometry and Western blot analysis. JAM-A mediates differentiation of CD34 + cells to endothelial progenitor cells and facilitates CD34 + cell-induced reendothelialization in vitro. Pretreatment of human CD34 + cells with sJAM-A-Fc resulted in increased neointima formation 3 weeks after endothelial denudation in the carotid arteries of nonobese diabetic/severe combined immunodeficient mice. Conclusion— These results indicate that the expression of JAM-A on CD34 + cells mediates adhesion to the vascular wall after injury and differentiation into endothelial progenitor cells, a mechanism potentially involved in vascular regeneration. Human CD34 + cells express JAM-A, mediating their interaction with platelets and endothelial cells. Specifically, JAM-A expressed on human CD34 + progenitor cells regulates their adhesion over immobilized platelets or inflammatory endothelium under high shear stress in vitro and after carotid ligation in vivo or ischemia/reperfusion injury in the microcirculation of mice. Moreover, it mediates differentiation of CD34 + cells to endothelial progenitor cells and facilitates reendothelialization.
Implications of magnetar non-precession
2010-04-09

Abstract The objects known as anomalous X-ray pulsars and soft gamma repeaters are commonly identified with magnetars, neutron stars with ultrastrong magnetic fields. The rotational history of these objects has, so far, revealed no evidence of free precession. At the same time, these objects do not generally appear to have magnetic axes nearly parallel or orthogonal to their spin axes. In this Letter we show that the combination of these two observations, together with simple rigid-body dynamics, leads to non-trivial predictions about the interior properties of magnetars: either (i) elastic stresses in magnetar crusts are close to the theoretical upper limit above which the crustal matter yields or (ii) there is a ‘pinned’ superfluid component in the magnetar interior. As a potentially observable consequence of these ideas we point out that in the case of no pinned superfluidity, magnetars of stronger magnetic field strength than those currently observed would have to be nearly aligned/orthogonal rotators.
Guidelines for treatment of autoimmune neuromuscular transmission disorders
2010-04-12

Background: Important progress has been made in our understanding of the autoimmune neuromuscular transmission (NMT) disorders; myasthenia gravis (MG), Lambert–Eaton myasthenic syndrome (LEMS) and neuromyotonia (Isaacs’ syndrome). Methods: To prepare consensus guidelines for the treatment of the autoimmune NMT disorders, references retrieved from MEDLINE, EMBASE and the Cochrane Library were considered and statements prepared and agreed on by disease experts. Conclusions: Anticholinesterase drugs should be given first in the management of MG, but with some caution in patients with MuSK antibodies (good practice point). Plasma exchange is recommended in severe cases to induce remission and in preparation for surgery (recommendation level B). IvIg and plasma exchange are effective for the treatment of MG exacerbations (recommendation level A). For patients with non‐thymomatous MG, thymectomy is recommended as an option to increase the probability of remission or improvement (recommendation level B). Once thymoma is diagnosed, thymectomy is indicated irrespective of MG severity (recommendation level A). Oral corticosteroids are first choice drugs when immunosuppressive drugs are necessary (good practice point). When long‐term immunosuppression is necessary, azathioprine is recommended to allow tapering the steroids to the lowest possible dose whilst maintaining azathioprine (recommendation level A). 3,4‐Diaminopyridine is recommended as symptomatic treatment and IvIG has a positive short‐term effect in LEMS (good practice point). Neuromyotonia patients should be treated with an antiepileptic drug that reduces peripheral nerve hyperexcitability (good practice point). For paraneoplastic LEMS and neuromyotonia optimal treatment of the underlying tumour is essential (good practice point). Immunosuppressive treatment of LEMS and neuromyotonia should be similar to MG (good practice point).
Oscillations and instabilities of fast and differentially rotating relativistic stars
2010-04-12

We study non-axisymmetric oscillations of rapidly and differentially rotating\\nrelativistic stars in the Cowling approximation. Our equilibrium models are\\nsequences of relativistic polytropes, where the differential rotation is\\ndescribed by the relativistic -constant law. We show that a small degree of\\ndifferential rotation raises the critical rotation value for which the\\nquadrupolar f-mode becomes prone to the CFS instability, while the critical\\nvalue of at the mass-shedding limit is raised even more. For softer\\nequations of state these effects are even more pronounced. When increasing\\ndifferential rotation further to a high degree, the neutral point of the CFS\\ninstability first reaches a local maximum and is lowered afterwards. For stars\\nwith a rather high compactness we find that for a high degree of differential\\nrotation the absolute value of the critical is below the corresponding\\nvalue for rigid rotation. We conclude that the parameter space where the CFS\\ninstability is able to drive the neutron star unstable is increased for a small\\ndegree of differential rotation and for a large degree at least in stars with a\\nhigher compactness.\\n
Dual role of protein kinase C on BK channel regulation
2010-04-12

Large conductance voltage- and Ca 2+ -activated potassium channels (BK channels) are important feedback regulators in excitable cells and are potently regulated by protein kinases. The present study reveals a dual role of protein kinase C (PKC) on BK channel regulation. Phosphorylation of S 695 by PKC, located between the two regulators of K + conductance (RCK1/2) domains, inhibits BK channel open-state probability. This PKC-dependent inhibition depends on a preceding phosphorylation of S 1151 in the C terminus of the channel α-subunit. Phosphorylation of only one α-subunit at S 1151 and S 695 within the tetrameric pore is sufficient to inhibit BK channel activity. We further detected that protein phosphatase 1 is associated with the channel, constantly counteracting phosphorylation of S 695 . PKC phosphorylation at S 1151 also influences stimulation of BK channel activity by protein kinase G (PKG) and protein kinase A (PKA). Though the S 1151 A mutant channel is activated by PKA only, the phosphorylation of S 1151 by PKC renders the channel responsive to activation by PKG but prevents activation by PKA. Phosphorylation of S 695 by PKC or introducing a phosphomimetic aspartate at this position (S 695 D) renders BK channels insensitive to the stimulatory effect of PKG or PKA. Therefore, our findings suggest a very dynamic regulation of the channel by the local PKC activity. It is shown that this complex regulation is not only effective in recombinant channels but also in native BK channels from tracheal smooth muscle.
Clinical pharmacodynamics and pharmacokinetics of the antifungal extended‐spectrum triazole posaconazole: an overview
2010-04-12

In recent years, the antifungal triazole posaconazole has become increasingly important for the prophylaxis and treatment of systemic mycoses. Although oral bioavailability of posaconazole can be enhanced by concomitant food intake and administration in divided daily doses, increased gastric pH or gut motility, as well as enzyme‐inducing drugs, can result in lower plasma concentrations than expected. Whether therapeutic drug monitoring can reduce the risk of treatment failures by avoiding sub‐therapeutic plasma concentrations needs further examination. Based on the ability of posaconazole to inhibit cytochrome P450 3A4, several drug interactions can be expected, especially with agents that undergo extensive first‐pass effect through the gut and the liver. However, more information is needed regarding dose modifications during concomitant administration of posaconazole with drugs in certain categories, such as vinca alkaloids and retinoids, along with selected individual drugs such as everolimus.
Modeling familial Danish dementia in mice supports the concept of the amyloid hypothesis of Alzheimer's disease
2010-04-12

Familial Danish dementia (FDD) is a progressive neurodegenerative disease with cerebral deposition of Dan-amyloid (ADan), neuroinflammation, and neurofibrillary tangles, hallmark characteristics remarkably similar to those in Alzheimer's disease (AD). We have generated transgenic (tg) mouse models of familial Danish dementia that exhibit the age-dependent deposition of ADan throughout the brain with associated amyloid angiopathy, microhemorrhage, neuritic dystrophy, and neuroinflammation. Tg mice are impaired in the Morris water maze and exhibit increased anxiety in the open field. When crossed with TauP301S tg mice, ADan accumulation promotes neurofibrillary lesions, in all aspects similar to the Tau lesions observed in crosses between β-amyloid (Aβ)-depositing tg mice and TauP301S tg mice. Although these observations argue for shared mechanisms of downstream pathophysiology for the sequence-unrelated ADan and Aβ peptides, the lack of codeposition of the two peptides in crosses between ADan- and Aβ-depositing mice points also to distinguishing properties of the peptides. Our results support the concept of the amyloid hypothesis for AD and related dementias, and suggest that different proteins prone to amyloid formation can drive strikingly similar pathogenic pathways in the brain.
A self-consistent approach to the hard and soft states of 4U 1705-44
2010-04-12

We analyzed two XMM-Newton observations of the bright atoll source 4U\\n1705-44, which can be considered a prototype of the class of the persistent NS\\nLMXBs showing both hard and soft states. The first observation was performed\\nwhen the source was in a hard low flux state, the second during a soft,\\nhigh-flux state. Both the spectra show broad iron emission lines. We fit the\\nspectra using a two-component model, together with a reflection model\\nspecifically suited to the case of a neutron star, where the incident spectrum\\nhas a blackbody shape. In the soft state, the reflection model, convolved with\\na relativistic smearing component, consistently describes the broad features\\npresent in the spectrum, and we find a clear relation between the temperature\\nof the incident flux and the temperature of the harder X-ray component that we\\ninterpret as the boundary layer emission. In this state we find converging\\nevidence that the boundary layer outer radius is ~ 2 times the neutron star\\nradius. In the low flux state, we observe a change in the continuum shape of\\nthe spectrum with respect to the soft state. Still, the broad local emission\\nfeatures can be associated with a disk reflecting matter, but in a lower\\nionization state, and possibly produced in an accretion disk truncated at\\ngreater distance. Our analysis provides strong evidence that the reflection\\ncomponent in soft states of LMXBs comes from to hard X-ray thermal irradiation,\\nwhich we identify with the boundary layer emission, also present in the\\ncontinuum model. In the hard state, the broad iron line if also produced by\\nreflection, and the continuum disk emission can be self-consistently accounted\\nif the disk is truncated at a greater distance than the soft state.\\n
Online coupling of enantioselective capillary gas chromatography with proton nuclear magnetic resonance spectroscopy
2010-04-12

Abstract The hyphenation of enantioselective capillary gas chromatography and mass spectrometry is not always sufficient to distinguish between structural isomers, thus requiring peak identification by NMR spectroscopy. Here the first online coupling of enantioselective capillary gas chromatography with proton nuclear resonance spectroscopy is described for the unfunctionalized chiral alkane 2,4‐dimethylhexane resolved on octakis(6‐ O ‐methyl‐2,3‐di‐ O ‐pentyl)‐γ‐cyclodextrin at 60°C. NMR allows constitutional and configurational isomers (diastereomers and enantiomers) to be distinguished. Enantiomers display identical spectra at different retention times, which enable an indirect identification of these unfunctionalized alkanes. The presented method is still at an early development stage, and will require instrumental optimization in the future. Chirality 2010. © 2010 Wiley‐Liss, Inc.
Rare Earth Carbodiimide Silicates: RE2(CN2)(SiO4)
2010-04-12

Abstract Rare earth carbodiimide silicates RE 2 (CN 2 )(SiO 4 ) with RE = Y, La, and Pr were synthesised by solid state metathesis reactions of RE Cl 3 , Li 2 (CN 2 ), and SiO 2 or Li 2 SiO 4 , respectively, in silica tubes at 550 °C. All three compounds crystallise with different structures, although all of them represent distorted derivatives of the sodium chloride type structure. The structure of Y 2 (CN 2 )(SiO 4 ) was refined monoclinically ( C 2/ m , Z = 2, a = 1301.382(5) pm, b = 377.630(1) pm, c = 527.656(2) pm, β = 93.9816(2) °) from X‐ray powder data. The crystal structure of La 2 (CN 2 )(SiO 4 ) was refined in a different monoclinic space group ( P 2 1 / c , Z = 4, a = 660.3(1) pm, b = 1282.0(2) pm, c = 656.2(1) pm, β = 105.23(2) °), and the structure of Pr 2 (CN 2 )(SiO 4 ) was refined triclinically ( P \\bar{1} , Z = 2, a = 646.7(2) pm, b = 669.2(2) pm, c = 671.8(2) pm, α = 86.18(3) °, β = 73.22(3) °, γ = 74.08(3) °) from X‐ray single crystal data.
Comparison of Female Foot Morphology and Last Design in Athletic Footwear—Are Men's Lasts Appropriate for Women?
2010-04-13

The purpose of this study was to investigate differences between female feet and last design. Four hundred twenty-four feet and four men's running shoe lasts (U.S. women 6.0–9.5), which also are used for the manufacturing of women's shoes, were scanned in three dimensions. Six foot measures were quantified. Different foot types were classified using a cluster analysis. Comparisons were made between last measures and averaged as well as foot type specific foot measures. Differences in width measures between lasts and foot types vary substantially (0–9 mm). Length grading is similar for lasts and feet (differences < 1mm). Width grading is larger in lasts in comparison with average grading in feet (3.5–5.9 mm). Last design and grading should account for the sex-specific allometry in foot measures. The use of down-graded men's lasts for women's shoes has to be questioned. Therefore, sex-specific reference measures and wear tests should incorporate different foot types in different sizes to allow suitable implications for a proper design and grading of lasts.
Mistletoe lectin‐I augments antiproliferative effects of the PPARγ agonist rosiglitazone on human malignant melanoma cells
2010-04-13

Abstract As malignant melanoma cells are highly resistant to conventional chemotherapy, survival rates after tumor spread remain poor and hence there is an urgent need for new therapeutic options. For both mistletoe lectin‐I (ML‐I) and the thiazolidinediones as synthetic ligands of the peroxisome proliferator‐activated receptor γ (PPARγ) an antiproliferative effect on malignant melanoma cells has previously been shown. Hence, the aim of this study was to investigate whether the combination of ML‐I and the PPARγ ligand rosiglitazone is more efficacious in the treatment of malignant melanoma cells than either agent alone. Proliferation of three human melanoma cell lines treated with ML‐I, rosiglitazone and the combination of both was measured in a broad concentration range (0.0001–100 μg/mL) using the XTT cell proliferation assay. Combined application tremendously increased the antiproliferative effect on all three melanoma cell lines compared with single agent treatment. In comparison with the single use of rosiglitazone, the combination with ML‐I significantly increased the inhibition of cell growth by 51–79% and in comparison with the single use of ML‐I by 9–32%, respectively. In conclusion, this study shows that the combination of ML‐I with rosiglitazone significantly augments their antiproliferative effect on malignant melanoma cells in comparison with their single agent application, which might be a promising tool for further therapeutic studies. Copyright © 2010 John Wiley &amp; Sons, Ltd.
International Bank Portfolios: Short- and Long-Run Responses to Macroeconomic Conditions
2010-04-14

International bank portfolios constitute a large component of international country portfolios. Yet, banks' response to international macroeconomic conditions remains largely unexplored. We use a novel dataset on banks' international portfolios to answer three questions. First, what are the long-run determinants of banks' international portfolios? Second, how do banks' international portfolios adjust to short-run macroeconomic developments? Third, does the speed of adjustment change with the degree of financial integration? We find that, in the long-run, market size has a positive impact on foreign assets and liabilities. An increase in the interest differential between the home and the foreign economy lowers foreign assets and increases foreign liabilities. Foreign trade has a positive impact on international bank portfolios, which is independent from the effect of other macroeconomic variables. Short-run dynamics show heterogeneity across countries, but these dynamics can partly be explained with gravity-type variables. Copyright © 2010 Blackwell Publishing Ltd.
Left ventricular hypertrophy, geometric patterns and clinical correlates among treated hypertensive Nigerians
2010-04-14

Concentric remodeling is the commonest pattern of left ventricular geometric pattern of the left ventricle among hypertensive subjects. Left ventricular geometry is associated with the chamber and wall dimensions. Eccentric hypertrophy is associated with the lowest left ventricular systolic function and therefore possibly an herald to progressive systolic impairment.
Controlling the optical properties of quantum emitters by optical confinement in a tunable microcavity
2010-04-14

Optical microresonators are structures which confine light to a small region in the range of one wavelength. The radiation of a quantum emitter is coupled to cavity resonances which leads to an optical confinement of the broadband fluorescence. A practical design for this single-mode microresonator is formed by two silver mirrors enclosing a transparent dielectric medium with single quantum emitters. In our tunable microresonator, the resonator length can be changed reversibly with piezoelectric elements to a distinct position corresponding to a specific emission wavelength. The local mode structure of the electromagnetic field is changed at this position which results in a redistribution of the fluorescence and a modification of the lifetime for the same single molecule. The radiative coupling of the emitter to the electromagnetic field is also determined by the orientation of its transition dipole moment with respect to the cavity normal. The doughnut laser modes used for illumination of the single molecule allow us by analyzing the excitation patterns to determine its three-dimensional orientation in the microresonator. In addition, these modes provide an excitation pattern which can be used to detect the longitudinal position of a fluorescent bead in the microresonator with an accuracy of a few nanometers.
Epithelial Cells and Innate Antifungal Defense
2010-04-15

The human pathogenic fungus Candida albicans is the predominant cause of both superficial and invasive forms of candidiasis. Clinical observations indicate that mucocutaneous Candida infections are commonly associated with defective cell-mediated immune responses. The importance of the innate immune system as a first-line defense against pathogenic challenge has long been recognized. Over the last decade, many key molecules mediating innate host defense have been identified. Central to these developments is the discovery of pattern recognition receptors such as Toll-like receptors and C-type lectin-receptors that induce innate immune responses and also modulate cellular and humoral adaptive immunity during Candida infections. Although a large amount of information is now available in systemic infections, little is known about localized infections. We address the most relevant pattern recognition receptors and their signaling mechanisms in oral epithelial cells, to gain a better understanding of their contributions to antifungal innate immunity.
Antibiotics: Biosynthesis, Generation of Novel Compounds
2010-04-15

Abstract Many antibiotics and other bioactive molecules originate from biological sources, mainly bacteria and fungi. In this article, the biosynthetic principles of the three most important classes of antibiotics are discussed and examples of the biotechnological potential of pathway engineering are presented. Polyketides, among them medically important antibacterial drugs like tetracycline or erythromycin, are assembled from basic acyl‐CoA building blocks by a mechanism that is closely related to fatty acid synthesis. Another important group of antibiotics are modified peptides like penicillin or vancomycin which are synthesized by complex modular megaenzymes. These nonribosomal peptide synthetases use proteinogenic as well as nonproteinogenic amino acids as substrates. In addition some other peptide antibiotics, like the lantibiotic nisin which is widely used as a food additive, are synthesized by the cellular ribosomal protein biosynthesis machinery and subsequently modified by specific enzymes. Aminoglycoside antibiotics like streptomycin are assembled from complex sugar or sugar‐like molecules which are specifically synthesized during secondary metabolite production. The elucidation of the molecular machinery of antibiotic biosynthesis enabled technologies that can be used to optimize the secondary metabolites by genetic engineering. In this article, some strategies are highlighted which allow the modification of secondary metabolites in ways that were hard to achieve using only synthetic chemistry approaches.