Intracapillary leucocyte accumulation as a novel antihaemorrhagic mechanism in acute pancreatitis in mice

Background: Pancreatic infiltration by leucocytes represents a hallmark in acute pancreatitis. Although leucocytes play an active role in the pathophysiology of this disease, the relation between leucocyte activation, microvascular injury and haemorrhage has not been adequately addressed.Methods: We investigated intrapancreatic leucocyte migration, leucocyte extravasation and pancreatic microperfusion in different models of oedematous and necrotising acute pancreatitis in lys-EGFP-ki mice using fluorescent imaging and time-lapse intravital microscopy.Results: In contrast to the current paradigm of leucocyte recruitment, the initial event of leucocyte activation in acute pancreatitis was represented through a dose- and time-dependent occlusion of pancreatic capillaries by intraluminally migrating leucocytes. Intracapillary leucocyte accumulation (ILA) resulted in dense filling of almost all capillaries close to the area of inflammation and preceded transvenular leucocyte extravasation. ILA was also initiated by isolated exposure of the pancreas to interleukin 8 or fMLP, demonstrating the causal role of chemotactic stimuli in the induction of ILA. The onset of intracapillary leucocyte accumulation was strongly inhibited in LFA-1-/- and ICAM-1-/- mice, but not in Mac-1-/- mice. Moreover, prevention of intracapillary leucocyte accumulation led to the development of massive capillary haemorrhages and transformed mild pancreatitis into lethal haemorrhagic disease.Conclusions: ILA represents a novel protective and potentially lifesaving mechanism of haemostasis in acute pancreatitis. This process depends on expression of LFA-1 and ICAM-1 and precedes the classical steps of the leucocyte recruitment cascade

On the Detection of Supermassive Primordial Stars. II. Blue Supergiants

Supermassive primordial stars in hot, atomically-cooling haloes at $z \sim$ 15 - 20 may have given birth to the first quasars in the universe. Most simulations of these rapidly accreting stars suggest that they are red, cool hypergiants, but more recent models indicate that some may have been bluer and hotter, with surface temperatures of 20,000 - 40,000 K. These stars have spectral features that are quite distinct from those of cooler stars and may have different detection limits in the near infrared (NIR) today. Here, we present spectra and AB magnitudes for hot, blue supermassive primordial stars calculated with the TLUSTY and CLOUDY codes. We find that photometric detections of these stars by the James Webb Space Telescope (JWST) will be limited to $z \lesssim$ 10 - 12, lower redshifts than those at which red stars can be found, because of quenching by their accretion envelopes. With moderate gravitational lensing, Euclid and the Wide-Field Infrared Space Telescope (WFIRST) could detect blue supermassive stars out to similar redshifts in wide-field surveys.Comment: 9 pages, 5 figures, accepted by MNRA

The influence of laser relative intensity noise in the Laser Interferometer Space Antenna

LISA is an upcoming ESA mission that will detect gravitational waves in spaceby interferometrically measuring the separation between free-falling testmasses at picometer precision. To reach the desired performance, LISA willemploy the noise reduction technique time-delay interferometry (TDI), in whichmultiple raw interferometric readouts are time shifted and combined into thefinal scientific observables. Evaluating the performance in terms of these TDIvariables requires careful tracking of how different noise sources propagatethrough TDI, as noise correlations might affect the performance in unexpectedways. One example of such potentially correlated noise is the relativeintensity noise (RIN) of the six lasers aboard the three LISA satellites, whichwill couple into the interferometric phase measurements. In this article, wecalculate the expected RIN levels based on the current mission architecture andthe envisaged mitigation strategies. We find that strict requirements on thetechnical design reduce the effect from approximately 8.7 pm/rtHz perinter-spacecraft interferometer to that of a much lower sub-1 pm/rtHz noise,with typical characteristics of an uncorrelated readout noise after TDI. Ourinvestigations underline the importance of sufficient balanced detection of theinterferometric measurements.<br

Raising a Small Flock of Sheep in Ohio

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Associative Stimulation of the Supraorbital Nerve Fails to Induce Timing-Specific Plasticity in the Human Blink Reflex

BACKGROUND: Associative high-frequency electrical stimulation (HFS) of the supraorbital nerve in five healthy individuals induced long-term potentiation (LTP)-like or depression (LTD)-like changes in the human blink reflex circuit according to the rules of spike timing-dependent plasticity (Mao and Evinger, 2001). HFS given at the onset of the R2 component of the blink reflex (HFS(LTP)) produced a lasting facilitation of the R2, whereas HFS given shortly before R2 (HFS(LTD)) caused a lasting suppression of the R2. In patients with benign essential blepharospasm (BEB), a focal dystonia affecting the orbicularis oculi muscles, HFS(LTP) induced excessive LTP-like associative plasticity relative to healthy controls, which was normalized after botulinum toxin (BTX) injections (Quartarone et al, 2006). METHODOLOGY/PRINCIPAL FINDINGS: We used HFS conditioning of the supraorbital nerve to study homeostatic metaplasticity of the blink reflex circuit in healthy subjects and dystonic patients. On separate days, we tested the conditioning effects on the R2 response and paired-pulse R2 inhibition after (i) HFS(LTP), (ii) HFS(LTP) followed by HFS(LTP), and (iii) HFS(LTP) followed by HFS(LTD). Controls also received (iv) HFS(LTD) alone and (v) a non-intervention protocol. In BEB patients, HFS(LTP) followed by HFS(LTD) was given before and after BTX treatment. We were not able to replicate the bidirectional timing-dependent effects of HFS(LTP) and HFS(LTD) alone. All HFS protocols produced a non-specific reduction of the R2 response and a relative decrease in paired-pulse inhibition. These R2 changes also occurred in controls when no HFS was applied. There was also no trace of a homeostatic response pattern in BEB patients before or after BTX treatment. CONCLUSION/SIGNIFICANCE: Our data challenge the efficacy of associative HFS to produce bidirectional plasticity in the human blink reflex circuit. The non-specific decrease of the R2 response might indicate habituation of the blink reflex following repeated electrical supraorbital stimulation. The increase of inhibition after paired pulse stimulation might reflect homeostatic behaviour to prevent further down regulation of the R2 response to preserve the protection of this adverse-effects reflex

Differential Calculi on Associative Algebras and Integrable Systems

After an introduction to some aspects of bidifferential calculus on associative algebras, we focus on the notion of a "symmetry" of a generalized zero curvature equation and derive Backlund and (forward, backward and binary) Darboux transformations from it. We also recall a matrix version of the binary Darboux transformation and, inspired by the so-called Cauchy matrix approach, present an infinite system of equations solved by it. Finally, we sketch recent work on a deformation of the matrix binary Darboux transformation in bidifferential calculus, leading to a treatment of integrable equations with sources.Comment: 19 pages, to appear in "Algebraic Structures and Applications", S. Silvestrov et al (eds.), Springer Proceedings in Mathematics & Statistics, 202

The resultant on compact Riemann surfaces

We introduce a notion of resultant of two meromorphic functions on a compact Riemann surface and demonstrate its usefulness in several respects. For example, we exhibit several integral formulas for the resultant, relate it to potential theory and give explicit formulas for the algebraic dependence between two meromorphic functions on a compact Riemann surface. As a particular application, the exponential transform of a quadrature domain in the complex plane is expressed in terms of the resultant of two meromorphic functions on the Schottky double of the domain.Comment: 44 page

Atherosclerotic plaque destabilization in Mice: A comparative study

Atherosclerosis-Associated diseases are the main cause ofmortality and morbidity in western societies. The progression of atherosclerosis is a dynamic process evolving from early to advanced lesions thatmay become rupture-prone vulnerable plaques. Acute coronary syndromes are the clinical manifestation of life-Threatening thrombotic events associated with high-risk vulnerable plaques. Hyperlipidemic mouse models have been extensively used in studying the mechanisms controlling initiation and progression of atherosclerosis. However, the understanding of mechanisms leading to atherosclerotic plaque destabilization has been hampered by the lack of proper animalmodelsmimicking this process. Although various mouse models generate atherosclerotic plaques with histological features of human advanced lesions, a consensus model to study atherosclerotic plaque destabilization is still lacking. Hence, we studied the degree and features of plaque vulnerability in different mouse models of atherosclerotic plaque destabilization and find that the model based on the placement of a shear stress modifier in combination with hypercholesterolemia represent with high incidence the most human like lesions compared to the other models