Autonomic angiotensinergic fibres in the human heart with an efferent sympathetic cophenotype

AIM The autonomic innervation of the heart consists of sympathetic and parasympathetic nerve fibres, and fibres of the intrinsic ganglionated plexus with noradrenaline and acytylcholine as principal neurotransmitters. The fibres co-release neuropeptides to modulate intracardiac neurotransmission by specific presynaptic and postsynaptic receptors. The coexpression of angiotensin II in sympathetic fibres of the human heart and its role are not known so far. METHODS Autopsy specimens of human hearts were studied (n=3; ventricles). Using immunocytological methods, cryostat sections were stained by a murine monoclonal antibody (4B3) directed against angiotensin II and co-stained by polyclonal antibodies against tyrosine hydroxylase, a catecholaminergic marker. Visualisation of the antibodies was by confocal light microscopy or laser scanning microscopy. RESULTS Angiotensin II-positive autonomic fibres with and without a catecholaminergic cophenotype (hydroxylase-positive) were found in all parts of the human ventricles. In the epicardium, the fibres were grouped in larger bundles of up to 100 and more fibres. They followed the preformed anatomic septa and epicardial vessels towards the myocardium and endocardium where the bundles dissolved and the individual fibres spread between myocytes and within the endocardium. Generally, angiotensinergic fibres showed no synaptic enlargements or only a few if they were also catecholaminergic. The exclusively catechalominergic fibres were characterised by multiple beaded synapses. CONCLUSION The autonomic innervation of the human heart contains angiotensinergic fibres with a sympathetic efferent phenotype and exclusively angiotensinergic fibers representing probably afferents. Angiotensinergic neurotransmission may modulate intracardiac sympathetic and parasympathetic activity and thereby influence cardiac and circulatory function.

Transmission electron microscopy of the bacterial nucleoid.

Water-containing biological material cannot withstand the vacuum of the transmission electron microscope. The classical solution to this problem has been to dehydrate chemically fixed biological samples and then embed them in resin. During such treatment, the bacterial nucleoid is especially prone to aggregation, which affects its global shape and fine structure. Initial attempts to deal with aggregation by optimizing chemical fixation yielded contradictory results. Two decades ago, the situation improved with the introduction of freeze-substitution. This method is based on dehydration of unfixed cryo-immobilized samples at low temperature, which substantially reduces aggregation. As a result, the global shape of the nucleoid can be fairly well defined. Overall, in actively growing bacteria, the nucleoids are dispersed and "coralline" but become more confined when growth ceases. However, it is usually impossible to determine the molecular arrangement of DNA in the nucleoids of freeze-substituted bacteria because crystallization and the subsequent removal of water during substitution result in unavoidable distortions at the ultrastructural level. Recently, cryo-electron microscopy of vitreous sections has enabled the fully hydrated bacterial nucleoid to be studied close to the native state. Such studies have revealed aspects of bacterial nucleoid organization that are not preserved by freeze-substitution, including locally parallel or twisted bundles of DNA filaments, which are more frequently observed once bacterial growth has stopped, whereas in actively growing bacteria, the DNA is seen to be in a mostly disordered pattern.

Multibranched acquired periungual fibrokeratomas with confounding histopathologic findings resembling papillomavirus infection: a report of two cases

Acquired periungual fibrokeratomas are benign fibrous tissue tumors and are considered as the topographical variant of acquired digital fibrokeratoma. They usually present as solitary tumors. In some instance, the entity may appear in multibranched fashion. The main histopathologic features consist of acanthosis, thick collagen bundles mainly oriented in a vertical axis forming a central core, and numerous proliferating fibroblasts. In this article, we present two cases of acquired multibranched periungual fibrokeratoma and depict their varying clinical features over time. Binucleation and perinuclear halos of keratinocytes mimicking human papillomavirus (HPV) infection were detected microscopically, but there was no reactivity with HPV immunostaining. In context, anti-HPV immunostaining may be helpful in the differentiation of fibrokeratomas from HPV infection. On the other hand, it should be kept in mind that these histopathologic findings may be found in acral biopsies independent of viral effects.

Bloodstream infection in paediatric cancer centres--leukaemia and relapsed malignancies are independent risk factors.

UNLABELLED In a prospective multicentre study of bloodstream infection (BSI) from November 01, 2007 to July 31, 2010, seven paediatric cancer centres (PCC) from Germany and one from Switzerland included 770 paediatric cancer patients (58% males; median age 8.3 years, interquartile range (IQR) 3.8-14.8 years) comprising 153,193 individual days of surveillance (in- and outpatient days during intensive treatment). Broviac catheters were used in 63% of all patients and Ports in 20%. One hundred forty-two patients (18%; 95% CI 16 to 21%) experienced at least one BSI (179 BSIs in total; bacteraemia 70%, bacterial sepsis 27%, candidaemia 2%). In 57%, the BSI occurred in inpatients, in 79% after conventional chemotherapy. Only 56 % of the patients showed neutropenia at BSI onset. Eventually, patients with acute lymphoblastic leukaemia (ALL) or acute myeloblastic leukaemia (AML), relapsed malignancy and patients with a Broviac faced an increased risk of BSI in the multivariate analysis. Relapsed malignancy (16%) was an independent risk factor for all BSI and for Gram-positive BSI. CONCLUSION This study confirms relapsed malignancy as an independent risk factor for BSIs in paediatric cancer patients. On a unit level, data on BSIs in this high-risk population derived from prospective surveillance are not only mandatory to decide on empiric antimicrobial treatment but also beneficial in planning and evaluating preventive bundles. WHAT IS KNOWN • Paediatric cancer patients face an increased risk of nosocomial bloodstream infections (BSIs). • In most cases, these BSIs are associated with the use of a long-term central venous catheter (Broviac, Port), severe and prolonged immunosuppression (e.g. neutropenia) and other chemotherapy-induced alterations of host defence mechanisms (e.g. mucositis). What is New: • This study is the first multicentre study confirming relapsed malignancy as an independent risk factor for BSIs in paediatric cancer patients. • It describes the epidemiology of nosocomial BSI in paediatric cancer patients mainly outside the stem cell transplantation setting during conventional intensive therapy and argues for prospective surveillance programmes to target and evaluate preventive bundle interventions.

A versatile toolkit to produce sensitive FRET biosensors to visualize signaling in time and space

Genetically encoded, ratiometric biosensors based on fluorescence resonance energy transfer (FRET) are powerful tools to study the spatiotemporal dynamics of cell signaling. However, many biosensors lack sensitivity. We present a biosensor library that contains circularly permutated mutants for both the donor and acceptor fluorophores, which alter the orientation of the dipoles and thus better accommodate structural constraints imposed by different signaling molecules while maintaining FRET efficiency. Our strategy improved the brightness and dynamic range of preexisting RhoA and extracellular signal-regulated protein kinase (ERK) biosensors. Using the improved RhoA biosensor, we found micrometer-sized zones of RhoA activity at the tip of F-actin bundles in growth cone filopodia during neurite extension, whereas RhoA was globally activated throughout collapsing growth cones. RhoA was also activated in filopodia and protruding membranes at the leading edge of motile fibroblasts. Using the improved ERK biosensor, we simultaneously measured ERK activation dynamics in multiple cells using low-magnification microscopy and performed in vivo FRET imaging in zebrafish. Thus, we provide a construction toolkit consisting of a vector set, which enables facile generation of sensitive biosensors.

Dynamic Intraligamentary Stabilization (DIS) for treatment of acute anterior cruciate ligament ruptures: case series experience of the first three years.

BACKGROUND In recent years, the scientific discussion has focused on new strategies to enable a torn anterior cruciate ligament (ACL) to heal into mechanically stable scar tissue. Dynamic intraligamentary stabilization (DIS) was first performed in a pilot study of 10 patients. The purpose of the current study was to evaluate whether DIS would lead to similarly sufficient stability and good clinical function in a larger case series. METHODS Acute ACL ruptures were treated by using an internal stabilizer, combined with anatomical repositioning of torn bundles and microfracturing to promote self-healing. Clinical assessment (Tegner, Lysholm, IKDC, and visual analogue scale [VAS] for patient satisfaction scores) and assessment of knee laxity was performed at 3, 6, 12, and 24 months. A one-sample design with a non-inferiority margin was chosen to compare the preoperative and postoperative IKDS and Lysholm scores. RESULTS 278 patients with a 6:4 male to female ratio were included. Average patient age was 31 years. Preoperative mean IKDC, Lysholm, and Tegner scores were 98.8, 99.3, and 5.1 points, respectively. The mean anteroposterior (AP) translation difference from the healthy contralateral knee was 4.7 mm preoperatively. After DIS treatment, the mean 12-month IKDC, Lysholm, and Tegner scores were 93.6, 96.2, and 4.9 points, respectively, and the mean AP translation difference was 2.3 mm. All these outcomes were significantly non-inferior to the preoperative or healthy contralateral values (p < 0.0001). Mean patient satisfaction was 8.8 (VAS 0-10). Eight ACL reruptures occurred and 3 patients reported insufficient subjective stability of the knee at the end of the study period. CONCLUSIONS Anatomical repositioning, along with DIS and microfracturing, leads to clinically stable healing of the torn ACL in the large majority of patients. Most patients exhibited almost normal knee function, reported excellent satisfaction, and were able to return to their previous levels of sporting activity. Moreover, this strategy resulted in stable healing of all sutured menisci, which could lower the rate of osteoarthritic changes in future. The present findings support the discussion of a new paradigm in ACL treatment based on preservation and self-healing of the torn ligament.

Trade Costs, Quality, and The Skill Premium

We develop a monopolistic competition model with nonhomothetic factor input bundles where increasing quality requires increasing use of skilled workers. As a result more skill abundant countries export higher quality, higher priced goods. Using a multicountry dataset we test and confirm the findings in Schott (2004) of a positive effect of skill abundance on unit values identified with US data. We extend the core model with per unit trade costs leading to the Washington-apples effect that goods shipped over larger distance are of higher quality. The combination of high-quality goods being relatively skill intensive with the Washington-apples effect implies that countries at a larger distance from their trading partners display a higher skill premium. Simulating our model we find that a doubling of distance of a country relative to all its trading partners raises the skill premium in a country by about 2.3 percent.

Calibrating a CGE model with NTBs that Incorporates Standard Models of Modern Trade Theory

We propose a way to incorporate NTBs for the four workhorse models of the modern trade literature in computable general equilibrium models (CGEs). CGE models feature intermediate linkages and thus allow us to study global value chains (GVCs). We show that the Ethier-Krugman monopolistic competition model, the Melitz firm heterogeneity model and the Eaton and Kortum model can be defined as an Armington model with generalized marginal costs, generalized trade costs and a demand externality. As already known in the literature in both the Ethier-Krugman model and the Melitz model generalized marginal costs are a function of the amount of factor input bundles. In the Melitz model generalized marginal costs are also a function of the price of the factor input bundles. Lower factor prices raise the number of firms that can enter the market profitably (extensive margin), reducing generalized marginal costs of a representative firm. For the same reason the Melitz model features a demand externality: in a larger market more firms can enter. We implement the different models in a CGE setting with multiple sectors, intermediate linkages, non-homothetic preferences and detailed data on trade costs. We find the largest welfare effects from trade cost reductions in the Melitz model. We also employ the Melitz model to mimic changes in Non tariff Barriers (NTBs) with a fixed cost-character by analysing the effect of changes in fixed trade costs. While we work here with a model calibrated to the GTAP database, the methods developed can also be applied to CGE models based on the WIOD database.

Physical properties of four profiles from the Triassic in Germany

The Norian Steinmergel-Keuper (SMK) represents a low-latitude cyclically-bedded playa system of the Mid-German Basin. We investigated a drilling site (core Morsleben) and sections from marginal positions. Dolomite/red mudstone beds form rhythmic alternations that were associated with varying monsoon activity. Hence, low K/Al ratios of dolomite beds suggest increased chemical weathering of the crystalline hinterland and therefore increased monsoonal rainfall. High K/Al ratios in red mudstone beds reflect increased physical weathering of the hinterlands during dryer periods. Dolomite layers reflect the lake stage (maximum monsoon) while red mudstones indicate the dry phase (minimum monsoon) of the playa cycle. We distinguished five major types of cyclic facies alternations, representing specific facies zones in the playa system. We have implemented spectrophotometry as a tool for high-resolution cyclostratigraphy. The dense sampling increment (up to 1 cm) allows for the recognition of all orbital frequencies. Sediment colour profiles reveal striking hierarchical cycles from semi-precession (SP, 99 kyr) over precession (P, 19.8 kyr) and obliquity (O, 36 kyr) to eccentricity (E1-2 109 kyr; E3, 413 kyr). A significant about 2 Myr-signal is attributed to the longer-term eccentricity E4. One monsoonal (precession) cycle includes two carbonate precipitation events. We propose that stratified mudstone and red mudstone are associated with maximum and minimum monsoon during the transition of the solstices in perihelion and aphelion, respectively. The two carbonate precipitation events were most likely created when equinoxes were in perihelion and aphelion, respectively. A sedimentary semi-precession response cycle is a novel finding for the Norian strata. The obliquity signal is attributed to incoming atmospheric moisture from the northeast of the SMK basin. The E4 cycle controls lake-level changes over long times. Apparently, E4 is responsible whether or not a threshold value is crossed. Bundles of 109 kyr and 413 kyr in red mudstones suggest a dry system with reduced monsoonal activity. In contrast, humid periods reveal thick layers of dolomite beds, indicating that during those intervals the monsoonal activity was strong enough to prevent the playa system from drying out completely.

Examples of PDEs all whose points are characteristic

Let π : FM ! M be the bundle of linear frames of a manifold M. A basis Lijk , j < k, of diffeomorphism invariant Lagrangians on J1 (FM) was determined in [J. Muñoz Masqué, M. E. Rosado, Invariant variational problems on linear frame bundles, J. Phys. A35 (2002) 2013-2036]. The notion of a characteristic hypersurface for an arbitrary first-order PDE system on an ar- bitrary bred manifold π : P → M, is introduced and for the systems dened by the Euler-Lagrange equations of Lijk every hypersurface is shown to be characteristic. The Euler-Lagrange equations of the natural basis of Lagrangian densities Lijk on the bundle of linear frames of a manifold M which are invariant under diffeomorphisms, are shown to be an underdetermined PDEs systems such that every hypersurface of M is characteristic for such equations. This explains why these systems cannot be written in the Cauchy-Kowaleska form, although they are known to be formally integrable by using the tools of geometric theory of partial differential equations, see [J. Muñoz Masqué, M. E. Rosado, Integrability of the eld equations of invariant variational problems on linear frame bundles, J. Geom. Phys. 49 (2004), 119-155]

The logarithmic spiral, autoisoptic curve

In the Line of Investigation that in the department of “Technical Drawing” in the School of Agriculture Engineering of Madrid, we carry out on the study of The Technical Curves and his singularities, we demonstrate an interesting property of the Logarithmic Spiral. The demonstrated property consists of which the logarithmic spiral is a autoisoptic curve, that is to say that if from a point P anyone of the spiral tangent straight lines draw up to the previous arc, these form a constant angle α. This demonstration is novel and in addition we get to contribute a method to calculate the angle α given the equation of the spiral.

A robust numerical framework for the analysis of material failure of fibre reinforced soft tissue

In this work, robustness and stability of continuum damage models applied to material failure in soft tissues are addressed. In the implicit damage models equipped with softening, the presence of negative eigenvalues in the tangent elemental matrix degrades the condition number of the global matrix, leading to a reduction of the computational performance of the numerical model. Two strategies have been adapted from literature to improve the aforementioned computational performance degradation: the IMPL-EX integration scheme [Oliver,2006], which renders the elemental matrix contribution definite positive, and arclength-type continuation methods [Carrera,1994], which allow to capture the unstable softening branch in brittle ruptures. The IMPL-EX integration scheme has as a major drawback the need to use small time steps to keep numerical error below an acceptable value. A convergence study, limiting the maximum allowed increment of internal variables in the damage model, is presented. Finally, numerical simulation of failure problems with fibre reinforced materials illustrates the performance of the adopted methodology.

Advances in the SMS design method for imaging optics

In this work, two SMS algorithms are presented for an objective design with different selected ray-bundles: three meridian ray-bundles (3M) and one meridian and two skew ray-bundles (1M-2S), the latter from pin hole point of view, provides a better sampling of the phase space. Results obtained with different algorithms will be compared.

Progress in the SMS design method for imaging optics

In this work, two SMS algorithms are presented for an objective design with different selected ray-bundles: three meridian ray-bundles (3M) and one meridian and two skew ray-bundles (1M-2S), the latter from pin hole point of view, provides a better sampling of the phase space. Results obtained with different algorithms will be compared

Raman spectrum of group IV nanowires: influence of temperature

Group IV semiconductor nanowires are characterized by Raman spectroscopy. The results are analyzed in terms of the heating induced by the laser beam on the nanowires. By solving the heat transport equation one can simulate the temperature reached by the NWs under the exposure to a laser beam. The results are illustrated with Si and Si1-xGex nanowires. Both bundles of nanowires and individual nanowires are studied. The main experimental conditions contributing to the nanowire heating are discussed