Vitamin D3 receptor is highly expressed in Hodgkin's lymphoma

Background: Hodkin s lymphoma is one of the most frequent lymphoma in western world. Despite an overall good prognosis some patients suffer relapsing tumors which are difficult to cure. Over a long period Vitamin D has been shown to be a potential treatment for cancer. Vitamin D acts via the vitamin D receptor, a nuclear receptor, acting as an inducible transcription factor. We aimed to investigate the expression of vitamin D receptor as potential therapeutic target structure in Hodgkin s lymphoma as well as in non Hodgkin s lymphoma. Methods: We used a panel of 193 formalin fixed tissues of lymphoma cases consisting of 55 cases of Hodgkin s lymphoma and 138 cases on several non Hodgkin s lymphoma entities. Results: Vitamin D receptor is strongly expressed in Hodgkin s lymphoma, regardless of the subentity with an overall positivity of 80% of all Hodgkin lymphoma cases. In contrast, only about 17% of the analyzed non Hodgkin s lymphoma of B-cell origin showed positivity for vitamin D receptor. Predominant nuclear localization of vitamin D receptor in Hodgkin s lymphoma suggests activated status of the vitamin D receptor. Conclusions: From this study, we conclude that vitamin D receptor plays a potentially important role in pathogenesis of Hodgkin s lymphoma but not in non Hodgkin s lymphoma. Further investigations of mutational status and functional studies may shed some light in functional relevance of vitamin D receptor signaling in Hodgkin s lymphoma

Electrodynamic modeling of strong coupling between a metasurface and intersubband transitions in quantum wells

Strong light-matter coupling has recently been demonstrated in sub-wavelength volumes by coupling engineered optical transitions in semiconductor heterostructures (e.g., quantum wells) to metasurface resonances via near fields. It has also been shown that different resonator shapes may lead to different Rabi splittings, though this has not yet been well explained. In this paper, our aim is to understand the correlation between resonator shape and Rabi splitting, and in particular determine and quantify the physical parameters that affect strong coupling by developing an equivalent circuit network model whose elements describe energy and dissipation. Because of the subwavelength dimension of each metasurface element, we resort to the quasi-static (electrostatic) description of the near-field and hence define an equivalent capacitance associated to each dipolar element of a flat metasurface, and we show that this is also able to accurately model the phenomenology involved in strong coupling between the metasurface and the intersubband transitions in quantum wells. We show that the spectral properties and stored energy of a metasurface/quantum-well system obtained using our model are in good agreement with both full-wave simulation and experimental results. We then analyze metasurfaces made of three different resonator geometries and observe that the magnitude of the Rabi splitting increases with the resonator capacitance in agreement with our theory, providing a phenomenological explanation for the resonator shape dependence of the strong coupling process.Comment: 10 pages, 10 figure

miR-19b - ein essentieller Regulator der Länge und Form des ventrikulären Aktionspotentials im Zebrafisch

Sudden cardiac death (SCD) is a common mode of death in heart failure (HF) and results from prolonged action potential duration (APD) and ventricular arrhythmias. During the pathogenesis and progression of HF, a myriad number of signaling pathways are altered, including microRNAs. microRNAs are small noncoding RNAs that fine-tune gene expression by translational repression or transcript destabilization. Interestingly, microRNAs are dysregulated during HF, suggesting a potential involvement in the development and progression of the disease. Here, miR-19 was identified as an important regulator of heart function. Zebrafish lacking miR-19 developed severe bradycardia and reduced cardiac contractility. While mammals express two isoforms of miR-19, the zebrafish genome encodes for four members (19a-d). The reduction of miR-19b specifically was found to be sufficient to reduce heart rate by 30 % and to induce heart failure. Patch-clamp experiments from whole hearts showed that miR-19b deficient zebrafish exhibit significantly prolonged ventricular APD caused by impaired repolarization. Additionally these fish show increased sensitivity to an AV-Block, which is a characteristic feature of long QT-Syndrome in zebrafish. qRT-PCR revealed that miR-19b directly and indirectly regulates the expression of cardiac ion channels and thereby modulates APD and shape. This study describes miR-19b as an essential regulator of electrical activity of the heart and identifies it as a potential candidate gene causative for human long QT syndrome

Vitamin D3receptor is highly expressed in Hodgkin’s lymphoma

BACKGROUND: Hodgkin lymphoma (HL) is one of the most frequent lymphoma in the western world. Despite a good overall prognosis, some patients suffer relapsing tumors which are difficult to cure. Over a long period Vitamin D has been shown to be a potential treatment for cancer. Vitamin D acts via the vitamin D receptor, a nuclear receptor, acting as an inducible transcription factor. We aimed to investigate the expression of vitamin D receptor as a possible diagnostic marker and potential therapeutic target in HL as well as in B-cell derived non-Hodgkin lymphoma (B-NHL). METHODS: We used a panel of 193 formalin fixed tissues of lymphoma cases consisting of 55 cases of HL and 138 cases on several B-NHL entities. RESULTS: Vitamin D receptor is strongly expressed in tumor cells of HL, regardless of the sub entity with an overall positivity of 80% of all HL cases. In contrast, only about 17% of the analyzed origin-NHL showed positivity for vitamin D receptor. The detection of nuclear localization of vitamin D receptor in the tumor cells of HL suggests activated status of the vitamin D receptor. CONCLUSIONS: Our study suggests VDR as a specific marker for tumor cells of HL, but not of B-NHL subtypes. Further, the observed nuclear localization suggests an activated receptor status in tumor cells of HL. Further investigations of mutational status and functional studies may shed some light in functional relevance of vitamin D receptor signaling in HL

A Combined Score of Circulating miRNAs Allows Outcome Prediction in Critically Ill Patients

Background and aims: Identification of patients with increased risk of mortality represents an important prerequisite for an adapted adequate and individualized treatment of critically ill patients. Circulating micro-RNA (miRNA) levels have been suggested as potential biomarkers at the intensive care unit (ICU), but none of the investigated miRNAs displayed a sufficient sensitivity or specificity to be routinely employed as a single marker in clinical practice. Methods and results: We recently described alterations in serum levels of 7 miRNAs (miR-122, miR-133a, miR-143, miR-150, miR-155, miR-192, and miR-223) in critically ill patients at a medical ICU. In this study, we re-analyzed these previously published data and performed a combined analysis of these markers to unravel their potential as a prognostic scoring system in the context of critical illness. Based on the Youden’s index method, cut-off values were systematically defined for dysregulated miRNAs, and a “miRNA survival score” was calculated. Patients with high scores displayed a dramatically impaired prognosis compared to patients with low values. Additionally, the predictive power of our score could be further increased when the patient’s age was additionally incorporated into this score. Conclusions: We describe the first miRNA-based biomarker score for prediction of medical patients’ outcome during and after ICU treatment. Adding the patients’ age into this score was associated with a further increase in its predictive power. Further studies are needed to validate the clinical utility of this score in risk-stratifying critically ill patients

Relations between concurrent hard X-ray sources in solar flares

Context: Solar flares release a large fraction of their energy into non-thermal electrons, but it is not clear where and how. Bremsstrahlung X-rays are observed from the corona and chromosphere. Aims: We aim to characterize the acceleration process by the coronal source and its leakage toward the footpoints in the chromosphere. The relations between the sources reflect the geometry and constrict the configuration of the flare. Methods: We studied solar flares of GOES class larger than M1 with three or more hard X-ray sources observed simultaneously in the course of the flare. The events were observed with the X-ray satellite RHESSI from February 2002 until July 2005. We used imaging spectroscopy methods to determine the spectral evolution of each source in each event. The images of all of the five events show two sources visible only at high energies (footpoints) and one source only visible at low energies (coronal or looptop source, in two cases situated over the limb). Results: We find soft-hard-soft behavior in both, coronal source and footpoints. The coronal source is nearly always softer than the footpoints. The footpoint spectra differ significantly only in one event out of five. Conclusions: The observations are consistent with acceleration in the coronal source and an intricate connection between the corona and chromosphere.Comment: accepted for publication in A&A, 11 pages, 9 figure

Collapse of a molecular cloud core to stellar densities: the radiative impact of stellar core formation on the circumstellar disc

We present results from the first three-dimensional radiation hydrodynamical calculations to follow the collapse of a molecular cloud core beyond the formation of the stellar core. We find the energy released by the formation of the stellar core, within the optically-thick first hydrostatic core, is comparable to the binding energy of the disc-like first core. This heats the inner regions of the disc, drives a shock wave through the disc, dramatically decreases the accretion rate on to the stellar core, and launches a temporary bipolar outflow perpendicular to the rotation axis that travels in excess of 50 AU into the infalling envelope. This outburst may assist the young protostar in launching a conventional magnetic jet. Furthermore, if these events are cyclic, they may provide a mechanism for intense bursts of accretion separated by long periods of relatively quiescent accretion which can potentially solve both the protostellar luminosity problem and the apparent age spread of stars in young clusters. Such outbursts may also provide a formation mechanism for the chondrules found in meteorites, with the outflow transporting them to large distances in the circumstellar disc.Comment: Accepted by MNRAS Letters. 6 pages, 4 figures. Animations can be found at http://www.astro.ex.ac.uk/people/mbate/Animations/Stellar

A comprehensive set of simulations of high-velocity collisions between main sequence stars

We report on a very large set of simulations of collisions between two main sequence (MS) stars. These computations were done with the ``Smoothed Particle Hydrodynamics'' method. Realistic stellar structure models for evolved MS stars were used. In order to sample an extended domain of initial parameters space (masses of the stars, relative velocity and impact parameter), more than 15000 simulations were carried out. We considered stellar masses ranging between 0.1 and 75 Msun and relative velocities up to a few thousands km/s. To limit the computational burden, a resolution of 2000-30000 particles per star was used. The primary goal of this study was to build a complete database from which the result of any collision can be interpolated. This allows us to incorporate the effects of stellar collisions with an unprecedented level of realism into dynamical simulations of galactic nuclei and other dense stellar clusters. We make the data describing the initial condition and outcome (mass and energy loss, angle of deflection) of all our simulations freely available on the Internet. We find that the outcome of collisions depends sensitively on the stellar structure and that, in most cases, using polytropic models is inappropriate. Published fitting formulas for the collision outcomes, established from a limited set of collisions, prove of limited use because they do not allow robust extrapolation to other stellar structures or relative velocities.Comment: 45 pages, 44 figures. Modified to reflect the changes in the published version (MNRAS). PDF version with high-res figures at http://obswww.unige.ch/~freitag/papers/article_collisions.pdf, simulation data at http://obswww.unige.ch/~freitag/MODEST_WG4/FB_Collision_Data/, movies at http://obswww.unige.ch/~freitag/collisions/animations/index.htm