Protective mechanisms and current clinical evidence of hypothermic oxygenated machine perfusion (HOPE) in preventing post-transplant cholangiopathy

The development of cholangiopathies after liver transplantation impacts on the quality and duration of graft and patient survival, contributing to higher costs as numerous interventions are required to treat strictures and infections at the biliary tree. Prolonged donor warm ischaemia time in combination with additional cold storage are key risk factors for the development of biliary strictures. Based on this, the clinical implementation of dynamic preservation strategies is a current hot topic in the field of donation after circulatory death (DCD) liver transplantation. Despite various retrospective studies reporting promising results, also regarding biliary complications, there are only a few randomised-controlled trials on machine perfusion. Recently, the group from Groningen has published the first randomised-controlled trial on hypothermic oxygenated perfusion (HOPE), demonstrating a significant reduction of symptomatic ischaemic cholangiopathies with the use of a short period of HOPE before DCD liver implantation. The most likely mechanism for this important effect, also shown in several experimental studies, is based on mitochondrial reprogramming under hypothermic aerobic conditions, e.g. exposure to oxygen in the cold, with a controlled and slow metabolism of ischaemically accumulated succinate and simultaneous ATP replenishment. This unique feature prevents mitochondrial oxidative injury and further downstream tissue inflammation. HOPE treatment therefore supports livers by protecting them from ischaemia-reperfusion injury (IRI), and thereby also prevents the development of post-transplant biliary injury. With reduced IRI-associated inflammation, recipients are also protected from activation of the innate immune system, with less acute rejections seen after HOPE

Restoration of Sensitivity in Chemo

Glioblastoma (GBM) is the most common and aggressive brain tumor in adults. Despite multimodal treatments including surgery, chemotherapy and radiotherapy the prognosis remains poor and relapse occurs regularly. The alkylating agent temozolomide (TMZ) has been shown to improve the overall survival in patients with malignant gliomas, especially in tumors with methylated promoter of the O6-methylguanine-DNA-methyltransferase (MGMT) gene. However, intrinsic and acquired resistance towards TMZ makes it crucial to find new therapeutic strategies aimed at improving the prognosis of patients suffering from malignant gliomas. Cold atmospheric plasma is a new auspicious candidate in cancer treatment. In the present study we demonstrate the anti-cancer properties of different dosages of cold atmospheric plasma (CAP) both in TMZ-sensitive and TMZ-resistant cells by proliferation assay, immunoblotting, cell cycle analysis, and clonogenicity assay. Importantly, CAP treatment restored the responsiveness of resistant glioma cells towards TMZ therapy. Concomitant treatment with CAP and TMZ led to inhibition of cell growth and cell cycle arrest, thus CAP might be a promising candidate for combination therapy especially for patients suffering from GBMs showing an unfavorable MGMT status and TMZ resistance

Viability Assessment in Liver Transplantation—What Is the Impact of Dynamic Organ Preservation?

Based on the continuous increase of donor risk, with a majority of organs classified as marginal, quality assessment and prediction of liver function is of utmost importance. This is also caused by the notoriously lack of effective replacement of a failing liver by a device or intensive care treatment. While various parameters of liver function and injury are well-known from clinical practice, the majority of specific tests require prolonged diagnostic time and are more difficult to assess ex situ. In addition, viability assessment of procured organs needs time, because the development of the full picture of cellular injury and the initiation of repair processes depends on metabolic active tissue and reoxygenation with full blood over several hours or days. Measuring injury during cold storage preservation is therefore unlikely to predict the viability after transplantation. In contrast, dynamic organ preservation strategies offer a great opportunity to assess organs before implantation through analysis of recirculating perfusates, bile and perfused liver tissue. Accordingly, several parameters targeting hepatocyte or cholangiocyte function or metabolism have been recently suggested as potential viability tests before organ transplantation. We summarize here a current status of respective machine perfusion tests, and report their clinical relevance

Spitzer observations of Abell 1763 - I: infrared and optical photometry

We present a photometric analysis of the galaxy cluster Abell 1763 at visible and infrared wavelengths. Included are fully reduced images in r', J, H, and Ks obtained using the Palomar 200in telescope, as well as the IRAC and MIPS images from Spitzer. The cluster is covered out to approximately 3 virial radii with deep 24um imaging (a 5? depth of 0.2 mJy). This same field of 40' by 40' is covered in all four IRAC bands as well as the longer wavelength MIPS bands (70 and 160um). The r' imaging covers 0.8 deg2 down to 25.5 magnitudes, and overlaps with most of the MIPS field of view. The J, H, Ks images cover the cluster core and roughly half of the filament galaxies, which extend towards the neighboring cluster, Abell 1770. This first, in a series of papers on Abell 1763, discusses the data reduction methods and source extraction techniques used for each dataset. We present catalogs of infrared (IR) sources (with 24 and/or 70um emission) and their corresponding emission in the optical (u', g', r', i', z'), and Near- to Far-IR (J, H, Ks, IRAC, and MIPS 160um). We provide the catalogs and reduced images to the community through the NASA/IPAC Infrared Science Archive (IRSA).Comment: 25 pages, 16 figure

The Home of the Bison : An Ethnographic and Ethnohistorical Study of Traditional Cultural Affiliations to Wind Cave National Park

When Wind Cave National Park celebrated its Fiftieth Anniversary in 1953, a Lakota delegation from the Pine Ridge Reservation was invited to attend the festivities. As a way of honoring the event, the Lakotas adopted the park s superintendent, Earl M. Semingsen and named him Tatanka Tokahe [First Bison Bull]. Two things are significant about this name. On the one hand, it associates the park with bison, a culturally important connection for the Lakotas, who have long believed that Wind Cave is the home of the Buffalo Nation; and on the other, it refers to the name of the first human to emerge from the subterranean depths of the Black Hills through the portal that many Lakotas identify as Wind Cave. Much of the landscape of Wind Cave National Park, both above and below ground, is sacred to the Lakotas because it is a site of genesis and because it holds important teachings at the foundation of the way Lakotas have come to identify themselves as a people. The same holds true for the Cheyennes who hold the geological depression known as the Race Track in high regard and associate it with important cosmological precepts and the origins of their Sun Dance. The Lakotas identify the Race Track with an important spiritual pilgrimage their ancestors followed and that some have tried to recreate in modem times. In the traditions of both tribal nations, the story of the Great Race tells how the nature of relationships between humans and animals was established and how various topographic features of the Black Hills came into being

The Determination Of Reddening From Intrinsic VR Colors Of RR Lyrae Stars

New R-band observations of 21 local field RR Lyrae variable stars are used to explore the reliability of minimum light (V-R) colors as a tool for measuring interstellar reddening. For each star, R-band intensity mean magnitudes and light amplitudes are presented. Corresponding V-band light curves from the literature are supplemented with the new photometry, and (V-R) colors at minimum light are determined for a subset of these stars as well as for other stars in the literature. Two different definitions of minimum light color are examined, one which uses a Fourier decomposition to the V and R light curves to find (V-R) at minimum V-band light, (V-R)_{min}^F, and the other which uses the average color between the phase interval 0.5-0.8, (V-R)_{min}^{\phi(0.5-0.8)}. From 31 stars with a wide range of metallicities and pulsation periods, the mean dereddened RR Lyrae color at minimum light is (V-R)_{min,0}^F = 0.28 pm 0.02 mag and (V-R)_{min,0}^{\phi(0.5-0.8)} = 0.27 pm 0.02 mag. As was found by Guldenschuh et al. (2005) using (V-I) colors, any dependence of the star's minimum light color on metallicity or pulsation amplitude is too weak to be formally detected. We find that the intrinsic (V-R) of Galactic bulge RR Lyrae stars are similar to those found by their local counterparts and hence that Bulge RR0 Lyrae stars do not have anomalous colors as compared to the local RR Lyrae stars.Comment: accepted by A

The enigmatic pair of dwarf galaxies Leo IV and Leo V: coincidence or common origin?

We have obtained deep photometry in two 1x1 degree fields covering the close pair of dwarf spheroidal galaxies (dSph) Leo IV and Leo V and part of the area in between. We find that both systems are significantly larger than indicated by previous measurements based on shallower data and also significantly elongated. With half-light radii of r_h=4'.6 +- 0'.8 (206 +- 36 pc) and r_h=2'.6 +- 0'.6 (133 +- 31 pc), respectively, they are now well within the physical size bracket of typical Milky Way dSph satellites. Their ellipticities of epsilon ~0.5 are shared by many faint (M_V>-8) Milky Way dSphs. The large spatial extent of our survey allows us to search for extra-tidal features with unprecedented sensitivity. The spatial distribution of candidate red giant branch and horizontal branch stars is found to be non-uniform at the ~3 sigma level. This substructure is aligned along the direction connecting the two systems, indicative of a possible `bridge' of extra-tidal material. Fitting the stellar distribution with a linear Gaussian model yields a significance of 4 sigma for this overdensity, a most likely FWHM of ~16 arcmin and a central surface brightness of ~32 mag arcsec^{-2}. We investigate different scenarios to explain the close proximity of Leo IV and Leo V and the possible tidal bridge between them. Orbit calculations demonstrate that they are unlikely to be remnants of a single disrupted progenitor, while a comparison with cosmological simulations shows that a chance collision between unrelated subhalos is negligibly small. Leo IV and Leo V could, however, be a bound `tumbling pair' if their combined mass exceeds 8 +- 4 x 10^9 M_sun. The scenario of an internally interacting pair appears to be the most viable explanation for this close celestial companionship. (abridged)Comment: 9 pages, 8 figures, small number of minor textual changes, accepted for publication in Astrophysical Journa

New fundamental parameters of the Galactic open clusters Berkeley 26, Czernik 27, Melotte 72, NGC 2479 and BH 37

We have obtained CCD UBVI_{KC} photometry down to V ~ 21.0 for the open clusters Berkeley 26, Czernik 27, Melotte 72, NGC 2479 and BH 37. The latter has never been studied before. Cluster stellar density profiles were obtained from star counts in appropriate-sized boxes distributed throughout the entire observed fields. Based on different measured indices, we estimate the ages of Berkeley 26, Melotte 72 and NGC 2479. On the other hand, we indicate possible solutions for the cluster fundamental parameters by matching theoretical isochrones which reasonably reproduce the main cluster features in their CMDs. In the case of NGC 2479, the cluster E(B-V) and E(V-I) colour excesses and apparent distance modulus were estimated from the fit of the Zero-Age Main Sequence (ZAMS) to the colour-colour and colour-magnitude diagrams, respectively.Comment: MNRAS accepte