Despite advances in diagnosis and treatment, the overall outcomes for patients with brain tumors remain unpredictable. New prognostic markers are still needed to identify high-risk patients for whom ...the standard treatment has poor outcomes and would thus be well suited for more aggressive therapies. Neovascularization has long been implicated as a salient feature of glioma progression. In fact, high-grade gliomas are among the most vascular of all solid tumors, and vascular proliferation is a pathological hallmark of glioblastomas. Galectins are known to play important roles in cancer biology, including cancer cell migration, tumor immune escape or tumor angiogenesis. Moreover, galectins were reported to be involved in glioma progression. Given the key role of angiogenesis in brain tumors, the expression of galectins in tumor-associated endothelial cells (EC) and the implication of galectins in angiogenesis, the present review will focus on the expression of galectins in ECs of normal brain and brain tumors.
Lipoprotein(a), Lp(a), is a modified low-density lipoprotein particle that contains apolipoprotein(a), encoded by LPA, and is a highly heritable, causal risk factor for cardiovascular diseases that ...varies in concentrations across ancestries. Here, we use deep-coverage whole genome sequencing in 8392 individuals of European and African ancestry to discover and interpret both single-nucleotide variants and copy number (CN) variation associated with Lp(a). We observe that genetic determinants between Europeans and Africans have several unique determinants. The common variant rs12740374 associated with Lp(a) cholesterol is an eQTL for SORT1 and independent of LDL cholesterol. Observed associations of aggregates of rare non-coding variants are largely explained by LPA structural variation, namely the LPA kringle IV 2 (KIV2)-CN. Finally, we find that LPA risk genotypes confer greater relative risk for incident atherosclerotic cardiovascular diseases compared to directly measured Lp(a), and are significantly associated with measures of subclinical atherosclerosis in African Americans.
Toxicities of high-dose conditioning regimens have limited the use of conventional unrelated donor hematopoietic cell transplantation (HCT) to younger, medically fit patients. Based on preclinical ...studies, an HCT approach has been developed for elderly or medically infirm patients with HLA-matched or mismatched unrelated donors. In this study, 52 patients with hematological diseases were included. Most (88%) had preceding unsuccessful conventional HCT or refractory/advanced disease. Patients were treated with fludarabine 30 mg/m2/d from days −4 to −2, 2 Gy total body irradiation on day 0, cyclosporine at 6.25 mg/kg twice daily from day −3, and mycophenolate mofetil at 15 mg/kg twice daily from day 0. Durable donor chimerism was attained in 88% of the patients. By day 28, a median of 100% of CD56+ cells were of donor origin. Granulocyte and T-cell donor chimerism increased to medians of 100% on day 56 and day 180 (range, 55%-100%), respectively. Acute GVHD, grade II, was seen in 42% (CI, 29%-56%); grade III in 8% (CI, 0%-15%); and grade IV in 13% (CI, 4%-23%) of patients; it was fatal in 9%. The 100-day transplantation-related mortality was 11%. Complete remissions, including molecular remissions, were seen in 45% of patients with measurable disease before transplantation. Mortality from disease progression was 27% at one year. With a median follow-up of 19 months, 18 of the 52 patients (35%) were alive and 25% were in remission. HCT from HLA-matched or mismatched unrelated donors can be performed with a reduced intensity conditioning regimen in patients ineligible for conventional HCT.
Data from the Pierre Auger Observatory are analyzed to search for anisotropies near the direction of the Galactic Centre at EeV energies. The exposure of the surface array in this part of the sky is ...already significantly larger than that of the fore-runner experiments. Our results do not support previous findings of localized excesses in the AGASA and SUGAR data. We set an upper bound on a point-like flux of cosmic rays arriving from the Galactic Centre which excludes several scenarios predicting sources of EeV neutrons from Sagittarius A. Also the events detected simultaneously by the surface and fluorescence detectors (the ‘hybrid’ data set), which have better pointing accuracy but are less numerous than those of the surface array alone, do not show any significant localized excess from this direction.
The Pierre Auger Observatory is making significant contributions towards understanding the nature and origin of ultra-high energy cosmic rays. One of its main challenges is the monitoring of the ...atmosphere, both in terms of its state variables and its optical properties. The aim of this work is to analyse aerosol optical depth τa(z) values measured from 2004 to 2012 at the observatory, which is located in a remote and relatively unstudied area of Pampa Amarilla, Argentina. The aerosol optical depth is in average quite low – annual mean τa(3.5km)∼0.04 – and shows a seasonal trend with a winter minimum – τa(3.5km)∼0.03 –, and a summer maximum – τa(3.5km)∼0.06 –, and an unexpected increase from August to September — τa(3.5km)∼0.055. We computed backward trajectories for the years 2005 to 2012 to interpret the air mass origin. Winter nights with low aerosol concentrations show air masses originating from the Pacific Ocean. Average concentrations are affected by continental sources (wind-blown dust and urban pollution), whilst the peak observed in September and October could be linked to biomass burning in the northern part of Argentina or air pollution coming from surrounding urban areas.
•Aerosol optical depth measurements at the Pierre Auger Observatory are presented.•We examine correlations between aerosol optical depth values and air masses.•A seasonal trend is observed and explained by air masses coming from the Pacific Ocean.•Validity of GDAS model and HYSPLIT calculations is checked with in-situ measurements.
The energy spectrum of ultra-high energy cosmic rays above 10
18
eV is measured using the hybrid events collected by the Pierre Auger Observatory between November 2005 and September 2010. The large ...exposure of the Observatory allows the measurement of the main features of the energy spectrum with high statistics. Full Monte Carlo simulations of the extensive air showers (based on the CORSIKA code) and of the hybrid detector response are adopted here as an independent cross check of the standard analysis (Phys. Lett. B
685
, 239 (2010)). The dependence on mass composition and other systematic uncertainties are discussed in detail and, in the full Monte Carlo approach, a region of confidence for flux measurements is defined when all the uncertainties are taken into account. An update is also reported of the energy spectrum obtained by combining the hybrid spectrum and that measured using the surface detector array.
PDF
