New predictive markers for managing prostate cancer are urgently required because of the highly variable natural history of this disease. At the time of diagnosis, Gleason score provides the gold ...standard for assessing the aggressiveness of prostate cancer. However, the recent discovery of TMPRSS2 fusions to the ERG gene in prostate cancer raises the possibility of using alterations at the ERG locus as additional mechanism-based prognostic indicators. Fluorescence in situ hybridization (FISH) assays were used to assess ERG gene status in a cohort of 445 prostate cancers from patients who had been conservatively managed. The FISH assays detected separation of 5' (labelled green) and 3' (labelled red) ERG sequences, which is a consequence of the TMPRSS2-ERG fusion, and additionally identify interstitial deletion of genomic sequences between the tandemly located TMPRSS2 and ERG gene sequences on chromosome 21. Cancers lacking ERG alterations exhibited favourable cause-specific survival (90% survival at 8 years). We identify a novel category of prostate cancers, characterized by duplication of the fusion of TMPRSS2 to ERG sequences together with interstitial deletion of sequences 5' to ERG (called '2+Edel'), which by comparison exhibited extremely poor cause-specific survival (hazard ratio=6.10, 95% confidence ratio=3.33-11.15, P<0.001, 25% survival at 8 years). In multivariate analysis, '2+Edel' provided significant prognostic information (P=0.003) in addition to that provided by Gleason score and prostate-specific antigen level at diagnosis. Other individual categories of ERG alteration were associated with intermediate or good prognosis. We conclude that determination of ERG gene status, including duplication of the fusion of TMPRSS2 to ERG sequences in 2+Edel, allows stratification of prostate cancer into distinct survival categories.
The cytokine interleukin-12 (IL-12) was thought to have a central role in T cell-mediated responses in inflammation for more than a decade after it was first identified. Discovery of the cytokine ...IL-23, which shares a common p40 subunit with IL-12, prompted efforts to clarify the relative contribution of these two cytokines in immune regulation. Ustekinumab, a therapeutic agent targeting both cytokines, was recently approved to treat psoriasis and psoriatic arthritis, and related agents are in clinical testing for a variety of inflammatory disorders. Here we discuss the therapeutic rationale for targeting these cytokines, the unintended consequences for host defense and tumor surveillance and potential ways in which these therapies can be applied to treat additional immune disorders.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UILJ, UKNU, UL, UM, UPUK
3.
Scenarios for Global Biodiversity in the 21st Century Pereira, Henrique M.; Leadley, Paul W.; Proença, Vânia ...
Science (American Association for the Advancement of Science),
12/2010, Letnik:
330, Številka:
6010
Journal Article
Recenzirano
Odprti dostop
Quantitative scenarios are coming of age as a tool for evaluating the impact of future socioeconomic development pathways on biodiversity and ecosystem services. We analyze global terrestrial, ...freshwater, and marine biodiversity scenarios using a range of measures including extinctions, changes in species abundance, habitat loss, and distribution shifts, as well as comparing model projections to observations. Scenarios consistently indicate that biodiversity will continue to decline over the 21st century. However, the range of projected changes is much broader than most studies suggest, partly because there are major opportunities to intervene through better policies, but also because of large uncertainties in projections.
The Pearl River Delta (PRD) region in southeastern China is one of the most polluted industrial and metropolitan areas in the world. We report single‐particle measurements of the refractory black ...carbon (rBC) component in ambient aerosol in the region, and we interpret the results to improve understanding of the importance of rBC for radiative forcing in this region and others like it. A Single‐Particle Soot Photometer (SP2) provided rBC mass loadings, size distributions, and mixing state information. Average rBC loadings are approximately an order of magnitude higher than those measured near Houston, Texas, a major U.S. metropolitan area. The rBC in the PRD is also more often internally mixed with nonrefractory materials than is rBC around Houston. Localized atmospheric heating from rBC solar absorption reached an average rate of 0.4 K d−1. A one‐dimensional discrete ordinates radiative transfer (DISORT) model coupled with the average measured rBC is used to illustrate the potential local contribution of rBC mass and associated scattering aerosol to the radiative forcing. Solar energy deposition rates in the atmosphere at the sampling site due to rBC absorption are estimated to have an average value of 17 W m−2 and be largest in the first 1 km above the ground. These results indicate that rBC has significant potential to influence local meteorology and climate parameters in the PRD region.
Key Points
We performed black carbon measurements in China
A single‐particle soot photometer was used to determine black carbon properties
Solar energy deposition rates due to the black carbon were estimated
We present new flow‐weighted data for δ18OH2O, dissolved organic carbon (DOC), dissolved barium and total alkalinity from the six largest Arctic rivers: the Ob', Yenisey, Lena, Kolyma, Yukon and ...Mackenzie. These data, which can be used to trace runoff, are based upon coordinated collections between 2003 and 2006 that were temporally distributed to capture linked seasonal dynamics of river flow and tracer values. Individual samples indicate significant variation in the contributions each river makes to the Arctic Ocean. Use of these new flow‐weighted estimates should reduce uncertainties in the analysis of freshwater transport and fate in the upper Arctic Ocean, including the links to North Atlantic thermohaline circulation, as well as regional water mass analysis. Additional improvements should also be possible for assessing the mineralization rate of the globally significant flux of terrigenous DOC contributed to the Arctic Ocean by these major rivers.
Introduction
MR imaging can noninvasively visualize tumor phenotype characteristics at the macroscopic level. Here, we investigated whether somatic mutations are associated with and can be predicted ...by MRI-derived tumor imaging features of glioblastoma (GBM).
Methods
Seventy-six GBM patients were identified from The Cancer Imaging Archive for whom preoperative T1-contrast (T1C) and T2-FLAIR MR images were available. For each tumor, a set of volumetric imaging features and their ratios were measured, including necrosis, contrast enhancing, and edema volumes. Imaging genomics analysis assessed the association of these features with mutation status of nine genes frequently altered in adult GBM. Finally, area under the curve (AUC) analysis was conducted to evaluate the predictive performance of imaging features for mutational status.
Results
Our results demonstrate that MR imaging features are strongly associated with mutation status. For example, TP53-mutated tumors had significantly smaller contrast enhancing and necrosis volumes (
p
= 0.012 and 0.017, respectively) and RB1-mutated tumors had significantly smaller edema volumes (
p
= 0.015) compared to wild-type tumors. MRI volumetric features were also found to significantly predict mutational status. For example, AUC analysis results indicated that TP53, RB1, NF1, EGFR, and PDGFRA mutations could each be significantly predicted by at least one imaging feature.
Conclusion
MRI-derived volumetric features are significantly associated with and predictive of several cancer-relevant, drug-targetable DNA mutations in glioblastoma. These results may shed insight into unique growth characteristics of individual tumors at the macroscopic level resulting from molecular events as well as increase the use of noninvasive imaging in personalized medicine.
Aim
To investigate the effects of ultrasonic activation file type, lateral canal location and irrigant on the removal of a biofilm‐mimicking hydrogel from a fabricated lateral canal. Additionally, ...the amount of cavitation and streaming was quantified for these parameters.
Methodology
An intracanal sonochemical dosimetry method was used to quantify the cavitation generated by an IrriSafe 25 mm length, size 25 file inside a root canal model filled with filtered degassed/saturated water or three different concentrations of NaOCl. Removal of a hydrogel, demonstrated previously to be an appropriate biofilm mimic, was recorded to measure the lateral canal cleaning rate from two different instruments (IrriSafe 25 mm length, size 25 and K 21 mm length, size 15) activated with a P5 Suprasson (Satelec) at power P8.5 in degassed/saturated water or NaOCl. Removal rates were compared for significant differences using nonparametric Kruskal–Wallis and/or Mann–Whitney U‐tests. Streaming was measured using high‐speed particle imaging velocimetry at 250 kfps, analysing both the oscillatory and steady flow inside the lateral canals.
Results
There was no significant difference in amount of cavitation between tap water and oversaturated water (P = 0.538), although more cavitation was observed than in degassed water. The highest cavitation signal was generated with NaOCl solutions (1.0%, 4.5%, 9.0%) (P < 0.007) and increased with concentration (P < 0.014). The IrriSafe file outperformed significantly the K‐file in removing hydrogel (P < 0.05). Up to 64% of the total hydrogel volume was removed after 20 s. The IrriSafe file typically outperformed the K‐file in generating streaming. The oscillatory velocities were higher inside the lateral canal 3 mm compared to 6 mm from WL and were higher for NaOCl than for saturated water, which in turn was higher than for degassed water.
Conclusions
Measurements of cavitation and acoustic streaming have provided insight into their contribution to cleaning. Significant differences in cleaning, cavitation and streaming were found depending on the file type and size, lateral canal location and irrigant used. In general, the IrriSafe file outperformed the K‐file, and NaOCl performed better than the other irrigants tested. The cavitation and streaming measurements revealed that both contributed to hydrogel removal and both play a significant role in root canal cleaning.
We report an extended measurement of the neutron cross section on argon in the energy range of 95-720 MeV. The measurement was obtained with a 4.3-hour exposure of the Mini-CAPTAIN detector to the ...WNR/LANSCE beam at LANL. Compared to an earlier analysis of the same data, this extended analysis includes a reassessment of systematic uncertainties, in particular related to unused wires in the upstream part of the detector. Using this information we doubled the fiducial volume in the experiment and increased the statistics by a factor of 2.4. Here we also shifted the analysis from energy bins to time-of-flight bins. This change reduced the overall considered energy range, but improved the understanding of the energy spectrum of incoming neutrons in each bin. Overall, the new measurements are extracted from a fit to the attenuation of the neutron flux in five time-of-flight regions: 140ns-180ns, 120ns-140ns, 112ns-120ns, 104ns-112ns, 96ns-104ns. The final cross sections are given for the flux-averaged energy in each time-of-flight bin with statistical and systematic (syst) uncertainties: σ(146 MeV) = 0.60 $^{+0.14}_{-0.14}$ ±0.08(syst) b, σ(236 MeV) = 0.72 $^{+0.10}_{-0.10}$ ± 0.04(syst) b, σ(319 MeV) = 0.80 $^{+0.13}_{-0.12}$ ±0.040(syst) b, σ(404 MeV) = 0.74 $^{+0.14}_{-0.09}$ ±0.04(syst) b, σ(543 MeV) = 0.74 $^{±0.09}_{-0.09}$ ± 0.04(syst) b.
Dynamic compressive behavior of dry quartz sand (Quikrete #1961 sand quarried in Pensacola, FL) under confinement was characterized using a modified long split Hopkinson pressure bar (SHPB). Sand ...grains were confined inside a hollow cylinder of hardened steel and capped by cemented tungsten carbide cylindrical rods. This assembly was subjected to repeated shaking to consolidate sand to attain precise bulk mass densities. It is then sandwiched between incident and transmission bars on SHPB for dynamic compression measurements. Sand specimens of five initial mass densities, namely, 1.51, 1.57, 1.63, 1.69, and 1.75 g/cm
3
, were characterized at high strain rates near 600 s
−1
, to determine the volumetric and deviatoric behaviors through measurements of both axial and transverse responses of a cylindrical sand sample under confinement. The stress–strain relationship was found to follow a power law relationship with the sand initial bulk density, with an exponent of 8.25, indicating a behavior highly sensitive to mass density. The energy absorption density and compressibility of sand were determined as a function of axial stress.
We present the results of a 4‐year collaborative sampling effort that measuredδ18O, δ2H values and 3H activities in the six largest Arctic rivers (the Ob, Yenisey, Lena, Kolyma, Yukon and Mackenzie). ...Using consistent sampling and data processing protocols, these isotopic measurements provide the best available δ2H and 3H estimates for freshwater fluxes from the pan‐Arctic watershed to the Arctic Ocean and adjacent seas, which complements previous efforts withδ18O and other tracers. Flow‐weighted annualδ2H values vary from −113.3‰ to −171.4‰ among rivers. Annual 3H fluxes vary from 0.68 g to 4.12 g among basins. The integration of conventional hydrological and landscape observations with stable water isotope signals, and estimation of areal yield of 3H provide useful insights for understanding water sources, mixing and evaporation losses in these river basins. For example, an inverse correlation between the slope of the δ18O‐δ2H relation and wetland extent indicates that wetlands play comparatively important roles affecting evaporation losses in the Yukon and Mackenzie basins. Tritium areal yields (ranging from 0.760 to 1.695 10−6 g/km2per year) are found to be positively correlated with permafrost coverage within the studied drainage basins. Isotope‐discharge relationships demonstrate both linear and nonlinear response patterns, which highlights the complexity of hydrological processes in large Arctic river basins. These isotope observations and their relationship to discharge and landscape features indicate that basin‐specific characteristics significantly influence hydrological processes in the pan‐Arctic watershed.
Key Points
Provide best available d2H and 3H estimates labeling river inputs to the Arctic
Provide basin‐specific d18O‐d2H correlations for future applications
Explored linkage between land covers, hydrological variations, and isotope signals
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