Neoadjuvant sipuleucel-T induces both Th1 activation and immune regulation in localized prostate cancer.

Sipuleucel-T is the only FDA-approved immunotherapy for metastatic castration-resistant prostate cancer. The mechanism by which this treatment improves survival is not fully understood. We have previously shown that this treatment can induce the recruitment of CD4 and CD8 T cells to the tumor microenvironment. In this study, we examined the functional state of these T cells through gene expression profiling. We found that the magnitude of T cell signatures correlated with the frequency of T cells as measured by immunohistochemistry. Sipuleucel-T treatment was associated with increased expression of Th1-associated genes, but not Th2-, Th17 - or Treg-associated genes. Post-treatment tumor tissues with high CD8+T cell infiltration was associated with high levels of CXCL10 expression. On in situ hybridization, CXCL10+ cells colocalized with CD8+T cells in post-treatment prostatectomy tumor tissue. Neoadjuvant sipuleucel-T was also associated with upregulation of immune inhibitory checkpoints, including CTLA4 and TIGIT, and downregulation of the immune activation marker, dipeptidylpeptidase, DPP4. Treatment-associated declines in serum PSA were correlated with induction of Th1 response. In contrast, rises in serum PSA while on treatment were associated with the induction of multiple immune checkpoints, including CTLA4, CEACAM6 and TIGIT. This could represent adaptive immune resistance mechanisms induced by treatment. Taken together, neoadjuvant sipuleucel-T can induce both a Th1 response and negative immune regulation in the prostate cancer microenvironment

Avalanche breakdown characteristics of Al1-xGaxAs0.56Sb0.44 quaternary alloys

Avalanche breakdown characteristics are essential for designing avalanche photodiodes. In this work, we investigated the effects of adding Ga to Al1-xGaxAs0.56Sb0.44 quaternary alloys. Using p-i-n diodes with a 100 nm i –region and alloy composition ranging from x = 0 to 0.15, we found that the bandgap energy of Al1-xGaxAs0.56Sb0.44 reduces from 1.64 to 1.56 eV. The corresponding avalanche breakdown voltage decreases from 13.02 to 12.05 V, giving a reduction of 64.7 mV for every percent addition of Ga. The surface leakage current was also found to be significantly lower in the diodes with x = 0.10 and 0.15 suggesting that Ga can be added to reduce the surface leakage current while still preserving the lattice match to InP substrate

An inventory of glacier changes between 1973 and 2011 for the Geladandong Mountain area, China.

This is the publisher's version, also available electronically from http://www.the-cryosphere-discuss.net/7/507/2013/tcd-7-507-2013.htmlThe snow and ice of the Geladangong Mountain area supply the headwaters of the Yangtze River, and long-term changes to glaciers and ice masses in this region due to a warming climate are of great concern. An inventory of glacier boundaries and changes over decades for the Geladandong Mountain area in China has been conducted using remote sensing imagery from Landsat (MSS, TM, ETM+), CERBES CCD, and GIS techniques. Variations in glacier extent has been measured using a~series of digital images since 1973, including Landsat MSS in 1973, Landsat TM in 1992, Landsat ETM+ in 2004, and CBERS CCD in 2011. All Landsat data are snow-free outside the glacier boundaries, allowing an unsupervised classification method to be used to extract glacier area. For the CBERS CCD data, some areas were covered by clouds and snow, requiring an initial unsupervised classification method to divide glacier, clouds and snow from other land types, followed by a supervised visual interpretation to extract glacier area. The results show a decrease in glacier ice cover in the study area during the past 38 yr. From 1973 to 2011, glacier area decreased from 107 105 hectares to 94 220 hectares, or a change of −12%. The speed at which ice cover is being lost has been decreasing during the past 38 yr. The rate of glacier area loss was 0.47% yr−1 from 1973–1992, 0.19% yr−1 from 1992–2004, and 0.14% yr−1 from 2004–2011. While most of the glaciers are shrinking, some are expanding. For the 1973 to 2004 period, retreating glaciers exposed 14 447 hectares of land, and advancing glaciers spread over 2682 hectares that were not covered by ice in 1973. The net glacier area decrease is 11 765 hectares from 1973–2004. For the 1973 to 2011 period, glaciers expanded over 3791 hectares, and retreated from 16 504 hectares

Exploring Lightweight Interventions at Posting Time to Reduce the Sharing of Misinformation on Social Media

When users on social media share content without considering its veracity, they may unwittingly be spreading misinformation. In this work, we investigate the design of lightweight interventions that nudge users to assess the accuracy of information as they share it. Such assessment may deter users from posting misinformation in the first place, and their assessments may also provide useful guidance to friends aiming to assess those posts themselves. In support of lightweight assessment, we first develop a taxonomy of the reasons why people believe a news claim is or is not true; this taxonomy yields a checklist that can be used at posting time. We conduct evaluations to demonstrate that the checklist is an accurate and comprehensive encapsulation of people's free-response rationales. In a second experiment, we study the effects of three behavioral nudges -- 1) checkboxes indicating whether headings are accurate, 2) tagging reasons (from our taxonomy) that a post is accurate via a checklist and 3) providing free-text rationales for why a headline is or is not accurate -- on people's intention of sharing the headline on social media. From an experiment with 1668 participants, we find that both providing accuracy assessment and rationale reduce the sharing of false content. They also reduce the sharing of true content, but to a lesser degree that yields an overall decrease in the fraction of shared content that is false. Our findings have implications for designing social media and news sharing platforms that draw from richer signals of content credibility contributed by users. In addition, our validated taxonomy can be used by platforms and researchers as a way to gather rationales in an easier fashion than free-response.Comment: To appear in CSCW'2

Exogenous erythropoietin administration attenuates intermittent hypoxia-induced cognitive deficits in a murine model of sleep apnea

Background: In rodents, exposure to intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), is associated with neurobehavioral impairments, increased apoptosis in the hippocampus and cortex, as well as increased oxidant stress and inflammation. Such findings are markedly attenuated in rodents exposed to sustained hypoxia 9SH) of similar magnitude. The hypoxia-sensitive gene erythropoietin (EPO) has emerged as a major endogenous neuroprotectant, and could be involved in IH-induced neuronal dysfunction. Methods and Results: IH induced only transiently increased expression of EPO mRNA in hippocampus, which was continued in (SH)-exposed mice. IH, but not SH, adversely affected two forms of spatial learning in the water maze, and increased markers of oxidative stress. However, on a standard place training task, mice treated with exogenously administered EPO displayed normal learning, and were protected from the spatial learning deficits observed in vehicle-treated (C) littermates exposed to IH. Moreover, anxiety levels were increased in IH as compared to normoxia, while no changes in anxiety emerged in EPO-treated mice. Additionally, C mice, but not EPO-treated IH-exposed mice had significantly elevated levels of NADPH oxidase expression, as well as increased MDA and 8-OHDG levels in cortical and hippocampal lysates. Conclusions: The oxidative stress responses and neurobehavioral impairments induced by IH during sleep are mediated, at least in part, by imbalances between EPO expression and increased NADPH oxidase activity, and thus pharmacological agents targeting EPO expression in CNS may provide a therapeutic strategy in sleep-disordered breathing

Deposition of La2Zr2O7 Film by Chemical Solution Deposition

La2Zr2O7 (LZO) formation of bulk powders and of films by Chemical Solution Deposition (CSD) process have been studied using propionates. The treatment involved a one step cycle in the reducing forming gas (Ar-5%H2) to be compatible with Ni-5at%W RABITS. Large amount of residual carbon was found in LZO powders formed in these conditions (10 wt %). The volume fraction of the cube texture in LZO films on Ni-5at%w RABITS was found to be a function of the speed of the gas flown above sample. This phenomenon is discussed in considering the C deposited from the carbon-containing gases emitted during the pyrolysis of the precursor. Using proper conditions (950 ^\circC and the speed of gas of 6.8\times10^{-2} m/s), LZO films with good surface crystallinity could be obtained on Ni-5at%W RABITS as demonstrated by X-ray diffraction, electron backscattered diffraction and RHEED. The existence of residual carbon in oxide films is a common question to films deposited by CSD processes under reducing condition

Flaw-driven Failure in Nanostructures

Understanding failure in nanomaterials is critical for the design of reliable structural materials and small-scale devices that have components or microstructural elements at the nanometer length scale. No consensus exists on the effect of flaws on fracture in bulk nanostructured materials or in nanostructures. Proposed theories include nanoscale flaw tolerance and maintaining macroscopic fracture relationships at the nanoscale with virtually no experimental support. We explore fracture mechanisms in nanomaterials via nanomechanical experiments on nanostructures with pre-fabricated surface flaws in combination with molecular dynamics simulations. Nanocrystalline Pt cylinders with diameters of ~120 nm with intentionally introduced surface notches were created using a template-assisted electroplating method and tested in uniaxial tension in in-situ SEM. Experiments demonstrate that 8 out of 12 samples failed at the notches and that tensile failure strengths were ~1.8 GPa regardless of whether failure occurred at or away from the flaw. These findings suggest that failure location was sensitive to the presence of flaws, while strength was flaw-insensitive. Molecular dynamics simulations support these observations and show that incipient plastic deformation commences via nucleation and motion of dislocations in concert with grain boundary sliding. We postulate that such local plasticity reduces stress concentration ahead of the flaw to levels comparable with the strengths of intrinsic microstructural features like grain boundary triple junctions, a phenomenon unique to nano-scale solids that contain an internal microstructural energy landscape. This mechanism causes failure to occur at the weakest link, be it an internal inhomogeneity or a surface feature with a high local stress