EMP2 regulates angiogenesis in endometrial cancer cells through induction of VEGF.

Understanding tumor-induced angiogenesis is a challenging problem with important consequences for the diagnosis and treatment of cancer. In this study, we define a novel function for epithelial membrane protein-2 (EMP2) in the control of angiogenesis. EMP2 functions as an oncogene in endometrial cancer, and its expression has been linked to decreased survival. Using endometrial cancer xenografts, modulation of EMP2 expression resulted in profound changes to the tumor microvasculature. Under hypoxic conditions, upregulation of EMP2 promoted vascular endothelial growth factors (VEGF) expression through a HIF-1α-dependent pathway and resulted in successful capillary-like tube formation. In contrast, reduction of EMP2 correlated with reduced HIF-1α and VEGF expression with the net consequence of poorly vascularized tumors in vivo. We have previously shown that targeting of EMP2 using diabodies in endometrial cancer resulted in a reduction of tumor load, and since then we have constructed a fully human EMP2 IgG1. Treatment of endometrial cancer cells with EMP2-IgG1 reduced tumor load with a significant improvement in survival. These results support the role of EMP2 in the control of the tumor microenvironment and confirm the cytotoxic effects observed by EMP2 treatment in vivo

Deep Learning Research: Scientometric Assessment of Global Publications Output during 2004 -17

The paper provides a quantitative and qualitative description of deep learning research using bibliometric indicators covering global research publications published during 14-year period 2004-17. Global deep learning research registered 106.76% high growth per annum, and averaged 7.99 citations per paper. Top 10 countries world- over dominate the research field with their 99.74% global publications share and more than 100% global citations share. China ranks the top with the highest (29.25%) global publications share, followed by USA (26.46%), U.K. (6.40%), etc. during the period. Canada tops in relative citation index (5.30). International collaboration has been a major driver of research in the subject with 14.96% to 53.76% of national-level share of top 10 countries output appeared as international collaborative publications. Computer Science is one of the most popular areas of research in deep learning research (76.85% share). The study identifies top 50 most productive organizations and 50 most productive authors and top 20 most productive journals reporting deep learning research and 118 highly cited papers with 100+ citations per paper

Multi-messenger constraints on the Hubble constant through combination of gravitational waves, gamma-ray bursts and kilonovae from neutron star mergers

The simultaneous detection of gravitational waves and light from the binary neutron star merger GW170817 led to independent measurements of distance and redshift, providing a direct estimate of the Hubble constant $H_0$ that does not rely on a cosmic distance ladder nor assumes a specific cosmological model. By using gravitational waves as ''standard sirens'', this approach holds promise to arbitrate the existing tension between the $H_0$ value inferred from the cosmic microwave background and those obtained from local measurements. However, the known degeneracy in the gravitational-wave analysis between distance and inclination of the source lead to a $H_0$ value from GW170817 that was not precise enough to resolve the existing tension. In this review, we summarize recent works exploiting the viewing-angle dependence of the electromagnetic signal, namely the associated short gamma-ray burst and kilonova, to constrain the system inclination and improve on $H_0$. We outline the key ingredients of the different methods, summarize the results obtained in the aftermath of GW170817 and discuss the possible systematics introduced by each of these methods

Mobile computing: a scientometric assessment of global publications output

The paper examines 34641 global publications output on mobile computing research, as covered in Scopus database during 2007-16. The study finds that mobile computing research is growing at 9.35% rate per annum and its citation impact averaged to 3.39 citations per paper. The global share of top 10 most productive countries ranged from 3.29% to 31.06%, with largest global publication share coming from China (31.06%), followed by USA (15.35%), etc. Together, the top 10 most productive countries accounted for 81.24% global publication share during 2007-16. Seven of top 10 countries achieved relative citation index above world average of 1: USA (2.37), U.K. (1.78), Italy (1.72), Canada (1.64), etc. International collaborative publications share of top 10 most productive countries in mobile computing research during 2007-16 varied from 11.55% to 48.16%. Computer Science, among subjects, accounted for the largest publication share (89.55%), followed by engineering (33.58%), social sciences (18.67%), mathematics (8.74%), etc. during 2007-16. The top 20 most productive organizations and authors contributed 14.79% and 1.76% global publication share respectively and accounted for 9.5% and 5.11% global citation share respectively during 2007-16. The top 20 journals accounted for 24.11% share of total journals output of 5673 papers during 2007-16. The top 50 highly cited publications registered citations in the range from 164 to 1235 citations per paper and together these top 50 papers cumulated 16822 citations, with an average of 336.4 citations per paper. These 50 highly cited papers resulted from participation of 184 authors and 103 organizations, and were published in 31 journals, including 4 in IEEE Transactions on Mobile Computing, 2 papers each in Decision Support System, IEEE Communication Magazine, IEEE Pervasive Computing and IEEE Communication Surveys & Tutorials and 1 paper each in other 26 journals.

Radio Spectral Index Analysis and Classes of Ejection in LS I +61 303

LS I +61303 is a gamma-ray binary with periodic radio outbursts coincident with the orbital period of P=26.5 d. The origin of the radio emission is unclear,it could be due either to a jet, as in microquasars, or to the shock boundary between the Be star and a possible pulsar wind. We here analyze the radio spectral index over 6.7 yr from Green Bank Interferometer data at 2.2 GHz and 8.3 GHz. We find two new characteristics in the radio emission. The first characteristic is that the periodic outbursts indeed consist of two consecutive outbursts; the first outburst is optically thick, whereas the second outburst is optically thin. The spectrum of LS I +61 303 is well reproduced by the shock-in-jet model commonly used in the context of microquasars and AGNs: the optically thin spectrum is due to shocks caused by relativistic plasma ("transient jet") traveling through a pre-existing much slower steady flow ("steady jet"). This steady flow is responsible for the preceding optically thick spectrum. The second characteristic we find is that the observed spectral evolution, from optically thick to optically thin emission, occurs twice during the orbital period. We observed this occurrence at the orbital phase of the main 26.5 d outburst and also at an earlier phase, shifted by $\Delta \Phi \sim$ 0.3 (i.e almost 8 days before). We show that this result qualitatively and quantitatively agrees with the two-peak accretion/ejection model proposed in the past for LS I +61303. We conclude that the radio emission in LS I +61303 originates from a jet and suggest that the variable TeV emission comes from the usual Compton losses expected as an important by-product in the shock-in-jet theory.Comment: 27 pages, 7 figures, accepted for publication in Ap

A Parallax Distance to the Microquasar GRS 1915+105 and a Revised Estimate of its Black Hole Mass

Using the Very Long Baseline Array, we have measured a trigonometric parallax for the micro quasar GRS 1915+105, which contains a black hole and a K-giant companion. This yields a direct distance estimate of 8.6 (+2.0,-1.6) kpc and a revised estimate for the mass of the black hole of 12.4 (+2.0,-1.8) Msun. GRS 1915+105 is at about the same distance as some HII regions and water masers associated with high-mass star formation in the Sagittarius spiral arm of the Galaxy. The absolute proper motion of GRS 1915+105 is -3.19 +/- 0.03 mas/y and -6.24 +/- 0.05 mas/y toward the east and north, respectively, which corresponds to a modest peculiar speed of 22 +/-24 km/s at the parallax distance, suggesting that the binary did not receive a large velocity kick when the black hole formed. On one observational epoch, GRS 1915+105 displayed superluminal motion along the direction of its approaching jet. Considering previous observations of jet motions, the jet in GRS 1915+105 can be modeled with a jet inclination to the line of sight of 60 +/- 5 deg and a variable flow speed between 0.65c and 0.81c, which possibly indicates deceleration of the jet at distances from the black hole >2000 AU. Finally, using our measurements of distance and estimates of black hole mass and inclination, we provisionally confirm our earlier result that the black hole is spinning very rapidly.Comment: 20 pages; 2 tables; 6 figure

Nebular spectroscopy of SN 2014J: Detection of stable nickel in near infrared spectra

We present near infrared (NIR) spectroscopy of the nearby supernova 2014J obtained $\sim$450 d after explosion. We detect the [Ni II] 1.939 $\mu$m line in the spectra indicating the presence of stable $^{58}$Ni in the ejecta. The stable nickel is not centrally concentrated but rather distributed as the iron. The spectra are dominated by forbidden [Fe II] and [Co II] lines. We use lines, in the NIR spectra, arising from the same upper energy levels to place constraints on the extinction from host galaxy dust. We find that that our data are in agreement with the high $A_V$ and low $R_V$ found in earlier studies from data near maximum light. Using a $^{56}$Ni mass prior from near maximum light $\gamma$-ray observations, we find $\sim$0.05 M$_\odot$ of stable nickel to be present in the ejecta. We find that the iron group features are redshifted from the host galaxy rest frame by $\sim$600 km s$^{-1}$.Comment: 6 pages, 4 figures, submitted to A&

Beta amyloid oligomers and fibrils stimulate differential activation of primary microglia

<p>Abstract</p> <p>Background</p> <p>Beta amyloid (Aβ) peptides are the major constituents of the senile plaques present in Alzheimer's diseased brain. Pathogenesis has been associated with the aggregated form of the peptide as these fibrils are the conformation readily found in the plaques. However, recent studies have shown that the nonaggregated, soluble assemblies of Aβ have the potential to stimulate neuronal dysfunction and may play a prominent role in the pathogenesis of Alzheimer's disease.</p> <p>Methods</p> <p>Soluble, synthetic Aβ1–42 oligomers were prepared producing mainly dimer-trimer conformations as assessed by SDS-PAGE. Similar analysis demonstrated fibril preparations to produce large insoluble aggregates unable to migrate out of the stacking portion of the gels. These peptide preparations were used to stimulate primary murine microglia and cortical neuron cultures. Microglia were analyzed for changes in signaling response and secretory phenotype via Western analysis and ELISA. Viability was examined by quantifying lactate dehydrogenase release from the cultures.</p> <p>Results</p> <p>Aβ oligomers and fibrils were used to stimulate microglia for comparison. Both the oligomers and fibrils stimulated proinflammatory activation of primary microglia but the specific conformation of the peptide determined the activation profile. Oligomers stimulated increased levels of active, phosphorylated Lyn and Syk kinase as well as p38 MAP kinase compared to fibrils. Moreover, oligomers stimulated a differential secretory profile for interleukin 6, monocyte chemoattractant protein-1 and keratinocyte chemoattractant when compared to fibrils. Finally, soluble oligomers stimulated death of cultured cortical neurons that was exacerbated by the presence of microglia.</p> <p>Conclusion</p> <p>These data suggest that fibrils and oligomers stimulate unique signaling responses in microglia leading to discrete secretory changes and effects on neuron survival. This suggests that inflammation changes during disease may be the consequence of unique peptide-stimulated events and each conformation may represent an individual anti-inflammatory therapeutic target.</p