Gluon polarization in the proton

We combine heavy-quark renormalization group arguments with our understanding of the nucleon's wavefunction to deduce a bound on the gluon polarization Delta g in the proton. The bound is consistent with the values extracted from spin experiments at COMPASS and RHIC.Comment: 4 page

Industrial-Scale Manufacture of Oleosin 30G for Use as Contrast Agent in Echocardiography

In ultrasound sonography, microbubbles are used as contrasting agents to improve the effectiveness of ultrasound imaging. Monodisperse microbubbles are required to achieve the optimal image quality. In order to achieve a uniform size distribution, microbubbles are stabilized with surfactant molecules. One such molecule is Oleosin, an amphiphilic structural protein found in vascular plant oil bodies that contains one hydrophobic and two hydrophilic sections. Controlling the functionalization of microbubbles is a comprehensive and versatile process using recombinant technology to produce a genetically engineered form of Oleosin called Oleosin 30G. With the control of a microfluidic device, uniformly-sized and resonant microbubbles can be readily produced and stored in stable conditions up to one month. Currently, Oleosin microbubbles are limited to the lab-scale; however, through development of an integrated batch bioprocessing model, the overall product yield of Oleosin 30G can be increased to 7.39 kg/year to meet needs on the industrial-scale. An Oleosin-stabilized microbubble suspension as a contrast agent is in a strong position to take a competitive share of the current market, capitalizing on needs unmet by current market leader, Definity®. Based on market dynamics and process logistics, scaled-up production of Oleosin 30G for use as a contrast agent is expected to be both a useful and profitable venture

A multidimensional metabolomics workflow to image biodistribution and evaluate pharmacodynamics in adult zebrafish

An integrated evaluation of the tissue distribution and pharmacodynamic properties of a therapeutic is essential for successful translation to the clinic. To date, however, cost-effective methods to measure these parameters at the systems level in model organisms are lacking. Here, we introduce a multidimensional workflow to evaluate drug activity that combines mass spectrometry-based imaging, absolute drug quantitation across different biological matrices, in vivo isotope tracing and global metabolome analysis in the adult zebrafish. As a proof of concept, we quantitatively determined the whole-body distribution of the anti-rheumatic agent hydroxychloroquine sulfate (HCQ) and measured the systemic metabolic impacts of drug treatment. We found that HCQ distributed to most organs in the adult zebrafish 24 h after addition of the drug to water, with the highest accumulation of both the drug and its metabolites being in the liver, intestine and kidney. Interestingly, HCQ treatment induced organ-specific alterations in metabolism. In the brain, for example, HCQ uniquely elevated pyruvate carboxylase activity to support increased synthesis of the neuronal metabolite, N-acetylaspartate. Taken together, this work validates a multidimensional metabolomics platform for evaluating the mode of action of a drug and its potential off-target effects in the adult zebrafish. This article has an associated First Person interview with the first author of the paper

Microbiological, Physicochemical, and Immunological Analysis of a Commercial Cashew Nut-Based Yogurt

Nut-based milks and yogurts are gaining popularity, but may not offer the same benefits as dairy yogurts to consumers. Cashew nuts often cause severe allergic reactions, and cashew nut allergens are stable to several types of processing. To compare its characteristics to dairy yogurt and characterize the effects of fermentation on the Ana o 1-3 cashew nut allergens, a commercial yogurt made from cashew nuts (Cashewgurt) was evaluated for microbiological, physiochemical, and immunological properties. Average counts for lactobacilli and Streptococcus thermophilus were greater than 10 million colony forming units per milliliter, indicating the capacity to provide a health benefit. Cashewgurt pH and viscosity values were comparable to cow milk yogurts, and it was off white in color. SDS-PAGE analysis indicated a clear reduction in Ana o 1 and 2, and immuno-assay with polyclonal anti-cashew IgG antibody and cashew-allergic IgE indicated an overall reduction in allergen content. In contrast, SDS-PAGE, mass spectrometry, immunoblot, and ELISA all revealed that Ana o 3 was relatively unaffected by the fermentation process. In conclusion, Ana o 1 and Ana o 2 are sensitive to degradation, while Ana o 3 survives lactic acid bacterial fermentation during yogurt production. The analysis presented here indicates that cashew nut yogurt is not suitable for those with cashew nut allergy

Breaking the Curve with CANDELS: A Bayesian Approach to Reveal the Non-Universality of the Dust-Attenuation Law at High Redshift

Dust attenuation affects nearly all observational aspects of galaxy evolution, yet very little is known about the form of the dust-attenuation law in the distant Universe. Here, we model the spectral energy distributions (SEDs) of galaxies at z = 1.5--3 from CANDELS with rest-frame UV to near-IR imaging under different assumptions about the dust law, and compare the amount of inferred attenuated light with the observed infrared (IR) luminosities. Some individual galaxies show strong Bayesian evidence in preference of one dust law over another, and this preference agrees with their observed location on the plane of infrared excess (IRX, $L_{\text{TIR}}/L_{\text{UV}}$) and UV slope ($\beta$). We generalize the shape of the dust law with an empirical model, $A_{\lambda,\delta}=E(B-V)\ k_\lambda\ (\lambda/\lambda_V)^\delta$ where $k_\lambda$ is the dust law of Calzetti et al. (2000), and show that there exists a correlation between the color excess ${E(B-V)}$ and tilt $\delta$ with ${\delta=(0.62\pm0.05)\log(E(B-V))}$+ ${(0.26~\pm~0.02)}$. Galaxies with high color excess have a shallower, starburst-like law, and those with low color excess have a steeper, SMC-like law. Surprisingly, the galaxies in our sample show no correlation between the shape of the dust law and stellar mass, star-formation rate, or $\beta$. The change in the dust law with color excess is consistent with a model where attenuation is caused by by scattering, a mixed star-dust geometry, and/or trends with stellar population age, metallicity, and dust grain size. This rest-frame UV-to-near-IR method shows potential to constrain the dust law at even higher ($z>3$) redshifts.Comment: 20 pages, 18 figures, resubmitted to Ap

An Increasing Stellar Baryon Fraction in Bright Galaxies at High Redshift

Recent observations have shown that the characteristic luminosity of the rest-frame ultraviolet (UV) luminosity function does not significantly evolve at 4 < z < 7 and is approximately M*_UV ~ -21. We investigate this apparent non-evolution by examining a sample of 178 bright, M_UV < -21 galaxies at z=4 to 7, analyzing their stellar populations and host halo masses. Including deep Spitzer/IRAC imaging to constrain the rest-frame optical light, we find that M*_UV galaxies at z=4-7 have similar stellar masses of log(M/Msol)=9.6-9.9 and are thus relatively massive for these high redshifts. However, bright galaxies at z=4-7 are less massive and have younger inferred ages than similarly bright galaxies at z=2-3, even though the two populations have similar star formation rates and levels of dust attenuation. We match the abundances of these bright z=4-7 galaxies to halo mass functions from the Bolshoi Lambda-CDM simulation to estimate the halo masses. We find that the typical halo masses in ~M*_UV galaxies decrease from log(M_h/Msol)=11.9 at z=4 to log(M_h/Msol)=11.4 at z=7. Thus, although we are studying galaxies at a similar mass across multiple redshifts, these galaxies live in lower mass halos at higher redshift. The stellar baryon fraction in units of the cosmic mean Omega_b/Omega_m rises from 5.1% at z=4 to 11.7% at z=7; this evolution is significant at the ~3-sigma level. This rise does not agree with simple expectations of how galaxies grow, and implies that some effect, perhaps a diminishing efficiency of feedback, is allowing a higher fraction of available baryons to be converted into stars at high redshifts.Comment: Accepted to ApJ. 15 pages, 5 figures, 6 table

The Evolution of the Galaxy Stellar Mass Function at z= 4-8: A Steepening Low-mass-end Slope with Increasing Redshift

We present galaxy stellar mass functions (GSMFs) at $z=$ 4-8 from a rest-frame ultraviolet (UV) selected sample of $\sim$4500 galaxies, found via photometric redshifts over an area of $\sim$280 arcmin$^2$ in the CANDELS/GOODS fields and the Hubble Ultra Deep Field. The deepest Spitzer/IRAC data yet-to-date and the relatively large volume allow us to place a better constraint at both the low- and high-mass ends of the GSMFs compared to previous space-based studies from pre-CANDELS observations. Supplemented by a stacking analysis, we find a linear correlation between the rest-frame UV absolute magnitude at 1500 \AA\ ($M_{\rm UV}$) and logarithmic stellar mass ($\log M_*$) that holds for galaxies with $\log(M_*/M_{\odot}) \lesssim 10$. We use simulations to validate our method of measuring the slope of the $\log M_*$-$M_{\rm UV}$ relation, finding that the bias is minimized with a hybrid technique combining photometry of individual bright galaxies with stacked photometry for faint galaxies. The resultant measured slopes do not significantly evolve over $z=$ 4-8, while the normalization of the trend exhibits a weak evolution toward lower masses at higher redshift. We combine the $\log M_*$-$M_{\rm UV}$ distribution with observed rest-frame UV luminosity functions at each redshift to derive the GSMFs, finding that the low-mass-end slope becomes steeper with increasing redshift from $\alpha=-1.55^{+0.08}_{-0.07}$ at $z=4$ to $\alpha=-2.25^{+0.72}_{-0.35}$ at $z=8$. The inferred stellar mass density, when integrated over $M_*=10^8$-$10^{13} M_{\odot}$, increases by a factor of $10^{+30}_{-2}$ between $z=7$ and $z=4$ and is in good agreement with the time integral of the cosmic star formation rate density.Comment: 27 pages, 17 figures, ApJ, in pres

Phase II assessment of talabostat and cisplatin in second-line stage IV melanoma

<p>Abstract</p> <p>Background</p> <p>Metastatic melanoma is an incurable disease with an average survival of less than one year. Talabostat is a novel dipeptidyl peptidase inhibitor with immunostimulatory properties.</p> <p>Methods</p> <p>This phase II, open label, single arm study was conducted to evaluate the safety and efficacy of 75–100 mg/m²cisplatin combined with 300–400 mcg talabostat bid for 6, 21-day cycles. The primary endpoint was overall response. The rate of complete responses, duration of overall objective response, progression-free survival (PFS), and overall survival were the secondary endpoints.</p> <p>Results</p> <p>Six objective partial responses were recorded in the 74 patients (8.1%) in the intention-to-treat population. Five of these responses involved the 40 evaluable patients (12.5%). Thirty-one percent of patients reported SAEs to the combination of talabostat and cisplatin.</p> <p>Conclusion</p> <p>Acceptable tolerability was observed in the intention-to-treat population and antitumor activity was observed in 12.5% of evaluable patients, which is not greater than historical expectation with cisplatin alone.</p

Colorectal cancer linkage on chromosomes 4q21, 8q13, 12q24, and 15q22

A substantial proportion of familial colorectal cancer (CRC) is not a consequence of known susceptibility loci, such as mismatch repair (MMR) genes, supporting the existence of additional loci. To identify novel CRC loci, we conducted a genome-wide linkage scan in 356 white families with no evidence of defective MMR (i.e., no loss of tumor expression of MMR proteins, no microsatellite instability (MSI)-high tumors, or no evidence of linkage to MMR genes). Families were ascertained via the Colon Cancer Family Registry multi-site NCI-supported consortium (Colon CFR), the City of Hope Comprehensive Cancer Center, and Memorial University of Newfoundland. A total of 1,612 individuals (average 5.0 per family including 2.2 affected) were genotyped using genome-wide single nucleotide polymorphism linkage arrays; parametric and non-parametric linkage analysis used MERLIN in a priori-defined family groups. Five lod scores greater than 3.0 were observed assuming heterogeneity. The greatest were among families with mean age of diagnosis less than 50 years at 4q21.1 (dominant HLOD = 4.51, α = 0.84, 145.40 cM, rs10518142) and among all families at 12q24.32 (dominant HLOD = 3.60, α = 0.48, 285.15 cM, rs952093). Among families with four or more affected individuals and among clinic-based families, a common peak was observed at 15q22.31 (101.40 cM, rs1477798; dominant HLOD = 3.07, α = 0.29; dominant HLOD = 3.03, α = 0.32, respectively). Analysis of families with only two affected individuals yielded a peak at 8q13.2 (recessive HLOD = 3.02, α = 0.51, 132.52 cM, rs1319036). These previously unreported linkage peaks demonstrate the continued utility of family-based data in complex traits and suggest that new CRC risk alleles remain to be elucidated. © 2012 Cicek et al

Functional and symptom impact of trametinib versus chemotherapy in BRAF V600E advanced or metastatic melanoma: quality-of-life analyses of the METRIC study

We report the first quality-of-life assessment of a MEK inhibitor in metastatic melanoma from a phase III study. Trametinib prolonged progression-free survival and improved overall survival versus chemotherapy in patients with BRAF V600 mutation-positive melanoma. Less functional impairment, smaller declines in health status, and less exacerbation of symptoms were observed with trametini