Salivary total Immunoglobulin G as a surrogate marker of oral immune activity in salivary bioscience research

The integration of salivary biomeasures in biobehavioral, psychophysiological, and clinical research has greatly expanded our ability to study the biopsychosocial processes underlying health. Much of this research, however, has failed to adequately assess and adjust for the impact of oral immune activity on salivary biomeasure concentrations and associations with serum levels. Aiming to improve the validity and reliability of salivary biomeasure data, we examine salivary total Immunoglobulin G (IgG) as a potential surrogate marker of oral inflammation and immune activity. During a single study visit in Baltimore, Maryland, healthy young adult participants provided matched blood and saliva samples (N=99; age 18–37 years, 42% female) and completed an oral health questionnaire. Biospecimens were assayed for total IgG and immune markers related to inflammation (cytokines), blood in saliva (transferrin), and tissue remodeling (matrix metalloproteinase-8). Total IgG (μg/mL) concentrations were higher in serum than saliva. Salivary total IgG was associated with some self-reported oral health measures, and strongly positively associated with all salivary immune markers. Controlling for salivary total IgG may be a feasible, affordable approach to adjusting salivary biomeasure findings for the influence of the oral immune environment when it is not possible or practical to obtain clinical oral health data

Therapy of pancreatic cancer via an EphA2 receptor-targeted delivery of gemcitabine.

First line treatment for pancreatic cancer consists of surgical resection, if possible, and a subsequent course of chemotherapy using the nucleoside analogue gemcitabine. In some patients, an active transport mechanism allows gemcitabine to enter efficiently into the tumor cells, resulting in a significant clinical benefit. However, in most patients, low expression of gemcitabine transporters limits the efficacy of the drug to marginal levels, and patients need frequent administration of the drug at high doses, significantly increasing systemic drug toxicity. In this article we focus on a novel targeted delivery approach for gemcitabine consisting of conjugating the drug with an EphA2 targeting agent. We show that the EphA2 receptor is highly expressed in pancreatic cancers, and accordingly, the drug-conjugate is more effective than gemcitabine alone in targeting pancreatic tumors. Our preliminary observations suggest that this approach may provide a general benefit to pancreatic cancer patients and offers a comprehensive strategy for enhancing delivery of diverse therapeutic agents to a wide range of cancers overexpressing EphA2, thereby potentially reducing toxicity while enhancing therapeutic efficacy

Type III Effector Activation via Nucleotide Binding, Phosphorylation, and Host Target Interaction

The Pseudomonas syringae type III effector protein avirulence protein B (AvrB) is delivered into plant cells, where it targets the Arabidopsis RIN4 protein (resistance to Pseudomonas maculicula protein 1 [RPM1]–interacting protein). RIN4 is a regulator of basal host defense responses. Targeting of RIN4 by AvrB is recognized by the host RPM1 nucleotide-binding leucine-rich repeat disease resistance protein, leading to accelerated defense responses, cessation of pathogen growth, and hypersensitive host cell death at the infection site. We determined the structure of AvrB complexed with an AvrB-binding fragment of RIN4 at 2.3 Å resolution. We also determined the structure of AvrB in complex with adenosine diphosphate bound in a binding pocket adjacent to the RIN4 binding domain. AvrB residues important for RIN4 interaction are required for full RPM1 activation. AvrB residues that contact adenosine diphosphate are also required for initiation of RPM1 function. Nucleotide-binding residues of AvrB are also required for its phosphorylation by an unknown Arabidopsis protein(s). We conclude that AvrB is activated inside the host cell by nucleotide binding and subsequent phosphorylation and, independently, interacts with RIN4. Our data suggest that activated AvrB, bound to RIN4, is indirectly recognized by RPM1 to initiate plant immune system function

An Optically Pure Apogossypolone Derivative as Potent Pan-Active Inhibitor of Anti-Apoptotic Bcl-2 Family Proteins

Our focus in the past several years has been on the identification of novel and effective pan-Bcl-2 antagonists. We have recently reported a series of Apogossypolone (ApoG2) derivatives, resulting in the chiral compound (±) BI97D6. We report here the synthesis and evaluation on its optically pure (−) and (+) atropisomers. Compound (−) BI97D6 potently inhibits the binding of BH3 peptides to Bcl-XL, Bcl-2, Mcl-1, and Bfl-1 with IC50 values of 76 ± 5, 31 ± 2, 25 ± 8, and 122 ± 28 nM, respectively. In a cellular assay, compound (−) BI97D6 effectively inhibits cell growth in the PC-3 human prostate cancer and H23 human lung cancer cell lines with EC50 values of 0.22 ± 0.08 and 0.14 ± 0.02 μM, respectively. Similarly, compound (−) BI97D6 effectively induces apoptosis in the BP3 human lymphoma cell line in a dose-dependent manner. The compound also shows little cytotoxicity against bax−/−/bak−/− cells, suggesting that it kills cancers cells predominantly via a Bcl-2 pathway. Moreover, compound (−) BI97D6 displays in vivo efficacy in both a Bcl-2-transgenic mouse model and in a prostate cancer xenograft model in mice. Therefore, compound (−) BI97D6 represents a promising drug lead for the development of novel apoptosis-based therapies for cancer

Space Based Gravitational Wave Astronomy Beyond LISA

The Laser Interferometer Space Antenna (LISA) will open three decades of gravitational wave(GW) spectrum between 0.1 and 100 mHz, the mHz band [1]. This band is expected to be the richest part of the GW spectrum, in types of sources, numbers of sources, signal-to-noise ratios and discovery potential. When LISA opens the low-frequency window of the gravitational wave spectrum,around 2034, the surge of gravitational-wave astronomy will strongly compel a subsequent mission to further explore the frequency bands of the GW spectrum that can only be accessed from space. The 2020's is the time to start developing technology and studying mission concepts for a large-scale mission to be launched in the 2040's. The mission concept would then be proposed to Astro2030. Only space-based missions can access the GW spectrum between 108 and 1 Hz because of the Earth's seismic noise. This white paper surveys the science in this band and mission concepts that could accomplish that science. The proposed small scale activity is a technology development program that would support a range of concepts and a mission concept study to choose a specific mission concept for Astro2030. In this white paper, we will refer to a generic GW mission beyond LISA as bLISA

Toward an indexing approach to evaluate fly ashes for geopolymer manufacture

Variations between fly ashes can lead to significant differences in the geopolymers derived from them, in both microstructural and mechanical properties. This study assesses the effect of physical, crystallographic and chemical characteristics of fly ash on geopolymerisation performance and the strength of the resulting binders. Physical and glass chemistry factors are combined to develop a comprehensive index to evaluate the suitability of fly ashes for the production of high-strength geopolymers. An equation for this index is proposed, developed using five typical low-calcium fly ashes and then validated against a further eight literature datasets, showing a good relationship between the ranking order of the calculated index and the compressive strengths of geopolymer pastes produced with comparable activator and paste workability. This index can be used to screen the source materials, which is of significant value in moving alkali activated cements towards acceptance in practice

KL Estimation of the Power Spectrum Parameters from the Angular Distribution of Galaxies in Early SDSS Data

We present measurements of parameters of the 3-dimensional power spectrum of galaxy clustering from 222 square degrees of early imaging data in the Sloan Digital Sky Survey. The projected galaxy distribution on the sky is expanded over a set of Karhunen-Loeve eigenfunctions, which optimize the signal-to-noise ratio in our analysis. A maximum likelihood analysis is used to estimate parameters that set the shape and amplitude of the 3-dimensional power spectrum. Our best estimates are Gamma=0.188 +/- 0.04 and sigma_8L = 0.915 +/- 0.06 (statistical errors only), for a flat Universe with a cosmological constant. We demonstrate that our measurements contain signal from scales at or beyond the peak of the 3D power spectrum. We discuss how the results scale with systematic uncertainties, like the radial selection function. We find that the central values satisfy the analytically estimated scaling relation. We have also explored the effects of evolutionary corrections, various truncations of the KL basis, seeing, sample size and limiting magnitude. We find that the impact of most of these uncertainties stay within the 2-sigma uncertainties of our fiducial result.Comment: Fig 1 postscript problem correcte

Galaxy Clustering in Early SDSS Redshift Data

We present the first measurements of clustering in the Sloan Digital Sky Survey (SDSS) galaxy redshift survey. Our sample consists of 29,300 galaxies with redshifts 5,700 km/s < cz < 39,000 km/s, distributed in several long but narrow (2.5-5 degree) segments, covering 690 square degrees. For the full, flux-limited sample, the redshift-space correlation length is approximately 8 Mpc/h. The two-dimensional correlation function \xi(r_p,\pi) shows clear signatures of both the small-scale, ``fingers-of-God'' distortion caused by velocity dispersions in collapsed objects and the large-scale compression caused by coherent flows, though the latter cannot be measured with high precision in the present sample. The inferred real-space correlation function is well described by a power law, \xi(r)=(r/6.1+/-0.2 Mpc/h)^{-1.75+/-0.03}, for 0.1 Mpc/h < r < 16 Mpc/h. The galaxy pairwise velocity dispersion is \sigma_{12} ~ 600+/-100 km/s for projected separations 0.15 Mpc/h < r_p < 5 Mpc/h. When we divide the sample by color, the red galaxies exhibit a stronger and steeper real-space correlation function and a higher pairwise velocity dispersion than do the blue galaxies. The relative behavior of subsamples defined by high/low profile concentration or high/low surface brightness is qualitatively similar to that of the red/blue subsamples. Our most striking result is a clear measurement of scale-independent luminosity bias at r < 10 Mpc/h: subsamples with absolute magnitude ranges centered on M_*-1.5, M_*, and M_*+1.5 have real-space correlation functions that are parallel power laws of slope ~ -1.8 with correlation lengths of approximately 7.4 Mpc/h, 6.3 Mpc/h, and 4.7 Mpc/h, respectively.Comment: 51 pages, 18 figures. Replaced to match accepted ApJ versio