Localized In‐Band Rotational Phonons in Mixed Molecular Crystals: Electronic Spectra of Naphthalene Doped Biphenyl and Durene

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/70064/2/JCPSA6-56-7-3716-1.pd

Interleukin 1: a mitogen for human vascular smooth muscle cells that induces the release of growth-inhibitory prostanoids.

There is much interest in defining the signals that initiate abnormal proliferation of cells in a variety of states characterized by the presence of mononuclear phagocytes. Since IL-1 is a major secretory product of activated human monocytes we examined whether this cytokine can stimulate the growth of human vascular smooth muscle cells (SMC). Neither recombinant IL-1 (rIL-1) alpha (less than or equal to 5.0 ng/ml) nor beta (less than or equal to 100 ng/ml) stimulated SMC growth during 2-d incubations under usual conditions. IL-1 did stimulate SMC to produce prostanoids such as PGE1 or PGE2 that can inhibit SMC proliferation. When prostaglandin synthesis was inhibited by indomethacin or aspirin both rIL-1 alpha and beta (greater than or equal to 1 ng/ml) markedly increased SMC growth. In longer-term experiments (7-28 d) rIL-1 stimulated the growth of SMC even in the absence of cyclooxygenase inhibitors. The addition of exogenous PGE1 or PGE2 (but not PGF1 alpha, PGF2 alpha, PGI2) to indomethacin-treated SMC blocked their mitogenic response to rIL-1. Antibody to IL-1 (but not to platelet-derived growth factor [PDGF]) abolished the mitogenic response of SMC to rIL-1. Exposure of SMC to rIL-1 or PDGF caused rapid (maximal at 1 h) and transient (baseline by 3 h) expression of the c-fos proto-oncogene, determined by Northern analysis. We conclude that IL-1 is a potent mitogen for human SMC. Endogenous prostanoid production simultaneously induced by IL-1 appears to antagonize this growth-promoting effect in the short term (2 d) but not during more prolonged exposures. IL-1 produced by activated monocytes at sites of tissue inflammation or injury may thus mediate both positive and negative effects on SMC proliferation that are temporally distinct

Immune interferon inhibits proliferation and induces 2'-5'-oligoadenylate synthetase gene expression in human vascular smooth muscle cells.

Proliferation of vascular smooth muscle cells (SMC) contributes to formation of the complicated human atherosclerotic plaque. These lesions also contain macrophages, known to secrete SMC mitogens, and T lymphocytes. Many of the SMC in the lesions express class II major histocompatibility antigens, an indication that activated T cells secrete immune IFN-gamma locally in the plaque. We therefore studied the effect of IFN-gamma on the proliferation of cultured SMC derived from adult human blood vessels. IFN-gamma (1,000 U/ml) reduced [3H]thymidine (TdR) incorporation into DNA by SMC stimulated with the well-defined mitogens IL 1 (from 15.3 +/- 0.7 to 6.2 +/- 0.7 dpm X 10(-3)/24 h) or platelet-derived growth factor (PDGF) (from 18.5 +/- 1.0 to 7.3 +/- 0.7 dpm X 10(-3)/24 h). Kinetic and nuclear labeling studies indicated that this effect of IFN-gamma was not due to altered thymidine transport or specific radioactivity of TdR in the cell. In longer term experiments (4-16 d) IFN-gamma prevented net DNA accumulation by SMC cultures stimulated by PDGF. IFN-gamma also delayed (from 30 to 60 min) the time to peak level of c-fos RNA in IL 1-treated SMC. It is unlikely that cytotoxicity caused these effects of IFN-gamma, as the inhibition of growth was reversible and we detected no cell death in SMC cultures exposed to this cytokine. Activation of 2'-5' oligoadenylate synthetase gene expression may mediate certain antiproliferative and antiviral effects of interferons. Both IFN-gamma and type I IFNs (IFN-alpha or IFN-beta) induced 2'-5' oligoadenylate synthetase mRNA and enzyme activity in SMC cultures, but with concentration dependence and time course that may not account for all of IFN-gamma's cytostatic effect on SMC. The accumulation of SMC in human atherosclerotic lesions is a long-term process that must involve altered balance between growth stimulatory and inhibitory factors. The cytostatic effect of IFN-gamma on human SMC demonstrated here may influence this balance during human atherogenesis, because T cells present in the complicated atherosclerotic plaque likely produce this cytokine

Time series gene expression profiling and temporal regulatory pathway analysis of BMP6 induced osteoblast differentiation and mineralization

Background: BMP6 mediated osteoblast differentiation plays a key role in skeletal development and bone disease. Unfortunately, the signaling pathways regulated by BMP6 are largely uncharacterized due to both a lack of data and the complexity of the response. Results: To better characterize the signaling pathways responsive to BMP6, we conducted a time series microarray study to track BMP6 induced osteoblast differentiation and mineralization. These temporal data were analyzed using a customized gene set analysis approach to identify temporally coherent sets of genes that act downstream of BMP6. Our analysis identified BMP6 regulation of previously reported pathways, such as the TGF-beta pathway. We also identified previously unknown connections between BMP6 and pathways such as Notch signaling and the MYB and BAF57 regulatory modules. In addition, we identify a super-network of pathways that are sequentially activated following BMP6 induction. Conclusion: In this work, we carried out a microarray-based temporal regulatory pathway analysis of BMP6 induced osteoblast differentiation and mineralization using GAGE method. This novel temporal analysis is more informative and powerful than the classical static pathway analysis in that: (1) it captures the interconnections between signaling pathways or functional modules and demonstrates the even higher level organization of molecular biological systems; (2) it describes the temporal perturbation patterns of each pathway or module and their dynamic roles in osteoblast differentiation. The same set of experimental and computational strategies employed in our work could be useful for studying other complex biological processes

Type II Supernova Light Curves and Spectra From the CfA

We present multiband photometry of 60 spectroscopically-confirmed supernovae (SN): 39 SN II/IIP, 19 IIn, one IIb and one that was originally classified as a IIn but later as a Ibn. Forty-six have only optical photometry, six have only near infrared (NIR) photometry and eight have both optical and NIR. The median redshift of the sample is 0.016. We also present 192 optical spectra for 47 of the 60 SN. All data are publicly available. There are 26 optical and two NIR light curves of SN II/IIP with redshifts z > 0.01, some of which may give rise to useful distances for cosmological applications. All photometry was obtained between 2000 and 2011 at the Fred Lawrence Whipple Observatory (FLWO), via the 1.2m and 1.3m PAIRITEL telescopes for the optical and NIR, respectively. Each SN was observed in a subset of the $u'UBVRIr'i'JHK_s$ bands. There are a total of 2932 optical and 816 NIR light curve points. Optical spectra were obtained using the FLWO 1.5m Tillinghast telescope with the FAST spectrograph and the MMT Telescope with the Blue Channel Spectrograph. Our photometry is in reasonable agreement with other samples from the literature. Comparison with Pan-STARRS shows that two-thirds of our individual star sequences have weighted-mean V offsets within $\pm$0.02 mag. In comparing our standard-system SN light curves with common Carnegie Supernova Project objects using their color terms, we found that roughly three-quarters have average differences within $\pm$0.04 mag. The data from this work and the literature will provide insight into SN II explosions, help with developing methods for photometric SN classification, and contribute to their use as cosmological distance indicators.Comment: Accepted to ApJS. TAR of light curves and star sequences here: https://www.cfa.harvard.edu/supernova/fmalcolm2017/cfa_snII_lightcurvesndstars.june2017.tar ... Spectra can be found here: https://www.cfa.harvard.edu/supernova/fmalcolm2017/cfaspec_snII.tar.gz ... Passbands and plot of spectra can be found here: https://www.cfa.harvard.edu/supernova/SNarchive.htm

Multi-color Optical and NIR Light Curves of 64 Stripped-Envelope Core-Collapse Supernovae

We present a densely-sampled, homogeneous set of light curves of 64 low redshift (z < 0.05) stripped-envelope supernovae (SN of type IIb, Ib, Ic and Ic-bl). These data were obtained between 2001 and 2009 at the Fred L. Whipple Observatory (FLWO) on Mt. Hopkins in Arizona, with the optical FLWO 1.2-m and the near-infrared PAIRITEL 1.3-m telescopes. Our dataset consists of 4543 optical photometric measurements on 61 SN, including a combination of UBVRI, UBVr'i', and u'BVr'i', and 2142 JHKs near-infrared measurements on 25 SN. This sample constitutes the most extensive multi-color data set of stripped-envelope SN to date. Our photometry is based on template-subtracted images to eliminate any potential host galaxy light contamination. This work presents these photometric data, compares them with data in the literature, and estimates basic statistical quantities: date of maximum, color, and photometric properties. We identify promising color trends that may permit the identification of stripped-envelope SN subtypes from their photometry alone. Many of these SN were observed spectroscopically by the CfA SN group, and the spectra are presented in a companion paper (Modjaz et al. 2014). A thorough exploration that combines the CfA photometry and spectroscopy of stripped-envelope core-collapse SN will be presented in a follow-up paper.Comment: 26 pages, 17 figures, 8 tables. Revised version resubmitted to ApJ Supplements after referee report. Additional online material is available through http://cosmo.nyu.edu/SNYU

Real-time analysis of T cell receptors in naive cells in vitro and in vivo reveals flexibility in synapse and signaling dynamics

Real-time imaging defines the dynamics of TCR and T cell motility during early T cell activation in lymph nodes

GAGE: generally applicable gene set enrichment for pathway analysis

<p>Abstract</p> <p>Background</p> <p>Gene set analysis (GSA) is a widely used strategy for gene expression data analysis based on pathway knowledge. GSA focuses on sets of related genes and has established major advantages over individual gene analyses, including greater robustness, sensitivity and biological relevance. However, previous GSA methods have limited usage as they cannot handle datasets of different sample sizes or experimental designs.</p> <p>Results</p> <p>To address these limitations, we present a new GSA method called Generally Applicable Gene-set Enrichment (GAGE). We successfully apply GAGE to multiple microarray datasets with different sample sizes, experimental designs and profiling techniques. GAGE shows significantly better results when compared to two other commonly used GSA methods of GSEA and PAGE. We demonstrate this improvement in the following three aspects: (1) consistency across repeated studies/experiments; (2) sensitivity and specificity; (3) biological relevance of the regulatory mechanisms inferred.</p> <p>GAGE reveals novel and relevant regulatory mechanisms from both published and previously unpublished microarray studies. From two published lung cancer data sets, GAGE derived a more cohesive and predictive mechanistic scheme underlying lung cancer progress and metastasis. For a previously unpublished BMP6 study, GAGE predicted novel regulatory mechanisms for BMP6 induced osteoblast differentiation, including the canonical BMP-TGF beta signaling, JAK-STAT signaling, Wnt signaling, and estrogen signaling pathways–all of which are supported by the experimental literature.</p> <p>Conclusion</p> <p>GAGE is generally applicable to gene expression datasets with different sample sizes and experimental designs. GAGE consistently outperformed two most frequently used GSA methods and inferred statistically and biologically more relevant regulatory pathways. The GAGE method is implemented in R in the "gage" package, available under the GNU GPL from <url>http://sysbio.engin.umich.edu/~luow/downloads.php</url>.</p

Development of a plasma panel radiation detector: recent progress and key issues

A radiation detector based on plasma display panel technology, which is the principal component of plasma television displays is presented. Plasma Panel Sensor (PPS) technology is a variant of micropattern gas radiation detectors. The PPS is conceived as an array of sealed plasma discharge gas cells which can be used for fast response (O(5ns) per pixel), high spatial resolution detection (pixel pitch can be less than 100 micrometer) of ionizing and minimum ionizing particles. The PPS is assembled from non-reactive, intrinsically radiation-hard materials: glass substrates, metal electrodes and inert gas mixtures. We report on the PPS development program, including simulations and design and the first laboratory studies which demonstrate the usage of plasma display panels in measurements of cosmic ray muons, as well as the expansion of experimental results on the detection of betas from radioactive sources.Comment: presented at IEEE NSS 2011 (Barcelona