Message Delivery: A Revised Approach for Public Relations Measurement

The measurement of communication impact has become a long-standing discussion in the public relations research community. While discussions about standardized measurement date back decades (Lindenmann, 2005, pp. 3-4), the current debates about standardized measurement became prominent with the work of Michaelson and Stacks (Michaelson & Stacks, 2011). In their 2011 article, they argued that public relations measurement needed to be standardized to demonstrate communication activity impact on absolute levels of impact as well as on relative measures. The question this paper explored is “What is the root cause for the lack of adoption of standardized measurement by the public relations profession?” In so doing, this paper proposes a revised approach to standardized measurement that is based on message delivery based on a revision of an analytic approach originally proposed by Michaelson and Griffin (2005) that is steeped in message level content analysis. It expands this approach by creating a unified message delivery-scoring model that provides for the inclusion of intended messages, the omission of intended messages, and the presence of negative messages in media. The research includes rigorous testing that demonstrates the validity and statistical reliability of the proposed model and its relationship to sentiment analysis. The analysis also examines the statistical impact of negative messages in media and concludes that the presence of negative messages effectively detracts from the overall sentiment of an article just as the presence of positive messages increases overall sentiment

Urinary TWEAK as a biomarker of lupus nephritis: a multicenter cohort study

Introduction: TNF-like weak inducer of apoptosis (TWEAK) has been implicated as a mediator of chronic inflammatory processes via prolonged activation of the NF-κB pathway in several tissues, including the kidney. Evidence for the importance of TWEAK in the pathogenesis of lupus nephritis (LN) has been recently introduced. Thus, TWEAK levels may serve as an indication of LN presence and activity. Methods: Multicenter cohorts of systemic lupus erythematosus (SLE) patients and controls were recruited for cross-sectional and longitudinal analysis of urinary TWEAK (uTWEAK) and/or serum TWEAK (sTWEAK) levels as potential biomarkers of LN. The performance of TWEAK as a biomarker for nephritis was compared with routinely used laboratory tests in lupus patients, including anti-double stranded DNA antibodies and levels of C3 and C4. Results: uTWEAK levels were significantly higher in LN patients than in non-LN SLE patients and other disease control groups (P = 0.039). Furthermore, uTWEAK was better at distinguishing between LN and non-LN SLE patients than anti-DNA antibodies and complement levels, while high uTWEAK levels predicted LN in SLE patients with an odds ratio of 7.36 (95% confidence interval = 2.25 to 24.07; P = 0.001). uTWEAK levels peaked during LN flares, and were significantly higher during the flare than at 4 and 6 months prior to or following the flare event. A linear mixed-effects model showed a significant association between uTWEAK levels in SLE patients and their disease activity over time (P = 0.008). sTWEAK levels, however, were not found to correlate with the presence of LN or the degree of nephritis activity. Conclusions: High uTWEAK levels are indicative of LN, as opposed to non-LN SLE and other healthy and disease control populations, and reflect renal disease activity in longitudinal follow-up. Thus, our study further supports a role for TWEAK in the pathogenesis of LN, and provides strong evidence for uTWEAK as a candidate clinical biomarker for LN

Pulse‐labeling studies of carbon cycling in arctic tundra ecosystems: Contribution of photosynthates to soil organic matter

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95486/1/gbc827.pd

Body Mass Index, PAM50 Subtype, and Outcomes in Node-Positive Breast Cancer: CALGB 9741 (Alliance)

Obesity at diagnosis is associated with poor prognosis in women with breast cancer, but few reports have been adjusted for treatment factors

Learning Transcriptional Regulatory Relationships Using Sparse Graphical Models

Understanding the organization and function of transcriptional regulatory networks by analyzing high-throughput gene expression profiles is a key problem in computational biology. The challenges in this work are 1) the lack of complete knowledge of the regulatory relationship between the regulators and the associated genes, 2) the potential for spurious associations due to confounding factors, and 3) the number of parameters to learn is usually larger than the number of available microarray experiments. We present a sparse (L1 regularized) graphical model to address these challenges. Our model incorporates known transcription factors and introduces hidden variables to represent possible unknown transcription and confounding factors. The expression level of a gene is modeled as a linear combination of the expression levels of known transcription factors and hidden factors. Using gene expression data covering 39,296 oligonucleotide probes from 1109 human liver samples, we demonstrate that our model better predicts out-of-sample data than a model with no hidden variables. We also show that some of the gene sets associated with hidden variables are strongly correlated with Gene Ontology categories. The software including source code is available at http://grnl1.codeplex.com

Plant succession in the University of Michigan burn plots in northern lower Michigan.

Secondary succession is the progressive replacement of the species in a community after a disturbance has occurred on the community. Seres of succession are determined by the existing vegetation. Three experimental burn plots (1911, 1948, 1980) were sampled on the University of Michigan Biological Station set up to observe secondary succession after clearcutting and burning. Species diversity, richness, composition and abundance of woody and herbaceous species was examined. Significant differences were found in species of woody and herbaceous. Total species diversity in plots was found to be similar. Differences were found among species richness and woody and herbaceous composition among plots. Relative abundance of herbaceous plants decreased as the relative abundance of woody plants increased with time among the plots. From the plant species found the burn plots were determined to be at different seres of secondary succession.http://deepblue.lib.umich.edu/bitstream/2027.42/54684/1/3124.pdfDescription of 3124.pdf : Access restricted to on-site users at the U-M Biological Station

Homeodomain-Interacting Protein Kinase 1 Modulates Daxx Localization, Phosphorylation, and Transcriptional Activity

We describe an interaction between homeodomain-interacting protein kinase 1 (HIPK1) and Daxx, two transcriptional regulators important in transducing growth-regulatory signals. We demonstrate that HIPK1 is ubiquitously expressed in mice and humans and localizes predominantly to the nucleus. Daxx normally resides within the nucleus in promyelocytic leukemia protein (PML) oncogenic domains (PODs), where it physically interacts with PML. Under certain circumstances, Daxx is relocalized from PODs to chromatin, where it then acts as a transcriptional repressor through an association with histone deacetylase (HDAC1). We propose two novel mechanisms for regulating the activity of Daxx, both mediated by HIPK1. First, HIPK1 physically interacts with Daxx in cells and consequently relocalizes Daxx from PODs. Daxx relocalization disrupts its interaction with PML and augments its interaction with HDAC1, likely influencing Daxx activity. Although the relocalization of Daxx from PODs is phosphorylation independent, an active HIPK1 kinase domain is required, suggesting that HIPK1 autophosphorylation is important in this interaction. Second, HIPK1 phosphorylates Daxx on Ser 669, and phosphorylation of this site is important in modulating the ability of Daxx to function as a transcriptional repressor. Mutation of Daxx Ser 669 to Ala results in increased repression in three of four transcriptional reporters, suggesting that phosphorylation by HIPK1 diminishes Daxx transcriptional repression of specific promoters. Taken together, our results indicate that HIPK1 and Daxx collaborate in regulating transcription

CLN-978, a novel half-life extended CD19/CD3/HSA-specific T cell-engaging antibody construct with potent activity against B-cell malignancies with low CD19 expression

Background Despite significant progress in the development of T cell-engaging therapies for various B-cell malignancies, a high medical need remains for the refractory disease setting, often characterized by suboptimal target levels.Methods To address this issue, we have developed a 65-kDa multispecific antibody construct, CLN-978, with affinities tuned to optimize the killing of low-CD19 expressing tumor cells. CLN-978 bound to CD19 on B cells with picomolar affinity, and to CD3ε on T cells with nanomolar affinity. A serum albumin binding domain was incorporated to extend serum half-life. In this setting, we biophysically characterize and report the activities of CLN-978 in cell co-culture assays, multiple mouse models and non-human primates.Results Human T cells redirected by CLN-978 could eliminate target cells expressing less than 300 copies of CD19 on their surface. The half-life extension and high affinity for CD19 led to significant antitumor activity in murine lymphoma models at very low doses of CLN-978. In primates, we observed a long serum half-life, deep and sustained depletion of normal B cells, and remarkable tolerability, in particular, reduced cytokine release when CLN-978 was administered subcutaneously.Conclusions CLN-978 warrants further exploration. An ongoing clinical phase 1 trial is investigating safety, pharmacokinetics, pharmacodynamics, and the initial therapeutic potential of subcutaneously administered CLN-978 in patients with non-Hodgkin’s lymphoma