Exploring the Potential Use of a PBMC-Based Functional Assay to Identify Predictive Biomarkers for Anti-PD-1 Immunotherapy

The absence of reliable, robust, and non-invasive biomarkers for anti- Programmed cell death protein 1 (PD-1) immunotherapy is an urgent unmet medical need for the treatment of cancer patients. No predictive biomarkers have been established based on the direct assessment of T cell functions, the primary mechanism of action of anti-PD-1 therapy. In this study, we established a model system to test T cell functions modulated by Nivolumab using anti-CD3 monoclonal antibody (mAb)-stimulated peripheral blood mononuclear cells (PBMCs), and characterized T cell functions primarily based on the knowledge gained from retrospective observations of patients treated with anti-PD-1 immunotherapy. During a comprehensive cytokine profile assessment to identify potential biomarkers, we found that Nivolumab increases expression of T helper type 1 (Th1) associated cytokines such as interferon-γ (IFN-γ) and interleukin-2 (IL-2) in a subset of donors. Furthermore, Nivolumab increases production of Th2, Th9, and Th17 associated cytokines, as well as many proinflammatory cytokines such as IL-6 in a subset of donors. Conversely, Nivolumab treatment has no impact on T cell proliferation, expression of CD25, CD69, or Granzyme B, and only modestly increases in the expansion of regulatory T cells. Our results suggest that assessment of cytokine production using a simple PBMC-based T cell functional assay could be used as a potential predictive marker for anti-PD-1 immunotherapy.     

Advancing the assessment of automated deception detection systems: Incorporating base rate and cost into system evaluation

In the last two decades, there has been an increased interest in automated deception detection systems (ADDs) for use in screening, although little attention has been paid to the usefulness of these systems. ADDs use various means, both invasive and non‐invasive, to ascertain individual intent to deceive or engage in malicious behaviour. Many papers introducing ADDs use signal detection theory to compare a technique's ability to detect malicious intent with other techniques, but in doing so, they do not include contextual information such as base rate and cost. In this paper, we aim to improve future research by showing how the inclusion of contextual information provides a more realistic picture of the research. Through both theoretical arguments and a real‐data example, we show that especially for those contexts where malicious intent is infrequent (ie, with low base rates of deception) that not factoring in the base rate overestimates the accuracy and therefore usefulness. We conclude with recommendations for how future research should provide a fuller picture of the accuracy and usefulness of ADDs.     

Resin Bonding to Silicatized Zirconia with Two Isocyanatosilanes and a Cross-linking Silane. Part I: Experimental

In this paper we discuss and interpret the results of shear bond strengths achieved after the use of two silane coupling agents with isocyanato functionality, viz. 3-isocyanatopropyltrimethoxysilane and 3-isocyanatopropyltriethoxysilane. The silanes were used alone and also blended with a non-functional cross-linking silane on silicatized zirconia before light-curing of resin stubs on the surface, as described elsewhere in the first part of our study (see “Part I: Experimental”). A series of reaction mechanisms and conceptual diagrams are also presented. The reaction mechanisms illustrating the effect of adding a cross-linking silane into a silane blend, the silane hydrolysis and the behavior of two organofunctional groups (isocyanate and alkene) of silanes upon reaction with Rely X Unicem Aplicap resin-composite cement are discussed in detail.     

Ink‐jet printing process for lyocell and cotton fibres. Part 2: The relationship of colour strength and dye fixation to ink penetration

The colour appearance on ink‐jet printed textiles is influenced by a range of factors, including the chemical and physical nature of the fibre, dye–fibre affinity, pretreatment and fabric structure. Regression analyses were conducted to study the correlation between colour strength, fixation and ink penetration obtained by ink‐jet printing lyocell fibres (standard Tencel and Tencel A100) and cotton with an ink based on a monofunctional reactive red dye. The fixation was highest on Tencel A100, followed by standard Tencel and then cotton, while colour strength was highest on standard Tencel followed by cotton and Tencel A100. A linear relationship between colour strength and ink penetration was found with cotton, indicating greater dependence of depth of shade on ink penetration than on standard Tencel and Tencel A100 fabrics, where the interrelationships were more complex, but of low statistical significance. A schematic representation is proposed illustrating the mechanism of ink penetration into pretreated fibres, which provides a reasonable interpretation of the events occurring as dye penetrates into and fixes onto the fibres.     

Peace psychology for a peaceful world.

Although the literature in peace psychology has been growing rapidly, many American psychologists are unaware of how conflict is resolved and peace is conceptualized and achieved. This article reviews the long history and broadening scope of peace psychology and introduces a model of peace that is useful for organizing the literature. The model suggests that peace can be facilitated at four different points of intervention. The authors discuss relationships between positive and negative peace, structural and direct violence, and peacekeeping, peacemaking, and peacebuilding. They advance some challenges for peace psychologists and conclude that peace psychology is a crucial field for grappling with humanity's most pressing problems in the coming decades. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Textile applications of photochromic dyes. Part 5: application of commercial photochromic dyes to polyester fabric by a solvent‐based dyeing method

A series of commercial photochromic dyes was applied to polyester by a solvent dyeing process followed by thermal fixation using dichloromethane as the solvent. The process was optimised in terms of solvent/fabric ratio, dye concentration and the conditions of thermal fixation. The dyed fabrics showed reversible photochromism, developing colour on ultraviolet exposure and fading after removal of the ultraviolet source. The degree of photocoloration, background colours, fading characteristics, fatigue resistance and storage stability of the dyes were evaluated and comparisons made with the outcomes of a traditional aqueous disperse dyeing method. A study of the visible spectra of concentrated solutions of the dyes in a range of solvents provided evidence for the origin of the permanent background colours on the fabric when applied from solvents. Relationships were established between the magnitudes of the visible absorption in solution and the background colours developed, in relation to the nature of the solvents. The results suggest that toluene and ethyl acetate may offer certain advantages as solvents for the application of these dyes.     

Recommendations for mass spectrometry data quality metrics for open access data (corollary to the Amsterdam principles)

Policies supporting the rapid and open sharing of proteomic data are being implemented by the leading journals in the field. The proteomics community is taking steps to ensure that data are made publicly accessible and are of high quality, a challenging task that requires the development and deployment of methods for measuring and documenting data quality metrics. On September 18, 2010, the U.S. National Cancer Institute (NCI) convened the "International Workshop on Proteomic Data Quality Metrics" in Sydney, Australia, to identify and address issues facing the development and use of such methods for open access proteomics data. The stakeholders at the workshop enumerated the key principles underlying a framework for data quality assessment in mass spectrometry data that will meet the needs of the research community, journals, funding agencies, and data repositories. Attendees discussed and agreed up on two primary needs for the wide use of quality metrics: (i) an evolving list of comprehensive quality metrics and (ii) standards accompanied by software analytics. Attendees stressed the importance of increased education and training programs to promote reliable protocols in proteomics. This workshop report explores the historic precedents, key discussions, and necessary next steps to enhance the quality of open access data. By agreement, this article is published simultaneously in Proteomics, Proteomics Clinical Applications, Journal of Proteome Research, and Molecular and Cellular Proteomics, as a public service to the research community. The peer review process was a coordinated effort conducted by a panel of referees selected by the journals.     

A branch and bound algorithm for numerical Max-CSP

The Constraint Satisfaction Problem (CSP) framework allows users to define problems in a declarative way, quite independently from the solving process. However, when the problem is over-constrained, the answer “no solution” is generally unsatisfactory. A Max-CSP \(\mathcal{P}_m = \langle V, \textbf{D}, C \rangle\) is a triple defining a constraint problem whose solutions maximize the number of satisfied constraints. In this paper, we focus on numerical CSPs, which are defined on real variables represented as floating point intervals and which constraints are numerical relations defined in intension. Solving such a problem (i.e., exactly characterizing its solution set) is generally undecidable and thus consists in providing approximations. We propose a Branch and Bound algorithm that provides under and over approximations of a solution set that maximize the maximum number \({m_{\mathcal P}}\) of satisfied constraints. The technique is applied on three numeric applications and provides promising results.