The Innovation Threshold

In this paper, we propose an economic model to analyse the sales out of new products. This model accounts for the fact that even among firms for which R&D is a permanent activity, a fraction of firms does not have sales of innovative products during a two-year observation period. We propose a model in which the fixed costs of introduction is a major concern in the decision making process. In a structural model we estimate the fixed costs of the market introduction of new products and explain subsequent sales of innovative products. We examine an indicator of innovative output, i.e. sales of products 'new to the firm'. We estimate fixed costs thresholds using data from the Dutch part of the Community Innovation Survey (CIS) from 1998. R&D intensity, competition and market structure have a positive impact on sales of new products. The most important factors to decrease the fixed costs threshold of introduction are product related R&D investments, R&D subsidies and knowledge spillovers.Innovation;Product R&D;Threshold model

Body Satisfaction and Maladaptive Relationships with Food in African American Women

The purpose of this study was to investigate the complexities of body satisfaction and maladaptive relationships with food as it related to ethnic identity for college-aged African American women. I explored how maladaptive relationships with food may be moderated by ethnic identity (Rogers-Wood & Petrie, 2010), and associated with concerns for body image ideals (Capodilupo & Kim, 2013; Cheney, 2011;) or concerns related to health (Di Noia et al., 2009; Rich & Thomas, 2008). The sample consisted of 189 undergraduate and graduate African American women at a southeastern university in the United States, with a mean age of 22.87. Analyses of correlations suggested that maladaptive eating was associated with low body satisfaction and high concerns for appearance. Findings also suggested that higher levels of ethnic identity were associated with lower levels of body satisfaction. Body satisfaction was inversely related to body mass index. There was no significant relationship between ethnic identity and maladaptive eating. Higher levels of ethnic identity were associated with lower levels of health consciousness. Body image satisfaction and concerns for appearance were positively correlated with health consciousness. Multiple regression analyses indicated significant moderating effects of ethnic identity only for the relationship between maladaptive eating and health consciousness. Ethnic identity moderated the relationship between maladaptive eating and health consciousness particularly for women with low levels of ethnic identity, while accounting for body mass index and body image concerns. Clinical implications for addressing body image concerns, maladaptive eating, and concerns about health with African American women are discussed

Itinéraire d’une œuvre

Generation of a stable, soluble mimic of the HIV-1 envelope glycoprotein (Env) trimer on the virion surface has been considered an important first step for developing a successful HIV-1 vaccine. Recently, a soluble native-like Env trimer (BG505 SOSIP.664) has been described. This protein has facilitated major advances in the HIV-1 vaccine field, since it was the first Env immunogen that induced consistent neutralizing antibodies against a neutralization-resistant (tier 2) virus. Moreover, BG505 SOSIP.664 enabled elucidation of the atomic resolution structure of the Env trimer and facilitated the isolation and characterization of new broadly neutralizing antibodies against HIV-1. Here, we designed and characterized the BG505 SOSIP.664 trimer fused to fluorescent superfolder GFP (sfGFP), a GFP variant that allows efficient folding (BG505 SOSIP.664-sfGFP). Despite the presence of the sfGFP, the Env protein largely retained its morphology, antigenicity, glycan composition, and thermostability. In addition, we show that BG505 SOSIP.664-sfGFP can be used for fluorescence-based assays, such as flow cytometry.</p

The Fragmented Digital Gaze: The Effects of Multimodal Composition on Narrative Perspective

As society as a whole moves more and more into the multiplicative frames of the digital world, it is important to understand how using these interfaces affects how we think and how we communicate. In this article, the focus is on a creative genre of human communication: narrative. Emerging technologies have historically had various impacts on narrative fiction, from the emergence of mimetic narratives in novel form, to the camera’s influence on techniques such as flashback, and character gaze and perspective. These technologies can be seen to engage in an authorial partnership with the composer, “collaborating to create new media,” new narrative forms and practices. The specific affordances of digital media introduce multimodality, polylinearity, and reader/player interaction to fiction; the practice of composing such multimodal works affects narrative perspective, leading to fragmented and layered narration, metalepsis, and “unnatural narrators.” This article presents research based in the practice of creating a multimodal project, Færwhile (the digital component of this article), examining the progression of narrative perspective from mimetic to unnatural, analyzing the various narrative perspectives. While Richardson argues that the postmodern narrative perspective (utilizing contradictory, permeable, and dis-framed narrators) leads to “postmodern unreliability,” this examination of the Færwhile multimodal narrative will argue that a cohesive voice and its communicated metaphor can be created from the layering of disparate narrative perspectives. The effects described herein have implications for digital engagement and communication on a wider scale, as we attempt to understand how our rapidly evolving technology is also effecting change in our cognition, composition, and understanding of events communicated in digital spaces

Increased aortic stiffness and blood pressure in non-classic Pompe disease

Vascular abnormalities and glycogen accumulation in vascular smooth muscle fibres have been described in Pompe disease. Using carotid-femoral pulse wave velocity (cfPWV), the gold standard methodology for determining aortic stiffness, we studied whether aortic stiffness is increased in patients with Pompe disease. Eighty-four adult Pompe patients and 179 age- and gender-matched volunteers participated in this cross-sectional case-controlled study. Intima media thickness and the distensibility of the right common carotid artery were measured using a Duplex scanner. Aortic augmentation index, central pulse pressure, aortic reflexion time and cfPWV were assessed using the SphygmoCor® system. CfPWV was higher in patients than in volunteers (8.8 versus 7.4 m/s, p < 0.001). This difference was still present after adjustment for age, gender, mean arterial blood pressure (MAP), heart rate and diabetes mellitus (p = 0.001), and was shown by subgroup analysis to apply to the 40-59 years age group (p = 0.004) and 60+ years age group (p = 0.01), but not to younger age groups (p = 0.99)

High Proliferation Rate and a Compromised Spindle Assembly Checkpoint Confers Sensitivity to the MPS1 Inhibitor BOS172722 in Triple-Negative Breast Cancers

BOS172722 (CCT289346) is a highly potent, selective, and orally bioavailable inhibitor of spindle assembly checkpoint kinase MPS1. BOS172722 treatment alone induces significant sensitization to death, particularly in highly proliferative triple-negative breast cancer (TNBC) cell lines with compromised spindle assembly checkpoint activity. BOS172722 synergizes with paclitaxel to induce gross chromosomal segregation defects caused by MPS1 inhibitor-mediated abrogation of the mitotic delay induced by paclitaxel treatment. In in vivo pharmacodynamic experiments, BOS172722 potently inhibits the spindle assembly checkpoint induced by paclitaxel in human tumor xenograft models of TNBC, as measured by inhibition of the phosphorylation of histone H3 and the phosphorylation of the MPS1 substrate, KNL1. This mechanistic synergy results in significant in vivo efficacy, with robust tumor regressions observed for the combination of BOS172722 and paclitaxel versus either agent alone in long-term efficacy studies in multiple human tumor xenograft TNBC models, including a patient-derived xenograft and a systemic metastasis model. The current target indication for BOS172722 is TNBC, based on their high sensitivity to MPS1 inhibition, the well-defined clinical patient population with high unmet need, and the synergy observed with paclitaxel

The puzzling issue of silica toxicity: are silanols bridging the gaps between surface states and pathogenicity?

Background: Silica continues to represent an intriguing topic of fundamental and applied research across various scientific fields, from geology to physics, chemistry, cell biology, and particle toxicology. The pathogenic activity of silica is variable, depending on the physico-chemical features of the particles. In the last 50 years, crystallinity and capacity to generate free radicals have been recognized as relevant features for silica toxicity. The ‘surface’ also plays an important role in silica toxicity, but this term has often been used in a very general way, without defining which properties of the surface are actually driving toxicity. How the chemical features (e.g., silanols and siloxanes) and configuration of the silica surface can trigger toxic responses remains incompletely understood. Main body: Recent developments in surface chemistry, cell biology and toxicology provide new avenues to improve our understanding of the molecular mechanisms of the adverse responses to silica particles. New physicochemical methods can finely characterize and quantify silanols at the surface of silica particles. Advanced computational modelling and atomic force microscopy offer unique opportunities to explore the intimate interactions between silica surface and membrane models or cells. In recent years, interdisciplinary research, using these tools, has built increasing evidence that surface silanols are critical determinants of the interaction between silica particles and biomolecules, membranes, cell systems, or animal models. It also has become clear that silanol configuration, and eventually biological responses, can be affected by impurities within the crystal structure, or coatings covering the particle surface. The discovery of new molecular targets of crystalline as well as amorphous silica particles in the immune system and in epithelial lung cells represents new possible toxicity pathways. Cellular recognition systems that detect specific features of the surface of silica particles have been identified. Conclusions: Interdisciplinary research bridging surface chemistry to toxicology is progressively solving the puzzling issue of the variable toxicity of silica. Further interdisciplinary research is ongoing to elucidate the intimate mechanisms of silica pathogenicity, to possibly mitigate or reduce surface reactivity. Keywords: Silica, Silicosis, Lung cancer, Auto-immune diseases, Surface reactivity, Silanol, Coating, Modelling, Spectroscopy, Atomic force microscop