Archivitalization of science archives: new techniques in making science archives understandable

How can archivists analyse science archives? Science archives are like DNA for the human body: unique and essential. The analysis of DNA and science archives is a very difficult process. Archivists in a scientific environment need to develop new techniques complementary to the traditional methodologies. In this paper an overview of these old and new techniques will be given. It will also show how these techniques can be worked out in practice

Multinationalisme en coördinatie: De internationale strategie van Nederlandse ondernemingen nader beschouwd

Multinational Companies;international economics

Adapting to Complexities in Dialogue

The world is getting a VUCA place. A world that is more volatile, uncertain, complex and ambiguous. Changing conditions can be seen at a global level, on the level of societies and organizations but also at a micro level of people. Dealing with differences requires awareness about our own world views, and an open mind to understand the viewpoint of others. For interaction to be productive, participants need to recognize the different voices that come into play. This ‘social complexity’ is a underlying aspect relevant for understanding how to cope with VUCA situations. The aim of this chapter is to describe the conversational processes that take place during interactions between different professionals in organizations. Applying the ‘ladder of complexity’ and discourse analysis in three cases reveal that different ‘voices’ can be distinguished in the process of organizational change. We promote incorporating sociolinguistics into the field of organizational change. Section 1 introduces the ‘playground’ we live in followed by different paradigms about communicating and change management. Section 3 introduces the ‘ladder of complexity’ aligning social complexity and dialogue. Section 4 describes 3 cases using discourse analysis to understand the interaction in conversations. Section 5 draws conclusions and give directions for future research

Weekly self-monitoring and treatment adjustment benefit patients with partly controlled and uncontrolled asthma: an analysis of the SMASHING study

<p>Abstract</p> <p>Background</p> <p>Internet-based self-management has shown to improve asthma control and asthma related quality of life, but the improvements were only marginally clinically relevant for the group as a whole. We hypothesized that self-management guided by weekly monitoring of asthma control tailors pharmacological therapy to individual needs and improves asthma control for patients with partly controlled or uncontrolled asthma.</p> <p>Methods</p> <p>In a 1-year randomised controlled trial involving 200 adults (18-50 years) with mild to moderate persistent asthma we evaluated the adherence with weekly monitoring and effect on asthma control and pharmacological treatment of a self-management algorithm based on the Asthma Control Questionnaire (ACQ). Participants were assigned either to the Internet group (n = 101) that monitored asthma control weekly with the ACQ on the Internet and adjusted treatment using a self-management algorithm supervised by an asthma nurse specialist or to the usual care group (UC) (n = 99). We analysed 3 subgroups: patients with well controlled (ACQ ≤ 0.75), partly controlled (0.75>ACQ ≤ 1.5) or uncontrolled (ACQ>1.5) asthma at baseline.</p> <p>Results</p> <p>Overall monitoring adherence was 67% (95% CI, 60% to 74%). Improvements in ACQ score after 12 months were -0.14 (p = 0.23), -0.52 (p < 0.001) and -0.82 (p < 0.001) in the Internet group compared to usual care for patients with well, partly and uncontrolled asthma at baseline, respectively. Daily inhaled corticosteroid dose significantly increased in the Internet group compared to usual care in the first 3 months in patients with uncontrolled asthma (+278 μg, p = 0.001), but not in patients with well or partly controlled asthma. After one year there were no differences in daily inhaled corticosteroid use or long-acting β₂-agonists between the Internet group and usual care.</p> <p>Conclusions</p> <p>Weekly self-monitoring and subsequent treatment adjustment leads to improved asthma control in patients with partly and uncontrolled asthma at baseline and tailors asthma medication to individual patients' needs.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN79864465</p

Leishmania donovani-induced expression of signal regulatory protein α on Kupffer cells enhances hepatic invariant NKT-cell activation

Signal regulatory protein α (SIRPα) and its cognate ligand CD47 have been documented to have a broad range of cellular functions in development and immunity. Here, we investigated the role of SIRPα–CD47 signalling in invariant NKT (iNKT) cell responses. We found that CD47 was required for the optimal production of IFN-γ from splenic iNKT cells following exposure to the αGalCer analogue PBS-57 and in vivo infection of mice with Leishmania donovani. Surprisingly, although SIRPα was undetectable in the liver of uninfected mice, the hepatic iNKT-cell response to infection was also impaired in CD47−/− mice. However, we found that SIRPα was rapidly induced on Kupffer cells following L. donovani infection, via a mechanism involving G-protein-coupled receptors. Thus, we describe a novel amplification pathway affecting cytokine production by hepatic iNKT cells, which may facilitate the breakdown of hepatic tolerance after infection

Polynomial chaos-based extended Padé expansion in structural dynamics

The response of a random dynamical system is totally characterized by its probability density function (pdf). However, determining a pdf by a direct approach requires a high numerical cost; similarly, surrogate models such as direct polynomial chaos expansions are not generally efficient, especially around the eigenfrequencies of the dynamical system. In the present study, a new approach based on Padé approximants to obtain moments and pdf of the dynamic response in the frequency domain is proposed. A key difference between the direct polynomial chaos representation and the Padé representation is that the Padé approach has polynomials in both numerator and denominator. For frequency response functions, the denominator plays a vital role as it contains the information related to resonance frequencies, which are uncertain. A Galerkin approach in conjunction with polynomial chaos is proposed for the Padé approximation. Another physics-based approach, utilizing polynomial chaos expansions of the random eigenmodes, is proposed and compared with the proposed Padé approach. It is shown that both methods give accurate results even if a very low degree of the polynomial expansion is used. The methods are demonstrated for two degree-of-freedom system with one and two uncertain parameters

Daedalus: a robust, turnkey platform for rapid production of decigram quantities of active recombinant proteins in human cell lines using novel lentiviral vectors

A key challenge for the academic and biopharmaceutical communities is the rapid and scalable production of recombinant proteins for supporting downstream applications ranging from therapeutic trials to structural genomics efforts. Here, we describe a novel system for the production of recombinant mammalian proteins, including immune receptors, cytokines and antibodies, in a human cell line culture system, often requiring <3 weeks to achieve stable, high-level expression: Daedalus. The inclusion of minimized ubiquitous chromatin opening elements in the transduction vectors is key for preventing genomic silencing and maintaining the stability of decigram levels of expression. This system can bypass the tedious and time-consuming steps of conventional protein production methods by employing the secretion pathway of serum-free adapted human suspension cell lines, such as 293 Freestyle. Using optimized lentiviral vectors, yields of 20–100 mg/l of correctly folded and post-translationally modified, endotoxin-free protein of up to ~70 kDa in size, can be achieved in conventional, small-scale (100 ml) culture. At these yields, most proteins can be purified using a single size-exclusion chromatography step, immediately appropriate for use in structural, biophysical or therapeutic applications

Inhibition of Effector Function but Not T Cell Activation and Increase in FoxP3 Expression in T Cells Differentiated in the Presence of PP14

Background: T-helper polarization of naïve T cells is determined by a complex mechanism that involves many factors, eventually leading to activation of Th1, Th2, or Th17 responses or alternatively the generation of regulatory T cells. Placental Protein 14 (PP14) is a 28 kDa glycoprotein highly secreted in early pregnancy that is able to desensitize T cell receptor (TCR) signaling and modulate T cell activation. Methodology/Principal Findings: Prolonged antigen-specific stimulation of T cells in the presence of PP14 resulted in an impaired secretion of IFN-c, IL-5 and IL-17 upon restimulation, although the cells proliferated and expressed activation markers. Furthermore, the generation of regulatory CD4 + CD25 high Foxp3 + T cells was induced in the presence of PP14, in both antigen-specific as well as polyclonal stimulation. In accordance with previous reports, we found that the induction of FoxP3 expression by PP14 is accompanied by down regulation of the PI3K-mTOR signaling pathway. Conclusions/Significance: These data suggest that PP14 arrests T cells in a unique activated state that is not accompanied with the acquisition of effector function, together with promoting the generation of regulatory T cells. Taken together, our results may elucidate the role of PP14 in supporting immune tolerance in pregnancy by reducing T cell effector function