Molecular imaging applications of antibody-based immunotherapeutics to understand cancer drug distribution

With the landscape-transforming arrival of cancer immunotherapy, such as drugs that block immune checkpoints, durable responses are observed for several different cancer types. Regrettably, only part of the patients initially respond, and once responded, resistance to immune checkpoint blockade may occur. Therefore, new treatment options are explored to enhance the immune system. These approaches include engaging T cells or inhibit immunosuppressive cell types like tumor-associated macrophages (TAMs). T-cell activating drugs include bispecific T cell engagers (BiTEs) and T cell-redirecting antibodies, both redirect T cells to a predefined tumor target for subsequent infiltration and cytotoxicity. Another approach are drugs that inhibit TAMs, resulting in an enhanced tumor immune response. Limited information is available regarding the pharmacological behavior of these new molecular entities. Radiolabeling these types of drugs with positron emission tomography (PET) isotopes allows molecular imaging using PET to assess whole-body drug distribution and tumor targeting. Ex vivo, techniques like tissue autoradiography, radioactive gel electrophoresis of plasma or tissue lysate, and ex vivo biodistribution complement PET imaging. The research described in this thesis aims to gain insight with molecular imaging in the pharmacological behavior of antibody-based immunotherapeutics using molecular imaging. We show the tumor targeting properties of BiTES in both the preclinical as clinical setting. In addition we preclinically studied the distribution of a T cell-redirecting antibody and a TAM-directed antibody. Overall, molecular imaging of new radiolabeled cancer drugs could provide information to support drug development

Scientific workflows for bibliometrics

Scientific workflows organize the assembly of specialized software into an overall data flow and are particularly well suited for multi-step analyses using different types of software tools. They are also favorable in terms of reusability, as previously designed workflows could be made publicly available through the myExperiment community and then used in other workflows. We here illustrate how scientific workflows and the Taverna workbench in particular can be used in bibliometrics. We discuss the specific capabilities of Taverna that makes this software a powerful tool in this field, such as automated data import via Web services, data extraction from XML by XPaths, and statistical analysis and visualization with R. The support of the latter is particularly relevant, as it allows integration of a number of recently developed R packages specifically for bibliometrics. Examples are used to illustrate the possibilities of Taverna in the fields of bibliometrics and scientometrics

Quantized careers : origins and consequences of the preponderance of temporary and junior jobs in academia

  A lack of career opportunities and long spells of temporary employment are seen as major problems in science, and are thought to decrease the attractiveness of the scientific profession. In the long run, this could hurt countries’ ability to conduct high-quality research and innovation. This dissertation examines the origin and effects of the preponderance of junior and temporary jobs in science. The research described in the dissertation shows how career prospects and employment conditions have changed in Germany since the emergence of the research university, and how publications careers of PhD graduates have changed in the United States since the 1950s. Furthermore, the dissertation describes how career prospects and employment conditions affect the job choice of recent PhD graduates. Women are more negative about career prospects and employment conditions in science and are therefore more affected by these issues when choosing a job. In addition, the dissertation describes how student status of PhD candidates limits the availability of material research infrastructure. Finally, the research in the dissertation shows that temporary employment decreases job satisfaction and affects the personal life of PhD graduates.  Leids Universiteits Fonds, grant #5519Merit, Expertise and Measuremen

The coming of age of the academic career: Differentiation and professionalization of German academic positions from the 19th century to the present

In modern academic career systems there are a large number of entry positions, much smaller numbers of intermediate positions, and still fewer full professorships. We examine how this system has developed in Germany, the country where the modern academic system was introduced, tracing the historical development of academic positions since the early 19th century. We show both a differentiation and professionalization. At first, professorships and private lecturer positions were the only formal positions, but later, lower formal academic positions emerged. Over the whole period, the share of higher academic positions steadily decreased. This differentiation process was closely connected to professionalization: remuneration through salaries was extended from professors to almost everyone working in the German academic system. We propose that the process of differentiation and professionalization was induced by the expansion and democratization of higher education. Finally, our study shows that the opportunities for PhDs to obtain salaried (post-)doctoral positions have increased since the 1950s. On the other hand, opportunities for PhDs to become a professor or obtain another tenured job have decreased since the 1980s due to a slowdown of higher education expansion.Merit, Expertise and Measuremen

Scientific workflows for bibliometrics

Scientific workflows organize the assembly of specialized software into an overall data flow and are particularly well suited for multi-step analyses using different types of software tools. They are also favorable in terms of reusability, as previously designed workflows could be made publicly available through the myExperiment community and then used in other workflows. We here illustrate how scientific workflows and the Taverna workbench in particular can be used in bibliometrics. We discuss the specific capabilities of Taverna that makes this software a powerful tool in this field, such as automated data import via Web services, data extraction from XML by XPaths, and statistical analysis and visualization with R. The support of the latter is particularly relevant, as it allows integration of a number of recently developed R packages specifically for bibliometrics. Examples are used to illustrate the possibilities of Taverna in the fields of bibliometrics and scientometrics.Proteomic

Notaris en de prejudiciële vraag

Coherent privaatrech

Stability and longevity in the publication careers of U.S. doctorate recipients

Since the 1950s, the number of doctorate recipients has risen dramatically in the United States. In this paper, we investigate whether the longevity of doctorate recipients’ publication careers has changed. This is achieved by matching 1951–2010 doctorate recipients with rare names in astrophysics, chemistry, economics, genetics and psychology in the dissertation database ProQuest to their publications in the publication database Web of Science. Our study shows that pre-PhD publication careers have changed: the median year of first publication has shifted from after the PhD to several years before PhD in most of the studied fields. In contrast, post-PhD publication career spans have not changed much in most fields. The share of doctorate recipients who have published for more than twenty years has remained stable over time; the shares of doctorate recipients publishing for shorter periods also remained almost unchanged. Thus, though there have been changes in pre-PhD publication careers, post-PhD career spans remained quite stable

Het Kielerkastje en zo meer

Omdat imker Roelof Waaijer zich al jarenlang op Duitsland heeft georiënteerd - zelfs zijn BMW voert een Duits nummerbord - is hem het Kielerkastje allerminst vreemd. Hij heeft er zeker zo'n tien jaar mee gewerkt en heeft er nu een flink aantal bestemd voor de aanstaande 'boeldag', want hij gebruikt ze niet meer. Voor de Duitse Waddeneilanden is het EWK-verplicht en voor eigen gebruik (het standbevruchten van zijn Carnica-koninginnen) hanteert hij het zgn. kleine Cellerkastje. Beide komen hieronder aan de ord