Wie präzise lässt sich sedentäres Verhalten von Kindern unter Einbezug realitätsna-her Kontexte mit Daten automatisierter, tragbarer Kameras erfassen?

Hintergrund: Sedentäres Verhalten (SB) ist ein Teilaspekt von Körperlicher Aktivität (PA) und hat spezifische negative Einflüsse auf die Gesundheit. SB ist jedoch insbesondere bei Kindern und Jugendlichen noch kaum erforscht. Zudem fehlen geeignete Messverfahren, welche SB in freier Umgebung objektiv und ganzheitlich erfassen können. Erste Pilotstudien zeigen, dass automatisierte, tragbare Kameras eine Lösung dieses Problems versprechen. Die Methode ist jedoch nicht ausreichend validiert. In dieser Masterarbeit wurde die Konvergenzvalidität der Kameramethode im Vergleich mit Akzelerometerdaten untersucht. Zudem wurde basierend auf dem Framework von Kelly et al. (2016) erstmals ein entsprechendes Auswertungsverfahren ausgearbeitet. Methode: Bei 18 Kindern (12 ♀ / 6 ♂, 10.28 Jahre, SD = 0.56) wurden während fünf aufeinanderfolgenden Tagen mit automatisierten, tragbaren Kameras (Autographer) und Akzelerometern (GT3X ActiGraph) Daten zum Bewegungsverhalten in freier Umgebung erhoben und mit einem eigens dafür entwickelten Auswertungsverfahren von drei Experten codiert. Die in den Kameradaten identifizierten sedentären Phasen wurden anschliessend mit den entsprechenden Akzelerometerwerten verglichen. Ergebnisse: Die Übereinstimmung der beiden Messmethoden lag dabei bei 10-70% bei nicht bildschirmbezogenen Aktivitäten und 57-100% bei bildschirmbezogenen Aktivitäten. Die Konvergenzvalidität konnte nicht abschliessend bestimmt werden. Das verwendete Auswertungsverfahren wurde erprobt und ist gut anwendbar. Dies zeigt sich in einer (fast) perfekten Interrater-Reliabilität (Light’s κ = 0.853). Diskussion: Die Ergebnisse des Methodenvergleichs variieren stark und sind noch zu sehr abhängig von Auswertungsvorgängen (beider Methoden), welche noch nicht standardisiert sind. Dies erschwert eine abschliessende Aussage zur Konvergenzvalidität der Kameramethode. Eine weitere Ausarbeitung des Verfahrens, sowie eine Standardisierung der Vorgänge sind jedoch nötig, um aussagekräftigere Ergebnisse zu erhalten. Schlüsselwörter: Sedentäres Verhalten, Körperliche Aktivität, Kinder und Jugendliche, Autographer, GT3X ActiGraph, Konvergenzvaliditä

The social-business hybrid organization : the long-desired answer to the BOP dilemma?

The purpose of this research is to understand how the hybrid character of social business hybrids can contribute to their success on the BOP markets. To answer the research question, I conducted a comparative case study on two companies that can be categorized as social business hybrids and operate in BOP markets. I relied on secondary sources, which mainly consisted of secondary interviews and publicly available third-party sources. To analyze the data collected, I used the framework "value-capturing elements" elaborated by von der Heydte (2020). The results of the study show that both investigated companies can contribute to overcome the challenges of BOP markets due to their hybrid institutional form. Moreover, this research demonstrates that an institutional hybridity is most effective when it harmonizes and aligns with the company's mission. To particularly benefit from hybridity in BOP markets, the following elements prove to be particularly useful: achieving a competitive strategy, implementing value propositions and building a network of strategic partners.O objectivo desta investigação é compreender como o carácter híbrido dos “social business hybrids” pode contribuir para o seu sucesso nos mercados de BOP. Para responder à questão da investigação, realizei um estudo de caso comparativo sobre duas empresas que podem ser categorizadas como social business hybrids e operar nos mercados de BOP. Confiei em fontes secundárias, que consistiam principalmente em entrevistas secundárias e fontes de terceiros disponíveis ao público. Para analisar os dados recolhidos, utilizei o quadro "elementos de captura de valor" elaborado por von der Heydte (2020). Os resultados do estudo mostram que ambas as empresas investigadas podem contribuir para superar os desafios dos mercados BOP devido à sua forma institucional híbrida. Além disso, esta investigação demonstra que um híbrido institucional é mais eficaz quando harmoniza e se alinha com a missão da empresa. Para beneficiar particularmente do hibridismo nos mercados de BOP, os seguintes elementos revelam-se particularmente úteis: alcançar uma estratégia competitiva, implementar propostas de valor e construir uma rede de parceiros estratégicos

Small molecules as research tools for studying the biology of the tumour suppressor p53

p53 is a potent tumour suppressor that is inactivated in the majority, if not all human cancers. In about 50% of the cases, the gene is mutated and in the rest it is rendered inactive mainly by deregulation of its negative regulators such as Hdm2 and HdmX. Targeting p53 has been shown to be a promising strategy to fight cancer and the first compounds reactivating p53 have reached the stage of clinical trials. In addition to immediate clinical use, compounds that activate p53 are valuable tools to increase the knowledge about fundamental p53 biology. RITA is an example for such a compound activating p53. We found that it induces decreased protein levels of the negative regulator of p53, HdmX, in a p53-dependent manner. This is mediated by ATM-induced phosphorylation. In addition expression of Wip1 is inhibited. Wip1 depletion is an important event for HdmX decrease, as Wip1 reverses ATM mediated phosphorylation and thus can prevent ATM-induced HdmX decline. The biological significance of HdmX and Wip1 inhibition is highlighted by the fact that a knockdown of either of them enhances cell killing by the p53-activating drugs RITA and nutlin3a. To get insight into mechanisms of p53 mediated transcriptional regulation, we compared genome-wide chromatin occupancy by p53 upon its activation by three different compounds, RITA, nutlin3a and 5-FU that cause different biological outcomes. We compared genome-wide chromatin occupancy by p53. Surprisingly, the regions that were bound by p53 to the highest extent were the same after all three treatments, despite their different biological outcomes. Comparison of the p53- occupied sites with gene expression changes upon p53 activation by nutlin3a allowed identifying 280 previously unknown target genes. The common p53 binding motif is present much more frequently in the promoter region of induced genes than in that of repressed genes. This suggests different mechanisms for gene induction versus repression by p53, presumably distinguished by the involvement of cofactors. This is in line with our finding that binding sites for cofactors in the proximity of p53 sites are distinct for induced and repressed genes. We identified AURKA (Aurora kinase A) as a novel p53-repressed target gene, and found that STAT3 also regulates it, antagonising p53. Finally we found, that expression of our newly identified panel of p53 target genes correlated with the p53 status, the grade of tumours and the long-term survival in a set of 250 breast cancer patients. Malignant melanomas have very poor prognosis with extremely low long-term survival once the metastatic stage is reached. It has been shown that in 3-dimensional collagen type I matrix that mimics the microenvironment of the human dermis, melanoma cells induce integrin-dependent inactivation of p53, rescuing the cells from apoptosis. Thus, reactivation of p53 might be a promising strategy to kill melanoma cells. To test this, we treated melanoma cells that were grown in 3D conditions with the p53 reactivating compound PRIMA-1 MET/APR-246. Indeed, this induced apoptosis in the cells in a p53 dependent manner. Consistently, the growth of melanoma xenografts in mice was suppressed in a p53-dependent manner after PRIMA-1 MET treatment. In summary, this thesis demonstrates examples for both the use of p53 activating compounds as research tools to uncover new details of p53 biology as well as their application for therapy, exemplified by effects of PRIMA-1 MET in malignant melanomas in vitro and in vivo

Non-formal star-exponential on contracted one-sheeted hyperboloids

In this paper, we exhibit the non-formal star-exponential of the Lie group SL(2,R) realized geometrically on the curvature contraction of its one-sheeted hyperboloid orbits endowed with its natural non-formal star-product. It is done by a direct resolution of the defining equation of the star-exponential and produces an expression with Bessel functions. This yields a continuous group homomorphism from SL(2,R) into the von Neumann algebra of multipliers of the Hilbert algebra underlied by this natural star-product. As an application, we prove a new identity on Bessel functions.Comment: 33 pages, 3 figures, v2: changes in section 3, references adde

Follow-up of 53 Alzheimer patients with the MODA (Milan Overall Dementia Assessment)

Fifty-three patients affected by Alzheimer's disease entered a longitudinal survey aimed at studying which factors influence the rate of progression, assessed by means of the Milan Overall Dementia Assessment (MODA). The second examination was carried out, on average, after 16 months from the first assessment. Only age proved to influence the decline rate, which was faster in elders

Synthetic mammalian trigger-controlled bipartite transcription factors

Synthetic biology has significantly advanced the design of synthetic control devices, gene circuits and networks that can reprogram mammalian cells in a trigger-inducible manner. Prokaryotic helix-turn-helix motifs have become the standard resource to design synthetic mammalian transcription factors that tune chimeric promoters in a small molecule-responsive manner. We have identified a family of Actinomycetes transcriptional repressor proteins showing a tandem TetR-family signature and have used a synthetic biology-inspired approach to reveal the potential control dynamics of these bi-partite regulators. Daisy-chain assembly of well-characterized prokaryotic repressor proteins such as TetR, ScbR, TtgR or VanR and fusion to either the Herpes simplex transactivation domain VP16 or the Krueppel-associated box domain (KRAB) of the human kox-1 gene resulted in synthetic bi- and even tri-partite mammalian transcription factors that could reversibly program their individual chimeric or hybrid promoters for trigger-adjustable transgene expression using tetracycline (TET), γ-butyrolactones, phloretin and vanillic acid. Detailed characterization of the bi-partite ScbR-TetR-VP16 (ST-TA) transcription factor revealed independent control of TET- and γ-butyrolactone-responsive promoters at high and double-pole double-throw (DPDT) relay switch qualities at low intracellular concentrations. Similar to electromagnetically operated mechanical DPDT relay switches that control two electric circuits by a fully isolated low-power signal, TET programs ST-TA to progressively switch from TetR-specific promoter-driven expression of transgene one to ScbR-specific promoter-driven transcription of transgene two while ST-TA flips back to exclusive transgene 1 expression in the absence of the trigger antibiotic. We suggest that natural repressors and activators with tandem TetR-family signatures may also provide independent as well as DPDT-mediated control of two sets of transgenes in bacteria, and that their synthetic transcription-factor analogs may enable the design of compact therapeutic gene circuits for gene and cell-based therapie

Analysis of complexity and power consumption in DSP-based optical modulation formats

This work was supported by UK EPSRC via the INTERNET project.This is the accepted manuscript version. The final public version is available from the publisher at http://www.opticsinfobase.org/abstract.cfm?uri=SPPCom-2014-SM2D.5

Basler Africa Portal

The article aims to present the project "Africa Portal" in which five institutions located in Basel create an integrated search interface in order to make their data accessible. Following a description of the process concerning normalizing different data structures and formats, the article also focuses on the outcomes and the possible developments of the "Africa Portal" in the future