1,252 research outputs found
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 Ă© compreender como o carácter hĂbrido 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
disponĂveis ao pĂşblico. 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 Ă sua forma institucional hĂbrida. AlĂ©m disso, esta investigação demonstra que um
hĂbrido institucional Ă© mais eficaz quando harmoniza e se alinha com a missĂŁo 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), Îł-butyrolactones, phloretin and vanillic acid. Detailed characterization of the bi-partite ScbR-TetR-VP16 (ST-TA) transcription factor revealed independent control of TET- and Îł-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
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