147 research outputs found
S288c
No full textCell-cell and cell-surface adherence represents initial steps in forming multicellular aggregates or in establishing cell-surface interactions. The commonly used Saccharomyces cerevisiae laboratory strain S288c carries a flo8 mutation, and is only able to express the flocculin-encoding genes FLO1 and FLO11, when FLO8 is restored. We show here that the two flocculin genes exhibit differences in regulation to execute distinct functions under various environmental conditions. In contrast to the laboratory strain Sigma 1278b, haploids of the S288c genetic background require FLO1 for cell-cell and cell-substrate adhesion, whereas FLO11 is required for pseudohyphae formation of diploids. In contrast to FLO11, FLO1 repression requires the Sin4p mediator tail component, but is independent of the repressor Sfl1p. FLO1 regulation also differs from FLO11, because it requires neither the KSS1 MAP kinase cascade nor the pathways which lead to the transcription factors Gcn4p or Msn1p. The protein kinase A pathway and the transcription factors Flo8p and Mss11p are the major regulators for FLO1 expression. Therefore, S. cerevisiae is prepared to simultaneously express two genes of its otherwise silenced FLO reservoir resulting in an appropriate cellular surface for different environments
The Yeast HtrA Orthologue Ynm3 Is a Protease with Chaperone Activity that Aids Survival Under Heat Stress
No full textYnm3 is the only budding yeast protein possessing a combination of serine protease and postsynaptic density 95/disclarge/zona occludens domains, a defining feature of the high temperature requirement A (HtrA) protein family. The bacterial HtrA/DegP is involved in protective stress response to aid survival at higher temperatures. The role of mammalian mitochondrial HtrA2/Omi in protein quality control is unclear, although loss of its protease activity results in susceptibility toward Parkinson's disease, in which mitochondrial dysfunction and impairment of protein folding and degradation are key pathogenetic features. We studied the role of the budding yeast HtrA, Ynm3, with respect to unfolding stresses. Similar to Escherichia coli DegP, we find that Ynm3 is a dual chaperone-protease. Its proteolytic activity is crucial for cell survival at higher temperature. Ynm3 also exhibits strong general chaperone activity, a novel finding for a eukaryotic HtrA member. We propose that the chaperone activity of Ynm3 may be important to improve the efficiency of proteolysis of aberrant proteins by averting the formation of nonproductive toxic aggregates and presenting them in a soluble state to its protease domain. Suppression studies with Delta ynm3 led to the discovery of chaperone activity in a nucleolar peptidyl-prolyl cis-trans isomerase, Fpr3, which could partly relieve the heat sensitivity of Delta ynm3
HMCLab: a framework for solving diverse geophysical inverse problems using the Hamiltonian Monte Carlo method
No full textThe use of the probabilistic approach to solve inverse problems is becoming
more popular in the geophysical community, thanks to its ability to address
nonlinear forward problems and to provide uncertainty quantification. However,
such strategy is often tailored to specific applications and therefore there is
a lack of a common platform for solving a range of different geophysical
inverse problems and showing potential and pitfalls. We demonstrate a common
framework to solve such inverse problems ranging from, e.g, earthquake source
location to potential field data inversion and seismic tomography. Within this
approach, we can provide probabilities related to certain properties or
structures of the subsurface. Thanks to its ability to address high-dimensional
problems, the Hamiltonian Monte Carlo (HMC) algorithm has emerged as the
state-of-the-art tool for solving geophysical inverse problems within the
probabilistic framework. HMC requires the computation of gradients, which can
be obtained by adjoint methods, making the solution of tomographic problems
ultimately feasible. These results can be obtained with "HMCLab", a tool for
solving a range of different geophysical inverse problems using sampling
methods, focusing in particular on the HMC algorithm. HMCLab consists of a set
of samplers and a set of geophysical forward problems. For each problem its
misfit function and gradient computation are provided and, in addition, a set
of prior models can be combined to inject additional information into the
inverse problem. This allows users to experiment with probabilistic inverse
problems and also address real-world studies. We show how to solve a selected
set of problems within this framework using variants of the HMC algorithm and
analyze the results. HMCLab is provided as an open source package written both
in Python and Julia, welcoming contributions from the community.Comment: 21 pages, 4 figure
Efficacy and Safety of an Everolimus- vs. a Mycophenolate Mofetil-Based Regimen in Pediatric Renal Transplant Recipients.
No full textData on the efficacy and safety of everolimus in pediatric renal transplantation compared to other immunosuppressive regimens are scarce.We therefore performed a multicenter, observational, matched cohort study over 4 years post-transplant in 35 patients on everolimus plus low-dose cyclosporine, who were matched (1:2) with a control group of 70 children receiving a standard-dose calcineurin-inhibitor- and mycophenolate mofetil-based regimen.Corticosteroids were withdrawn in 83% in the everolimus vs. 39% in the control group (p<0.001). Patient and graft survival were comparable. The rate of biopsy-proven acute rejection episodes Banff score ≥ IA during the first year post-transplant was 6% in the everolimus vs. 13% in the control group (p = 0.23). The rate of de novo donor-specific HLA antibodies (11% in everolimus, 18% in controls) was comparable (p = 0.55). At 4 years post-transplant, mean eGFR in the everolimus group was 56±33 ml/min per 1.73 m² vs. 63±22 ml/min per 1.73 m² in the control group (p = 0.14). Everolimus therapy was associated with less BK polyomavirus replication (3% vs. 17% in controls; p = 0.04), but with a higher percentage of arterial hypertension and more hyperlipidemia (p<0.001).In pediatric renal transplantation, an everolimus-based regimen with low-dose cyclosporine yields comparable four year results as a standard regimen, but with a different side effect profile
Full waveform inversion of the African crust and mantle: strategies for accelerating model convergence
No full textMaster of Science in Applied Geophysics at Delft University of Technology, ETH Zürich and RWTH Aachen University. - The continent of Africa is one of the most geophysically interesting regions on the planet. More specifically, Africa contains the Afar Depression, which is the only place on Earth where incipient sea-floor spreading is sub-aerially exposed, along with other anomalous features such as the unexplained topography in the south. Despite its geophysical significance, relatively few tomographic images exist of Africa. This stems mainly from the sparse distribution of seismic monitoring stations on the continent, which itself is a result of the political instability and general geographical remoteness. As a result, the debate on the geophysical origins of Africa's anomalies is rich and ongoing. In this project a tomographic image is produced using the technique of elastic Full Waveform Inversion (FWI). To our knowledge this is the first attempt at performing a continental-scale FWI of the region. Data recorded from 100 earthquakes has been used as input for the inversion. The adjoint method was used to iteratively update the initial model, which was extracted from the Collaborative Seismic Earth Model. Forward and adjoint modelling were performed in the regional version of SPECFEM3D GLOBE, a global wave propagation solver based on the spectral element method. Over the course of ten iterations, the time-frequency phase misfit decreased satisfactorily, and additional details were added to the starting model. The final model was validated by evaluating the change in misfit for ten earthquakes not previously used in the inversion. All of these events showed a decrease in misfit.Civil Engineering and GeosciencesGeoscience & EngineeringIDEA League Joint Master's in Applied Geophysic
Ein Quantenmodell der Signalerkennung im Hirn
No full textIn dieser Dissertation wurde ein mathematisches Modell der Signalerkennung entwickelt. Ausgehend von den Erkenntnissen der aktuellen Hirnforschung über die Funktionsweisen und Beschaffenheit des Hirns wurde der Rahmen des besagten Modells festgelegt. Da einige nachgewiesene Funktionen, wie etwa das Bindungsproblem in seinen verschiedenen Facetten keinesfalls basierend auf klassischer Physik erklärt werden können, wurde in diesem Modell Bezug auf die Quantentheorie genommen. Diese Art der Physik kann subjektiv sehr kompliziert und kaum nachvollziehbar erscheinen. Deshalb wird davon in der Regel ausserhalb der Physik kaum Gebrauch gemacht. Da andererseits die Quantentheorie die Modellierung aller an dieser Stelle betrachteten Effekte ermöglicht, wurde in dieser Arbeit auf etablierte, und nicht anzweifelbare Methoden der Quantentheorie zurückgegriffen. Beginnend mit der Schilderung aktueller Erkenntnisse der modernen Hirnforschung wird in der vorliegenden Dissertation in den folgenden Kapiteln das Modell auf mathematisch präzise Art und Weise eingeführt. Die Arbeitsweise des Modells wird später noch durch Betrachtung von Beispielen illustriert. Generell ist das hier erklärte Modell nicht konkret auf bestimmte Lebensformen, wie zum Beispiel den Menschen, zugeschnitten. Es handelt sich hierbei eher um ein universelles Modell der Signalerkennung, was nach Belieben, dafür aber mit immensem Aufwand konkretisiert werden kann. Die aktuelle Fassung bietet sozusagen das Fundament für weitere Spezialisierungen, um auch konkrete Prozesse des Hirns modellieren bzw. simulieren zu können.
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