921 research outputs found
Punktmutationsanalysen bei GLI3-assoziierten Krankheitsbildern: Greig Cephalopolysyndaktylie-Syndrom, Pallister-Hall-Syndrom und isolierte Polydaktylien
FĂŒr die Ausbildung der ExtremitĂ€ten ist eine Vielzahl von Genen verantwortlich. Eine SchlĂŒsselrolle in der Entstehung der anterior-posterioren PolaritĂ€t der ExtremitĂ€ten spielt die Sonic Hedgehog-Patched-GLI Signalkaskade (SHH-PTCH-GLI Signalkaskade). Kommt es durch Mutationen zur Fehlregulation eines der beteiligten Faktoren im SHH-Pathway, so resultieren in der Regel, aber nicht ausschlieĂlich, Dysmorphogenesen der GliedmaĂen. Zu diesen zĂ€hlen auch die in dieser Arbeit untersuchten GLI3- assoziierten Morphopathien. Verschiedene Punktmutationen konnten im humanen GLI3-Gen (7p13), das fĂŒr einen Transkriptionsfaktor mit Zinkfingermotiven kodiert, detektiert werden. Bisher wurden vier autosomal-dominant vererbte Fehlbildungssyndrome GLI3-Mutationen zugeordnet:
1. Greig Cephalopolysyndaktylie-Syndrom (GCPS)
2. Pallister-Hall-Syndrom (PHS)
3. Postaxiale Polydaktylie Typ A (PAP-A)
4. PrÀaxiale Polydaktylie Typ IV (PPD-IV)
Im Rahmen dieser Arbeit konnten die Fallzahlen der GLI3-assoziierten Morphopathien erhöht werden. Als molekulargenetische Methode kamen fĂŒr die Untersuchung der Patienten-DNA die nicht-radioaktive Einzelstrang-Konformationsananlyse (SSCA) sowie die Sequenzierung zur Anwendung.
Insgesamt konnten 12 Mutationen bei Patienten mit klinisch diagnostiziertem GCPS, 2 Mutationen bei Patienten mit klinisch gesichertem PHS, sowie 2 weitere Mutationen bei Patienten mit PPD-IV im GLI3-Gen identifiziert werden. Dabei betreffen 9 Mutationen den N-Terminus oder die zentralen Zinkfingermotive der DNA-bindenden DomÀne des GLI3-Transkriptionsfaktors. Weitere 7 Mutationen betreffen den C-terminalen Bereich. Die Erhöhung der Fallzahlen bestÀtigt und ergÀnzt das bekannte Spektrum der GLI3-Mutationen.
Mindestens 8 der 16 detektierten Mutationen fĂŒhren, durch den Einbau eines vorzeitigen Stoppcodons, zu einem verkĂŒrzten Protein und somit vermutlich zum Verlust einiger oder aller Funktionen des GLI3-Transkriptionsfaktors. Der Mechanismus der Haploinsuffizienz scheint in diesen FĂ€llen den PhĂ€notyp zu bedingen.
Dagegen kann fĂŒr die 4 identifizierten Missense-Mutationen sowie fĂŒr die 3 SpleiĂstellenmutationen keine eindeutige Aussage ĂŒber die Auswirkung auf Protein-ebene und somit ĂŒber den molekularen Mechanismus, der den PhĂ€notyp bedingt, getroffen werden.
Entgegen der bisher angenommen 100%igen Penetranz von GLI3-Mutationen konnte eine MutationsĂŒbertragung ĂŒber eine phĂ€notypisch gesunde Probandin im Fall der Missense-Mutation R625W nachgewiesen werden. Vor dem Hintergrund einer nicht vollstĂ€ndigen Penetranz sollten in Zukunft auch seltene Sequenzvarianten auf Proteinebene hinsichtlich verĂ€nderter GLI3 Funktionen und möglicher Interaktion mit anderen Faktoren untersucht werden.
Die Entstehung der unterschiedlichen PhĂ€notypen durch Mutationen im GLI3-Gen bleibt weiterhin unklar, denn die erhobenen Daten von nunmehr annĂ€hernd 50 Mutationen lassen keine eindeutige Genotyp-PhĂ€notyp Korrelation an Hand von Lage und Art der Mutationen zu. Zur KlĂ€rung könnten weiterfĂŒhrende Experimente auf funktioneller Ebene (mRNA Transkript- und Proteinebene) beitragen.
Drei Punktmutationen konnten mehrfach bei unverwandten Familien identifiziert werden, jedoch ist die HÀufigkeit wiederholt auftretender Mutationen zu gering, um von sogenannten Mutations-Hotspots ausgehen zu können. Daher muss auch in Zukunft die molekulare AufklÀrung von Defekten das gesamte GLI3-Gen erfassen
Deep Visual Reasoning: Learning to Predict Action Sequences for Task and Motion Planning from an Initial Scene Image
In this paper, we propose a deep convolutional recurrent neural network that
predicts action sequences for task and motion planning (TAMP) from an initial
scene image. Typical TAMP problems are formalized by combining reasoning on a
symbolic, discrete level (e.g. first-order logic) with continuous motion
planning such as nonlinear trajectory optimization. Due to the great
combinatorial complexity of possible discrete action sequences, a large number
of optimization/motion planning problems have to be solved to find a solution,
which limits the scalability of these approaches.
To circumvent this combinatorial complexity, we develop a neural network
which, based on an initial image of the scene, directly predicts promising
discrete action sequences such that ideally only one motion planning problem
has to be solved to find a solution to the overall TAMP problem. A key aspect
is that our method generalizes to scenes with many and varying number of
objects, although being trained on only two objects at a time. This is possible
by encoding the objects of the scene in images as input to the neural network,
instead of a fixed feature vector. Results show runtime improvements of several
magnitudes. Video: https://youtu.be/i8yyEbbvoEkComment: Robotics: Science and Systems (R:SS) 202
Investigating the trimethylaluminium/water ALD process on mesoporous silica by in situ gravimetric monitoring
A low amount of AlOx was successfully deposited on an unordered, mesoporous SiO2 powder using 1â3 ALD (Atomic Layer Deposition) cycles of trimethylaluminium and water. The process was realized in a self-built ALD setup featuring a microbalanceand a fixed particle bed. The reactor temperature was varied between 75, 120, and 200 °C. The self-limiting nature of the deposition was verified by in situ gravimetric monitoring for all temperatures. The coated material was further analyzed by nitrogen sorption, inductively coupled plasma-optical emission spectroscopy, powder X-ray diffraction, high-resolution transmission electron microscopy, attenuated total reflection Fourier transformed infrared spectroscopy, and elemental analysis. The obtained mass gains correspond to average growth between 0.81â1.10 Ă
/cycle depending on substrate temperature. In addition, the different mass gains during the half-cycles in combination with the analyzed aluminum content after one, two, and three cycles indicate a change in the preferred surface reaction of the trimethylaluminium molecule from a predominately two-ligand exchange with hydroxyl groups to more single-ligand exchange with increasing cycle number. Nitrogen sorption isotherms demonstrate (1) homogeneously coated mesopores, (2) a decrease in surface area, and (3) a reduction of the pore size. The experiment is successfully repeated in a scale-up using a ten times higher substrate batch size.DFG, 325093850, Open Access Publizieren 2017 - 2018 / Technische UniversitÀt Berli
Oxygen Evolution Activity of Amorphous Cobalt Oxyhydroxides: Interconnecting Precatalyst Reconstruction, LongâRange Order, BufferâBinding, Morphology, Mass Transport, and Operation Temperature
Nanocrystalline or amorphous cobalt oxyhydroxides (CoCat) are promising electrocatalysts for the oxygen evolution reaction (OER). While having the same shortârange order, CoCat phases possess different electrocatalytic properties. This phenomenon is not conclusively understood, as multiple interdependent parameters affect the OER activity simultaneously. Herein, a layered cobalt borophosphate precatalyst, Co(H2O)2[B2P2O8(OH)2]·H2O, is fully reconstructed into two different CoCat phases. In contrast to previous reports, this reconstruction is not initiated at the surface but at the electrode substrate to catalyst interface. Ex situ and in situ investigations of the two borophosphate derived CoCats, as well as the prominent CoPi and CoBi identify differences in the Tafel slope/range, buffer binding and content, longârange order, number of accessible edge sites, redox activity, and morphology. Considering and interconnecting these aspects together with proton massâtransport limitations, a comprehensive picture is provided explaining the different OER activities. The most decisive factors are the buffers used for reconstruction, the number of edge sites that are not inhibited by irreversibly bonded buffers, and the morphology. With this acquired knowledge, an optimized OER system is realized operating in nearâneutral potassium borate medium at 1.62 ± 0.03 VRHE yielding 250 mA cmâ2 at 65 °C for 1 month without degrading performance
Robust Task and Motion Planning for Long-Horizon Architectural Construction Planning
Integrating robotic systems in architectural and construction processes is of
core interest to increase the efficiency of the building industry. Automated
planning for such systems enables design analysis tools and facilitates faster
design iteration cycles for designers and engineers. However, generic
task-and-motion planning (TAMP) for long-horizon construction processes is
beyond the capabilities of current approaches. In this paper, we develop a
multi-agent TAMP framework for long horizon problems such as constructing a
full-scale building. To this end we extend the Logic-Geometric Programming
framework by sampling-based motion planning,a limited horizon approach, and a
task-specific structural stability optimization that allow an effective
decomposition of the task. We show that our framework is capable of
constructing a large pavilion built from several hundred geometrically unique
building elements from start to end autonomously
Yttrium complexes of Arsine, Arsenide, and Arsinidene Ligands
Deprotonation of the yttriumâarsine complex [CpâČ3Y{As(H)2Mes}] (1) (CpâČ=η5-C5H4Me, Mes=mesityl) by nBuLi produces the ÎŒ-arsenide complex [{CpâČ2Y[ÎŒ-As(H)Mes]}3] (2). Deprotonation of the As[BOND]H bonds in 2 by nBuLi produces [Li(thf)4]2[{CpâČ2Y(ÎŒ3-AsMes)}3Li], [Li(thf)4]2[3], in which the dianion 3 contains the first example of an arsinidene ligand in rare-earth metal chemistry. The molecular structures of the arsine, arsenide, and arsinidene complexes are described, and the yttriumâarsenic bonding is analyzed by density functional theory
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