24 results on '"Huber, Matthias"'
Search Results
2. Programming protein phase-separation employing a modular library of intrinsically disordered precision block copolymer-like proteins creating dynamic cytoplasmatic compartmentalization.
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Huber, Matthias C., Schreiber, Andreas, Stühn, Lara G., and Schiller, Stefan M.
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ESCHERICHIA coli , *PROTEINS , *SYNTHETIC biology , *EUKARYOTIC cells , *BLOCK copolymers , *DIBLOCK copolymers - Abstract
The control of supramolecular complexes in living systems at the molecular level is an important goal in life-sciences. Spatiotemporal organization of molecular distribution & flow of such complexes are essential physicochemical processes in living cells and important for pharmaceutical processes. Membraneless organelles (MO) found in eukaryotic cells, formed by liquid-liquid phase-separation (LLPS) of intrinsically disordered proteins (IDPs) control and adjust intracellular organization. Artificially designed compartments based on LLPS open up a novel pathway to control chemical flux and partition in vitro and in vivo. We designed a library of chemically precisely defined block copolymer-like proteins based on elastin-like proteins (ELPs) with defined charge distribution and type, as well as polar and hydrophobic block domains. This enables the programmability of physicochemical properties and to control adjustable LLPS in vivo attaining control over intracellular partitioning and flux as role model for in vitro and in vivo applications. Tailor-made ELP-like block copolymer proteins exhibiting IDP-behavior enable LLPS formation in vitro and in vivo allowing the assembly of membrane-based and membraneless superstructures via protein phase-separation in E. coli. Subsequently, we demonstrate the responsiveness of protein phase-separated spaces (PPSSs) to environmental physicochemical triggers and their selective, charge-dependent and switchable interaction with DNA or extrinsic and intrinsic molecules enabling their selective shuttling across semipermeable phase boundaries including (cell)membranes. This paves the road for adjustable artificial PPSS-based storage and reaction spaces and the specific transport across phase boundaries for applications in pharmacy and synthetic biology. • An amphiphilic protein (aELP) library allows for adjustable compartments in vivo. • Extrinsic stimuli modulate protein-phase separated spaces (PPSS) in E. coli. • PPSS formed by charged aELPs direct DNA localization. • Charged aELP forming PPSS can control molecular flux of molecules in vivo. • Responsive PPSS can be used in pharmaceutical applications and synthetic biology. [ABSTRACT FROM AUTHOR]
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- 2023
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3. Improving Accuracy and Efficiency of Start-Up Cost Formulations in MIP Unit Commitment by Modeling Power Plant Temperatures.
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Silbernagl, Matthias, Huber, Matthias, and Brandenberg, Rene
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RENEWABLE energy source research , *MIXED integer linear programming , *TEMPERATURE , *POWER plants , *ELECTRIC power - Abstract
This paper presents an improved mixed-integer model for the thermal unit commitment problem. By introducing new variables for the temperature of each thermal unit, the off-time-dependent start-up costs are modeled accurately and with a lower integrality gap than state-of-the-art formulations. This new approach significantly improves computational efficiency compared to existing formulations, even if they only model a rough approximation of the start-up costs. Our findings were validated on real-world test cases using CPLEX. [ABSTRACT FROM PUBLISHER]
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- 2016
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4. Challenges and opportunities of power systems from smart homes to super-grids.
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Kuhn, Philipp, Huber, Matthias, Dorfner, Johannes, and Hamacher, Thomas
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HOME automation , *ELECTRIC power systems , *ELECTRIC power distribution grids , *RENEWABLE energy sources , *SUSTAINABILITY - Abstract
The world's power systems are facing a structural change including liberalization of markets and integration of renewable energy sources. This paper describes the challenges that lie ahead in this process and points out avenues for overcoming different problems at different scopes, ranging from individual homes to international super-grids. We apply energy system models at those different scopes and find a trade-off between technical and social complexity. Small-scale systems would require technological breakthroughs, especially for storage, but individual agents can and do already start to build and operate such systems. In contrast, large-scale systems could potentially be more efficient from a techno-economic point of view. However, new political frameworks are required that enable long-term cooperation among sovereign entities through mutual trust. Which scope first achieves its breakthrough is not clear yet. [ABSTRACT FROM AUTHOR]
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- 2016
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5. A Single Nucleotide Polymorphism near the CYP17A1 Gene Is Associated with Left Ventricular Mass in Hypertensive Patients under Pharmacotherapy.
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Huber, Matthias, Lezius, Susanne, Reibis, Rona, Treszl, Andras, Kujawinska, Dorota, Jakob, Stefanie, Wegscheider, Karl, Völler, Heinz, and Kreutz, Reinhold
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CYTOCHROME P-450 , *DRUG therapy , *CYTOCHROMES , *HYPERTENSION , *METALLOENZYMES , *MONOOXYGENASES , *MEDICAL care - Abstract
Cytochrome P450 17A1 (CYP17A1) catalyses the formation and metabolism of steroid hormones. They are involved in blood pressure (BP) regulation and in the pathogenesis of left ventricular hypertrophy. Therefore, altered function of CYP17A1 due to genetic variants may influence BP and left ventricular mass. Notably, genome wide association studies supported the role of this enzyme in BP control. Against this background, we investigated associations between single nucleotide polymorphisms (SNPs) in or nearby the CYP17A1 gene with BP and left ventricular mass in patients with arterial hypertension and associated cardiovascular organ damage treated according to guidelines. Patients (n = 1007, mean age 58.0 ± 9.8 years, 83% men) with arterial hypertension and cardiac left ventricular ejection fraction (LVEF) ≥40% were enrolled in the study. Cardiac parameters of left ventricular mass, geometry and function were determined by echocardiography. The cohort comprised patients with coronary heart disease (n = 823; 81.7%) and myocardial infarction (n = 545; 54.1%) with a mean LVEF of 59.9% ± 9.3%. The mean left ventricular mass index (LVMI) was 52.1 ± 21.2 g/m2.7 and 485 (48.2%) patients had left ventricular hypertrophy. There was no significant association of any investigated SNP (rs619824, rs743572, rs1004467, rs11191548, rs17115100) with mean 24 h systolic or diastolic BP. However, carriers of the rs11191548 C allele demonstrated a 7% increase in LVMI (95% CI: 1%-12%, p = 0.017) compared to non-carriers. The CYP17A1 polymorphism rs11191548 demonstrated a significant association with LVMI in patients with arterial hypertension and preserved LVEF. Thus, CYP17A1 may contribute to cardiac hypertrophy in this clinical condition. [ABSTRACT FROM AUTHOR]
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- 2015
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6. Optimizing long-term investments for a sustainable development of the ASEAN power system.
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Huber, Matthias, Roger, Albert, and Hamacher, Thomas
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SUSTAINABLE development , *ENERGY consumption , *GREENHOUSE gases , *CLIMATE change , *ELECTRICAL load - Abstract
The electricity consumption in the ASEAN (Association of East Asian Nations) region is one of the fastest growing in the world and will lead to a dramatic increase in greenhouse gas emissions in the next decades. A decarbonization of the region's electricity supply is thus a very important measure when taking action on global climate change. This paper defines cost-optimal pathways towards a sustainable power system in the region by employing linear optimization. The proposed model simultaneously optimizes the required capacities and the hourly operation of generation, transmission, and storage. The obtained results show that all different kinds of renewable sources will have to be utilized, while none of them should have a share of more than one third. The findings give reason for setting up an ASEAN power grid, as it enables the transportation of electricity from the best sites to load centers and leads to a balancing of the fluctuations from wind and solar generation. We suggest fostering a diversified extension of renewables and to elaborate on political and technical solutions that enable the build up an transnational supergrid. [ABSTRACT FROM AUTHOR]
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- 2015
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7. Metamizole-induced agranulocytosis revisited: results from the prospective Berlin Case-Control Surveillance Study.
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Huber, Matthias, Andersohn, Frank, Sarganas, Giselle, Bronder, Elisabeth, Klimpel, Andreas, Thomae, Michael, Konzen, Christine, Kreutz, Reinhold, and Garbe, Edeltraut
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AGRANULOCYTOSIS , *CONFIDENCE intervals , *HEADACHE , *LONGITUDINAL method , *NONSTEROIDAL anti-inflammatory agents , *RESEARCH funding , *SURGICAL complications , *CASE-control method , *DESCRIPTIVE statistics , *DIAGNOSIS - Abstract
Purpose: Treatment with metamizole (dipyrone) has steadily increased in Germany over the last decade. The consequences of this increase for metamizole-induced agranulocytosis (MIA) are unclear. The present study addressed this topic using data from the Berlin Case-Control Surveillance Study. Methods: Adult patients (≥18 years of age) with acute nonchemotherapy-induced agranulocytosis were identified by active surveillance in all 51 Berlin hospitals between 2000 and 2010. Cases related to metamizole were ascertained applying the drug causality criteria of the World Health Organization. The incidence rate of MIA was calculated and standardised by age and sex based on the German standard population in 2010. Results: Twenty-six MIA cases out of 88 (30 %) patients with validated agranulocytosis were ascertained. The incidence of MIA was 0.96 (95 % confidence interval (CI) 0.95-0.97) cases per million per year. The median age of MIA cases was 50 years (quartile (Q)1 31 years; Q3 68 years) and 19 (73 %) of them were women. In 17 (65 %) cases, neutrophil granulocytes dropped below the value of 0.1 × 10 cells/L with three patients suffering from sepsis. Headache and postoperative pain were the most frequent indications for metamizole in outpatients ( n = 16) and inpatients ( n = 10), respectively. The median treatment duration was 6 days (Q1 4 days; Q3 19 days). Conclusions: MIA persists as a severe condition in current pharmacotherapy. The continuous increase of metamizole applications should be critically assessed, especially in regard to indications in the outpatient setting and with respect to metamizole treatment duration. [ABSTRACT FROM AUTHOR]
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- 2015
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8. Designer amphiphilic proteins as building blocks for the intracellular formation of organelle-like compartments.
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Huber, Matthias C., Schreiber, Andreas, von Olshausen, Philipp, Varga, Balázs R., Kretz, Oliver, Joch, Barbara, Barnert, Sabine, Schubert, Rolf, Eimer, Stefan, Kele, Péter, and Schiller, Stefan M.
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AMPHIPHILES , *PROTEINS , *ORGANELLES , *INTRACELLULAR membranes , *MOLECULAR self-assembly , *BIOSYNTHESIS - Abstract
Nanoscale biological materials formed by the assembly of defined block-domain proteins control the formation of cellular compartments such as organelles. Here, we introduce an approach to intentionally 'program' the de novo synthesis and self-assembly of genetically encoded amphiphilic proteins to form cellular compartments, or organelles, in Escherichia coli. These proteins serve as building blocks for the formation of artificial compartments in vivo in a similar way to lipid-based organelles. We investigated the formation of these organelles using epifluorescence microscopy, total internal reflection fluorescence microscopy and transmission electron microscopy. The in vivo modification of these protein-based de novo organelles, by means of site-specific incorporation of unnatural amino acids, allows the introduction of artificial chemical functionalities. Co-localization of membrane proteins results in the formation of functionalized artificial organelles combining artificial and natural cellular function. Adding these protein structures to the cellular machinery may have consequences in nanobiotechnology, synthetic biology and materials science, including the constitution of artificial cells and bio-based metamaterials. [ABSTRACT FROM AUTHOR]
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- 2015
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9. Introducing a combinatorial DNA-toolbox platform constituting defined protein-based biohybrid-materials.
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Huber, Matthias C., Schreiber, Andreas, Wild, Wiltrud, Benz, Karin, and Schiller, Stefan M.
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NANOBIOTECHNOLOGY , *REGENERATIVE medicine , *NUCLEOTIDE sequence , *GENETIC engineering , *MOLECULAR self-assembly , *ELASTIN , *EXTRACELLULAR matrix - Abstract
The access to defined protein-based material systems is a major challenge in bionanotechnology and regenerative medicine. Exact control over sequence composition and modification is an important requirement for the intentional design of structure and function. Herein structural- and matrix proteins provide a great potential, but their large repetitive sequences pose a major challenge in their assembly. Here we introduce an integrative "one-vector-toolbox-platform" (OVTP) approach which is fast, efficient and reliable. The OVTP allows for the assembly, multimerization, intentional arrangement and direct translation of defined molecular DNA-tecton libraries, in combination with the selective functionalization of the yielded protein-tecton libraries. The diversity of the generated tectons ranges from elastine-, resilin, silk- to epitope sequence elements. OVTP comprises the expandability of modular biohybrid-materials via the assembly of defined multi-block domain genes and genetically encoded unnatural amino acids (UAA) for site-selective chemical modification. Thus, allowing for the modular combination of the protein-tecton library components and their functional expansion with chemical libraries via UAA functional groups with bioorthogonal reactivity. OVTP enables access to multitudes of defined protein-based biohybrid-materials for self-assembled superstructures such as nanoreactors and nanobiomaterials, e.g. for approaches in biotechnology and individualized regenerative medicine. [ABSTRACT FROM AUTHOR]
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- 2014
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10. Comparing a virtual reality head-mounted display to on-screen three-dimensional visualization and two-dimensional computed tomography data for training in decision making in hepatic surgery: a randomized controlled study.
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Preukschas, Anas Amin, Wise, Philipp Anthony, Bettscheider, Lisa, Pfeiffer, Micha, Wagner, Martin, Huber, Matthias, Golriz, Mohammad, Fischer, Lars, Mehrabi, Arianeb, Rössler, Fabian, Speidel, Stefanie, Hackert, Thilo, Müller-Stich, Beat Peter, Nickel, Felix, and Kenngott, Hannes Götz
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LIVER histology , *LIVER tumors , *THREE-dimensional imaging , *CANCER invasiveness , *COMPUTED tomography , *STATISTICAL sampling , *QUESTIONNAIRES , *DECISION making in clinical medicine , *RANDOMIZED controlled trials , *VIRTUAL reality , *MEDICAL students , *HEPATECTOMY , *COMPARATIVE studies , *USER interfaces - Abstract
Objective: Evaluation of the benefits of a virtual reality (VR) environment with a head-mounted display (HMD) for decision-making in liver surgery. Background: Training in liver surgery involves appraising radiologic images and considering the patient's clinical information. Accurate assessment of 2D-tomography images is complex and requires considerable experience, and often the images are divorced from the clinical information. We present a comprehensive and interactive tool for visualizing operation planning data in a VR environment using a head-mounted-display and compare it to 3D visualization and 2D-tomography. Methods: Ninety medical students were randomized into three groups (1:1:1 ratio). All participants analyzed three liver surgery patient cases with increasing difficulty. The cases were analyzed using 2D-tomography data (group "2D"), a 3D visualization on a 2D display (group "3D") or within a VR environment (group "VR"). The VR environment was displayed using the "Oculus Rift ™" HMD technology. Participants answered 11 questions on anatomy, tumor involvement and surgical decision-making and 18 evaluative questions (Likert scale). Results: Sum of correct answers were significantly higher in the 3D (7.1 ± 1.4, p < 0.001) and VR (7.1 ± 1.4, p < 0.001) groups than the 2D group (5.4 ± 1.4) while there was no difference between 3D and VR (p = 0.987). Times to answer in the 3D (6:44 ± 02:22 min, p < 0.001) and VR (6:24 ± 02:43 min, p < 0.001) groups were significantly faster than the 2D group (09:13 ± 03:10 min) while there was no difference between 3D and VR (p = 0.419). The VR environment was evaluated as most useful for identification of anatomic anomalies, risk and target structures and for the transfer of anatomical and pathological information to the intraoperative situation in the questionnaire. Conclusions: A VR environment with 3D visualization using a HMD is useful as a surgical training tool to accurately and quickly determine liver anatomy and tumor involvement in surgery. [ABSTRACT FROM AUTHOR]
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- 2024
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11. French coastal network for carbonate system monitoring: the CocoriCO2 dataset.
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Petton, Sébastien, Pernet, Fabrice, Le Roy, Valérian, Huber, Matthias, Martin, Sophie, Macé, Éric, Bozec, Yann, Loisel, Stéphane, Rimmelin-Maury, Peggy, Grossteffan, Émilie, Repecaud, Michel, Quemener, Loïc, Retho, Michael, Manac'h, Soazig, Papin, Mathias, Pineau, Philippe, Lacoue-Labarthe, Thomas, Deborde, Jonathan, Costes, Louis, and Polsenaere, Pierre
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ATMOSPHERIC carbon dioxide , *GROUNDWATER monitoring , *SENSOR networks , *OCEAN acidification , *MARINE ecology , *CARBON dioxide - Abstract
Since the beginning of the industrial revolution, atmospheric carbon dioxide (CO 2) concentrations have risen steadily and have induced a decrease of the averaged surface ocean pH by 0.1 units, corresponding to an increase in ocean acidity of about 30 %. In addition to ocean warming, ocean acidification poses a tremendous challenge to some marine organisms, especially calcifiers. The need for long-term oceanic observations of pH and temperature is a key element to assess the vulnerability of marine communities and ecosystems to these pressures. Nearshore productive environments, where a large majority of shellfish farming activities are conducted, are known to present pH levels as well as amplitudes of daily and seasonal variations that are much larger than those observed in the open ocean. Yet, to date, there are very few coastal observation sites where these parameters are measured simultaneously and at high frequency. To bridge this gap, an observation network was initiated in 2021 in the framework of the CocoriCO 2 project. Six sites were selected along the French Atlantic and Mediterranean coastlines based on their importance in terms of shellfish production and the presence of high- and low-frequency monitoring activities. At each site, autonomous pH sensors were deployed, both inside and outside shellfish production areas, next to high-frequency CTD (conductivity–temperature–depth) probes operated through two operating monitoring networks. pH sensors were set to an acquisition rate of 15 min, and discrete seawater samples were collected biweekly in order to control the quality of pH data (laboratory spectrophotometric measurements) as well as to measure total alkalinity and dissolved inorganic carbon concentrations for full characterization of the carbonate system. While this network has been up and running for more than 2 years, the acquired dataset has already revealed important differences in terms of pH variations between monitored sites related to the influence of diverse processes (freshwater inputs, tides, temperature, biological processes). Data are available at 10.17882/96982 (Petton et al., 2023a). [ABSTRACT FROM AUTHOR]
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- 2024
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12. French coastal network for carbonate system monitoring: The CocoriCO2 dataset.
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Petton, Sébastien, Pernet, Fabrice, Roy, Valérian Le, Huber, Matthias, Martin, Sophie, Macé, Éric, Bozec, Yann, Loisel, Stéphane, Rimmelin-Maury, Peggy, Grossteffan, Émilie, Repecaud, Michel, Quemener, Loïc, Retho, Michael, Manac’h, Soazig, Papin, Mathias, Pineau, Philippe, LacoueLabarthe, Thomas, Deborde, Jonathan, Costes, Louis, and Polsenaere, Pierre
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ATMOSPHERIC carbon dioxide , *GROUNDWATER monitoring , *OCEAN acidification , *SENSOR networks , *MARINE ecology , *CARBONATES - Abstract
Since the beginning of the industrial revolution, atmospheric carbon dioxide (CO2) concentrations have risen steadily and have induced a decrease of the averaged surface ocean pH by 0.1 units, corresponding to an increase in ocean acidity of about 30 %. In addition to ocean warming, ocean acidification poses a tremendous challenge to some marine organisms, especially calcifiers. The need for long-term oceanic observations of pH and temperature is a key element to assess the vulnerability of marine communities and ecosystems to these pressures. Nearshore productive environments, where a large majority of shellfish farming activities are conducted, are known to present pH levels as well as amplitudes of daily and seasonal variations that are much larger than those observed in the open ocean. Yet, to date, there are very few coastal observation sites where these parameters are measured simultaneously and at high frequency. To bridge this gap, an observation network was initiated in 2021 in the framework of the CocoriCO2 project. Six sites were selected along the French Atlantic and Mediterranean coastlines based on their importance in terms of shellfish production and the presence of high- and low-frequency monitoring activities. At each site, autonomous pH sensors were deployed both inside and outside shellfish production areas, next to high-frequency CTD (conductivity- temperature-depth) probes operated through two operating monitoring networks. pH sensors were set to an acquisition rate of 15 min and discrete seawater samples were collected biweekly in order to control the quality of pH data (laboratory spectrophotometric measurements) as well as to measure total alkalinity and dissolved inorganic carbon concentrations for full characterization of the carbonate system. While this network has been up and running for more than two years, the acquired dataset has already revealed important differences in terms of pH variations between monitored sites related to the influence of diverse processes (freshwater inputs, tides, temperature, biological processes). [ABSTRACT FROM AUTHOR]
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- 2023
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13. Atomic-Resolution Three-Dimensional Structure of Amyloid β Fibrils Bearing the Osaka Mutation.
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Schütz, Anne K., Vagt, Toni, Huber, Matthias, Ovchinnikova, Oxana Y., Cadalbert, Riccardo, Wall, Joseph, Güntert, Peter, Böckmann, Anja, Glockshuber, Rudi, and Meier, Beat H.
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GENETICS of Alzheimer's disease , *NUCLEAR magnetic resonance , *AMYLOID beta-protein , *DELETION mutation , *NEURODEGENERATION , *GENETICS - Abstract
Despite its central importance for understanding the molecular basis of Alzheimer's disease (AD), high-resolution structural information on amyloid β-peptide (Aβ) fibrils, which are intimately linked with AD, is scarce. We report an atomic-resolution fibril structure of the Aβ1-40 peptide with the Osaka mutation (E22Δ), associated with early-onset AD. The structure, which differs substantially from all previously proposed models, is based on a large number of unambiguous intra- and intermolecular solid-state NMR distance restraints. [ABSTRACT FROM AUTHOR]
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- 2015
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14. Die atomare dreidimensionale Struktur von Amyloid-β-Fibrillen mit der Osaka-Mutation.
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Schütz, Anne K., Vagt, Toni, Huber, Matthias, Ovchinnikova, Oxana Y., Cadalbert, Riccardo, Wall, Joseph, Güntert, Peter, Böckmann, Anja, Glockshuber, Rudi, and Meier, Beat H.
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Trotz der zentralen Bedeutung für das Verständnis der molekularen Grundlage der Alzheimer ‐ Krankheit (AK), gibt es bisher wenig Wissen über die hochaufgelösten Strukturen von Fibrillen des Amyloid ‐ β(Aβ) ‐ Peptids. Wir präsentieren hier eine atomar aufgelöste Struktur von Fibrillen des Aβ1 ‐ 40 ‐ Peptids mit der Osaka ‐ Mutation (E22Δ), die mit früh auftretender AK in Zusammenhang steht. Die Struktur, die sich grundlegend von allen bisher vorgestellten Aβ ‐ Modellen unterscheidet, basiert auf einer großen Anzahl eindeutiger intra ‐ und intermolekularer Abstandsbeschränkungen (“distance restraints”). Die Fibrillenstruktur des Aβ1 ‐ 40 ‐ Peptids mit der Osaka ‐ Mutation (E22Δ), die mit früh auftretender Alzheimer ‐ Erkrankung in Zusammenhang steht, wurde in atomarer Auflösung erhalten und unterscheidet sich grundlegend von allen bisher vorgeschlagenen Aβ ‐ Modellen: Sie ist komplex geordnet, wobei sich die Deletionsmutation in einer β ‐ Schleife der Struktur befindet. [ABSTRACT FROM AUTHOR]
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- 2015
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15. Dynamic Structural Changes and Thermodynamics in Phase Separation Processes of an Intrinsically Disordered–Ordered Protein Model.
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Lüdeke, Steffen, Lohner, Philipp, Stühn, Lara G., Betschart, Martin U., Huber, Matthias C., Schreiber, Andreas, and Schiller, Stefan M.
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PHASE separation , *PROTEIN models , *THERMODYNAMICS , *SMART materials , *CIRCULAR dichroism - Abstract
Elastin‐like proteins (ELPs) are biologically important proteins and models for intrinsically disordered proteins (IDPs) and dynamic structural transitions associated with coacervates and liquid–liquid phase transitions. However, the conformational status below and above coacervation temperature and its role in the phase separation process is still elusive. Employing matrix least‐squares global Boltzmann fitting of the circular dichroism spectra of the ELPs (VPGVG)20, (VPGVG)40, and (VPGVG)60, we found that coacervation occurs sharply when a certain number of repeat units has acquired β‐turn conformation (in our sequence setting a threshold of approx. 20 repeat units). The character of the differential scattering of the coacervate suspensions indicated that this fraction of β‐turn structure is still retained after polypeptide assembly. Such conformational thresholds may also have a role in other protein assembly processes with implications for the design of protein‐based smart materials. [ABSTRACT FROM AUTHOR]
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- 2022
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16. Dynamische Strukturänderung und Thermodynamik von Phasentrennprozessen eines Proteinmodells mit intrinsisch ungeordneter/geordneter Struktur.
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Lüdeke, Steffen, Lohner, Philipp, Stühn, Lara G., Betschart, Martin U., Huber, Matthias C., Schreiber, Andreas, and Schiller, Stefan M.
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Elastin‐artige Proteine (ELPs) haben neben ihrer biologischen Funktion auch Bedeutung als Modelle für intrinsisch ungeordnete Proteine und dynamische Strukturübergänge, die mit Koazervation und Flüssig‐flüssig‐Phasenübergängen einhergehen. Über den Konformerenzustand direkt unter‐ und oberhalb der Koazervationstemperatur und dessen Rolle im Phasentrennprozess ist allerdings nach wie vor wenig bekannt. Durch globales Matrix‐kleinste‐Quadrate‐Boltzmann‐Fitting der Zirkulardichroismus‐Spektren dreier ELPs deckten wir auf, dass es unmittelbar zur Koazervation kommt, wenn eine bestimmte Anzahl von Wiederholungseinheiten β‐Turn‐Konformation angenommen hat (hier etwa 20 Wiederholungseinheiten). Der Charakter der differenziellen Streuung der Koazervat‐Suspensionen wies darauf hin, dass dieser Anteil an β‐Turn‐Struktur auch nach der Zusammenlagerung der Polypeptide erhalten bleibt. Möglicherweise spielen derartige "Konformationsschwellenwerte" auch in anderen Protein‐Zusammenlagerungsprozessen eine Rolle. [ABSTRACT FROM AUTHOR]
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- 2022
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17. IMHOTEP: cross-professional evaluation of a three-dimensional virtual reality system for interactive surgical operation planning, tumor board discussion and immersive training for complex liver surgery in a head-mounted display.
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Kenngott, Hannes Götz, Pfeiffer, Micha, Preukschas, Anas Amin, Bettscheider, Lisa, Wise, Philipp Anthony, Wagner, Martin, Speidel, Stefanie, Huber, Matthias, Nickel, Felix, Mehrabi, Arianeb, and Müller-Stich, Beat Peter
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LIVER surgery , *OPERATIVE surgery , *VIRTUAL reality , *HEAD-mounted displays , *MEDICAL care , *MEDICAL students - Abstract
Background: Virtual reality (VR) with head-mounted displays (HMD) may improve medical training and patient care by improving display and integration of different types of information. The aim of this study was to evaluate among different healthcare professions the potential of an interactive and immersive VR environment for liver surgery that integrates all relevant patient data from different sources needed for planning and training of procedures. Methods: 3D-models of the liver, other abdominal organs, vessels, and tumors of a sample patient with multiple hepatic masses were created. 3D-models, clinical patient data, and other imaging data were visualized in a dedicated VR environment with an HMD (IMHOTEP). Users could interact with the data using head movements and a computer mouse. Structures of interest could be selected and viewed individually or grouped. IMHOTEP was evaluated in the context of preoperative planning and training of liver surgery and for the potential of broader surgical application. A standardized questionnaire was voluntarily answered by four groups (students, nurses, resident and attending surgeons). Results: In the evaluation by 158 participants (57 medical students, 35 resident surgeons, 13 attending surgeons and 53 nurses), 89.9% found the VR system agreeable to work with. Participants generally agreed that complex cases in particular could be assessed better (94.3%) and faster (84.8%) with VR than with traditional 2D display methods. The highest potential was seen in student training (87.3%), resident training (84.6%), and clinical routine use (80.3%). Least potential was seen in nursing training (54.8%). Conclusions: The present study demonstrates that using VR with HMD to integrate all available patient data for the preoperative planning of hepatic resections is a viable concept. VR with HMD promises great potential to improve medical training and operation planning and thereby to achieve improvement in patient care. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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18. The toxic dinoflagellate Alexandrium minutum impairs the performance of oyster embryos and larvae.
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Castrec, Justine, Hégaret, Hélène, Huber, Matthias, Le Grand, Jacqueline, Huvet, Arnaud, Tallec, Kevin, Boulais, Myrina, Soudant, Philippe, and Fabioux, Caroline
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ALEXANDRIUM , *PACIFIC oysters , *OYSTERS , *LARVAE , *EMBRYOS , *GYMNODINIUM , *FISH spawning , *DINOFLAGELLATES - Abstract
• Strain-specific toxicities of Alexandrium minutum upon early-larval development were observed. • Among oyster free-living stages, embryos are the most sensitive stage to A. minutum. • A non-PST-producing strain altered larval feeding, growth, survival, and settlement. • Oyster larvae fed with toxic A. minutum accumulated PST. The dinoflagellate genus Alexandrium comprises species that produce highly potent neurotoxins known as paralytic shellfish toxins (PST), and bioactive extracellular compounds (BEC) of unknown structure and ecological significance. The toxic bloom-forming species, Alexandrium minutum , is distributed worldwide and adversely affects many bivalves including the commercially and ecologically important Pacific oyster, Crassostrea gigas. In France, recurrent A. minutum blooms can co-occur with C. gigas spawning and larval development, and may endanger recruitment and population renewal. The present study explores how A. minutum affects oyster early development by exposing embryos and larvae, under controlled laboratory conditions, to two strains of A. minutum , producing only BEC or both PST and BEC. Results highlight the major role of BEC in A. minutum toxicity upon oyster development. The BEC strain caused lysis of embryos, the most sensitive stage to A. minutum toxicity among planktonic life stages. In addition, the non-PST-producing A. minutum strain inhibited hatching, disrupted larval swimming behavior, feeding, growth, and induced drastic decreases in survival and settlement of umbonate and eyed larvae (9 and 68 %, respectively). The findings indicated PST accumulation in oyster larvae (e.g. umbonate stages), possibly impairing development and settlement of larvae in response to the PST-producing strain. This work provides evidences that A. minutum blooms could hamper settlement of shellfish. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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19. Dissecting the region around IceCube-170922A: the blazar TXS 0506+056 as the first cosmic neutrino source.
- Author
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Glauch, Theo, Padovani, Paolo, Giommi, Paolo, Resconi, Elisa, Arsioli, Bruno, Sahakyan, Narek, Huber, Matthias, and Spiering, C.
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NEUTRINO detectors , *BL Lacertae objects , *NEUTRINOS , *FLUX (Energy) , *NEUTRINO astrophysics - Abstract
On MJD 58018 the IceCube neutrino observatory detected a highlyenergetic, well-reconstructed neutrino, IceCube-170922A, at a distance of 0:1° to a γ-ray flaring blazar, TXS 0506+056. Follow-up searches in archival data additionally revealed a larger flare of neutrinos from the same direction. In order to complete the picture we present here a full multi-wavelength study of the region around IceCube-170922A. While we identify also other non-thermal counterpart candidates, we show that all the evidence points to TXS 0506+056 as the dominant neutrino emitter. Additionally, an analysis of all the available Fermi-LAT data indicates a hard spectrum/low flux of TXS 0506+056 during the neutrino flare in contrast to a soft spectrum/high flux at the arrival time of IceCube-170922A. Putting all the pieces together we conclude that the SED of TXS 0506+056 can be energetically reconnected for both neutrino observations. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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20. Targeted resequencing of a locus for heparin-induced thrombocytopenia on chromosome 5 identified in a genome-wide association study.
- Author
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Witten, Anika, Bolbrinker, Juliane, Barysenka, Andrei, Huber, Matthias, Rühle, Frank, Nowak-Göttl, Ulrike, Garbe, Edeltraut, Kreutz, Reinhold, and Stoll, Monika
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LOCUS (Genetics) , *THROMBOCYTOPENIA , *HEPARIN , *CHROMOSOMES , *DRUG side effects , *GENETICS of disease susceptibility - Abstract
Abstract: Immune-mediated heparin-induced thrombocytopenia (HIT) is the clinically most important adverse drug reaction (ADR) in response to heparin therapy characterized by a prothrombotic state despite a decrease in platelet count. We conducted a genome-wide association study in 96 suspected HIT cases and 96 controls to explore the genetic predisposition for HIT within a case-control pharmacovigilance study followed by replication in additional 86 cases and 86 controls from the same study. One single nucleotide polymorphism (SNP, rs1433265, P = 6.5 × 10−5, odds ratio (OR) 2.79) from 16 identified SNPs was successfully replicated (P = 1.5 × 10−4, OR 2.77; combined data set P = 2.7 × 10−8, OR 2.77) and remained the most strongly associated SNP after imputing locus genotypes. Fine mapping revealed a significantly associated risk-conferring haplotype (P = 4.9 × 10−6, OR 2.41). In order to find rare variants contributing to the association signals, we applied a targeted resequencing approach in a subgroup of 73 HIT patients and 23 controls for the regions with the 16 most strongly HIT-associated SNPs. C-alpha testing was applied to test for the impact of rare variants and we detected two candidate genes, the discoidin domain receptor tyrosine kinase 1 (DDR1, P = 3.6 × 10−2) and the multiple C2 and transmembrane domain containing 2 (MCTP2, P = 4.5 × 10−2). For the genes interactor of little elongation complex ELL subunit 1 (ICE1) and a disintegrin-like and metalloproteinase with thrombospondin type 1 motif, 16 (ADAMTS16) nearby rs1433265, we identified several missense variants. Although replication in an independent population is warranted, these findings provide a basis for future studies aiming to identify and characterize genetic susceptibility factors for HIT.Key messages: We identified and validated a HIT-associated locus on chromosome 5.Targeted NGS analysis for rare variants identifies DDR1 and MCTP2 as novel candidates.In addition, missense variants for ADAMTS16 and ICE1 were identified in the locus. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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21. Structure and assembly of the mouse ASC inflammasome by combined NMR spectroscopy and cryo-electron microscopy.
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Sborgi, Lorenzo, Ravotti, Francesco, Dandey, Venkata P., Dick, Mathias S., Mazur, Adam, Reckel, Sina, Chami, Mohamed, Scherer, Sebastian, Huber, Matthias, Böckmann, Anja, Egelman, Edward H., Stahlberg, Henning, Broz, Petr, Meier, Beat H., and Hiller, Sebastian
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ADAPTOR protein genetics , *NUCLEAR magnetic resonance spectroscopy , *CRYOELECTRONICS , *CYTOKINES , *APOPTOSIS - Abstract
Inflammasomes are multiprotein complexes that control the innate immune response by activating caspase-1, thus promoting the secretion of cytokines in response to invading pathogens and endogenous triggers. Assembly of inflammasomes is induced by activation of a receptor protein. Many inflammasome receptors require the adapter protein ASC [apoptosis-associated speck-like protein containing a caspase-recruitment domain (CARD)], which consists of two domains, the N-terminal pyrin domain (PYD) and the C-terminal CARD. Upon activation, ASC forms large oligomeric filaments, which facilitate procaspase-1 recruitment. Here, we characterize the structure and filament formation of mouse ASC in vitro at atomic resolution. Information from cryo-electron microscopy and solid-state NMR spectroscopy is combined in a single structure calculation to obtain the atomic-resolution structure of the ASC filament. Perturbations of NMR resonances upon filament formation monitor the specific binding interfaces of ASC-PYD association. Importantly, NMR experiments show the rigidity of the PYD forming the core of the filament as well as the high mobility of the CARD relative to this core. The findings are validated by structure-based mutagenesis experiments in cultured macrophages. The 3D structure of the mouse ASC-PYD filament is highly similar to the recently determined human ASC-PYD filament, suggesting evolutionary conservation of ASC-dependent inflammasome mechanisms. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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22. Decarbonization pathways of worldwide energy systems – Definition and modeling of archetypes.
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Kueppers, Martin, Paredes Pineda, Stephany Nicole, Metzger, Michael, Huber, Matthias, Paulus, Simon, Heger, Hans Joerg, and Niessen, Stefan
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- *
ARCHETYPES , *ENERGY futures , *PHOTOVOLTAIC power generation - Abstract
• Archetypes to summarize countries globally regarding their energy system. • Framework to define, model and validate these archetypes. • Archetype classification 44% better than simple geographic grouping. • Photovoltaics and flexibility are identified and quantified as global challenges by the archetype modeling. • Country modeling validates archetype approach with few outliers. Energy system models help to find the optimal technology mixes for decarbonization strategies in countries worldwide. To reduce the modeling effort and analyze as many countries as possible, this paper proposes a novel approach of energy system archetypes which can be directly evaluated. These archetypes classify similar countries worldwide independently from their geographic location. Advantages of this idea are the setup of a transferable global database allowing for data reconstruction between countries, market size estimations, and the ability to compare peer countries facing similar challenges. To enable such modeling, a framework is developed in which the archetypes are defined, standardized modeling rules are developed, and the results are evaluated for validation. In a benchmark against simple geographic classifications, the presented clustering approach, which results in 15 archetypes, improves the variance between all countries and their corresponding archetypes by 44% compared to the variance between the countries and their geographic sub-regions. The model results of these archetypes state the need of balancing technologies for the daily cycle of photovoltaic generation and the general importance of flexibility in future decarbonized energy systems. Overall, the results confirm that archetypes are an adequate approach to derive the set of solutions for the decarbonization of worldwide countries. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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23. Pathways toward a Decarbonized Future—Impact on Security of Supply and System Stability in a Sustainable German Energy System.
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Metzger, Michael, Duckheim, Mathias, Franken, Marco, Heger, Hans Joerg, Huber, Matthias, Knittel, Markus, Kolster, Till, Kueppers, Martin, Meier, Carola, Most, Dieter, Paulus, Simon, Wyrwoll, Lothar, Moser, Albert, and Niessen, Stefan
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NUCLEAR power plant shutdowns , *SECURITY systems , *CARBON offsetting , *ENERGY futures , *ELECTRICITY markets - Abstract
Pathways leading to a carbon neutral future for the German energy system have to deal with the expected phase-out of coal-fired power generation, in addition to the shutdown of nuclear power plants and the rapid ramp-up of photovoltaics and wind power generation. An analysis of the expected impact on electricity market, security of supply, and system stability must consider the European context because of the strong coupling—both from an economic and a system operation point of view—through the cross-border power exchange of Germany with its neighbors. This analysis, complemented by options to improve the existing development plans, is the purpose of this paper. We propose a multilevel energy system modeling, including electricity market, network congestion management, and system stability, to identify challenges for the years 2023 and 2035. Out of the results, we would like to highlight the positive role of innovative combined heat and power (CHP) solutions securing power and heat supply, the importance of a network congestion management utilizing flexibility from sector coupling, and the essential network extension plans. Network congestion and reduced security margins will become the new normal. We conclude that future energy systems require expanded flexibilities in combination with forward planning of operation. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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24. Data-Driven Regionalization of Decarbonized Energy Systems for Reflecting Their Changing Topologies in Planning and Optimization.
- Author
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Kueppers, Martin, Perau, Christian, Franken, Marco, Heger, Hans Joerg, Huber, Matthias, Metzger, Michael, and Niessen, Stefan
- Subjects
- *
RENEWABLE energy sources , *TOPOLOGY , *MODEL-driven software architecture - Abstract
The decarbonization of energy systems has led to a fundamental change in their topology since generation is shifted to locations with favorable renewable conditions. In planning, this change is reflected by applying optimization models to regions within a country to optimize the distribution of generation units and to evaluate the resulting impact on the grid topology. This paper proposes a globally applicable framework to find a suitable regionalization for energy system models with a data-driven approach. Based on a global, spatially resolved database of demand, generation, and renewable profiles, hierarchical clustering with fine-tuning is performed. This regionalization approach is applied by modeling the resulting regions in an optimization model including a synthesized grid. In an exemplary case study, South Africa's energy system is examined. The results show that the data-driven regionalization is beneficial compared to the common approach of using political regions. Furthermore, the results of a modeled 80% decarbonization until 2045 demonstrate that the integration of renewable energy sources fundamentally changes the role of regions within South Africa's energy system. Thereby, the electricity exchange between regions is also impacted, leading to a different grid topology. Using clustered regions improves the understanding and analysis of regional transformations in the decarbonization process. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
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