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  1. Book ; Thesis: Ermittlung der prädikativen Aussagekraft laborchemischer Surrogatparameter zum Zeitpunkt einer MDCT-Untersuchung bei Patienten mit Verdacht auf eine akute Pankreatitis

    Kraus, Thomas Fabian

    2018  

    Author's details vorgelegt von: Thomas Fabian Kraus
    Language German
    Size 53 Blätter, Illustrationen, Diagramme, 30 cm
    Publishing place Hamburg
    Publishing country Germany
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Dissertation, Universität Hamburg, 2018
    Note Text deutsch, Zusammenfassung in deutscher und englischer Sprache ; Literaturverzeichnis: Seite 39-48
    HBZ-ID HT020456822
    Database Catalogue ZB MED Medicine, Health

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  2. Article ; Online: Improving CBCA synthase activity through rational protein design.

    Thomas, Fabian / Kayser, Oliver

    Journal of biotechnology

    2023  Volume 363, Page(s) 40–49

    Abstract: Global interest for the minor cannabinoid cannabichromene (CBC) is growing steadily, as potential pharmaceutical applications continue to emerge. Due to low-yielding and unspecific extraction processes from its plant host Cannabis sativa, a ... ...

    Abstract Global interest for the minor cannabinoid cannabichromene (CBC) is growing steadily, as potential pharmaceutical applications continue to emerge. Due to low-yielding and unspecific extraction processes from its plant host Cannabis sativa, a biotechnological production is desirable. The complete heterologous biosynthesis of several other cannabinoids has recently been demonstrated as an accessible platform. However, the enzyme involved in the biosynthesis of CBC precursor cannabichromenic acid (CBCA) suffers from comparatively low catalytic efficiency, has not been crystallized, and remains poorly characterized. This study contributes to overcoming these challenges in three unique aspects. A deep‑learning‑assisted prediction of the CBCA synthase crystal structure using DeepMinds AlphaFold is performed and evaluated. The predicted CBCA synthase structure scored considerably higher in various quality assessments than the alternative template‑based homology modeling approach. A robust and practical understanding of crucial structure-function relationships for CBCA synthase is provided and a new binding mode for the substrate uncovered. Rational design approaches and computational analyses to suggest CBCAS variants with facilitated activity are applied. Through subsequent screening the substrate conversion of those variants is compared to the native enzyme. The best variant presented in this study increases CBCA production from crude lysate 22-fold and is one of five positions where substitutions had a significantly favorable impact on product formation.
    MeSH term(s) Cannabinoids/metabolism ; Cannabis ; Biotechnology
    Chemical Substances cannabichromenic acid synthase (EC 1.3.99.-) ; cannabichromene (K4497H250W) ; Cannabinoids
    Language English
    Publishing date 2023-01-18
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 843647-2
    ISSN 1873-4863 ; 0168-1656 ; 1389-0352
    ISSN (online) 1873-4863
    ISSN 0168-1656 ; 1389-0352
    DOI 10.1016/j.jbiotec.2023.01.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Book ; Online: Ein neuer Gesellschaftsvertrag für eine nachhaltige Landwirtschaft : Wege zu einer integrativen Politik für den Agrarsektor

    Feindt, Peter H. / Krämer, Christine / Früh-Müller, Andrea / Heißenhuber, Alois / Pahl-Wostl, Claudia / Purnhagen, Kai P. / Thomas, Fabian / van Bers, Caroline / Wolters, Volkmar

    2019  

    Keywords Business & the environment, 'Green' approaches to business ; International law ; Sustainability ; Law ; Law-Europe ; Industrial management-Environmental aspects ; Economic development-Environmental aspects
    Size 1 electronic resource (323 pages)
    Publisher Springer Nature
    Publishing place Berlin, Heidelberg
    Document type Book ; Online
    Note German ; Open Access
    HBZ-ID HT021027005
    ISBN 978-3-662-58656-3 ; 3-662-58656-8
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  4. Book ; Online: Ein neuer Gesellschaftsvertrag für eine nachhaltige Landwirtschaft

    Feindt, Peter H. / Krämer, Christine / Früh-Müller, Andrea / Heißenhuber, Alois / Pahl-Wostl, Claudia / Purnhagen, Kai P. / Thomas, Fabian / van Bers, Caroline / Wolters, Volkmar

    Wege zu einer integrativen Politik für den Agrarsektor

    2019  

    Author's details von Peter H. Feindt, Christine Krämer, Andrea Früh-Müller, Alois Heißenhuber, Claudia Pahl-Wostl, Kai P. Purnhagen, Fabian Thomas, Caroline van Bers, Volkmar Wolters
    Keywords Law—Europe ; Industrial management—Environmental aspects ; Economic development—Environmental aspects ; Agrarpolitik ; Umweltpolitik ; Nachhaltigkeit
    Subject Nachhaltige Entwicklung ; Langfristige Entwicklung ; Sustainable Development ; Dauerhafte Entwicklung ; Zukunftsfähige Entwicklung ; Umweltschutz ; Umweltschutzpolitik ; Landwirtschaftspolitik
    Subject code 341.2422
    Language German
    Size 1 Online-Ressource (XX, 323 S. 15 Abb., 12 Abb. in Farbe)
    Edition 1st ed. 2019
    Publisher Springer Berlin Heidelberg ; Imprint: Springer
    Publishing place Berlin, Heidelberg
    Document type Book ; Online
    HBZ-ID HT020260770
    ISBN 978-3-662-58656-3 ; 9783662586556 ; 3-662-58656-8 ; 366258655X
    DOI 10.1007/978-3-662-58656-3
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  5. Article: Natural deep eutectic solvents enhance cannabinoid biotransformation

    Thomas, Fabian / Kayser, Oliver

    Biochemical engineering journal. 2022 Mar., v. 180

    2022  

    Abstract: Numerous studies in cannabinoid biotechnology focus extensively on cytosolic biosynthesis or biotransformation, neglecting to consider non-aqueous solvents. In this study, we show that it is advantageous to perform cannabinoid biotransformations in ... ...

    Abstract Numerous studies in cannabinoid biotechnology focus extensively on cytosolic biosynthesis or biotransformation, neglecting to consider non-aqueous solvents. In this study, we show that it is advantageous to perform cannabinoid biotransformations in natural deep eutectic solvents (NADES). NADES are composed of two or more natural compounds, which, when mixed lower the melting point of the solution significantly below those of the individual components. Thus, initially solid sugars, amino acids, or organic acids are complexed into solvents that are liquids at room temperature. We comprehensively assess these novel "green solvents" for their capabilities to facilitate in vitro biotransformations by the three known cannabinoid synthases. Compared to aqueous biosynthesis, NADES doubled cannabinoid production of tetrahydrocannabinolic acid synthase and more than tripled production of cannabichromenic acid synthase. Data allows us to suggest solvent compositions that flexibly boost total cannabinoid content or alter cannabinoid specificity. This knowledge can equip researchers and bioengineers with the tools to tailor cannabinoid production to their needs without taking on the demanding task of enzyme engineering.
    Keywords ambient temperature ; biosynthesis ; biotechnology ; biotransformation ; cannabinoids ; enzymes ; solvents
    Language English
    Dates of publication 2022-03
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 2012139-8
    ISSN 1369-703X
    ISSN 1369-703X
    DOI 10.1016/j.bej.2022.108380
    Database NAL-Catalogue (AGRICOLA)

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  6. Book ; Online: Reviving Meltdown 3a

    Weber, Daniel / Thomas, Fabian / Gerlach, Lukas / Zhang, Ruiyi / Schwarz, Michael

    2023  

    Abstract: Since the initial discovery of Meltdown and Spectre in 2017, different variants of these attacks have been discovered. One often overlooked variant is Meltdown 3a, also known as Meltdown-CPL-REG. Even though Meltdown-CPL-REG was initially discovered in ... ...

    Abstract Since the initial discovery of Meltdown and Spectre in 2017, different variants of these attacks have been discovered. One often overlooked variant is Meltdown 3a, also known as Meltdown-CPL-REG. Even though Meltdown-CPL-REG was initially discovered in 2018, the available information regarding the vulnerability is still sparse. In this paper, we analyze Meltdown-CPL-REG on 19 different CPUs from different vendors using an automated tool. We observe that the impact is more diverse than documented and differs from CPU to CPU. Surprisingly, while the newest Intel CPUs do not seem affected by Meltdown-CPL-REG, the newest available AMD CPUs (Zen3+) are still affected by the vulnerability. Furthermore, given our attack primitive CounterLeak, we show that besides up-to-date patches, Meltdown-CPL-REG can still be exploited as we reenable performance-counter-based attacks on cryptographic algorithms, break KASLR, and mount Spectre attacks. Although Meltdown-CPL-REG is not as powerful as other transient-execution attacks, its attack surface should not be underestimated.

    Comment: published at ESORICS 2023
    Keywords Computer Science - Cryptography and Security
    Publishing date 2023-10-06
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Book ; Online: Indirect Meltdown

    Weber, Daniel / Thomas, Fabian / Gerlach, Lukas / Zhang, Ruiyi / Schwarz, Michael

    Building Novel Side-Channel Attacks from Transient-Execution Attacks

    2023  

    Abstract: The transient-execution attack Meltdown leaks sensitive information by transiently accessing inaccessible data during out-of-order execution. Although Meltdown is fixed in hardware for recent CPU generations, most currently-deployed CPUs have to rely on ... ...

    Abstract The transient-execution attack Meltdown leaks sensitive information by transiently accessing inaccessible data during out-of-order execution. Although Meltdown is fixed in hardware for recent CPU generations, most currently-deployed CPUs have to rely on software mitigations, such as KPTI. Still, Meltdown is considered non-exploitable on current systems. In this paper, we show that adding another layer of indirection to Meltdown transforms a transient-execution attack into a side-channel attack, leaking metadata instead of data. We show that despite software mitigations, attackers can still leak metadata from other security domains by observing the success rate of Meltdown on non-secret data. With LeakIDT, we present the first cache-line granular monitoring of kernel addresses. LeakIDT allows an attacker to obtain cycle-accurate timestamps for attacker-chosen interrupts. We use our attack to get accurate inter-keystroke timings and fingerprint visited websites. While we propose a low-overhead software mitigation to prevent the exploitation of LeakIDT, we emphasize that the side-channel aspect of transient-execution attacks should not be underestimated.

    Comment: published at ESORICS 2023
    Keywords Computer Science - Cryptography and Security
    Subject code 303 ; 005
    Publishing date 2023-10-06
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article: Neural Correlates of Age-Related Changes in Precise Grip Force Regulation: A Combined EEG-fNIRS Study.

    Berger, Alisa / Steinberg, Fabian / Thomas, Fabian / Doppelmayr, Michael

    Frontiers in aging neuroscience

    2020  Volume 12, Page(s) 594810

    Abstract: Motor control is associated with suppression of oscillatory activity in alpha (8-12 Hz) and beta (12-30 Hz) ranges and elevation of oxygenated hemoglobin levels in motor-cortical areas. Aging leads to changes in oscillatory and hemodynamic brain activity ...

    Abstract Motor control is associated with suppression of oscillatory activity in alpha (8-12 Hz) and beta (12-30 Hz) ranges and elevation of oxygenated hemoglobin levels in motor-cortical areas. Aging leads to changes in oscillatory and hemodynamic brain activity and impairments in motor control. However, the relationship between age-related changes in motor control and brain activity is not yet fully understood. Therefore, this study aimed to investigate age-related and task-complexity-related changes in grip force control and the underlying oscillatory and hemodynamic activity. Sixteen younger [age (mean ± SD) = 25.4 ± 1.9, 20-30 years] and 16 older (age = 56.7 ± 4.7, 50-70 years) healthy men were asked to use a power grip to perform six trials each of easy and complex force tracking tasks (FTTs) with their right dominant hand in a randomized within-subject design. Grip force control was assessed using a sensor-based device. Brain activity in premotor and primary motor areas of both hemispheres was assessed by electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS). Older adults showed significantly higher inaccuracies and higher hemodynamic activity in both FTTs than did young adults. Correlations between grip force control owing to task complexity and beta activity were different in the contralateral premotor cortex (PMC) between younger and older adults. Collectively, these findings suggest that aging leads to impairment of grip force control and an increase in hemodynamic activity independent of task complexity. EEG beta oscillations may represent a task-specific neurophysiological marker for age-related decline in complex grip force control and its underlying compensation strategies. Further EEG-fNIRS studies are necessary to determine neurophysiological markers of dysfunctions underlying age-related motor disabilities for the improvement of individual diagnosis and therapeutic approaches.
    Language English
    Publishing date 2020-12-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2558898-9
    ISSN 1663-4365
    ISSN 1663-4365
    DOI 10.3389/fnagi.2020.594810
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Bioengineering studies and pathway modeling of the heterologous biosynthesis of tetrahydrocannabinolic acid in yeast.

    Thomas, Fabian / Schmidt, Christina / Kayser, Oliver

    Applied microbiology and biotechnology

    2020  Volume 104, Issue 22, Page(s) 9551–9563

    Abstract: Heterologous biosynthesis of tetrahydrocannabinolic acid (THCA) in yeast is a biotechnological process in Natural Product Biotechnology that was recently introduced. Based on heterologous genes from Cannabis sativa and Streptomyces spp. cloned into ... ...

    Abstract Heterologous biosynthesis of tetrahydrocannabinolic acid (THCA) in yeast is a biotechnological process in Natural Product Biotechnology that was recently introduced. Based on heterologous genes from Cannabis sativa and Streptomyces spp. cloned into Saccharomyces cerevisiae, the heterologous biosynthesis was fully embedded as a proof of concept. Low titer and insufficient biocatalytic rate of most enzymes require systematic optimization of recombinant catalyst by protein engineering and consequent C-flux improvement of the yeast chassis for sufficient precursor (acetyl-CoA), energy (ATP), and NADH delivery. In this review basic principles of in silico analysis of anabolic pathways towards olivetolic acid (OA) and cannabigerolic acid (CBGA) are elucidated and discussed to identify metabolic bottlenecks. Based on own experimental results, yeasts are discussed as potential platform organisms to be introduced as potential cannabinoid biofactories. Especially feeding strategies and limitations in the committed mevalonate and olivetolic acid pathways are in focus of in silico and experimental studies to validate the scientific and commercial potential as a realistic alternative to the plant Cannabis sativa.Key points• First time critical review of the heterologous process for recombinant THCA/CBDA production and critical review of bottlenecks and limitations for a bioengineered technical process• Integrative approach of protein engineering, systems biotechnology, and biochemistry of yeast physiology and biosynthetic cannabinoid enzymes• Comparison of NphB and CsPT aromatic prenyltransferases as rate-limiting catalytic steps towards cannabinoids in yeast as platform organisms Graphical abstract.
    MeSH term(s) Bioengineering ; Cannabinoids ; Cannabis ; Dronabinol ; Saccharomyces cerevisiae/genetics
    Chemical Substances Cannabinoids ; Dronabinol (7J8897W37S)
    Language English
    Publishing date 2020-10-12
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 392453-1
    ISSN 1432-0614 ; 0171-1741 ; 0175-7598
    ISSN (online) 1432-0614
    ISSN 0171-1741 ; 0175-7598
    DOI 10.1007/s00253-020-10798-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Bioengineering studies and pathway modeling of the heterologous biosynthesis of tetrahydrocannabinolic acid in yeast

    Thomas, Fabian / Schmidt, Christina / Kayser, Oliver

    Applied microbiology and biotechnology. 2020 Nov., v. 104, no. 22

    2020  

    Abstract: Heterologous biosynthesis of tetrahydrocannabinolic acid (THCA) in yeast is a biotechnological process in Natural Product Biotechnology that was recently introduced. Based on heterologous genes from Cannabis sativa and Streptomyces spp. cloned into ... ...

    Abstract Heterologous biosynthesis of tetrahydrocannabinolic acid (THCA) in yeast is a biotechnological process in Natural Product Biotechnology that was recently introduced. Based on heterologous genes from Cannabis sativa and Streptomyces spp. cloned into Saccharomyces cerevisiae, the heterologous biosynthesis was fully embedded as a proof of concept. Low titer and insufficient biocatalytic rate of most enzymes require systematic optimization of recombinant catalyst by protein engineering and consequent C-flux improvement of the yeast chassis for sufficient precursor (acetyl-CoA), energy (ATP), and NADH delivery. In this review basic principles of in silico analysis of anabolic pathways towards olivetolic acid (OA) and cannabigerolic acid (CBGA) are elucidated and discussed to identify metabolic bottlenecks. Based on own experimental results, yeasts are discussed as potential platform organisms to be introduced as potential cannabinoid biofactories. Especially feeding strategies and limitations in the committed mevalonate and olivetolic acid pathways are in focus of in silico and experimental studies to validate the scientific and commercial potential as a realistic alternative to the plant Cannabis sativa.Key points• First time critical review of the heterologous process for recombinant THCA/CBDA production and critical review of bottlenecks and limitations for a bioengineered technical process• Integrative approach of protein engineering, systems biotechnology, and biochemistry of yeast physiology and biosynthetic cannabinoid enzymes• Comparison of NphB and CsPT aromatic prenyltransferases as rate-limiting catalytic steps towards cannabinoids in yeast as platform organisms Graphical abstract
    Keywords Cannabis sativa ; Saccharomyces cerevisiae ; Streptomyces ; acetyl coenzyme A ; biosynthesis ; biotechnology ; cannabinoids ; catalysts ; computer simulation ; dimethylallyltranstransferase ; energy ; yeasts
    Language English
    Dates of publication 2020-11
    Size p. 9551-9563.
    Publishing place Springer Berlin Heidelberg
    Document type Article
    Note NAL-AP-2-clean ; Review
    ZDB-ID 392453-1
    ISSN 1432-0614 ; 0171-1741 ; 0175-7598
    ISSN (online) 1432-0614
    ISSN 0171-1741 ; 0175-7598
    DOI 10.1007/s00253-020-10798-3
    Database NAL-Catalogue (AGRICOLA)

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