Sergey Zhukov  Heinz von Seggern  Xiaoqing Zhang  Yuan Xue  Omar Ben Dali  Perceval Pondrom  Gerhard M. Sessler  Mario Kupnik 《Advanced Engineering Materials》2020,22(5)

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Mohammadhossein Dabaghi  Niels Rochow  Neda Saraei  Rupesh Kumar Mahendran  Gerhard Fusch  Anthony K. C. Chan  John L. Brash  Christoph Fusch  Ponnambalam Ravi Selvaganapathy 《Advanced Materials Technologies》2020,5(7)

Artificial lungs support patients undergoing open‐heart surgery, organ transplantation, and in serious lung injury by providing oxygenation support through an extracorporeal circuit. Some patients require partial support for durations of a few weeks or months even after the surgery. Therefore, a portable or wearable lung assist device which can be operated for several weeks with minimum maintenance would be ideal. Miniaturization of blood oxygenators, using microfluidic technology, is a promising avenue for the realization of such portable artificial lungs. The microfluidic blood oxygenators (MBOs) are also suitable for neonates with respiratory failure due to their low priming volume and pressure drop. Herein, the history of microfluidic oxygenator development and recent progress in miniaturized artificial lungs are discussed. The MBOs have made significant advances in 1) reducing device size, 2) providing biomimetic blood flow paths, 3) enabling operation in room air, and 4) operating without the need of an external pump. Recent work has demonstrated throughput of up to 150 mL min^‐1 of blood and oxygen transfer rate of 60 mL O₂ per L of blood. The challenges faced by this technology in practical applications as well as future improvements to meet the requirements for older neonates and even adults are also presented.  相似文献   

    

Benjamin Seisenbacher  Matthias Hofinger  Gerhard Winter  Florian Grün 《Fatigue & Fracture of Engineering Materials & Structures》2020,43(1):191-200

Dual hardening steels are a group of metals, which reach their material properties through a combination of strengthening via carbides and intermetallic precipitates. Because of their combination of mechanical properties, dual hardening steels are a promising alloying concept for hot‐work applications. The applied materials for hot‐work applications have to meet certain requirements, such as high hardness, high thermal strength, thermal stability, and fracture toughness. In this paper, a dual hardening steel in different heat treatment conditions was tested under out‐of‐phase thermomechanical loading conditions. All tests were done under full reverse strain control and the minimum temperature was kept constant. In the thermomechanical fatigue tests, solution annealed samples reached higher lifetimes compared with aged specimens. The hardness measurements show that the starting procedure of the thermomechanical fatigue leads to an increase of the hardness approximate to the values of the specimens with the ageing heat treatment. Cyclic softening can be observed in the test with the highest maximum temperature of 600°C. An increase of the maximum temperature also causes a decrease of the lifetime.  相似文献   

    

Gerhard Knothe  Kevin R. Steidley 《European Journal of Lipid Science and Technology》2019,121(5)

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Daniel Feder  Prof. Lawrence R. Gahan  Prof. Ross P. McGeary  Prof. Luke W. Guddat  Prof. Gerhard Schenk 《Chembiochem : a European journal of chemical biology》2019,20(12):1536-1540

Purple acid phosphatases (PAPs) are members of the large family of metallohydrolases, a group of enzymes that perform a wide range of biological functions, while employing a highly conserved catalytic mechanism. PAPs are found in plants, animals and fungi; in humans they play an important role in bone turnover and are thus of interest for developing treatments for osteoporosis. The majority of metallohydrolases use a metal-bound hydroxide to initiate catalysis, which leads to the formation of a proposed five-coordinate oxyphosphorane species in the transition state. In this work, we crystallized PAP from red kidney beans (rkbPAP) in the presence of both adenosine and vanadate. The in crystallo-formed vanadate analogue of ADP provides detailed insight into the binding mode of a PAP substrate, captured in a structure that mimics the putative fivecoordinate transition state. Our observations not only provide unprecedented insight into the mechanism of metallohydrolases, but might also guide the structure-based design of inhibitors for application in the treatment of several human illnesses.  相似文献   

    

Giles Grainge  Kazumi Nakabayashi  Felipe Iza  Gerhard Leubner-Metzger  Tina Steinbrecher 《International journal of molecular sciences》2022,23(12)

Seeds sense temperature, nutrient levels and light conditions to inform decision making on the timing of germination. Limited light availability for photoblastic species results in irregular germination timing and losses of population germination percentage. Seed industries are therefore looking for interventions to mitigate this risk. A growing area of research is water treated with gas plasma (GPAW), in which the formed solution is a complex consisting of reactive oxygen and nitrogen species. Gas plasma technology is widely used for sterilisation and is an emerging technology in the food processing industry. The use of the GPAW on seeds has previously led to an increase in germination performance, often attributed to bolstered antioxidant defence mechanisms. However, there is a limited understanding of how the solution may influence the mechanisms that govern seed dormancy and whether photoreceptor-driven germination mechanisms are affected. In our work, we studied how GPAW can influence the mechanisms that govern photo-dependent dormancy, isolating the effects at low fluence response (LFR) and very low fluence response (VLFR). The two defined light intensity thresholds affect germination through different phytochrome photoreceptors, PHYB and PHYA, respectively; we found that GPAW showed a significant increase in population germination percentage under VLFR and further described how each treatment affects key physiological regulators.  相似文献   

    

Fan Yang  Sijie Liu  Gerhard Wolber  Matthias Bureik  Maria Kristina Parr 《International journal of molecular sciences》2022,23(13)

Propranolol is a competitive non-selective beta-receptor antagonist that is available on the market as a racemic mixture. In the present study, glucuronidation of propranolol and its equipotent phase I metabolite 4-hydroxypropranolol by all 19 members of the human UGT1 and UGT2 families was monitored. UGT1A7, UGT1A9, UGT1A10 and UGT2A1 were found to glucuronidate propranolol, with UGT1A7, UGT1A9 and UGT2A1 mainly acting on (S)-propranolol, while UGT1A10 displays the opposite stereoselectivity. UGT1A7, UGT1A9 and UGT2A1 were also found to glucuronidate 4-hydroxypropranolol. In contrast to propranolol, 4-hydroxypropranolol was found to be glucuronidated by UGT1A8 but not by UGT1A10. Additional biotransformations with 4-methoxypropanolol demonstrated different regioselectivities of these UGTs with respect to the aliphatic and aromatic hydroxy groups of the substrate. Modeling and molecular docking studies were performed to explain the stereoselective glucuronidation of the substrates under study.  相似文献   

    

Nicole Hauptmann  Johanna Ludolph  Holger Rothe  Jürgen Rost  Alexander Krupp  Jrg Lechner  Svenja Kohlhaas  Manuela Winkler  Benedikt Stender  Gerhard Hildebrand  Klaus Liefeith 《International journal of molecular sciences》2022,23(6)

An aging population and injury-related damage of the bone substance lead to an increasing need of innovative materials for the regeneration of osteochondral defects. Biodegradable polymers form the basis for suitable artificial implants intended for bone replacement or bone augmentation. The great advantage of these structures is the site-specific implant design, which leads to a considerable improvement in patient outcomes and significantly reduced post-operative regeneration times. Thus, biomechanical and biochemical parameters as well as the rate of degradation can be set by the selection of the polymer system and the processing technology. Within this study, we developed a polymer platform based on the amino acid Alanine and ε-Caprolacton for use as raw material for osteochondral implants. The biomechanical and degradation properties of these Poly-(Alanine-co-ε-Caprolacton)-Methacrylate (ACM) copolymers can be adjusted by changing the ratio of the monomers. Fabrication of artificial structures for musculo-skeletal tissue engineering was done by Two-Photon-Polymerization (2PP), which represents an innovative technique for generating defined scaffolds with tailor-made mechanical and structural properties. Here we show the synthesis, physicochemical characterization, as well as first results for structuring ACM using 2PP technology. The data demonstrate the high potential of ACM copolymers as precursors for the fabrication of biomimetic implants for bone-cartilage reconstruction.  相似文献   

    

Katharina Stadlbauer  Peter Andorfer  Gerhard Stadlmayr  Florian Rüker  Gordana Wozniak-Knopp 《International journal of molecular sciences》2022,23(9)

Inhibition of complement activation via the overexpression of complement-regulatory proteins (CRPs), most notably CD46, CD55 and CD59, is an efficient mechanism of disguise of cancer cells from a host immune system. This phenomenon extends to counteract the potency of therapeutic antibodies that could lyse target cells by eliciting complement cascade. The manifold functions and ubiquitous expression of CRPs preclude their systemic specific inhibition. We selected CD59-specific Fc fragments with a novel antigen binding site (Fcabs) from yeast display libraries using recombinant antigens expressed in bacterial or mammalian cells. To produce a bispecific antibody, we endowed rituximab, a clinically applied anti-CD20 antibody, used for therapy of various lymphoid malignancies, with an anti-CD59 Fcab. This bispecific antibody was able to induce more potent complement-dependent cytotoxicity for CD20 and CD59 expressing Raji cell line measured with lactate dehydrogenase-release assay, but had no effect on the cells with lower levels of the primary CD20 antigen or CD20-negative cells. Such molecules are promising candidates for future therapeutic development as they elicit a higher specific cytotoxicity at a lower concentration and hence cause a lower exhaustion of complement components.  相似文献   

    

Laura Marinela Ailioaie  Constantin Ailioaie  Gerhard Litscher 《International journal of molecular sciences》2022,23(21)

Systemic juvenile idiopathic arthritis (sJIA) and its complication, macrophage activation syndrome (sJIA-MAS), are rare but sometimes very serious or even critical diseases of childhood that can occasionally be characterized by nonspecific clinical signs and symptoms at onset—such as non-remitting high fever, headache, rash, or arthralgia—and are biologically accompanied by an increase in acute-phase reactants. For a correct positive diagnosis, it is necessary to rule out bacterial or viral infections, neoplasia, and other immune-mediated inflammatory diseases. Delays in diagnosis will result in late initiation of targeted therapy. A set of biomarkers is useful to distinguish sJIA or sJIA-MAS from similar clinical entities, especially when arthritis is absent. Biomarkers should be accessible to many patients, with convenient production and acquisition prices for pediatric medical laboratories, as well as being easy to determine, having high sensitivity and specificity, and correlating with pathophysiological disease pathways. The aim of this review was to identify the newest and most powerful biomarkers and their synergistic interaction for easy and accurate recognition of sJIA and sJIA-MAS, so as to immediately guide clinicians in correct diagnosis and in predicting disease outcomes, the response to treatment, and the risk of relapses. Biomarkers constitute an exciting field of research, especially due to the heterogeneous nature of cytokine storm syndromes (CSSs) in the COVID era. They must be selected with utmost care—a fact supported by the increasingly improved genetic and pathophysiological comprehension of sJIA, but also of CSS—so that new classification systems may soon be developed to define homogeneous groups of patients, although each with a distinct disease.  相似文献