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2-methylacetoacetyl-coenzyme A thiolase (beta-ketothiolase) deficiency: one disease - two pathways
(2020)
Background: 2-methylacetoacetyl-coenzyme A thiolase deficiency (MATD; deficiency of mitochondrial acetoacetyl-coenzyme A thiolase T2/ “beta-ketothiolase”) is an autosomal recessive disorder of ketone body utilization and isoleucine degradation due to mutations in ACAT1.
Methods: We performed a systematic literature search for all available clinical descriptions of patients with MATD. Two hundred forty-four patients were identified and included in this analysis. Clinical course and biochemical data are presented and discussed.
Results: For 89.6% of patients at least one acute metabolic decompensation was reported. Age at first symptoms ranged from 2 days to 8 years (median 12 months). More than 82% of patients presented in the first 2 years of life, while manifestation in the neonatal period was the exception (3.4%). 77.0% (157 of 204 patients) of patients showed normal psychomotor development without neurologic abnormalities. Conclusion: This comprehensive data analysis provides a systematic overview on all cases with MATD identified in the literature. It demonstrates that MATD is a rather benign disorder with often favourable outcome, when compared with many other organic acidurias.
Background: 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMGCLD) is an autosomal recessive disorder of ketogenesis and leucine degradation due to mutations in HMGCL.
Method: We performed a systematic literature search to identify all published cases. Two hundred eleven patients of whom relevant clinical data were available were included in this analysis. Clinical course, biochemical findings and mutation data are highlighted and discussed. An overview on all published HMGCL variants is provided.
Results: More than 95% of patients presented with acute metabolic decompensation. Most patients manifested within the first year of life, 42.4% already neonatally. Very few individuals remained asymptomatic. The neurologic long-term outcome was favorable with 62.6% of patients showing normal development.
Conclusion: This comprehensive data analysis provides a systematic overview on all published cases with HMGCLD including a list of all known HMGCL mutations.
The simultaneous operation of multiple different semiconducting metal oxide (MOX) gas sensors is demanding for the readout circuitry. The challenge results from the strongly varying signal intensities of the various sensor types to the target gas. While some sensors change their resistance only slightly, other types can react with a resistive change over a range of several decades. Therefore, a suitable readout circuit has to be able to capture all these resistive variations, requiring it to have a very large dynamic range. This work presents a compact embedded system that provides a full, high range input interface (readout and heater management) for MOX sensor operation. The system is modular and consists of a central mainboard that holds up to eight sensor-modules, each capable of supporting up to two MOX sensors, therefore supporting a total maximum of 16 different sensors. Its wide input range is archived using the resistance-to-time measurement method. The system is solely built with commercial off-the-shelf components and tested over a range spanning from 100Ω to 5 GΩ (9.7 decades) with an average measurement error of 0.27% and a maximum error of 2.11%. The heater management uses a well-tested power-circuit and supports multiple modes of operation, hence enabling the system to be used in highly automated measurement applications. The experimental part of this work presents the results of an exemplary screening of 16 sensors, which was performed to evaluate the system’s performance.
Failure prognostic builds up on constant data acquisition and processing and fault diagnosis and is an essential part of predictive maintenance of smart manufacturing systems enabling condition based maintenance, optimised use of plant equipment, improved uptime and yield and to prevent safety problems. Given known control inputs into a plant and real sensor outputs or simulated measurements, the model-based part of the proposed hybrid method provides numerical values of unknown parameter degradation functions at sampling time points by the evaluation of equations that have been derived offline from a bicausal diagnostic bond graph. These numerical values are computed concurrently to the constant monitoring of a system and are stored in a buffer of fixed length. The data-driven part of the method provides a sequence of remaining useful life estimates by repeated projection of the parameter degradation into the future based on the use of values in a sliding time window. Existing software can be used to determine the best fitting function and can account for its random parameters. The continuous parameter estimation and their projection into the future can be performed in parallel for multiple isolated simultaneous parametric faults on a multicore, multiprocessor computer.
The proposed hybrid bond graph model-based, data-driven method is verified by an offline simulation case study of a typical power electronic circuit. It can be used to implement embedded systems that enable cooperating machines in smart manufacturing to perform prognostic themselves.
Striated muscle contraction is regulated by the translocation of troponin-tropomyosin strands over the thin filament surface. Relaxation relies partly on highly-favorable, conformation-dependent electrostatic contacts between actin and tropomyosin, which position tropomyosin such that it impedes actomyosin associations. Impaired relaxation and hypercontractile properties are hallmarks of various muscle disorders. The α-cardiac actin M305L hypertrophic cardiomyopathy-causing mutation lies near residues that help confine tropomyosin to an inhibitory position along thin filaments. Here, we investigate M305L actin in vivo, in vitro, and in silico to resolve emergent pathological properties and disease mechanisms. Our data suggest the mutation reduces actin flexibility and distorts the actin-tropomyosin electrostatic energy landscape that, in muscle, result in aberrant contractile inhibition and excessive force. Thus, actin flexibility may be required to establish and maintain interfacial contacts with tropomyosin as well as facilitate its movement over distinct actin surface features and is, therefore, likely necessary for proper regulation of contraction.
Are There Extended Cognitive Improvements from Different Kinds of Acute Bouts of Physical Activity?
(2020)
Acute bouts of physical activity of at least moderate intensity have shown to enhance cognition in young as well as older adults. This effect has been observed for different kinds of activities such as aerobic or strength and coordination training. However, only few studies have directly compared these activities regarding their effectiveness. Further, most previous studies have mainly focused on inhibition and have not examined other important core executive functions (i.e., updating, switching) which are essential for our behavior in daily life (e.g., staying focused, resisting temptations, thinking before acting), as well. Therefore, this study aimed to directly compare two kinds of activities, aerobic and coordinative, and examine how they might affect executive functions (i.e., inhibition, updating, and switching) in a test-retest protocol. It is interesting for practical implications, as coordinative exercises, for example, require little space and would be preferable in settings such as an office or a classroom. Furthermore, we designed our experiment in such a way that learning effects were controlled. Then, we tested the influence of acute bouts of physical activity on the executive functioning in both young and older adults (young 16–22 years, old 65–80 years). Overall, we found no differences between aerobic and coordinative activities and, in fact, benefits from physical activities occurred only in the updating tasks in young adults. Additionally, we also showed some learning effects that might influence the results. Thus, it is important to control cognitive tests for learning effects in test-retest studies as well as to analyze effects from physical activity on a construct level of executive functions.
In der heutigen Zeit nimmt die Bedeutung schlanker und effektiver Prozesse in Unternehmen vor dem Hintergrund des Wettbewerbs sowie Kostendrucks stetig zu. Um dieser Herausforderung entgegenzuwirken, fokussieren sich Unternehmen auf die Identifikation neuer innovativer Potenziale. Aufgrund der Tatsache, dass monotone und regelbasierte Prozesse durch Softwareroboter automatisiert werden können, ist das Interesse an Robotic Process Automation (RPA) in den letzten Jahren stetig gestiegen. Bevor sich Unternehmen allerdings für oder gegen den Einsatz von RPA entscheiden, ist es zunächst notwendig, dass die Entscheidungsträger ein Verständnis von RPA erlangen sowie die entsprechenden Einsatzpotenziale und Risiken einschätzen können. Dieser Artikel trägt diesem Bedürfnis Rechnung, indem es diese auf Basis einer Literaturrecherche ermittelt und bewertet. Im Ausblick wird das zukünftige Potenzial von RPA eingeschätzt.
Carbachol dimers with primary carbamate groups as homobivalent modulators of muscarinic receptors
(2020)
Background: Coniferous woods (Abies nordmanniana (Stev.) Spach, Abies procera Rehd, Picea abies (L.) H.Karst, and Picea pungens Engelm.) could contain useful secondary metabolites to produce sustainable packaging materials, e.g., by substitution of harmful petrol-based additives in plastic packaging. This study aims to characterise the antioxidant and light-absorbing properties and ingredients of different coniferous wood extracts with regard to different plant fragments and drying conditions. Furthermore, the valorisation of used Christmas trees is evaluated. Methods: Different drying and extraction techniques were applied with the extracts being characterised by determining the total phenolic content (TPC), total antioxidant capacity (TAC), and absorbance in the ultraviolet range (UV). Gas chromatography coupled with mass spectrometry (GC-MS) and an acid–butanol assay (ABA) were used to characterise the extract constituents. Results: All the extracts show a considerably high UV absorbance while interspecies differences did occur. All the fresh and some of the dried biomass extracts reached utilisable TAC and TPC values. A simplified extraction setup for industrial application is evaluated; comparable TAC results could be reached with modifications. Conclusion: Coniferous woods are a promising renewable resource for preparation of sustainable antioxidants and photostabilisers. This particularly applies to Christmas trees used for up to 12 days. After extraction, the biomass can be fully valorised by incorporation in paper packaging.
Miscanthus crops possess very attractive properties such as high photosynthesis yield and carbon fixation rate. Because of these properties, it is currently considered for use in second-generation biorefineries. Here we analyze the differences in chemical composition between M. x giganteus, a commonly studied Miscanthus genotype, and M. nagara, which is relatively understudied but has useful properties such as increased frost resistance and higher stem stability. Samples of M. x giganteus (Gig35) and M. nagara (NagG10) have been separated by plant portion (leaves and stems) in order to isolate the corresponding lignins. The organosolv process was used for biomass pulping (80% ethanol solution, 170 °C, 15 bar). Biomass composition and lignin structure analysis were performed using composition analysis, Fourier-transform infrared (FTIR), ultraviolet-visible (UV-Vis) and nuclear magnetic resonance (NMR) spectroscopy, thermogravimetric analysis (TGA), size exclusion chromatography (SEC) and pyrolysis gas-chromatography/mass spectrometry (Py-GC/MS) to determine the 3D structure of the isolated lignins, monolignol ratio and most abundant linkages depending on genotype and harvesting season. SEC data showed significant differences in the molecular weight and polydispersity indices for stem versus leaf-derived lignins. Py-GC/MS and hetero-nuclear single quantum correlation (HSQC) NMR revealed different monolignol compositions for the two genotypes (Gig35, NagG10). The monolignol ratio is slightly influenced by the time of harvest: stem-derived lignins of M. nagara showed increasing H and decreasing G unit content over the studied harvesting period (December–April).
Comparing Non-Visual and Visual Guidance Methods for Narrow Field of View Augmented Reality Displays
(2020)
Coumarin as a structural component of substrates and probes for serine and cysteine proteases
(2020)
This article explores the opportunities, challenges, as well as the activities of the Chinese governmental and commercial stakeholders to promote cross-border e-commerce trade between China and Africa, based on the classification and correlation analysis of the literature from 2011 to 2019. The results show that the biggest driver for the development of China-Africa cross-border e-commerce trade is the gap between the rapid growth of the African population, especially the middle class, and the limited local capability to satisfy their demand. The rapid development of the internet and mobile internet is another driving factor. The biggest challenge is the last mile delivery of logistics, and online payment issues in Africa. At the macro-level the Chinese government has promoted measures such as infrastructure investment, e-commerce test zones and the establishment of pilot projects. At the firm level, Chinese companies have focused on solving practical micro-level local operational problems such as logistics, online payment, and talent training. The results also show that the referred literature is still in its infancy, mostly theoretical and less practical, and requires more in-depth domain specific analysis in the future.