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ドイツで学んだ研究の方法と働き方
(2018)
Mehr machen, weniger planen!
(2018)
Preleukemic clones carrying BCR-ABLp190 oncogenic lesions are found in neonatal cord blood, where the majority of preleukemic carriers do not convert into precursor B-cell acute lymphoblastic leukemia (pB-ALL). However, the critical question of how these preleukemic cells transform into pB-ALL remains undefined. Here we model a BCR-ABLp190 preleukemic state and show that limiting BCR-ABLp190 expression to hematopoietic stem/progenitor cells (HS/PC) in mice (Sca1-BCR-ABLp190) causes pB-ALL at low penetrance, which resembles the human disease. pB-ALL blast cells were BCR-ABL-negative and transcriptionally similar to pro-B/pre-B cells, suggesting disease onset upon reduced Pax5 functionality. Consistent with this, double Sca1-BCR-ABLp190+Pax5+/- mice developed pB-ALL with shorter latencies, 90% incidence, and accumulation of genomic alterations in the remaining wild-type Pax5 allele. Mechanistically, the Pax5-deficient leukemic pro-B cells exhibited a metabolic switch towards increased glucose utilization and energy metabolism. Transcriptome analysis revealed that metabolic genes (IDH1, G6PC3, GAPDH, PGK1, MYC, ENO1, ACO1) were upregulated in Pax5-deficient leukemic cells, and a similar metabolic signature could be observed in human leukemia. Our studies unveil the first in vivo evidence that the combination between Sca1-BCR-ABLp190 and metabolic reprogramming imposed by reduced Pax5 expression is sufficient for pB-ALL development. These findings might help to prevent conversion of BCR-ABLp190 preleukemic cells.
For the last 20 years, solid-phase microextraction (SPME) in headspace (HS) mode has been used as a valuable sample preparation technique for identifying degradation products in polymers and the determination of residual monomers and other light-boiling substances in polymeric materials. For more than 10 years, our laboratory has been involved in projects focused on the application of HS-SPME-gas chromatography–mass spectrometry (GC–MS) for the characterization of polymeric materials from many branches of manufacturing and building industries. This article describes the application of this technique for identifying volatile organic compounds (VOCs), additives, and degradation products in industrial rubber, car labeling reflection foil, and bone cement materials. The obtained analytical results were then used for troubleshooting and remedial action of the technological processes as well as for the health protection of producers and users.
For many different applications, current information about the bandwidth-related metrics of the utilized connection is very useful as they directly impact the performance of throughput sensitive applications such as streaming servers, IPTV and VoIP applications. In literature, several tools have been proposed to estimate major bandwidth-related metrics such as capacity, available bandwidth and achievable throughput. The vast majority of these tools fall into one of Packet Pair (PP), Variable Packet Size (VPS), Self-Loading of Periodic Streams (SLoPS) or Throughput approaches. In this study, seven popular bandwidth estimation tools including nettimer, pathrate, pathchar, pchar, clink, pathload and iperf belonging to these four well-known estimation techniques are presented and experimentally evaluated in a controlled testbed environment. Differently from the rest of studies in literature, all tools have been uniformly classified and evaluated according to an objective and sophisticated classification and evaluation scheme. The performance comparison of the tools incorporates not only the estimation accuracy but also the probing time and overhead caused.
In Form der Nachhaltigkeitsberichterstattung werden erstmals sämtliche darauf bezogenen Daten im Unternehmen zusammengestellt und zu Indikatoren aggregiert. Im vorliegenden Beitrag wird überprüft, inwieweit dieser Datenpool für die Produktionsplanung und -Steuerung (PPS) genutzt werden kann. Dazu werden die Berichterstattungsstandards GRI und SASB herangezogen. Die Qualität der Nachhaltigkeitsindikatoren wird anhand der Kriterien Fehlerfreiheit, Aktualität, Relevanz und Angemessener Umfang hinterfragt. Der Lösungsansatz besteht zunächst darin, die für die Nachhaltigkeitsindikatoren aggregierten Daten wieder in ihre Komponenten zu separieren. Bei Daten ohne klaren Bezug zum Produktionsprozess (z.B. gemischte Abfallsammelbehälter) liefert das Erfahrungswissen der Mitarbeiter vor Ort die Basis für einen weiteren Regelkreis, der als Kontinuierlicher Verbesserungsprozess (KVP bzw. Kaizen) innerhalb der Produktion und Montage auf gebaut werden kann. Die Langform des Beitrags wurde online auf ERP-Management.de veröffentlicht.
The epithelial sodium channel (ENaC) is a critical regulator of vertebrate electrolyte homeostasis. ENaC is the only constitutively open ion channel in the degenerin/ENaC protein family, and its expression, membrane abundance, and open probability therefore are tightly controlled. The canonical ENaC is composed of three subunits (, , and ), but a fourth -subunit may replace and form atypical -ENaCs. Using Xenopus laevis as a model, here we found that mRNAs of the - and -subunits are differentially expressed in different tissues and that -ENaC predominantly is present in the urogenital tract. Using whole-cell and single-channel electrophysiology of oocytes expressing Xenopus - or -ENaC, we demonstrate that the presence of the -subunit enhances the amount of current generated by ENaC due to an increased open probability, but also changes current into a transient form. Activity of canonical ENaCs is critically dependent on proteolytic processing of the - and -subunits, and immunoblotting with epitope-tagged ENaC subunits indicated that, unlike -ENaC, the -subunit does not undergo proteolytic maturation by the endogenous protease furin. Furthermore, currents generated by -ENaC were insensitive to activation by extracellular chymotrypsin, and presence of the -subunit prevented cleavage of -ENaC at the cell surface. Our findings suggest that subunit composition constitutes an additional level of ENaC regulation, and we propose that the Xenopus -ENaC subunit represents a functional example that demonstrates the importance of proteolytic maturation during ENaC evolution.
Evolutionary conservation of the antimicrobial function of mucus: a first defence against infection
(2018)
Mucus layers often provide a unique and multi-functional hydrogel interface between the epithelial cells of organisms and their external environment. Mucus has exceptional properties including elasticity, changeable rheology and an ability to self-repair by reannealing, and is therefore an ideal medium for trapping and immobilising pathogens and serving as a barrier to microbial infection. The ability to produce a functional surface mucosa was an important evolutionary step, which evolved first in the Cnidaria, which includes corals, and the Ctenophora. This allowed the exclusion of non-commensal microbes and the subsequent development of the mucus-lined digestive cavity seen in higher metazoans. The fundamental architecture of the constituent glycoprotein mucins is also evolutionarily conserved. Although an understanding of the biochemical interactions between bacteria and the mucus layer are important to the goal of developing new antimicrobial strategies, they remain relatively poorly understood. This review summarises the physicochemical properties and evolutionary importance of mucus, which make it so successful in the prevention of bacterial infection. In addition, the strategies developed by bacteria to counteract the mucus layer are also explored.
In recent years, a variety of methods have been introduced to exploit the decrease in visual acuity of peripheral vision, known as foveated rendering. As more and more computationally involved shading is requested and display resolutions increase, maintaining low latencies is challenging when rendering in a virtual reality context. Here, foveated rendering is a promising approach for reducing the number of shaded samples. However, besides the reduction of the visual acuity, the eye is an optical system, filtering radiance through lenses. The lenses create depth-of-field (DoF) effects when accommodated to objects at varying distances. The central idea of this article is to exploit these effects as a filtering method to conceal rendering artifacts. To showcase the potential of such filters, we present a foveated rendering system, tightly integrated with a gaze-contingent DoF filter. Besides presenting benchmarks of the DoF and rendering pipeline, we carried out a perceptual study, showing that rendering quality is rated almost on par with full rendering when using DoF in our foveated mode, while shaded samples are reduced by more than 69%.
Maintaining orientation in an environment with non-Earth gravity (1 g) is critical for an astronaut's operational performance. Such environments present a number of complexities for balance and motion. For example, when an astronaut tilts due to ascending or descending an inclined plane on the moon, the gravity vector will be tilted correctly, but the magnitude will be different from on earth. If this results in a mis-perceived tilt, then that may lead to postural and perceptual errors, such as mis-perceiving the orientation of oneself or the ground plane and corresponding errors in task judgment.
Smallholder farmers as a backbone for the implementation of the Sustainable Development Goals
(2018)
The use of wearable devices or “wearables” in the physical activity domain has been increasing in the last years. These devices are used as training tools providing the user with detailed information about individual physiological responses and feedback to the physical training process. Advantages in sensor technology, miniaturization, energy consumption and processing power increased the usability of these wearables. Furthermore, available sensor technologies must be reliable, valid, and usable. Considering the variety of the existing sensors not all of them are suitable to be integrated in wearables. The application and development of wearables has to consider the characteristics of the physical training process to improve the effectiveness and efficiency as training tools. During physical training, it is essential to elicit individual optimal strain to evoke the desired adjustments to training. One important goal is to neither overstrain nor under challenge the user. Many wearables use heart rate as indicator for this individual strain. However, due to a variety of internal and external influencing factors, heart rate kinetics are highly variable making it difficult to control the stress eliciting individually optimal strain. For optimal training control it is essential to model and predict individual responses and adapt the external stress if necessary. Basis for this modeling is the valid and reliable recording of these individual responses. Depending on the heart rate kinetics and the obtained physiological data, different models and techniques are available that can be used for strain or training control. Aim of this review is to give an overview of measurement, prediction, and control of individual heart rate responses. Therefore, available sensor technologies measuring the individual heart rate responses are analyzed and approaches to model and predict these individual responses discussed. Additionally, the feasibility for wearables is analyzed.
3-Hydroxy-3-methylglutaryl-coenzyme A lyase (HMGCL, HMGCL) deficiency is a rare inborn error of ketogenesis. Even if the ketogenic enzyme is fully disrupted, an elevated signal for the ketone body acetoacetic acid is a frequent observation in the analysis of urinary organic acids, at least if derivatization is performed by methylation. We provide an explanation for this phenomenon and trace it back to degradation of the derivatized 3-hydroxy-3-methylglutaric acid and high temperature of the injector of the gas chromatograph.
Amino acids perform multiple essential physiological roles in humans, and accordingly, their importance to health has been the subject of extensive attention. In this special issue of the Journal of Nutrition and Metabolism, we focus on the various inborn errors of amino acid metabolism, their diagnostic challenges, new treatment approaches, and recent advances in patient monitoring as well as clinical outcomes.
Background: Local injection of autologous conditioned serum (ACS) is a well-known therapy for inflammatory diseases (IDs). While patients’ blood is incubated to generate ACS (with subsequent centrifugation), immune cells produce high amounts of growth factors and cytokines. This include, amongst others, interleukin-1 receptor antagonist (IL-1ra), interleukins 6 and 10, tumour necrosis factor alpha (TNF-α) and transforming growth factor beta 1 (TGF-β1). The aim of this study was to analyse exosomes release into ACS as well as their cytokine cargo.
Major progress occurred in understanding inborn errors of ketone body transport and metabolism between the International Congresses on Inborn Errors of Metabolism in Barcelona (2013) and Rio de Janeiro (2017). These conditions impair either ketogenesis (presenting as episodes of hypoketotic hypoglycemia) or ketolysis (presenting as ketoacidotic episodes); for both groups, immediate intravenous glucose administration is the most critical and (mHGGCS, HMGCS2) effective treatment measure.