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排序方式: 共有641条查询结果,搜索用时 500 毫秒
11.
Jan H. Dring Julian Schrter Jerome Jüngling Saskia Biskup Kerstin A. Klotz Thomas Bast Tobias Dietel G. Christoph Korenke Sophie Christoph Heiko Brennenstuhl Guido Rubboli Rikke S. Mller Gaetan Lesca Yves Chaix Stefan Klker Georg F. Hoffmann Johannes R. Lemke Steffen Syrbe 《International journal of molecular sciences》2021,22(6)
Pathogenic variants in KCNA2, encoding for the voltage-gated potassium channel Kv1.2, have been identified as the cause for an evolving spectrum of neurological disorders. Affected individuals show early-onset developmental and epileptic encephalopathy, intellectual disability, and movement disorders resulting from cerebellar dysfunction. In addition, individuals with a milder course of epilepsy, complicated hereditary spastic paraplegia, and episodic ataxia have been reported. By analyzing phenotypic, functional, and genetic data from published reports and novel cases, we refine and further delineate phenotypic as well as functional subgroups of KCNA2-associated disorders. Carriers of variants, leading to complex and mixed channel dysfunction that are associated with a gain- and loss-of-potassium conductance, more often show early developmental abnormalities and an earlier onset of epilepsy compared to individuals with variants resulting in loss- or gain-of-function. We describe seven additional individuals harboring three known and the novel KCNA2 variants p.(Pro407Ala) and p.(Tyr417Cys). The location of variants reported here highlights the importance of the proline(405)–valine(406)–proline(407) (PVP) motif in transmembrane domain S6 as a mutational hotspot. A novel case of self-limited infantile seizures suggests a continuous clinical spectrum of KCNA2-related disorders. Our study provides further insights into the clinical spectrum, genotype–phenotype correlation, variability, and predicted functional impact of KCNA2 variants. 相似文献
12.
Sulfuric acid-catalyzed hydrolysis of cellulose commonly isolates cellulose nanocrystals (CNCs). Neutralizing the reactant solution with sodium hydroxide facilitates efficient downstream processing, but residual salt remains in the product. This study examines the reinforcing effects of CNCs from suspensions that contain residual salt on the mechanical properties of thermoplastic starch nanocomposites. By reinforcing starch films with up to 5 wt% CNCs, stiffness and strength are improved by 118% and 79%, respectively, indicating a good dispersion of CNCs in the starch matrix. Compared to nanocomposites incorporating salt-free CNCs, the remaining salt has no significant impact on the material's mechanical performance. The results indicate great potential of CNCs containing residual salt as biobased, low-cost nanofiller in hydrophilic polymer matrices. 相似文献
13.
W. R. Vogler A. C. Olson S. Okamoto M. Shoji R. L. Raynor J. F. Kuo W. E. Berdel H. Eibl J. Hajdu H. Nomura 《Lipids》1991,26(12):1418-1423
Alkyl lysophospholipids have been shown to be cytooxic to a number of neoplastic tissues. One, ET-18-OCH3, has been used to selectively purge leukemic cells from mixtures with normal marrow progenitor cells,in vitro andin vivo. We have measured the 50% inhibitory (IC50) effect of a series of ether, lipids (EL) on leukemic cells (HL60, K562, Daudi, KG-1, KG-1a) and normal marrow progenitor
cells. Cells were incubated with varying concentrations of EL for 4 hr and assayed for viability, [3H]thymidine incorporation and clonogenicity in semi-solid media. The effect on protein kinase C (PKC) activity was assayed
for each compound. Compounds tested included three glycerophosphocholine analogs-ET-18-OCH3, ET-16-NHCOCH3, and BM 41.440. In addition, a lipoidal amine, CP 46665, an ethyleneglycolphospholipid, AEPL, and four single chain alkylphosphocholine
analogs, HePC2, HePC3, HePC4 and HePC6 were also tested. During the period of incubation, the cells remained viable (>70%) as judged by trypan blue dye exclusion.
The glycerophosphocholines were the most active and showed the highest therapeutic index. The lipoidal amine was active, but
toxic to normal marrow progenitor cells. The ethyleneglycolphospholipid was active against HL60, but not against the other
cell lines. The single chain alkylphosphocholine analogs were less active. All of the compounds inhibited PKC activity; however,
the glycerophosphocholines were the most inhibitory.
Based on a paper presented at the Third International Conference on Platelet-Activating Factor and Structurally Related Alkyl
Ether Lipids, Tokyo, Japan, May 1989. 相似文献
14.
We study asynchronously communicating open systems modeled as Petri nets with an interface. An accordance preorder describes when one open system can be safely replaced by another open system without affecting some behavioral property of the overall system. Although accordance is decidable for several behavioral properties if we assume a previously known bound on the maximal number of pending messages, we show that it is not decidable without this assumption. 相似文献
15.
Andrea Ciancone Mauro Luigi Drago Antonio Filieri Vincenzo Grassi Heiko Koziolek Raffaela Mirandola 《Software and Systems Modeling》2014,13(4):1269-1290
Automatic prediction tools play a key role in enabling the application of non-functional requirements analysis, to simplify the selection and the assembly of components for component-based software systems, and in reducing the need for strong mathematical skills for software designers. By exploiting the paradigm of Model-Driven Engineering (MDE), it is possible to automatically transform design models into analytical models, thus enabling formal property verification. MDE is the core paradigm of the KlaperSuite framework presented in this paper, which exploits the KLAPER pivot language to fill the gap between design and analysis of component-based systems for reliability properties. KlaperSuite is a family of tools empowering designers with the ability to capture and analyze quality of service views of their systems, by building a one-click bridge towards a number of established verification instruments. In this article, we concentrate on the reliability-prediction capabilities of KlaperSuite and we evaluate them with respect to several case studies from literature and industry. 相似文献
16.
Heiko Koziolek Bastian Schlich Steffen Becker Michael Hauck 《Empirical Software Engineering》2013,18(4):746-790
During software system evolution, software architects intuitively trade off the different architecture alternatives for their extra-functional properties, such as performance, maintainability, reliability, security, and usability. Researchers have proposed numerous model-driven prediction methods based on queuing networks or Petri nets, which claim to be more cost-effective and less error-prone than current practice. Practitioners are reluctant to apply these methods because of the unknown prediction accuracy and work effort. We have applied a novel model-driven prediction method called Q-ImPrESS on a large-scale process control system from ABB consisting of several million lines of code. This paper reports on the achieved performance prediction accuracy and reliability prediction sensitivity analyses as well as the effort in person hours for achieving these results. 相似文献
17.
The current Web Services Agreement specification draft proposes a simple request-response protocol for agreement creation
only addressing bilateral offer exchanges. This paper proposes a framework augmenting this WS-Agreement to enable negotiations
according to a variety of bilateral and multilateral negotiation protocols. The framework design is based on a thorough analysis
of taxonomies for negotiations from the literature in order to allow for capturing a variety of different negotiation models
within a single, WS-Agreement compatible, framework. In order to provide for the intended flexibility, the proposed protocol
takes a two-stage approach: a meta-protocol is conducted among interested parties to agree on a common negotiation protocol
first before the real negotiation is carried out in the second step due to the protocol established in the first step. 相似文献
18.
Anne Martens Heiko Koziolek Lutz Prechelt Ralf Reussner 《Empirical Software Engineering》2011,16(5):587-622
Model-based performance evaluation methods for software architectures can help architects to assess design alternatives and save costs for late life-cycle performance fixes. A recent trend is component-based performance modelling, which aims at creating reusable performance models; a number of such methods have been proposed during the last decade. Their accuracy and the needed effort for modelling are heavily influenced by human factors, which are so far hardly understood empirically. Do component-based methods allow to make performance predictions with a comparable accuracy while saving effort in a reuse scenario? We examined three monolithic methods (SPE, umlPSI, Capacity Planning (CP)) and one component-based performance evaluation method (PCM) with regard to their accuracy and effort from the viewpoint of method users. We conducted a series of three experiments (with different levels of control) involving 47 computer science students. In the first experiment, we compared the applicability of the monolithic methods in order to choose one of them for comparison. In the second experiment, we compared the accuracy and effort of this monolithic and the component-based method for the model creation case. In the third, we studied the effort reduction from reusing component-based models. Data were collected based on the resulting artefacts, questionnaires and screen recording. They were analysed using hypothesis testing, linear models, and analysis of variance. For the monolithic methods, we found that using SPE and CP resulted in accurate predictions, while umlPSI produced over-estimates. Comparing the component-based method PCM with SPE, we found that creating reusable models using PCM takes more (but not drastically more) time than using SPE and that participants can create accurate models with both techniques. Finally, we found that reusing PCM models can save time, because effort to reuse can be explained by a model that is independent of the inner complexity of a component. The tasks performed in our experiments reflect only a subset of the actual activities when applying model-based performance evaluation methods in a software development process. Our results indicate that sufficient prediction accuracy can be achieved with both monolithic and component-based methods, and that the higher effort for component-based performance modelling will indeed pay off when the component models incorporate and hide a sufficient amount of complexity. 相似文献
19.
Andreas Birk Burkhard Wiggerich Heiko Bülow Max Pfingsthorn Sören Schwertfeger 《Journal of Intelligent and Robotic Systems》2011,64(1):57-76
Several missions with an Unmanned Aerial Vehicle (UAV) in different realistic safety, security, and rescue field tests are
presented. First, results from two safety and security missions at the 2009 European Land Robot Trials (ELROB) are presented.
A UAV in form of an Airrobot AR100-B is used in a reconnaissance and in a camp security scenario. The UAV is capable of autonomous
waypoint navigation using onboard GPS processing. A digital video stream from the vehicle is used to create photo maps—also
known as mosaicking—in real time at the operator station. This mapping is done using an enhanced version of Fourier Mellin
based registration, which turns out to be very fast and robust. Furthermore, results from a rescue oriented scenario at the
2010 Response Robot Evaluation Exercises (RREE) at Disaster City, Texas are presented. The registration for the aerial mosaicking
is supplemented by an uncertainty metric and embedded into Simultaneous Localization and Mapping (SLAM), which further enhances
the photo maps as main mission deliveries. 相似文献
20.
3D mapping is very challenging in the underwater domain, especially due to the lack of high resolution, low noise sensors.
A new spectral registration method is presented that can determine the spatial 6 DOF transformation between pairs of very
noisy 3D scans with only partial overlap. The approach is hence suited to cope with sonar as the predominant underwater sensor.
The spectral registration method is based on Phase Only Matched Filtering (POMF) on non-trivially resampled spectra of the
3D data. 相似文献