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排序方式: 共有1322条查询结果,搜索用时 15 毫秒
51.
Sebastian Kummer Susanne Rinn Gunnar Seemann Nadine Bachmann Katherine Timothy Paul S. Thornton Frank Pillekamp Ertan Mayatepek Carsten Bergmann Thomas Meissner Niels Decher 《International journal of molecular sciences》2022,23(15)
The voltage-dependent L-type calcium channel isoform CaV1.2 is critically involved in many physiological processes, e.g., in cardiac action potential formation, electromechanical coupling and regulation of insulin secretion by beta cells. Gain-of-function mutations in the calcium voltage-gated channel subunit alpha 1 C (CACNA1C) gene, encoding the CaV1.2 α1-subunit, cause Timothy syndrome (TS), a multisystemic disorder that includes autism spectrum disorders and long QT (LQT) syndrome. Strikingly, TS patients frequently suffer from hypoglycemia of yet unproven origin. Using next-generation sequencing, we identified a novel heterozygous CACNA1C mutation in a patient with congenital hyperinsulinism (CHI) and associated hypoglycemic episodes. We characterized the electrophysiological phenotype of the mutated channel using voltage-clamp recordings and in silico action potential modeling experiments. The identified CaV1.2L566P mutation causes a mixed electrophysiological phenotype of gain- and loss-of-function effects. In silico action potential modeling supports that this mixed electrophysiological phenotype leads to a tissue-specific impact on beta cells compared to cardiomyocytes. Thus, CACNA1C variants may be associated with non-syndromic hyperinsulinemic hypoglycemia without long-QT syndrome, explained by very specific electrophysiological properties of the mutated channel. We discuss different biochemical characteristics and clinical impacts of hypoglycemia in the context of CACNA1C variants and show that these may be associated with significant morbidity for Timothy Syndrome patients. Our findings underline that the potential of hypoglycemia warrants careful attention in patients with CACNA1C variants, and such variants should be included in the differential diagnosis of non-syndromic congenital hyperinsulinism. 相似文献
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The scarcity of bandwidth in the radio spectrum has become more vital since the demand for more and more wireless applications has increased. Most of the spectrum bands have been allocated although many studies have shown that these bands are significantly underutilized most of the time. The problem of unavailability of spectrum and inefficiency in its utilization has been smartly addressed by the cognitive radio (CR) technology which is an opportunistic network that senses the environment, observes the network changes, and then uses knowledge gained from the prior interaction with the network to make intelligent decisions by dynamically adapting their transmission characteristics. In this paper, some of the decentralized adaptive medium access control (MAC) protocols for CR networks have been critically analyzed, and a novel adaptive MAC protocol for CR networks, decentralized non-global MAC (DNG-MAC), has been proposed. The results show the DNG-MAC outperforms other CR-MAC protocols in terms of time and energy efficiency. 相似文献
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对高铝无磁钢20Mn23AIV(/%:0.14~0.20C、21.50~25.00Mn、1.50~2.50Al、0.04~0.10V)200 mm板坯连铸过程结晶器保护渣液渣和渣圈的化学组成、理化性能和结晶矿相进行了对比分析。保护渣原渣组成为(/%):31.91CaO、30.30SiO2、6.58Al2O3、1.12MgO、3.02MnO、7.73Na20、7.10F。结果表明,连铸开浇后15 min,液渣和渣圈中的SiO2含量分别降低至22%和18%, Al2O3含量分别提高至20.5%和25.5%,其碱度由原渣的1.05分别提高至1.7和2.0。此时液渣及渣圈的熔化温度和粘度大幅度增加,转折温度大幅度降低;渣圈的化学成分及理化性能的变化幅度均大于液渣。连铸开浇15 min后液渣及渣圈的成分与性能均趋于稳定。高熔点相钙铝黄长石的析出是促使渣圈形成的重要原因。 相似文献
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A Systematic Structure–Activity Study of a New Type of Small Peptidic Transfection Vector Reveals the Importance of a Special Oxo-Anion-Binding Motif for Gene Delivery
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Dr. Sandra Junghänel Sarah Karczewski Sandra Bäcker Prof. Dr. Shirley K. Knauer Prof. Dr. Carsten Schmuck 《Chembiochem : a European journal of chemical biology》2017,18(22):2268-2279
We discovered a new class of artificial peptidic transfection vectors based on an artificial anion-binding motif, the guanidiniocarbonylpyrrole (GCP) cation. This new type of vector is surprisingly smaller than traditional systems, and our previous work suggested that the GCP group was important for promoting critical endosomal escape. We now present here a systematic comparison of similar DNA ligands featuring our GCP oxo-anion-binding motif with DNA ligands only consisting of naturally occurring amino acids. Structure–activity studies showed that the artificial binding motif clearly outperformed natural amino acids such as histidine, lysine, and arginine. It improved the ability to shuttle foreign genetic material into cells, yet successfully mediated endosomal escape. Also, plasmids that were complexed by our artificial ligands were stabilized against cytosolic degradation to some extent. This resulted in the successful expression of plasmid information (comparable to gold standards such as polyethyleneimine). Hence, our study clearly demonstrates the importance of the tailor-made GCP anion-binding site for efficient gene transfection. 相似文献
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Carsten Svaneborg 《Computer Physics Communications》2012,183(8):1793-1802
We have extended the Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) to support directional bonds and dynamic bonding. The framework supports stochastic formation of new bonds, breakage of existing bonds, and conversion between bond types. Bond formation can be controlled to limit the maximal functionality of a bead with respect to various bond types. Concomitant with the bond dynamics, angular and dihedral interactions are dynamically introduced between newly connected triplets and quartets of beads, where the interaction type is determined from the local pattern of bead and bond types. When breaking bonds, all angular and dihedral interactions involving broken bonds are removed. The framework allows chemical reactions to be modeled, and use it to simulate a simplistic, coarse-grained DNA model. The resulting DNA dynamics illustrates the power of the present framework.Program summaryProgram title: LAMMPS Framework for Directional Dynamic BondingCatalogue identifier: AEME_v1_0Program summary URL: http://cpc.cs.qub.ac.uk/summaries/AEME_v1_0.htmlProgram obtainable from: CPC Program Library, Queen?s University, Belfast, N. IrelandLicensing provisions: GNU General Public LicenceNo. of lines in distributed program, including test data, etc.: 2 243 491No. of bytes in distributed program, including test data, etc.: 771Distribution format: tar.gzProgramming language: C++Computer: Single and multiple core serversOperating system: Linux/Unix/WindowsHas the code been vectorized or parallelized?: Yes. The code has been parallelized by the use of MPI directives.RAM: 1 GbClassification: 16.11, 16.12Nature of problem: Simulating coarse-grain models capable of chemistry e.g. DNA hybridization dynamics.Solution method: Extending LAMMPS to handle dynamic bonding and directional bonds.Unusual features: Allows bonds to be created and broken while angular and dihedral interactions are kept consistent.Additional comments: The distribution file for this program is approximately 36 Mbytes and therefore is not delivered directly when download or E-mail is requested. Instead an html file giving details of how the program can be obtained is sent.Running time: Hours to days. The examples provided in the distribution take just seconds to run. 相似文献
59.
It is of high technical importance to consider the loading and unloading dynamics of hydride-based hydrogen storage tanks, which are mainly influenced by the heat and gas transfer properties inside the reaction bed. In this regard, hydride-graphite composites offer improved heat transfer properties and higher volumetric storage capacities compared to commonly used powder beds. 相似文献
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Dual phosphorylation of proteins is a principal component of intracellular signalling. Bistability is considered an important property of such systems and its origin is not yet completely understood. Theoretical studies have established parameter values for multistationarity and bistability for many types of proteins. However, up to now no formal criterion linking multistationarity and bistability to the parameter values characterizing dual phosphorylation has been established. Deciding whether an unclassified protein has the capacity for bistability, therefore requires careful numerical studies. Here, we present two general algebraic conditions in the form of inequalities. The first employs the catalytic constants, and if satisfied guarantees multistationarity (and hence the potential for bistability). The second involves the catalytic and Michaelis constants, and if satisfied guarantees uniqueness of steady states (and hence absence of bistability). Our method also allows for the direct computation of the total concentration values such that multistationarity occurs. Applying our results yields insights into the emergence of bistability in the ERK–MEK–MKP system that previously required a delicate numerical effort. Our algebraic conditions present a practical way to determine the capacity for bistability and hence will be a useful tool for examining the origin of bistability in many models containing dual phosphorylation. 相似文献