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排序方式: 共有437条查询结果,搜索用时 15 毫秒
51.
O. A. Val'dner A. K. Gus'kova P. A. Yakovleva U. L. Lawrence C. Lancros R. W. Christy A. Pytte I. Ebert G. Seifert J. W. Emsley J. Feeney L. H. Suttcliffe Eckart vom Braum Yu. V. Sivintsev E. Bagge J. Meissner A. S. Zaimovskii V. V. Kalashnikov I. S. Tolovnii L. P. Kimel' V. P. Mashkovich 《Atomic Energy》1967,22(1):78-83
52.
Probenahme und kontinuierliche Temperaturmessung. Temperaturverlauf während des Blasens. Verhalten der Roheisenbegleitelemente im Zusammenhang mit der Veränderung der Schlackenzusammensetzung. Kalkauflösung. Einfluß der Kalkbeschaffenheit auf die Entschwefelung. 相似文献
53.
Douglas Weber David Patsch Annika Neumann Dr. Margit Winkler Prof. Dr. Dörte Rother 《Chembiochem : a European journal of chemical biology》2021,22(10):1823-1832
Accessing aldehydes from carboxylate moieties is often a challenging task. In this regard, carboxylate reductases (CARs) are promising catalysts provided by nature that are able to accomplish this task in just one step, avoiding over-reduction to the alcohol product. However, the heterologous expression of CARs can be quite difficult due to the excessive formation of insoluble protein, thus hindering further characterization and application of the enzyme. Here, the heterologous production of the carboxylate reductase from Nocardia otitidiscaviarum (NoCAR) was optimized by a combination of i) optimized cultivation conditions, ii) post-translational modification with a phosphopantetheinyl transferase and iii) selection of an appropriate expression strain. Especially, the selection of Escherichia coli tuner cells as host had a strong effect on the final 110-fold increase in the specific activity of NoCAR. This highly active NoCAR was used to reduce sodium benzoate to benzaldehyde, and it was successfully assembled with an in vitro regeneration of ATP and NADPH, being capable of reducing about 30 mM sodium benzoate with high selectivity in only 2 h of reaction. 相似文献
54.
Ruirui Lu Katharina Metzner Fangyuan Zhou Cathrin Flauaus Annika Balzulat Patrick Engel Jonas Petersen Rebekka Ehinger Anne Bausch Peter Ruth Robert Lukowski Achim Schmidtko 《International journal of molecular sciences》2021,22(1)
The sodium-activated potassium channel Slack (KNa1.1, Slo2.2, or Kcnt1) is highly expressed in populations of sensory neurons, where it mediates the sodium-activated potassium current (IKNa) and modulates neuronal activity. Previous studies suggest that Slack is involved in the processing of neuropathic pain. However, mechanisms underlying the regulation of Slack activity in this context are poorly understood. Using whole-cell patch-clamp recordings we found that Slack-mediated IKNa in sensory neurons of mice is reduced after peripheral nerve injury, thereby contributing to neuropathic pain hypersensitivity. Interestingly, Slack is closely associated with ATP-sensitive P2X3 receptors in a population of sensory neurons. In vitro experiments revealed that Slack-mediated IKNa may be bidirectionally modulated in response to P2X3 activation. Moreover, mice lacking Slack show altered nocifensive responses to P2X3 stimulation. Our study identifies P2X3/Slack signaling as a mechanism contributing to hypersensitivity after peripheral nerve injury and proposes a potential novel strategy for treatment of neuropathic pain. 相似文献
55.
Dr. Santina Maiorana Prof. Roberta Ettari Dr. Santo Previti Dr. Giorgio Amendola Dr. Annika Wagner Prof. Sandro Cosconati Prof. Ute A. Hellmich Prof. Tanja Schirmeister Prof. Maria Zappalà 《ChemMedChem》2020,15(16):1552-1561
In this paper, we report the design, synthesis and biological investigation of a series of peptidyl vinyl ketones obtained by modifying the P2 fragment of previously reported highly potent inhibitors of rhodesain, the main cysteine protease of Trypanosoma brucei rhodesiense. Investigation of the structure–activity relationship led us to identify new rhodesain inhibitors endowed with an improved selectivity profile (a selectivity index of up to 22 000 towards the target enzyme), and/or an improved antitrypanosomal activity in the sub-micromolar range. 相似文献
56.
Maryam Oroujeni Sara S. Rinne Anzhelika Vorobyeva Annika Loftenius Joachim Feldwisch Per Jonasson Vladimir Chernov Anna Orlova Fredrik Y. Frejd Vladimir Tolmachev 《International journal of molecular sciences》2021,22(5)
Radionuclide imaging of HER2 expression in tumours may enable stratification of patients with breast, ovarian, and gastroesophageal cancers for HER2-targeting therapies. A first-generation HER2-binding affibody molecule [99mTc]Tc-ZHER2:V2 demonstrated favorable imaging properties in preclinical studies. Thereafter, the affibody scaffold has been extensively modified, which increased its melting point, improved storage stability, and increased hydrophilicity of the surface. In this study, a second-generation affibody molecule (designated ZHER2:41071) with a new improved scaffold has been prepared and characterized. HER2-binding, biodistribution, and tumour-targeting properties of [99mTc]Tc-labelled ZHER2:41071 were investigated. These properties were compared with properties of the first-generation affibody molecules, [99mTc]Tc-ZHER2:V2 and [99mTc]Tc-ZHER2:2395. [99mTc]Tc-ZHER2:41071 bound specifically to HER2 expressing cells with an affinity of 58 ± 2 pM. The renal uptake for [99mTc]Tc-ZHER2:41071 and [99mTc]Tc-ZHER2:V2 was 25–30 fold lower when compared with [99mTc]Tc-ZHER2:2395. The uptake in tumour and kidney for [99mTc]Tc-ZHER2:41071 and [99mTc]Tc-ZHER2:V2 in SKOV-3 xenografts was similar. In conclusion, an extensive re-engineering of the scaffold did not compromise imaging properties of the affibody molecule labelled with 99mTc using a GGGC chelator. The new probe, [99mTc]Tc-ZHER2:41071 provided the best tumour-to-blood ratio compared to HER2-imaging probes for single photon emission computed tomography (SPECT) described in the literature so far. [99mTc]Tc-ZHER2:41071 is a promising candidate for further clinical translation studies. 相似文献
57.
Medication packaging is essential to provide patients with guidance and correct use of their medicines for effective treatment. This research aims to increase knowledge about the medication packaging innovation process and its uptake towards patient‐centered packaging design. The study applied a qualitative research approach based on data from 25 in‐depth interviews with stakeholders involved in medication packaging design. The empirical data analysis revealed four themes that can improve and advance user‐centered packaging design: medication packaging innovation process, medication packaging functions and features, medication packaging design constraints, and patient‐centered medication packaging design. The findings suggest that medication packaging design is strongly affected by an emphasis on protective and safety packaging functions rather than on patients' needs. Packaging innovation usually is constrained by rigid incremental development processes, where compliance with regulations, extensive documentation, avoidance of manufacturing complexity, and considerations on cost prevail. These findings are discussed in relation to the three most evident trade‐offs for patient‐centered design: protection versus openability, utility versus cost, and complexity of manufacturability versus complexity of use. This research contributes with valuable input and additional evidence about the necessary shift to a user‐centered approach in a field that has not been design driven. This input complements previous research and provides an opportunity for industry decision makers and policy makers to lead patient‐centered packaging design that can benefit patients and relieve overloaded health care systems. 相似文献
58.
59.
Mass Spectrometric Analysis of Cerebrospinal Fluid Ubiquitin in Alzheimer's Disease and Parkinsonian Disorders
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Simon Sjödin Oskar Hansson Annika Öhrfelt Gunnar Brinkmalm Henrik Zetterberg Ann Brinkmalm Kaj Blennow 《Proteomics. Clinical applications》2017,11(11-12)
1 Purpose
Dysfunctional proteostasis, with decreased protein degradation and an accumulation of ubiquitin into aggregated protein inclusions, is a feature of neurodegenerative diseases. Identifying new potential biomarkers in cerebrospinal fluid (CSF) reflecting this process could contribute important information on pathophysiology.2 Experimental design
A developed method combining SPE and PRM‐MS is employed to monitor the concentration of ubiquitin in CSF from subjects with Alzheimer's disease (AD), Parkinson's disease (PD), and progressive supranuclear palsy (PSP). Four independent cross‐sectional studies are conducted, studies 1–4, including controls (n = 86) and participants with AD (n = 60), PD (n = 15), and PSP (n = 11).3 Results
The method shows a repeatability and intermediate precision not exceeding 6.1 and 7.9%, respectively. The determined LOD is 0.1 nm and the LOQ range between 0.625 and 80 nm . The CSF ubiquitin concentration is 1.2–1.5‐fold higher in AD patients compared with controls in the three independent AD‐control studies (Study 1, p < 0.001; Study 2, p < 0.001; and Study 3, p = 0.003). In the fourth study, there is no difference in PD or PSP, compared to controls.4 Conclusion and clinical relevance
CSF ubiquitin may reflect dysfunctional proteostasis in AD. The described method can be used for further exploration of ubiquitin as a potential biomarker in neurodegenerative diseases. 相似文献60.
Thomas Küstner Annika Liebgott Lukas Mauch Petros Martirosian Fabian Bamberg Konstantin Nikolaou Bin Yang Fritz Schick Sergios Gatidis 《Magma (New York, N.Y.)》2018,31(2):243-256