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41.
Xiaoyu Yang Wei Xu Svetlana Dukleska Sabrina Benchaar Selina Mengisen Valentyn Antochshuk Jason Cheung Leslie Mann Zulfia Babadjanova Jason Rowand Rico Gunawan Alexander McCampbell Maribel Beaumont David Meininger Daisy Richardson Alexandre Ambrogelly 《MABS-AUSTIN》2013,5(5):787-794
Monoclonal antibodies constitute a robust class of therapeutic proteins. Their stability, resistance to stress conditions and high solubility have allowed the successful development and commercialization of over 40 antibody-based drugs. Although mAbs enjoy a relatively high probability of success compared with other therapeutic proteins, examples of projects that are suspended due to the instability of the molecule are not uncommon. Developability assessment studies have therefore been devised to identify early during process development problems associated with stability, solubility that is insufficient to meet expected dosing or sensitivity to stress. This set of experiments includes short-term stability studies at 2−8 þC, 25 þC and 40 þC, freeze-thaw studies, limited forced degradation studies and determination of the viscosity of high concentration samples. We present here three case studies reflecting three typical outcomes: (1) no major or unexpected degradation is found and the study results are used to inform early identification of degradation pathways and potential critical quality attributes within the Quality by Design framework defined by US Food and Drug Administration guidance documents; (2) identification of specific degradation pathway(s) that do not affect potency of the molecule, with subsequent definition of proper process control and formulation strategies; and (3) identification of degradation that affects potency, resulting in program termination and reallocation of resources. 相似文献
42.
Jing Rao Sergey Varlamov Jongsung Park Svetlana Dligatch Anatoli Chtanov 《Plasmonics (Norwell, Mass.)》2013,8(2):785-791
Surface plasmonic-enhanced light trapping from metal nanoparticles is a promising way of increasing the light absorption in the active silicon layer and, therefore, the photocurrent of the silicon solar cells. In this paper, we applied silver nanoparticles on the rear side of polycrystalline silicon thin film solar cell and systematically studied the dielectric environment effect on the absorption and short-circuit current density (Jsc) of the device. Three different dielectric layers, magnesium fluoride (MgF2, n?=?1.4), tantalum pentoxide (Ta2O5, n?=?2.2), and titanium dioxide (TiO2, n?=?2.6), were investigated. Experimentally, we found that higher refractive index dielectric coatings results in a redshift of the main plasmonic extinction peak and higher modes were excited within the spectral region that is of interest in our thin film solar cell application. The optical characterization shows that nanoparticles coated with highest refractive index dielectric TiO2 provides highest absorption enhancement 75.6 %; however, from the external quantum efficiency characterization, highest short-circuit current density Jsc enhancement of 45.8 % was achieved by coating the nanoparticles with lower refractive index MgF2. We also further optimize the thickness of MgF2 and a final 50.2 % Jsc enhancement was achieved with a 210-nm MgF2 coating and a back reflector. 相似文献
43.
Eugenia M. Rapoport Ekaterina V. Moiseeva Dmitry A. Aronov Sergey V. Khaidukov Galina V. Pazynina Svetlana V. Tsygankova Ivan M. Ryzhov Ivan M. Belyanchikov Tatiana V. Tyrtysh Kenneth C. McCullough Nicolai V. Bovin 《Glycoconjugate journal》2020,37(1):129-138
Modification of vaccine carriers by decoration with glycans can enhance binding to and even targeting of dendritic cells (DCs), thus augmenting vaccine efficacy. To find a specific glycan-“vector” it is necessary to know glycan-binding profile of DCs. This task is not trivial; the small number of circulating blood DCs available for isolation hinders screening and therefore advancement of the profiling. It would be more convenient to employ long-term cell cultures or even primary DCs from murine blood. We therefore examined whether THP-1 (human monocyte cell line) and DC2.4 (immature murine DC-like cell line) could serve as a model for human DCs. These cells were probed with a set of glycans previously identified as binding to circulating human CD14low/-CD16+CD83+ DCs. In addition, we tested a subpopulation of murine CD14low/-CD80+СD11c+CD16+ cells reported as relating to the human CD14low/-CD16+CD83+ cells. Manα1–3(Manα1–6)Manβ1–4GlcNAcβ1–4GlcNAcβ bound to both the cell lines and the murine CD14low/-CD80+СD11c+CD16+ cells. Primary cells, but not the cell cultures, were capable of binding GalNAcα1–3Galβ (Adi), the most potent ligand for binding to human circulating DCs. In conclusion, not one of the studied cell lines proved an adequate model for DCs processes involving lectin binding. Although the glycan-binding profile of BYRB-Rb (8.17)1Iem mouse DCs could prove useful for assessing human DCs, important glycan interactions were missing, a situation which was aggravated when employing cells from the BALB/c strain. Accordingly, one must treat results from murine work with caution when seeking vaccine targeting of human DCs, and certainly should avoid cell lines such as THP-1 and DC2.4 cells. 相似文献
44.
Altúzar-Molina Alma Lozano Luis Ortíz-Berrocal Marlene Ramírez Mario Martínez Lourdes de Lourdes Velázquez-Hernández María Dhar-Ray Swatismita Silvente Sonia Mariano Néstor Shishkova Svetlana Hernández Georgina Reddy Pallavolu M. 《Plant Molecular Biology Reporter》2020,38(2):262-281
Plant Molecular Biology Reporter - Legumes form symbiosis with rhizobia, which fix nitrogen for the benefit of host plant in return for carbon resources. Development of this unique symbiosis in... 相似文献
45.
The phyllosphere is one of the largest habitats for terrestrial microorganisms. To gain a better insight into the factors underlying the composition of bacterial communities inhabiting leaf surfaces we performed culture-dependent and independent (Denaturing Gradient Gel Electrophoresis) analyses on the bacteria associated with the leaves of three plant species: Amygdalus communis, Citrus paradisi, and Nicotiana glauca. We found that the culturable classes Bacilli and Actinobacteria were the predominant classes on the phyllosphere of all three plant species. In contrast to this consistency on the bacterial class level, we found a significant variation on the bacterial species-level based on the culturable methods. Although some variation was detected among individual plants within one plant species, the inter-specific variability exceeded the intra-specific variability. C. paradisi leaf surface had the highest predicted total species richness (Chao 2 and ICE) and the highest species diversity (βw) among the three plant species. Our findings demonstrate that environmental conditions, mainly the plant species within a site, govern the bacterial community composition on leaf surfaces. 相似文献
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49.
Svetlana V. Osipova Aleksey V. Permyakov Marina D. Permyakova Tatyana A. Pshenichnikova Mikhail A. Genaev Andreas Börner 《Acta Physiologiae Plantarum》2013,35(8):2455-2465
Understanding of the genetic basis of physiological properties, which are most relevant to water-deficit tolerance would be helpful for genomic-assisted improvement of bread wheat. A set of bread wheat inter-varietal single chromosome substitution lines (ISCSLs) of variety ‘Janetzkis Probat’ (JP) in the genetic background of ‘Saratovskaya’ 29 (S29) were used to reveal the critical chromosomes in wheat genome controlling tolerance to water deficit. The same lines were involved in the identification of chromosomes associated with the activity of antioxidant enzymes that are closely related to the detoxification of H2O2 [catalase (CAT), ascorbate peroxidase, dehydroascorbate reductase and glutathione reductase (GR)]. The recipient cultivar S29 was highly drought tolerant while the donor JP was sensitive. Using non-metric multidimensional scaling of yield components and indices of drought tolerance/susceptibility chromosomes 2A and 4D, substitution in the genetic background of S29 was found to lead to a critical decrease of water-deficit tolerance. The drop of tolerance correlated with a sharp decline of cumulative activity of the catalase and the enzymes of ascorbate–glutathione cycle in wheat leaves. Clear evidence was obtained for the involvement of genes present on the homoeologous group 2 chromosomes in the control of GR and CAT activity. Substitution of the chromosome 4D had a significant reducing impact on the CAT activity level. 相似文献
50.
Malgorzata M. Barczyk Ning Lu Svetlana N. Popova Anne Isine Bolstad Donald Gullberg 《Journal of cellular physiology》2013,228(5):1108-1119
We have previously determined that integrin α11β1 is required on mouse periodontal ligament (PDL) fibroblasts to generate the force needed for incisor eruption. As part of the phenotype of α11?/? mice, the incisor PDL (iPDL) is thickened, due to disturbed matrix remodeling. To determine the molecular mechanism behind the disturbed matrix dynamics in the PDL we crossed α11?/? mice with the Immortomouse and isolated immortalized iPDL cells. Microarray analysis of iPDL cells cultured inside a 3D collagen gel demonstrated downregulated expression of a number of genes in α11‐deficient iPDL cells, including matrix metalloproteinase‐13 (MMP‐13) and cathepsin K. α11?/? iPDL cells in vitro displayed disturbed interactions with collagen I during contraction of attached and floating collagen lattices and furthermore displayed reduced MMP‐13 protein expression levels. The MMP‐13 specific inhibitor WAY 170523 and the Cathepsin K Inhibitor II both blocked part of the α11 integrin‐mediated collagen remodeling. In summary, our data demonstrate that in iPDL fibroblasts the mechanical strain generated by α11β1 integrin regulates molecules involved in collagen matrix dynamics. The positive regulation of α11β1‐dependent matrix remodeling, involving MMP‐13 and cathepsin K, might also occur in other types of fibroblasts and be an important regulatory mechanism for coordinated extracellular and intracellular collagen turnover in tissue homeostasis. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc. 相似文献