478,802 research outputs found
A coacervate-based platform for growth factor delivery
No full textGrowth factors participating in a variety of biological processes have great potential in regenerative medicine. However, unprotected growth factors degrade quickly and have little efficacy at tissue repair. Delivery of growth factors with different vehicles has been examined to prolong the half-lives of growth factors and therefore increase its therapeutic efficacy. After decades of research, controlled delivery of growth factor still faces some significant limitations, and none has reached clinical translation.
Heparin, a highly sulfated macromolecule, is used as an anticoagulant clinically. In addition, it has high affinity to a large number of biomolecules, including many growth factors. The interaction between heparin and heparin-binding growth factors is known to adjust their conformation, protect them from proteolytic degradation and regulate their activities. Incorporation of heparin in growth factor delivery is consequently a strategy to potentiate the bioactivity of growth factors. Currently, most approaches used to immobilize heparin on the delivery vehicles rely on covalent modification of heparin that may alter its inherent properties. To maximize the efficacy of heparin, we developed a coacervate-based delivery platform in which heparin is utilized to complex with a polycation without any modification. The polycation neutralizes the negative charges of heparin and precipitates it out of solution. This approach allows spatiotemporal control of the release of heparin-binding growth factors. This dissertation covers the design, production, characterization and application of heparin-based coacervate in controlled release of growth factors
正常ヒト肝細胞による補体D因子産生(予報)(自然科学系)
No full textThe biosynthesis of complement components by normal human hepatocytes was studied in vitro. In culture supernatants of normal hepatocytes [human primary hepatocytes (epithelial) cells] , many complement components including factor D were distinctly detected by immunoblot analysis. In our studies focusing on factor D production by these cells, we have found the following: (i) normal hepatocytes produced increasing amounts of factor D over a 5-day period; (ii) when hepatocytes were cultured for 5 days without addition of any stimulator, 331.1±41.38ng (/10^8 cells, n=12) of factor D was secreted; (iii) addition of TNF-α, IFN-γ, IL-1β or LPS in the culture medium did not show any distinct effect on the amounts of secreted factor D; and (iv) reversible inhibition of factor D secretion was observed when the cells were cultured in the presence of cycloheximide, indicating that factor D is synthesized de novo. These findings suggest the possibility of factor D synthesis by the liver in vivo, to be contradictory to the previous reports that factor D is identical to adipsin secreted by adipocytes in adipose tissue but not by the liver
ヒト乳腺上皮細胞による補体D因子産生(自然科学系)
No full textComplement components were assayed in culture supernatants of normal human mammary epithelial cells (HMEC) and 3 kinds of mammary cancer-derived cell lines, MRK-nu-1, YMB-1 and YMB-1 E. When these cells were cultured In medium without addition of any stimulator for 3 days, Clq, C4, C3 and factor D were clearly detected In the supernatants of all these cells. Further studies were carried out to analyze factor D production by these cells. Mammary cancer-derived cell lines, as well as normal HMEC, produced and released 0.35-1.72 ng of factor D/l0^6cells/day in the supernatants. When IFN (interferon)-γ was added in culture medium, the factor D level in the supernatants increased in a dose-dependent manner. Addition of histamine or LPS (lipopolysaccharide) did not significantly effect the factor D level. Factor D production by these cells was inhibited by the presence of 1.0μg/mL of cycloheximide reversibly, indicating de novo synthesis of factor D by these cells. This is the first report on factor D synthesis by mammary epithelial cells
胃癌由来培養細胞による補体D因子産生(自然科学系)
No full textFactor D, a serum protein of the alternative pathway of the complement system, was assayed by sandwich ELISA in culture supernatants of 4 kinds of gastric cancer-derived cell lines, MKN28, MKN74, MKN45 and KATO-III. When these cells were cultured in protein-free hybridoma medium for 3 days without addition of any stimulator, 0.918±0.987, 1.953±0.489, 7.096±4.273 and 2.041±0.786 ng factor D/l0^6 cells were detected in the culture supernatants of MKN28, MKN74, MKN45 and KATO-III, respectively. Addition of TNF to the culture medium did not affect the factor D level significantly, while the C3 level increased in a dose-dependent manner. Factor D production by these cells was inhibited by the presence of 1.0 μg/mL of cycloheximide reversibly, indicating de novo synthesis of factor D by these cells. Since all of the cell lines tested in this study synthesize factor D, it is possible that factor D is synthesized by gastric epithelial cells physiologically. This is the first report on factor D synthesis by gastric epithelial cells
Total Factor Productivity and R&D Capital in Manufacturing Industries
No full textThis study analyzes total factor productivity in manufacturing industries for a sample of OECD countries. The estimates of Malmquist indexes clearly indicate that research and development (R&D) capital is an important determinant of productivity growth in manufacturing industries. The empirical results also show that it is the pace, not the intensity, of R&D investment that is significantly related to the extent to which R&D capital formation contributes to output growth. Furthermore, this study finds that productivity gains in manufacturing industries depend importantly on R&D spillovers as well.
Supplementary materials for the article: Factor recovery by principal axis factoring and maximum likelihood factor analysis as a function of factor pattern and sample size.
No full textSupplementary materials for the article: De Winter, J. C. F., & Dodou, D. (2012). Factor recovery by principal axis factoring and maximum likelihood factor analysis as a function of factor pattern and sample size. Journal of Applied Statistics, 39, 695-710. https://doi.org/10.1080/02664763.2011.61044
Deletion of vitamin D receptor leads to premature emphysema/COPD by increased matrix metalloproteinases and lymphoid aggregates formation
No full textDeficiency of vitamin D is associated with accelerated decline in lung function. Vitamin D is a ligand for nuclear hormone vitamin D receptor (VDR), and upon binding it modulates various cellular functions. The level of VDR is reduced in lungs of patients with chronic obstructive pulmonary disease (COPD) which led us to hypothesize that deficiency of VDR leads to significant alterations in lung phenotype that are characteristics of COPD/emphysema associated with increased inflammatory response. We found that VDR knock-out (VDR(-/-)) mice had increased influx of inflammatory cells, phospho-acetylation of nuclear factor-kappaB (NF-κB) associated with increased proinflammatory mediators, and up-regulation of matrix metalloproteinases (MMPs) MMP-2, MMP-9, and MMP-12 in the lung. This was associated with emphysema and decline in lung function associated with lymphoid aggregates formation compared to WT mice. These findings suggest that deficiency of VDR in mouse lung can lead to an early onset of emphysema/COPD because of chronic inflammation, immune dysregulation, and lung destruction
Vascular endothelial growth factor restores delayed tumor progression in tumors depleted of macrophages
No full textGenetic depletion of macrophages in Polyoma Middle T oncoprotein (PyMT)-induced mammary tumors in mice delayed the angiogenic switch and the progression to malignancy. To determine whether vascular endothelial growth factor A (VEGF-A) produced by tumor-associated macrophages regulated the onset of the angiogenic switch, a genetic approach was used to restore expression of VEGF-A into tumors at the benign stages. This stimulated formation of a high-density vessel network and in macrophage-depleted mice, was followed by accelerated tumor progression. The expression of VEGF-A led to a massive infiltration into the tumor of leukocytes that were mostly macrophages. This study suggests that macrophage-produced VEGF regulates malignant progression through stimulating tumor angiogenesis, leukocytic infiltration and tumor cell invasion
Open access self-archiving: An author study
No full textThis, our second author international, cross-disciplinary study on open access had 1296 respondents. Its focus was on self-archiving. Almost half (49%) of the respondent population have self-archived at least one article during the last three years. Use of institutional repositories for this purpose has doubled and usage has increased by almost 60% for subject-based repositories. Self-archiving activity is greatest amongst those who publish the largest number of papers. There is still a substantial proportion of authors unaware of the possibility of providing open access to their work by self-archiving. Of the authors who have not yet self-archived any articles, 71% remain unaware of the option. With 49% of the author population having self-archived in some way, this means that 36% of the total author population (71% of the remaining 51%), has not yet been appraised of this way of providing open access. Authors have frequently expressed reluctance to self-archive because of the perceived time required and possible technical difficulties in carrying out this activity, yet findings here show that only 20% of authors found some degree of difficulty with the first act of depositing an article in a repository, and that this dropped to 9% for subsequent deposits. Another author worry is about infringing agreed copyright agreements with publishers, yet only 10% of authors currently know of the SHERPA/RoMEO list of publisher permissions policies with respect to self-archiving, where clear guidance as to what a publisher permits is provided. Where it is not known if permission is required, however, authors are not seeking it and are self-archiving without it. Communicating their results to peers remains the primary reason for scholars publishing their work; in other words,
researchers publish to have an impact on their field. The vast majority of authors (81%) would willingly comply with a mandate from their employer or research funder to deposit copies of their articles in an institutional or subject-based repository. A further 13% would comply reluctantly; 5% would not comply with such a mandate
MeSH term explosion and author rank improve expert recommendations
No full textInformation overload is an often-cited phenomenon that reduces the productivity, efficiency and efficacy of scientists. One challenge for scientists is to find appropriate collaborators in their research. The literature describes various solutions to the problem of expertise location, but most current approaches do not appear to be very suitable for expert recommendations in biomedical research. In this study, we present the development and initial evaluation of a vector space model-based algorithm to calculate researcher similarity using four inputs: 1) MeSH terms of publications; 2) MeSH terms and author rank; 3) exploded MeSH terms; and 4) exploded MeSH terms and author rank. We developed and evaluated the algorithm using a data set of 17,525 authors and their 22,542 papers. On average, our algorithms correctly predicted 2.5 of the top 5/10 coauthors of individual scientists. Exploded MeSH and author rank outperformed all other algorithms in accuracy, followed closely by MeSH and author rank. Our results show that the accuracy of MeSH term-based matching can be enhanced with other metadata such as author rank
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