Academic literature on the topic '2-Cells stage'
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Journal articles on the topic "2-Cells stage"
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Vanhecke, D., B. Verhasselt, V. Debacker, G. Leclercq, J. Plum, and B. Vandekerckhove. "Differentiation to T helper cells in the thymus. Gradual acquisition of T helper cell function by CD3+CD4+ cells." Journal of Immunology 155, no. 10 (November 15, 1995): 4711–18. http://dx.doi.org/10.4049/jimmunol.155.10.4711.
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Abstract We investigated at which point during thymocyte differentiation functions were acquired that are characteristic for mature Th cells. Differentiation from CD3+CD69-, CD4+CD8+ double-positive (DP) cells to terminally differentiated CD3+, CD4+CD8- single-positive (SP) cells was broken down into six discrete stages that were purified by four-color sorting: CD69-CD3+DP (stage 0), CD69+CD27-DP (stage 1), CD69+CD27-CD4+SP (stage 2), CD27+CD1+CD4+SP (stage 3), CD1-CD45RO+CD4+SP (stage 4), and CD1-CD45RO-CD4+SP cells (stage 5). Phenotypically, these stages seem to describe consecutive steps in differentiation from immature stage 0 to the terminally matured stage 5. Functionally, the capacity to proliferate on IL-2 after stimulation was absent in CD69- stage 0 cells, but was acquired gradually during stages 1 to 4. Clonal expandability and the capacity to respond to stimulation with the production of cytokines were acquired later and rather abruptly by CD1- stage 4 and 5 cells. Activation markers such as CD69 expression and in vivo IL-2 gene transcription came up simultaneously at the DP stage and peaked at stage 3 to 4. These data suggest that functional maturation of Th cells occurs over an extended period in differentiation, stages 1 to 4, and coincides with a gradual increase in activation markers. After completion of functional differentiation, at stage 5, in vivo IL-2 mRNA transcription and CD69 expression are down-regulated, and the cells become functionally resting naive T cells expressing CD45RA+.
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Mower, D. A., D. W. Peckham, V. A. Illera, J. K. Fishbaugh, L. L. Stunz, and R. F. Ashman. "Decreased membrane phospholipid packing and decreased cell size precede DNA cleavage in mature mouse B cell apoptosis." Journal of Immunology 152, no. 10 (May 15, 1994): 4832–42. http://dx.doi.org/10.4049/jimmunol.152.10.4832.
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Abstract Mature resting mouse spleen B cells progress stochastically into apoptosis at a uniform rate over the first 16 h in vitro in 3 stages. In stage 1, early apoptotic B cells decreased the normal phospholipid packing of their plasma membranes, detected as increased binding of the lipophilic dye merocyanine 540, and also decreased in volume, detected as decreased forward scatter. In stage 2 there was abrupt internucleosomal cleavage of DNA, quantitated as hypodiploid nuclei by flow cytometry. Some stage 2 cells entered stage 3, where the plasma membrane became permeable to propidium iodide. B cells in later stages of this sequence retained the characteristics of earlier stages, whereas nonapoptotic B cells remained in their original state. Cycloheximide increased the progression of B cells through these three stages, whereas dextran sulfate inhibited stage 1 more effectively than stages 2 or 3. Increased orthogonal scatter also occurred late in some of the cells that had passed through stage 1, but did not correlate well with propidium iodide permeability. Fresh small dense spleen B cells contained 5% to 7% stage 1 cells but only about 1% stage 2 cells. Macrophages have been reported to destroy preferentially apoptotic thymocytes by recognizing plasma membrane alterations deriving from loose packing of phospholipid head groups. The recognition of stage 1 rather than stage 2 B cells by macrophages may help to keep the proportion of apoptotic cells low in vivo.
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Bai, L., G. Meredith, and B. E. Tuch. "Glucagon-like peptide-1 enhances production of insulin in insulin-producing cells derived from mouse embryonic stem cells." Journal of Endocrinology 186, no. 2 (August 2005): 343–52. http://dx.doi.org/10.1677/joe.1.06078.
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Embryonic stem cells (ESCs) can be differentiated into insulin-producing cells by a five-stage procedure involving altering culture conditions and addition of nicotinamide. The amounts of insulin in these cells are lower than those found in pancreatic β cells. Glucagon-like peptide-1 (GLP-1) induces the differentiation of β cells from ductal progenitor cells. We examined the possibility of GLP-1, and its long-acting agonist exendin-4, enhancing the differentiation of insulin-producing cells from mouse ESCs (mESCs). A five-stage culturing strategy starting with embryoid bodies (EBs) was used in this study. mRNA for pancreatic duodenal homeobox gene 1 (PDX-1) and neurogenic differentiation (NeuroD) was detected from stage 1, hepatocyte nuclear factor 3 beta (HNF3β) and insulin 2 from stage 2, Ngn3 and glucose transporter 2 (GLUT2) from stage 3, and insulin 1 and other β-cell markers, at stages 4–5. Cells at stage 5 secreted C-peptide, being 0.68 ± 0.01 pmol/106 cells per 2 days, and had an immunoreactive insulin content of 13.5 ± 0.7 pmol/106 cells. Addition of GLP-1 (100 nM) and nicotinamide (10 mM) at stage 5 resulted in a 50% and 48% increase in insulin content and C-peptide secretion respectively compared with nicotinamide alone. Glucose-induced insulin secretion was enhanced 4-fold by addition of both growth factors. The GLP-1 receptor was present at all five stages of the culture. Addition of exendin-4 to cells at stage 2 resulted in a 4.9-fold increase in expression of the gene for insulin 1 and a 2-fold increase in insulin content compared with the effect of nicotinamide alone at stage 5. It is concluded that both GLP-1 and exendin-4 enhance the level of expression of insulin in glucose-responsive insulin-producing cells derived from the R1 mESC line.
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Ruggeri, Rosaria Maddalena, Salvatore Sciacchitano, Enrica Vitarelli, Francesco Trimarchi, Gaetano Barresi, and Maria Trovato. "Immunoexpression of Multidrug-Resistance Protein 2 and Cyclooxygenase 2 in Medullary Thyroid Carcinomas." Archives of Pathology & Laboratory Medicine 130, no. 7 (July 1, 2006): 1014–19. http://dx.doi.org/10.5858/2006-130-1014-iompac.
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Abstract Context.—Chemoresistance is due to the expression of multidrug-resistance proteins (MRPs). Cyclooxygenase 2 (COX2), a key enzyme in prostaglandins synthesis, upregulates MRP1. MRP1 is overexpressed in medullary thyroid carcinomas (MTCs), but it is not involved in resistance to doxorubicin and cisplatin, which are commonly used in MTC treatment. MRP2 is specifically involved in resistance to both chemotherapeutic agents, but no data exist on the expression of MRP2 and COX2 in MTC. Objective.—To evaluate MRP2 and COX2 expressions in MTC. Design.—We analyzed immunohistochemical expression of MRP2 and COX2 in 12 MTCs and in 6 lymph node metastases. Results were correlated with pTNM and clinical stage. Results.—MRP2 and COX2 expressions were observed only in tumor samples and metastases. Nine MTCs, all pTNM stage T4, were positive for MRP2, whereas 3 MTCs, pTNM stages T2 and T3, were unreactive for MRP2. Six metastatic MTCs at stage T4 showed higher proportion of MRP2+ cells, compared with primary tumors. All 12 MTCs were positive for COX2. Three MTCs, pTNM stage T2 and T3, showed COX2 positivity in all cells. The proportion of COX2+ cells decreased with increased pTNM stage. Four out of 6 metastatic MTCs, stage T4, showed a lower proportion of COX2+ cells, compared with primary tumors. The proportion of MRP2+ cells was inversely related to the proportion of COX2+ cells. Conclusions.—MRP2 and COX2 expression correlated with pTNM stage. High MRP2 and low COX2 expression may explain resistance to doxorubicin and cisplatin, which is observed in advanced stage MTC. Evaluation of the expression pattern of these 2 proteins may be useful to predict chemosensitivity of these types of tumors.
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Jones, E. A., and H. R. Woodland. "The development of animal cap cells in Xenopus: a measure of the start of animal cap competence to form mesoderm." Development 101, no. 3 (November 1, 1987): 557–63. http://dx.doi.org/10.1242/dev.101.3.557.
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Grafting, together with tissue identification by monoclonal antibodies, has been used to study the allocation of Xenopus animal cap cells to the ectodermal or mesodermal lineages. Animal cap cells become responsive at stage 61/2 and lose responsiveness to mesodermal induction at, or just after, stage 101/2 (depending on the batch of embryos). The ability of the vegetal yolky cells to induce mesoderm disappears between stages 101/2 and 11. It is present at stage 6–61/2 and may exist before this. The emergence of competence to respond at stage 61/2, coupled with the fact that the endoderm is already capable of induction at this stage, suggests that mesodermal induction begins at this point in the intact embryo.
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Rybicka, Krystyna. "Histogenesis of alveolar cell carcinoma." Proceedings, annual meeting, Electron Microscopy Society of America 45 (August 1987): 626–27. http://dx.doi.org/10.1017/s0424820100127566.
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Alveolar cell carcinoma (ACC) is a lung neoplasm characterized by the presence of lamellar bodies specific for normal type 2 alveolar cells. Tumor histogenesis is uncertain. The present study indicates that ACC originates from dedifferentiation of hyperplastic type 2 alveolar cells rather than migration of bronchial stem cells into alveoli as suggested earlier.An aliquot of human lung biopsy diagnosed as ACC was fixed in glutaraldehyde and osmium, treated with 1% aqueous uranyl acetate, and embedded in epoxy resin. Sections were stained for glycogen by periodic acid - thiosemicarbazide - silver proteinate, and post-stained by uranyl acetate and lead citrate.The tumor contained morphologically distinct cell clusters. Each cluster consisted of identical cells. Differences between clusters resulted from synchronous alterations in lamellar bodies, mitochondria, glycosomes, and ribosomes. These alterations revealed distinct stages in cell differentiation classified here as follows: stage 1-hyperplastic cells (Fig.1), stage 2-dedifferentiating cells (Fig.2), stage 3-undifferentiated cells (Fig.3), stage 4-differentiating cells (Fig.4).
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Loncarevic, Slobodan, Denis Brajkovic, Milka Gardasevic, Olivera Loncarevic, Nebojsa Ladjevic, Dejan Nesic, Dusica Stamenkovic, Ivana Likic-Ladjevic, Nikola Ladjevic, and Nemanja Rancic. "Expression of PCNA, CD-31 and HER-2 in Serbian patients with oral squamous cell carcinoma." Archives of Biological Sciences 71, no. 4 (2019): 703–10. http://dx.doi.org/10.2298/abs190705053l.
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Several studies have investigated the expression of tumor markers, including p53, HER-2, PCNA, EGFR, VEGFR CD-31 and Bcl-2 in patients with oral squamous carcinoma (OSC). This study aimed to determine the expression of proliferating cell nuclear antigen (PCNA), endothelial functions of platelet/endothelial cell adhesion molecule-1 (CD31) and human epidermal growth factor receptor-2 (HER-2) according to OSC stage. The prospective study included 62 patients diagnosed with OSC stages II and III. Surgical specimens were obtained from tumor and peritumoral tissues. We determined the pathohistological degree of tumor differentiation and the immunohistochemical expression of PCNA, CD-31 and HER-2 for each specimen. Immunohistochemical analysis of the expression of PCNA in tumor cells demonstrated poor staining of immunoreactive tumor cells in 23 patients (10 in stage II, 7 in stage IIIa and 6 in stage IIIb). Moderately expressed PCNA-immunoreactivity in the tumor cells in 17 patients (7 in stage II, 6 in stage IIIa and 4 in stage III), and extremely strong PCNA-immunoreactive staining in tumor cells of 10 patients with IIIb stage, was observed. These results suggest that PCNA expression combined with pathohistological findings could possess a prognostic value in determining the survival rates for patients with oral squamous cell carcinoma.
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Sepulveda-Rincon, L. P., D. Dube, P. Adenot, L. Laffont, S. Ruffini, L. Gall, W. E. Maalouf, V. Duranthon, and N. Beaujean. "78 NONINVASIVE CELL LINEAGE TRACING IN BOVINE EMBRYOS FROM 2-CELL STAGE UP TO BLASTOCYST STAGE." Reproduction, Fertility and Development 27, no. 1 (2015): 132. http://dx.doi.org/10.1071/rdv27n1ab78.
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The first lineage specification occurs during pre-implantation mammalian development. At the blastocyst stage, 2 cell lineages can be distinguished: the inner cell mass (ICM) and the trophectoderm (TE). The exact timing when embryo cells are skewed to these lineages is not clearly determined in mammalian species. In murine embryos, it has been suggested that the first cleavage plane might be related to the embryonic-abembryonic (Em-Ab) axis at blastocyst stage. Thus, the daughter cells of the 2-cell embryo might already be predisposed to a specific cell lineage further on development. The objective of the present study was to observe how the first cleavage in bovine embryos may be related to cell lineage allocation at the blastocyst stage, using a noninvasive tracing approach. Bovine oocytes were harvested, in vitro matured, and fertilised. At the 2-cell stage, embryos were injected in one blastomere with the membrane tracer DiI. At the blastocyst stage, embryos (n = 346) were classified as orthogonal when the Em-Ab axis was orthogonally divided by the borderline between labelled and non-labelled cells; as deviant if the borderline was overlapping the Em-Ab axis; and as random when the labelled and non-labelled cells were randomly distributed. Total cell count (TCC) and the ICM/TE ratio was allowed by DNA staining with 4′,6-diamidino-2-phenylindole (DAPI) and by immunostaining of the ICM with Sox2 antibody. Analysis of variance was performed by one-way ANOVA employing IBM SPSS v21 (SPSS Inc., Chicago, IL, USA) to determine any difference between the cell lineage allocation patterns, TCC, and the ICM/TE ratio. P-values = 0.05 were considered significant. All values are reported as mean ± standard error of mean. Within 40 repetitions, the blastocyst classification was as follows: orthogonal 14.9% (±2.32, n = 56), deviant 22.2% (±2.58, n = 80), and random 62.9% (±2.64, n = 210). A significant difference was found in the incidence between the random group against the orthogonal and deviant, but not between the latter two. Regarding TCC, a significant difference was observed only between the orthogonal (99.6 ± 11.7 cells, n = 15) and deviant (135 ± 7.3 cells, n = 25) groups, but not with random embryos (116 ± 5.5 cells, n = 42). Finally, no significant difference was found among the groups concerning the ICM/TE ratio (0.43 ± 0.07 for orthogonal, n = 7; 0.54 ± 0.06 for deviant, n = 14; and 0.40 ± 0.03 for random embryos, n = 26). In conclusion, bovine embryos present a marked tendency for a random distribution of the daughter cells derived from the 2-cell blastomeres. However, around 37% of the blastocysts present a patterned cell division, where the daughter cells remain together through pre-implantation development. The effect of these cell lineage allocation patterns on implantation and further embryo development needs to be addressed.The authors acknowledge Laboratoire d'Excellence Revive (Investissement d'Avenir, ANR-10-LABX-73) and CONACyT Mexico for funding.
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Hughes, Tiffany L., Michael Brian Becknell, Aharon Freud, Susan E. Schmidt, Jianhua Yu, Charlene Mao, Mikhail Gavrilin, Mark Wewers, and Michael A. Caligiuri. "The Stage-Specific Effect of Interleukin-1 Beta (IL-1β) during Human Natural Killer Cell Development." Blood 112, no. 11 (November 16, 2008): 3746. http://dx.doi.org/10.1182/blood.v112.11.3746.3746.
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Abstract Developmental intermediates of human natural killer (NK) cells are found within secondary lymphoid tissue (SLT), and five distinct stages of these intermediates have been identified. While it is well documented that developing NK cells are reliant on interleukin (IL)-15 as a survival factor, it is likely that additional cytokines and growth factors are required for complete NK cell differentiation. Microarray transcriptional profiling of purified stage 1–4 cells from human tonsil and stage 4 and 5 cells from peripheral blood (PB) identified a developmental window of interleukin-1 receptor 1 (IL-1R1) messenger RNA (mRNA) expression restricted to stages 2 and 3. We confirmed this finding by quantitative RT-PCR, and analysis of IL-1R1 surface protein expression revealed that, on average, 81% of stage 3 immature NK cells are IL-1R1(+), whereas the majority of cells from stages 1, 2, and 4 are IL-1R1(−). When cultured in vitro with IL-1β, a physiologic ligand for IL-1R1, cells from all four stages died within 48 hours, consistent with an absolute requirement for IL-15 as a survival factor. However, the combination of IL-1β and IL-15 led to a significant and reproducible 4.64±−0.68–fold increase in stage 3 cell number over that seen with IL-15 alone (p < 0.0005). This phenomenon was completely restricted to stage 3 immature NK cells, and is attributed to increased proliferation. The effects of IL-1β were abrogated by a molar excess of IL-1 receptor antagonist (IL-1RA), a physiologic competitor for IL-1R1 binding. Collectively, our data indicate that IL-1R1 expression fluctuates dramatically during NK cell development, and that unique responses of IL-1R1(+) stage 3 cells to IL-1β and IL-15 govern the expansion of these immature NK cells. Our findings support a model in which IL-1β promotes stage 3 proliferation and survival in vivo, driving stage 3 cells to be the most prevalent NK cell intermediates within SLT.
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Novikova, I. A., and O. I. Kit. "Expression of epithelial-mesenchymal transition markers E-cadherin and ZEB1 in colorectal cancer." Research and Practical Medicine Journal 8, no. 2 (June 23, 2021): 23–33. http://dx.doi.org/10.17709/2410-1893-2021-8-2-2.
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Purpose of the study. Evaluation of expression of the epithelial-mesenchymal transition markers E-cadherin and ZEB1 in patients with stage II-IV colorectal cancer (CRC).Materials and methods. The study included operational material obtained from 299 patients aged 42–86 years (mean age 64.2±1.7 years) with stage II-IV CRC treated at National Medical Research Centre for Oncology in 2013-2017. Stage II CRC (T3-4 N0 M0 ) was diagnosed in 110 patients, stage III (T1-4 N1-2 M0 ) – in 88 patients, stage IV (T1-4 N0-2 M1 ) – in 101 patients. Polyclonal rabbit antibodies to ZEB1 (Biorbyt Ltd., UK) and mouse monoclonal antibodies to E-cadherin (Diagnostic BioSystems, USA) were used for an IHC analysis. The intensity and degree of tumor cell staining, percentage of stained tumor cells in the sample and the number of patients with positive and negative marker expression were determined. Groups were compared using the Mann–Whitney U test and the Pearson's chi-square test.Results. Positive expression of E-cadherin was found in 64.5 % (193 of 299 patients), ZEB1 – in 80.6 % (241 of 299 patients). The number of patients with E-cadherin-positive tumors statistically significantly decreased (χ2 =15.888 at p<0.001) from stage II to stage IV, while for ZEB1, on the contrary, it statistically significantly increased (χ2 =43.912 at p><0.001) from stage II to stage IV. The mean values of expression in positively stained cells were: in stage II – E-cadherin 55.3±6.8 %, ZEB1 43.0±5.9 %; in stage III – E-cadherin 38.4±5.8 %, ZEB1 77.0±5.5 %; in stage IV – E-cadherin 14.7±4.7 %, ZEB1 76.9±3.5 %. Significant differences were observed between the mean values of ZEB1 expression in stages III and IV compared to stage II, as well as between the mean values of E-cadherin expression in stages II and III compared to stage IV (p><0.05). No significant differences were found in the mean values of ZEB1 and E-cadherin expression in stages III and IV, II and III respectively.Conclusions. The study demonstrated statistically significant relationship between tumor stages and expression of E-cadherin and ZEB1 in the epithelial-mesenchymal transition. The loss of the E-cadherin expression in tumor cells of patients from stage II to stage IV and increased expression of ZEB1 in the studied groups were statistically significant (p<0.05).
Dissertations / Theses on the topic "2-Cells stage"
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Pethe, Shirish. "Optimization Of The Two Stage Process For Cu(In,Ga)Se2 Solar Cells." Scholar Commons, 2004. https://scholarcommons.usf.edu/etd/1194.
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Copper Indium Gallium DiSelenide absorber layers are fabricated using a two stage manufacturing friendly process. The first step involves the sequential deposition of Copper and Gallium and co-deposition of indium and selenium at 275oC. This is followed by the second stage where the substrate is annealed in the presence of Selenium and a thin layer of copper is deposited to neutralize the excess Indium and Gallium on the surface to form the CIGS absorber layer. The top copper thickness as well as the time of deposition was varied to study the effect of Copper on the performance of the cells.
Another recipe was developed for the precursor formation, where Gallium was co-evaporated with Indium and Selenium. A large bandgap shift was seen with this recipe and the open circuit voltage was increased.
The performance of CIGS/CdS/ZnO solar cells thus fabricated was characterized using techniques like I-V, C-V, Spectral Response and EDS/SEM. Cells with open circuit voltages of 420-450 mV, short circuit currents of 33-38 mA/cm², fill factors of 58-62% and efficiencies of 9-11% were routinely fabricated.
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Wang, Yejiao. "Fabrication of Cu2ZnSnSe4 Thin-film Solar Cells by a Two-stage Process." Scholar Commons, 2016. http://scholarcommons.usf.edu/etd/6154.
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Copper zinc tin selenide (Cu2ZnSnSe4 or CZTSe) is a quaternary compound semiconductor material that has attained more and more attention for thin film photovoltaic applications. CZTSe is only comprised of abundant and non-toxic elements. People have concerns about availability and cost of indium from CIGS and tellurium from CdTe, also about cadmium’s toxicity. These concerns have promoted CZTSe as an alternative thin film solar cell material. The major issues about CZTSe absorber fabrication are: tin loss during selenization process and existence of secondary phases. Recent improvements of CZTSe absorber have increased the efficiency of CZTSe thin film solar cell to 9.7% in laboratory, and this was accomplished by using H2Se as selenium source in a “two-stage” process. [1] However “one-stage” vacuum co-evaporation technique is still the most popular technique for CZTSe thin-film solar cells fabrication.
In this research, Cu2ZnSnSe4 thin-film solar cells have been fabricated by using a two-step rapid thermal selenization process. The first step selenization is operated at 375℃, a relatively low annealing temperature, which helps avoiding the most common issue of tin loss. The second step selenization is carried out at a higher annealing temperature, 400℃ to 500℃, at where the formation of CZTSe quaternary compound can be completed, and fewer secondary phases remain in the CZTSe absorber bulk. A specially designed metallic precursor stacks deposition order has been developed to inhibit tin loss and zinc loss during selenization. Vacuum co-evaporation technique is not feasible to mass production, due to facility difficulty and bad uniformity. And H2Se is toxic and dangerous. We have developed these metallic precursor stacks vacuum deposition process and two-step selenium vapor selenization process. We believe this technique is more suitable for potential mass production in future.
The properties of CZTSe thin-films and the performance of CZTSe thin-film solar cells have been characterized using techniques, including J-V, Raman spectroscopy, spectral response, and SEM/EDS. The best performance CZTSe thin-film solar cell that have been accomplished, has an open circuit voltage of 0.42 volt, shirt circuit current densities of 14.5 mA/cm2, fill factor of 47%, and efficiency of 2.86%.
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GNOCCHI, ANDREA. "UNDERSTANDING THE IMPACT OF REPLICATION STRESS ON THE EXPRESSION OF EARLY GENES IN MOUSE EMBRYONIC STEM CELLS." Doctoral thesis, Università degli Studi di Milano, 2021. http://hdl.handle.net/2434/814703.
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Embryonic stem cells (ESCs) are characterized by a rapid cell cycle, which leads to high replication stress (RS) in otherwise unperturbed conditions. The mechanisms that ESCs adopt to cope with their endogenous RS, however, remain to this day elusive. In our recent work we demonstrated that the activation of the checkpoint kinase ATR in response to RS leads to a broad activation of 2-cells stage specific genes in mouse ESCs. This response relies on the up-regulation of Dux, a transcription factor encoded in a macrosatellite sequence repeated in tandem. Dux is repressed by variant Polycomb repressive complex 1 (vPRC1) in unperturbed ESCs, independently from PRC2 presence.
Here we demonstrate that RS causes a major rearrangement of both PRC1 and PRC2 in ESCs nuclei, resulting in a major loss of both repressive marks in correspondence to target promoters. Surprisingly, Dux undergoes an increase in vPRC1 occupancy upon RS in an ATR-dependent manner, possibly due to PRC1 involvement in the replication of highly repeated DNA sequences. More interestingly, Dux activation upon RS requires the presence of PRC2. This result is possibly due to PRC2 proved role in the processing of stalled replication forks, which are the main structure signaling RS. In agreement to this data, also the fork remodeling translocases HLTF and ZRANB3 displayed an effect in Dux activation following RS.
Taken together, our results show that the up-regulation of 2-cells genes following RS not only requires ATR activation, but also downstream remodeling processes.
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Rooj, Arun Kumar. "THE INFLUENCE OF PROBIOTIC LACTOBACILLI ON GLUCOSE UPTAKE BY CACO-2 CELLS." MSSTATE, 2007. http://sun.library.msstate.edu/ETD-db/theses/available/etd-07052007-141908/.
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The resident microbes of human gastrointestinal tract cause both harmful and beneficial effects and these effects can be modulated by the administration of beneficial probiotic bacteria. Probiotics attribute several therapeutic and preventive beneficial effects, for both humans and animals. Despite the good effects of probiotic bacteria, the role of probiotic bacteria or their metabolites on the nutrient uptake by enterocytes is very less known. Most studies describe the genomic effects of probiotic bacteria on the transport properties. This thesis describes the short term (10 min or less) non-genomic effects of probiotic bacteria on the glucose uptake by human enterocytes like Caco-2 cells. The focus of the present study was to identify if metabolites of Lactobacilli sp. trigger a rapid non genomic regulation of glucose transporter proteins of enterocytes. The findings indicate that the regulatory molecules of bacterial metabolites can cause a rapid increase in glucose uptake by enterocytes.
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Stein, Merle [Verfasser], and Hans-Martin [Gutachter] Jäck. "A defined mitochondrial metabolic state in pre-B cells contributes to B cell homeostasis and is modulated by Swiprosin-2 / EFhd1 / Merle Stein ; Gutachter: Hans-Martin Jäck." Erlangen : Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2016. http://d-nb.info/1114989932/34.
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Stein, Merle Verfasser], and Hans-Martin [Gutachter] [Jäck. "A defined mitochondrial metabolic state in pre-B cells contributes to B cell homeostasis and is modulated by Swiprosin-2 / EFhd1 / Merle Stein ; Gutachter: Hans-Martin Jäck." Erlangen : Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2016. http://d-nb.info/1114989932/34.
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Poirier, Luc. "The degradation of the stem-loop binding protein at the late 2-cell stage of mouse embryogenesis /." Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=80351.
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The efficient processing of replication-dependent histone mRNA requires the Stem-Loop Binding Protein (SLBP). SLBP is also involved in regulating histone mRNA half-life, their nucleocytoplasmic transport, and their translation. Unlike somatic cells, where SLBP protein accumulates only in S-phase, SLBP protein is present throughout the first two embryonic cell cycles in mice. We report here that in late 2-cell mouse embryos there is a substantial, proteasome-dependent decrease in SLBP throughout the cell. Based on chromosome morphology, the degradation of SLBP protein in late 2-cell embryos is most likely a late G2-phase event. The degradation of SLBP protein is not simply a zygotic clock event, but requires development to the late 2-cell stage. Furthermore, SLBP protein degradation in 2-cell mouse embryos requires cyclin-dependent kinase (Cdk) activity, DNA replication, and zygotic genome activation. A model for SLBP protein degradation is proposed based on observations made in both early mouse embryos and somatic cells.
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Little, Scott Alan. "Enhancement of Cu(In,Ga)Se2 Solar Cells and Materials via the Incorporation of Silver." University of Toledo / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1333734769.
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Carvalho, Cyntia Helena Pereira de. "Estudo in vitro dos efeitos da BMP-2 e do seu antagonista Noggin sobre a prolifera??o e migra??o celulares em carcinoma epiderm?ide de l?ngua." Universidade Federal do Rio Grande do Norte, 2014. http://repositorio.ufrn.br:8080/jspui/handle/123456789/17166.
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Previous issue date: 2014-02-27Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico
Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy in the oral cavity and reach a large number of individuals, has become an important public health problem. Studies have demonstrated changes in pathway components BMP in various types of cancers as prostate, colon, breast, gastric and OSCCs. Is the current knowledge that these proteins may exert pro-tumor effect in more advanced stages of neoplastic development coming to favor progression and invasion tumor. The inhibition of the signaling pathway BMP-2 through its antagonists, have shown positive results of antitumor activity and use of Noggin may be a novel therapeutic target for cancer. Given this evidence and the few studies with BMP-2, Noggin and OSCC, the objective of this research was to evaluate the effect of BMP-2 and its antagonist Noggin on proliferation and migration cell in line of cell cultures of human tongue squamous cell carcinoma (SCC25). The study was divided in three groups, a control group, where SCC25 cells suffered no treatment, a BMP-2 group, in which cells were treated with 100ng/ml of BMP-2 and a group of cells that were treated with 100ng/ml of Noggin. For the proliferation assay and cell cycle were established three time intervals (24, 48 and 72 hours). Proliferative activity was investigated by trypan blue and cell cycle analysis by staining with propidium iodide flow cytometry. The potential for migration / invasion of SCC25 cells was performing by a cell invasion assay using Matrigel in a 48-hour interval. The proliferation curve showed a higher proliferation in cells treated with BMP-2 in 72 hours (p < 0.05), and lower overgrowth and cell viability in Noggin group. Recombinant proteins favored a greater percentage of cells in cell cycle phase Go/G1 with a statistically significant difference in the interval of 24 hours (p < 0.05). BMP- 2 produced a greater invasion of cells studied as well as its antagonist Noggin inhibits invasion of cells (p < 0.05). Thus, these results indicate that BMP-2 promotes malignant phenotype, dues stimulates proliferation and invasion of SCC25 cells and, its antagonist Noggin may be an alternative treatment, due to inhibit the tumor progression
O carcinoma epiderm?ide oral (CEO) representa a neoplasia maligna mais prevalente na cavidade oral e por atingir um grande n?mero de indiv?duos, acaba se tornado um relevante problema de sa?de p?blica. Muitos estudos demonstram altera??es nos componentes da via BMP em v?rios tipos de tumores, como os de pr?stata, c?lon, mama, g?stricos e CEOs. ? do conhecimento atual que essas prote?nas podem exercer efeito pr?-tumoral em est?gios mais avan?ados do desenvolvimento neopl?sico vindo a favorecer a progress?o e invas?o tumoral. A inibi??o da via de sinaliza??o da BMP-2, atrav?s dos seus antagonistas, tem mostrado resultados positivos de a??o antitumoral e que assim, o uso do Noggin pode ser um novo alvo terap?utico contra o c?ncer. Diante destas evid?ncias e dos escassos trabalhos com BMP-2, Noggin e CEO, o objetivo desta pesquisa foi avaliar o efeito da BMP-2 e seu antagonista Noggin sobre a prolifera??o e migra??o celulares em culturas de c?lulas de carcinoma epiderm?ide de l?ngua humana (SCC25). Foi feita a divis?o em tr?s grupos de estudo, um grupo controle, onde as c?lulas SCC25 n?o sofriam tratamento com subst?ncia alguma, um grupo BMP-2, no qual as c?lulas eram tratadas com 100ng/ml de BMP-2 e um grupo de c?lulas que eram tratadas com 100ng/ml de Noggin. Para o ensaio de prolifera??o e ciclo celular foram estabelecidos tr?s intervalos de tempo (24, 48 e 72 horas). A atividade proliferativa foi investigada por azul de tripan e a an?lise do ciclo celular atrav?s da marca??o por iodeto de prop?dio em Citometria de fluxo. O potencial de migra??o/invas?o das c?lulas SCC25 foi avaliado atrav?s da realiza??o de um ensaio de invas?o celular utilizando o matrigel em um intervalo de 48 horas. A curva de prolifera??o revelou maior crescimento celular nas c?lulas tratadas com BMP-2 no intervalo de 72 horas (p<0.05) e menor crecimento e viabilidade celular no grupo Noggin. As prote?nas recombinantes favoreceram a maior porcentagem das c?lulas na fase do ciclo celular Go/G1 com diferen?a estatisticamente significativa no intervalo de 24 horas (p<0,05). A BMP-2 promoveu uma maior invas?o das c?lulas estudadas, assim como o seu antagonista Noggin inibiu a invas?o das c?lulas estudadas (p<0,05). Dessa forma, os resultados indicam que a BMP-2 favorece o fen?tipo maligno, pois estimula a prolifera??o e invas?o das c?lulas SCC25 e seu antagonista Noggin pode ser uma alternativa terap?utica pois inibiu essas caracter?sticas pr?-tumorais
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Wallgren, Marcus. "Insight into the mitochondrial apoptotic pathway : The interplay of the pro-apoptotic Bax protein with oxidized phospholipids and its counterplayer, the pro-survival Bcl-2 protein." Doctoral thesis, Umeå universitet, Kemiska institutionen, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-61290.
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Apoptosis plays a crucial role in multicellular organisms by preserving tissue homeostasis and removing harmful cells. The anti-apoptotic B-cell CLL/lymphoma 2 (Bcl-2) and the pro-apoptotic Bcl-2-associated X protein (Bax) act as major regulators of the mitochondrial apoptotic pathway. Activation of Bax via stress signals causes its translocation to the mitochondrial outer membrane (MOM). There, Bax forms homo-oligomeric pores, leading to the release of apoptogenic factors, caspase activation and ultimately cell death. However, the underlying mechanism for the recruitment and pore forming activity of Bax is still not elucidated. Nevertheless, the mitochondrial membrane system seems to play an active and crucial role, presumably being directly involved in the onset of the mitochondrial apoptosis. Since the formation of reactive oxygen species (ROS) is a common stress signal and one of the hallmarks of the mitochondrial apoptosis, direct damage can occur to these membranes by the generation of oxidized phospholipids (OxPls), whose presence can crucially influence the pro-apoptotic action of Bax there. To better understand the impact of OxPls on membranes as well as their potential role in the mitochondrial apoptotic process, defined OxPl species were incorporated into phospholipid vesicles and studied with various biophysical techniques. Differential scanning calorimetry (DSC) and solid state nuclear magnetic resonance (NMR) spectroscopy were used to gain insight into changes in membrane properties in the presence of OxPls. In addition to circular dichroism (CD) spectroscopy, DSC and solid state NMR were furthermore performed to elucidate the impact of OxPls on Bax-membrane interactions. The occurrence of OxPls gave rise to dramatic changes in membrane organization and dynamics, manifested as lateral phase separation into OxPl-rich and -poor domains and modified hydration at the membrane interface. The presence of OxPls also had a great impact on the interaction between Bax and mitochondria-mimicking vesicles, strongly promoting the association of the protein with the membrane. At the MOM, Bax is believed to be inhibited by Bcl-2. How this inhibition occurs is still a mystery due to the lack of biophysical information on Bcl-2, in particular on the full-length protein variant. Since Bcl-2 is also one of the main culprits in the progression of various forms of cancer, knowledge of the structural and mechanistic properties of the full-length protein is essential for a fundamental understanding of its function at a molecular level. To this end, a method for the production of full-length Bcl-2 was developed. By performing cell-free protein synthesis, preparative amounts of the protein were obtained, which enabled a biophysical characterization of the putative interaction between Bax and Bcl-2 using CD and fluorescence spectroscopy. A protocol for the reconstitution of Bcl-2 into proteoliposomes was also developed, promising for future studies of the full-length protein in its native membrane environment; a prerequisite to fully understand its pro-survival functions as well as providing crucial information for the design of novel anti-cancer drugs.
Books on the topic "2-Cells stage"
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Blake, Levitt B., and Berkshire-Litchfield Environmental Council, eds. Cell towers: Wireless convenience or environmental hazard? : proceedings of the "Cell Towers Forum", State of the Science/State of the Law, December 2, 2000. Markham, Ont: Safe Goods/New Century Pub., 2001.
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Di Rosa, Francesca, and Tania H. Watts, eds. Bone Marrow T Cells at the Center Stage in Immunological Memory. Frontiers Media SA, 2017. http://dx.doi.org/10.3389/978-2-88945-093-0.
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Lloyd, Peter, Sarah Doaty, and Bevra H. Hahn. Aetiopathogenesis of systemic lupus erythematosus. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780198739180.003.0002.
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Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of immune dysregulation, autoreactive B and T cells, and the production of a broad, heterogeneous group of autoantibodies (autoAb). The pathogenesis of lupus can be divided into three stages: 1) genetic predisposition and environmental exposures, 2) loss of tolerance, and 3) immune activation. In this chapter we will discuss the aetiopathogenesis of systemic lupus erythematosus with emphasis placed on key autoantibodies, cytokines, the innate and adaptive immune system, tolerance, NETosis, genetics and epigenetics, environmental triggers and the role of gender.
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Almatar, Ashraf, and Michael A. S. Jewett. Treatment of localized renal cell cancer. Edited by James W. F. Catto. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199659579.003.0086.
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The incidence of localized renal cell carcinoma (RCC) has increased due to the widespread use of abdominal imaging, often for unrelated conditions. Despite improved understanding of the natural history of slow growth in many tumours and the impact of ageing and co-morbidities on patient survival, RCC is still the most lethal of genitourinary cancers and surgery remains the mainstay of treatment. Localized RCC is defined as stages T1-2 N0 M0. The relatively safe needle core biopsy is increasingly used, especially for small renal masses (SRMs), as we now know that up to 30% are benign and that RCC subtypes differ in biology and behaviour. Radical nephrectomy, either performed by open or laparoscopic technique, is indicated for stage T2 tumours or when partial nephrectomy (PN) is not believed to be feasible.
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Curry, Nicola, and Raza Alikhan. Normal platelet function. Edited by Patrick Davey and David Sprigings. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199568741.003.0281.
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The platelet is a small (2–4 µm in diameter), discoid, anucleate cell that circulates in the blood. In health, it plays a vital role in haemostasis, and in disease it contributes to disorders of bleeding and thrombosis. Platelets are produced from the surface of megakaryocytes in the bone marrow, under tight homeostatic control regulated by the cytokine thrombopoietin. Platelets have a lifespan of approximately 7–10 days, and usually circulate in the blood stream in a quiescent state. Intact, undamaged vessel walls help to maintain platelets in this inactive state by releasing nitric oxide, which acts both to dilate the vessel wall and to inhibit platelet adhesion, activation, and aggregation. After trauma to the blood vessel wall, platelets are activated and, acting in concert with the endothelium and coagulation factors, form a stable clot. This chapter addresses platelet structure and function, and the response of platelets to vessel injury.
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Erickson, Stephen B., Hatem Amer, and Timothy S. Larson. Urolithiasis, Kidney Transplantation, and Pregnancy and Kidney Disease. Oxford University Press, 2012. http://dx.doi.org/10.1093/med/9780199755691.003.0475.
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It was previously assumed that all kidney stones crystallized as urine passed through the renal tubules and were retained by means of crystal-tubular cell interactions. Recently uroscopy with papillary biopsies has shown 2 different pathways for stone formation, both mediated by calcium phosphate crystals. Kidney transplant has become the preferred treatment for patients with end-stage renal disease. Those benefiting from transplant included patients who would be deemed "high risk," such as those with diabetes mellitus and those older than 70 years. Anatomical changes associated with pregnancy are renal enlargement and dilatation of the calyces, renal pelvis, and ureters. Physiologic changes include a 30% to 50% increase in glomerular filtration rate and renal blood flow; a mean decrease of 0.5 mg/dL in the creatinine level and a mean decrease of 18 mg/dL in the serum urea nitrogen level; intermittent glycosuria independent of plasma glucose; proteinuria; aminoaciduria; increased uric acid excretion; increased total body water, with osmostat resetting; 50% increase in plasma volume and cardiac output; and increased ureteral peristalsis.
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Launay, Jean-Pierre, and Michel Verdaguer. Electrons in Molecules. Oxford University Press, 2018. http://dx.doi.org/10.1093/oso/9780198814597.001.0001.
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The book treats in a unified way electronic properties of molecules (magnetic, electrical, photophysical), culminating with the mastering of electrons, i.e. molecular electronics and spintronics and molecular machines. Chapter 1 recalls basic concepts. Chapter 2 describes the magnetic properties due to localized electrons. This includes phenomena such as spin cross-over, exchange interaction from dihydrogen to extended molecular magnetic systems, and magnetic anisotropy with single-molecule magnets. Chapter 3 is devoted to the electrical properties due to moving electrons. One considers first electron transfer in discrete molecular systems, in particular in mixed valence compounds. Then, extended molecular solids, in particular molecular conductors, are described by band theory. Special attention is paid to structural distortions (Peierls instability) and interelectronic repulsions in narrow-band systems. Chapter 4 treats photophysical properties, mainly electron transfer in the excited state and its applications to photodiodes, organic light emitting diodes, photovoltaic cells and water photolysis. Energy transfer is also treated. Photomagnetism (how a photonic excitation modifies magnetic properties) is introduced. Finally, Chapter 5 combines the previous knowledge for three advanced subjects: first molecular electronics in its hybrid form (molecules connected to electrodes acting as wires, diodes, memory elements, field-effect transistors) or in the quantum computation approach. Then, molecular spintronics, using, besides the charge, the spin of the electron. Finally the theme of molecular machines is presented, with the problem of the directionality control of their motion.
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Kuypers, Dirk R. J., and Maarten Naesens. Immunosuppression. Edited by Jeremy R. Chapman. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199592548.003.0281_update_001.
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Combination immunosuppressive therapy produces excellent short-term results after kidney transplantation. Long-term graft survival has improved, but less dramatically. Death with a functioning graft remains the primary cause of graft loss. Dosing of current immunosuppressive therapy balances between careful clinical interpretation of time-driven immunological risk assessments and drug-related toxicity on the one hand, and the use of simple surrogate drug exposure indicators like blood/plasma concentrations on the other. The combined use of calcineurin-inhibitors (CNIs) with mycophenolic acids and corticosteroids has been fine-tuned over the last decade, based on empirically derived observations as well as on the results of large multicentre randomized clinical studies. Corticosteroid withdrawal and avoidance are feasible, at least in patients with a low immunological risk, but CNI-free protocols have had few long-term successes. Some minimization strategies have increased risk of developing acute rejection or (donor-specific) anti-HLA antibodies, with deleterious effects on the graft. Mammalian target of rapamycin inhibitors (mTORi) have shown limited benefit in early CNI replacement regimens and their long-term use as primary drug is hampered by intolerance. In the setting of particular malignant disease occurring after transplantation, such as squamous cell carcinoma of the skin and Kaposi’s sarcoma, mTORi seem promising. Induction agents (anti-interleukin 2 receptor monoclonal antibodies, antithymocyte globulins) effectively diminish the risk of early immunological graft loss in recipients with moderate to high immunological risk but at the price of more infectious or malignant complications. While personalized transplantation medicine is only in its early stages of development, attempts are made to quantitatively measure the clinical degree of immunosuppression, to tailor immunosuppressive therapy more specifically to the patient’s individual profile, and to monitor graft status by use of invasive (e.g. surveillance renal biopsies) and non-invasive biomarkers. These scientific endeavours are a necessity to further optimize the current immunosuppressive therapy which will remain for some time to come.
Book chapters on the topic "2-Cells stage"
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Kirsch, Brian James, Shu-Jyuan Chang, Michael James Betenbaugh, and Anne Le. "Non-Hodgkin Lymphoma Metabolism." In The Heterogeneity of Cancer Metabolism, 103–16. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-65768-0_7.
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AbstractNon-Hodgkin lymphomas (NHLs) are a heterogeneous group of lymphoid neoplasms with different biological characteristics. About 90% of all lymphomas in the United States originate from B lymphocytes, while the remaining originate from T cells [1]. The treatment of NHLs depends on the neoplastic histology and stage of the tumor, which will indicate whether radiotherapy, chemotherapy, or a combination is the best suitable treatment [2]. The American Cancer Society describes the staging of lymphoma as follows: Stage I is lymphoma in a single node or area. Stage II is when that lymphoma has spread to another node or organ tissue. Stage III is when it has spread to lymph nodes on two sides of the diaphragm. Stage IV is when cancer has significantly spread to organs outside the lymph system. Radiation therapy is the traditional therapeutic route for localized follicular and mucosa-associated lymphomas. Chemotherapy is utilized for the treatment of large-cell lymphomas and high-grade lymphomas [2]. However, the treatment of indolent lymphomas remains problematic as the patients often have metastasis, for which no standard approach exists [2].
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Rodríguez-Otero, Paula, and Jesús F. San Miguel. "Post-CAR-T Cell Therapy (Consolidation and Relapse): Multiple Myeloma." In The EBMT/EHA CAR-T Cell Handbook, 173–76. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-030-94353-0_34.
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AbstractAdoptive cell therapy with BCMA-directed autologous CAR-T cells has shown very encouraging results in end-stage relapse and refractory multiple myeloma (MM), with overall response rates ranging between 73% and 96.9%, complete response (CR) rates between 33% and 67.9%, and MRD negativity in 50–74% of patients in the two largest phase 2 studies of ide-cel (idecabtagene autoleucel, KarMMa) and cilta-cel (ciltacabtagene autoleucel, CARTITUDE 1) reported thus far (Madduri et al. 2020; Munshi et al. 2021). Unfortunately, responses are usually not maintained, and no plateau has yet been seen in the survival curves. The median progression-free survival (PFS) in the KarMMa study of ide-cel was 8.8 months (95% CI, 5.6–11.6) among all 128 patients infused, increased to 12.1 months (95% CI, 8.8–12.3) among patients receiving the highest dose (450 × 106 CAR + T cells) and increased to 20.2 months (95% CI, 12.3–NE) among those achieving a CR. In the CARTITUDE-1 study, with a median follow-up of 12.4 months, the median PFS has not yet been reached, and the 12-month PFS rate was 76.6% (95% CI; 66.0–84.3). The absence of a clear plateau in PFS differs from what has been observed in DLBCL or B-ALL with currently approved CD-19-directed CAR-T cells, where (albeit with a shorter PFS and lower rates of CR) patients remaining free from relapse beyond 6 months are likely to enjoy prolonged disease control or even be cured.
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Li, Wei-bang, Ngoc Thanh Thuy Tran, and Shih-Yang Lin. "Diverse Phenomena in Stage-n Graphite Alkali-Intercalation Compounds." In Lithium-Ion Batteries and Solar Cells, 19–43. First edition. | Boca Raton, FL : CRC Press/ Taylor & Francis Group, LLC, 2021.: CRC Press, 2020. http://dx.doi.org/10.1201/9781003138327-2.
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Blaise, Didier, and Sabine Fürst. "Post-CAR-T Cell Therapy (Consolidation and Relapse): Lymphoma." In The EBMT/EHA CAR-T Cell Handbook, 169–71. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-030-94353-0_33.
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AbstractEven after a decade of use, CAR-T cell therapy for non-Hodgkin lymphoma (NHL) is still evolving, and disease control is now the main concern in the majority of experienced centres. Indeed, despite highly appealing objective response (OR) rates in refractory patients, the long-term overall survival (OS) of this population has only slightly improved. Pivotal studies have suggested that 2-year OS rates do not surpass 30%, even though results improve when complete response (CR) is achieved within the first 3 months after treatment (Wang et al. 2020; Schuster et al. 2019; Neelapu et al. 2017). Although achieving this exceptionally high level of OR is praiseworthy, similar improvements have not been made regarding OS, and current OS probabilities are not satisfactory. Of course, there are multiple reasons for this; a substantial proportion of patients either do not achieve an initial response or experience progression very soon after treatment, with poor OS (Chow et al. 2019). Both populations present with disease burden or aggressive cancer prior to CAR-T cell therapy, possibly having been referred too late in the course of treatment or waited too long before CAR-T cells were processed for them. Both of these issues have potential solutions, such as more widely publicizing the efficacy of CAR-T cells, which may increase referrals at an earlier stage, and developing methods, which are already being heavily investigated, for shortening the manufacturing process (Rafiq et al. 2020). In the latter case, the use of allogeneic lymphocytes could allow for already prepared cells to be readily used when needed and would most likely be the most efficient strategy as long as the risk of graft-versus host disease is offset (Graham and Jozwik 2018). Thus, achieving CR is a crucial step in increasing OS, as patients with partial response (PR) or stable disease (SD) present with lower OS, while currently, recurrence appears to be rare when CR is maintained for more than 6 months (Komanduri 2021). However, the disease will likely recur in more than half of patients in the months following treatment, possibly due to issues such as the poor persistence of CAR-T cells (which may not be as crucial as once thought for acute lymphoblastic leukaemia (Komanduri 2021)) or the loss of target antigen expression (which has been regularly documented (Rafiq et al. 2020)). Both of these mechanisms could potentially be used to develop methods that reduce recurrence after CAR-T cell therapy. In fact, the most popular approaches currently being investigated are attempting to either use two CAR-T cell types that each target different antigens or to create CAR-T cell constructs that target either multiple antigens or an antigen other than CD19 (Shah et al. 2020). The concomitant infusion of CAR-T cells with targeted therapies is also being explored in other B-cell malignancies and appears to both increase the CR rate and decrease recurrence (Gauthier et al. 2020). When recurrence does occur, patient OS is rather dismal, and the best remaining option would most likely be inclusion in a clinical trial. If this option is not available, salvage therapy may be attempted, although cytotoxic treatments are extremely limited given that most diseases have been refractory to numerous lines of treatment prior to immunotherapy. A few case reports and studies with a small patient population receiving anti-PD-1 antibodies, ibrutinib, or ImiDs have been reported with largely anecdotal supporting evidence (Byrne et al. 2019). However, even in the case of a new objective response (OR), the subsequent risk of recurrence is substantial and may invite further consolidation with allogeneic haematopoietic stem cell transplantation (Byrne et al. 2019), which has already been performed in patients treated for acute lymphoblastic leukaemia (Hay et al. 2019). However, the efficacy of this strategy remains to be validated in NHL patients in clinical trials. Further supporting evidence, although limited, has recently been reported concerning an additional treatment with CAR-T cells inducing an OR. Of the 21 NHL patients included in the study, the OR rate after the second infusion was 52% (CR, n = 4; PR, n = 7), with some durable responses inviting further investigations (Gauthier et al. 2021). Overall, with such poor outcomes after recurrence, current efforts are also focused on predicting the patients most likely to experience disease progression and that are potential candidates for preemptive consolidation therapy, although there is no doubt that patients who do not achieve a rapid CR should be the first candidates. Additionally, immune monitoring should encompass not only CAR-T cell survival but also the detection of circulating tumour DNA (Komanduri 2021) because this could aid in detecting subclinical recurrence and in deciding whether consolidation or maintenance therapy should be administered. However, currently, all these approaches are highly speculative and require further clinical study.
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Malik, Sajid, and Sujith Wijerathne. "Laparoscopic Sleeve Gastrectomy." In Mastering Endo-Laparoscopic and Thoracoscopic Surgery, 285–90. Singapore: Springer Nature Singapore, 2022. http://dx.doi.org/10.1007/978-981-19-3755-2_41.
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AbstractBariatric surgery (BS) has proved its role in treating obesity and related comorbidities. The number of Laparoscopic Sleeve Gastrectomies (LSGs) performed globally has increased markedly and has become “trendy” among bariatric surgeons in the last few years [1]. LSG has attained its position as the primary procedure of choice in bariatric surgery for morbid obesity. In this procedure, 80% of the stomach, mainly the body and fundus are removed longitudinally, leaving behind a sleeve of the stomach along the lesser curve [2, 3]. The procedure can be performed by minimally invasive approaches as well as single incision access or even robotic surgery with comparable results [4, 5]. The weight loss is achieved by restricting the food entering the stomach. Another factor in the effectiveness of weight loss in sleeve gastrectomy is the decrease in blood levels of ghrelin, “the hormone that stimulates hunger,” and a majority of cells responsible for producing this hormone is found in the fundus which is removed during this procedure. This procedure can be performed as the first stage in more complex bariatric cases including cases of super-obesity before procedures like Roux-en-Y gastric bypass or the duodenal switch can be performed [6]. The objective is to achieve an initial weight loss that would help to perform more extensive mixed restrictive or malabsorptive procedures safely and effectively [7–9].
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Symes, M. O., C. M. P. Collins, T. Lai, and P. J. B. Smith. "The influence of tumour stage on in vitro sensitivity of renal carcinoma cells to Mitozantrone." In Proceedings of the 3rd International Congress on Neo-Adjuvant Chemotherapy, 392–94. Paris: Springer Paris, 1991. http://dx.doi.org/10.1007/978-2-8178-0782-9_95.
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Kim, Myoung Sub, Jin Hyung Jun, Jin Ho Oh, Hyeong Joon Kim, Jae Sung Roh, Suk Kyoung Hong, and Doo Jin Choi. "Electrical Switching Characteristics of Nitrogen Doped Ge2Sb2Te5 Based Phase Change Random Access Memory Cell." In Solid State Phenomena, 21–24. Stafa: Trans Tech Publications Ltd., 2007. http://dx.doi.org/10.4028/3-908451-31-0.21.
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Kim, Ki Hyun, Se Jin Ahn, Byung Tae Ahn, and Kyung Hoon Yoon. "Effects of Se Atmosphere on the Densification of Absorber Layer Using Cu(In,Ga)Se2 Nanoparticles for Solar Cells." In Solid State Phenomena, 983–86. Stafa: Trans Tech Publications Ltd., 2007. http://dx.doi.org/10.4028/3-908451-31-0.983.
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Hong, Tae Whan, Dong Hun Lee, Hae Suck Park, Dong Hwan Suh, and Whan Gi Kim. "Nano Composite Membranes of Branched Sulfonated Poly(Ether Ketone Sulfone) and SiO2 for Fuel Cell Application." In Solid State Phenomena, 943–46. Stafa: Trans Tech Publications Ltd., 2007. http://dx.doi.org/10.4028/3-908451-31-0.943.
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Mushinski, J. F., J. D. Mountz, J. H. Pierce, J. G. Pumphrey, R. M. Skurla, F. D. Finkelman, D. Givol, and W. F. Davidson. "Expression of the Murine Proto-Oncogene bcl-2 Is Stage Specific and Cell-Type Specific." In Current Topics in Microbiology and Immunology, 332–36. Berlin, Heidelberg: Springer Berlin Heidelberg, 1988. http://dx.doi.org/10.1007/978-3-642-74006-0_44.
Full textConference papers on the topic "2-Cells stage"
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Wang, Ziwei, Bin Li, Junbin Liu, Jingfan Chen, and Yao Liu. "Post-stall behavior of 2-stage compressor." In GPPS Xi'an21. GPPS, 2022. http://dx.doi.org/10.33737/gpps21-tc-300.
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Rotating stall in the high speed compressor can lead to violent disruption of flow, damage to the blade structures and, eventually, engine shutdown. To investigate the mechanism of stall inception and stall propagation in multi-stage compressor, the onset and transient behavior of rotating stall in a transonic 2-stage compressor are simulated with full-annulus unsteady method, based on the in-house software ASPAC. The choked throttle model is adopted. The results indicate that, in the 2-stage compressor, stall cells exist in rotors of both compressor stages, which propagate at 43% and 25% of the shaft rotational speed respectively. Meanwhile, the rotating stall disturbance can be suppressed by stator of the first stage, which will weaken the influence of rotating stall on the compressor stage downstream.
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Hayashi, Takao, Takashi Minemoto, Tsutomu Araki, and Hideyuki Takakura. "Fabrication of Cu(In,Al)Se 2 solar cells by three-stage evaporation process." In Solar Energy + Applications, edited by Bolko von Roedern and Alan E. Delahoy. SPIE, 2007. http://dx.doi.org/10.1117/12.731718.
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Henslee, Erin A., Mike B. Sano, Eva M. Schmelz, and Rafael V. Davalos. "Isolation of Human Breast Cancer Cells by Metastatic Stage Using Contactless Dielectrophoresis." In ASME 2010 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2010. http://dx.doi.org/10.1115/sbc2010-19650.
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Dielectrophoresis (DEP) has become a promising technique to separate and identify cells and microparticles suspended in a medium based on their physical and electrical properties. DEP is the motion of a particle in a suspending medium due to the presence of a nonuniform electric field [1]. We have recently developed a robust, simple, and inexpensive technique, contactless dielectrophoresis (cDEP), to provide non uniform electric fields in microfluidic channels required for DEP cell manipulation without direct contact between the electrodes and the sample [2]. In this method, an electric field is created in the sample microchannel using electrodes inserted into two conductive microchambers, which are separated from the sample channel by thin insulating barriers. These insulating barriers exhibit a capacitive behaviour and therefore an electric field can be produced in the main channel by applying an AC field across the barriers [2]. The absence of contact between electrodes and the sample fluid inside the channel prevents bubble formation and avoids any contaminating effects the electrodes may have on the sample. Furthermore, reduced joule heating and a simplified inexpensive fabrication process are the other noticeable advantages of this new technique.
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Tang, Xin, Tony Cappa, Theresa Kuhlenschmidt, Mark Kuhlenschmidt, and Taher A. Saif. "A Novel Way to Characterize the Non-Specific Surface Adhesion of Cancer Cells and Understand Cancer Metastasis." In ASME 2009 International Mechanical Engineering Congress and Exposition. ASMEDC, 2009. http://dx.doi.org/10.1115/imece2009-11953.
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Cancer deaths are mostly caused by the metastasis of the malignant cells, not by the primary tumor itself. During metastasis, cancer cells detach from the primary tumor, spread to different tissues via blood circulation or lymph system, and reattach to invade new tissues and organs. In this project, we hypothesize that cancer cells manage their invasion by changing their surface adhesivity. To study the cell surface adhesivity, a novel and versatile microelectromechanical systems (MEMS) force sensor is developed to quantify the strength of adhesion between living cancer cells and a probe. The Silicon sensors consist of a probe and 2 flexible cantilever beams, while the probe is used to contact the cancer cell and the flexible beams are used to measure the cell force response in the range from nN to uN. The spring constant of the sensor is 14 nN/ μm. Our results demonstrate that the aggressive HCT-8 cells (from human colon adenocarcinoma) show high nonspecific adhesivity when they aggregate into cell islands, and low surface non-specific adhesivity after they disassociate from the cell islands. The surface adhesivity of less aggressive Caco-2 cells (from human colon carcinoma) and normal MA104 cell (from monkey kidney) are found to be lower than that of before-disassociation HCT-8 cells. Furthermore, the adhesion force response of cancer cells is found to show 2-slope force behavior, which is different from previous results of focal-adhesion detachment experiments. The 2-stage force bearing model is proposed to interpret the underlying mechanism.
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Saxer-Felici, H. M., A. P. Saxer, F. Ginter, A. Inderbitzin, and G. Gyarmathy. "Structure and Propagation of Rotating Stall in a Single- and a Multi-Stage Axial Compressor." In ASME 1999 International Gas Turbine and Aeroengine Congress and Exhibition. American Society of Mechanical Engineers, 1999. http://dx.doi.org/10.1115/99-gt-452.
Full textAbstract:
The structure and propagation of rotating stall cells in a single- and a two-stage subsonic axial compressor is addressed in this paper using computational and experimental analysis. Unsteady solutions of the 2-D inviscid compressible (Euler) equations of motion are presented for one operating point in the fully-developed rotating stall regime for both a single- and a two-stage compressor. The inviscid assumption is verified by comparing the single-stage 2-D in viscid/compressible solution with an equivalent 2-D viscous (Navier-Stokes) result for incompressible flow. The structure of the rotating stall cell is analyzed and compared for the single- and two-stage cases. The numerical solutions are validated against experimental data consisting of flow visualization and unsteady row-by-row static pressure measurements obtained in a four-stage water model of a subsonic compressor. The CFD solutions supply a link between the observed experimental features and provide additional information on the structure of the stall flow. Based on this study. supporting assumptions regarding the driving mechanisms for the propagation of fully-developed rotating stall cells and their structure are postulated. In methodical respect the results suggest that the inviscid model is able to reproduce the essentials of the flow physics associated with the propagation of fully-developed, full-span rotating stall in a subsonic axial compressor.
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Best, R. C., J. G. C. LaFlamme, and W. C. Moffatt. "Flow Measurements in Rotating Stall in a Gas Turbine Engine Compressor." In ASME 1988 International Gas Turbine and Aeroengine Congress and Exposition. American Society of Mechanical Engineers, 1988. http://dx.doi.org/10.1115/88-gt-219.
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For many years, there has been a significant effort, both experimental and theoretical, to better understand the rotating stall phenomenon. For very practical reasons, most of the experimental investigations have focussed on laboratory compressors with very low stage pressure ratios. The aim of the present study was to extend the range of available data to industrial-size compressors operating in a typical real life environment. This paper reports results of detailed flow measurements made on the first four stages of a 10 stage compressor operating as part of a turbojet engine mounted on a test stand. Hot sensor anemometer measurements made at a number of axial and tangential locations showed clear evidence of rotating stall in the front stages during part-speed operation of the engine. Stall cell configuration and rotative speed, and details of flow speed and angle at hub, mid and tip radii are presented in the paper. On the basis of the measurements it is concluded that (1) although rotating stall has its origins in a flow instability, it is a highly reproducible phenomenon, (2) reverse flow can occur within the cells, as has been reported by several other observers and (3) the cells retain an axial (as opposed to helical) configuration on passing from stage to stage through the compressor.
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Levy, Y., J. Pismenny, A. Reissner, and W. Riess. "Experimental Study of Rotating Stalls in a Four-Stage Axial Compressor." In ASME Turbo Expo 2002: Power for Land, Sea, and Air. ASMEDC, 2002. http://dx.doi.org/10.1115/gt2002-30362.
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The relationships between the frequencies of pressure oscillation ωOSC and the rotor speed (frequencies of rotor rotation) ωRR, as well as between the phases of pressure oscillation and geometrical angles of the sensor locations on the compressor casing (in the transverse cross-section) were determined experimentally. In addition, the phase–location relation permitted determination of the number of stall cells under established rotating stall. Literature on rotating stall in axial compressors typically refers to rotating stall with frequencies less than the rotor speed. This paper is concerned with two types of rotating stall, observed during experiments in a four-stage axial compressor, operating at the same rotor speed, n/nd = 0.95, where n is the rotor speed and nd the rotor data-sheet speed. The rotating stall frequencies were both, smaller and larger than the rotor speed. The relationships between ωOSC and ωRR were determined by four methods: directly from the time diagram of the pressure oscillation, from the diagrams of pressure variation in space and time, from the autocorrelation characteristics, and from the frequency characteristics of the pressure signals. All methods indicated values of ωOSC/ωRR in the form of integer ratios, 3:7 and 11:2. The phases of pressure oscillation in the transverse cross-section are equal to the sensor angles in compressor stator (in the case ωOSC/ωRR = 3:7) or are three times larger (in the case ωOSC/ωRR = 11:2), in accordance with the classical theory of single-cell and three-cell configurations of rotating stall, respectively.
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Nagayama, Kazuaki, Yuki Yahiro, and Takeo Matsumoto. "In Situ Observation of Nuclear Behavior During Laser Nano-Dissection of Actin Stress Fibers: Mechanical Interaction Between Actin Stress Fibers and Nucleus." In ASME 2011 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2011. http://dx.doi.org/10.1115/sbc2011-53264.
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In order to elucidate the mechanotransduction mechanism of adherent cells, it is crucial to clarify how forces applied to cells are transmitted through intracellular components. Actin stress fibers (SFs) play important roles in various cellular events including cell proliferation [1], differentiation [2] and gene expression [3]. SFs generate internal forces and contribute to physical interactions between cells and extracellular matrices [4]. It has recently been suggested that cytoskeletons have the potential to interact with nuclei via certain nuclear membrane proteins [5, 6]. However, it remains unclear at this stage whether SFs are involved in a mechanical interaction with the cell nucleus and their internal forces are transmitted directly to the nucleus.
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van Turnhout, Mark C., Stefan A. H. de Vries, Corrinus C. van Donkelaar, and Cees W. J. Oomens. "Mechanical Chondrocyte Damage Thresholds." In ASME 2012 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/sbc2012-80426.
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Chondrocyte content in articular cartilage is very low. Only 2% to 5% of the tissue volume consists of chondrocytes [1]. Yet, these cells are responsible for maintenance of the tissue. Hence, the loss of chondrocytes that is often occurring at an early stage of cartilage degeneration is detrimental to articular cartilage. Excessive mechanical loading is known to be a cause of cell death. However, mechanical thresholds beyond which chondrocyte apoptosis would be induced are unknown.
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Saxer-Felici, H. M., A. P. Saxer, A. Inderbitzin, and G. Gyarmathy. "Prediction and Measurement of Rotating Stall Cells in an Axial Compressor." In ASME 1998 International Gas Turbine and Aeroengine Congress and Exhibition. American Society of Mechanical Engineers, 1998. http://dx.doi.org/10.1115/98-gt-067.
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This paper presents a parallel numerical and experimental study of rotating stall cells in an axial compressor. Based on previous theoretical and experimental studies stressing the importance of fluid inertia and momentum exchange mechanisms in rotating stall, a numerical simulation using the Euler equations is conducted. Unsteady 2-D solutions of rotating stall behavior are obtained in a one-stage low subsonic axial compressor. The structure and speed of propagation of one fully developed rotating stall cell together with its associated unsteady static pressure and throughflow field distributions are presented. The numerical capture of a stalled flow region starting from a stable high-flow operating point with an axisymmetric flow distribution and evolving at a reduced mass flow operating point into a rotating stall pattern is also discussed. The experimental data (flow visualization, time-averaged and unsteady row-by-row static pressure measurements) acquired in a four-stage water model of a subsonic axial compressor covers a complete characteristic line ranging from high mass flow in the stable regime to zero throughflow. Stall inception is presented together with clearly marked different operating zones within the unstable regime. For one operating point in the unstable regime, the speed of propagation of the cell as well as the static pressure spikes at the front and rear boundaries of the rotating stall cell are compared between computations, measurements and an idealized theory based on momentum exchange between blade rows entering and leaving the stalled cell. In addition, the time-evolution of the pressure trace at the rotor/stator interface is presented. This study seems to support the assumption that the cell structure and general mechanism of full-span rotating stall propagation are essentially governed by inertial effects and momentum exchange between the sound and stalled flow at the cell edges.
Reports on the topic "2-Cells stage"
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Petitte, James, Hefzibah Eyal-Giladi, and Malka Ginsburg. The Study of Primordial Germ Cell Development as a Tool for Gene Transfer in Chickens. United States Department of Agriculture, October 1991. http://dx.doi.org/10.32747/1991.7561071.bard.
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The ability to introduce novel genetic material into the genome of commercial poultry has been impeded by a lack of kowledge regarding the origin in the early embryo of the target cell of interest, namely, the germ cell. Hence, this project investigated the emergence of primordial germ cells (PGCs) during the early development of the avian embryo to aid in efforts to produce transgenic poultry on a routine basis. The strategy was to introduce foreign DNA into the area of the unincubated embryo that is destined to give rise to the germ line. The objectives of this project were: 1) to identify and localize a subpopulation of cells in the early embryo which will give rise to PGCs, 2) to determine the best location and stage of development to transfer donor cells for efficient germline chimerism, and 3) to transfect donor cells to produce transgenic/germline chimeric embryos. We show that by using the monoclonal antibody SSEA-1 and by various cell culture techniques that germ cells appear to segregate from the somatic lineages at St. X., a process that is gradual and continues through St. XIV. Using microsurgical transplantation between quail and chick embryos, we demonstrated that the inner 1/3 of the area pellucida between states X-XII gives rise to about 2/3 of the germ cell population at the time of their residence in the germinal crescent. Because of the non-localized emergence of PGCs, attempts to introduce foreign DNA into clonal precursors of germ cells through liposome-mediated transfection yielded unacceptable levels of efficiency. However, through our investigation of germ cell origins, an in vitro model of germ cell differentiation was developed that could offer a means of determining the factors required for the long term culture of avian PGCs thereby providing a convenient means of manipulating the avian genome.
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Blumwald, Eduardo, and Avi Sadka. Sugar and Acid Homeostasis in Citrus Fruit. United States Department of Agriculture, January 2012. http://dx.doi.org/10.32747/2012.7697109.bard.
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Citrus fruit quality standards have been determined empirically, depending on species and on the particular growing regions. In general, the TSS (total soluble solids) to total acidity (TA) ratio determines whether citrus fruit can be marketed. Soluble sugars account for most of the TSS during harvest while TA is determined almost solely by the citric acid content, which reaches levels of 1-5% by weight in many cultivated varieties. Acid and sugar homeostasis in the fruit is critical for the management of existing cultivars, the development of new cultivars, the improvement of pre- and post-harvest strategies and the control of fruit quality and disorders. The current proposal (a continuation of a previous proposal) aimed at: (1) completing the citrus fruit proteome and metabolome, and establish a citrus fruit functional database, (2) further characterization of the control of fruit acidity by studying the regulation of key steps affecting citrate metabolism, and determine the fate of citrate during acid decline stage, and (3) Studying acid and sugar homeostasis in citrus fruits by characterizing transport mechanisms across membranes. These aims were completed as the following: (1) Our initial efforts were aimed at the characterization and identification of citric acid transporters in citrus juice cells. The identification of citrate transporters at the vacuole of the citrus juice cell indicated that the steady-state citrate cytosolic concentration and the action of the cytosolic aconitase were key elements in establishing the pH homeostat in the cell that regulates the metabolic shift towards carbon usage in the fruit during the later stages of fruit development. We focused on the action of aconitase, the enzyme mediating the metabolic use of citric acid in the cells, and identified processes that control carbon fluxes in developing citrus fruits that control the fruit acid load; (2) The regulation of aconitase, catalyzing a key step in citrate metabolism, was further characterized by using two inhibitors, citramalte and oxalomalte. These compounds significantly increased citrate content and reduced the enzyme’s activity. Metabolite profiling and changes of amino-acid metabolizing enzymes in oxalomalate- treated cells suggested that the increase in citrate, caused by aconitase inhibition, induces amino acid synthesis and the GABA shunt, in accordance with the suggested fate of citrate during the acid decline stage in citrus fruit. (3) We have placed a considerable amount of time on the development of a citrus fruit proteome that will serve to identify all of the proteins in the juice cells and will also serve as an aid to the genomics efforts of the citrus research community (validating the annotation of the fruit genes and the different ESTs). Initially, we identified more than 2,500 specific fruit proteins and were able to assign a function to more than 2,100 proteins (Katz et al., 2007). We have now developed a novel Differential Quantitative LC-MS/MS Proteomics Methodology for the identification and quantitation of key biochemical pathways in fruits (Katz et al., 2010) and applied this methodology to identify determinants of key traits for fruit quality (Katz et al., 2011). We built “biosynthesis maps” that will aid in defining key pathways associated with the development of key fruit quality traits. In addition, we constructed iCitrus (http://wiki.bioinformatics.ucdavis.edu/index.php/ICitrus), a “functional database” that is essentially a web interface to a look-up table that allows users to use functional annotations in the web to identify poorly annotated citrus proteins. This resource will serve as a tool for growers and field extension specialists.
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Splitter, Gary, Zeev Trainin, and Yacov Brenner. Lymphocyte Response to Genetically Engineered Bovine Leukemia Virus Proteins in Persistently Lymphocytic Cattle from Israel and the U.S. United States Department of Agriculture, July 1995. http://dx.doi.org/10.32747/1995.7570556.bard.
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The goal of this proposal was to identify proteins of BLV recognized by lymphocyte subpopulations and determine the contribution of these proteins to viral pathogenesis. Our hypothesis was that BLV pathogenesis is governed by the T-cell response and that the immune system likely plays an important role in controlling the utcome of infection. Our studies presented in ths final report demonstrate that T cell competency declines with advancing stages of infection. Dramatic differences were observed in lymphocyte proliferation to recombinant proteins encoded by BLV gag (p12, p15, and p24) and env (gp30 and gp15) genes in different disease stages. Because retroviruses are known to mutate frequently, examinatin of infected cattle from both Israel and the United States will likely detect variability in the immune response. This combined research approach provides the first opportunity to selectively address the importance of T-cell proliferation to BLV proteins and cytokines produced during different stages of BLV infection. Lack of this information regarding BLV infection has hindered understanding lympocyte regulation of BLV pathogenesis. We have developed the essential reagents necessary to determine the prominence of different lymphocyte subpopulations and cytokines produced during the different disease stages within the natural host. We found that type 1 cytokines (IL-2 and IFN-g) increased in PBMCs from animals in early disease, and decreasd in PBMCs from animals in late disease stages of BLV infection, while IL-10, increased with disease progression. Recently, a dichotomy between IL-12 and IL-10 has emerged in regards to progression of a variety of diseases. IL-12 activates type 1 cytokine production and has an antagonistic effect on type 2 cytokines. Here, using quantitative competitive PCR, we show that peripheral blood mononuclear cells from bovine leukemia virus infected animals in the alymphocytotic disease stage express increased amount of IL-12 p40 mRNA. In contrast, IL-12 p40 mRNA expression by PL animals was significantly decreased compared to normal and alymphocytotic animals. To examine the functions of these cytokines on BLV expression, BLV tax and pol mRNA expression and p24 protein production were quantified by competitive PCR, and by immunoblotting, respectively. IL-10 inhibited BLV tax and pol mRNA expression by BLV-infected PBMCs. In addition, we determined that macrophages secret soluble factor(s) that activate BLV expression, and that secretion of the soluble factor(s) could be inhibited by IL-10. In contrast, IL-2 increased BLV tax and pol mRNA, and p24 protein production. These findings suggest that macrophages have a key role in regulating BLV expression, and IL-10 produced by BLV-infected animals in late disease stages may serve to control BLV expression, while IL-2 in the early stage of disease may activate BLV expression. PGE2 is an important immune regulator produced only by macrophages, and is known to facilitate HIV replication. We hypothesized that PGE2 may regulate BLV expression. Here, we show that cyclooxygenase-2 (COX-2) mRNA expression was decreased in PBMCs treated with IL-10, while IL-2 enhanced COX-2 mRNA expression. In contrast, addition of PGE2 stimulated BLV tax and pol mRNA expression. In addition, the specific COX-2 inhibitor, NS-398, inhibited BLV expression, while addition of PGE2 increased BLV tax expression regardless of NS-398. These findings suggest that macrophage derived cyclooxygenase -2 products, such as PGE2, may regulate virus expression and disease rogression in BLV infection, and that cytokines (IL-2 and IL-10) may regulate BLV expression through PGE2 production.
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Liang, BiYan, BiYan Liang, and Jian Wang. A Meta Analysis of the Efficacy of Tonic Method in Traditional Chinese Medicine for AIDS Immunological Nonresponses. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, April 2022. http://dx.doi.org/10.37766/inplasy2022.4.0077.
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Review question / Objective: To evaluate the efficacy of tonic method in treating AIDS immunological nonresponses. Eligibility criteria: ①Study type: RCT based on tonic method in TCM for AIDS INRs. The language was limited to Chinese and English. ②The research object: HIV/AIDS patients with any disease stage; the intervention objects were adults with no gender restrictions. ③Intervention measures: The treatment group was treated with tonic prescriptions combined with ART, including four types of prescriptions for nourishing qi, nourishing blood, nourishing yin, or nourishing yang; the dosage, frequency, and method were not limited. The control group was treated with ART or mock agent and placebo. ④Outcome indicators: The observation indicators reported in the included studies should include at least one of the following indicators: 1) Effective rate of immune function reconstruction: formulated in accordance with "AIDS (Adult) Chinese Medicine Diagnosis and Treatment Program" (2016 Edition) , effective: CD4 + T lymphocyte counts increased by ≥ 50 cells/l or ≥ 30%, invalid: CD4+ T lymphocyte counts decreased by ≥ 50 cells/l or ≥ 30%; total effective rate = effective number/total number; 2) CD4+T lymphocyte counts level.
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Carpita, Nicholas C., Ruth Ben-Arie, and Amnon Lers. Pectin Cross-Linking Dynamics and Wall Softening during Fruit Ripening. United States Department of Agriculture, July 2002. http://dx.doi.org/10.32747/2002.7585197.bard.
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Our study was designed to elucidate the chemical determinants of pectin cross-linking in developing fruits of apple and peach and to evaluate the role of breakage cross-linkages in swelling, softening, and cell separation during the ripening. Peaches cell walls soften and swell considerably during the ripening, whereas apples fruit cells maintain wall firmness but cells separate during late stages of ripening. We used a "double-reduction" technique to show that levels of non-methyl esters of polyuronic acid molecules were constant during the development and ripening and decreased only in overripe fruit. In peach, methyl and non-methyl esters increased during the development and decreased markedly during the ripening. Non-methyl ester linkages in both fruit decreased accompanied fruit softening. The identity of the second component of the linkage and its definitive role in the fruit softening remain elusive. In preliminary examination of isolated apples cell walls, we found that phenolic compounds accumulate early in wall development but decrease markedly during ripening. Quantitative texture analysis was used to correlate with changes to wall chemistry from the fresh-picked ripe stage to the stage during storage when the cell separation occurs. Cell wall composition is similar in all cultivars, with arabinose as the principal neutral sugar. Extensive de-branching of these highly branched arabinans pre-stages softening and cell-cell separation during over-ripening of apple. The longer 5-arabinans remain attached to the major pectic polymer rhamnogalacturonan I (RG I) backbone. The degree of RG I branching, as judged from the ratios of 2-Rha:2,4-Rha, also decreases, specially after an extensive arabinan de-branching. Loss of the 4-Rham linkages correlated strongly with the softening of the fruit. Loss of the monomer or polymer linked to the RG I produce directly or indirectly the softening of the fruit. This result will help to understand the fruit softening and to have better control of the textural changes in fruit during the ripening and especially during the storage. 'Wooliness', an undesirable mealy texture that is induced during chilling of some peach cultivars, greatly reduces the fruit storage possibilities. In order to examine the hypothesis that the basis for this disorder is related to abnormality in the cell wall softening process we have carried out a comparative analysis using the resistant cultivar, Sunsnow, and a sensitive one, Hermosa. We investigated the activity of several pectin- and glycan-modifying enzymes and the expression of their genes during ripening, chilling, and subsequent shelf-life. The changes in carbohydrate status and in methyl vs. non-methyl uronate ester levels in the walls of these cultivars were examined as well to provide a basis for comparison of the relevant gene expression that may impact appearance of the wooly character. The activities of the specific polygalacturonase (PGase) and a CMC-cellulase activities are significantly elevated in walls of peaches that have become wooly. Cellulase activities correlated well with increased level of the transcript, but differential expression of PGase did not correspond with the observed pattern of mRNA accumulation. When expression of ethylene biosynthesis related genes was followed no significant differences in ACC synthase gene expression was observed in the wooly fruit while the normal activation of the ACC oxidase was partially repressed in the Hermosa wooly fruits. Normal ripening-related loss of the uronic acid-rich polymers was stalled in the wooly Hermosa inconsistent with the observed elevation in a specific PGase activity but consistent with PG gene expression. In general, analysis of the level of total esterification, degree of methyl esterification and level of non-methyl esters did not reveal any major alterations between the different fruit varieties or between normal and abnormal ripening. Some decrease in the level of uronic acids methyl esterification was observed for both Hermosa and Sunsnow undergoing ripening following storage at low temperature but not in fruits ripening after harvest. Our results support a role for imbalanced cell wall degradation as a basis for the chilling disorder. While these results do not support a role for the imbalance between PG and pectin methyl esterase (PME) activities as the basis for the disorder they suggest a possible role for imbalance between cellulose and other cell wall polymer degradation during the softening process.
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Barg, Rivka, Erich Grotewold, and Yechiam Salts. Regulation of Tomato Fruit Development by Interacting MYB Proteins. United States Department of Agriculture, January 2012. http://dx.doi.org/10.32747/2012.7592647.bard.
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Background to the topic: Early tomato fruit development is executed via extensive cell divisions followed by cell expansion concomitantly with endoreduplication. The signals involved in activating the different modes of growth during fruit development are still inadequately understood. Addressing this developmental process, we identified SlFSM1 as a gene expressed specifically during the cell-division dependent stages of fruit development. SlFSM1 is the founder of a class of small plant specific proteins containing a divergent SANT/MYB domain (Barg et al 2005). Before initiating this project, we found that low ectopic over-expression (OEX) of SlFSM1 leads to a significant decrease in the final size of the cells in mature leaves and fruits, and the outer pericarp is substantially narrower, suggesting a role in determining cell size and shape. We also found the interacting partners of the Arabidopsis homologs of FSM1 (two, belonging to the same family), and cloned their tomato single homolog, which we named SlFSB1 (Fruit SANT/MYB–Binding1). SlFSB1 is a novel plant specific single MYB-like protein, which function was unknown. The present project aimed at elucidating the function and mode of action of these two single MYB proteins in regulating tomato fruit development. The specific objectives were: 1. Functional analysis of SlFSM1 and its interacting protein SlFSB1 in relation to fruit development. 2. Identification of the SlFSM1 and/or SlFSB1 cellular targets. The plan of work included: 1) Detailed phenotypic, histological and cellular analyses of plants ectopically expressing FSM1, and plants either ectopically over-expressing or silenced for FSB1. 2) Extensive SELEX analysis, which did not reveal any specific DNA target of SlFSM1 binding, hence the originally offered ChIP analysis was omitted. 3) Genome-wide transcriptional impact of gain- and loss- of SlFSM1 and SlFSB1 function by Affymetrix microarray analyses. This part is still in progress and therefore results are not reported, 4) Search for additional candidate partners of SlFSB1 revealed SlMYBI to be an alternative partner of FSB1, and 5) Study of the physical basis of the interaction between SlFSM1 and SlFSB1 and between FSB1 and MYBI. Major conclusions, solutions, achievements: We established that FSM1 negatively affects cell expansion, particularly of those cells with the highest potential to expand, such as the ones residing inner to the vascular bundles in the fruit pericarp. On the other hand, FSB1 which is expressed throughout fruit development acts as a positive regulator of cell expansion. It was also established that besides interacting with FSM1, FSB1 interacts also with the transcription factor MYBI, and that the formation of the FSB1-MYBI complex is competed by FSM1, which recognizes in FSB1 the same region as MYBI does. Based on these findings a model was developed explaining the role of this novel network of the three different MYB containing proteins FSM1/FSB1/MYBI in the control of tomato cell expansion, particularly during fruit development. In short, during early stages of fruit development (Phase II), the formation of the FSM1-FSB1 complex serves to restrict the expansion of the cells with the greatest expansion potential, those non-dividing cells residing in the inner mesocarp layers of the pericarp. Alternatively, during growth phase III, after transcription of FSM1 sharply declines, FSB1, possibly through complexing with the transcription factor MYBI serves as a positive regulator of the differential cell expansion which drives fruit enlargement during this phase. Additionally, a novel mechanism was revealed by which competing MYB-MYB interactions could participate in the control of gene expression. Implications, both scientific and agricultural: The demonstrated role of the FSM1/FSB1/MYBI complex in controlling differential cell growth in the developing tomato fruit highlights potential exploitations of these genes for improving fruit quality characteristics. Modulation of expression of these genes or their paralogs in other organs could serve to modify leaf and canopy architecture in various crops.
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Fields, Michael J., Mordechai Shemesh, and Anna-Riitta Fuchs. Significance of Oxytocin and Oxytocin Receptors in Bovine Pregnancy. United States Department of Agriculture, August 1994. http://dx.doi.org/10.32747/1994.7568790.bard.
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Oxytocin has multiple actions in bovine reproductive tract and it was our purpose to determine the nature of these actions and their significance for the physiology of bovine reproduction. The bovine oxytocin receptors (OTR) gene was cloned and its expression studied during the cycle and pregnancy. OTR mRNA changed in parallel with OTR with control occurring mainly at the transcriptional level. However, the endocrine regulation of OTR were found in endometrium and cervical mucosa at estrus and at parturition. In both tissues OTR were suppressed in the luteal phase and early pregnancy. Whereas cervical OTR remained suppressed throughout pregnancy, endometrial OTR began to increase soon after implantation and reached higher concentrations in midpregnancy than at estrus. OTR in caruncles did not increase until third trimester, and OTR in cervical mucosa, cotyledons and fetal membranes increased only at term. Myometrial OTR showed less variation and OTR were present throughout the cycle and pregnancy but increased significantly during mid- and late pregnancy. OTR were localized in endometrial epithelial cells and lumina epithelial cells of cervical mucosa as determined by immunohistochemistry. Endometrial OTR were functional throughout pregnancy and mediated PGF release from day 50 onwards in a receptor density related manner. OTR in cervical mucosa mediated PGE release both in vivo and in vitro, as shown in cyclic cows. The ontogeny of uterine OTR was studied from third trimester fetal stage until puberty. OTR were present in endometrium and cervical mucosa in high concentrations throughout this period; myometrial OTR began to increase somewhat later but also reached adult values by 6-mo of age. In the prepuberal heifers OT injections failed to initiate PGF2a, release. The influence of steroids on the effect of OT was examined. Ovariectomy and E2 were without effect, but P4 with or without E2 induced a massive PGF2a release in response to OT in spite of reduced OTR. Bovine cyclooxygenases (COX-1 and COX-2) were cloned and their expression studied in the endometrium of prepuberal heifers and pregnant cows. Untreated and E2 treated prepuberal heifers did not express COX-2 but P4 treated heifers did express the mRNA for COX-2, albeit weakly. During the second half of pregnancy COX-2 mRNA was strongly expressed in cotyledons and somewhat less in caruncles, whereas endometrium, myometrium and cervical mucosa showed only weak, if any, COX-2 mRNA under basal conditions. However, 2 h after OT injection significant increases in COX-2 mRNA were found in endometrial RNA. Thus OT is capable of inducing the expression of the inducible COX-2 gene, and hence the conversion of arachidonic acid to prostanoids. The results indicate that the functions of OT are numerous and probably essential for successful pregnancy and parturition.
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Shpigel, Muki, Allen Place, William Koven, Oded (Odi) Zmora, Sheenan Harpaz, and Mordechai Harel. Development of Sodium Alginate Encapsulation of Diatom Concentrates as a Nutrient Delivery System to Enhance Growth and Survival of Post-Larvae Abalone. United States Department of Agriculture, September 2001. http://dx.doi.org/10.32747/2001.7586480.bard.
Full textAbstract:
The major bottlenecks in rearing the highly priced gastropod abalone (Haliotis spp.) are the slow growth rate and the high mortality during the first 8 to 12 weeks following metamorphosis and settling. The most likely reason flor these problems is related to nutritional deficiencies in the diatom diet on which the post larvae (PL) feed almost exclusively in captivity. Higher survival and improved growth rate will reduce the considerable expense of hatchery-nursery resisdence time and thereflore the production costs. BARD supported our research for one year only and the support was given to us in order to prove that "(1) Abalone PL feed on encapsulated diatoms, and (2) heterotrophic diatoms can be mass produced." In the course of this year we have developed a novel nutrient delivery system specifically designed to enhance growth and survival of post-larval abalone. This approach is based on the sodium-alginate encapsulation of heterotrophically grown diatoms or diatom extracts, including appetite-stimulating factors. Diatom species that attract the PL and promote the highest growth and survival have been identified. These were also tested by incorporating them (either intact cells or as cell extracts) into a sodium-alginate matrix while comparing the growth to that achieved when using diatoms (singel sp. or as a mixture). A number of potential chemoattractants to act as appetite-stimulating factors for abalone PL have been tested. Preliminary results show that the incorporation of the amino acid methionine at a level of 10-3M to the sodim alginate matrix leads to a marked enhancement of growth. The results ol these studies provided basic knowledge on the growth of abalone and showed that it is possible to obtain, on a regular basis, survival rates exceeding 10% for this stage. Prior to this study the survival rates ranged between 2-4%, less than half of the values achieved today. Several diatom species originated from the National Center for Mariculture (Nitzchia laevis, Navicula lenzi, Amphora T3, and Navicula tennerima) and Cylindrotheca fusiformis (2083, 2084, 2085, 2086 and 2087 UTEX strains, Austin TX) were tested for heterotrophic growth. Axenic colonies were initially obtained and following intensive selection cycles and mutagenesis treatments, Amphora T3, Navicula tennerima and Cylindrotheca fusiformis (2083 UTEX strain) were capable of growing under heterotrophic conditions and to sustain highly enriched mediums. A highly efficient selection procedure as well as cost effective matrix of media components were developed and optimized. Glucose was identified as the best carbon source for all diatom strains. Doubling times ranging from 20-40 h were observed, and stable heterotroph cultures at a densities range of 103-104 were achieved. Although current growth rates are not yet sufficient for full economical fermentation, we estimate that further selections and mutagenesis treatments cycles should result in much faster growing colonies suitable for a fermentor scale-up. As rightfully pointed out by one of the reviewers, "There would be no point in assessing the optimum levels of dietary inclusions into micro-capsules, if the post-larvae cannot be induced to consume those capsules in the first place." We believe that the results of the first year of research provide a foundationfor the continuation of this research following the objectives put forth in the original proposal. Future work should concentrate on the optimization of incorporation of intact cells and cell extracts of the developed heterotrophic strains in the alginate matrix, as well as improving this delivery system by including liposomes and chemoattractants to ensure food consumption and enhanced growth.
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McClure, Michael A., Yitzhak Spiegel, David M. Bird, R. Salomon, and R. H. C. Curtis. Functional Analysis of Root-Knot Nematode Surface Coat Proteins to Develop Rational Targets for Plantibodies. United States Department of Agriculture, October 2001. http://dx.doi.org/10.32747/2001.7575284.bard.
Full textAbstract:
The goal of this research was to provide a better understanding of the interface between root-knot nematodes, Meloidogyne spp., and their host in order to develop rational targets for plantibodies and other novel methods of nematode control directed against the nematode surface coat (SC). Specific objectives were: 1. To produce additional monoclonal SC antibodies for use in Objectives 2, 3, and 4 and as candidates for development of plantibodies. 2. To determine the production and distribution of SC proteins during the infection process. 3. To use biochemical and immunological methods to perturbate the root-knot nematode SC in order to identify SC components that will serve as targets for rationally designed plantibodies. 4. To develop SC-mutant nematodes as additional tools for defining the role of the SC during infection. The external cuticular layer of nematodes is the epicuticle. In many nematodes, it is covered by a fuzzy material termed "surface coat" (SC). Since the SC is the outermost layer, it may playa role in the interaction between the nematode and its surroundings during all life stages in soil and during pathogenesis. The SC is composed mainly of proteins, carbohydrates (which can be part of glycoproteins), and lipids. SC proteins and glycoproteins have been labeled and extracted from preparasitic second-stage juveniles and adult females of Meloidogyne and specific antibodies have been raised against surface antigens. Antibodies can be used to gain more information about surface function and to isolate genes encoding for surface antigens. Characterization of surface antigens and their roles in different life-stages may be an important step towards the development of alternative control. Nevertheless, the role of the plant- parasitic nematode's surface in plant-nematode interaction is still not understood. Carbohydrates or carbohydrate-recognition domains (CROs) on the nematode surface may interact with CROs or carbohydrate molecules, on root surfaces or exudates, or be active after the nematode has penetrated into the root. Surface antigens undoubtedly play an important role in interactions with microorganisms that adhere to the nematodes. Polyclonal (PC) and monoclonal (MC) antibodies raised against Meloidogyne javanica, M. incognita and other plant-parasitic nematodes, were used to characterize the surface coat and secreted-excreted products of M. javanica and M. incognita. Some of the MC and PC antibodies raised against M. incognita showed cross-reactivity with the surface coat of M. javanica. Further characterization, in planta, of the epitopes recognized by the antibodies, showed that they were present in the parasitic juvenile stages and that the surface coat is shed during root penetration by the nematode and its migration between root cells. At the molecular level, we have followed two lines of experimentation. The first has been to identify genes encoding surface coat (SC) molecules, and we have isolated and characterized a small family of mucin genes from M. incognita. Our second approach has been to study host genes that respond to the nematode, and in particular, to the SC. Our previous work has identified a large suite of genes expressed in Lycopersicon esculentum giant cells, including the partial cDNA clone DB#131, which encodes a serine/threonine protein kinase. Isolation and predicted translation of the mature cDNA revealed a frame shift mutation in the translated region of nematode sensitive plants. By using primers homologous to conserved region of DB#131 we have identified the orthologues from three (nematode-resistant) Lycopersicon peruvianum strains and found that these plants lacked the mutation.
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Barash, Itamar, and Robert Rhoads. Translational Mechanisms Governing Milk Protein Levels and Composition. United States Department of Agriculture, 2006. http://dx.doi.org/10.32747/2006.7696526.bard.
Full textAbstract:
Original objectives: The long-term goal of the research is to achieve higher protein content in the milk of ruminants by modulating the translational apparatus of the mammary gland genetically, nutritionally, or pharmacologically. The short-term objectives are to obtain a better understanding of 1) the role of amino acids (AA) as regulators of translation in bovine and mouse mammary epithelial cells and 2) the mechanism responsible for the synergistic enhancement of milk-protein mRNA polyadenylation by insulin and prolactin. Background of the topic: In many cell types and tissues, individual AA affect a signaling pathway which parallels the insulin pathway to modulate rates and levels of protein synthesis. Diverse nutritional and hormonal conditions are funneled to mTOR, a multidomain serine/threonine kinase that regulates a number of components in the initiation and elongation stages of translation. The mechanism by which AA signal mTOR is largely unknown. During the current grant period, we have studied the effect of essential AA on mechanisms involved in protein synthesis in differentiated mammary epithelial cells cultured under lactogenic conditions. We also studied lactogenic hormone regulation of milk protein synthesis in differentiated mammary epithelial cells. In the first BARD grant (2000-03), we discovered a novel mechanism for mRNA-specific hormone-regulated translation, namely, that the combination of insulin plus prolactin causes cytoplasmic polyadenylation of milk protein mRNAs, which leads to their efficient translation. In the current BARD grant, we have pursued the signaling pathways of this novel hormone action. Major conclusions/solutions/achievements: The positive and negative signaling from AA to the mTOR pathway, combined with modulation of insulin sensitization, mediates the synthesis rates of total and specific milk proteins in mammary epithelial cells. The current in vitro study revealed cryptic negative effects of Lys, His, and Thr on cellular mechanisms regulating translation initiation and protein synthesis in mammary epithelial cells that could not be detected by conventional in vivo analyses. We also showed that a signaling pathway involving Jak2 and Stat5, previously shown to lead from the prolactin receptor to transcription of milk protein genes, is also used for cytoplasmic polyadenylation of milk protein mRNAs, thereby stabilizing these mRNAs and activating them for translation. Implications: In vivo, plasma AA levels are affected by nutritional and hormonal effects as well as by conditions of exercise and stress. The amplitude in plasma AA levels resembles that applied in the current in vitro study. Thus, by changing plasma AA levels in the epithelial cell microenvironment or by sensitizing the mTOR pathway to their presence, it should be possible to modulate the rate of milk protein synthesis. Furthermore, knowledge that phosphorylation of Stat5 is required for enhanced milk protein synthesis in response to lactogenic opens the possibility for pharmacologic approaches to increase the phosphorylation of Stat5 and, thereby, milk protein production.