350,986 research outputs found

    The granulocytic inducer C/EBPalpha inactivates the myeloid master regulator PU.1

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    Verschiedene Transkriptionsfaktoren spielen eine Rolle in der Entwicklung myeloischer Zellen. PU.1, ein Transkriptionsfaktor aus der ETS-Familie, ist sowohl für die Entwicklung lymphatischer als auch für die Entwicklung myeloischer Zellen von Bedeutung. Der Transkriptions faktor C/EBPalpha, ein an den CCAAT-Enhancer bindendes Protein, ist hingegen wesentlich verantwortlich für die Entwicklung von Granulozyten. Wir stellen hier den ersten Nachweis dafür vor, dass C/EBPalpha die Funktion von PU.1 blockiert. PU.1 und C/EBPalpha können einander binden und sind in myeloischen Zellen kolokalisiert. Wenn C/EBPalpha PU.1 bindet, kann PU.1 einen minimalen Promotor mit Bindungsstelle für PU.1 nicht mehr aktivieren. Wir zeigen, dass der Leuzin-Zipper in der DNA-bindenden Domäne von C/EBPalpha mit der beta3/beta4-Region in der DNA-bindenden Domäne von PU.1 interagieren kann. Dadurch wird der Koaktivator von PU.1, c-jun, aus seiner Bindung mit PU.1 verdrängt. C/EBPalpha hemmt PU.1 nicht, indem es Korepressoren rekrutiert. Vielmehr vermindert C/EBPalpha die Expression von PU.1 in U-937-Zellen mit induzierbarem C/EBPalpha, indem es den autoregulatorischen Effekt PU.1 auf den PU.1-Promotor hemmt. Ausserdem blockiert C/EBPalpha die durch PU.1 bedingte Entwicklung dendritischer Zellen aus CD34+ menschlichen Nabel blutzellen. Diese funktionelle Blockade von PU.1 durch C/EBPalpha könnte einer der Mechanismen sein, mit denen C/EBPalpha den durch PU.1 determinierten Weg der Zelldifferenzierung hemmt und sich Zellen unter dem Einfluss von C/EBPalpha zu Granulozyten entwickeln.Several transcription factors have been shown to play a role in myelopoiesis. PU.1, an ets-family transcription factor, is required for the development of both myeloid and lymphoid lineages while the transcription factor CCAAT/enhancer binding protein family member C/EBPalpha is essential for granulocytic development. We present here the first evidence that C/EBPalpha blocks the function of PU.1. PU.1 and C/EBPalpha interact physically and co-localize in myeloid cells. As a consequence of this interaction C/EBPalpha can inhibit the function of PU.1 to activate a minimal promoter containing only PU.1 DNA binding sites. We further demonstrate that the leucine zipper in the DNA binding domain of C/EBPalpha interacts with the beta3/beta4 region in the DNA binding domain of PU.1, and as a result displaces the PU.1 co-activator c-Jun. Finally, C/EBPalpha blocks PU.1 induced dendritic cell development from CD34+ human cord blood cells. The functional blocking of PU.1 by C/EBPalpha could be the mechanism by which C/EBPalpha inhibits the cell fates specified by PU.1, and directs cell development to the granulocytic lineage

    Differentiation of the mononuclear phagocyte system during mouse embryogenesis:the role of transcription factor PU.1

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    During mouse embryogenesis, macrophage-like cells arise first in the yolk sac and are produced subsequently in the liver. The onset of liver hematopoiesis is associated with the transition from primitive to definitive erythrocyte production. This report addresses the hypothesis that a similar transition in phenotype occurs in myelopoiesis. We have used whole mount in situ hybridization to detect macrophage-specific genes expressed during mouse development. The mouse c-fms mRNA, encoding the receptor for macrophage colony-stimulating factor (CSF-1), was expressed on phagocytic cells in the yolk sac and throughout the embryo before the onset of liver hematopoiesis. Similar cells were detected using the mannose receptor, the complement receptor (CR3), or the Microphthalmia transcription factor (MITF) as mRNA markers. By contrast, other markers including the F4/80 antigen, the macrophage scavenger receptor, the S-100 proteins, S100A8 and S100A9, and the secretory product lysozyme appeared later in development and appeared restricted to only a subset of c-fms-positive cells. Two-color immunolabeling on disaggregated cells confirmed that CR3 and c-fms proteins are expressed on the same cells. Among the genes appearing later in development was the macrophage-restricted transcription factor, PU.1, which has been shown to be required for normal adult myelopoiesis. Mice with null mutations in PU.1 had normal numbers of c-fms-positive phagocytes at 11.5dpc. PU.1(-/-) embryonic stem cells were able to give rise to macrophage-like cells after cultivation in vitro. The results support previous evidence that yolk sac-derived fetal phagocytes are functionally distinct from those arising in the liver and develop via a different pathway

    Dry demoulding - cost-effective PU components through permanent release coatings

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    S.232-235In an IGF cooperation project at the Institute for Plastics Processing (IKV), Aachen, and the Fraunhofer Institute for Manufacturing Technology and Advanced Materials (IFAM), Bremen, a permanent release coating was investigated as an alternative to conventional release agents in polyurethane (PU) processing. Central aspects are the influence of catalysis in the PU formulations on the demoulding behaviour and the transfer of the technology to industrial standards. Casting experiments and near-surface analysis were used to determine a catalyst class compatible with the release coating. New requirements for process control and mould design were defined for the industrial application of the technology and implemented in an innovative mould concept.16Nr.

    The T-cell oncogene Tal2 is a Target of PU.1 and upregulated during osteoclastogenesis

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    Transcription factors play a crucial role in regulating differentiation processes during human life and are important in disease. The basic helix-loop-helix transcription factors Tal1 and Lyl1 play a major role in the regulation of gene expression in the hematopoietic system and are involved in human leukemia. Tal2, which belongs to the same family of transcription factors as Tal1 and Lyl1, is also involved in human leukaemia. However, little is known regarding the expression and regulation of Tal2 in hematopoietic cells. Here we show that Tal2 is expressed in hematopoietic cells of the myeloid lineage. Interestingly, we found that usage of the Tal2 promoter is different in human and mouse cells. Two promoters, hP1 and hP2 drive Tal2 expression in human erythroleukemia K562 cells, however in mouse RAW cells only the mP1 promoter is used. Furthermore, we found that Tal2 expression is upregulated during oesteoclastogenesis. We show that Tal2 is a direct target gene of the myeloid transcription factor PU.1, which is a key transcription factor for osteoclast gene expression. Strikingly, PU.1 binding to the P1 promoter is conserved between mouse and human, but PU.1 binding to P2 was only detected in human K562 cells. Additionally, we provide evidence that Tal2 influences the expression of the osteoclastic differentiation gene TRACP. These findings provide novel insight into the expression control of Tal2 in hematopoietic cells and reveal a function of Tal2 as a regulator of gene expression during osteoclast differentiation

    Comparison of Quality Characteristic and Antioxidant Potential of Cultivated Pu-erh and Gushu Pu-erh Tea Extracts at Two Temperatures

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    Pu-erh, a type of post-fermented dark tea, has attracted much attention of food scientists because of its health-promoting effects. pH, titratable acidity, color value, antioxidant potential and free amino acid contents of cultivated Pu-erh and Gushu Pu-erh teas extracted at 90 and 100°C were compared in this study. The pH of Gushu Pu-erh tea extract was slightly acidic than cultivated Pu-erh. Gushu Pu-erh contained higher antioxidant potentials and free amino acid content at the both extraction temperatures than the cultivated Pu-erh. The antioxidant potentials and free amino acid content were high in the tea extracted at 100°C. The results of this study showed that Gushu Pu-erh tea extracted at 100°C for 3 min with 30 s of shaking yields high amounts of phenolics and free amino acids

    On the S-(nS)PU-SPU and S-(nS)PU-2SPU Under-Actuated Wrists

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    In a previous work, this author showed that ten topologies for under-actuated parallel wrists can be generated from the fully-parallel wrist. Three of them are obtained by simply replacing a spherical pair (S) with a nonholonomic spherical pair (nS). The S-(nS)PU-SPU, and S-(nS)PU-2SPU wrists are two of these three. The position analysis of these two wrists is studied in this paper. In particular, all the four position-analysis problems, which are necessary for implementing their path planning, are addressed and solved in closed-form. Despite their different topology, the position-analysis of these two wrists can be practically solved by using the same formulas and algorithms. Based on the deduced formulas, a path-planning algorithm is proposed. The obtained results make the studied wrist topologies able to replace “ordinary” wrists in the manipulation tasks which do not require tracking

    Kinetostatics of S-(nS)PU-SPU and S-(nS)PU-2SPU Nonholonomic Parallel Wrists

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    S-(nS)PU-SPU and S-(nS)PU-2SPU are two types of nonholonomic wrists that are generated from the “ordinary” wrists of type S-3SPU (fully parallel wrists (FPW)), by replacing a spherical pair (S) with a nonholonomic spherical pair (nS) according to the rules stated by Grosch et al. (2010, “Generation of Under-Actuated Manipulators With Nonholonomic Joints From Ordinary Manipulators,” ASME J. Mech. Rob., 2(1), p. 011005). Position analysis, controllability, and path planning of these two wrist types have been addressed and solved in two previous papers (Di Gregorio, R., 2012, “Type Synthesis of Underactuated Wrists Generated From Fully-Parallel Wrists,” ASME J. Mech. Des., 134(12), p. 124501 and Di Gregorio, R., 2012, “Position Analysis and Path Planning of the S-(nS)PU-SPU and S-(nS)PU-2SPU Underactuated Wrists,” ASME J. Mech. Rob., 4(2), p. 021006) of this author, which demonstrated that simple closed-form formulas are sufficient to control their configuration and to implement their path planning. Their kinetostatics and singularity analysis have not been addressed, yet; and they are studied in this paper. Here, the singularity analysis will reveal, for the first time, the existence of a somehow novel type of singularities, here named “jamming singularity,” that jams the platform motion in some directions and that is also present in all the parallel manipulators with SPU limbs (e.g., Gough-Stewart platforms) where it can be considered a particular type of “leg singularity.” Moreover, the static analysis will demonstrate that the reaction forces due to the static friction, in the nonholonomic constraint, can be controlled in the same way as the generalized forces exerted by the actuators, and that the possible slippage, in the same constraint, can be easily monitored and compensated

    Position analysis and path planning of the S-(nS)PU-SPU and S-(nS)PU-2SPU underactuated wrists

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    In a previous work, this author showed that ten topologies for underactuated parallel wrists can be generated from a fully parallel wrist (FPW). Three of them are obtained by simply replacing a spherical pair (S) with a nonholonomic spherical pair (nS). The S-(nS)PU-SPU and S-(nS)PU-2SPU wrists are two among these three. The position analysis of these two wrists is studied here. In particular, all the four position-analysis problems, which are necessary for implementing their path planning, are addressed and solved in closed form. Despite their different topology, the position analysis of these two wrists can be practically solved by using the same formulas and algorithms. Based on the deduced formulas, a path-planning algorithm is proposed. The obtained results make the studied wrist topologies able to replace “ordinary” wrists in the manipulation tasks which do not require tracking

    Reducing scaling effect on downscaled land surface temperature maps in heterogenous urban environments

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    The literature review indicates that a scaling effect does exist in downscaling land surface temperature (DLST) processes, and no substantial methods were specially developed for addressing it. In this research, the main aim is to develop a new method to reduce the scaling effect on DLST maps at high resolutions. A thermal component-based thermal spectral unmixing (TSU) model was modified and a multiple regression (REG) model was adopted to create DLST maps at high resolutions. A combined variance of red and NIR bands at a very high resolution with a difference image between upscaled LST and DLST was used to develop a new method. With two case data sets, LSTs at coarse resolutions were downscaled by using the modified TSU model and the REG model to create DLST results. The new method with a correction term expression (a linear model created by using a semi-empirical approach) was used to improve the DLST maps in the two case study areas. The experimental results indicate that the new method could reduce the root mean square error and the mean absolute error >30% and >33%, respectively, and thus demonstrate that the proposed method was effective and significant, especially reducing the scaling effect on DLST results at very high resolutions. The novel significance for the new method is directly reducing the scaling effect on DLST maps at high resolutions

    Correcting Scaling Effect in Downscaling Surface Temperature at High Resolutions with a Multiple Regional Correction Approach

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    There exists a scaling error in currently downscaling land surface temperature (DLST) processes and it is necessary to develop substantial methods specially for reducing it. In this letter, a multiple regional correction (MRC) approach with multiple correction terms (mCTs) was proposed to correct scaling errors in DLST processes. The test results indicate that (1) the proposed approach can effectively correct the scaling effects in DLST processes at high resolutions by reducing root mean square error by ~ 55%; (2) all initial resolutions considered for optical data (0.5 m – 4 m) were effective for developing the MRC approach with mCTs in correcting the scaling errors. Overall, this novel approach can significantly improve the accuracy of DLST maps at very high resolutions
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