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The Fusion program, a method for agile, flexible computer integrated manufacturing (CIM) at Motorola's Paging Products Group, is discussed. Fusion's CIM and automated assembly system can manufacture a wide variety of different products on the same production line. The development of the Fusion program and how it differs from its predecessor, the Bandit program, are described  相似文献   
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Targeting molecular alterations as an effective treatment for isocitrate dehydrogenase-wildtype glioblastoma (GBM) patients has not yet been established. Sterol-O-Acyl Transferase 1 (SOAT1), a key enzyme in the conversion of endoplasmic reticulum cholesterol to esters for storage in lipid droplets (LD), serves as a target for the orphan drug mitotane to treat adrenocortical carcinoma. Inhibition of SOAT1 also suppresses GBM growth. Here, we refined SOAT1-expression in GBM and IDH-mutant astrocytoma, CNS WHO grade 4 (HGA), and assessed the distribution of LD in these tumors. Twenty-seven GBM and three HGA specimens were evaluated by multiple GFAP, Iba1, IDH1 R132H, and SOAT1 immunofluorescence labeling as well as Oil Red O staining. To a small extent SOAT1 was expressed by tumor cells in both tumor entities. In contrast, strong expression was observed in glioma-associated macrophages. Triple immunofluorescence labeling revealed, for the first time, evidence for SOAT1 colocalization with Iba1 and IDH1 R132H, respectively. Furthermore, a notable difference in the amount of LD between GBM and HGA was observed. Therefore, SOAT1 suppression might be a therapeutic option to target GBM and HGA growth and invasiveness. In addition, the high expression in cells related to neuroinflammation could be beneficial for a concomitant suppression of protumoral microglia/macrophages.  相似文献   
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Preferential binding of an enzyme to the transition state relative to the ground state is a key strategy for enzyme catalysis. When there is a difference between the ground and transition state charge distributions, enzymes maximize electrostatic interactions to achieve this enhanced transition state binding. Although the transition state is difficult to observe directly by structural methods, the chemical details of this transient species can be characterized by studies of substituent effects (Br?nsted, Hammett, Swain-Scott, etc.) and isotope effects. Br?nsted analysis can provide an estimate of transition state charges for the nucleophile and leaving group of a reaction. This Account will discuss the theoretical basis of Br?nsted analysis and describe its practical application to the study of transacylase enzyme systems including the peptidyl transferase reaction of the ribosome. The Br?nsted coefficient is derived from the linear free energy relationship (LFER) that correlates the acidity (pK(a)) of a reactive atom to the log of its rate constant. The Br?nsted coefficient establishes the change in atomic charge as the reaction proceeds from the ground state to the transition state. Bonding events alter the electrostatics of atoms and the extent of bonding can be extrapolated from transition state charges. Therefore, well-defined nucleophile and leaving group transition state charges limit the number of mechanisms that are consistent with a particular transition state. Br?nsted results are most informative when interpreted in the context of other mechanistic data, especially for enzymatic studies where an active site may promote a transition state that differs significantly from a prediction based on uncatalyzed solution reactions. Here we review Br?nsted analyses performed on transacylases to illustrate how these data enhanced the enzymatic mechanistic studies. Through a systematic comparison of five enzymes, we reveal a wide spectrum of Br?nsted values that are possible for what otherwise appear to be similar chemical reactions. The variations in the Br?nsted coefficients predict different transition states for the various enzymes. This Account explores an overriding theme in the enzymatic mechanisms that catalysis enhances commensurate bond formation and proton abstraction events. The extent of the two bonding events in relationship to each other can be inferred from the Br?nsted coefficient. When viewed in the context of recent ribosomal studies, this interpretation provides mechanistic insights into peptide bond formation.  相似文献   
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High surface area Pt/K/Al2O3 catalysts were prepared with a 2-nozzle flame spray method resulting in Pt clusters on γ-Al2O3 and amorphous K storage material as evidenced by Raman spectroscopy. The powders had a high NO x storage capacity and were regenerated fast in a model exhaust gas environment. From 300 to 400 °C no excess NO x was detected in the off gas during transition from fuel lean to fuel rich conditions, resulting in a highly effective NO x removal performance. Above 500 °C, the NSR activity was lost and not recovered at lower temperatures as K-compounds were partially crystallized on the catalyst.  相似文献   
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Site-specific strategies for exchanging segments of dsDNA are important for DNA library construction and molecular tagging. Deoxyuridine (dU) excision is an approach for generating 3’ ssDNA overhangs in gene assembly and molecular cloning procedures. Unlike approaches that use a multi-base pair motif to specify a DNA cut site, dU excision requires only a dT→dU substitution. Consequently, excision sites can be embedded in biologically active DNA sequences by placing dU substitutions at non-perturbative positions. In this work, I describe a molecular tagging method that uses dU excision to exchange a segment of a dsDNA strand with a long synthetic oligonucleotide. The core workflow of this method, called deoxyUridine eXcision-tagging (dUX-tagging), is an efficient one-pot reaction: strategically positioned dU nucleotides are excised from dsDNA to generate a 3’ overhang so that additional sequence can be appended by annealing and ligating a tagging oligonucleotide. The tagged DNA is then processed by one of two procedures to fill the 5’ overhang and remove excess tagging oligo. To facilitate its widespread use, all dUX-tagging procedures exclusively use commercially available reagents. As a result, dUX-tagging is a concise and easily implemented approach for high-efficiency linear dsDNA tagging.  相似文献   
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PURPOSE: The present study was conducted to evaluate the role of the duration of exercise and the impact of the exercise type for exercise-induced activation of coagulation. METHODS: Eleven male triathletes were subjected to stepwise maximal (17 min) and 1-h maximal exercise in swimming, cycling, and running. Changes of hemostatic variable sand of plasma thrombomodulin, a marker of endothelial cell activation, were monitored. RESULTS: Irrespective of the type of exercise, alterations in markers of thrombin (prothrombin fragment 1 + 2, thrombin-antithrombin III complexes) and fibrin formation (fibrinopeptide A) were more pronounced after 1-h exercise than after stepwise maximal exercise. Hemostatic parameters rose to the highest levels after running resulting in substantial fibrin formation as indicated by fibrinopeptide A increasing from 1.33 ng.mL-1 to 2.25 ng.mL (P < 0.05) after 1-h exercise testing. Significant changes of plasma thrombomodulin were detected exclusively after running with increases from 38.2 ng.mL-1 to 44.2 ng.mL-1 (1 h, P < 0.01). CONCLUSIONS: The data demonstrated that prolonged exercise is necessary for exercise-induced activation of coagulation resulting in thrombin and fibrin formation and suggested that endothelial cell activation possibly due to mechanical factors associated with running might play a role.  相似文献   
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Flame synthesis is one of the most versatile and promising technologies for large-scale production of nanoscale materials. Pyrolysis has recently been shown to be a useful route for the production of single-walled nanotubes, quantum dots and a wide variety of nanostructured ceramic oxides for catalysis and electrochemical applications. An understanding of the mechanisms of nanostructural growth in flames has been hampered by a lack of direct observations of particle growth, owing to high temperatures (2,000 K), rapid kinetics (submillisecond scale), dilute growth conditions (10(-6) volume fraction) and optical emission of synthetic flames. Here we report the first successful in situ study of nanoparticle growth in a flame using synchrotron X-ray scattering. The results indicate that simple growth models, first derived for colloidal synthesis, can be used to facilitate our understanding of flame synthesis. Further, the results indicate the feasibility of studies of nanometre-scale aerosols of toxicological and environmental concern.  相似文献   
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Single-crystal electron diffraction patterns were obtained on five specimens of -MnO2: one natural, two electrolytical (EMD) and two chemical (CMD) samples. EMDs are best described by the orthorhombic structure proposed by De Wolff which is derived from the ramsdellite structure. A CMD prepared from MnCO3 fits the hexagonal cell of -MnO2. Flaky grains from the natural sample and fibres from a CMD prepared from Mn(NO3)2 are hexagonal with a new cell:a 0.494,c 0.539 nm. No simple relation between chemical composition, morphology and structure could be found.  相似文献   
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