1,462 research outputs found
Development of QSAR models for predicting anti-HIV-1 activity using the Monte Carlo method
Inhibition of the peptidyl-prolyl-isomerase Pin1 enhances the responses of acute myeloid leukemia cells to retinoic acid via stabilization of RARand PML-RAR
The peptidyl-prolyl-isomerase Pin1 interacts with phosphorylated proteins, altering their conformation. The retinoic acid receptor RARalpha and the acute-promyelocytic-leukemia-specific counterpart PML-RARalpha directly interact with Pin1. Overexpression of Pin1 inhibits ligand-dependent activation of RARalpha and PML-RARalpha. Inhibition is relieved by Pin1-targeted short interfering RNAs and by pharmacologic inhibition of the catalytic activity of the protein. Mutants of Pin1 catalytically inactive or defective for client-protein-binding activity are incapable of inhibiting ligand-dependent RARalpha transcriptional activity. Functional inhibition of RARalpha and PML-RARalpha by Pin1 correlates with degradation of the nuclear receptors via the proteasome-dependent pathway. In the acute myelogenous leukemia cell lines HL-60 and NB4, Pin1 interacts with RARalpha in a constitutive fashion. Suppression of Pin1 by a specific short hairpin RNA in HL-60 or NB4 cells stabilizes RARalpha and PML-RARalpha, resulting in increased sensitivity to the cytodifferentiating and antiproliferative activities of all-trans retinoic acid. Treatment of the two cell lines and freshly isolated acute myelogenous leukemia blasts (M1 to M4) with ATRA and a pharmacologic inhibitor of Pin1 causes similar effects. Our results add a further layer of complexity to the regulation of nuclear retinoic acid receptors and suggest that Pin1 represents an important target for strategies aimed at increasing the therapeutic index of retinoids
A model of telephone network development in the rural area of Bali: Taakverslag
The telephone facility for rural areas is being developed and actually has been used, especially for the villages in the third world countries. In this report the reason of such development is described, and a model is made to illustrate the topographic conditions, the situation in the villages and the possibilities for the telephone users. From the available data, a rural area in Bali island, Indonesia, is chosen as the object location. The Delft Rural Telephony System (DRTS) which is being developed and tested in the laboratory is explained as a possible system application in the area. The designed network and the used equipment cost is then calculated. In this report the suggestions for further extension of the Interactive Telephone network Optimization in Rural Areas (ITORA) program and for simulating the model with this program are given.Applied SciencesElectrotechniekTelecommunicatie- en Verkeersbegeleidingssysteme
A Wideband 2x13-bit All-Digital I/Q RF-DAC
This paper presents a wideband 2 13-bit in-phase/quadrature-phase (I/Q) RF digital-to-analog converter-based all-digital modulator realized in 65-nm CMOS. The isolation between I and Q paths is guaranteed employing 25% duty-cycle differential quadrature clocks. With a 1.3-V supply and an on-chip power combiner, the digital I/Q transmitter provides more than 21-dBm RF output power within a frequency range of 1.36–2.51 GHz. The peak RF output power, overall system, and drain efficiencies of the modulator are 22.8 dBm, 34%, and 42%, respectively. The measured static noise floor is below 160 dBc/Hz. The digital I/Q RF modulator demonstrates an IQ image rejection and local oscillator leakage of 65 and 68 dBc, respectively. It could be linearized using either of the two digital predistortion (DPD) approaches: a memoryless polynomial or a lookup table. Its linearity is examined using single-carrier 4/16/64/256/1024 quadrature amplitude modulation (QAM), as well as multi-carrier 256-QAM orthogonal frequency-division multiplexing baseband signals while their related modulation bandwidth can be as high as 154 MHz. Employing DPD improves the third-order intermodulation product (IM3) by more than 25 dB, while the measured error vector magnitude for a “single-carrier 22-MHz 64-QAM” signal is better than 28 dB.Microelectronics & Computer EngineeringElectrical Engineering, Mathematics and Computer Scienc
Microvascular permeability and endothelial cell morphology associated with low-flow ischemia/reperfusion injury in the equine jejunum
Microvascular permeability of the jejunum of clinically normal equids and microvascular permeability associated with 60 minutes of ischemia (25% baseline blood flow) and subsequent reperfusion were investigated. Eight adult horses were randomly allotted to 2 equal groups: normal and ischemic/reperfusion injury. Lymphatic flow rates, mesenteric blood flow, and lymph and plasma protein concentrations were determined at 15-minute intervals throughout the study. Microvascular permeability was determined by estimates of the osmotic reflection coefficient, which was determined when the ratio of lymphatic protein to plasma protein concentration reached a constant minimal value as lymph flow rate increased (filtration-independent lymph flow rate), which occurred at venous pressure of 30 mm of Hg. Full-thickness jejunal biopsy specimens were obtained at the beginning and end of each experiment, and were prepared for light microscopy to estimate tissue volume (edema) and for transmission electron microscopy to evaluate capillary endothelial cell morphology. The osmotic reflection coefficient for normal equine jejunum was 0.19 +/- 0.06, and increased significantly (P < or = 0.0001) to 0.48 +/- 0.05 after the ischemia/reperfusion period. Microscopic evaluation revealed a significant increase (P < or = 0.0001) in submucosal and serosal volume and capillary endothelial cell damage in horses that underwent ischemia/reperfusion injury. Results indicate that ischemia/reperfusion of the equine jejunum caused a significant increase in microvascular permeability
Comprehensive Business Modelling: Hydrogen and its Integration in the Dutch Energy System: Business modelling from the perspective of a public-private partnership for the case of ‘H-vision’, a project for the implementation of blue hydrogen in the Port of Rotterdam
The goal of this thesis is to determine the effects of integrating blue hydrogen into the Dutch energy system. A new framework is presented to assess several different designs for the business model, infrastructure, and market. This framework is applied to the case of the H-vision project. Three business models are tested against three energy system designs. As such we can determine if which of the three combinations presents the most benefits and also which combination is the most likely to be executed. I invite everyone to read this thesis with a heuristic perspective to learn more about the hydrogen economy and the Dutch energy system. I hope it will be as educating for you as it has been for me.H-visionManagement of Technology (MoT
Refinement of the DRTS exchange and a PCM generator for operational use: Laboratory Assignment Report
The Delft Rural Telephone System project is aimed at developing an affordable digital telephone system for use in low subscriber density areas, most commonly found in third world countries. For this project a PCM generator and a digital telephone node were developed. The PCM generator generates a 30 channel first order PCM multiplex, both in TI L and HDB3 format. Two analog I/O channels and a test channel are available to the user. The telephone node had not previously been tested. In order to be able to test the node, several modifications were necessary to make the PCM generator and node work together. These modifications are described in this report. Besides these modifications, a control program was also developed for the node. With this program it is possible to initialize, control and monitor the node. The design and use of the program is described. The node and generator are now both operational, but it is advisable to rebuild them. Several improvements should be made. The node should be based on a more advanced memory time switch and its construction should be improved. The generator is just about ready for production with printed circuit boards after a few minor points are solved.Applied SciencesElectrical EngineeringTelecommunications and Traffic-Control Systems Grou
A classical problem in linear regression or how to estimate the mean of a univariate normal distribution with known variance
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