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排序方式: 共有793条查询结果,搜索用时 15 毫秒
1.
Jasmin Kuhn Philipp M. Klein Nader Al Danaf Joel Z. Nordin Sren Reinhard Dominik M. Loy Miriam Hhn Samir El Andaloussi Don C. Lamb Ernst Wagner Yoshitsugu Aoki Taavi Lehto Ulrich Lchelt 《Advanced functional materials》2019,29(48)
Phosphorodiamidate morpholino oligomers (PMOs) are oligonucleotide analogs that can be used for therapeutic modulation of pre‐mRNA splicing. Similar to other classes of nucleic acid‐based therapeutics, PMOs require delivery systems for efficient transport to the intracellular target sites. Here, artificial peptides based on the oligo(ethylenamino) acid succinyl‐tetraethylenpentamine (Stp), hydrophobic modifications, and an azide group are presented, which are used for strain‐promoted azide‐alkyne cycloaddition conjugation with splice‐switching PMOs. By systematically varying the lead structure and formulation, it is determined that the type of contained fatty acid and supramolecular assembly have a critical impact on the delivery efficacy. A compound containing linolenic acid with three cis double bonds exhibits the highest splice‐switching activity and significantly increases functional protein expression in pLuc/705 reporter cells in vitro and after local administration in vivo. Structural and mechanistic studies reveal that the lipopeptide PMO conjugates form nanoparticles, which accelerate cellular uptake and that the content of unsaturated fatty acids enhances endosomal escape. In an in vitro Duchenne muscular dystrophy exon skipping model using H2K‐mdx52 dystrophic skeletal myotubes, the highly potent PMO conjugates mediate significant splice‐switching at very low nanomolar concentrations. The presented aminoethylene‐lipopeptides are thus a promising platform for the generation of PMO‐therapeutics with a favorable activity/toxicity profile. 相似文献
2.
Pai H. Chou Jinfeng Liu Dexin Li Nader Bagherzadeh 《Design Automation for Embedded Systems》2002,7(3):205-232
Power-aware systems are those that must exploit a widerange of power/performance trade-offs in order to adapt to the power availabilityand application requirements. They require the integration of many novel powermanagement techniques, ranging from voltage scaling to subsystem shutdown.However, those techniques do not always compose synergistically with eachother; in fact, they can combine subtractively and often yield counterintuitive,and sometimes incorrect, results in the context of a complete system. Thiscan become a serious problem as more of these power aware systems are beingdeployed in mission critical applications.To address the problem of technique integration for power-aware embedded systems, we propose a new design tool framework called IMPACCT and the associated design methodology. The system modeling methodology includes application model for capturing timing/powerconstraints and mode dependencies at the system level. The tool performs power-awarescheduling and mode selection to ensure that all timing/power constraintsare satisfied and that all overhead is taken into account. IMPACCT then synthesizesthe implementation targeting a symmetric multiprocessor platform. Experimentalresults show that the increased dynamic range of power/performance settingsenabled a Mars rover to achieve significant acceleration while using lessenergy. More importantly, our tool correctly combines the state-of-the-arttechniques at the system level, thereby saving even experienced designersfrom many pitfalls of system-level power management. 相似文献
3.
The dynamic response of highway bridges subjected to moving truckloads has been observed to be dependent on (1) dynamic characteristics of the bridge; (2) truck configuration, speed, and lane position on the bridge; and (3) road surface roughness profile of the bridge and its approach. Historically, truckloads were measured to determine the load spectra for girder bridges. However, truckload measurements are either made for a short period of time [for example, weigh-in-motion (WIM) data] or are statistically biased (for example, weigh stations) and cost prohibitive. The objective of this paper is to present results of a 3D computer-based model for the simulation of multiple trucks on girder bridges. The model is based on the grillage approach and is applied to four steel girder bridges tested under normal truck traffic. Actual truckload data collected using a discrete bridge WIM system are used in the model. The data include axle loads, truck gross weight, axle configuration, and statistical data on multiple presence (side by side or following). The results are presented as a function of the static and dynamic stresses in each girder and compared with code provisions for dynamic load factor. The study provides an alternate method for the development of live-load models for bridge design and evaluation. 相似文献
4.
This paper evaluates the behavior and performance of laminated circular elastomeric bearings and compares them to those of square and rectangular bearings. The study included an experimental evaluation and a nationwide survey of state Department of Transportations on the use and performance of circular bearings and bearings in general in their states. The experimental investigation studied the bearings' behavior in compression, compression and rotation, and compression and shear. Results from this limited study showed that the three bearings have similar stress-strain behavior in compression and they are in agreement with the AASHTO LRFD guide stress–strain curves. In compression and rotation, the AASHTO LRFD substructure moments are slightly less than the measured values for circular bearings and rectangular bearings rotated about their strong axis for a compressive stress of 10.3?MPa (1.5?ksi) and slightly higher than those of rectangular bearings rotated about their weak axis. In compression and shear, the shear stiffness of circular and square bearings is in agreement with theoretical values within the range of design displacements. Results from the survey showed that many states are using circular bearings and more states would consider using them, however no maintenance or monitoring data were available on their short-term and long-term performance. 相似文献
5.
MJ Prado AL Nicastri PL Costa T Rockman IL Tersariol HB Nader RT Barros EB Prado 《Canadian Metallurgical Quarterly》1997,30(7):865-872
The aim of the present study was to evaluate renal and liver distribution of two monoclonal immunoglobulin light chains. The chains were purified individually from the urine of patients with multiple myeloma and characterized as lambda light chains with a molecular mass of 28 kDa. They were named BJg (high amount of galactose residues exposed) and BJs (sialic acid residues exposed) on the basis of carbohydrate content. A scintigraphic study was performed on male Wistar rats weighing 250 g for 60 min after i.v. administration of 1 mg of each protein (7.4 MBq), as the intact proteins and also after carbohydrate oxidation. Images were obtained with a Siemens gamma camera with a high-resolution collimator and processed with a MicroDelta system. Hepatic and renal distribution were established and are reported as percent of injected dose. Liver uptake of BJg was significantly higher than liver uptake of BJs (94.3 vs 81.4%) (P < 0.05). This contributed to its greater removal from the intravascular compartment, and consequently lower kidney accumulation of BJg in comparison to BJs (5.7 vs 18.6%) (P < 0.05). After carbohydrate oxidation, there was a decrease in hepatic accumulation of both proteins and consequently a higher renal overload. The tissue distribution of periodate-treated BJg was similar to that of native BJs: 82.7 vs 81.4% in the liver and 17.3 vs 18.6% in the kidneys. These observations indicate the important role of sugar residues of Bence Jones proteins for their recognition by specific membrane receptors, which leads to differential tissue accumulation and possible toxicity. 相似文献
6.
Real-time processing and compression of DNA microarray images. 总被引:1,自引:0,他引:1
Shadrokh Samavi Shahram Shirani Nader Karimi 《IEEE transactions on image processing》2006,15(3):754-766
In this paper, we present a pipeline architecture specifically designed to process and compress DNA microarray images. Many of the pixilated image generation methods produce one row of the image at a time. This property is fully exploited by the proposed pipeline that takes in one row of the produced image at each clock pulse and performs the necessary image processing steps on it. This will remove the present need for sluggish software routines that are considered a major bottleneck in the microarray technology. Moreover, two different structures are proposed for compressing DNA microarray images. The proposed architecture is proved to be highly modular, scalable, and suited for a standard cell VLSI implementation. 相似文献
7.
Influence of thermal boundary conditions on natural convection in a square enclosure partially heated from below 总被引:1,自引:0,他引:1
Nader Ben Cheikh Brahim Ben BeyaTaieb Lili 《International Communications in Heat and Mass Transfer》2007
Natural convection in air-filled 2D square enclosure heated with a constant source from below and cooled from above is studied numerically for a variety of thermal boundary conditions at the top and sidewalls. Simulations are performed for two kinds of lengths of the heated source, i.e., a small and a large source corresponding to 20% and 80% of the total length of the bottom wall, respectively. The Rayleigh number varied from 103 to 107. Results are presented in the form of streamline and isotherm plots as well as the variation of the Nusselt number and maximum temperature at the heat source surface. Comparisons among the different thermal configurations considered are reported. 相似文献
8.
Novel hybrid DNN approaches for speaker verification in emotional and stressful talking environments
Shahin Ismail Nassif Ali Bou Nemmour Nawel Elnagar Ashraf Alhudhaif Adi Polat Kemal 《Neural computing & applications》2021,33(23):16033-16055
Neural Computing and Applications - In this work, we conducted an empirical comparative study of the performance of text-independent speaker verification in emotional and stressful environments.... 相似文献
9.
10.
V.V. Pani? V.M. Jovanovi? M.W. Barsoum A.B. Dekanski 《Surface & coatings technology》2007,202(2):319-324
Electroactive oxide coatings on titanium, known in industrial chlorine production as dimensionally stable anodes (DSA), are of limited service life owing to the dissolution of active oxide, but also due to low corrosion stability of titanium, at high anodic potentials and elevated temperatures. In order to improve the anode stability, ternary carbide, Ti3SiC2, could be a promising material for the coating support, since chemical corrosion stability of Ti3SiC2 is significantly higher if compared to Ti. In this work, the possibility of the sol-gel preparation of RuO2-TiO2 coating on Ti3SiC2 is investigated and comparison of the basic characteristics of sol-gel processed oxide coating, Ru0.5Ti0.5O2, applied onto Ti3SiC2 and Ti, is reported. Microscopic investigation of the coating surface showed that considerably less cracked coating is formed onto the Ti3SiC2 support. Slightly higher voltammetric currents are registered for Ti3SiC2-supported coating in H2SO4 and NaCl solution. The activity for chlorine evolution is higher, while the currents of oxygen evolution reaction are lower for Ru0.5Ti0.5O2/Ti3SiC2 anode in comparison to Ru0.5Ti0.5O2/Ti anode. Even though these preliminary results on the basic electrochemical properties of Ru0.5Ti0.5O2/Ti3SiC2 anode and chemical stability of Ti3SiC2 are promising, the accelerated stability test in NaCl solution showed that coated Ti3SiC2 is not anodically stable and lasts considerably shorter than Ru0.5Ti0.5O2/Ti anode prepared and tested under the same conditions. 相似文献