Analysis of crossing fibers is a challenging topic in recent diffusion-weighted imaging (DWI). Resolving crossing fibers is expected to bring major changes to present tractography results based on the standard tensor model. Model free approaches, like Q-ball or diffusion spectrum imaging, as well as multi-tensor models are used to unfold the different diffusion directions mixed in a voxel of DWI data. Due to its seeming simplicity, the two-tensor model (TTM) is applied frequently to provide two positive-definite tensors and the relative population fraction modeling two crossing fiber branches. However, problems with uniqueness and noise instability are apparent. To stabilize the fit, several of the 13 physical parameters are fixed ad hoc, before fitting the model to the data. Our analysis of the TTM aims at fitting procedures where ad hoc parameters are avoided. Revealing sources of instability, we show that the model's inherent ambiguity can be reduced to one scalar parameter which only influences the fraction and the eigenvalues of the TTM, whereas the diffusion directions are not affected. Based on this, two fitting strategies are proposed: the parsimonious strategy detects the main diffusion directions without extra parameter fixation, to determine the eigenvalues and the population fraction an empirically motivated condition must be added. The expensive strategy determines all 13 physical parameters of the TTM by a fit to DWIs alone; no additional assumption is necessary. Ill-posedness of the model in case of noisy data is cured by denoising of the data and by L-curve regularization combined with global minimization performing a least-squares fit of the full model. By model simulations and real data applications, we demonstrate the feasibility of our fitting strategies and achieve convincing results. Using clinically affordable diffusion acquisition paradigms (encoding numbers: 21, 2*15, 2*21) and b values (b = 500–1500 s/mm2), this methodology can place the TTM parameters involved in crossing fibers on a more empirical basis than fitting procedures with technical assumptions. 相似文献
The neuraminidase (NA) inhibitor, oseltamivir, is a widely used anti‐influenza drug. However, oseltamivir‐resistant H1N1 influenza viruses carrying the H275Y NA mutation spontaneously emerged as a result of natural genetic drift and drug treatment. Because H275Y and other potential mutations may generate a future pandemic influenza strain that is oseltamivir‐resistant, alternative therapy options are needed. Herein, we show that a structure‐based computational method can be used to identify existing drugs that inhibit resistant viruses, thereby providing a first line of pharmaceutical defense against this possible scenario. We identified two drugs, nalidixic acid and dorzolamide, that potently inhibit the NA activity of oseltamivir‐resistant H1N1 viruses with the H275Y NA mutation at very low concentrations, but have no effect on wild‐type H1N1 NA even at a much higher concentration, suggesting that the oseltamivir‐resistance mutation itself caused susceptibility to these drugs. 相似文献
Rotaviruses are the leading cause of diarrhoea in infants around the globe and, under certain conditions they can be present in drinking water sources and systems. Ingestion of 10–100 viral particles is enough to cause disease, emphasizing the need for sensitive diagnostic methods. In this study we have optimized the concentration of rotavirus particles using methacrylate monolithic chromatographic supports. Different surface chemistries and mobile phases were tested. A strong anion exchanger and phosphate buffer (pH 7) resulted in the highest recoveries after elution of the bound virus with 1 M NaCl. Using this approach, rotavirus particles spiked in 1 l volumes of tap or river water were efficiently concentrated. The developed concentration method in combination with a real time quantitative polymerase chain reaction assay detected rotavirus concentrations as low as 100 rotavirus particles/ml. 相似文献
We developed a new method for real‐time, three‐dimensional tracking of fluorescent particles. The instrument is based on a laser‐scanning confocal microscope where the focus of the laser beam is scanned or orbited around the particle. Two confocal pinholes are used to simultaneously monitor regions immediately above and below the particle and a feedback loop is used to keep the orbit centered on the particle. For moderate count rates, this system can track particles with 15 nm spatial resolution in the lateral dimensions and 50 nm in the axial dimension at a temporal resolution of 32 ms. To investigate the interaction of the tracked particles with cellular components, we have combined our orbital tracking microscope with a dual‐color, wide‐field setup. Dual‐color fluorescence wide‐field images are recorded simultaneously in the same image plane as the particle being tracked. The functionality of the system was demonstrated by tracking fluorescent‐labeled artificial viruses in tubulin‐eGFP expressing HUH7 cells. The resulting trajectories can be used to investigate the microtubule network with super resolution.相似文献
The structure and electronic structure of different high-symmetry surfaces of either quasicrystalline or approximant Al–Pd–Mn were studied by means of photoemission-based techniques such as X-ray photoelectron diffraction (XPD) and ultraviolet photoelectron spectroscopy. We find that the twofold (2f), 3f and 5f surfaces of icosahedral Al–Pd–Mn exhibit all the symmetry elements of the icosahedral non-crystallographic group. These XPD experiments can be modeled by single-scattering cluster calculations.
The bulk-terminated icosahedral or approximant surfaces are recovered after ion sputtering followed by annealing at T≈500–600 °C. A wealth of ordered surface phases (with different compositions) are found after sputtering and depending on the annealing temperature as, for example, a crystalline bcc multitwinned phase (for T<400 °C) or a stable decagonal quasicrystalline surface (for T>650 °C).
The icosahedral surfaces are characterised by a lowering of the density of states close to the Fermi edge, compatible with the opening of a pseudogap, as expected for a quasicrystal. The crystalline overlayers are characterised by a sharp Fermi edge, while the approximant and decagonal quasicrystalline surfaces also have a lowered density of states. 相似文献
The self-assembly of protein polymers is a promising route to prepare sophisticated functional nanostructures. However, the interplay between protein self-assembly by itself and its co-assembly with a template is not well understood. Silk-based protein polymers that co-assemble with DNA to form rod-like artificial viruses are herein developed and the effects of silk block length, concentration, and temperature in the self-assembly of the proteins alone are characterized by using a combination of bulk dynamic light scattering (DLS) and single-molecule atomic force microscopy (AFM). Protein nanorods were slowly formed (up to hours) through the interaction of the silk-like blocks. The proteins present a silk-length dependent critical elongation concentration, and above it the amount and size of nanorods rapidly increase. Temperature-dependent light scattering data was adequately fitted into a cooperative model of nucleation–elongation. These results are also important to understand the self-assembly of designed viral coat proteins with DNA templates to form artificial virus-like particles and help us to define general guidelines to design proteins with the ability to precisely organize matter at the nanoscale. 相似文献