Tensile creep behaviors of a hot compressed Mg-4Y-2Nd-0.2Zn-0.5Zr alloy with aging (the AA sample) and without aging (the AS sample) are studied at 473, 493 and 523 K under a wide range of applied stresses. The creep mechanism of the AS sample is dislocation viscous gliding. For the AA sample, the creep mechanism is cross-slip during the early creep stage and dislocation climb and pyramidal slip during the late. Furthermore, the precipitates can be dissolved into the matrix and restarted during the subsequent creep stages. At 473 and 493 K, the AA sample has a better creep resistance than the AS sample, due to the hindering effect of the precipitates on dislocation movement. At 523 K and higher stress levels, the precipitates have limited hindering effect on dislocation movement in the AA sample while the kink bands continue to serve as the strengthening mechanism in the AS sample. The creep resistance of the AA sample becomes lower than that of the AS sample. It is recommended that the AA sample be used in the applications where their service temperature is lower than the pre-aging temperature while the AS sample be used where service temperature is higher than the pre-aging temperature.

Object proposals are an ensemble of bounding boxes with high potential to contain objects. In order to determine a small set of proposals with a high recall, a common scheme is extracting multiple features followed by a ranking algorithm which however, incurs two major challenges: 1) The ranking model often imposes pairwise constraints between each proposal, rendering the problem away from an efficient training/testing phase; 2) Linear kernels are utilized due to the computational and memory bottleneck of training a kernelized model. In this paper, we remedy these two issues by suggesting a kernelized partial ranking model. In particular, we demonstrate that i) our partial ranking model reduces the number of constraints from O(n(2)) to 0(nk) where n is the number of all potential proposals for an image but we are only interested in top-k of them that has the largest overlap with the ground truth; ii) we permit non-linear kernels in our model which is often superior to the linear classifier in terms of accuracy. For the sake of mitigating the computational and memory issues, we introduce a consistent weighted sampling (CWS) paradigm that approximates the non-linear kernel as well as facilitates an efficient learning. In fact, as we will show, training a linear CWS model amounts to learning a kernelized model. Extensive experiments demonstrate that equipped with the non-linear kernel and the partial ranking algorithm, recall at top-k proposals can be substantially improved. (C) 2017 Elsevier Ltd. All rights reserved.

Failure of oligodendrocyte precursor cells (OPCs) to differentiate and remyelinate axons is thought to be a major cause of the limited ability of the central nervous system to repair plaques of immune-mediated demyelination in multiple sclerosis (MS). Current therapies for MS aim to lessen the immune response in order to reduce the frequency and severity of attacks, but these existing therapies do not target remyelination or stimulate repair of the damaged tissue. Thus, the promotion of OPC differentiation and remyelination is potentially an important therapeutic goal. Previous studies have shown that a recombinant human-derived monoclonal IgM antibody, designated rHIgM22, promotes remyelination, particularly of the spinal cord in rodent models of demyelination. Here, we examined the effects of rHIgM22 in remyelination in the brain using the mouse model of cuprizone-induced demyelination, which is characterized by spontaneous remyelination. The myelination state of the corpus callosum of cuprizone-fed mice treated with rHIgM22 was examined immediately after the end of the cuprizone diet as well as at different time points during the recovery period with regular food, and compared with that of cuprizone-fed animals treated with either vehicle or human IgM isotype control antibody. Mice fed only regular food were used as controls. We demonstrate that treatment with rHIgM22 accelerated remyelination of the demyelinated corpus callosum. The remyelination-enhancing effects of rHIgM22 were found across different, anatomically distinct regions of the corpus callosum, and followed a spatiotemporal pattern that was similar to that of the spontaneous remyelination process. These enhancing effects were also accompanied by increased differentiation of OPCs into mature oligodendrocytes. Our data indicate strong remyelination-promoting capabilities of rHIgM22 and further support its therapeutic potential in MS. (C) 2017 The Authors. Published by Elsevier Inc.

Self-ion irradiation is widely used as a method to simulate neutron damage in reactor structural' materials. Accelerator-based simulation of void swelling, however, introduces a number of neutron-atypical features which require careful data extraction and, in some cases, introduction of innovative irradiation techniques to alleviate these issues. We briefly summarize three such atypical features: defect imbalance effects, pulsed beam effects, and carbon contamination. The latter issue has just been recently recognized as being relevant to simulation of void swelling and is discussed here in greater detail. It is shown that carbon ions are entrained in the ion beam by Coulomb force drag and accelerated toward the target surface. Beam-contaminant interactions are modeled using molecular dynamics simulation. By applying a multiple beam deflection technique, carbon and other contaminants can be effectively filtered out, as demonstrated in an irradiation of HT-9 alloy by 3.5 MeV Fe ions. (C) 2017 Elsevier B.V. All rights reserved.

Nanoscale carriers with an acid-labile linker between the carrier and drug are commonly used for drug delivery. However, their efficacy is potentially limited by inefficient linker cleavage, and lysosomal entrapment of drugs. To address these critical issues, we developed a new imaging method that spatially overlays the location of a nanoparticle and the released drug from the nanoparticle, on a map of the local intracellular pH that delineates individual endosomes and lysosomes, and the therapeutic intracellular target of the drug-the nucleus. We used this method to quantitatively map the intracellular fate of micelles of a recombinant polypeptide conjugated with doxorubicin via an acid-labile hydrazone linker as a function of local pH and time within live cells. We found that hydrolysis of the acid-labile linker is incomplete because the pH range of 4-7 in the endosomes and lysosomes does not provide complete cleavage of the drug from the nanoparticle, but that once cleaved, the drug escapes the acidic endo-lysosomal compartment into the cytosol and traffics to its therapeutic destination-the nucleus. This study also demonstrated that unlike free drug, which enters the cytosol directly through the cell membrane and then traffics into the nucleus, the nanoparticle-loaded drug almost exclusively traffics into endosomes and lysosomes upon intracellular uptake, and only reaches the nucleus after acid-triggered drug release in the endo-lysosomes. This methodology provides a better and more quantitative understanding of the intracellular behavior of drug-loaded nanoparticles, and provides insights for the design of the next-generation of nanoscale drug delivery systems.