BackgroundGliomas account for the major part of primary brain tumors. Based on their histology and molecular alternations, adult gliomas have been classified into four grades, each with distinct biology and outcome. Previous studies have focused on cell-line-based models and patient-derived xenografts (PDXs) from patient-derived glioma cultures for grade IV glioblastoma. However, the PDX of lower grade diffuse gliomas, particularly those harboring the endogenous IDH mutation, are scarce due to the difficulty growing glioma cells in vitro and in vivo. The purpose of this study was to develop a panel of patient-derived subcutaneous xenografts of different grade gliomas that represented the heterogeneous histopathologic and genetic features of human gliomas.MethodsTumor pieces from surgical specimens were subcutaneously implanted into flanks of NOD-Prkdcscid ll2rgnull mice. Then, we analyzed the association between the success rate of implantation with clinical parameters using the Chi square test and resemblance to the patient’s original tumor using immunohistochemistry, immunofluorescence, short tandem repeat analysis, quantitative real-time polymerase chain reaction, and whole-exome sequencing.ResultsA total of 11 subcutaneous xenografts were successfully established from 16 surgical specimens. An increased success rate of implantation in gliomas with wild type isocitrate dehydrogenase (IDH) and high Ki67 expression was observed compared to gliomas with mutant IDH and low Ki67 expression. Recurrent and distant aggressive xenografts were present near the primary implanted tumor fragments from WHO grades II to IV. The xenografts histologically represented the corresponding patient tumor and reconstituted the heterogeneity of different grade gliomas. However, increased Ki67 expression was found in propagated xenografts. Endothelial cells from mice in patient-derived xenografts over several generations replaced the corresponding human tumor blood vessels. Short tandem repeat and whole-exome sequencing analyses indicated that the glioma PDX tumors maintained their genomic features during engraftments over several generations.ConclusionsThe panel of patient-derived glioma xenografts in this study reproduced the diverse heterogeneity of different grade gliomas, thereby allowing the study of the growth characteristics of various glioma types and the identification of tumor-specific molecular markers, which has applications in drug discovery and patient-tailored therapy.

Learning in many visual perceptual tasks has been shown to be specific to practiced stimuli, while new stimuli have to be learned from scratch. Here we demonstrate generalization using a novel paradigm in motion discrimination where learning has been previously shown to be specific. We trained subjects to discriminate directions of moving dots, and verified the previous results that learning does not transfer from a trained direction to a new one. However, by tracking the subjects' performance across time in the new direction, we found that their speed of learning doubled. Therefore, we found generalization in a task previously considered too difficult to generalize. We also replicated, in a second experiment, transfer following training with 'easy' stimuli, when the difference between motion directions is enlarged. In a third experiment we found a new mode of generalization: after mastering the task with an easy stimulus, subjects who have practiced briefly to discriminate the easy stimulus in a new direction generalize to a difficult stimulus in that direction. This generalization depends on both the mastering and the brief practice. The specificity of perceptual learning and the dichotomy between learning of 'easy' versus 'difficult' tasks have been assumed to involve different learning processes at different cortical areas. Here we show how to interpret these results in terms of signal detection theory. With the assumption of limited computational capacity, we obtain the observed phenomena--direct transfer and acceleration of learning--for increasing levels of task difficulty. Human perceptual learning and generalization, therefore, concur with a generic discrimination system.

The electrochemical reduction of CO to syngas with a tunable CO/H ratio is regarded as an economical and promising method for the future. Herein, a series of earth-abundant Zn catalysts with different crystal facet ratios of Zn(002) to Zn(101) in the bulk phase have been prepared on electrochemically polished Cu foam by the electrochemical deposition method. The Zn catalyst with more (101) crystal facets show good electrochemical activity for the CO reduction reaction (CORR) to CO and that with more (002) crystal facets favor the hydrogen evolution reaction. The linear relationship between the crystal facet ratio of Zn(101) to Zn(002) and the Faradaic efficiency (FE) of CORR to CO has been revealed for the first time. The prepared catalyst with more (101) facets show greater than 85% FE to syngas at -0.9 V (vs reversible hydrogen electrode) in aqueous electrolyte, with tunable CO/H ratios ranging from 0.2 to 2.31 that can be used in existing industrial systems. Meanwhile, the mechanism of electroreduction of CO on the Zn electrode has been studied by in situ infrared absorption spectroscopy. The highly selective role of the Zn(101) crystal facet in the CORR to CO has been evidenced by density functional theory calculations.

We describe a novel approach, based on ideal observer analysis, for measuring the ability of human observers to use image information for 3D object perception. We compute the statistical efficiency of subjects relative to an ideal observer for a 3D object classification task. After training to 11 different views of a randomly shaped thick wire object, subjects were asked which of a pair of noisy views of the object best matched the learned object. Efficiency relative to the actual information in the stimuli can be as high as 20%. Increases in object regularity (e.g. symmetry) lead to increases in the efficiency with which novel views of an object could be classified. Furthermore, such increases in regularity also lead to decreases in the effect of viewpoint on classification efficiency. Human statistical efficiencies relative to a 2D ideal observer exceeded 100%, thereby excluding all models which are sub-optimal relative to the 2D ideal.

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