Overshadowing and CS duration: counteraction and a reexamination of the role of within-compound associations in cue competition

In the present experiments, we examined the role of within-compound associations in the interaction of the overshadowing procedure with conditioned stimulus (CS) duration, using a conditioned suppression procedure with rats. In Experiment 1, we found that, with elemental reinforced training, conditioned suppression to the target stimulus decreased as CS duration increased (i.e., the CS duration effect), whereas, with compound reinforced training (i.e., the overshadowing procedure), conditioned suppression to the target stimulus increased as CS duration increased. In subsequent experiments, we replicated these findings with sensory preconditioning and demonstrated that extinction of the overshadowing stimulus results in retrospective revaluation with short CSs and in mediated extinction with long CSs. These results highlight the role of the duration of the stimulus in behavioral control. Moreover, these results illuminate one cause (the CS duration) of whether retrospective revaluation or mediated extinction will be observed.     

Spacing extinction trials alleviates renewal and spontaneous recovery

Studies of extinction in classical conditioning situations can reveal techniques that maximize the effectiveness of exposure-based behavior therapies. In three experiments, we investigated the effect of varying the intertrial interval during an extinction treatment in a fear-conditioning preparation with rats as subjects. In Experiment 1, we found less fear at test (i.e., more effective extinction) when extinction trials were widely spaced, relative to intermediate or massed extinction trials. In Experiment 2, we used an ABA renewal procedure and observed that spaced trials attenuated renewal of conditioned fear relative to massed trials. In Experiment 3, we used a similar design, but instead of changing the physical context at the time of testing, we interposed a retention interval after the extinction treatment to produce a change in the temporal context. The results showed less spontaneous recovery of fear after spaced than after massed extinction trials. These results suggest that extinction is more enduring when the extinction trials are spaced rather than massed. Although the benefits of spacing trials are small when there is no contextual change from extinction to testing, a change in either physical or temporal context following massed extinction trials leads to a recovery from extinction, which is reduced when the trials are spaced.     

试论图书馆员国际交流项目及其评估——以四川大学和亚利桑那州立大学图书馆员交流项目为例

[目的/意义] 针对图书馆员国际交流项目缺乏评估研究的现状,提出一种有借鉴意义的测量工具来评估其实际效果和价值。[方法/过程] 以四川大学和亚利桑那州立大学图书馆员交流项目为例,参考D. Bachner和U. Zeutschel对国际青年交流项目的测量和评估方法确定评估标准,引入李克特五分量表,结合要求详细阐述的开放式问题,形成一个定性和定量相结合的评估工具。[结果/结论] 通过评估,对馆员交流项目进行全面审视,确定其在个人、机构、制度层面的影响和效果,发现项目决策、实施过程中的亮点与不足,提出促进馆员国际交流项目进一步发展的建议。     

Rare cell isolation and profiling on a hybrid magnetic/size-sorting chip

We present a hybrid magnetic/size-sorting (HMSS) chip for isolation and molecular analyses of circulating tumor cells (CTCs). The chip employs both negative and positive cell selection in order to provide high throughput, unbiased CTC enrichment. Specifically, the system utilizes a self-assembled magnet to generate high magnetic forces and a weir-style structure for cell sorting. The resulting device thus can perform multiple functions, including magnetic depletion, size-selective cell capture, and on-chip molecular staining. With such capacities, the HMSS device allowed one-step CTC isolation and single cell detection from whole blood, tested with spiked cancer cells. The system further facilitated the study of individual CTCs for heterogeneity in molecular marker expression.Circulating tumor cells (CTCs) have emerged as an important biomarker in clinical practice as well as in fundamental research.^{1, 2} CTCs, shed from primary tumors, have been shown to be an early harbinger of tumor expansion and metastasis³ and have been used to predict disease progression, response to treatment, relapse, and overall survival.^{4, 5, 6} Recent work has shown that CTCs display distinct proteomic and genetic profiles; for example, CTCs in pancreatic cancer, have increased RNA expression of Wnt, implicating this pathway in metastasis.⁷ Proteomic characterization of proliferative markers such as Ki-67, and hormonal markers such as androgen receptor in prostate cancer, also have been shown to be predictive of treatment outcome.^{8, 9}Despite such clinical potential of CTCs, their routine detection and characterization still remains a significant technical challenge.¹⁰ The task requires screening of a large number of cells (e.g., > 10⁷ cells in 10 ml blood) and enrichment of heterogeneous targets against a complex biological background. Two main methods of CTC isolation are typically used: positive and negative selection. In positive selection, CTCs are directly isolated from blood via size-based filtration^{11, 12, 13, 14, 15, 16, 17, 18, 19, 20} or antibody-based capture.^{1, 8, 21} Negative depletion reduces abundant blood cells, often by immunomagnetic separation, for downstream CTC enrichment.²² Both approaches have been used for high throughput CTC isolation from whole blood (SI Table 1).²³ Each method, however, has its own inherent limitations. Positive enrichment could be biased by its selection criteria (e.g., cell size and cell surface markers). Negative selection, albeit unbiased, often requires complex sample processing (e.g., multiple washing steps for CTC isolation) that could result in cell loss.We hypothesized that both positive and negative selection could be combined in a single platform to enable (1) highly efficient and unbiased CTC purification, and (2) in-situ molecular analyses of collected cells. As a proof-of-concept, we herein describe a hybrid magnetic/size-sorting (HMSS) system that integrates magnetic and size-based isolation into a compact microfluidic chip. The HMSS first uses a magnetic filter to deplete leukocytes through immunomagnetic capture. Samples then pass through a size-sorter region that traps individual cells at predefined locations. Since abundant leukocytes are removed by the magnetic filter, the size-sorter could have a low size cut-off (∼5 μm), which allows for the unbiased capture of even small cancer cells. Furthermore, molecular probes can be introduced to perform on-chip, multiplexed analyses at single-cell resolution. We evaluated the utility of the developed system by capturing and profiling tumor cells in whole blood. The HMSS offers the advantages of both negative and positive selection and thereby differs from the recently reported iChip system²⁴ which can operate only in either a negative or a positive selection mode.     

Massive preexposure and preexposure in multiple contexts attenuate the context specificity of latent inhibition

Latent inhibition, which refers to attenuated responding to a conditioned stimulus (CS) after CS-unconditioned stimulus (CS-US) pairings as a result of CS-alone presentations prior to the pairings, is often attenuated if preexposure and conditioning occur in different contexts (i.e., it is context specific). Here we report two conditioned lick suppression experiments, using rat subjects, that examined whether manipulations known to attenuate the context specificity of extinction could also eliminate the context specificity of latent inhibition. Context specificity of latent inhibition was eliminated when the CS was preexposed in multiple contexts (Experiment 1) and when the CS was massively pre-exposed in the training context alone (Experiment 2). These results and their practical implications are discussed in the framework of contemporary theories of latent inhibition.     

A mixed design reveals that glucose moieties facilitate extinction of a conditioned taste aversion in rats

Separate groups of water-deprived rats had four trials with 15-min access to 0.0073 M saccharin, 0.3 M alanine, 0.3 M glucose, 0.1 M maltose, 0.3 M fructose, 0.06 M sucrose, or 0.03 M Polycose. Trials 1–3 were followed by injections of either 0.15 M LiCl (1.33 ml/100 g b.w., i.p.) or saline; Trial 4 (Test) was CS only. Extinction included either 48-h access to water alone or to the appropriate CS, both followed by a 24-h, two-bottle choice of CS and water. This 3-day cycle was repeated five to six times. All rats acquired comparable conditioned taste aversions (CTAs), but extinction rates varied with the test and the taste CS. No CTA extinguished during the two-bottle choices following 2 water days. During one-bottle CS exposure, all CTAs extinguished, but the aversion continued longer in the probe two-bottle tests. Intake of glucose moieties recovered rapidly, often in two cycles; the other CSs took four to six cycles. Thus, CTA extinction varies with the nature of the taste CS.     

Young Children's Ability to Adapt their Drawings of the Human Figure

5‐year‐olds, 7‐year‐olds and 9‐year‐olds were asked to draw three figures, one standing still and facing them, one standing still in profile and one running in profile. Half drew from imagination and half drew from models. The 5‐year‐olds made fewest distinctions in the way they drew the figures, the most notable being the greater spread of the legs of the running figure. With increasing age, more features were used to differentiate the three figures. There was little evidence of 5‐year‐olds adapting their figures in the presence of a model. Only among the older children was there a significant effect of the presence of a model when the 7‐year‐olds and, to a greater extent, the 9‐year‐olds drew their running figure with bent arms and legs and also with more transparencies and partial occlusions.