Charlie Chen

Cardiac Arrest leads to a global hypoxic-ischemic injury in the brain leading to a poor neurological outcome. Understanding the mechanisms of functional disruption in various regions of the brain may be essential for the development of improved diagnostic and therapeutic solutions. Using controlled laboratory experiment with animal models of CA, our primary focus here is on understanding the functional changes in the thalamus and the cortex, associated with the injury and acute recovery upon resuscitation. Specifically, to study the changes in thalamocortical synchrony through these periods, we acquired local field potentials from the ventroposterior lateral nucleus of the thalamus and the forelimb somatosensory cortex in rats after asphyxial CA. Band-specific relative Hilbert phases were used to analyze synchrony between the LFPs. We observed that the CA induced global ischemia changes the local phase-relationships by introducing a phase-lag in both the thalamus and the cortex, while the synchrony between the two regions is nearly completely lost after CA. © 2013 IEEE.

Exaggerated contraction of airway smooth muscle is the major cause of symptoms in asthma, but the mechanisms that prevent exaggerated contraction are incompletely understood. Here, we showed that integrin α 9β 1on airway smooth muscle localizes the polyamine catabolizing enzyme spermidine/spermine N 1-acetyltransferase in close proximity to the lipid kinase PIP5K1γ. As PIP5K1γ is the major source of PIP2 in airway smooth muscle and its activity is regulated by higher-order polyamines, this interaction inhibited IP3-dependent airway smooth muscle contraction. Mice lacking integrin α 9β 1 in smooth muscle had increased airway responsiveness in vivo, and loss or inhibition of integrin α 9β 1 increased in vitro airway narrowing and airway smooth muscle contraction in murine and human airways. Contraction was enhanced in control airways by the higher-order polyamine spermine or by cell-permeable PIP2, but these interventions had no effect on airways lacking integrin α 9β 1 or treated with integrin α 9β 1-blocking antibodies. Enhancement of SSAT activity or knockdown of PIP5K1γ inhibited airway contraction, but only in the presence of functional integrin α 9β 1. Therefore, integrin α 9β 1 appears to serve as a brake on airway smooth muscle contraction by recruiting SSAT, which facilitates local catabolism of polyamines and thereby inhibits PIP5K1γ. Targeting key components of this pathway could thus lead to new treatment strategies for asthma.

We report the design and characterization of a CMOS pixel direct charge sensor, Topmetal-II-, fabricated in a standard 0.35 μm CMOS Integrated Circuit process. The sensor utilizes exposed metal patches on top of each pixel to directly collect charge. Each pixel contains a low-noise charge-sensitive preamplifier to establish the analog signal and a discriminator with tunable threshold to generate hits. The analog signal from each pixel is accessible through time-shared multiplexing over the entire array. Hits are read out digitally through a column-based priority logic structure. Tests show that the sensor achieved a <15e- analog noise and a 200e- minimum threshold for digital readout per pixel. The sensor is capable of detecting both electrons and ions drifting in gas. These characteristics enable its use as the charge readout device in future Time Projection Chambers without gaseous gain mechanism, which has unique advantages in low background and low rate-density experiments.

© 2013, Springer-Verlag Berlin Heidelberg.Overweight and obesity are rapidly becoming a central public health challenge around the world. Previous studies have suggested that elevated Body Mass Index might be associated with structural changes in both gray and white matter, but this association is still not well understood. The present study aimed to investigate the relationship between BMI and brain structure with a relatively large sample of young adults in a small age range. Voxel-based morphometry results showed significant negative correlations between BMI and gray-matter volumes in the midcingulate cortex, left orbital frontal cortex, and left ventromedial prefrontal cortex. There was also a significant negative correlation between BMI and white matter integrity as indexed by fractional anisotropy in bilateral cingulum. Further tractography analysis showed a significant negative correlation between BMI and the number of fibers passing the MCC region. Regression analysis showed that gray matter and white matter in these regions both contributed to the variance of BMI. These results remained significant even when analysis was restricted to the subjects with normal weights. Finally, we found that decision-making ability mediated the association between the structure of the MCC and BMI. These results shed light on the structural neural basis of weight variations.

This study examined risk and protection for adolescent problem behavior and depressive symptomatology in an average-risk sample of 11th graders. Using a socioecological perspective, we aggregated risk factors for adolescent problem behavior and depressed mood by 3 social contexts: i.e., family and peer contexts, and a context comprising the most important nonparental adult in respondents' lives. Protective factors associated with these 3 contexts were also included in the analyses. We tested separate models for predicting problem behaviors and depressive symptoms; the models demonstrated divergent validity. Risk and protective factors accounted for 49% of the variance in problem behavior and 49% in depressive symptoms. Tests of interactions between risk-aggregates and protective factors yielded several significant cross-context buffering effects in the problem behavior model, but none in the depressive symptoms model. Parents' and VIP's perceived sanctions buffered adolescents against high risk for problem behavior emanating from the peer context. Additionally, perceived peers' sanctions buffered youths against risk emanating from each of the 3 contexts.

American, 1,633 Chinese, and 1,247 Japanese eleventh‐grade students, 5 indices of maladjustment included measures of stress, depressed mood, academic anxiety, aggression, and somatic complaints. Asian students reported higher levels of parental expectation and lower levels of parental satisfaction concerning academic achievement than their American peers. Nevertheless, Japanese students reported less stress, depressed mood, aggression, academic anxiety, and fewer somatic complaints than did American students. Chinese students reported less stress, academic anxiety, and aggressive feelings than their American counterparts, but did report higher frequencies of depressed mood and somatic complaints. High academic achievement as assessed by a test of mathematics was generally not associated with psychological maladjustment. The only exception was in the United States, where high achievers indicated more frequent feelings of stress than did low achievers. Copyright © 1994, Wiley Blackwell. All rights reserved.

Objectives: The aim of the current study was to differentiate between neural activity that represents neural anomalies that are responsible for persistent developmental stuttering from the activity that is a result of compensating for stuttering. This was done by investigating alterations to the intrinsic functional architecture of speech-language processes of patients with PDS before and after a short-term intervention. Methods: The resting-state functional connectivity and cortical thickness were examined before and after the intervention. The structural data were used to validate the functional results. Fifteen stuttering patients who received intervention, 13 stuttering patients who did not receive intervention, and 13 fluent controls participated. Results: Before the intervention, both groups of PDS patients showed significant RSFC and cortical thickness reductions in the left pars-opercularis and RSFC increases in the cerebellum, as compared to fluent controls. The intervention was effective in reducing stuttering in PDS- patients and lowering their RSFC in the cerebellum to the level of fluent controls. The intervention effect was specific to the PDS-group. The intervention did not change RSFC and cortical thickness in the left PO, which remained at its preintervention level. Conclusions: The results suggest that the left PO is a locus where the intrinsic functional architecture of speech-language processes is altered in PDS patients, suggesting an etiologic role of this region in PDS. The cerebellum showed intervention-induced neural reorganization, suggesting a compensatory response when stuttering occurs. Copyright © 2012 by AAN Enterprises, Inc.

Previous research has consistently demonstrated the importance of parents' expectations and adolescents' expectations on adolescents' academic achievement. Less is known, however, about the reciprocal relationships among these constructs. To address this issue, we analyzed two waves of data from the National Education Longitudinal Study of 1988 using longitudinal cross-lagged path models. The sample consisted of 14,376 students. Results indicated that there was a reciprocal relationship between parents' expectations and adolescents' expectations. Moreover, there was a reciprocal relationship between expectations and adolescents' academic achievement. Multiple-group analyses of gender and ethnicity revealed that the effects of parents' expectations on students' expectations were stronger among males than among females. With respect to ethnic differences, the effects of adolescents' expectations were weakest on parents' expectations among African Americans as compared to the other ethnic groups. Implications of these findings are discussed. © 2010 The Author.

Using the ER-fMRI technique, the present study was designed to investigate the neural substrates of language switching among second-language learners. Twelve Chinese college students who were learning English were scanned when they performed language switching tasks. Compared to non-switching conditions, language switching elicited greater activation in the right superior prefrontal cortex, left middle and superior frontal cortex, and right middle cingulum and caudate. When the direction of switching was considered, forward switching, but not backward switching, activated several brain regions related to executive functions relative to non-switching conditions. These results suggest that neural correlates of language switching differ depending on the direction of the switch and that there does not seem to be a specific brain area acting as a "language switch". © 2006.

There are great individual differences in learning abilities, but their neural bases, especially among normal populations, are not well understood. Using functional magnetic resonance imaging and a training paradigm, the present study investigated individual differences in cerebral asymmetry in fusiform regions when processing a new writing system and their correlation to subsequent visual character learning. Twelve Chinese adults underwent a 2-week training to learn 120 Korean characters and they were scanned before and after the training. Results showed that left-hemispheric dominance during the pretraining task was predictive of better posttraining performance. These results have significant implications for our understanding of the neural basis of language learning, especially in terms of individual differences. © 2006 Massachusetts Institute of Technology.

Existing cognitive and neural imaging studies have suggested a frontoparietal network of multiple, cooperative components for verbal working memory. We used functional MRI to investigate whether this neural network is also involved in the processing of second language by nonfluent bilinguals. Twelve native Chinese speakers who had limited English proficiency were scanned while performing working memory tasks in Chinese and English. They were asked to make judgment continuously whether the word presented on the screen was semantically related to another word presented two words earlier. On a different task, they were asked to make judgment whether the target word rhymed with the other word. A naming and judgment task in each language was adopted to control for the visual process, initial lexical process, and motor responses. Behavioral data showed that subjects performed better at tasks in their native language than in English. Imaging results showed that all working memory tasks in both L1 and L2 elicited a very similar pattern of left-hemisphere-dominated activation in the dorsolateral prefrontal cortex, pars opercularis region, pars triangularis region, precentral cortex, and parietal lobule. Consistent with the behavioral data, the volume of activation in the left opercularis region, left parietal lobule, and right precentral region was greater for L2 than for L1. These results suggest that working memory in L1 and L2 is mediated by a unitary neural system, which is capable of recruiting surrounding cortical resources to meet the increased computational demand caused by low L2 proficiency. © 2004 Elsevier Inc. All rights reserved.

As part of a larger program of research on the nature of adolescents' relationships with very important nonparental adulis, a community sample of 243 eleventh graders was surveyed, and a subgroup of 55 adolescents and their VIPs were interviewed about the nature and quality of their relationships. Results showed that adolescent-VIP relationships were a normative component of adolescent development, not a result of problems in adolescents' lives; adolescent-VIP relationships were generally of high quality ; there were significant differences between kin and nonkin VIPs in terms of the duration of relationships and frequency of contact, but not in the quality of relationships; and VIPs whom, adolescents designated as extremely important were distinguished from other VIPs in terms of providing a higher level of social support and a higher frequency of contact. Theoretical and practical implications of these findings are discussed.

A decade of heightened emphasis in the United States on mathematics and science education has had little influence on academic achievement or parental attitudes. American elementary school children in 1990 lagged behind their Chinese and Japanese peers to as great a degree as they did in 1980. Comparison of the performance of elementary and secondary school students between 1980 and 1990 reveals a decline from first to eleventh grade in the relative position of American students in mathematics. Parental satisfaction with American students' achievement and education remains high and standards remain low. Innate ability continues to be emphasized by Americans as a basis for achievement. American eleventh graders report more indications of stress than do their Chinese and Japanese counterparts.

Analyses were conducted of data from 5 studies related to the academic achievement and cognitive abilities of students in Japan, Taiwan, Mainland China, and the United States. Cross-sectional and longitudinal data were available for students in kindergarten and grades 1, 5, and 11. The analyses compared the top 10 percent of students with the 10 percent of the students whose scores clustered most closely to the average on tests of cognitive ability and then on tests of mathematics achievement. The high ability students in Asian samples outperformed high ability American students in mathematics at grade level 1, 5, and 11 but not in reading. Parents of high ability students in the United States had a higher opinion of their children's ability and performance than did Japanese parents of high ability students. Many factors related to high ability and/or to high achievement are discussed, including mothers’ and students'evaluations of the students’ abilities and personality characteristics, attributional beliefs, sources of motivation, psychological well-being, and demographic factors. The relation of cognitive ability to academic achievement is also discussed. © 1993, The Association of the Gifted. All rights reserved.

A total of 1151 children from indigenous Quechua-speaking families residing in squatter settlements of the city and in two remote rural environments in Peru was given a battery of 16 tests of academic achievement and cognitive abilities. The former tests assessed reading and mathematics achievement and the latter tapped a broad range of cognitive functions. Children were enrolled in first, second, or third grade or did not attend school. "Younger" children were from 6 to 8 years old, and "older" children were from 9 to 12 years old. Large differences in cognitive functioning were associated with attendance at school, grade in school, age, and urban-rural residence. Gender was found to account for less than 5% of the variance in children's performance on cognitive and academic tasks. Gender effects appeared to decline with increased amount of schooling. This was reflected in interactions involving gender and schooling and in a greater number of significant gender effects for children who did not attend school or were in first grade. The results present a complicated picture of various interactional effects of task, location, age, and schooling on the detected gender differences in cognitive abilities and academic achievement. © 1990 Plenum Publishing Corporation.

This study explores the effect of attending school on children's achievement in reading and mathematics and on a test of general information. The major focus was on the interaction between three variables: children's age [young or old ], location, and the number of years of schooling. A follow-up study was conducted nine years after the original testing. Schooling had a positive effect on children's performance, but the degree of influence depended upon all three of the major variables. Schooling tended to have a greater effect on the achievement scores than on the general information scores. In general, scores were highest among children residing in the city and lowest among children living in the remote jungle areas. After controlling for location, age, and years of education, family variables such as parental education and home quality had a small, but significant influence on children's knowledge of reading, mathematics, and general information. © 1990.

This study reports cross-linguistic differences in forward digit span between 4-, 5-, and 6-year-old American and Chinese children. Several explanations for the remarkable superiority of Chinese children are examined. Hypotheses concerning practice, counting systems, and use of strategies were not supported. Analyses related to pronunciation duration of digits favored the temporally limited store hypothesis. Nonsignificant cross-linguistic differences were found in backward digit span. The results support the notion that forward and backward digit span involve different mechanisms. © 1988.

First and fifth graders in Beijing and Chicago were given a battery of mathematics tests. Whether tested with problems requiring solely computation or with ones requiring application of knowledge about mathematics, American children's performance was consistently inferior to that of Chinese children. Interviews with American children suggested that they like mathematics, believe they are doing well in mathematics, and do not perceive mathematics as a difficult subject. American children's poor performance appears to be attributable, in part, to low motivation for devoting more attention to mathematics. Low standards held by American parents for academic achievement and lower interest in teaching mathematics by American teachers appear to contribute to American children's poor performance. Copyright © 1990, Wiley Blackwell. All rights reserved.

This study examined the motivation and mathematics achievement of Asian‐American, Caucasian‐American, and East Asian students. Subjects were 304 Asian‐American, 1,958 Caucasian‐American, 1,475 Chinese, and 1,120 Japanese eleventh graders. Students were given a curriculum‐based mathematics test and a questionnaire. Mathematics scores of the Asian‐American students were higher than those of Caucasian‐American students but lower than those of Chinese and Japanese students. Factors associated with the achievement of Asian‐American and East Asian students included having parents and peers who hold high standards, believing that the road to success is through effort, having positive attitudes about achievement, studying diligently, and facing less interference with their schoolwork from jobs and informal peer interactions. Contrary to the popular belief that Asian‐American students' high achievement necessarily takes a psychological toll, they were found not to report a greater frequency of maladjustive symptoms than Caucasian‐American students. Copyright © 1995, Wiley Blackwell. All rights reserved.

Increased airway smooth muscle contractility and the development of airway hyperresponsiveness are cardinal features of asthma, but the signaling pathways that promote these changes are poorly understood. Tyrosine phosphorylation is tightly regulated by the opposing actions of protein tyrosine kinases and phosphatases, but little is known about whether tyrosine phosphatases influence AHR. Here, we demonstrate that genetic inactivation of receptor-like protein tyrosine phosphatase J, which encodes CD148, protected mice from the development of increased AHR in two different asthma models. Surprisingly, CD148 deficiency minimally affected the inflammatory response to allergen, but significantly altered baseline pulmonary resistance. Mice specifically lacking CD148 in smooth muscle had decreased AHR, and the frequency of calcium oscillations in CD148-deficient ASM was substantially attenuated, suggesting that signaling pathway alterations may underlie ASM contractility. Biochemical analysis of CD148-deficient ASM revealed hyper-phosphorylation of the C-terminal inhibitory tyrosine of SRC family kinases, implicating CD148 as a critical positive regulator of SFK signaling in ASM. The effect of CD148 deficiency on ASM contractility could be mimicked by treatment of both mouse trachea and human bronchi with specific SFK inhibitors. Our studies identify CD148 and the SFKs it regulates in ASM as potential targets for the treatment of AHR.

Integrins are transmembrane heterodimeric receptors that contribute to diverse biological functions and play critical roles in many human diseases. Studies using integrin subunit knockout mice and inhibitory antibodies have identified important roles for nearly every integrin heterodimer and led to the development of a number of potentially useful therapeutics. One notable exception is the α v β 1 integrin. α v and β 1 subunits are individually present in numerous dimer pairs, making it challenging to infer specific roles for α v β 1 by genetic inactivation of individual subunits, and α v β 1 complex-specific blocking antibodies do not yet exist. We therefore developed a potent and highly specific small-molecule inhibitor of α v β 1 to probe the function of this understudied integrin. We found that α v β 1, which is highly expressed on activated fibroblasts, directly binds to the latency-associated peptide of transforming growth factor-β 1 and mediates TGFb1 activation. Therapeutic delivery of this α v β 1 inhibitor attenuated bleomycin-induced pulmonary fibrosis and carbon tetrachloride-induced liver fibrosis, suggesting that drugs based on this lead compound could be broadly useful for treatment of diseases characterized by excessive tissue fibrosis.

© The Author 2017.Topological Weyl semimetal, a new state of quantum matter, has sparked enormous research interest recently. Possessing unique Weyl fermions in the bulk and Fermi arcs on the surface, TWSs offer a rare platform for realizing many exotic physical phenomena. TWSs can be classified into type-I that respect Lorentz symmetry and type-II that do not. Here, we directly visualize the electronic structure of MoTe 2, a recently proposed type-II TWS. Using angle-resolved photoemission spectroscopy, we unravel the unique surface Fermi arcs, in good agreement with our ab initio calculations that have nontrivial topological nature. Our work not only leads to new understandings of the unusual properties discovered in this family of compounds, but also allows for the further exploration of exotic properties and practical applications of type-II TWSs, as well as the interplay between superconductivity and their topological order.