Li Zhang

Multimodal neuroimaging provides a rich source of data for identifying brain regions associated with disease progression and aging. However, present studies still typically analyze modalities separately or aggregate voxel-wise measurements and analyses to the structural level, thus reducing statistical power. As a central example, previous works have used two quantitative MRI parameters—R2* and quantitative susceptibility —to study changes in iron associated with aging in healthy and multiple sclerosis subjects, but failed to simultaneously account for both. In this article, we propose a unified framework that combines information from multiple imaging modalities and regularizes estimates for increased interpretability, generalizability, and stability. Our work focuses on joint region detection problems where overlap between effect supports across modalities is encouraged but not strictly enforced. To achieve this, we combine L1, total variation, and L2 group lasso penalties. While the TV penalty encourages geometric regularization by controlling estimate variability and support boundary geometry, the group lasso penalty accounts for similarities in the support between imaging modalities. We address the computational difficulty in this regularization scheme with an alternating direction method of multipliers optimizer. In a neuroimaging application, we compare our method against independent sparse and joint sparse models using a dataset of R2* and QS maps derived from MRI scans of 113 healthy controls: our method produces clinically-interpretable regions where specific iron changes are associated with healthy aging. Together with results across multiple simulation studies, we conclude that our approach identifies regions that are more strongly associated with the variable of interest, more accurate, and more stable with respect to training data variability. This work makes progress toward a stable and interpretable multimodal imaging analysis framework for studying disease-related changes in brain structure and can be extended for classification and disease prediction tasks.

Patent strategy is increasingly recognized as a vital contributor in promoting core competitiveness of an enterprise. A top management team has been indicated as one of the key factors driving changes in patent strategy. Based on upper echelons theory, this study examines how TMT characteristics, including, team diversity, emotional intelligence, and safety climate, influence enterprise patent strategic change and, hence, the business outcome. The data from 930 top managers in 228 enterprises showed that the changes in patent strategies are significantly influenced by the characteristics of top managers. These aforementioned internal TMT factors have diverse effects on the speed and scope of the enterprise patent strategic change, which in turn affects firm performance in a positive and negative way, respectively.

As professional football stadiums continue to grow in popularity worldwide, fans are able to watch the game in closer proximity, but the design of professional football stadiums to shorten the distance between fans and the playing field also exacerbates the impact of the home advantage on the referee’s decision to call a penalty. Studies have confirmed the existence of the home advantage and found that experienced referees can reduce the impact of this interference, but the neural mechanisms behind this phenomenon have not been adequately investigated. In this study, we designed a soccer referee decision making task based on a home field effect scenario in a real soccer game, and used event-related potentials to compare the decision making and EEG differences between individuals with different experience levels when faced with foul actions under spectator noise interference. The experiments showed that individuals with different experience levels triggered a significant ERN EEG component when performing the penalty decision task under the home field effect factor, suggesting that the interference of the home field effect may lead referees to correct their previous decision-making behavior patterns in the penalty decision and reduce unfavorable calls against the home team. In contrast, referees with officiating experience elicited smaller ERN amplitudes compared to other subjects, suggesting that experience factors may inhibit this tendency to change behavioral patterns. This study suggests that in response to the increasing trend of professional football stadiums, policy makers should place more emphasis on enhancing the experience level of referees in the training of referees to ensure the fairness of the game.

With the service-dominant logic gradually replacing the traditional commodity-dominant reason, co-creating value with consumers has become an essential marketing practice for enterprises. As a critical information carrier in enterprise marketing communication, the co-creation signal impacts co-creation observers. Enterprises are now exploring how to effectively release co-creation signals to attract most observers to participate in value creation activities actively. Based on self-determination theory, this study investigates the influence mechanism of co-creation signals on observers’ willingness to co-create and the moderating role of mental simulation through the experimental method. The conclusions are as follows: The co-creation signal has a significant positive effect on the co-creation intention of observers. Self-designed co-creation signals generate more important co-creation willingness than self-produced co-creation signals; Self-determination and its dimensions mediate the relationship between co-creation signals and the observer’s co-creation willingness; and Mental simulation moderates the relationship between co-creation signal and self-determination. This study has important theoretical significance in enriching co-creation signals and mental simulation research. It also provides management implications for enterprises to release co-creation signals and optimize co-creation marketing practices effectively.

A burgeoning body of research has shown that authoritarian leadership embodies the characteristics of “light” and “dark,” meaning that it does not always have a negative impact on employees’ creative activities. However, studies explaining this potential positive effect are insufficient. To extend the AL and creativity literature, we draw on self-determination theory and event system theory, and elicit discipline-focused AL and appointment event criticality to examine whether, when, and how authoritarian leaders affect employee creativity positively. With time-lagged data collected from 435 employees and their direct leaders in China, we found that discipline-focused AL has an indirect positive effect on employee creativity through creative self-efficacy. Additionally, appointment event criticality strengthens the positive relationship between discipline-focused AL and creative self-efficiency, and the indirect impact of discipline-focused AL on employee creativity through creative self-efficiency. The theoretical and practical implications are discussed.

Neurons encode and transmit signals through chemical synaptic or electrical synaptic connections in the actual nervous system. Exploring the biophysical properties of coupling channels is of great significance for further understanding the rhythm transitions of neural network electrical activity patterns and preventing neurological diseases. From the perspective of biophysics, the activation of magnetic field coupling is the result of the continuous release and propagation of intracellular and extracellular ions, which is very similar to the activation of chemical synaptic coupling through the continuous release of neurotransmitters. In this article, an induction coil is used to connect two HR neurons to stimulate the effect of magnetic field coupling. It is inevitable that time delays can affect the coupling process in the transmission of information, and it should be considered in the coupled model. Firstly, the firing characteristics and bifurcation modes of two coupled HR neurons are studied by using one parameter and two parameters bifurcation. With the increase of propagation delay and coupling gain, the chaotic state of neurons disappears and the high-period window decreases due to the influence of energy transfer between neurons. Then, the synchronization patterns of two HR neurons with different stimulation are analyzed by error diagrams and time series diagrams. It is confirmed that the synchronous pattern has certain regularity and is related not only to the neurons with large stimulation current but also to the time delay and coupling gain. The research conclusions of this article will provide the corresponding theoretical basis for medical experiments.

Background: Losing one’s only child may lead to post-traumatic stress disorder, of which re-experiencing is the core symptom. However, neuroimaging studies of sex differences in re-experiencing in the context of the trauma of losing one’s only child and PTSD are scarce; comparisons of the functional networks from the hippocampal subfields to the thalamus might clarify the neural basis.Methods: Thirty couples without any psychiatric disorder who lost their only child, 55 patients with PTSD, and 50 normal controls underwent resting-state functional magnetic resonance imaging. The functional connectivity from the hippocampal subregions to the thalamus and the correlations of FC with re-experiencing symptoms were analyzed within and between the sexes.Results: Compared with husbands without PTSD, wives without PTSD had higher re-experiencing symptoms and weaker FC between the right hippocampal cornu ammonis 3 and the right thalamus. Moreover, only the correlation between the RCA3-RT FC and re-experiencing in wives without PTSD was significant. Among the three groups, only the RCA3-RT FC in female subjects was markedly different. Additionally, the RCA3-RT FC in wives without PTSD was remarkably lower relative to female patients with PTSD.Conclusion: Wives without PTSD who lost their only child had worse re-experiencing symptoms relative to their husbands, which was associated with the FC alteration between the hippocampal subregions and the thalamus. Importantly, the low level of the RCA3-RT FC may play a potentially protective role against the development of PTSD in wives who have lost their only child.

This study explores the dynamic feature of organizational citizenship behaviors under the condition of challenge stressors, as this has not been addressed by previous research. Combining the cybernetic theory of stress and social exchange theory, this study builds a dynamic computational model regarding the circular causality between challenge stressors and organizational citizenship behaviors. By conducting a series of simulation experiments, we validated and demonstrated important questions regarding organizational citizenship behaviors. Specifically, when both the initial value of challenge stressors and the importance of challenge appraisal are higher, organizational citizenship behaviors tend to show a sharped inverted U shape at the early stage. When both the equilibrium level of job satisfaction and the initial value of challenge stressors are higher, organizational citizenship behaviors will show an inverted N shape over time. The number and frequency of assigned challenge tasks have an interactive effect on the accumulation of organizational citizenship behaviors within a period. Our theory contributes to identifying the dynamic relationship between challenge stressors and organizational citizenship behaviors. Findings from dynamic computational theory can offer suggestions for managers to encourage employees’ engagement in organizational citizenship behaviors.

Choice revision is a sort of non-prioritized multiple revision, in which the agent partially accepts the new information represented by a set of sentences. We investigate the construction of choice revision based on a new approach to belief change called descriptor revision. We prove that each of two variants of choice revision based on such construction is axiomatically characterized with a set of plausible postulates, assuming that the object language is finite. Furthermore, we introduce an alternative modelling for choice revision, which is based on a type of relation on sets of sentences, named multiple believability relation. We show without assuming a finite language that choice revision constructed from such relations is axiomatically characterized with the same sets of postulates that we proposed for the choice revision based on descriptor revision, whenever the relations satisfy certain rationality conditions.

Contactin-Associated protein-like 2 is a large multidomain neuronal adhesion molecule implicated in a number of neurological disorders, including epilepsy, schizophrenia, autism spectrum disorder, intellectual disability, and language delay. We reveal here by electron microscopy that the architecture of CNTNAP2 is composed of a large, medium, and small lobe that flex with respect to each other. Using epitope labeling and fragments, we assign the F58C, L1, and L2 domains to the large lobe, the FBG and L3 domains to the middle lobe, and the L4 domain to the small lobe of the CNTNAP2 molecular envelope. Our data reveal that CNTNAP2 has a very different architecture compared with neurexin 1α, a fellow member of the neurexin superfamily and a prototype, suggesting that CNTNAP2 uses a different strategy to integrate into the synaptic protein network. We show that the ectodomains of CNTNAP2 and contactin 2 bind directly and specifically, with low nanomolar affinity. We show further that mutations in CNTNAP2 implicated in autism spectrum disorder arenot segregated but are distributed over the whole ectodomain. The molecular shape and dimensions of CNTNAP2 place constraints on how CNTNAP2 integrates in the cleft of axo-glial and neuronal contact sites and how it functions as an organizing and adhesive molecule.

Cholesteryl ester transfer protein mediates the transfer of cholesterol esters from atheroprotective high-density lipoproteins to atherogenic low-density lipoproteins. CETP inhibition has been regarded as a promising strategy for increasing HDL levels and subsequently reducing the risk of cardiovascular diseases. Although the crystal structure of CETP is known, little is known regarding how CETP binds to HDL. Here, we investigated how various HDL-like particles interact with CETP by electron microscopy and molecular dynamics simulations. Results showed that CETP binds to HDL via hydrophobic interactions rather than protein-protein interactions. The HDL surface lipid curvature generates a hydrophobic environment, leading to CETP hydrophobic distal end interaction. This interaction is independent of other HDL components, such as apolipoproteins, cholesteryl esters and triglycerides. Thus, disrupting these hydrophobic interactions could be a new therapeutic strategy for attenuating the interaction of CETP with HDL.

Since the discovery and implication of N-ethylmaleimide-sensitive factor -attachment protein receptor proteins in membrane fusion almost two decades ago, there have been significant efforts to understand their involvement at the molecular level. In the current study, we report for the first time the molecular interaction between full-length recombinant t-SNAREs and v-SNARE present in opposing liposomes, leading to the assembly of a t-/v-SNARE ring complex. Using high-resolution electron microscopy, the electron density maps and 3D topography of the membrane-directed SNARE ring complex was determined at nanometre resolution. Similar to the t-/v-SNARE ring complex formed when 50 nm v-SNARE liposomes meet a t-SNARE-reconstituted planer membrane, SNARE rings are also formed when 50 nm diameter isolated synaptic vesicles meet a t-SNARE-reconstituted planer lipid membrane. Furthermore, the mathematical prediction of the SNARE ring complex size with reasonable accuracy, and the possible mechanism of membrane-directed t-/v-SNARE ring complex assembly, was determined from the study. Therefore in the present study, using both lipososome-reconstituted recombinant t-/v-SNARE proteins, and native v-SNARE present in isolated SV membrane, the membrane-directed molecular assembly of the neuronal SNARE complex was determined for the first time and its size mathematically predicted. These results provide a new molecular understanding of the universal machinery and mechanism of membrane fusion in cells, having fundamental implications in human health and disease. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

The dynamic personalities and structural heterogeneity of proteins are essential for proper functioning. Structural determination of dynamic/heterogeneous proteins is limited by conventional approaches of X-ray and electron microscopy of single-particle reconstruction that require an average from thousands to millions different molecules. Cryo-electron tomography is an approach to determine three-dimensional reconstruction of a single and unique biological object such as bacteria and cells, by imaging the object from a series of tilting angles. However, cconventional reconstruction methods use large-size whole-micrographs that are limited by reconstruction resolution, especially for small and low-symmetric molecule. In this study, we demonstrated the adverse effects from image distortion and the measuring tilt-errors both play a major role in limiting the reconstruction resolution. Therefore, we developed a "focused electron tomography reconstruction" algorithm to improve the resolution by decreasing the reconstructing image size so that it contains only a single-instance protein. FETR can tolerate certain levels of image-distortion and measuring tilt-errors, and can also precisely determine the translational parameters via an iterative refinement process that contains a series of automatically generated dynamic filters and masks. To describe this method, a set of simulated cryoET images was employed; to validate this approach, the real experimental images from negative-staining and cryoET were used. Since this approach can obtain the structure of a single-instance molecule/particle, we named it individual-particle electron tomography as a new robust strategy/approach that does not require a pre-given initial model, class averaging of multiple molecules or an extended ordered lattice, but can tolerate small tilt-errors for high-resolution single "snapshot" molecule structure determination. Thus, FETR/IPET provides a completely new opportunity for a single-molecule structure determination, and could be used to study the dynamic character and equilibrium fluctuation of macromolecules.

The production of distinct sets of T cell receptor γδ+ T cells occurs in an ordered fashion in thymic development. The Vγ3 and Vγ4 genes, located downstream in the TCRγ Cγ1 gene cluster, are expressed by the earliest waves of developing TCRγδ+ T cells in the fetal thymus, destined for intraepithelial locations. Upstream Vγ2 and Vγ5 genes are expressed in later waves in the adult and constitute most TCRγδ + T cells in secondary lymphoid tissue. This developmental pattern is caused in part by a preference for rearrangements of the downstream Vγ3 and Vγ4 genes in the early fetal stage, which switches to a preference for rearrangements of the upstream Vγ2 and Vγ5 gene rearrangements in the adult. Our gene targeting studies show that the downstream Vγ genes rearrange preferentially in the early fetal thymus because of their downstream location, independent of promoter or recombination signal sequences and unrelated to the extent of germline transcription. Remarkably, gene deletion studies show that the downstream Vγ genes competitively inhibit upstream Vγ rearrangements at the fetal stage. These data provide a mechanism for specialization of the fetal thymus for the production of T cells expressing specific Vγ genes. JEM © The Rockefeller University Press.