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As financial markets continue to evolve, high-frequency trading (HFT) has become an important force in the market, which involves the execution of large numbers of orders at extremely fast speeds. These strategies rely on the ability to process large amounts of real-time data in order to make split-second decisions using small price differences between various trading venues. However, the efficiency and effectiveness of HFT strategies are largely affected by delays in data processing and order execution. In order to overcome data processing and execution delays, edge computing technology has gradually emerged. Edge computing allows real-time data processing closer to the data source, reducing data transfer times and improving response speed. In high-frequency trading, this means faster decision making and order execution, allowing traders to better take advantage of price movements in the market. This paper introduces data privacy and security through edge computing, as data does not have to travel long distances over the network, but can be processed locally. This is particularly important for high-frequency trading, where leakage or tampering of trading data can lead to significant risks and losses. In conclusion, the application of edge computing technology in high-frequency trading is expected to improve the efficiency and reliability of strategies and enhance traders' competitiveness in a rapidly changing market environment. This development reflects the ongoing exploration of emerging technologies in the financial sector to improve the competitive advantage of trading strategies and highlights the potential applications of edge computing in financial markets.

We have developed a set of four fully coupled Boltzmann equations to precisely determine the relic density and temperature of dark matter by including three distinct sectors: dark matter, light scalar, and standard model sectors. The intricacies of heat transfer between DM and the SM sector through a light scalar particle are explored, inspired by stringent experimental constraints on the scalar-Higgs mixing angle and the DM-scalar coupling. Three distinct sectors emerge prior to DM freeze-out, requiring fully coupled Boltzmann equations to accurately compute relic density. Investigation of forbidden, resonance, and secluded DM scenarios demonstrates significant deviations between established methods and the novel approach with fully coupled Boltzmann equations. Despite increased computational demands, this emphasizes the need for improved precision in relic density calculations, underlining the importance of incorporating these equations in comprehensive analyses., Comment: 38 pages, 10 figures

The wiring of visual circuits requires that retinal neurons functionally connect to specific brain targets, a process that involves activity-dependent signaling between retinal axons and their postsynaptic targets. Vision loss in various ophthalmological and neurological diseases is caused by damage to the connections from the eye to the brain. How postsynaptic brain targets influence retinal ganglion cell (RGC) axon regeneration and functional reconnection with the brain targets remains poorly understood. Here, we established a paradigm in which the enhancement of neural activity in the distal optic pathway, where the postsynaptic visual target neurons reside, promotes RGC axon regeneration and target reinnervation and leads to the rescue of optomotor function. Furthermore, selective activation of retinorecipient neuron subsets is sufficient to promote RGC axon regeneration. Our findings reveal a key role for postsynaptic neuronal activity in the repair of neural circuits and highlight the potential to restore damaged sensory inputs via proper brain stimulation.

An efficient alkoxyl radical-triggered ring expansion/cross-coupling cascade was developed under cheap metal catalysis. Through the metal-catalyzed radical relay strategy, a wide range of medium-sized lactones (9-11 membered) and macrolactones (12, 13, 15, 18, and 19-membered) were constructed in moderate to good yields, along with diverse functional groups including CN, N3, SCN, and X groups installed concurrently. Density functional theory (DFT) calculations revealed that reductive elimination of the cycloalkyl-Cu(iii) species is a more favorable reaction pathway for the cross-coupling step. Based on the results of experiments and DFT, a Cu(i)/Cu(ii)/Cu(iii) catalytic cycle is proposed for this tandem reaction.

Scleractinian cold-water corals (CWCs) are one of the most important habitat engineers of the deep sea. Although the South China Sea (SCS) abuts the biodiversity center of scleractinian CWCs in the western Pacific, only a few sporadic records are available. We discovered new CWC sites by means of trawl sampling and video observation along the continental shelf of the northwestern SCS. All trawled scleractinian CWC specimens were identified to species level according to skeleton morphology and structure. The living CWCs and associated fauna recorded in the video were -identified to a higher level of classification. Scleractinian corals were identified to genus level, while non-scleractinian CWCs were identified to family level and given general names such as gorgonian corals, bamboo corals and black corals. Associated benthic dwellers were divided into major categories. A total of 28 scleractinian CWC species were identified to 7 families, 15 genera, and 1 additional subgenus. Among them, 13 species were colonial, including important habitat-forming species in the genera Eguchipsammia, Dendrophyllia and Cladopsammia. Non-scleractinian CWCs were identified to 7 families, including 4 families gorgonian corals, 1 family bamboo corals, and 2 families black corals. Gorgonian corals were the most abundant non-scleractinian CWCs in this region. Meanwhile, starfish, sea anemones, fish, gastropods, echinoderms, and other associated benthic fauna were recorded in the CWC habitats, with starfish belonging to the order Brisingida being most common. New scleractinian CWC assemblages were discovered along the continental seabed mounds in the northwestern SCS. This study highlights the remarkable diversity of cold-water scleractinian corals in the whole SCS, and shows the potential widespread distribution and conservation prospect of CWC habitats in this region. © 2023 Elsevier Ltd

Large-scale screening of molecules in organisms requires high-throughput and cost-effective evaluating tools during preclinical development. Here, a novel in vivo screening strategy combining hierarchically structured biohybrid triboelectric nanogenerators (HB-TENGs) arrays with computational bioinformatics analysis for high-throughput pharmacological evaluation using Caenorhabditis elegans is described. Unlike the traditional methods for behavioral monitoring of the animals, which are laborious and costly, HB-TENGs with micropillars are designed to efficiently convert animals’ behaviors into friction deformation and result in a contact-separation motion between two triboelectric layers to generate electrical outputs. The triboelectric signals are recorded and extracted to various bioinformation for each screened compound. Moreover, the information-rich electrical readouts are successfully demonstrated to be sufficient to predict a drug’s identity by multiple-Gaussian-kernels-based machine learning methods. This proposed strategy can be readily applied to various fields and is especially useful in in vivo explorations to accelerate the identification of novel therapeutics.

BACKGROUND: Increasing evidence implicates the signaling kinase mTOR complex-2 (mTORC2) in rapid renal responses to changes in plasma potassium concentration [K+]. However, the underlying cellular and molecular mechanisms that are relevant in vivo for these responses remain controversial. METHODS: We used Cre-Lox-mediated knockout of rapamycin-insensitive companion of TOR (Rictor) to inactivate mTORC2 in kidney tubule cells of mice. In a series of time-course experiments in wild-type and knockout mice, we assessed urinary and blood parameters and renal expression and activity of signaling molecules and transport proteins following a K+ load via gavage. RESULTS: A K+ load rapidly stimulated epithelial sodium channel (ENaC) processing, plasma membrane localization, and activity in wild-type but not in knockout mice. Downstream targets of mTORC2 implicated in ENaC regulation (SGK1 and Nedd4-2) were concomitantly phosphorylated in wild-type but not knockout mice. We observed differences in urine electrolytes within 60 minutes, and plasma [K+] was greater in knockout mice within 3 hours of gavage. Renal outer medullary potassium (ROMK) channels were not acutely stimulated in wild-type or knockout mice, nor were phosphorylation of other mTORC2 substrates (PKC and Akt). CONCLUSIONS: The mTORC2-SGK1-Nedd4-2-ENaC signaling axis is a key mediator of rapid tubule cell responses to increased plasma [K+] in vivo. The effects of K+ on this signaling module are specific, in that other downstream mTORC2 targets such as PKC and Akt are not acutely affected, and ROMK and BK channels are not activated. These findings provide new insight into the signaling network and ion transport systems that underlie renal responses to K+in vivo.

This paper studies co-segmenting the common semantic object in a set of images. Existing works either rely on carefully engineered networks to mine the implicit semantic information in visual features or require extra data (i.e., classification labels) for training. In this paper, we leverage the contrastive language-image pre-training framework (CLIP) for the task. With a backbone segmentation network that independently processes each image from the set, we introduce semantics from CLIP into the backbone features, refining them in a coarse-to-fine manner with three key modules: i) an image set feature correspondence module, encoding global consistent semantic information of the image set; ii) a CLIP interaction module, using CLIP-mined common semantics of the image set to refine the backbone feature; iii) a CLIP regularization module, drawing CLIP towards this co-segmentation task, identifying the best CLIP semantic and using it to regularize the backbone feature. Experiments on four standard co-segmentation benchmark datasets show that the performance of our method outperforms state-of-the-art methods.

Across neurodegenerative diseases, common mechanisms may reveal novel therapeutic targets based on neuronal protection, repair, or regeneration, independent of etiology or site of disease pathology. To address these mechanisms and discuss emerging treatments, in April, 2021, Glaucoma Research Foundation, BrightFocus Foundation, and the Melza M. and Frank Theodore Barr Foundation collaborated to bring together key opinion leaders and experts in the field of neurodegenerative disease for a virtual meeting titled "Solving Neurodegeneration". This "think-tank" style meeting focused on uncovering common mechanistic roots of neurodegenerative disease and promising targets for new treatments, catalyzed by the goal of finding new treatments for glaucoma, the world's leading cause of irreversible blindness and the common interest of the three hosting foundations. Glaucoma, which causes vision loss through degeneration of the optic nerve, likely shares early cellular and molecular events with other neurodegenerative diseases of the central nervous system. Here we discuss major areas of mechanistic overlap between neurodegenerative diseases of the central nervous system: neuroinflammation, bioenergetics and metabolism, genetic contributions, and neurovascular interactions. We summarize important discussion points with emphasis on the research areas that are most innovative and promising in the treatment of neurodegeneration yet require further development. The research that is highlighted provides unique opportunities for collaboration that will lead to efforts in preventing neurodegeneration and ultimately vision loss.

Across neurodegenerative diseases, common mechanisms may reveal novel therapeutic targets based on neuronal protection, repair, or regeneration, independent of etiology or site of disease pathology. To address these mechanisms and discuss emerging treatments, in April, 2021, Glaucoma Research Foundation, BrightFocus Foundation, and the Melza M. and Frank Theodore Barr Foundation collaborated to bring together key opinion leaders and experts in the field of neurodegenerative disease for a virtual meeting titled "Solving Neurodegeneration". This "think-tank" style meeting focused on uncovering common mechanistic roots of neurodegenerative disease and promising targets for new treatments, catalyzed by the goal of finding new treatments for glaucoma, the world's leading cause of irreversible blindness and the common interest of the three hosting foundations. Glaucoma, which causes vision loss through degeneration of the optic nerve, likely shares early cellular and molecular events with other neurodegenerative diseases of the central nervous system. Here we discuss major areas of mechanistic overlap between neurodegenerative diseases of the central nervous system: neuroinflammation, bioenergetics and metabolism, genetic contributions, and neurovascular interactions. We summarize important discussion points with emphasis on the research areas that are most innovative and promising in the treatment of neurodegeneration yet require further development. The research that is highlighted provides unique opportunities for collaboration that will lead to efforts in preventing neurodegeneration and ultimately vision loss.

In this issue of Neuron, three studies establish new strategies to uncover mediators of retinal neuroprotection and optic nerve regeneration. Tian et al. (2022) carry out a multi-omics screen and identify transcriptional regulators of axon injury signaling leading to cell death; Jacobi et al. (2022) and Li et al. (2022) combine retrograde tracing and single-cell RNA-seq (scRNA-seq) to uncover molecular targets for axon regeneration.

Breathing, and the motor circuits that control it, is essential for life. At the core of respiratory circuits are Dbx1-derived interneurons, which generate the rhythm and pattern of breathing, and phrenic motor neurons (MNs), which provide the final motor output that drives diaphragm muscle contractions during inspiration. Despite their critical function, the principles that dictate how respiratory circuits assemble are unknown. Here, we show that coordinated activity of a type I cadherin (N-cadherin) and type II cadherins (Cadherin-6, -9, and -10) is required in both MNs and Dbx1-derived neurons to generate robust respiratory motor output. Both MN- and Dbx1-specific cadherin inactivation in mice during a critical developmental window results in perinatal lethality due to respiratory failure and a striking reduction in phrenic MN bursting activity. This combinatorial cadherin code is required to establish phrenic MN cell body and dendritic topography; surprisingly, however, cell body position appears to be dispensable for the targeting of phrenic MNs by descending respiratory inputs. Our findings demonstrate that type I and II cadherins function cooperatively throughout the respiratory circuit to generate a robust breathing output and reveal novel strategies that drive the assembly of motor circuits.

Retinal ganglion cells (RGCs) are heterogeneous projection neurons that convey distinct visual features from the retina to brain. Here, we present a high-throughput in vivo RGC activity assay in response to light stimulation using noninvasive Ca2+ imaging of thousands of RGCs simultaneously in living mice. Population and single-cell analyses of longitudinal RGC Ca2+ imaging reveal distinct functional responses of RGCs and unprecedented individual RGC activity conversions during traumatic and glaucomatous degeneration. This study establishes a foundation for future in vivo RGC function classifications and longitudinal activity evaluations using more advanced imaging techniques and visual stimuli under normal, disease, and neural repair conditions. These analyses can be performed at both the population and single-cell levels using temporal and spatial information, which will be invaluable for understanding RGC pathophysiology and identifying functional biomarkers for diverse optic neuropathies.

This paper proposes an automatic image co-segmentation algorithm based on deep reinforcement learning (RL). Existing co-segmentation tasks mainly rely on deep learning methods, and the obtained foreground edges are often rough. In order to obtain more precise foreground edges, we use deep RL to solve this problem and achieve the finer segmentation. To our best knowledge, this is the first work to apply RL methods to co-segmentation. We define the problem as a Markov Decision Process (MDP) and optimize it by RL with asynchronous advantage actor-critic (A3C). The RL image co-segmentation network uses the correlation between images to segment common and salient objects from a set of related images. In order to achieve automatic segmentation, our RL-CoSeg method eliminates user's hints. For the image co-segmentation problem, we propose a collaborative RL algorithm based on the A3C model. We propose a Siamese RL co-segmentation network structure to obtain the co-attention of images for co-segmentation. We improve the self-attention for automatic RL algorithm to obtain long-distance dependence and enlarge the receptive field. The image feature information obtained by self-attention can be used to supplement the deleted user's hints and help to obtain more accurate actions. Experimental results have shown that our method can improve the performance effectively on both coarse and fine initial segmentations, and it achieves the state-of-the-art performance on Internet dataset, iCoseg dataset and MLMR-COS dataset.

The central nervous system (CNS) is composed of precisely assembled circuits which support a variety of physiological functions and behaviors. These circuits include multiple subtypes of neurons with unique morphologies, electrical properties, and molecular identities. How these component parts are precisely wired-up has been a topic of great interest to the field of developmental neurobiology and has implications for our understanding of the etiology of many neurological disorders and mental illnesses. To date, many molecules involved in synaptic choice and specificity have been identified, including members of several families of cell-adhesion molecules (CAMs), which are cell-surface molecules that mediate cell-cell contacts and subsequent intracellular signaling. One favored hypothesis is that unique expression patterns of CAMs define specific neuronal subtype populations and determine compatible pre- and postsynaptic neuronal partners based on the expression of these unique CAMs. The mouse retina has served as a beautiful model for investigations into mammalian CAM interactions due to its well-defined neuronal subtypes and distinct circuits. Moreover, the retina is readily amenable to visualization of circuit organization and electrophysiological measurement of circuit function. The advent of recent genetic, genomic, and imaging technologies has opened the field up to large-scale, unbiased approaches for identification of new molecular determinants of synaptic specificity. Thus, building on the foundation of work reviewed here, we can expect rapid expansion of the field, harnessing the mouse retina as a model to understand the molecular basis for synaptic specificity and functional circuit assembly. This article is categorized under: Nervous System Development > Vertebrates: General Principles Nervous System Development > Vertebrates: Regional Development.

Knowledge embedded in the weights of the artificial neural network can be used to improve the network structure, such as in network compression. However, the knowledge is set up by hand, which may not be very accurate, and relevant information may be overlooked. Inspired by how learning works in the mammalian brain, we mine the knowledge contained in the weights of the neural network toward automatic architecture learning in this paper. We introduce a switcher neural network (SNN) that uses as inputs the weights of a task-specific neural network (called TNN for short). By mining the knowledge contained in the weights, the SNN outputs scaling factors for turning off and weighting neurons in the TNN. To optimize the structure and the parameters of TNN simultaneously, the SNN and TNN are learned alternately under the same performance evaluation of TNN using stochastic gradient descent. We test our method on widely used datasets and popular networks in classification applications. In terms of accuracy, we outperform baseline networks and other structure learning methods stably and significantly. At the same time, we compress the baseline networks without introducing any sparse induction mechanism, and our method, in particular, leads to a lower compression rate when dealing with simpler baselines or more difficult tasks. These results demonstrate that our method can produce a more reasonable structure.

Distinct neuronal types connect in complex ways to generate functional neural circuits. The molecular diversity required to specify this connectivity could be supplied by multigene families of synaptic recognition molecules, but most studies to date have assessed just one or a few members at a time. Here, we analyze roles of cadherins (Cdhs) in formation of retinal circuits comprising eight neuronal types that inform the brain about motion in four directions. We show that at least 15 classical Cdhs are expressed by neurons in these circuits and at least 6 (Cdh6-10 and 18) act individually or in combinations to promote specific connectivity among the cells. They act in part by directing the processes of output neurons and excitatory interneurons to a cellular scaffold formed by inhibitory interneurons. Because Cdhs are expressed combinatorially by many central neurons, similar interactions could be involved in patterning circuits throughout the brain.

Axon injury is a hallmark of many neurodegenerative diseases, often resulting in neuronal cell death and functional impairment. Dual leucine zipper kinase (DLK) has emerged as a key mediator of this process. However, while DLK inhibition is robustly protective in a wide range of neurodegenerative disease models, it also inhibits axonal regeneration. Indeed, there are no genetic perturbations that are known to both improve long-term survival and promote regeneration. To identify such a neuroprotective target, we conducted a set of complementary high-throughput screens using a protein kinase inhibitor library in human stem cell-derived retinal ganglion cells (hRGCs). Overlapping compounds that promoted both neuroprotection and neurite outgrowth were bioinformatically deconvoluted to identify specific kinases that regulated neuronal death and axon regeneration. This work identified the role of germinal cell kinase four (GCK-IV) kinases in cell death and additionally revealed their unexpected activity in suppressing axon regeneration. Using an adeno-associated virus (AAV) approach, coupled with genome editing, we validated that GCK-IV kinase knockout improves neuronal survival, comparable to that of DLK knockout, while simultaneously promoting axon regeneration. Finally, we also found that GCK-IV kinase inhibition also prevented the attrition of RGCs in developing retinal organoid cultures without compromising axon outgrowth, addressing a major issue in the field of stem cell-derived retinas. Together, these results demonstrate a role for the GCK-IV kinases in dissociating the cell death and axonal outgrowth in neurons and their druggability provides for therapeutic options for neurodegenerative diseases.

Li Chen,1,2,* Jiaxin Liu,1,* Ming Guan,2,3 Tongqing Zhou,2 Xin Duan,1 Zhou Xiang1 1Department of Orthopedics, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People’s Republic of China; 2School of Dentistry, University of Michigan, Ann Arbor, MI, 48109, USA; 3Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xin Duan Tel +86-28-85422426Email dxbaal@hotmail.comZhou Xiang Tel +86-28-85422605Email xiangzhou15@hotmail.comAbstract: The development of biomaterials, stem cells and bioactive factors has led to cartilage tissue engineering becoming a promising tactic to repair cartilage defects. Various polymer three-dimensional scaffolds that provide an extracellular matrix (ECM) mimicking environment play an important role in promoting cartilage regeneration. In addition, numerous growth factors have been found in the regenerative process. However, it has been elucidated that the uncontrolled delivery of these factors cannot fully exert regenerative potential and can also elicit undesired side effects. Considering the complexity of the ECM, neither scaffolds nor growth factors can independently obtain successful outcomes in cartilage tissue engineering. Therefore, collectively, an appropriate combination of growth factors and scaffolds have great potential to promote cartilage repair effectively; this approach has become an area of considerable interest in recent investigations. Of late, an increasing trend was observed in cartilage tissue engineering towards this combination to develop a controlled delivery system that provides adequate physical support for neo-cartilage formation and also enables spatiotemporally delivery of growth factors to precisely and fully exert their chondrogenic potential. This review will discu

Axon injury is a hallmark of many neurodegenerative diseases, often resulting in neuronal cell death and functional impairment. Dual leucine zipper kinase (DLK) has emerged as a key mediator of this process. However, while DLK inhibition is robustly protective in a wide range of neurodegenerative disease models, it also inhibits axonal regeneration. Indeed, there are no genetic perturbations that are known to both improve long-term survival and promote regeneration. To identify such a neuroprotective target, we conducted a set of complementary high-throughput screens using a protein kinase inhibitor library in human stem cell-derived retinal ganglion cells (hRGCs). Overlapping compounds that promoted both neuroprotection and neurite outgrowth were bioinformatically deconvoluted to identify specific kinases that regulated neuronal death and axon regeneration. This work identified the role of germinal cell kinase four (GCK-IV) kinases in cell death and additionally revealed their unexpected activity in suppressing axon regeneration. Using an adeno-associated virus (AAV) approach, coupled with genome editing, we validated that GCK-IV kinase knockout improves neuronal survival, comparable to that of DLK knockout, while simultaneously promoting axon regeneration. Finally, we also found that GCK-IV kinase inhibition also prevented the attrition of RGCs in developing retinal organoid cultures without compromising axon outgrowth, addressing a major issue in the field of stem cell-derived retinas. Together, these results demonstrate a role for the GCK-IV kinases in dissociating the cell death and axonal outgrowth in neurons and their druggability provides for therapeutic options for neurodegenerative diseases.

Background and purposeTetramethylpyrazine (TMP) was originally isolated from the traditional Chinese herb ligusticum and the fermented Japanese food natto and has since been synthesized. TMP has a long history of beneficial effects in the treatment of many cardiovascular diseases. Here we have evaluated the therapeutic effects of TMP on pulmonary hypertension (PH) in animal models and in patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH).Experimental approachThree well-defined models of PH -chronic hypoxia (10% O2 )-induced PH (HPH), monocrotaline-induced PH (MCT-PH) and Sugen 5416/hypoxia-induced PH (SuHx-PH) - were used in Sprague-Dawley rats, and assessed by echocardiography, along with haemodynamic and histological techniques. Primary cultures of rat distal pulmonary arterial smooth muscle cells (PASMCs) were used to study intracellular calcium levels. Western blots and RT-qPCR assays were also used. In the clinical cohort, patients with PAH or CTEPH were recruited. The effects of TMP were evaluated in all systems.Key resultsTMP (100 mg·kg-1 ·day-1 ) prevented rats from developing experimental PH and ameliorated three models of established PH: HPH, MCT-PH and SuHx-PH. The therapeutic effects of TMP were accompanied by inhibition of intracellular calcium homeostasis in PASMCs. In a small cohort of patients with PAH or CTEPH, oral administration of TMP (100 mg, t.i.d. for 16 weeks) increased the 6-min walk distance and improved the 1-min heart rate recovery.Conclusion and implicationsOur results suggest that TMP is a novel and inexpensive medication for treatment of PH. Clinical trial is registered with www.chictr.org.cn (ChiCTR-IPR-14005379).

The development of single-cell RNA sequencing (scRNA-seq) has allowed high-resolution analysis of cell-type diversity and transcriptional networks controlling cell-fate specification. To identify the transcriptional networks governing human retinal development, we performed scRNA-seq analysis on 16 time points from developing retina as well as four early stages of retinal organoid differentiation. We identified evolutionarily conserved patterns of gene expression during retinal progenitor maturation and specification of all seven major retinal cell types. Furthermore, we identified gene-expression differences between developing macula and periphery and between distinct populations of horizontal cells. We also identified species-specific patterns of gene expression during human and mouse retinal development. Finally, we identified an unexpected role for ATOH7 expression in regulation of photoreceptor specification during late retinogenesis. These results provide a roadmap to future studies of human retinal development and may help guide the design of cell-based therapies for treating retinal dystrophies.

Li Chen,1,2,* Jiaxin Liu,1,* Ming Guan,2,3 Tongqing Zhou,2 Xin Duan,1 Zhou Xiang1 1Department of Orthopedics, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People’s Republic of China; 2School of Dentistry, University of Michigan, Ann Arbor, MI, 48109, USA; 3Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xin Duan Tel +86-28-85422426Email dxbaal@hotmail.comZhou Xiang Tel +86-28-85422605Email xiangzhou15@hotmail.comAbstract: The development of biomaterials, stem cells and bioactive factors has led to cartilage tissue engineering becoming a promising tactic to repair cartilage defects. Various polymer three-dimensional scaffolds that provide an extracellular matrix (ECM) mimicking environment play an important role in promoting cartilage regeneration. In addition, numerous growth factors have been found in the regenerative process. However, it has been elucidated that the uncontrolled delivery of these factors cannot fully exert regenerative potential and can also elicit undesired side effects. Considering the complexity of the ECM, neither scaffolds nor growth factors can independently obtain successful outcomes in cartilage tissue engineering. Therefore, collectively, an appropriate combination of growth factors and scaffolds have great potential to promote cartilage repair effectively; this approach has become an area of considerable interest in recent investigations. Of late, an increasing trend was observed in cartilage tissue engineering towards this combination to develop a controlled delivery system that provides adequate physical support for neo-cartilage formation and also enables spatiotemporally delivery of growth factors to precisely and fully exert their chondrogenic potential. This review will discu

Mixed reality headsets, such as the Microsoft HoloLens 2, are powerful sensing devices with integrated compute capabilities, which makes it an ideal platform for computer vision research. In this technical report, we present HoloLens 2 Research Mode, an API and a set of tools enabling access to the raw sensor streams. We provide an overview of the API and explain how it can be used to build mixed reality applications based on processing sensor data. We also show how to combine the Research Mode sensor data with the built-in eye and hand tracking capabilities provided by HoloLens 2. By releasing the Research Mode API and a set of open-source tools, we aim to foster further research in the fields of computer vision as well as robotics and encourage contributions from the research community.

Image co-segmentation is important for its advantage of alleviating the ill-pose nature of image segmentation through exploring the correlation between related images. Many automatic image co-segmentation algorithms have been developed in the last decade, which are investigated comprehensively in this paper. We firstly analyze visual/semantic cues for guiding image co-segmentation, including object cues and correlation cues. Then we describe the traditional methods in three categories of object elements based, object regions/contours based, common object model based. In the next part, deep learning based methods are reviewed. Furthermore, widely used test datasets and evaluation criteria are introduced and the reported performances of the surveyed algorithms are compared with each other. Finally, we discuss the current challenges and possible future directions and conclude the paper. Hopefully, this comprehensive investigation will be helpful for the development of image co-segmentation technique.

Xin Duan, Guangcheng Guo, Xinhong Pei, Xinxing Wang, Lin Li, Youyi Xiong, Xinguang Qiu Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Xinguang QiuDepartment of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou, Henan 450000, People’s Republic of ChinaTel +86 371-67967247Email xfcl6782619qiang@163.comBackground: Baicalin is a natural compound from the roots of Scutellaria lateriflora Georgi, which plays anti-cancer role in multiple cancers. However, the exact role and potential underlying mechanism of baicalin in breast cancer (BC) remain poorly understood.Methods: Thirty BC patients were recruited in this study. MCF-10A, MCF-7 and MDA-MB-231 cells were used to investigate the anti-cancer role of baicalin in vitro. Cell viability, migration, invasion and apoptosis were measured by MTT, trans-well and flow cytometry, respectively. The expression levels of microRNA-338-3p (miR-338-3p) and microrchidia family CW-type zinc-finger 4 (MORC4) were measured by quantitative real-time polymerase chain reaction or Western blot. The interaction between miR-338-3p and MORC4 was explored by luciferase reporter assay and RNA immunoprecipitation.Results: We found that Baicalin treatment inhibited cell viability, migration and invasion but promoted apoptosis of BC cells. The expression of miR-338-3p was decreased in BC tissues and cells and miR-338-3p overexpression suppressed cell viability, migration and invasion but induced apoptosis. MiR-338-3p expression was reversed by baicalin exposure and inhibition of miR-338-3p attenuated the role of baicalin in viability, apoptosis, migration and invasion. MORC4 mRNA level was increased in BC tissues and cells, which was decreased by baicalin exposure. MORC4 was a target of miR-338-3p and its overexpression alleviated the effect of miR-338-3p on cell viability, apoptos

Transgenic mouse lines are routinely employed to label and manipulate distinct cell types. The transgene generally comprises cell-type specific regulatory elements linked to a cDNA encoding a reporter or other protein. However, off-target expression seemingly unrelated to the regulatory elements in the transgene is often observed, it is sometimes suspected to reflect influences related to the site of transgene integration in the genome. To test this hypothesis, we used a proximity ligation-based method, Targeted Locus Amplification (TLA), to map the insertion sites of three well-characterized transgenes that appeared to exhibit insertion site-dependent expression in retina. The nearest endogenous genes to transgenes HB9-GFP, Mito-P, and TYW3 are Cdh6, Fat4 and Khdrbs2, respectively. For two lines, we demonstrate that expression reflects that of the closest endogenous gene (Fat4 and Cdh6), even though the distance between transgene and endogenous gene is 550 and 680 kb, respectively. In all three lines, the transgenes decrease expression of the neighboring endogenous genes. In each case, the affected endogenous gene was expressed in at least some of the cell types that the transgenic line has been used to mark and study. These results provide insights into the effects of transgenes and endogenous genes on each other's expression, demonstrate that mapping insertion site is valuable for interpreting results obtained with transgenic lines, and indicate that TLA is a reliable method for integration site discovery.

Transgenic mouse lines are routinely employed to label and manipulate distinct cell types. The transgene generally comprises cell-type specific regulatory elements linked to a cDNA encoding a reporter or other protein. However, off-target expression seemingly unrelated to the regulatory elements in the transgene is often observed, it is sometimes suspected to reflect influences related to the site of transgene integration in the genome. To test this hypothesis, we used a proximity ligation-based method, Targeted Locus Amplification (TLA), to map the insertion sites of three well-characterized transgenes that appeared to exhibit insertion site-dependent expression in retina. The nearest endogenous genes to transgenes HB9-GFP, Mito-P, and TYW3 are Cdh6, Fat4 and Khdrbs2, respectively. For two lines, we demonstrate that expression reflects that of the closest endogenous gene (Fat4 and Cdh6), even though the distance between transgene and endogenous gene is 550 and 680 kb, respectively. In all three lines, the transgenes decrease expression of the neighboring endogenous genes. In each case, the affected endogenous gene was expressed in at least some of the cell types that the transgenic line has been used to mark and study. These results provide insights into the effects of transgenes and endogenous genes on each other's expression, demonstrate that mapping insertion site is valuable for interpreting results obtained with transgenic lines, and indicate that TLA is a reliable method for integration site discovery.

Hippocampal CA3 neurons form synapses with CA1 neurons in two layers, stratum oriens (SO) and stratum radiatum (SR). Each layer develops unique synaptic properties but molecular mechanisms that mediate these differences are unknown. Here, we show that SO synapses normally have significantly more mushroom spines and higher-magnitude long-term potentiation (LTP) than SR synapses. Further, we discovered that these differences require the Type II classic cadherins, cadherins-6, -9, and -10. Though cadherins typically function via trans-cellular homophilic interactions, our results suggest presynaptic cadherin-9 binds postsynaptic cadherins-6 and -10 to regulate mushroom spine density and high-magnitude LTP in the SO layer. Loss of these cadherins has no effect on the lower-magnitude LTP typically observed in the SR layer, demonstrating that cadherins-6, -9, and -10 are gatekeepers for high-magnitude LTP. Thus, Type II cadherins may uniquely contribute to the specificity and strength of synaptic changes associated with learning and memory.

Introducing the hole-transporting carbazole moiety into an aggregation-induced emissive tetraarylethene skeleton and attaching electron-transporting dimesitylboron groups to the periphery, we obtain two novel electroluminescent materials. Their structures are fully characterized by elemental analysis, mass spectrometry, NMR spectroscopy and X-ray crystallography. Furthermore, their thermal, electro-chemical, as well as photophysical properties including AIE-behavior are systematically investigated not only by experimental methods but also by DFT computation. Thereby, we show that the two compounds possess high thermal and electrochemical stability with a remarkable AIE-behavior. X-ray crystal analyses aided by DFT calculations provide insights in the origin of the luminescent properties and AIE features. Ultimately, two non-doped OLEDs (Device A and Device B) were fabricated by using PDPBCE and BDPBCE as light-emitting layer, respectively. Device A showed yellowish-green light with a turn-on voltage of 3.8 V, a maximum brightness of 59130 cd m(-2) and a maximum current efficiency of 6.43 cd A(-1). Device B exhibited greenish-yellow light with a turn-on voltage of 3.0 V, a maximum brightness of 67,500 cd m(-2) and a maximum current efficiency of 11.2 cd A(-1). (C) 2016 Elsevier B. V. All rights reserved.

Introducing the hole-transporting carbazole moiety into an aggregation-induced emissive tetraarylethene skeleton and attaching electron-transporting dimesitylboron groups to the periphery, we obtain two novel electroluminescent materials. Their structures are fully characterized by elemental analysis, mass spectrometry, NMR spectroscopy and X-ray crystallography. Furthermore, their thermal, electro-chemical, as well as photophysical properties including AIE-behavior are systematically investigated not only by experimental methods but also by DFT computation. Thereby, we show that the two compounds possess high thermal and electrochemical stability with a remarkable AIE-behavior. X-ray crystal analyses aided by DFT calculations provide insights in the origin of the luminescent properties and AIE features. Ultimately, two non-doped OLEDs (Device A and Device B) were fabricated by using PDPBCE and BDPBCE as light-emitting layer, respectively. Device A showed yellowish-green light with a turn-on voltage of 3.8 V, a maximum brightness of 59130 cd m(-2) and a maximum current efficiency of 6.43 cd A(-1). Device B exhibited greenish-yellow light with a turn-on voltage of 3.0 V, a maximum brightness of 67,500 cd m(-2) and a maximum current efficiency of 11.2 cd A(-1). (C) 2016 Elsevier B. V. All rights reserved.

Introducing the hole-transporting carbazole moiety into an aggregation-induced emissive tetraarylethene skeleton and attaching electron-transporting dimesitylboron groups to the periphery, we obtain two novel electroluminescent materials. Their structures are fully characterized by elemental analysis, mass spectrometry, NMR spectroscopy and X-ray crystallography. Furthermore, their thermal, electro-chemical, as well as photophysical properties including AIE-behavior are systematically investigated not only by experimental methods but also by DFT computation. Thereby, we show that the two compounds possess high thermal and electrochemical stability with a remarkable AIE-behavior. X-ray crystal analyses aided by DFT calculations provide insights in the origin of the luminescent properties and AIE features. Ultimately, two non-doped OLEDs (Device A and Device B) were fabricated by using PDPBCE and BDPBCE as light-emitting layer, respectively. Device A showed yellowish-green light with a turn-on voltage of 3.8 V, a maximum brightness of 59130 cd m(-2) and a maximum current efficiency of 6.43 cd A(-1). Device B exhibited greenish-yellow light with a turn-on voltage of 3.0 V, a maximum brightness of 67,500 cd m(-2) and a maximum current efficiency of 11.2 cd A(-1). (C) 2016 Elsevier B. V. All rights reserved.

Adult hippocampal neurogenesis is thought to be essential for learning and memory, and has been implicated in the pathogenesis of several disorders. Although recent studies have identified key factors regulating neuroprogenitor proliferation in the adult hippocampus, the mechanisms that control the migration and integration of adult-born neurons into circuits are largely unknown. Reelin is an extracellular matrix protein that is vital for neuronal development. Activation of the Reelin cascade leads to phosphorylation of Disabled-1, an adaptor protein required for Reelin signaling. Here we used transgenic mouse and retroviral reporters along with Reelin signaling gain-of-function and loss-of-function studies to show that the Reelin pathway regulates migration and dendritic development of adultgenerated hippocampal neurons. Whereas overexpression of Reelin accelerated dendritic maturation, inactivation of the Reelin signaling pathway specifically in adult neuroprogenitor cells resulted in aberrant migration, decreased dendrite development, formation of ectopic dendrites in the hilus, and the establishment of aberrant circuits. Our findings support a cell-autonomous and critical role for the Reelin pathway in regulating dendritic development and the integration of adult-generated granule cells and point to this pathway as a key regulator of adult neurogenesis. Moreover, our data reveal a novel role of the Reelin cascade in adult brain function with potential implications for the pathogenesis of several neurological and psychiatric disorders. © 2012 the authors.

Duan, Xin., Thesis (M.Phil.)--Chinese University of Hong Kong, 2007., Includes bibliographical references (leaves 36-43)., s in English and Chinese., p.i-ii, Acknowledgement --- p.iii, Table of Contents --- p.iv, Chapter Chapter 1 --- Introduction --- p.1, Chapter Chapter 2 --- Related Literature --- p.6, Chapter 2.1 --- Exchange Market Pressure Index --- p.6, Chapter 2.2 --- The Sentiment Index --- p.11, Chapter Chapter 3 --- Stock market sentiment --- p.16, Chapter 3.1 --- Data --- p.16, Chapter 3.2 --- Methodology --- p.23, Chapter 3.3 --- Estimated Results --- p.25, Chapter Chapter 4 --- Application to the Hong Kong stock market --- p.28, Chapter 4.1 --- Threshold Model Estimation --- p.28, Chapter 4.2 --- Trading Strategy --- p.30, Chapter Chapter 5 --- Conclusion --- p.32, Appendix: Principle Component --- p.34, References --- p.36, http://library.cuhk.edu.hk/record=b5893308, Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Duan, Xin., Thesis (M.Phil.)--Chinese University of Hong Kong, 2007., Includes bibliographical references (leaves 36-43)., s in English and Chinese., p.i-ii, Acknowledgement --- p.iii, Table of Contents --- p.iv, Chapter Chapter 1 --- Introduction --- p.1, Chapter Chapter 2 --- Related Literature --- p.6, Chapter 2.1 --- Exchange Market Pressure Index --- p.6, Chapter 2.2 --- The Sentiment Index --- p.11, Chapter Chapter 3 --- Stock market sentiment --- p.16, Chapter 3.1 --- Data --- p.16, Chapter 3.2 --- Methodology --- p.23, Chapter 3.3 --- Estimated Results --- p.25, Chapter Chapter 4 --- Application to the Hong Kong stock market --- p.28, Chapter 4.1 --- Threshold Model Estimation --- p.28, Chapter 4.2 --- Trading Strategy --- p.30, Chapter Chapter 5 --- Conclusion --- p.32, Appendix: Principle Component --- p.34, References --- p.36, http://library.cuhk.edu.hk/record=b5893308, Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Experiments were conducted in a tank-type microwave reactor at 550-950 degrees C using a Zn residue from Yunnan, China, containing ZnFe2O4, PbSO4 and SiO2. Five different size fractions were employed with compositions in the range 12.36%-12.80 % Zn, 20.36%-21.75% Fe, 12.07%-12.50% Pb and 6.95%-7.10% SiO2. The mechanism of the formation of ZnO and Fe3O4/FeO by the decomposition of ZnFe2O4 was investigated using equilibrium calculations and thermodynamic analysis with the HSC software. Zn recovery of up to 97.93% was obtained at a temperature of 750 degrees C, C/ZnFe2O4 ratio of 1:3, particle size of 61-74 micrometres and microwave power of 1 200 W. The reaction kinetics involved a carbon gasification control mechanism and the activation energy for the carbon gasification reaction was determined to be 38.21 kJ/mol., Experiments were conducted in a tank-type microwave reactor at 550-950 degrees C using a Zn residue from Yunnan, China, containing ZnFe2O4, PbSO4 and SiO2. Five different size fractions were employed with compositions in the range 12.36%-12.80 % Zn, 20.36%-21.75% Fe, 12.07%-12.50% Pb and 6.95%-7.10% SiO2. The mechanism of the formation of ZnO and Fe3O4/FeO by the decomposition of ZnFe2O4 was investigated using equilibrium calculations and thermodynamic analysis with the HSC software. Zn recovery of up to 97.93% was obtained at a temperature of 750 degrees C, C/ZnFe2O4 ratio of 1:3, particle size of 61-74 micrometres and microwave power of 1 200 W. The reaction kinetics involved a carbon gasification control mechanism and the activation energy for the carbon gasification reaction was determined to be 38.21 kJ/mol.