65 research outputs found

    VisForum: A visual analysis system for exploring user groups in online forums

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    User grouping in asynchronous online forums is a common phenomenon nowadays. People with similar backgrounds or shared interests like to get together in group discussions. As tens of thousands of archived conversational posts accumulate, challenges emerge for forum administrators and analysts to effectively explore user groups in large-volume threads and gain meaningful insights into the hierarchical discussions. Identifying and comparing groups in discussion threads are nontrivial, since the number of users and posts increases with time and noises may hamper the detection of user groups. Researchers in data mining fields have proposed a large body of algorithms to explore user grouping. However, the mining result is not intuitive to understand and difficult for users to explore the details. To address these issues, we present VisForum, a visual analytic system allowing people to interactively explore user groups in a forum. We work closely with two educators who have released courses in Massive Open Online Courses (MOOC) platforms to compile a list of design goals to guide our design. Then, we design and implement a multi-coordinated interface as well as several novel glyphs, i.e., group glyph, user glyph, and set glyph, with different granularities. Accordingly, we propose the group Detecting 8 Sorting Algorithm to reduce noises in a collection of posts, and employ the concept of “forum-index” for users to identify high-impact forum members. Two case studies using real-world datasets demonstrate the usefulness of the system and the effectiveness of novel glyph designs. Furthermore, we conduct an in-lab user study to present the usability of VisForum.</jats:p

    Inside-out Ca2+ signalling prompted by STIM1 conformational switch

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    Store-operated Ca(2+) entry mediated by STIM1 and ORAI1 constitutes one of the major Ca(2+) entry routes in mammalian cells. The molecular choreography of STIM1–ORAI1 coupling is initiated by endoplasmic reticulum (ER) Ca(2+) store depletion with subsequent oligomerization of the STIM1 ER-luminal domain, followed by its redistribution towards the plasma membrane to gate ORAI1 channels. The mechanistic underpinnings of this inside-out Ca(2+) signalling were largely undefined. By taking advantage of a unique gain-of-function mutation within the STIM1 transmembrane domain (STIM1-TM), here we show that local rearrangement, rather than alteration in the oligomeric state of STIM1-TM, prompts conformational changes in the cytosolic juxtamembrane coiled-coil region. Importantly, we further identify critical residues within the cytoplasmic domain of STIM1 (STIM1-CT) that entail autoinhibition. On the basis of these findings, we propose a model in which STIM1-TM reorganization switches STIM1-CT into an extended conformation, thereby projecting the ORAI-activating domain to gate ORAI1 channels

    Bioengineered MSC-derived exosomes in skin wound repair and regeneration

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    Refractory skin defects such as pressure ulcers, diabetic ulcers, and vascular ulcers represent a challenge for clinicians and researchers in many aspects. The treatment strategies for wound healing have high cost and limited efficacy. To ease the financial and psychological burden on patients, a more effective therapeutic approach is needed to address the chronic wound. MSC-derived exosomes (MSC-exosomes), the main bioactive extracellular vesicles of the paracrine effect of MSCs, have been proposed as a new potential cell-free approach for wound healing and skin regeneration. The benefits of MSC-exosomes include their ability to promote angiogenesis and cell proliferation, increase collagen production, regulate inflammation, and finally improve tissue regenerative capacity. However, poor targeting and easy removability of MSC-exosomes from the wound are major obstacles to their use in clinical therapy. Thus, the concept of bioengineering technology has been introduced to modify exosomes, enabling higher concentrations and construction of particles of greater stability with specific therapeutic capability. The use of biomaterials to load MSC-exosomes may be a promising strategy to concentrate dose, create the desired therapeutic efficacy, and maintain a sustained release effect. The beneficial role of MSC-exosomes in wound healing is been widely accepted; however, the potential of bioengineering-modified MSC-exosomes remains unclear. In this review, we attempt to summarize the therapeutic applications of modified MSC-exosomes in wound healing and skin regeneration. The challenges and prospects of bioengineered MSC-exosomes are also discussed

    The application and progress of tissue engineering and biomaterial scaffolds for total auricular reconstruction in microtia

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    Microtia is a congenital deformity of the ear with an incidence of about 0.8–4.2 per 10,000 births. Total auricular reconstruction is the preferred treatment of microtia at present, and one of the core technologies is the preparation of cartilage scaffolds. Autologous costal cartilage is recognized as the best material source for constructing scaffold platforms. However, costal cartilage harvest can lead to donor-site injuries such as pneumothorax, postoperative pain, chest wall scar and deformity. Therefore, with the need of alternative to autologous cartilage, in vitro and in vivo studies of biomaterial scaffolds and cartilage tissue engineering have gradually become novel research hot points in auricular reconstruction research. Tissue-engineered cartilage possesses obvious advantages including non-rejection, minimally invasive or non-invasive, the potential of large-scale production to ensure sufficient donors and controllable morphology. Exploration and advancements of tissue-engineered cartilaginous framework are also emerging in aspects including three-dimensional biomaterial scaffolds, acquisition of seed cells and chondrocytes, 3D printing techniques, inducing factors for chondrogenesis and so on, which has greatly promoted the research process of biomaterial substitute. This review discussed the development, current application and research progress of cartilage tissue engineering in auricular reconstruction, particularly the usage and creation of biomaterial scaffolds. The development and selection of various types of seed cells and inducing factors to stimulate chondrogenic differentiation in auricular cartilage were also highlighted. There are still confronted challenges before the clinical application becomes widely available for patients, and its long-term effect remains to be evaluated. We hope to provide guidance for future research directions of biomaterials as an alternative to autologous cartilage in ear reconstruction, and finally benefit the transformation and clinical application of cartilage tissue engineering and biomaterials in microtia treatment

    Impact of Ligand and Silane on the Regioselectivity in Catalytic Aldehyde–Alkyne Reductive Couplings: A Theoretical Study

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    The reaction mechanisms of the (NHC)­Ni(0)-catalyzed aldehyde–alkyne reductive couplings with silanes as reducing agent have been theoretically investigated with the aid of DFT calculations. The impacts of N-heterocyclic carbene (NHC) ligands and silanes on the reversal of regioselectivity and the rate-limiting step alteration were rationalized. It is found that the steric effects play a dominant role. The reversal of the regioselectivity is found to be related to the switching of the steric effect, from the aldehyde phenyl hindrance with the adjacent alkyne substituent to the NHC ligand hindrance with the adjacent alkyne substituent, when the NHC ligand employed is changed from small to large. The rate-limiting step alteration caused by using bulkier silanes is due to the generated strong steric effect, which makes the σ-bond metathesis transition state relatively high in enthalpic energy, thus with the entropy penalty making the metathesis step rate-limiting instead of the oxidative cyclization step

    Impact of Ligand and Silane on the Regioselectivity in Catalytic Aldehyde–Alkyne Reductive Couplings: A Theoretical Study

    No full text
    The reaction mechanisms of the (NHC)­Ni(0)-catalyzed aldehyde–alkyne reductive couplings with silanes as reducing agent have been theoretically investigated with the aid of DFT calculations. The impacts of N-heterocyclic carbene (NHC) ligands and silanes on the reversal of regioselectivity and the rate-limiting step alteration were rationalized. It is found that the steric effects play a dominant role. The reversal of the regioselectivity is found to be related to the switching of the steric effect, from the aldehyde phenyl hindrance with the adjacent alkyne substituent to the NHC ligand hindrance with the adjacent alkyne substituent, when the NHC ligand employed is changed from small to large. The rate-limiting step alteration caused by using bulkier silanes is due to the generated strong steric effect, which makes the σ-bond metathesis transition state relatively high in enthalpic energy, thus with the entropy penalty making the metathesis step rate-limiting instead of the oxidative cyclization step

    Theoretical Study Of The Cl-Initiated Atmospheric Oxidation Of Methyl Isopropenyl Ketone

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    The Cl-initiated atmospheric oxidation mechanism of methyl isopropenyl ketone (MIK) has been investigated at the CCSD(T)/6-311++G(d,p)//MP2/6-311G(d,p) level of theory. Two reaction types initiated from Cl-addition and H-abstraction, respectively, and the key intermediates involved, IM1, IM2 (obtained from Cl-addition) and IM6 (obtained from H-abstraction), are presented and discussed. The calculated results supported the experimental results that Cl addition dominates the initial reactions of MIK with Cl atoms, and the most energetically favorable pathway is the Cl addition to the terminal carbon of CC bond. Among the four proposed H abstraction processes, our study clearly indicated that the H-abstraction by Cl only takes place at the methyl linking to the internal alkenfinic carbon rather than the one at the methyl linking to the carbonyl carbon, which resolves the uncertainty of H-abstraction encountered in experiment. In addition, the isomerization processes involved in the Cl addition mechanism (1,4-H shift isomerization of IMa3 and 1,5-H shift isomerization of IMb3) were proposed in this work and found to be feasible. Both the major products experimentally detected and those derived from our theoretical study have been identified. The rate constants of the initial reactions over the atmospheric temperature range of 180-380 K have been determined using the MESMER program on the basis of Rice-Ramsperger-Kassel-Marcus (RRKM) theory. One the basis of the kinetic data we obtained, the Arrhenius formula of the total rate constant has been deduced: ktot = (5.31 × 10-11)exp(-335.24/T) cm3 per molecule per s. The atmospheric lifetime of MIK in the presence of Cl atoms is calculated to be about 170.01 h
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