10 research outputs found

    An Exploratory Study on Two-Dimensional Project Management Maturity Model

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    Based on the analysis of the existing project management maturity models and software capability maturity models, this study proposes a novel two-dimensional project management maturity (TPMM) model, which emphasizes the project business management (PBM) and information technology application (ITA) simultaneously. It is the first to present the TPMM concept with PBM maturity and ITA maturity, and the first to evaluate ITA maturity based on the 49 processes of PMBOK. After the PBM and ITA maturities of 49 management processes are obtained using an expert evaluation method, the two-dimensional maturity of the knowledge area and enterprise layers can be calculated by statistical method. The comparison of maturities at three layers and two dimensions is helpful for enterprises to find problems in PBM and ITA, and to find the right direction for advancement. It is also helpful for enterprises to take corresponding improvement measures. The integrated framework provides a new perspective on improving the efficiency and capability of project management through positive cycle development between PBM and ITA. The application case sets an example for other enterprises to improve their project management capability and efficiency along a maturity ladder.</p

    Molecular Insights into the Improved Bioactivity of Interferon Conjugates Attached to a Helical Polyglutamate

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    Attaching polymers, especially polyethylene glycol (PEG), to protein drugs has emerged as a successful strategy to prolong circulation time in the bloodstream. The hypothesis is that the flexible chain wobbles on the protein’s surface, thus resisting potential nonspecific adsorption. Such a theoretical framework may be challenged when a helical polyglutamate is used to conjugate with target proteins. In this study, we investigated the structure–activity relationships of polyglutamate-interferon conjugates P(EG3Glu)-IFN using molecular simulations. Our results show that the local crowding effect induced by oligoethylene glycols (i.e., EG3) is the primary driving force for helix formation in P(EG3Glu), and its helicity can be effectively increased by reducing the free volume of the two termini. Furthermore, it was found that the steric hindrance induced by IFN is not conductive to the helicity of P(EG3Glu) but contributes to its dominant orientation relative to interferon. The orientation of IFN relative to the helical P(EG3Glu) can help to protect the protein drug from neutralizing antibodies while maintaining its bioactivity. These findings suggest that the helical structure and its orientation are critical factors to consider when updating the theoretical framework for protein–polymer conjugates

    Mismatch Negativity of Sad Syllables Is Absent in Patients with Major Depressive Disorder

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    <div><p>Background</p><p>Major depressive disorder (MDD) is an important and highly prevalent mental disorder characterized by anhedonia and a lack of interest in everyday activities. Additionally, patients with MDD appear to have deficits in various cognitive abilities. Although a number of studies investigating the central auditory processing of low-level sound features in patients with MDD have demonstrated that this population exhibits impairments in automatic processing, the influence of emotional voice processing has yet to be addressed. To explore the automatic processing of emotional prosodies in patients with MDD, we analyzed the ability to detect automatic changes using event-related potentials (ERPs).</p><p>Method</p><p>This study included 18 patients with MDD and 22 age- and sex-matched healthy controls. Subjects were instructed to watch a silent movie but to ignore the afferent acoustic emotional prosodies presented to both ears while continuous electroencephalographic activity was synchronously recorded. Prosodies included meaningless syllables, such as “dada” spoken with happy, angry, sad, or neutral tones. The mean amplitudes of the ERPs elicited by emotional stimuli and the peak latency of the emotional differential waveforms were analyzed.</p><p>Results</p><p>The sad MMN was absent in patients with MDD, whereas the happy and angry MMN components were similar across groups. The abnormal sad emotional MMN component was not significantly correlated with the HRSD-17 and HAMA scores, respectively.</p><p>Conclusion</p><p>The data indicate that patients with MDD are impaired in their ability to automatically process sad prosody, whereas their ability to process happy and angry prosodies remains normal. The dysfunctional sad emotion-related MMN in patients with MDD were not correlated with depression symptoms. The blunted MMN of sad prosodies could be considered a trait of MDD.</p></div

    Mean values (with <i>SD</i>) of demographic and clinical variables in MDD patients and healthy controls.

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    <p>HRSD-17, Hamilton Rating Scale of Depression-17; HAMA, Hamilton Anxiety Rating Scale;</p><p>MMSE, Mini-Mental State Examination.</p

    Grand averaged mean amplitudes of MMN.

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    <p>Emotional MMN under happy, angry, and sad conditions in HC and MDD groups. Error bars indicate standard deviations from the mean.</p

    DataSheet1_Automatic quantifying and monitoring follow-ups for implantable collamer lens implantation using AS-OCT images.docx

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    Purpose: To develop a deep learning method to automatically monitor the implantable collamer lens (ICL) position and quantify subtle alterations in the anterior chamber using anterior segment optical coherence tomography (AS-OCT) images for high myopia patients with ICL implantation.Methods: In this study, 798 AS-OCT images of 203 patients undergoing ICL implantation at our eye center from April 2017 to June 2021 were involved. A deep learning system was developed to first isolate the corneoscleral, ICL, and lens, and then quantify clinical important parameters in AS-OCT images (central corneal thickness, anterior chamber depth, and lens vault).Results: The deep learning system was able to accurately isolate the corneoscleral, ICL, and lens with the Dice coefficient ranging from 0.911 to 0.960, and all the F1 scores >0.900. The relative error between automated measurements and the ground truth for 95% (188 images out of 198) of LVs was within 10%. Intraclass correlation coefficients (ICCs) of the machine-ground truth measurements ranged from 0.928 to 0.995. The deep learning method also showed better repeatability than human graders.Conclusion: The deep learning method provides reliable detection and quantification of AS-OCT scans for postoperative ICL implantation, which can simplify and optimize the management of clinical outcomes of ICL implantations. Also, this is a step towards an objective measurement of the postoperative vault, making the data more comparable and repeatable to each other.</p

    Discovery of Substituted 1<i>H</i>‑Pyrazolo[3,4‑<i>b</i>]pyridine Derivatives as Potent and Selective FGFR Kinase Inhibitors

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    Fibroblast growth factor receptors (FGFRs) are important targets for cancer therapy. Herein, we describe the design, synthesis, and biological evaluation of a novel series of 1<i>H</i>-pyrazolo­[3,4-<i>b</i>]­pyridine derivatives as potent and selective FGFR kinase inhibitors. On the basis of its excellent <i>in vitro</i> potency and favorable pharmacokinetic properties, compound <b>7n</b> was selected for <i>in vivo</i> evaluation and showed significant antitumor activity in a FGFR1-driven H1581 xenograft model. These results indicated that <b>7n</b> would be a promising candidate for further drug development

    Competition between Metallic and Vacancy Defect Conductive Filaments in a CH<sub>3</sub>NH<sub>3</sub>PbI<sub>3</sub>‑Based Memory Device

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    Ion migration, which can be classified into cation migration and anion migration, is at the heart of redox-based resistive random access memory. However, the coexistence of these two types of ion migration and the resultant conductive filaments (CFs) have not been experimentally demonstrated in a single memory cell. Here we investigate the competition between metallic and vacancy defect CFs in a Ag/CH<sub>3</sub>NH<sub>3</sub>PbI<sub>3</sub>/Pt structure, where Ag and CH<sub>3</sub>NH<sub>3</sub>PbI<sub>3</sub> serve as the top electrode and memory medium, respectively. When the medium layer thickness is hundreds of nanometers, the formation/diffusion of iodine vacancy (V<sub>I</sub>) CFs dominates the resistive switching behaviors. The V<sub>I</sub>-based CFs provide a unique opportunity for the electrical-write and optical-erase operation in a memory cell. The Ag CFs emerge and coexist with V<sub>I</sub> ones as the medium layer thickness is reduced to ∼90 nm. Our work not only enriches the mechanisms of the resistive switching but also would advance the multifunctionalization of resistive random access memory
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