Commercial participation continues to grow in open source software (OSS) projects and novel arrangements appear to emerge in company-dominated projects and ecosystems. What is the nature of these ...novel arrangements? Does volunteers' participation remain critical for these ecosystems? Despite extensive research on commercial participation in OSS, the exact nature and extent of company contributions to OSS development, and the impact of this engagement may have on the volunteer community have not been clarified. To bridge the gap, we perform an exploratory study of OpenStack: a large OSS ecosystem with intense commercial participation. We quantify companies' contributions via the developers that they provide and the commits made by those developers. We find that companies made far more contributions than volunteers and the distribution of the contributions made by different companies is also highly unbalanced. We observe eight unique contribution models based on companies' commercial objectives and characterize each model according to three dimensions: contribution intensity, extent, and focus. Companies providing full cloud solutions tend to make both intensive (more than other companies) and extensive (involving a wider variety of projects) contributions. Usage-oriented companies make extensive but less intense contributions. Companies driven by particular business needs focus their contributions on the specific projects addressing these needs. Minor contributors include community players (e.g., the Linux Foundation) and research groups. A model relating the number of volunteers to the diversity of contribution shows a strong positive association between them.
Sarco/endoplasmic reticulum Ca2+ ATPase 2b (SERCA2b), a member of the SERCA family, is expressed ubiquitously and transports Ca2+ into the sarco/endoplasmic reticulum using the energy provided by ATP ...binding and hydrolysis. The crystal structure of SERCA2b in its Ca2+‐ and ATP‐bound (E1∙2Ca2+‐ATP) state and cryo‐electron microscopy (cryo‐EM) structures of the protein in its E1∙2Ca2+‐ATP and Ca2+‐unbound phosphorylated (E2P) states have provided essential insights into how the overall conformation and ATPase activity of SERCA2b is regulated by the transmembrane helix 11 and the subsequent luminal extension loop, both of which are specific to this isoform. More recently, our cryo‐EM analysis has revealed that SERCA2b likely adopts open and closed conformations of the cytosolic domains in the Ca2+‐bound but ATP‐free (E1∙2Ca2+) state, and that the closed conformation represents a state immediately prior to ATP binding. This review article summarizes the unique mechanisms underlying the conformational and functional regulation of SERCA2b.
Recent cryo‐electron microscopy analyses revealed mechanisms of structural and functional regulation of SERCA2b by its specific 11th transmembrane helix (TM11) and luminal extension tail (LE). During the SERCA catalytic cycle, ATP binding and hydrolysis in the cytosolic domains are closely coupled to Ca2+ binding and release in the transmembrane domain.
The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global crisis. There is no therapeutic treatment specific for COVID-19. It is highly ...desirable to identify potential antiviral agents against SARS-CoV-2 from existing drugs available for other diseases and thus repurpose them for treatment of COVID-19. In general, a drug repurposing effort for treatment of a new disease, such as COVID-19, usually starts from a virtual screening of existing drugs, followed by experimental validation, but the actual hit rate is generally rather low with traditional computational methods. Here we report a virtual screening approach with accelerated free energy perturbation-based absolute binding free energy (FEP-ABFE) predictions and its use in identifying drugs targeting SARS-CoV-2 main protease (Mpro). The accurate FEP-ABFE predictions were based on the use of a restraint energy distribution (RED) function, making the practical FEP-ABFE–based virtual screening of the existing drug library possible. As a result, out of 25 drugs predicted, 15 were confirmed as potent inhibitors of SARS-CoV-2 Mpro. The most potent one is dipyridamole (inhibitory constant Ki = 0.04 μM)which has shown promising therapeutic effects in subsequently conducted clinical studies for treatment of patients with COVID-19. Additionally, hydroxychloroquine (Ki = 0.36 μM) and chloroquine (Ki = 0.56 μM) were also found to potently inhibit SARS-CoV-2 Mpro. We anticipate that the FEP-ABFE prediction-based virtual screening approach will be useful in many other drug repurposing or discovery efforts.
Two-dimensional (2D) materials have generated great interest in the past few years opening up a new dimension in the development of optoelectronics and photonics. In this paper, we demonstrate 6.5 ...GHz fundamentally Q-switched mode-locked lasers with high performances in the femtosecond laser-written waveguide platform by applying graphene, MoS
and Bi
Se
as saturable absorbers (SAs). The minimum mode-locked pulse duration was measured to be as short as 26 ps in the case of Bi
Se
SA. The maximum slope efficiency reached 53% in the case of MoS
SA. This is the first demonstration of Q-switched mode-locked waveguide lasers based on MoS
and Bi
Se
in the waveguide platform. These high-performance Q-switched mode-locked waveguide lasers based on 2D materials pave the way for practical applications of compact ultrafast photonics.
DDX58/RIG-I, is a critical pattern recognition receptor for viral RNA, which plays an essential role in antiviral immunity. Its posttranslational modifications and stability are tightly regulated to ...mediate the moderate production of type I IFN to maintain the immune homeostasis. Recently, we reported that macroautophagy/autophagy balances type I IFN signaling through selective degradation of ISG15-associated DDX58 via LRRC25. However, the regulatory mechanism about the autophagic degradation of DDX58 remains largely undefined. Here, we identified LRRC59 as a vital positive regulator of DDX58-mediated type I IFN signaling. Upon virus infection, LRRC59 specifically interacted with ISG15-associated DDX58 and blocked its association with LRRC25, the secondary receptor to deliver DDX58 to autophagosomes for SQSTM1/p62-dependent degradation, leading to the stronger antiviral immune responses. Thus, our study reveals a novel regulatory role of selective autophagy in innate antiviral responses mediated by the cross-regulation of LRRC family members. These data further provide insights into the crosstalk between autophagy and innate immune responses.
ATG: Autophagy-related; Baf A
1
: Bafilomycin A
1
; DDX58/RIG-I: DEAD Asp-Glu-Ala-Asp box polypeptide 58; EV: Empty vector; IC polyI:C: Intracellular polyriboinosinic polyribocytidylic acid; IFIH1/MDA5: Interferon induced with helicase C domain 1; IFN: Interferon; ISG15: ISG15 ubiquitin like modifier; IKBKE: Inhibitor of nuclear factor kappa B kinase subunit epsilon; IRF3: Interferon regulatory factor 3; KO: Knockout; LRRC: Leucine rich repeat containing; MAVS: Mitochondrial antiviral signaling protein; CGAS/MB21D1: Cyclic GMP-AMP synthase; SeV: Sendai virus; siRNA: small interfering RNA; SQSTM1/p62: Sequestosome 1; TBK1: TANK binding kinase 1; TLR: Toll like receptor; TMEM173/STING: Transmembrane protein 173; VSV: Vesicular stomatitis virus; WT: Wild type
Metal-free photocatalysts have received increasing attention as nonmetal elements are abundant in the earth and friendly to the environment. Graphitic carbon nitride (g-C3N4) as a typical ...two-dimensional (2D) metal-free photocatalysts for water splitting has attracted increasing interest due to its economic production and environmentally friend features. However, the high photocarriers recombination rate constraint its catalytic activity. Combining the single- or few-layered g-C3N4 nanosheets with other 2D functional materials to form efficient metal-free heterojunction photocatalysts is one of the effective strategies to improve the photocarriers separation. Herein, we introduce a simple and efficient method to scalable preparation few-layered g-C3N4 nanosheets using gas exfoliation of bulk g-C3N4 in liquid nitrogen. Then we introduce the g-C3N4 nanosheets into construct a 2D/2D heterojunction of g-C3N4/graphdiyne by π-π interaction, where graphdiyne (GDY) as a new 2D carbon allotrope, has excellent holes transfer nature. We find that the 2D/2D g-C3N4/GDY photocatalyst with 1% GDY is the optimum condition, with the highest H2 evolution rate of 454.28 μmol h−1. The superior photocatalytic performance may be attributed to the excellent photocarriers separation in g-C3N4 under the built-in field, where GDY can rapid transport holes from g-C3N4 to the sacrificial agents.
Herein, we report a simple and efficient method to scalable preparation few-layered g-C3N4 nanosheets using gas exfoliation of bulk g-C3N4 in liquid nitrogen. The photocatalytic hydrogen evolution performance for the g-C3N4 nanosheets is significantly enhanced by formation the heterojunction of g-C3N4/graphdiyne through π-π interaction, where graphdiyne (GDY) as a new 2D carbon allotrope, has excellent hole transfer nature. The 2D-2D g-C3N4/GDY photocatalyst with 1% GDY has the highest H2 evolution rate of 454.28 μmol h−1, which is about 3 times faster than that of the pure g-C3N4 NS. Display omitted
•Scalable synthesis of few-layered g-C3N4 nanosheets via gas exfoliation approach.•The g-C3N4 nanosheets show great photocatalytic H2 performance.•The g-C3N4/GDY heterojunction exhibits great photocatalytic H2 performance.•The superior photocatalytic performance mechanism is proposed.
Nonalcoholic fatty liver disease (NAFLD) is the most common type of chronic liver disease in the Western countries, affecting up to 25% of the general population and becoming a major health concern ...in both adults and children. NAFLD encompasses the entire spectrum of fatty liver disease in individuals without significant alcohol consumption, ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) and cirrhosis. NASH is a manifestation of the metabolic syndrome and hepatic disorders with the presence of steatosis, hepatocyte injury (ballooning), inflammation, and, in some patients, progressive fibrosis leading to cirrhosis. The pathogenesis of NASH is a complex process and implicates cell interactions between liver parenchymal and nonparenchymal cells as well as crosstalk between various immune cell populations in liver. Lipotoxicity appears to be the central driver of hepatic cellular injury via oxidative stress and endoplasmic reticulum (ER) stress. This review focuses on the contributions of hepatocytes and nonparenchymal cells to NASH, assessing their potential applications to the development of novel therapeutic agents. Currently, there are limited pharmacological treatments for NASH; therefore, an increased understanding of NASH pathogenesis is pertinent to improve disease interventions in the future.
MicroRNAs contribute to cancer development by acting as oncogenes or tumor suppressor genes. However, only a few microRNA target genes were determined. We identified a nearly perfect complementarity ...between miR-206 and the 3′-untranslated regions of both mouse and human notch3. Expression of miR-206 decreased the luciferase activity dose-dependently when cotransfected with the mouse or human notch3 3′-untranslated region-luciferase reporter containing the miR-206 target site in HeLa cells. This suppression was relieved by deletion and mutation of the miR-206-binding site and was partially recovered by expression of notch3 or by a specific inhibitor of miR-206. Interestingly, overexpression of miR-206 decreased the levels of both Notch3 protein and mRNA. Expression of miR-206 markedly induced apoptotic cell death and blocked the anti-apoptotic activity of Notch3. In addition, ectopic expression of miR-206 inhibited HeLa cell migration and focus formation. Therefore, we identified miR-206 as a pro-apoptotic activator of cell death, which was associated with its inhibition of notch3 signaling and tumor formation. The inhibition of cancer cell migration and focus formation by miR-206 strongly suggests that miR-206 may function as a novel tumor suppressor.
In this paper, we investigate the violation of the quantum witness, the entropic Leggett-Garg inequality (LGI) and the no-coherence-generating-and-detecting (NCGD) dynamics, under projective and ...coarsening measurements. We consider a qubit in the three scenarios: coherent dynamics, in the presence of dissipation, and in the presence of dephasing. For the pure qubit, we find that in the case of the projective measurement, the non-violation conditions of the quantum witness and the NCGD are the same; while the non-violation conditions of the entropic LGI and the quantum witness do not contain each other, i.e., a suitable conjunction of the quantum witness and the entropic LGI may be better for testing macrorealism. Also, for the pure qubit with coarsening measurement similar results can be obtained. For the dissipative qubit with projective measurement, the quantum witness and the NCGD can be both violated for a wider parameter regime than the entropic LGI. For the dissipative qubit with coarsening measurement, the violation of the NCGD is the most robust compared to the quantum witness and the entropic LGI. For the dephasing qubit with projective and coarsening measurements, the relationship among the quantum witness, the entropic LGI and the NCGD is similar to that of the pure qubit. In addition, we find that for pure, dissipative and dephasing qubits, the robustness of the coarsening measurement in final resolution is more vulnerable than that of the coarsening measurement in reference for the entropic LGI.
In this paper, we consider a qubit in four scenarios: with drive, without drive, and in the presence of dissipation and dephasing, to investigate the quantum violation of the Leggett-Garg inequality ...(LGI) in an energy constraint. In the case of the energy constraint, we find that under the coarsening measurement in reference and final resolution, the quantum violation of the LGI for the pure qubit is the most robust; on the other hand, the quantum violation of the LGI for the dephasing qubit is the most vulnerable, and the quantum violation of the LGI for driven qubit lies between that of pure qubit and dissipation qubit. Under the coarsening of measurement temporal reference, the quantum violation of the LGI for the pure qubit is more robust than that of the qubit with driven. Moreover, in the case of a qubit that is subjected to driving and is in the presence of dissipation and dephasing, the robustness of quantum violations of the LGI for these scenario systems will become vulnerable, with the driven intensity and the rate of spontaneous emission increasing, respectively, for coarsening measurement both in reference and in final resolution. In addition, in the energy constraint and the projective measurement, the LGI can attain its maximum violation value, 1.5, for the coherent dynamics; while for drive, dissipative and dephasing qubits, the LGI cannot attain the value of 1.5. For systems in the presence of dissipation and dephasing, we find that in the energy constraint, the robustness of the coarsening measurement in final resolution exhibits more vulnerable than that of the coarsening measurement in reference. And for systems with drive and without drive, the robustness of the coarsening measurement in temporal reference is the most robust, and the robustness of the coarsening of measurement final measurement resolution is the most vulnerable.
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