30 research outputs found

    Addressing Wealth Inequality Problem in Blockchain-Enabled Knowledge Community with Reputation-Based Incentive Mechanism

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    An increasing number of online knowledge communities have started incorporating the cut-edge FinTech, such as the tokenbased incentive mechanism running on blockchain, into their ecosystems. However, the improper design of incentive mechanisms may result in reward monopoly, which has been observed to harm the ecosystems of exiting communities. This study is aimed to ensure that the key factors involved in users’ reward distribution can truly reflect their contributions to the community so as to increase the equity of wealth distribution. It is one of the first to comprehensively balance a user’s historical and current contributions in reward distribution, which has not received sufficient attention from extant research. The simulation analysis demonstrates that the proposed solution of amending the existing incentive mechanism by incorporating a refined reputation indicator significantly increases the equity of rewards distribution and effectively enlarges the cost of achieving reward monopoly

    Alternatively folded proteins with unexpected beneficial functions

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    HAMLET (human alpha-lactalbumin made lethal to tumour cells) and its related partially unfolded protein-fatty acid complexes are novel biomolecular nanoparticles that possess relatively selective cytotoxic activities towards tumour cells. One of the key characteristics is the requirement for the protein to be partially unfolded, hence endowing native proteins with additional functions in the alternatively folded states. Beginning with the history of its discovery and development, the cellular targets that appear to be strongly correlated with tumour cell death are introduced in the present article

    High-throughput and high-sensitivity N-Glycan profiling: A platform for biopharmaceutical development and disease biomarker discovery

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    Protein glycosylation contributes to critical biological function of glycoproteins. Glycan analysis is essential for the production of biopharmaceuticals as well as for the identification of disease biomarkers. However, glycans are highly heterogeneous, which has considerably hampered the progress of glycomics. Here, we present an improved 96-well plate format platform for streamlined glycan profiling that takes advantage of rapid glycoprotein denaturation, deglycosylation, fluorescent derivatization, and on-matrix glycan clean-up. This approach offers high sensitivity with consistent identification and quantification of diverse N-glycans across multiple samples on a high-throughput scale. We demonstrate its capability for N-glycan profiling of glycoproteins from various sources, including two recombinant monoclonal antibodies produced from Chinese Hamster Ovary cells, EG2-hFc and rituximab, polyclonal antibodies purified from human serum, and total glycoproteins from human serum. Combined with the complementary information obtained by sequential digestion from exoglycosidase arrays, this approach allows the detection and identification of multiple N-glycans in these complex biological samples. The reagents, workflow, and Hydrophilic interaction liquid chromatography with fluorescence detection (HILIC-FLD), are simple enough to be implemented into a straightforward user-friendly setup. This improved technology provides a powerful tool in support of rapid advancement of glycan analysis for biopharmaceutical development and biomarker discovery for clinical disease diagnosis

    Mammalian cell culture for production of recombinant proteins: A review of the critical steps in their biomanufacturing

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    The manufacturing of recombinant protein is traditionally undertaken in mammalian cell culture. Today, speed, cost and safety are the primary considerations for process improvements in both upstream and downstream manufacturing. Leaders in the biopharmaceutical industry are striving for continuous improvements to increase throughput, lower costs and produce safer more efficacious drugs. This can be achieved through advances in cell line engineering, process development of cell culture, development of chemically defined media and increased emphasis on product characterization. In the first part, this review provides a historical perspective on approved biotherapeutics by regulatory bodies which pave the way for next-generation products (including gene therapy). In the second part, it focuses on the application of in vitro and in vivo cell line engineering approaches, modern process development improvements including continuous manufacturing, recent developments in media formulation, and improvements in critical quality attribute determinations for products produced predominantly in mammalian cells

    Antitumor activity and safety of camrelizumab combined with apatinib in patients with relapsed or refractory peripheral T-cell lymphoma: An open-label, multicenter, phase II study

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    IntroductionThe treatment for relapsed/refractory peripheral T-cell lymphoma (r/r PTCL) is suboptimal. This open-label, multicenter, single-arm study aimed to investigate the antitumor activity and safety of camrelizumab (a PD-1 blockade) plus apatinib (an antiangiogenic agent) for patients with r/r PTCL.MethodsEligible patients with r/r PTCL were enrolled and received camrelizumab 200 mg intravenously every 2 weeks and apatinib 500 or 250 mg orally once daily, 4 weeks as a cycle. The primary endpoint was overall response rate (ORR).ResultsA total of 20 patients were enrolled and received study medications in the study, with a median number of prior treatment line of 3 (range 1-6). At the cutoff date of March 4, 2022, the median follow-up was 27.2 months (range: 0.5-39.9), and three patients remained on treatment. Six patients had early discontinuation without tumor response evaluation. For all patients, the ORR was 30% (6/20) (95% confidence interval [CI], 11.9% to 54.3%), with two patients (10%) achieving complete response. The median progression-free survival (PFS) and median overall survival for all patients were 5.6 months (95% CI, 1.8 to not reached) and 16.7 months (95% CI, 2.8 to not reached), respectively. Patients with PD-L1 expression ≥50% (3 patients) had a numerically higher ORR and longer median PFS than those with PD-L1 expression < 50% (5 patients). The most commonly reported grade 3 or higher adverse events were hyperlipidemia (15%), hypokalemia (15%) and anemia (15%). No treatment-related deaths occurred.DiscussionIn this study, PD-1 inhibitors plus low-dose antiangiogenic drugs presented preliminary antitumor activity and manageable toxicity in patients with r/r PTCL

    High-amylose starch-based gel as green adhesive for plywood:Adhesive property, water-resistance, and flame-retardancy

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    The escalating demand for environmentally sustainable and cost-effective adhesives in the wood processing and manufacturing sector has prompted exploration into innovative solutions. This study introduces a novel gel adhesive composed of chemically unmodified high-amylose starch (G70, with 68 % amylose content) with a minimal proportion of urea-formaldehyde (UF) (UF/starch = 1:10, w/w). This G70/UF gel demonstrates remarkable adhesive capabilities for wooden boards under both dry conditions (with a shear stress of 4.13 ± 0.12 MPa) and wet conditions (with a shear strength of 0.93 ± 0.07 MPa after 2 h of water soaking). The study unveils that the elevated amylose content in the starch, coupled with a meticulously controlled isothermal process during bonding, is crucial for these enhancements. Specifically, the robust cohesion of amylose chains expedites phase separation between starch and UF, while the isothermal process facilitates the migration and enrichment of UF molecules at the gel-board and gel-air interfaces. Lacking these mechanisms, conventional amylopectin-rich starch/UF gels (27 % amylose content) show minimal improvement. Moreover, the G70/UF gel showcases exceptional fire retardancy. In all, the G70/UF gel presents a promising alternative for plywood production, reducing reliance on unhealthy UF resin while offering satisfactory bonding resistance in diverse conditions and superior flame retardancy.</p

    High-amylose starch-based gel as green adhesive for plywood:Adhesive property, water-resistance, and flame-retardancy

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    The escalating demand for environmentally sustainable and cost-effective adhesives in the wood processing and manufacturing sector has prompted exploration into innovative solutions. This study introduces a novel gel adhesive composed of chemically unmodified high-amylose starch (G70, with 68 % amylose content) with a minimal proportion of urea-formaldehyde (UF) (UF/starch = 1:10, w/w). This G70/UF gel demonstrates remarkable adhesive capabilities for wooden boards under both dry conditions (with a shear stress of 4.13 ± 0.12 MPa) and wet conditions (with a shear strength of 0.93 ± 0.07 MPa after 2 h of water soaking). The study unveils that the elevated amylose content in the starch, coupled with a meticulously controlled isothermal process during bonding, is crucial for these enhancements. Specifically, the robust cohesion of amylose chains expedites phase separation between starch and UF, while the isothermal process facilitates the migration and enrichment of UF molecules at the gel-board and gel-air interfaces. Lacking these mechanisms, conventional amylopectin-rich starch/UF gels (27 % amylose content) show minimal improvement. Moreover, the G70/UF gel showcases exceptional fire retardancy. In all, the G70/UF gel presents a promising alternative for plywood production, reducing reliance on unhealthy UF resin while offering satisfactory bonding resistance in diverse conditions and superior flame retardancy.</p

    Feasibility of high-helium natural gas exploration in the Presinian strata, Sichuan Basin

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    Helium in China highly depends on import at present, so the most practical way to change the situation is searching for medium-to-large natural gas fields with high helium content. Therefore, the hydrocarbon accumulation mechanism and the helium origin of the Weiyuan high-helium natural gas reservoir have been analyzed to find out the feasibility of finding natural gas field with high helium content in the Presinian strata of the Sichuan Basin. Based on twelve outcrop sections and drilling data of four wells encountering the Presinian strata, the petrological features, sedimentary facies and source rocks of Presinian strata were systematically analyzed, which shows that the sedimentary formation developed in the Presinian is the Nanhua system, and the stratigraphic sequence revealed by outcrop section in the eastern margin includes the Nantuo, Datangpo, Gucheng and Liantuo Fms, and it is inferred that the same stratigraphic sequence may occur inside the basin. The Nantuo, Gucheng and Liantuo Fms are mainly glacial deposits of glutenite interbedded with mudstone; the Datangpo Fm is interglacial deposits of sandstone and shale, the lower part shale, rich in organic matter, is fairly good source rock. Further study showed that the Nantuo coarse-grained clastic reservoir, Datangpo source rock and the intruded granite “helium source rock” make up a good high-helium gas system. Controlled by the early rift, the thick Presinian sedimentary rocks occur primarily inside the rift. The distribution of sedimentary rocks and granite in the basin was predicted by use of the seismic data, which shows that the feasibility of finding high-helium gas reservoirs in Ziyang area of the Sichuan Basin is great

    Characteristics and phylogenetic analysis of the complete chloroplast genome of Primulina hedyotidea

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    Primulina hedyotidea (Woon Young Chun) Yin Zheng Wang 2011 is an important medicinal plant that has a long history of medicinal use in China. In this experiment, the whole chloroplast genome of P. hedyotidea was determined by next-generation sequencing technology. The total base length of P. hedyotidea was 153,297 bp, the GC content was 37.62%, the inverted repeat (IR) region length was 25,494 bp, the large single copy (LSC) region was 84,158 bp and the small single copy (SSC) region was 18,151 bp. In addition, the genome consisted of 80 protein-coding genes, 4 rRNA genes, and 28 tRNA genes, for a total of 112 genes. A phylogenetic tree was constructed to explore the evolutionary relationship between P. hedyotidea and other species. The findings of phylogenetic tree analysis show that Primulina huaijiensis and P. hedyotidea have a close relationship, and this study can help with species identification and phylogenetic analysis within Primulina and Gesneriaceae species

    Mechanical Behavior of Al-Si10-Mg P-TPMS Structure Fabricated by Selective Laser Melting and a Unified Mathematical Model with Geometrical Parameter

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    Compared with the traditional lattice structure, the triply periodic minimal surface (TPMS) structure can avoid stress concentration effectively. Here, it is promising in the fields of lightweight and energy absorption. However, the number of structural parameters and mechanical properties of the TPMS structure is plentiful, and the relationship between them is unclassified. In this paper, for the first time, a unified mathematical model was proposed to establish the relationship between TPMS structural design parameters and mechanical properties. Fifteen primitive models were designed by changing the structural parameters (level-set value C and thickness T) and manufacturing by selective laser melting. The geometric defects and surface quality of the structures were explored by optical microscope and scanning electron microscopy (SEM). The mechanical properties were investigated by quasi-static compression test and finite element simulation. The influence of building direction on structural mechanical behavior (failure mode, stress-strain curve) was studied. The real mechanical properties (Young’s modulus and plateau stress) of the structure could be predicted according to different C and T combinations. Finally, the energy absorption characteristics were explored. The results showed that when the C value is 0.6 in the range of 0–0.6, the energy absorption performance of the structure is at the maximum level
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