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In this paper, a rib layout optimization method that can efficiently reduce the radiated noise of gearboxes is proposed. Taking the secondary gearbox as the research object, the radiated noise of the housing is calculated using the FEM/BEM method, the process of determining the region with the maximum acoustic contribution is illustrated, and a topology optimization model that can reduce the air noise on the field points of the gearbox is established with the surface normal velocity of the region as the optimization target. The method is applied to add new noise reduction ribs on the surface of the gearbox. The results show that after combining the topology optimization with the acoustic contribution analysis, the sound pressure in the area with the highest sound pressure on the gearbox sound field is significantly reduced by adding new noise reduction ribs according to the optimization results.

The purpose of this study was to examine the nexus amid economic growth, energy consumption and carbon emissions in G20 countries for the period 1992 to 2014. In order to obtain valid and reliable outcomes, more robust econometric techniques were employed. From the results, the studied panel was heterogeneous and cross-sectionally dependent. Also, the series of observed variables were first-differenced stationary and co-integrated. The key findings from the CCEMG and the AMG regression estimators adopted showed that economic growth and energy consumption promoted the emission of carbon in the countries. In addition, urbanization and foreign direct investments as control variables escalated the rate of the countries’ CO2 emissions. From the discoveries of the Dumitrescu and Hurlin panel causality test, a feedback causality between economic growth and CO2 emissions; energy consumption and CO2 emissions; and between urbanization and CO2 emissions were correspondingly unveiled. Howerver, a one-way caual link was evidenced from foreign direct investments to CO2 emissions. This exploration is vital because it will propel the countries to formulate policies that could help them to minimize their dependence on environmentally unfriendly energy sources, while promoting the usage of clean energies like solar, wind, biogas, biomass and hydropower among others. The study is also pertinent because it will aid the countries to plan, organize and implement environmental policies in compliance to their macroeconomic objectives. When this is accomplished, energy conservation policies implemented to minimize the emanation of CO2 will improve the countries’ economic growth.

The purpose of this study was to examine the nexus amid economic growth, energy consumption and carbon emissions in G20 countries for the period 1992 to 2014. In order to obtain valid and reliable outcomes, more robust econometric techniques were employed. From the results, the studied panel was heterogeneous and cross-sectionally dependent. Also, the series of observed variables were first-differenced stationary and co-integrated. The key findings from the CCEMG and the AMG regression estimators adopted showed that economic growth and energy consumption promoted the emission of carbon in the countries. In addition, urbanization and foreign direct investments as control variables escalated the rate of the countries’ CO2 emissions. From the discoveries of the Dumitrescu and Hurlin panel causality test, a feedback causality between economic growth and CO2 emissions; energy consumption and CO2 emissions; and between urbanization and CO2 emissions were correspondingly unveiled. Howerver, a one-way caual link was evidenced from foreign direct investments to CO2 emissions. This exploration is vital because it will propel the countries to formulate policies that could help them to minimize their dependence on environmentally unfriendly energy sources, while promoting the usage of clean energies like solar, wind, biogas, biomass and hydropower among others. The study is also pertinent because it will aid the countries to plan, organize and implement environmental policies in compliance to their macroeconomic objectives. When this is accomplished, energy conservation policies implemented to minimize the emanation of CO2 will improve the countries’ economic growth.

Ulva prolifera is the dominant species of green macroalgal blooms in the Yellow Sea, China. In this study, we sequenced and annotated the complete chloroplast genome of U. prolifera (GenBank accession number: KX342867). The genome of circular chromosomes consists of 93,066 including 66 protein-encoding genes, 26 tRNA genes, and 3 rRNA genes. Compared with the 16 species from Chlorophyta, it has eight genes in expansion and 15 genes in shrink. Phylogenetic analysis shows positioned U. prolifera with U. linza, while Ulva sp.UNA00071828 is closely allied with Ulva fasciata.

This study examined the connection between liquidity, capital structure, and the financial sustainability of 28 quoted non-financial establishments in Ghana. Panel data for the period from 2008 to 2019 was used for the analysis. In the study, liquidity was proxied by the current ratio, while the debt ratio was used as a surrogate of capital structure. Additionally, return on equity (ROE) was employed as a measure of sustainability. This indicator was used because of its flexibility as it can be applied to any line of business or product. From the results, the studied panel was cross-sectionally independent. Furthermore, the series were first differenced stationary and cointegrated in the long-run. The elasticities of the predictors were determined through the generalized method of moments (GMM) estimator, and from the results, liquidity proxied by the current ratio improved the entities’ financial sustainability. In addition, capital structure surrogated by the debt ratio promoted the financial sustainability of the establishments. Moreover, the interaction between capital structure and liquidity advanced the corporates’ financial sustainability. Size, growth, and operational efficiency were significantly positive determinants of the sustainability of firms, but asset tangibility had a trivial effect on the entities’ sustainability. On the causal relations among the variables, there was a bilateral connection amidst current ratio and return on equity; between cash flow ratio and return on equity; between debt ratio and return on equity; between size and return on equity; between operational efficiency and return on equity. Additionally, a single-headed causality moving from growth to return on equity was uncovered. Finally, there was no causal liaison amidst tangibility and return on equity. Based on the findings, it was recommended, amongst other suggestions, that an optimal liquidity level that is capable of supplying the firms with sufficient liquid resources should be maintained. Furthermore, the firms should use more internal funds to back their activities because that choice is safer than the alternatives. The corporates should also prefer that option because it has no associated costs that could adversely impact their sustainability.

SARS-CoV-2 variants could induce immune escape by mutations on the receptor-binding domain (RBD) and N-terminal domain (NTD). Here we report the humoral immune response to circulating SARS-CoV-2 variants, such as 501Y.V2 (B.1.351), of the plasma and neutralizing antibodies (NAbs) elicited by CoronaVac (inactivated vaccine), ZF2001 (RBD-subunit vaccine) and natural infection. Among 86 potent NAbs identified by high-throughput single-cell VDJ sequencing of peripheral blood mononuclear cells from vaccinees and convalescents, near half anti-RBD NAbs showed major neutralization reductions against the K417N/E484K/N501Y mutation combination, with E484K being the dominant cause. VH3-53/VH3-66 recurrent antibodies respond differently to RBD variants, and K417N compromises the majority of neutralizing activity through reduced polar contacts with complementarity determining regions. In contrast, the 242–244 deletion (242–244Δ) would abolish most neutralization activity of anti-NTD NAbs by interrupting the conformation of NTD antigenic supersite, indicating a much less diversity of anti-NTD NAbs than anti-RBD NAbs. Plasma of convalescents and CoronaVac vaccinees displayed comparable neutralization reductions against pseudo- and authentic 501Y.V2 variants, mainly caused by E484K/N501Y and 242–244Δ, with the effects being additive. Importantly, RBD-subunit vaccinees exhibit markedly higher tolerance to 501Y.V2 than convalescents, since the elicited anti-RBD NAbs display a high diversity and are unaffected by NTD mutations. Moreover, an extended gap between the third and second doses of ZF2001 leads to better neutralizing activity and tolerance to 501Y.V2 than the standard three-dose administration. Together, these results suggest that the deployment of RBD-vaccines, through a third-dose boost, may be ideal for combating SARS-CoV-2 variants when necessary, especially for those carrying mutations that disrupt the NTD supersite.

Discontinuous phase flooding (such as polymer microspheres) is an important method for enhancing oil recovery. With the hydration swelling and elastic properties, a unique “migration–entrapment–remigration” discontinuous flow behavior is identified during flooding. And a more pronounced conformance control effect is observed in high-permeability flow channels and deeper reservoir regions compared to continuous phase flooding. These complex seepage mechanisms pose significant challenges to reservoir numerical simulation. Based upon a chemical reaction framework, a multi-component mathematical model comprising oil, gas, water, pre-discontinuous phase, and discontinuous phase components is developed in this study. The discontinuous phase is generated through chemical reactions involving the pre-discontinuous phase. A minimum reaction porosity is first introduced in the chemical reaction process to enhance the discontinuous phase generation in high-permeability regions. A threshold pressure is incorporated into the discontinuous phase equation for the “migration–entrapment–remigration” discontinuous flow characteristics. The model is subsequently solved using a fully implicit finite volume method. A new numerical simulator implementing this approach is developed in C++. Validation through physical experiments confirms the method’s accuracy. The discontinuous migration process of “migration–entrapment–remigration” is clearly reflected through the injection pressure fluctuations during simulation. Mechanistic models and field-scale simulations both confirm that discontinuous phase flooding significantly enhances oil recovery efficiency, outperforming both water flooding and continuous phase flooding. The novel reaction specification enhances conformance control in high-permeability channels, as demonstrated by the simulation results. The proposed model accurately captures the migration characteristics of the discontinuous phase and holds important practical value for reservoirs with discontinuous phase flooding.

Background Metazoan cells only utilize a small subset of the potential DNA replication origins to duplicate the whole genome in each cell cycle. Origin choice is linked to cell growth, differentiation, and replication stress. Although various genetic and epigenetic signatures have been linked to the replication efficiency of origins, there is no consensus on how the selection of origins is determined. Results We apply dual-color stochastic optical reconstruction microscopy (STORM) super-resolution imaging to map the spatial distribution of origins within individual topologically associating domains (TADs). We find that multiple replication origins initiate separately at the spatial boundary of a TAD at the beginning of the S phase. Intriguingly, while both high-efficiency and low-efficiency origins are distributed homogeneously in the TAD during the G1 phase, high-efficiency origins relocate to the TAD periphery before the S phase. Origin relocalization is dependent on both transcription and CTCF-mediated chromatin structure. Further, we observe that the replication machinery protein PCNA forms immobile clusters around TADs at the G1/S transition, explaining why origins at the TAD periphery are preferentially fired. Conclusion Our work reveals a new origin selection mechanism that the replication efficiency of origins is determined by their physical distribution in the chromatin domain, which undergoes a transcription-dependent structural re-organization process. Our model explains the complex links between replication origin efficiency and many genetic and epigenetic signatures that mark active transcription. The coordination between DNA replication, transcription, and chromatin organization inside individual TADs also provides new insights into the biological functions of sub-domain chromatin structural dynamics.

Neurofibromatosis type 1 (NF1) plexiform neurofibromas (PNs) are progressive, multicellular neoplasms that cause morbidity and may transform to sarcoma. Treatment of Nf1 fl/fl ; Postn -Cre mice with cabozantinib, an inhibitor of multiple tyrosine kinases, caused a reduction in PN size and number and differential modulation of kinases in cell lineages that drive PN growth. Based on these findings, the Neurofibromatosis Clinical Trials Consortium conducted a phase II, open-label, nonrandomized Simon two-stage study to assess the safety, efficacy and biologic activity of cabozantinib in patients ≥16 years of age with NF1 and progressive or symptomatic, inoperable PN ( NCT02101736 ). The trial met its primary outcome, defined as ≥25% of patients achieving a partial response (PR, defined as ≥20% reduction in target lesion volume as assessed by magnetic resonance imaging (MRI)) after 12 cycles of therapy. Secondary outcomes included adverse events (AEs), patient-reported outcomes (PROs) assessing pain and quality of life (QOL), pharmacokinetics (PK) and the levels of circulating endothelial cells and cytokines. Eight of 19 evaluable (42%) trial participants achieved a PR. The median change in tumor volume was 15.2% (range, +2.2% to −36.9%), and no patients had disease progression while on treatment. Nine patients required dose reduction or discontinuation of therapy due to AEs; common AEs included gastrointestinal toxicity, hypothyroidism, fatigue and palmar plantar erythrodysesthesia. A total of 11 grade 3 AEs occurred in eight patients. Patients with PR had a significant reduction in tumor pain intensity and pain interference in daily life but no change in global QOL scores. These data indicate that cabozantinib is active in NF1-associated PN, resulting in tumor volume reduction and pain improvement. Cabozantinib, an inhibitor of multiple receptor tyrosine kinases, has efficacy in a mouse model of neurofibromatosis type I and has clinical activity in reducing plexiform neurofibroma volume in a phase II trial of patients with NF1.

ABSTRACT Background: T-cell-mediated immunity is crucial for the effective clearance of viral infection, but the T-cell-mediated immune responses that are induced by booster doses of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in people living with human immunodeficiency virus (PLWH) remain unclear. Methods: Forty-five PLWH who had received antiretroviral therapy (ART) for more than two years and 29 healthy controls (HCs) at Beijing Youan Hospital were enrolled to assess the dynamic changes in T-cell responses between the day before the third vaccine dose (week 0) and 4 or 12 weeks (week 4 or week 12) after receiving the third dose of inactivated SARS-CoV-2 vaccine. Flow cytometry, enzyme-linked immunospot (ELISpot), and multiplex cytokines profiling were used to assess T-cell responses at the three timepoints in this study. Results: The results of the ELISpot and activation-induced marker (AIM) assays showed that SARS-CoV-2-specific T-cell responses were increased in both PLWH and HCs after the third dose of the inactivated SARS-CoV-2 vaccine, and a similar magnitude of immune response was induced against the Omicron (B.1.1.529) variant compared to the wild-type strain. In detail, spike-specific T-cell responses (measured by the ELISpot assay for interferon γ [IFN-γ] release) in both PLWH and HCs significantly increased in week 4, and the spike-specific T-cell responses in HCs were significantly stronger than those in PLWH 4 weeks after the third vaccination. In the AIM assay, spike-specific CD4+ T-cell responses peaked in both PLWH and HCs in week 12. Additionally, significantly higher spike-specific CD8+ T-cell responses were induced in PLWH than in HCs in week 12. In PLWH, the release of the cytokines interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-α), and IL-22 by peripheral blood mononuclear cells (PBMCs) that were stimulated with spike peptides increased in week 12. In addition, the levels of IL-4 and IL-5 were higher in PLWH than in HCs in week 12. Interestingly, the magnitude of SARS-CoV-2-specific T-cell responses in PLWH was negatively associated with the extent of CD8+ T-cell activation and exhaustion. In addition, positive correlations were observed between the magnitude of spike-specific T-cell responses (determined by measuring IFN-γ release by ELISpot) and the amounts of IL-4, IL-5, IL-2 and IL-17F. Conclusions: Our findings suggested that SARS-CoV-2-specific T-cell responses could be enhanced by the booster dose of inactivated COVID-19 vaccines and further illustrate the importance of additional vaccination for PLWH.