Are metabolic factors still important in the era of direct antiviral agents in patients with chronic hepatitis C?

The high rate of sustained viral response(SVR)to boceprevir or telaprevir-based triple therapy in hepatitis C(HCV)-related,non-cirrhotic na ve patients or relapsers to previous antiviral treatment leads clinicians to believe that the impact of metabolic host factors on SVR is minimal when triple therapy is used,unlike what is observed with the peginterferon and ribavirin schedules.This concept is strongly expressed by some opinion leaders on the basis of the data derived from subanalyses of registrative trials as well as from a post-hoc analysis of the phaseⅡC208 clinical trial.The perception of unrestrainable therapeutic success with the use of newer,more powerful antivirals is now reinforced by the brilliant results obtained with sofosbuvir,an HCV NS5B polymerase inhibitor,as well as by the data from the phaseⅡandⅢstudies on the various combinations of second-generation NS3/4A inhibitors and NS5A and/or NS5B inhibitors.However,a great deal of concern has emerged from the real world scenario in which patients are often older and have more comorbidities than patients in the"world of trials".Furthermore,many of them have advanced fibrosis and previous failure with peginterferon and ribavirin treatment.Some data from the recent literature suggest that the host metabolic factors may play a minor but non-negligible role in these difficult-to-treat patients,an issue that will hopefully be investigated in further studies.This editorial aims to provide a detailed analysis of the role that host metabolic factors played in the past and what role they may play in the era of direct antiviral agents.

Effects of environmental factors on corrosion behaviors of metal-fiber porous components in a simulated direct methanol fuel cell environment

Abstract： To enable the use of metallic components in direct methanol fuel cells （DMFCs）, issues related to corrosion resistance must be considered because of an acid environment induced by the solid electrolyte. In this study, we report the electrochemical behaviors of metal-fiber-based porous sintered components in a simulated corrosive environment of DMFCs. Three materials were evaluated： pure copper, AISI304, and AISI316L. The environmental factors and related mechanisms affecting the corrosion behaviors were analyzed. The results demonstrated that AISI316L exhibits the best performance. A higher SO4^2- concentration increases the risk of material corrosion, whereas an increase in methanol concentration inhibits corrosion. The morphological features of the corroded samples were also characterized in this study.

Using transcription factors for direct reprogramming of neurons in vitro

Cell therapy offers great promises in replacing the neurons lost due to neurodegenerative diseases or injuries.However,a key challenge is the cellular source for transplantation which is often limited by donor availability.Direct reprogramming provides an exciting avenue to generate specialized neuron subtypes in vitro,which have the potential to be used for autologous transplantation,as well as generation of patient-specific disease models in the lab for drug discovery and testing gene therapy.Here we present a detailed review on transcription factors that promote direct reprogramming of specific neuronal subtypes with particular focus on glutamatergic,GABAergic,dopaminergic,sensory and retinal neurons.We will discuss the developmental role of master transcriptional regulators and specification factors for neuronal subtypes,and summarize their use in promoting direct reprogramming into different neuronal subtypes.Furthermore,we will discuss up-and-coming technologies that advance the cell reprogramming field,including the use of computational prediction of reprogramming factors,opportunity of cellular reprogramming using small chemicals and microRNA,as well as the exciting potential for applying direct reprogramming in vivo as a novel approach to promote neuro-regeneration within the body.Finally,we will highlight the clinical potential of direct reprogramming and discuss the hurdles that need to be overcome for clinical translation.

Determination of stress intensity factor with direct stress approach using finite element analysis

In this article, a direct stress approach based on finite element analysis to determine the stress intensity factor is improved. Firstly, by comparing the rigorous solution against the asymptotic solution for a problem of an infinite plate embedded a central crack, we found that the stresses in a restrictive interval near the crack tip given by the rigorous solution can be used to determine the stress intensity factor, which is nearly equal to the stress intensity factor given by the asymptotic solution. Secondly, the crack problem is solved numerically by the finite element method. Depending on the modeling capability of the software, we designed an adaptive mesh model to simulate the stress singularity. Thus, the stress result in an appropriate interval near the crack tip is fairly approximated to the rigorous solution of the corresponding crack problem. Therefore, the stress intensity factor may be calculated from the stress distribution in the appropriate interval, with a high accuracy.

Effects on coagulation factor production following primary hepatomitogen-induced direct hyperplasia

AIM： To investigate the molecular mechanisms involved in coagulation factor expression and/or function during direct hyperplasia （DH）-mediated liver regeneration. METHODS： Direct hyperplasia-mediated liver regeneration was induced in female C57BL/6 mice by administering 1,4-bisr2-（3,5-dichloropyridyloxy）] benzene （TCPOBOP）, a representative hepatomitogen. Mice were weighed and sacrificed at various time points [Day 0 （D0： prior to injection）, 3 h, D1, D2, D3, and D10] after TCPOBOP administration to obtain liver and blood samples. Using the RNA samples extracted from the liver, a comprehensive analysis was performed on the hepatic gene expression profiling of coagulation-related factors by real-time RT-PCR （fibrinogen, prothrombin, factors Ⅴ, Ⅶ, Ⅷ, Ⅸ, Ⅹ, Ⅺ, Ⅻ, ⅩⅢβ , plasminogen, antithrombin, protein C, protein S, ADAMTS13, and VWF）. The corresponding plasma levels of coagulation factors （fibrinogen, prothrombin, factors Ⅴ, Ⅶ, Ⅷ, Ⅸ, Ⅹ, Ⅺ, Ⅻ, ⅩⅢ, and VWF） were also analyzed and compared with their mRNA levels. RESULTS： Gavage administration of TCPOBOP （3 mg/kg body weight） resulted in a marked and gradual increase in the weight of the mouse livers relative to the total body weight to 220% by D10 relative to the DO （control） ratios. At the peak of liver regeneration （D1 and D2）, the gene expression levels for most of the coagulationrelated factors （fibrinogen, prothrombin, factors Ⅴ, Ⅶ, Ⅷ, Ⅸ,Ⅺ, Ⅻ, ⅩⅢβ, plasminogen, antithrombin, protein C, ADAMTS13, VWF） were found to be downregulated in a time-dependent manner, and gradually recovered by D10 to the basal levels. Only mRNA levels of factor X and protein S failed to show any decrease during the regenerative phase. As for the plasma levels, 5 clotting factors （prothrombin, factors Ⅷ, Ⅸ, Ⅺ, and Ⅻ） demonstrated a significant decrease （P 〈 0.05） during the regeneration phase compared with DO. Among these 5 factors, factor Ⅸ and factor Ⅺ showed the most dramatic decline in their activities by about 50% at D2 compared to the basal levels, and these reductions in plasma activity for both factors were consistent with our RT-PCR findings. In contrast, the plasma activities of the other coagulation factors （fibrinogen, factors Ⅴ, Ⅶ, ⅩⅢ, and VWF） were not significantly reduced, despite the reduction in the liver mRNA levels. Unlike the other factors, FX showed a temporal increase in its plasma activity, with significant increases （P 〈 0.05） detected at DI. CONCLUSION： Investigating the coagulation cascade protein profiles during liver regeneration by DH may help to better understand the basic biology of the liver under normal and pathological conditions.

Directional induction of dopaminergic neurons from neural stem cells using substantia nigra homogenates and basic fibroblast growth factor

To date, complex components of available reagents have been used for directional induction of neural stem cells into dopaminergic neurons, resulting in a poor ability to repeat experiments. This study sought to investigate whether a homogenate of the substantia nigra of adult rats and/or basic fibroblast growth factor could directionally induce neural stem cells derived from the subventricular zone of embryonic rats to differentiate into dopaminergic neurons. Tyrosine hydroxylase-positive cells were observed exclusively after induction with the homogenate supernatant of the substantia nigra from adult rats and basic fibroblast growth factor for 48 hours in vitro. However, in the groups treated with homogenate supernatant or basic fibroblast growth factor alone, tyrosine hydroxylase expression was not observed. Moreover, the content of dopamine in the culture medium of subventricular zone neurons was significantly increased at 48 hours after induction with the homogenate supernatant of the substantia nigra from adult rats and basic fibroblast growth factor. Experimental findings indicate that the homogenate supernatant of the substantia nigra from adult rats and basic fibroblast growth factor could directionally induce neural stem cells derived from the subventricular zone of embryonic rats to differentiate into dopaminergic neurons in the substantia nigra with the ability to secrete dopamine.

The Security Correction of Large Consumers Long-Term Direct Power Trading Based on DC Power Transfer Distribution Factor

The experiments of large consumers direct power trading is conducting in china nationwide, and it’s important to the reform of electricity market. To compensated efficiencies in security correction of large consumers direct power trading, a novel security correction method based on DC power transfer distribution factor was proposed. Using the presented method to comply security correction, all the transactions that satisfy the specific requirements of maximizing social welfare are able to enter security correction process, and when the power of transmission line is out of limit, this method avoid the transaction which causes this problem is abandoned directly by introducing supplement transactions. The simulation has shown that the proposed security correction method of large consumers direct power trading based on DC power transfer distribution factor is effective.

Investigating the Effect of Weather and Seasonal Factors on Root Stability Using Dynamic Measurements

The dynamic tree stability assessment technique allows trees to be measured efficiently, under realistic weather conditions. In this study, the stability of four trees, including two conifers and two broad-leaved species was assessed in the Botanical Gardens of the University of Sopron, Hungary. The examined trees included Horse chestnut, Japanese zelkova, Douglas fir and Giant sequoia. Each tree was measured in various weather and seasonal conditions. Results show that the seasons affected the stability of broadleaved trees significantly, due to considerable changes in the crown surface area, while this difference was much lower in softwoods. Rainy weather loosens the topsoil, which adversely affects the stability of trees with relatively shallow roots. Lower layers take longer to saturate, and therefore trees with very deep roots are usually unaffected by the looser topsoil, while the increased weight of the top layer compacts the lower layers and improves stability, as evidenced by results measured on Sequoia. Snow accumulation on the branches increases the inertia of the tree, which imposes higher torque on the root collar, decreasing stability. In the meantime, the increased resistance offered by frozen ground stabilizes the tree, which more-or-less counterbalances this effect. A more extensive database of tree stability under different conditions is being built to allow for more comprehensive analysis of various factors, like wind direction, tree health and morphology, shading, etc.

Types of Infertility and Its Risk Factors among Infertile Women: A Prospective Study in Dhaka City

Background: Infertility is a global health issue, and it is a multidimensional problem with social, economic, and cultural influences. Objectives: The study aimed to determine types of infertility and their contributing factors among the respondent infertile women. Methods: This prospective cross-sectional study was conducted among infertile women visiting Sir Salimullah Medical College and Hospital, Dhaka. From January to December 2020, 111 infertile women were included and evaluated for infertility types and their contributing factors. Data were collected by face-to-face interviewing, and data were analyzed statistically. Results: Primary infertility was found among 90 (81%) and secondary infertility among 21 (18.9%). Among the direct risk factors of female infertility, ovulation failure was the majority of the cases, 74 (35.1%), and its mainly observed in primarily infertile women 58 (33.9%). These observations were statistically significant. Conclusions: Infertility should be treated as a public health problem, government and non-government organizations should develop a basic policy to create effective fertility centers.

Factors Associated with Maternal Mortality at Gynecology and Obstetrics Department in Departmental University Hospital Center of Borgou

Introduction: Maternal mortality is a robust indicator of human development. Most of it occurs in developing countries. Objectives: This study aims to determine the factors associated with maternal mortality in Gynecology and Obstetrics Department of Borgou Departmental University Hospital Center (CHUD-B). Study method: Our study took place at Gynecology and Obstetrics Department in Borgou Departmental University Hospital Center. This was a descriptive and analytical case-control study, covering a period of 7 years from January 1, 2012 to December 31, 2018. Results: Two hundred and twelve patients have been recruited consisting of 106 deceased women and 106 controls. The intra-hospital mortality ratio was 1100 deaths per 100,000 live births (LB). The mean age of deceased women was 27.06 ± 6.45 years with the extremes of 15 and 45 years. Direct obstetric causes were the most frequent causes of maternal death. They were dominated by immediate postpartum hemorrhage (32.93%), followed by High Blood Pressure (26.83%) and infections (17.07%). The general condition of patients on admission (p-0.000) and inadequate management (p-0.001) was associated with maternal mortality. Conclusion: Patients’ general condition on admission and inadequate management was factors associated with maternal mortality.

Non-cropping period accounting for over a half of annual nitric oxide releases from cultivated calcareous-soil alpine ecosystems with marginally low emission factors

Nitric oxide(NO)emissions from alpine ecosystems conventionally being long-term cultivated with feed crops are not well quantified.The authors attempted to address this knowledge gap by performing a year-round experimental campaign in the northeastern Tibetan Plateau.Fertilized(F)and unfertilized(UF)treatments were established within a flat calcareous-soil site for the long-term cultivation of feed oats.NO fluxes and five soil variables were simultaneously measured.A single plow tillage accounted for approximately 54%–73%of the NO releases during the cropping period(CP);and the non-cropping period(NCP)contributed to 51%–58%of the annual emissions.The direct NO emissions factor(EFd)was 0.021%±0.021%.Significantly lower Q10 values(p<0.01)occurred in the F treatment during the CP(approximately 3.6)compared to those during the other period or in the other treatment(approximately 4.9?5.1),indicating a fertilizer-induced reduction in the temperature sensitivity.The selected soil variables jointly accounted for up to 72%(p<0.01)of the variance for all the fluxes across both treatments.This finding suggests that temporally and/or spatially distributed fluxes from alpine calcareous-soil ecosystems for feed crop production may be easily predicted if data on these soil variables are available.Further studies are needed to test the hypothesis that the EFd is larger in alpine feed-oat fields than those in this study if the soil moisture content is higher during the period following the basal application of ammoniumor urea-based fertilizer.

A Novel CCA-NMF Whitening Method for Practical Machine Learning Based Underwater Direction of Arrival Estimation

Underwater direction of arrival(DOA)estimation has always been a very challenging theoretical and practical problem.Due to the serious non-stationary,non-linear,and non-Gaussian characteristics,machine learning based DOA estimation methods trained on simulated Gaussian noised array data cannot be directly applied to actual underwater DOA estimation tasks.In order to deal with this problem,environmental data with no target echoes can be employed to analyze the non-Gaussian components.Then,the obtained information about non-Gaussian components can be used to whiten the array data.Based on these considerations,a novel practical sonar array whitening method was proposed.Specifically,based on a weak assumption that the non-Gaussian components in adjacent patches with and without target echoes are almost the same,canonical cor-relation analysis(CCA)and non-negative matrix factorization(NMF)techniques are employed for whitening the array data.With the whitened array data,machine learning based DOA estimation models trained on simulated Gaussian noised datasets can be used to perform underwater DOA estimation tasks.Experimental results illustrated that,using actual underwater datasets for testing with known machine learning based DOA estimation models,accurate and robust DOA estimation performance can be achieved by using the proposed whitening method in different underwater con-ditions.

Hybrid Multi-Infeed Interaction Factor Calculation Method Considering Voltage Regulation Control Characteristics of Voltage Source Converter

Voltage source converter based high voltage direct current(VSC-HVDC)can participate in voltage regulation by flexible control to help maintain the voltage stability of the power grid.In order to quantitatively evaluate its influence on the voltage interaction between VSC-HVDC and line commutated converter based high voltage direct current(LCC-HVDC),this paper proposes a hybrid multi-infeed interaction factor(HMIIF)calculation method considering the voltage regulation control characteristics of VSC-HVDC.Firstly,for a hybrid multi-infeed high voltage direct current system,an additional equivalent operating admittance matrix is constructed to characterize HVDC equipment characteristics under small disturbance.Secondly,based on the characteristic curve between the reactive power and the voltage of a certain VSC-HVDC project,the additional equivalent operating admittance of VSC-HVDC is derived.The additional equivalent operating admittance matrix calculation method is proposed.Thirdly,the equivalent bus impedance matrix is obtained by modifying the alternating current(AC)system admittance matrix with the additional equivalent operating admittance matrix.On this basis,the HMIIF calculation method based on the equivalent bus impedance ratio is proposed.Finally,the effectiveness of the proposed method is verified in a hybrid dual-infeed high voltage direct current system constructed in Power Systems Computer Aided Design(PSCAD),and the influence of voltage regulation control on HMIIF is analyzed.

Potential and Efficiency of Agricultural Pollution Control in China and Its Influential Factors

Agricultural pollution has become the dominant source of water pollution in China and the carbon reduction in agricultural aspect is pressing.Based on list analysis method,the COD,TN and TP in agriculture in 28 provinces in China from 1995 to 2010 were evaluated and compared.By dint of directional distance function,the economics mechanism to reduce carbon emission was discussed.The reduction efficiency and potential of three kinds of pollutants were estimated.The regression indicates that the educational degree,income level and work play a crucial role in carbon emission.

A study on the factor market distortion and the carbon emission scale effect of two-way FDI

Based on the data of 30 Chinese provinces for the period from 2004 to 2015,this paper expounds the carbon emissions effect of two-way foreign direct investment (FDI) from the perspective of scale effect and factor market distortions.This study uses Kaya identity to decompose carbon emission and construct simultaneous equations model to empirically examine the factor market distortion and the carbon emission scale effect of two-way FDI.The results show that the inward foreign direct investment (IFDI) increase regional carbon emission through scale effect and also exacerbates factor market distortion in China,whereas the outward FDI trends reduce carbon emission and reduces factor market distortions in China.The study also shows that human capital,research and development (R&D),trade openness,and capital accumulation are important determinants of two-way FDI.Therefore,the study proposes that IFDI policies should focus on acquiring green technologies.In addition,the domestic enterprises should be encouraged to participate in global business.

Hepatocellular carcinoma after direct-acting antiviral hepatitis C virus therapy:A debate near the end

Direct acting antivirals(DAAs)have revolutionized the treatment of hepatitis C virus(HCV)infection,achieving high rates(≥95%)of sustained virological response,with a good safety profile and high compliance rates.Consequently,it had been expected that viral clearance will reduce morbidity and mortality rates,as well as the risk of hepatocellular carcinoma(HCC).However,since 2016,concerns have been raised over an unexpected high rate of HCC occurrence and recurrence after DAA therapy,which led to an avalanche of studies with contradictory results.We aimed to review the most recent and relevant articles regarding the risk of HCC after DAA treatment and identify the associated risk factors.

Dynamic analysis of spatial convergence of green total factor productivity in China's primary provinces along its Belt and Road Initiative

This paper focuses on China's primary provinces along its Belt and Road Initiative,measures and analyses the provincial green total factor productivity (GTFP) development by GML index based on SBM directional distance function,discusses the temporal evolution characteristics of spatial convergence of the provincial GTFP under multiple spatial weight matrices,and estimates the net effect of China's Belt and Road Initiative on the development gap of provincial GTFP by regression discontinuity.The research shows that the provincial GTFP is generally good while the internal gap is relatively large.There is spatial absolute βconvergence and condition βconvergence in provincial GTFP,and the convergence speed has been signifcantly accelerated since the construction of China's Belt and Road Initiative.The current low economy level and infrastructure allocation efficiency of primary provinces restrict the GTFP development,while government expenditure has promoted the GTFP development,trade between provinces and countries along China's Belt and Road Initiative is negative to GTFP.China's Belt and Road Initiative has significantly narrowed the gap of provincial GTFP development with the net effect of-0.016.

CREEP CRACK PROPAGATION IN CONVENTIONAL CAST AND DIRECTIONALLY SOLIDIFIED SUPERALLOY RENE 80

The creep crack propagation in superalloy René80 of two different microstructures,i.e., equiaxed grain structure by conventional casting and columnar grain by directional solidification,was investigated under static load at 1123 K.The creep crack growth rate, da/dt,seems to be correlated with the stress intensity factor,K.The creep crack growth rate in the directionally solidified alloy is lower than that in the conventional cast alloy,owing to the elimination of transverse grain boundaries.The effect of microstructure on creep crack propagation has also been discussed.

A Straightforward Direct Traction Boundary Integral Method for Two-Dimensional Crack Problems Simulation of Linear Elastic Materials

This paper presents a direct traction boundary integral equation method(DTBIEM)for two-dimensional crack problems of materials.The traction boundary integral equation was collocated on both the external boundary and either side of the crack surfaces.The displacements and tractions were used as unknowns on the external boundary,while the relative crack opening displacement(RCOD)was chosen as unknowns on either side of crack surfaces to keep the single-domain merit.Only one side of the crack surfaces was concerned and needed to be discretized,thus the proposed method resulted in a smaller system of algebraic equations compared with the dual boundary element method(DBEM).A new set of crack-tip shape functions was constructed to represent the strain field singularity exactly,and the SIFs were evaluated by the extrapolation of the RCOD.Numerical examples for both straight and curved cracks are given to validate the accuracy and efficiency of the presented method.

New-Wave Emerging Multinational Companies： The Determinants of Their Outward Foreign Direct Investment

Focusing on the fast growth of BRICS＇ outward foreign direct investment （OFDI） and multinational companies during the crisis has left unheeded that some other emerging economies also grow much faster than average in the global economy and has become significant and fast-growing direct investors abroad. A sample of such （thirteen） new-wave emerging countries （NWECs） is gathered on the criterion of being ranked among the most significant foreign direct investors in the global economy. The literature review exhibits only very few articles existing on such a topic so far. Descriptive statistics enable tracing OFDI by NWECs-based multinational companies back to the 1970s, checking its geographical orientation and industrial structure, and assessing the relative importance of cross-border mergers and acquisitions. Econometric estimation exhibits that direct investment moving off the NWECs is explained by so-called push factors such as the home country＇s GDP, GDP per capita, GDP rate of growth, the share of high-technology exported products in overall export, the number of technological patents registered, and how much inward foreign direct investment discussed in the light of Dunning＇s investment development hypothesis. stock has previously been hosted. These results are path model and Matthews＇ linkage-leverage learning