Inconsistency of Classical Penalized Likelihood Approaches under Endogeneity

With the high speed development of information technology, contemporary data from a variety of fields becomes extremely large. The number of features in many datasets is well above the sample size and is called high dimensional data. In statistics, variable selection approaches are required to extract the efficacious information from high dimensional data. The most popular approach is to add a penalty function coupled with a tuning parameter to the log likelihood function, which is called penalized likelihood method. However, almost all of penalized likelihood approaches only consider noise accumulation and supurious correlation whereas ignoring the endogeneity which also appeared frequently in high dimensional space. In this paper, we explore the cause of endogeneity and its influence on penalized likelihood approaches. Simulations based on five classical pe-nalized approaches are provided to vindicate their inconsistency under endogeneity. The results show that the positive selection rate of all five approaches increased gradually but the false selection rate does not consistently decrease when endogenous variables exist, that is, they do not satisfy the selection consistency.

The effect of online reviews on addressing endogeneity in discrete choice models

This paper investigates the effectiveness of online reviews on addressing price endogeneity issue in an application to consumer demand for smartphone.We consider review variables as the substitutes of unobserved product quality in terms of a scalar variable as seen in previous methods.An aspect-based sentiment classification technique is designed to construct feature-related review variables from millions of review contents.We discuss the performance of review variables both in a hedonic pricing model and a conditional logit discrete choice model.Our results demonstrate that review variables show a good performance either as instruments for price or as explicit control variables in demand models.In detail,the pricing prediction accuracy increases 3.4%,which is considered as a significant improvement in the practice of forecasting.In the discrete choice model,the estimated price coefficient is biased in the positive direction without endogeneity correction.It is adjusted in the expected way after including review variables.The findings indicate that online reviews provide alternative sources of information in dealing with endogeneity in discrete choice models.We also analyze the differences in the preferences and needs of individual consumers to provide some practical implications of marketing.

Endogeneity of WTO in the gravity model： China and ASEAN

This paper studies the endogeneity of WTO dummy variable in the gravity model about the trade in the region of China and ASEAN. We first present a two-stage test approach for the endogeneity of WTO dummy, then transform the endogeneity problem to a simultaneous system about WTO and trade, and construct an MLE estimation approach to the simultaneous model. The estimate of the coefficient of WTO dummy is positive, as opposed to the negative sign in the exogeneity case. From the estimation of the endogenous model, WTO has creation fold effect and strong trade diversion effect on export model in the region.

Exploring influential factors and endogeneity of traffic flow of different lanes on urban freeways using Bayesian multivariate spatial models

The traffic flow pertinent modelling is essential for distinct strategy formulations.However,the present literature illustrated some needed improvements for such models,especially those related to lane-specific flow.Given such context,this study aims to bridge the research gap by generating regression models to investigate influential factors for traffic flow based on the data collected from one multilane freeway.With the Full Bayesian specification,the hierarchical models were built by accounting for three types of random effects:the structured and unstructured spatial effects,and the one addressing the multivariate heterogeneity across multiple lanes.The endogenous relationship of traffic flow of adjacent lanes was also explored by utilizing the capability of multivariate correlation structure for simultaneous estimation of lane flow.The model estimates revealed the presence of endogeneity with statistical significance for the flow of neighbouring lanes for both directions of travel.The impact of flow was not only limited to the adjacent lanes but also to non-adjacent lanes.The multivariate specification also confirmed interdependency for lane flows.Compared to conventional approaches,the more accurate model estimation in the study indicates the advantage of incorporating the various correlation structures in the models.

Exploration of the contributing factors to the walking and biking travel frequency using multi-level joint models with endogeneity

The enormous advantages of active transportation lead the transportation research focus towards enhancing the walking and biking trips.The present study explored the influential factors to the walking and biking travel frequency based on data obtained from the National Household Travel Survey California add-on survey.The study features some highlights.First,bivariate models were used to account for the common unobserved heterogeneity shared at both household and personal levels.Second,endogeneity was explicitly considered.Third,both variable importance ranking and correlation analysis are employed to determine the different features to be fed into each of the joint models.The results illustrated that the models developed with endogeneity performed better than the models without endogeneity.Four influential variables which includes mode to work by bicycle,public transit usage,count of household members,and multiple race responses,tend to have statistically significant impacts on walking and biking trips.

Variable Selection for Structural Equation with Endogeneity

This paper studies variable selection problem in structural equation of a two-stage least squares （2SLS） model in presence of endogeneity which is commonly encountered in empirical economic studies. Model uncertainty and variable selection in the structural equation is an important issue as described in Andrews and Lu （2001） and Caner （2009）. The authors propose an adaptive Lasso 2SLS estimator for linear structural equation with endogeneity and show that it enjoys the oracle properties, i.e., the consistency in both estimation and model selection. In Monte Carlo simulations, the authors demonstrate that the proposed estimator has smaller bias and MSE compared with the bridge-type GMM estimator （Caner, 2009）. In a case study, the authors revisit the classic returns to education problem （Angrist and Krueger, 1991） using the China Population census data. The authors find that the education level not only has strong effects on income but also shows heterogeneity in different age cohorts.

Human endogenous retrovirus type-W and multiple sclerosis–related smoldering neuroinflammation

Introduction to human endogenous retrovirus type-W(HERV-W): Genomic inheritance from the past includes retroviral sequences that have been stably incorporated into our genomes and account for up to 8% of human DNA.

Exosomes originating from neural stem cells undergoing necroptosis participate in cellular communication by inducing TSC2 upregulation of recipient cells following spinal cord injury

We previously demonstrated that inhibiting neural stem cells necroptosis enhances functional recovery after spinal cord injury.While exosomes are recognized as playing a pivotal role in neural stem cells exocrine function,their precise function in spinal cord injury remains unclear.To investigate the role of exosomes generated following neural stem cells necroptosis after spinal cord injury,we conducted singlecell RNA sequencing and validated that neural stem cells originate from ependymal cells and undergo necroptosis in response to spinal cord injury.Subsequently,we established an in vitro necroptosis model using neural stem cells isolated from embryonic mice aged 16-17 days and extracted exosomes.The results showed that necroptosis did not significantly impact the fundamental characteristics or number of exosomes.Transcriptome sequencing of exosomes in necroptosis group identified 108 differentially expressed messenger RNAs,104 long non-coding RNAs,720 circular RNAs,and 14 microRNAs compared with the control group.Construction of a competing endogenous RNA network identified the following hub genes:tuberous sclerosis 2(Tsc2),solute carrier family 16 member 3(Slc16a3),and forkhead box protein P1(Foxp1).Notably,a significant elevation in TSC2 expression was observed in spinal cord tissues following spinal cord injury.TSC2-positive cells were localized around SRY-box transcription factor 2-positive cells within the injury zone.Furthermore,in vitro analysis revealed increased TSC2 expression in exosomal receptor cells compared with other cells.Further assessment of cellular communication following spinal cord injury showed that Tsc2 was involved in ependymal cellular communication at 1 and 3 days post-injury through the epidermal growth factor and midkine signaling pathways.In addition,Slc16a3 participated in cellular communication in ependymal cells at 7 days post-injury via the vascular endothelial growth factor and macrophage migration inhibitory factor signaling pathways.Collectively,these findings confirm that exosomes derived from neural stem cells undergoing necroptosis play an important role in cellular communication after spinal cord injury and induce TSC2 upregulation in recipient cells.

A New Regime Switching Model with State-Varying Endogeneity

In this paper,we propose a state-varying endogenous regime switching model(the SERS model),which includes the endogenous regime switching model by Chang et al.,the CCP model,as a special case.To estimate the unknown parameters in the SERS model,we propose a maximum likelihood estimation method.Monte Carlo simulation results show that in the absence of state-varying endogeneity,the SERS model and the CCP model perform similarly,while in the presence of state-varying endogeneity,the SERS model performs much better than the CCP model.Finally,we use the SERS model to analyze Chinese stock market returns,and our empirical results show that there exists strongly state-varying endogeneity in volatility switching for the Shanghai Composite Index returns.Moreover,the SERS model can indeed produce a much more realistic assessment for the regime switching process than the one obtained by the CCP model.

Activation of adult endogenous neurogenesis by a hyaluronic acid collagen gel containing basic fibroblast growth factor promotes remodeling and functional recovery of the injured cerebral cortex

The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.

Activation of endogenous neurogenesis and angiogenesis by basic fibroblast growth factor-chitosan gel in an adult rat model of ischemic stroke

Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still unknown.In this study,we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in rats.The gel slowly released basic fibroblast growth factor,which improved the local microenvironment,activated endogenous neural stem/progenitor cells,and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons,while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional recovery.This study revealed the mechanism by which bioactive materials repair ischemic strokes,thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.

Strain-dependent alpha-synuclein spreading in Parkinson's disease and multiple system atrophy

Parkinson's disease(PD) and atypical Parkinsonian syndromes,such as multiple system atrophy(MSA) and Dementia with Lewy bodies,are neurodegenerative movement disorders characterized by the accumulation of alphasynuclein(a-syn) aggregates.These a-syn aggregates propagate throughout the brain in a prion-like manner,where pathological a-syn recruits endogenous a-syn to form insoluble aggregates.Oligomeric forms representing intermediates on the way to insoluble aggregates result in the most pronounced neurotoxic effects.

Transcriptomic and bioinformatics analysis of the mechanism by which erythropoietin promotes recovery from traumatic brain injury in mice

Recent studies have found that erythropoietin promotes the recovery of neurological function after traumatic brain injury.However,the precise mechanism of action remains unclea r.In this study,we induced moderate traumatic brain injury in mice by intrape ritoneal injection of erythro poietin for 3 consecutive days.RNA sequencing detected a total of 4065 differentially expressed RNAs,including 1059 mRNAs,92 microRNAs,799 long non-coding RNAs,and 2115circular RNAs.Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses revealed that the coding and non-coding RNAs that were differentially expressed after traumatic brain injury and treatment with erythropoietin play roles in the axon guidance pathway,Wnt pathway,and MAPK pathway.Constructing competing endogenous RNA networks showed that regulatory relationship between the differentially expressed non-coding RNAs and mRNAs.Because the axon guidance pathway was repeatedly enriched,the expression of Wnt5a and Ephb6,key factors in the axonal guidance pathway,was assessed.Ephb6 expression decreased and Wnt5a expression increased after traumatic brain injury,and these effects were reversed by treatment with erythro poietin.These findings suggest that erythro poietin can promote recove ry of nerve function after traumatic brain injury through the axon guidance pathway.

RPLP0/TBP are the most stable reference genes for human dental pulp stem cells under osteogenic differentiation

BACKGROUND Validation of the reference gene(RG)stability during experimental analyses is essential for correct quantitative real-time polymerase chain reaction(RT-qPCR)data normalisation.Commonly,in an unreliable way,several studies use genes involved in essential cellular functions[glyceraldehyde-3-phosphate dehydro-genase(GAPDH),18S rRNA,andβ-actin]without paying attention to whether they are suitable for such experimental conditions or the reason for choosing such genes.Furthermore,such studies use only one gene when Minimum Information for Publication of Quantitative Real-Time PCR Experiments guidelines recom-mend two or more genes.It impacts the credibility of these studies and causes dis-tortions in the gene expression findings.For tissue engineering,the accuracy of gene expression drives the best experimental or therapeutical approaches.We cultivated DPSCs under two conditions:Undifferentiated and osteogenic dif-ferentiation,both for 35 d.We evaluated the gene expression of 10 candidates for RGs[ribosomal protein,large,P0(RPLP0),TATA-binding protein(TBP),GAPDH,actin beta(ACTB),tubulin(TUB),aminolevulinic acid synthase 1(ALAS1),tyro-sine 3-monooxygenase/tryptophan 5-monooxygenase activation protein,zeta(YWHAZ),eukaryotic translational elongation factor 1 alpha(EF1a),succinate dehydrogenase complex,subunit A,flavoprotein(SDHA),and beta-2-micro-globulin(B2M)]every 7 d(1,7,14,21,28,and 35 d)by RT-qPCR.The data were analysed by the four main algorithms,ΔCt method,geNorm,NormFinder,and BestKeeper and ranked by the RefFinder method.We subdivided the samples into eight subgroups.RESULTS All of the data sets from clonogenic and osteogenic samples were analysed using the RefFinder algorithm.The final ranking showed RPLP0/TBP as the two most stable RGs and TUB/B2M as the two least stable RGs.Either theΔCt method or NormFinder analysis showed TBP/RPLP0 as the two most stable genes.However,geNorm analysis showed RPLP0/EF1αin the first place.These algorithms’two least stable RGs were B2M/GAPDH.For BestKeeper,ALAS1 was ranked as the most stable RG,and SDHA as the least stable RG.The pair RPLP0/TBP was detected in most subgroups as the most stable RGs,following the RefFinfer ranking.CONCLUSION For the first time,we show that RPLP0/TBP are the most stable RGs,whereas TUB/B2M are unstable RGs for long-term osteogenic differentiation of human DPSCs in traditional monolayers.

Stromal thrombospondin 1 suppresses angiogenesis in oral submucous fibrosis

A decline in mucosal vascularity is a histological hallmark of oral submucous fibrosis (OSF), a premalignant disease that is largely induced by betel quid chewing. However, the lack of available models has challenged studies of angiogenesis in OSF. Here, we found that the expression of thrombospondin 1 (THBS1), an endogenous angiostatic protein, was elevated in the stroma of tissues with OSF. Using a fibroblast-attached organoid (FAO) model, the overexpression of THBS1 in OSF was stably recapitulated in vitro. In the FAO model,treatment with arecoline, a major pathogenic component in areca nuts, enhanced the secretion of transforming growth factor (TGF)-β1 by epithelial cells, which then promoted the expression of THBS1 in fibroblasts. Furthermore, human umbilical vein endothelial cells (HUVECs)were incorporated into the FAO to mimic the vascularized component. Overexpression of THBS1 in fibroblasts drastically suppressed the sprouting ability of endothelial cells in vascularized FAOs (v FAOs). Consistently, treatment with arecoline reduced the expression of CD31in v FAOs, and this effect was attenuated when the endothelial cells were preincubated with neutralizing antibody of CD36, a receptor of THBS1. Finally, in an arecoline-induced rat OSF model, THBS1 inhibition alleviated collagen deposition and the decline in vascularity in vivo. Overall, we exploited an assembled organoid model to study OSF pathogenesis and provide a rationale for targeting THBS1.

Transcriptomic and metabolomic analysis of changes in grain weight potential induced by water stress in wheat

The sink strength of developing ovaries in wheat determines the grain weight potential.The period from booting to the grain setting stage is critical for ovary growth and development and potential sink capacity determination.However,the underlying regulatory mechanism during this period by which the wheat plant balances and coordinates the floret number and ovary/grain weight under water stress has not been clarified.Therefore,we designed two irrigation treatments of W0(no seasonal irrigation)and W1(additional 75 mm of irrigation at the jointing stage)and analyzed the responses of the ovary/grain weight to water stress at the phenotypic,metabolomic,and transcriptomic levels.The results showed that the W0 irrigation treatment reduced the soil water content,plant height,and green area of the flag leaf,thus reducing grain number,especially for the inferior grains.However,it improved the grain weight of the superior and inferior grains as well as average grain weight at maturity,while the average ovary/grain weight and volume during–3 to 10 days after anthesis(DAA)also increased.Transcriptomic analysis indicated that the genes involved in both sucrose metabolism and phytohormone signal transduction were prominently accelerated by the W0 treatment,accompanied by greater enzymatic activities of soluble acid invertase(SAI)and sucrose synthase(Sus)and elevated abscisic acid(ABA)and indole-3-acetic acid(IAA)levels.Thus,the sucrose content decreased,while the glucose and fructose contents increased.In addition,several TaTPP genes(especially TaTPP-6)were down-regulated and the IAA biosynthesis genes TaTAR1 and TaTAR2 were up-regulated under the W0 treatment before anthesis,which further increased the IAA level.Collectively,water stress reduced the growth of vegetative organs and eliminated most of the inferior grains,but increased the ABA and IAA levels of the surviving ovaries/grains,promoting the enzymatic activity of Sus and degrading sucrose into glucose and fructose.As a result,the strong sucrose utilization ability,the enhanced enzymatic activity of SAI and the ABA-and IAA-mediated signaling jointly increased the weight and volume of the surviving ovaries/grains,and ultimately achieved the tradeoff between ovary/grain weight and number in wheat under water stress.

Elucidation of potential relationship between endogenous proteases and key flavor substances in dry-cured pork coppa

Dry-cured meat products are considerably popular around the world due to unique flavor.Proteolysis is one of the enzymatic reactions from which flavor substances are derived,which is affected by endogenous proteases.The purpose aimed to reveal the potential relationship between endogenous proteases and key flavor substances in dry-cured pork coppa in this paper.The dynamic changes of endogenous proteases activity,free amino acids,and volatiles during dry-cured pork coppa processing were characterized.The results showed that 5 kinds of free amino acids,Glu,Lys,Val,Ala,and Leu,were identified as significant contributors to taste.Meanwhile,key volatiles,such as hexanal,nonanal,octanal,benzaldehyde,3-methyl butanoic acid,2-methyl propanoic acid,and ethyl octanoate,greatly contributed to the flavor characteristics of dry-cured pork coppa.Further partial correlation analysis was performed to better elucidate the relationship among parameters.The results revealed that close relationship between endogenous proteases and key substances.RAP not only significantly affected the accumulation of key active-amino acids,but also affected the accumulation of ethyl octanoate,2,3-pentanedione,and 2,3-octanedione by regulating the accumulation of octanoic acid and Leu.In addition,cathepsin B and D,DPP II,DPP IV and RAP notably affected accumulation of hexanal.

One-time application of controlled-release bulk blending fertilizer enhances yield,quality and photosynthetic efficiency in late japonica rice

Controlled-release urea(CRU)releases nitrogen(N)at the same pace that rice takes it up,which can effectively improve N use efficiency,increase rice yield and improve rice quality.However,few studies have described the effects of CRU application on the photosynthetic rate and endogenous enzyme activities of rice.Accordingly,a twoyear field trial was conducted with a total of seven treatments:CK,no N fertilizer;BBF,regular blended fertilizer;RBBF,20%N-reduced regular blended fertilizer;CRF1,70%CRU+30%regular urea one-time base application;CRF2,60%CRU+40%regular urea one-time base application;RCRF1,CRF1 treatment with 20%N reduction;and RCRF2,CRF2 treatment with 20%N reduction.Each treatment was conducted in triplicate.The results showed that the N recovery efficiency(NRE)of the controlled-release bulk blending fertilizer(CRBBF)treatments was significantly greater over the two years.There were significant yield increases of 4.1–5.9%under the CRF1treatment and 5.6–7.6%under the CRF2 treatment compared to the BBF treatment,but the differences between the reduced-N treatments RBBF and RCRF2 were not significant.Photosynthetic rates under the CRF1 and CRF2treatments were significantly higher than under the other treatments,and they had significantly greater RuBPCase,RuBisCO,glutamate synthase(GOGAT)and glutamine synthetase(GS)enzyme activities.Additionally,the soil NH_(4)^(+)-N and NO_(3)^(–)-N contents under the CRBBF treatments were significantly higher at the late growth stage of rice,which was more in-line with the fertilizer requirements of rice throughout the reproductive period.CRBBF also led to some improvement in rice quality.Compared with the BBF and RBBF treatments,the protein contents under the CRBBF treatments were reduced but the milling,appearance,eating and cooking qualities of the rice were improved.These results showed that the application of CRBBF can improve the NRE,photosynthetic rate and endogenous enzyme activities of rice,ensuring sufficient N nutrition and photosynthetic material production during rice growth and thereby achieving improved rice yield and quality.

Are dogs not susceptible to retroviral infections?

Retroviruses have been proven to cause infections and diseases in a series of mammalian hosts but not in dogs.Then,this letter discussed the dog susceptibility to retrovirus infection,encompassing arguments to understand why dogs may have not been infected by retroviruses thus far.The potential resistance of retrovirus in dogs enables this provocative short communication to discuss this question,looking at some evolutive aspects.The lineage of canids has shown,throughout its evolutionary history,a smaller accumulation of retroviruses in canid genomes,classifed as endogenous retroviruses.In this context,the genomes of canids seem to ofer obstacles,which have been evolutionarily conserved,in the face of retroviral infection.

A chemical odyssey:Exploring renal stone diversity by age and sex in Punjab,Pakistan

Dear Editor,Renal calculosis is one of the most common urological disorders worldwide,with a prevalence ranging from 1%to 13%across different regions[1].Renal stones are crystal concretions that form on the inner surface of the kidney,resulting from disruptions in the metabolism,the excretion of stone constituents,or the formation of Randall's plaques and plugs.These stones are a result of various endogenous factors.