Estimating fixed-effect panel stochastic frontier models by model transformation

Traditional panel stochastic frontier models do not distinguish between unobserved individual heterogeneity and inefficiency. They thus force all time-invariant individual heterogeneity into the estimated inefficiency. Greene (2005) proposes a true fixed-effect stochastic frontier model which, in theory, may be biased by the incidental parameters problem. The problem usually cannot be dealt with by model transformations owing to the nonlinearity of the stochastic frontier model. In this paper, we propose a class of panel stochastic frontier models which create an exception. We show that first-difference and within-transformation can be analytically performed on this model to remove the fixed individual effects, and thus the estimator is immune to the incidental parameters problem. Consistency of the estimator is obtained by either N→∞ or T→∞, which is an attractive property for empirical researchersStochastic frontier models; Fixed effects; Panel data

Estimating fixed-effect panel stochastic frontier models by model transformation

Traditional panel stochastic frontier models do not distinguish between unobserved individual heterogeneity and inefficiency. They thus force all time-invariant individual heterogeneity into the estimated inefficiency. Greene (2005) proposes a true fixed-effect stochastic frontier model which, in theory, may be biased by the incidental parameters problem. The problem usually cannot be dealt with by model transformations owing to the nonlinearity of the stochastic frontier model. In this paper, we propose a class of panel stochastic frontier models which create an exception. We show that first-difference and within-transformation can be analytically performed on this model to remove the fixed individual effects, and thus the estimator is immune to the incidental parameters problem. Consistency of the estimator is obtained by either N→∞ or T→∞, which is an attractive property for empirical researcher

Estimating fixed-effect panel stochastic frontier models by model transformation

Traditional panel stochastic frontier models do not distinguish between unobserved individual heterogeneity and inefficiency. They thus force all time-invariant individual heterogeneity into the estimated inefficiency. Greene (2005) proposes a true fixed-effect stochastic frontier model which, in theory, may be biased by the incidental parameters problem. The problem usually cannot be dealt with by model transformations owing to the nonlinearity of the stochastic frontier model. In this paper, we propose a class of panel stochastic frontier models which create an exception. We show that first-difference and within-transformation can be analytically performed on this model to remove the fixed individual effects, and thus the estimator is immune to the incidental parameters problem. Consistency of the estimator is obtained by either N→∞ or T→∞, which is an attractive property for empirical researcher

Sialylation of vasorin by ST3Gal1 facilitates TGF-β1-mediated tumor angiogenesis and progression.

ST3Gal1 is a key sialyltransferase which adds α2,3-linked sialic acid to substrates and generates core 1 O-glycan structure. Upregulation of ST3Gal1 has been associated with worse prognosis of breast cancer patients. However, the protein substrates of ST3Gal1 implicated in tumor progression remain elusive. In our study, we demonstrated that ST3GAL1-silencing significantly reduced tumor growth along with a notable decrease in vascularity of MCF7 xenograft tumors. We identified vasorin (VASN) which was shown to bind TGF-β1, as a potential candidate that links ST3Gal1 to angiogenesis. LC-MS/MS analysis of VASN secreted from MCF7, revealed that more than 80% of its O-glycans are sialyl-3T and disialyl-T. ST3GAL1-silencing or desialylation of VASN by neuraminidase enhanced its binding to TGF-β1 by 2- to 3-fold and thereby dampening TGF-β1 signaling and angiogenesis, as indicated by impaired tube formation of HUVECs, suppressed angiogenesis gene expression and reduced activation of Smad2 and Smad3 in HUVEC cells. Examination of 114 fresh primary breast cancer and their adjacent normal tissues showed that the expression levels of ST3Gal1 and TGFB1 were high in tumor part and the expression of two genes was positively correlated. Kaplan Meier survival analysis showed a significantly shorter relapse-free survival for those with lower expression VASN, notably, the combination of low VASN with high ST3GAL1 yielded even higher risk of recurrence (p = 0.025, HR = 2.967, 95% CI = 1.14-7.67). Since TGF-β1 is known to transcriptionally activate ST3Gal1, our findings illustrated a feedback regulatory loop in which TGF-β1 upregulates ST3Gal1 to circumvent the negative impact of VASN

Assembling a cellulase cocktail and a cellodextrin transporter into a yeast host for CBP ethanol production

Background: Many microorganisms possess enzymes that can efficiently degrade lignocellulosic materials, but donot have the capability to produce a large amount of ethanol. Thus, attempts have been made to transform suchenzymes into fermentative microbes to serve as hosts for ethanol production. However, an efficient host for aconsolidated bioprocess (CBP) remains to be found. For this purpose, a synthetic biology technique that cantransform multiple genes into a genome is instrumental. Moreover, a strategy to select cellulases that interactsynergistically is needed.Results: To engineer a yeast for CBP bio-ethanol production, a synthetic biology technique, called “promoter-basedgene assembly and simultaneous overexpression” (PGASO), that can simultaneously transform and express multiplegenes in a kefir yeast, Kluyveromyces marxianus KY3, was recently developed. To formulate an efficient cellulasecocktail, a filter-paper-activity assay for selecting heterologous cellulolytic enzymes was established in this study andused to select five cellulase genes, including two cellobiohydrolases, two endo-β-1,4-glucanases and onebeta-glucosidase genes from different fungi. In addition, a fungal cellodextrin transporter gene was chosen totransport cellodextrin into the cytoplasm. These six genes plus a selection marker gene were one-step assembledinto the KY3 genome using PGASO. Our experimental data showed that the recombinant strain KR7 could expressthe five heterologous cellulase genes and that KR7 could convert crystalline cellulose into ethanol.Conclusion: Seven heterologous genes, including five cellulases, a cellodextrin transporter and a selection marker,were simultaneously transformed into the KY3 genome to derive a new strain, KR7, which could directly convertcellulose to ethanol. The present study demonstrates the potential of our strategy of combining a cocktailformulation protocol and a synthetic biology technique to develop a designer yeast host

Introduction of a strong temperature-sensitive phenotype into enterovirus 71 by altering an amino acid of virus 3D polymerase

AbstractIn 1998, an enterovirus 71 (EV71) epidemic in Taiwan resulted in 78 deaths; however, the molecular basis of EV71 pathogenicity remains poorly understood. Comparison of the deduced amino acid sequences in 3D polymerases of EV71clinical isolates showed the T251V or T251I substitution from 1986 and 1998 outbreaks. An EV71 replicon system showed that introducing an I251T mutation did not affect luciferase activities at 35 °C when compared with wild type; however, lower luciferase activities were observed when they were incubated at 39.5 °C. In addition, the I251T mutation in the EV71 infectious clone not only reduced viral replication at 39.5 °C in vitro but also decreased the virulence of the mouse adaptive strain MP4 in neonatal mice in an i.p. infection model. Therefore, these results suggested that the threonine at position 251 results in a temperature sensitivity phenotype of EV71 which may contribute to the attenuation of circulating strains

Switch activation of PI-PLC downstream signals in activated macrophages with wortmannin

AbstractPhosphatidylinositol (4,5)-bisphosphate (PtdIns(4,5)P2) has been known to serve as a substrate for phosphatidylinositol 3-kinase (PI3K) and phosphoinositide-specific phospholipase C (PI-PLC), which can produce PtdIns(3,4,5)P3 and inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) and diacylglycerol (DAG), respectively. In this study, we elucidated the role of PI-PLC during the LPS-activated mouse macrophages RAW264.7 treated with PI3K inhibitor wortmannin. First, wortmannin treatment enhanced Ins(1,4,5)P3 production and iNOS expression in LPS-activated macrophages. Inhibition of PI3K by p85 siRNA also showed an enhancement of iNOS expression. On the other hand, overexpression of PI3K by ras-p110 expression plasmid significantly decreased iNOS expression in LPS-activated macrophages. In addition, overexpression of wild-type or dominant-negative Akt expression plasmid did not affect the iNOS expression in LPS-activated macrophages. Second, treatment of PI-PLC inhibitor U73122 reversed the enhancement of iNOS expression, the increase of phosphorylation level of ERK, JNK and p38, and the increase of AP-1-dependent gene expression in wortmannin-treated and LPS-activated macrophages. However, NF-κB activity determined by EMSA assay and reporter plasmid assay did not change during LPS-activated macrophages with or without wortmannin. We propose that the inhibition of PI3K by wortmannin in mouse macrophages enhances the PI-PLC downstream signals, and subsequently increases the LPS induction of iNOS expression independently of Akt pathway