Bartlett-type Correction of Distance Metric Test

We derive a corrected distance metric (DM) test of general restrictions. The correction factor depends on the value of the uncorrected statistic and the new statistic is Bartlett-type. In the setting of covariance structure models, we show using simulations that the quality of the new approximation is good and often remarkably good. Especially at around the 95th percentile, the distribution of the corrected test statistic is strikingly close to the relevant asymptotic distribution. This is true for various sample sizes, distributions, and degrees of freedom of the model. As a by-product we provide an intuition for the well-known observation in labor economic applications that using longer panels results in a reversal of the original inference.Distance Metric, GMM, Asymptotic expansion, Bartlett-type correction

Essays in theoretical and applied econometrics

This thesis investigates three topics in theoretical and applied econometrics: Bartlett-type correction of the Distance Metric (DM) test, a Generalized Method of Moments (GMM) study of the effect of the North American Free Trade Agreement (NAFTA) on Quebec manufacturing industries, and a goodness-of-fit test for copulas. The first topic derives an Edgeworth approximation of the distribution of the DM test statistic and obtains a Bartlett-type correction factor, then it uses examples of covariance structures to illustrate the theoretical results and applies the theoretical results to study the covariance structure of earnings. The second topic calculates Canadian tariff rates over the period 1991-2007 for manufacturing industries, classified using the North American Industry Classification System (NAICS), proposes a simulation-based moment selection procedure to improve the properties of the system GMM estimator, and analyzes the effect of NAFTA on earnings of Quebec manufacturing industries. The third topic proposes a new rank-based goodness-of-fit test for copulas, conducts a power study to show that the new test has reasonable properties, and presents an applicatio

STING activation in TET2-mutated hematopoietic stem/progenitor cells contributes to the increased self-renewal and neoplastic transformation

Somatic loss-of-function mutations of the dioxygenase Ten-eleven translocation-2 (TET2) occur frequently in individuals with clonal hematopoiesis (CH) and acute myeloid leukemia (AML). These common hematopoietic disorders can be recapitulated in mouse models. However, the underlying mechanisms by which the deficiency in TET2 promotes these disorders remain unclear. Here we show that the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway is activated to mediate the effect of TET2 deficiency in dysregulated hematopoiesis in mouse models. DNA damage arising in Tet2-deficient hematopoietic stem/progenitor cells (HSPCs) leads to activation of the cGAS-STING pathway which in turn promotes the enhanced self-renewal and development of CH. Notably, both pharmacological inhibition and genetic deletion of STING suppresses Tet2 mutation-induced aberrant hematopoiesis. In patient-derived xenograft (PDX) models, STING inhibition specifically attenuates the proliferation of leukemia cells from TET2-mutated individuals. These observations suggest that the development of CH associated with TET2 mutations is powered through chronic inflammation dependent on the activated cGAS-STING pathway and that STING may represent a potential target for intervention of relevant hematopoietic diseases

Moniezia benedeni drives CD3+ T cells residence in the sheep intestinal mucosal effector sites

IntroductionT cells are the core of the cellular immunity and play a key role in the regulation of intestinal immune homeostasis. In order to explore the impact Moniezia benedeni (M. benedeni) infection on distributions of CD3+ T cells in the small intestine of the sheep.MethodsIn this study, sheep pET-28a-CD3 recombinant plasmid were constructed and expressed in BL21 receptor cells, then the rabbit anti-sheep CD3 polyclonal antibody was prepared through recombinant protein inducing. The M. benedeni-infected sheep (infection group, n = 6) and healthy sheep (control group, n = 6) were selected, and the distributions of CD3+ T cells in intestinal laminae propria (LP) and mucous epitheliums were observed and analyzed systematically.ResultsThe results showed that the rabbit anti-sheep CD3 polyclonal antibody had good potency and specificity. In the effector area of small intestine, a large number of CD3+ T cells were mainly diffusely distributed in the intestinal LP as well as in the mucous epitheliums, and the densities of intestinal LP from duodenum to jejunum to ileum were 6.01 cells/104 μm2, 7.01 cells/104 μm2 and 6.43 cells/104 μm2, respectively. Their distribution densities in mucous epitheliums were 6.71 cells/104 μm2, 7.93 cells/104 μm2 and 7.21 cells/104 μm2, respectively; in the infected group, the distributions of CD3+ T cells were similar to that of the control group, and the densities in each intestinal segment were all significantly increased (p < 0.05), meanwhile, the total densities of CD3+ T cells in duodenum, jejunum and ileum were increased by 33.43%, 14.50%, and 34.19%. In LP and mucous epitheliums, it was increased by 33.57% and 27.92% in duodenum; by 25.82% and 7.07% in jejunum, and by 27.07% and 19.23% in ileum, respectively.DiscussionIt was suggested that M. benedeni infection did not change the spatial distributions of CD3+ T cells in the small intestine of sheep, but significantly increased their densities, which lays a foundation for further research on the regulatory mechanism of sheep intestinal mucosal immune system against M. benedeni infection

Inferring the diagnostic potential of 18F-FDG-PET/CT in post-renal transplantation from a unique case harboring multiple rare complications

Renal transplantation is undoubtedly an effective treatment for patients with end-stage renal disease, but it is certainly not a cure. Patients require lifelong immunosuppression to maintain optimal allograft function, and post-operative risk complications such as cancer in the transplant recipient cannot be ignored. Besides, infection is a silent complication that follows transplantation. Relatedly, herein, we present a report of a 40-year-old patient who underwent renal transplantation and promptly developed a diffuse large B-cell tumor in the liver and Aspergillus infection in the trachea. In addition, an inflammatory necrotizing granuloma was also observed in the muscles. Of importance, we also described the potential of 18F-FDG-PET/CT, which was instrumental in monitoring and evaluating these relevant post-operative complications in this rare case