Employment Flows with Endogenous Financing Constraints

Empirical studies document that resource reallocation across production units plays an important role in accounting for aggregate productivity growth in the U.S. manufacturing. Distortions in financial market could hinder the reallocation process and hencemay adversely affect aggregate productivity growth. This paper studies the quantitative impact of costly external finance on aggregate productivity through resource reallocation across firms with idiosyncratic productivity shocks. A partial equilibrium model calibrated to the U.S. manufacturing data shows that costly external finance causes inefficient output reallocation from high productivity firms to low productivity firms and as a result leads to a 1 percent loss in aggregate TFP.Costly external Finance; Reallocation; Output weighted aggregate productivity

Costly External Finance, Reallocation, and Aggregate Productivity

This paper develops an industry evolution model to explore the quantitative implications of endogenous financing constraints for job reallocation. In the model firms finance entry costs and per period labor costs with long-term financial contracts signed with banks, which are subject to asymmetric information and limited commitment problems. Financing constraints arise as a feature of the optimal contract. The model generates endogenous firm exit and job reallocation in a stationary industry equilibrium. A quantitative analysis shows that endogenous financing constraints can account for a substantial amount of job reallocation observed in U.S. manufacturing and the observed negative relationship between job reallocation rates and firm size as measured by employment.Asymmetric information; Limited liability; Limited commitment; Dynamiccontract; Job reallocation; Stationary competitive equilibrium; Stationary firm distribution.

The Composition of Government Expenditure in an Overlapping Generations Model

This paper examines the choice of government expenditure on public goods and transfer payments (in the form of pension) in an overlapping generations model, in which individuals live for two ‘periods’ and expenditure is financed on a pay-as-you-go (PAYG) basis. The condition required for majority support of the social contract involved in the PAYG scheme is established and shown to be independent of tax rates and expenditure levels. The choice of expenditure composition can thus be made conditional on acceptance of the social contract. Two decision mechanisms regarding the choice of government expenditure are considered. The first is positive and involves majority voting and the second is normative and involves maximizing a social welfare function. In each case the ratio of the transfer payment to public goods expenditure depends, among other things, on the ratio of median to mean income. A reduction in the skewness of the income distribution is associated with a reduction in this ratio, at a decreasing rate.Overlapping Generations Equilibrium Growth Median Voter Optimal Expenditure Public Goods Pensions

The role of market orientation in developing and sustaining market relationships: an empirical study in Taiwan.

Significant work has taken place in the development of our understanding of business dyadic relationships but much work remains to be done in determining the antecedents, particularly our understanding of cultural contexts. This research aims to add to the debate about what counts in developing a long-term orientation in channel relationships by investigating the role of the concept of market orientation; it explores the possible interface existing between the marketing concept and development of channel relationships. The context is relationships between distributors and suppliers in Taiwan. This study examines the relationship literature from a social exchange theoretical perspective and conducts multiple-case in-depth interviews at the dyadic ends to develop an integrated research model for analysing potential effects of market orientation on the relationship factors influencing long-term oriented relationship building. Quantitative mixed-mode questionnaire surveys were undertaken to test the research model and hypotheses drawn from the model. Data were collected from 158 distributors from four selected business sectors, including both commodity and noncommodity ones. The results confirm the applicability of the marketing concept to an eastern country: Taiwan, and provide empirical evidence that adoption of the marketing concept can be a strategy for stimulating and sustaining long-term oriented channel relationships while mediated by a number of relationship constructs. Communication and shared value are highlighted as the primary mediators while satisfaction signals an inclination to continue a relationship. Market orientation is found to exert significant direct effects on communication and shared value and indirect effects on the other relationship components: trust, cooperation, commitment, conflict and satisfaction, which all contribute to a continuing relationship

Maternal metabolic health and neurodevelopmental conditions in offspring

Background Observational studies published in the last decade have indicated relationships between maternal “overnutrition” states and offspring neurodevelopmental conditions (NDCs), such as autism, attention deficit/hyperactivity disorder (ADHD), and intellectual disability (ID). “Maternal overnutrition” states have been characterized by a series of metabolic conditions before pregnancy (i.e., overweight/obesity, Type I [T1DM] and II [T2DM] diabetes) and during pregnancy (i.e., gestational diabetes mellitus [GDM] and excessive gestational weight gain [GWG]). NDCs often co-occur and have multifactorial etiologies, shaped by both genetic and environmental factors. However, previous studies have not thoroughly considered these complex etiologies when examining associations. For instance, they did not explore whether the relationships between maternal diabetes and offspring NDCs could differ based on the cooccurrence of NDCs or be influenced by genetic predispositions. Moreover, as the fetal brain evolves dramatically and sequentially during pregnancy, it accentuates the need for epidemiological studies to account for the timing and intensity of perturbations during this period. Prior research hasn’t determined whether relationships between maternal conditions such as excessive GWG or hyperglycemia and offspring NDCs could differ based on the GWG rate and glucose concentrations at different pregnancy phases. Maternal overweight/obesity and diabetes might be associated with offspring NDCs due to complications encountered during pregnancy, childbirth, and the neonatal period. Research has suggested that these complications lie at the intersection of, and relate to, maternal metabolic conditions and offspring NDCs. Grasping the mediation of these complications can offer deeper insights into preventative measures during these stages; however, no studies have yet quantified these complications’ mediating impact on the associations. Lastly, the causal influence of BMI, including maternal BMI, on offspring autism and ADHD has seldom been thoroughly explored. In the absence of compelling evidence, the question remains as to whether better weight management among obese women before conception could help reduce the potential risks of offspring NDCs. Methods We used two databases, “Psychiatry Sweden (PS), 1987-2016” and “Developmental Origins of Health And Disease (DOHAD), 1997-2021”, which are register linkages across Swedish nationwide registers using the unique identification number assigned to each Swedish resident. Offspring were linked to their biological mothers, fathers, and maternal grandparents using the Total Population Register (Study I, IV, V). We also used a series of maternal weight and capillary glucose records across pregnancy from the Stockholm Obstetrix system, an electronic medical journal of antenatal care, which was nested within the “Stockholm Youth Cohort (SYC)”. The SYC is a part of PS that also includes regional health and administrative registers (Study II, III). In Studies I, IV, and V, we used the National Patient Register to identify offspring NDCs (i.e., autism, ADHD, and ID), which was supplemented by regional register information in Studies II and III as well as the National Prescribed Drug Register (for ADHD). Finally, we utilized genetic data and information from mothers and children in the “Avon Longitudinal Study of Parents and Children (ALSPAC)” cohort (Study V). In Study I, we utilized a generalized estimating equation (GEE)/population average model with a logit link. This model was clustered based on pseudonymized maternal identification numbers and employed robust standard errors for the computation of odds ratios (ORs) and 95% confidence intervals (CIs) regarding neurodevelopmental conditions (NDCs) in offspring. In Study II, we used Cox regression models, again clustered on maternal numbers and with robust standard errors, to determine hazard ratios (HRs) and 95% CIs for offspring NDCs. In Study III, we employed group-based trajectory modeling (GBTM) to ascertain the varying patterns of glucose alteration throughout pregnancy. GEE models were utilized to evaluate the associations with both obstetric and neonatal outcomes and offspring NDCs. In Study IV, we used a parametric regression approach within a counterfactual framework to conduct both single and multiple mediation analyses. This study aimed to quantify the total effect (TE), natural indirect effects (NIE), and natural direct effects (NDE) in the associations of maternal diabetes (both pregestational diabetes mellitus [PGDM] and GDM) and overweight/obesity with NDCs through individual components of mediators. We employed a paternal negative control comparison analysis in Study I to examine if the associations of maternal T1DM and T2DM with offspring NDCs could be confounded by genetic predispositions to diabetes and NDCs. In Study V, we applied a “triangulation” approach. Analyses were performed using maternal cousin and full sibling comparisons to address unobserved, shared genetic and environmental factors in the associations between maternal BMI and offspring autism and ADHD. In addition, we explored the genetic correlation through Linkage Disequilibrium Score Regression (LDSC). Moreover, we examined the association between the genetic predisposition to both maternal and children’s BMI and various traits of children’s autism and ADHD using Polygenic Risk Score (PRS) analysis. Lastly, we employed a two-sample Mendelian randomization analysis (MR) in Study V to evaluate the causal impacts of BMI on NDCs, including autism and ADHD. Results Maternal T1DM, T2DM, and GDM were all associated with offspring autism, ADHD, and ID, with greater risks linked to comorbid diagnoses involving ID. Stronger associations with GDM were observed when diagnosed between 27-30 wkGA. Paternal T1DM and T2DM were also associated with offspring NDCs, though the strength of these associations was less than those observed with maternal diabetes (Study I). Lower rates of GWG in the second trimester and higher rates of GWG in the third trimester were associated with increased risks for offspring NDCs (Study II). Among those without PGDM, persistently high glucose levels throughout pregnancy demonstrated the strongest association with adverse obstetric/neonatal complications. Transient hyperglycemic states followed by periods of potential glycemic control were also associated with these complications but to a lesser extent. Notably, subclinical states of hyperglycemia, which were less likely to receive a GDM diagnosis, remained associated with these complications, albeit to a lesser degree. A similar pattern of associations was observed for offspring NDCs. Persistently high glucose levels showed stronger associations with offspring NDCs (i.e., ADHD only), while weaker associations were identified with transient hyperglycemic states followed by improved glucose control. Notably, we found that hyperglycemia in early pregnancy, but not in mid-pregnancy, was associated with offspring NDCs when followed by improved glucose control. However, none of these associations regarding NDC outcomes survived the false discovery rate correction using the Benjamini- Hochberg approach (Study III). The joint mediating effects of all obstetric and neonatal complications were more pronounced in the associations between PGDM and offspring NDCs (accounting for 30-50% of the association) than in those concerning maternal GDM and overweight/obesity. Although the mediating effects of obstetric and neonatal complications were generally insignificant for GDM and minor for maternal overweight/obesity, we observed direct associations between GDM (10-30% increased risks compared to non-diabetes) and maternal overweight/obesity (30-60% increased risks compared to normal weight) with the risks of offspring NDCs. However, these associations might still contain residual confounding due to unobserved factors. The combined mediating effects of these complications, especially those emerging during the neonatal period, were particularly strong in the relationship between maternal PGDM and offspring NDCs. For individual mediators, the effects were generally minimal, except for complications such as pregnancy hypertensive diseases, preterm birth, neonatal asphyxia, and hematological comorbidities in the association between PGDM and offspring NDCs (with proportions mediated exceeding 10%) (Study IV). Maternal obesity was linked to increased risks of autism and ADHD in both the full cohort analysis and family designs (i.e., maternal cousin comparisons and full sibling analyses). It is worth noting that when accounting for shared familial factors in family designs, the associations were attenuated but modest associations remained. For instance, among full siblings, children exposed to maternal obesity had a 0.87% higher risk of autism and a 2.13% higher risk of ADHD at age 16, compared to those exposed to mothers of normal weight. The LDSC analysis showed a genetic correlation between BMI and ADHD, but not with autism. The PRS analysis provided less evidence suggesting a relationship between maternal and children’s genetic liability to BMI and various autism and ADHD traits. Specifically, a one-unit increase in BMI was associated with a 12% higher risk for autism and a 77% increased risk for ADHD (Study V). Conclusions In conclusion, my research has reaffirmed known associations between maternal metabolic conditions and offspring NDCs while providing new insights into the underlying mechanisms and causal relationships. Greater associations between maternal diabetes and NDCs involving ID suggested distinct pathophysiological mechanisms. The associations involving PGDM and offspring NDCs might be partially confounded by a genetic predisposition to both the exposure and outcomes; however, its intrauterine effects cannot be completely discounted. Further investigation into the causal link is still warranted in the future. To reduce the risk of offspring NDCs associated with maternal PGDM, it can be beneficial to manage specific obstetric and neonatal complications, especially those arising during the neonatal period. For maternal GDM and overweight/obesity, although we found direct associations with NDCs without evident mediating effects from obstetric and neonatal complications, these direct associations might still contain residual confounding due to unobserved factors. GDM during weeks 27-30 of gestation showed a more pronounced association with offspring NDCs. However, women with hyperglycemia in mid-pregnancy who subsequently achieved effective glucose control did not have a notable increased risk of NDCs among their offspring. While this suggests that effective glucose management during mid-pregnancy might benefit offspring neurodevelopment, further studies are needed to confirm a causal link. My research provides evidence of a modest causal relationship between maternal BMI and offspring autism and ADHD. Further, a lower rate of GWG in the second trimester and a higher rate in the third trimester were more strongly associated with offspring NDCs. This suggests that continuous monitoring and potential interventions related to weight and weight gain from conception onward could have a positive, albeit modest, impact on reducing the risks of offspring NDCs, such as autism and ADHD

HLA Class II Allele Polymorphisms and the Clinical Outcomes of HBV Infection

In 2016, the global health sector strategy (GHSS) on viral hepatitis called for elimination of hepatitis B as a major public health threat by 2030 (i.e., 90% reduction in incidence and 65% in mortality). But persistence or clearance of hepatitis B virus (HBV) infection mainly depends upon host immune responses. The human leukocyte antigen (HLA) system is the center of host immune responses. HLA genes are located in chromosome 6p21.31 and cover 0.13% of the human genome and show a high degree of polymorphism and extensive patterns of linkage disequilibrium (LD), which differ among populations. The HLA genes include HLA class I, HLA class II, and other non-HLA alleles. HLA class II gene polymorphisms are strongly associated with not only persistent HBV infection but also spontaneous HBV clearance and seroconversion, disease progression, and the development of liver cirrhosis (LC) and HBV-related hepatocellular carcinoma (HCC) in chronic hepatitis B. This chapter summarizes the reported associations of HLA class II gene polymorphisms with the outcomes of HBV infection and their related mechanisms

Transcript-Specific Cytoplasmic Degradation of YRA1 Pre-mRNA Mediated by the Yeast EDC3 Protein: A Dissertation

mRNA degradation is a fundamental process that controls both the level and the fidelity of gene expression. Using a combination of bioinformatic, genomic, genetic, and molecular biology approaches, we have shown that Edc3p, a yeast mRNA decay factor, controls the stability of the intron-containing YRA1 pre-mRNA. We found that Edc3p-mediated degradation of YRA1 pre-mRNA: 1) is a component of a negative feedback loop involved in the autoregulation of YRA1, 2) takes place in the cytoplasm, 3) is independent of translation, 4) occurs through a deadenylation-independent decapping and 5΄ to 3΄ exonucleotic decay mechanism, and 5) is controlled by specific cis-acting elements and trans-regulatory factors. Cis-regulation of YRA1 pre-mRNA degradation is complicated and precise. Sequences in exon1 inhibit YRA1 pre-mRNA splicing and/or promote pre-mRNA export in a size-dependent but sequence-independent manner. Sequences in the intron dictate the substrate specificity for Edc3p-mediated decay. Five structurally different but functionally interdependent modules were identified in the YRA1 intron. Two modules, designated Edc3p-responsive elements (EREs), are required for triggering an Edc3p-response. Three other modules, designated translational repression elements (TREs), are required for repressing translation of YRA1 pre-mRNA. TREs enhance the efficiency of the response of the EREs to Edc3p by inhibiting translation-dependent nonsense-mediated mRNA decay (NMD). Trans-regulation of YRA1 pre-mRNA is governed by Yra1p, which inhibits YRA1 pre-mRNA splicing and commits the pre-mRNA to nuclear export, and the RNP export factors, Mex67p and Crm1p, which jointly promote YRA1 pre-mRNA export. Mex67p also appears to interact with sequences in the YRA1 intron to promote translational repression and to enhance the Edc3p response of YRA1 pre-mRNA. These results illustrate how common steps in the nuclear processing, export, and degradation of a transcript can be uniquely combined to control the expression of a specific gene and suggest that Edc3p-mediated decay may have additional regulatory functions in eukaryotic cells