Does investment in national highways help or hurt hinterland city growth?

We investigate the effects of the recently constructed Chinese national highway system on local economic outcomes. On average, roads that improve access to local markets have small or negative effects on prefecture economic activity and population. However, these averages mask a distinct pattern of winners and losers. With better regional highways, economic output and population increase in regional primates at the expense of hinterland prefectures. Highways also affect patterns of specialization. With better regional highways, regional primates specialize more in manufacturing and services, while peripheral areas lose manufacturing but gain in agriculture. Better access to international ports promotes greater population, GDP, and private sector wages on average, effects that are probably larger in hinterland than primate prefectures. An important policy implication is that investing in local transport infrastructure to promote growth of hinterland prefectures has the opposite effect, causing them to specialize more in agriculture and lose economic activity

Transport Infrastructure, Urban Growth and Market Access in China

This paper quantifies the causal effects of various types of investments in the road and railroad networks on economic growth in Chinese cities and regions. We separate out the influences of changes in access to markets that have come through better inter-regional and international transport links from the more direct effects of transport infrastructure on city level productivity, which may operate through various channels. We find strong evidence that improved integration with nearby markets significantly promoted local growth in China since 1990. In particular, expansions of road infrastructure leading to a 10 percent increase in economic activity within a six hours' travel time led to an estimated 1.4 percent more rapid prefecture GDP growth and 1.1 percent more rapid prefecture city GDP growth. Expansions of road infrastructure leading to a 10 percent increase in population within six hours caused an estimated 1.6 percent increase in prefecture GDP growth and an imprecisely estimated 1.3 percent increase in prefecture city GDP growth. Estimated causal effects of more theoretically grounded measures of market access on local growth are consistent with these effects of more reduced form market potential measures. While we find that improved regional integration promoted local GDP growth in China, we find no significant effects of regional integration on prefecture or city population growth. Instead, we find evidence that improved access to international ports promoted population growth. A 10 percent decline in travel time to an international port caused a 0.6 to 0.7 percent increase in prefecture and city population growth. The context of severe migration restrictions in many cities and policies promoting foreign investment in other cities is important for interpreting these results. Our investigation of the effects of highways and railroads serving prefecture cities is less conclusive. While point estimates tend to be positive, they are generally imprecise. This study innovates on the existing literature about the effects of reduced domestic trade costs on local growth in several ways. First, we consider both highways and railroads. Second we primarily examine cities, rather than rural counties or small towns. Third we examine the effects of transport infrastructure on the growth and redistribution output and population simultaneously, rather than on inferred income or the output of specific commodities. Finally, we examine the responses to various measures of the composition of output in the regions surrounding cities in various distance and travel time bands. Critical to this evaluation is the use of pseudo-random variation in the allocation of transport networks to cities and their surrounding regions

When models fall short: Evidence from Chinese road infrastructure investments

Despite limits to data quality and to the possibilities for recovering causal relationships between infrastructure investment, urbanisation and economic growth, quantitative models may prove to be weak substitutes for direct empirical evidence. For evidence based policymaking, research technique matters

Roads, railroads and decentralization of Chinese cities

We investigate how configurations of urban railroads and highways influenced urban form in Chinese cities since 1990. Each radial highway displaces about 4 percent of central city population to surrounding regions and ring roads displace about an additional 20 percent, with stronger effects in the richer coastal and central regions. Each radial railroad reduces central city industrial GDP by about 20 percent, with ring roads displacing an additional 50 percent. Similar estimates for the locations of manufacturing jobs and residential location of manufacturing workers is evidence that radial highways decentralize service sector activity, radial railroads decentralize industrial activity and ring roads decentralize both. Historical transportation infrastructure provides identifying variation in more recent measures of infrastructure

Roads, Railroads and Decentralization of Chinese Cities

Abstract: We investigate how the configurations of urban railroads and highways have influenced urban form in Chinese cities since 1990. Each radial highway displaces at least 5 percent of central city population to surrounding regions and ring roads displace an additional 20 percent. Each radial railroad displaces 26 percent of central city industrial GDP with ring roads displacing an additional 50 percent. Products with high weight-to-value ratios appear unresponsive to transport changes. However, products with medium and low weight-to-value ratios decentralize in response to radial railroads and ring roads. Historical transportation infrastructure provides identifying variation in more recent measures of infrastructure. J.E.L.: R4, O

Altered versican cleavage in ADAMTS5 deficient mice : a novel etiology of myxomatous valve disease

AbstractIn fetal valve maturation the mechanisms by which the relatively homogeneous proteoglycan-rich extracellular matrix (ECM) of endocardial cushions is replaced by a specialized and stratified ECM found in mature valves are not understood. Therefore, we reasoned that uncovering proteases critical for ‘remodeling’ the proteoglycan rich (extracellular matrix) ECM may elucidate novel mechanisms of valve development. We have determined that mice deficient in ADAMTS5, (A Disintegrin-like And Metalloprotease domain with ThromboSpondin-type 1 motifs) which we demonstrated is expressed predominantly by valvular endocardium during cardiac valve maturation, exhibited enlarged valves. ADAMTS5 deficient valves displayed a reduction in cleavage of its substrate versican, a critical cardiac proteoglycan. In vivo reduction of versican, in Adamts5−/− mice, achieved through Vcan heterozygosity, substantially rescued the valve anomalies. An increase in BMP2 immunolocalization, Sox9 expression and mesenchymal cell proliferation were observed in Adamts5−/− valve mesenchyme and correlated with expansion of the spongiosa (proteoglycan-rich) region in Adamts5−/− valve cusps. Furthermore, these data suggest that ECM remodeling via ADAMTS5 is required for endocardial to mesenchymal signaling in late fetal valve development. Although adult Adamts5−/− mice are viable they do not recover from developmental valve anomalies and have myxomatous cardiac valves with 100% penetrance. Since the accumulation of proteoglycans is a hallmark of myxomatous valve disease, based on these data we hypothesize that a lack of versican cleavage during fetal valve development may be a potential etiology of adult myxomatous valve disease

Phenotype plasticity and altered sensitivity to chemotherapeutic agents in aggressive prostate cancer cells

In 2023, approximately 288,300 new diagnoses of prostate cancer will occur, with 34,700 disease-related deaths. Death from prostate cancer is associated with metastasis, enabled by progression of tumor phenotypes and successful extracapsular extension to reach Batson’s venous plexus, a specific route to the spine and brain. Using a mouse-human tumor xenograft model, we isolated an aggressive muscle invasive cell population of prostate cancer, called DU145J7 with a distinct biophysical phenotype, elevated histone H3K27, and increased matrix metalloproteinase 14 expression as compared to the non-aggressive parent cell population called DU145WT. Our goal was to determine the sensitivities to known chemotherapeutic agents of the aggressive cells as compared to the parent population. High-throughput screening was performed with 5,578 compounds, comprising of approved and investigational drugs for oncology. Eleven compounds were selected for additional testing, which revealed that vorinostat, 5-azacitidine, and fimepinostat (epigenetic inhibitors) showed 2.6-to-7.5-fold increases in lethality for the aggressive prostate cancer cell population as compared to the parent, as judged by the concentration of drug to inhibit 50% cell growth (IC50). On the other hand, the DU145J7 cells were 2.2-to-4.0-fold resistant to mitoxantrone, daunorubicin, and gimatecan (topoisomerase inhibitors) as compared to DU145WT. No differences in sensitivities between cell populations were found for docetaxel or pirarubicin. The increased sensitivity of DU145J7 prostate cancer cells to chromatin modifying agents suggests a therapeutic vulnerability occurs after tumor cells invade into and through muscle. Future work will determine which epigenetic modifiers and what combinations will be most effective to eradicate early aggressive tumor populations

Epstein-Barr virus: clinical and epidemiological revisits and genetic basis of oncogenesis

Epstein-Barr virus (EBV) is classified as a member in the order herpesvirales, family herpesviridae, subfamily gammaherpesvirinae and the genus lymphocytovirus. The virus is an exclusively human pathogen and thus also termed as human herpesvirus 4 (HHV4). It was the first oncogenic virus recognized and has been incriminated in the causation of tumors of both lymphatic and epithelial nature. It was reported in some previous studies that 95% of the population worldwide are serologically positive to the virus. Clinically, EBV primary infection is almost silent, persisting as a life-long asymptomatic latent infection in B cells although it may be responsible for a transient clinical syndrome called infectious mononucleosis. Following reactivation of the virus from latency due to immunocompromised status, EBV was found to be associated with several tumors. EBV linked to oncogenesis as detected in lymphoid tumors such as Burkitt's lymphoma (BL), Hodgkin's disease (HD), post-transplant lymphoproliferative disorders (PTLD) and T-cell lymphomas (e.g. Peripheral T-cell lymphomas; PTCL and Anaplastic large cell lymphomas; ALCL). It is also linked to epithelial tumors such as nasopharyngeal carcinoma (NPC), gastric carcinomas and oral hairy leukoplakia (OHL). In vitro, EBV many studies have demonstrated its ability to transform B cells into lymphoblastoid cell lines (LCLs). Despite these malignancies showing different clinical and epidemiological patterns when studied, genetic studies have suggested that these EBV- associated transformations were characterized generally by low level of virus gene expression with only the latent virus proteins (LVPs) upregulated in both tumors and LCLs. In this review, we summarize some clinical and epidemiological features of EBV- associated tumors. We also discuss how EBV latent genes may lead to oncogenesis in the different clinical malignancie

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC