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

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

Beyond behavior: An intersectional analysis of the impact of sexual networks, segregation, and incarceration on disparities in STDs

There are approximately 19 million new cases of sexually transmitted diseases (STDs) in the United States every year (Satterwhite et al., 2008).. Although the entire society is encumbered by the economic impact of STDs, the burden of these diseases is not equally borne along racial and gender lines. In particular, African Americans report substantially higher rates of chlamydia, gonorrhea, and syphilis than do Whites. Generally, women report higher rates of these diseases than do men. Using an intersectional analytical framework, the first part of this research analyzes data from the 2006-2010 National Survey of Family Growth to examine the extent to which sexual network factors matter above and beyond individual-level sexual behavior and sociodemographic factors in accounting for STDs. In addition, it seeks to determine the degree to which sexual network factors account for the gaps in STDs among various race by gender groups. The results from multivariate logistic regression analyses suggest that, net of sociodemographic and behavioral factors, the main effects of the sexual network factors are consistent with the predictions derived from sexual network theory (i.e., four out of five hypotheses). However, factors associated with sexual network theory do not appear to go very far in terms of explaining the racial and gender gaps in STDs. The second part of the research uses an intersectional analytical framework to assess factors consistent with an “American apartheid” perspective. It uses indicators compiled into a single dataset in which county (n=3,089) is the unit of analysis. The analysis examines the relationship of chlamydia rates and gonorrhea rates to racial isolation—a type of residential segregation that measures the extent to which a member of a racial or ethnic group is likely to be in contact with members of this same group (as opposed to members of other groups). The analysis examines the relationship between both black isolation and white isolation and STD rates, net of other community-level factors that are associated with STDs. The analysis also compares the relationship of black isolation and white isolation to chlamydia rates for “white” counties, “integrated” counties, and “disproportionately black” counties. This research lends support to earlier studies that demonstrate that concentrated disadvantage through high black isolation is related to higher STD rates. But this research also adds to the literature by also showing that white isolation is associated with lower rates of chlamydia. Disparities in STD rates between disproportionately black counties and white counties would be greatly diminished if racial isolation were eliminated. Overall rates of chlamydia would decline by more than 33% if black isolation were eliminated. The results illustrate how powerfully residential segregation is related to STDs rates. The third part of the research uses an intersectional analytical framework to examine the relationship between incarceration rates, being a community that serves as a reentry point for those formerly incarcerated, and STD rates. The analysis is based on county-level indicators compiled into a single dataset in which county (n=3,089) is the unit of analysis. The analysis examines the relationship of reentry locations and incarceration rates to STD rates, net of other community-level factors that are associated with STDs. These relationships are examined in disproportionately black communities, white communities, and integrated communities. The results suggest that communities that serve as reentry points for those who have been incarcerated have significantly higher rates of STDs, net of other community-level factors that are associated with STDs. These reentry locations are more likely to be located in disproportionately black communities, and they help explain part of the relationship between racial isolation and STDs. This study remains faithful to the tenets of intersectionality not only because it examines differences in race by gender groups, but also by taking into account residential segregation and contextual variables that are related to disparities in STDs. Moreover, this research looks at reentry locations as a way of measuring the impact of incarceration on the communities to which former prisoners return. This study is first to use national data to examine these factors in this way. Persisting disparities in STDs in the U.S. is a stubborn problem that defies simple explanations. Differences in sexual behaviors do not account for the disparities. When sexual network factors are taken into account, the gaps become even larger. Community-level factors such as racial segregation and incarceration reentry location appear to hold promise