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This study was conducted to demonstrate whether puerarin regulates glutamine synthetase (GS) activity following intraocular hypertension and has therapeutic potential in ophthalmology for the protection of optic nerves in patients with glaucoma. This study used a Wistar rat model of acute closed-angle glaucoma to investigate the effect of puerarin on GS activity in rat retina following intraocular hypertension. Acute intraocular hypertension was induced by increasing anterior chamber pressure to 110 mmHg for 30 min in the left eyes of 50 Wistar rats, while 5 additional Wistar rats lacking intraocular hypertension were used as a control group. Retinal GS activity was measured at 4, 12, 24, 36 and 72 h after induction of acute intraocular hypertension with/without puerarin treatment. Compared to the control group that lacked intraocular hypertension, GS activity in the intraocular hypertension group significantly decreased at 4 and 12 h (P

Uveal melanoma (UM) is one of the primary intraocular malignancies. Emerging studies have confirmed dysregulation of microRNA (miRNA/miR) in UM. The present study focused on the biofunctions of miR-137 in UM.MiR-137 expressions in tissue samples were analyzed by qRT-PCR. MTT and transwell assays were applied to investigate the impacts of miR-137 on UM cell proliferation, invasion and migration. Luciferase assay was carried out to explore the downstream target of miR-137. Western blot was used to analyze the roles of miR-137 in UM cells, Wnt/β-catenin pathway and epithelial-mesenchymal transition (EMT).qRT-PCR showed that miR-137 expressions were lower in UM tissue samples than para-carcinoma tissues, whereas EZH2 was simultaneously upregulated. MiR-137 overexpression evidently suppressed UM cell proliferation, invasion and migration. The findings also indicated that miR-137 restoration could block Wnt/β-catenin pathway and EMT in UM cells thus resulting in downregulation of malignant behaviors. EZH2 was a downstream target of miR-137 as demonstrated by luciferase assay.The present study indicated that EZH2 participated in the anti-UM functions of miR-137. Taken together, the data in our study established miR-137/EZH2 axis in regulating UM progression, suggesting that miR-137 may function as a novel therapeutic biomarker for UM patients.

We analyze a large sample of participants in mixed-gender Rubik’s Cube competitions. Focusing on participants who barely made or missed the cut for the second round in a competition, we examine their likelihood of joining another competition in the future. We find a significant gender difference: Whereas boys are slightly discouraged by failing to qualify for the second round, girls are affected more and are more likely to give up forever. Furthermore, we find that this gender difference is most significant in countries with larger gender gaps in labor market outcomes.

For the treatment of malignant tumors, drug nanocarriers with long blood circulation time and ability to target the tumor microenvironment are promising therapeutic abilities. In this work, to systematically investigate the roles and functions of polysaccharides as drug nanocarriers targeting the tumor microenvironment, different types of polysaccharides (alginic acid (Alg), hyaluronic acid (HA), and dextran (Dex)) were covalently bonded with doxorubicin (DOX) through a Schiff base reaction to form a pH-sensitive polysaccharide-DOX prodrug having an acid-sensitive imine bond. After screening, Dex-DOX exhibited high drug loading content and good stability, while Alg-DOX and HA-DOX may have disadvantages such as low degree of oxidation, limited drug loading capacity, or instability in physiological conditions. Dex-DOX prodrugs were able to self-assemble into stable nanoparticles in phosphate buffered saline (PBS). Then, Dex6k-DOX and Dex150k-DOX were selected for further comparisons since they had similar drug-binding rates and long circulation time. When compared with Dex6k-DOX, the longer main-chain Dex150k-DOX showed a higher drug release rate under simulated acidic conditions in vitro, which significantly inhibited cell proliferation. Further in vivo experiments showed that Dex150k-DOX could more effectively improve the antitumor efficiency and survival rate while reducing side-effects. Overall, the screening and comparisons provided detailed and systematical information about the polysaccharide-DOX prodrug platform as potential antitumor drugs.

Throughout the imperial era, defensive walls surrounded Chinese cities. Although most city walls have vanished, the cities have survived. We analyze a sample of nearly 300 prefectural-level cities in China, among which about half historically had city walls. We document that cities that had walls in late imperial China have higher population and employment density today, despite the fact that their walls have long gone. Using data from various sources, we test several possible explanations of this fact, including (1) walled cities have a well-defined historical core that helps hold economic activity close to the city center today; (2) walled cities today tend to have different industry compositions that are less conducive to decentralization; (3) walled cities are situated in regions where the local geographies make it less desirable to build out; (4) walled cities have more compact shapes that facilitate high density development; and (5) walled cities are located in regions where rural land is more valuable today and discourages urban sprawl. We find that historically walled cities still have higher density after taking into account all of these factors, which we interpret as evidence of economic persistence.

This paper develops a new approach for measuring the stringency of a major form of land use regulation, building height restrictions, and applies it to an extraordinary data set of land-lease transactions from China. Our theory shows that the elasticity of land price with respect to the floor area ratio (FAR), a building height indicator, is a measure of the regulation's stringency (the extent to which FAR is kept below the free-market level). Using a national sample, estimation allowing this elasticity to be city-specific shows variation in the stringency of FAR regulation across Chinese cities. Single-city estimation for Beijing shows that stringency varies with site characteristics.

As a significant part of molecular-targeted therapies, small-molecule agents (SMAs) have been increasingly used for cancer treatment. Nevertheless, most SMAs are currently administered orally due to their poor solubility, resulting in a low bioavailability and unavoidable side effects. Herein, we proposed a promising SMA delivery strategy using a biocompatible and redox-responsive nanoparticle (NP) delivery system to improve their bioavailability, alleviate side effects and enhance therapeutic performance. To demonstrate the feasibility of this strategy, a type of cysteine-based hydrophobic polymer was employed to construct a redox-sensitive nanoplatform for the delivery of various hydrophobic oral SMAs. These SMA-loaded nanoparticles (SMA-NPs) all have a small particle size and good drug-loading capacity. Particularly, lapatinib-loaded nanoparticles (LAP-NPs) with a minimal particle size (79.71 nm) and an optimal drug-loading capacity (12.5%) were utilized as a model to systemically explore the in vitro and in vivo anticancer potential of SMA-NPs. As expected, the LAP-NPs exhibited rapid redox-responsive drug release, enhanced in vitro cytotoxicity and cell apoptosis, and demonstrated notable anti-metastasis ability and desirable intracellular localization. Additionally, the in vivo results demonstrated the preferential accumulation of LAP-NPs in tumor tissues and the significant suppression of tumor growth. Therefore, the generated SMA-NP delivery system shows great SMA delivery potential for advanced molecular-targeted therapies.

In Chinese cities, migrants with rural hukou, compared to residents with local urban hukou, face more uncertainty, have limited access to mortgage finance, and are less eligible for low-cost housing. A simple model demonstrates that for these reasons, rural-to-urban migrants are less likely to own housing units in cities and as a result accumulate less wealth. Our empirical analysis examines a nationally representative household survey from 2013 and uses mother's hukou status as an instrumental variable. We find that household heads with rural hukou are about 20 percentage points less likely to own housing units in cities than comparable household heads with local urban hukou. Consequently, the average household head with a rural hukou owns 315 thousand yuan less housing wealth and 226 thousand yuan less total wealth than comparable household heads with local urban hukou. The average household head with a rural hukou has 288 thousand yuan less in housing capital gains than comparable household heads with local urban hukou. Moreover, we find that these differences are much larger in the first- and second-tier cities, cities with more stringent hukou regulations, and among younger cohorts.

The Chinese government has been using annual quotas to control the amount of farmland that can be converted for urban uses. Using an analysis sample of more than 1.5 million land-lease transactions during 2007–2016, we document facts on land conversion for urban development in China. We present evidence that land conversion quotas have been increasingly misallocated across cities in that a growing share of land conversion is occurring in less productive cities. A city-level production function is estimated for counterfactual analysis. Based on estimated parameters, we assess the economic losses from misallocation of land conversion quotas across cities in China and calculate the potential gains from reallocating land quotas to cities where urban land is more productive.

For thousands of years, the Chinese and many other nations around the world built defensive walls around their cities. This phenomenon is not well understood from an economic perspective. We rationalize the existence of city walls by developing a simple model that relates the dimensions and quality of city walls to a set of economic and geographic variables. We report an empirical analysis using hand-collected and previously unutilized data on city walls in the Ming (1368–1644) and Qing (1644–1911) Dynasties. We find that the circumference of a city wall is correlated with local economic and geographic conditions, that wall size is positively correlated with population size in the jurisdiction, and that frontier cities subject to a higher probability of attack tend to have stronger city walls. We examine the physical size distribution of walled cities in late imperial China and show that city sizes above a certain cutoff follow a Pareto law, although the Pareto coefficient decreases algebraically with the cutoff point. This result complements findings in the existing literature that focuses almost exclusively on the population size distribution of cities. We also find that cities with walls in the past have higher employment and population densities at the present time.

The Chinese government has been using annual quotas to control the amount of farm-land that can be converted for urban uses in cities. Using a sample of more than 1.5 million land-lease transactions during 2007-2016, we document facts on land conversion for urban development in China. We present evidence that land conversion quotas have been increasingly misallocated across cities in that a growing share of land conversion is occurring in less productive cities. A city-level production function is estimated for counterfactual analysis. Based on estimated parameters, we assess the economic losses from misallocation of land conversion quotas across cities in China and calculate the potential gains from reallocating land quotas to cities where urban land is more productive.

Traditional prostate cancer therapy and especially chemotherapy has faced many challenges. Low accumulation levels, rapid clearance or drug resistance at the tumor site have been central to why the effect of chemotherapy drugs has declined. Applications of nanotechnology to biomedicine have enabled the development of nanoparticle therapeutic carriers suited for the delivery of chemotherapeutics in cancer therapy. This review describes the current nature of nanoparticle therapeutic carriers for prostate cancer. It describes typical nanocarriers commonly used for the delivery of chemotherapy or for imaging examination. Targeting strategies and related influencing factors are investigated to find ways of enhancing treatment effects of nanoparticles. The overall purpose of this review is to further understanding and to offer recommendations on the design and development of therapeutic nanoparticles for prostate cancer.

Time-dependent reliability method for mechanisms predicts the probability of satisfying the motion requirement in a predefined period of time. The current reliability methods do not consider the random clearances in mechanism joints. This work extends the current methods into function generation mechanisms on which the effect of random joint clearances is significant. The motion output is approximated in the first order with respect to random dimension variables and in a higher order with respect to random joint clearances by the Hybrid Dimension Reduction Method. This treatment achieves an optimal balance between accuracy and efficiency. Then an envelope method is used to calculate the time-dependent reliability. The method is demonstrated by the analysis of three four-bar function generation mechanisms.

It is difficult to determine whether racial housing segregation is socially desirable, because segregation has some effects that are hard to measure. To overcome this challenge, we estimate a migration choice model to measure the willingness to pay for reduced segregation. The key idea underlying our empirical approach is that if segregation is undesirable, migrants should be willing to give up some earnings to avoid living in segregated cities. Using decennial census data from 1980 to 2000, we provide evidence that segregation is an urban disamenity. It is shown that both black and white migrants prefer to live in less segregated cities. For example, for a one percentage point reduction in the dissimilarity index, the estimated marginal willingness to pay of blacks is $436 (in 1999 dollars) in 2000. Among whites, this marginal willingness to pay is $301.

Donggen Jiang,1,* Chutian Xiao,1,* Tuzeng Xian,1 Liantao Wang,2 Yunhua Mao,1 Junfu Zhang,1 Jun Pang1,3 1Department of Urology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China; 2Department of General Surgery, Shenzhen Shajing Affiliated Hospital of Guangzhou Medical University, Shenzhen, China; 3Department of Urology, the Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China *These authors contributed equally to this work Background: Doublecortin-like kinase 1 (DCLK1) has been proven to be involved in numerous tumors, while its role in prostate cancer (PCa) is still unclear. This study aimed at investigating the expression pattern and prognostic value of DCLK1 in PCa.Patients and methods: Real-time polymerase chain reaction and Western blot were employed to determine DCLK1 mRNA and protein levels in 25 paired fresh samples of PCa and benign prostatic hyperplasia (BPH) as well as in PCa cell lines. Immunohistochemistry (IHC) was also performed in 125 PCa and 65 BPH tissues to assess DCLK1 expression. Then, the association of DCLK1 expression with clinicopathological parameters and biochemical recurrence (BCR) after radical prostatectomy was statistically analyzed. In addition, the role of DCLK1 in PCa cell proliferation, migration, and invasion was evaluated by using MTT and transwell assays.Results: The mRNA and protein levels of DCLK1 were markedly higher in the fresh samples of PCa than that in BPH. Consistently, IHC revealed increased expression of DCLK1 in PCa paraffin-embedded tissues compared with BPH. Moreover, increased DCLK1 expression was significantly associated with postoperative Gleason grading (P=0.012), pathological T stage (P=0.001), seminal vesicle invasion (P=0.026), and lymph node involvement (P=0.017), respectively. The Kaplan–Meier curve analysis demonstrated that high DCLK1 expression was associated with lower postoperative BCR-free survival (bRFS). Furthermore, multivariate Cox analysis showed that postoperative Gleason grading (P=0.018), pathological T stage (P

We study whether subways alleviate road congestion by examining 45 subway line launches in China and by using detailed data on road speed. Our difference-in-differences estimation finds that in the first year after a subway line is launched, rush hour speed on nearby roads increases by about 4 percent. The effect is most prominent in initially congested roads and declines over distance to the new subway line. Evidence on road speed is corroborated with substitution patterns among modes of transportation. Using auxiliary data from Beijing, we calculate that the time savings for each automobile or bus commute from faster speed is worth US$0.10. (JEL O18, P25, R41)

Evidence suggests that the long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is upregulated in cancer tissues, and its elevated expression is associated with hyperproliferation. However, the underlying mechanisms regarding the role of MALAT1 in retinoblastoma (RB) remain unclear. This study aimed to explore the functional role of MALAT1 in RB by targeting miR-124. The results showed that the expression of MALAT1 was significantly higher in the Y79 cell line than in the ARPE-19 cell line (p p p p p p p p p p p p

Uncertainty is unavoidable in engineering and has been intensively studied. Most of the studies focus on time invariant uncertainty. In many applications, uncertainty is time dependent. This paper reviews several progresses in time-dependent uncertainty methodologies. The task at the analysis level is to quantify the effect of time-dependent uncertainty on product performance, such as the probability of failure for a given period of time. The task at the design level is to identify optimal design variables that not only optimize the performance of the product but also mitigate the effect of uncertainty so that design requirements are satisfied during the entire product lifetime. Examples are given to show the benefits of considering time-dependent uncertainty during the design process.

Randomness in mechanism dimensions and joints makes the mechanism motion deviate from its designed motion. The probability (reliability) that such deviation is within an error tolerance limit should be invariably large. This study shows that the accuracy of the reliability analysis for dependent joint clearances is insufficient by existing kinematic reliability methods, such as the First Order Second Moment (FOSM) Method and First Order Reliability Method (FORM). We therefore propose a Hybrid Dimension Reduction Method (HDRM) to better handle the dependent joint clearance variables. With the first order Taylor expansion for independent dimension variables and bivariate dimension reduction for dependent joint clearance variables, HDRM produces more accurate solutions than the FOSM and FORM while maintains higher efficiency than FORM and Monte Carlo simulation. A slider-crank mechanism is used as an example for the methodology demonstration and validation.

In traditional probabilistic mechanism synthesis, point kinematic reliability is employed. Point kinematic reliability is the probability that the motion error is within a specified limit at a specific instant of time regardless if the mechanism failed before that instant. For function generator mechanisms, using the point kinematic reliability cannot satisfy the reliability requirement for the time interval where the desired function is defined. In this work a probabilistic mechanism synthesis method is proposed with the interval (or time-dependent) kinematic reliability, which is the probability of the motion error less than the specified limit over the time interval where the mechanism is supposed to perform its intended function. As a result, the new synthesis method can guarantee the satisfaction of the kinematic reliability requirement not only over the time interval but also at all the points within the interval. The interval reliability is calculated with the integration of the First Order Second Moment method and the first-passage Poisson approximation method. The method is demonstrated by the synthesis of a four-bar function generator mechanism.

In the attempt to compete for foreign investment, local jurisdictions in China set up a large number of development zones for industrial and commercial uses. Many of these areas never received any investment and sat idle for years as undeveloped sites. In several periods of time, development zones mushroomed at such a rampant pace that the central government had to intervene in order to prevent the rapid reduction of agricultural land. In this paper, we propose a model to account for the “development zone fever” experienced in China. We consider local jurisdictions as participants in an all-pay auction competing for investment projects. An investment always goes to a jurisdiction with the highest-quality infrastructure in its development zone. A jurisdiction has to pay the cost of infrastructure in advance, which is irrecoverable whether it wins the investment or not. In equilibrium, many jurisdictions set up economic development zones and spend on infrastructure, although some of these sites will not receive any investment. Potential effects of several policies are examined. The model suggests that to reduce land use by development zones, the central government could either claim a larger share of the tax revenue generated by foreign investments or raise the tax on the land used for development zones. Other policies, such as putting a budget constraint on infrastructure spending or restricting some jurisdictions from competing, are either ineffective or have some undesirable effects.

We use a new database, the National Establishment Time Series (NETS), to revisit the debate about the role of small businesses in job creation. Birch (e.g., 1987) argued that small firms are the most important source of job creation in the U.S. economy. But Davis et al. (1996a) argued that this conclusion was flawed, and based on improved methods and using data for the manufacturing sector, they concluded that there was no relationship between establishment size and net job creation. Using the NETS data, we examine evidence for the overall economy, as well as for different sectors. The results indicate that small firms and small establishments create more jobs, on net, although the difference is much smaller than what is suggested by Birch's methods. Moreover, in the recent period we study, a negative relationship between establishment size and job creation holds for both the manufacturing and services sectors.

In this study, I identify academic entrepreneurs using biographical information on start-up founders contained in a comprehensive venture capital database. Multivariate analyses are conducted to investigate why some US universities generate more venture-backed academic entrepreneurs than others. I find that national academy membership and total faculty awards are the most significant variables in explaining the number of venture-backed entrepreneurs from a university. In contrast, the abundance of venture capital near the university has no significant effect, which is surprising given that this study focuses exclusively on venture-backed entrepreneurs.

University spin-offs are defined as firms founded by university employees. Using a large database on venture-backed start-up companies, I describe the characteristics of university spin-offs and investigate whether they perform differently than other firms. I find that venture-backed university spin-offs are concentrated in the biotechnology and information technology industries. Moreover, a spin-off tends to stay close to the university, suggesting that technology transfer through spin-offs is largely a local phenomenon. Multivariate regression analyses show that university spin-offs have a higher survival rate but are not significantly different from other start-ups in terms of the amount of venture capital raised, the probability of completing an initial public offering (IPO), the probability of making a profit, or the size of employment.

This paper uses the 2011 China Household Finance Survey data to estimate the effect of changes in housing value on homeowners’ labor force participation. Using the average housing capital gains of other homes in the same community as an instrument for the housing capital gains of a given household, we find that a 100,000 yuan increase in housing value leads to a 1.37 percentage point decrease in female homeowners’ probability of participating in the labor force and a 1.49 percentage point increase in their probability of becoming housewives. We find little effect on men's labor force participation.

This article examines start-ups' access to venture capital in Silicon Valley using a comprehensive database. The author finds that Silicon Valley consistently absorbs 20% to 26% of the total venture capital investment in the United States, and start-ups in this region benefit from the abundance of local venture capital. Venture-backed firms in Silicon Valley receive venture capital at a younger age and complete more rounds of financing. On one hand, this better access to capital makes start-ups in Silicon Valley more likely than start-ups elsewhere to complete initial public offerings and helps offset some of the negative effects of intense competition in the region. On the other hand, better access to venture capital is associated with a higher bankruptcy rate, possibly because competition for new ventures makes it more likely that poor business plans will get funding.

Limbal stem cell (LSC) on the basal layer of cornea plays an important role in the epithelial repair after corneal injury as it can proliferate, differentiate and migrate into injury sites under the direction of cytokines. This study explored the signaling pathway and cellular mechanism between corneal epithelial cells LSC, on a mouse model with mechanic corneal injury. Ipsilateral corneal mechanic injury model was prepared on mice using the contralateral eye as the control. Tissues from both central and peripheral regions of cornea were collected, cultured and quantified for expression of various cytokines including epidermal growth factor (EGF), fibroblast growth factor-β (FGF-β), heparin-like growth factor (HGF), keratinocyte growth factor (KGF), transforming growth factor-β1 (TGF-β1), IGF-1 and IGF-2. The effects of these factors on the differentiation of LSC and fibroblasts were also studied. Most of those cytokines had elevated gene expressions after the corneal injury. Among those IGF-2 had significantly increased expression, along with the high expression of IGF-2 receptor in corneal peripheral cells. IGF-2 also induced the differentiation of LSC into keratin-12-positive cells. Further studies showed the prominent expression of α-actin in injured tissues, suggesting the potential transformation of fibroblasts into myofibroblasts. Both IGF-2 and its receptor had elevated expressions after corneal injury. They may facilitate the transformation of LSC into epithelial cells, in addition to the role in transformation from fibroblasts to myofibroblasts.