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"Chang, Eric C."
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Electoral systems and the balance of consumer-producer power
\"This book investigates the effects of electoral systems on the relative legislative and, hence, regulatory influence of competing interests in society. Building on Ronald Rogowski and Mark Andreas Kayser's extension of the classic Stigler-Peltzman model of regulation, the authors demonstrate that majoritarian electoral arrangements should empower consumers relative to producers. Employing real price levels as a proxy for consumer power, the book rigorously establishes this proposition over time, within the OECD, and across a large sample of developing countries. Majoritarian electoral arrangements depress real prices by approximately ten percent, all else equal. The authors carefully construct and test their argument and broaden it to consider the overall welfare effects of electoral system design and the incentives of actors in the choice of electoral institutions\"-- Provided by publisher.
Book
Corruption predictability and corruption voting in Asian democracies
I examine how the structure of corrupt exchanges between voters and politicians—an important-yet-underexplored form of informal institutions—shapes voters’ electoral behavior toward corruption. I argue that when voters have a clear idea of whom to bribe to secure desired services and how much they need to offer, they are less likely to engage in corruption voting and hold corrupt incumbents electorally accountable for their malfeasance. Utilizing the World Business Environment Survey on corruption predictability and the Asian Barometer survey on voters’ electoral behaviors, I report empirical evidence that institutionalized corruption promotes greater electoral tolerance of corrupt politicians in Asian democracies. The results hold against a number of robustness checks. The paper thus furthers our understanding of the effect of informal political institutions on corruption voting as well as Asia’s corruption exceptionalism.
Journal Article
The prognostic effects of somatic mutations in ER-positive breast cancer
Here we report targeted sequencing of 83 genes using DNA from primary breast cancer samples from 625 postmenopausal (UBC-TAM series) and 328 premenopausal (MA12 trial) hormone receptor-positive (HR+) patients to determine interactions between somatic mutation and prognosis. Independent validation of prognostic interactions was achieved using data from the METABRIC study. Previously established associations between MAP3K1 and PIK3CA mutations with luminal A status/favorable prognosis and TP53 mutations with Luminal B/non-luminal tumors/poor prognosis were observed, validating the methodological approach. In UBC-TAM,
NF1
frame-shift nonsense
(FS/NS)
mutations were also a poor outcome driver that was validated in METABRIC. For MA12, poor outcome associated with PIK3R1 mutation was also reproducible. DDR1 mutations were strongly associated with poor prognosis in UBC-TAM despite stringent false discovery correction (
q
= 0.0003). In conclusion, uncommon recurrent somatic mutations should be further explored to create a more complete explanation of the highly variable outcomes that typifies ER+ breast cancer.
Unravelling the link between somatic mutation and prognosis in estrogen positive (ER+) breast cancer requires the use of long-term follow-up data. Here, combining archival formalin-fixed paraffin embedded tissue and targeted sequencing in three cohorts of ER+ breast cancer, the authors find associations with clinical outcome for NF1 frame-shift nonsense mutations, PIK3R1 mutation, and DDR1 mutations.
Journal Article
Legislative Malfeasance and Political Accountability
Utilizing a unique data set from the Italian Ministry of Justice reporting the transmission to the Chamber of Deputies of more than the thousand requests for the removal of parliamentary immunity from deputies suspected of criminal wrongdoing, the authors analyze the political careers of members of the Chamber during the first eleven postwar legislatures (1948–94). They find that judicial investigation typically did not discourage deputies from standing for reelection in Italy's large multimember electoral districts. They also show that voters did not punish allegedly malfeasant legislators with loss of office until the last (Eleventh) legislature in the sample. To account for the dramatic change in voter behavior that occurred in the early 1990s, the investigation focuses on the roles of the judiciary and the press. The results are consistent with a theory that a vigilant and free press is a necessary condition for political accountability in democratic settings. An independent judiciary alone is ineffective in ensuring electoral accountability if the public is not informed of political malfeasance.
Journal Article
Short-Sales Constraints and Price Discovery: Evidence from the Hong Kong Market
Short-sales practices in the Hong Kong stock market are unique in that only stocks on a list of designated securities can be sold short. By analyzing the price effects following the addition of individual stocks to the list, we find that short-sales constraints tend to cause stock overvaluation and that the overvaluation effect is more dramatic for individual stocks for which wider dispersion of investor opinions exists. These findings are consistent with Miller's (1977) intuition and other optimism models. We also document higher volatility and less positive skewness of individual stock returns when short sales are allowed.
Journal Article
Elevated NRAS expression during DCIS is a potential driver for progression to basal-like properties and local invasiveness
Background
Ductal carcinoma in situ (DCIS) is the most common type of in situ premalignant breast cancers. What drives DCIS to invasive breast cancer is unclear. Basal-like invasive breast cancers are aggressive. We have previously shown that NRAS is highly expressed selectively in basal-like subtypes of invasive breast cancers and can promote their growth and progression. In this study, we investigated whether
NRAS
expression at the DCIS stage can control transition from luminal DCIS to basal-like invasive breast cancers.
Methods
Wilcoxon rank-sum test was performed to assess expression of
NRAS
in DCIS compared to invasive breast tumors in patients.
NRAS
mRNA levels were also determined by fluorescence in situ hybridization in patient tumor microarrays (TMAs) with concurrent normal, DCIS, and invasive breast cancer, and association of
NRAS
mRNA levels with DCIS and invasive breast cancer was assessed by paired Wilcoxon signed-rank test. Pearson’s correlation was calculated between
NRAS
mRNA levels and basal biomarkers in the TMAs, as well as in patient datasets. RNA-seq data were generated in cell lines, and unsupervised hierarchical clustering was performed after combining with RNA-seq data from a previously published patient cohort.
Results
Invasive breast cancers showed higher
NRAS
mRNA levels compared to DCIS samples. These
NRAS
high
lesions were also enriched with basal-like features, such as basal gene expression signatures, lower ER, and higher p53 protein and Ki67 levels. We have shown previously that NRAS drives aggressive features in DCIS-like and basal-like SUM102PT cells. Here, we found that
NRAS
-silencing induced a shift to a luminal gene expression pattern. Conversely,
NRAS
overexpression in the luminal DCIS SUM225 cells induced a basal-like gene expression pattern, as well as an epithelial-to-mesenchymal transition signature. Furthermore, these cells formed disorganized mammospheres containing cell masses with an apparent reduction in adhesion.
Conclusions
These data suggest that elevated NRAS levels in DCIS are not only a marker but can also control the emergence of basal-like features leading to more aggressive tumor activity, thus supporting the therapeutic hypothesis that targeting NRAS and/or downstream pathways may block disease progression for a subset of DCIS patients with high
NRAS
.
Journal Article
Corruption and Trust: Exceptionalism in Asian Democracies?
While voluminous studies have attributed the continuing decline of institutional trust to political corruption, the link between corruption and institutional trust in Asia has yet to be explored systematically. Testing the effect of corruption on institutional trust is theoretically important and empirically challenging, since many suggest that contextual factors in Asia, such as political culture and electoral politics, might neutralize the negative impact of corruption. Utilizing data from the East Asia Barometer, we find a strong trust-eroding effect of political corruption in Asian democracies. We also find no evidence that contextual factors lessen the corruption-trust link in Asia. The trust-eroding effect holds uniformly across all countries examined in this study and remains robust even after taking into account the endogenous relationship between corruption and trust.
Journal Article
Electoral Systems, District Magnitude and Corruption
The relationship between electoral systems and corruption in a large sample of contemporary democratic nations is analysed in this article. Whereas previous studies have shown that closed-list proportional representation is associated with greater (perceived) corruption than open-list PR, it is demonstrated here that this relationship fails to hold once district magnitude is considered. The theory underlying this study draws on work on ‘the personal vote’ that suggests that the incentives to amass resources – and perhaps even to do so illegally – increase with district magnitude in open-list settings but decrease in closed-list contexts. Extending this insight, it is shown that political corruption gets more (less) severe as district magnitude increases under open-list PR (closed-list PR) systems. In addition, once district magnitude exceeds a certain threshold – the estimates here are that this is as low as fifteen – corruption is greater under open lists than closed lists. Only at small district magnitudes (below fifteen) is closed-list PR associated with more corruption, as conventionally held. These results hold for alternative measures of corruption, for different sets of countries analysed, for different measures of district magnitude and regardless of whether the political system is presidential or parliamentary, and of the number of parties. Using an objective measure of corruption in public works contracting, corroborating evidence is also presented from Italian electoral districts. In Italy's open-list environment in the period prior to 1994, larger districts were more susceptible to corruption than smaller ones.
Journal Article
Induction of N-Ras degradation by flunarizine-mediated autophagy
Ras GTPases are powerful drivers for tumorigenesis, but directly targeting Ras for treating cancer remains challenging. The growth and transforming activity of the aggressive basal-like breast cancer (BLBC) are driven by N-Ras. To target N-Ras in BLBC, this study screened existing pharmacologically active compounds for the new ability to induce N-Ras degradation, which led to the identification of flunarizine (FLN), previously approved for treating migraine and epilepsy. The FLN-induced N-Ras degradation was not affected by a 26S-proteasome inhibitor. Rather, it was blocked by autophagy inhibitors. Furthermore, N-Ras can be seen co-localized with active autophagosomes upon FLN treatment, suggesting that FLN alters the autophagy pathway to degrade N-Ras. Importantly, FLN treatment recapitulated the effect of
N-RAS
silencing
in vitro
by selectively inhibiting the growth of BLBC cells, but not that of breast cancer cells of other subtypes. In addition,
in vivo
FLN inhibited tumor growth of a BLBC xenograft model. In conclusion, this proof-of-principle study presents evidence that the autophagy pathway can be coerced by small molecule inhibitors, such as FLN, to degrade Ras as a strategy to treat cancer. FLN has low toxicity and should be further investigated to enrich the toolbox of cancer therapeutics.
Journal Article
Compartmentalized signaling of Ras in fission yeast
Compartment-specific Ras signaling is an emerging paradigm that may explain the multiplex outputs from a single GTPase. The fission yeast, Schizosaccharomyces pombe, affords a simple system in which to study Ras signaling because it has a single Ras protein, Ras1, that regulates two distinct pathways: one that controls mating through a Byr2-mitogen-activated protein kinase cascade and one that signals through Scd1-Cdc42 to maintain elongated cell morphology. We generated Ras1 mutants that are restricted to either the endomembrane or the plasma membrane. Protein binding studies showed that each could interact with the effectors of both pathways. However, when examined in ras1 null cells, endomembrane-restricted Ras1 supported morphology but not mating, and, conversely, plasma membrane-restricted Rasl supported mating but did not signal to Scd1-Cdc42. These observations provide a striking demonstration of compartment-specific Ras signaling and indicate that spatial specificity in the Ras pathway is evolutionarily conserved.
Journal Article