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In order to improve the mixing effect of the traditional Kenics static mixer, a new type of static mixer with a perforated structure added to the spiral insertion band of the existing mixer is proposed. The results show that the perforated structure can change the flow state of the fluid, and accelerate the flow in the perforated area, thus improving the mixing performance of the mixer. With the increase of the perforation diameter, the mixing performance of the mixer is gradually enhanced. However, when the perforation diameter continues to increase, the spiral channel inside the mixer is destroyed, and the mixing effect is weakened. Only changing the perforation spacing has no obvious effect on the mixing effect. For the same mixer length, the reduction of the length-diameter ratio of mixing unit leads to the increase of the number of mixing units, the better mixing effect of the mixer.

Supplemental material, sj-docx-1-pie-10.1177_09544089231151536 for Study on damaged micro-mechanism of pipe wall during braking and anchoring process of pipeline intelligent plugging robot by Yang Tang, Zhou Minghai, Peng Sun, Jie Wu, Qiang Wang and Ju Wu in Proceedings of the Institution of Mechanical Engineers, Part E: Journal of Process Mechanical Engineering

The packer is a key tool to isolate downhole pressure during well testing and completion operations. The compression packer in the oil and gas wellbore needs to be anchored by hard contact between the slips and the casing when setting, which will cause the casing to suffer from occlusal damage and shorten the working life. It is necessary to combine casing damage and anchoring performance of the slip, select suitable packer slip material, and optimize its structural parameters to reduce casing hard contact damage and increase the working life of the slips and casing. Based on mechanical analysis and hard contact mechanism of the slip during the packer setting process, and selecting the slip material lower than the mechanical properties of the casing material, a finite element analysis model of interaction between the slips and the casing was established. The changes of slip equivalent plastic strain, maximum Mises stress, and CPRESS stress under three parameters of slip tooth number, tooth space, and tooth top angle were comprehensively evaluated. The results of analysis show that with the increase in the tooth number of slips, the tooth space or the top angle, the bending moment of slips increased, and the anchoring performance decreased. As the tooth number of slips, the tooth space or the top angle decreased, the damage of slip teeth increased. The combination optimization analysis of the above parameters was carried out using the orthogonal experiment method, and the optimal top angle of the slip structure of the compression packer is 90°, the tooth space is 4 mm, and the tooth number is 20. Compared with the anchoring performance of soluble metal slips, the optimized slips significantly reduce the damage to the casing. The study will provide a theoretical basis and date support for further analysis of the anchoring performance of the slip, the reduction of casing damage, and the design of new slips.

In underground coal gasification, crude gas carrying coal ash and cinder has a serious significant erosion effect on the gas extraction area of a wellhead device. To study the erosion of the wellhead device, based on the gas-solid two-phase flow theory, this study uses the discrete phase model to describe the kinematics and trajectories of discrete solid particles and uses the Reynolds-averaged Navier-Stokes equation to calculate the fluid dynamics of the continuous phase. This study determines the main erosion position and the maximum erosion angle range of the wellhead device through numerical analysis, as well as the influence of the changes in solid particle size, particle mass flow rate, and crude gas flow rate on the erosion rate, and predicts the service lifetime of the small four-way and side valve I. The gas-solid erosion experiment verified the maximum erosion angle of the wellhead device. The experimental results were consistent with the numerical analysis results. This study also proposes an optimization method of surfacing to reduce the erosion of gas-solid two-phase flow on wellhead devices. The results show that the inner walls of the small four-way and side valve I are the most eroded. Factors such as particle size, particle mass flow rate, and crude gas flow rate have a greater impact on the erosion rate of the device, and the particle size has the greatest impact. Surfacing the severely eroded area of the wellhead device can effectively reduce the erosion and wear of the wellhead device caused by the gas-solid two-phase flow. This study provides guidance for the reasonable prediction and effective protection of severe erosion areas of wellhead devices.

This paper investigates the impact of import liberalization induced labor demand shocks on male and female employment in China. Combining data from population and firm censuses between 1990 and 2005, we relate prefecture-level employment by gender to the exposure to tariff reductions on locally imported products. Our empirical results show that increasing import competition has kept more females in the workforce, reducing an otherwise growing gender employment gap in the long run. These dynamics were present both in local economies as a whole and among formal private industrial firms. Examining channels through which tariff reductions differentially affect males and females, we find that trade-induced competitive pressures contributed to a general expansion of female-intensive industries, a shift in sectoral gender segregation, reductions in gender discrimination in the labor market, technological upgrading through computerization, and general income growth.

The share of the service sector in China is significantly lower than that in most countries at the same level of income. Figures reveal that an insufficiency in both consumer and producer demand may be one of the reasons. We find that the demand insufficiency mainly stems from high consumer preferences for saving and China’s export-oriented trade structure. These excessive saving tendencies limit consumer demand for service products and thus hamper the development of consumer services in China. The rapid development of the processing trade also impedes the interrelation between the domestic manufacturing and service industries, reduces the effective demand for local producer services from the manufacturing industry, and ultimately restricts the growth of the producer service industry in China.

Exposure of cultured primary neurons to preformed α-synuclein fibrils (PFFs) leads to the recruitment of endogenous α-synuclein and its templated conversion into fibrillar phosphorylated α-synuclein (pα-synF) aggregates resembling those involved in Parkinson's disease (PD) pathogenesis. Pα-synF was described previously as inclusions morphologically similar to Lewy bodies and Lewy neurites in PD patients. We discovered the existence of a conformationally distinct, nonfibrillar, phosphorylated α-syn species that we named "pα-syn*." We uniquely describe the existence of pα-syn* in PFF-seeded primary neurons, mice brains, and PD patients' brains. Through immunofluorescence and pharmacological manipulation we showed that pα-syn* results from incomplete autophagic degradation of pα-synF. Pα-synF was decorated with autophagic markers, but pα-syn* was not. Western blots revealed that pα-syn* was N- and C-terminally trimmed, resulting in a 12.5-kDa fragment and a SDS-resistant dimer. After lysosomal release, pα-syn* aggregates associated with mitochondria, inducing mitochondrial membrane depolarization, cytochrome C release, and mitochondrial fragmentation visualized by confocal and stimulated emission depletion nanoscopy. Pα-syn* recruited phosphorylated acetyl-CoA carboxylase 1 (ACC1) with which it remarkably colocalized. ACC1 phosphorylation indicates low ATP levels, AMPK activation, and oxidative stress and induces mitochondrial fragmentation via reduced lipoylation. Pα-syn* also colocalized with BiP, a master regulator of the unfolded protein response and a resident protein of mitochondria-associated endoplasmic reticulum membranes that are sites of mitochondrial fission and mitophagy. Pα-syn* aggregates were found in Parkin-positive mitophagic vacuoles and imaged by electron microscopy. Collectively, we showed that pα-syn* induces mitochondrial toxicity and fission, energetic stress, and mitophagy, implicating pα-syn* as a key neurotoxic α-syn species and a therapeutic target.

We analyze the effect of China's integration into the world economy on workers in the country and show that one important channel of impact has been internal migration. Specifically, we study the changes in internal migration rates triggered by the reduction in trade policy uncertainty faced by Chinese exporters in the U.S. This reduction is characterized by plausibly exogenous variation across products, which we use to construct a local measure of treatment, at the level of a Chinese prefecture, following Bartik (1991). This allows us to estimate a difference-in-difference empirical specification based on variation across Chinese prefectures before and after 2001. We find that prefectures facing the average decline in trade policy uncertainty experienced a 24% increase in their internal in-migration rate – this result is driven by migrants who are “non-hukou”, skilled, and in their prime working age. Finally, in those prefectures, working hours of “native” unskilled workers significantly increased, and internal migrants found employment in the places they migrated to.

The mechanisms of neuronal death in protein misfolding neurodegenerative diseases such as Alzheimer's, Parkinson's and prion diseases are poorly understood. We used a highly toxic misfolded prion protein (TPrP) model to understand neurotoxicity induced by prion protein misfolding. We show that abnormal autophagy activation and neuronal demise is due to severe, neuron-specific, nicotinamide adenine dinucleotide (NAD(+)) depletion. Toxic prion protein-exposed neuronal cells exhibit dramatic reductions of intracellular NAD(+) followed by decreased ATP production, and are completely rescued by treatment with NAD(+) or its precursor nicotinamide because of restoration of physiological NAD(+) levels. Toxic prion protein-induced NAD(+) depletion results from PARP1-independent excessive protein ADP-ribosylations. In vivo, toxic prion protein-induced degeneration of hippocampal neurons is prevented dose-dependently by intracerebral injection of NAD(+). Intranasal NAD(+) treatment of prion-infected sick mice significantly improves activity and delays motor impairment. Our study reveals NAD(+) starvation as a novel mechanism of autophagy activation and neurodegeneration induced by a misfolded amyloidogenic protein. We propose the development of NAD(+) replenishment strategies for neuroprotection in prion diseases and possibly other protein misfolding neurodegenerative diseases.

Despite their theoretical value in tackling principal–agent problems at low cost to firms there is almost no empirical literature on the prevalence and correlates of performance bonds posted by corporate executives. We show that they are an important feature in today's CEO labour market in China: around one-tenth of corporations deploy performance bonds and they are equivalent to around 14% of CEO cash compensation. Consistent with principal–agent theory bonds are negatively associated with firm sales volatility. The complementarity between bonds and other incentive mechanisms such as bonuses and stock holding is consistent with optimal reward structures for multi-tasking agents. Those CEOs posting bonds are higher in the Communist Party ranks, were promoted via tournaments, and run larger firms, findings consistent with using bonds as an incentive to attract and retain the most able workers. Although state-owned enterprises are just as likely as privately owned ones to use bonds in CEO contracts, some of the theoretical predictions which assume profit-maximising firms do not hold where the state has an ownership stake.

Prion diseases such as Creutzfeldt–Jakob disease (CJD) are incurable and rapidly fatal neurodegenerative diseases. Because prion protein (PrP) is necessary for prion replication but dispensable for the host, we developed the PrP–FRET-enabled high throughput assay (PrP–FEHTA) to screen for compounds that decrease PrP expression. We screened a collection of drugs approved for human use and identified astemizole and tacrolimus, which reduced cell-surface PrP and inhibited prion replication in neuroblastoma cells. Tacrolimus reduced total cellular PrP levels by a nontranscriptional mechanism. Astemizole stimulated autophagy, a hitherto unreported mode of action for this pharmacophore. Astemizole, but not tacrolimus, prolonged the survival time of prion-infected mice. Astemizole is used in humans to treat seasonal allergic rhinitis in a chronic setting. Given the absence of any treatment option for CJD patients and the favorable drug characteristics of astemizole, including its ability to cross the blood–brain barrier, it may be considered as therapy for CJD patients and for prophylactic use in familial prion diseases. Importantly, our results validate PrP-FEHTA as a method to identify antiprion compounds and, more generally, FEHTA as a unique drug discovery platform.

This paper examines whether only children have poor vision by exploiting the quasinatural experiment generated by the Chinese One‐Child Policy. The results suggest that being an only child increases the incidence of myopia by 9.1 percentage points. We further investigate the mechanisms through which being an only child affects the myopia and find that only children, as the only hope in a household, receive higher expectations in terms of academic performance and future educational attainment and pressure to succeed in life from parents, which contribute to the increased myopia. We also find that the school quality of only children is significantly higher than that of non‐only children. This study provides new insights into an important health consequence of One‐Child Policy in China.

This chapter discusses the research development of factor income distribution. In the following, we are going to review related research about labor’s share of income, which is a commonly used proxy for factor income distribution. We will not only discuss the research development based on the decline of labor’s share of income mainly in European countries from 1980s, but also examine the development of literature on the recent decline of labor’s share of income in China, starting from mid-1990s. By reviewing past research outcomes both at home and abroad, it is found that the decline of labor’s share of income is closely related to “two transitions” of world economy after the middle of 20th century.

This chapter decomposes the movement of labor’s share of income into employment, compensation and output effects since China’s reform and opening up. We find that the movement of labor’s share of income is mainly determined by the net effects of the opposite movement of compensation and output, and the employment effect is relatively small. Meanwhile, the paper distinguishes the decomposition of nominal and real labor’s share of income, and finds that the real labor’s share of income by considering the price factors reflects the current situation of national income distribution of China.

This chapter decomposes the labor’s share of income in industrial sector and finds the movement of industrial structure within the industrial sector explains minor part of the reason for declining labor’s share of income. We also analyze the effects of trade, technological progress and state-owned monopoly power by using the production cost model. It indicates that technological progress and decrease of monopoly power will impose a decrease on labor’s share of income. Ceteris paribus, the coefficient of import penetration rate in the trade variables is positive and significant. Regression in different stages shows that the changing of trade mode is main reason for declining labor’s share of income. In the time of import–export related processing trade in Pearl River delta, import penetration rate promote labor demand thus raise the labor’s share of income. While, in the time of export-led processing trade in Yangtze River delta, the simultaneous decline of import penetration rate and labor’s share of income is the result of lowering raw material and labor cost from profit maximizing enterprises. Therefore, the import penetration has different mechanisms on labor’s share of income in different development stages in China.

This chapter re-measures the labor’s share of income of income since the reform and opening up by amending and supplementing the corresponding data during 2004–2007. We find that the labor’s share of income decreases steadily after 1998. This chapter also further divides labor into raw labor and human capital. By using the individual level data of UHS, we find the human capital’s share of income has increased rapidly while the raw labor’s share of income decreases steadily during 1988–2007. By using extended MRW growth framework, we find that the movement of China’s national income distribution pattern is closely related to the unbalanced growth of three factors which are physical capital, human capital and raw labor.

Income distribution, as a research topic, has never lost its attractions to economists. Since the research about income distribution by Ricardo (1981), classical theory, neoclassical theory, Keynesian theory and modern economic theory have never stopped their study about income distribution throughout the history of past 200 years. Generally, income distribution can be divided into two aspects, i.e., size income distribution and functional income distribution. Size income distribution discusses the distributional relationship among different groups while functional income distribution focuses on distributional relationship of income among different factors.

This chapter provides new estimation of the labor’s share of income, distinguishes the nominal and real labor’s share of income, and discusses the impacts of such distinction on the movement trends of China’s labor’s share of income. We find that the real labor’s share of income by considering the price factors is lower than the estimated nominal value in the literature by 6–14 % with higher and longer decreasing trend, indicating the worsening situation of national income distribution and matching with the direct feeling of income distribution by ordinary workers.

This chapter constructs a theoretical model from the micro firm perspective and analyses the firm heterogeneity that will lead to significant differences among different types of firms. The theoretical model is extended to three types of firms those that are state-owned, private and foreign enterprises. Thus, this chapter discusses the impact of ownership restructuring of state-owned enterprises, privatization, and entry of foreign investment on the labor’s share of income during China’s economic transition and opening process. Utilizing the World Bank Investment Climate Survey, the paper investigates the difference of the labor’s share of income by types of ownership, and claims that change of ownership structure will reduce factor distortion and promote economic efficiency, which in turn will impose a positive and transitory impact on the decreasing labor’s share of income. By using System-GMM estimation, it shows that, after controlling for other factors, firm with private and foreign ownership have negative impacts on the labor’s share of income. By examining time series change of state-owned enterprises, it finds that their productivity rises dramatically two years after the ownership restructuring. The chapter also introduces the government enterprise relationship variable, which shows that competition among local government in attracting foreign enterprises in order to pursue GDP does exist. Finally, it is shown that the “foreign investment led” feature of China’s export enterprises may be the reason of the failure of neoclassic trade theory prediction for China.

The rapid pace of China’s economic and trade development has been considered as a great success since the entry of WTO in 2001. Most recently, China has succeeded in coping with the global financial crisis and achieved a rapid V-shaped recovery which rebounded to two digit growth rate and lead to strengthening its international status. Nevertheless, China has exposed many potential problems in face of the financial crisis which due to international and domestic unbalanced features of China’s economic operation system. The pattern of ‘China Manufacturing and World Consuming’ is a game with no winners, while the investment leaded economic development mode achieves high growth rate but without enriches its own residents. The current imbalanced economic development mode cannot be sustained and shall be changed in the future which is not only the consensus of economists at home and abroad, but also a striving goal for the Chinese government for its ‘12th Five-Year Plan’. However, China will face great and formidable challenges by changing the economic development mode to achieve an equilibrium state.

In this paper we focus on the changes in internal migration flows triggered by China's 2001 entry into the World Trade Organization (WTO). We use a difference-in-difference empirical specification based on variation across Chinese prefectures before and after 2001. We relate changes in internal migration rates to the reduction in trade policy uncertainty faced by Chinese exporters to the U.S., as measured by the normal-trade-relations (NTR) gap (Handley and Limao 2013, Pierce and Schott 2015). We find that Chinese prefectures facing a larger decline in their average NTR-gap experience a greater increase in internal migration. Our results also show that the impact on skilled and unskilled internal migration rates is consistent with the average skill intensity of export industries of a prefecture.

Severe acute respiratory syndrome (SARS) is a highly contagious and life-threatening disease that emerged in China in November 2002. A novel SARS-associated coronavirus was identified as its principal etiologic agent; however, the immunopathogenesis of SARS and the role of special CTLs in virus clearance are still largely uncharacterized. In this study, potential HLA-A*0201-restricted spike (S) and nucleocapsid protein-derived peptides were selected from an online database and screened for potential CTL epitopes by in vitro refolding and T2 cell-stabilization assays. The antigenicity of nine peptides which could refold with HLA-A*0201 molecules was assessed with an IFN-γ ELISPOT assay to determine the capacity to stimulate CTLs from PBMCs of HLA-A2+ SARS-recovered donors. A novel HLA-A*0201-restricted decameric epitope P15 (S411–420, KLPDDFMGCV) derived from the S protein was identified and found to localize within the angiotensin-converting enzyme 2 receptor-binding region of the S1 domain. P15 could significantly enhance the expression of HLA-A*0201 molecules on the T2 cell surface, stimulate IFN-γ-producing CTLs from the PBMCs of former SARS patients, and induce specific CTLs from P15-immunized HLA-A2.1 transgenic mice in vivo. Furthermore, significant P15-specific CTLs were induced from HLA-A2.1-transgenic mice immunized by a DNA vaccine encoding the S protein; suggesting that P15 was a naturally processed epitope. Thus, P15 may be a novel SARS-associated coronavirus-specific CTL epitope and a potential target for characterization of virus control mechanisms and evaluation of candidate SARS vaccines.

All that we know about the Chief Executive Officer (CEO) labour market in China comes from the studies of public listed companies and State-owned Enterprises (SOEs). This is the first attempt to examine the operation of the CEO labour market across all industrial sectors of the Chinese economy. We find that the influence of the State extends beyond SOEs into many privately owned firms. Government is often involved in CEO appointments in domestic firms and, when this is the case, the CEO has less job autonomy and is less likely to have pay linked to firm performance. Nevertheless, we find that incentive schemes are commonplace and include contracts linking CEO pay directly to firm performance, annual bonus schemes, the posting of performance bonds, and holding company stock. The elasticity of pay with respect to company performance is one or more in two-fifths of the cases where CEOs have performance contracts, suggesting many face high-powered incentives. We also show that State-owned and domestic privately owned firms are more likely than foreign-owned firms to use incentive contracts.

CEO incentive contracts are commonplace in China but their incidence varies significantly across Chinese cities. We show that city and provincial policy experiments help explain this variance. We examine the role of two policy experiments: the use of Special Economic Zones (SEZs) to attract Foreign Direct Investment (FDI), and the privatisation of State-Owned Enterprises (SOEs). The introduction of SEZs is found to be uncorrelated with the prevalence of CEO incentive contracts. However, firms are more likely to use such contracts in areas that saw rapid SOE privatisation, irrespective of the firm’s own current ownership status and irrespective of the size of the SOE sector in the late 1970s. The positive effect of privatisation is robust to various estimation techniques and model specifications. These findings suggest that domestic privatisation policies have been more influential than FDI in driving the expansion of incentive contracts in China.

The Unfolded Protein Response (UPR) indirectly regulates extracellular proteostasis through transcriptional remodeling of endoplasmic reticulum (ER) proteostasis pathways. This remodeling attenuates secretion of misfolded, aggregation-prone proteins during ER stress. Through these activities, the UPR has a critical role in preventing the extracellular protein aggregation associated with numerous human diseases. Here, we demonstrate that UPR activation also directly influences extracellular proteostasis through the upregulation and secretion of the ER HSP40 ERdj3/DNAJB11. Secreted ERdj3 binds misfolded proteins in the extracellular space, substoichiometrically inhibits protein aggregation, and attenuates proteotoxicity of disease-associated toxic prion protein. Moreover, ERdj3 can co-secrete with destabilized, aggregation-prone proteins in a stable complex under conditions where ER chaperoning capacity is overwhelmed, preemptively providing extracellular chaperoning of proteotoxic misfolded proteins that evade ER quality control. This regulated co-secretion of ERdj3 with misfolded clients directly links ER and extracellular proteostasis during conditions of ER stress. ERdj3 is, to our knowledge, the first metazoan chaperone whose secretion into the extracellular space is regulated by the UPR, revealing a new mechanism by which UPR activation regulates extracellular proteostasis.

CEO incentive contracts are commonplace in China but their incidence varies significantly across Chinese cities. We show that city and provincial policy experiments help explain this variance. We examine the role of two policy experiments: the use of Special Economic Zones (SEZs) to attract foreign direct investment (FDI), and the rate at which state owned enterprises (SOEs) were privatised. CEO incentive contracts are negatively correlated with foreign ownership and with the introduction of FDI via SEZs. However, the SEZ effect disappears having accounted for the city-level composition of firms and executives. Rapid SOE privatisation is associated with higher city and firm-level adoption of CEO incentive contracts, irrespective of the firm's own current ownership status. The positive effect of privatisation is robust to various estimation techniques and model specifications.

All that we know about the CEO labour market in China comes from studies of public listed companies and state-owned enterprises (SOEs). This paper is the first to examine the operation of the CEO labour market across all sectors of the Chinese economy. We do so using World Bank enterprise data for the first part of the 21st Century. Incentive schemes are commonplace throughout the economy and include contracts linking CEO pay directly to firm performance, annual bonus schemes, the posting of performance bonds, and holding company stock. These incentive mechanisms appear to complement rather than substitute for one another. The elasticity of pay with respect to company performance is one or more in two-fifths of the cases where CEO's have performance contracts, suggesting many face high-powered incentives. CEO's also face a real dismissal threat and financial penalties if they fail to deliver. Incentive contracts are used to attract the most talented executives, as indicated by educational attainment and position in the Communist Party. However, government involvement in the appointment of a CEO reduces the likelihood that the CEO will receive an incentives-based contract, perhaps because governments appoint "bureaucrats" to perform roles which incorporate social and political as well as economic goals. Firms with good corporate governance are more likely to deploy incentive contracts. A picture emerges of a well-functioning labour market for executives in China that exhibits many of the traits common to CEO labour markets in the West.

Prion diseases are lethal infectious neurode -generative diseases affecting both animals and humans. In humans, Creutzfeldt–Jakob disease is sporadic, affecting mainly people over 60 years of age, and it is either iatrogenic or genetic with a penetrance of 1. While scrapie in sheep seems to be nontransmissi -ble to humans, bovine spongiform encepha -lopathy, a disease that ravaged British and, to a lesser extent, European cattle herds in the 1990s, is a zoonosis. Chronic wasting disease in cervids is a concern as the disease is geographically expanding in the USA.Prion diseases are characterized by the accumulation, in brain and lymphoid tis-sue, of PrP

Using panel data for all of China's public listed firms over the period 2001-2010 we examine how firms have recruited and rewarded their executives over a decade of huge growth and turbulence. CEO pay is sensitive to firm performance, although the elasticities are lower than for the United States and Europe, especially with respect to returns on assets (ROA). CEO pay rises with firm size and growth, with elasticities resembling those for the United States. We find no dramatic response to the stock market crash of 2007/08. The elasticity of pay to stock returns falls to zero after the crash, while elasticities with respect to sales and ROA remain significant. Executive cash compensation rose steeply throughout the period - in contrast to the United States. There are steep gradients in executive compensation within firms, consistent with tournament prizes, and around two-thirds of CEO appointments are internal promotions. Within-firm executive compensation rose at a faster rate than executive compensation across firms, helping to explain why CEO turnover rates declined a little over the decade. Turnover rates did not spike with the stock market crash. Privatisation and reforms to corporate governance contributed to growth in executive compensation. A picture emerges of an executive labour market in which firms are linking pay to performance and relying on incentive structures within firms to foster executive talent.

Despite their theoretical value in tackling principal-agent problems at low cost to firms there is almost no empirical literature on the prevalence and correlates of performance bonds posted by corporate executives. Using data for China we examine their incidence and test propositions from principal-agent theory regarding their correlates. Around one-tenth of corporations deploy performance bonds. They are sizeable relative to CEO cash compensation. Ceteris paribus, CEO's posting performance bonds are more likely than other CEO's to have their compensation linked to firm performance in other ways and the elasticity of their pay with respect to firm performance is greater. They are also more likely to hold company stock. Thus bonds appear to be complements to rather than substitutes for other forms of corporate incentive. The negative association between bonds and sales volatility is consistent with principal-agent theory. Positive associations between performance bonds and firm age, the CEOs ranking in the Communist Party, and city-level clustering in the use of bonds are all consistent with 'legacy' effects dating back to the use of performance bonds in the early reform period. The only corporate governance measure that is strongly and robustly associated with an increased use of bonds is employee representation on the board of directors.

Prion diseases are infectious and belong to the group of protein misfolding neurodegenerative diseases. In these diseases, neuronal dysfunction and death are caused by the neuronal toxicity of a particular misfolded form of their cognate protein. The ability to specifically target the toxic protein conformer or the neuronal death pathway would provide powerful therapeutic approaches to these diseases. The neurotoxic forms of the prion protein (PrP) have yet to be defined but there is evidence suggesting that at least some of them differ from infectious PrP (PrP Sc ). Herein, without making an assumption about size or conformation, we searched for toxic forms of recombinant PrP after dilution refolding, size fractionation, and systematic biological testing of all fractions. We found that the PrP species most neurotoxic in vitro and in vivo (toxic PrP, TPrP) is a monomeric, highly α-helical form of PrP. TPrP caused autophagy, apoptosis, and a molecular signature remarkably similar to that observed in the brains of prion-infected animals. Interestingly, highly α-helical intermediates have been described for other amyloidogenic proteins but their biological significance remains to be established. We provide unique experimental evidence that a monomeric α-helical form of an amyloidogenic protein represents a cytotoxic species. Although toxic PrP has yet to be purified from prion-infected brains, TPrP might be the equivalent of one highly neurotoxic PrP species generated during prion replication. Because TPrP is a misfolded, highly neurotoxic form of PrP reproducing several features of prion-induced neuronal death, it constitutes a useful model to study PrP-induced neurodegenerative mechanisms.

Previously, we reported that a 7-mer HLA-A11-restricted peptide (YVNTNMG) of hepatitis B virus (HBV) core Ag (HBcAg88–94) was associated with heat shock protein (HSP) gp96 in liver tissues of patients with HBV-induced hepatocellular carcinoma (HCC). This peptide is highly homologous to a human HLA-A11-restricted 9-mer peptide (YVNVNMGLK) and to a mouse H-2-Kd-restricted 9-mer peptide (SYVNTNMGL). To further characterize its immunogenicity, BALB/c mice were vaccinated with the HBV 7-mer peptide. It was found that a specific CTL response was induced by the 7-mer peptide, although the response was ∼50% of that induced by the mouse H-2-Kd-restricted 9-mer peptide, as detected by ELISPOT, tetramer, and 51Cr release assays. To evaluate the adjuvant effect of HSP gp96, mice were coimmunized with gp96 and the 9-mer peptide, and a significant adjuvant effect was observed with gp96. To further determine whether the immune effect of gp96 was dependent on peptide binding, the N- and C-terminal fragments of gp96, which are believed to contain the putative peptide-binding domain, were cloned and expressed in Escherichia coli. CTL assays indicated that only the N-terminal fragment, but not the C-terminal fragment, was able to produce the adjuvant effect. These results clearly demonstrated the potential of using gp96 or its N-terminal fragment as a possible adjuvant to augment CTL response against HBV infection and HCC.

AIM: Most studies on the immune effect of gp96 were focused on its enhancement of CTLs. It is interesting to know whether gp96 could influence the humoral immune response, and whether the recombinant N-terminal fragment of gp96 could substitute native gp96 to stimulate the immune system. METHODS: gp96 isolated from livers of normal mice and its N-terminal fragment (amino acid 22-355) expressed in E coli were used for immunization of BALb/c mice. Eight groups of mice received one of the following regiments subcutaneously in 100 μL phosphate buffered saline (PBS) at an interval of 3 wk. Group 1: PBS only; group 2: gp96 only; group 3: N-terminal fragment only; group 4: HBsAg only; group 5: HBsAg+gp96; group 6: HBsAg+N-terminal fragment; group 7: HBsAg+incomplete Freud’s adjuvant; group 8: HBsAg+N-terminal fragment (95 °C heated for 30 min). Serum anti-HBsAg antibody levels were assayed by ELISA. CTL responses in splenocytes were analyzed by ELISPOT after the last vaccination. RESULTS: The average titer of serum anti-HBsAg antibody in the mice immunized with HBsAg together with gp96 or its N-terminal fragment were much higher than those immunized with HBsAg alone detected by ELISA. The cellular immune response of the mice immunized with HBsAg together with gp96 or its N-terminal fragment was not different with those immunized with HBsAg alone measured by ELISPOT assay. CONCLUSION: gp96 or its N-terminal fragment greatly improved humoral immune response induced by HBsAg, but failed to enhance the CTL response, which demonstrated the potential of using gp96 or its N-terminal fragment as a possible adjuvant to augment humoral immune response against HBV infection.