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Background Crohn's disease (CD) is a chronic nonspecific inflammatory bowel disease. Current CD therapeutics cannot fundamentally change the natural course of CD and therefore it is of great significance to find new treatment strategy for CD. Preclinical and clinical studies have shown that mesenchymal stromal cells (MSCs) are a promising therapeutic approach, However，the mechanism of MSC alleviating CD and how MSC affects gut microbes is still unclear and needs to be further elucidated. MethodsWe used 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce experimental colitis in mice, and analyzed the microbiota in the fecal samples, which come from the control group, the TNBS group and the TNBS+MSC group with fecal 16S rDNA sequencing. Subsequent analysis of alpha and beta diversity were all performed based on the rarified data. PICRUStII analysis was subsequently performed from 16S rRNA gene sequences to infer gut microbiome functions. ResultsMSCs treatment improved the TNBS-induced colitis by increasing survival rates, relieving symptoms. A distinct bacterial signature was found in the TNBS group that differed from the TNBS+MSC group and controls. MSC alleviated the increased activities of sulfur and riboflavin metabolism.Meanwhile some metabolisms such as biosynthesis of amino acids，lysine biosynthesis, sphingolipid metabolism，secondary bile acid biosynthesis were decreased in the TNBS group when compared with the control group and the TNBS+MSC group.ConclusionsMSC treatment could modulate the dysregulated metabolism pathways in mice with colitis, restoring the abnormal microbiota function to a normal situation as the control group.

Photocatalytic CO2 reduction to CO by a Ni(II) complex with an S2N2-type tetradentate ligand exhibits high efficiency and selectivity. Here, a density functional theory (DFT) study of the reaction ...

Infection with syphilis is still a major public health problem. The precise data for syphilis seroprevalence in the populations will help to develop a strategy for prevention and treatment of it. However, the data for syphilis prevalence in continuous years among volunteer blood donors in China is rare.A retrospective study forA total of 992,646 volunteer blood donors were analyzed and the positive rate of TP antibody in the blood donors was 0.43%. From 2010 to 2019, the positive rates of TP antibody were 0.53%, 0.51%, 0.51%, 0.43%, 0.36%, 0.18%, 0.11%, 0.12%, 0.11%, and 0.10%, respectively. The positive rates of TP antibody were significantly different among blood donor age group (The syphilis seroprevalence is low in the blood donors of the Hangzhou area, and the positive rate of blood donors is associated with age, educational level, and times of blood donation. Increasing the number of repeat blood donations is helpful to improve blood safety.

We examine why many firms disclose internal control weaknesses (ICW) under section 404 of Sarbanes-Oxley Act after previously reporting effective internal control (IC). We find that about half of the cross-sectional ICW determinant variables either do not change significantly from Year T-1 to Year T or change in a direction that is not expected to cause IC deterioration. The reported deterioration in IC can be attributed to increases in audit fee, management turnover, restatement, financial distress, firm size, and decrease in financial activities. Consistent with an agency hypothesis that managers try to manipulate the IC process when firm performance declines, the reported deterioration in IC is also associated with poor stock returns in the year before disclosure. ICW disclosure is more likely when poor stock return is combined with higher sensitivity of executive compensation to stock price change.

We examine the decision to list in the U.S. markets by foreign firms through American Depository Receipts (ADRs). There is a high positive correlation between the valuation of existing ADRs and the number of new ADR listings next year. ADR listing is more likely when existing ADRs are valued higher. The subsequent operating and stock performance of ADR firms listed in hot years is significantly worse than those of ADR firms listed in cold years. These results are consistent with the hypothesis that market timing is an important motivation for foreign firms to list in the U.S. equity markets.

Background and objectives A worldwide pandemic of coronavirus disease 2019 (COVID-19) has affected millions of people. A 'closed-off management' protocol has been launched nationwide in China to cope with this major public health emergency. However, these procedures may cause a crisis for blood donation and blood supply. In this study, we assessed the impact of the COVID-19 pandemic on blood donation and supply in Zhejiang province, which could provide reference and insight for developing countermeasures in other countries. Materials and methods Blood donor and supply information from 38 blood centres during the Spring Festival of 2019 and 2020 were reviewed. A self-administered questionnaire was carried out. Results Due to the COVID-19 pandemic, the number of whole blood donors dropped by 67%. The success rate of recruitment for donations dropped by 60%. Most respondents (81·2%) were worried about the 'possibility of acquiring COVID-19 during blood donation'. The total amount of RBCs supply dropped by 65%. In the first week of the outbreak, the weekly amount of issued RBC units (10171·5 u) was almost six times higher than the collected units (1347·5 u). The mean haemoglobin value for RBCs transfusion was about 6·3 g/dl. About 4% of RBCs and 2·8% of frozen plasma were used in COVID-19 patients. Conclusion The secondary consequences of the COVID-19 pandemic are blood shortages caused by the unavailability of blood donors, and this is likely to be replicated in many countries with high burdens of COVID-19. Practical actions to broaden sources and reduce use for the global crisis must be taken proactively.

We examine insider selling for initial public offering (IPO) firms using a sample of 1868 IPOs between 1988 and 2012. We find that overvalued IPOs have higher probability of offering secondary shar...

We propose reduced investment as a potential explanation for why firms with internal control weakness (ICW) exhibit lower valuation relative to non-ICW firms. We show that ICW firms significantly reduce investment around ICW disclosure and also have poor stock performance. Additional evidence shows that many of the investment reductions have been announced during the year before ICW disclosure. A possible explanation for investment reductions is the higher costs of financial friction associated with ICW. Consistent with this explanation, we show that ICW firms with credit ratings do not reduce their investment as much and have much better stock performance than ICW firms without credit ratings.

We examine the valuation of ADR IPOs and find that they are valued similarly to U.S. domestic IPOs but significantly higher than U.S. seasoned firms. This higher valuation is not caused by differences in firm size, growth opportunity, profitability, listing exchange, diversification benefit, foreign exchange risk, investor protection, or market liquidity as suggested by previous studies. Moreover, they experience significant declines in earnings and their stocks underperform U.S. seasoned by more than 20% in the three years after IPO. We show that ADR IPOs are timed to take advantage of overoptimistic in U.S. equity markets, supporting windows of opportunity theory.

Using a sample of 4441 IPOs from the US, we find that IPO firms with larger proportional offering size have lower valuation. The sizes of both primary share offering and secondary share offering are negatively related to IPO firm valuation. The valuation measures are positively related to the levels of capital expenditure and R&D before IPO, lending support to explanations based on Jensen (JAMA 76:323–329, 1986)’s free cash flow hypothesis. We also find evidence consistent with negative signals from larger secondary share offering size. Results of tests about long-run IPO stock performance do not support the hypothesis that IPO stock demand curve is downward sloping.

PurposeThe purpose of this paper is to answer the following three questions about the new capital raised in initial public offerings (IPOs): why do some IPO companies raise a lot of new capital while some others do not? Where do the IPO companies use the new capital they raise in IPOs? How does the use of new capital affect the operating performance of IPO companies?Design/methodology/approachMatching firm approach, univariate and regression tests.FindingsThis paper finds that companies with higher research and development (R&D) spending, higher capital expenditure, lower working capital and more long-term debt tend to raise more capital in IPOs. These firms also spend more on R&D and capital expenditure. The results also suggest that the more the new capital firms raise in IPOs, the lower operating performance they have in subsequent years. However, firms spending more new capital on R&D and capital expenditure seem to perform better.Originality/valueThese results help us understand the behavior of IPO firms.

Understanding the sorption states of shale gas on shale has an important significance for the exploration and development of shale gas. In the present study, the adsorption mechanisms of CH4, CO2, and H2O molecules on the undoped and Al or Al&Mg doped illite (001) surfaces have been investigated using density functional theory. The nine different adsorption sites (H1-H3, T1-T3, and B1-B3) on the surfaces were considered. The calculations show that for all the three molecules, the Al&Mg-doped illite (001) surface has the strongest adsorption ability while the undoped one is the weakest. Besides, the adsorption ability on each of the three surfaces increases in the order of CH4, CO2 and H2O. The H2O molecule having the strongest adsorption on the three surfaces is ascribed to the formation of hydrogen bonds between the adsorbate and adsorbent. The adsorption of the CH4 and CO2 molecules on each of the three surfaces is characterized as a physical adsorption, but that of the H2O molecule is not. In-depth PDOS (partial density of states) and Hirshfeld charge analyses suggest that there exists a small amount of electron transfer from the adsorbent to adsorbate after their adsorptions on the three surfaces. The Al&Mg-doped illite surface having the strongest adsorption ability for each of the three molecules should be attributed to its surface O atoms having more negative charges.

We examine whether alleviating financial constraints is one of the motives for non-U.S. firms to cross-list in stock markets in the United States. Using payout ratio, payout level, and WW index (Whited and Wu, 2006) as measures of financial constraints, we find that firms with higher financial constraints are more likely to cross-list in the U.S. This pattern is driven by small firms, which tend to be financially constrained. After firms cross-list, they significantly increase their payout ratio and payout level. Small firms have more increases in payouts than large firms. WW index decreases for small firms after cross-listing. Tests about cash flow sensitivities of cash also suggest that the decline in financial constraints is more significant for small firms. Overall the results suggest that relief from financial constraints may be an important motive for cross-listing, especially for small firms.

We find that firms reporting internal control material weakness (ICW) under Section 404 of Sarbanes–Oxley Act (SOX) have 13% lower valuation than non-ICW firms based on Tobin's q. This valuation difference is mainly driven by stock underperformance of more than 13% during the year before ICW disclosure. The ICW firms that remedy the internal control weakness in the subsequent year have much better stock performance compared to those firms that fail to remedy existing ICW problems. We further show a better stock performance in the year before disclosure if a SOX 404 ICW firm has prior SOX 302 ICW disclosure more than one year earlier. All these results are consistent with the hypothesis that the equity market has incorporated the negative information associated with SOX 404 ICW reports before the actual disclosures are made.

Introduction This paper proposes a method for profile-decomposing the output from a segmented multi-subpixels 2-D sensor array, that is, a method for obtaining the spatial concentration distribution of each component odor using the output from the image sensor. Image sensors corresponding to our sense of vision and the advanced image analysis technology have greatly changed our social life. Similarly, the development of an odor image sensor capable of measuring odor characteristics in space and the method for profile-decomposing the output from the sensor is expected to bring a great change to our social life. Two of the co-authors of this paper developed an odor image sensor device to measure residual odor traces on the surface. In the device, many chips composing of 4 different odor sensors that response differently to odors (we call this chip as a segmented 4-subpixels sensor) are arranged in 2-dimmensions. The schematic is shown in Figure1. This odor image sensor can be used to measure four-dimensional odor characteristics at each point. Non-negative Matrix Factorization is a method of decomposing a non-negative matrix into a non-negative weight matrix and a non-negative feature matrix. When the number of component odors, that is, the number of basis vectors is given, the output data from device can be decomposed to a concentration matrix expressing concentration of each component odor at each point and a profile matrix expressing response pattern of segmented 4-subpixels sensor to each component odor with Non-negative Matrix Factorization (NMF). We assume the followings: A linear relationship holds true between the concentration of component odor and the output of each segmented subpixel sensor. All segmented C-subpixels sensor chips arranged in 2 dimensions have the same response property to odors. The concentration of component odor in the segmented C-subpixels sensor chip is uniform. If these three assumptions hold true, the output data of device can be completely expressed as the product of the concentration matrix and the profile matrix. However, in reality these assumptions do not always hold and we consider these assumptions to be approximately true by miniaturization of the chip and calibration of the sensor output.As for determining the number of component odors, in this study, we verified how effective the four information criteria are for estimating the number of component odors in profile-decomposition by simulation experiments using artificial data including noise with various variance. In addition, profile-decomposition and four kinds of information criteria are performed on the data when using the device to measure the mixture of two component odors. Applying NMF and model selection We assume that there are I chips on the device, and C sensors on each chip, there are K component odors on the area covered by I chips. Let the element aik in the matrix A (concentration matrix) denote the concentration of the k-th component odor at the position i, and the element bkc in matrix B (profile matrix) represent the output of the c-th odor sensor when measuring unit concentration of k-th component odor. According to the three assumptions mentioned in the introduction, the output of the device represented by matrix X can be expressed as (1), here E is a noise matrix that follows a normal distribution. In practical applications, on the contrary, the output matrix is decomposed into the concentration matrix and the profile matrix. In this paper, we use (2) as the objective function. The algorithm proposed by Daniel D. Lee and H. Sebastian Seung is shown as Figure2. An example of decomposing artificial output data without noise is shown in Figure3. The number of component odors is the number of basis vectors in NMF. In this study, we conducted four kinds of information criterion to estimate the number of component odors. Equation (3), (4), (5), (6) are the formulas for calculating the four information criteria which are AIC, AICc, BIC and MDL. Here k is the degree of freedom of the model, N is the number of elements in the X, L is the maximum likelihood function. Experiment In the simulation experiment, we randomly generate matrices A and B. The values of the elements in matrix A range from 0 to 1, and the values of the elements in matrix B range from 0 to 25. According to (1), the elements in the matrix X is calculated as (7), eij is generated from normal distribution N(0, σ2 ) . Here if xij < 0, xij = 0. We used each of four information criteria to estimate the number of component odors with different σ2 . We conducted the estimation experiments 360 times for one value of σ2 . The results are shown in Figure4. For the real data, we decomposed the data obtained by the odor image sensor device and estimated the number of component odors. The actual number of component odors was two. The results are shown in Table1. Among the three methods, only AICc correctly estimated the number of component odors. Conclusion We propose the method based on NMF and information criterion for analyzing the output data obtained by the odor image sensor device. We used four kinds of information criterion to estimate the number of component odors. For the actual observed data by the odor image sensor device, AICc correctly estimated the number of component odors. Figure 1

We examine private issuance of public equity (PIPE) in China, and our results suggest that PIPE investors benefit from the price manipulation before and after issuance. These investors tend to cash out after lockup expiration and make large profits. We also find evidence that the trading of PIPE investors after lockup expiration is informed. Tests about the abnormal returns in the three years after lockup expiration suggest that at least part of the benefits PIPE investors receive come from wealth transfer from outside investors. Overall, PIPE issuers in China seem to use an opaque mechanism to compensate PIPE investors.

We examine the information content of changes in shareholdings after private issuance of public equity (PIPE) by mutual funds that participate in PIPEs in China. The results show that the changes in shareholdings are positively related to alpha and cumulative abnormal return (CAR) for PIPE issuers with high information asymmetry, suggesting that the participating mutual funds have superior information. These results are robust after controlling for investment skill, geographic location, and alumni relation. The positive relation between shareholding change and information content is driven by PIPE issuers with weaker corporate governance. In addition, the positive relation is stronger when the placement discount is lower. These results are consistent with a hypothesis that controlling shareholders/management in Chinese PIPE firms may collude with mutual funds to do tunneling.

A static output feedback fuzzy (SOFF) control approach is proposed in order to deal with the problem of syn- chronization of two identical hyperchaotic systems. The T-S fuzzy model with its small number of fuzzy IF-THEN rules is employed to represent many typical nonlinear hyperchaotic systems. Based on the T-S fuzzy hyperchaotic models and Lyapunov stability theory, a necessary condition for the existence of robust SOFF controllers is presented in terms of a set of matrix inequalities, which guarantees the stable synchronization of two different hyperchaotic systems. An iterative lin- ear matrix inequality (ILMI) algorithm is proposed to compute the feedback gains of the suboptimal SOFF controller. Fi- nally, numerical examples are given to demonstrate the validity and effectiveness of the proposed fuzzy modeling and synchronization scheme of the hyper chaotic systems.

Described herein are structure-activity relationship studies that resulted in the optimization of the activity of members of a class of cyclopropyl-fused indolobenzazepine HCV NS5B polymerase inhibitors. Subsequent iterations of analogue design and syntheses successfully addressed off-target activities, most notably human pregnane X receptor (hPXR) transactivation, and led to significant improvements in the physicochemical properties of lead compounds. Those analogues exhibiting improved solubility and membrane permeability were shown to have notably enhanced pharmacokinetic profiles. Additionally, a series of alkyl bridged piperazine carboxamides was identified as being of particular interest, and from which the compound BMS-791325 (2) was found to have distinguishing antiviral, safety, and pharmacokinetic properties that resulted in its selection for clinical evaluation.

We examine the regression model used in the literature to test the signaling model in Leland and Pyle [7] and find that the model may produce positive and significant coefficients for the independent variables even when the inputs are randomly generated. The problem is illustrated by two examples: a theoretical proof based on a uniform distribution and a bootstrap simulation based on actual data. Our studies show that the misleading results are caused by some natural constraints in the regression model.

Presented here are initial structure-activity relationship (SAR) studies on a series of novel heteroaryl fused tetracyclic indole-based inhibitors of the hepatitis C viral polymerase, NS5B. The introduction of alternative heterocyclic moieties into the indolo-fused inhibitor class significantly expands the reported SAR and resulted in the identification of pyridino analogs, typified by compounds 44 and 45 that displayed excellent potency against the NS5B polymerase of both HCV 1a and HCV 1b genotypes.

Structure based rationales for the activities of potent N-benzyl-4-heteroaryl-1-(phenylsulfonyl)piperazine-2-carboxamide inhibitors of the hepatitis C viral polymerase are described herein. These compounds bind to the hepatitis C virus non-structural protein 5B (NS5B), and co-crystal structures of select examples from this series with NS5B are reported. Comparison of co-crystal structures of a potent analog with both NS5B genotype 1a and genotype 1b provides a possible explanation for the genotype-selectivity observed with this compound class and suggests opportunities for the further optimization of the series.

We revisit the relationship between ownership dispersion and market liquidity. For ownership dispersion, we consider two dimensions: number of shareholders and blockholder ownership. For market liquidity, we consider four categories of liquidity measures: spreads, probability of informed trading (PIN), depth, and volume. Our sample includes NASDAQ firms in addition to NYSE and AMEX firms. We find several relations that are not documented in the extant Finance literature. Overall, our test results are consistent with the idea that higher ownership dispersion improves market liquidity.

BACKGROUND: In 2001, the blood collection agencies of Zhejiang Province adopted a unified information system, but when a blood product was transferred from the collection and processing facility inventory to some other inventories, because of lacking the unique identifying ability between facilities, the numbers might be overlapped. The exchange of blood units between agencies needed change of labels, and it was very complicated. The SARS outbreak in 2003 made this problem more prominent. Therefore, we decided to redevelop a new information system based on ISBT 128 to solve this problem. STUDY DESIGN AND METHODS: We registered with ICCBBA and obtained the technical documentation and database. We requested the new product description code from ICCBBA and properly adjusted the incompatibility between ISBT 128 and the national standards. We redesigned the information system and labels and validated some related equipment and the laboratory information system. RESULTS: In May 2005, we completed the development of the new information system based on ISBT 128, and by the end of 2005, all the blood collection agencies of the Zhejiang Province began to use ISBT 128. As a result, the product information in blood collection agencies of Zhejiang Province can be shared, and the exchange of blood products between agencies became safe and rapid. It was highly praised by the nation's Ministry of Health. CONCLUSIONS: ISBT 128 was successfully implemented in Zhejiang Province.

Booth and Chua [Booth J., Chua L. Ownership dispersion, costly information, and IPO underpricing. Journal of Financial Economics 1996; 41; 291–310] hypothesize that IPOs are underpriced to promote ownership dispersion, which in turn increases aftermarket liquidity of IPO stocks. We examine a sample of 1179 Nasdaq IPOs and find that underpricing is positively correlated with the number of non-block institutional shareholders after IPO but negatively correlated with the changes in the total number of shareholders. Firms with many non-block institutional shareholders tend to have high liquidity in the secondary market. These results provide support to Booth and Chua's hypothesis. Underpricing also has direct effects on secondary market liquidity after controlling for ownership structure and other factors.

Assuming that initial public offering (IPO) issuers can value their own firms more accurately, we test the hypothesis that the stock markets tend to overvalue IPOs. Using the lower limit of initial filing price range as issuers’ reservation price, we estimate the premiums of IPO first day closing price and first month closing price over the reservation price using 3,138 initial public offerings (IPOs) from 1983 to 2012. We find that the price premiums are positively related to proxies for market over-optimism and uncertainty. IPOs with higher price premiums have worse stock performance in the long run. The results are robust to various economic specifications. The findings are consistent with the argument that the stock markets get over- optimistic about IPOs from time to time.

We fi nd that IPO underpricing is positively related to post-IPO growth in sales and EBITDA, but is not signifi cantly related to growth in earnings. Our evidence suggests that accrual reversals or earnings management may cause this inconsistency. We interpret the growth rates of sales and EBITDA as measures of fi rm quality, and conclude that our evidence supports the notion that IPO fi rms with greater underpricing are of better quality. Our tests on analysts’ earnings forecast errors show that analysts are less positively biased in their earnings forecasts for IPO fi rms that have greater underpricing. In this paper we examine the relation between initial public offering (IPO) underpricing and postIPO growth rates of accounting performance variables. Previous research on IPOs suggests that IPO underpricing is related to the quality of the IPO fi rms (Allen and Faulhaber, 1989, Welch, 1989, Grinblatt and Hwang, 1989, and Rock, 1986). If we use growth rates of accounting performance variables (such as earnings) as measures of fi rm quality, then this suggestion implies a positive relation between IPO underpricing and growth rates. Our hypothesis is that IPO fi rms with greater underpricing should have higher post-IPO growth rates of accounting performance variables. However, rather than just concentrate on growth in earnings, we also include growth in EBITDA and growth in sales. Relative to earnings, these latter variables are more diffi cult for managers to manipulate. Thus, to reduce the possible contamination of our analysis by earnings management strategies, we consider the growth rates of earnings, EBITDA, and sales, and how they relate to IPO underpricing. Consistent with our hypothesis, we fi nd that underpricing is positively related to growth in sales and EBITDA in the fi ve years following an IPO. These results suggest that the IPOs with greater underpricing have higher quality. We also fi nd that IPO growth rates in earnings are much lower than the growth rates in sales and EBITDA. Further tests show that this inconsistency is likely caused by earnings management at the time of the IPO, which infl ates earnings initially and thus reduces earnings growth rates in subsequent years. This result suggests that earnings growth rates may not be accurate measures of IPO fi rm quality compared to sales and EBITDA growth rates. We fi nd that the fi rms with greater underpricing experience larger decreases in accruals after the fi rst year. This fi nding implies that earnings management may also reduce the correlation between IPO underpricing and earnings growth rates. We examine the accuracy of analysts’ earnings forecasts to determine how analysts react to the relation between IPO growth rates and IPO underpricing. If analysts are misled by earnings We thank Mark Huson, participants at the 2005 Northern Finance Association Conference, and, in particular, Bill Christie (the Editor) and an anonymous referee for helpful comments and suggestions. The authors gratefully acknowledge the contribution of Thompson Financial for providing earnings forecast data, available through I/B/E/S (Institutional Brokers Estimate System).

Purnanandam and Swaminathan [Purnanandam, A., Swaminathan, B. 2004. Are IPOs really underpriced? Review of Financial Studies, 17, 811–848.] find that IPOs are overvalued at the offer price relative to value metrics based on industry peer price multiples. I discuss some possible problems in their valuation methodology and find that IPOs are not overvalued after steps are taken to address the problems. More importantly, when I examine the long-run performance of IPO firms and their industry peers, I find that IPOs do not underperform their industry peers in the 5 years after IPO. This casts doubt to the argument that IPOs are overvalued.

I examine the relation between initial public offering (IPO) long-run stock performance and the amount of cash raised by the firm in the offering. I find that IPOs raising more cash have poorer long-run performance. The result is robust to different measurement methods. The evidence suggests that the market underreacts to free cash flow related agency problems in IPOs. Consistent with this interpretation, I find that IPO long-run performance is more sensitive to the new cash raised in the offering if an IPO firm has lower capital expenditure or higher opening bid-ask spread.

N-Benzylic-substituted glycine sulfonamides that reversibly inhibit diacylglycerol (DAG) lipases are reported. Detailed herein are the structure activity relationships, profiling characteristics and physico-chemical properties for the first reported series of DAG lipase (DAGL) inhibitors that function without covalent attachment to the enzyme. Highly potent examples are presented that represent valuable tool compounds for studying DAGL inhibition and constitute important leads for future medicinal chemistry efforts.

A phenotypic high-throughput cell culture screen was performed to identify compounds that prevented proliferation of the human Papilloma virus type 16 (HPV-16) transformed cell line Ca Ski. A series of quinoxaline compounds exemplified by Compound 1 was identified. Testing against a panel of cell lines demonstrated that Compound 1 selectively inhibited replication of all HPV-16, HPV-18, and HPV-31 transformed cell lines tested with 50% Inhibitory Concentration (IC50) values of 2 to 8 μM relative to IC50 values of 28 to 73 μM in HPV-negative cell lines. Treatment with Compound 1 resulted in a cascade of multiple apoptotic events, including selective activation of effector caspases 3 and 7, fragmentation of cellular DNA, and PARP (poly(ADP-ribose) polymerase) cleavage in HPV-positive cells relative to HPV-negative cells. Unregulated proliferation of HPV transformed cells is dependent on the viral oncogenes, E6 and E7. Treatment with Compound 1 resulted in a decrease in HPV E7 protein in Ca Ski cells. However, the timing of this reduction relative to other effects of compound treatment suggests that this was a consequence, rather than a cause, of the apoptotic cascade. Likewise, compound treatment resulted in no obvious effects on the E6- and E7- mediated down regulation of p53 and Rb, or their downstream effectors, p21 or PCNA. Further investigation of apoptotic signals induced by Compound 1 revealed cleavage of Caspase-8 in HPV-positive cells as early as 2 hours post-treatment, suggesting the compound initiates apoptosis through the extrinsic, death receptor-mediated, pathway of cell death. These studies provide proof of concept that cells transformed by oncogenic Papillomaviruses can be selectively induced to undergo apoptosis by compound treatment.

We argue that in an initial public offering (IPO), pre-IPO owners make decisions regarding underpricing, share retention, and share lockup simultaneously and optimally to maximize aftermarket liquidity. We predict that underpricing fosters higher trading volume in both the short run and the long run. Also, liquidity is negatively related to the proportion of shares retained by pre-IPO owners, ceteris paribus, so IPO underpricing should be positively related to the proportion of shares retained, as an offset. We document evidence consistent with these predictions. In addition, we find that, for IPOs with a lockup restriction, underpricing is more substantial and the positive relation between share retention and underpricing is much stronger. We also find that the relationship between underpricing and trading volume is stronger for IPOs with lockup. IPOs with lockup have higher trading volume, and a significant portion of this difference is associated with the effect of underpricing.

PurposeTo test the effects of underpricing and share retention (i.e. the proportion of shares retained by the pre‐initial‐public‐offering (IPO) owners) on IPO aftermarket liquidity.Design/methodology/approachUses both percentage spread and turnover ratio to measure liquidity. The percentage spread is the quoted bid‐ask spread divided by the quoted midpoint and measures the trading cost relative to share price. Turnover ratio is the daily trading volume divided by the number of shares offered and measures the speed of transaction. Both non‐parametric analyses and multiple regressions are conducted to investigate the effects of underpricing and share retention on liquidity.FindingsResults indicate that initial return is positively related to turnover ratio and negatively related to percentage spread. These relations are significant even after controlling for other factors. Also finds that the pre‐IPO owners’ retention rate is positively related to turnover ratio and negatively related to percentage spread. High retention rates attract more trades, provide quality assurance, and improve IPO aftermarket liquidity.Originality/valueThis paper investigates the theoretical links between underpricing and liquidity and provides direct evidence on Booth and Chua's liquidity theory. In addition, this is one of the first empirical studies to analyze the effect of share retention on aftermarket liquidity.

Several semi-synthetic bis- and mono- O -alkyl nocathiacin derivatives were synthesized and evaluated for antibacterial activity. Mono- O -alkyl N -hydroxyindole analogues 3a – l were prepared by regioselective alkylation. Bis- O -alkyl nocathiacins 4a – f were obtained by treatment with base and excess electrophile. A one-pot protection–alkylation–deprotection strategy was developed for the preparation of mono- O -alkyl hydroxypyridine analogues 5a , b . Most of the bis- and mono- O -alkyl nocathiacins maintained good in vitro activity but showed reduced in vivo efficacy when compared with the natural product. The excellent in vivo activity and improved water solubility of phosphate analogues 3m and 4g suggest their use as potential pro-drugs.