Characterization of host substrates of SARS-CoV-2 main protease

The main protease (Mpro) plays a crucial role in coronavirus, as it cleaves viral polyproteins and host cellular proteins to ensure successful replication. In this review, we discuss the preference in the recognition sequence of Mpro based on sequence-based studies and structural information and highlight the recent advances in computational and experimental approaches that have aided in discovering novel Mpro substrates. In addition, we provide an overview of the current understanding of Mpro host substrates and their implications for viral replication and pathogenesis. As Mpro has emerged as a promising target for the development of antiviral drugs, further insight into its substrate specificity may contribute to the design of specific inhibitors

The Relationship between Stock Price and EPS: Evidence Based on Taiwan Panel Data

In this study, we use panel cointegration methods to investigate the relationship between stock prices and earnings-per-share (EPS). Furthermore, we consider whether stock prices respond to EPS under the different level of growth rate of operating revenue. The empirical result indicated that the cointegration relationship existed between stock prices and EPS in the long-run. Furthermore, we found that for the firm with a high level of growth rate, EPS has less power in explaining the stock prices however, for the firm with a low level of growth rate, EPS has a strong impact in stock prices.Earnings Response Coefficient (ERC)

A Bayesian measurement error model for two-channel cell-based RNAi data with replicates

RNA interference (RNAi) is an endogenous cellular process in which small double-stranded RNAs lead to the destruction of mRNAs with complementary nucleoside sequence. With the production of RNAi libraries, large-scale RNAi screening in human cells can be conducted to identify unknown genes involved in a biological pathway. One challenge researchers face is how to deal with the multiple testing issue and the related false positive rate (FDR) and false negative rate (FNR). This paper proposes a Bayesian hierarchical measurement error model for the analysis of data from a two-channel RNAi high-throughput experiment with replicates, in which both the activity of a particular biological pathway and cell viability are monitored and the goal is to identify short hair-pin RNAs (shRNAs) that affect the pathway activity without affecting cell activity. Simulation studies demonstrate the flexibility and robustness of the Bayesian method and the benefits of having replicates in the experiment. This method is illustrated through analyzing the data from a RNAi high-throughput screening that searches for cellular factors affecting HCV replication without affecting cell viability; comparisons of the results from this HCV study and some of those reported in the literature are included.Comment: Published in at http://dx.doi.org/10.1214/11-AOAS496 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

A CMMI-based approach for medical software project life cycle study

In terms of medical techniques, Taiwan has gained international recognition in recent years. However, the medical information system industry in Taiwan is still at a developing stage compared with the software industries in other nations. In addition, systematic development processes are indispensable elements of software development. They can help developers increase their productivity and efficiency and also avoid unnecessary risks arising during the development process. Thus, this paper presents an application of Light-Weight Capability Maturity Model Integration (LW-CMMI) to Chang Gung Medical Research Project (CMRP) in the Nuclear medicine field. This application was intended to integrate user requirements, system design and testing of software development processes into three layers (Domain, Concept and Instance) model. Then, expressing in structural System Modeling Language (SysML) diagrams and converts part of the manual effort necessary for project management maintenance into computational effort, for example: (semi-) automatic delivery of traceability management. In this application, it supports establishing artifacts of “requirement specification document”, “project execution plan document”, “system design document” and “system test document”, and can deliver a prototype of lightweight project management tool on the Nuclear Medicine software project. The results of this application can be a reference for other medical institutions in developing medical information systems and support of project management to achieve the aim of patient safety. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2193-1801-2-266) contains supplementary material, which is available to authorized users

The inevitable role of El Ni~no: a fresh insight into the oil market

This paper explores the time-varying interaction between El Ni~no phenomenon and the oil market by applying the wavelet analysis. Few studies have explored the time-varying interrelationship between El Ni~no phenomenon and oil price (also the prices of petroleum products) by considering the time and frequency domains, and this paper will fill the above gaps. The empirical results reveal that El Ni~no index (NINO) which reflects the strength of El Ni~no phenomenon has a negative influence on oil price (OP) in the long run, but this view does not hold in the short and medium terms. These results are not consistent with the intertemporal capital asset pricing model (ICAPM), which indicates that there is a positive influence from NINO to OP. In turn, OP positively affects NINO in the medium term. Through comparing the five petroleum products, we can conclude that heating oil price (HOP) is the most relevant to NINO, while gasoline price (GOP) and diesel fuel price (DOP) have relatively weak relationships with it. Understanding the interactions between El Ni~no phenomenon and the oil market can provide insights for the investors, oil enterprises and related authorities

Trickle-Down Technology and Screening of a Durable Goods Monopolist

We show that when it takes time for a durable goods monopolist to make its high-end new technology accessible to low-end market (the trickle-down technology constraint), the monopolist's high-end product might have a higher-than-optimum quality. This result differs from conventional screening models, in which the qualities of non-durable goods supplied by a monopolist never exceed the optimum, and only consumers with the highest valuation consume the efficient quality. In another literature discussing a durable goods monopolist who delays the introduction of low-end product as a marketing strategy, but not due to the trickle-down constraint, the qualities will not exceed the optimum either. Our results show that the trickle-down constraint will make the monopolist chooses a higher-than-optimum quality when the difference of the valuations of high demand and low demand consumers are in certain ranges. The intuition follows Spence (1975): the efficient quality is determined by the marginal cost and the average of all consumers' marginal valuations, while the monopolist chooses quality such that the marginal cost equals the marginal consumer's marginal valuation

Chondrosterins A–E, Triquinane-Type Sesquiterpenoids from Soft Coral-Associated Fungus Chondrostereum sp.

The marine fungus Chondrostereum sp. was collected from a soft coral Sarcophyton tortuosum from the South China Sea. This fungus was cultured in potato dextrose broth medium and the culture broth was extracted with EtOAc. Five new triquinane-type sesquiterpenoids, chondrosterins A–E (1–5), and the known sesquiterpenoid hirsutanol C (6), were isolated. The structures were elucidated mainly on the basis of NMR, MS, and X-ray single-crystal diffraction data. Chondrosterin A (1) showed significant cytotoxic activities against cancer lines A549, CNE2, and LoVo with IC50 values of 2.45, 4.95, and 5.47 μM, respectively

A Retrospective Cohort Study Comparing Stroke Recurrence Rate in Ischemic Stroke Patients With and Without Acupuncture Treatment.

Little was known about the effects of acupuncture on stroke recurrence. The aim of this study is to investigate whether ischemic stroke patients receiving acupuncture treatment have a decreased risk of stroke recurrence. A retrospective cohort study of 30,058 newly diagnosed cases of ischemic stroke in 2000 to 2004 was conducted based on the claims of Taiwan National Health Insurance Research Database. The use of acupuncture treatment and stroke recurrence were identified during the follow-up period from 2000 to 2009. This study compared the risk of stroke recurrence between ischemic stroke cohorts with and without acupuncture treatment by calculating adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of acupuncture associated with stroke recurrence in the Cox proportional hazard model. The stroke recurrence rate per 1000 person-years decreased from 71.4 without to 69.9 with acupuncture treatment (P < 0.001). Acupuncture treatment was associated with reduced risk of stroke recurrence (HR 0.88; 95% CI 0.84-0.91). The acupuncture effect was noted in patients with or without medical treatment for stroke prevention but its impact decreased with aging of stroke patients. Compared with stroke patients without acupuncture treatment and medication therapy, the hazard ratios of stroke recurrence for those had medication therapy only, acupuncture only, and both were 0.42 (95% CI 0.38-0.46), 0.50 (95% CI 0.43-0.57), and 0.39 (95% CI 0.35-0.43), respectively. This study raises the possibility that acupuncture might be effective in lowering stroke recurrence rate even in those on medications for stroke prevention. Results suggest the need of prospective sham-controlled and randomized trials to establish the efficacy of acupuncture in preventing stroke

The Potential Utility of Curcumin in the Treatment of HER-2-Overexpressed Breast Cancer: An In Vitro and In Vivo Comparison Study with Herceptin

HER-2 is an important oncoprotein overexpressed in about 15–25% of breast cancers. We hypothesized that the ability of curcumin to downregulate HER-2 oncoprotein and inhibit the signal transduction pathway of PI3K/Akt, MAPK, and NF-κB activation may be important in the treatment of HER-2-overexpressed breast cancer. To examine the effect of curcumin on breast cancer cells, MCF-7, MDA-MB-231, MCF-10A, BT-474, and SK-BR-3-hr (a herceptin resistant strain from SK-BR-3) cells were used for in vitro analysis. The in vivo effect of curcumin on HER-2-overexpressed breast cancer was investigated with the HER-2-overexpressed BT-474 xenograft model. Cell growth, cell cycle change, the antimobility effect, signal transduction, and xenograft volume analysis between groups treated with herceptin and/or curcumin were tested. Curcumin decreased the cell growth of various breast cancer cell lines (MCF-7, MDA-MB-231, MCF-10A, BT-474, and SK-BR-3-hr). In Western blot analysis, the phosphorylation of Akt, MAPK, and expression of NF-κB were reduced in BT-474 cells, but not in SK-BR-3-hr cells, after treatment with herceptin. When treated with curcumin, the HER-2 oncoprotein, phosphorylation of Akt, MAPK and expression of NF-κB were decreased in both BT-474 and SK-BR-3-hr cells. In the BT-474 xenograft model, though not as much as herceptin, curcumin did effectively decrease the tumor size. The combination of curcumin with herceptin was not better than herceptin alone; however, the combination of taxol and curcumin had an antitumor effect comparable with taxol and herceptin. The results suggested that curcumin has potential as a treatment for HER-2-overexpressed breast cancer