Horizontal mergers with synergies: first-price vs. profit-share auction

We consider takeover bidding in a Cournot oligopoly when firms have private information concerning the synergy effect of merging with a takeover target. Two auction rules are considered: standard first-price and profit-share auctions, supplemented by entry fees. Since non-merged firms benefit from a merger if the synergies are low, bidders are subject to a positive externality. Nevertheless, pooling does not occur; and the profit-share auction is strictly more profitable than the first-price auction, regardless of whether firms observe the synergy parameter or only the winning bid before they play the oligopoly game

Horizontal mergers with synergies: first-price vs. profit-share auction

We consider takeover bidding in a Cournot oligopoly when firms have private information concerning the synergy effect of merging with a takeover target. Two auction rules are considered: standard first-price and profit-share auctions, supplemented by entry fees. Since non-merged firms benefit from a merger if the synergies are low, bidders are subject to a positive externality. Nevertheless, pooling does not occur; and the profit-share auction is strictly more profitable than the first-price auction, regardless of whether firms observe the synergy parameter or only the winning bid before they play the oligopoly game.Horizontal mergers; takeovers; auctions; externalities; oligopoly

Revolutionising health care: Exploring the latest advances in medical sciences

Recent years have seen a revolution in the domain of medical science, with ground-breaking discoveries changing health care as we once knew it [1]. These advances have considerably improved disease diagnosis, treatment, and management, improving patient outcomes and quality of life [2–5]. . .

Reap success from persistence

The road to success is long and arduous. Almost all Nobel prize laureates experienced tremendous efforts and countless failures before they made their scientific breakthroughs. Hypothesis-driven, independent and critical thinking, passion, repeated experiments and repetitive failures and running in circles on the entire scientific process finally approved their hypotheses

Monitoring Enzyme Reaction and Screening of Inhibitors of Acetylcholinesterase by Quantitative Matrix-Assisted Laser Desorption/Ionization Fourier Transform Mass Spectrometry

A matrix-assisted laser desorption/ionization Fourier transform mass spectrometry (MALDI-FTMS)–based assay was developed for kinetic measurements and inhibitor screening of acetylcholinesterase. Here, FTMS coupled to MALDI was applied to quantitative analysis of choline using the ratio of choline/acetylcholine without the use of additional internal standard, which simplified the experiment. The Michaelis constant (Km) of acetylcholinesterase (AChE) was determined to be 73.9 μmol L−1 by this approach. For Huperzine A, the linear mixed inhibition of AChE reflected the presence of competitive and noncompetitive components. The half maximal inhibitory concentration (IC50) value of galantamine obtained for AChE was 2.39 μmol L−1. Inhibitory potentials of Rhizoma Coptidis extracts were identified with the present method. In light of the results the referred extracts as a whole showed inhibitory action against AChE. The use of high-resolution FTMS largely eliminated the interference with the determination of ACh and Ch, produced by the low-mass compounds of chemical libraries for inhibitor screening. The excellent correlation with the reported kinetic parameters confirms that the MS-based assay is both accurate and precise for determining kinetic constants and for identifying enzyme inhibitors. The obvious advantages were demonstrated for quantitative analysis and also high-throughput characterization. This study offers a perspective into the utility of MALDI-FTMS as an alternate quantitative tool for inhibitor screening of AChE

Diagnostic accuracy of autoverification and guidance system for COVID-19 RT-PCR results

Background: To date, most countries worldwide have declared that the pandemic of COVID-19 is over, while the WHO has not officially ended the COVID-19 pandemic, and China still insists on the personalized dynamic COVID-free policy. Large-scale nucleic acid testing in Chinese communities and the manual interpretation for SARS-CoV-2 nucleic acid detection results pose a huge challenge for labour, quality and turnaround time (TAT) requirements. To solve this specific issue while increase the efficiency and accuracy of interpretation, we created an autoverification and guidance system (AGS) that can automatically interpret and report the COVID-19 reverse transcriptase-polymerase chain reaction (RT-PCR) results relaying on computer-based autoverification procedure and then validated its performance in real-world environments. This would be conductive to transmission risk prediction, COVID-19 prevention and control and timely medical treatment for positive patients in the context of the predictive, preventive and personalized medicine (PPPM). Methods: A diagnostic accuracy test was conducted with 380,693 participants from two COVID-19 test sites in China, the Hong Kong Hybribio Medical Laboratory (n = 266,035) and the mobile medical shelter at a Shanghai airport (n = 114,658). These participants underwent SARS-CoV-2 RT-PCR from March 28 to April 10, 2022. All RT-PCR results were interpreted by laboratorians and by using AGS simultaneously. Considering the manual interpretation as gold standard, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were applied to evaluate the diagnostic value of the AGS on the interpretation of RT-PCR results. Results: Among the 266,035 samples in Hong Kong, there were 16,356 (6.15%) positive, 231,073 (86.86%) negative, 18,606 (6.99%) indefinite, 231,073 (86.86%, negative) no retest required and 34,962 (13.14%, positive and indefinite) retest required; the 114,658 samples in Shanghai consisted of 76 (0.07%) positive, 109,956 (95.90%) negative, 4626 (4.03%) indefinite, 109,956 (95.90%, negative) no retest required and 4702 (4.10%, positive and indefinite) retest required. Compared to the fashioned manual interpretation, the AGS is a procedure of high accuracy [99.96% (95%CI, 99.95–99.97%) in Hong Kong and 100% (95%CI, 100–100%) in Shanghai] with perfect sensitivity [99.98% (95%CI, 99.97–99.98%) in Hong Kong and 100% (95%CI, 100–100%) in Shanghai], specificity [99.87% (95%CI, 99.82–99.90%) in Hong Kong and 100% (95%CI, 99.92–100%) in Shanghai], PPV [99.98% (95%CI, 99.97–99.99%) in Hong Kong and 100% (95%CI, 99.99–100%) in Shanghai] and NPV [99.85% (95%CI, 99.80–99.88%) in Hong Kong and 100% (95%CI, 99.90–100%) in Shanghai]. The need for manual interpretation of total samples was dramatically reduced from 100% to 13.1% and the interpretation time fell from 53 h to 26 min in Hong Kong; while the manual interpretation of total samples was decreased from 100% to 4.1% and the interpretation time dropped from 20 h to 16 min at Shanghai. Conclusions: The AGS is a procedure of high accuracy and significantly relieves both labour and time from the challenge of large-scale screening of SARS-CoV-2 using RT-PCR. It should be recommended as a powerful screening, diagnostic and predictive system for SARS-CoV-2 to contribute timely the ending of the COVID-19 pandemic following the concept of PPPM

Association between Percentage of Neutrophils at Admission and in-Hospital Events in Patients ≥75 Years of Age with Acute Coronary Syndrome

Objective: The study aimed to evaluate the role of the neutrophil percentage (N%) at admission in predicting in-hospital major adverse cardiovascular events (MACE) in patients ≥75 years of age with acute coronary syndrome (ACS).Methods: A total of 1189 patients above 75 years of age with ACS hospitalized at the Second Xiangya Hospital between January 2013 and December 2017 were enrolled in this retrospective study. Receiver operator characteristic curve analysis was performed to calculate the optimal N% cut-off value for patient grouping. The in-hospital MACE consisted of acute left heart failure, stroke and any cause of death. Multivariable logistic analyses were used to assess the role of N% in predicting MACE in older patients with ACS.Results: The patients were divided into a high N% group (N% ≥74.17%, n=396) and low N% group (N%<74.17%, n=793) according to the N% cut-off value (N%=74.17%). The rate of MACEs during hospitalization was considerably higher in the high N% group than the low N% group (27.5% vs. 9.6%, P<0.001). After adjustment for other factors, high N% remained an independent risk factor for in-hospital MACE in older patients with ACS (odds ratio 1.779, 95% confidence interval 1.091–2.901, P=0.021).Conclusion: High N% at admission is an independent risk factor for in-hospital MACE in patients above 75 years of age with ACS

RPRD1A and RPRD1B Are Human RNA Polymerase II C-Terminal Domain Scaffolds for Ser5 Dephosphorylation

The RNA polymerase II (RNAPII) carboxyl-terminal domain (CTD) heptapeptide repeats (Y1-S2-P3-T4-S5-P6-S7) undergo dynamic phosphorylation and dephosphorylation during the transcription cycle to recruit factors that regulate transcription, RNA processing and chromatin modification. We show here that RPRD1A and RPRD1B form homodimers and heterodimers through their coiled-coil domains and interact preferentially via CTD interaction domains (CIDs) with CTD repeats phosphorylated at S2 and S7. Our high resolution crystal structures of the RPRD1A, RPRD1B and RPRD2 CIDs, alone and in complex with CTD phosphoisoforms, elucidate the molecular basis of CTD recognition. In an interesting example of cross-talk between different CTD modifications, our data also indicate that RPRD1A and RPRD1B associate directly with RPAP2 phosphatase and, by interacting with CTD repeats where phospho-S2 and/or phospho-S7 bracket a phospho-S5 residue, serve as CTD scaffolds to coordinate the dephosphorylation of phospho-S5 by RPAP2

Transcriptional regulation of the asparagine synthetase gene in Chinese hamster ovary cells

grantor: University of TorontoAmino acid biosynthetic genes in mammalian cells are responsible for the biosynthesis of non-essential amino acids. Their regulation is poorly understood in spite of their physiological and pathological significance. In bacteria and yeast, amino acid synthesis genes are turned on by amino acid starvation and the molecular mechanisms in these two systems are well understood. In mammalian cells, including Chinese hamster ovary (CHO) cells, the asparagine synthetase (AS) enzymatic activity is up-regulated in response to amino acid starvation. This indicates a conserved adaptation response. The AS gene of CHO cells has been extensively studied at the biochemical level. It provides a model system to study the underlying molecular mechanism of the cellular response to amino acid starvation. The AS gene is a housekeeping gene; its promoter region is devoid of TATA and CAAT consensus sequences, but is GC rich. To investigate AS regulation, we first analyzed a 1.1 kb 5' genomic fragment of the AS gene in wild-type CHO cells under normal growth conditions. The minimal promoter was determined to lie within the -47 to +199 region. Two upstream GC boxes and a GC box in intron 1 were found to correspond to positive cis-elements for AS transcription. Specific DNA-protein interactions were detected within the AS minimal promoter region. Transcriptional regulation of the AS promoter was studied under amino acid starvation conditions. We found that AS promoter constructs were induced by asparagine depletion and that the level of induction was parallel to the level of induced AS enzymatic activity. A novel cis-element 5'-GATGAAACTTCCC-3 ' termed AARECHO was defined by mutational analyses. Chimeric promoter analysis indicated that a 24 bp AARECHO sequence could up-regulate activity of the thymidine kinase (TK) basal promoter upon asparagine depletion. A specific nuclear protein bound to the. AARE CHO containing probe. When AS was up-regulated by amino acid depletion, the uncharged tRNAs appeared to play a role downstream of the amino acid starvation signal and lead to AS up-regulation at the transcriptional level. The data lead us to propose a model for how mammalian cells increase amino acid synthesis upon amino acid starvation.Ph.D