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In April 2018, Sir John Kingman was asked by the Secretary of State for Business, Energy and Industrial Strategy (BEIS) of the United Kingdom (UK) to undertake an independent review of the Financial Reporting Council. The Kingman review which was published in December 2018 made recommendations for a major overhaul of the UK corporate financial reporting and audit regulations. A key recommendation made in the Kingman review is that the UK should consider introducing tougher regulation in respect of listed companies’ internal controls, similar to that applying in the United States (US) under the Sarbanes-Oxley Act (SOX). This article is written against such background and examines what lessons and experiences can regulators and companies in the UK learn from the other side of the Atlantic in strengthening internal controls. It seeks to recommend what measures UK regulators and companies can adopt to prepare themselves for the likely introduction of a SOX-style regime of internal controls.

In 2015/2016 the United Kingdom (UK) became the first country to implement the People with Significant Control (PSC) regime which requires disclosure of beneficial ownership of companies. With relative success in the implementation of such regime, the UK authorities have decided to further enhance it by making the identity verification of PSC compulsory and placing the responsibility on PSCs themselves to verify their identity with Companies House. This article examines the background of introducing such a regime in the UK and explores the recent proposal in its further enhancement. It is ultimately argued that it was correct for the UK to enact such a regime back in 2016 and why making the identity verification of PSC compulsory is the right step in enhancing corporate transparency and is beneficial to its economic competitiveness. Corporate law, Corporate disclosure and transparency, Beneficial ownership, PSC regime, United Kingdom

Gas-phase ion/molecule reactions have been used extensively for the structural elucidation of organic compounds in tandem mass spectrometry. Reagents for ion/molecule reactions can be introduced into a mass spectrometer via a continuous flow apparatus or through a pulsed inlet system. However, most of these approaches enable the use of only a single reagent at a time. In this work, a multichannel pulsed-valve inlet system was developed for the rapid consecutive introduction of up to nine different reagents or reagent systems into a linear quadrupole ion trap mass spectrometer for diagnostic gas-phase ion/molecule reactions. Automated triggering of the pulsed valves enabled these experiments to be performed on the high-performance liquid chromatography (HPLC) time scale. This enables high-throughput screening of several functionalities in analytes as they elute from an HPLC column.

Glucuronidation, a common phase II biotransformation reaction, is one of the major in vitro and in vivo metabolism pathways of xenobiotics. In this process, glucuronic acid is conjugated to a drug ...

The levels of potentially mutagenic impurities (PMIs) in active pharmaceutical ingredients are highly regulated and must be below a critical safety threshold. One class of PMIs is primary carbamates, which are formed during drug manufacturing and formulation. To comply with safety regulations, it is critically important to develop analytical techniques that enable the identification of primary carbamates during the drug development process. In this study, tandem mass spectrometry combined with gas-phase ion–molecule reactions as well as collision-activated dissociation (CAD) is demonstrated to enable the identification of protonated primary carbamates. Primary carbamates were protonated via atmospheric pressure chemical ionization (APCI) in a linear quadrupole ion trap mass spectrometer, isolated, and allowed to react with trimethoxymethylsilane (TMMS) introduced into the ion trap via an external reagent mixing manifold. Protonated primary carbamates reacted with TMMS to form an adduct ion, [M + H + TMMS]...

Quantitation of isomeric pneumococcal polysaccharides in vaccines is a challenging task due to mixture complexity, their low quantities, and identical monosaccharide compositions. Differentiation and quantitation of isomeric pneumococcal polysaccharides were investigated here based on a partial chemical degradation mass spectrometry approach to generate an oligosaccharide marker for one isomer, and not the other. Mild base conditions were successful at generating unique ions for the isomers with the weakest glycosidic bonds, while strong base and acid conditions were successful at generating unique ions for the more stable isomers. Linear relationships between the ion abundance of the oligosaccharide marker and the starting pneumococcal polysaccharides concentration were established for all isomers. Furthermore, precision measurements for each method were below 12% demonstrating good robustness. Therefore, partial chemical degradation followed by mass spectrometry was successful at differentiating and quantifying isomeric pneumococcal polysaccharides and may be adopted for other bacterial types.

[Image: see text] Several PEGylated therapeutic proteins are approved drugs, and more are under development. However, the synthesis and characterization of these bioconjugates, especially heterogeneous mixtures of PEGylated proteins, are challenging. The present study focuses on the development of PEG linkers that can be installed through biocatalytic route and render much simpler and insightful analytical characterization of PEG–protein conjugates. This linker enables traditional peptide mapping assay to determine protein sequence coverage, natural PTMs, and PEG attachment sites. Novel PEG linkers are cleavable during traditional sample preparation, leaving behind reporter amino acids to allow the determination of PEG attachment sites by peptide mapping. Products of transglutaminase-catalyzed bioconjugation of 5K PEG to Interferon α-2b were analyzed, and K31, K134, and K164 were identified as the PEGylation sites; the former two being newly determined sites demonstrates the sensitivity of the approach. In another instance, conjugation sites on Interleukin-2-PEG conjugation were found to be K31, K47, K48, and K75.

Molecular profiling of crude oil is a tremendous challenge due to its inherent complexity. An accurate molecular fingerprint of a crude oil may facilitate rational design of crude oil recovery efforts, such as enhanced oil recovery, improve the efficiencies of the refining processes, and enable a better assessment of the value of the crude oil. Herein, a new approach (Distillation Precipitation Fractionation Mass Spectrometry (DPF-MS) method) is introduced for the molecular level characterization of crude oil. This method involves the separation of crude oil into six fractions followed by high-resolution mass spectral analysis optimized for each individual fraction. The separation methods are distillation, precipitation, and fractionation in an auto column followed by solid phase extraction. Initially, the fractions were examined by using Fourier transform infrared spectroscopy to determine the bulk chemical nature of each individual fraction, such as the extent of aromaticity, degree of polarity, etc. Based on this bulk information, model compounds representative of compounds in each fraction were selected and employed to develop the optimal high-resolution mass spectrometric analysis method for each fraction. An especially important aspect of this work was the optimization of the ionization method separately for each fraction by using appropriate model compounds so that most compounds in each fraction are ionized at approximately the same efficiency to generate only one type of stable ions (either molecular ions, protonated molecules or cations formed by hydride abstraction) containing the intact analyte molecule. This allows the DPF-MS method to produce reasonably accurate relative abundances for compounds present in each fraction, thereby making the method semi-quantitative. The compositional data thus obtained for the individual fractions were utilized to provide meaningful molecular level information for the crude oil. Inclusion of a mass balance for each fraction allows for data consolidation, which provides an accurate overall analysis of the crude oil, including average molecular weight and weight percentages of different compound classes.

The request of Alibaba, China’s largest e-commerce company, to allow a self-selected group of its past and present management known as the ‘partners’ the right to nominate a majority of the directors in its negotiation with the Hong Kong Stock Exchange (HKEx) for an initial public offering (IPO) in 2013 reignited a new round of debate over the one share, one vote policy, which has survived for three decades in Hong Kong. Alibaba’s IPO application to list on the HKEx was eventually rejected which ultimately led to the company’s decision to list on the New York Stock Exchange. In late 2017, the debate on whether companies with dual-class share (DCS) structure should be allowed to list in Hong Kong re-emerged as the HKEx has announced that it would amend its listing rules to enable companies with DCS structure to list on its exchange, subject to certain safeguards and restrictions. This article examines what measures Hong Kong could adopt to allow companies with DCS structure to list on its exchange despite legal and institutional shortcomings of its financial market. In doing so, it will also make reference to other major financial markets in the world and examine how other jurisdictions have handled the issue of DCS structure companies.

A method is presented for the rapid identification of tertiary aliphatic and aromatic N-oxide functionalities in protonated analytes via ion-molecule reactions with dimethylamine (DMA) in a linear quadrupole ion trap mass spectrometer (LQIT). DMA was leaked into the trapping region of the mass spectrometer and allowed to react with protonated analytes (ionized by electrospray ionization) for 500 ms, after which all ions were detected. Protonated analytes with the tertiary N-oxide functionality react with DMA to yield exclusively product ions with m/z-values that are 45 units greater than that of the protonated analyte, corresponding to a stable DMA adduct. Collision-activated dissociation of the adduct ions suggests that formation of a hydrogen bond between DMA and the protonated analytes is responsible for the formation of the stable adduct. Hydrogen bond energies were calculated for several adducts at the B3LYP/6-31++G(d,p) level of theory (including correction for basis-set superposition error) to define the potential energy wells for the formation of [M+H+DMA]+ adduct ions. The relative enthalpies calculated for the [M+H+DMA]+ adduct ions were found to be lower than those of the products resulting from proton transfer from protonated tertiary N-oxides and one aromatic ketone, ketoprofen, to DMA. On the other hand, a protonated primary N-oxide, nitrosobenzene, exclusively reacts via proton transfer with DMA, which was calculated to be more exothermic than formation of an adduct ion. Collisional cooling was found to be crucial to the formation of an adduct ion for analytes with proton affinities lower than that of DMA. Ion-molecule reactions of protonated 4-nitro-2-picoline N-oxide (PA = 206 kcal mol−1) with DMA (PA = 222 kcal mol−1) in an FT-ICR at ultra-high vacuum with no buffer gas resulted solely in proton transfer to DMA. Finally, examination of the reactions of DMA with protonated clozapine and clozapine-4′-N-oxide demonstrated that DMA can be used to identify the N-oxide functionality in the presence of other basic functionalities. Compared to other reagents reported for the identification of tertiary N-oxide functionalities via ion-molecule reactions in a mass spectrometer, DMA is the only one volatile enough to be used in a multi-ported pulsed valve system designed for rapid introduction of several reagents, each diagnostic for a different functionality, for characterization of analytes as they elute from an HPLC.

In early 2017, the Financial Services and the Treasury Bureau of Hong Kong conducted a consultation and proposed to put in place a regime under its Companies Ordinance to enhance the transparency of beneficial ownership of companies by requiring them to publish the names of their ultimate owners on company registers in an effort to meet prevailing international standards to combat money laundering and terrorist financing. The consultation conclusion was published in April 2017 which stated that based on the overall support for the proposed legislation, it seeks to introduce such regime by late 2017. This article is written against such background and highlights the rationales for Hong Kong in introducing such a law. In doing so, the article will make reference to the United Kingdom and Singapore which have also recently implemented a similar regime under their company law.

Glucuronidation, a common phase II biotransformation reaction, is one of the major

In March 2016, the Financial Services Development Council (FSDC) of Hong Kong published a paper to examine whether the financial market of Hong Kong should introduce regulatory framework to promote equity crowdfunding. This article examines the recent experiences of the United States and United Kingdom in setting a regulatory framework on equity crowdfunding and seeks to identify what Hong Kong can learn from its Anglo-American counterparts in regulating such activity. It is ultimately argued that these experiences provide a good platform for implementing a broadly similar regime in Hong Kong by permitting crowdfunding within the scope of current regulated activities.

In spite of the emergence of genome editing tools, ES cell mediated transgenesis remains the most controllable way of creating genetically modified animals. Although tetraploid (4N) complementation of 4N host embryos and ES cells, is the only method guaranteeing that offspring are entirely ES cell derived, this technique is challenging, not always successful and difficult to implement in some laboratory settings. The current study shows that pretreatment of host blastocysts with FGF4 prior to ES cell injection can provide an alternative method for the generation of animals displaying high rates of chimaerism. Chimaerism assessment in E11 fetuses and born pups shows that a large percentage of resulting conceptuses show a high ES cell contribution from implantation onwards and that developing pups do not necessitate c-section for delivery.

In March 2015, the Securities and Futures Commission (SFC) of Hong Kong launched a consultation to examine whether the financial market of Hong Kong should implement the Principles of Responsible Ownership, based on the Stewardship Code which was first introduced into the United Kingdom’s (UK) financial market in 2010. One year later, in March 2016, the SFC announced in its consultation conclusions that it would adopt the Principles subject to some amendments. This article examines as to whether the implementation of such Principles would be effective in encouraging shareholder activism and engagement in the corporate governance of Hong Kong. Contrary to the SFC’s conclusions, it is argued here that due to the nature and characteristics of Hong Kong’s financial market, the Principles are unlikely to foster greater shareholder involvement. The article will suggest alternative legal and institutional mechanisms that can better enhance investor engagement.

Rationale The oxidation of sulfur atoms is an important biotransformation pathway for many sulfur-containing drugs. In order to rapidly identify the sulfone functionality in drug metabolites, a tandem mass spectrometric method based on ion–molecule reactions was developed. Methods A phosphorus-containing reagent, trimethyl phosphite (TMP), was allowed to react with protonated analytes with various functionalities in a linear quadrupole ion trap mass spectrometer. The reaction products and reaction efficiencies were measured. Results Only protonated sulfone model compounds were found to react with TMP to form a characteristic [TMP adduct–MeOH] product ion. All other protonated compounds investigated, with functionalities such as sulfoxide, N-oxide, hydroxylamino, keto, carboxylic acid, and aliphatic and aromatic amino, only react with TMP via proton transfer and/or addition. The specificity of the reaction was further demonstrated by using a sulfoxide-containing anti-inflammatory drug, sulindac, as well as its metabolite sulindac sulfone. Conclusions A method based on functional group-selective ion–molecule reactions in a linear quadrupole ion trap mass spectrometer has been demonstrated for the identification of the sulfone functionality in protonated analytes. A characteristic [TMP adduct–MeOH] product ion was only formed for the protonated sulfone analytes. The applicability of the TMP reagent in identifying sulfone functionalities in drug metabolites was also demonstrated. Copyright © 2016 John Wiley & Sons, Ltd.

The reactivity of a carbon-centered σ,σ,σ,σ-type singlet-ground-state tetraradical containing two meta-benzyne moieties was examined in the gas phase. Surprisingly, the tetraradical showed higher reactivity than its individual meta-benzyne counterparts. The reactivity of meta-benzynes is controlled by their (calculated) distortion energy ΔE2.3 , singlet-triplet spitting ΔES-T , and electron affinity (EA2.3 ) of the meta-benzyne moiety at the transition state geometry for hydrogen-atom abstraction reactions. The addition of a second meta-benzyne moiety to a meta-benzyne does not significantly change EA2.3 . However, ΔE2.3 is substantially decreased for both meta-benzyne moieties in the tetraradical, and this explains their higher reactivities. The decrease in ΔE2.3 for each meta-benzyne moiety in the tetraradical is rationalized by stabilizing spin-spin coupling between one radical site in each meta-benzyne moiety. Therefore, spin-spin coupling between the meta-benzyne moieties in this tetraradical increases its reactivity, whereas spin-spin coupling within each meta-benzyne moiety decreases its reactivity.

Isomeric O- and N-glucuronides are common drug metabolites produced in phase II of drug metabolism. Distinguishing these isomers by using common analytical techniques has proven challenging. A tandem mass spectrometric method based on gas-phase ion/molecule reactions of deprotonated glucuronide drug metabolites with trichlorosilane (HSiCl3) in a linear quadrupole ion trap mass spectrometer is reported here to readily enable differentiation of the O- and N-isomers. The major product ion observed upon reactions of HSiCl3 with deprotonated N-glucuronides is a diagnostic HSiCl(3) adduct that has lost two HCl molecules ([M − H + HSiCl3 − 2HCl]-). This product ion was not observed for deprotonated O-glucuronides. Reaction mechanisms were explored with quantum chemical calculations at the M06-2X/6-311++G(d,p) level of theory.

Western companies, professionals and regulators new to handling matters involving the People's Republic of China (PRC) often learn that the legal instincts developed in their home countries cannot ...

Gas-phase reactivity of protonated model compounds with different functional groups toward trimethoxymethylsilane (TMMS) was studied to explore the utility of this reagent in mass spectrometric identification of specific functionalities for potentially rapid characterization of drug metabolites. Only protonated analytes with a carboxylic acid, a sulfone, or a sulfonamide functionality formed diagnostic adducts that had lost a methanol molecule upon reactions with TMMS. Collisionally activated dissociation (CAD) of these methanol-eliminated adduct ions (MS3 experiments) produced characteristic fragment ions of m/z 75, 105, and 123 for sulfones, while an additional methanol elimination was observed for carboxylic acids and sulfonamides. CAD of latter products (MS4 experiments) resulted in elimination of diagnostic neutral molecules CO2 (44 Da) and C2H6O2Si (90 Da) for aromatic carboxylic acids. Both aliphatic carboxylic acids and sulfonamides yield several fragment ions in these MS4 experiments that are dif...

The absolute configurations of the separated enantiomers of fluralaner, a racemic animal health product used to prevent fleas and ticks, have been assigned using vibrational circular dichroism (VCD). The crystallographic structure of the active enantiomer (+)-fluralaner has previously been shown to have the (S) configuration using small molecule crystallography. We sought a faster analytical method to determine the absolute configuration of the separated enantiomers. When comparing the measured IR (infrared) and VCD spectra, it is apparent that the amide carbonyl groups appear in the IR but are nearly absent in the VCD. Computational work to calculate the VCD and IR using in vacuo models, implicit solvation, and explicitly solvated complexes has implicated conformational averaging of the carbonyl VCD intensities.

Following the lead of the UK and Australia, Hong Kong recently proposed the tightening up of access by the public to directors' residential addresses and identity card or passport numbers during its reform of the Companies Ordinance, but encountered strong opposition from the media and various professional bodies, leading to the government's decision to shelve the proposal. This paper highlights the lessons that the Hong Kong government should learn from this failure to transplant a corporate law reform, which overlooked the differences in the unique local situations.

Growing applications for astronomical ground-based adaptive systems and air-born telescope systems demand complex optical surface designs combined with ultra-smooth finishing. The use of more sophisticated and accurate optics, especially aspheric ones, allows for shorter optical trains with smaller sizes and a reduced number of components. This in turn reduces fabrication and alignment time and costs. These aspheric components include the following: steep surfaces with large aspheric departures; more complex surface feature designs like stand-alone off-axis-parabola (OAP) and free form optics that combine surface complexity with a requirement for ultra-high smoothness, as well as special optic materials such as lightweight silicon carbide (SiC) for air-born systems. Various fabrication technologies for finishing ultra-smooth aspheric surfaces are progressing to meet these growing and demanding challenges, especially Magnetorheological Finishing (MRF) and ion-milling. These methods have demonstrated some good success as well as a certain level of limitations. Amongst them, computer-controlled asphere surface-finishing technology (CAST), developed by Precision Asphere Inc. (PAI), plays an important role in a cost effective manufacturing environment and has successfully delivered numerous products for the applications mentioned above. One of the most recent successes is the Gemini Planet Imager (GPI), the world’s most powerful planet-hunting instrument, with critical aspheric components (seven OAPs and free form optics) made using CAST technology. GPI showed off its first images in a press release on January 7, 2014 . This paper reviews features of today’s technologies in handling the ultra-smooth aspheric optics, especially the capabilities of CAST on these challenging products. As examples, three groups of aspheres deployed in astronomical optics systems, both polished and finished using CAST, will be discussed in detail.

The request of Alibaba, China's largest e-commerce firm, to allow a self-selected group of its past and present management known as the ‘partners' the right to nominate a majority of the directors in its negotiation with the Hong Kong Stock Exchange for an initial public offering has reignited a new round of debate over the one share, one vote policy, which has survived for 27 years in Hong Kong. This paper discusses the viability of allowing the dual-class share structure in the city. Although the United States has adopted dual-class share structures for decades, this paper identifies the major institutional differences between Hong Kong and the United States and argues that Hong Kong should not follow suit due to these differences.

Tandem mass spectrometry based on ion–molecule reactions has emerged as a powerful tool for structural elucidation of ionized analytes. However, most currently used reagents were designed to react with protonated analytes, making them suboptimal for acidic analytes that are preferentially detected in negative ion mode. In this work we demonstrate that the phenoxide, carboxylate, and phosphate functionalities can be identified in deprotonated molecules by use of a combination of two reagents, diethylmethoxyborane (DEMB) and water. A novel reagent introduction setup that allowed DEMB and water to be separately introduced into the ion trap region of the mass spectrometer was developed to facilitate fundamental studies of this reaction. A new reagent, diethylhydroxyborane (DEHB), was generated inside the ion trap by hydrolysis of DEMB on introduction of water. Most carboxylates and phenoxides formed a DEHB adduct, followed by addition of one water molecule and subsequent ethane elimination (DEHB adduct +H2O − CH3CH3) as the major product ion. Phenoxides with a hydroxy group adjacent to the deprotonation site and phosphates formed a DEHB adduct, followed by ethane elimination (DEHB adduct − CH3CH3). Deprotonated molecules with strong intramolecular hydrogen bonds or without the aforementioned functionalities, including sulfates, were unreactive toward DEHB/H2O. Reaction mechanisms were explored via isotope labeling experiments and quantum chemical calculations. The mass spectrometry method allowed the differentiation of phenoxide-, carboxylate-, phosphate-, and sulfate-containing analytes. Finally, it was successfully coupled with high-performance liquid chromatography for the analysis of a mixture containing hymecromone, a biliary spasm drug, and its three possible metabolites.

The transcription factor Runx1/AML1 is an important regulator of hematopoiesis and is critically required for the generation of the first definitive hematopoietic stem cells (HSCs) in the major vasculature of the mouse embryo. As a pivotal factor in HSC ontogeny, its transcriptional regulation is of high interest but is largely undefined. In this study, we used a combination of comparative genomics and chromatin analysis to identify a highly conserved 531-bp enhancer located at position + 23.5 in the first intron of the 224-kb mouse Runx1 gene. We show that this enhancer contributes to the early hematopoietic expression of Runx1. Transcription factor binding in vivo and analysis of the mutated enhancer in transient transgenic mouse embryos implicate Gata2 and Ets proteins as critical factors for its function. We also show that the SCL/Lmo2/Ldb-1 complex is recruited to the enhancer in vivo. Importantly, transplantation experiments demonstrate that the intronic Runx1 enhancer targets all definitive HSCs in the mouse embryo, suggesting that it functions as a crucial cis-regulatory element that integrates the Gata, Ets, and SCL transcriptional networks to initiate HSC generation.

This article assesses the significance of the colonial period in the development of the Hong Kong Chinese identity and the way it is expressed through discriminatory legal settings against Mainland Chinese. The central argument is that British-led social welfare initiatives in the mid-1950s and the border-crossing restrictions in the early 19605 had the inevitable effect of assimilating extant refugee populations and creating the Hong Kong identity on a foundation of Mainlander 'otherness'. In light of the economic convergence of the Mainland and Hong Kong, the article contends that current controversies - such as Mainland women seeking to have their babies in Hong Kong - are transitional as economic convergence with the Mainland will render Hong Kong identity a cultural rather than political or legal subject.

This article argues that each of the US, the UK and Australia could take inspiration from Hong Kong's Protection of Wages on Insolvency Fund (POWIF) because it has the makings of a world-leading model for the protection of employee entitlements in circumstances of business failure. In particular, it is argued that although POWIF is open to fraud by unscrupulous employers it does not unduly increase moral hazard because its coverage provides only a modest safety net, it is funded by a mandatory private sector levy and it operates on a self-sustaining basis.

The much debated Minimum Wage Ordinance eventually secured passage in the Hong Kong Legislative Council on 17 July 2010 and is to take effect on 1 May 2011. A Minimum Wage Council established under the Ordinance has made recommendations to the Chief Executive on the initial minimum wage level. This paper compares the minimum wage legislation in Hong Kong with that of other Western jurisdictions and seeks to identify what the former can learn from these international experiences in setting a statutory minimum wage. In the final analysis, it is argued that these experiences provide a good platform for implementing a broadly similar regime in the Special Administrative Region, albeit one with ‘Hong Kong characteristics’.

In October 2009, the Financial Services and the Treasury Bureau of the Hong Kong Government published a consultation paper to review corporate rescue procedure with the aim of reforming key issues relating to corporate rescue. This paper compares the proposed reform in Hong Kong and the debtor-in-possession concept of the United States of America in Chapter 11 corporate rescue, and seeks to identify the reasoning behind the differences.

Section 172 of the UK Companies Act 2006 is arguably one of the most controversial provisions that has been introduced into the company law of the UK. It incorporates the concept of enlightened shareholder value, together with a list of non-exhaustive factors that directors ought to take into account in promoting the success of the company. The discussion focuses on a recent review undertaken by the Hong Kong Standing Committee on Company Law Reform (SCCLR) as to whether Hong Kong should follow the UK by incorporating a similar provision to section 172 of the Companies Act 2006 in its Companies Bill. Contrary to the SCCLR recommendation, the primary conclusion drawn is that it makes commercial sense for a similar provision to be introduced in Hong Kong. A careful examination of section 172 of the Companies Act 2006 shows that it simply reflects existing law and modern business practices. Therefore, the purpose of implementing such duty on directors does no more than reinstate the practical reality.