Thi-Thao-Phuong Hoang, Lili Ju, Wei Leng and Zhu Wang
Math. Comp. 89 (2020), 1807-1842.
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Ricardo G. Durán, Enrique Otárola and Abner J. Salgado
Math. Comp. 89 (2020), 1581-1603.
Abstract, references and article information

Côme Huré, Huyên Pham and Xavier Warin
Math. Comp. 89 (2020), 1547-1579.
Abstract, references and article information

Health startups are being corralled by the NHS and the government to point their talents at the COVID-19 pandemic, while others are volunteering services to help stymie the spread of the infectious new disease

Yifei Zhu
Trans. Amer. Math. Soc. 373 (2020), 3733-3764.
Abstract, references and article information

Robert Grizzard and Jeffrey D. Vaaler
Trans. Amer. Math. Soc. 373 (2020), 3235-3259.
Abstract, references and article information

T. Bodnar, S. Mazur, S. Muhinyuza and N. Parolya
Theor. Probability and Math. Statist. 99 (2020), 39-52.
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N. V. Krylov
St. Petersburg Math. J. 31 (2020), 509-520.
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Joseph Reid
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The first batch of about 300 Hong Kong residents stranded in Pakistan will take a chartered flight tentatively scheduled to leave Islamabad on the morning of April 30 and arrive in Hong Kong in the afternoon.

In a statement today, the Security Bureau said the returnees upon arrival at Hong Kong International Airport will proceed to the Temporary Specimen Collection Centre at AsiaWorld-Expo by coach for compulsory COVID-19 testing before they are transferred to the quarantine centre at Chun Yeung Estate for a 14-day quarantine.

In view of the COVID-19 situation, the Pakistan Government banned all international flight movements since late March, resulting in Hong Kong residents there being unable to return to Hong Kong through normal means.

The Immigration Department has received requests for assistance from Hong Kong residents stranded there and as at yesterday, it has successfully contacted about 1,600 of them.

Due to the large number of people requesting assistance and having regard to the returnees' quarantine arrangements, the capacities for testing, and the quarantine and treatment facilities, the Hong Kong Special Administrative Region Government must adopt a phased approach in assisting their return, subject to the circumstances.

The first batch of Hong Kong residents on the chartered flight are those staying in Islamabad and its surrounding areas. They also include people with special needs such as those with illnesses and pregnant women.

The cost of taking the chartered flight is about $6,000 per person and is borne by the user.

The Security Bureau said the chartered flight could not have been arranged smoothly without the staunch support of the Office of the Commissioner of the Ministry of Foreign Affairs of the People's Republic of China in the Hong Kong Special Administrative Region (OCMFA) and the Chinese Embassy in Pakistan, as well as the full co-operation rendered by the Pakistan Government and the Consulate General of Pakistan in Hong Kong.

The bureau said the Hong Kong SAR Government will continue to liaise with the residents still in Pakistan and assist in their return.

Meanwhile, a flight will arrive from Doha this afternoon carrying about 170 Hong Kong residents returning from Pakistan themselves.

The bureau added that upon their arrival in Hong Kong, they will be arranged to leave deep throat saliva samples at the Temporary Specimen Collection Centre before being admitted to the quarantine centre at Chun Yeung Estate for a 14-day quarantine.

Apart from Pakistan, the Indian Government has also since late March banned all international flight movements. As at yesterday, the Immigration Department has successfully contacted about 3,100 Hong Kong residents stranded there who sought assistance to return home.

The Hong Kong SAR Government is maintaining close contact with the OCMFA, the Chinese Embassy in India and the Consulate General of India in Hong Kong, while also contacting several airlines to arrange return flights to Hong Kong.

After the outbreak of the novel coronavirus, the Government has announced a series of prevention and control measures to reduce the risk of spread of the disease in the community. Compulsory quarantine, on the basis of a public health emergency (under Cap. 599 Prevention & Control of Disease Ordinance), is one of the measures in place. From February 8 onwards, all people entering Hong Kong from the Mainland, including Hong Kong residents, Mainland residents as well as other visitors, are required to be subject to mandatory quarantine for 14 days upon their arrival. Even if they are entering from other places, if they have visited the Mainland over the past 14 days, mandatory quarantine is still applicable upon their arrival. Anyone who violates the regulation may face a maximum penalty of imprisonment for six months and a fine of $25,000 upon conviction. We hope that the new measures could further reduce the flow of people between Hong Kong and the Mainland, reducing the risks for a spread of the disease in Hong Kong.

The Department of Health would gather evidence and conduct investigations into any contravention of quarantine orders before referring the cases to the Department of Justice for making prosecutorial decisions. Our prosecutors would make such decisions based on available evidence, applicable laws and the Prosecution Code. A prosecution would be commenced if there is sufficient admissible evidence for a reasonable prospect of conviction.

Minimising social contact in the community is another key measure to curb the spread of the virus. Hence, we only arranged for a certain number of colleagues, including government counsel, paralegals and supporting staff, to return to the office to handle urgent matters and provide basic public services. The reception counters of the Prosecutions Division and the Civil Division have remained open over the past few weeks to allow members of the public and the legal profession to serve court documents. The shroff office is also partly open for payment service. Details of the service hours are available from our press release.

There are colleagues from different divisions returning to the office to handle emergency works including attending urgent court hearings, processing court documents and attending urgent meetings. We have arranged for sufficient manpower to provide cleansing services at the office to safeguard the health of colleagues. For others, who are given laptops and electronic communication devices, are advised to work at home. I am heartened to learn that the Department of Justice is largely functioning well.

The Judiciary announced that court hearings would be generally adjourned in view of public health considerations but the courts would continue to handle urgent and essential hearings. Colleagues from the Department of Justice have been deployed to attend such hearings to deal with cases including bail applications and sentencing.

I am grateful to all my colleagues for remaining steadfast at their posts at this difficult time. I also urge those who are required to stay at home or other dwelling places for a 14-day quarantine to abide by the law and strictly comply with the quarantine orders. Violation of orders causes a spread of the disease and leads to criminal prosecution. Last but not the least, I appeal to all members of the public to join hands with the Government to do their best to prevent and curb the spread of COVID-19 by maintaining good personal hygiene, thereby ending the epidemic as soon as possible.

Secretary for Justice Teresa Cheng wrote this article and posted it on her blog on February 17.

Last month, I paid a visit to Yuen Long where I met a few families at Long Shin Estate. Apart from distributing face masks and anti-epidemic supplies to them, I was also given a better understanding of the impact brought by the epidemic on their daily lives. To show our concerted support in the fight against the disease, the Department of Justice (DoJ) Staff Club organised a volunteer activity on Sunday, which I joined with my fellow colleagues in offering our help to those in need.

To echo the Government's move to stay united, the DoJ Staff Club put forth a cash contribution campaign to buy anti-epidemic supplies for donation. The staff club volunteers acquired face masks and alcohol-based handrub in different ways - some were purchased through online shopping and some were bought at medicine stores. Last Sunday, I joined the volunteers in packing the anti-epidemic supplies, supermarket cash coupons and leaflets with health information. Our volunteers took the care packs in person to a non-governmental organisation a few days ago for passing to the elderly and low-income groups.

The staff club has been participating in volunteer services now and then. Given the overwhelming response this time, I am glad to know that more volunteer activities would be organised in the future. I would definitely be joining as many as I could. Through offering our efforts to help those in need, we hope to show our care for the less privileged in society and contribute to building a caring and inclusive community.

The public services of the DoJ, like all other government departments, have gradually resumed back to normal. I inspected the Justice Place on Monday to learn more about the infection control measures in place, such as the body temperature checking arrangement, provision of hand sanitisers and sanitising mats at building entrances.

We must remain vigilant as the epidemic is still severe, and more importantly, we also need to stand in solidarity in the fight against the disease.

Secretary for Justice Teresa Cheng wrote this article and posted it on her blog on March 5.

During the third month of our fight against COVID-19, Hong Kong has experienced daunting challenges posed by the epidemic with no room to let down our guard.  Though we are a bit relieved to see a significant drop in the number of confirmed cases recently, the Government needs to remain alert given the volatility of the epidemic.

Developments of the epidemic

In the past month, the epidemic continued to spread rapidly in many countries around the world. The number of confirmed cases increased from 400,000 a month ago to 2.6 million today, an increase of some 600%, with over 180,000 deaths.  Many governments had little choice but to take extreme measures such as a city lockdown. During the same period, the overseas epidemic situation resulted in a large number of Hong Kong residents abroad, including students studying in the United States and Europe, particularly in the United Kingdom, to return to Hong Kong. Due to the large number of imported cases, Hong Kong’s epidemic situation, which had remained stable for a period up to mid-March, started to become severe and reached its peak at the end of March. On March 27, 28 and 29, Hong Kong recorded 65, 64 and 59 confirmed cases respectively on a single day. We were then extremely worried because if 60 new cases have to be admitted to hospital and placed in isolation each day (according to Hospital Authority statistics every confirmed case stays in hospital for 15 to 20 days on average) and if this number of new confirmed cases continued for one month then the Hospital Authority’s 1,200 or so isolation beds would be fully occupied and our hospital system would face unimaginable pressure.

Although deeply anxious, we did not lose our composure but continued to respond promptly to the developments of the epidemic taking account of expert advice. We bit the bullet and resolutely took stringent measures in response to the situation. The number of confirmed cases has dropped from the peak at end-March to single digits since April 12, with the great majority of cases being imported or their close contacts (See Graphic 1). This shows we have prevented local transmission and that Hong Kong, once again, has overcome the challenge.

Anti-epidemic efforts

Since the Government implemented stringent border control measures before end-March, including denying the entry to Hong Kong by plane of all non-Hong Kong residents arriving from overseas countries or regions from March 25, the anti-epidemic measures introduced over the past month focused on enhancing virus testing for inbound travellers and restricting social interactions to prevent the spread of the disease. However, we have not prohibited people from going out as many overseas countries have done. Most restaurants and shops have remained open.  People by and large can maintain their daily life.

Major measures implemented by the Government to respond to the developments of the epidemic in the past month are set out in the following table:  

Date

Event

March 25-26

Four chartered flights were sent over two days to bring back to Hong Kong the second batch of 558 Hong Kong residents stranded in Hubei Province.

March 25-26

The Centre for Health Protection (CHP) extended the Enhanced Laboratory Surveillance Programme and set up a temporary specimen collection centre at AsiaWorld-Expo to provide virus testing for asymptomatic inbound travellers arriving from the UK and other countries in Europe as well as the US.

March 27

The Government announced that catering premises must comply with six disease control requirements and six types of premises (ie amusement game centres, bathhouses, fitness centres, places of amusement, places of public entertainment and premises for hire for holding social gatherings) must close from 6pm on March 28; and gatherings of more than four people in a public place would be prohibited from midnight on March 29.  At the same time, the Chief Executive announced the preparation of the second round of the Anti-epidemic Fund to provide further assistance to individuals and businesses.

April 1-2

The Government announced that karaoke establishments, mahjong-tin kau establishments and nightclubs must be closed and beauty parlours, clubhouses and massage establishments must step up epidemic control measures from 6pm on April 1; and bars must close from 6pm on April 3.

April 5

Sixty-five Hong Kong residents who took the chartered flights arranged by the Hong Kong Special Administrative Region Government arrived in Hong Kong from Peru. Upon arrival, they were taken to the temporary specimen collection centre at AsiaWorld-Expo to undergo virus testing and were admitted to hospital or put under home quarantine subject to the test results.

April 8

The Government announced the closure of beauty parlours and massage establishments from midnight on April 10, and the extension of measures regulating catering businesses and scheduled premises as well as prohibiting group gatherings until April 23.

April 8

The Chief Executive announced the second round of the Anti-epidemic Fund and other related measures involving over $130 billion, including an $80 billion Employment Support Scheme. The Legislative Council Finance Committee approved the funding on April 18.

April 8

The Department of Health (DH) mandated all asymptomatic inbound travellers arriving at the Hong Kong International Airport to proceed to the temporary specimen collection centre to collect deep throat saliva samples according to instructions before undergoing compulsory quarantine at their place of accommodation. Besides, specimen collection containers will be provided to inbound travellers arriving via land boundary control points who have been to Hubei Province in the past 14 days.

April 9

The DH required all asymptomatic inbound travellers arriving on flights from the UK to stay and wait for the test results at the temporary specimen collection centre, and they can continue their quarantine at their place of accommodation only if the test result is negative. The arrangement was extended to asymptomatic inbound travellers arriving on flights from the US and other areas in Europe from April 13.

April 10

Twenty-seven Hong Kong residents who left Morocco on a chartered flight arranged by the Chinese Embassy in the Kingdom of Morocco arrived in Guangzhou. Apart from one Hong Kong resident who chose to stay in Guangzhou, all others returned to Hong Kong by prearranged coaches and were taken to AsiaWorld-Expo to undergo virus testing.

April 11

To ensure adequate quarantine facilities to cope with the development of the epidemic, the CHP will, where necessary, arrange for people under compulsory quarantine to stay at quarantine centres for the first 10 days and then continue quarantine at home for the remaining four days after virus testing.

April 19

The DH required all asymptomatic inbound travellers arriving on flights landing in the morning to stay and wait for the test results at the temporary specimen collection centre. They can continue quarantine at their place of accommodation only if the test result is negative.

April 19

With a declining number of inbound travellers, the Hospital Authority suspended the operation of the test centre at AsiaWorld-Expo from noon. Inbound travellers with symptoms will be admitted to public hospitals to undergo testing.

April 20

The DH started a trial to provide an extra specimen collection container to inbound travellers arriving at the Hong Kong International Airport for the submission of samples for another round of virus testing (on the 12th day) before the completion of home quarantine. The quarantine can be completed only if the test result is negative.

April 21

The Government announced the extension of all statutory measures to enhance social distancing for 14 days until May 7.

April 22

The DH required all asymptomatic inbound travellers arriving on flights landing in the afternoon or at night to stay and wait for virus test results at the holding centre in the Regal Oriental Hotel. They can continue quarantine at their place of accommodation only if the test result is negative. Upon implementation of the measure, all inbound travellers arriving at Hong Kong International Airport will be required to undergo testing and can return to the community only if the test result is negative.

The decision to extend various enhanced social distancing measures to early May is no doubt a further blow to the affected business sectors. The Government fully understands the disappointment and frustration of these sectors, but we dare not let down our guard as we look at the second or third wave of outbreaks around the world. In addressing the public health crisis, the Government also needs to consider the impact of the measures on the economy, livelihood and the daily lives of people.  I recall that Prof Gabriel Leung, one of the experts for the Government’s anti-epidemic work, once described the difficulty of the Government in making its decisions as a three-way tug of war (See Graphic 2).

We will continue to listen to the views of the experts and various sectors and constantly adjust the suppress and lift strategy according to the actual situation of the epidemic. The target is to achieve the optimal level of controls at all times.

Supporting individuals and businesses affected by the disease

The epidemic has lasted for more than three months and presents unprecedented challenges to our economy. Many businesses are facing pressure to close down or resort to massive staff layoffs, and many families and members of the public are facing severe hardship. According to the latest labour force statistics released by the Census & Statistics Department, the seasonally adjusted unemployment rate for January to March 2020 increased worryingly to 4.2%, the highest level in over nine years.

The Government will continue to make an all-out effort to keep our workers employed, relieve the financial burden of businesses and members of the public, and pave the way for post-epidemic economic recovery. The two rounds of the Anti-epidemic Fund and related relief measures, together with the relief package in the 2020-21 Budget announced by the Financial Secretary earlier on (yet to be approved by the LegCo), amount to $287.5 billion, representing 10% of gross domestic product. These measures are being implemented progressively to help businesses and members of the public tide over the difficult times.

Fighting the virus together

The hard-earned results of our anti-epidemic work over the past month are due to the togetherness of the community at large, the unswerving commitment of our healthcare professionals, the collaborative efforts of various government departments and the understanding of all sectors in society. I am confident that Hong Kong will come through the epidemic and the economic downturn. As long as we can hold on for some more time, we will soon see a bright tomorrow.

Chief Executive Carrie Lam issued this article entitled Three Months into Our Fight Seeing the Arrival of Dawn on April 25.

Rare artefacts from Afghanistan will be on display at the Museum of History from November 6 until February 10, 2020.

Ancient Artefacts of Afghanistan - Glistening Treasures in the Dust will display 231 artefacts, including gold and glass wares, bronze sculptures and ivory carvings unearthed from four famous archaeological sites in Afghanistan.

Highlight exhibits include a golden bowl with a bearded-bull motif unearthed in Tepe Fullol and pendants with styles that were common in the Mesopotamian and Persian Plateau regions.

The precious relics are on loan from the National Museum of Afghanistan.

The museum’s director Mohammad Rahimi said that because Afghanistan borders many countries including China, the artefacts attest to the role ancient Afghanistan played as the cultural crossroads of the Silk Road.

“Afghanistan has been given the title of the crossroads of the ancient civilisation by different scholars of the world. So we had very good relations with different civilisations in the past so that’s why we can see a lot of influences of different cultures in our objects.”

Mr Rahimi added that Afghanistan is sharing its exhibit with Hong Kong as a gesture of goodwill and friendship and with the hope of strengthening relations with China.

“We have also seen different examples of our ancient relations with China. Because of that, we want to build on our relations with China through this exhibition and we have shown that we have had very good connections in the past.”

Many of the exhibits will be equipped with interactive designs so that visitors can compare and contrast the displayed treasures with similar artefacts.

Click here for details.

The Minimum Wage Commission today launched an eight-week public consultation to review the statutory minimum wage rate.

The commission said it adopts an evidence-based approach in conducting the minimum wage rate review and will consider the community's views.

Views can be sent by email before June 16.

Click here for information.

The Government said it will continue to spare no effort in improving workers' benefits and protection and enhance occupational safety and health in various industries at a pace commensurate with Hong Kong's overall socio-economic development.

The Government made the statement today in response to the demands of different labour groups, noting that it would take into account both employees' interests and employers' abilities to afford the benefits, despite the severe blow dealt by the COVID-19 epidemic to the local economy.

"The seasonally adjusted unemployment and underemployment rates for January to March this year have soared to their highest levels in recent years. The labour market will continue to face significant pressure in the near term.

“The Government has rolled out relief measures of unprecedented scale, including the one-off measures in the 2020-21 Budget and two rounds of measures under the Anti-epidemic Fund (AEF) totalling $287.5 billion, with a view to preserving the vitality of the economy and relieving people's financial burden.

“The Government will launch as soon as possible the Employment Support Scheme under the second round of the AEF, with a total commitment of $81 billion, to provide time-limited financial support to employers to help them retain employees who will otherwise be made redundant.”

Moreover, the Government explained that it has earmarked $6 billion to create around 30,000 time-limited jobs in the public and private sectors in the coming two years for people with different skills and academic qualifications.

It emphasised that the Labour Department will raise the ceiling of on-the-job training allowance payable to employers under the Employment Programme for the Elderly & Middle-aged, the Youth Employment & Training Programme and the Work Orientation & Placement Scheme in the second half of this year.

It will also launch a pilot scheme to encourage eligible participants of these programmes to undergo and complete the training by offering a retention allowance.

On improvements to other labour benefits, the Government pointed out that it is working at full steam on the preparatory work to abolish the arrangement of 'offsetting' severance payments and long service payments with employers' mandatory contributions under the Mandatory Provident Fund System.

It stressed that it will strive to introduce the enabling bill into the Legislative Council by the end of this year, aiming to secure its passage by 2022.

Meanwhile, the Government introduced the Employment (Amendment) Bill 2019 into LegCo on January 8 this year. The bill, which proposes to extend statutory maternity leave by four weeks, is now being handled by the LegCo Panel on Manpower.

The Chief Executive announced on January 14 this year 10 new initiatives on improving people's livelihood, one of which is to increase progressively the number of statutory holidays so that it will be on par with that of general holidays.

The Government stated that it will work out the relevant proposal, invite the Labour Advisory Board to discuss, and will facilitate and support its work.

The Minimum Wage Commission is conducting a new round of review on the Statutory Minimum Wage rate and will submit a report on its recommendation to the Chief Executive in Council by end-October.

The Government added that it attaches great importance to employees' occupational safety and health.

It said the Labour Department has been adjusting its strategies of inspection and enforcement, publicity and promotion, education and training according to the occupational safety and health risk levels of different industries as well as taking sufficient precautionary measures to prevent accidents by driving employers and employees to work together.

Carla E. Cox
Aug 1, 2017; 30:157-160
From Research to Practice

Betsy B. Dokken
Jul 1, 2007; 20:166-170
Articles

Priscilla Hollander
Jul 1, 2007; 20:159-165
Articles

Marion J. Franz
Jul 1, 2007; 20:133-136
Editorials

Companies with large numbers of furloughed workers are offering staff an introductory course in JavaScript coding, thanks to the European coding bootcamp, Codeworks.

(Arizona State University) Cun-Zheng Ning, a professor of electrical engineering in the Ira A. Fulton Schools of Engineering at Arizona State University, and collaborators from Tsinghua University in China discovered a process of physics that enables low-power nanolasers to be produced in 2D semiconductor materials. Understanding the physics behind lasers at nanoscale and how they interact with semiconductors can have major implications for high-speed communication channels for supercomputers and data centers.

(ICFO-The Institute of Photonic Sciences) ICFO researchers report on a new method to obtain high color purity 3D objects with the use of a new class of nanoparticles.

Pyruvate kinase muscle isoform 2 (PKM2) is a key glycolytic enzyme involved in ATP generation and critical for cancer metabolism. PKM2 is expressed in many human cancers and is regulated by complex mechanisms that promote tumor growth and proliferation. Therefore, it is considered an attractive therapeutic target for modulating tumor metabolism. Various stimuli allosterically regulate PKM2 by cycling it between highly active and less active states. Several small molecules activate PKM2 by binding to its intersubunit interface. Serine and cysteine serve as an activator and inhibitor of PKM2, respectively, by binding to its amino acid (AA)-binding pocket, which therefore represents a potential druggable site. Despite binding similarly to PKM2, how cysteine and serine differentially regulate this enzyme remains elusive. Using kinetic analyses, fluorescence binding, X-ray crystallography, and gel filtration experiments with asparagine, aspartate, and valine as PKM2 ligands, we examined whether the differences in the side-chain polarity of these AAs trigger distinct allosteric responses in PKM2. We found that Asn (polar) and Asp (charged) activate PKM2 and that Val (hydrophobic) inhibits it. The results also indicate that both Asn and Asp can restore the activity of Val-inhibited PKM2. AA-bound crystal structures of PKM2 displayed distinctive interactions within the binding pocket, causing unique allosteric effects in the enzyme. These structure-function analyses of AA-mediated PKM2 regulation shed light on the chemical requirements in the development of mechanism-based small-molecule modulators targeting the AA-binding pocket of PKM2 and provide broader insights into the regulatory mechanisms of complex allosteric enzymes.

Purinergic signaling by extracellular ATP regulates a variety of cellular events and is implicated in both normal physiology and pathophysiology. Several molecules have been associated with the release of ATP and other small molecules, but their precise contributions have been difficult to assess because of their complexity and heterogeneity. Here, we report on the results of a gain-of-function screen for modulators of hypotonicity-induced ATP release using HEK-293 cells and murine cerebellar granule neurons, along with bioluminescence, calcium FLIPR, and short hairpin RNA–based gene-silencing assays. This screen utilized the most extensive genome-wide ORF collection to date, covering 90% of human, nonredundant, protein-encoding genes. We identified two ABCG1 (ABC subfamily G member 1) variants, which regulate cellular cholesterol, as modulators of hypotonicity-induced ATP release. We found that cholesterol levels control volume-regulated anion channel–dependent ATP release. These findings reveal novel mechanisms for the regulation of ATP release and volume-regulated anion channel activity and provide critical links among cellular status, cholesterol, and purinergic signaling.

Cytochrome c oxidase (CcO) reduces O2 to water, coupled with a proton-pumping process. The structure of the O2-reduction site of CcO contains two reducing equivalents, Fea32+ and CuB1+, and suggests that a peroxide-bound state (Fea33+–O−–O−–CuB2+) rather than an O2-bound state (Fea32+–O2) is the initial catalytic intermediate. Unexpectedly, however, resonance Raman spectroscopy results have shown that the initial intermediate is Fea32+–O2, whereas Fea33+–O−–O−–CuB2+ is undetectable. Based on X-ray structures of static noncatalytic CcO forms and mutation analyses for bovine CcO, a proton-pumping mechanism has been proposed. It involves a proton-conducting pathway (the H-pathway) comprising a tandem hydrogen-bond network and a water channel located between the N- and P-side surfaces. However, a system for unidirectional proton-transport has not been experimentally identified. Here, an essentially identical X-ray structure for the two catalytic intermediates (P and F) of bovine CcO was determined at 1.8 Å resolution. A 1.70 Å Fe–O distance of the ferryl center could best be described as Fea34+ = O2−, not as Fea34+–OH−. The distance suggests an ∼800-cm−1 Raman stretching band. We found an interstitial water molecule that could trigger a rapid proton-coupled electron transfer from tyrosine-OH to the slowly forming Fea33+–O−–O−–CuB2+ state, preventing its detection, consistent with the unexpected Raman results. The H-pathway structures of both intermediates indicated that during proton-pumping from the hydrogen-bond network to the P-side, a transmembrane helix closes the water channel connecting the N-side with the hydrogen-bond network, facilitating unidirectional proton-pumping during the P-to-F transition.

The C-type lectin receptors (CLRs) form a family of pattern recognition receptors that recognize numerous pathogens, such as bacteria and fungi, and trigger innate immune responses. The extracellular carbohydrate-recognition domain (CRD) of CLRs forms a globular structure that can coordinate a Ca2+ ion, allowing receptor interactions with sugar-containing ligands. Although well-conserved, the CRD fold can also display differences that directly affect the specificity of the receptors for their ligands. Here, we report crystal structures at 1.8–2.3 Å resolutions of the CRD of murine dendritic cell-immunoactivating receptor (DCAR, or Clec4b1), the CLR that binds phosphoglycolipids such as acylated phosphatidyl-myo-inositol mannosides (AcPIMs) of mycobacteria. Using mutagenesis analysis, we identified critical residues, Ala136 and Gln198, on the surface surrounding the ligand-binding site of DCAR, as well as an atypical Ca2+-binding motif (Glu-Pro-Ser/EPS168–170). By chemically synthesizing a water-soluble ligand analog, inositol-monophosphate dimannose (IPM2), we confirmed the direct interaction of DCAR with the polar moiety of AcPIMs by biolayer interferometry and co-crystallization approaches. We also observed a hydrophobic groove extending from the ligand-binding site that is in a suitable position to interact with the lipid portion of whole AcPIMs. These results suggest that the hydroxyl group-binding ability and hydrophobic groove of DCAR mediate its specific binding to pathogen-derived phosphoglycolipids such as mycobacterial AcPIMs.

pncRNA-D is an irradiation-induced 602-nt long noncoding RNA transcribed from the promoter region of the cyclin D1 (CCND1) gene. CCND1 expression is predicted to be inhibited through an interplay between pncRNA-D and RNA-binding protein TLS/FUS. Because the pncRNA-D–TLS interaction is essential for pncRNA-D–stimulated CCND1 inhibition, here we studied the possible role of RNA modification in this interaction in HeLa cells. We found that osmotic stress induces pncRNA-D by recruiting RNA polymerase II to its promoter. pncRNA-D was highly m6A-methylated in control cells, but osmotic stress reduced the methylation and also arginine methylation of TLS in the nucleus. Knockdown of the m6A modification enzyme methyltransferase-like 3 (METTL3) prolonged the half-life of pncRNA-D, and among the known m6A recognition proteins, YTH domain-containing 1 (YTHDC1) was responsible for binding m6A of pncRNA-D. Knockdown of METTL3 or YTHDC1 also enhanced the interaction of pncRNA-D with TLS, and results from RNA pulldown assays implicated YTHDC1 in the inhibitory effect on the TLS–pncRNA-D interaction. CRISPR/Cas9-mediated deletion of candidate m6A site decreased the m6A level in pncRNA-D and altered its interaction with the RNA-binding proteins. Of note, a reduction in the m6A modification arrested the cell cycle at the G0/G1 phase, and pncRNA-D knockdown partially reversed this arrest. Moreover, pncRNA-D induction in HeLa cells significantly suppressed cell growth. Collectively, these findings suggest that m6A modification of the long noncoding RNA pncRNA-D plays a role in the regulation of CCND1 gene expression and cell cycle progression.

The dextransucrase DSR-OK from the Gram-positive bacterium Oenococcus kitaharae DSM17330 produces a dextran of the highest molar mass reported to date (∼109 g/mol). In this study, we selected a recombinant form, DSR-OKΔ1, to identify molecular determinants involved in the sugar polymerization mechanism and that confer its ability to produce a very-high-molar-mass polymer. In domain V of DSR-OK, we identified seven putative sugar-binding pockets characteristic of glycoside hydrolase 70 (GH70) glucansucrases that are known to be involved in glucan binding. We investigated their role in polymer synthesis through several approaches, including monitoring of dextran synthesis, affinity assays, sugar binding pocket deletions, site-directed mutagenesis, and construction of chimeric enzymes. Substitution of only two stacking aromatic residues in two consecutive sugar-binding pockets (variant DSR-OKΔ1-Y1162A-F1228A) induced quasi-complete loss of very-high-molar-mass dextran synthesis, resulting in production of only 10–13 kg/mol polymers. Moreover, the double mutation completely switched the semiprocessive mode of DSR-OKΔ1 toward a distributive one, highlighting the strong influence of these pockets on enzyme processivity. Finally, the position of each pocket relative to the active site also appeared to be important for polymer elongation. We propose that sugar-binding pockets spatially closer to the catalytic domain play a major role in the control of processivity. A deep structural characterization, if possible with large-molar-mass sugar ligands, would allow confirming this hypothesis.

VOLUME 289 (2014) PAGES 30635–30644This article has been withdrawn by Guangnan Chen, Dongkyoo Park, Francis A. Cucinotta, David S. Yu, Xingming Deng, William S. Dynan, Paul W. Doetsch, and Ya Wang. Hongyan Wang, Xiang Wang, Xiangming Zhang, and Xiaobing Tang could not be reached. The last two lanes of the actin immunoblot in Fig. 1A were reused in the last two lanes of the actin immunoblot in Fig. 1C. In Fig. 2A, the γ-H2AX and the merge with DAPI images for no IR treatment do not match. In Fig. 3A, lanes 3 and 4 of the γ-H2AX immunoblot were reused in lanes 7 and 8, and lanes 5 and 6 of the H2A immunoblot were reused in lanes 7 and 8. In Fig. 3B, lanes 5 and 6 of the H2A immunoblot were reused in lanes 7 and 8. In Fig. 3C, lanes 5 and 6 of the γ-H2AX immunoblot were reused in lanes 7 and 8. Additionally, lanes 1 and 2 of the H2A immunoblot were reused in lanes 3 and 4. In Fig. 3D, lanes 1 and 2 of the Mre11 immunoblot from lysates were reused in lanes 4 and 5. In the γ-H2AX immunoblot, lane 3 was reused in lane 7, and lane 4 was reused in lanes 6 and 8. Also in the H2A immunoblot, lanes 1 and 2 were reused in lanes 3 and 4. In Fig. 4B, lanes 2 and 6 of the Mre11 immunoblot from Ogg1−/− cells are the same. In the Ape1...

The protein-tyrosine phosphatase SHP2 is an allosteric enzyme critical for cellular events downstream of growth factor receptors. Mutations in the SHP2 gene have been linked to many different types of human diseases, including developmental disorders, leukemia, and solid tumors. Unlike most SHP2-activating mutations, the T507K substitution in SHP2 is unique in that it exhibits oncogenic Ras-like transforming activity. However, the biochemical basis of how the SHP2/T507K variant elicits transformation remains unclear. By combining kinetic and biophysical methods, X-ray crystallography, and molecular modeling, as well as using cell biology approaches, here we uncovered that the T507K substitution alters both SHP2 substrate specificity and its allosteric regulatory mechanism. We found that although SHP2/T507K exists in the closed, autoinhibited conformation similar to the WT enzyme, the interactions between its N-SH2 and protein-tyrosine phosphatase domains are weakened such that SHP2/T507K possesses a higher affinity for the scaffolding protein Grb2-associated binding protein 1 (Gab1). We also discovered that the T507K substitution alters the structure of the SHP2 active site, resulting in a change in SHP2 substrate preference for Sprouty1, a known negative regulator of Ras signaling and a potential tumor suppressor. Our results suggest that SHP2/T507K's shift in substrate specificity coupled with its preferential association of SHP2/T507K with Gab1 enable the mutant SHP2 to more efficiently dephosphorylate Sprouty1 at pTyr-53. This dephosphorylation hyperactivates Ras signaling, which is likely responsible for SHP2/T507K's Ras-like transforming activity.

Prominins (proms) are transmembrane glycoproteins conserved throughout the animal kingdom. They are associated with plasma membrane protrusions, such as primary cilia, as well as extracellular vesicles derived thereof. Primary cilia host numerous signaling pathways affected in diseases known as ciliopathies. Human PROM1 (CD133) is detected in both somatic and cancer stem cells and is also expressed in terminally differentiated epithelial and photoreceptor cells. Genetic mutations in the PROM1 gene result in retinal degeneration by impairing the proper formation of the outer segment of photoreceptors, a modified cilium. Here, we investigated the impact of proms on two distinct examples of ciliogenesis. First, we demonstrate that the overexpression of a dominant-negative mutant variant of human PROM1 (i.e. mutation Y819F/Y828F) significantly decreases ciliary length in Madin–Darby canine kidney cells. These results contrast strongly to the previously observed enhancing effect of WT PROM1 on ciliary length. Mechanistically, the mutation impeded the interaction of PROM1 with ADP-ribosylation factor–like protein 13B, a key regulator of ciliary length. Second, we observed that in vivo knockdown of prom3 in zebrafish alters the number and length of monocilia in the Kupffer's vesicle, resulting in molecular and anatomical defects in the left-right asymmetry. These distinct loss-of-function approaches in two biological systems reveal that prom proteins are critical for the integrity and function of cilia. Our data provide new insights into ciliogenesis and might be of particular interest for investigations of the etiologies of ciliopathies.

(Florida Atlantic University) Despite PPE use, reports show that many health care workers contracted COVID-19. A novel training technique reinforces the importance of using proper procedures to put on and take off PPE when caring for patients during the pandemic. Researchers vividly demonstrate how aerosol-generating procedures can lead to exposure of the contagion with improper PPE use. The most common error made by the health care workers was contaminating the face or forearms during PPE removal.

The traditionally blue-collar neighbourhood of Sham Shui Po is home to a kaleidoscopic collection of landmarks, streets and shops.

Participants of the Sham Shui Po Ensemble project explored the area and told its story through video and music production.

One of the project’s creative productions, the short film Collage created by Cobe Yau and her team, documented the daily lives of the area’s residents.

Ms Yau said Sham Shui Po’s diversity inspired her team to combine footage of residents’ daily activities, such as the unloading of meat and vegetables in wet markets and hawkers selling their wares.

“We hope our viewers can realise that although there are some street sleepers and it may be a bit grimy in some parts of Sham Shui Po, there are also many interesting aspects that make this community stand out.”

Creative journeys

Sham Shui Po Ensemble is under the Community Record Company, an 18-month community-based programme which also showcases two other unique locales.

Last year, participants explored Sai Ying Pun under the West Side Re-Discovery project. Sham Shui Po Ensemble was launched in April and concluded in late July, while the Wander in To Kwa Wan project began this month.

Local documentary maker Wong Siu-pong, the Community Curator of the Sham Shui Po project, hopes participants are able to explore the community without bias.

“Apart from the basics of film production, I did not teach them a lot of filmmaking skills. I hope they learn to be humble when making a documentary.

“A lot of the time, we read the news to learn about a community. I hope they can discover these places without prejudice, this is important.”

Project participants were also able to paint a picture of the community with music.

Warren Luk joined the project’s music stream and wrote the song Rich on Life with his team.

“People always have preconceived ideas of Sham Shui Po. But when you walk through the neighbourhood, you can find lots of quirky and interesting landmarks.

“When you observe the interactions between residents there, you can see that although their lives may be tough, they are enjoying themselves a lot. It is very inspiring.”

The Community Record Company programme is organised by non-governmental organisation MaD Institute and sponsored by the Home Affairs Bureau’s Arts Capacity Development Funding Scheme, which seeks to strengthen Hong Kong’s cultural software and build up the arts sector.

Application details for the next funding exercise will be available in November.

Problems might occur when using SAS Enterprise Guide with dual monitors. For example, it might appear there is a performance problem with the query builder or other task, or it might appear that code or a task is hung, or

(Impact Journals LLC) Oncotarget Volume 11, Issue 12 reported that the p16 tumor suppressor is coded by CDKN2A and plays an important role during carcinogenesis and tumor progression in numerous tumor entities.

(Luxembourg Institute of Health) Scientists at the Department of Infection and Immunity of the Luxembourg Institute of Health (LIH) revealed a novel mechanism through which the immune system controls autoimmunity and cancer. In the special focus of the researchers were regulatory T cells -- a type of white blood cells that act as a brake on the immune system.

(King's College London) A study of female astronauts has assessed the risk of blood clots associated with spaceflight.The study, published in Aerospace Medicine and Human Performance, in collaboration with King's College London, the Centre for Space Medicine Baylor College of Medicine, NASA Johnson Space Centre and the International Space University, examines the potential risk factors for developing a blood clot (venous thromboembolism) in space.

(Kobe University) Hydrogen is a possible next generation energy solution, and it can be produced from sunlight and water using photocatalysts. A research group from Kobe University has developed a strategy that greatly increases the amount of hydrogen produced using hematite photocatalysts. In addition to boosting the high efficiency of what is thought to be the world's highest performing photoanode, this strategy will be applied to artificial photosynthesis and solar water-splitting technologies via university-industry collaborations.

(American Chemical Society) Modern society relies on polymers, such as polypropylene or polyethylene plastic, for a wide range of applications, from food containers to automobile parts to medical devices. However, like people, polymers age, and when they do, the materials become prone to cracking or breaking. Now, researchers reporting in ACS Central Science have developed a method to visualize variations in polymers that arise with age.

(Tokyo University of Science) Plastic waste often ends up in river bodies and oceans, posing a serious threat to the marine ecosystem. To prevent the accumulation of plastic debris, we must find out where plastic emission is prevalent. To this end, scientists in Japan have come up with a new method to track plastic emissions from inland areas to sea. This method is useful to identify the 'hotspots' of plastic emission and can even help to implement appropriate measures to avoid plastic pollution.

(University of Warwick) 21st century X-ray technology has allowed University of Warwick scientists to peer back through time at the production of the armour worn by the crew of Henry VIII's favoured warship, the Mary Rose.

(University of Chicago Press Journals) Extensive cooperation among biologically unrelated individuals is uniquely human. It would be surprising if this uniqueness were not related to other uniquely human characteristics, yet current theories of human cooperation tend to ignore the human aspects of human behavior. This paper presents a theory of cooperation that draws on social, cultural, and psychological aspects of human uniqueness for which current theories have little or no explanation.

(Florida Museum of Natural History) More than a thousand years ago, people from across the Southeast regularly traveled to a small island on Florida's Gulf Coast to bond over oysters, likely as a means of coping with climate change and social upheaval.

(King Abdullah University of Science & Technology (KAUST)) Optical fibers wrapped around date palm trunks could help detect this tree's most destructive pest early enough to save it.