Shi-Zhong Du
Proc. Amer. Math. Soc. 148 (2020), 2631-2643.
Abstract, references and article information

Yingxiang Hu and Shicheng Xu
Proc. Amer. Math. Soc. 148 (2020), 2609-2615.
Abstract, references and article information

Mohamed Jleli, Bessem Samet and Philippe Souplet
Proc. Amer. Math. Soc. 148 (2020), 2579-2593.
Abstract, references and article information

Bin Li and Jieqiong Shen
Proc. Amer. Math. Soc. 148 (2020), 2565-2578.
Abstract, references and article information

S. Waleed Noor and Osmar R. Severiano
Proc. Amer. Math. Soc. 148 (2020), 2469-2476.
Abstract, references and article information

Naoya Hiramatsu and Ryo Takahashi
Proc. Amer. Math. Soc. 148 (2020), 2359-2369.
Abstract, references and article information

Joseph Reid
Proc. Amer. Math. Soc. 148 (2020), 2331-2343.
Abstract, references and article information

Hong Kong has, for the first time, held the Willem C Vis (East) International Commercial Arbitration Moot (VEM) through an online platform amidst the COVID-19 pandemic. While most of the competitions in other jurisdictions have been cancelled or postponed due to challenges posed by the pandemic, the 17th VEM was the only international mooting which went ahead as scheduled through an online dispute resolution (ODR) platform.

Though the outbreak of COVID-19 has changed our travel patterns and presented many challenges, advance in modern technology has helped us to address them. For the first time in the moot’s history, the mooting competition was conducted completely online with the support of Electronic Business Related Arbitration & Mediation (eBRAM). The platform supported by eBRAM accommodated 71 teams from 21 jurisdictions and about 250 arbitrators from 52 jurisdictions to take part in the moot which started on March 22. This exemplifies the importance of technological developments in the legal field.

The audience, with the latest lawtech support by eBRAM, watched the lively and intensive oral arguments online with participants of the finalists showing considerable flair and aptitude in trying their best to present their case to an international panel of distinguished arbitrators. The Chinese University of Hong Kong won the competition after rounds of rigorous and remarkable oral submissions before the panel.

The Government has always been supportive of the development of lawtech spearheaded by, amongst others, eBRAM, which is expected to be launched this year to resolve cross-boundary disputes online. If funding is approved by the Legislative Council Finance Committee on time, eBRAM would be able to provide an efficient, cost-effective and safe online platform for deal-making and resolution of cross-boundary commercial and investment disputes. We understand that eBRAM also plans to develop an online dispute resolution platform to support cross-boundary business-to-business transactions in the Asia-Pacific Economic Cooperation region.

We would continue to offer our support to the VEM as part of our legal education campaign. However, the VEM would not have been held smoothly without the technical support provided by eBRAM and also the tenacity and determination displayed by the Vis East Moot Foundation. The successful conclusion of the moot proved that Hong Kong has the capability of developing lawtech.

Changes are inevitable, including technological changes. The COVID-19 pandemic posed new challenges to Hong Kong, but it also provides an opportunity for us to explore lawtech in the provision of legal services. We all should join hands to make the best use of the technologies to develop ODR to assist all parties in resolving disputes in an efficient, effective and fair manner with a view to bringing rule of law and justice for all.

Secretary for Justice Teresa Cheng wrote this article and posted it on her blog on March 31.

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.

About 200 archaeological Song-Yuan period finds unearthed at Kai Tak will go on display in an exhibition at the Heritage Discovery Centre from tomorrow until February 26.

Following the closure of Kai Tak Airport in 1998, the planning work for the Kai Tak Development Area created opportunities for archaeological studies around the former Sacred Hill in Kowloon Bay.

An abundance of Song-Yuan period cultural remains were subsequently unearthed, including a huge amount of ceramics produced by various kilns in Zhejiang, Fujian and Jiangxi.

Similar products from the same period were exported widely and could be found in shipwrecks along the maritime ceramics route.

Highlights of the Treasures from the Sacred Hill: Song-Yuan Period Archaeological Discoveries from Kai Tak exhibition include green glazed incense burners with an eight trigrams pattern and a green glazed dish with a moulded double fish pattern produced by Longquan Kiln.

Other highlights include a brown glazed dragon jar with lugs and a green glazed basin with a phoenix pattern produced by Cizao Kiln and a Daguan Tongbao bronze coin.

Ceramics from the same period on loan from the Art Museum of the Chinese University of Hong Kong will also be displayed.

Curated by the Antiquities & Monuments Office, admission to the exhibition is free.

Call 2208 4400 for details.

The Space Museum is staging a special exhibition 2020 Astronomical Events to highlight six major astronomical events happening this year.

The events include grouping of the four planets with the moon in late March, the serial phenomena of Jupiter's moons on June 11 and 12, and the partial solar eclipse on June 21.

Information on the Perseid meteor shower in mid-August, the Geminid meteor shower in mid-December and the Jupiter-Saturn conjunction on December 21 will also be featured.

The exhibit explains details and phenomena of these events, while serving as a practical guide to help visitors pick the best dates, times, locations and tools to observe them.

It will run until September 21 in two phases. The first three events will be presented during the first phase from January to June, while the second phase events will be shown from June to September.

Admission is free.

Call 2721 0226 for enquiries.

Why did the undergraduates cross the road? Extra credit. In concept as well as in practice, I have never understood extra credit. As someone who was home-schooled by a former Catholic high-school principal, “extra credit” was never a part of … Continue reading →

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The pilot month-long Spring Virtual Expo, organised by the Hong Kong Trade Development Council (HKTDC) on its online marketplace hktdc.com Sourcing, concluded successfully on 30 April. It drew 1.4 million online buyers from around the...

The 52nd edition of the Index of Streets, House Numbers & Lots in Hong Kong, Kowloon & New Kowloon, and the 21st edition of the New Territories Lot/Address Cross Reference Table on compact disc are now on sale.

Licences for using the street index and the cross reference table on computer networks are also available for sale.

An online version of the new street index and cross reference table is available on the Land Registry's website or the Integrated Registration Information System Online Services website.

They are designed to facilitate land record searches by correlating property addresses, building names or lot numbers.

The latest edition of the index features 444 amendments, 11 new streets, and the addition of 30 new lots, sections or subsections.

The latest edition of the table features 1,522 amendments, 10 new streets, and 1,146 new lots, sections or subsections.

Click here for order forms.

(To watch the full press conference with sign language interpretation, click here.)

The Government is confident that the Hong Kong Diploma of Secondary Education (DSE) Examination could be held on April 24.

Secretary for Education Kevin Yeung made the statement when explaining the arrangements for the DSE examination at a press conference today.

Mr Yeung said the Government understands that some DSE candidates are concerned about their safety.

He said measures will be taken to make sure that examination venues will be as safe as possible.

Exam candidates will have to wear masks, which have already been distributed, before entering the examination centres. Hand sanitisers will also be given to them.

If a candidate has a fever or upper respiratory tract symptoms, they will not be allowed to take the exam.

Additionally, more classrooms will be turned into examination centres and desks will be separated by at least 1.8m in most centres.

Mr Yeung said: “We are now confident that the exam could be held on April 24.

“We believe that with everyone’s effort and hopefully with the support of the community in trying to control the spread of the disease, we will be able to complete the DSE exam by the end of May.”

Secretary for Education Kevin Yeung said all the examination centres for the Hong Kong Diploma of Secondary Education (DSE) Examination are well prepared to provide a very safe environment for candidates to take the exams.

Mr Yeung made the statement when asked by reporters this morning about the arrangements schools have made to prepare for the DSE to be held on April 24.

He said: “In terms of the distance between the seats, in terms of all the procedures for cleansing, and also the detailed arrangements including the toilet arrangement and other things, all the schools, all the examination centres, are well prepared to provide a very safe environment for our candidates to take the examinations.”

Regarding school resumption, Mr Yeung said the Government has not made any firm decision nor set any deadline for schools to resume classes.

Chief Secretary Matthew Cheung today visited Queen Elizabeth School to inspect the preparatory work of an examination centre for the Hong Kong Diploma of Secondary Education (DSE) Examination.

Mr Cheung was briefed on anti-epidemic precautionary measures for candidates and examination personnel before they enter the centres.

They will be required to wear masks, make health declarations, undergo temperature checks, disinfect the soles of their shoes and clean their hands with alcohol-based sanitiser.

He then visited the school hall to understand the preparation required for an examination centre, such as disinfection and widening the distance between candidates’ seats to 1.8m as much as possible.

The Chief Secretary also learnt about the arrangements for candidates during the sessional break and the use of washrooms to help ensure that social distancing is maintained.

Mr Cheung was pleased to know that the Education Bureau had earlier distributed masks to candidates and made available about 200,000 bottles of alcohol-based sanitiser for candidates at examination centres.

The bureau has also set fallback dates, should the DSE examination be halted if the epidemic situation worsens.

He thanked the bureau, relevant government departments, the Examinations & Assessment Authority, principals, teachers and school staff for the additional work they have done to protect the candidates’ health and safety.

He encouraged the some 50,000 candidates to tackle the examinations positively and optimistically and reminded them to heighten their anti-epidemic awareness and strictly follow examination arrangements.

Additionally, Mr Cheung appealed to all employers to allow their staff to follow flexible working hours to divert passenger flows on public transport during the morning peak hours between 7am and 8am, thus enabling candidates to reach examination centres on time.

Recipients of the Individual-based Work Incentive Transport Subsidy (I-WITS) will receive a one-off extra allowance after the passage of the Appropriation Bill 2020, the Government announced today.

The extra allowance was proposed in the 2020-21 Budget and would be disbursed one month after the bill’s passage at the earliest.

Eligible recipients are those whose I-WITS applications were made in the applicable period - from the first day of the month in which the bill is passed to the date of the bill’s passage, and six calendar months before that month.

New applicants or previous I-WITS recipients who have yet to submit applications in the applicable period should do so on or before the date of the bill’s passage to be eligible for the extra allowance.

The extra allowance will be the average monthly amount of approved months payable to the applicants in their I-WITS applications which were most recently submitted in the applicable period and eventually approved.

Click here for details.

The deadline for applications under the first round of funding from the Elder Academy Development Foundation in 2020 has been extended to June 30, the Labour & Welfare Bureau announced today.

The decision aims to provide sufficient time for primary and secondary school sponsoring bodies, post-secondary institutions and organisations, which may be affected by the COVID-19 epidemic, to prepare their submissions.

The fund’s committee accepts funding applications all year round and conducts vetting and disburses funding twice a year. The deadlines were generally May 31 and October 31 respectively.

The committee will continue to monitor the situation and announce arrangements for the next round in due course.

To tie in with the Elder Academy Scheme, the fund mainly provides funding for primary and secondary schools as well as post-secondary institutions to set up academies to provide learning opportunities in a school setting for the elderly.

Funding is also provided for activities that encourage elderly learning and inter-generational harmony.

Call 3655 5861 or 3655 5007 for enquiries.

Geralyn Spollett
Jan 1, 2003; 16:
Case Studies

The Government today announced the mechanism for Hong Kong enterprises with manufacturing operations in the Mainland to apply for exemption from the compulsory quarantine arrangement. 

It said the Trade & Industry Department has started processing applications.

The Chief Secretary may designate anybody or category of people for exemption from quarantine if their travelling is necessary for purposes relating to manufacturing operations in the interest of Hong Kong's economic development.

With effect from May 4, the Chief Secretary has exempted two categories of people from the quarantine arrangement.

They include owners of Hong Kong enterprises with a valid business registration certificate and with manufacturing operations in the Mainland and up to one person employed and authorised by the enterprise, as well as up to two people employed and authorised by such an enterprise.

Exempted people must only travel to and stay in the city where the Mainland factory of their Hong Kong enterprise's manufacturing operations is located and must take every precautionary measure to ensure personal hygiene and avoid unnecessary social contact. 

After returning to Hong Kong, they will be subject to medical surveillance arranged by the Department of Health during their stay in Hong Kong and will be required to wear masks and have their body temperatures checked daily.

They will also have to report any discomfort to the Department of Health.

Click here for more information.

The Mortgage Corporation today announced that the pilot scheme for fixed-rate mortgages will start receiving applications from May 7.

The aggregate loan amount of the Fixed-rate Mortgage Pilot Scheme is $1 billion, subject to a maximum loan amount of each private residential mortgage of $10 million.

Financial Secretary Paul Chan said the pilot scheme, announced in the 2020-21 Budget, provides an alternative financing option to homebuyers for mitigating their risks arising from interest rate volatility, thereby promoting the development of the mortgage market in the long run.

In response to the change in market interest rates, mortgage interest rates under the pilot scheme have been lowered, as compared to the levels previously announced in the Budget. The interest rates per annum for 10, 15 and 20 years are 2.55%, 2.65% and 2.75%.

Mortgages under the pilot scheme will be offered through Bank of China, Chong Hing Bank, Dah Sing Bank, Industrial & Commercial Bank of China, Shanghai Commercial Bank, Standard Chartered Bank and The Bank of East Asia.

At the end of the fixed-rate period, borrowers may either re-fix the mortgage rate under fixed-rate mortgages or convert the mortgage to a loan on a floating rate, which is the prime rate minus 2.35%.

The pilot scheme will be effective until October 31.

Secretary for Constitutional & Mainland Affairs Erick Tsang today visited the temporary operation centre for the special scheme for delivering urgently needed prescription medication to Hong Kong people in Guangdong and Fujian.

Under the compulsory quarantine arrangements, many Hong Kong people who are staying in Guangdong and Fujian provinces are unable to attend follow-up consultations in Hong Kong to replenish their prescription medication and return to the Mainland on the same day.

The Government introduced a special scheme on February 24 to deliver medicine to them, with priority given to those who would run out of prescription medication by end-April.

Mr Tsang was pleased to learn that as of April 29, prescription medication deliveries had been made to more than 7,600 Hong Kong residents in need.

He thanked the Hong Kong Federation of Trade Unions for offering voluntary services for the drug delivery scheme with its well-established service networks on the Mainland.

Mr Tsang also thanked the Pharmaceutical Society of Hong Kong and Hong Kong Pharmaceutical Care Foundation for deploying pharmacists to the temporary operation centre to help verify drug records and patients' information.

During his visit, he gave encouragement to participating volunteers and thanked them for their support for the scheme.

Mr Tsang said as the expiry date for the Compulsory Quarantine of Certain Persons Arriving at Hong Kong Regulation has been extended to June 7, the special scheme will be extended and give priority to cases in which prescription drugs will run out on or before that date.

Call 2343 2255 for enquiries about the scheme.

(To watch the full media session with sign language interpretation, click here.)

Chief Executive Carrie Lam today said the prevailing chairwoman of the Legislative Council House Committee should have the responsibility and power to deal with the matters of the committee.

Mrs Lam made the statement ahead of the Executive Council meeting this morning, noting LegCo President Andrew Leung had sought advice from outside senior counsel on how to address the delay in electing the committee’s chairman.

She said the senior counsels have observed that many of the matters raised in the House Committee’s meetings by the presiding member in the past six months have been irrelevant to the purpose of electing the committee’s chairman and vice-chairman.

“The second point that the senior counsels have observed during their very detailed scrutiny of the deliberations is that there was at least one occasion on March 13 in the House Committee meeting that gave people a very clear impression that the delaying of the election by the presiding member of the House Committee was quite deliberate and deliberate for political reasons.

“And the third thing that I observed from the senior counsels’ advice is, having regard to all these circumstances, they are of the firm view - this is the word taken from the senior counsels’ statement - that the prevailing chairwoman of the House Committee should have the responsibility and the power to deal with the business of the House Committee.”

The Chief Executive added that she expects the committee’s prevailing chairwoman Starry Lee to exercise her power.

The 2020 honours and awards selection and appointment of Justices of the Peace (JPs) exercise will be postponed, as well as the announcement of the list of honours and awards and JP appointments, the Government announced today.

It decided to defer the exercise to accord top priority to the ongoing anti-epidemic work and implementation of measures to retain employment, support businesses and ease people's livelihood in the face of challenges arising from the COVID-19 epidemic.

The Honours List and JP appointments will be announced on October 1 instead of July 1 as in previous years, the Government added.

The US-based 'startup studio' will launched a London office to welcome European startups

Hong Kong Exchanges & Clearing Limited (HKEx) today announced that Charles Li will not seek reappointment as Chief Executive at the end of his current contract in October 2021.

The Government said it respected Mr Li's decision and expressed deep appreciation for his exemplary contribution to the development of the financial market during his tenure as HKEx Chief Executive in the past decade.

Since taking the helm in January 2010, he has led HKEx and Hong Kong’s capital market in achieving important breakthroughs one after another.

The vibrancy and growth that Mr Li has brought to Hong Kong in the capital market helps reinforce the status of Hong Kong as a leading international financial centre.

Financial Secretary Paul Chan said: "Thanks to his vision and leadership, Mr Li has laid a solid and strong foundation for our stock market, rendering Hong Kong the largest IPO market in the world for seven times in the past 11 years.

"He has been instrumental in the successful launch of mutual market access programmes between Hong Kong and the Mainland, notably the Shanghai-Hong Kong Stock Connect in 2014, which was expanded to include Shenzhen-Hong Kong Stock Connect in 2016 and Bond Connect in 2017.

"He also played a pivotal role in the launch of new listing regime in Hong Kong, the enhanced internationalisation of HKEx and its international visibility. These are all important achievements of HKEx in the past few years under Mr Li’s able leadership."

Mr Chan added that the Government is confident the HKEx board will continue to ensure the success of HKEx in the years to come.

General Stations: 1 to 2 (Health Risk: Low)

Roadside Stations: 2 (Health Risk: Low)

(University of Southampton) Scientists have published highly detailed images of lab-grown neurons using Extreme Ultraviolet radiation that could aid the analysis of neurodegenerative diseases.

(Ecole Polytechnique Fédérale de Lausanne) EPFL chemists have developed sponges to capture various target substances, like gold, mercury and lead, dissolved in solution. The sponges are actually porous crystals called metal organic frameworks, and now one exists for capturing toxic hexavalent chromium from water.

(To watch the full press conference with sign language interpretation, click here.)

The relaxation of anti-epidemic measures is a step in the right direction, Chief Executive Carrie Lam said today.

Mrs Lam made the statement at a press conference this afternoon.

She said the Government will relax the requirement limiting group gatherings in public places to a maximum of four people. Starting from Friday, up to eight people can gather in public places.

"So raising the number from four to eight for the catering business and also for the prohibition against group gatherings under Cap 599G is not an exact science, but this is a step in the right direction of relaxation.

"Maybe in another 14 days’ time we will raise the number of eight to 10, to 12, to 15 and so on."

Regarding bars and pubs, Mrs Lam said these venues will be able to reopen but the Government will put in place requirements to prevent physical interactions.

"We have decided that perhaps to strike a pragmatic balance is to allow them to reopen for business but to put in far more stringent requirements."

Such requirements include no live music, band performances or dancing in bar premises.

"That would be another way to keep the social distance and prevent as much as possible physical interactions."

Click here for the latest measures.

(To watch the full press briefing with sign language interpretation, click here.)

The Centre for Health Protection today said recovered COVID-19 patients or those who did not have any symptoms may be discharged from hospital 10 days after the onset of symptoms or a positive test result.

Its Communicable Disease Branch Head Dr Chuang Shuk-kwan told a press briefing that the revised discharge criteria was based on the latest scientific evidence.

“Our Scientific Committee on Emerging & Zoonotic Diseases met yesterday and examined the latest scientific evidence on whether the virus will be viable from a patient.

“And the available evidence showed that this virus is usually not detected after 10 days since the onset of symptoms of patients. Some patients may have persistent positive PCR (polymerase chain reaction) for a long period of time.”

Dr Chuang noted that patients still had to meet the criteria of having two clinical specimens test negative, or testing positive for the SARS-CoV-2 antibody to be discharged.

“We have revised the discharge criteria to include the patient who (must have) been staying in the hospital for at least 10 days after the onset of symptoms. So this is the additional criteria, in addition to the previous criteria of two consecutive negative specimens.

“We added another criteria (which is) in case a patient has stayed in the hospital for a long time, more than 10 days since the onset of symptoms, but he or she has persistent positive PCR despite the Ct (cycle threshold) value being very high, they can check their serology, the antibody. So if the antibody turns positive, usually it is after 10 days, then he or she can be discharged.

“So this is based on the latest scientific evidence.”

The 2020 Mathematical Art Exhibition Awards were made at the Joint Mathematics Meetings last week "for aesthetically pleasing works that combine mathematics and art." The chosen works were selected from the exhibition of juried works in various media by over 90 mathematicians and artists from around the world.

"Suspended Helical Stair," by Mark Donohue (California College of the Arts, San Francisco, CA), was awarded Best textile, sculpture, or other medium. "A unique cable system to suspend a stair was developed in collaboration with a leading structural engineer. The suspended cables form a double helicoid nested within an ascending spiral hyperboloid to create the necessary points of support for the gravity loads and lateral bracing for the seismic loads. Each concrete stair tread was designed as an independent element that is strung together with the stairs above and below it to form a single spiral stair when the steel cables that run through them are post tensioned. The entire stair tread and suspension cable system can be understood as a play of ruled surfaces with each part related to the other through their shared geometric lineage." The work is string and plywood,45 x 23 x 23 cm, 2018.

2018

"A Unit Domino," by Douglas McKenna (Mathemaesthetics, Inc., Boulder, CO), was awarded Best photograph, painting, or print. "This piece is based upon an artist-discovered "half-domino" space-filling curve. The drawing comprises some half-million connected line segments, arranged in two perfectly recursive levels of double-spiral pairs, slowly changing color, in a single, over-one-mile-long self-avoiding path from lower left to lower right (the lower right square that sticks out is an integral part of its self-negative structure). The limiting curve covers a self-similar gasket tile with an infinitely long, almost-everywhere linear border. With an upside-down copy of itself, two such gaskets of unit area exactly cover a 1x2 domino, without overlap. The artist's app/eBook "Hilbert Curves" for iPad/iPhone explains how he discovered these beautiful constructions." The work is a glicée print,106 x 66 cm, 2015.

"Computational Wings," by David Bachman (Pitzer College, Claremont, CA), received Honorable Mention. "The body of this dragonfly is taken from a photograph, while the wings were computationally generated. A variety of algorithms were used to create them. First, a set of points were randomly populated across each wing and moved by a circle packing algorithm, where the radius of each circle was inversely proportional to the distance from the body. Next, those points were used to create a Voronoi diagram. Main veins were located by a shortest walk algorithm through the edges of this diagram, and those veins were given a variable thickness according to the distance travelled as you traverse them outward from the body." The work is laser etched acrylic, 23 x 35 x 3 cm, 2019.

(Click on the thumbnails to see larger versions of the images.)

The Mathematical Art Exhibition Award "for aesthetically pleasing works that combine mathematics and art" was established in 2008 through an endowment provided to the American Mathematical Society by an anonymous donor who wishes to acknowledge those whose works demonstrate the beauty and elegance of mathematics expressed in a visual art form. The awards are $400 for Best photograph, painting, or print; $400 for Best textile, sculpture, or other medium; and $200 for Honorable Mention. The Mathematical Art Exhibition of juried works in various media is held at the annual Joint Mathematics Meetings of the American Mathematical Society (AMS) and Mathematical Association of America (MAA). a gallery of works in the 2020 exhibition will be on AMS Mathematical Imagery.

Find out more about the Mathematical Art Exhibition Award and see past recipients.

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The American Mathematical Society is dedicated to advancing research and connecting the diverse global mathematical community through our publications, meetings and conferences, MathSciNet, professional services, advocacy, and awareness programs.

VOLUME 285 (2010) PAGES 13742–13747In Fig. 1E, passage 10, the splicing of a non-adjacent lane from the same immunoblot was not marked. This error has now been corrected and does not affect the results or conclusions of this work.jbc;295/16/5533/F1F1F1Figure 1E.

Neoantimycins are anticancer compounds of 15-membered ring antimycin-type depsipeptides. They are biosynthesized by a hybrid multimodular protein complex of nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS), typically from the starting precursor 3-formamidosalicylate. Examining fermentation extracts of Streptomyces conglobatus, here we discovered four new neoantimycin analogs, unantimycins B–E, in which 3-formamidosalicylates are replaced by an unusual 3-hydroxybenzoate (3-HBA) moiety. Unantimycins B–E exhibited levels of anticancer activities similar to those of the chemotherapeutic drug cisplatin in human lung cancer, colorectal cancer, and melanoma cells. Notably, they mostly displayed no significant toxicity toward noncancerous cells, unlike the serious toxicities generally reported for antimycin-type natural products. Using site-directed mutagenesis and heterologous expression, we found that unantimycin productions are correlated with the activity of a chorismatase homolog, the nat-hyg5 gene, from a type I PKS gene cluster. Biochemical analysis confirmed that the catalytic activity of Nat-hyg5 generates 3-HBA from chorismate. Finally, we achieved selective production of unantimycins B and C by engineering a chassis host. On the basis of these findings, we propose that unantimycin biosynthesis is directed by the neoantimycin-producing NRPS–PKS complex and initiated with the starter unit of 3-HBA. The elucidation of the biosynthetic unantimycin pathway reported here paves the way to improve the yield of these compounds for evaluation in oncotherapeutic applications.

Previous studies have shown that sphingosine kinase interacting protein (SKIP) inhibits sphingosine kinase (SK) function in fibroblasts. SK phosphorylates sphingosine producing the potent signaling molecule sphingosine-1-phosphate (S1P). SKIP gene (SPHKAP) expression is silenced by hypermethylation of its promoter in acute myeloid leukemia (AML). However, why SKIP activity is silenced in primary AML cells is unclear. Here, we investigated the consequences of SKIP down-regulation in AML primary cells and the effects of SKIP re-expression in leukemic cell lines. Using targeted ultra-HPLC-tandem MS (UPLC-MS/MS), we measured sphingolipids (including S1P and ceramides) in AML and control cells. Primary AML cells had significantly lower SK activity and intracellular S1P concentrations than control cells, and SKIP-transfected leukemia cell lines exhibited increased SK activity. These findings show that SKIP re-expression enhances SK activity in leukemia cells. Furthermore, other bioactive sphingolipids such as ceramide were also down-regulated in primary AML cells. Of note, SKIP re-expression in leukemia cells increased ceramide levels 2-fold, inactivated the key signaling protein extracellular signal-regulated kinase, and increased apoptosis following serum deprivation or chemotherapy. These results indicate that SKIP down-regulation in AML reduces SK activity and ceramide levels, an effect that ultimately inhibits apoptosis in leukemia cells. The findings of our study contrast with previous results indicating that SKIP inhibits SK function in fibroblasts and therefore challenge the notion that SKIP always inhibits SK activity.

The transcription factor forkhead box P3 (FOXP3) is a biomarker for regulatory T cells and can also be expressed in cancer cells, but its function in cancer appears to be divergent. The role of hepatocyte-expressed FOXP3 in hepatocellular carcinoma (HCC) is unknown. Here, we collected tumor samples and clinical information from 115 HCC patients and used five human cancer cell lines. We examined FOXP3 mRNA sequences for mutations, used a luciferase assay to assess promoter activities of FOXP3's target genes, and employed mouse tumor models to confirm in vitro results. We detected mutations in the FKH domain of FOXP3 mRNAs in 33% of the HCC tumor tissues, but in none of the adjacent nontumor tissues. None of the mutations occurred at high frequency, indicating that they occurred randomly. Notably, the mutations were not detected in the corresponding regions of FOXP3 genomic DNA, and many of them resulted in amino acid substitutions in the FKH region, altering FOXP3's subcellular localization. FOXP3 delocalization from the nucleus to the cytoplasm caused loss of transcriptional regulation of its target genes, inactivated its tumor-inhibitory capability, and changed cellular responses to histone deacetylase (HDAC) inhibitors. More complex FKH mutations appeared to be associated with worse prognosis in HCC patients. We conclude that mutations in the FKH domain of FOXP3 mRNA frequently occur in HCC and that these mutations are caused by errors in transcription and are not derived from genomic DNA mutations. Our results suggest that transcriptional mutagenesis of FOXP3 plays a role in HCC.

Prostate cancer (PCa) cells heavily rely on an active androgen receptor (AR) pathway for their survival. Enzalutamide (MDV3100) is a second-generation antiandrogenic drug that was approved by the Food and Drug Administration in 2012 to treat patients with castration-resistant prostate cancer (CRPC). However, emergence of resistance against this drug is inevitable, and it has been a major challenge to develop interventions that help manage enzalutamide-resistant CRPC. Erythropoietin-producing human hepatocellular (Eph) receptors are targeted by ephrin protein ligands and have a broad range of functions. Increasing evidence indicates that this signaling pathway plays an important role in tumorigenesis. Overexpression of EPH receptor B4 (EPHB4) has been observed in multiple types of cancer, being closely associated with proliferation, invasion, and metastasis of tumors. Here, using RNA-Seq analyses of clinical and preclinical samples, along with several biochemical and molecular methods, we report that enzalutamide-resistant PCa requires an active EPHB4 pathway that supports drug resistance of this tumor type. Using a small kinase inhibitor and RNAi-based gene silencing to disrupt EPHB4 activity, we found that these disruptions re-sensitize enzalutamide-resistant PCa to the drug both in vitro and in vivo. Mechanistically, we found that EPHB4 stimulates the AR by inducing proto-oncogene c-Myc (c-Myc) expression. Taken together, these results provide critical insight into the mechanism of enzalutamide resistance in PCa, potentially offering a therapeutic avenue for enhancing the efficacy of enzalutamide to better manage this common malignancy.

Telomeres are specific nucleoprotein structures that are located at the ends of linear eukaryotic chromosomes and play crucial roles in genomic stability. Telomere DNA consists of simple repeats of a short G-rich sequence: TTAGGG in mammals and TTTAGGG in most plants. In recent years, the mammalian telomeric G-rich repeats have been shown to form G-quadruplex (G4) structures, which are crucial for modulating telomere functions. Surprisingly, even though plant telomeres are essential for plant growth, development, and environmental adaptions, only few reports exist on plant telomeric G4 DNA (pTG4). Here, using bulk and single-molecule assays, including CD spectroscopy, and single-molecule FRET approaches, we comprehensively characterized the structure and dynamics of a typical plant telomeric sequence, d[GGG(TTTAGGG)3]. We found that this sequence can fold into mixed G4s in potassium, including parallel and antiparallel structures. We also directly detected intermediate dynamic transitions, including G-hairpin, parallel G-triplex, and antiparallel G-triplex structures. Moreover, we observed that pTG4 is unfolded by the AtRecQ2 helicase but not by AtRecQ3. The results of our work shed light on our understanding about the existence, topological structures, stability, intermediates, unwinding, and functions of pTG4.

Prevention of aberrant cutaneous wound repair and appropriate regeneration of an intact and functional integument require the coordinated timing of fibroblast and keratinocyte migration. Here, we identified a mechanism whereby opposing cell-specific motogenic functions of a multifunctional intracellular and extracellular protein, the receptor for hyaluronan-mediated motility (RHAMM), coordinates fibroblast and keratinocyte migration speed and ensures appropriate timing of excisional wound closure. We found that, unlike in WT mice, in Rhamm-null mice, keratinocyte migration initiates prematurely in the excisional wounds, resulting in wounds that have re-surfaced before the formation of normal granulation tissue, leading to a defective epidermal architecture. We also noted aberrant keratinocyte and fibroblast migration in the Rhamm-null mice, indicating that RHAMM suppresses keratinocyte motility but increases fibroblast motility. This cell context–dependent effect resulted from cell-specific regulation of extracellular signal-regulated kinase 1/2 (ERK1/2) activation and expression of a RHAMM target gene encoding matrix metalloprotease 9 (MMP-9). In fibroblasts, RHAMM promoted ERK1/2 activation and MMP-9 expression, whereas in keratinocytes, RHAMM suppressed these activities. In keratinocytes, loss of RHAMM function or expression promoted epidermal growth factor receptor–regulated MMP-9 expression via ERK1/2, which resulted in cleavage of the ectodomain of the RHAMM partner protein CD44 and thereby increased keratinocyte motility. These results identify RHAMM as a key factor that integrates the timing of wound repair by controlling cell migration.