Pietro Mercuri and René Schoof
Math. Comp. 89 (2020), 1969-1991.
Abstract, references and article information

Roberto Ferretti and Michel Mehrenberger
Math. Comp. 89 (2019), 1783-1805.
Abstract, references and article information

Telehealth and GP service Babylon has rolled out a "COVID-19 Care Assistant" with a raft of features designed to help subscribers cope with symptoms during the pandemic, from the safety of their phone screen

Weimin Chen
Proc. Amer. Math. Soc. 148 (2020), 2707-2716.
Abstract, references and article information

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.

The coach and rail journey app has launched a new AI voice app for automated disruption alerts

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.

Treatment of patients with chronic lymphocytic leukemia (CLL) with inhibitors of Bruton's tyrosine kinase (BTK), such as ibrutinib, is limited by primary or secondary resistance to this drug. Examinations of CLL patients with late relapses while on ibrutinib, which inhibits BTK's catalytic activity, revealed several mutations in BTK, most frequently resulting in the C481S substitution, and disclosed many mutations in PLCG2, encoding phospholipase C-γ2 (PLCγ2). The PLCγ2 variants typically do not exhibit constitutive activity in cell-free systems, leading to the suggestion that in intact cells they are hypersensitive to Rac family small GTPases or to the upstream kinases spleen-associated tyrosine kinase (SYK) and Lck/Yes-related novel tyrosine kinase (LYN). The sensitivity of the PLCγ2 variants to BTK itself has remained unknown. Here, using genetically-modified DT40 B lymphocytes, along with various biochemical assays, including analysis of PLCγ2-mediated inositol phosphate formation, inositol phospholipid assessments, fluorescence recovery after photobleaching (FRAP) static laser microscopy, and determination of intracellular calcium ([Ca2+]i), we show that various CLL-specific PLCγ2 variants such as PLCγ2S707Y are hyper-responsive to activated BTK, even in the absence of BTK's catalytic activity and independently of enhanced PLCγ2 phospholipid substrate supply. At high levels of B-cell receptor (BCR) activation, which may occur in individual CLL patients, catalytically-inactive BTK restored the ability of the BCR to mediate increases in [Ca2+]i. Because catalytically-inactive BTK is insensitive to active-site BTK inhibitors, the mechanism involving the noncatalytic BTK uncovered here may contribute to preexisting reduced sensitivity or even primary resistance of CLL to these drugs.

VOLUME 292 (2017) PAGES 3531–3540This article has been withdrawn by Shuofeng Hu, Xiaomin Ying, Xiangming Zhang, and Ya Wang. Baocheng Hu, Xiang Wang, Ping Wang, Jian Wang, and Hongyan Wang could not be reached. In Fig. 1C, the DAPI and merged images for the no IR control were switched. The DNA-PKcs and actin immunoblots on the left appear to have been spliced. In Fig. 4C, the DNA-PKcs immunoblot appears to have been spliced. In Fig. 4D, lanes 1 and 5; lanes 2, 6, and 8; and lanes 3 and 7 of the DNA-PKcs immunoblot are the same. In the p-DNA-PKcs immunoblot, lanes 1 and 8, lanes 2 and 6, and lanes 3 and 7 are the same. In the CRY2 immunoblot, lanes 5 and 7 are the same. In the CDC25A immunoblot, lanes 3 and 8 are the same. In the GSK3B immunoblot, lanes 1 and 5 and lanes 3 and 7 are the same. Also in the GSK3B immunoblot, the upper GSK3B bands in lanes 6 and 8 are the same. Lanes 4 and 8 of the cyclin D1 immunoblot are the same. In Fig. 5A, the CDC25A immunoblot appears to have been spliced. Also in Fig. 5A, lanes 2–4 and lanes 6–8 of the CDC25A immunoblot are the same. Lanes 4–6 and 7–9 of the actin immunoblot are the same. In Fig. 5C, lane 1 of the CDC25A immunoblot was reused in lane 5, and lanes 3 and 4 were reused in lanes 7 and 8. In the...

The rapid emergence and dissemination of methicillin-resistant Staphylococcus aureus (MRSA) strains poses a major threat to public health. MRSA possesses an arsenal of secreted host-damaging virulence factors that mediate pathogenicity and blunt immune defenses. Panton–Valentine leukocidin (PVL) and α-toxin are exotoxins that create lytic pores in the host cell membrane. They are recognized as being important for the development of invasive MRSA infections and are thus potential targets for antivirulence therapies. Here, we report the high-resolution X-ray crystal structures of both PVL and α-toxin in their soluble, monomeric, and oligomeric membrane-inserted pore states in complex with n-tetradecylphosphocholine (C14PC). The structures revealed two evolutionarily conserved phosphatidylcholine-binding mechanisms and their roles in modulating host cell attachment, oligomer assembly, and membrane perforation. Moreover, we demonstrate that the soluble C14PC compound protects primary human immune cells in vitro against cytolysis by PVL and α-toxin and hence may serve as the basis for the development of an antivirulence agent for managing MRSA infections.

We previously reported that overexpression of cytochrome P450 family 24 subfamily A member 1 (CYP24A1) increases lung cancer cell proliferation by activating RAS signaling and that CYP24A1 knockdown inhibits tumor growth. However, the mechanism of CYP24A1-mediated cancer cell proliferation remains unclear. Here, we conducted cell synchronization and biochemical experiments in lung adenocarcinoma cells, revealing a link between CYP24A1 and anaphase-promoting complex (APC), a key cell cycle regulator. We demonstrate that CYP24A1 expression is cell cycle–dependent; it was higher in the G2-M phase and diminished upon G1 entry. CYP24A1 has a functional destruction box (D-box) motif that allows binding with two APC adaptors, CDC20-homologue 1 (CDH1) and cell division cycle 20 (CDC20). Unlike other APC substrates, however, CYP24A1 acted as a pseudo-substrate, inhibiting CDH1 activity and promoting mitotic progression. Conversely, overexpression of a CYP24A1 D-box mutant compromised CDH1 binding, allowing CDH1 hyperactivation, thereby hastening degradation of its substrates cyclin B1 and CDC20, and accumulation of the CDC20 substrate p21, prolonging mitotic exit. These activities also occurred with a CYP24A1 isoform 2 lacking the catalytic cysteine (Cys-462), suggesting that CYP24A1's oncogenic potential is independent of its catalytic activity. CYP24A1 degradation reduced clonogenic survival of mutant KRAS-driven lung cancer cells, and calcitriol treatment increased CYP24A1 levels and tumor burden in Lsl-KRASG12D mice. These results disclose a catalytic activity-independent growth-promoting role of CYP24A1 in mutant KRAS-driven lung cancer. This suggests that CYP24A1 could be therapeutically targeted in lung cancers in which its expression is high.

The Airport Authority expanded the scope of its food waste recycling programme in 2011 to cover Hong Kong International Airport business partners, including restaurants and lounges operating in terminal buildings, as well as airline catering companies, hotels and cargo terminals.

In 2017-18, over 2,000 tonnes of food waste from 17 airport business partners were collected for recycling.

Rainie Ho, the supervisor of one participating restaurant, said staff make every effort to collect food waste on a constant basis.

“We have three bins of recycled food waste, including eggs, toast, bread, chicken, meat, pork bones, tea and coffee every day.”

Ms Ho gave kudos to the Airport Authority for making the process simple.

“The Airport Authority provides us with garbage bags every month. We explain to our staff that the red bags are for food waste, while the black ones are for general rubbish. This makes it easier for them to remember and handle.”

Airport Authority Assistant General Manager (Sustainability) Mike Kilburn is the facilitator of the food waste recycling programme. He hoped to encourage more business partners to join by making the scheme as trouble-free as possible.

“This is an example of an easy, useful and free programme because the contractor comes to collect from each company and the contractor provides a clean rubbish bin for the food waste, they take the food waste away, they wash the bin and then they bring it back clean.

“And it is useful because the food waste is not just sent to the landfill, but it is turned into fish meal so it goes back into the food chain because the fish meal is fed to the fish and the people can eat the fish, so it is a very complete system.”

Surplus food collection

In addition to food waste recycling, the authority promotes the Food Rescue Programme in co-operation with a local non-governmental organisation called Food Angel.

In 2013, the authority helped Food Angel to purchase a refrigerated truck and covered the cost of collecting surplus food from business partners on the airport island.

By 2014, a central storage room was set up in the terminal building to collect even more surplus food from catering outlets.

By proving it can reduce its environmental impact by working closely with the entire airport community, the authority was recognised at the 2018 Hong Kong Awards for Environmental Excellence where it won the Gold Award for the Public & Community Services Sector.

Future prep

In 2018, the authority launched a voluntary municipal solid waste charging pilot scheme to achieve waste reduction.

It has assisted more than 200 tenants with measuring their waste generation and calculating what it would cost to dump it in the future.

Another participating restaurant manager Alfred Lau explained that the pilot scheme helps restaurants gear up for the polluter-pays principle.

“A mock monthly invoice was issued to us, showing the quantity of waste disposed and the estimated disposal charge. Now we understand that by reducing our waste, we will pay less in the end.”

Mr Lau believes the pilot scheme encourages eateries to alter their disposal behaviour by recycling as much food waste as possible.

“Our disposed waste amount fell sharply once we learnt useful ways to recycle. Our restaurant is located in the restricted area of the airport where drinks are not allowed to be brought inside. So many passengers buy bottled drinks and create a large amount of plastic waste. Just by recycling plastic bottles, our waste decreased significantly.”

The authority said it is proud to be the driving force behind waste reduction.

“We make it easy for them because we do all the organisation, we make it useful because they can help them to prepare, and it is free for them to join the programme. This is very important for us because as the Airport Authority, our job is to create a concept that other people can follow and if you address those three criteria, you make it very hard for them to say no to you. We take away their reasons to say no, so it is easy for them to join our scheme,” said Mr Kilburn.

The Hong Kong Awards for Environmental Excellence is led by the Environmental Campaign Committee alongside the Environmental Protection Department and in conjunction with nine organisations. The objective is to reduce Hong Kong’s environmental impact by promoting environmental management.

The Airport Authority’s current target is to reduce, recycle and recover 50% of all its waste by 2021.