The challenger brand launched by the high street bank will be shutting down after informing customers that it is closing down the app-only bank

dlberek posted a photo:

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C. De Filippis and G. Mingione
St. Petersburg Math. J. 31 (2020), 455-477.
Abstract, references and article information

N. Arcozzi, K. Domelevo and S. Petermichl
Proc. Amer. Math. Soc. 148 (2020), 2433-2446.
Abstract, references and article information

Two short films have made it one step closer to an Oscar nomination after picking up a Light in Motion (LIM) award at the Foyle Film Festival’s closing ceremony in Brunswick Moviebowl.

(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.”

The seasonally adjusted unemployment rate increased to 4.2% in the period between January and March, up from 3.7% for the period between December 2019 and February, the Census & Statistics Department announced today.

The underemployment rate also increased to 2.1% in the period.

Total employment dropped by 48,800 to 3,720,000 while the labour force fell by 20,800 to 3,882,200.

There were 134,100 unemployed people in the period, an increase of 28,100 from the period between December 2019 and February, and the number of underemployed people rose by 23,700 to 82,800.

Secretary for Labour & Welfare Dr Law Chi-kwong said that the labour market further deteriorated as the COVID-19 pandemic severely disrupted a wide range of economic activities.

The unemployment rate soared by 0.5 percentage point to 4.2% for the period, the highest in more than nine years, while the underemployment rate likewise surged 0.6 percentage point to 2.1%, the highest in nearly a decade, he said.

The year-on-year declines in total employment and labour force widened further to 3.6% and 2.2%, both the largest on record.

The combined unemployment rate of the consumption and tourism-related sectors of retail, accommodation and food services soared to 6.8%, the highest since the period between August and October in 2009 following the global financial crisis, while the underemployment rate rose to 3.9%, the highest since the period between June and August of 2003 following the onslaught of SARS.

Dr Law added the situation in food and beverage service activities was severe, with the unemployment and underemployment rates surging to 8.6% and 5.4%.

Meanwhile, the unemployment and underemployment rates of the construction sector went up drastically to 8.5% and 7.1% amid a visible slowdown in construction activities.

The unemployment and underemployment situation worsened visibly in the transportation and education sectors as well. Labour market conditions in most other sectors also saw deterioration of various degrees.

Dr Law said: "The labour market will continue to face significant pressure from the economic fallout arising from the pandemic 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 the two rounds of measures under the Anti-epidemic Fund totalling $287.5 billion, with a view to preserving the vitality of the economy and relieving people's financial burdens.

“Some specific measures, in particular the Employment Support Scheme and various types of support for specific sectors, should help keep workers in employment.

“The Government will closely monitor the developments, including the progress and effectiveness of the various relief measures.”

The value of total retail sales in March, provisionally estimated at $23 billion, fell 42% compared with the same month in 2019, the Census & Statistics Department announced today.

After netting out the effect of price changes over the same period, the volume of total retail sales decreased 43.8% year-on-year.

The value of sales of food, alcoholic drinks and tobacco decreased 21.2%.

This was followed by commodities in department stores (-42.7% in value); other consumer goods, not elsewhere classified (-29.1%); electrical goods and other consumer durable goods, not elsewhere classified (-39.6%); jewellery, watches and clocks, and valuable gifts (-75.2%); medicines and cosmetics (-63.8%); wearing apparel (-67.2%); motor vehicles and parts (-19.8%); fuels (-8%); furniture and fixtures (-14.4%); books, newspapers, stationery and gifts (-48.4%); Chinese drugs and herbs (-51.7%); footwear, allied products and other clothing accessories (-60.6%); and optical shops (-46.6%).

The value of sales of commodities in supermarkets increased 16.1% for the period.

The Government said retail sales continued to plummet in March as the COVID‑19 pandemic and resulting anti-epidemic measures brought inbound tourism to a standstill and seriously disrupted consumption-related activities.

For the first quarter as a whole, the volume of retail sales fell 36.9% year-on-year, the largest decline for a single quarter on record.

Noting that the business environment for retail trade will remain very difficult in the near term amid the deep economic recession and sharp deterioration in the labour market, the Government said it will closely monitor the developments.

To align with the phased resumption of public services, various government departments have announced their latest arrangements.

The Department of Justice’s public services will resume normal from May 4. The reception counters of the department’s Prosecutions Division and Civil Division will be open Monday to Friday from 9am to 1pm and 2pm to 6pm.

The Legal Aid Department’s offices will resume normal office hours on May 4 to provide public services including civil and criminal legal aid application and litigation services.

The Government Logistics Department’s collection office will resume normal operation from May 4 and open Monday to Friday from 8.30am to 1pm and 2pm to 5pm.

The Lands Department's offices will resume public counter services and enquiry telephone lines on May 4, providing services such as payment of government rent and premiums, map sales, and collection of compensation for land resumption.

Except for the surveying services to be conducted outside Hong Kong, all services of the Marine Department will resume starting May 4.

The Rating & Valuation Department will resume normal operation of public services from May 4, with its enquiry counters opening from 8.15am to 6pm from Monday to Friday, except on public holidays.

The Civil Engineering & Development Department said office hours for the Civil Engineering Library, applications for dumping licences and sand removal permits, and the Mines Division’s Permit & Licensing Office will return to normal on May 4.

Public services of the Water Supplies Department, the Planning Department, the Drainage Services Department and the Inland Revenue Department will resume normal on May 4.

Starting from May 4, the Registration & Electoral Office’s enquiry counter and offices, the Buildings Department and the Environmental Protection Department’s public counter services and service counters under the Labour Department will reopen.

The Independent Commission Against Corruption's headquarters and regional offices will also resume normal services from May 4.

The Housing Authority's estate management offices, Public Rental Housing Application Office in the Lok Fu Customer Service Centre, the Clearance Housing Office and the Redevelopment Sub-section Offices will reinstate normal services from that date.

Flat selection sessions of the Territory-wide Overcrowding Relief Exercise, the Living Space Improvement Transfer Scheme and Sale of Home Ownership Scheme Flats 2019 will gradually resume from May 8.

Click here for the latest public service arrangements.

To align with the phased resumption of public services, the Information Services Department, Government Records Service and Civil Aviation Department have announced their latest arrangements.

The Information Services Department will resume sales counter services at its Publications Sales Unit and Photo Library at North Point Government Offices from May 4.

The sales office will be open from 9am to 12.30pm and from 2pm to 6pm from Monday to Friday.

To reduce social contact and avoid people gathering, citizens are encouraged to purchase government publications and photos through the online bookstore and photo store.

The Government Records Service's Public Records Office will provide search room services, including onsite loan and circulation services, from Monday to Friday, 9am to 5.45pm, for people who have made reservations through the online catalogue.

The office will also resume search room services from 9am to 1pm on Saturdays for people to inspect holdings which have been reserved online. 

Requests by up to 15 users will be accepted for search room services for each open day on a first-come, first-served basis. Users will be notified of the reservation results by email.

Visitor and public education programmes will continue to be suspended, while the Exhibition Hall at the Public Records Building will be temporarily closed for preparation of the new thematic exhibition until further notice.

Enquiries can be made to 2195 7700 or via email.

The Civil Aviation Department’s Personnel Licensing Office will continue to provide counter services from next Monday and resume relevant licensing examinations.

The office's opening hours are 8.45am to 12.45pm and 1.45pm to 5pm, Monday to Friday. Enquiries can be made to 2910 6046 or via email.

Click here for the latest public service arrangements.

The Centre for Health Protection today announced it is investigating four additional confirmed COVID-19 cases.

The newly reported cases involve four males aged between 11 and 47. All of them travelled during the incubation period.

Epidemiological investigations and relevant contact tracing on the confirmed cases are ongoing.

The centre again urged the public to maintain an appropriate social distance from other people as much as possible to minimise the risk of infection.

People should go out less and avoid social activities such as having meals out or other gatherings to minimise the risk of outbreak clusters emerging in the community.

As the COVID-19 situation remains severe and the number of cases reported around the world continues to rise, people are strongly advised to avoid all non-essential travel outside Hong Kong as well as maintain strict personal and environmental hygiene at all times.

Additionally, the Hospital Authority reported that there are currently 120 patients under isolation and that 944 patients have been discharged upon recovery.

For information and health advice on COVID-19, visit the Government's dedicated webpage.

More than 8,200 applications for the Anti-epidemic Support Scheme for Property Management Sector (ASPM) have been received, with over 3,850 approved, the Government announced today.

The approved applications involve subsidies of more than $140 million and will benefit around 22,000 building blocks and about 35,750 frontline property management workers.

Launched under the Anti-epidemic Fund, the ASPM provides subsidies to owners' organisations or property management companies of eligible buildings to provide hardship allowance to frontline property management workers.

It also provides the Anti-epidemic Cleansing Subsidy to owners' organisations or property management companies.

The scheme’s first phase covers private residential and composite buildings, while its second phase covers industrial and commercial buildings.

The ASPM is still open for applications and continues to disburse subsidies.

Contact the Property Management Services Authority at 3696 1156 or 3696 1166, or visit its website for details.

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.

Mammalian cytochrome P450 enzymes often metabolize many pharmaceuticals and other xenobiotics, a feature that is valuable in a biotechnology setting. However, extant P450 enzymes are typically relatively unstable, with T50 values of ∼30–40 °C. Reconstructed ancestral cytochrome P450 enzymes tend to have variable substrate selectivity compared with related extant forms, but they also have higher thermostability and therefore may be excellent tools for commercial biosynthesis of important intermediates, final drug molecules, or drug metabolites. The mammalian ancestor of the cytochrome P450 1B subfamily was herein characterized structurally and functionally, revealing differences from the extant human CYP1B1 in ligand binding, metabolism, and potential molecular contributors to its thermostability. Whereas extant human CYP1B1 has one molecule of α-naphthoflavone in a closed active site, we observed that subtle amino acid substitutions outside the active site in the ancestor CYP1B enzyme yielded an open active site with four ligand copies. A structure of the ancestor with 17β-estradiol revealed only one molecule in the active site, which still had the same open conformation. Detailed comparisons between the extant and ancestor forms revealed increases in electrostatic and aromatic interactions between distinct secondary structure elements in the ancestral forms that may contribute to their thermostability. To the best of our knowledge, this represents the first structural evaluation of a reconstructed ancestral cytochrome P450, revealing key features that appear to contribute to its thermostability.

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.

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