N. O. Malykh and I. S. Postevoy
Theor. Probability and Math. Statist. 99 (2020), 189-198.
Abstract, references and article information

Jeremy Brazas
Proc. Amer. Math. Soc. 148 (2019), 2655-2670.
Abstract, references and article information

Qingying Bu
Proc. Amer. Math. Soc. 148 (2020), 2459-2467.
Abstract, references and article information

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

The Science Museum is presenting the special Unlocking the Secrets - The Science of Conservation at The Palace Museum exhibition to tie in with the 600th anniversary of the Forbidden City in 2020.

More than 100 artefacts from the Palace Museum collection are being showcased to highlight the application of science and technology in conservation.

They include bronzes, clocks, textiles, thangkas, wood furniture, lacquerware and inlaid works along with ceramics, calligraphy and hand-painted copies of ancient paintings.

The show also presents the Conservation Office’s work by showcasing intriguing restoration cases so that visitors can learn more about the work and skills of conservators as well as their mission to preserve Hong Kong’s heritage assets.

The Science Museum will launch a series of interactive family activities, including demonstrations and workshops conducted by Palace Museum conservators, guided tours featuring theatrical plays and storytelling, and visits to conservation laboratories.

Jointly presented by the Leisure & Cultural Services Department and the Palace Museum, the exhibition will run until March 18 next year.

Call 2732 3232 for enquiries.

The Les Arcs Co-Production village, running December 13-16 within the Les Arcs European Film Festival (Dec 13-20), will present 25 projects in development and a further 10 works-in-progress. Several of the projects chosen for this year’s event are Irish films and films with Irish producers’ backing.

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.

Janine Freeman
Jul 1, 2004; 17:137-140
Nutrition FYI

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

Secretary for the Civil Service Patrick Nip today visited the Transport Department (TD) and the Social Welfare Department (SWD) to learn more about the preparations made by both departments to resume public services.

The Government announced that the resumption of public services will start from May 4 under a phased approach.

While the TD will resume road tests on that day, written tests will resume on May 26.

The SWD will also gradually resume the services of its Integrated Family Service Centres (IFSC).

Mr Nip first visited the driving test centre in Ho Man Tin where he was briefed by the Commissioner for Transport Mable Chan on arrangements for the resumption of road tests and the implementation of infection control measures at driving test centres.

Such measures will require candidates to wear surgical masks and undergo body temperature screening at entrances.

As for the written tests, Mr Nip said he was pleased to learn that the TD will keep seats apart at appropriate distances and step up cleansing of computers at test centres.

Mr Nip then visited the Causeway Bay Integrated Family Service Centre where he was briefed on the plan to gradually resume services at IFSCs and measures to reduce social contact.

Mr Nip also learned that various infection control measures to safeguard the health of colleagues as well as service users will be put in place. For example, group activities will be conducted for no more than four participants and physical partitioning will be erected in meeting rooms for counselling services.

Mr Nip emphasised that many people hope that the Government can provide more public services when the epidemic situation becomes stable.

“I am pleased to learn that the departments have made all the necessary preparations for providing the services needed by the public while striving to safeguard public health.

“Government departments will continue to maintain a high degree of vigilance and adopt all the necessary precautionary measures. The Government will also closely monitor the situation and determine when to embark on a full resumption of normal business.”

Mr Nip expressed hope that the public will continue to fight the virus together with the Government.

He also thanked civil servants for their commitment and dedicated efforts to serve the public during the epidemic.

The partnership will join hands with four UK startups as it hopes to reduce plastic waste as part of its retail tech initiative, JLAB

(University of South Florida (USF Health)) A new preclinical study by researchers at the University of South Florida Health (USF Health) Morsani College of Medicine and Johns Hopkins University School of Medicine offers promise of a specific treatment for NEC, a rare inflammatory bowel disease that is a leading cause of death in premature infants. The team found that inhibiting the inflammatory and blood-clotting molecule thrombin with targeted nanotherapy can protect against NEC-like injury in newborn mice.

Chief Executive Carrie Lam inspected one of the CuMask production sites in Tsuen Wan today and expressed gratitude to those manufacturing the reusable masks for Hong Kong residents to fight against the COVID-19 epidemic.

She chatted with the staff and noted that many of them are retired textile industry workers who have re-joined the production workforce to combat the virus.

Mrs Lam praised them for their commitment to serving the community and thanked them for their hard work.

The masks produced in the workshop will be delivered to a clean workspace for sterilising with ozone and packing before distribution. There is no need to wash the mask before it is used for the first time.

In the face of the tight supply of masks amid the epidemic, the Government set aside funds to subsidise projects on technology applications of reusable masks under the first round of the Anti-epidemic Fund.

The CuMask complies with the American Society for Testing & Materials F2100 Level 1 standard and can be washed up to 60 times. It can also be used for a longer period after replacing the filter.

Mrs Lam said she is pleased to note that CuMask is well received by the public and the registration process has been very smooth.

“CuMask is a home-grown scientific research achievement with local application. The whole process has involved co-operation between the Government, industry, academia and the research sector and is an outstanding example of the use of technology to improve people’s lives.

“It will also help solve the problem of the supply of face masks during an epidemic in the long run. I highly commend all the people who have participated in the relevant work and I am fully confident in the development of innovation and technology in Hong Kong.”

Mrs Lam appealed to the public to make use of the registration quota of up to six people to minimise delivery resources and enhance efficiency.

She added that relevant departments will deliver the masks as soon as possible.

Cas12a (Cpf1) is an RNA-guided endonuclease in the bacterial type V-A CRISPR-Cas anti-phage immune system that can be repurposed for genome editing. Cas12a can bind and cut dsDNA targets with high specificity in vivo, making it an ideal candidate for expanding the arsenal of enzymes used in precise genome editing. However, this reported high specificity contradicts Cas12a's natural role as an immune effector against rapidly evolving phages. Here, we employed high-throughput in vitro cleavage assays to determine and compare the native cleavage specificities and activities of three different natural Cas12a orthologs (FnCas12a, LbCas12a, and AsCas12a). Surprisingly, we observed pervasive sequence-specific nicking of randomized target libraries, with strong nicking of DNA sequences containing up to four mismatches in the Cas12a-targeted DNA-RNA hybrid sequences. We also found that these nicking and cleavage activities depend on mismatch type and position and vary with Cas12a ortholog and CRISPR RNA sequence. Our analysis further revealed robust nonspecific nicking of dsDNA when Cas12a is activated by binding to a target DNA. Together, our findings reveal that Cas12a has multiple nicking activities against dsDNA substrates and that these activities vary among different Cas12a orthologs.

(Carnegie Mellon University) A new study sought to determine how the impact of recommender systems (also called recommenders) is affected by factors such as product type, attributes, and other sources of information about products on retailers' websites. The study found that recommenders increased the number of consumer views of product pages as well as the number of products consumers consider, but that the increase was moderated by product attributes and review ratings.

(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.

(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.

Alumni inspired by the scientific response to the SARS outbreak are developing a platform to help researchers collaborate on global challenges.

Invitation Only Research Event

Event participants

Jason Pack, Non-Resident Fellow, Middle East Institute
Tim Eaton, Senior Research Fellow, Middle East and North Africa Programme, Chatham House
Chair: Elham Saudi, Director, Lawyers for Justice Libya

Research Event

Event participants

Glada Lahn, Senior Research Fellow, Energy, Environment and Resources Programme, Chatham House
Greg Shapland, Associate Fellow, Middle East and North Africa Programme, Chatham House 
Moderator: Sanam Vakil, Deputy Director and Senior Research Fellow, Middle East and North Africa Programme, Chatham House

7 April 2020

The prostate-specific membrane antigen (PSMA) is an excellent target for theranostic applications in prostate cancer (PCa). However, PSMA-targeted radioligand therapy can cause undesirable effects due to high accumulation of PSMA radiotracers in salivary glands and kidneys. This study assessed orally administered monosodium glutamate (MSG) as a potential means of reducing kidney and salivary gland radiation exposure using a PSMA targeting radiotracer. Methods: This prospective, double-blind, placebo-controlled study enrolled 10 biochemically recurrent PCa patients. Each subject served as his own control. [¹⁸F]DCFPyl PET/CT imaging sessions were performed 3 – 7 days apart, following oral administration of either 12.7 g of MSG or placebo. Data from the two sets of images were analyzed by placing regions of interest on lacrimal, parotid and submandibular glands, left ventricle, liver, spleen, kidneys, bowel, urinary bladder, gluteus muscle and malignant lesions. The results from MSG and placebo scans were compared by paired analysis of the ROI data. Results: A total of 142 pathological lesions along with normal tissues were analyzed. As hypothesized a priori, there was a significant decrease in maximal standardized uptake values corrected for lean body mass (SULmax) on images obtained following MSG administration in the parotids (24 ± 14%, P = 0.001), submandibular glands (35 ± 11%, P<0.001) and kidneys (23 ± 26%, P = 0.014). Significant decreases were also observed in lacrimal glands (49 ± 13%, P<0.001), liver (15 ± 6%, P<0.001), spleen (28 ± 13%, P = 0.001) and bowel (44 ± 13%, P<0.001). Mildly lower blood pool SULmean was observed after MSG administration (decrease of 11 ± 13%, P = 0.021). However, significantly lower radiotracer uptake in terms of SULmean, SULpeak, and SULmax was observed in malignant lesions on scans performed after MSG administration compared to the placebo studies (SULmax median decrease 33%, range -1 to 75%, P<0.001). No significant adverse events occurred and vital signs were stable following placebo or MSG administration. Conclusion: Orally administered MSG significantly decreased salivary gland, kidney and other normal organ PSMA radiotracer uptake in human subjects, using [¹⁸F]DCFPyL as an exemplar. However, MSG caused a corresponding reduction in tumor uptake, which may limit the benefits of this approach for diagnostic and therapeutic applications.

Research Event

Event participants

Alan Boswell, Senior Analyst for South Sudan, International Crisis Group
Miklos Gosztonyi, Conflict Analyst, South Sudan, Norwegian Refugee Council
Naomi Pendle, Research Fellow, Firoz Lalji Centre for Africa, London School of Economics
Golda Abbé, Founding Member, Ghidam (Via Skype)
Chair: Teohna Williams, CEO, Business Plan for Peace

Research Event

Event participants

Tutu Alicante, Executive Director, EG Justice
Chair: Dr Alex Vines OBE, Managing Director, Ethics, Risk & Resilience; Director, Africa Programme, Chatham House

Phosphoglycerate kinase 1 (PGK1) plays important roles in glycolysis, yet its forward reaction kinetics are unknown, and its role especially in regulating cancer cell glycolysis is unclear. Here, we developed an enzyme assay to measure the kinetic parameters of the PGK1-catalyzed forward reaction. The Km values for 1,3-bisphosphoglyceric acid (1,3-BPG, the forward reaction substrate) were 4.36 μm (yeast PGK1) and 6.86 μm (human PKG1). The Km values for 3-phosphoglycerate (3-PG, the reverse reaction substrate and a serine precursor) were 146 μm (yeast PGK1) and 186 μm (human PGK1). The Vmax of the forward reaction was about 3.5- and 5.8-fold higher than that of the reverse reaction for the human and yeast enzymes, respectively. Consistently, the intracellular steady-state concentrations of 3-PG were between 180 and 550 μm in cancer cells, providing a basis for glycolysis to shuttle 3-PG to the serine synthesis pathway. Using siRNA-mediated PGK1-specific knockdown in five cancer cell lines derived from different tissues, along with titration of PGK1 in a cell-free glycolysis system, we found that the perturbation of PGK1 had no effect or only marginal effects on the glucose consumption and lactate generation. The PGK1 knockdown increased the concentrations of fructose 1,6-bisphosphate, dihydroxyacetone phosphate, glyceraldehyde 3-phosphate, and 1,3-BPG in nearly equal proportions, controlled by the kinetic and thermodynamic states of glycolysis. We conclude that perturbation of PGK1 in cancer cells insignificantly affects the conversion of glucose to lactate in glycolysis.

Research Event

Event participants

Takehiko Nakao, President, Asian Development Bank
Chair: Champa Patel, Head, Asia-Pacific Programme, Chatham House

Sookyoung Jeon
Apr 1, 2020; 61:470-479
Reviews

Inga Nilsson
Mar 10, 2020; 0:jlr.RA120000654v1-jlr.RA120000654
Research Articles

Chelsea DeLeon
May 1, 2020; 61:767-777
Research Articles

In this week's fiery episode host Matt Egan talks war and gaming with Macworld UK's David Price, the greatest graphics ever with Christopher Minasians of PC Advisor and Macworld UK (14:21), and the best networks in the UK with fellow PCA and MWUK stalwart Henry Burrell (25:23). Expect songs and laughter, and tech ever after.  

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Gram-negative bacteria possess an asymmetric outer membrane (OM) composed primarily of lipopolysaccharides (LPS) on the outer leaflet and phospholipids (PLs) on the inner leaflet. Loss of this asymmetry due to mutations in the lipopolysaccharide (LPS) biosynthesis or transport pathways causes externalization of PLs to the outer leaflet of the OM and leads to OM permeability defects. Here, we employed metabolic labeling to detect a compromised OM in intact bacteria. Phosphatidylcholine synthase (Pcs) expression in Escherichia coli allowed for incorporation of exogenous propargylcholine (PCho) into phosphatidyl(propargyl)choline (PPC) and for incorporation of exogenous 1-azidoethyl-choline (AECho) into phosphatidyl(azidoethyl)choline (AEPC) as confirmed by LC-MS analyses. A fluorescent copper-free click reagent poorly labeled AEPC in intact wild-type cells, but readily labeled AEPC from lysed cells. Fluorescence microscopy and flow cytometry analyses confirmed the absence of significant AEPC labeling from intact wild-type E. coli strains, and revealed significant AEPC labeling in an E. coli LPS transport mutant (lptD4213) and an LPS biosynthesis mutant (E. coli lpxC101). Our results suggest that metabolic PL labeling with AECho is a promising tool to detect a compromised bacterial OM, reveal aberrant PL externalization, and identify or characterize novel cell-active inhibitors of LPS biosynthesis or transport.

7 April 2020

Ceramides (Cers) with ultralong (~32-carbon) chains and -esterified linoleic acid, composing a subclass called omega-O-acylceramides (acylCers), are indispensable components of the skin barrier. Normal barriers typically contain acylCer concentrations of ~10 mol%; diminished concentrations, along with altered or missing long periodicity lamellar phase (LPP), and increased permeability accompany an array of skin disorders, including atopic dermatitis, psoriasis, and ichthyoses. We developed model membranes to investigate the effects of the acylCer structure and concentration on skin lipid organization and permeability. The model membrane systems contained six to nine Cer subclasses as well as fatty acids, cholesterol, and cholesterol sulfate; acylCer content—namely, acylCers containing sphingosine (Cer EOS), dihydrosphingosine (Cer EOdS), and phytosphingosine (Cer EOP) ranged from zero to 30 mol%. Systems with normal physiologic concentrations of acylCer mixture mimicked the permeability and nanostructure of human skin lipids (with regard to LPP, chain order, and lateral packing). The models also showed that the sphingoid base in acylCer significantly affects the membrane architecture and permeability and that Cer EOP, notably, is a weaker barrier component than Cer EOS and Cer EOdS. Membranes with diminished or missing acylCers displayed some of the hallmarks of diseased skin lipid barriers (i.e., lack of LPP, less ordered lipids, less orthorhombic chain packing, and increased permeability). These results could inform the rational design of new and improved strategies for the barrier-targeted treatment of skin diseases.

Bile acids (BAs) facilitate intestinal absorption of lipid-soluble nutrients and modulate various metabolic pathways through the farnesoid X receptor (FXR) and Takeda G-protein-coupled receptor 5. These receptors are targets for therapy in cholestatic and metabolic diseases. However, dissimilarities in BA metabolism between humans and mice complicate translation of preclinical data. Cytochrome P450 family 2 subfamily c polypeptide 70 (CYP2C70) was recently proposed to catalyze the formation of rodent-specific muricholic acids (MCAs). With CRISPR/Cas9-mediated somatic genome editing, we generated an acute hepatic Cyp2c70 knockout mouse model (Cyp2c70^ako) to clarify the role of CYP2C70 in BA metabolism in vivo and evaluate whether its activity modulates effects of pharmacologic FXR activation on cholesterol homeostasis. In Cyp2c70^ako mice, chenodeoxycholic acid (CDCA) increased at the expense of βMCA, resulting in a more hydrophobic human-like BA pool. Tracer studies demonstrated that, in vivo, CYP2C70 catalyzes the formation of βMCA primarily by sequential 6β-hydroxylation and C7-epimerization of CDCA, generating αMCA as an intermediate metabolite. Physiologically, the humanized BA composition in Cyp2c70^ako mice blunted the stimulation of fecal cholesterol disposal in response to FXR activation compared with WT mice, predominantly due to reduced stimulation of transintestinal cholesterol excretion. Thus, deletion of hepatic Cyp2c70 in adult mice translates into a human-like BA pool composition and impacts the response to pharmacologic FXR activation. This Cyp2c70^ako mouse model may be a useful tool for future studies of BA signaling and metabolism that informs human disease development and treatment.

Alcoholic liver disease (ALD) is the most prevalent type of chronic liver disease with significant morbidity and mortality worldwide. ALD begins with simple hepatic steatosis and progresses to alcoholic steatohepatitis, fibrosis, and cirrhosis. The severity of hepatic steatosis is highly associated with the development of later stages of ALD. This review explores the disturbances of alcohol-induced hepatic lipid metabolism through altered hepatic lipid uptake, de novo lipid synthesis, fatty acid oxidation, hepatic lipid export, and lipid droplet formation and catabolism. In addition, we review emerging data on the contributions of genetics and bioactive lipid metabolism in alcohol-induced hepatic lipid accumulation.

Many clinical studies and epidemiological investigations have clearly demonstrated that women are twice as likely to develop cholesterol gallstones as men, and oral contraceptives and other estrogen therapies dramatically increase that risk. Further, animal studies have revealed that estrogen promotes cholesterol gallstone formation through the estrogen receptor (ER) α, but not ERβ, pathway. More importantly, some genetic and pathophysiological studies have found that G protein-coupled estrogen receptor (GPER) 1 is a new gallstone gene, Lith18, on chromosome 5 in mice and produces additional lithogenic actions, working independently of ERα, to markedly increase cholelithogenesis in female mice. Based on computational modeling of GPER, a novel series of GPER-selective antagonists were designed, synthesized, and subsequently assessed for their therapeutic effects via calcium mobilization, cAMP, and ERα and ERβ fluorescence polarization binding assays. From this series of compounds, one new compound, 2-cyclohexyl-4-isopropyl-N-(4-methoxybenzyl)aniline (CIMBA), exhibits superior antagonism and selectivity exclusively for GPER. Furthermore, CIMBA reduces the formation of 17β-estradiol-induced gallstones in a dose-dependent manner in ovariectomized mice fed a lithogenic diet for 8 weeks. At 32 μg/day/kg CIMBA, no gallstones are found, even in ovariectomized ERα (^–/–) mice treated with 6 μg/day 17β-estradiol and fed the lithogenic diet for 8 weeks. In conclusion, CIMBA treatment protects against the formation of estrogen-induced cholesterol gallstones by inhibiting the GPER signaling pathway in female mice. CIMBA may thus be a new agent for effectively treating cholesterol gallstone disease in women.­

When you run 32-bit SAS on Windows and disconnect from the Oracle database server, you might see the error: "ERROR: ORACLE disconnect error: ORA-03135: connection lost contact."

An issue occurs when code contains a complex SQL procedure query with a WHERE clause that contains multiple subselects. Incorrect results might be returned. Click the Hot Fix tab in this note to