Jonathan P. Sorenson and Jonathan Webster
Math. Comp. 89 (2020), 1953-1968.
Abstract, references and article information

Long Chen and Xuehai Huang
Math. Comp. 89 (2019), 1711-1744.
Abstract, references and article information

While only a small group of North Koreans have access to the global internet, usage patterns are changing among the elites of Pyongyang – with those in military intelligence circles now exhibiting stronger security chops, a report from Recorded Future has found

While coordinated action is urgently needed, should we be racing to download everything that promises a solution?

Kamen G. Ivanov and Pencho Petrushev
Trans. Amer. Math. Soc. 373 (2020), 3117-3176.
Abstract, references and article information

Boris Adamczewski, Julien Cassaigne and Marion Le Gonidec
Trans. Amer. Math. Soc. 373 (2020), 3085-3115.
Abstract, references and article information

peterphotographic posted a photo:

Airfix 1:72 RNLI Severn Class - Plymouth Lifeboat

Walthamstow, East London, UK

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

Ştefan O. Tohǎneanu and Yu Xie
Proc. Amer. Math. Soc. 148 (2020), 2411-2419.
Abstract, references and article information

Alexander J. Rasmussen
Proc. Amer. Math. Soc. 148 (2020), 2345-2357.
Abstract, references and article information

Police today welcomed the Communications Authority’s decision that Radio Television Hong Kong (RTHK) should be seriously warned regarding complaints against an episode of its programme Pentaprism broadcast on November 20, 2019.

Police said it had taken note of the press release issued by the authority on April 20 about its decision.

The authority found that the host’s remarks made in the programme were irresponsible and could be regarded as hate speech with the effect of inciting hatred against Police.

The remarks were also unfair to and were capable of adversely affecting Police’s reputation.

The authority took the view that the complaints in respect of accuracy, incitement of hatred and fairness were substantiated and decided that RTHK should be seriously warned.

Since the anti-extradition bill protests in June last year, rumours have been circulating to defame and smear Police in an attempt to disrupt its relations with the community, the force said.

Police reiterated that they are willing to accept criticisms which are constructive and based on goodwill, but they do not accept inaccurate or misleading reports and remarks, and will follow up as appropriate.

The Financial Secretary just delivered the latest Budget on Wednesday. The Department of Justice would foster the policy initiatives relating to "Diversified Economy" and continue our ongoing works. The Inclusive Dispute Avoidance & Resolution Office (IDAR Office, email: idar@doj.gov.hk), which was set up in January last year, is to better co-ordinate and implement initiatives in the areas of dispute avoidance and resolution, thereby further consolidating our position as an international legal and dispute resolution services centre in the Asia-Pacific region.

The Department of Justice has always been actively striving for the presence of international dispute resolution bodies in Hong Kong in order to meet the upsurge in demand for legal and dispute resolution services arising from the Belt & Road Initiative and the Greater Bay Area Plan. Their presence in Hong Kong would also enhance our status as a leading centre for international legal and dispute resolution services. With the support of the Central People's Government, we are now exploring the possibility for the Asian-African Legal Consultative Organization (AALCO) to establish a regional centre for international commercial arbitration in Hong Kong.

Last year, the inter-sessional meetings of the Judgments Project of the Hague Conference on Private International Law were successfully concluded in Hong Kong. This invaluable experience has reinforced our determination in looking for decision-making meetings of international and intergovernmental organisations to be held in Hong Kong, including hosting the 59th Annual Session of AALCO and an intersessional meeting of UNCITRAL's Working Group III this year. High ranking government officials and legal experts from member states would take part in these meetings to discuss matters such as maritime law and cyber space law.

In addition, we are committed to strengthening Hong Kong's status as a regional capacity building centre which seeks to enhance legal infrastructure in the neighbouring regions and facilitate cross-border mobility and business activities. For instance, the Department of Justice organised the Investment Law & Investor-State Mediator Training Course for two consecutive years since 2018. World-renowned trainers were invited to share with the participants their experience in international investment law and investor-state mediation. We would be stepping up our efforts in organising capacity building courses in dispute resolution.

At the same time, the Department of Justice has reached an agreement with the Hague Academy of International Law, one of the world's leading academic institutes on international law, to support them in organising law courses in Hong Kong regularly in collaboration with the Asian Academy of International Law from this year. We anticipate this cooperation would provide Hong Kong and the neighbouring regions with high quality training for legal professionals, which helps further raise our international profile.

Looking ahead, colleagues in the Department of Justice would keep pursuing co-operation or partnership agreements with other jurisdictions and international organisations and host important events in Hong Kong, with a view to raising the international profile of Hong Kong in deal-making and dispute resolution through overseas capacity building and promotional activities.

Secretary for Justice Teresa Cheng wrote this article and posted it on her blog on March 1.

Start-up Express, a development programme launched by the Hong Kong Trade Development Council (HKTDC) in 2018, is returning for its third edition to help local start-ups build connections, explore markets, seek partners and enhance...

Amy P. Campbell
May 1, 2017; 30:76-81
From Research to Practice

Education secretary, Damian Hinds, wants schools across the UK to “take advantage of all of the opportunities available through Edtech” in the government's new strategy

The 'unicorn letter', sent by some of the best-funded private technology companies in the country, asks the chancellor to form an urgent taskforce to give them access to government-backed lending schemes during the pandemic

The Treasury has announced a new set of financial measures aimed at helping startups during the coronavirus pandemic, including a £250 Future Fund for startups with at least £250,000 in funding

Emily Riehl, Johns Hopkins University, received the university's $250,000 President's Frontier Award, whose purpose is to nurture individuals at Johns Hopkins University who are breaking new ground and poised to become leaders in their field. Riehl studies category theory and says that "I just thought the proofs were the most beautiful of any of the other areas I've encountered. ... It was sort of love at first sight and I am lucky to be able to do what I love." The award is considered a "$250,000 investment in doing more of what she loves."

Also see and hear this coverage: "Johns Hopkins Mathematician from B-N [Bloomington-Normal, IL] Breaks Barriers and Wins Research Grant, by Jolie Sherman, WGLT, February 27, 2020.

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.

ATP plays important roles outside the cell, but the mechanism by which it is arrives in the extracellular environment is not clear. Dunn et al. now show that decreases in cellular cholesterol levels mediated by the ABCG1 transporter increase ATP release by volume-regulated anion channels under hypotonic conditions. Importantly, these results may imply that cells that handle cholesterol differently might experience differential extracellular ATP release during hypotonicity.

VOLUME 295 (2020) PAGES 3285–3300An incorrect graph was used in Fig. 5C. This error has now been corrected. Additionally, some of the statistics reported in the legend and text referring to Fig. 5C were incorrect. The F statistics for Fig. 5C should state Fken(3,16) = 7.454, p < 0.01; FCCCP(1,16) = 102.9, p < 0.0001; Finteraction(3,16) = 7.480, p < 0.01. This correction does not affect the results or conclusions of this work.jbc;295/17/5835/F5F1F5Figure 5C.

In cyanobacteria, metabolic pathways that use the nitrogen-rich amino acid arginine play a pivotal role in nitrogen storage and mobilization. The N-terminal domains of two recently identified bacterial enzymes: ArgZ from Synechocystis and AgrE from Anabaena, have been found to contain an arginine dihydrolase. This enzyme provides catabolic activity that converts arginine to ornithine, resulting in concomitant release of CO2 and ammonia. In Synechocystis, the ArgZ-mediated ornithine–ammonia cycle plays a central role in nitrogen storage and remobilization. The C-terminal domain of AgrE contains an ornithine cyclodeaminase responsible for the formation of proline from ornithine and ammonia production, indicating that AgrE is a bifunctional enzyme catalyzing two sequential reactions in arginine catabolism. Here, the crystal structures of AgrE in three different ligation states revealed that it has a tetrameric conformation, possesses a binding site for the arginine dihydrolase substrate l-arginine and product l-ornithine, and contains a binding site for the coenzyme NAD(H) required for ornithine cyclodeaminase activity. Structure–function analyses indicated that the structure and catalytic mechanism of arginine dihydrolase in AgrE are highly homologous with those of a known bacterial arginine hydrolase. We found that in addition to other active-site residues, Asn-71 is essential for AgrE's dihydrolase activity. Further analysis suggested the presence of a passage for substrate channeling between the two distinct AgrE active sites, which are situated ∼45 Å apart. These results provide structural and functional insights into the bifunctional arginine dihydrolase–ornithine cyclodeaminase enzyme AgrE required for arginine catabolism in Anabaena.

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

Although a robust inflammatory response is needed to combat infection, this response must ultimately be terminated to prevent chronic inflammation. One mechanism that terminates inflammatory signaling is the production of alternative mRNA splice forms in the Toll-like receptor (TLR) signaling pathway. Whereas most genes in the TLR pathway encode positive mediators of inflammatory signaling, several, including that encoding the MyD88 signaling adaptor, also produce alternative spliced mRNA isoforms that encode dominant-negative inhibitors of the response. Production of these negatively acting alternatively spliced isoforms is induced by stimulation with the TLR4 agonist lipopolysaccharide (LPS); thus, this alternative pre-mRNA splicing represents a negative feedback loop that terminates TLR signaling and prevents chronic inflammation. In the current study, we investigated the mechanisms regulating the LPS-induced alternative pre-mRNA splicing of the MyD88 transcript in murine macrophages. We found that 1) the induction of the alternatively spliced MyD88 form is due to alternative pre-mRNA splicing and not caused by another RNA regulatory mechanism, 2) MyD88 splicing is regulated by both the MyD88- and TRIF-dependent arms of the TLR signaling pathway, 3) MyD88 splicing is regulated by the NF-κB transcription factor, and 4) NF-κB likely regulates MyD88 alternative pre-mRNA splicing per se rather than regulating splicing indirectly by altering MyD88 transcription. We conclude that alternative splicing of MyD88 may provide a sensitive mechanism that ensures robust termination of inflammation for tissue repair and restoration of normal tissue homeostasis once an infection is controlled.