The proptech startup wanted to democratise investment in prime real estate projects through crowdfunding, but government regulations have limited its reach to high net worth individuals

D. V. Gusak and E. V. Karnaukh
Theor. Probability and Math. Statist. 99 (2020), 77-89.
Abstract, references and article information

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

The Security Bureau today said that the last Hong Kong resident who had contracted COVID-19 while aboard the Diamond Princess cruise ship and was hospitalised in Japan has returned to Hong Kong.

Immigration Department staff that assisted Hong Kong residents in Japan have completed their mission and returned to Hong Kong as well.

In early February, a cluster of COVID-19 infection cases occurred on the Diamond Princess cruise docked in Yokohama.

Of some 3,700 passengers and crew, about 370 were from Hong Kong. The 712 confirmed COVID-19 cases associated with the cruise included 76 Hong Kong residents who were hospitalised in Japan for isolation and treatment.

While three Hong Kong residents passed away, the remaining 73 patients returned to Hong Kong or their places of residence after being discharged from the hospital.

As for other Hong Kong residents on the cruise, the bureau noted that the Hong Kong Special Administrative Region Government arranged three flights, between February 19 and 23, to escort 193 of them back to the city.

Upon arrival, they were transferred to the quarantine centre at Chun Yeung Estate to undergo 14 days of quarantine.

Another 144 Hong Kong residents returned on their own via other flights, including 25 close contacts of the patients who had completed quarantine in Japan.

For those who returned to Hong Kong on their own and did not complete 14 days of quarantine in Japan, they were required to complete the remaining quarantine period at a quarantine centre.

Of the 231 cruise passengers admitted to the quarantine centre at Chun Yeung Estate, nine tested positive for COVID-19 and were sent to hospitals for isolation and treatment.

The Hong Kong SAR Government expressed profound condolences on the passing of the Hong Kong patients and its deepest sympathies to their families.

The SAR Government emphasised that the incident could not have been resolved 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, the Embassy of the People’s Republic of China in Japan and Japanese authorities.

The SAR Government also thanked Cathay Pacific Airways and the Airport Authority for their assistance, the bureau added.

"Driverless cars, robot butlers and reusable rockets--if the big inventions of the past decade and the artificial intelligence developed to create them have taught us anything, it's that maths is undeniably cool. And if you’re still not convinced, chances are you’ve never had it explained to you via a live experiment with a pigeon before. Temporary pigeon handler and queen of making numbers fun is Dr Hannah Fry, the host of this year's annual Royal Institution Christmas Lectures." Learn more in "Christmas Lectures presenter Dr Hannah Fry on pigeons, AI and the awesome power of maths," by Rachael Pells, inews, December 23, 2019.

The actin cytoskeleton is extremely dynamic and supports diverse cellular functions in many physiological and pathological processes, including tumorigenesis. However, the mechanisms that regulate the actin-related protein 2/3 (ARP2/3) complex and thereby promote actin polymerization and organization in cancer cells are not well-understood. We previously implicated the proline-rich 11 (PRR11) protein in lung cancer development. In this study, using immunofluorescence staining, actin polymerization assays, and siRNA-mediated gene silencing, we uncovered that cytoplasmic PRR11 is involved in F-actin polymerization and organization. We found that dysregulation of PRR11 expression results in F-actin rearrangement and nuclear instability in non-small cell lung cancer cells. Results from molecular mechanistic experiments indicated that PRR11 associates with and recruits the ARP2/3 complex, facilitates F-actin polymerization, and thereby disrupts the F-actin cytoskeleton, leading to abnormal nuclear lamina assembly and chromatin reorganization. Inhibition of the ARP2/3 complex activity abolished irregular F-actin polymerization, lamina assembly, and chromatin reorganization due to PRR11 overexpression. Notably, experiments with truncated PRR11 variants revealed that PRR11 regulates F-actin through different regions. We found that deletion of either the N or C terminus of PRR11 abrogates its effects on F-actin polymerization and nuclear instability and that deletion of amino acid residues 100–184 or 100–200 strongly induces an F-actin structure called the actin comet tail, not observed with WT PRR11. Our findings indicate that cytoplasmic PRR11 plays an essential role in regulating F-actin assembly and nuclear stability by recruiting the ARP2/3 complex in human non-small cell lung carcinoma cells.

Accumulating evidence suggests that brown adipose tissue (BAT) is a potential therapeutic target for managing obesity and related diseases. PGAM family member 5, mitochondrial serine/threonine protein phosphatase (PGAM5), is a protein phosphatase that resides in the mitochondria and regulates many biological processes, including cell death, mitophagy, and immune responses. Because BAT is a mitochondria-rich tissue, we have hypothesized that PGAM5 has a physiological function in BAT. We previously reported that PGAM5-knockout (KO) mice are resistant to severe metabolic stress. Importantly, lipid accumulation is suppressed in PGAM5-KO BAT, even under unstressed conditions, raising the possibility that PGAM5 deficiency stimulates lipid consumption. However, the mechanism underlying this observation is undetermined. Here, using an array of biochemical approaches, including quantitative RT-PCR, immunoblotting, and oxygen consumption assays, we show that PGAM5 negatively regulates energy expenditure in brown adipocytes. We found that PGAM5-KO brown adipocytes have an enhanced oxygen consumption rate and increased expression of uncoupling protein 1 (UCP1), a protein that increases energy consumption in the mitochondria. Mechanistically, we found that PGAM5 phosphatase activity and intramembrane cleavage are required for suppression of UCP1 activity. Furthermore, utilizing a genome-wide siRNA screen in HeLa cells to search for regulators of PGAM5 cleavage, we identified a set of candidate genes, including phosphatidylserine decarboxylase (PISD), which catalyzes the formation of phosphatidylethanolamine at the mitochondrial membrane. Taken together, these results indicate that PGAM5 suppresses mitochondrial energy expenditure by down-regulating UCP1 expression in brown adipocytes and that its phosphatase activity and intramembrane cleavage are required for UCP1 suppression.

The developing nervous system is remarkably sensitive to environmental signals, including disruptive toxins, such as polybrominated diphenyl ethers (PBDEs). PBDEs are an environmentally pervasive class of brominated flame retardants whose neurodevelopmental toxicity mechanisms remain largely unclear. Using dissociated cortical neurons from embryonic Rattus norvegicus, we found here that chronic exposure to 6-OH–BDE-47, one of the most prevalent hydroxylated PBDE metabolites, suppresses both spontaneous and evoked neuronal electrical activity. On the basis of our previous work on mitogen-activated protein kinase (MAPK)/extracellular signal-related kinase (ERK) (MEK) biology and our observation that 6-OH–BDE-47 is structurally similar to kinase inhibitors, we hypothesized that certain hydroxylated PBDEs mediate neurotoxicity, at least in part, by impairing the MEK–ERK axis of MAPK signal transduction. We tested this hypothesis on three experimental platforms: 1) in silico, where modeling ligand–protein docking suggested that 6-OH–BDE-47 is a promiscuous ATP-competitive kinase inhibitor; 2) in vitro in dissociated neurons, where 6-OH–BDE-47 and another specific hydroxylated BDE metabolite similarly impaired phosphorylation of MEK/ERK1/2 and activity-induced transcription of a neuronal immediate early gene; and 3) in vivo in Drosophila melanogaster, where developmental exposures to 6-OH–BDE-47 and a MAPK inhibitor resulted in offspring displaying similarly increased frequency of mushroom-body β–lobe midline crossing, a metric of axonal guidance. Taken together, our results support that certain ortho-hydroxylated PBDE metabolites are promiscuous kinase inhibitors and can cause disruptions of critical neurodevelopmental processes, including neuronal electrical activity, pre-synaptic functions, MEK–ERK signaling, and axonal guidance.

Bacterial products such as lipopolysaccharides (or endotoxin) cause systemic inflammation, resulting in a substantial global health burden. The onset, progression, and resolution of the inflammatory response to endotoxin are usually tightly controlled to avoid chronic inflammation. Members of the NF-κB family of transcription factors are key drivers of inflammation that activate sets of genes in response to inflammatory signals. Such responses are typically short-lived and can be suppressed by proteins that act post-translationally, such as the SOCS (suppressor of cytokine signaling) family. Less is known about direct transcriptional regulation of these responses, however. Here, using a combination of in vitro approaches and in vivo animal models, we show that endotoxin treatment induced expression of the well-characterized transcriptional repressor Krüppel-like factor 3 (KLF3), which, in turn, directly repressed the expression of the NF-κB family member RELA/p65. We also observed that KLF3-deficient mice were hypersensitive to endotoxin and exhibited elevated levels of circulating Ly6C+ monocytes and macrophage-derived inflammatory cytokines. These findings reveal that KLF3 is a fundamental suppressor that operates as a feedback inhibitor of RELA/p65 and may be important in facilitating the resolution of inflammation.

Kindlins are focal adhesion proteins that regulate integrin activation and outside-in signaling. The kindlin family consists of three members, kindlin-1, -2, and -3. Kindlin-2 is widely expressed in multiple cell types, except those from the hematopoietic lineage. A previous study has reported that the Drosophila Fit1 protein (an ortholog of kindlin-2) prevents abnormal spindle assembly; however, the mechanism remains unknown. Here, we show that kindlin-2 maintains spindle integrity in mitotic human cells. The human neuroblastoma SH-SY5Y cell line expresses only kindlin-2, and we found that when SH-SY5Y cells are depleted of kindlin-2, they exhibit pronounced spindle abnormalities and delayed mitosis. Of note, acetylation of α-tubulin, which maintains microtubule flexibility and stability, was diminished in the kindlin-2–depleted cells. Mechanistically, we found that kindlin-2 maintains α-tubulin acetylation by inhibiting the microtubule-associated deacetylase histone deacetylase 6 (HDAC6) via a signaling pathway involving AKT Ser/Thr kinase (AKT)/glycogen synthase kinase 3β (GSK3β) or paxillin. We also provide evidence that prolonged hypoxia down-regulates kindlin-2 expression, leading to spindle abnormalities not only in the SH-SY5Y cell line, but also cell lines derived from colon and breast tissues. The findings of our study highlight that kindlin-2 regulates mitotic spindle assembly and that this process is perturbed in cancer cells in a hypoxic environment.

(University of Tennessee Institute of Agriculture) David Mercker, an Extension forestry specialist with the University of Tennessee Department of Forestry, Wildlife and Fisheries, has been named 2020 Extension Forester of the Year by the Forest Landowners Association (FLA). FLA is a national organization that promotes and protects the interests of private forest landowners and bestows this award annually as determined by its board of directors.

The budget carrier will begin conducting temperature checks via touchless thermometers on June 1. Passengers have to start wearing masks Friday.

It may not be a pardon. But the Justice Department has dropped charges against Donald Trump’s former national security adviser Michael Flynn, who pleaded guilty to lying to the FBI.Retired Army Lt. Gen. Flynn, an important figure in the war on terror who gave Trump’s 2016 run military validation, will avoid prison time after the Justice Department provided a deliverance on Thursday that Flynn had long sought. It is also the second redemption that Trump has provided the general, who served as his first national security adviser for less than a month. “The Government has determined, pursuant to the Principles of Federal Prosecution and based on an extensive review and careful consideration of the circumstances, that continued prosecution of this case would not serve the interests of justice,” wrote Timothy Shea, the interim U.S. attorney for the District of Columbia and a former senior aide to Attorney General William Barr. Shortly before the filing, lead prosecutor Brandon Von Grack abruptly withdrew from the case.The Justice Department filing, in essence, portrays Flynn as the victim of an FBI frame-up job, and his lies to the FBI as legally marginal. Shea wrote that Flynn’s lies needed to have been “not simply false, but ‘materially’ false with respect to a matter under investigation.” Later in the filing, Shea referred to those lies as “gaps in [Flynn’s] memory,” rather than deliberate falsehoods Flynn conceded. “Even if he told the truth, Mr. Flynn’s statements could not have conceivably ‘influenced’ an investigation that had neither a legitimate counterintelligence nor criminal purpose,” Shea wrote.It was an astonishing turnaround since 2018, when a federal judge said to Flynn in a sentencing hearing, “arguably, you sold your country out.” That judge, Emmet Sullivan, could still decide to reject Shea’s filing and continue with Flynn’ sentencing. Michael Bromwich, a former federal prosecutor and Justice Department inspector general, tweeted that the extraordinary move represented “a pardon by another name” and called it a “black day in DOJ history.”Rep. Jerrold Nadler (D-NY), chairman of the House Judiciary Committee, said the decision to drop charges was “outrageous” and revealed “a politicized and thoroughly corrupt Department of Justice.” Sen. Ron Wyden (D-OR) added, “If Barr’s Justice Department will drop charges against someone who twice pleaded guilty to lying to the FBI and who the White House publicly fired for lying to the vice president, there’s nothing it won’t do, no investigation it won’t taint.”Neither Flynn nor his attorney, Sidney Powell, responded immediately to requests for comment.Speaking to reports on Thursday afternoon, Trump said he had no prior knowledge of the Justice Department’s decision. “He was an innocent man,” Trump said, of Flynn. “Now in my book he’s an even greater warrior.”The dropped charges follow a years-long groundswell from Trump’s base, and particularly Fox News, to clear Flynn. His advocates claim that Flynn was set up by the same disreputable FBI figures who they believe persecuted Trump over phantom collusion with Russia.Flynn’s guilty plea, in December, 2017, has been no obstacle to the narrative, particularly since Flynn sought afterwards, unsuccessfully, to withdraw his plea. His sentencing, initially set for February, had also been delayed.Last month, agitation for a Flynn pardon intensified after documents emerged from two of Trump’s most hated ex-FBI figures, counterintelligence official Peter Strzok and attorney Lisa Page, discussing Flynn’s fateful January 2017 interview with the FBI. Page asked when and how to “slip it in” to Flynn that lying to an FBI agent is a crime, something that Flynn’s advocates believed showed the general being railroaded from the start. But veteran FBI agents and prosecutors have pointed out that the FBI is not legally obligated to inform an interview subject that lying to them is illegal. “Michael Flynn was very familiar with the FBI,” said Stephanie Douglas, a former executive assistant director of the FBI’s National Security Branch. “He would certainly have been aware of his obligation to provide candid and truthful information. His claim he was tricked and manipulated doesn’t sound valid to me.” Shea, in his Thursday court filing, suggested the FBI officials were “fishing for falsehoods merely to manufacture jurisdiction over any statement.” In Shea’s view, Flynn’s lies were less germane to the prosecution than the FBI “lack[ing] sufficient basis to sustain its initial counterintelligence investigation,” and its pre-interview position that it ought to close the investigation before speaking with the then national security adviser.Former FBI deputy head Andrew McCabe said on Thursday that the suggestion there was no reason to interview Flynn was “patently false, and ignores the considerable national security risk his contacts raised.” He said Flynn’s lies added to the FBI’s concerns about his relationship with Russia. “Today’s move... is pure politics designed to please the president,” he added.U.S. Attorney Jeff Jensen, who was appointed by Barr to review Flynn’s and other high-profile cases, said on Thursday that he concluded “the proper and just course” was to dismiss the case. “I briefed Attorney General Barr on my findings, advised him on these conclusions, and he agreed,” he said.The FBI Didn’t Frame Michael Flynn. That’s Just Trump’s Excuse for a Prospective Pardon.While serving as national security adviser, Flynn misled FBI interviewers about conversations he had with the then-Russian ambassador, Sergei Kislyak. In one of those late 2016 conversations, according to court filings, Flynn asked the Russians to avoid escalatory actions in response to sanctions and diplomatic expulsions then President Barack Obama enacted as reprisal for Russian electoral interference. Shea, in his filing, called Flynn’s Kislyak calls “entirely appropriate on their face.”The national security adviser’s lies prompted the holdover attorney general, Sally Yates, to warn the White House that Flynn had given the Russians leverage to blackmail him. But it would take weeks before Trump fired Flynn over “an eroding level of trust” concerning misleading Vice President Mike Pence on the Kislyak contacts. By May, Trump was said to have regretted dismissing the general.  Flynn in 2017 agreed to cooperate with Special Counsel Robert Mueller’s investigation. The general avoided charges for taking $530,000 in unregistered money from interests connected to the Turkish government—something he only declared with the Justice Department after his downfall as national security adviser. During a sentencing hearing in 2018, a federal judge castigated Flynn for disgracing the uniform Flynn wore for three decades. “Arguably, you sold your country out,” Judge Emmet Sullivan said. Two years earlier, on stage at the Republican national convention, Flynn had led a chant of “lock her up” about Hillary Clinton. Protesters outside Flynn’s courtroom did not let the general forget it. Trump’s enduring bond with Flynn is a testament to the importance of the role the general played in 2016.A host of national security officials, many aligned with the Republican Party, rejected Trump in 2016 as unfit to be president owing to his nativism, his penchant for brutality and his benign view of dictators like Russia’s Vladimir Putin. Flynn was the exception. And the general was an exceptional figure. As the intelligence chief for the Joint Special Operations Command during the mid-2000s, Flynn is one of a select few people who can be said to have personally prosecuted the most sensitive missions of the war on terror. Michael Flynn Putting Mueller Deal at Risk in ‘Dangerous’ New TrialIt was a pivotal credential in another way. Flynn emerged from the war on terror endorsing Trump’s view that the security apparatus, abetted by hidebound liberals and cowardly conservatives, had neutered the war on terror by refusing to see it was a civilizational conflict with Islam. “Islam is a political ideology” that “hides behind this notion of being a religion,” Flynn told the Islamophobic group ACT for America shortly after the 2016 convention. His hostility to Islam informed his sanguine view of Russia, which both Flynn and Trump saw as naturally aligned with the U.S. against what they called “Radical Islamic Terror.”It also meant that Trump and Flynn shared a common bureaucratic enemy. James Clapper, then the director of national intelligence, was a lead architect of an intelligence assessment finding Russia intervened in the election on Trump’s behalf. In 2014, Clapper fired Flynn as director of the Defense Intelligence Agency. It was deeply embittering. Just four years earlier, Flynn had been hailed as an innovator after claiming U.S. military intelligence had misunderstood the Afghanistan war. While Flynn portrayed himself as a martyr, victimized by the ‘Deep State’ for daring to warn about radical Islam, Clapper and other intelligence leaders had fallen out with Flynn over what they considered an incompetent management style and an iffy relationship with the truth. Reportedly, Flynn believed Iran was involved in the 2012 assault on a CIA compound in Benghazi that killed four Americans, and claimed incorrectly that Iran was responsible for more American deaths than al-Qaeda. Aides referred to such untruths as “Flynn facts.” Flynn facts did not disturb Trump. They validated his instincts on national security. Trump rewarded Flynn by making him national security adviser, one of the most important positions in the U.S. security apparatus. It was the first time Trump redeemed Flynn. Thursday’s dropped charges represent the second. Read more at The Daily Beast.Get our top stories in your inbox every day. Sign up now!Daily Beast Membership: Beast Inside goes deeper on the stories that matter to you. Learn more.

Russia's GRU military intelligence service appears to have got hold of many emails from Chancellor Angela Merkel's constituency office in a 2015 hack attack on Germany's parliament, Der Spiegel magazine reported on Friday, without citing its sources. A spokesman for the German government had no immediate comment. Der Spiegel said federal criminal police and the federal cyber agency had been able to partially reconstruct the attack and found that two email inboxes from Merkel's office had been targeted.

(American Geriatrics Society) The COVID-19 pandemic has placed unprecedented pressure on societies worldwide, given the pandemic's rapid, often deadly spread. In health care, the pandemic has raised the pressing question of how society should allocate scarce resources during a crisis. This is the question experts addressed today in a new position statement published by the American Geriatrics Society (AGS) in the Journal of the American Geriatrics Society (DOI: 10.1111/jgs.16537).

Jan Pearson
Apr 1, 2001; 14:
Articles

10 December 2018

Clarification of international humanitarian law is important in ensuring compliance with the rule of proportionality, but a culture of compliance within armed forces and groups is also crucial.

Research Event

Event participants

James Harrison, Reader and Associate Professor, University of Warwick School of Law
Richard James, Evaluation Co-ordinator, Directorate-General for Trade European Commission
Jennifer Zerk, Associate Fellow, International Law Programme, Chatham House
Chair: Andrea Shemberg, Chair, Global Business Initiative on Human Rights

The developing nervous system is remarkably sensitive to environmental signals, including disruptive toxins, such as polybrominated diphenyl ethers (PBDEs). PBDEs are an environmentally pervasive class of brominated flame retardants whose neurodevelopmental toxicity mechanisms remain largely unclear. Using dissociated cortical neurons from embryonic Rattus norvegicus, we found here that chronic exposure to 6-OH–BDE-47, one of the most prevalent hydroxylated PBDE metabolites, suppresses both spontaneous and evoked neuronal electrical activity. On the basis of our previous work on mitogen-activated protein kinase (MAPK)/extracellular signal-related kinase (ERK) (MEK) biology and our observation that 6-OH–BDE-47 is structurally similar to kinase inhibitors, we hypothesized that certain hydroxylated PBDEs mediate neurotoxicity, at least in part, by impairing the MEK–ERK axis of MAPK signal transduction. We tested this hypothesis on three experimental platforms: 1) in silico, where modeling ligand–protein docking suggested that 6-OH–BDE-47 is a promiscuous ATP-competitive kinase inhibitor; 2) in vitro in dissociated neurons, where 6-OH–BDE-47 and another specific hydroxylated BDE metabolite similarly impaired phosphorylation of MEK/ERK1/2 and activity-induced transcription of a neuronal immediate early gene; and 3) in vivo in Drosophila melanogaster, where developmental exposures to 6-OH–BDE-47 and a MAPK inhibitor resulted in offspring displaying similarly increased frequency of mushroom-body β–lobe midline crossing, a metric of axonal guidance. Taken together, our results support that certain ortho-hydroxylated PBDE metabolites are promiscuous kinase inhibitors and can cause disruptions of critical neurodevelopmental processes, including neuronal electrical activity, pre-synaptic functions, MEK–ERK signaling, and axonal guidance.

Sperm head shaping is a key event in spermiogenesis and is tightly controlled via the acrosome–manchette network. Linker of nucleoskeleton and cytoskeleton (LINC) complexes consist of Sad1 and UNC84 domain–containing (SUN) and Klarsicht/ANC-1/Syne-1 homology (KASH) domain proteins and form conserved nuclear envelope bridges implicated in transducing mechanical forces from the manchette to sculpt sperm nuclei into a hook-like shape. However, the role of LINC complexes in sperm head shaping is still poorly understood. Here we assessed the role of SUN3, a testis-specific LINC component harboring a conserved SUN domain, in spermiogenesis. We show that CRISPR/Cas9-generated Sun3 knockout male mice are infertile, displaying drastically reduced sperm counts and a globozoospermia-like phenotype, including a missing, mislocalized, or fragmented acrosome, as well as multiple defects in sperm flagella. Further examination revealed that the sperm head abnormalities are apparent at step 9 and that the sperm nuclei fail to elongate because of the absence of manchette microtubules and perinuclear rings. These observations indicate that Sun3 deletion likely impairs the ability of the LINC complex to transduce the cytoskeletal force to the nuclear envelope, required for sperm head elongation. We also found that SUN3 interacts with SUN4 in mouse testes and that the level of SUN4 proteins is drastically reduced in Sun3-null mice. Altogether, our results indicate that SUN3 is essential for sperm head shaping and male fertility, providing molecular clues regarding the underlying pathology of the globozoospermia-like phenotype.

Daniella H Hock
Apr 21, 2020; 0:RA120.002076v1-mcp.RA120.002076
Research

Sonia Podvin
Apr 15, 2020; 0:RA120.002079v1-mcp.RA120.002079
Research

Eva Griesser
May 1, 2020; 19:839-851
Research

1 July 2019

Almost all modern military engagements rely on space-based assets, but cyber vulnerabilities can undermine confidence in the performance of strategic systems. This paper will evaluate the threats, vulnerabilities and consequences of cyber risks to strategic systems.

8 August 2019

Invitation Only Research Event

Event participants

Beyza Unal, Senior Research Fellow, International Security Department, Chatham House
Patricia Lewis, Research Director, International Security Department, Chatham House