A chronology of key events

A chronology of key events

Key facts, figures and dates

Key facts, figures and dates

Pulitzer-winning editorial artists aim to find deadline satire in the televised inquiry.

Pulitzer-winning cartoonists use humor to peer behind all the political posturing.

Cartoonists who have lampooned both administrations take aim differently now.

“People who have the most exaggerated features tend to make the worst caricature subjects, and in that sense, I hate drawing Bernie,” says one.

Three Pulitzer-winning cartoonists say covering the crisis requires careful aim.

Chen Weng was born in Wuhan and lives in Seattle. Both connections inspire her "Messycow Comics" strips about panic and hoarding.

New York humorist Jason Chatfield chronicled his experience with the illness, from symptoms to recovery.

The vice president's visit inspired reactions from cartoonists on both sides of the political aisle.

• Dockworkers in Belgium are wearing bracelets to enforce social distancing.
• The bracelets were already used to detect if someone fell into the water, but now they will sound an alarm if workers get to close to each other.
• Manufacturers say there is no privacy issue and the bracelets don't track workers' locations, despite concerns.
• Visit Business Insider's homepage for more stories.

Quarantine and social distancing are going high-tech as countries and companies embrace wearables. In Antwerp, Belgium, dockworkers are instructed to wear bracelets that enforce social distancing rules while they work.

Europe, where more than 100,000 people have died from COVID-19, is slowly starting to reopen in some places. Stay at home orders are expiring in many countries, while nonessential travel has stopped across the EU, and countries look towards the summer to anticipate what kind of travel might be possible. 

People are beginning to go back to work, which in some sectors means inevitable close contact, especially in many essential jobs. Social distancing bracelets in Belgium are one idea bing tested to see what the future of work might look like after coronavirus.

Here's how it works. 

SEE ALSO: People arriving in Hong Kong must wear tracking bracelets for 2 weeks or face jail time. Here's how they work.

The black, plastic bracelets are worn on the wrist like a watch.

They're made by Belgian company Rombit, which says that they are "a fully integrated personal safety and security device, specifically designed for highly industrial environments."

Source: Romware

Rombit already made bracelets useful in the port setting, which could be used to call for help if a worker fell into the water or another accident occurred.

Europe is slowly starting to go back to work, but fears of a second wave are making officials cautious.

Contact tracing is one solution being explored around the world, and the manufacturers of the bracelet believe it could also be used for contact tracing.

Source: The Associated Press

European health guidances say to wash hands, wear masks, and keep at least 1.5 meters, or about five feet, apart.

When two workers are less than five feet apart, the bracelets will sound warnings.

Rombit CEO John Baekelmans told Reuters that the bracelets won't allow companies to track employees' locations, because the devices are only connected to each other. He says there is no central server.

Source: Reuters

Workers in the control tower will be the first to test the bracelets early this month.

Then, the Port of Antwerp will likely expand the devices to tug boat workers.

Baekelmans told Reuters that Rombit already had hundreds of requests in 99 countries, and is hoping to ramp up production to 25,000 in a few weeks.

The former scandal figure is mining what was a traumatic experience for some dark humor.

This sector has long been battered by forces beyond its control.

The administration is celebrating the brain drain and helping the real swamp.

Every single one of them is supposed to be exercising oversight of the executive branch.

He did it in the Ukraine affair, of course, but most of his abuses have happened closer to home.

Money needs to get spent fast. Money needs to get spent well. To some extent, those objectives are in tension.

So far, I have explained the literacy environment, print awareness, and sight word teaching that were part of teaching my daughters to read, but phonics also played an important role.

strataconf: Humans as nodes, pills & electronic tattoo password authenticators & hiding data in temporal cloaks http://t.co/vRgkRtTTKe #strataconf

Recently, The Washington Post published an article about the latest hostilities in the “reading wars.” I noticed it because the columnist, Jay Matthews, quoted from this blog.

Recently, The Washington Post published an article about the latest hostilities in the “reading wars.” I noticed it because the columnist, Jay Matthews, quoted from this blog.

In line with new evolving computer technologies, a lot of issues previously found complicated are now seen as an easygoing task, for example, e-commerce, contactless payment, secured online transactions, and ride-hailing. All thanks to blockchain, a new technology that massively revitalized all-around sectors, equipping the financial industry with enhanced solutions with less or no additional […]

The post 6 Industries Blockchain Technology Will Revolutionize appeared first on ReadWrite.

This week has been a tough one.  It has just become more and more clear that the global travel situation isn’t going to clear up until at least early in the fall.  So while we’re still very hopeful that our Namibia trips starting in September will still happen, we’ve sadly had to cancel or postpone […]

The post Cancelling/Postponing Photography Trips appeared first on Brendan van Son Photography.

The Amateur Traveler talks to travel writer Jeanine Barone about Estonia. Estonia is a small forested country with picturesque islands, medieval fortifications, a thriving design community, a great restaurant scene and a young and vibrant culture. Estonia only recently regained its independence from the U.S.S.R. (1991) but is thriving and filled with innovation. This interview, like all the Amateur Traveler interviews, was recorded with Skype… which is headquartered in Estonia. We talked about hotels, restaurants, guide books, wine bars and chocolate.

The Amateur Traveler talks to Carlos Gutierrez about his home town of San Antonio, Texas. Carlos gives us a guide to some of the obvious spots like the Alamo but also shares some of his favorite hole in the wall restaurants, a tip about the best time to come to San Antonio, and a great drive in the Texas countryside.

Hear about travel to Macedonia as the Amateur Traveler talks to Kelsey of CineTraveler.com about her recent trip to this country in the Balkans. Macedonia is just north of Greece and probably best known as the home for Alexander the Great but Kelsey found much more to recommend in this much too overlooked country. In a week they were able to see much of the country.

Hear about travel to Patagonia as the Amateur Traveler talks to Jackie Nourse about this region of southern Argentina.

Hear about travel to New Caledonia as the Amateur Traveler talks to CJ Johnson from the MOVIELAND ABC Radio Show and Podcast about his recent trip to this part of France in the South Pacific.

Hear about travel to Patagonia in Chile as the Amateur Traveler talks to Talek Nantes about her recent trip to the bottom of South America.

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Wellness is a buzzy word lately. Over the past few years, we’ve seen a surge in all things health, wellness, and spirituality. Juice bars are popping up, boutique studios are becoming more accessible, and essential oils are chilling us out. Self-care is becoming more of the norm too, but amidst all this hype, it can be challenging to find the right routine that promotes good exercise, sleep, vitals, and mindset.  Read more...

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.

Carbon monoxide (CO) remains the most common cause of human poisoning. The consequences of CO poisoning include cardiac dysfunction, brain injury, and death. CO causes toxicity by binding to hemoglobin and by inhibiting mitochondrial cytochrome c oxidase (CcO), thereby decreasing oxygen delivery and inhibiting oxidative phosphorylation. We have recently developed a CO antidote based on human neuroglobin (Ngb-H64Q-CCC). This molecule enhances clearance of CO from red blood cells in vitro and in vivo. Herein, we tested whether Ngb-H64Q-CCC can also scavenge CO from CcO and attenuate CO-induced inhibition of mitochondrial respiration. Heart tissue from mice exposed to 3% CO exhibited a 42 ± 19% reduction in tissue respiration rate and a 33 ± 38% reduction in CcO activity compared with unexposed mice. Intravenous infusion of Ngb-H64Q-CCC restored respiration rates to that of control mice correlating with higher electron transport chain CcO activity in Ngb-H64Q-CCC–treated compared with PBS-treated, CO-poisoned mice. Further, using a Clark-type oxygen electrode, we measured isolated rat liver mitochondrial respiration in the presence and absence of saturating solutions of CO (160 μm) and nitric oxide (100 μm). Both CO and NO inhibited respiration, and treatment with Ngb-H64Q-CCC (100 and 50 μm, respectively) significantly reversed this inhibition. These results suggest that Ngb-H64Q-CCC mitigates CO toxicity by scavenging CO from carboxyhemoglobin, improving systemic oxygen delivery and reversing the inhibitory effects of CO on mitochondria. We conclude that Ngb-H64Q-CCC or other CO scavengers demonstrate potential as antidotes that reverse the clinical and molecular effects of CO poisoning.

The plasmas of diabetic or uremic patients and of those receiving peritoneal dialysis treatment have increased levels of the glucose-derived dicarbonyl metabolites like methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG). The elevated dicarbonyl levels can contribute to the development of painful neuropathies. Here, we used stimulated immunoreactive Calcitonin Gene–Related Peptide (iCGRP) release as a measure of nociceptor activation, and we found that each dicarbonyl metabolite induces a concentration-, TRPA1-, and Ca2+-dependent iCGRP release. MGO, GO, and 3-DG were about equally potent in the millimolar range. We hypothesized that another dicarbonyl, 3,4-dideoxyglucosone-3-ene (3,4-DGE), which is present in peritoneal dialysis (PD) solutions after heat sterilization, activates nociceptors. We also showed that at body temperatures 3,4-DGE is formed from 3-DG and that concentrations of 3,4-DGE in the micromolar range effectively induced iCGRP release from isolated murine skin. In a novel preparation of the isolated parietal peritoneum PD fluid or 3,4-DGE alone, at concentrations found in PD solutions, stimulated iCGRP release. We also tested whether inflammatory tissue conditions synergize with dicarbonyls to induce iCGRP release from isolated skin. Application of MGO together with bradykinin or prostaglandin E2 resulted in an overadditive effect on iCGRP release, whereas MGO applied at a pH of 5.2 resulted in reduced release, probably due to an MGO-mediated inhibition of transient receptor potential (TRP) V1 receptors. These results indicate that several reactive dicarbonyls activate nociceptors and potentiate inflammatory mediators. Our findings underline the roles of dicarbonyls and TRPA1 receptors in causing pain during diabetes or renal disease.

Amelia C. Peterson
Nov 1, 2012; 11:1475-1488
Technological Innovation and Resources

Leigh Anderson
Apr 1, 2006; 5:573-588
Research

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.

Glial cell line–derived neurotrophic factor (GDNF) is a growth factor that regulates the health and function of neurons and other cells. GDNF binds to GDNF family receptor α1 (GFRa1), and the resulting complex activates the RET receptor tyrosine kinase and subsequent downstream signals. This feature restricts GDNF activity to systems in which GFRa1 and RET are both present, a scenario that may constrain GDNF breadth of action. Furthermore, this co-dependence precludes the use of GDNF as a tool to study a putative functional cross-talk between GFRa1 and RET. Here, using biochemical techniques, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and immunohistochemistry in murine cells, tissues, or retinal organotypic cultures, we report that a naphthoquinone/quinolinedione family of small molecules (Q compounds) acts as RET agonists. We found that, like GDNF, signaling through the parental compound Q121 is GFRa1-dependent. Structural modifications of Q121 generated analogs that activated RET irrespective of GFRa1 expression. We used these analogs to examine RET–GFRa1 interactions and show that GFRa1 can influence RET-mediated signaling and enhance or diminish AKT Ser/Thr kinase or extracellular signal-regulated kinase signaling in a biased manner. In a genetic mutant model of retinitis pigmentosa, a lead compound, Q525, afforded sustained RET activation and prevented photoreceptor neuron loss in the retina. This work uncovers key components of the dynamic relationships between RET and its GFRa co-receptor and provides RET agonist scaffolds for drug development.

Actinobacillus pleuropneumoniae (App) is the etiological agent of acute porcine pneumonia and responsible for severe economic losses worldwide. The capsule polymer of App serotype 1 (App1) consists of [4)-GlcNAc-β(1,6)-Gal-α-1-(PO4-] repeating units that are O-acetylated at O-6 of the GlcNAc. It is a major virulence factor and was used in previous studies in the successful generation of an experimental glycoconjugate vaccine. However, the application of glycoconjugate vaccines in the animal health sector is limited, presumably because of the high costs associated with harvesting the polymer from pathogen culture. Consequently, here we exploited the capsule polymerase Cps1B of App1 as an in vitro synthesis tool and an alternative for capsule polymer provision. Cps1B consists of two catalytic domains, as well as a domain rich in tetratricopeptide repeats (TPRs). We compared the elongation mechanism of Cps1B with that of a ΔTPR truncation (Cps1B-ΔTPR). Interestingly, the product profiles displayed by Cps1B suggested processive elongation of the nascent polymer, whereas Cps1B-ΔTPR appeared to work in a more distributive manner. The dispersity of the synthesized products could be reduced by generating single-action transferases and immobilizing them on individual columns, separating the two catalytic activities. Furthermore, we identified the O-acetyltransferase Cps1D of App1 and used it to modify the polymers produced by Cps1B. Two-dimensional NMR analyses of the products revealed O-acetylation levels identical to those of polymer harvested from App1 culture supernatants. In conclusion, we have established a protocol for the pathogen-free in vitro synthesis of tailored, nature-identical App1 capsule polymers.

Corporate Members Event Webinar

Event participants

Professor Tim Benton, Research Director, Emerging Risks and Director, Energy, Environment and Resources Programme, Chatham House

Creon Butler, Research Director, Trade, Investment & New Governance Models; Director, Global Economy and Finance Programme, Chatham House

Elsa Palanza, Managing Director, Global Head of Sustainability and ESG, Barclays

Chair: Laura Wellesley, Research Fellow, Energy, Environment and Resources Programme, Chatham House

Jorge H. Capdevila
Feb 1, 2000; 41:163-181
Reviews

Invitation Only Research Event

Event participants

Professor Philippe Sands QC, Professor of Law, UCL 
Richard Burt, Managing Partner, McLarty Associates
Chair: Dr Leslie Vinjamuri, Director, US and Americas Programme; Dean, Queen Elizabeth II Academy, Chatham House

Invitation Only Research Event

Event participants

John Zogby, Founder and Senior Partner, John Zogby Strategies
Chair: Dr Lindsay Newman, Senior Research Fellow, US and Americas Programme, Chatham House

Glial cell line–derived neurotrophic factor (GDNF) is a growth factor that regulates the health and function of neurons and other cells. GDNF binds to GDNF family receptor α1 (GFRa1), and the resulting complex activates the RET receptor tyrosine kinase and subsequent downstream signals. This feature restricts GDNF activity to systems in which GFRa1 and RET are both present, a scenario that may constrain GDNF breadth of action. Furthermore, this co-dependence precludes the use of GDNF as a tool to study a putative functional cross-talk between GFRa1 and RET. Here, using biochemical techniques, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, and immunohistochemistry in murine cells, tissues, or retinal organotypic cultures, we report that a naphthoquinone/quinolinedione family of small molecules (Q compounds) acts as RET agonists. We found that, like GDNF, signaling through the parental compound Q121 is GFRa1-dependent. Structural modifications of Q121 generated analogs that activated RET irrespective of GFRa1 expression. We used these analogs to examine RET–GFRa1 interactions and show that GFRa1 can influence RET-mediated signaling and enhance or diminish AKT Ser/Thr kinase or extracellular signal-regulated kinase signaling in a biased manner. In a genetic mutant model of retinitis pigmentosa, a lead compound, Q525, afforded sustained RET activation and prevented photoreceptor neuron loss in the retina. This work uncovers key components of the dynamic relationships between RET and its GFRa co-receptor and provides RET agonist scaffolds for drug development.

The plasmas of diabetic or uremic patients and of those receiving peritoneal dialysis treatment have increased levels of the glucose-derived dicarbonyl metabolites like methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG). The elevated dicarbonyl levels can contribute to the development of painful neuropathies. Here, we used stimulated immunoreactive Calcitonin Gene–Related Peptide (iCGRP) release as a measure of nociceptor activation, and we found that each dicarbonyl metabolite induces a concentration-, TRPA1-, and Ca2+-dependent iCGRP release. MGO, GO, and 3-DG were about equally potent in the millimolar range. We hypothesized that another dicarbonyl, 3,4-dideoxyglucosone-3-ene (3,4-DGE), which is present in peritoneal dialysis (PD) solutions after heat sterilization, activates nociceptors. We also showed that at body temperatures 3,4-DGE is formed from 3-DG and that concentrations of 3,4-DGE in the micromolar range effectively induced iCGRP release from isolated murine skin. In a novel preparation of the isolated parietal peritoneum PD fluid or 3,4-DGE alone, at concentrations found in PD solutions, stimulated iCGRP release. We also tested whether inflammatory tissue conditions synergize with dicarbonyls to induce iCGRP release from isolated skin. Application of MGO together with bradykinin or prostaglandin E2 resulted in an overadditive effect on iCGRP release, whereas MGO applied at a pH of 5.2 resulted in reduced release, probably due to an MGO-mediated inhibition of transient receptor potential (TRP) V1 receptors. These results indicate that several reactive dicarbonyls activate nociceptors and potentiate inflammatory mediators. Our findings underline the roles of dicarbonyls and TRPA1 receptors in causing pain during diabetes or renal disease.