In just under five months, both President Donald Trump and former Vice President Joe Biden will, one assumes, step onto a debate stage at the University of Notre Dame in South Bend, Indiana. It’s one heck of an assumption, and for more reasons than one. We don’t know if there are going to be debates…

The post With Debate Months Away, It’s Clear Biden Isn’t Ready for a 1-on-1 with Trump appeared first on The Western Journal.

Google’s (and now Alphabet’s) CEO opines in the FT (sub required) on why AI needs to be regulated, joining the chorus of tech leaders who have taken the apparent high road when it comes to regulation, even as governments around the world have shown next to no ability to actually regulate anything (well, I guess … Continue reading "Sundar Pichai in the FT: Please Regulate Us (And Good Luck with All That)"

As ISIS expands its reach into Afghanistan, it is training children and teenagers to become the next generation of jihadis.

For many low income college students, school closures due to COVID-19 has affected the way they feed themselves. Read more...

TL;DR: A one-year subscription to Norton Secure VPN is on sale for £2.50 per month, saving you 50% on list price.

It feels like the world of VPNs is expanding, with more and more providers entering the market and increased demand from users. 

This market can be a daunting place, especially as you probably won't be familiar with most of the available providers. This doesn't mean you shouldn't consider these services, but we totally understand if you're reluctant to invest in an unknown provider.

Fortunately for those who would prefer to subscribe to an established provider, there are plenty of options from the leading names in securityNorton is one such brand, with a comprehensive VPN service on sale for just £2.50 per month. Read more...

TL;DR: You don't have to buy a drum set to learn how to play the drums. Instead, just grab the Senstroke by Redison bluetooth drum kit for $189.95, on sale for 5% off as of May 9.

If you want to learn how to play the drums, then a quality set may cost you upwards of $1,000. Not only is this a hefty price to play for individuals who aren't fully committed to the instrument yet, but their massive size may be impossible to fit inside your space. Or at least your housemates may not appreciate it.

With the Senstroke by Redison Bluetooth Drum Kit and App Bundle, you can practice, play, and record on just about any surface for a much more affordable price — and it'll take up little to no space.  Read more...

TL;DR: Give a meaningful gift during these difficult times with a Tribute Video Montage for $64.99, a 34% saving as of May 9.

A Zoom happy hour only goes so far.

If you're looking for a way to celebrate and send affection to your loved ones, regardless of the reason, check out Tribute Video Montage as an alternative to those wonky (and sometimes awkward) video calls. 

Sending a Tribute might just be one of the best morale-boosting presents you can send during these trying times. It's a way for friends and family to share their love and appreciation for someone they want to celebrate, whether for a major milestone, like a 50th anniversary or 30th birthday or just because. The platform is super easy to use and breaks a 10-hour process down to just 10 minutes. Read more...

Rita J. King, co-director and EVP for business development at Science House, recently conducted a series of interviews with business leaders, exploring the challenges and hurdles companies face in evolving business landscapes. In this interview, King chats with James Jorasch, founding CEO of Science House, about the importance of innovation and how to inspire and […]

Drummers hear all the jokes. What do you call a drummer with half a brain? Gifted. How is a drum solo like a sneeze? You know it's coming, but there's nothing you can do about it. What do you call a drummer that breaks up with his girlfriend? Homeless.

Drummers hear the jokes — and laugh. Because they know they’re the thumping heartbeat of any band. They’re the ones with loads of equipment. And they’re the ones making all that noise while practicing. Yet try to play almost any song without drums and the lack of propulsion and power is instantly palpable.

Drummers are essential. Now, users can join their ranks — and they don’t even need to buy a massive drum kit or rattle their walls to do it. Created by drummers, Senstroke by Redison is the first sensor device that can teach anyone to play the drums and even reproduce the drummer experience, all without any physical drum set.

Just attach the patented Senstroke sensors to a pair of drumsticks and your feet, connect via Bluetooth, and instantly you can turn any surface into a virtual drumhead. Using the impact of the drumsticks and your feet positioning, the sensors reproduce the exact sounds your chosen drum element would make through the Senstroke app. 

Your legs, some cushions, a coffee table, they all become fair game as a drum surface while you refine your skills. And when you attach a pair of headphones, no one else even has to know you’re playing...well, Read the rest

The "transient bazaar" known as Lost Horizon Night Market is a covert operation. Worlds are imagined and then built inside the blank canvasses of empty box trucks. For the event, all the "proprietors," and their appointed box trucks, convene in an unsanctioned, though discreet, location. This location is disclosed to would-be "shoppers" via text just a few hours before it starts. Word of the market generally spreads rapidly but not publicly, definitely not by social media. If you're lucky enough to hear about it, you should go.

So, Happy Mutants, this is your heads up. Lost Horizon Night Market: Quarantine Edition is happening Saturday, May 9, from 6:59p EST until 11:59p EST, "rain or shine." This one is a little different, as the spaces are virtual, not in actual, physical trucks. I got a sneak peek yesterday of what's been created and can't wait to dive in deeper. Admission is free, though tips are appreciated. RSVP here.

Previously: Secret box truck 'night market' pops up again in NYC Read the rest

Game designer and publisher Dave Gilbert founded Wadjet Eye Games in 2006.  This interview features conversation about point and click adventure games; digital game development, marketing and publishing; and the relationship between art, passion and real world commerce.

Jeffery Klaehn: How did you first become interested in point and click adventure games?

Dave Gilbert: I played King’s Quest at a very impressionable age! I typed the word “jump” and I saw Graham actually jump, and I was so blown away that I’ve been playing them ever since.

JK: You founded Wadjet Eye Games in 2006 to sell your game, The Shivah, commercially, then moved to pursue game design on a full-time basis and released The Blackwell Legacy, the first in what would become a series of five games.  What are your thoughts on these games and on the market then compared to now?

Dave Gilbert: I am Blackwell Legacy’s biggest critic. It was the first game I wrote with the intention of selling commercially – The Shivah was originally freeware, so I don’t count it – and it shows every inch of my inexperience. The gameplay is clunky, the story is told in three giant infodumps, and the main characters weren’t very likable. But that said, I know with absolute certainty that it was the very best game I could have made with the experience, resources and time I had available. So I stand by it.

As for the market, everything is different. Back in 2006, indie games in general were a very new thing. Read the rest

My pal Jake has been taking regular "cigar walks" (as he calls them) here in our lovely island city of Alameda, California. On those walks, he started spotting some creative flyers...

(I saved the best two for last...)

photos by Jake Schaffer, used with permission

Thanks, Susie! Read the rest

Phishing is incredibly common, yet most people feel it has gotten harder to spot in recent years. Cyber criminals rely on their knowledge of human psychology to make you do things you wouldn’t normally do. They also know that if they scare you enough they can manipulate you into doing what they want you to […]

The post Preventing Phishing With Education appeared first on Dumb Little Man.

Rare coins can add beauty and value to any collection. It is a piece of history that any man or woman hold in their hand. It could belong to an ancient era and certain empires such as the Romanian world or maybe it’s a silver dollar that pioneered in the wild east. Coin collectors are […]

The post Start Your Coin Collection With These Rare Coins appeared first on Dumb Little Man.

February 20, 2020 (New York, NY) –For the first time, eMarketer is estimating the number of people who watch Twitch on a regular basis in its latest forecast.  Twitch hosts streaming […]

TV time among adult viewers up 10 minutes per day in 2020 April 23, 2020 (London, UK) – The UK’s social distancing measures due to coronavirus are having a measurable […]

Our Estimate for Time Spent with TV in 2020 Is Revised Upward by 5 Minutes April 24, 2020 (New York, NY) – Over the course of just a few months, […]

I’m excited to introduce something I’ve wanted to do for quite a long time — private one-on-one calls between me and my readers! This new product is a way for us to have private one-on-one conversations tailored to whatever you want. I got into this business is because I wanted to help women achieve their …

INTRODUCING One-on-Ones with Adventurous Kate! Read More »

The post INTRODUCING One-on-Ones with Adventurous Kate! appeared first on Adventurous Kate.

From better campsite cooking to car maintenance to smartphone-free communication, here are 12 gadgets to up your car camping game.

The post Up Your Car Camping Game with These 12 Clever Gadgets appeared first on Vagabondish.

With a bright, 8.2-inch HD display and the flexibility to work in almost any vehicle, the Lanmodo Automotive Vast Night Vision System is a near-perfect alternative to factory-installed systems.

The post Brighten Up Your After-Dark Road-Tripping with Lanmodo’s Vast Automotive Night Vision System appeared first on Vagabondish.

Basecamp’s newest product HEY has lived on Kubernetes since development first began. While our applications are majestic monoliths, a product like HEY has numerous supporting services that run along-side the main app like our mail pipeline (Postfix and friends), Resque (and Resque Scheduler), and nginx, making Kubernetes a great orchestration option for us. As you… keep reading

There’s no perfect process for hiring great programmers, but there are plenty of terrible ways to screw it up. We’ve rejected the industry stables of grilling candidates in front of a whiteboard or needling them with brain teasers since the start at Basecamp. But you’re not getting around showing real code when applying for a… keep reading

We’ve been teaching people how to do remote work well for the better part of two decades. We wrote a whole book about the topic in 2013, called REMOTE: Office Not Required. Basecamp has been a remote company since day one, and our software is sold as an all-in-one toolkit for remote work. Yeah, we’re… keep reading

[update 2011-01-18 @ 16:07:40: We're up!]

5by5 Live

Before Christ was a corporal, Dan Benjamin was already a bit of a hero to me.

Since the early aughts–long before his insanely great 5by5.tv podcast network–Dan’s Hivelogic Enkoder was saving us millions of spam messages. His thoughtful tutorials on OS X (including unmissable advice on doing sane installs of MySQL and Rails, among others) are among the best on the web. His CSS has been widely stolen and reused without acknowledgment by thieves as diverse as other people and me. And his polymath posts on everything from Buddhism to The Paleo Diet to how to record a “Double-ender” have shown a charming combination of curiosity and empathy that, amongst numerous other reasons, clearly makes Dan a better human than me.

A propos of nothing, Dan’s also the guy who conducted one of (mp3) the three best interviews with me in which it’s been my good fortune to participate.1

Today, I’m honored to say that Dan and I are starting a thing together.

If it suits you, drop by 5by5.tv/live in about 35 minutes–at Noon Eastern/9am Pacific–to find out what we’re up to. I think it might be good. I’ll just say I’m as excited about this as I’ve been about any new project I’ve started in the past year or so.

Anyway. You can judge for yourself. Whether you can tolerate me or otherwise, definitely do not miss the work Dan’s doing at 5by5. Because it really is outstanding and very polished stuff.

As for our thing? My own goal, to paraphrase a bit from that interview with Dan, is to help you get excited, get better–and then?–Back to Work.

More soon. Thanks.

And...we're up

Back to Work | Ep.#1: Alligator in the Bathroom

Download MP3 of "'Back to Work,' Ep. 1"

In the inaugural episode of Back to Work, Merlin Mann and Dan Benjamin discuss why they’re doing this show, getting back to work instead of buying berets, the lizard brain, and compare the Shadow of the Mouse to San Francisco, and eventually get to some practical tips for removing friction.

It's a start.

Sexy Audio RSS Feed
Sexy Subscription via iTunes

Episode Links

• Welcome to BrettTerpstra.com, home of Brett Terpstra and his nerdery
• carlhuda/janus – GitHub
• practically efficient — technology, workflows, life
• MacSparky – Blog
• The Brooks Review
• And now it’s all this
• Dan Rodney’s List of Mac OS X Keyboard Shortcuts & Keystrokes
• 43f Podcast: John Gruber & Merlin Mann’s Blogging Panel at SxSW | 43 Folders
• waffle software · ThisService
• One Thing Well
• html2text: THE ASCIINATOR (aka html2txt)
• The Conversation #27: Missionless Statements – 5by5

The DML News App offers the best in news reporting.

The post REPORT: Recent documents reveal number of Secret Service agents with COVID-19 appeared first on Dennis Michael Lynch.

School bus drivers in the Upper Grand District School Board are transporting school work instead of students.

A woman in her 90s living at the Bradford Valley Care Community is the latest coronavirus victim in the region.

An eight-year-old boy with good intentions sparked a missing person search on Tuesday.

After seven weeks, Honda Canada in Alliston will gradually begin operations next week.

While infection rates remain steady across the region, the Simcoe Muskoka District Health Unit is reporting more than half of all 360 cases have now recovered.

The calendar may say May, but that didn't stop Mother Nature from blasting some wintry weather in Muskoka on Friday.

As British Columbians digest the implications in the steps the premier announced in reopening the province's economy, some residents have come to the conclusion they’re too much too soon.

The following article, BREAKING: MI Lawmakers File Lawsuit Challenging Governor’s “Improper” and “Invalid” Emergency Orders: “We’ve attempted to partner with our governor, but she’s rejected”, was first published on 100PercentFedUp.com.

In addition to crushing Michigan's economy, the governor's reckless, one-size-fits-all executive orders are harming an untold number of Michigan citizens.

Continue reading: BREAKING: MI Lawmakers File Lawsuit Challenging Governor’s “Improper” and “Invalid” Emergency Orders: “We’ve attempted to partner with our governor, but she’s rejected” ...

The following article, Chicago Inmate Switches Identities While Wearing Mask…Is Released from Jail, was first published on 100PercentFedUp.com.

A Cook County, Chicago inmate, was able to switch identities with another inmate allowing the wrong inmate to be released. How did they carry that off without anyone catching them? The inmate was wearing a mask when he was released, so it wasn’t as easy to identify him. Last Saturday, Quintin Henderson (pictured below), 28, […]

Continue reading: Chicago Inmate Switches Identities While Wearing Mask…Is Released from Jail ...

The following article, MSNBC’s Brian Williams Chuckles With Dem Strategist as He Gloats, Mocks Trump About Tragic Downturn in Economy: “They were going to lose before this hit. They’re just going to lose worse now”, was first published on 100PercentFedUp.com.

James Carville spoke out before the coronavirus crisis to say that there is no way  Joe Biden has a chance at beating President Trump in the 2020 election. Well, He’s singing a different tune now at the expense of Americans suffering through this horrible pandemic and economic crisis. James Carvill is a Democratic strategist who […]

Continue reading: MSNBC’s Brian Williams Chuckles With Dem Strategist as He Gloats, Mocks Trump About Tragic Downturn in Economy: “They were going to lose before this hit. They’re just going to lose worse now” ...

The following article, BREAKING: Ex-Cop Father and Son Arrested and Charged With Murder of Black Man Jogging In Neighborhood…President Trump Responds [VIDEO], was first published on 100PercentFedUp.com.

The Georgia Bureau of Investigations has arrested a father and son duo, 64-year-old ex-cop, Gregory McMichael, and his son, 34-year-old Travis McMichael for the February murder of  24-year-old Ahmaud Arbery, a black man who was jogging through their neighborhood when they jumped in their truck and pursued him. Yashar Ali shared the news of the […]

Continue reading: BREAKING: Ex-Cop Father and Son Arrested and Charged With Murder of Black Man Jogging In Neighborhood…President Trump Responds [VIDEO] ...

The following article, BREAKING: President Trump’s Fiery Interview On Fox & Friends…”These are dirty politicians and dirty cops…They put our nation in danger with other nations, including Russia” [VIDEO], was first published on 100PercentFedUp.com.

This morning during a nearly one hour interview with Fox & Friends, President Trump addressed the decision by the DOJ to drop the case against the innocent General Michael Flynn. Trump ripped into the “dirty politicians and dirty cops” who went after General Michael Flynn. President Trump called the players involved in the horrible plot […]

Continue reading: BREAKING: President Trump’s Fiery Interview On Fox & Friends…”These are dirty politicians and dirty cops…They put our nation in danger with other nations, including Russia” [VIDEO] ...

The following article, Greg Gutfeld Levels Ilhan Omar With Epic Response To Her Claim That “White Privilege” Is Reason Charges Were Dropped Against General Flynn, was first published on 100PercentFedUp.com.

Yesterday, after 3 1/2 years of having his character and integrity called into question, President Trump's first NSA, General Michael Flynn was finally...

Continue reading: Greg Gutfeld Levels Ilhan Omar With Epic Response To Her Claim That “White Privilege” Is Reason Charges Were Dropped Against General Flynn ...

The provincial government has announced it will support child care centres that have been closed since March with their fixed operating costs as the fight against COVID-19 continues.

27 April 2020

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.

Invitation Only Research Event

Event participants

Ali Farhan Hamid, Governor of Anbar Province
Chair: Dr Renad Mansour, Senior Research Fellow, Middle East and North Africa Programme, Chatham House

Research Event

Event participants

Neoantimycins are anticancer compounds of 15-membered ring antimycin-type depsipeptides. They are biosynthesized by a hybrid multimodular protein complex of nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS), typically from the starting precursor 3-formamidosalicylate. Examining fermentation extracts of Streptomyces conglobatus, here we discovered four new neoantimycin analogs, unantimycins B–E, in which 3-formamidosalicylates are replaced by an unusual 3-hydroxybenzoate (3-HBA) moiety. Unantimycins B–E exhibited levels of anticancer activities similar to those of the chemotherapeutic drug cisplatin in human lung cancer, colorectal cancer, and melanoma cells. Notably, they mostly displayed no significant toxicity toward noncancerous cells, unlike the serious toxicities generally reported for antimycin-type natural products. Using site-directed mutagenesis and heterologous expression, we found that unantimycin productions are correlated with the activity of a chorismatase homolog, the nat-hyg5 gene, from a type I PKS gene cluster. Biochemical analysis confirmed that the catalytic activity of Nat-hyg5 generates 3-HBA from chorismate. Finally, we achieved selective production of unantimycins B and C by engineering a chassis host. On the basis of these findings, we propose that unantimycin biosynthesis is directed by the neoantimycin-producing NRPS–PKS complex and initiated with the starter unit of 3-HBA. The elucidation of the biosynthetic unantimycin pathway reported here paves the way to improve the yield of these compounds for evaluation in oncotherapeutic applications.

Nucleoside analogues are a valuable experimental tool. Incorporation of these molecules into newly synthesized DNA (i.e. pulse-labeling) is used to monitor cell proliferation or to isolate nascent DNA. Some of the most common nucleoside analogues used for pulse-labeling of DNA in cells are the deoxypyrimidine analogues 5-ethynyl-2'-deoxyuridine (EdU) and 5-ethynyl-2'-deoxycytidine (EdC). Click chemistry enables conjugation of an azide molecule tagged with a fluorescent dye or biotin to the alkyne of the analog, which can then be used to detect incorporation of EdU and EdC into DNA. The use of EdC is often recommended because of the potential cytotoxicity associated with EdU during longer incubations. Here, by comparing the relative incorporation efficiencies of EdU and EdC during short 30-min pulses, we demonstrate significantly lower incorporation of EdC than of EdU in noninfected human fibroblast cells or in cells infected with either human cytomegalovirus or Kaposi's sarcoma-associated herpesvirus. Interestingly, cells infected with herpes simplex virus type-1 (HSV-1) incorporated EdC and EdU at similar levels during short pulses. Of note, exogenous expression of HSV-1 thymidine kinase increased the incorporation efficiency of EdC. These results highlight the limitations when using substituted pyrimidine analogues in pulse-labeling and suggest that EdU is the preferable nucleoside analogue for short pulse-labeling experiments, resulting in increased recovery and sensitivity for downstream applications. This is an important discovery that may help to better characterize the biochemical properties of different nucleoside analogues with a given kinase, ultimately leading to significant differences in labeling efficiency of nascent DNA.

Support from the Bill & Melinda Gates Foundation has enabled Chatham House to develop a global health security track at the Munich Security Conference (MSC).

26 March 2020

Roland Bruderer
May 1, 2015; 14:1400-1410
Research

Christian Tagwerker
Apr 1, 2006; 5:737-748
Research