Kevin Worrell

1-3 years of laboratory experience in biotechnology or pharmaceutical industry. Experience with biologics formulation development, DP process design and…
From Sangamo Therapeutics - Wed, 24 Feb 2021 02:25:14 GMT - View all Brisbane, CA jobs

The Supreme Court on Monday morning issued more orders from the justices’ private conference last week. After adding 14 new cases to their docket for the term on Friday afternoon, the justices were not expected to grant review in additional cases on Monday – and they did not. Monday’s order list was nonetheless noteworthy because the justices turned down a group of requests to expedite the consideration of petitions for review in cases seeking to undo the results of the 2020 presidential election. The denial confirms that the justices will not consider the petitions until after the inauguration of President-elect Joe Biden, effectively rendering the disputes moot.

The eight petitions challenge the election procedures and results in the four battleground states of Arizona, Georgia, Pennsylvania and Wisconsin, all of which Biden won. Numerous lower courts rejected the challenges, prompting President Donald Trump’s campaign along with Republican allies of the president to file last-ditch appeals to the Supreme Court. Lawyers for the challengers had asked the justices to fast-track the court’s consideration of the petitions, generally requesting that responses opposing review be filed by late December or early January, to allow the court to weigh in before Congress counted the electoral votes on Jan. 6. But the justices – whose last regularly scheduled conference before Jan. 6 took place on Dec. 11 – declined to consider the requests to fast-track until their next regularly scheduled conference, on Jan. 8, and then denied them without explanation. The justices are now not likely to consider any of the petitions until mid- to late February at the earliest, well after Biden’s inauguration on Jan. 20, when it will be too late for the court to grant any of the relief related to the 2020 election that the challengers seek.

Two other election-related petitions out of Pennsylvania still stand a chance of getting taken up by the Supreme Court after the inauguration – though not in a posture that would affect the 2020 election. The petitions in Republican Party of Pennsylvania v. Boockvar and Scarnati v. Pennsylvania Democratic Party involve challenges to the Pennsylvania Supreme Court’s extension of an absentee-voting deadline last year. The challengers originally sought to undo the Pennsylvania results, but after the justices declined to intervene on an expedited basis, Republicans acknowledged in a brief on Dec. 15 that the case “cannot change the outcome” of the 2020 election. They argued nonetheless that the court should grant review in order to clarify the law for future elections.

The court considered the Boockvar and Scarnati petitions for the first time at the Jan. 8 conference. The court took no action on the petitions, and docket entries for the cases indicate they have been relisted for further consideration at this Friday’s conference.

The justices did place a different dispute, over the constitutionality of Nevada’s stay-at-home orders to deal with the COVID-19 crisis, on a fast track. The justices ordered the state to respond by Jan. 19 to a petition by Calvary Chapel Dayton Valley, a church that argues that the state’s more favorable treatment of secular venues like casinos, while restricting attendance at churches, violates the First Amendment. The Supreme Court turned down a request in July from the church for emergency relief, but the make-up of the court has changed since then, with the more conservative Justice Amy Coney Barrett replacing the late Justice Ruth Bader Ginsburg. The justices directed the church to respond by noon on Jan. 21, potentially allowing them to consider the case at their Jan. 22 conference – the last conference before their winter recess – and, if they grant review, to hear oral argument and decide the case this term.

The justices turned down Bruni v. City of Pittsburgh, a challenge to a Pittsburgh ordinance that creates a “buffer zone” around abortion clinics. Anti-abortion activists who want to be able to speak to patients entering the clinic went to court, arguing that the ordinance violates their First Amendment rights. The U.S. Court of Appeals for the 3rd Circuit concluded that the ordinance allows “sidewalk counseling,” and the challengers appealed to the Supreme Court, which on Monday announced that it would not weigh in.

Justice Clarence Thomas filed a statement regarding the court’s decision to stay out of the dispute. He wrote that “buffer zones” like Pittsburgh’s “often impose serious limits on free speech.” Moreover, he observed, the test that the Supreme Court used in upholding the constitutionality of a “buffer zone” law in a 2000 case conflicts with the court’s “current First Amendment doctrine.” Thomas agreed that the court was right to deny review in this case “because it involves unclear, preliminary questions about the proper interpretation of state law.” But he added that the justices should “take up this issue in an appropriate case to resolve the glaring tension in our precedents.”

The justices did not act on several other high-profile cases, including Dobbs v. Jackson Women’s Health Org., the challenge to a Mississippi law that generally bans abortions after 15 weeks of pregnancy, and United States v. Tsarnaev, the federal government’s petition to review the case of Boston Marathon bomber Dzhokhar Tsarnaev, whose death sentences the 1st Circuit vacated. The justices considered all of these cases for the first time at last week’s conference, and they have already been relisted for consideration again at Friday’s conference.

This post was originally published at Howe on the Court.

The post Justices issue more orders from Friday’s conference, decline to fast-track election-related cases appeared first on SCOTUSblog.

Nature Chemistry, Published online: 21 December 2020; doi:10.1038/s41557-020-00604-y

Mimicking biosynthetic pathways can provide access to medicinally important natural products, but generating the reactive species used by nature can often be difficult. Now, a photoredox-based strategy has been developed to access a reactive radical intermediate postulated to be involved in complex lignan biosynthesis.

The last time Dalbello had a true ski mountaineering boot, the Sherpa, was 2011, almost a decade ago. Since then Dalbello has tipped their hat to the backcountry realm by including a walk mode on a few of their awesome alpine boot models. With the Panterra and the Lupo TI models they even included tech fittings for compatibility with true backcountry bindings. However, these weren’t contenders for serious backcountry tours due to excessive weight and a limited range of motion for walk mode.

At the latest Outdoor Retailer/SIA Snow Show, held at the Denver Convention Center, Dalbello showed off their return to the ski mountaineering realm with a backcountry boot called the Quantum. It will come in three versions, with the lightest, the Quantum Asolo Factory, a carbon-infused version weighing just over 2 lbs per boot (2 lbs., 1.5 oz / 950 grams). Besides being ultra lightweight each boot features a huge cuff range of motion thanks to what Dalbella refers to as a dual-link cuff.

Cuff Range of Motion

The best way to describe it might be a split-cuff, or a clam-shell style cuff, with a front and back half that pivot on separate axes. This allows a HUGE range of motion. The front half of the cuff lays down so low there is absolutely zero resistance from the cuff to forward leg movement in tour mode. Range of motion to the rear is almost as large. The net effect is a touring mobility where the only resistance to movement is the flex resistance of the liner which, as I found out at the recent WWSRA demo day at Winter Park, isn’t much.

What? No Buckles?

Notably absent from the Quantum are any toothed buckles; there aren’t any. Instead the boot is secured around the lower foot with Dalbello’s version of a BOA lacing system called the Quick Lacing System. Like BOA it sports a lace system using Dyneema cord that is tightened by a racheted wheel. Unlike the BOA system, you can loosen the tension on the laces just by turning the dial backwards, allowing you to fine tune compression on your lower foot.

The cuff is tightened around the lower leg via the tension on a Dyneema cord that is secured on the front half of the cuff by a clamp. The cord runs from the touring mode lever on the back, through some eyelets on the side to the front where the overall length is clamped with a cleat. It is simple, and effective. In downhill mode it exhibited a similar level of control as a Scarpa F1 LT.

Two-Piece Bonded Scafa

Something Dalbello is touting is the construction of the lower shell. It is built as two pieces, a left and right half, that have a tongue-and groove interface which is bonded using infra-red light and some chemical wizardry. They developed this method of construction to allow for greater sculpting of the shape of the scafa. Ordinarily the degree of sculpting they wanted can’t be done because it prevents the shell from being popped off the mold. With the option to “weld” two halves together those shaping limits could be overcome. The benefit is that there is more allowance provided for bony ankles without post production punching of the shell, hence more comfort for more people out of the box. However, I found that the lower shell was harder to get in to than a typical overlap shell. It also begs the question of whether the tech inserts in the toe can maintain dimensional tolerances to work reliably with all tech bindings on the market. In my limited test run it was not an issue.

Conclusion

There are a fair number of new concepts in this boot that might arouse the average consumers skepticism. On the other hand, the Quantum is aimed at the section of the backcountry market that is more likely to give new technology a try. Boots like the Alien already pioneered using Dyneema^® cord to hold the cuff together, and BOA proved the durability of a wind up lace system. The main difference between each version is the plastic used. All use a polyamide plastic, but the Quantum Asolo Factory has carbon in the lower shell and cuff. The Asolo has carbon in the cuff only, and the basic Quantum uses no carbon in the plastic, lowering the price and the flex stiffness. If the two-piece bonded scafa proves durable Dalbello should have a winner here.

Dalbello
Quantum Asolo Factory
MSRP: $750
Weight: 2 lbs, 1.5 oz (950 g)
Size range: 22.5 – 30.5

Quantum Asolo
MSRP: $700
Weight: 2 lbs, 5 oz (1050 g)
Size range: 22.5 – 30.5

Quantum
MSRP: $650
Weight: 2 lbs, 8.5 oz (1150 g)
Size range: 22.5 – 30.5

The post First Look: Dalbello Quantum Ski Touring Boot first appeared on EarnYourTurns.

The Coyote Bar & Grill gets a whole new look

A longtime fixture in Carlsbad, popular with locals since it first started operating in 1989, has been given a thoroughly modern makeover. The Coyote Bar & Grill’s 30-year residence in Carlsbad’s Village Faire plaza, a prime location just a block from the beach, was uninterrupted, as the restaurant was able to stay open during its remodel.

Exchanging the previous dated look for an updated Southwestern vibe, local designer Melissa Young of MY Studio ID (Waterbar, Madero’s) has transformed the 4,000-square-foot space, which includes an outdoor area with fire pits. A section of high-top tables has been replaced with a new lounge space, which makes more room for group seating and bottle service. On-trend cacti are a key element of the decoration, which includes custom murals, rustic materials, and variety of eclectic lighting.

Though the design has been refreshed, the food menu remains unchanged, ranging from its crowd-pleasing shrimp and cream cheese-stuffed jalapenos dubbed rattlesnake eggs to lobster and sweet corn chowder, smoked chicken enchiladas, and baby back ribs with tequila barbecue sauce. Known for offering live entertainment and dancing throughout the week, The Coyote Bar & Grill regularly hosts bands, DJs, and karaoke nights.

If you can beat the heat, make some Japanese burgers and read about “Bojack Horseman.”

A reader says it best about where I’m now at with respect to Israel/Palestine:

You quote Goldblog:

A moderate-minded Palestinian who watches Israel expand its settlements on lands that most of the world believes should fall within the borders of a future Palestinian state might legitimately come to doubt Israel’s intentions.

This is really the whole Israeli-Palestinian problem in a nutshell. For 47 of my 56 years, Israel has occupied the West Bank and Gaza. (Yes, Israel “withdrew” from Gaza some time ago, but it is still very much Israel’s captive.) In modern times, there is no single other example of a nation that supposedly shares “western” values sustaining such a long occupation of another people. Yes, Israel has a right to defend itself. Yes, Israel has every right to question whether it has a partner to make peace. Of course I don’t trust Hamas. Of course the rockets merit a vigorous no-nonsense response. But one question sticks in my mind about the position of Israel: If Israel really wanted peace, why does it keep building those darn settlements?

Every answer I’ve ever heard – the irrelevant “there never really was a Palestinian state on this land”, the hopeless “even if Israel did that what makes you think they’d suddenly change their stripes?”, or the more limited “construction is for the most part only expansion of existing settlements anyway”, whatever – all of them only go so far as to try to justify why Israel should be permitted to continue to build. It doesn’t explain why it is a good idea for Israel to continue to build.

Just because you can do something, doesn’t mean you should. And in that sense, there is no justification I have ever heard for the settlements that one can reconcile with trying to make the two state solution a reality, or indeed even with leaving it open as a possibility. Just the opposite. Until there is an answer to that question, in my mind, Israel cannot and will not be guilt-free. Maybe if those of us who love Israel but think it has lost its way focused on that one simple question until it is answered, we might get somewhere.

That’s where I’m at as well. At some point, the denials and equivocations and diversions and distractions fade away to that core reality: why are they continuing to settle the West Bank? It empowers Hamas, it weakens the Palestinian Authority, it is a constant grinding of salt into an open wound.

The Israelis had a golden opportunity with Barack Obama’s presidency to make a historic peace; and they didn’t just throw it away, they treated the US president with contempt for even trying and now cast ugly, public insults at the secretary of state. If the settlements had been reversed, if Abbas and Fayyad had been given the autonomy they needed, this war in Gaza would appear as something very different. It would be much simpler to condemn Hamas’ extremism, if there was clearly another way forward. But Netanyahu – because of the settlements – has blocked any way forward. The Palestinians have two options: bombardment and blockade or the humiliation of more settlements. Which is why I have come to the conclusion these past six years that Greater Israel is the goal, that nothing else really matters, and anyone who doesn’t see that is a useful idiot.

Today, in non-war-and-dead children coverage, we looked forward to an app that will guide you to a scenic route across town; we celebrated the better late than never endorsement of legal weed by the NYT (by the way, try watching the David Gregory segment on the question yesterday without needing to toke from the instant nausea); and cheered a new study on sponsored content that proves it’s deceptive to readers, great for advertisers for only a while, and damaging to publications for ever. I also happened to love the window view today – from Buffalo.

The most popular post of the day was The Lie Behind The War; followed by Why Am I Moving Left?

A few of today’s posts were updated with your emails – read them here. You can always leave your unfiltered comments at our Facebook page and @sullydish. 19 more readers became subscribers today. You can join them here – and get access to all the readons and Deep Dish – for a little as $1.99 month. Gift subscriptions are available here. One writes:

Andrew, you and I don’t always agree. But today I became a paid subscriber. This post alone – “Why Am I Moving Left?” – was worth the $20. It is what I have been posting and commenting on, over and over, to anyone who will listen, for three years. As someone who once would have been considered a pro-business Centrist and registered Independent, there is absolutely no way I can comprehend anyone can feel any sense of pride and honor in identifying as a Republican in the current climate. Just the thought causes a disconnect. And like you, it isn’t me that changed. Thanks for speaking for me.

See you in the morning.

(Photos: Yeoman Serjeant Bob Loughlin admires a section of an installation entitled ‘Blood Swept Lands and Seas of Red’ by artist Paul Cummins, made up of 888,246 ceramic poppies in the moat of the Tower of London, to commemorate the First World War on July 28, 2014 in London, England. Each ceramic poppy represents an allied victim of the First World War and the display is due to be completed by Armistice Day on November 11, 2014. After Armistice Day each poppy from the installation will be available to buy for 25 GBP. By Oli Scarff/Getty Images; Smoke trails over Gaza city after Israeli shelling on July 25, 2014. By Ashraf Amra/Anadolu Agency/Getty Images.)

As I stated yesterday I felt like taking a vacation of sorts.  Mentally I could but unfortunately, physically I could not.  Part of what helped me mentally was dressing down.  So I decided to dress somewhere between business casual and casual.  The trousers and button down shirt are much in the casual realm of things so I used the dress loafers and belt to up the formality ever so slightly.  I didn’t want to take things too seriously so I opted for my mock field watch from my beloved Murray’s Toggery with a navy blue nylon strap.  Continuing along this line I choose to keep my socks more casual so I donned sky blue over the calfs.  Unfortunately, today it is not slated to be so nice out, but I guess it is only March…

 

Filed under: Accessories, Casual, Style Photographs

Whether it's because of the evergreen interest in Carl Djerassi, the discovery of a (new-to-me!) blog, or Percy Julian's recent Google Doodle, everything in the blogosphere seems to be coming up steroids.

Take a peek at these back-to-back OPRD articles, both from chemists at the former Satori Pharmaceuticals.

As a "cub blogger" for CENtral Science, I still remember gaping at how radically different their root-derived phytosterols were from the rest of the anti-Alzheimer's medicines. Now, almost a year to the day after Satori shut its doors, we have some insight from the team responsible, just before they scattered to the winds.*

So, that means 6.99 tons of plant waste to dispose? [rubs eyes] OPRD, 2014 ASAP

To access their preclinical candidate, Satori scientists first needed a reliable supply of the glycosylated intermediate. Enter seven metric tons of dried black cohosh, a traditional medicine used as a pain reliever by Native American healers. A third-party vendor crushed the root and sent it to another firm, where they extracted it with ethanol, passing about 300 kg of "solids" back to Satori. Suspension in brine / DCM partitioned the desired compounds into the organic phase, which was treated with triethylamine and catalytic zirconium tetrachloride. This ejects the pesky E-ring alcohol, and the resulting compound performs a net oxidation to yield a diastereomeric mixture of ketones (above).


(Warning: I guess you haven't lived 'til you've purified 70 kg of crude, brown extract with DCM over silica...yuck!)

So, once Satori had in hand ~11 kg of compounds 1 + 2 (see right), they needed to advance the structures to their desired candidate (below) which you'll notice has a few little changes from the plant-derived drug. Gone are the acetyl group. Reduced is the ketone. Ripped apart is the sugar, making way for a morpholine.

The scientists' first-gen synthesis, an 8-step sequence, wasn't up to snuff for kilogram work. The trouble? Too many chemically similar hydroxyls, prompting some protecting group manipulation to target one or two selectively. Process work on the ethyl ether step - utilizing diethylsulfate / tert-butoxide in place of an earlier NaH / EtI mix - allowed a telescoped 5 step route, cutting out 2 silica gel columns and upgrading the final process purity to >95%.


Interestingly, the authors, ever circumspect, reflected on the limitations of their final process:

"While this reported route was sufficient to provide the kg-scale quantities of target compound for preclinical studies, we acknowledge that it has limitations that would make it impractical at the 100 kg scale."

Silica gel chromatography strikes again! Still, their candidate came through on 1 kilo, at about 30% overall yield after HCl salt formation. Not too shabby.

Update (5/30/14): Want to see how Satori chose these molecules? One of the authors (Hubbs) writes in to recommend their 2012 J. Med. Chem. optimization paper.

*According to the author lists, everyone on the team ended up in a different place: Enanta, AstraZeneca, Celgene, ETH, Genzyme, Resilientx, Sanofi.

daviddelruelle:

"Gourmande"

A collaboration with Adrian Velazco http://adriancollage.tumblr.com

The Congressional Budget Office forecasts that raising the minimum wage to $10.10 an hour, as Obama and the Democrats in Congress hope to do, would give 16.5 million American workers a raise and lift 900,000 out of poverty – but it would also lead to 500,000 job losses. Barro thinks this is a pretty good deal:

As economist Richard Thaler puts it, “All methods of helping the poor cause distortions”; a minimum wage increase can cause a modest rise in unemployment and still be a good policy idea, so long as it has more than offsetting positive effects.

And the minimum wage trade-off presented by CBO looks awfully favorable. For every person put out of work by the minimum wage increase, more than 30 will see rises in income, often on the order of several dollars an hour. Low- and moderate-income families will get an extra $17 billion a year in income, even after accounting for people who get put out of work; for reference, that’s roughly equivalent to a 25% increase in the Earned Income Tax Credit.

Mike Konczal accuses the CBO of “putting a thumb on the scale” to inflate the number of job losses:

[T]he CBO’s methodology is weighed to overstate the impact of a $10.10 minimum wage on jobs, while also understating the benefits. Even then there’s a clear tradeoff – a minor fall in jobs for serious real gains again inequality and wage security.

Never mind the scary headlines, or the report that unfortunately plays to them: When you consider that the academy is far more ambiguous about the costs of giving the country a raise, and more bullish on the benefits, this is still an excellent deal for working Americans.

To Jared Bernstein, the report confirms the wisdom of raising the minimum wage:

As I’ve stressed many times on this blog, policy makers need to be concerned about the quantity of jobs, and pursue policies that will increase that number.  But they also have to worry about job quality, especially in the low-wage sector, where the decline in the real value of the minimum wage, the increase in earnings inequality (meaning less growth finds its way to the low end of the wage scale), and the low bargaining power of the work force have placed strong, negative pressure on wage trends for decades.

With such job-quality concerns in mind, I’d say the long history of research shows that increasing the minimum wage is a simple, effective policy that achieves its goal of raising the value of low-wage work with minimal distortions at no cost to the federal budget.  The Congressional Budget Office report further confirms that conclusion.

The administration is disputing the job loss numbers, but Yglesias argues that they really shouldn’t be:

If the White House genuinely believes that a hike to $10.10 would have zero negative impact on job creation, then the White House is probably proposing too low a number. The outcome that the CBO is forecasting—an outcome where you get a small amount of disemployment that’s vastly outweighed by the increase in income among low-wage families writ large—is the outcome that you want. If $10.10 an hour would raise incomes and cost zero jobs, then why not go up to $11 and raise incomes even more at the cost of a little bit of disemployment?

Cowen sees it differently:

Spin it as you wish, we should not have a major party promoting, as a centerpiece initiative and for perceived electoral gain, a law that might put half a million vulnerable people out of work, and that during a slow labor market.

Philip Klein seizes on the contradiction between the CBO report and the president’s promises:

The bottom line is that Obama has presented hiking the minimum wage as a no-brainer that would boost the economy, increase wages and immediately reduce poverty without adverse effects. CBO has estimated that in reality, the action would raise unemployment among lower-income workers, deliver most of its benefits to families living above the poverty level, and have offsetting adverse effects on businesses and consumers. To the extent that it will reduce poverty, according to the CBO, the effect will be less significant and less immediate than what Obama has claimed.

Jordan Weissmann puts the numbers in perspective:

[T]he report … demonstrates the limits of the minimum wage as a policy tool for curing poverty or bolstering the middle class. There are currently about 45 million people living in poverty—the CBO’s estimate suggests the wage hike being debated in Washington would only reduce that number by 2 percent. Among families under the poverty line, average incomes wouldn’t increase any more than 3 percent.

For liberals looking for ways to combat inequality and poverty, raising the minimum wage would be a good start, but no more.

Bouie chimes in:

I should also say that this gets to why—as far as raising incomes is concerned—the minimum wage isn’t the greatest option. An expansion of the Earned Income Tax Credit—to raise payments and include single, childless workers—could increase incomes without the hit to the labor market. Indeed, a combination of the two policies—a larger EITC and higher minimum wage—could substantially boost incomes and provide enough stimulus to the economy to completely outweigh the adverse effects.

But, with the notable exception of Florida Senator Marco Rubio, it’s hard to find Republicans who would support a stronger EITC, or any measure that would move funds from the wealthy to the poor. Which leaves the minimum wage at a disadvantage as well. The difference, of course, is that the EITC is a federal policy, while individual states can set a minimum wage. And it’s for this reason that Democrats have committed to the latter; even if they lose in Congress, they can still take their fight to America’s statehouses.

Suderman cautions against reading too much into the CBO’s findings:

It’s complex and highly politicized, and the CBO tries hard to avoid politicization to the extent that it’s possible. So this report is probably best taken as a wonky but readable guide to the economic research on the topic. And it’s probably not worth investing too much in the specific point projections about jobs lost and incomes raised. Instead, it’s best to think of the report as highlighting the variety of economic costs and trade-offs that would come with a hike in the minimum wage, including job loss, and a reminder that the administration has an incentive to downplay potential negatives and paint its policy proposals in the most positive possible light.

And Drum wonders why the office bothered to take up this issue in the first place:

[T]his is a report that I suspect CBO shouldn’t have bothered doing. Their value-add lies in assessing the effects of legislation that no one else is studying. But the minimum wage has been studied to death. CBO really has nothing to add here except its own judgment about how to average out the dozens of estimates in published academic papers. In other words, they aren’t adding anything important to the conversation at all. This report is going to get a lot of attention, but it really doesn’t teach us anything new.

The California Conference of Catholic Bishops asked people of all faiths to join in prayers for rain as reservoirs in the state dipped to historic lows after one of the driest calendar years on record.