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I have the rare Alice in Wonderland syndrome, here’s what it’s like – Insider – INSIDER

Posted: October 25, 2020 at 11:56 am

It would always happen late at night.

I would be lying in bed and gently winding down into sleep. My eyes would begin to feel peculiar, as though they were being squeezed. Suddenly, I would notice that the room around me had begun to appear as if I were looking at it down the wrong end of a telescope.

My bedroom furniture, my posters and ornaments, and the walls looked tiny, as though they were dollhouse-sized. At the same time, I felt huge, like I could reach out and touch the ceiling with my fingertips.

Everything I could see had a warped, fish-eye quality to it. If I turned on my bedroom light, the room would suddenly switch back to normal, but the only other "cure" for this odd phenomenon was falling asleep.

This happened to me frequently when I was a kid, most often when I was especially tired, ill, or stressed. I didn't have the words to explain what was happening to me at night, I only knew that it felt unusual and dream-like but I knew that I wasn't dreaming.

When I told my parents that sometimes at night "everything looked small" they took me to an optician, where I discovered that I needed glasses and my prescription meant that I had a problem with depth perception.

Problem solved, I thought. But the episodes kept happening.

Sometimes everything around me would look dollhouse-sized. zef art/Shutterstock

I wasn't frightened by these episodes where everything around me looked like a reflection in a fun-house mirror. I loved fairy tales, and what I was experiencing didn't seem odd in the context of magic wands, evil stepmothers, and kids being able to talk to animals.

As I grew older, the episodes became more infrequent and, eventually, I forgot they had ever happened. But recently one night I was lying in bed, feeling tired and stressed, and I felt the same familiar tightening around my temples.

Suddenly, the room around me shrunk to dollhouse proportions.

Amazed, I stretched out my seemingly giant hand and felt as though I could easily touch the far-off wall opposite my bed.

Later that same week, I happened to discover a New York Times article that finally had an explanation, a name, and a diagnosis for what was happening to me I had Alice in Wonderland syndrome.

Discovered in 1955 by British psychiatrist John Todd, episodes of this rare curiosity, also known as Todd's syndrome, tend to involve macropsia (objects appearing larger than they are), teleopsia (objects appearing further away than they are), and micropsia (objects appearing smaller than they are).

Some people who experience this perceive their own body parts as being larger or smaller than in reality, and the whole episode can be accompanied by a sense of derealization (feeling like things around you aren't real) and depersonalization (feeling detached from your own body or mind).

It's sort of similar to what Alice experienced when she ate the mushroom in Lewis Carroll's famous book "Alice's Adventures in Wonderland" and altered the size of her body hence the name of the syndrome.

The syndrome has been linked to migraines, epilepsy, strokes, head trauma, infections, drugs, and stress but it's not known to be dangerous.

It's also not yet clear what causes the illusions and distortions, although it's not believed to be a hallucination or an eyesight problem.

Alice and the mushroom pieces in "Alice in Wonderland" (1951). Disney

Some who have studied this under-researched syndrome believe it's caused by changes in the portion of the brain that processes how we see our environment, possibly because of electrical activity which causes abnormal blood flow to that area.

Some doctors also believe it to be a type of migraine aura, which are sensory disturbances that can sometimes alter one's vision just before a migraine.

Dr. Grant Liu, a pediatric neuro-ophthalmologist at the Children's Hospital of Philadelphia, said he's seen a lot of patients with "odd complaints" over the years.

"Kids complain of seeing things that are too small, too large, too close, and too far away," he told Insider.

A few years ago, he conducted a study into Alice in Wonderland syndrome where he examined and spoke to 48 patients who experienced symptoms between 1993 and 2013.

He was able to link 33% of cases of the syndrome to exposure to infections (such as the flu), 6% to head trauma, and 6% to migraines. But in 52% of the cases, no cause was found.

His research also found that although the syndrome typically affects young children, it continued until later in life for about a third of patients he studied.

Miniature Alice and the Mad Hatter in "Alice in Wonderland" (2010). Walt Disney Studios

ButDr. Liu said he was most fascinated by the familial link he's seen with the syndrome, which makes him think that it could be more common than people think.

"For the study, we called families to follow up five to 15 years after diagnosing their children with Alice in Wonderland syndrome," he told Insider. "During those phone calls, lots of parents admitted that they too had experienced symptoms as children but when they were in the exam room, they were too embarrassed to admit it."

Although Dr. Liu said people experiencing Alice in Wonderland syndrome should see a specialist, as it can be a manifestation of a seizure or a migraine, he was quick to assure me that "there's no treatment necessary, it's really just reassurance."

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I have the rare Alice in Wonderland syndrome, here's what it's like - Insider - INSIDER

Recommendation and review posted by G. Smith

Biomarkers Market Size, Share & Industry Analysis, By Indication (Oncology, Cardiology, Neurology, and Others), By End User (Pharmaceutical &…

Posted: October 25, 2020 at 11:56 am

Trusted Business Insights answers what are the scenarios for growth and recovery and whether there will be any lasting structural impact from the unfolding crisis for the Biomarkers Market.

Trusted Business Insights presents an updated and Latest Study on Biomarkers Market. The report contains market predictions related to market size, revenue, production, CAGR, Consumption, gross margin, price, and other substantial factors. While emphasizing the key driving and restraining forces for this market, the report also offers a complete study of the future trends and developments of the market.The report further elaborates on the micro and macroeconomic aspects including the socio-political landscape that is anticipated to shape the demand of the Biomarkers Market during the forecast period.It also examines the role of the leading market players involved in the industry including their corporate overview, financial summary, and SWOT analysis.

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This report focuses on the Biomarkers market and value at the global level, regional level, and company level. From a global perspective, this report represents the overall Biomarkers market size by analyzing historical data and future prospects. Regionally, this report focuses on several key regions: North America, Europe, Japan, China, Southeast Asia, India, Latin America, and South America.

Global Biomarkers Market: Segment Analysis

The research report includes specific segments by region (country), by Company, by Type, and by Application. This study provides information about the sales and revenue during the historic and forecasted period of 2019 to 2029. An in-depth analysis of the segments assists in identifying the different factors that will aid market growth.

Global Biomarkers Market: Regional Analysis

The research report includes a detailed study of regions of North America, Europe, Japan, China, Southeast Asia, India, Latin America, and South America. The report has been curated after observing and studying various factors that determine regional growth such as the economic, environmental, social, technological, and political status of the particular region. Researchers have studied the data of revenue, sales, and manufacturers of each mentioned region. This section analyses region-wise revenue and volume for the forecast period of 2019 to 2029.

Global Biomarkers Market: Competitive Landscape

This section of the report identifies various key manufacturers of the market. It helps the reader understand the strategies and collaborations that players are focusing on combat competition in the market. The comprehensive report provides a significant microscopic look at the market. The reader can identify the footprints of the manufacturers by knowing about the global revenue of manufacturers, the global price of manufacturers, and sales by manufacturers during the forecast period of 2019 to 2029.List of Companies Profiled

F. Hoffmann-La Roche Ltd., Abbott, and Thermo Fisher Scientific, Inc. are Leading Market PlayersThe biomarkers market is a highly fragmented market. To strengthen their position, key market players are focusing on the introduction of novel biomarker tests, and entering in mergers and partnerships with other prominent companies with an aim to establish a strong brand presence. F. Hoffmann-La Roche Ltd., Abbott, and Thermo Fisher Scientific, Inc. dominated the biomarkers market share in 2018. Other players operating in the market are Bio-Rad Laboratories, Inc., Sino Biological Inc., BioVision Inc., Myriad RBM, R&D System, Axon Medchem, CENTOGENE N.V., and others.

List of key Companies Covered:

REPORT COVERAGE

The biomarker market report provides detailed information regarding various insights of the market. Some of them are growth drivers, restraints, competitive landscape, regional analysis, and challenges. It further offers an analytical depiction of the biomarkers market trends and estimations to illustrate the forthcoming investment pockets. The market is quantitatively analyzed from 2021 to 2026 to provide the financial competency of the market. The information gathered in the report has been taken from several primary and secondary sources.

Report Scope & Segmentation

By Indication

By End User

By Geography

INDUSTRY DEVELOPMENT:

May 2019: QIAGEN received FDA approval for therascreen RGQ PCR Kit. The therascreenPIK3CA Kit is the first companion diagnostic assay approved to identify breast cancer patients eligible for treatment with PIQRAY (alpelisib). PIQRAY (alpelisib), a newly approved therapy for breast cancer developed by Novartis AG.

May 2017: F. Hoffmann-La Roche Ltd., received the U.S. Food and Drug Administration (FDA) for biomarker assay for bladder cancer. This biomarker assay evaluates the status of patient PD-L1 by using both immune cell staining and tumor cell staining and scoring within the tumor.

 

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Biomarkers Market Size, Share & Industry Analysis, By Indication (Oncology, Cardiology, Neurology, and Others), By End User (Pharmaceutical &...

Recommendation and review posted by G. Smith

Chemistry professor had the right formula for how to live and die – South Bend Tribune

Posted: October 25, 2020 at 11:55 am

I wish that I had known Roger Schmitz, the former dean of the Notre Dame chemistry department and later a vice-president and associate provost at the university.

He loved to run and was still winning his age group into his 70s even though he laughingly admitted he sometimes didnt have any opponents.

He threw snowballs at his three girls, the three Js Jan, Joy and Joni even when they were adults and coached them in softball, sometimes having to nudge them off the bench for their two-inning minimum in the field. He loved giving them nicknames.

He enjoyed a wide variety of music from Bobby Darins Mack the Knife to the English folk song Greensleeves, from Roger Millers King of the Road to the Notre Dame Fight Song, of course.

He collected 200 autographs of major league ballplayers when he was growing up in Carlyle, Ill. His collection included 22 Hall of Famers with names like Musial, DiMaggio and Robinson.

He died of ALS (amyotrophic lateral sclerosis) in October of 2013 while the World Series played soothingly by his bedside.

During his 78 years, Roger Schmitz knew how to live and love and then leave this world in both a courageous and dignified way.

I dont think I ever met anyone who didnt enjoy being around my father, says Jan Schmitz Mathew, Rogers oldest daughter. And he demonstrated the same incredible grace and presence when he was dying that he had shown throughout his life.

To honor her dad, Jan has written a book, Surrounded by Love: My Familys Journey Through ALS. It is available at corbybooks.com, Amazon and the Hammes Notre Dame Book Store.

It is about Rogers life with his wife, Ruth, and their three daughters and the battle they faced together against Lou Gehrigs disease that took him in just seven months.

When his diagnosis was confirmed, he wrote his daughters. Everything else has been ruled out. Thats a bummer but it doesnt surprise me There will be bumps ahead, but we can handle them as you know.

Yes, they knew. Their dad had never been about self-pity or bitterness. He accepted what he couldnt change and moved on just as he had during an earlier bout with bladder cancer.

But in not much more than a years time, Roger went from still being able to jog around the block to needing a walker and then a motorized wheelchair and finally a scooter he bonded with.

And he kept his quirky sense of humor, Jan says.

When he once banged his scooter into a doorway, Jan remembers him saying, Well &$$%, Roger. Do you think you could clobber the wall just one more time today?

He never built walls around himself, though. He never tried to push his family away and go it alone.

Love is costly, the Rev. Paul Doyle wrote in the foreword of Jans book. And when we love, we carry crosses with each other. On the day Roger died, his last words to his daughters Jan, Joy and Joni were I love my Js. They and his wife Ruth had carried this cross with him.

Surrounded by Love is the story of that sad yet sometimes sweet journey of this uncommon man.

Heres another story about the late great Chicago Bear star and Wakarusa resident Gale Sayers from reader Michael Myers:

Its 1995 or so, and my son Matthew and I are walking down the midway at the Elkhart County Fair and I see Gale Sayers, Michael recalls. He was by himself, nobody bothering him, so I decided to change that. We approached him and I apologized for bothering him.

He was very friendly and I told him I wanted my son, who played football, to meet the greatest Bears running back ever. He then said as he was shaking Matthews hand, Is Walter Payton here?

You gotta love a humble man like that.

Congrats to the whole town of Buchanan for garnering the top honor on Reader Digests list of The Nicest Places in America.

Yeah, Ive always thought Buchanan was pretty cool. A couple of my friends come from there even though they probably should have been kicked out of town.

The Redbud City earned the accolades because of its 150-year-old tradition of honoring our fallen veterans on Memorial Day a summer march for racial justice with police chief Tim Ganus joining in Red Bud Area Ministries, which helps so many of the less fortunate the Scarecrow Factory and the Buchanan Promise scholarship fund to name a few reasons.

Life is better here, is Buchanans motto, and its citizens seem to believe that. Buchanan is a very supportive community, says 27-year-old Megan Goodrich, who sets up donation boxes for the homeless, according to the article. If you have an idea and want to do something, theres bound to be people here who will try to help you figure out how to make it happen.

Buchanan obviously is a happening place and now Readers Digests nicest of nicest places, too.

I was trying to out-drive my wife on Studebaker Golf Courses seventh hole when a ball plunked down on the No. 9 green and rolled into the hole not 30 yards from us.

Then Tribune sports editor Mike Wanbaugh came whooping down the hill like a banshee. Our buddy Kirby Sprouls had just made a double eagle/hole-in- one on the 265-yard hole.

In the last year, Ive been in the vicinity of two of my buddies making aces at Studebaker. If you pay my way ha, ha (it costs only $6 for a senior to walk), Ill serve as your lucky charm.

But then Kirby had to come clean: OK, before anyone calls Sports Illustrated because it was a heckuva shot, if I say so myself it was a mulligan. My first tee shot was a little left and a little short. With no one behind us, I decided to hit a second tee shot. The rest is history. But if I dont come clean on the mulligan, I would owe Wanbaugh drinks from Hammer & Quill for the rest of my life.

Sadly, Wanbaugh is like that ha, ha. But as groundskeeper Carl Spackler (Bill Murray) said in Caddyshack, Its in the hole!

Continued here:
Chemistry professor had the right formula for how to live and die - South Bend Tribune

Recommendation and review posted by G. Smith

Using Analytical Chemistry To Put an End to Corked Wine – Technology Networks

Posted: October 25, 2020 at 11:55 am

The sound when the cork pops out of the bottle is satisfying isnt it? But what disappointment if at that very first sip the look of pleasure and anticipation turns to disgust when the off flavors of a faulty wine hit your tongue thats if it even gets past your nose.

There are seven common faults that can be identified in wines, although a limited degree of some may be appreciated as pleasant by some consumers. These faults include oxidation (in excess), reduction, Brett (caused by Brettanomyces yeast), excess sulfur dioxide (SO2) (naturally produced during wine making and used to stabilize wines), volatile acidity, out of condition (over-age, bad storage) and last but by no means least 2,4,6-trichloroanisole (TCA), more commonly known as cork taint.

In the article we are going to focus on cork taint a fault not appreciated by anyone in the wine production, retail or consumer chain.

Cork is a natural product, stripped bark from the cork oak (Quercus suber). Consequently, as with any food or beverage product, good agricultural practice is necessary to minimize contamination by unwanted microbes during processing, transport and storage. Because of the nature of corks source, typical contaminants include soil-borne bacteria, yeasts and most commonly fungi. It is a subset of these fungi that are associated with cork taint. Species most frequently associated with cork taint include isolates from the genera Trichoderma and Fusarium, although other fungal species are also known to be involved.

To defend itself from fungal attackers, the tree produces phenolic compounds. In retaliation the fungi defend themselves by methylating the phenolic compounds which makes them less toxic, resulting in compounds such as anisole. When anisole then comes into contact with chlorine, which is frequently used as an antimicrobial during cork sterilization, it is converted to TCA et voila! If an affected cork is then used to stopper a bottle of wine, the compound is transferred into the wine as it comes into direct contact.

Cork taint is a harmless to health, naturally-occurring fault in bottles of wines closed by corks. It results in a very unattractive, moldy, wet cardboard smell that additionally reduces the fruit character of wine (it has nothing to do with pieces of cork breaking off and being seen in the bottle or glass). It can be detected by tasters at very low concentrations commented David Way, Wine Qualifications Developer at the Wine and Spirit Education Trust (WSET). Whilst the characteristics of cork taint have been described as a fault for decades, it wasnt until the 1980s that the compound responsible for taint was actually identified1, 2.

It has been estimated that 2-7% of wines suffer from cork taint3, 4; not only disappointing for the consumer but resulting in economic loss for producers and retailers. Thats aside from the sacrilege of potentially losing rare fine wines. However, these figures are reducing as the cork industry seek to address the issue.

A group of trained wine judges were put to the test and a geometric mean of the minimum detectable concentrations of TCA determined at 4.6 ng/L. Levels in the wines themselves below this should theoretically be undetectable to consumers and therefore offer a maximal threshold for acceptable limits of cork-to-wine transfer.

A host of laboratory-based analytical techniques can be applied to wines to determine if they contain TCA. Headspace solid phase microextraction (SPME) in combination with gas chromatography-mass spectrometry/ selective ion monitoring (GC/MS-SIM) has been shown to work well in detecting TCA in wines. SPME has also been used on wines and cork material to detect TCA at levels beyond olfactory detection. Headspace SPME and heart-cut multidimensional gas chromatography with tandem mass spectrometric detection has also proved effective. However, from a production point of view, every cork is an individual, so short of uncorking and testing every wine before it is sold, these techniques are not helpful in preventing cork taint in the first place.

In terms of whole, natural corks, the primary focus of efforts has been on identifying corks that contain TCA to prevent them reaching the bottling line.

A non-destructive technique called the dry-soak method was and is still used in some places to detect individual corks containing TCA. Here, every large format cork is held individually in a sealed glass jar containing 5-10 drops of de-mineralized water. Over 48 hours, the moist environment volatizes the TCA and then the corks are sniffed by a human expert panel. A study comparing this technique to chemical analysis by GC-MS found the dry-soak method effective in detecting tainted corks. However, this technique is labor intensive and due to sensory fatigue, only around 200 corks can be sniffed in one sitting, stopping for breaks every 50 corks. It may be effective, but this is therefore certainly not a method suited to a high throughput environment.

Given the sheer volume of corks used in the wine industry there is clearly a need for a quantitative, automated system for accurately detecting and rejecting affected corks.

A number of groups in both academia and industry, fostering collaboration between chemists and the cork industry, have successfully sought non-invasive, sensing device solutions that detect volatile organic compounds (VOCs), including TCA, on individual corks, rapidly.

A multi-center EU-funded project successfully developed an electronic nose, consisting of a sensor array, capable of detecting TCA down to 2 ng/L at a rate of 250 corks per hour. Whilst promising, the project has however not produced a solution available to producers. Whilst they can be useful technology, electronic noses lack the sensitivity required to detect TCA at the levels required and as such dont provide a solution for detecting affected corks currently commented Professor Ulrich Fischer, Head of the Institute for Viticulture and Oenology, Service Center for Rural Areas (DLR) Rheinpfalz, Germany.

A partnership was able to create a similar GC-based system with an analytical detection limit of a mere 0.5 ng/L, well below that detectable by a consumer. Each cork is checked individually with the cork sniffers currently able to test one cork every 16 seconds, each typically checking around 34,650 corks a week. But the goal is one every 10 seconds!

An alternative based on gas phase spectroscopy, also a result of industry-academia collaboration, analyzes corks one-by-one in an automated system and can be used on washed and unwashed corks. It too has a limit of detection of 0.5 ng/L and takes just 5 seconds to analyze each cork.

Seems like a huge waste of natural resources you may be thinking but fear not! Rejected corks can still find a useful life in applications such as flooring and gaskets.

An alternative approach is to prevent the formation of TCA in the first place by sterilizing and reconstituting the cork. The cork industry has responded with two main approaches cleaning cork with steam or creating closures with recomposed cork particles that have been cleaned and reconstituted with plastic. These responses are probably what has led to the reduction in corked bottles in recent years and give wine consumers the familiar ritual of opening a bottle with a corkscrew commented Way.

Corks fragments that have been sterilized with supercritical CO2 and glued back together have been a huge success in the wine industry. As the compounds used to reform them do not contain plasticizers they have been well received and accepted by many as a good and safe alternative to whole natural corks commented Fischer. He continued, Reconstitution also enables manufacturers to control the porosity of the corks to oxygen so they can be tailored to different types of wine. A red Bordeaux for example may benefit from a cork that enables greater oxygenation to develop its character, whilst a Riesling from Germany may benefit from less oxygenation to retain the floral aromatic character of the wine.

Recently, a Swiss group have developed a membrane that is able to filter TCA out of wines. Fischer continued, This is an exciting development for wine producers and suppliers. Whilst not economically viable for wines at the cheaper end of the market, it ensures rare and expensive wines are not lost and means suppliers are able to provide the vintages their customers want.

Plastic corks and screw cap closures have gained popularity in many parts of the world, particularly in New World wines. However, they are still fallible with compromised seals resulting in leakage and spoiled wines from excessive oxidation.

Synthetic closures avoid the hazards associated with TCA, but they lack the microporous properties of cork that allow minute quantities of oxygen into the bottle. Whilst excessive oxygenation is undesirable, small quantities of oxygen are a necessary part of the bottle ageing process that help to develop the tertiary characteristics of the wine think savory, meaty notes in a red, or honeyed, dried fruit in a white wine.

Therefore, whilst rubber corks and screw caps may be a good solution to protecting wines bottled for immediate consumption, they are not appropriate for premium wines that are designed to be bottle matured for a number of years.

Non-traditional corks are a very much contentious subject within the industry and the strength of opposition such that in some regions any closure except natural cork is banned under local wine production regulations.

The main approaches to dealing with cork taint have been either to use other types of closure, especially screw caps, or to ensure that corks do not contain TCA. Screw caps have been widely adopted in Australia and especially New Zealand (among many other countries) and have been accepted, especially for inexpensive and mid-priced wines in some markets, for example, the UK. There has been less take up by wine makers in Europe and less acceptance of alternative closures in some major market, such as France, Italy and the USA (although attitudes are changing in the last named) concluded Way.

Researchers have been developing new cork-free screw caps that incorporate a breathable liner, enabling micro dosing of oxygen into the bottle. It is still however early days and they have not been widely adopted so it is unlikely you will pick one up off the supermarket shelf anytime soon.

Aside from their physical and chemical properties, studies have shown that many consumers prefer natural corks and it impacts their perception of quality, an important consideration for wine producers and retailers wishing to get the best price for their wines.

Despite the potential shortcomings of natural cork. It is worth considering the green, biodegradable and renewable nature of cork over alternatives. Cork oaks grow for around 25 years before the first harvest, benefitting the environment and providing habitat. Once harvested a skillful job, the bark of the cork oak regrows too, and can be harvested every 8-14 years, offering long-term productivity.

References

1.Tanner H, Zanier C, Buser HR. 2,4,6-Trichloranisol: Eine dominierende komponente des korkgeschmacks, Schweiz. Z. Obst-Weinbau. 1981;117:97-103.

2.Buser H, Zanier C, Tanner H. Identification of 2,4,6-trichloroanisole as a potent compound causing cork taint, J. Agric. Food Chem. 1982;30:359-362.

3.Silva Pereira C, Figueiredo Marques JJ & San Romo MV. Cork taint in wine: Scientific knowledge and public perception A critical review. Critical Reviews in Microbiology. 2010;26(3):147-162. doi:10.1080/10408410008984174

4.Butzke CE, Evans TJ, Ebeler SE. Detection of cork taint in wine using automated solid-phase micro extraction in combination with GC/MS-SIM. Chemistry of Wine Flavor, 1998;15:208-216. doi:10.1021/bk-1998-0714.ch015

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Using Analytical Chemistry To Put an End to Corked Wine - Technology Networks

Recommendation and review posted by G. Smith

Locker room chemistry is a key component the Steelers success in 2020 – Behind the Steel Curtain

Posted: October 25, 2020 at 11:55 am

The 2020 Pittsburgh Steelers have something special going on. Yes, they are 5-0 as they head to Nashville to take on the only other remaining undefeated team in the AFC. But there is something else to the Steelers team, and the more Steelers fans understand it the more they need to appreciate the Steelers front offices willingness to protect it.

The Steelers locker room is really something special.

Sometimes fans get it and sometimes they just dont see this aspect of the game. When a team comes together in the locker room, theres so much more they can do on the field. Of course its easier to have a good locker room when a team is winning, but this started long before the Steelers took the field for the first time in 2020.

Going through the different training camp setting required this season, the Steelers had a different mentality. From the beginning head coach Mike Tomlin made the statement of Its one fail, all fail which speaks both to the teams mentality when it comes to Covid procedures as well as the season in general. By players and personnel needing to take the precautions needed to in order to make this season happen, it appears it has brought this team together even more. Add the fact not one single Steelers player opted out for the season already and it felt like something special was going on with this team from the very beginning.

As the season progresses, more evidence continues to emerge about the quality the Steelers locker room. Ben Roethlisberger cannot say enough about his young wide receivers. Remember, Roethlisberger is only seven games removed from having a team which included Antonio Brown. Seeing the Steelers Pro Bowl wide receiver JuJu Smith-Schuster smiling and happy after a win where he had a minimal contribution shows the difference in this wide receivers room which Roethlisberger hasnt seen for a long time.

For those who may not have seen Thursdays Minkah Fitzpatrick interview, T.J. Watt and Bud Dupree decided to drop in and take over for a while. It was quite comical for anyone watching as Fitzpatrick burst out into laughter at their responses. While many may put this into just people having fun, the fact that they can have fun and not feel like theyre stealing each other spotlight is something to be noted.

Another example of the Steelers locker room being different is Steelers tight end Eric Ebron. One of the biggest complaints about Ebron coming into 2020 was his presence in the locker room in his previous stops in the NFL. What has happened since hes come to the Steelers? There havent been any problems reported. Additionally, Ebron is jumping for joy on the sidelines at Steelers games.

So whats the big deal? Why even talk about the Steelers locker room chemistry? Whether its great or if its terrible, does it really matter if the team is winning?

Yes, it does.

The biggest thing the Steelers need to make sure they do this season is not screw it up. As the trade deadline approaches, many feel the Steelers could possibly make a move to bolster their roster. But as much as a player can bring to the field, the Steelers also need to be aware of what the player would bring to the locker room.

I understand that just because someone has a black and gold T-shirt and a smart phone it doesnt mean they speak for Steelers Nation. There are plenty of takes presented on social media, many of which are absolutely terrible. Im going to highlight one or two that Ive seen from multiple places and show how little they consider locker room chemistry.

The Steelers need to trade JuJu NOW! Theyre going to get nothing from him if they dont.

Why are the Steelers concerned about getting something in return for a player who may or may not leave via free agency following this season? The Steelers are 5-0. This year is what its all about. Not only that, why would the Steelers even consider taking their locker room leader in the wide receivers room and shipping him off somewhere else? What message does that send to the other young players on the team? What if JuJu Smith-Schuster is the glue that holds them all together?

Im not going to quote the next one exactly, but even some former Steelers has chimed in on the topic of the Steelers trading for Dwayne Haskins. I dont understand the point. First, what are they going to have to give up to get him? Next, how is he going to help the Steelers win in 2020? And finally, why would the Steelers disrupt a quarterback room which appears to be functioning quite well?

In case youre wondering why I make the statement about a well-functioning quarterback room, its based on the James Washington touchdown in Week 6 against the Cleveland Browns. The story about this play is it was presented to Ben Roethlisberger on the sidelines by third-string quarterback Josh Dobbs who saw something where he thought it would work.

The reason this is such a big deal is Ben Roethlisberger is trusting the other players in the quarterback room. Why would Ben Roethlisberger listen to Dobbs unless these guys have something going on? Roethlisberger has been doing this more than all the other guys in the room combined, but yet Roethlisberger listened to Dobbs, Steelers scored a touchdown, and Roethlisberger gave Dobbs the credit.

How much do fans really know about the Steelers locker room? We can look for evidence through various things, but its really difficult to find out the information with certainty. After the fact, we found out so much about Steelers superstars from several years ago and the issues going on. But from everything that is coming out in 2020, this is not the case with this team. This team is rolling on and off the field.

As a Steelers fan, remember the importance of locker room chemistry, specifically in season. Yes, it would be nice if the Steelers could go out and compile as much talent as possible before the trade deadline. But if theres any question as to whether or not its going to upset the balance in the locker room while this team is on a roll, then dont even bother picking up the phone.

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Locker room chemistry is a key component the Steelers success in 2020 - Behind the Steel Curtain

Recommendation and review posted by G. Smith

Are Medicinal Chemists Taking It Too Easy? | In the Pipeline – Science Magazine

Posted: October 25, 2020 at 11:55 am

I was speaking to a university audience the other day (over Zoom, of course) and as I often do I mentioned the studies that have looked at what kinds of reactions medicinal chemists actually use. The clich is that we spend most of our time doing things like metal-catalyzed couplings and amide formation, and well, theres a reason that got to be such a clich, because theres a lot of truth in that.

At the same time, theres some evidence that innovative drug molecules come with innovative structures, more often than youd expect by chance. Its for sure that some of the hottest research areas right now (such as bifunctional protein degraders) can produce some rather off-the-beaten-track structures. So how do we reconcile these? Can we be making innovative drugs using a bunch of boring reactions?

This new paper (open access) says that yes, we sure can. The authors (from AstraZeneca) first note that about a third of all the reactions in AZs electronic notebooks are amide couplings, which sounds about right. They assembled two random sets of 10,000 compounds that had been made and screened in at least two assays, with one of them featuring amide formation and the other with it specifically excluded. These sets (Amide Formation and Other Reactions) were then evaluated by various techniques to roughly measure structural complexity, diversity, and novelty, and in addition the targets that they had hit in past AZ screens were examined.

And as it happens, the Amide Formation set had similar, but slightly higher complexity than the Other Reactions set. The two sets were virtually identical in lipophilicity and percent of saturated carbon atoms, but the amide group was slightly higher in molecular weight and the the number of chiral centers. As for molecular diversity, two different measurements broadly agreed: the Other Reactions set covered more diversity space, but the two sets also had significant non-overlapping regions. That is, the Amide Formation set was not just contained inside the larger diversity space carved out by the Other Reactions set, but had space all its own as well. And there was no real difference in novelty between the two sets, as measured by the number of structures that already occurred in databases such as ChEMBL. And when historical assay behavior was examined, the Amide Formation set had more active compounds in it, while the Other Reactions set covered a slightly wider range of assays themselves. But the two sets had a large overlap in the actual targets covered, so there was, in the end, not a significant difference between the two in target space.

The authors suggest that one reason that so simple a reaction as amide formation can hold its own (versus so many other possibilities) is that there are more and more unique amines available for such reactions. They looked through the ELNs for one-step amide couplings that made compounds for testing and examined the amines involved. On average, 8,000 different amines were used each year for such reactions, and every year about 2,000 of them were new. The authors:

In practice, building-block availability is one of the main determining factors. If the desired building blocks are unavailable, the chemist is faced with the decision whether to invest in new route development, or to make analogs with established routes, or to avoid making the target molecule at all. Given the uncertain nature of drug design, investing more time and resources in making a compound does not guarantee improved molecular quality.. .

. . .In medicinal chemistry, we have now reached a state where millions of building blocks have previously been engineered and can now be used in molecular design and synthesis. In addition to the increase in the number of new amines, boronic acids have been another fast-expanding reagent class since the introduction of the Suzuki coupling method

That really has been a change over my career. There are just so many more neat little functionalized compounds available now; its become an entire business of its own. As the paper notes, you even have setups such as Enamines REAL compound set, which is a virtual-but-easily-made collection via mixing and matching their available building blocks. That one would come out to well over a billion compounds if someone placed an order for the whole collection.

And if we can get our work done via such easy reactions plenty of experience in doing the reactions, relatively easy purifications, existing scaleup expertise, and so on then why shouldnt we? (I should note that the paper under discussion has a lot of good references to past arguments about this issue). That gets to another point I was emphasizing to my university audience: medicinal chemistry is a means to an end. The end, of course, is the discovery of useful drug molecules, and if the synthetic chemistry can (as much as possible) get out of the way of all the other tricky steps in that process, then so much the better.

Thats not to say that we shouldnt try new reactions or new technologies. Among other things, these can lead to even more new building blocks that can feed into the easy reactions themselves. And God knows, as you develop the SAR of a compound series you may find yourself unavoidably being pushed into difficult chemistry, where you will need all the help you can get and throwing amide couplings and Suzukis at the problem will avail you not. No, we definitely need our skills and our imaginations but we need them for the times we need them, and when we dont need them we should speed drug discovery along with the best tools we have for it. To paraphrase Einstein about physical theories, a synthetic route should be as simple as possible, but not any simpler. Getting as much done as you can with the easy methods leaves you more time to tackle the hard stuff. Get flashy only when you have to.

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Are Medicinal Chemists Taking It Too Easy? | In the Pipeline - Science Magazine

Recommendation and review posted by G. Smith


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