Researchers from theGIGA CRC In vivo Imagingat the University of Lige (Belgium), the EPF Lausanne and the University of Geneva publish a study that shows that the phenomenology of "mind blanking" challenges the belief that the human mind is always thinking. The study is published in the journalProceedings of the National Academy of Sciences.

We generally consider that our mind is full of thoughts when we are awake. Like a river stream always running, similarly we entertain our own dynamic mental stream: a thought can lead to another, relevant to what we do or not, ebbing between our inner life and the outer environment. How can the brain sustain such a thought-related mode constantly, though? A study just published in theProceedings of the National Academy of Sciencesindicates that it actually cannot, and that our brains also need to go offline for some moments, which we can experience as blanks in the mind.

Researchers from the University of Lige and EPF Lausanne & University of Geneva re-analyzed apreviously collected datasetwhere healthy participants were reporting their mental state as this was before hearing an auditory probe (beep) while resting in the MRI scanner. The choices were among perceptions of the environment, stimulus-dependent thoughts, stimulus-independent thoughts, and mental absences. Functional images were being collected during this experience-sampling method. The researchers found that mind blanking episodes were reported quite rarely compared to the other states, and that they were re-appearing also scarcely across time. Using machine learning, the researchers further found that our brains during mind-blanking episodes organized in a way where all brain regions were communicating with each other at the same time. This ultra-connected brain pattern was further characterized by high amplitude of the fMRI global signal, which is a proxy of low cortical arousal. In other words, when reporting mind blanking our brains seem to be in a mode similar to that of deep sleep, only that we are awake.

Mind blanking is a relatively new mental state within the study of spontaneous cognition. It opens exciting avenues about the underlying biological mechanisms that happen during waking life. It might be that the boundaries of sleep and wakefulness might not be that discrete as they appear to be after all, says the principal investigator Dr. Demertzi Athena, FNRS researcher at GIGA ULige. The continuously and rapidly changing brain activity requires robust analysis methods to confirm the specific signature of mind blanking, continues Dr. Van De Ville Dimitri.

The researchers claim that the rigid neurofunctional profile of mind blanking could account for the inability to report mental content due to the brains inability to differentiate signals in an informative way. While waiting for the underlying mechanisms to be illuminated, this work suggests that instantaneous non-reportable mental events can happen during wakefulness, setting mind blanks as a prominent mental state during ongoing experience.

Reference:

Mortaheb S, Van Calster L, Raimondo F, et al. Mind blanking is a distinct mental state linked to a recurrent brain profile of globally positive connectivity during ongoing mentation. Proceedings of the National Academy of Sciences. 2022;119(41):e2200511119. doi:10.1073/pnas.2200511119

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What "Mind Blanking" Tell Us About How We Think - Technology Networks

Today, Bonnie Raitt is rightfully considered one of the greatest guitarists alive, and a poignant singer-songwriter as well.

But for years, the music industry had absolutely no idea what to do with her.

In 1971, at age 21, she released her critically acclaimed debut, Bonnie Raitt. But after a long string of poor-selling albums, Warner Bros. Records finally threw up its hands and dropped her.

I was kind of a cult artist for 20 years, she says. It was only after I had some success with the Grammys that I crossed over a little bit.

Shes referring to 1989s Nick of Time, her first album for Capitol Records: It won three Grammys, including Album of the Year, and topped the pop charts.

Earlier this year, she released her 18th studio album, Just Like That..., her first album in six years. We spoke with Raitt by phone from her home north of San Francisco. Our conversation has been edited for length.

Your new song Livin For The Ones sounds like a joyous rocker at first listen. But its actually a song about mortality, with some of the most serious lyrics youve ever written.

These last two years have been an unbelievable train wreck of loss. But the song is also about all the people Ive lost in my life. Im at the age where a lot more people are succumbing to cancer, and Ive had friends pass away from accidental overdoses or suicide.

It takes its toll. I started feeling that way, about livin for the ones who didnt make it, when my brother lost his eight-year battle with brain cancer in 2009. I told him, Im going to live every day for the life you didnt get to have.

Its fun to put a serious song to a rockin beat. Its actually cathartic. Every night when I sing it, its a call to arms for me to remind myself not to bitch and moan and whine.

Waitin for You to Blow is funny at times, but you also seem to be saying some deeper things about addiction and compulsive behavior.

I was definitely inspired by Mose Allison and Randy Newman. I love their satirical point of view and their ability to skewer human foibles and be half serious and half joking.

Ive been in recovery from drugs and alcohol for 35 years. And Ive been lucky to manage to stay on that path, a day at a time. But there are still personality defects and ways we slip up, either in white lies we tell our friends, or ways we kid ourselves when we know better, like, Its OK to have another piece of cake at midnight.

I wanted to write about the little devil on your shoulder thats urging you to mess up, whether youre an addict or not. Were all human, and were all struggling.

Youve given credit to several musicians, including Stevie Ray Vaughan, for helping you overcome drug and alcohol addiction. How did they help you?

For a lot of us, when we were in our mid-30s, [substance abuse] was no longer working so great. It became a lot harder for you to recover and remember what you said the night before, and then you couple that with anger and unresolved issues: I got dropped by my label right before a big, long tour and had a romance fall apart, and I kind of medicated myself. Therapy wasnt going to do it for me.

So I looked around and saw some friends of mine that clearly were in better versions of themselves. I saw Stevie come out of recovery and play one night in Atlanta: He wasnt sure, but the first time he picked up the guitar, he just burned a hole in the sun. It was a real inspiration.

When I saw him that night, I said, You know what? Thats it. No more excuses. It was the last straw. I made the decision, and within a couple of months, I got sober.

Youve been a strong role model for so many female musicians. What were your experiences in the male-dominated music business decades before the #MeToo movement?

I grew up in show business with my dad [actor John Raitt], so I got a window on how women were devalued and treated as sex objects. As burgeoning feminists in the late 60s and early 70s, we were already blazing a trail, demanding equal treatment and saying, Dont talk to me like that.

Im not, like, drop-dead gorgeous, so I probably didnt get hit on like some less sophisticated young women that are super-gorgeous and not as experienced in show business. I spoke my mind, and I put out a vibe I used to sing Under My Thumb with the sex changed.

When people met me, they met me with respect. I just was never in a position to be treated that way, and if I was, I wouldnt have put up with it. I would have fought back.

Today, the business itself hasnt changed as much as it could have. Men are still running the entertainment industry. But its great that now, nobody is going to put up with that kind of misogyny and inappropriate behavior. Its been great that all that got blown out of the water.

Ive seen you several times in concert where youve told some very funny risqu jokes. Have any uptight concertgoers ever complained about your off-color sense of humor?

Not that I ever heard about. Mae West was a big hero of mine from when I was a little kid, and in my 20s, I was definitely playing the part of a blues mama. It was an attempt to get rid of this little high soprano voice and a wimpy exterior. I was trying to seem road-worn.

But theres a fine line before it becomes grossly raunchy. And eventually, after I got sober and I had enough therapy, I realized I didnt have to hide behind that persona. I didnt have to smoke cigarettes and try to be like my older blues heroes.

My brain still comes up with [raunchy] stuff, but Im able to catch it nowadays. The other night, I told the audience, I almost said something that the old Bonnie would have said. After the show, my band said, What was it? And I told them. They just rolled their eyes.

Ive settled down a bit. Im more mature now. Thank God I came to my senses.

Bonnie Raitt and opening act Marc Cohn perform Oct. 8 at 8 p.m. at Texas Trust CU Theatre, 1001 Texas Trust Way, Grand Prairie. axs.com.

Link:
Im more mature now: Bonnie Raitt talks about writing deep lyrics and finding her voice - The Dallas Morning News

Analysis DeepMind's AlphaFold model has predicted nearly all known protein structures discovered yet, though its ability to help scientists discover new drugs remains unproven.

Proteins are complex molecules created by organisms to carry out the biological functions necessary for life. Generally made up of a string of 20 amino acids, these chains fold up in countless ways, with their final shape determining how they work and interact with other things.

It's not a straightforward process determining how a protein will fold. For example, let's say you wanted to synthesize a protein or slightly alter its operation. You can't adjust its amino acids or come up with a new string of them and know for sure how they will turn out and work when folded. This is where computers come into it.

Advances in AI algorithms and training have led to the development of software, such as AlphaFold, that can accurately predict the 3D shapes of proteins given their amino acid combinations.

AlphaFold is impressive, and has now predicted over 200 million proteins from their amino acid strings. Researchers hoped that building such a large database would allow scientists to develop treatments targeting specific proteins associated with diseases such as cancer or dementia. Coming up with such medicines may require you to know the physical structure of the protein, which is where programs like AlphaFold can be used.

An investigation led by academics at MIT in America, however, shows just how difficult the task is in practice. Essentially, the AI software is useful in one step of the process structure prediction but can't help in other stages, such as modeling how drugs and proteins would physically interact.

"Breakthroughs such as AlphaFold are expanding the possibilities for in silico (computer simulation) drug discovery efforts, but these developments need to be coupled with additional advances in other aspects of modeling that are part of drug discovery efforts," James Collins, lead author of the study published in Molecular Systems Biology and a bioengineering professor at MIT, said in a statement.

"Our study speaks to both the current abilities and the current limitations of computational platforms for drug discovery."

Collins and his colleagues used AlphaFold to simulate interactions between bacterial proteins and antibacterial compounds, a task known as molecular docking. The goal was to use molecular docking to rank the candidate compounds by how strongly they bind to the target protein. A molecule that binds strongly to a protein is more likely to be an effective drug; it could be more effective at preventing the protein from carrying out a pathogenic function, such as tumor growth, for example.

The team tested AlphaFold's ability to model interactions between 296 essential proteins from E. coli bacteria with 218 antibacterial compounds, including antibiotics such as tetracyclines. AlphaFold was not very effective for modelling molecular docking simulations accurately.

"Utilizing these standard molecular docking simulations, we obtained an auROC value of roughly 0.5, which basically says you're doing no better than if you were randomly guessing," Collins said.

Other machine learning models were more accurate than AlphaFold for some simulations, according to Felix Wong, co-author of the paper and a postdoctoral researcher at MIT.

"The machine-learning models learn not just the shapes, but also chemical and physical properties of the known interactions, and then use that information to reassess the docking predictions," he said. "We found that if you were to filter the interactions using those additional models, you can get a higher ratio of true positives to false positives."

Derek Lowe, a longtime drug discovery chemist and science writer, told The Register he wasn't surprised with the results given that AlphaFold was not really trained for molecular docking simulations. "Docking small molecules into a given protein structure is really a different problem than determining that protein structure in the first place," he said.

Being able to model these types of chemical interactions is an unsolved problem. No algorithm is perfect. Even if scientists have a good model of the protein, its shape changes when it is interacting with a potential drug candidate in mysterious ways.

"Virtual screening has never yet reached the 'works every time' level - sometimes it provides useful information and sometimes it doesn't, and you are never sure up front which of those regimes you're working in. Added to that is the way that different docking software will give you different answers, and for any given target one of them might give notably more useful answers than another - but again, you don't know up front which of those it'll be," Lowe said.

"Even with perfect protein structures, some of them are going to be better 'fits' for a docking-and-scoring approach than others, and AlphaFold structures, while impressive, are not perfect, either. But to me, this isn't so much on AlphaFold as it is on docking technology."

AlphaFold may prove useful for other parts of the drug discovery pipeline, where comparing protein structures obtained via different methods against the model's predictions is valuable.

"The biggest problems in drug discovery are the ones that contribute to our roughly 85 percent failure rate in the clinic. And those are picking the right targets and getting early warnings about toxicity. Neither of those are helped much at all by knowing protein structures," Lowe added.

We had some questions for Felix Wong and Aarti Krishnan, the lead authors for the MIT study. They got back to us with these answers:

The Reg: Why does AlphaFold struggle to simulate docking accurately? Was it trained for this task?

MIT team: "AlphaFold was trained to predict the three-dimensional structures of proteins from amino acid sequences; these structures can then be used in downstream applications, including molecular docking to predict drug-protein interactions. While this is one of AlphaFold's most anticipated use cases, AlphaFold can likely be improved to better facilitate this. For instance, AlphaFold predicts only static and rigid protein structures that are stuck in time, and it's possible that knowing the dynamical and disordered properties of these structures can better enable us to predict drug binding."

What types of software do practitioners use in the drug industry to simulate model docking? Why is this task difficult, and how does AlphaFold compare?

"Molecular docking has evolved and improved over the past 40 years, and nowadays open-source (eg, AutoDock Vina and DOCK6) and proprietary (eg, Schrdinger) software are commonly used. Predicting drug binding is probably one of the most difficult tasks in biology: these are many-atom interactions between complex molecules with many potential conformations, and the aim of docking is to pinpoint just one of them.

Predicting drug binding is probably one of the most difficult tasks in biology

"We've all heard the analogy of a needle in a haystack, but this is even more challenging because conformational space is huge. Even the first step of guessing the general region of the protein to look at (the binding pocket) is difficult, since having just a 3D toy model doesn't tell you how a protein functions.

"One of AlphaFold's main contributions thus far has been to provide a comprehensive resource of predicted protein structures that we can now use for docking. These predictions complement all the experimental structures that we already had, because there were some structures that we didn't have and we can now go through the structures more holistically.

"When we were performing our benchmarking analyses using 12 well-characterized E. coli proteins, we found that the ability of molecular docking to accurately predict drug-protein interactions was similar when using AlphaFold as opposed to experimentally-determined structures. This strongly suggests that the bottleneck is not the quality of AlphaFold-predicted structures, but rather the molecular docking approach and our current, limited ways of harnessing structural information to accurately predict drug-protein interactions."

Why is it important to measure the binding between a protein and molecule?

"The binding between a protein and a molecule underlies how many drugs, including antibiotics, work. Most antibiotics, like penicillin, are simply small molecules that bind specifically to bacterial proteins.

"By binding to their protein targets, these drugs can interfere with the normal functions of proteins in many ways, including competing against physiological substrates and inducing protein conformational changes that render proteins inactive. For antibiotics, we want these proteins to be needed for the cell to survive, so that the drugs targeting these proteins would lead to bacterial death.

"This paradigm works similarly for anti-cancer and anti-viral drugs, and there are also cases where inhibiting the activity of some protein might be beneficial to a cell.

"In general, being able to measure the binding between a protein and a molecule tells you about how a drug works and is a critical part of any drug development process. Many cases in which a drug succeeds or fails can be informed by knowing the protein target (or targets). A common reason for drugs failing is that they turn out to have multiple targets, and this promiscuity is often associated with drug side-effects."

Excerpt from:
Hype versus reality: What you can't do with DeepMind's AlphaFold in drug discovery - The Register

When news of Matt Chandlers inappropriate online relationship popped up in my phone notifications last week, I was in the middle of a church staff retreat with my copastors, who are all male. I interrupted one of them to read the story aloud.

The news landed like a lead balloon between us, and then we came together as a group and talked about how stories like this make us feel and whether our own ministry friendships might be inappropriate.

The larger evangelical world was shaken too. Twitter exploded with a reanimated debate over the Billy Graham Rule, and many called on The Village Church to publicly release the investigation report. It is always best practice to release the result of an independent assessment, said Rachael Denhollander to The New York Times.

Gods call for truth and justice demand that leaders get to the bottom of what happened at The Village Church. But as one of the pastors of my local village-with-a-small-v church, thats not the most important story for me to pay attention to. The question that matters more is not What happened there? but Whats happening here, in me and among us, when we read stories like this?

More specifically, how do scandals both small and large distort our view of male-female friendships in Christ? And when we read these narrativesone after another in the midst of an ever-accruing abuse crisishow do our minds close off to the possibility of healthy brother-sister relationships in the church?

The stories we hear powerfully shape our imaginations, both positively and negatively.

For example, seeing Beth Moore teach the Bible has inspired a generation of women to pursue ministry they might not have otherwise considered. In the context of marriage, focusing on good stories from our shared pasts can help heal and improve those relationships. And on social justice issues, representation matters, because stories kindle our imagination for the diverse good thats possible.

But painful news of scandal and failure affect us, too. They disciple us to be afraid, says Catherine McNiel, author of Fearing Bravely. Those fears are both particular and personal: For the 1 in 3 women (and 1 in 4 men) who are survivors of sexual assault, reading headlines about abuse and impropriety might trigger deep-seated trauma.

For those in vocational ministry, these scandals can leave us feeling trapped in a Catch-22 situation.

It makes me second-guess everything I do, one male pastor shared with me. I could get in trouble for reaching out to a woman Im pastoring, or in trouble for failing to care for the flock if I dont. Im damned if I do, and damned if I dont.

Women feel a similar tension in the wake of community reactions to sexual scandal. Will we be frozen out as men retreat behind the safety lines of the Billy Graham Rule? Or will we get hurt if we stay engaged?

Horror stories of abuse and scandal trigger our lizard-brain fears, writes Russell Moore, and we run the risk of being paralyzed with despair. In those situations, says Bren Brown, always ask: Whats the story youre telling yourself?

For many men and women, the story they might be tellinglearned from headlines over the yearsis that any male-female relationship is fraught with danger.

A case like Chandlers yet again sends the message that men, especially pastors, cannot have healthy sibling relationships with women, writes Aimee Byrd, author of Why Cant We Be Friends? Be careful not to talk frequently with us! Be careful not to be too familiar with us! Be careful not to joke around us! You will not be above reproach.

In the wake of scandal and sin, our deep-seated desire to protect the church from future harm often works itself out in a fresh iteration of policies and principles that are meant to demarcate male-female boundaries. In this case, for example, some leaders instincts to double down on the Billy Graham Rule seems understandable.

But, as Ive written elsewhere, its not enough to legislate against sin. We need the Cross, and we need Gods grace. If all we do is avoid getting things wrong, we cant grow a community of thriving relationships. The fear of the Lordnot the fear of sinis the beginning of wisdom (Prov. 9:10).

Our news feeds contribute to this problem. A bad-news diet gives us a partial and distorted vision of whats possible. The stories out there tacitly teach us that healthy community isnt realistic or even desirable for my church in here.

Im concerned by this dynamic. Im concerned that when stories of scandal ring in our ears and wring out our hearts, our vision for what the community of faith could and should look like becomes stunted and malformed by fear. Im concerned that we despair, withdraw, and give up because our fear of getting it wrong overrules the command to love the brother and sister right next to us.

How, then, can we cultivate communities with healthy male-female relationships?

The gospel does instruct us to take an honest and unflinching look at sin, but it also calls us to look beyond it. We are brothers and sisters in Christ, and avoiding each other for fear of doing harm falls far short of what the Father envisions for his family.

Just as I ultimately want more from my marriage than to avoid having an affair, and I want more for my children than not landing in jail, so too the Scriptures call us to a bigger vision for church than We had no sex or abuse scandals. We are called to love one another, which includes but far exceeds the bar of Dont hurt each other.

To be clear, Im not suggesting that we avoid telling or reading stories of sin in the church. Im not advocating for naivet, gaslighting, or silencing. What I am saying is that we must take care to be formed by other stories too.

We need narratives that teach us what to aim for. We need a biblically based (but not fear-fueled) theology of men and women, fleshed out by real-life, godly examples of men and women in partnership together. And we need to seek out and share testimonies of health where we see them: places where men have not given up working with women, and where marriages can flourish without going all Billy Graham Rule or Bust.

Redirecting our gaze is critical to this project. The mission of God depends on men and women faithfully working together in gospel work. We cannot afford to shrink back from that work just because were too afraid to put our hand to the plough with someone of the opposite sex.

Testimonies of those whove done this well are gateways to hope, guiding our minds and imaginations back toward what is beautiful, lovely, excellent, true, and praiseworthy (Phil. 4:8). Proclaiming Gods faithfulness in the past is a powerful way to store up our hope in the future (see Psalms 105 and 106).

For example, when I first started dating, I quickly realized that my own upbringing had taught me firsthand how infidelity, addiction, and hostility could wreck things. When I tried to envision myself as a happily married person in my 70s, my imagination sputtered.

So as a 20-year-old student, I started working with a therapist, but I also went looking for incarnational stories of hope among our congregation. I invited myself to dinner and asked time-tested couples to tell me their stories. Slowly, my vision for what was possible grew.

The same holds true for male-female friendship. Ive seen it in my own work life. As my copastors and I sat together last week and talked about the news of yet another scandal, we felt the pull to shrug and sigh. We mourned and then half-joked about quitting.

But then we took the opportunity to reflect on our own relationships. We told one another stories of healthy male-female friendships from our own community and beyond. We gave reminders of decades-long marriages and fruitful ministry partnerships. And we told quiet stories of a long obedience in the same directionstories that would never make the news but that shored up our hope in Gods church.

Bronwyn Lea is the author of Beyond Awkward Side Hugs: Living as Christian Brothers and Sisters in a Sex-Crazed World and the pastor of discipleship and women at First Baptist Church of Davis.

Original post:
Sex Scandals and the Evangelical Mind - ChristianityToday.com