How I Think About My Life and Work

I often think about my life as a flow of experiential explorations.

I’ve found it overwhelming to consider the vast array of possibilities that life presents objectively. Traversing just a fraction of this space could occupy endless lifetimes, so that framing doesn’t bring much clarity and leaves me adrift.

Instead I create clarity by thinking of experiences as a summation of different vibes. A vibe is the inner, subjective flavor of an experience, similar to qualia. It’s what I experience internally when living through an outer experience. This includes my emotions and the thoughts I have along the way.

I typically find it much easier to create clarity regarding the inner experience I want. Even when I don’t have clarity about the outer experience, I can collapse the inner experience into something relatively crisp.

My inner desires are often reactive. If I’m over-stressed, I automatically want to feel more relaxed and at ease. If I’m bored, I want to experience more excitement and stimulation. If I feel happy and engaged with life or if I’m in a nice productive flow, I usually want more of the same – until my inner mood tells me I want to shift. When I take stock of any inner experience, I naturally think about what I’d like to experience next, like I’m laying out some kind of story progression.

Most of the time this is an unconscious process. The conscious part is simply paying attention to what’s arising. I notice whatever vibes I’m experiencing in the moment, especially the pervasive ones that have been with me for days. Once I clarify where I am, I tend sense a pulling sensation to move in a new direction.

Sometimes I feel pulled in multiple directions, but if I consciously list out the vibes that are pulling at me, it’s not hard to clarify my preferences. In those cases usually all of those vibes are correct, and I really want to experience a combo of them, such as a peaceful adventure or a cozy connection.

Guided by Inner Experience

So generally I like to think about life based on the inner quality of my experience. I like to make decisions about my human life as if it’s the same as my spiritual (or inner) life. I find that my life works better when I do that. By contrast when I make decisions that only seem reasonable on the physical plane but feel misaligned at the level of energy, emotions, and inner experiences, the results are usually poor. Not only do I not enjoy those experiences, but I usually fail to get the physical reality results I was aiming for.

However, when I flip this around and focus primarily on the inner experience – meaning that this inner world is where I set my true priorities – my outer world seems to flow along pretty well too. Where the outer world isn’t working so well for me, I normally sense that it’s because I haven’t assumed enough responsibility for the vibes I want to explore and express into that part of life. Or I’m still dealing with internally conflicted vibes in those areas, and I need to resolve those objections.

When choosing work and personal projects, I like to think about the vibes I want to explore. I think deeply about what the inner experience will be like from start to finish. I want to create interesting, varied, and meaningful inner explorations. Overall that approach keeps me feeling satisfied and fulfilled with life.

When I complete a major project, I like to do a postmortem on it. I’ve included a couple of those as bonuses with the Amplify course. I think about what went right and what could be improved for next time. I also journal a lot about the project, taking note of what I enjoyed and what I wish I’d done differently. I use those insights to make choices for future projects.

I think many people choose projects based on the external results they seek to gain. Or they get projects assigned to them by others. I like to choose projects mainly based on what the inner adventure will be like. I make those choices differently each time, which naturally infuses my projects with plenty of variety.

Beyond Happiness

Choosing to be happy is too vague for me. Happiness doesn’t have enough resolution. There are many different vibes that I enjoy and appreciate when I experience them, and they’re more specific than happiness.

Here’s how I think about my life purpose these days. I recently updated it to this:

Consistently invest my precious freedom to create, invite, attract, and enjoy the exploration of different vibrational combos, such as: abundance, wealth, intensity, coziness, lightness, relaxation, oneness, presence, optimism, fun, playfulness, vibrancy, sexiness, ease, comfort, power, order, love, warmth, nurturing, inspiration, wonder, beauty, awe, gracefulness, appreciation, caring, compassion, generosity, adventure, trust, honesty, stability, openness, curiosity, courage, wildness, boldness, pleasure, silliness, mischief, indulgence, excitement, naughtiness, freedom, immersion, imagination, connection, self-expression, creativity, cooperation, co-creation, service, simplifying, accessibility, accomplishment, achievement, speed, efficiency, intelligence, patience, reflection, and celebration. Expand my experiential range and abundantly serve the expansion of life’s range.

I think of my life as an exploration of different vibes. When I was younger, I often focused on vibes I could express with single words, such as abundance or courage. At this time in my life, I prefer mash-ups of different combos. I especially like exploring vibes that may seem a bit contradictory.

For instance, I enjoy caring about people while also challenging them. I love being honest and mischievous. Mixing coziness with wildness is a fun combo too.

You could say that I love being a vibrational mixologist. I love exploring the rich complexity of which vibes combine well, like complementary flavors in a drink.

It’s easy to use my inner purpose to as a basis for the purpose of my business and work as well:

Invite our community members (and other growth-oriented people) to explore different vibrational combos to expand their experiential range, such as: abundance, wealth, intensity, coziness, lightness, relaxation, oneness, presence, optimism, fun, playfulness, vibrancy, sexiness, ease, comfort, power, order, love, warmth, nurturing, inspiration, wonder, beauty, awe, gracefulness, appreciation, caring, compassion, generosity, adventure, trust, honesty, stability, openness, curiosity, courage, wildness, boldness, pleasure, silliness, mischief, indulgence, excitement, naughtiness, freedom, immersion, imagination, connection, self-expression, creativity, cooperation, co-creation, service, simplifying, accessibility, accomplishment, achievement, speed, efficiency, intelligence, patience, reflection, and celebration. Help them invest in growth explorations and meaningful upgrades they’ll treasure!

It takes time to get used to different vibes and to integrate them into our lives. Initially we may want to practice certain vibes individually, and then we can build upon that with endless combos.

Serving the Flow of Life

I feel that this kind of exploration is what life wants from me – and from all of us. When I look at life, I see the ongoing exploration of possibilities. I find that when I support this expansion by doing my part to contribute some interesting explorations, life seems to give me plenty of support as well. Perhaps that’s why I haven’t had a job in more than 30 years.

I consider freedom to be a precious gift because with sufficient freedom, I can access more of the possibility space. I can explore some aspect of life deeply for many weeks in a row. I can go on fun travel adventures. I can connect with a variety of different people. And I have lots of space for reflecting on experiences and considering next steps, especially through journaling.

A nice way to create value for people is to invite them into vibrational explorations together. This can be done in so many ways. Writing blog posts can have that effect by invite people to consider fresh possibilities. I also love doing this through speaking, workshops, coaching, courses, and Conscious Growth Club.

What surprised me was that just sharing more of my inner and outer journey also created a lot of value for people. As long as I keep having new growth experiences, I can share what I learn from them. People have expressed lots of appreciation for this type of sharing over the years. And these explorations have helped me clarify more vibrational combos that I love. For instance, I think of this writing session as inspired cozy reflection time.

Fresh Vibrational Combos Create Fresh Solutions

A key benefit of this type of exploration is that I discover solutions where I didn’t expect to find them. I think we have a tendency to mono-focus on some vibes to the point of stuckness.

For instance, I often see people trying to create more success, achievement, or efficiency in their lives, but they get stuck pretty easily with those vibes. I get more success by not focusing on success. Instead I like to move towards vibes like curiosity and playfulness and learning.

When I focused intensely on success and achievement, I went bankrupt. That made me feel humble enough to start looking at different vibrational directions, and I found that other vibes were much better for me. I eventually became a millionaire with that approach, and it happened with a nice easy flow and wasn’t a struggle to get there. Financial abundance showed up without trying to force it so directly. I got there by exploring other vibes like fun, curiosity, adventure, compassion, wonder, service, etc. I rekindled an adventurous spirit, which has served me well.

That makes sense to me because when I think of abundance, I think of spaciousness and freedom, and those vibes seem more proximate to playfulness and curiosity than they do to a hard-ass focus on success. If I’m vibing with abundance, how much do I really care about traditional business success? That kind of success usually seems boring, stressful, or shallow to me. It lacks nuance.

I think the reason that kind of success doesn’t appeal to me is because it’s too rooted in this physical reality and doesn’t translate well to the spiritual side. When I think of spiritual success, I imagine being able to float freely across a wide range of interesting vibes and having the ability to explore them adeptly in many diverse combinations. So it’s a much broader framing of success. It’s also more resilient because I can develop these skills with or without money. Money often seems to enjoy participating in these explorations, but money doesn’t fuel them. The vibes summon the experiences, including the experience of financial flow.

Vibrational Practice

A key skill is to deliberately practice experiencing vibes that seem interesting. I still like to do this by relaxing on a couch and just imagining scenes that encapsulate certain vibes. I try to go beyond overly simplistic vibes like happiness, and I like to imagine more sophisticated combos playing out. It’s the difference between visualizing a very on-the-nose scene from a straightforward action movie versus visualizing a multi-layered dialogue from a movie like Casablanca, where characters communicate a great deal through subtext and body language.

I realize now that my inner visualization skill was pretty weak when I was younger. I imagined my goals coming through very directly, like an action movie explosion or car chase. But I eventually realized that reality appreciates vibrational richness and complexity. People like this too. I think that most of us don’t want overly simplistic and routine lives. We want to explore many different subtleties with lots of variety.

I love to think about life and business in terms of vibrational range. When I see a part of the vibrational space that I haven’t explored yet, I feel drawn to go explore it sooner or later. This gradually expands my vibrational range.

It’s like training to be a chef and learning to work with a greater variety of ingredients, so many more delicious meals can be created, not just for oneself but for the benefit of others as well.

When I think about serving others, I figure that a good way to help people is to encourage and invite them to expand their vibrational range. Help them to explore areas of the possibility space where they haven’t explored very much yet. Show them where the open waters are. Play the role of tour guide for the areas that are familiar to me, and also encourage people to keep exploring beyond that, so they can serve the expansion of life as well.

Confidence Doesn’t Matter

In addition to the success vibe, another vibe that I consider to be overstretched is confidence. Many people seem to think they need more confidence to get what they want. I find this vibe overly blunt and shallow though. What’s actually interesting about it? Not much. I generally see confidence as a pretty lame and uninteresting vibe.

When I’m really engaged with life in ways that resonate with me, I’m not really vibing with confidence. If you told me I seemed confident when speaking, for instance, I might give you a confused look. I really don’t care about feeling confident or being seen as confident. For whatever reason that vibe just looks and feels really dorky to me.

Instead of confidence, I’d rather explore more interesting combos like curiosity, playfulness, and honesty. Confidence is a confusing vibe because when a person looks confident, that may not actually be what they’re experiencing on the inside. In situations where I might appear confident, like while coaching someone, I’m actually experiencing something quite different internally, such as curiosity or compassion. Or I’m tuning in to a flow of inspired ideas. Or I’m focused on co-creating solutions together. There’s no need for confidence there – that isn’t part of my framing.

Telling yourself to be confident is like eating bread for every meal. You can surely concoct more interesting vibrational meals. Even if you sense that some form of confidence is present, it’s probably the least interesting part of the experience.

Vibes can be funny that way. Some vibes that seem popular in the outer world just don’t align with my actual inner experiences. Paying too much attention to popular vibes tripped me up a lot. It took years to unload enough of that social conditioning, so I could figure out what actually worked for me and which vibrational combos I enjoy and appreciate.

Once I know which vibes I want to move towards, it becomes much easier to choose external experiences then. In those cases it’s mainly a matter of identifying accessible actions to shift my outer reality into alignment with those vibes. To do this I get into resonance with the vibes I want, and then I let them guide my actions. I pay attention to what I feel naturally inspired to do when I’m connecting with those vibes. This leads me to take a lot of action, and my reality gradually shifts.

Personalizing Vibes

I like the exploration process of personalizing vibes and figuring out how they best resonate with me. Consider a vibe like wealth. Do you want to feel wealthy? What does that vibe mean to you? I had mixed associations to that vibe for a while. I associated it with greed, unfairness, and injustice. So of course I couldn’t get into resonance with it. But I also liked some things about it, like how it could connect with freedom, abundance, and more possibilities. So I pulled this vibe away from the negative associations, and I framed my version of wealth as being about gaining more access to possibilities. So it’s not material wealth per se. It’s experiential wealth. My version of wealth isn’t about acquiring. It’s about living and experiencing.

I also like to pull my version of wealth further into the service side. I think about wealth as enriching people’s lives, sharing a wealth of ideas, and inviting people into worthwhile experiences together. This helps my mind explore this type of vibe within an appealing range, so it doesn’t conflict with other vibes I like.

Otherwise if I don’t personalize a vibe to strip out the unwanted bits, those mixed associations can block me from exploring it altogether. Then I have to take a deeper look at my objections to a vibe and resolve those objections. I see this as part of the personalization process, so I take my objections seriously and treat them as problems that need to be solved. I don’t try to ram a vibe into my life when I don’t feel aligned with it. I prefer to sculpt a misshapen vibe into one that looks beautiful to me, so it naturally harmonizes with other vibes that I like.

Productivity is another interesting vibe. My objections are that it can be boring, stressful, or overly routine. I might even associate it with being caged and losing freedom. So I have to pull this vibe to better align with fun, freedom, and exploration. That’s why I like to work in waves that align with motivation and inspiration as opposed to following a rigid routine. This approach works well for me. When I want to be lazy, I give myself full permission to be intensely lazy. When I crave adventure, I go out and explore. And when I’m inspired by fascinating creative ideas, I love to intensely focus on the creative process and see it all the way across the finish line.

Exploring Harmonious Co-Creation

One experience I really want to have next is to do this kind of exploration socially with other people who resonate with it. That’s why I’m hosting a fresh deep dive into the Submersion course soon. We’ll be starting on November 1st and running through December 30th, with weekly Zoom calls along the way. On those calls we can practice together, pooling our collective intentions to summon interesting vibrational combos to invite into our lives. If you’re signed up for my email newsletter or if you already bought the Submersion course, I’ll email you an invite for this between now and November 1st. It’s free for everyone who bought the course already, and for everyone else, all you need to do is get the course between now and November 1st, and you can participate in the social exploration for no extra cost. This is one of our most popular courses, so I imagine that a lot of people will want to explore it as a social experience.

I’m especially curious to see what effect it has if we focus our intentional energy for our good and for the highest good of all. Imagine lots of people holding the intention to help uplift each other. Imagine people sending you love and healing energy from all around the world. And let’s also send vibes of peace, healing, forgiveness, freedom, and positive transformation to the people on earth who most appear to need it right now. Let’s send more energy into the vision of a world we want to create and experience together. I’m really craving this kind of collective exploration right now.

On the inside I want immerse myself in the feeling of all of us stepping into our collective power and intentionality together. I want to mash-up the vibes of oneness, power, love, connection, abundance, and creativity. I want us to harmonize beautifully together. This is a really nice fit for going through the Submersion course together because the course is about upgrading your relationship with reality. I’d love to go through this upgrade process with a very aligned group who resonates with doing this together.

I want to have the experience of co-creating a renewed sense of hope and positive energy flow. I want to invite people to release misaligned vibes and to shift back into alignment with lightness, creativity, and optimism. Remember that we’re all powerful creators here.

So that’s how I’ve been thinking about my life and work lately. I see life as a flow of vibrational explorations. Reality offers a vast field of possibilities to navigate. When I create vibrational clarity – by understanding what kind of inner experience I want next – that level of clarity trickles down to all the low-level decisions and gets me into a lovely and sustainable flow of action.

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BioNTech: Could Covid vaccine technology crack cancer?

BioNTech’s mRNA cancer trials started long before the pandemic, and have shown some early encouraging signals.

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How fluctuating oxygen levels may have accelerated animal evolution

Oxygen levels in the Earth’s atmosphere are likely to have “fluctuated wildly” one billion years ago, creating conditions that could have accelerated the development of early animals, say researchers.

Scientists believe atmospheric oxygen developed in three stages, starting with what is known as the Great Oxidation Event around two billion years ago, when oxygen first appeared in the atmosphere. The third stage, around 400 million years ago, saw atmospheric oxygen rise to levels that exist today. 

What is uncertain is what happened during the second stage, in a time known as the Neoproterozoic Era, which started about one billion years ago and lasted for around 500 million years, during which time early forms of animal life emerged.  

The question scientists have tried to answer is - was there anything extraordinary about the changes to oxygen levels in the Neoproterozoic Era that may have played a pivotal role in the early evolution of animals - did oxygen levels suddenly rise or was there a gradual increase? 

Fossilised traces of early animals - known as Ediacaran biota, multi-celled organisms that required oxygen - have been found in sedimentary rocks that are 541 to 635 million years old. 

To try to answer the question, a research team at the University of Leeds supported by the Universities of Lyon, Exeter and UCL, used measurements of the different forms of carbon, or carbon isotopes, found in limestone rocks taken from shallow seas. Based on the isotope ratios of the different types of carbon found, the researchers were able to calculate photosynthesis levels that existed millions of years ago and infer atmospheric oxygen levels. 

As a result of the calculations, they have been able to produce a record of oxygen levels in the atmosphere over the last 1.5 billion years, which tells us how much oxygen would have been diffusing into the ocean to support early marine life.

Dr Alex Krause, a biogeochemical modeller who completed his PhD in the School of Earth and Environment at Leeds and was the lead scientist on the project, said the findings give a new perspective on the way oxygen levels were changing on Earth. 

He added: “The early Earth, for the first two billion years of its existence, was anoxic, devoid of atmospheric oxygen. Then oxygen levels started to rise, which is known as the Great Oxidation Event.  

“Up until now, scientists had thought that after the Great Oxidation Event, oxygen levels were either low and then shot up just before we see the first animals evolve, or that oxygen levels were high for many millions of years before the animals came along.

“But our study shows oxygen levels were far more dynamic. There was an oscillation between high and low levels of oxygen for a long time before early forms of animal life emerged. We are seeing periods where the ocean environment, where early animals lived, would have had abundant oxygen — and then periods where it does not.”

Dr Benjamin Mills, who leads the Earth Evolution Modelling Group at Leeds and supervised the project, said: “This periodic change in environmental conditions would have produced evolutionary pressures where some life forms may have become extinct and new ones could emerge.” 

Dr Mills said the oxygenated periods expanded what are known as “habitable spaces” — parts of the ocean where oxygen levels would have been high enough to support early animal life forms. 

He said: “It has been proposed in ecological theory that when you have a habitable space that is expanding and contracting, this can support rapid changes to the diversity of biological life. 

“When oxygen levels decline, there is severe environmental pressure on some organisms which could drive extinctions. And when the oxygen-rich waters expand, the new space allows the survivors to rise to ecological dominance. 

“These expanded habitable spaces would have lasted for millions of years, giving plenty of time for ecosystems to develop.”

The findings - “Extreme variability in atmospheric oxygen levels in the late Precambrian”  - are published in the journal Science Advances.

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3D printing plant cells shows promise for studying cell function

A new study from North Carolina State University shows a reproducible way of studying cellular communication among varied types of plant cells by “bioprinting” these cells via a 3D printer. Learning more about how plant cells communicate with each other — and with their environment — is key to understanding more about plant cell functions and could ultimately lead to creating better crop varieties and optimal growing environments.

The researchers bioprinted cells from the model plant Arabidopsis thaliana and from soybeans to study not just whether plant cells would live after being bioprinted — and for how long — but also to examine how they acquire and change their identity and function.

“A plant root has a lot of different cell types with specialized functions,” said Lisa Van den Broeck, an NC State postdoctoral researcher who is the first author of a paper describing the work. “There are also different sets of genes being expressed; some are cell-specific. We wanted to know what happens after you bioprint live cells and place them into an environment that you design: Are they alive and doing what they should be doing?”

The process of 3D bioprinting plant cells is mechanically similar to printing ink or plastics, with a few necessary tweaks.

“Instead of 3D printing ink or plastic, we use ‘bioink,’ or living plant cells,” Van den Broeck said. “The mechanics are the same in both processes with a few notable differences for plant cells: an ultraviolet filter used to keep the environment sterile and multiple print heads — rather than just one — to print different bioinks simultaneously.”

Live plant cells without cell walls, or protoplasts, were bioprinted along with nutrients, growth hormones and a thickening agent called agarose — a seaweed-based compound. Agarose helps provide cells strength and scaffolding, similar to mortar that supports bricks in the wall of a building.

“We found that it is critical to use proper scaffolding,” said Ross Sozzani, professor of plant and microbial biology at NC State and a co-corresponding author of the paper. “When you print the bioink, you need it to be liquid, but when it comes out, it needs to be solid. Mimicking the natural environment helps keep cellular signals and cues occurring as they would in soil.”

The research showed that more than half of the 3D bioprinted cells were viable and divided over time to form microcalli, or small colonies of cells.

“We expected good viability on the day the cells were bioprinted, but we had never maintained cells past a few hours after bioprinting, so we had no idea what would happen days later,” Van den Broeck said. “Similar viability ranges are shown after manually pipetting cells, so the 3D printing process doesn’t seem to do anything harmful to cells.”

“This is a manually difficult process, and 3D bioprinting controls the pressure of the droplets and the speed at which the droplets are printed,” Sozzani said. “Bioprinting provides better opportunity for high throughput processing and control over the architecture of the cells after bioprinting, such as layers or honeycomb shapes.”

The researchers also bioprinted individual cells to test whether they could regenerate, or divide and multiply. The findings showed that Arabidopsis root and shoot cells needed different combinations of nutrients and scaffolding for optimal viability.

Meanwhile, more than 40% of individual soybean embryonic cells remained viable two weeks after bioprinting and also divided over time to form microcalli.

“This shows that 3D bioprinting can be useful to study cellular regeneration in crop plants,” Sozzani said.

Finally, the researchers studied the cellular identity of the bioprinted cells. Arabidopsis root cells and embryonic soybean cells are known for high proliferation rates and a lack of fixed identities. In other words, like animal or human stem cells, these cells can become different cell types.

“We found that bioprinted cells can take on the identity of stem cells; they divide and grow and express specific genes,” Van den Broeck said. “When you bioprint, you print a whole population of cell types. We were able to examine the genes expressed by individual cells after 3D bioprinting to understand any changes in cell identity.”

The researchers plan to continue their work studying cellular communication after 3D bioprinting, including at the single-cell level.

“All told, this study shows the powerful potential of using 3D bioprinting to identify the optimal compounds needed to support plant cell viability and communication in a controlled environment,” Sozzani said.

The research appears in Science Advances and was supported by National Science Foundation EAGER grant MCB #203928 and by BASF Plant Sciences. Tim Horn, assistant professor of mechanical and aerospace engineering at NC State, is a co-corresponding author of the paper.

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Pain-sensing gut neurons protect against inflammation

Neurons that sense pain protect the gut from inflammation and associated tissue damage by regulating the microbial community living in the intestines, according to a study from researchers at Weill Cornell Medicine.

The researchers, whose report appears Oct. 14 in Cell, found in a preclinical model that pain-sensing neurons in the gut secrete a molecule called substance P, which appears to protect against gut inflammation and related tissue damage by boosting the population of beneficial microbes in the gut. The researchers also found that these pain-sensing nerves are diminished in number, with significant disruptions to their pain-signaling genes, in people who have inflammatory bowel disease (IBD).

“These findings reshape our thinking about chronic inflammatory disease, and open up a whole new approach to therapeutic intervention,” said study senior author Dr. David Artis, director of the Jill Roberts Institute for Research in Inflammatory Bowel Disease, director of the Friedman Center for Nutrition and Inflammation and the Michael Kors Professor of Immunology at Weill Cornell Medicine.

The study’s first author, Dr. Wen Zhang, a postdoctoral researcher in the Artis laboratory, added, “Defining a previously unknown sensory function for these specific neurons in influencing the microbiota adds a new level of understanding to host-microbiota interactions.”

IBD covers two distinct disorders, Crohn’s disease and ulcerative colitis, and is believed to affect several million people in the United States. Typically it is treated with drugs that directly target elements of the immune system. Scientists now appreciate that gut-dwelling bacteria and other microbes also help regulate gut inflammation.

As Dr. Artis’s laboratory and others have shown in recent years, the nervous system, which is “wired” into most organs, appears to be yet another powerful regulator of the immune system at the body’s barrier surfaces. In the new study, Dr. Artis and his team specifically examined pain neurons that innervate — extend their nerve endings into — the gut.

These gut-innervating pain neurons, whose cell bodies sit in the lower spine, express a surface protein called TRPV1, which serves as a receptor for pain-related signals. TRPV1 can be activated by high heat, acid, and the chili-pepper compound capsaicin, for example — and the brain translates this activation into a sense of burning pain. The researchers found that silencing these TRPV1 receptors in gut nerves, or deleting TRPV1-expressing neurons, led to much worse inflammation and tissue damage in IBD mouse models, whereas activating the receptors had a protective effect.

The investigators observed that the worsened inflammation and tissue damage in TRPV1-blocked mice were associated with changes in the relative populations of different species of gut bacteria. When this altered bacterial population was transplanted into normal mice, it caused the same worsened susceptibility to inflammation and damage. By contrast, broad-spectrum antibiotic treatment could reverse this susceptibility even in TRPV1-blocked mice. This result demonstrated that TRPV1-expressing nerves protect the gut mainly by helping to maintain a healthy gut microbe population.

The scientists found strong evidence that a large part of this microbe-influencing effect of TRPV1-expressing nerves comes from a molecule the nerves secrete called substance P — which they observed could reverse, on its own, most of the harmful effects of blocking TRPV1. Experiments also suggested that the signaling between neurons and microbes was two-way — some bacterial species could activate TRPV1-expressing nerves to get them to produce more substance P.

To confirm the relevance to humans, the researchers examined gut tissue from IBD patients, and found abnormal TRPV1 and substance P gene activity as well as fewer signs of TRPV1 nerves overall.

“These patients had disrupted pain-sensing nerves, which may have contributed to their chronic inflammation,” Dr. Zhang said.

Precisely how substance P exerts its effects on the gut microbe population, and how these microbes “talk back,” are questions that the researchers are now trying to answer in ongoing studies. But the results so far suggest that the next generation of anti-inflammatory drugs for IBD and other disorders could be compounds that target the nervous system.

“A lot of current anti-inflammatory drugs work in only some patients, and pharma companies really haven’t known why,” Dr. Artis said. “Maybe it’s because, when it comes to chronic inflammation, we’ve been seeing only some of the picture — and now the rest, including the role of the nervous system, is starting to come into focus.”

This research at Weill Cornell Medicine was supported in part by grants from the National Institutes of Health (AI172027, AI151599, AI095466, AI095608, AR070116, DK126871, DK132244, F32AI124517), the LEO Foundation, CURE for IBD, the Jill Roberts Institute, the Sanders Family, the Rosanne H. Silbermann Family Foundation, and a Crohn’s and Colitis Foundation Research Fellowship Award.

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Deep learning makes X-ray CT inspection of 3D-printed parts faster, more accurate

A new deep-learning framework developed at the Department of Energy’s Oak Ridge National Laboratory is speeding up the process of inspecting additively manufactured metal parts using X-ray computed tomography, or CT, while increasing the accuracy of the results. The reduced costs for time, labor, maintenance and energy are expected to accelerate expansion of additive manufacturing, or 3D printing.

“The scan speed reduces costs significantly,” said ORNL lead researcher Amir Ziabari. “And the quality is higher, so the post-processing analysis becomes much simpler.”

The framework is already being incorporated into software used by commercial partner ZEISS within its machines at DOE’s Manufacturing Demonstration Facility at ORNL, where companies hone 3D-printing methods.

ORNL researchers had previously developed technology that can analyze the quality of a part while it is being printed. Adding a high level of imaging accuracy after printing provides an additional level of trust in additive manufacturing while potentially increasing production.

“With this, we can inspect every single part coming out of 3D-printing machines,” said Pradeep Bhattad, ZEISS business development manager for additive manufacturing. “Currently CT is limited to prototyping. But this one tool can propel additive manufacturing toward industrialization.”

X-ray CT scanning is important for certifying the soundness of a 3D-printed part without damaging it. The process is similar to medical X-ray CT. In this case, an object set inside a cabinet is slowly rotated and scanned at each angle by powerful X-rays. Computer algorithms use the resulting stack of two-dimensional projections to construct a 3D image showing the density of the object’s internal structure. X-ray CT can be used to detect defects, analyze failures or certify that a product matches the intended composition and quality.

However, X-ray CT is not used at large scale in additive manufacturing because current methods of scanning and analysis are time-intensive and imprecise. Metals can totally absorb the lower-energy X-rays in the X-ray beam, creating image inaccuracies that can be further multiplied if the object has a complex shape. The resulting flaws in the image can obscure cracks or pores the scan is intended to reveal. A trained technician can correct for these problems during analysis, but the process is time- and labor-intensive.

Ziabari and his team developed a deep-learning framework that rapidly provides a clearer, more accurate reconstruction and an automated analysis. He will present the process his team developed during the Institute of Electrical and Electronics Engineers International Conference on Image Processing in October.

Training a supervised deep-learning network for CT usually requires many expensive measurements. Because metal parts pose additional challenges, getting the appropriate training data can be difficult. Ziabari’s approach provides a leap forward by generating realistic training data without requiring extensive experiments to gather it.

A generative adversarial network, or GAN, method is used to synthetically create a realistic-looking data set for training a neural network, leveraging physics-based simulations and computer-aided design. GAN is a class of machine learning that utilizes neural networks competing with each other as in a game. It has rarely been used for practical applications like this, Ziabari said.

Because this X-ray CT framework needs scans with fewer angles to achieve accuracy, it has reduced imaging time by a factor of six, Ziabari said — from about one hour to 10 minutes or less. Working that quickly with so few viewing angles would normally add significant “noise” to the 3D image. But the ORNL algorithm taught on the training data corrects this, even enhancing small flaw detection by a factor of four or more.

The framework developed by Ziabari’s team would allow manufacturers to rapidly fine-tune their builds, even while changing designs or materials. With this approach, sample analysis can be completed in a day instead of six to eight weeks, Bhattad said.

“If I can very rapidly inspect the whole part in a very cost-effective way, then we have 100% confidence,” he said. “We are partnering with ORNL to make CT an accessible and reliable industry inspection tool.”

ORNL researchers evaluated the performance of the new framework on hundreds of samples printed with different scan parameters, using complicated, dense materials. These results were good, and ongoing trials at MDF are working to verify that the technique is equally effective with any type of metal alloy, Bhattad said.

That’s important, because the approach developed by Ziabari’s team could make it far easier to certify parts made from new metal alloys. “People don’t use novel materials because they don’t know the best printing parameters,” Ziabari said. “Now, if you can characterize these materials so quickly and optimize the parameters, that would help move these novel materials into additive manufacturing.”

In fact, Ziabari said, the technology can be applied in many fields, including defense, auto manufacturing, aerospace and electronics printing, as well as nondestructive evaluation of electric vehicle batteries.

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Clarification of material properties for clearly better displays

A new material is set to provide us with faster and higher resolution displays. Hokkaido University researchers could explain what makes this material so special, opening the door to its application and further development.

All displays consist of a lattice of tiny dots of light, called pixels, the brightness of which can be individually controlled. The total number of pixels — and therefore, the resolution and display size — is limited by how many of these pixels can be addressed within a given fraction of a second. Therefore, display manufacturers try to use in the pixel control units materials that exhibit a very high “electron mobility,” which is a measure for how quickly current will start to flow through such a control unit as a response to voltage being applied — and thus, how “quick” the pixel is.

A new material called “ITZO” (for its constituent elements indium, tin, zinc and oxygen) promises to be up to seven times faster than the current state-of-the-art material. However, it has not been clear where this improvement comes from, hampering its adoption for industrial applications.

Hokkaido University material scientist Hiromichi Ohta and his team used their unique measurement technique to clarify this point. In their recent paper published in the journal Applied Electronic Materials, they showed that the higher electron mobility results from the unusual fact that in ITZO films of sufficient thickness, free charges accumulate at the interface with the carrier material and thus enable passing-through electrons to travel through the bulk of the material unhindered.

The unique ability of the group around Ohta comes down to a very simple formula: The electron mobility is proportional to the free travel time of the charge carriers — electrons in this case — divided by their effective mass. And while the measurement of the electron mobility itself is a relatively standard technique, effective mass and free travel time cannot be measured as easily, and therefore it is difficult to tell what factor is responsible for the electron mobility.

But by measuring how the electric field inside the material changes in response to an applied magnetic field as well as to a temperature gradient, Ohta’s team could deduce the effective mass of the electrons — and then calculate the free travel time, as well. It turns out that both the effective mass is significantly smaller than in current state-of-the-art materials and the free travel time is much higher and, therefore, both factors contribute to the higher electron mobility. In addition, by observing how their results depend on the thickness of the ITZO material, they could deduce how interface and bulk of the material contribute to these effects.

Ohta explains the significance of this analysis: “Using the knowledge we gained from this study, we may in the future design other transparent oxide semiconductor thin-film transistors with different chemical compositions that exhibit even better electron mobility properties.” Thus, this study is a major step towards the next generation of ultra high-resolution displays.

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Materials provided by Hokkaido University. Note: Content may be edited for style and length.

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Too much motivation affects our decision-making

In a good or a bad mood, focused or distracted, in dire or no need: our internal states directly influence our perceptions and decision-making. While the role of motivation on the performance of behavioural tasks has been known for more than a century — thanks to the work of psychologists Robert Yerkes and John Dilligham Dodson — its precise effect on the brain remains unclear. A team from the University of Geneva (UNIGE), in collaboration with the EPFL, has revealed how motivation alters the neural circuits responsible for sensory perception preceding decision-making in mice. This study reveals why a level of motivation that is too high or too low can affect our perception and therefore our choices. These results, featured in the journal Neuron, open up new perspectives in learning methods.

Going to work early in the morning, choosing a restaurant at lunchtime: many of our decisions are motivated by needs, such as earning a living or satisfying our hunger. However, decision-making is a complex process, which can also be influenced by external factors, such as the environment or other individuals, and by our internal states, such as our mood, our level of attention or our degree of motivation.

The laboratory of Sami El-Boustani, Assistant Professor in the Department of Basic Neurosciences at the Faculty of Medicine of the UNIGE and recipient of an Eccellenza fellowship (SNSF), is studying the neural circuits involved in decision-making. In recent work, carried out in collaboration with Professor Carl Petersen’s team at EPFL, his lab has studied the role played by a specific internal state — motivation — in perception and decision-making. For more than a century it has been known that a relationship between motivation and performance exists thanks to the work of American psychologists Robert Yerkes and John Dilligham Dodson. Too much or too little motivation is detrimental to performance. However, the way in which this impacts our neural circuits remains unclear. ”We wanted to observe how sensory information transmitted by neurons in the cortex is altered by the degree of motivation and to what extent the latter can have an effect on learning and performance in a decision-making task,” explains Sami El-Boustani, the lead author of the study.

The research team developed a behavioral paradigm involving mice in a controlled water consumption regime. They first trained these rodents to respond to tactile stimuli via two whiskers (A and B) and to produce an action — licking a spout — only for whisker A in order to obtain a drop of water. Following this training, these mice reacted mainly to the stimulation of whisker A, thus indicating their ability to discriminate between these two sensations. Finally, the researchers conducted these experiments at decreasing levels of thirst in order to vary the motivation of the rodents to participate in the task.

State of hyper-motivation blurs sensory information

In a state of great thirst — therefore of great motivation — rodents performed poorly. They licked the spout indiscriminately, without distinguishing between the whiskers stimulated. In contrast, in a state of moderate thirst, the choice of their action became optimal. They mainly licked the spout when whisker A was stimulated. Finally, when they were not very thirsty, their performance in the task dropped again.

By observing the activity of neuronal populations responsible for perceptual decision-making in these mice, the researchers discovered that neurons in these circuits were flooded with electrical signals when mice were hyper-motivated. Conversely, in a state of low-motivation, the signals were too weak. ”Hyper-motivation leads to strong stimulation of cortical neurons, which causes a loss of precision in the perception of tactile stimuli,” says Giulio Matteucci, a Postdoctoral Fellow in Sami El-Boustani’s laboratory and the study’s first author.

In contrast, in the low-motivation state, the accuracy of the sensory information was recovered, but the strength of the signal was too low for it to be transferred correctly. As a result, the perception of the stimuli was also impaired.

A new understanding of learning

These results open up new perspectives. They provide a possible neural basis for the Yerkes-Dodson Law. ”They also reveal that the level of motivation does not only impact decision-making but also the perception of sensory information, which leads to the decision”, explains Carl Petersen, Full Professor at the Brain Mind Institute of EPFL and co-senior author in the study.

This work also suggests that it is necessary to decouple acquisition and expression of new knowledge. ”We observed that mice understood the rule very quickly but could only express this learning much later, depending on an altered perception linked to their level of motivation.” This unraveling of the role of motivation in learning opens the way to new adaptive methods that aim to maintain an optimal level of motivation during learning.

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Materials provided by Université de Genève. Note: Content may be edited for style and length.

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Changing direction: Research team discovers switchable electronic chirality in an achiral Kagome superconductor

Whether or not an object is indistinguishable from its mirror image has important consequences for its physical behavior. Say you watch a basketball player in a mirror. The ball, the player and their surroundings are, at first glance, just the same in the mirror as in real life. But if observed closely, some details are different. The ball in the player’s right hand now appears in their left hand in the mirror. While the mirror image still shows the same hand, it has clearly changed from a left to a right hand or vice versa. Many other physical objects also have mirror images that differ in a key aspect, just like hands, which is why scientists call them handed or chiral (from Greek Image = hand). Others, like the ball, cannot be distinguished from their mirror image, which makes them achiral.

Chirality is one of the most fundamental geometric properties and plays a special role in biology, chemistry and physics. It can cause surprising effects: One version of the carvone molecule, for example, produces a spearmint smell but its chiral — mirrored — equivalent smells of caraway. In material science, one distinguishes between crystals in which the periodic arrangement of the atoms is chiral or not. If it is, the electrons and electric currents flowing within it must also differ somehow from their mirror image, a property that can lead to exotic responses and novel applications.

One example is a diode-like effect where the electric currents flowing from left to right are different from those flowing right to left, a property called electronic magneto-chiral anisotropy (eMChA). So far, this phenomenon has only been found in structurally chiral crystals. Now, however, a team of researchers from Germany, Switzerland, and Spain has reported the first observation of this chiral transport in a structurally achiral crystal, the Kagome superconductor CsV3Sb5.

The quantum puzzle is as simple as it is deep: If the atomic positions in the crystal are just the same as in their mirror image, how is it possible that its electrons are not? Clearly a novel mechanism beyond a simple shape effect as in our hands must be at play. Unlike structural chirality, which is as firmly imprinted in a crystal as it is in a human hand, this new electronic chirality can be switched using magnetic fields. Switchable chirality has never before been observed and may well find its application in future technology. It is clear that this unusual behavior is directly linked to the strong electronic interactions. The team proposes a model in which the electrons arrange themselves in patterns that violate mirror symmetry, even though the atoms are arranged symmetrically. CsV3Sb5 is already known for many such interacting electronic structures, such as the formation of an unconventional chiral charge order featuring a tantalizing charge modulation. These chiral electronic structures may rotate spontaneously, causing an orbital magnetic response associated to a behavior known as ‘loop currents’, as described by C. Mielke et al., Nature (2022),

CsV3Sb5 appears to be a fantastic sandbox to probe correlated quantum phenomena, including the first example of switchable electronic chirality. The next steps include increasing the operational range from cryogenic to room temperature and enhancing the magnitude of this response. Clearly, much more is to come from interacting systems on geometrically frustrated lattices.

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Materials provided by Max Planck Institute for Chemical Physics of Solids. Note: Content may be edited for style and length.

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Antisepsis agents interchangeable in reducing infection risk in open fracture surgeries

Orthopaedics faculty at LSU Health New Orleans participated in a study comparing two antisepsis aqueous solutions in reducing the risk of infection in patients requiring surgery for open fractures. In the largest known randomized-controlled trial, the research team found that contrary to current international recommendations, chlorhexidine gluconate was not superior to povidone-iodine in an alcohol or aqueous solution in preventing surgical site infection. The results suggesting health care practitioners can select either aqueous-based antisepsis solution when treating open fractures on the basis of solution availability, patient contraindications, or product cost are published in The Lancet, available here.

Robert Zura, MD, Professor and Head of Orthopaedics, and Jessica Rivera, MD, PhD, Associate Professor of Orthopaedics, at LSU Health New Orleans School of Medicine, are also co-authors on the paper.

The authors highlight WHO estimates of millions of patients worldwide each year who have surgical site infections. The inherent risk of using fracture fixation in a contaminated or dirty wound is realized in about 10% of open fractures developing surgical site infections. Orthopaedic surgical procedures have the highest infection rate, greater than 20% for severe open tibia shaft fractures.

Previous reviews of general surgery, obstetrics and gynecology trials suggested the superiority of chlorhexidine over iodine. The Aqueous-PREP multiple-period, cluster-randomized,

crossover trial included 14 hospitals in Canada, Spain and the United States and 1,638 adults who underwent surgery for an open extremity fracture. It found that the odds of surgical site infection or unplanned fracture-related reoperations did not differ between patients assigned to receive skin antisepsis with aqueous 10% povidone or aqueous 4% chlorhexidine gluconate. The authors wrote, “Our findings contrast the superiority of chlorhexidine in alcohol that has been shown in clean or clean-contaminated surgery.”

The authors note their findings could have particular relevance to low- and middle-income countries, where both antiseptic solutions might not be readily available or procuring both products is unnecessarily costly.

They conclude, “Our findings are not only relevant to the management of open fractures but might also be applicable to the surgical treatment of other traumatic wounds.”

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Materials provided by Louisiana State University Health Sciences Center. Note: Content may be edited for style and length.

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