A Continuation in the Search for the Function of Sleep: Commentary from On Your Mind Podcast

This morning, I had the pleasure on being a guest host for one of the more entertaining, informative neuroscience podcasts of today’s smart technology society: On Your Mind. We talked about the job market, my new book–Meathead: Unraveling the Athletic Brain, and wrapped up with discussion of some peer-reviewed literature.

ResearchBlogging.orgIt turned out that I gave the show hosts–Kathryn Vaillancourt and Liam Crapper–the wrong but related paper out of the same collaboration. I meant to give them this one which focused on sleep deprivation, while the one that I sent was actually more focused on disease: insomnia. It worked out beautifully  though because there was much overlap in the results, presentation of data, and technique as this is where my initial confusion actually arose.

The group of researchers used a very sophisticated form of magnetic resonance imaging that we have yet to fully comprehend. The three of us–Kathryn, Liam, and myself–decided that this technology known as “31-Phosphorus Magnetic Resonance Spectroscopy Study at 4 Tesla” is basically a hybrid of MRI and PET imaging coupled with analysis similar to mass spectrometry to quantify amounts of phosphorus-containing compounds. I think Figure 1 of both papers nicely helps the reader visualize the technique.

4 Tesla technology



The researchers were interested in specific cellular energy metabolites that have long been forgotten about or fully considered in the field of sleep–ATP, ADP, phosphocreatine–as well as constituents of the cell membrane like phosphocholine. In the insomnia paper, these cellular constituents were examined in a group of individuals with clinically diagnosed insomnia. In the sleep deprivation paper, changes in these cellular constituents were quantified before and after a brief bout of sleep deprivation as well as across a two day recovery period from sleep deprivation. The researchers also dissected differences in these cellular constituents between the grey and white matter of the brain which are very different in architectural makeup: the former containing the nerve cells with the latter containing glia.

In both papers, there was a decrease in phosphocreatine which is required to keep up with energy demands in individuals diagnosed with insomnia or after a night of sleep deprivation. This was specific to the grey matter.

PCr changes in the grey matter


This is basically the most important and consistent finding of the two papers. In discussing the presentation of data, we all agreed that the data could have been presented better to separate out tissue-specific differences as well as interactions. The biggest hiccup is this general fitting curve to show the direction of change for both tissues regardless if one had a significant effect (grey matter) or not (white matter). This is a bit disingenuous. We also agreed that the title would have been perfectly fine up until the placement of the colon and mention of the technique. Sure, the technology adds to the attention grabbiness of the paper but is it really necessary? Anyways, I don’t want to take away from the impact of these two studies by focusing on minute details. It is awesome that we now have human data to support the animal work from 2010 in regards to how cellular energy metabolites change across a protocol of sleep deprivation or spontaneous sleep and wake. Truly there is more than just one function of sleep. Even more reason as to why we should take advantage of a good night’s sleep.

Harper, D., Plante, D., Jensen, J., Ravichandran, C., Buxton, O., Benson, K., O’Connor, S., Renshaw, P., & Winkelman, J. (2013). Energetic and Cell Membrane Metabolic Products in Patients with Primary Insomnia: A 31-Phosphorus Magnetic Resonance Spectroscopy Study at 4 Tesla SLEEP DOI: 10.5665/sleep.2530

Plante, D., Trksak, G., Jensen, J., Penetar, D., Ravichandran, C., Riedner, B., Tartarini, W., Dorsey, C., Renshaw, P., Lukas, S., & Harper, D. (2014). Gray Matter-Specific Changes in Brain Bioenergetics after Acute Sleep Deprivation: A 31P Magnetic Resonance Spectroscopy Study at 4 Tesla SLEEP DOI: 10.5665/sleep.4242



Meathead, now available!

I have been working on this book for over three years. It combines athletic anecdotes with scientific discoveries in a very under appreciated field of exercise physiology. Whether you are looking for  motivation to continue working out or want to bring your athletic training to the next level, this book can help you accomplish both. One of my pet peeves as a scientist is when scientists resist in making complex information understandable to the general public. This is our civic duty yet many scientists fail at doing this. I hope that this book has inspired the lives of many; whether it means it got you off the couch or to train smarter. Also, the foreword is really touching and written by a very talented and strong woman of sport and life. The book is available in all e-book platforms as well as a soft and hardcover edition. However, I receive more royalties if you order it directly from the publisher:


Humans in the Wild.

This recent publication comes out of the lab of my graduate mentor. Adam, DG, and a group of undergrads sorted through the power grid of the Northwest Pacific which is easily and freely available online. After importing this data into Clocklab which is used in circadian research to track and collate daily rhythms of ResearchBlogging.orgbehavior (wheel running) and physiology (core body temperature), I present to you an activity record of humans in their natural habitat (in January).

You may be surprised to know (or not) that the length of the night becomes progressively shorter as the summer approaches and longer as winter approaches. I doubt this means that humans are going to bed earlier and waking up later– therefore getting more sleep–but perhaps this is true : )

At any rate, this is a really simplistic and cool way to think about human behavior and how lifestyle and climate shapes our environment. I wonder how different this power grid would be for Europe? Or Africa? You should know that this power grid data does not differentiate between city and rural areas.

humans in the wild, changes in light use

Stowie, A., Amacarelli, M., Crosier, C., Mymko, R., & Glass, J. (2014). Circadian analysis of large human populations: Inferences from the power grid Chronobiology International, 1-7 DOI: 10.3109/07420528.2014.965316


6 years of Dormivigilia and how to get that Science paper

It’s hard to believe that Dormivigilia is going six years strong. Sure, I don’t post as often as I did in graduate school, but hopefully my readers haven’t given up total hope. From being selected as the official neuroblogger of the neuroendocrine and homeostatic section at the annual Society for Neuroscience meeting five times in a row to having more than 10,000 viewed posts in the past year alone, I am honored. So thank y’all!

What I want to discuss now is advice for those struggling postdocs feeling the pressure to get that Science, Nature, or Cell paper. I’m with you. Since being on the job market, I thought that I was competitive with my sustained NIH funding and 10+ original research publications in respectable journals–broad and/or field-specific–but nope! Funding is tight and job search committees want you to have that “R”-equivalent grant coupled with an “S” “N” or “C” paper. Well, I’d like to think that the project that I have been working on since starting my postdoc and one that was already five years in the works is close to being an “SNC” paper. But to be totally sure, I contacted a colleague of mine in chronobiology who recently got a beautifully designed study published in Science without using any gee whiz techniques that most scientists seem to think is a priori for funding and high-impact publication nowadays. You’re wrong. Here is a paraphrased email exchange between myself and the last author. Basically, you have to be committed to getting an SNC paper on many levels. It’s not just about the science, but the writing and making it clearly understandable to a skeptic/curmudgeon (ie, reviewer) outside of your field.

“I spent a long time thinking about what I wanted to say, and then wrote the first draft in an hour.  The paper then went through about 10 full revisions with my collaborator.  We nitpicked over every word, period, comma, etc.  Long talks on the phone going over it together.  Sleepless nights, etc.  I sent it in, without any supplementary materials, and was shocked when they actually sent it out for review.  The important point there is that your cover letter really matters.  They rejected the paper.  One reviewer loved it, the other hated it.  The hater was rather angry that we didn’t have any electrophysiology or molecular biology.  Predictable.  Healso listed several things that he felt we should have done.  Those things were already in the paper, however.  I emailed the editor, pointed out the fact that he was not being responsible, and she said, too bad, go elsewhere.  I protested again, and she took the issue to her colleagues.  They offered to send it out for arbitration, which I didn’t know even existed outside of labor unions.  I was then invited to rewrite it and resubmit, i.e., start all over.  So, I incorporated the helpful comments and resubmitted.”

“Three single-spaced pages of comments came back from the arbitrator, and a single paragraph from a new reviewer, who thought it was fine as is.  The arbitrator clearly had no background in rhythms or learning and memory.  I spent 6 weeks 24/7 doing nothing but generating all of the data in the supplementary materials, writing it up, and calling ex-students to see if they could locate information that we usually don’t keep track of.  My cover letter in the reply was 15 single spaced pages with 25 references going back to the 1970′s.  I had to explain the history of SCN lesions, detailed discussions of statistics, and so on.  That letter and the supp materials went through at least 8 revisions each.  It was accepted 4 days after submission, at the end of a 5 month process.”
So yes the bottom line is that if you want to dream big, you have to be willing to put in the work and time.

A decade’s worth of data on alcohol and circadian rhythms

Many of you may recall that I spent five years in graduate school investigating how alcohol acts on the circadian timing system- behaviorally and physiologically. This was the basis of my dissertation and a research direction that has been pursued by my graduate school mentors for almost a decade. As Drs. Dave Glass and Rebecca Prosser can attest to, it was not an easy journey. Both of them had no formal training in the alcohol field which as we have discovered can be cliquish, placing a HUGE emphasis on pedigree. Hey, I get it. The sleep field is no different and I’m very much part of that pedigree trajectory. However, they both overcame this barrier by proposing and doing fantastic, mechanistic science that has resulted in over 10 original research articles on how long-term and binge-like consumption of alcohol affects circadian timekeeping on many levels.

ResearchBlogging.orgTheir research has combined in vivo (live animal) and in vitro (isolated tissue) experiments that have produced overlapping results, strengthening the body of evidence that alcohol severely disrupts circadian timekeeping. And so, let’s go over this decade of findings.

1. One-time and high (binge-like) doses  of alcohol block the ability of behavioral rhythms to adjust/adapt to unanticipated light. The mechanism involves glutamate. 

This hypothesis was first investigated in hamsters which have very robust rhythms of wheel running and are highly responsive and adaptive to unexpected presentations of light. From here, the same experiments were conducted in mice since this is the “preferred” model of biomedical research given the ability to manipulate its genome. Regardless of the species of study, alcohol inhibited the ability of hamsters and mice to either advance (for hamsters) or delay (for mice) their rhythms to light. These experiments were undertaken by my lab mates and me.

Alcohol dose-dependently prevents animals from adapting to unanticipated light

Dr. Prosser’s lab found that the reason alcohol blocks this adaptation to light is because alcohol blocks glutamate signaling which has been known for over 20 years to affect this adaptation to light.

2. Long-term consumption of alcohol destabilizes daily rhythms of activity. 

These experiments were the most intriguing to me because our hamsters and mice could tolerate drinking a 20% (for hamsters) or 15% (for mice) concentrated alcohol solution and ONLY this alcohol solution for months on end. The deleterious effects of alcohol on daily activity rhythms were striking and present early on. It doesn’t take an expert in circadian rhythms to notice differences in the intensity of daily activity levels between these activity records of mice drinking water (bottom) or drinking alcohol (top) for months on end.

Long-term alcohol intake (top) results in sporadic activity

3. Exercise is an effective substitute for alcohol

Our hamsters inspired us to undertake this experiment because they love to run, running anywhere from 3-5 miles every day, and they love to drink alcohol, drinking 50x as much as the average human male every day. So what we did was to give these “booze-soaked fur balls” access to alcohol in the presence of a locked or unlocked running wheel. When the wheel was unlocked, they ran more and drank less. When the wheel was locked, they drank more. They were also extremely cantankerous during this time, making it very difficult to clean their cages.

Hamsters who run more, drink less

4. Genetic disruption to circadian rhythms (via Per2) increases binge-like, compulsive drinking. 

This work was the most time-consuming for me for several reasons. First, it involved the study of drinking in over 300 mice across 3 years and many, many rounds of microdialysis collection which is one of the more physiologically revealing techniques in neuroscience, but yet very cumbersome because of the low success rate. However, largely thanks to the fact that Kent State University does not charge per diem for animal care, I was able to breed many animals at once to complete this experiment in a timely manner. While this may have taken 3 years at Kent, per diem at most universities could have pushed this project to take 6 years to complete. At any rate, we found that the reason that mice lacking Per2 (in protein form) drink more is because they are awake for two, additional hours during the night and are heavily drinking during this time. This is reflected in the left-side panels of these activity (top) and drinking (bottom) records in comparison to wild-type mice (right-side panels).

Per2 mutant mice are awake more and therefore drink more

5. Acamprosate (market name: Campral) acts in reward-processing and (surprisingly) circadian areas of the brain to reduce alcohol intake

Acamprosate has been on the market for years and yet little attention has been paid to how it acts in the brain. So we used a relatively simple yet under-appreciated and undervalued approach to see where acamprosate acts in the brain. The simplicity resided in mixing up the acamprosate in wax and then popping these tiny wax pellets into the edges of brain areas regulating rewarding behavior and circadian timekeeping. This was complex because these brain areas are relatively small and so our coordinates had to be very precise. Actually, it was through missed targets that we discovered that some brain areas like the hippocampus are not responsive to acamprosate. This figure took over 60 hours to make (seriously) and does a nice job of detailing where in the brain and how effectively acamprosate acts.

Brain areas where acamprosate acts


And that’s a wrap. This research direction is far from complete but golly, we sure made an impact on the alcohol field in just ten short years.

Prosser RA, & Glass JD (2014). Assessing ethanol’s actions in the suprachiasmatic circadian clock using in vivo and in vitro approaches. Alcohol (Fayetteville, N.Y.) PMID: 25457753

Best of 2014: #pandanation #allbridgers #rabs #SfN #cashmoneyscience

I can’t believe that I am approaching my 7th year of neuroblogging. This year was so so. There were some good parts in the middle but it started and ended on crappier moments. However, I’m looking forward to some promising moments in 2015, including the publishing of Meathead: Unraveling the Athletic Brain–a book that I have been working on for a few years–as well as competing in the 2015 Reebok Crossfit Games with #pandanation.

January: I went to an awesome workshop on visual presentation of scientific data taught by Edward Tufte. The bottom line is less is more.

I also presented an article in journal club about the athletic consequences of game day travel across time zones. The bottom line is that if you have Vegas stakes on the line and a West Coast team is playing an East Coast team in Sunday, Monday, or Thursday night football at home, bet on the West Coast team even if it is the San Diego Chargers. Trust me.

February: The “road to the fittest on earth” (i.e., Crossfit season) began once again. Our very own #pandanation at Crossfit Terminus made an appearance in the commercial. And I got to begin participating in an exercise physiology study at Kennesaw State University that focused on cardiorespiratory fitness in elite Crossfitters.

I also blogged about the very disturbing research field of plant neurobiology. It is true that plants experience adapt and respond to stressors, but to say they have an intact nervous system is a bit too much.

Finally, the world record in men’s pole vault set by Sergei Bubka of the Ukraine was broken by Renaud Lavillenie of France in Bubka’s home country of Ukraine. Unbelievable.

March: March was cool. I attended the first Gordon Research Conference on Sleep Regulation in Galveston, TX and met some cool dudes and peeps who will be lifelong friends and colleagues. I also worked my ass off to qualify as an individual in the Reebok Crossfit Regionals after a very disappointing opener workout. With Montegraphia’s vast, statistical knowledge, I was able to figure out what I needed to place in each week’s workouts to be in the top 48. And I did it! I crawled back from 292nd to 43rd in the Southeast (FL, GA, SC, AL) region with the final two workouts clutching this spot.

April: April was a month of grueling training in preparation for the Southeast Crossfit Regionals. In the blogging world, this infographic went viral in regards to the pathetic, academic job market for newly minted PhDs in science. I also presented this article in our quarterly journal club with the cardiovascular institute that finally did an impressive empirical investigation on risks for cardiovascular events around Daylight Savings.

May: The first half of the month was spent preparing for the Reebok Crossfit Regionals while the second half was spent recovering from the “shoulder annihilation” of Regionals. Check out 3:07:00 onward in this video:

But the greatest part of the weekend was seeing my long-time training partner qualify for the 2014 Reebok Crossfit Games after years of hard work and patience. Also, my most popular post of the year was in response to this egotistical, conceited fitness brat.

June: I spent most of the month on the road traveling to professional society meetings. The first half of the month was spent in Minneapolis attending SLEEP. From there, I went to Big Sky, Montana for SRBR which was absolutely stunning in scenery and science. We saw moose trek into our yard every day, snow-capped mountains, and lots of Glass lab shenanigans, mostly involving “Turn Down for What.”

After Montana, I traveled to Berkeley to give a talk and to spend a week in Napa with the in-laws. It started out beautifully and ended poorly when I got my most sentimental shit stolen, including my wedding ring, Crossfit Games gear and general Crossfit gear as well as my most sentimental possession which was my four-year varsity jacket from Brown track and field.

July: This was the month of the World Cup as well as Em’s debut in the Crossfit Games. To address the former, I re-blogged about a research article that first appeared in the Journal of Neuroscience. I also went to a phenomenal grant writing workshop on writing R grants. But I’m not about to publicly reveal those secrets ; ) Lastly, I went home to Ohio for the funeral of my younger cousin who tragically died from a motorcycle accident. It had been a very stressful two years for our family.

August: Blood made a comeback in neuroscience research. From genomic screens of blood to how donating blood taken from one mouse affects the brain of another, it looks like we are back to where we started hundreds of years ago.

September: This month I attended one of the most enlightening conferences in research ever. It was basically a science camp for grant writing, research ethics, and new technologies at the edge of the San Bernardino mountain range in Lake Arrowhead, California. I also competed in a grueling three-day Crossfit competition in Pensacola, FL.

October: Blood control of brain function continued to make an appearance in peer-reviewed journals. I also griped about gender inequality in academia in regards to respect for women scientists, not representation of women scientists. This post was my second most popular post aside from the Erin Simmons one. Also, my young adult fictional book that I wrote ten years ago was re-released in a second edition and became an e-book! Buy it NOW for $1.99.


November: This month was busy prepping for upcoming job interviews as well as for the annual neuroscience meeting which was held in DC this year. For the sixth year in a row I was selected as a neuroblogger. I also traveled to Southern Mexico at the end of the month but came back with Montezuma’s revenge a few days before some on-campus interviews.

December:  I spent a good portion of the month interviewing (unsuccessfully) for jobs but gained some important insight for future job prospects (hopefully).

Happy New Year and blogging in 2015!


Insights from an Academic on the Market

The past four months have been a whirlwind. I’ve been mindlessly applying to positions; sending nearly the same generic application to 70-80 schools hoping for at least a phone call. It turns out even this was a poor strategy. Because even though search committees know the market is tight, they want to see some bit of personal, university-specific narrative in the application. They’ve got hundreds to sift through and are most interested in “fit” scientifically and who they can have coffee with. So, after going through several phone interviews, a few on-campus interviews  from very contrasting institutions–the former being a huge academic (and athletic) enterprise and the latter being a liberal arts college–I feel that I have SOME experience. Plus, I was actively part of a massive job search in graduate school so I already have some advice to lend.

First off, when you are on the market, scour how the Internet perceives you as a being. If you have had some alternative, questionable, or controversial career path, press release, or images/videos of you, find a way to remove them and/or be ready to explain them and ask for forgiveness. Make your social media private. It is actually a violation of academic freedom for job search committees or universities to discriminate applicants based on social media and Internet excavations (see: http://www.aaup.org/news/social-media-policy-violates-academic-freedom), but humans thrive on gossip.

For the phone call…..

1. Don’t sell yourself short. It is OK to brag. I may have more reason to with a last name like “Brager” (terrible joke), but you’ve worked long days, late nights, and weekends to get to this moment. Embrace it.

2. Even if you don’t know where your research will take you in 10 years, find a way to have a 10 year plan. Science is a marathon not a sprint. Basically, I will do this in my pre-tenure years, then move onto this in my post-tenure years, etc. Or when I have this grant, I will then move on to that grant.

3. Have an idea of what you want to teach and are capable of teaching (even if you are applying to a medical school).

For the on-campus interview…..

4. Dress for the job you want not the job you have. Appearance does make a difference. You may wear jeans and sneaks in the lab (I do), but people won’t take you seriously talking about serious science if you are wearing ripped jeans, Rainbow sandals, and a “Keep Calm and Carry On” Shirt. Business casual it is.

5. Don’t go out with the graduate students and get drunk enough that you are puking for your talk and meetings with faculty the next day. You may laugh, but it has happened.

6. Expect hostility. Don’t let your ego get in the way and be defensive. Hostility and lack of emotion are part of the game the search committee is trying to play to see how well you can perform under pressure and confidently answer questions that may appear naive and rude like, “why do we care to study mice when we have the capability to study humans?” Also, don’t lose focus. If a faculty member asks if you can do this, answer honestly, and if it is a ” yes”, remind them  that getting your lab up-and-running and funded is priority.

7. Do your research on the faculty. You may have way more in common than you think. For example, at one of my interviews I discovered that one of the faculty members and I went to the same high school given that we are from the same hometown. But don’t do research just for “small talk” but for the purpose of cross-collaboration. Collaboration is key in today’s funding climate.

8. Even if you don’t feel the place is for you a few hours in, don’t burn bridges. Science is a small world. Real small.

9. Keep your head up if you get a rejection. It may not be you, it may be an issue of “fit”. Even if it is you, listen and correct. Besides, the market looks like this anyways.

Statistical breakdown of postdocs entering faculty positions

In the end, I’m taking a risk and holding out for that 60-40-ish balance of teaching and research. I’ve decided that I”m not going to settle for what I don’t truly want. 30 years is a LONG time.





Thanksgiving Travels to the Yucatan

For the second Thanksgiving, I travelled abroad. This one was just as eye-opening as the first; when my best friend from high school and I went to Venice and I saved her dignity after she fell into the Venetian Canal in the blistering cold (no, we weren’t drunk; the walkways were dimly lit and very dark outside). This time, Montegraphia and I went to the Yucatan to a small city called Merida staying with friends who recently moved there.

First off, I finally got to see flamingos in their natural environment. I have always been fascinated by the plumage of flamingos and how the coloration waxes and wanes with their diet; becoming pinker with more sustenance and white with less sustenance. We also ventured into the mangroves and saw HUGE termite nests and a variety of birds ranging from kingfishers to spoonbills. Oh yeah, we also saw a croc peek out above the surface.

We also ventured to one of the seventh wonders of the world; the Mayan pyramids and ruins. It is truly remarkable to see these monstrosities created long before contractors, construction crews, and modern day equipment. These carvings and artwork were also outstanding as there was lots of reproducibility despite everything being free-hand.

One of the seventh wonders

One of the most interesting ruins to see was the site of sacrifice. Within a 24 hour period of sacrifice, the heart would be carried on a tray up to this altar. Timing was crucial to the Mayans, who worshipped the sun, because the aim was to make it look as if the rising sun was eating the sacrificial heart.

Ancient Quidditch

We also visited the ruins of the violent sport played by the Mayans that is frankly similar to quidditch. Teams would wield long sticks and try to shoot these balls through hoops placed at least 40 feet high in the air. There was lots of sticking whipping, lashing, stabbing, and the captain of the losing team ALWAYS got his head sliced off. One cannot deny that humans gravitate towards watching violence in the realm of athletics. The gladiators were not the first.

The altar for sun consumption of hearts

And now for the most saddening experiences of our trips. First, we were forced to bribe a federal officer who “randomly” stopped us at a checkpoint. “Random” because we were gringos driving a Mexican rental car. The officer insisted that we carry our passports because there seems to be an issue with people smuggling Chinese folks into the US via Mexico. Oh, really? For the record, the Mexican consulate recommends that you NOT keep your passports on hand while traveling the country. The moment that we knew that we were being hustled came when the guy pointed to the camera and asked us to move away. And so we gave him 500 pesos and he happily shook our hands and sent us on our way. Basically, law enforcement does not make enough in this country and so they’ve developed a system to survive. I can’t blame them. The day before this bribe, we also learned about the roots of a really troubling riot taking place in Merida. It is interesting that this riot was concurrent with the Ferguson verdict because this was WAY worse. Not to be racially insensitive, but it is. Basically, this local politician and his wife were expecting 43 children to protest one of their public speeches. To circumvent this, the husband and wife hired the drug cartel to resolve it. The cartel stopped their bus en route to the protest, dragged them out to the desert, made half of them dig their own graves, shot them, burned the other half, and threw them on top of the ones who were shot. How is this not on some news channel in the US or elsewhere? Truly sickening.

The trip ended with a significant bout of Montezuma’s revenge but honestly, I was expecting it sooner than I got it.



Consider Funding This.

(Wealthier) readers in biomedical science. Here’s your chance to contribute to something BIG: Epigenetics and sleep. How sleep amounts alter gene function as to be studied by an elite group of folks in sleep research


Welcome to SfN y’all!

First day and great day. Please venture over to the Theme H posters on display til Sunday. In today’s funding climate, it’s great to see an emphasis on teaching and the history of our field. There are different teaching modalities for different demographics and that is the key to success.

As for science, the clocks symposium was intriguing because people are finally getting optogenetics in the biological clock to work! And they work not just on one gene or protein but the entire system affecting neuron output and behavior. Golly, it was impressive!

Follow my other random thoughts and pics from the conf @beastlyvaulter on twitter and IG

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