[Sciences] My Top 10 Sciences Discoveries of 2014

Here I am, a couple of hours before the end of 2014 and lots of excitement in science this year. Here are my top 10 discoveries that marked me this year. It is surely biased (stem cells, blood-brain barrier) but hey I am a scientist after all. There is no particular ranking, so do not use the numbers as a rank.

Note: I will update this blog post by adding additional contents.

1.STAP Cells

The latest blog post from Dr. Knoepfler on the STAP cells debacle

STAP cells: stimulus-triggered acquisition of pluripotency. This was certainly the buzzword of January. Imagine that. Cell reprogramming (following the Yamanaka protocol) of somatic cells into iPSCs is a daunting experience. It is long, expensive and low yield (0.1%). When the technique came, it brought 30% yield and sounded as easy as prepping kosher-dilled pickles. Yep, just that, plunge the tissue into some acidic bath (that is a scientific iteration of the pickling process) and you get 30% of iPSC-like cells (or STAP cells). Sound as easy as ABC, no? Well indeed it was not. And it turned sour very fast indeed with over 10 labs trying without success. First came some statement similar to “it’s complicated”, then inquiry from RIKEN university in Japan followed by obvious scientific misconduct and paper retraction as the first author failed to reproduce the original data. In addition, the senior author committed suicide. A tragic ending for a flawed study, a “too simple to be true”.

2. The first stem cell clinical trials for retinal macular degeneration

This year have seen the first stem cell clinical trials using hESCs and iPSCs in patients suffering from macular degeneration. Preliminary results are showing a relative safety of the technique (no tumor observed so far) and some reports of improvements in certain patients. It is still not known if such improvement is a “placebo effect” or real effects. Similar studies are ongoing for other cardiovascular diseases and for neurological disorders such as Lou Gehrig’s disease or Huntington’s disease at the Mayo Clinic. However, I would like to remind people that there is yet no stem cell cures or proven stem cell therapies. Please, please, please do not listen to those claiming “stem cell therapies” that are working. There is not such thing and there is not yet any FDA-approved guidelines for such. A lot of labs are working to bring stem cells from the bench top to the patient’s bedside but still a lot of way to go.

3. The gut-brain interactions: the blood-brain barrier as the middleman

Diffusion of an IR-dye across the blood-brain barrier in a “sterile” mouse compared to “pathogen-specific free” mice. Note the fluorescence intensity showing a leaky BBB. Courtesy Karolinska Institute.

This was the most interesting and the fast-pacing rise. Until a few years ago, we mostly believed that the gut microbiota would only affect the GI tract without any incidence on the rest of the organism. I was stunned by two studies: one study showing the impact of microbiota composition in the gut flora on autism-like symptoms (http://www.ncbi.nlm.nih.gov/pubmed/23307560) that shows how the alteration of the flora composition resulted in the display of autism-like phenotype. The mechanisms are unknown but it seems the presence of a leaky intestinal tract may trigger neurobehavioral changes. The second comes from http://www.ncbi.nlm.nih.gov/pubmed/25411471, in which they show that the absence of a gut microbiota results in an increase leakiness of the blood-brain barrier. It took 60 years for neuroscientists to admit the presence of a blood-brain barrier. Hopefully, by 2020, neuroscientists will finally understand how crucial the BBB is for the brain well-being and the salute of treating neurological diseases will only come when they will understand that we BBB scientists are as important as them.

4. Human induced pluripotent stem cells as disease modeling and drug toxicity screening

If one biomedical research field that quickly emerged in the last decade, it is certainly the field of induced pluripotent stem cells (iPSCs). For those who are not aware about iPSCs, this is an important discovery of this century. Once the egg is fertilized, it quickly divide into 2, 4, 8, 16 cells up to reaching a stage called a “morula” stage that ultimately evolve into a blastocyst. This blastocyst will eventually become…YOU! Interestingly, all these cells are called totipotent as they can form any type of cells. These are the classical “embryonic stem cells” that have raised hope and fears among the public.
All of our cells have the same genetic information but what makes a neuron from a muscle cell is the number and types of genes that are ON and OFF. This is what we call the epigenome. By reverse-engineering it, we can bring reverse the clock on these cells to bring them into a pluripotent stem cell stage. Once pluripotent, we can reprogram these cells into any type of cells. This dedifferentiation stage was developed by Yamanaka in 2006 (Nobel Prize 2013) and applied to human cells by Jamie Thomson in 2007. Since then, a lot of effort have been done to differentiate these cells into various cell types including neurons. This open a new perspective as we can now try to understand human diseases in a dish by directly having access to patients cells. And this have been successfully applied in these last five years for different types of neurological diseases. If we have to show a poster-child for personalized-medicine, that would be its first iteration. There are numerous studies showing the ability to differentiate neurons from patients suffering from Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, ALS, frontotemporal degeneration, Dravet Syndrome, Fragile X Syndrome, schizophrenia….
As we are just starting to understand the mechanism of diseases, we can now foresee the possible usage of these cells to identify novel compounds capable to slow or even relapse the disease.

5. The Edna Krabappel and Lisa Simpson peer-reviewed study

http://www.sciencealert.com/two-scientific-journals-have-accepted-a-study-by-maggie-simpson-and-edna-krabappel

This was one of the big bust, especially when you are in the academic field and know the calvary of publishing your manuscript. Getting your study is a long and patient process in which you have to deal with peer-review process, in which other scientists (anonymously) review your study and give their decision to the editor-in-chief about if your study is good for publishing or not.

In the classical model, the journal charges the authors of the study for publishing the study and the readers to access to the full journal. And having access to journals can be very expensive especially if you are in a small university or if you are located in a developing country. Still even with the best peer-review system, there are still flawed study that made it to publication and get retracted (http://retractionwatch.com). Since these last few years, an important step have been done to provide open-access to scientific papers. The authors pay a publication fee (usually higher than the traditional journal) but the paper is freely accessible to read it.

This new model has of course brought some interest for some people seeing “easy money” to be done, by accepting ANY studies, even from fictional characters. The fact that a paper authored by Edna Krabappel and Lisa Simpson filled of non-sense text fillings raise concerns and make a call to establish some guidelines and ways to select the “good open-access journals” from the bad ones. Also this year, the NIH Library of Medicine, the Pubmed portal (a well known scientific articles search engine for biomedical scientists) has launched the Pubmed Commons to provide an open, post-publication review mechanism in which anyone can comment on any paper presented in Pubmed.

I believe this is the first case of many uncovered and we are expecting to see more. It is a time we have to decide if we keep our science straight and well-sounded or if we let hijacked by flawed and manipulated studies.

6. Rosetta Stone and Philea probe

This was the biggest achievement of the European Space Agency (ESA). Can you imagine sending a remote probe, have it land on an asteroid. You have to imagine piloting a RC buggy car through a screen with 10 minutes delay between the time you see the obstacle and the time the command is executed. Imagine you drive your RC buggy see a tree in front of you, send the command to turn right and have to wait 10 minutes to get it done.

If I have one rant to make, it certainly on some trolls that pointed on Dr. Mark Taylor’s shirt and ignored the scientific achievement accomplished. Yes, having this shirt on live broadcasting was a terrible PR move, but putting on that shirt to blame the problem of women in science is wrong. The problem is much bigger than a shirt and those that are putting bars in the wheels of women in scientific careers are not wearing such shirts. We need to re-think about the whole system to better retain women in sciences, set maternity leaves and adapted schedule to have them the possibility to adapt their work to their schedule, tailor the tenure process to take in consideration that women have to deal with two important choices in their life in the same time and should not be forced to choose one  for the other.

Although Philea landed in a wrong place and rapidly died from low battery, it gave us some information. For a moment, I fell in love with Philea, like a real-life WALL-E. I am looking forward to have it back on track and running up soon.

The also interesting projects are the Mars Curiosity roving over the red planet and found some bursting methane (that could be some microbial life) and of course the Pluto mission coming in early this year.

7. Prosthetic arms and cyborgs

As a kid, I always got fascinated by robots, cyborgs and giant mechas. I grew up watching “UFO Grendizer”, “Star Wars”, “Transformers”, “The Terminator”, “The Million Dollar Man”, “Robocop” but also got frightened by “Galaxy Express 999” in which in a distant Earth future, humans have most of all acquired immortality by replacing their biological parts into robotical parts. Those who failed to afford or refused to become cyborgs are considered as sub-humans and hunted as preys.
Human-mechanical interfaces sounded like science fiction 20 years ago. As we have been progressing in neurosciences, we also have considerably improved in mechanical engineering and electronic. We are just assisting in the first trials in which prosthetic limbs are directly connected to the brain surface or capable to transduce electrical impulse from nearby muscles to execute movements. Two trials especially caught my attention: the one depicted in the picture and currently run at John Hopkins University in the Department of Applied Physics. The two robotic arms can sense muscle activity from the chest and transduce into complicated movements. Watch the video it is really impressive to see this man capable to regain functional from lost limbs.

http://bcove.me/vst8dnvp

The second one from the University of Pittsburgh allowed a quadriplegic woman to gain control of a robotic arm through a brain-connected interface. Look at the fluidity of the arm, the dexterity. Remember this is a robotic arm connected to the patients brain, it is just  awesome to see the improvement of such discipline over the years.

8. The lady with no “Little Brain” (Cerebellar agenesis)

Source: Cerebellar agenesis Luigi Titomanlio, Alfonso Romano and Ennio Del Giudice Neurology 2005;64;E21 DOI 10.1212/WNL.64.6.E21

Source: Cerebellar agenesis
Luigi Titomanlio, Alfonso Romano and Ennio Del Giudice Neurology 2005;64;E21
DOI 10.1212/WNL.64.6.E21

The cerebellum (or little brain in Latin), is an important piece of the central nervous system. Its function is essential in the locomotion and in the coordination of movements. This is also the primary target of ethanol, the active component of alcoholic beverages (or booze if you like it). Thats why when you are drunk you loose your reflexes and have the typical walking pattern of a drunk person.

We may think that the absence or severe malformation of this organ may significantly impact the locomotor function. Seems not according to a recent study from Fu and colleagues (http://brain.oxfordjournals.org/content/early/2014/08/22/brain.awu239.long). Apart from having trouble to keep an equilibrated statute and some episodes of nausea, the patient appears to have a normal life as she is reportedly married and has one daughter. It shows one thing: the brain appears very plastic and can rewire some of its functions if needed. The most interesting aspect now is how the cerebellar function is re-wired and compensated by the other brain area and which areas?

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[World War I] Merry Christmas, Verdun 1914

This is a continuation of my personal remembrance of the beginning of World War I. I will post more posts during the next couple of years to mark important events of the conflict.

One hundred year ago, the sound of cannon and artillery stopped. Something unusual happened then. For some accounts, the Germans started it by asking “no shoot!” and by starting Christmas Carols like “Holy Night”. Some other accounts pointed the facts that Germans hooked a “Christmas tree” over the trench.

For the first time, the silence of the cold winter let the spirit of human kindness rose from the trenches. This was a war that engulfed hundred of thousands young men, a whole generation sent to the “casse-pipe”, “chair a canon” (a French term equivalent to cannon fodder). A lot of them left their crops (August was the final declaration of war that started the war) with a mindset of a “quick war”, went “la fleur au fusil” to the battlefield. Only to end up into the construction of trenches from the Northern Sea down to Switzerland borderline.

Some people accounted for the some improvised football game between English and German but appears some historical distortions. It does not matter, the most important is how after a hundred years, we build a land of peace in Europe. With all its dysfunctions, the European Union is the remarkable conclusion on how after a hundred year and two tragic wars, they achieve peace and yesterday’s fiercest foes are now the powerhouses of the European Union, serving under a common army (Eurocorps).

If we have to learn a lesson from this war is that no matter which race, ethnicity, religion or nationality you are, we the “vulgate” are just cannon fodder for the ruling elite. At the end, the little people pays their price of their greed and bickering conflict.

I wish that such lesson of history may apply to other parts of the worlds: Israel and Palestine, Syria.

Merry Christmas everyone.

[Metal] My top 2014 Symphonic (Death) Metal albums

2014 is taking its last breath and as usual it is time when folks bring their compilations and ranking of best cultural experiences of this year. I can tell that this year was very prolific, thanks to iTunes Radio that introduced to a lots of different metal bands and sub-genre. I thought to share some of the albums that marked my mind this year. All of them were published this year and evolve around metal/symphonic metal/death metal. There is no particular order and I listed them as alphabetical order. I also give my rating of the album “a la Metal-Archives”. Here we go….

(NOTE: I will progressively update the page, consider it as a 12 days of Christmas and come check it out on regular basis)

Arch Enemy – War Eternal (80%)

This is my introductory album to the group so I am maybe immune to the fight between Alissa White-Gluz and Angela Gossow. What I like about this band is  the presence of harmonics in their style, that strikes from other death metal band that are more frugal. The other surprise I had was to get introduced to female growls, especially when you have been raised in soprano voices of Tarja, Sharon or Simone. Thats was a bit of a shocker at the beginning but I quickly adapted to Alissa vocals. Overall, I liked it, even if it got some bad reps in Metal-Archives. It was a good experience and the band has a very good musical outcome. Two tracks brought my attention” “War Eternal” that is very dynamic and heavy, a great way to start a day and “Avalanche” that has very good melodic components. If you want to get introduced to death metal and wonders how a girl would growl, well this is a great introductory way to get into it.

Deathtiny – In Creep Clothing (80%)

Deathtiny……a band that appeared in my Facebook feed. And a good surprise. It is a very small symphonic gothic metal band from Germany, from the Black Forest area (Karlsruhe, Baden-Wurttenberg) so I consider them as neighbors in terms of my hometown. I consider them as the micro-brewers of metal. A small band, that is touring in the local scene and try to get a reputation. “In Creeps Clothing” is their second album, that can be purchased from iTunes (great if you are oversea but if you are in Europe you can directly buy their album from their Facebook page).

Delain – The Human Contradiction (85%)

Some followers asked about my thoughts on Delain for a couple of times and I thought this can be a quick take before I write a dedicated blog on the band (waiting for the 10th anniversary of their first album “Lucidity”.  Delain is one of this young generation band rising and after exploring their own style got what I think in this one their best shot and maybe are holding the magic formula. Its loud, its heavy (much heavier than their previous album) and an enjoying experience. Charlotte Wessels give this nice “candy” taste to the band style that is not bad. I really liked their first albums “Lucidity” and “April Rain” but got lost with the album “We Are The Others” (altought some of their songs had this 80’s new-wave flavor that was not bad at all). In her songs, Charlotte talks about deluded love, heartbreaks and how it hurts badly. Even any tough headbanger remains a child at heart and you really feel miserable when you set back on your feet after a too-long crush. I consider this album as the natural evolution of “April Rain” with a much more darker and engaged content. Just listen to “Your Body is A Battleground”, “My Masquerade” or “The Tragedy of The Commons”. It is also noteworthy to note the featuring artists in this album just as Marco from Nightwish or Alissa White-Gluz from Arch Enemy. And what is make it a great album. The good news is Delain is coming to North America next year with Nightwish (with Floor as front singer!) and Sabaton. All three in the same concert venue? Thats a deal breaker.

Eluveitie – Origins (80%)

Ever heard about Celtic Metal? Never heard about….until I got my hands on Eluveitie “Origins”. That was a nice moment to listen, as the mix of celtic instruments with guitar riffs and growls as fusing so well. As a French, the closest region that comes to Celtic heritage is certainly Britain or “Breizh”. At the antipode of my hometown (I am from Elsass, at the eastern tip of France), “Breizh” has two meanings for me: my first love (I was a 4th grader, she was from Britain) and Cedric Labrousse, one of the best talented freelance chronicler on the Syrian conflict. The most surprising part was to learn that Eluveitie is far from being Celtic at its root. They are from Winterthur, Switzerland, the second most populous town in Zurich canton, just after Zurich-town. Nevertheless they are fairly amazing. I have not yet compared their latest album to the previous work but I really like this album with the exception of a couple of tracks that I would consider more aimed as “FM radio hooks”. If you are fond of folk-metal and are deep into the Celtic culture, I strongly recommend to discover this group.

Enemy of Reality – Rejected Gods (80%)

Another discovery of this year. Enemy of Reality is a Greek band, joining Elysion and Septicflesh in the few Greek metal bands I can cite. Their most recent album “Rejected Gods” is fairly unique as a symphonic metal as several of its tracks sounds like classical with a touch of metal, rather than having the classic metal riffs and drumbeats with a touch of classical. Iliana has a very powerful voice and deserve to gain some more public attention. I would give this band a software metal tone, almost a gothic aspect. If you need louder and faster pace albums, you may try to reach “Arch Enemy” or “The White Empress”. But if you are like nostalgic of the Nightwish “Oceanborn” era, then it can be a good tryout for this holidays. Favorite track: “Needle Bites” note the feature of Aylin from Sirenia in this track. “Sirenia” Veland and Aylin, looking for your next album!

Epica  – The Quantum Enigma (90%)

If there is a symphonic metal to be considered as a flagship one of the genre, it is certainly Epica. Simone Simons and Mark Jansen can be resumed into one sentence: a constant and great track record. 10 years, 5 albums, but always a consistent delivery of good albums (although the Requiem for Indifferent is the weakest link in my own opinion). Simone and Mark just keep refining their trademark and just ages as wine: just get better as it gets old. It is loud, powerful, the chorals are not too much abused and the symphonic arrangement is great. It certainly faster than their last album and maybe comparable to “Design Your Universe” in a faster pace. If you are looking for something stronger than Evanescence or Within Temptation, but not nihilist as death metal (because you appreciate classical music), this is the one. And if you like it, I strongly recommend to explore their discography.
I wanted to attend their concert in Dallas last fall, however a last minute cancellation from Children of Bodom vanished their USA tour. In the same time, it was heartbreaking that they came to my hometown (Strasbourg) last November with Dragonforce. So close….Really looking for their coming here in the Lone Star State.

Leaves Eyes – Symphony of The Night (85%)

 Leaves Eyes….A band that gives me some troubles because I find their music quality inconsistent to my ears or fails to make the chemistry. Its not because of Liv Kristin, she has a beautiful voice, its maybe the style that some qualify as “folk metal” or I would call it “Scandinavian metal” because it touches a lot of the Nordic mythology. The problem that I have with Leaves Eyes is that for most of their albums I would like a couple of their songs but despise the rest. For instance, “Njord” has a couple of songs that really trip me up like “Ragnarok”, “Northbound”, “The Holy Bond” or “Emerald Band” that have this magic in my brain. Maybe is their lack of heaviness int their sound that was missing. Their latest album seems to have solved that. It starts very loud with “Hell to The Heavens” with the pristine voice of Liv followed by heavy bass guitars and very aggressive growls. Its like Leaves Eyes went on steroids and thats good enough for me.

The only problem I have with this album is its cover. And the graphic designer in general. It seems that someone there has some “photoboobs” issues. I have nothing against generous breasts, i like big beautiful women indeed. Liv has surely a great set of vocal chords, but not a big pairs of boobs, even with a corset. And it seems such “boob job” just keep getting bigger with which new album. Want a proof look at “Njord” and “Symphonies of the Nights” cover albums. Guys, please stop that, it just getting ridiculous and not giving justice to Liv talent: her voice.

White Empress – Rise of The Empress (90%)

The White Empress is a brand new band, formed by ex-Cradle of Filth Paul Allender and ex-Ottoman Empire Mary Zimmer. It also has a special place in my heart as a good chance of the group is coming from the Twin Cities (Minnesota) and Madcity (Madison, Wisconsin). The style of the band is symphonic death metal, with Mary as the lead female growls. Their first album is very energetic, very aggressive and very cathartic for me when I have a bad day or when a band I liked just went “Gaga” with their latest release (Maria, do you hear me?). It has some rage that can be found in old punk bands and thats not bad. Just got infuriated the band played in Madison last Halloween, just wished they performed six months earlier when I was still there.

Whitin Temptation – Hydra (80%)

Within Temptation is the prototypical love-hate relationship you can have. Someone you liked for a long time and just decided to cut bonds for some artistic divergence. You have to know the discography of the band to feel the pain. I highly appreciate the “Heart of Everything” as their best album and of course “Black Symphony” that is the live version of it with a whole philarmonic orchestra. “Hydra” their latest album was for me feeling fighting a hydra. I severed my ties to the band a long time ago but seems one grew back enough to attract my attention. And in my personal, it is not bad, if you cut some non-sense duets. But it was a pleasure to hear a heavy sound, the energy of Sharon in several of their songs. There are songs with features such “Paradise” with Tarja, “Dangerous”, “Let it Burn”. They even were capable to make Imagine Dragon’s “Radioactive” that was some FM quality into something heavy and well designed.

My expectations for 2015?

A lot of expectations. Floor just joined Nightwish and I am seeing her as “the last hope” to bond again with the band. Annette Olzon is maybe a good singer but her vocals cannot sustain the soprano voice of Tarja. And Floor has the vocal range similar to Tarja that can really be a deal breaker. Floor reached artistic hell and came back, stronger than ever. Really looking for their concert in Dallas next May with Sabaton and Delain (one of the best lineup in one concert). The second is the new album from Sirenia. Aylin and Veland are on their way to finish their latest album and I hope they are leaving the abysmal depths of the Northern Sea. Up until today, “The Enigma of Life” still remains an enigmatic bust. For those who discovered Xandria with Manuella Kraller as front singer, I really wish her good luck in 2015 as a year for her to join a band. Manuella is extremely talented (at first I thought Tarja was singing, to give you an idea of her talent) and really she deserve to join a Symphonic Metal band and have her place among Simone, Sharon, Tarja, Liv and other metal divas. Viel Glueck Manuella! Finally it seems the French Symphonic metal band “Whyzdom” is on the way to release a new album in early 2015. Bonne chance les amis!

The other event I am looking for is seeing Serj getting back with SOAD for commemorating the 100th anniversary of the Armenian Genocide and thats for me some tragic events of my genome coming back to haunt.

And you? What was your discoveries and top albums? Feel free to leave your feedback.

World Stem Cell Summit 2014, wrapup and impressions

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Just coming out the #WSCS14 conference that was held in San Antonio this year. Oh boy, three days of intense scientific contents and networking, three days of running from one conference room to another and looking at the program to be sure to pick the most relevant one. Time to metabolize and put some thoughts on a blog.

This was a great meeting, especially for one that I just got introduced. Lots of good speakers, interactions with the exhibitors and with other presenters. It was a truly unique experience to get to know the San Antonio biomedical research area and strengths. It clearly seems to me that UTHSC San Antonio branch really try to built a strong research on stem cells research, including non-human primate based research. It was for me a particular chance to identify possible collaboration within the state of Texas.

The second aspect that i appreciate was the eclecticism of attendees at this meeting. Typically, you have conferences designed by scientists for scientists. Here I had the chance to discuss with scientists (sure it is a scientific meeting) but also with fundraising agencies, core facilities managers, patients and patients advocacy groups. And that is unique to have such patients advocacy groups that brings us back to what is our research is about: finding cures for patients because patients outside are suffering from their conditions and the medical advances are not reaching them. This is where as an outreach enthusiast I can grasp the need to scientists to reach out to the community and understand why their tax dollars means and how it get used.

Another session that i particularly appreciated was the “Ethics and Scientific Misconducts in Stem Cell Research” hosted by various speakers including “Retraction Watch” Ivan Oranovsky and Graham Parker, Stem Cell Development Chief-Editor. The stem research is a promising research field, a fantastic boat to sail on but because it has enormous potential and impact on medical research that can be easily hijacked by snake oil sellers (those claiming to have working stem cell therapies beyond the stage of clinical trials) and the forgery (remember the embryonic stem cell cloning fraud from South Korea in 2004)?

Here I am, waiting for my flight back to the Panhandle, now boosted more than ever to push on my research interests, developing new avenues of collaborations and hopefully developping the stemming stem cell research community in Texas.

How partnering with someone half way around the world could help develop new treatments here in California

The Stem Cellar

Much as we love California, and we really do, even we have to admit that genius knows no boundaries and that great scientific research is taking place all over the world. As our goal as an agency is to accelerate the development of successful therapies for people in need it only makes sense that we would try and tap into that genius, wherever it is, in whatever way we can. That’s where our Collaborative Funding Partnership (CFP) program comes in.

Michel Hivert, Executive Director at MATIMOP (L) and ICOC Chairman Jonathan Thomas Michel Hivert, Executive Director at MATIMOP (L) and ICOC Chairman Jonathan Thomas

Under Proposition 71, the voter-approved initiative that created the stem cell agency, all the research we fund has to be in California. But that doesn’t mean we can’t help create collaborations between researchers here – that we fund – and researchers in other parts of the world who get funding from other sources. And we do just that…

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