thescientist--2020-09-28--COVID-19 Ushers in the Future of Conferences

The Society for Mathematical Biology and the European Society for Mathematical and Theoretical Biology had planned to hold a joint conference this August in Heidelberg , Germany .
But by the time spring rolled around , and the pandemic took firm hold of global travel , that was looking less and less likely .
On May 9 , the organizers postponed the in-person meeting until 2021 .
Amber Smith , a mathematical biologist at the University of Tennessee Health Science Center , and her fellow conference organizers stepped in to put together a virtual conference to give researchers a chance @ @ @ @ @ @ @ .
“ We were really trying to have a meeting that was as close to an in-person meeting as we could possibly have , ” Smith tells The Scientist .
They found Sococo , a platform that allows users to create an online building .
The organizers worked closely with virtual event coordinators at MathDept.org to design the Sococo virtual space so it would provide for socializing , networking , and mentoring , as well as hearing talks , seeing posters , and visiting the meeting ’ s corporate sponsors .
The goal @ @ @ @ @ @ @ build an experience that was more than sitting on a Zoom call watching talk after talk .
Participants , represented by little colored dots , entered a room by clicking on it and socialized using a feature that finds and pings colleagues for a video chat within the Sococo platform .
Via Zoom and webinar integration , all the people in a virtual presentation space attended the same talks and could ask questions by chat , audio , or video .
“ We got a ton of feedback from people saying that they @ @ @ @ @ @ @ .
Plus , the roughly 1,800 attendees represented more than 90 different countries—two to three times as many as at previous in-person Society for Mathematical Biology meetings .
The organizers plan to incorporate some virtual components into future conferences , even post-pandemic , she adds .
Plenty of meetings have gone virtual—or been canceled all together—since the beginning of the COVID-19 pandemic .
Proponents of online conferences point to reduced carbon emissions and increased accessibility as they make the case for making many of the pandemic-induced changes to meetings permanent .
It remains @ @ @ @ @ @ @ will support science in the same way as those made in person , but researchers around the world are trying out strategies to make virtual interactions a success .
Even before the pandemic forced the issue , scientists had been thinking about ways to reduce their carbon footprints , often by cutting back on air travel .
Between the record number of hurricanes in the Atlantic and fires in the western US , “ there is an urgent climate emergency , ” Abraham Palmer , a geneticist at the University of California , @ @ @ @ @ @ @ He and Chloe Jordan of the National Institute on Drug Abuse wrote an editorial published on September 16 touting the climate benefits of virtual meetings and exhorting scientists to act .
In a comment published August 13 , Palmer and Jordan describe how well an online planning meeting for the annual American College of Neuropsychopharmacology conference worked , while detailing the high cost—both in finances and CO emissions—of flying everyone to previous planning sessions .
Meeting online , whether it ’ s for a conference , study section , or worldwide lab gathering @ @ @ @ @ @ @ and it ’ s more convenient and economical , Palmer says .
When colleagues talk about missing the in-person stuff—dinners , drinks , and chance meetings when sharing a cab to or from an airport—he reminds them of the climate , financial , and time burden of all of those things that they ’ re missing and of the benefits of changing things up .
“ I really do hope that we ’ re going to look back in five or ten years and this will really have been a turning point where @ @ @ @ @ @ @ had leading up to COVID are never going to get rebuilt the same way they were , ” he says .
“ If we could do it for coronavirus , then we can do it for the climate crisis , too.
” Another benefit of meeting virtually is how many more people can access the conferences .
Researchers with caregiving responsibilities , disabilities , travel restrictions , scheduling conflicts , or limited funds are more likely to be able to attend a meeting online , says Sarvenaz Sarabipour , a computational biologist at @ @ @ @ @ @ @ international group of other early-career researchers posted a preprint on bioRxiv in April in which they curated a database of more than 270 past in-person conferences across scientific disciplines and evaluated them for inclusivity and sustainability .
They found that nearly 860,000 people spent more than $ 1.288 billion and generated upwards of 2 million tons of CO attending these conferences between 2016 and 2020 .
And for the most part , the gatherings had no public diversity or gender equity policies and didn ’ t offer childcare or formal accommodations for nursing @ @ @ @ @ @ @ alternatives , including taking things online and putting emphasis on regional conferences or coordinating several hubs of one larger conference , so less air travel would be required to attend , an idea that Palmer favors as well .
One of the main objections that people make to virtual meetings is the loss of networking time , especially for early-career researchers looking for jobs .
That criticism is unfounded , according to Sarabipour , who says that the websites of scientific journals , Twitter , and , more recently , massive Slack communities @ @ @ @ @ @ @ sources for jobseekers than once-yearly scientific meetings .
And despite the objections , the widespread adoption of online interactions during the pandemic “ begs the question of why we had to get to this point to do something this good.
” Sarabipour says .
The future is now Even before the pandemic , some researchers were working on making meetings better .
Last summer , Dan Goodman , a computational neuroscientist at Imperial College London , was involved in discussions with various colleagues about how to reduce the climate impact of conferences .
@ @ @ @ @ @ @ them online , and I was very skeptical of that , because I understood that the point of conferences is not just to look at the talks , it ’ s to meet people and to make new connections , ” he tells The Scientist .
“ I wasn ’ t really convinced that it would work ” online .
Then , in September 2019 , Goodman headed to the Conference on Cognitive Computational Neuroscience in Berlin , where he participated in a so-called mind matching session .
Participants provided three abstracts representative @ @ @ @ @ @ @ an algorithm with up to six other scientists , with whom they had 15-minute conversations .
“ My mind was absolutely blown by it , because I sat down , and I met six people that I ’ d never met before .
Two of them were working on exactly the same problem that I was working on , and I ’ d never heard of them , ” Goodman says .
“ I thought , ‘ Okay , if you have something as powerful as this , maybe you can get rid @ @ @ @ @ @ @ that social element , which is the point of the whole thing.
’ ” Goodman got in touch with University of Pennsylvania computational neuroscientist Konrad Kording and Titipat Achakulvisut , a graduate student in Kording ’ s group who led the development of the algorithm behind the mind matching .
It works by analyzing the text supplied by each person , as well as people they already know and people they hope to meet , and using those analyses to create a matrix of compatibility from which they pull possible matches .
They @ @ @ @ @ @ @ with job listings at meetings .
Along with some other colleagues , Goodman , Kording , and Achakulvisut started to plan an online computational neuroscience “ unconference ” called neuromatch that , in addition to having live talks via Crowdcast , would offer attendees six suggestions of people to speak to .
When things started to shut down due to COVID-19 , they quickly planned to hold the first neuromatch in March .
It was free , and 3,000 people attended .
In a point-of-view published in eLife in April , the organizers @ @ @ @ @ @ @ unconference .
In May , they held neuromatch 2.0 , also attended by about 3,000 people , and they ’ re planning neuromatch 3.0 for October .
For the first time , at neuromatch 3.0 , the organizers are charging a $ 25 registration fee that anyone can waive , no questions asked , and have opened the unconference to all neuroscientists , not just those interested in computational neuro .
Achakulvisut predicts that both online and in-person conferences will exist in the future , but that many neuromatch attendees will probably keep @ @ @ @ @ @ @ have people from all over the world that typically can ’ t show up ” if the conference is somewhere hard to get to—because of visa restrictions , distance , expense , or something else .
The sort of reach that a conference like neuromatch offers is just the beginning of what Mike Morrison , a web developer–turned–Michigan State University PhD student in work psychology , would like to see for science .
In a commentary published September 3 , he and his coauthors propose that scientific conferences , especially now that so @ @ @ @ @ @ @ be venues to update the whole world about the progress of science , not just the attendees .
Making all conference products—talks , posters , and abstracts—available as YouTube videos , images via FigShare , and preprints , they argue , could be a way to accelerate the pace of discovery by reaching everyone who might possibly contribute .
Conference administrators want this bigger impact for their attendees , Morrison says .
“ I ’ m really looking forward to hearing from a scientific conference to see if they want to try it.
@ @ @ @ @ @ @ propose is the # TwitterPoster , a three–to–five–slide PowerPoint presentation optimized to be shared as a GIF on Twitter—a tool that could also work in poster sessions at virtual meetings .
Sharing information in this flipbook-like style was so successful for a group of psychology grad students at University College Dublin earlier this year that their hashtag # GIFsFromYourGaff started trending .
“ On the internet , it is the nature of content to be freely available , spread widely , and permanent , ” Morrison tells The Scientist .
“ In science @ @ @ @ @ @ @ kept to ourselves , and—especially in the case of conference content—ephemeral .
What I want for the future is for science to close the gap with modern publishing methods , so it can be as available and easy to access as the rest of humanity ’ s content.
” The Transforming Vaccinology meeting originally planned for March was canceled , but the organizers and facilitating nonprofit Keystone Symposia regrouped to offer a COVID-19–specific vaccinology conference online in June .
In the context of a pandemic , it was perhaps even more critical to @ @ @ @ @ @ @ Fauci , director of the National Institute of Allergy and Infectious Diseases—able to come together and trade ideas .
The meeting “ got tremendous interest , and a lot of unpublished data was shared , ” says Thale Jarvis , Keystone Symposia ’ s chief scientific officer .
“ The organizers commented on the amazing .
.
.
democratization of the access to science.
” Participants from more than 60 countries engaged in extensive Q & A sessions with speakers via chat and video , and session moderators moved unanswered questions over to @ @ @ @ @ @ @ “ We have a variety of different ways that we try to try to connect people and , obviously , it ’ s never going to quite replicate those random interactions that happen at a face-to-face meeting , where you strike up a conversation on the way over to breakfast and end up discovering you have something in common scientifically , ” she says , “ but the sort of kneejerk reaction that because it ’ s a virtual format it won ’ t give a satisfying outcome is a bit unfair.
” @ @ @ @ @ @ @ Dey , a postdoc at University College London , has co-organized an online seminar series called pombeTalks that draws around 150 fission yeast researchers to Zoom every other week .
He and organizers of other virtual seminar series published a perspective in the Journal of Cell Science on August 1 , giving tips for starting and supporting such a community .
“ The online formats , whether it ’ s a virtual conference format or a seminar series format , are extremely good at broadly disseminating information .
.
.
and to make @ @ @ @ @ @ @ as possible , ” he says .
“ But the thing that I anecdotally observe in those interactions is that they are , with some exceptions , built upon preexisting , real-world relationships between people that have built up over years , ” he adds .
“ To me , it seems very difficult to de novo generate new scientific connections between people through these virtual formats , whatever they are.
” Dey ’ s concern is neither uncommon nor unfounded .
Maria Roche , who studies knowledge production and innovation at Harvard @ @ @ @ @ @ @ studies have shown that colocation—even temporary colocation at an in-person conference—can have an effect on the rate and quality of scientific collaborations .
“ Especially for innovators , being physically close at some point is , as far as the research indicates , pretty important , ” she says .
Psychologist Anne Frenzel and chronobiologist Martha Merrow , both of Ludwig Maximilian University of Munich , have collaborated to study participant experiences in virtual conferences created to reduce carbon emissions .
In the first iteration , some participants gathered at regional hubs to @ @ @ @ @ @ @ fully online .
The researchers have been exploring “ whether conference participants experience different levels of subjective satisfaction of the three basic psychological needs of relatedness ( feeling connected with the other conference attendees ) , competence ( feeling capable , effective , and proficient ) , and autonomy ( having a sense of choice ) when attending virtual versus live conferences , ” Frenzel writes in an email to The Scientist .
“ The relatedness factor seems the one which is most at stake with virtual formats.
” According to Frenzel , @ @ @ @ @ @ @ analyses so far indicate “ that virtual attendance , as compared to live attendance at the hubs , did not substantially affect psychological experiences of basic need satisfaction.
” But she cautions that she is reluctant to interpret those findings in a way that suggests virtual conferences work just as well as live conferences from a psychological perspective .
Psychological research addressing the impact of digitally-based versus in-person interaction is fairly limited , she adds , but this “ striking research gap .
.
.
is certainly currently being addressed in many ongoing @ @ @ @ @ @ @ ”

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MAXKABAKOV
The Society for Mathematical Biology and the European Society for Mathematical and Theoretical Biology had planned to hold a joint conference this August in Heidelberg, Germany. But by the time spring rolled around, and the pandemic took firm hold of global travel, that was looking less and less likely. On May 9, the organizers postponed the in-person meeting until 2021. Amber Smith, a mathematical biologist at the University of Tennessee Health Science Center, and her fellow conference organizers stepped in to put together a virtual conference to give researchers a chance to share the research still advancing worldwide.
“We were really trying to have a meeting that was as close to an in-person meeting as we could possibly have,” Smith tells The Scientist. They found Sococo, a platform that allows users to create an online building. The organizers worked closely with virtual event coordinators at MathDept.org to design the Sococo virtual space so it would provide for socializing, networking, and mentoring, as well as hearing talks, seeing posters, and visiting the meeting’s corporate sponsors.
The goal, according to Smith, was to build an experience that was more than sitting on a Zoom call watching talk after talk. Participants, represented by little colored dots, entered a room by clicking on it and socialized using a feature that finds and pings colleagues for a video chat within the Sococo platform. Via Zoom and webinar integration, all the people in a virtual presentation space attended the same talks and could ask questions by chat, audio, or video.
“We got a ton of feedback from people saying that they absolutely loved it,” Smith says. Plus, the roughly 1,800 attendees represented more than 90 different countries—two to three times as many as at previous in-person Society for Mathematical Biology meetings. The organizers plan to incorporate some virtual components into future conferences, even post-pandemic, she adds.
If we could do it for coronavirus, then we can do it for the climate crisis, too. —Abraham Palmer, University of California, San Diego
Plenty of meetings have gone virtual—or been canceled all together—since the beginning of the COVID-19 pandemic. Proponents of online conferences point to reduced carbon emissions and increased accessibility as they make the case for making many of the pandemic-induced changes to meetings permanent. It remains to be seen whether connections made online will support science in the same way as those made in person, but researchers around the world are trying out strategies to make virtual interactions a success.
Online benefits
Even before the pandemic forced the issue, scientists had been thinking about ways to reduce their carbon footprints, often by cutting back on air travel.
Between the record number of hurricanes in the Atlantic and fires in the western US, “there is an urgent climate emergency,” Abraham Palmer, a geneticist at the University of California, San Diego, tells The Scientist. He and Chloe Jordan of the National Institute on Drug Abuse wrote an editorial published on September 16 touting the climate benefits of virtual meetings and exhorting scientists to act. In a comment published August 13, Palmer and Jordan describe how well an online planning meeting for the annual American College of Neuropsychopharmacology conference worked, while detailing the high cost—both in finances and CO 2 emissions—of flying everyone to previous planning sessions.
Participants video chatting in the Sococo platform at the Society for Mathematical Biology meeting held online in August AMBER SMITH
Meeting online, whether it’s for a conference, study section, or worldwide lab gathering, works better than people expect, and it’s more convenient and economical, Palmer says. When colleagues talk about missing the in-person stuff—dinners, drinks, and chance meetings when sharing a cab to or from an airport—he reminds them of the climate, financial, and time burden of all of those things that they’re missing and of the benefits of changing things up.
“I really do hope that we’re going to look back in five or ten years and this will really have been a turning point where a lot of the things that we had leading up to COVID are never going to get rebuilt the same way they were,” he says. “If we could do it for coronavirus, then we can do it for the climate crisis, too.”
Another benefit of meeting virtually is how many more people can access the conferences. Researchers with caregiving responsibilities, disabilities, travel restrictions, scheduling conflicts, or limited funds are more likely to be able to attend a meeting online, says Sarvenaz Sarabipour, a computational biologist at Johns Hopkins University. She and an international group of other early-career researchers posted a preprint on bioRxiv in April in which they curated a database of more than 270 past in-person conferences across scientific disciplines and evaluated them for inclusivity and sustainability.
They found that nearly 860,000 people spent more than $1.288 billion and generated upwards of 2 million tons of CO 2 attending these conferences between 2016 and 2020. And for the most part, the gatherings had no public diversity or gender equity policies and didn’t offer childcare or formal accommodations for nursing a baby. The authors propose several alternatives, including taking things online and putting emphasis on regional conferences or coordinating several hubs of one larger conference, so less air travel would be required to attend, an idea that Palmer favors as well.
One of the main objections that people make to virtual meetings is the loss of networking time, especially for early-career researchers looking for jobs. That criticism is unfounded, according to Sarabipour, who says that the websites of scientific journals, Twitter, and, more recently, massive Slack communities of early-career scientists have been more consistent sources for jobseekers than once-yearly scientific meetings. And despite the objections, the widespread adoption of online interactions during the pandemic “begs the question of why we had to get to this point to do something this good.” Sarabipour says.
The future is now
Even before the pandemic, some researchers were working on making meetings better. Last summer, Dan Goodman, a computational neuroscientist at Imperial College London, was involved in discussions with various colleagues about how to reduce the climate impact of conferences. “People were saying we should make them online, and I was very skeptical of that, because I understood that the point of conferences is not just to look at the talks, it’s to meet people and to make new connections,” he tells The Scientist. “I wasn’t really convinced that it would work” online.
One of the main objections that people make to virtual meetings is the loss of networking time, especially for early-career researchers looking for jobs.
Then, in September 2019, Goodman headed to the Conference on Cognitive Computational Neuroscience in Berlin, where he participated in a so-called mind matching session. Participants provided three abstracts representative of their research and were matched by an algorithm with up to six other scientists, with whom they had 15-minute conversations.
“My mind was absolutely blown by it, because I sat down, and I met six people that I’d never met before. Two of them were working on exactly the same problem that I was working on, and I’d never heard of them,” Goodman says. “I thought, ‘Okay, if you have something as powerful as this, maybe you can get rid of in-person conferences because you can replace that social element, which is the point of the whole thing.’”
Goodman got in touch with University of Pennsylvania computational neuroscientist Konrad Kording and Titipat Achakulvisut, a graduate student in Kording’s group who led the development of the algorithm behind the mind matching. It works by analyzing the text supplied by each person, as well as people they already know and people they hope to meet, and using those analyses to create a matrix of compatibility from which they pull possible matches. They use a similar strategy for matching jobseekers with job listings at meetings.
Along with some other colleagues, Goodman, Kording, and Achakulvisut started to plan an online computational neuroscience “unconference” called neuromatch that, in addition to having live talks via Crowdcast, would offer attendees six suggestions of people to speak to. When things started to shut down due to COVID-19, they quickly planned to hold the first neuromatch in March. It was free, and 3,000 people attended.
In a point-of-view published in eLife in April, the organizers explain their strategies for running the online unconference. In May, they held neuromatch 2.0, also attended by about 3,000 people, and they’re planning neuromatch 3.0 for October. For the first time, at neuromatch 3.0, the organizers are charging a $25 registration fee that anyone can waive, no questions asked, and have opened the unconference to all neuroscientists, not just those interested in computational neuro.
Achakulvisut predicts that both online and in-person conferences will exist in the future, but that many neuromatch attendees will probably keep coming to online conferences. “We have people from all over the world that typically can’t show up” if the conference is somewhere hard to get to—because of visa restrictions, distance, expense, or something else.
The sort of reach that a conference like neuromatch offers is just the beginning of what Mike Morrison, a web developer–turned–Michigan State University PhD student in work psychology, would like to see for science. In a commentary published September 3, he and his coauthors propose that scientific conferences, especially now that so many are taking place virtually, could be venues to update the whole world about the progress of science, not just the attendees.
Making all conference products—talks, posters, and abstracts—available as YouTube videos, images via FigShare, and preprints, they argue, could be a way to accelerate the pace of discovery by reaching everyone who might possibly contribute. Conference administrators want this bigger impact for their attendees, Morrison says. “I’m really looking forward to hearing from a scientific conference to see if they want to try it.”
Another democratizing strategy Morrison and colleagues propose is the #TwitterPoster, a three–to–five–slide PowerPoint presentation optimized to be shared as a GIF on Twitter—a tool that could also work in poster sessions at virtual meetings. Sharing information in this flipbook-like style was so successful for a group of psychology grad students at University College Dublin earlier this year that their hashtag #GIFsFromYourGaff started trending.
Michigan State University PhD student Mike Morrison introduces the #TwitterPoster, a strategy for sharing science quickly on Twitter. MIKE MOrrison
“On the internet, it is the nature of content to be freely available, spread widely, and permanent,” Morrison tells The Scientist. “In science, our content is still locked-down, kept to ourselves, and—especially in the case of conference content—ephemeral. What I want for the future is for science to close the gap with modern publishing methods, so it can be as available and easy to access as the rest of humanity’s content.”
Effectiveness: to be determined
The Transforming Vaccinology meeting originally planned for March was canceled, but the organizers and facilitating nonprofit Keystone Symposia regrouped to offer a COVID-19–specific vaccinology conference online in June. In the context of a pandemic, it was perhaps even more critical to have so many researchers—including keynote speaker Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases—able to come together and trade ideas.
The meeting “got tremendous interest, and a lot of unpublished data was shared,” says Thale Jarvis, Keystone Symposia’s chief scientific officer. “The organizers commented on the amazing . . . democratization of the access to science.”
Participants from more than 60 countries engaged in extensive Q&A sessions with speakers via chat and video, and session moderators moved unanswered questions over to the public forum for further discussion. “We have a variety of different ways that we try to try to connect people and, obviously, it’s never going to quite replicate those random interactions that happen at a face-to-face meeting, where you strike up a conversation on the way over to breakfast and end up discovering you have something in common scientifically,” she says, “but the sort of kneejerk reaction that because it’s a virtual format it won’t give a satisfying outcome is a bit unfair.”
Especially for innovators, being physically close at some point is, as far as the research indicates, pretty important. —Maria Roche, Harvard Business School
Since early in the pandemic, Gautam Dey, a postdoc at University College London, has co-organized an online seminar series called pombeTalks that draws around 150 fission yeast researchers to Zoom every other week. He and organizers of other virtual seminar series published a perspective in the Journal of Cell Science on August 1, giving tips for starting and supporting such a community.
“The online formats, whether it’s a virtual conference format or a seminar series format, are extremely good at broadly disseminating information . . . and to make that as inclusive and effectively carbon neutral as possible,” he says. “But the thing that I anecdotally observe in those interactions is that they are, with some exceptions, built upon preexisting, real-world relationships between people that have built up over years,” he adds. “To me, it seems very difficult to de novo generate new scientific connections between people through these virtual formats, whatever they are.”
Dey’s concern is neither uncommon nor unfounded. Maria Roche, who studies knowledge production and innovation at Harvard Business School, tells The Scientist that studies have shown that colocation—even temporary colocation at an in-person conference—can have an effect on the rate and quality of scientific collaborations. “Especially for innovators, being physically close at some point is, as far as the research indicates, pretty important,” she says.
Psychologist Anne Frenzel and chronobiologist Martha Merrow, both of Ludwig Maximilian University of Munich, have collaborated to study participant experiences in virtual conferences created to reduce carbon emissions. In the first iteration, some participants gathered at regional hubs to cut down on travel and others participated fully online.
The researchers have been exploring “whether conference participants experience different levels of subjective satisfaction of the three basic psychological needs of relatedness (feeling connected with the other conference attendees), competence (feeling capable, effective, and proficient), and autonomy (having a sense of choice) when attending virtual versus live conferences,” Frenzel writes in an email to The Scientist. “The relatedness factor seems the one which is most at stake with virtual formats.”
According to Frenzel, preliminary and “poorly statistically powered” analyses so far indicate “that virtual attendance, as compared to live attendance at the hubs, did not substantially affect psychological experiences of basic need satisfaction.” But she cautions that she is reluctant to interpret those findings in a way that suggests virtual conferences work just as well as live conferences from a psychological perspective. Psychological research addressing the impact of digitally-based versus in-person interaction is fairly limited, she adds, but this “striking research gap . . . is certainly currently being addressed in many ongoing projects inspired by the COVID crisis.”


thescientist--2020-09-29--Discovery of More Ponds on Mars Hints at Possibility of Life

Two years after discovering a large , subterranean lake on Mars , a team of scientists has reaffirmed its original finding and identified three additional ponds using reflectance data from a spacecraft orbiting the planet .
The results , published September 28 in Nature Astronomy , suggest that the red planet is home to several liquid bodies of water , kept from freezing due to their high salt content .
If confirmed by further research , the south pole of Mars could become a strong target in the search for extraterrestrial life .
“ Not only did we confirm the @ @ @ @ @ @ @ [ results ] from our 2018 study , but we found three new bright areas ” generated by the ponds , Elena Pettinelli , a geophysicist at Roma Tre University in Italy and a coauthor on the new study , tells BBC News .
Compared to Pettinelli and colleagues ’ previous work , the new study includes a wider area , imaged with finer detail over a longer period of time .
Previously , the lake was identified based on 29 observations made between 2012 and 2015 .
The current study includes 134 @ @ @ @ @ @ @ 2012 to 2019 , Nature reports .
See “ Mars Has a Lake of Liquid Water : Study ” To visualize the lake and the three ponds , which are hidden more than one mile beneath the planet ’ s frozen surface , the team relied on technology used to study lakes buried under the ice at the Earth ’ s poles , according to the Associated Press .
The observations were made using a radar sounder on the European Space Agency ’ s Mars Express orbiter called the Mars Advanced Radar for @ @ @ @ @ @ @ .
MARSIS bounces radio waves off the surface and subsurface of Mars .
The properties of the signals that return to the satellite , such as its reflectance , tell scientists something about the nature of the terrain below .
The identification of the lake in 2018 began “ a new line of inquiry that ’ s very exciting , ” Jim Green , NASA ’ s chief scientist , told Nature at the time .
Its confirmation now lends even greater weight to the idea that Mars can in fact support liquid @ @ @ @ @ @ @ the team was able to further detail the lake ’ s proportions—roughly 18.6 by 12.4 miles in area .
The three ponds are thought to be separated from the lake , although the resolution of the MARSIS data is not fine enough to definitively confirm .
Even so , Roberto Orosei , a radioastronomer at the Istituto Nazionale di Astrofisica and the chief scientist of the study , tells BBC News that “ the discovery of an entire system of lakes implies that their formation process is relatively simple and common , and @ @ @ @ @ @ @ much of Mars ’ history.
” Mars was once warm and wet , similar to Earth .
Orosei and his colleagues report that the lakes could be kept liquid by their high salt content , which lowers their freezing point .
While the new evidence has stirred discussion among astronomers , not everyone is sold on this explanation .
Because Mars does not have an intact atmosphere like Earth , the pressure on its surface is much lower , keeping any water locked up as ice .
“ If the bright material really @ @ @ @ @ @ @ ’ s more likely to represent some sort of slush or sludge , ” Mike Sori , a planetary geophysicist at Purdue University who was not involved in the current research , tells Nature .
Jack Holt , a planetary scientist at the University of Arizona , similarly tells Nature that although he thinks the data are sound , he doesn ’ t agree with the team ’ s interpretation .
“ I do not think there are lakes .
There is not enough heat flow to support a brine here , even @ @ @ @ @ @ @ has shown that water saturated with certain dissolved salts , such as magnesium and calcium perchlorate , can remain liquid even at –123 °C ; the surface temperature of the south pole of Mars is thought to be roughly –113 °C , getting slightly warmer nearer to the planet ’ s interior .
Speaking to BBC News , Graziella Caprarelli , a planetary scientist at the University of Southern Queensland and coauthor on the new study , says those experiments show that brines could exist as liquids under conditions similar to those found @ @ @ @ @ @ @ obvious question is whether such lakes or ponds could support life .
Microbes have previously been found in subglacial lakes beneath Antarctic glaciers , but the salt does pose one possible issue .
Life as we know it is able to persist in water up to five times the saltiness of Earth ’ s oceans , but beyond 20 times the level of salt found in seawater , it becomes very difficult to survive , John Priscu , an environmental scientist at Montana State University , tells Nature .
“ There ’ s @ @ @ @ @ @ @ pools in Antarctica , ” says Priscu , who studies microbiology in icy environments and was not involved in the current study .
“ They ’ re just pickled .
And that might be the case [ on Mars ] .
” See “ Search for Life on the Red Planet ”

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Two years after discovering a large, subterranean lake on Mars, a team of scientists has reaffirmed its original finding and identified three additional ponds using reflectance data from a spacecraft orbiting the planet. The results, published September 28 in Nature Astronomy, suggest that the red planet is home to several liquid bodies of water, kept from freezing due to their high salt content. If confirmed by further research, the south pole of Mars could become a strong target in the search for extraterrestrial life.
“Not only did we confirm the position, extent and strength of the [results] from our 2018 study, but we found three new bright areas” generated by the ponds, Elena Pettinelli, a geophysicist at Roma Tre University in Italy and a coauthor on the new study, tells BBC News.
Compared to Pettinelli and colleagues’ previous work, the new study includes a wider area, imaged with finer detail over a longer period of time. Previously, the lake was identified based on 29 observations made between 2012 and 2015. The current study includes 134 observations taken across 75,000 square kilometres from 2012 to 2019, Nature reports.
To visualize the lake and the three ponds, which are hidden more than one mile beneath the planet’s frozen surface, the team relied on technology used to study lakes buried under the ice at the Earth’s poles, according to the Associated Press. The observations were made using a radar sounder on the European Space Agency’s Mars Express orbiter called the Mars Advanced Radar for Subsurface and Ionosphere Sounding (MARSIS). MARSIS bounces radio waves off the surface and subsurface of Mars. The properties of the signals that return to the satellite, such as its reflectance, tell scientists something about the nature of the terrain below.
The identification of the lake in 2018 began “a new line of inquiry that’s very exciting,” Jim Green, NASA’s chief scientist, told Nature at the time. Its confirmation now lends even greater weight to the idea that Mars can in fact support liquid water. In the newest study, the team was able to further detail the lake’s proportions—roughly 18.6 by 12.4 miles in area.
The team looked at the reflectance of the surface of Mars to determine the properties of the terrain below. The blue areas correspond to the lake and ponds the researchers believe contain liquid water. lauro et al., Nat astron, doi:10.1038/s41550-020-1200-6, 2020.
The three ponds are thought to be separated from the lake, although the resolution of the MARSIS data is not fine enough to definitively confirm. Even so, Roberto Orosei, a radioastronomer at the Istituto Nazionale di Astrofisica and the chief scientist of the study, tells BBC News that “the discovery of an entire system of lakes implies that their formation process is relatively simple and common, and that these lakes have probably existed for much of Mars’ history.” Mars was once warm and wet, similar to Earth.
Orosei and his colleagues report that the lakes could be kept liquid by their high salt content, which lowers their freezing point. While the new evidence has stirred discussion among astronomers, not everyone is sold on this explanation. Because Mars does not have an intact atmosphere like Earth, the pressure on its surface is much lower, keeping any water locked up as ice. “If the bright material really is liquid water, I think it’s more likely to represent some sort of slush or sludge,” Mike Sori, a planetary geophysicist at Purdue University who was not involved in the current research, tells Nature.
Jack Holt, a planetary scientist at the University of Arizona, similarly tells Nature that although he thinks the data are sound, he doesn’t agree with the team’s interpretation. “I do not think there are lakes. There is not enough heat flow to support a brine here, even under the ice cap.”
Previous research has shown that water saturated with certain dissolved salts, such as magnesium and calcium perchlorate, can remain liquid even at –123 °C; the surface temperature of the south pole of Mars is thought to be roughly –113 °C, getting slightly warmer nearer to the planet’s interior. Speaking to BBC News, Graziella Caprarelli, a planetary scientist at the University of Southern Queensland and coauthor on the new study, says those experiments show that brines could exist as liquids under conditions similar to those found at the poles of Mars.
The obvious question is whether such lakes or ponds could support life. Microbes have previously been found in subglacial lakes beneath Antarctic glaciers, but the salt does pose one possible issue. Life as we know it is able to persist in water up to five times the saltiness of Earth’s oceans, but beyond 20 times the level of salt found in seawater, it becomes very difficult to survive, John Priscu, an environmental scientist at Montana State University, tells Nature.
“There’s not much active life in these briny pools in Antarctica,” says Priscu, who studies microbiology in icy environments and was not involved in the current study. “They’re just pickled. And that might be the case [on Mars].”
See “Search for Life on the Red Planet”


thescientist--2020-09-29--Kids' Severe COVID-19 Reaction Bears Unique Immune Signature

For months now during the COVID-19 pandemic , doctors have observed a rare but consistent scenario in a small number of kids : It starts with a SARS-CoV-2 infection , which can be mild , even asymptomatic .
But weeks after the children seem to have fully recovered , they suddenly come down with symptoms that may include fever , vomiting , diarrhea , and severe abdominal pain .
“ They had the infection , they got through it .
And then all of a sudden .
.
.
they can have this collapse in their bodies a few weeks @ @ @ @ @ @ @ a neonatologist at the University of Texas Health San Antonio who recently coauthored a review on the condition , known as multisystem inflammatory syndrome in children ( MIS-C ) .
MIS-C is rare , and not all children who become severely ill or die from COVID-19 develop it .
According to the Centers for Disease Control and Prevention ( CDC ) , fewer than 1,000 cases of MIS-C have been reported so far in the US , the country hardest-hit by the COVID-19 pandemic , with 19 deaths .
Early reports of cases @ @ @ @ @ @ @ and Kawasaki disease , a rare condition linked to viral infections that involves inflammation in the blood vessels .
But there were notable differences observed between the two , such as the fact that Kawasaki mainly affects children under five , while even teenagers have come down with MIS-C. A study published earlier this month in Cell examines the similarities and differences between MIS-C and Kawasaki , as well as immune responses to COVID-19 in children and adults , to find unique features of the new condition and clues to the immune missteps @ @ @ @ @ @ @ think that everyone has been waiting for something like this , ” says Moreira of the work , which he was not involved in .
“ This one is the first study that I ’ ve really seen that is looking at pathways , signaling mechanisms .
.
.
.
It ’ s still premature , but it will start to tell us a little bit more about what is happening at the molecular level.
” The study team had been investigating Kawasaki disease before the pandemic , and had collected blood samples @ @ @ @ @ @ @ 2017 and 2019 .
They compared levels of white blood cells and proteins in those samples with those of 12 healthy children , 13 with MIS-C , and 41 with COVID-19 who did not develop MIS-C , along with 17 adults with severe COVID-19 .
“ One of the first things that happened when these kids [ with MIS-C ] started coming into the hospital was that people said , ‘ Well , maybe we should treat them the same way as we treat adults with severe disease , ’ ” says coauthor @ @ @ @ @ @ @ the Karolinska Institute and the Karolinska University Hospital in Sweden .
But the study found that the inflammatory response in MIS-C is “ completely different , ” he adds , indicating that it should probably be treated differently .
Specifically , the severe adult COVID-19 patients and MIS-C cases had much different blood levels of the cytokines used to guide the immune response , particularly interleukin ( IL ) -8 and IL-7—both of which are associated with , among other things , the number of infection-fighting immune cells available in the blood .
@ @ @ @ @ @ @ higher in adults with COVID-19 than in either Kawasaki or MIS-C patients .
Brodin and his coauthors found more overlap in the profiles of MIS-C and Kawasaki disease than they did with MIS-C and severe COVID-19 in adults .
MIS-C and Kawasaki both had lower overall numbers of T cells compared with healthy children .
Both conditions also involved the presence of antibodies to some of the body ’ s own proteins , known as autoantibodies , Brodin notes .
“ Some of them overlapped between MIS-C and Kawasaki , and some were @ @ @ @ @ @ @ ’ t see them in any of the other groups , ” he says , which “ suggests that there ’ s a pathological process induced by [ SARS-CoV-2 ] that is unique to this particular virus.
” One possible explanation , he says , has to do with a phenomenon other studies have observed : that SARS-CoV-2 tamps down an early , innate immune defense cells mount to viral infections , known as the interferon response .
That could lead to a scenario where , in the later adaptive immune response , @ @ @ @ @ @ @ potentially then have a less-focused response and more of a wide response that might cross react and lead to autoimmunity , ” he says , adding that this has yet to be proven .
Another hypothesis , put forward in a study published yesterday in PNAS , is that a unique part of SARS-CoV-2 ’ s spike protein acts as a so-called superantigen that causes an excessive adaptive immune response .
Brodin says the idea is “ interesting , ” but adds that in his opinion , “ the evidence in the paper @ @ @ @ @ @ @ this is the principal mechanism ” in causing MIS-C .
The finding from Brodin ’ s Cell study that there are clear differences between the proteins found in the blood of Kawasaki and MIS-C patients jibes with what Betsy Herold , a pediatric infectious disease physician and virologist at Albert Einstein College of Medicine and Montefiore Health System , has seen in the clinic , she says .
( Herold was not involved in the Cell study . )
That finding , she says , “ is very important , because I think @ @ @ @ @ @ @ out there [ about ] , is this Kawasaki ?
And I think the answer is no , it has some overlap with Kawasaki , but it ’ s not the same thing.
” Herold , along with her spouse Kevan Herold , an immunobiologist at Yale University , recently led their own study that touched on MIS-C , although its primary aim was to ferret out differences in the immune responses to SARS-CoV-2 between children and adults .
In that study , the cytokine responses of infected children who later went on @ @ @ @ @ @ @ who did not , leading Betsy Herold to think that both groups of patients do indeed mount an effective innate response initially .
“ We postulate that [ the MIS-C patients ] made a good innate response and that they protected their lungs from disease , and then .
.
.
a few weeks later , when their antibody responses start kicking in , there ’ s something else that ’ s perhaps a little bit dysregulated , ” she says .
But , notes Kevan Herold , “ I think we still @ @ @ @ @ @ @ answer ” on what it is that causes some children to develop MIS-C after a SARS-CoV-2 infection , while most don ’ t .
The good news , says Moreira , is that “ even though we still don ’ t completely understand a lot of the mechanistic drivers of the disease , [ MIS-C patients ] are responding to common therapies that we use for Kawasaki disease.
” These include intravenous immunoglobulin and steroids .
“ So they work , but I think we would feel more comfortable if we knew how @ @ @ @ @ @ @ .
Consiglio et al.
, “ The immunology of multisystem inflammatory syndrome in children with COVID-19 , ” Cell , doi : https : //doi.org/10.1016/j.cell.2020.09.016 , 2020 .
C.A Pierce et al.
, “ Immune responses to SARS-CoV-2 infection in hospitalized pediatric and adult patients , ” Sci Transl Med , doi:10.1126/scitranslmed.abd5487 , 2020 .

ABOVE: © ISTOCK.COM, STUDIO9
For months now during the COVID-19 pandemic, doctors have observed a rare but consistent scenario in a small number of kids: It starts with a SARS-CoV-2 infection, which can be mild, even asymptomatic. But weeks after the children seem to have fully recovered, they suddenly come down with symptoms that may include fever, vomiting, diarrhea, and severe abdominal pain.
“They had the infection, they got through it. And then all of a sudden . . . they can have this collapse in their bodies a few weeks later,” says Alvaro Moreira, a neonatologist at the University of Texas Health San Antonio who recently coauthored a review on the condition, known as multisystem inflammatory syndrome in children (MIS-C).
MIS-C is rare, and not all children who become severely ill or die from COVID-19 develop it. According to the Centers for Disease Control and Prevention (CDC), fewer than 1,000 cases of MIS-C have been reported so far in the US, the country hardest-hit by the COVID-19 pandemic, with 19 deaths. Early reports of cases of MIS-C pointed to similarities between it and Kawasaki disease, a rare condition linked to viral infections that involves inflammation in the blood vessels. But there were notable differences observed between the two, such as the fact that Kawasaki mainly affects children under five, while even teenagers have come down with MIS-C. A study published earlier this month in Cell examines the similarities and differences between MIS-C and Kawasaki, as well as immune responses to COVID-19 in children and adults, to find unique features of the new condition and clues to the immune missteps that bring it about.
“I think that everyone has been waiting for something like this,” says Moreira of the work, which he was not involved in. “This one is the first study that I’ve really seen that is looking at pathways, signaling mechanisms. . . . It’s still premature, but it will start to tell us a little bit more about what is happening at the molecular level.”
The study team had been investigating Kawasaki disease before the pandemic, and had collected blood samples from 28 children with the condition between 2017 and 2019. They compared levels of white blood cells and proteins in those samples with those of 12 healthy children, 13 with MIS-C, and 41 with COVID-19 who did not develop MIS-C, along with 17 adults with severe COVID-19.
A comparison of the symptoms of Kawasaki disease and MIS-C MAREK SCUPINSKI, CONSIGLIO ET AL./CELL
“One of the first things that happened when these kids [with MIS-C] started coming into the hospital was that people said, ‘Well, maybe we should treat them the same way as we treat adults with severe disease,’” says coauthor Petter Brodin, a pediatric immunologist at the Karolinska Institute and the Karolinska University Hospital in Sweden. But the study found that the inflammatory response in MIS-C is “completely different,” he adds, indicating that it should probably be treated differently. Specifically, the severe adult COVID-19 patients and MIS-C cases had much different blood levels of the cytokines used to guide the immune response, particularly interleukin (IL)-8 and IL-7—both of which are associated with, among other things, the number of infection-fighting immune cells available in the blood. Levels of both of those cytokines were higher in adults with COVID-19 than in either Kawasaki or MIS-C patients.
Brodin and his coauthors found more overlap in the profiles of MIS-C and Kawasaki disease than they did with MIS-C and severe COVID-19 in adults. MIS-C and Kawasaki both had lower overall numbers of T cells compared with healthy children. Both conditions also involved the presence of antibodies to some of the body’s own proteins, known as autoantibodies, Brodin notes. “Some of them overlapped between MIS-C and Kawasaki, and some were unique to MIS-C, and we didn’t see them in any of the other groups,” he says, which “suggests that there’s a pathological process induced by [SARS-CoV-2] that is unique to this particular virus.”
One possible explanation, he says, has to do with a phenomenon other studies have observed: that SARS-CoV-2 tamps down an early, innate immune defense cells mount to viral infections, known as the interferon response. That could lead to a scenario where, in the later adaptive immune response, T cells and antibody-producing B cells “potentially then have a less-focused response and more of a wide response that might cross react and lead to autoimmunity,” he says, adding that this has yet to be proven.
Another hypothesis, put forward in a study published yesterday in PNAS, is that a unique part of SARS-CoV-2’s spike protein acts as a so-called superantigen that causes an excessive adaptive immune response. Brodin says the idea is “interesting,” but adds that in his opinion, “the evidence in the paper are not strong enough to conclude that this is the principal mechanism” in causing MIS-C.
The finding from Brodin’s Cell study that there are clear differences between the proteins found in the blood of Kawasaki and MIS-C patients jibes with what Betsy Herold, a pediatric infectious disease physician and virologist at Albert Einstein College of Medicine and Montefiore Health System, has seen in the clinic, she says. (Herold was not involved in the Cell study.) That finding, she says, “is very important, because I think there’s a lot of confusion out there [about], is this Kawasaki? And I think the answer is no, it has some overlap with Kawasaki, but it’s not the same thing.”
Herold, along with her spouse Kevan Herold, an immunobiologist at Yale University, recently led their own study that touched on MIS-C, although its primary aim was to ferret out differences in the immune responses to SARS-CoV-2 between children and adults. In that study, the cytokine responses of infected children who later went on to develop MIS-C matched those of kids who did not, leading Betsy Herold to think that both groups of patients do indeed mount an effective innate response initially. “We postulate that [the MIS-C patients] made a good innate response and that they protected their lungs from disease, and then . . . a few weeks later, when their antibody responses start kicking in, there’s something else that’s perhaps a little bit dysregulated,” she says. But, notes Kevan Herold, “I think we still don’t have a completely clear answer” on what it is that causes some children to develop MIS-C after a SARS-CoV-2 infection, while most don’t.
The good news, says Moreira, is that “even though we still don’t completely understand a lot of the mechanistic drivers of the disease, [MIS-C patients] are responding to common therapies that we use for Kawasaki disease.” These include intravenous immunoglobulin and steroids. “So they work, but I think we would feel more comfortable if we knew how, exactly, they work.”
C.R. Consiglio et al., “The immunology of multisystem inflammatory syndrome in children with COVID-19,” Cell, doi:https://doi.org/10.1016/j.cell.2020.09.016, 2020.
C.A Pierce et al., “Immune responses to SARS-CoV-2 infection in hospitalized pediatric and adult patients,” Sci Transl Med, doi:10.1126/scitranslmed.abd5487, 2020.


thescientist--2020-09-30--Sartorius Releases the 4th Edition of its Popular Live-Cell Analysis Handbook

The handbook was first launched in 2017 as a comprehensive reference guide for live-cell analysis technologies , with a focus on the complete suite of Incucyte® live-cell assays and reagents .
The handbook has been well received by Incucyte® users , generating over 2,500 requests of its 3rd edition .
The live-cell applications covered in the handbook include cell culture quality control assays and kinetic assays for cell health , proliferation , and viability ; cell migration and invasion , protein dynamics , complex cell models ; and neuronal models .
The 4th edition includes new sections on assays for @ @ @ @ @ @ @ , and Cell Cycle .
Additionally , there is a new chapter on kinetic assays for immune cell health and function .
“ This new edition truly encompasses the broad range of assays that can be accomplished across multiple therapeutic areas , allowing scientists to push the boundaries of cell-based assays .
Of particular interest in this edition are assays using live-cell indicators , such as CytoATP , for direct quantification of dynamic ATP changes in complex co-culture models .
With our unique assay , combining instrumentation , hardware and reagents , we @ @ @ @ @ @ @ tumor and stromal cells , which can mediate resistance to metabolically-targeted treatments , ” said Lindy O ’ Clair , Head of BioA Applications , Reagents and Consumables .
“ Giving scientists the tools they need to streamline their research and gain deeper biological insights , across a range of assay models , is imperative to driving novel advances in science.
” The Incucyte® Live-Cell Analysis System allows for real-time , uninterrupted monitoring of a range of cell types , from proliferating tumor cells to sensitive primary cells .
Validated Incucyte® live-cell assays @ @ @ @ @ @ @ to explore questions across a range of applications and research fields , without the limitations of end point assays .
The handbook is written by Sartorius scientists and product managers , and updated yearly to include the newest offerings .

The handbook was first launched in 2017 as a comprehensive reference guide for live-cell analysis technologies, with a focus on the complete suite of Incucyte® live-cell assays and reagents. The handbook has been well received by Incucyte® users, generating over 2,500 requests of its 3rd edition.
The live-cell applications covered in the handbook include cell culture quality control assays and kinetic assays for cell health, proliferation, and viability; cell migration and invasion, protein dynamics, complex cell models; and neuronal models. The 4th edition includes new sections on assays for evaluating Organoid Culture QC, ATP Metabolism, and Cell Cycle. Additionally, there is a new chapter on kinetic assays for immune cell health and function.
“This new edition truly encompasses the broad range of assays that can be accomplished across multiple therapeutic areas, allowing scientists to push the boundaries of cell-based assays. Of particular interest in this edition are assays using live-cell indicators, such as CytoATP, for direct quantification of dynamic ATP changes in complex co-culture models. With our unique assay, combining instrumentation, hardware and reagents, we are able to evaluate nutrient exchange between tumor and stromal cells, which can mediate resistance to metabolically-targeted treatments,” said Lindy O’Clair, Head of BioA Applications, Reagents and Consumables. “Giving scientists the tools they need to streamline their research and gain deeper biological insights, across a range of assay models, is imperative to driving novel advances in science.”
The Incucyte® Live-Cell Analysis System allows for real-time, uninterrupted monitoring of a range of cell types, from proliferating tumor cells to sensitive primary cells. Validated Incucyte® live-cell assays, reagents and protocols, allow scientists to explore questions across a range of applications and research fields, without the limitations of end point assays. The handbook is written by Sartorius scientists and product managers, and updated yearly to include the newest offerings.
To download the free 4th Edition Live-Cell Analysis Handbook, please visit: https://www.essenbioscience.com/en/communications/live-cell-analysis-handbook-4th-edition/


thescientist--2020-09-30--Baker is proud to announce the next generation of Cost of Ownership Calculator.

This version of the calculator allows you to compare an older generation of Baker ’ s biosafety cabinet or an average BSC .
Comparisons are available in multiple sizes ( 3ft , 4ft , 5ft , 6ft ) .
In addition , for those that have a very specific specification that they ’ d like to compare , a custom biosafety cabinet can be populated .
The model owned can then be compared against the latest Baker SterilGARD® biosafety cabinets so you can make an educated decision on for your next purchase !
Furthermore , this Cost of Ownership Calculator @ @ @ @ @ @ @ points than the previous version .
The additional data points include air conditioning and facility costs .
The results are calculated , and a number of categories are broken down to explain the total cost of ownership .
Results show the comparisons for the following categories : The final comparison takes into account all of the above and highlights the total cost to operate the cabinet ( $ /15 year ) with a note to show the savings from utilizing Baker ’ s Low Flow Mode .
From there , users can email @ @ @ @ @ @ @ edit any of their previous answers and generate a new set of results .
SterilGARD® e3 is an NSF* Class II Type A2 Biosafety Cabinet .
With the optimum balance of performance and energy efficiency , Baker ’ s biological safety cabinets protect personnel , product and the environment , all while increasing lab productivity and user comfort .

This version of the calculator allows you to compare an older generation of Baker’s biosafety cabinet or an average BSC. Comparisons are available in multiple sizes (3ft, 4ft, 5ft, 6ft). In addition, for those that have a very specific specification that they’d like to compare, a custom biosafety cabinet can be populated. The model owned can then be compared against the latest Baker SterilGARD® biosafety cabinets so you can make an educated decision on for your next purchase!
Furthermore, this Cost of Ownership Calculator uses different calculations and considers more data points than the previous version. The additional data points include air conditioning and facility costs.
The results are calculated, and a number of categories are broken down to explain the total cost of ownership. Results show the comparisons for the following categories:
Cabinet energy costs
Cost to condition room supply air due to cabinet head load
Cost to condition room supply exhausted air
Cost of facility to operate exhaust fan
Filter replacement costs
The final comparison takes into account all of the above and highlights the total cost to operate the cabinet ($/15 year) with a note to show the savings from utilizing Baker’s Low Flow Mode.
From there, users can email themselves or someone else the results or edit any of their previous answers and generate a new set of results.
SterilGARD® e3 is an NSF* Class II Type A2 Biosafety Cabinet. With the optimum balance of performance and energy efficiency, Baker’s biological safety cabinets protect personnel, product and the environment, all while increasing lab productivity and user comfort.


thescientist--2020-09-30--10x Genomics First to Market With Product to Simultaneously Capture Epigenome and Transcriptome

10x Genomics ( Nasdaq : TXG ) today announced it has begun shipping its Chromium Single Cell Multiome ATAC + Gene Expression solution to customers , marking the first commercial release of a product capable of simultaneously profiling the epigenome and transcriptome from the same single cell .
This multi-omic approach provides customers with the ability to link a cell ’ s epigenetic program to its transcriptional output , enabling a better understanding of cell functionality and bypassing the need to infer relationships through computer simulations .
“ This is one of our most ambitious undertakings at the company , @ @ @ @ @ @ @ Chief Scientific Officer of 10x Genomics .
“ By introducing the first solution that captures ATAC and gene expression simultaneously , researchers can gain even more clarity by combining two already powerful methods to profile biological systems at single cell resolution simultaneously for the first time.
” The new solution builds on an array of new products launched by the company this year for both its Chromium platform for single cell analysis as well as its Visium platform for spatial genomics .
Early customers already working with Chromium Single Cell Multiome ATAC + @ @ @ @ @ @ @ Medicine , Icahn School of Medicine at Mt .
Sinai and Spain ’ s Centro Nacional de Análisis Genómico .
“ My lab is interested in understanding why some immune cell types fail to fight the cancer , ” said Dr. Ansuman Satpathy , Assistant Professor of Pathology , Stanford University School of Medicine .
“ We plan to use 10x Genomics ' new assay to understand the epigenetic and transcriptional regulation of immune cell dysfunction directly in patient samples , and to use this information to precisely engineer more effective immunotherapies in @ @ @ @ @ @ @ we have relied on computational prediction to match a cell 's epigenome to a single-cell gene expression profile , ” said Dr. Holger Heyn , leader of the single cell genomics team at Spain ’ s Centro Nacional de Análisis Genómico that is working on delineating the dynamics underlying B-cell differentiation and activation .
“ 10x Genomics new multiome assay will allow us to directly measure what before could only be predicted , and offers a new gold standard that will confirm how accurate these predictions had been.
” '' With this new @ @ @ @ @ @ @ mechanisms affected by the non-coding risk genetic variation across a wide range of neuropsychiatric diseases , including Alzheimer ’ s , Parkinson ’ s , Schizophrenia , bipolar disorder and major depression , along with different severity of neuropathology and clinical symptomatology , '' added Dr. Panagiotis Roussos , Associate Professor of Genetics and Genomics Sciences , Icahn School of Medicine at Mount Sinai .
By using Chromium Single Cell Multiome ATAC + Gene Expression , researchers can : • Deepen their characterization of cell types and states with linked transcriptional and epigenomic @ @ @ @ @ @ @ profiles but functionally different chromatin landscapes • Combine discovery of regulatory elements with gene expression to explore gene regulatory interactions driving cell differentiation , development , and disease • Maximize insights from precious samples with multiple readouts from the same cell

10x Genomics (Nasdaq: TXG) today announced it has begun shipping its Chromium Single Cell Multiome ATAC + Gene Expression solution to customers, marking the first commercial release of a product capable of simultaneously profiling the epigenome and transcriptome from the same single cell. This multi-omic approach provides customers with the ability to link a cell’s epigenetic program to its transcriptional output, enabling a better understanding of cell functionality and bypassing the need to infer relationships through computer simulations.
“This is one of our most ambitious undertakings at the company,” said Ben Hindson, co-founder and Chief Scientific Officer of 10x Genomics. “By introducing the first solution that captures ATAC and gene expression simultaneously, researchers can gain even more clarity by combining two already powerful methods to profile biological systems at single cell resolution simultaneously for the first time.”
The new solution builds on an array of new products launched by the company this year for both its Chromium platform for single cell analysis as well as its Visium platform for spatial genomics. Early customers already working with Chromium Single Cell Multiome ATAC + Gene Expression include Stanford University School of Medicine, Icahn School of Medicine at Mt. Sinai and Spain’s Centro Nacional de Análisis Genómico.
“My lab is interested in understanding why some immune cell types fail to fight the cancer,” said Dr. Ansuman Satpathy, Assistant Professor of Pathology, Stanford University School of Medicine. “We plan to use 10x Genomics' new assay to understand the epigenetic and transcriptional regulation of immune cell dysfunction directly in patient samples, and to use this information to precisely engineer more effective immunotherapies in the future.”
“Until now, we have relied on computational prediction to match a cell's epigenome to a single-cell gene expression profile,” said Dr. Holger Heyn, leader of the single cell genomics team at Spain’s Centro Nacional de Análisis Genómico that is working on delineating the dynamics underlying B-cell differentiation and activation. “10x Genomics new multiome assay will allow us to directly measure what before could only be predicted, and offers a new gold standard that will confirm how accurate these predictions had been.”
"With this new technology, we can better understand the mechanisms affected by the non-coding risk genetic variation across a wide range of neuropsychiatric diseases, including Alzheimer’s, Parkinson’s, Schizophrenia, bipolar disorder and major depression, along with different severity of neuropathology and clinical symptomatology," added Dr. Panagiotis Roussos, Associate Professor of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai.
By using Chromium Single Cell Multiome ATAC + Gene Expression, researchers can:
Deepen their characterization of cell types and states with linked transcriptional and epigenomic analyses
Discover cells with similar transcriptional profiles but functionally different chromatin landscapes
Combine discovery of regulatory elements with gene expression to explore gene regulatory interactions driving cell differentiation, development, and disease
Easily interpret epigenetic profiles with key expression markers
Maximize insights from precious samples with multiple readouts from the same cell
Chromium Single Cell Multiome ATAC + Gene Expression is shipping to customers.


thescientist--2020-09-30--The Scientist Speaks Podcast - Episode 9

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In this month's episode, Repurposing Living Systems To Fight A Pandemic, brought to you by The Scientist and sponsored by Daicel Arbor Biosciences, Beckman Coulter Life Sciences, and PHC Corporation of North America, we discuss how one synthetic biologist pivoted his research to join the fight against the COVID-19 pandemic.
Tiffany Garbutt from The Scientist’s Creative Services team spoke with Michael Jewett, Walter P. Murphy Professor of Chemical and Biological Engineering in the McCormick School of Engineering and director of the Center for Synthetic Biology at Northwestern University, to learn more.
The Scientist Speaks is a podcast produced by The Scientist’s Creative Services team. Our podcast is by scientists and for scientists. Once a month, we will bring you the stories behind news-worthy molecular biology research.


thescientist--2020-09-30--Timothy Ray Brown, First Person to Be Cured of HIV, Dies

Timothy Ray Brown , who became the first HIV patient to be cured of the infection , died September 29 of leukemia—the very disease that led to the fortuitous eradication of the virus from his body .
He was 54 .
Until he disclosed his identity , Brown was known as the Berlin patient , whose HIV infection was eliminated in 2007 after undergoing a stem cell transplant to treat acute myeloid leukemia .
The bone marrow donor was selected to have a naturally occurring genetic variant that blocked HIV from entering cells .
The treatment worked—both for his cancer @ @ @ @ @ @ @ Timothy symbolized that it is possible , under special circumstances ” to cure HIV , Gero Hütter , the doctor who performed the stem cell transplant , tells the Associated Press .
Until 2016 , Brown remained the only person in the world to have been cured of AIDS using this approach and his unique experience motivated him to advocate for AIDS research .
As he told The Scientist in 2015 , “ I didn ’ t want to be the only one in my club.
” Brown was born in 1966 and @ @ @ @ @ @ @ living in Berlin when he received the diagnosis of leukemia and sought treatment from Hütter .
The doctor had previously read about individuals with variants in the CCR5 gene , which codes for a receptor on cell surfaces , that gives them natural immunity to HIV .
Upon finding out that Brown was HIV-positive , Hütter decided to look for a bone marrow donor who might have this variant .
As Hütter explained to The Scientist in 2015 , he screened dozens of donors until he found one with the so-called delta32 mutation @ @ @ @ @ @ @ the virus was gone from Brown ’ s cells , although his recovery was difficult and he required a second transplant to treat the leukemia .
In 2012 , Brown and activist Dave Purdy started the Cure for AIDS Coalition to raise awareness of HIV research .
According to a Facebook post by Brown ’ s partner , Tim Hoeffgen , “ Tim committed his life ’ s work to telling his story about his HIV cure and became an ambassador of hope .
Tim also gave numerous blood and tissue samples to @ @ @ @ @ @ @ of the bone marrow transplant precludes it from being applied more widely to HIV patients , but the insights gained from Brown ’ s successful cure have inspired further work on CCR5 .
For instance , in 2017 , researchers used CRISPR to disrupt the gene in human hematopoietic stem cells and demonstrated that these cells could ward off HIV infection in mice transplanted with them .
More recently , and controversially , the gene was a target of CRISPR-based editing in human embryos to make them resistant to HIV .
Brown never @ @ @ @ @ @ @ leukemia , however , relapsed five months ago .
“ Timothy was a champion and advocate for keeping an HIV cure on the political and scientific agenda , ” Sharon Lewin , the director of the Doherty Institute in Melbourne , Australia , tells the BBC .
“ It is the hope of the scientific community that one day we can honour his legacy with a safe , cost-effective and widely accessible strategy to achieve HIV remission and cure using gene editing or techniques that boost immune control .
”

ABOVE: SCOTT TABER
Timothy Ray Brown, who became the first HIV patient to be cured of the infection, died September 29 of leukemia—the very disease that led to the fortuitous eradication of the virus from his body. He was 54.
Until he disclosed his identity, Brown was known as the Berlin patient, whose HIV infection was eliminated in 2007 after undergoing a stem cell transplant to treat acute myeloid leukemia. The bone marrow donor was selected to have a naturally occurring genetic variant that blocked HIV from entering cells. The treatment worked—both for his cancer, and his viral infection.
“Timothy symbolized that it is possible, under special circumstances” to cure HIV, Gero Hütter, the doctor who performed the stem cell transplant, tells the Associated Press.
Until 2016, Brown remained the only person in the world to have been cured of AIDS using this approach and his unique experience motivated him to advocate for AIDS research. As he told The Scientist in 2015, “I didn’t want to be the only one in my club.”
Brown was born in 1966 and grew up in Seattle. He was living in Berlin when he received the diagnosis of leukemia and sought treatment from Hütter. The doctor had previously read about individuals with variants in the CCR5 gene, which codes for a receptor on cell surfaces, that gives them natural immunity to HIV. Upon finding out that Brown was HIV-positive, Hütter decided to look for a bone marrow donor who might have this variant. As Hütter explained to The Scientist in 2015, he screened dozens of donors until he found one with the so-called delta32 mutation.
Within months of the transplant, the virus was gone from Brown’s cells, although his recovery was difficult and he required a second transplant to treat the leukemia.
In 2012, Brown and activist Dave Purdy started the Cure for AIDS Coalition to raise awareness of HIV research. According to a Facebook post by Brown’s partner, Tim Hoeffgen, “Tim committed his life’s work to telling his story about his HIV cure and became an ambassador of hope. Tim also gave numerous blood and tissue samples to researchers after his cure.”
The invasiveness of the bone marrow transplant precludes it from being applied more widely to HIV patients, but the insights gained from Brown’s successful cure have inspired further work on CCR5. For instance, in 2017, researchers used CRISPR to disrupt the gene in human hematopoietic stem cells and demonstrated that these cells could ward off HIV infection in mice transplanted with them. More recently, and controversially, the gene was a target of CRISPR-based editing in human embryos to make them resistant to HIV.
Brown never again tested positive for HIV. His leukemia, however, relapsed five months ago.
“Timothy was a champion and advocate for keeping an HIV cure on the political and scientific agenda,” Sharon Lewin, the director of the Doherty Institute in Melbourne, Australia, tells the BBC. “It is the hope of the scientific community that one day we can honour his legacy with a safe, cost-effective and widely accessible strategy to achieve HIV remission and cure using gene editing or techniques that boost immune control.”


thescientist--2020-09-30--Sample Preparation with Single Cell Multiomics: Simultaneous Epigenomic and Transcriptomic Profiling

Sample Preparation with Single Cell Multiomics: Simultaneous Epigenomic and Transcriptomic Profiling from the Same Cell

Sample quality is key to running successful single cell multiomics experiments .
Beginning with nuclei suspensions , the Chromium Single @ @ @ @ @ Expression workflow generates paired RNA-seq and ATAC-seq libraries from the same single cell .
By @ @ @ @ @ with this new and innovative method , researchers can better characterize complex cell populations and @ @ @ @ @ development and disease .
In this webinar brought to you by 10x Genomics , experts @ @ @ @ @ prepare nuclei suspensions for Single Cell Multiome ATAC + Gene Expression experiments .
• Recommended @ @ @ @ @ cell lines , cryopreserved cells , and fresh and frozen tissue samples

FREE Webinar
Tuesday, November 10, 2020
12:00 - 1:30 PM, Eastern Time
Register Now
Sample quality is key to running successful single cell multiomics experiments. Beginning with nuclei suspensions, the Chromium Single Cell Multiome ATAC + Gene Expression workflow generates paired RNA-seq and ATAC-seq libraries from the same single cell. By capturing two modalities at once with this new and innovative method, researchers can better characterize complex cell populations and discover gene regulatory interactions driving development and disease. In this webinar brought to you by 10x Genomics, experts will discuss how to successfully prepare nuclei suspensions for Single Cell Multiome ATAC + Gene Expression experiments.
Topics to be covered
Recommended protocols for nuclei isolation from cell lines, cryopreserved cells, and fresh and frozen tissue samples
Sample preparation considerations, including cell sorting guidelines, for optimal library quality
Register Now
Meet the Speakers:
Sharmila Chatterjee, PhD
Scientist
10x Genomics
Zuleyma Peralta, PhD
Senior Support Scientist
10x Genomics


thescientist--2020-09-30--Digital PCR as a Universal Molecular Diagnostic Standard

Across all areas of life science research , scientists are increasingly aware of the need for the absolute quantification of nucleic acids .
To make their analyses actionable , they want to directly measure copies of a molecule , rather than rely on a simple positive or negative result .
The challenge , however , is that any tool that quantifies nucleic acids needs to be standardized against a universal reference material produced by an authoritative body such as the World Health Organization .
If this practice is not in place , the results obtained using this tool will not @ @ @ @ @ @ @ or locations .
Currently , there are no convenient primary reference measurement procedures for quantifying these standards .
As a result , it is difficult for research laboratories and diagnostics manufacturers to harmonize their nucleic acid quantification methods and produce reliable assays .
Fortunately , several metrology laboratories – labs that study the science of measurement – are seeking to develop a primary reference procedure using digital PCR technology .
This technique provides absolute quantification of nucleic acid samples without the need for calibration .
Metrology labs hope to prove digital PCR 's @ @ @ @ @ @ @ that could be used to quantify reference standards .
These standards could , in turn , be used to develop diagnostics and other tests with results that can be traced and trusted .
Developing a universal reference measurement procedure would impact every lab that handles nucleic acids .
However , one area where absolute RNA and DNA quantification would be especially useful is in clinical laboratories .
To create a reliable in vitro diagnostic , for instance , it needs to be calibrated against a standard that can be traced back to an @ @ @ @ @ @ @ compare the resulting data directly against different labs to ensure accurate interpretation .
Creating a traceable diagnostic starts with a hierarchy of successive calibration steps that ensure each test reports a true quantity based on a certified reference material ( CRM ) from a national metrology lab .
At the top of the hierarchy , metrologists calibrate a primary reference measurement procedure against the CRM .
This primary procedure ultimately supports the calibration of a diagnostic test and controls .
Each step in this hierarchy introduces uncertainty , so , according to the @ @ @ @ @ @ @ ( CCQM ) of the International Bureau of Weights and Measures ( BIPM ) , the primary reference measurement procedure must have “ the highest metrological properties.
” 1 It must operate according to a completed , described , and understood protocol , and must have its uncertainty completely written down in terms of SI units .
“ Any method that 's used as part of a primary reference measurement procedure , at its most accurate , would be SI-traceable , ” said Jim Huggett , Ph.D. , Principal Scientist ( Nucleic Acid @ @ @ @ @ @ @ and Innovation Division and Senior Lecturer in Analytical Microbiology at the University of Surrey .
Put another way : Its calibration should trace back to a universal standard , or CRM .
An SI-traceable reference measurement system for nucleic acids would benefit virtually all areas of research and medicine that rely on nucleic acid quantification .
In medicine , perhaps the biggest long-term impact will be seen with DNA quantification in cancer .
Accurately quantifying tumor load via circulating tumor DNA allows physicians to track both disease progression and treatment response .
But @ @ @ @ @ @ @ world and the greatest need for absolute quantification concerns the COVID-19 pandemic .
As authorities try to mitigate the spread of the virus , accurate quantification of SARS-CoV-2 viral loads in patients is critical .
This information helps authorities track the course of the disease and determine whether someone is contagious , with or without clinical symptoms .
In the absence of a reference standard , qPCR is only able to produce a qualitative result ( i.e .
Ct values ) .
Digital PCR , on the other hand , can fully quantify @ @ @ @ @ @ @ these areas , the current go-to method for quantifying primary reference materials is real-time quantitative polymerase chain reaction ( qPCR ) .
However , qPCR does not offer absolute quantitation .
To interpret a qPCR result in terms of nucleic acid quantity , users need to generate a standard curve using a serial dilution , a procedure that is prone to error and bias .
“ RT-PCR has played a big role in helping us quantify molecular DNA and RNA , and it ’ s used extensively , ” says Dr. Huggett .
@ @ @ @ @ @ @ s actually quite difficult to get a precise measurement and to know the trueness of the result because it ’ s on a log scale .
If you count 500 molecules , is it truly 500 molecules , or is it 50 or 5000 ?
That ’ s the type of variation you could see.
” In fact , digital PCR has already been used to quantify qPCR reference standards , exposing qPCR ’ s variability and inconsistency .
This variability makes qPCR less sensitive to rare genetic variants associated with cancer .
@ @ @ @ @ @ @ residual disease , as seen with low ctDNA concentrations or viral load , further complicating its role as a reliable and reproducible quantification method .
Another source of qPCR variability stems from differing amplification efficiencies of individual assays .
Researchers must interpret the quantity of a target nucleic acid sequence in a sample based on sequence amplification and the subsequently-generated fluorescent levels .
This can be an unreliable process , with several factors that can interfere with the results .
For example , samples containing highly variable sequences or mismatches between primers or @ @ @ @ @ @ @ and tertiary nucleic acid structures , can hamper the quantification of the target sequence .
qPCR can also be impacted by inhibitors in the sample that reduce the overall level of amplification and affect the final quantification .
For qPCR to be accurate , it must be calibrated using a standard curve , such as those produced using a primary reference measurement protocol that involves digital PCR .
Unlike qPCR , digital PCR doesn ’ t require calibration ; rather , it directly quantifies nucleic acid samples , making it eligible as an @ @ @ @ @ @ @ PCR works by directly counting the number of nucleic acid molecules in a sample , bypassing the need for a standard curve , and making it more precise and reliable .
The method uses a droplet reader to digitally count the number of target sequence copies in a sample that has been partitioned into tens of thousands of nanoliter-sized droplets .
“ Count ” is a recognized dimensionless SI unit , which means digital PCR could potentially serve as an SI-traceable primary reference measurement procedure for counting DNA copy number concentration .
Over @ @ @ @ @ @ @ across the globe have demonstrated the accuracy and sensitivity of digital PCR in many areas of research , supporting its potential role as a primary reference measurement procedure .
For example , David Dobnik , Ph.D. and his team at the National Institute of Biology , in Ljubljana , Slovenia have even shown that dPCR can accurately and precisely quantify viral titers in plants and genetic modifications in foods.3,4 Along with quantifying primary reference standards , digital PCR is being explored as a tool for evaluating the accuracy and clinical utility of laboratory @ @ @ @ @ @ @ National External Quality Assessment Service ( NEQAS ) in the UK , for example , uses digital PCR to score LDTs from 1,500 testing labs around the world .
Sandi Deans , Ph.D. , a member of the UK NEQAS Consortium , believes the biggest impact digital PCR will have as a reference measurement tool in medical testing labs is in cancer .
“ We do a lot of tumor testing , and tumor DNA tends to be present at low levels , ” Deans explained .
“ We need to make sure @ @ @ @ @ @ @ DNA present as possible to get a reportable result.
” Digital PCR helps Deans and her colleagues at NEQAS determine if the samples being used for medical testing contain sufficient quality DNA to produce a true and actionable result .
“ Detecting these ctDNA molecules means the difference between identifying sequence variants in tumors that can be treated using a personalized approach , or not , ” said Deans .
What Accurate DNA Quantification Means for the Future of Medicine At its core , a reliable primary reference measurement procedure is the key @ @ @ @ @ @ @ diverse range of scientific research .
In measuring nucleic acids , accurate calibration ensures that life science researchers and physicians can achieve a result they can trust , publish , and use to make clinical decisions that change lives .
With its ability to quantify nucleic acids without the need for calibration , digital PCR fits this need and will likely become an essential tool for laboratories around the world to calibrate their measurements against .
We can not yet predict the full impact of digital PCR 's adoption as a primary reference @ @ @ @ @ @ @ which the traceability of nucleic acid measurements will affect life science research , but it will undoubtedly bring positive change to clinical molecular laboratories and hospitals around the world .
Read more about the process of establishing digital PCR as an SI-traceable primary reference measurement tool in the whitepaper `` Counting DNA Molecule by Molecule '' .
• Bunk DM .
Reference materials and reference measurement procedures : an overview from a national metrology institute .
Clin Biochem Rev .
2007 ; 28 ( 4 ) :131-7 .
• Liu X , Feng @ @ @ @ @ @ @ .
Analytical comparisons of SARS-COV-2 detection by qRT-PCR and ddPCR with multiple primer/probe sets .
Emerg Microbes Infect .
2020 ; 9 ( 1 ) :1175-1179 .
• Mehle N , Dobnik D , Ravnikar M , Pompe novak M. Validated reverse transcription droplet digital PCR serves as a higher order method for absolute quantification of Potato virus Y strains .
Anal Bioanal Chem .
2018 ; 410 ( 16 ) :3815-3825 .

Across all areas of life science research, scientists are increasingly aware of the need for the absolute quantification of nucleic acids. To make their analyses actionable, they want to directly measure copies of a molecule, rather than rely on a simple positive or negative result. The challenge, however, is that any tool that quantifies nucleic acids needs to be standardized against a universal reference material produced by an authoritative body such as the World Health Organization. If this practice is not in place, the results obtained using this tool will not be reproducible across different tests, laboratories or locations.
Currently, there are no convenient primary reference measurement procedures for quantifying these standards. As a result, it is difficult for research laboratories and diagnostics manufacturers to harmonize their nucleic acid quantification methods and produce reliable assays. Fortunately, several metrology laboratories – labs that study the science of measurement – are seeking to develop a primary reference procedure using digital PCR technology. This technique provides absolute quantification of nucleic acid samples without the need for calibration. Metrology labs hope to prove digital PCR's worth as a primary reference measurement tool that could be used to quantify reference standards. These standards could, in turn, be used to develop diagnostics and other tests with results that can be traced and trusted.
Reliable RNA and DNA Quantification
Developing a universal reference measurement procedure would impact every lab that handles nucleic acids. However, one area where absolute RNA and DNA quantification would be especially useful is in clinical laboratories. To create a reliable in vitro diagnostic, for instance, it needs to be calibrated against a standard that can be traced back to an SI unit. This allows researchers to compare the resulting data directly against different labs to ensure accurate interpretation.
Creating a traceable diagnostic starts with a hierarchy of successive calibration steps that ensure each test reports a true quantity based on a certified reference material (CRM) from a national metrology lab. At the top of the hierarchy, metrologists calibrate a primary reference measurement procedure against the CRM. This primary procedure ultimately supports the calibration of a diagnostic test and controls. Each step in this hierarchy introduces uncertainty, so, according to the Consultative Committee for the Amount of Substance (CCQM) of the International Bureau of Weights and Measures (BIPM), the primary reference measurement procedure must have “the highest metrological properties.”1 It must operate according to a completed, described, and understood protocol, and must have its uncertainty completely written down in terms of SI units.
“Any method that's used as part of a primary reference measurement procedure, at its most accurate, would be SI-traceable,” said Jim Huggett, Ph.D., Principal Scientist (Nucleic Acid Research) in LGC's Health Science and Innovation Division and Senior Lecturer in Analytical Microbiology at the University of Surrey. Put another way: Its calibration should trace back to a universal standard, or CRM.
An SI-traceable reference measurement system for nucleic acids would benefit virtually all areas of research and medicine that rely on nucleic acid quantification. In medicine, perhaps the biggest long-term impact will be seen with DNA quantification in cancer. Accurately quantifying tumor load via circulating tumor DNA allows physicians to track both disease progression and treatment response.
But for now, the focus of the world and the greatest need for absolute quantification concerns the COVID-19 pandemic. As authorities try to mitigate the spread of the virus, accurate quantification of SARS-CoV-2 viral loads in patients is critical. This information helps authorities track the course of the disease and determine whether someone is contagious, with or without clinical symptoms. In the absence of a reference standard, qPCR is only able to produce a qualitative result (i.e. Ct values). Digital PCR, on the other hand, can fully quantify the virus in copies/μl.2
Variable qPCR Standards
In all of these areas, the current go-to method for quantifying primary reference materials is real-time quantitative polymerase chain reaction (qPCR). However, qPCR does not offer absolute quantitation. To interpret a qPCR result in terms of nucleic acid quantity, users need to generate a standard curve using a serial dilution, a procedure that is prone to error and bias.
“RT-PCR has played a big role in helping us quantify molecular DNA and RNA, and it’s used extensively,” says Dr. Huggett. “But in reality, it’s actually quite difficult to get a precise measurement and to know the trueness of the result because it’s on a log scale. If you count 500 molecules, is it truly 500 molecules, or is it 50 or 5000? That’s the type of variation you could see.”
In fact, digital PCR has already been used to quantify qPCR reference standards, exposing qPCR’s variability and inconsistency. This variability makes qPCR less sensitive to rare genetic variants associated with cancer. It also performs poorly when quantifying minimal residual disease, as seen with low ctDNA concentrations or viral load, further complicating its role as a reliable and reproducible quantification method.
Another source of qPCR variability stems from differing amplification efficiencies of individual assays. Researchers must interpret the quantity of a target nucleic acid sequence in a sample based on sequence amplification and the subsequently-generated fluorescent levels. This can be an unreliable process, with several factors that can interfere with the results. For example, samples containing highly variable sequences or mismatches between primers or probe sequences, as well as secondary and tertiary nucleic acid structures, can hamper the quantification of the target sequence. qPCR can also be impacted by inhibitors in the sample that reduce the overall level of amplification and affect the final quantification. For qPCR to be accurate, it must be calibrated using a standard curve, such as those produced using a primary reference measurement protocol that involves digital PCR.
Digital PCR as a Primary Reference Measurement Tool
Unlike qPCR, digital PCR doesn’t require calibration; rather, it directly quantifies nucleic acid samples, making it eligible as an SI-traceable primary reference measurement procedure. Digital PCR works by directly counting the number of nucleic acid molecules in a sample, bypassing the need for a standard curve, and making it more precise and reliable. The method uses a droplet reader to digitally count the number of target sequence copies in a sample that has been partitioned into tens of thousands of nanoliter-sized droplets. “Count” is a recognized dimensionless SI unit, which means digital PCR could potentially serve as an SI-traceable primary reference measurement procedure for counting DNA copy number concentration.
Over the past several years, metrology labs across the globe have demonstrated the accuracy and sensitivity of digital PCR in many areas of research, supporting its potential role as a primary reference measurement procedure. For example, David Dobnik, Ph.D. and his team at the National Institute of Biology, in Ljubljana, Slovenia have even shown that dPCR can accurately and precisely quantify viral titers in plants and genetic modifications in foods.3,4
Along with quantifying primary reference standards, digital PCR is being explored as a tool for evaluating the accuracy and clinical utility of laboratory developed tests (LDTs). The National External Quality Assessment Service (NEQAS) in the UK, for example, uses digital PCR to score LDTs from 1,500 testing labs around the world. Sandi Deans, Ph.D., a member of the UK NEQAS Consortium, believes the biggest impact digital PCR will have as a reference measurement tool in medical testing labs is in cancer.
“We do a lot of tumor testing, and tumor DNA tends to be present at low levels,” Deans explained. “We need to make sure we’ve got as much good-quality DNA present as possible to get a reportable result.” Digital PCR helps Deans and her colleagues at NEQAS determine if the samples being used for medical testing contain sufficient quality DNA to produce a true and actionable result. “Detecting these ctDNA molecules means the difference between identifying sequence variants in tumors that can be treated using a personalized approach, or not,” said Deans.
What Accurate DNA Quantification Means for the Future of Medicine
At its core, a reliable primary reference measurement procedure is the key to many forms of measurement across a diverse range of scientific research. In measuring nucleic acids, accurate calibration ensures that life science researchers and physicians can achieve a result they can trust, publish, and use to make clinical decisions that change lives. With its ability to quantify nucleic acids without the need for calibration, digital PCR fits this need and will likely become an essential tool for laboratories around the world to calibrate their measurements against. We cannot yet predict the full impact of digital PCR's adoption as a primary reference measurement tool or understand the extent to which the traceability of nucleic acid measurements will affect life science research, but it will undoubtedly bring positive change to clinical molecular laboratories and hospitals around the world.
Read more about the process of establishing digital PCR as an SI-traceable primary reference measurement tool in the whitepaper "Counting DNA Molecule by Molecule".
References