Category Archives: Uncategorized

Online Link to Intelligence Squared’s De-Extinction Debate in NYC on January 31, 2919 at 7 pm ET (or 4 pm PT)

Click https://www.youtube.com/embed/N-1iqmKlTs8 at 7 pm ET (or 4 pm PT) to listen on the De-Extinction debate.

The proposition for the debate is: “Don’t bring extinct creatures back to life” and arguing against are George Church, Professor of Genetics at Harvard and MIT & Founder, Personal Genome Project, and Stewart Brand, Co-Founder of Revive & Restore & Founder of Whole Earth Catalog and arguing for are Dr. Ross MacPhee: Curator, Department of Mammalogy, Division of Vertebrate Zoology at the American Museum of Natural History and Dr. Lynn J. Rothschild: Evolutionary Biologist & Astrobiologist. For more about the debate and the participants check my January 18, 2019 posting.

WordPress 5.0—Worse Christmas gift ever!

Without checking to see the reaction to this latest version, I updated this blog to the latest version of WordPress (WP). After using WP for over ten years and never having had a big problem, there was a surprise in store for me. There have been glitches in the past but for the most part, I have written, edited, and published my pieces with relative ease. This is no longer true.

First, I’m going to show some of the response from WordPress and from other users, then, I’m going to mention my specific issues with this ‘upgrade’, and finish with my sadder but wiser thoughts.

Shoulda, woulda, coulda

I should have … if only, I’d known, I would have … I could have … Only after days of struggling did I check for comments about this latest WordPress. First, I had to contend with a lot of ‘tech’ analysis. I don’t care about blocks, themes, ease of coding/programming, etc. All I wanted and still want to do is write and post my work. (sigh)

My first stop was wordpress.org and their forums. It was quite educational although perhaps not in the way that the developers might have hoped. Published in early December (probably Dec. 5 or 6, 2018), the ‘READ This First WordPress 5.0 Master List‘ by Marius L. J. starts out relatively well and then devolves to this (Note: Links have been removed),

Also keep in mind that not liking the direction of WordPress’s design is a not a bug. If you don’t like a feature, please don’t make a series of posts complaining about it. Look and see if someone already did, and post there, or consider joining the process earlier on (like in Beta or even test via SVN). What you’re seeing today is the result of thousands of hours of work and testing, and unless something is outright broken, it’s highly unlikely to be changed

Again, before you post

Make sure you’ve read this entire thread and New Features in 5.0 Article.
Go to your own install’s about page – example.com/wp-admin/about.php (or click the WordPress logo in the top corner) – to see what’s new.

Developers I once worked with used to joke bitterly that “there are no bugs just features,” meaning that developers can justify almost anything.

Getting back to the excerpt, the attitude seems a little less than welcoming . So, thank you, Marius L. J. for the gently scolding tone you’ve taken to address those of us who did not participate in beta or other testing. and for refusing to listen to anything other that reports on ‘bugs’.

Three other responses (Hint: they’re not happy either)

The first piece I’m highlighting is from a company that both provides a plug-in for the WordPress community and has a business based on their free product. From a December 4, 2018 posting on the Yoast SEO (search engine optimization) blog (Note: Links have been removed),

WordPress 5.0 is coming out December 6th [2018], or, as I’m writing this, the day after tomorrow. This came as a surprise to us, as this release date has only been communicated to the community today. Given this short notice, we thought it would be wise to give you advice on what you should do. Note that Yoast SEO has been ready for this release for a few weeks. [emphases mine]

If there is no compelling reason for you to update, our suggestion is going to be: wait. WordPress 5.0 will probably be more stable in January than it is now. Let’s be clear: we absolutely love Gutenberg and what Yoast SEO looks like in Gutenberg. The Schema blocks we’ve added are very cool. Yoast SEO is ready. We don’t think WordPress 5.0 is as stable as it should be.

Surprise? only? today? short notice? All of this conveys a less than happy response to the news from WordPress from people who know WordPress and likely did participate in beta testing and all the rest of it.

Sarah Gooding’s December 5, 2018 posting on WP Tavern provides some insight into some of the battles taking place amongst the hardcore WordPress community,


Official feedback channels and social media erupted with largely negative feedback on the decision, as the new release date has 5.0 landing the day before WordCamp US begins. This is a travel day for many attending the conference. It also means both of the planned follow-up releases will be expected during the upcoming weeks when many have scheduled time off for major world holidays

Yoast CEO Joost de Valk, one of the most vocal critics of the 5.0 timelime, posted a public message of dissent that resonated with many on Twitter

“We vehemently disagree with the decision to release WordPress 5.0 on December 6th, and think it’s irresponsible and disrespectful towards the community.

However, we’re now going to try and support the community as well as possible and we hope to show everyone that Gutenberg is indeed a huge step forward.”

There’s more in Goodings’s article,

“This decision was made in disregard to earlier specific timelines and promises, and does not take the realities on the ground into account,” Morten Rand-Hendricksen said. “I agree with @yoast it is both irresponsible and disrespectful.

Although reactions on Twitter run the gamut from unbridled optimism to full on outrage, many of those commenting on the schedule have fallen into resignation, convinced that community feedback never really mattered when it came to scheduling the release

Mullenweg’s [Matt Mullenweg, WordPress big cheese] rationale behind announcing the release date with three days notice is that Gutenberg and/or the Classic Editor are already active on more than 1.3 million sites. Users do not have to upgrade to WordPress 5.0 until they are ready. If they opt for the Classic Editor, the editing experience “will be indistinguishable from 4.9.8.”

Users who are informed enough to make this choice will be well-prepared when they see that 5.0 update in their dashboards. However, one of the chief concerns is that millions of WordPress users will update without testing. …

As noted, I am one of those millions who did “update without testing.”

Gooding finishes with this,

“I so want to be supportive of this release,” Teague [John Teague] said. “But between the top down, heavily Automattic managed process, poor release communication, super short RC2, RC3, punting on accessibility, and now this two-day notice to 5.0 release – it reminds me of an old Air Force saying when instructors sent barely trained pilots up for their first solo:

“Send em up and let God grade em.’”

Finally, there’s a December 7, 2018 posting on The Mud Room blog (from the Mudflower Media website) where you are warned specifically about the editor (Gutenberg), Note: Links have been removed,

Today I excitedly downloaded WordPress 5.0 with the much-touted Gutenberg Post Editor, and really looking forward to using what I was sure was going to be a massive upgrade to the classic WordPress editor. Well…trust me when I tell you it was massive, but an upgrade? Hardly.

Prince Charles was talking with some people many years ago, and the subject of the “king of books” the King James Bible was brought up. The prince and the men discussed at length the glorious history of the King James, and the impact it has had upon the world. All agreed it was something quite special.

  Then one of the men turned to Prince Charles and asked him what he thought about the new versions, written in “modern English”. The prince thought for a moment and then he said

“I think they’ve improved it worse”

I can think of no better description of the new WordPress Gutenberg Editor than to say “they’ve improved it worse”. Gutenberg was designed by people who design responsive websites, and it utilizes something called a “drag-and-drop” interface. This is a great feature when found living inside a WordPress theme. It makes new page creating and updating old ones a breeze.

But what drag-and-drop offers in benefits for theme builds, it takes that away inside an editor where a writer or an author is trying to compose something. As I type what you are reading right now, I am using WordPress 5.0, but have added the Classic plugin to restore the post editor to it’s previous glory. So as I create this article, the layout is nearly identical to how it will look on the front end when view online. This is not what Gutenberg provides.


The WordPress developers are just that, developers. They are not content creators and writers, as it is obvious in this new editor design. I have spend the better part of 20 years as a UI/UX [user interface/user experience] expert, working on huge multi-million dollar projects at the highest level of the Fortune 500 world. And the first thing that jumps out at me when I look at Gutenberg is how nothing makes sense, nothing is where you would expect it to be.

I am now a ‘sadder but wiser’ users. Next, specific issues

WordPress 5.0 editor issues from a writer’s perspective

A few things before I launch into my list, first, I waited almost a week before downloading the new version. Also, I work on a PC (personal computer as opposed to an Apple product). It’s a desktop system and I’m running it on Windows 7.0. Two plug-ins are currently enabled: Akismet and UpDraftPlus; I have the latest versions of both, which are supposedly compatible with WordPress 5.0 and I use the Twenty Twelve theme.

Invisibility

So, the almost invisible lines around the blocks are a feature? Also, does making some of my editing choices a slightly darker grey and disappearing some of those choices from the block when I make a decision about what I want to do in that text block also count as a feature?

Vocabulary

Seriously, is near invisibility a bug or a feature? Or, is it something the developers don’t care about consequently, it’s neither and not to be discussed?

Disappearing options

There’s one more than one kind of invisibility, things disappear. For example, if I write some text in a block and, then, change my mind, delete my text, and decide I’d like to embed image? I can’t.) Plus, the instant I put my cursor into the block, the options fade to a difficult-to-see grey. Not quite as hard to see as the lines around the blocks but making options harder to see seems like an odd choice to me. Is this another feature or dare I call it a bug?

Tags

I use the tagging function extensively and it is now broken. First, where there was once an ‘add tag’ box and a field below showing tags already added or not, there is now only an ‘add new tag’ box. What this means functionally (for me, if no one else) is that removing a tag has become too easy. in fact, this part of the feature could be described as designed for failure. I can guarantee that you will at some point inadvertently remove one or more of your tags without noticing.

Second, I have great difficulty saving my tags which I prepare in a group. (I put all of my post into a text file and then trim away most of the text leaving only the words that I want to use as tags and then copy into the ‘add new tag’ box. The new ‘save draft/saved’ function on the top right hand side of my screen doesn’t always register the addition of any tags. I can take many attempts before the system allows me to ‘save’. And, if I am allowed to save tags, they may disappear from my ‘add tag’ box anyway. Plus, if they don’t disappear in my now ‘saved’ draft, they may disappear when I ‘preview’ my post.

I have tried a few tactics to overcome this problem/bug/feature. (1) I have tried to add tags in groups and then saving, when and if I’m allowed to. (failure, most of the time) (2) I have tried to add each tag individually. (failure most of the time) (3) I have persisted in my efforts to add my tags by repeating the save over and over. (failure most of the time)

I have on occasion managed to force the system into accepting my tags using one or more of the above tactics. Weirdly, I have occasionally not had to use any of my tactics because the function worked. BTW, typing each tag individually seems to work best but it is the least efficient method for me.

Save Draft function

In addition to the problems noted previously with ‘Save Draft’, I have occasionally noted that the system doesn’t sense when I’ve made a change in my text and, in this latest WordPress, I can no longer override the system and force it to save.

One more thing, saving tags takes a much longer time even when the system fails to save them.

Talking with developers

Guess what? I don’t ‘beta test’. I don’t want to load software onto my system until I’m reasonably certain it won’t break anything. I don’t have the technical skills to fix the problems.

By the way, I worked with developers for years (I was the writer). At the best of times it can be difficult as we don’t use the same vocabulary or share a perspective on the problem. It’s easiest to do this in person. Second best, is the phone. However, writing it up is almost always a misery.

Even in person, I have found the inevitable questions from a developer difficult to understand and no matter how simply I describe my problem, the developer doesn’t understand me. Should we successfully pass that stage, I’m then presented with a solution that may require my intervention into the code. As I noted earlier, I don’t have the technical skills (or confidence, for that matter).

There is no one to blame for this communication problem; it’s a function of perspective and vocabulary. However, I do blame developers who don’t recognize there is a gap and/or arrogantly dismiss users’ concerns. Marius L.J.’s posting brought back memories.

Finding a fix, breaking faith, and moving on (maybe)

After struggling with this new WordPress for two and a half weeks (I think I downloaded it on Dec. 10, 2018), I’m ready to try the Classic Editor plug-in although I may wait until after the New Year to see if anything that matters to me has been fixed. Sadly, I don’t think the situation with the tags will be affected.

As for WordPress itself, my faith is shaken. I have depended on it and even taken it for granted but i can’t anymore. This build was not ready to be released and the person or persons who made the decision knew it and didn’t care. WordPress: Once you’ve shaken someone’s faith in your product or in you, it’s very hard to regain.

As a consequence of all this, I’m looking at the possibility of replacing WordPress. I’m not saying I’m going to do it but it is no longer unthinkable as it would have been at the beginning of December 2018.

‘One health in the 21st century’ event and internship opportunities at the Woodrow Wilson Center

One health

This event at the Woodrow Wilson International Center for Scholars (Wilson Center) is the first that I’ve seen of its kind (from a November 2, 2018 Wilson Center Science and Technology Innovation Program [STIP] announcement received via email; Note: Logistics such as date and location follow directly after),

One Health in the 21st Century Workshop

The  One Health in the 21st Century workshop will serve as a snapshot of government, intergovernmental organization and non-governmental organization innovation as it pertains to the expanding paradigm of One Health. One Health being the umbrella term for addressing animal, human, and environmental health issues as inextricably linked [emphasis mine], each informing the other, rather than as distinct disciplines.

This snapshot, facilitated by a partnership between the Wilson Center, World Bank, and EcoHealth Alliance, aims to bridge professional silos represented at the workshop to address the current gaps and future solutions in the operationalization and institutionalization of One Health across sectors. With an initial emphasis on environmental resource management and assessment as well as federal cooperation, the One Health in the 21st Century Workshop is a launching point for upcoming events, convenings, and products, sparked by the partnership between the hosting organizations. RSVP today.

Agenda:

1:00pm — 1:15pm: Introductory Remarks

1:15pm — 2:30pm: Keynote and Panel: Putting One Health into Practice

Larry Madoff — Director of Emerging Disease Surveillance; Editor, ProMED-mail
Lance Brooks — Chief, Biological Threat Reduction Department at DoD
Further panelists TBA

2:30pm — 2:40pm: Break

2:40pm — 3:50pm: Keynote and Panel: Adding Seats at the One Health Table: Promoting the Environmental Backbone at Home and Abroad

Assaf Anyamba — NASA Research Scientist
Jonathan Sleeman — Center Director for the U.S. Geological Survey’s National Wildlife Health Center
Jennifer Orme-Zavaleta — Principal Deputy Assistant Administrator for Science for the Office of Research and Development and the EPA Science Advisor
Further panelists TBA

3:50pm — 4:50pm: Breakout Discussions and Report Back Panel

4:50pm — 5:00pm: Closing Remarks

5:00pm — 6:00pm: Networking Happy Hour

Co-Hosts:

Sponsor Logos

You can register/RSVP here.

Logistics are:

November 26
1:00pm – 5:00pm
Reception to follow
5:00pm – 6:00pm

Flom Auditorium, 6th floor

Directions

Wilson Center
Ronald Reagan Building and
International Trade Center
One Woodrow Wilson Plaza
1300 Pennsylvania, Ave., NW
Washington, D.C. 20004

Phone: 202.691.4000

stip@wilsoncenter.org

Privacy Policy

Internships

The Woodrow Wilson Center is gearing up for 2019 although the deadline for a Spring 2019  November 15, 2018. (You can find my previous announcement for internships in a July 23, 2018 posting). From a November 5, 2018 Wilson Center STIP announcement (received via email),

Internships in DC for Science and Technology Policy

Deadline for Fall Applicants November 15

The Science and Technology Innovation Program (STIP) at the Wilson Center welcomes applicants for spring 2019 internships. STIP focuses on understanding bottom-up, public innovation; top-down, policy innovation; and, on supporting responsible and equitable practices at the point where new technology and existing political, social, and cultural processes converge. We recommend exploring our blog and website first to determine if your research interests align with current STIP programming.

We offer two types of internships: research (open to law and graduate students only) and a social media and blogging internship (open to undergraduates, recent graduates, and graduate students). Research internships might deal with one of the following key objectives:

  • Artificial Intelligence
  • Citizen Science
  • Cybersecurity
  • One Health
  • Public Communication of Science
  • Serious Games Initiative
  • Science and Technology Policy

Additionally, we are offering specific internships for focused projects, such as for our Earth Challenge 2020 initiative.

Special Project Intern: Earth Challenge 2020

Citizen science involves members of the public in scientific research to meet real world goals.  In celebration of the 50th anniversary of Earth Day, Earth Day Network (EDN), The U.S. Department of State, and the Wilson Center are launching Earth Challenge 2020 (EC2020) as the world’s largest ever coordinated citizen science campaign.  EC2020 will collaborate with existing citizen science projects as well as build capacity for new ones as part of a larger effort to grow citizen science worldwide.  We will become a nexus for collecting billions of observations in areas including air quality, water quality, biodiversity, and human health to strengthen the links between science, the environment, and public citizens.

We are seeking a research intern with a specialty in topics including citizen science, crowdsourcing, making, hacking, sensor development, and other relevant topics.

This intern will scope and implement a semester-long project related to Earth Challenge 2020 deliverables. In addition to this the intern may:

  • Conduct ad hoc research on a range of topics in science and technology innovation to learn while supporting department priorities.
  • Write or edit articles and blog posts on topics of interest or local events.
  • Support meetings, conferences, and other events, gaining valuable event management experience.
  • Provide general logistical support.

This is a paid position available for 15-20 hours a week.  Applicants from all backgrounds will be considered, though experience conducting cross and trans-disciplinary research is an asset.  Ability to work independently is critical.

Interested applicants should submit a resume, cover letter describing their interest in Earth Challenge 2020 and outlining relevant skills, and two writing samples. One writing sample should be formal (e.g., a class paper); the other, informal (e.g., a blog post or similar).

For all internships, non-degree seeking students are ineligible. All internships must be served in Washington, D.C. and cannot be done remotely.

Full application process outlined on our internship website.

I don’t see a specific application deadline for the special project (Earth Challenge 2010) internship. In any event, good luck with all your applications.

Body-on-a-chip (10 organs)

Also known as human-on-a-chip, the 10-organ body-on-a-chip was being discussed at the 9th World Congress on Alternatives to Animal Testing in the Life Sciences in 2014 in Prague, Czech Republic (see this July 1, 2015 posting for more). At the time, scientists were predicting success at achieving their goal of 10 organs on-a-chip in 2017 (the best at the time was four organs). Only a few months past that deadline, scientists from the Massachusetts Institute of Technology (MIT) seem to have announced a ’10 organ chip’ in a March 14, 2018 news item on ScienceDaily,

MIT engineers have developed new technology that could be used to evaluate new drugs and detect possible side effects before the drugs are tested in humans. Using a microfluidic platform that connects engineered tissues from up to 10 organs, the researchers can accurately replicate human organ interactions for weeks at a time, allowing them to measure the effects of drugs on different parts of the body.

Such a system could reveal, for example, whether a drug that is intended to treat one organ will have adverse effects on another.

A March 14, 2018 MIT news release (also on EurekAlert), which originated the news item, expands on the theme,

“Some of these effects are really hard to predict from animal models because the situations that lead to them are idiosyncratic,” says Linda Griffith, the School of Engineering Professor of Teaching Innovation, a professor of biological engineering and mechanical engineering, and one of the senior authors of the study. “With our chip, you can distribute a drug and then look for the effects on other tissues, and measure the exposure and how it is metabolized.”

These chips could also be used to evaluate antibody drugs and other immunotherapies, which are difficult to test thoroughly in animals because they are designed to interact with the human immune system.

David Trumper, an MIT professor of mechanical engineering, and Murat Cirit, a research scientist in the Department of Biological Engineering, are also senior authors of the paper, which appears in the journal Scientific Reports. The paper’s lead authors are former MIT postdocs Collin Edington and Wen Li Kelly Chen.

Modeling organs

When developing a new drug, researchers identify drug targets based on what they know about the biology of the disease, and then create compounds that affect those targets. Preclinical testing in animals can offer information about a drug’s safety and effectiveness before human testing begins, but those tests may not reveal potential side effects, Griffith says. Furthermore, drugs that work in animals often fail in human trials.

“Animals do not represent people in all the facets that you need to develop drugs and understand disease,” Griffith says. “That is becoming more and more apparent as we look across all kinds of drugs.”

Complications can also arise due to variability among individual patients, including their genetic background, environmental influences, lifestyles, and other drugs they may be taking. “A lot of the time you don’t see problems with a drug, particularly something that might be widely prescribed, until it goes on the market,” Griffith says.

As part of a project spearheaded by the Defense Advanced Research Projects Agency (DARPA), Griffith and her colleagues decided to pursue a technology that they call a “physiome on a chip,” which they believe could offer a way to model potential drug effects more accurately and rapidly. To achieve this, the researchers needed new equipment — a platform that would allow tissues to grow and interact with each other — as well as engineered tissue that would accurately mimic the functions of human organs.

Before this project was launched, no one had succeeded in connecting more than a few different tissue types on a platform. Furthermore, most researchers working on this kind of chip were working with closed microfluidic systems, which allow fluid to flow in and out but do not offer an easy way to manipulate what is happening inside the chip. These systems also require external pumps.

The MIT team decided to create an open system, which essentially removes the lid and makes it easier to manipulate the system and remove samples for analysis. Their system, adapted from technology they previously developed and commercialized through U.K.-based CN BioInnovations, also incorporates several on-board pumps that can control the flow of liquid between the “organs,” replicating the circulation of blood, immune cells, and proteins through the human body. The pumps also allow larger engineered tissues, for example tumors within an organ, to be evaluated.

Complex interactions

The researchers created several versions of their chip, linking up to 10 organ types: liver, lung, gut, endometrium, brain, heart, pancreas, kidney, skin, and skeletal muscle. Each “organ” consists of clusters of 1 million to 2 million cells. These tissues don’t replicate the entire organ, but they do perform many of its important functions. Significantly, most of the tissues come directly from patient samples rather than from cell lines that have been developed for lab use. These so-called “primary cells” are more difficult to work with but offer a more representative model of organ function, Griffith says.

Using this system, the researchers showed that they could deliver a drug to the gastrointestinal tissue, mimicking oral ingestion of a drug, and then observe as the drug was transported to other tissues and metabolized. They could measure where the drugs went, the effects of the drugs on different tissues, and how the drugs were broken down. In a related publication, the researchers modeled how drugs can cause unexpected stress on the liver by making the gastrointestinal tract “leaky,” allowing bacteria to enter the bloodstream and produce inflammation in the liver.

Kevin Healy, a professor of bioengineering and materials science and engineering at the University of California at Berkeley, says that this kind of system holds great potential for accurate prediction of complex adverse drug reactions.

“While microphysiological systems (MPS) featuring single organs can be of great use for both pharmaceutical testing and basic organ-level studies, the huge potential of MPS technology is revealed by connecting multiple organ chips in an integrated system for in vitro pharmacology. This study beautifully illustrates that multi-MPS “physiome-on-a-chip” approaches, which combine the genetic background of human cells with physiologically relevant tissue-to-media volumes, allow accurate prediction of drug pharmacokinetics and drug absorption, distribution, metabolism, and excretion,” says Healy, who was not involved in the research.

Griffith believes that the most immediate applications for this technology involve modeling two to four organs. Her lab is now developing a model system for Parkinson’s disease that includes brain, liver, and gastrointestinal tissue, which she plans to use to investigate the hypothesis that bacteria found in the gut can influence the development of Parkinson’s disease.

Other applications include modeling tumors that metastasize to other parts of the body, she says.

“An advantage of our platform is that we can scale it up or down and accommodate a lot of different configurations,” Griffith says. “I think the field is going to go through a transition where we start to get more information out of a three-organ or four-organ system, and it will start to become cost-competitive because the information you’re getting is so much more valuable.”

The research was funded by the U.S. Army Research Office and DARPA.

Caption: MIT engineers have developed new technology that could be used to evaluate new drugs and detect possible side effects before the drugs are tested in humans. Using a microfluidic platform that connects engineered tissues from up to 10 organs, the researchers can accurately replicate human organ interactions for weeks at a time, allowing them to measure the effects of drugs on different parts of the body. Credit: Felice Frankel

Here’s a link to and a citation for the paper,

Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies by Collin D. Edington, Wen Li Kelly Chen, Emily Geishecker, Timothy Kassis, Luis R. Soenksen, Brij M. Bhushan, Duncan Freake, Jared Kirschner, Christian Maass, Nikolaos Tsamandouras, Jorge Valdez, Christi D. Cook, Tom Parent, Stephen Snyder, Jiajie Yu, Emily Suter, Michael Shockley, Jason Velazquez, Jeremy J. Velazquez, Linda Stockdale, Julia P. Papps, Iris Lee, Nicholas Vann, Mario Gamboa, Matthew E. LaBarge, Zhe Zhong, Xin Wang, Laurie A. Boyer, Douglas A. Lauffenburger, Rebecca L. Carrier, Catherine Communal, Steven R. Tannenbaum, Cynthia L. Stokes, David J. Hughes, Gaurav Rohatgi, David L. Trumper, Murat Cirit, Linda G. Griffith. Scientific Reports, 2018; 8 (1) DOI: 10.1038/s41598-018-22749-0 Published online:

This paper which describes testing for four-, seven-, and ten-organs-on-a-chip, is open access. From the paper’s Discussion,

In summary, we have demonstrated a generalizable approach to linking MPSs [microphysiological systems] within a fluidic platform to create a physiome-on-a-chip approach capable of generating complex molecular distribution profiles for advanced drug discovery applications. This adaptable, reusable system has unique and complementary advantages to existing microfluidic and PDMS-based approaches, especially for applications involving high logD substances (drugs and hormones), those requiring precise and flexible control over inter-MPS flow partitioning and drug distribution, and those requiring long-term (weeks) culture with reliable fluidic and sampling operation. We anticipate this platform can be applied to a wide range of problems in disease modeling and pre-clinical drug development, especially for tractable lower-order (2–4) interactions.

Congratulations to the researchers!

How to prevent your scanning tunneling microscope probe’s ‘tip crashes’

The microscopes used for nanoscale research were invented roughly 35 years ago and as fabulous as they’ve been, there is a problem (from a February 12, 2018 news item on Nanowerk),

A University of Texas at Dallas graduate student, his advisor and industry collaborators believe they have addressed a long-standing problem troubling scientists and engineers for more than 35 years: How to prevent the tip of a scanning tunneling microscope from crashing into the surface of a material during imaging or lithography.

The researchers have prepared this video describing their work,

For those who like text, there’s more in this February 12, 2018 University of Texas at Dallas news release,

Scanning tunneling microscopes (STMs) operate in an ultra-high vacuum, bringing a fine-tipped probe with a single atom at its apex very close to the surface of a sample. When voltage is applied to the surface, electrons can jump or tunnel across the gap between the tip and sample.

“Think of it as a needle that is very sharp, atomically sharp,” said Farid Tajaddodianfar, a mechanical engineering graduate student in the Erik Jonsson School of Engineering and Computer Science. “The microscope is like a robotic arm, able to reach atoms on the sample surface and manipulate them.”

The problem is, sometimes the tungsten tip crashes into the sample. If it physically touches the sample surface, it may inadvertently rearrange the atoms or create a “crater,” which could damage the sample. Such a “tip crash” often forces operators to replace the tip many times, forfeiting valuable time.

Dr. John Randall is an adjunct professor at UT Dallas and president of Zyvex Labs, a Richardson, Texas-based nanotechnology company specializing in developing tools and products that fabricate structures atom by atom. Zyvex reached out to Dr. Reza Moheimani, a professor of mechanical engineering, to help address STMs’ tip crash problem. Moheimani’s endowed chair was a gift from Zyvex founder James Von Ehr MS’81, who was honored as a distinguished UTD alumnus in 2004.

“What they’re trying to do is help bring atomically precise manufacturing into reality,” said Randall, who co-authored the article with Tajaddodianfar, Moheimani and Zyvex Labs’ James Owen. “This is considered the future of nanotechnology, and it is extremely important work.”

Randall said such precise manufacturing will lead to a host of innovations.

“By building structures atom by atom, you’re able to create new, extraordinary materials,” said Randall, who is co-chair of the Jonsson School’s Industry Engagement Committee. “We can remove impurities and make materials stronger and more heat resistant. We can build quantum computers. It could radically lower costs and expand capabilities in medicine and other areas. For example, if we can better understand DNA at an atomic and molecular level, that will help us fine-tune and tailor health care according to patients’ needs. The possibilities are endless.”

In addition, Moheimani, a control engineer and expert in nanotechnology, said scientists are attempting to build transistors and quantum computers from a single atom using this technology.

“There’s an international race to build machines, devices and 3-D equipment from the atom up,” said Moheimani, the James Von Ehr Distinguished Chair in Science and Technology.

‘It’s a Big, Big Problem’

Randall said Zyvex Labs has spent a lot of time and money trying to understand what happens to the tips when they crash.

“It’s a big, big problem,” Randall said. “If you can’t protect the tip, you’re not going to build anything. You’re wasting your time.”

Tajaddodianfar and Moheimani said the issue is the controller.

“There’s a feedback controller in the STM that measures the current and moves the needle up and down,” Moheimani said. “You’re moving from one atom to another, across an uneven surface. It is not flat. Because of that, the distance between the sample and tip changes, as does the current between them. While the controller tries to move the tip up and down to maintain the current, it does not always respond well, nor does it regulate the tip correctly. The resulting movement of the tip is often unstable.”

It’s the feedback controller that fails to protect the tip from crashing into the surface, Tajaddodianfar said.

“When the electronic properties are variable across the sample surface, the tip is more prone to crash under conventional control systems,” he said. “It’s meant to be really, really sharp. But when the tip crashes into the sample, it breaks, curls backward and flattens.

“Once the tip crashes into the surface, forget it. Everything changes.”

The Solution

According to Randall, Tajaddodianfar took logical steps for creating the solution.

“The brilliance of Tajaddodianfar is that he looked at the problem and understood the physics of the tunneling between the tip and the surface, that there is a small electronic barrier that controls the rate of tunneling,” Randall said. “He figured out a way of measuring that local barrier height and adjusting the gain on the control system that demonstrably keeps the tip out of trouble. Without it, the tip just bumps along, crashing into the surface. Now, it adjusts to the control parameters on the fly.”

Moheimani said the group hopes to change their trajectory when it comes to building new devices.

“That’s the next thing for us. We set out to find the source of this problem, and we did that. And, we’ve come up with a solution. It’s like everything else in science: Time will tell how impactful our work will be,” Moheimani said. “But I think we have solved the big problem.”

Randall said Tajaddodianfar’s algorithm has been integrated with its system’s software but is not yet available to customers. The research was made possible by funding from the Army Research Office and the Defense Advanced Research Projects Agency.

Here’s a link to and a citation for the paper,

On the effect of local barrier height in scanning tunneling microscopy: Measurement methods and control implications by Farid Tajaddodianfar, S. O. Reza Moheimani, James Owen, and John N. Randall. Review of Scientific Instruments 89, 013701 (2018); https://doi.org/10.1063/1.5003851 Published Online: January 2018

This paper is behind a paywall.

Nanoparticle-based delivery platform for CRISPR-Cas9 (gene-editing technology)

A February 18, 2018 King Abdullah University of Science and Technology (KAUST; Saudi Arabia) news release (also on EurekAlert but published on Feb. 20, 2018) describes a new technology for delivering CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 into cells,

A new delivery system for introducing gene-editing technology into cells could help safely and efficiently correct disease-causing mutations in patients.

The system, developed by KAUST scientists, is the first to use sponge-like ensembles of metal ions and organic molecules to coat the molecular components of the precision DNA-editing technology known as CRISPR/Cas9, allowing efficient release of the genome-editing machinery inside the cell.

“This method presents an easy and economically feasible route to improve on the delivery problems that accompany RNA-based therapeutic approaches,” says Niveen Khashab, the associate professor of chemical sciences at KAUST who led the study. “This may permit such formulations to be eventually used for treating genetic diseases effectively in the future.”

CRISPR/Cas9 has a double delivery problem: For the gene-editing technology to work like a molecular Swiss Army knife, both a large protein (the Cas9 cutting enzyme) and a highly charged RNA component (the guide RNA used for DNA targeting) must each get from the outside of the cell into the cytoplasm and finally into the nucleus, all without getting trapped in the tiny intracellular bubbles that are known as endosomes.

To solve this problem, Khashab and her lab turned to a nano-sized type of porous material known as a zeolitic imidazolate framework, which forms a cage-like structure into which other molecules can be placed. The researchers encapsulated the Cas9 protein and guide RNA in this material and then introduced the resulting nanoparticles into hamster cells.

The encapsulated CRISPR-Cas9 constructs were not toxic to the cells. And because particles in the coating material become positively charged when absorbed into endosomes, they caused these membrane-bound bubbles to burst, freeing the CRISPR-Cas9 machinery to travel to the nucleus, home to the cell’s genome. There the gene-editing technology could get to work.

Using a guide RNA designed to target a gene that caused the cells to glow green under fluorescent light, Khashab and her team showed that they could reduce the expression of this gene by 37 percent over four days with their technology. “These cage-like structures are biocompatible and can be triggered on demand, making them smart options to overcome delivery problems of genetic materials and proteins,” says the study’s first author Shahad Alsaiari, a Ph.D. student in Khashab’s lab.

The researchers’ plan to test their system in human cells and in mice, and eventually, they hope, in clinical trials.

The zeolitic imidazolate framework forms a cage-like scaffold over the CRISPR/Cas9 machinery.. Reprinted (adapted) with permission from Alsaiari, S.K., Patil, S., Alyami, M., Alamoudi, K.O., Aleisa, F.A., Merzaban, J., Li M. & Khashab, N.M. Endosomal escape and delivery of CRISPR/Cas9 genome editing machinery enabled by nanoscale zeolitic imidazolate framework. Journal of the American Chemical Society 140, 143–146 (2018). © 2018 American Chemical Society; KAUST Xavier Pita and Heno Huang ][downloaded from https://discovery.kaust.edu.sa/en/article/475/a%250adelivery-platform-for-gene-editing-technology]

Here’s a link to and a citation for the paper,

Endosomal Escape and Delivery of CRISPR/Cas9 Genome Editing Machinery Enabled by Nanoscale Zeolitic Imidazolate Framework by Shahad K. Alsaiari, Sachin Patil, Mram Alyami, Kholod O. Alamoudi, Fajr A. Aleisa, Jasmeen S. Merzaban, Mo Li, and Niveen M. Khashab. J. Am. Chem. Soc., 2018, 140 (1), pp 143–146 DOI: 10.1021/jacs.7b11754 Publication Date (Web): December 22, 2017

Copyright © 2017 American Chemical Society

This paper is behind a paywall.

BIODESIGN : Nature + Science + Creativity call for artists and a job posting (Rhode Island School of Design)

h/t @raymondsbrain (Raymond Nakamura) for this item from the Rhode Island School of Design (RISD) BIODESIGN: Nature + Science + Creativity call for proposals webpage,

OPEN CALL for Proposals

Exhibition: Biodesign : From Inspiration to Integration

Venue: Rhode Island School of Design (RISD)

Submit your Biodesign or Bioart projects or ideas for programs and workshops

Funding available for production and transportation

Deadline for proposals: March 15, 2018

Curated by: William Myers & The Nature Lab @ RISD

Exhibition Dates: August 25 through September 27, 2018

Click [here] to download guidelines

Summary: The exhibition will showcase recent examples of design and art that help reform our relationship with nature, moving it from a destructive to a more integrated, mutually beneficial model. Major themes will include collaboration and co-creativity, presenting emerging best practices for working with living materials and with experts across fields. The presentation of approximately 20 projects will accompany programming including workshops, lectures, and panel discussions. This exhibition will welcome audiences curious about new experiments in designing, manufacturing and building that prioritize biodiversity protection and highlight new artistic practices that integrate biological processes or reflect on advances in the life sciences.

I followed the link to the guidelines and found some additional information,

The Nature Lab at RISD is pleased to announce Biodesign: From Inspiration to Integration, an exhibition curated by William Myers to mark the closing of our 80th anniversary celebrations. The exhibition will open in Spring 2018 and showcase recent examples of design and art that help reform our relationship with nature, moving it from a destructive to a more integrated, mutually beneficial model.

Please submit a 1–4 page summary of the work you propose for the exhibition, including
3 supporting images, via email. Also attach a current CV to your message and be sure to include your website or portfolio if applicable. Include any estimates of production, shipping or other related expenses for the project. Please keep the e-mail size under
10MB and include “RISD Exhibition Proposal” and your last name in the subject line. This call is open to everyone. Applicants can expect a response before the end of April [2018].

There is also a job, which is paid, part-time, and remote,

We are seeking a Curatorial Assistant to develop the exhibition. It is a paid, part-time post that can be located anywhere. Deadline to apply is March 2nd [2018]. Description here.

Brain composer

This is a representation of the work they are doing on brain-computer interfaces (BCI) at the Technical University of Graz (TU Graz; Austria),

A Sept. 11, 2017 news item on phys.org announces the research into thinking melodies turning them into a musical score,

TU Graz researchers develop new brain-computer interface application that allows music to be composed by the power of thought. They have published their results in the current issue of the journal PLOS ONE.

Brain-computer interfaces (BCI) can replace bodily functions to a certain degree. Thanks to BCI, physically impaired persons can control special prostheses via their minds, surf the internet and write emails.

A group led by BCI expert Gernot Müller-Putz from TU Graz’s Institute of Neural Engineering shows that experiences of quite a different tone can be sounded from the keys of brain-computer interfaces. Derived from an established BCI method for writing, the team has developed a new application by which music can be composed and transferred onto a musical score through the power of thought. It employs a special cap that measures brain waves, the adapted BCI, music composition software, and a bit of musical knowledge.

A Sept. 6, 2017 TU Graz press release by Suzanne Eigner, which originated the news item, explains the research in more detail,

The basic principle of the BCI method used, which is called P300, can be briefly described: various options, such as letters or notes, pauses, chords, etc. flash by one after the other in a table. If you’re trained and can focus on the desired option while it lights up, you cause a minute change in your brain waves. The BCI recognises this change and draws conclusions about the chosen option.

Musical test persons

18 test persons chosen for the study by Gernot Müller-Putz, Andreas Pinegger and Selina C. Wriessnegger from TU Graz’s Institute of Neural Engineering as well as Hannah Hiebel, meanwhile at the Institute of Cognitive Psychology & Neuroscience at the University of Graz, had to “think” melodies onto a musical score. All test subjects were of sound bodily health during the study and had a certain degree of basic musical and compositional knowledge since they all played musical instruments to some degree. Among the test persons was the late Graz composer and clarinettist, Franz Cibulka. “The results of the BCI compositions can really be heard. And what is more important: the test persons enjoyed it. After a short training session, all of them could start composing and seeing their melodies on the score and then play them. The very positive results of the study with bodily healthy test persons are the first step in a possible expansion of the BCI composition to patients,” stresses Müller-Putz.

Sideshow of BCI research

This little-noticed sideshow of the lively BCI research at TU Graz, with its distinct focus on disabled persons, shows us which other avenues may yet be worth exploring. Meanwhile there are some initial attempts at BCI systems on smart phones. This makes it easier for people to use BCI applications, since the smart phone as powerful computer is becoming part of the BCI system. It is thus conceivable, for instance, to have BCI apps which can analyse brain signals for various applications. “20 years ago, the idea of composing a piece of music using the power of the mind was unimaginable. Now we can do it, and at the same time have tens of new, different ideas which are in part, once again, a long way from becoming reality. We still need a bit more time before it is mature enough for daily applications. The BCI community is working in many directions at high pressure.

Here’s a link to and a citation for the paper,

Composing only by thought: Novel application of the P300 brain-computer interface by Andreas Pinegger, Hannah Hiebel, Selina C. Wriessnegger, Gernot R. Müller-Putz. PLOS https://doi.org/10.1371/journal.pone.0181584 Published: September 6, 2017

This paper is open access.

This BCI ‘sideshow’ reminded me of The Music Man, a musical by Meredith Wilson. It was both a play and a film  and I’ve only ever seen the 1962 film. It features a con man, Harold Hill, who sells musical instruments and uniforms in small towns in Iowa. He has no musical training but while he’s conning the townspeople he convinces them that he can provide musical training with his ‘think method’. After falling in love with one of the townsfolk, he is hunted down and made to prove his method works. This is a clip from a Broadway revival of the play where Harold Hill is hoping that his ‘think method’ while yield results,

Of course, the people in this study had musicaltraining so they could think a melody into a musical score but I find the echo from the past amusing nonetheless.

Bandage with a voice (sort of)

Researchers at Empa (Swiss Federal Laboratories for Materials Testing and Research) have not developed a talking bandage despite the title (Bandage with a Voice) for a July 4, 2017 Empa press release  (also a July 4, 2017 news item on Nanowerk),

A novel bandage alerts the nursing staff as soon as a wound starts healing badly. Sensors incorporated into the base material glow with a different intensity if the wound’s pH level changes. This way even chronic wounds could be monitored at home.

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Using a UV lamp, the pH level in the wound can be verified without removing the bandage and the healing process can continue unimpeded. Image: Empa / CSEM

All too often, changing bandages is extremely unpleasant, even for smaller, everyday injuries. It stings and pulls, and sometimes a scab will even start bleeding again. And so we prefer to wait until the bandage drops off by itself.

It’s a different story with chronic wounds, though: normally, the nursing staff has to change the dressing regularly – not just for reasons of hygiene, but also to examine the wound, take swabs and clean it. Not only does this irritate the skin unnecessarily; bacteria can also get in, the risk of infection soars. It would be much better to leave the bandage on for longer and have the nursing staff “read” the condition of the wound from outside.

The idea of being able to see through a wound dressing gave rise to the project Flusitex (Fluorescence sensing integrated into medical textiles), which is being funded by the Swiss initiative Nano-Tera. Researchers from Empa teamed up with ETH Zurich, Centre Suisse d’Electronique et de Microtechnique (CSEM) and University Hospital Zurich to develop a high-tech system that is supposed to supply the nursing staff with relevant data about the condition of a wound. As Luciano Boesel from Empa’s Laboratory for Biomimetic Membranes and Textiles, who is coordinating the project at Empa, explains: “The idea of a smart wound dressing with integrated sensors is to provide continuous information on the state of the healing process without the bandages having to be changed any more frequently than necessary.” This would mean a gentler treatment for patients, less work for the nursing staff and, therefore, lower costs: globally, around 17 billion $ were spent on treating wounds last year.

When wounds heal, the body produces specific substances in a complex sequence of biochemical processes, which leads to a significant variation in a number of metabolic parameters. For instance, the amount of glucose and oxygen rises and falls depending on the phase of the healing process; likewise does the pH level change. All these variations can be detected with specialized sensors. With this in mind, Empa teamed up with project partner CSEM to develop a portable, cheap and easy-to-use device for measuring fluorescence that is capable of monitoring several parameters at once. It should enable nursing staff to keep tabs on the pH as well as on glucose and oxygen levels while the wound heals. If these change, conclusions about other key biochemical processes involved in wound healing can be drawn.

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The bandage reveals ist measurings in UV light.
A high pH signals chronic wounds

The pH level is particularly useful for chronic wounds. If the wound heals normally, the pH rises to 8 before falling to 5 or 6. If a wound fails to close and becomes chronic, however, the pH level fluctuates between 7 and 8. Therefore, it would be helpful if a signal on the bandage could inform the nursing staff that the wound pH is permanently high. If the bandage does not need changing for reasons of hygiene and pH levels are low, on the other hand, they could afford to wait.

But how do the sensors work? The idea: if certain substances appear in the wound fluid, “customized” fluorescent sensor molecules respond with a physical signal. They start glowing and some even change color in the visible or ultra-violet (UV) range. Thanks to a color scale, weaker and stronger changes in color can be detected and the quantity of the emitted substance be deduced.

Empa chemist Guido Panzarasa from the Laboratory for Biomimetic Membranes and Textiles vividly demonstrates how a sample containing sensor molecules begins to fluoresce in the lab. He carefully drips a solution with a pH level of 7.5 into a dish. Under a UV light, the change is plain to see. He adds another solution and the luminescence fades. A glance at the little bottle confirms it: the pH level of the second solution is lower.

Luminous molecules under UV

The Empa team designed a molecule composed of benzalkonium chloride and pyranine. While benzalkonium chloride is a substance also used for conventional medical soap to combat bacteria, fungi and other microorganisms, pyranine is a dye found in highlighters that glows under UV light. “This biomarker works really well,” says Panzarasa; “especially at pH levels between 5.5 and 7.5. The colors can be visualized with simple UV lamps available in electronics stores.” The Empa team recently published their results in the journal “Sensors and Actuators”.

The designer molecule has another advantage: thanks to the benzalkonium chloride, it has an antimicrobial effect, as researchers from Empa’s Laboratory for Biointerfaces confirmed for the bacteria strain Staphylococcus aureus. Unwelcome bacteria might potentially also be combatted by selecting the right bandage material in future. As further investigations, such as on the chemical’s compatibility with cells and tissues, are currently lacking, however, the researchers do not yet know how their sensor works in a complex wound.

Keen interest from industry

In order to illustrate what a smart wound dressing might actually look like in future, Boesel places a prototype on the lab bench. “You don’t have to cover the entire surface of wound dressings with sensors,” he explains. “It’s enough for a few small areas to be impregnated with the pyranine benzalkonium molecules and integrated into the base material. This means the industrial wound dressings won’t be much pricier than they are now – only up to 20% more expensive.” Empa scientists are currently working on this in the follow-up project FlusiTex-Gateway in cooperation with industrial partners Flawa, Schöller, Kenzen and Theranoptics.
Panzarasa now drips various liquids with different pH levels onto all the little cylinders on the wound pad prototype. Sure enough, the lighter and darker dots are also clearly discernible as soon as the UV lamp is switched on. They are even visible to the naked eye and glow in bright yellow if liquids with a high pH come into contact with the sensor. The scientists are convinced: since the pH level is so easy to read and provides precise information about the acidic or alkaline state of the sample, this kind of wound dressing is just the ticket as a diagnostic tool. Using the fluorescence meter developed by CSEM, more accurate, quantitative measure-ments of the pH level can be accomplished for medical purposes.

According to Boesel, it might one day even be possible to read the signals with the aid of a smartphone camera. Combined with a simple app, nursing staff and doctors would have a tool that enables them to easily and conveniently read the wound status “from outside”, even without a UV lamp. And patients would then also have the possibility of detecting the early onset of a chronic wound at home.

I wonder how long or even if this innovation will ever make its way into medical practice. I’m guessing this stage would be described as ‘proof of concept’ and that clinical testing is still many years away.

The metaphor in the press release’s title helped to wake me up. Thank you to whoever wrote it.

Gold nanoparticles used to catalyze biofuel waste and create a useful additive

This work is the result of an international collaboration including Russia (from a May 23, 2017 news item on Nanowerk),

Gold nanoparticles serve as catalysts for obtaining valuable chemical products based on glycerol. Scientists from Tomsk Polytechnic University and their international colleagues are developing gold catalysts to recycle one of the main byproducts of biofuel production. The obtained products are in high demand in medicine, agriculture, cosmetic industry and other sectors.

Scientists from the University of Milano (Italy), the National Autonomous University of Mexico, the Institute of Catalysis and Petrochemistry of Madrid (Spain) and the University of Porto (Portugal) take part in the study of gold nanoparticles.

A May 23, 2027 Tomsk Polytechnic University press release, which originated the news item, expands on the theme,

Today the production of biofuels is an important area in many countries. They can be obtained from a great variety of biomasses. In Latin America it is orange and tangerine peel as well as banana skin. In USA biofuels are produced from corn, in the central part of Russia and Europe – from rape (Brassica napus). When processing these plants into biofuels a large amount of glycerol is formed. Its esters constitute the basis of oils and fats. Glycerol is widely used in cosmetic industry as an individual product. However, much more glycerol is obtained in the production of biofuels – many thousands of tons a year. As a result, unused glycerol merely becomes waste,’ describes the problem Alexey Pestryakov, the Head of the Department of Physical and Analytical Chemistry. ‘Now, a lot of research groups are engaged in this issue as to how to transform excess glycerol into other useful products. Along with our foreign colleagues we offered catalysts based on gold nanoparticles.’

The authors of the research note that catalytic oxidation on gold is one of the most effective techniques to obtain from glycerol such useful products as aldehydes, esters, carboxylic acids and other substances.

‘All these substances are products of fine organic chemistry and are in demand in a wide range of industries, first of all, in the pharmaceutical and cosmetic industries. In agriculture they are applied as part of different feed additives, veterinary drugs, fertilizers, plant treatment products, etc.

Thus, unused glycerol after being processed will further be applied,’ sums up Alexey Pestryakov.

Gold catalysts are super active. They can enter into chemical reactions with other substances at room temperature (other catalysts need to be heated), in some case even under zero. However, gold can be a catalyst only at the nanolevel.

‘If you take a piece of gold, even very tiny, there will be no chemical reaction. In order to make gold become chemically active, the size of its particle should be less than two nanometers. Only then it gets its amazing properties,’ explains the scientist.

As a catalyst gold was discovered not so long ago, in the early 1990s, by Japanese chemists.

To date, TPU scientists and their colleagues are not the only ones who develop such catalysts.

Unlike their counterparts the gold catalysts developed at TPU are more stable (they retain their activity longer).

‘A great challenge in this area is that gold catalysts are very rapidly deactivated, not only during work, but even during storage. Our objective is to ensure their longer shelf life. It is also important to use oxygen as an oxidizer, since toxic and corrosive peroxide compounds are often used for such purposes,’ says Alexey Petryakov.

Here’s a link to and a citation for the paper,

More Insights into Support and Preparation Method Effects in Gold Catalyzed Glycerol Oxidation by Nina Bogdanchikova, Inga Tuzovskaya, Laura Prati, Alberto Villa, Alexey Pestryakov, Mario Farías. Current Organic Synthesis VOLUME: 14 ISSUE: 3 Year: 2017Page: [377 – 382] Pages: 6 DOI: 10.2174/1570179413666161031114833

This paper is behind a paywall. (Scroll down the page to find the article.)