Monthly Archives: August 2012

Webinar on television and film productions collaborating with scientists

David Bruggeman in an Aug. 26, 2012 posting on his Pasco Phronesis blog features information about a webinar being co-hosted by the National Academies of Sciences (through their Science and Entertainment Exchange initiative) and the American Association for the Advancement of Science (AAAS),

The Science and Entertainment Exchange, a National Academies program to facilitate connections between entertainment productions and scientists and engineers that could serve as advisers for those productions.  On Wednesday [Aug. 29, 2102], the Exchange is holding a webinar to discuss recent productions and how various films and television programs are trying to maximize entertainment value and the accuracy of scientific and technical information.

Here’s a little more about the webinar from the AAAS event page,

Summer is synonymous with Hollywood blockbusters and the popular genre for these films (more often that not) is science fiction. “The Dark Knight Rises,” “Prometheus,” and “The Amazing Spider-Man” are just three of this summer’s box office heavyweights, each offering over the top special effects meant to wow audiences. But how much of what we are seeing is actually scientifically possible?

… Hollywood’s approach towards science, and scientists, has started to change.

In this hour-long webinar we’ll look at some TV and film collaborations that are bringing scientists and Hollywood professionals together in an effort to create programming that is both entertaining and more scientifically accurate.

Guest Speakers:

Kevin Grazier
Science Advisor/Researcher
NASA

Kevin Grazier is a writer/producer and also currently the science advisor on TNT’s “Falling Skies,” Syfy’s upcoming epic “Defiance,” and next summer’s blockbuster “Gravity.”  He formerly served as science advisor on “Eureka,” the Peabody-award-winning “Battlestar Galactica,” “The Event,” and several other series.  Grazier is a recovering rocket scientist, and spent 15 years on the Cassini/Huygens Mission to Saturn and Titan. Still an active researcher, his research areas are numerical method development and long-term large-scale computer simulations of Solar System dynamics, evolution, and chaos.

David Kirby
Senior Lecturer in Science Communication
University of Manchester, UK

David Kirby is an evolutionary geneticist and senior lecturer in science communication studies at the University of Manchester, UK. He has explored the collaboration between scientists and the entertainment industry and has publications in Social Studies of Science and Public Understanding of Science on this topic. His book Lab Coats in Hollywood: Science, Scientists and Cinema demonstrates scientists’ impact on the culturally powerful medium of cinema and how these texts have subsequently affected real world science and technology.

Ann Merchant
Deputy Executive Director for Communications
National Academies of Sciences

Ann Merchant is currently the Deputy Executive Director for Communications at the National Academies of Sciences in Washington, D.C., where she is responsible for a number of innovative outreach programs that contribute to an increased public understanding of science. She was instrumental in launching the Science & Entertainment Exchange (“The Exchange”), a program of the National Academy of Sciences that seeks to connect entertainment industry professionals with top scientists and engineers. Merchant is also an adjunct professor at the College of Professional Studies at the George Washington University where she teaches marketing in the masters-level publishing program.

Moderator:

Adam Ruben
Writer/Comedian/Molecular Biologist
Sanaria Inc.

Adam Ruben is a writer, comedian, storyteller, and molecular biologist in Washington, D.C. Ruben currently works at Sanaria Inc., a biotech company in Rockville, Maryland, developing a vaccine for malaria. Ruben has performed stand-up comedy for over ten years at clubs, colleges, and private venues. A former freelance writer for National Lampoon, Ruben is the author of the humor book Surviving Your Stupid, Stupid Decision to Go to Grad School (Broadway Books, 2010) and the monthly column “Experimental Error” in Science Careers.  He has appeared on NPR’s “All Things Considered,” the Food Network’s “Food Detectives,” and the Science Channel’s “Head Rush,” and will soon co-host a new show on the Discovery Channel called “You Have Been Warned.”

You will have to register for the free one hour long webinar which starts 9 am PDT, 12pm [noon] EDT, 5 pmUK on Wednesday, Aug. 29, 2012.

I have written previously about the Science and Entertainment Exchange in my Sept. 6, 2011 posting about the organization’s appearance at the American Chemical Society’s Fall 2011 national meeting and in a May 7, 2010 posting about scientists and their portrayal in movies and other media.

Using your microwave for DIY (do it yourself) solar panels?

The researchers at Oregon State University seem to think that their discovery will scale up to commercial levels for manufacturing solar panels that are cheaper and easier. Still, if all you need is a microwave, then I imagine some enterprising do-it-yourselfer will give this technique a try.

Microwave oven

This microwave oven technology is being used to produce solar cells with less energy, expense and environmental concerns. (Photo courtesy of Oregon State University Copied from: http://www.flickr.com/photos/oregonstateuniversity/7841150094/in/photostream)

From the Aug. 24, 2012 news item on Nanowerk,

The same type of microwave oven technology that most people use to heat up leftover food has found an important application in the solar energy industry, providing a new way to make thin-film photovoltaic products with less energy, expense and environmental concerns.

Engineers at Oregon State University have for the first time developed a way to use microwave heating in the synthesis of copper zinc tin sulfide, a promising solar cell compound that is less costly and toxic than some solar energy alternatives.

The Oregon State University Aug. 24, 2012 news release which originated the news item provides additional detail about the technology and future plans for commercializing it,

“All of the elements used in this new compound are benign and inexpensive, and should have good solar cell performance,” said Greg Herman, an associate professor in the School of Chemical, Biological and Environmental Engineering at OSU.

“Several companies are already moving in this direction as prices continue to rise for some alternative compounds that contain more expensive elements like indium,” he said. “With some improvements in its solar efficiency this new compound should become very commercially attractive.”

These thin-film photovoltaic technologies offer a low cost, high volume approach to manufacturing solar cells. A new approach is to create them as an ink composed of nanoparticles, which could be rolled or sprayed – by approaches such as old-fashioned inkjet printing – to create solar cells. [emphasis mine]

To further streamline that process, researchers have now succeeded in using microwave heating, instead of conventional heating, to reduce reaction times to minutes or seconds, and allow for great control over the production process. This “one-pot” synthesis is fast, cheap and uses less energy, researchers say, and has been utilized to successfully create nanoparticle inks that were used to fabricate a photovoltaic device.

From a do-it-yourself point of view, this technology sounds even more promising with the mention of an inkjet printer.

Medicine, nanoelectronics, social implications, and figuring it all out

Given today’s (Aug. 27, 2012) earlier posting about nanoelectronics and tissue engineering, I though it was finally time to feature Michael Berger’s Aug. 16, 2012 Nanowerk Spotlight essay, The future of nanotechnology electronics in medicine, which discusses the integration of electronics into the human body.

First, Berger offers a summary of some of the latest research (Note: I have removed  links),

In previous Nanowerk Spotlights we have already covered numerous research advances in this area: The development of a nanobioelectronic system that triggers enzyme activity and, in a similar vein, the electrically triggered drug release from smart nanomembranes; an artificial retina for color vision; nanomaterial-based breathalyzers as diagnostic tools; nanogenerators to power self-sustained biosystems and implants; future bio-nanotechnology might even use computer chips inside living cells.

A lot of nanotechnology work is going on in the area of brain research. For instance the use of a carbon nanotube rope to electrically stimlate neural stem cells; nanotechnology to repair the brain and other advances in fabricating nanomaterial-neural interfaces for signal generation.

International cooperation in this field has also picked up. Just recently, scientists have formed a global alliance for nanobioelectronics to rapidly find solutions for neurological disorders; the EuroNanoBio project is a Support Action funded under the 7th Framework Programme of the European Union; and ENIAC, the European Technology Platform on nanoelectronics, has decided to make the development of medical applications one of its main objectives.

Berger cites a recent article in the American Chemical Society’s (ACS) Nano (journal) by scientists in today’s earlier posting about tissue scaffolding and 3-D electrnonics,

In a new perspective article in the July 31, 2012, online edition of ACS Nano (“The Smartest Materials: The Future of Nanoelectronics in Medicine” [behind a paywall]), Tzahi Cohen-Karni (a researcher in Kohane’s lab), Robert Langer, and Daniel S. Kohane provide an overview of nanoelectronics’ potential in the biomedical sciences.

They write that, as with many other areas of scientific endeavor in recent decades, continued progress will require the convergence of multiple disciplines, including chemistry, biology, electrical engineering, computer science, optics, material science, drug delivery, and numerous medical disciplines. ”

Advances in this research could lead to extremely sophisticated smart materials with multifunctional capabilities that are built in – literally hard-wired. The impact of this research could cover the spectrum of biomedical possibilities from diagnostic studies to the creation of cyborgs.”

Berger finishes with this thought,

Ultimately, and here we are getting almost into science fiction territory, nanostructures could not only incorporate sensing and stimulating capabilities but also potentially introduce computational capabilities and energy-generating elements. “In this way, one could fabricate a truly independent system that senses and analyzes signals, initiates interventions, and is self-sustained. Future developments in this direction could, for example, lead to a synthetic nanoelectronic autonomic nervous system.”

This Nanowerk Spotlight essay provides a good overview of nanoelectronics  research in medicine and lots of  links to previous related essays and other related materials.

I am intrigued that there is no mention of the social implications for this research and I find social science or humanities research on social social implications of emerging technology rarely discusses the technical aspects revealing what seems to be an insurmountable gulf. I suppose that’s why we need writers, artists, musicians, dancers, pop culture, and the like to create experiences, installations, and narratives that help us examine the technologies and their social implications, up close.

The body as an electronic device—adding electronics to biological tissue

What makes this particular combination of electronic s  and living tissue special is t that it was achieved in 3-D rather than 2-D.  From the Boston Children’s Hospital Aug. 26, 2012 news release on EurekAlert,

A multi-institutional research team has developed a method for embedding networks of biocompatible nanoscale wires within engineered tissues. These networks—which mark the first time that electronics and tissue have been truly merged in 3D—allow direct tissue sensing and potentially stimulation, a potential boon for development of engineered tissues that incorporate capabilities for monitoring and stimulation, and of devices for screening new drugs.

The Aug. 27, 2012 news item on Nanowerk provides more detail about integration of the cells and electronics,

Until now, the only cellular platforms that incorporated electronic sensors consisted of flat layers of cells grown on planar metal electrodes or transistors. Those two-dimensional systems do not accurately replicate natural tissue, so the research team set out to design a 3-D scaffold that could monitor electrical activity, allowing them to see how cells inside the structure would respond to specific drugs.

The researchers built their new scaffold out of epoxy, a nontoxic material that can take on a porous, 3-D structure. Silicon nanowires embedded in the scaffold carry electrical signals to and from cells grown within the structure.

“The scaffold is not just a mechanical support for cells, it contains multiple sensors. We seed cells into the scaffold and eventually it becomes a 3-D engineered tissue,” Tian says [Bozhi Tian, a former postdoc at MIT {Massachusetts Institute of Technology} and Children’s Hospital and a lead author of the paper ].

The team chose silicon nanowires for electronic sensors because they are small, stable, can be safely implanted into living tissue and are more electrically sensitive than metal electrodes. The nanowires, which range in diameter from 30 to 80 nanometers (about 1,000 times smaller than a human hair), can detect voltages less than one-thousandth of a watt, which is the level of electricity that might be seen in a cell.

Here’s more about why the researchers want to integrate living tissue and electronics, from the Harvard University Aug. 26, 2012 news release on EurekAlert,

“The current methods we have for monitoring or interacting with living systems are limited,” said Lieber [Charles M. Lieber, the Mark Hyman, Jr. Professor of Chemistry at Harvard and one of the study’s team leaders]. “We can use electrodes to measure activity in cells or tissue, but that damages them. With this technology, for the first time, we can work at the same scale as the unit of biological system without interrupting it. Ultimately, this is about merging tissue with electronics in a way that it becomes difficult to determine where the tissue ends and the electronics begin.”

The research addresses a concern that has long been associated with work on bioengineered tissue – how to create systems capable of sensing chemical or electrical changes in the tissue after it has been grown and implanted. The system might also represent a solution to researchers’ struggles in developing methods to directly stimulate engineered tissues and measure cellular reactions.

“In the body, the autonomic nervous system keeps track of pH, chemistry, oxygen and other factors, and triggers responses as needed,” Kohane [Daniel Kohane, a Harvard Medical School professor in the Department of Anesthesia at Children’s Hospital Boston and a team leader] explained. “We need to be able to mimic the kind of intrinsic feedback loops the body has evolved in order to maintain fine control at the cellular and tissue level.”

Here’s a citation and a link to the paper (which is behind a paywall),

Macroporous nanowire nanoelectronic scaffolds for synthetic tissues by Bozhi Tian, Jia Lin, Tal Dvir, Lihua Jin, Jonathan H. Tsui, Quan  Qing, Zhigang Suo, Robert Langer, Daniel S. Kohane, and Charles M. Lieber in Nature Materials (2012) doi:10.1038/nmat3404 Published onlin26 August 2012.

This is the image MIT included with its Aug 27, 2012 news release (which originated the news item on Nanowerk),

A 3-D reconstructed confocal fluorescence micrograph of a tissue scaffold.
Image: Charles M. Lieber and Daniel S. Kohane.

At this point they’re discussing therapeutic possibilities but I expect that ‘enhancement’ is also being considered although not mentioned for public consumption.

Blood, tears, and urine for use in diagnostic tools

Frankly, I’d rather just spit into a cup or onto a slide for diagnostic tests than having to supply urine or have my blood drawn. I don’t think that day has arrived yet but scientists at Purdue University (Indiana, US) have made a breakthrough. From the Aug. 23, 2012 news item on ScienceDaily,

Researchers have created a new type of biosensor that can detect minute concentrations of glucose in saliva, tears and urine and might be manufactured at low cost because it does not require many processing steps to produce.

“It’s an inherently non-invasive way to estimate glucose content in the body,” said Jonathan Claussen, a former Purdue University doctoral student and now a research scientist at the U.S. Naval Research Laboratory. “Because it can detect glucose in the saliva and tears, it’s a platform that might eventually help to eliminate or reduce the frequency of using pinpricks for diabetes testing. We are proving its functionality.”

Claussen and Purdue doctoral student Anurag Kumar led the project, working with Timothy Fisher, a Purdue professor of mechanical engineering; D. Marshall Porterfield, a professor of agricultural and biological engineering; and other researchers at the university’s Birck Nanotechnology Center.

The originating Aug. 20, 2012 Purdue University news release by Emil Venere provides details as to how this biosensor works,

The sensor has three main parts: layers of nanosheets resembling tiny rose petals made of a material called graphene, which is a single-atom-thick film of carbon; platinum nanoparticles; and the enzyme glucose oxidase.

Each petal contains a few layers of stacked graphene. The edges of the petals have dangling, incomplete chemical bonds, defects where platinum nanoparticles can attach. Electrodes are formed by combining the nanosheet petals and platinum nanoparticles. Then the glucose oxidase attaches to the platinum nanoparticles. The enzyme converts glucose to peroxide, which generates a signal on the electrode.

“Typically, when you want to make a nanostructured biosensor you have to use a lot of processing steps before you reach the final biosensor product,” Kumar said. “That involves lithography, chemical processing, etching and other steps. The good thing about these petals is that they can be grown on just about any surface, and we don’t need to use any of these steps, so it could be ideal for commercialization.”

In addition to diabetes testing, the technology might be used for sensing a variety of chemical compounds to test for other medical conditions.

Here’s a representation of the ‘rose petal’ nanosheets,

These color-enhanced scanning electron microscope images show nanosheets resembling tiny rose petals. The nanosheets are key components of a new type of biosensor that can detect minute concentrations of glucose in saliva, tears and urine. The technology might eventually help to eliminate or reduce the frequency of using pinpricks for diabetes testing. (Purdue University photo/Jeff Goecker)
Download Photo

My most recent piece, prior to this, about less invasive diagnostic tests was this May 8, 2012 posting on a handheld diagnostic device that tests your breath for disease.

Clay and nanotechnology

There’s an interesting Aug. 23, 2012 essay by Will Soutter for Azonano about colloidal clay and some early nanotechnology products,

… colloid chemistry, which deals with the chemical and physical interactions of nanoscale particles, is a much older field – it has been studied and used in the chemical industry extensively since the early 19th century.

Even before colloids, or nanoparticles, were fully understood, they were used in many manufacturing techniques, to produce glass and ceramics with unusual, attractive properties.

I have come across reference to nanoparticles and glass (my Sept. 21, 2010 posting about the Lycurgus Cup) but this is the first I’ve heard of clay and nanoparticles,

Porcelain, which is a much finer-grained ceramic, does not require glazing – it is inherently waterproof, and has a more attractive appearance. These properties stem from the main constituent of the clay used for porcelain, called kaolinite, or china clay.

The colloids in this clay are extremely small, and behave differently to other clay particles when in solution. The particles, like most clay colloids, are platelet-shaped and have negatively-charged flat sections. Unlike most clay particles, however, they also have positively charged edges, which changes the colloid dynamics almost entirely and results in a different solid structure when the porcelain is fired.

The article is illustrated with images of porcelain and ruby glass demonstrating the effect that nanoparticles can have on materials.

How much more nanomaterial safety discussion do we need?

The report (Impact of Engineered Nanomaterials on Health: Considerations for Benefit-Risk Assessment) from Joint Research Centre (JRC) and the European Academies Science Advisory Council (EASAC) was issued in Sept. 2011 and the authors are still trying to get people to read it. The Aug. 16, 2012 online issue of Nature features correspondence from the authors citing the report,

Our analysis indicates that formulation of a coherent public policy will depend on scientists closing knowledge gaps in safety research, on gathering more data to connect science and regulation, and on training graduate students in nanotechnology research. Policies will need to be flexible to accommodate fresh discoveries in this rapidly advancing technology.

Getting notice for your work can be hugely difficult in an information-rich environment, so it’s not unusual to see efforts continuing over a year or more after publication.  Meanwhile a question persists, how many reports of this type do we need?

Camouflage face paint which protects soldiers from fire

They are very busy at the Fall 2012 (244th) meeting  of the American Chemical Society. Robert Lochhead, Ph.D., from the University of Southern Mississippi presented research on a new form of face paint(makeup) for the military which not only camouflages soldiers it can, for preciously seconds,  protect them from fire according to the Aug. 22, 2012 news release on EurekAlert,

Camouflage face makeup for warfare is undergoing one of the most fundamental changes in thousands of years, as scientists today described a new face paint that both hides soldiers from the enemy and shields their faces from the searing heat of bomb blasts. Firefighters also could benefit from the new heat-resistant makeup, according to the report.

Robert Lochhead, Ph.D., who presented the report, explained that soldiers have used face paint for centuries for one kind of protection ― to help their skin blend in with the natural environment and shield them from enemies. The new material continues that tradition, but also provides protection from the searing heat of roadside bomb blasts and other explosions that have claimed a terrible toll in Iraq, Afghanistan and other conflicts.

“The detonation of a roadside bomb or any other powerful explosive produces two dangerous blasts,” Lochhead said. “First comes a blast wave of high pressure that spreads out at supersonic speeds and can cause devastating internal injuries. A thermal blast follows almost instantaneously. It is a wave of heat that exceeds 1,112 degrees Fahrenheit. That’s as hot as a burning cigarette. The thermal blast lasts only two seconds, but it can literally cook the face, hands and other exposed skin.”

In an effort to protect soldiers from this threat, the U.S. Department of Defense has been seeking a solution that Lochhead initially regarded as an impossibility: A material that soldiers could smear on their faces like suntan lotion, leaving a coating that although thinner than a sheet of paper, could protect against that intense heat. Dr. Paige Buchanan, Kelli Booth, Michelle McClusky, Laura Anderson and Lochhead were the team that tackled the challenge. Not only did they succeed, but they discovered a formulation that protects in laboratory experiments way beyond the 2-second heat-wave threat from improvised explosive devices and other bombs.

The new camouflage makeup protects the face and hands for up to 15 seconds before its own temperature rises to the point where a first-degree burn, which is a mild burn, might occur. In some tests, the new face paint can protect for up to 60 seconds, which could be important in giving soldiers time to move away from blast-related fires and also for use by civilian firefighters.

I was able to find a few more details about the face paint in an Aug. 22, 2012 transcript of a podcast by Christopher Intagliata for Scientific American,

Conventional camo paint has tiny nanoparticles of pigment. They’re great at reflecting visible light—which is why the paint looks green or black or tan. But the particles don’t reflect longer wavelengths, like heat. To do that, you need larger globs of pigment.

So researchers bundled together a bunch of those smaller particles into chunks the size of grains of sand—large enough for heat rays to bounce right off. And they swapped out the grease for silicone which adds smoothness and spreadability to cosmetics, but won’t catch fire.

There were a number of requirements that the researchers had to meet (from the news release),

The trickiest part was that the University of Southern Mississippi team had to avoid the use of mineral oil, mineral spirits, fatty substances and other traditional hydrocarbon makeup ingredients. Hydrocarbons can burn in contact with intense heat in the flame spectrum. The team turned to silicones, which are not as flammable because they absorb radiation at wavelengths outside of the intense heat spectrum. Silicones have been replacing hydrocarbons in many commercial cosmetic makeup products as cosmetics companies improve products to confer better feel properties and transfer-resistance.

Another challenge was adding DEET, an insect repellent. The military mandates that all camouflage makeups contain 35 percent DEET. “DEET also is flammable, so when the Department of Defense asked us to incorporate it, we didn’t think we could do it,” Lochhead noted. But the team successfully included DEET by encapsulating it in a hydrogel substance, a water-rich material that prevented DEET from catching fire.

There are plans for future applications (from the news release),

It already has passed the preliminary laboratory tests needed to determine whether development should continue. Lochhead’s team also plans tests of the material on other surfaces to try to protect clothing, tents and other items from burning, and a colorless version is being developed for firefighters.

I’m glad to see this innovation which will hopefully cut down on some horrendous injuries.

Here’s final idle thought: I can’t imagine that soldiers use the term camouflage ‘makeup’; I wonder what they call instead?

Norwegians weigh in with research into wood nanocellulose healing application

It’s not just the Norwegians but they certainly seem to be leading the way on the NanoHeal project. Here’s a little more about the intricacies of healing wounds and why wood nanocellulose is being considered for wound healing, from the Aug. 23, 2012 news item on Nanowerk,

Wound healing is a complicated process consisting of several different phases and a delicate interaction between different kinds of cells, signal factors and connective tissue substance. If the wound healing does not function optimally, this can result in chronic wounds, cicatrisation or contractures. By having an optimal wound dressing such negative effects can be reduced. A modern wound dressing should be able to provide a barrier against infection, control fluid loss, reduce the pain during the treatment, create and maintain a moist environment in the wound, enable introduction of medicines into the wound, be able to absorb exudates during the inflammatory phase, have high mechanical strength, elasticity and conformability and allow for easy and painless release from the wound after use.

Nanocellulose is a highly fibrillated material, composed of nanofibrils with diameters in the nanometer scale (< 100 nm), with high aspect ratio and high specific surface area (“Cellulose fibres, nanofibrils and microfibrils: The morphological sequence of MFC components from a plant physiology and fibre technology point of view” [open access article in Nanoscale Research Letters]). Cellulose nanofibrils have many advantageous properties, such as high strength and ability to self-assembly.

Recently, the suitability of cellulose nanofibrils from wood for forming elastic cryo-gels has been demonstrated by scientists from Paper and Fibre Research Institute (PFI) and Lund University (“Cross-linking cellulose nanofibrils for potential elastic cryo-structured gels”  [open access in Nanoscale Research Letters). Cryogelation is a technique that makes it possible to engineer 3-D structures with controlled porosity. A porous structure with interconnected pores is essential for use in modern wound healing in which absorption of exudates, release of medicines into the wound or exchange of cells are essential properties.

The Research Council of Norway recently awarded a grant to the NanoHeal project, from the project page on the PFI (Pulp and Fibre Research Institute) website,

This multi-disciplinary research programme will develop novel material solutions for use in advanced wound healing based on nanofibrillated cellulose structures. This proposal requires knowledge on the effective production and application of sustainable and innovative micro- and nanofibres based on cellulose. The project will assess the ability of these nanofibres to interact with complementary polymers to form novel material structures with optimised adhesion and moulding properties, absorbance, porosity and mechanical performance.  The NanoHeal proposal brings together leading scientists in the fields of nanocellulose technology, polymer chemistry, printing and nanomedicine, to produce biocompatible and biodegradable natural polymers that can be functionalized for clinical applications. As a prototype model, the project will develop materials for use in wound healing. However, the envisaged technologies of synthesis and functionalization will have a diversity of commercial and industrial applications.

The project is funded by the Research Council of Norway/NANO2021, and is a cooperation between several leading R&D partners.

  • PFI
  • NTNU [Norwegian University of Science and Technology], Faculty of medicine
  • Cardiff University
  • Swansea University
  • Lund University
  • AlgiPharma

Project period: 2012-2016

I wonder when I’m going to start hearing about Canadian research into wood nanocellulose  (nanocrystalline cellulose or otherwise) applications.