Tag Archives: University of California San Diego

Alleviating joint damage and inflammation from arthritis with neutrophil nanosponges

Assuming you’d be happy with limiting the damage for rheumatoid arthritis, at some point in the future, this research looks promisin. Right now it appears the researchers aren’t anywhere close to a clinical trial. From a Sept. 3, 2018 news item on ScienceDaily,

Engineers at the University of California San Diego [UCSD] have developed neutrophil “nanosponges” that can safely absorb and neutralize a variety of proteins that play a role in the progression of rheumatoid arthritis. Injections of these nanosponges effectively treated severe rheumatoid arthritis in two mouse models. Administering the nanosponges early on also prevented the disease from developing.

A Sept. 3, 2018 UCSD press release (also on EurekAlert), which originated the news item, provides more detail,

“Nanosponges are a new paradigm of treatment to block pathological molecules from triggering disease in the body,” said senior author Liangfang Zhang, a nanoengineering professor at the UC San Diego Jacobs School of Engineering. “Rather than creating treatments to block a few specific types of pathological molecules, we are developing a platform that can block a broad spectrum of them, and this way we can treat and prevent disease more effectively and efficiently.”

This work is one of the latest examples of therapeutic nanosponges developed by Zhang’s lab. Zhang, who is affiliated with the Institute of Engineering in Medicine and Moores Cancer Center at UC San Diego, and his team previously developed red blood cell nanosponges to combat and prevent MRSA infections and macrophage nanosponges to treat and manage sepsis.

neutrophil nanosponge cartoon
Illustration of a neutrophil cell membrane-coated nanoparticle.

The new nanosponges are nanoparticles of biodegradable polymer coated with the cell membranes of neutrophils, a type of white blood cell.

Neutrophils are among the immune system’s first responders against invading pathogens. They are also known to play a role in the development of rheumatoid arthritis, a chronic autoimmune disease that causes painful inflammation in the joints and can ultimately lead to damage of cartilage and bone tissue.

When rheumatoid arthritis develops, cells in the joints produce inflammatory proteins called cytokines. Release of cytokines signals neutrophils to enter the joints. Once there, cytokines bind to receptors on the neutrophil surfaces, activating them to release more cytokines, which in turn draws more neutrophils to the joints and so on.

The nanosponges essentially nip this inflammatory cascade in the bud. By acting as tiny neutrophil decoys, they intercept cytokines and stop them from signaling even more neutrophils to the joints, reducing inflammation and joint damage.

These nanosponges offer a promising alternative to current treatments for rheumatoid arthritis. Some monoclonal antibody drugs, for example, have helped patients manage symptoms of the disease, but they work by neutralizing only specific types of cytokines. This is not sufficient to treat the disease, said Zhang, because there are so many different types of cytokines and pathological molecules involved.

“Neutralizing just one or two types might not be as effective. So our approach is to take neutrophil cell membranes, which naturally have receptors to bind all these different types of cytokines, and use them to manage an entire population of inflammatory molecules,” said Zhang.

“This strategy removes the need to identify specific cytokines or inflammatory signals in the process. Using entire neutrophil cell membranes, we’re cutting off all these inflammatory signals at once,” said first author Qiangzhe Zhang, a Ph.D. student in Professor Liangfang Zhang’s research group at UC San Diego.

To make the neutrophil nanosponges, the researchers first developed a method to separate neutrophils from whole blood. They then processed the cells in a solution that causes them to swell and burst, leaving the membranes behind. The membranes were then broken up into much smaller pieces. Mixing them with ball-shaped nanoparticles made of biodegradable polymer fused the neutrophil cell membranes onto the nanoparticle surfaces.

“One of the major challenges of this work was streamlining this entire process, from isolating neutrophils from blood to removing the membranes, and making this process repeatable. We spent a lot of time figuring this out and eventually created a consistent neutrophil nanosponge production line,” said Qiangzhe Zhang.

In mouse models of severe rheumatoid arthritis, injecting nanosponges in inflamed joints led to reduced swelling and protected cartilage from further damage. The nanosponges performed just as well as treatments in which mice were administered a high dose of monoclonal antibodies.

The nanosponges also worked as a preventive treatment when administered prior to inducing the disease in another group of mice.

Professor Liangfang Zhang cautions that the nanosponge treatment does not eliminate the disease. “We are basically able to manage the disease. It’s not completely gone. But swelling is greatly reduced and cartilage damage is minimized,” he said.

The team hopes to one day see their work in clinical trials.

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

Neutrophil membrane-coated nanoparticles inhibit synovial inflammation and alleviate joint damage in inflammatory arthritis by Qiangzhe Zhang, Diana Dehaini, Yue Zhang, Julia Zhou, Xiangyu Chen, Lifen Zhang, Ronnie H. Fang, Weiwei Gao, & Liangfang Zhang. Nature Nanotechnology (2018) DOI: https://doi.org/10.1038/s41565-018-0254-4 Published 03 September 2018

This paper is behind a paywall.

Using CRISPR to reverse retinosa pigmentosa (eye disease)

Years ago I worked as a publicist for the BC (British Columbia) Motorcycle Federation’s Ride for Sight; they were raising funds for research into retinitis pigmentosa (RP). I hadn’t thought about that in years but it all came back when I saw this April 21, 2017 news item on ScienceDaily,

Using the gene-editing tool CRISPR/Cas9, researchers at University of California San Diego [UCSD] School of Medicine and Shiley Eye Institute at UC San Diego Health, with colleagues in China, have reprogrammed mutated rod photoreceptors to become functioning cone photoreceptors, reversing cellular degeneration and restoring visual function in two mouse models of retinitis pigmentosa.

Caption: This is a confocal micrograph of mouse retina depicting optic fiber layer. Credit: Image courtesy of National Center for Microscopy and Imaging Research, UC San Diego.

An April 21, 2017 UCSD news release by Scott LaFee (also on EurekAlert), which originated the news item, delves further into retinitis pigmentosa and this CRISPR research,

Retinitis pigmentosa (RP) is a group of inherited vision disorders caused by numerous mutations in more than 60 genes. The mutations affect the eyes’ photoreceptors, specialized cells in the retina that sense and convert light images into electrical signals sent to the brain. There are two types: rod cells that function for night vision and peripheral vision, and cone cells that provide central vision (visual acuity) and discern color. The human retina typically contains 120 million rod cells and 6 million cone cells.

In RP, which affects approximately 100,000 Americans and 1 in 4,000 persons worldwide, rod-specific genetic mutations cause rod photoreceptor cells to dysfunction and degenerate over time. Initial symptoms are loss of peripheral and night vision, followed by diminished visual acuity and color perception as cone cells also begin to fail and die. There is no treatment for RP. The eventual result may be legal blindness.

In their published research, a team led by senior author Kang Zhang, MD, PhD, chief of ophthalmic genetics, founding director of the Institute for Genomic Medicine and co-director of biomaterials and tissue engineering at the Institute of Engineering in Medicine, both at UC San Diego School of Medicine, used CRISPR/Cas9 to deactivate a master switch gene called Nrl and a downstream transcription factor called Nr2e3.

CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats, allows researchers to target specific stretches of genetic code and edit DNA at precise locations, modifying select gene functions. Deactivating either Nrl or Nr2e3 reprogrammed rod cells to become cone cells.

“Cone cells are less vulnerable to the genetic mutations that cause RP,” said Zhang. “Our strategy was to use gene therapy to make the underlying mutations irrelevant, resulting in the preservation of tissue and vision.”

The scientists tested their approach in two different mouse models of RP. In both cases, they found an abundance of reprogrammed cone cells and preserved cellular architecture in the retinas. Electroretinography testing of rod and cone receptors in live mice show improved function.

Zhang said a recent independent study led by Zhijian Wu, PhD, at National Eye Institute, part of the National Institutes of Health, also reached similar conclusions.

The researchers used adeno-associated virus (AAV) to perform the gene therapy, which they said should help advance their work to human clinical trials quicker. “AAV is a common cold virus and has been used in many successful gene therapy treatments with a relatively good safely profile,” said Zhang. “Human clinical trials could be planned soon after completion of preclinical study. There is no treatment for RP so the need is great and pressing. In addition, our approach of reprogramming mutation-sensitive cells to mutation-resistant cells may have broader application to other human diseases, including cancer.”

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

Gene and mutation independent therapy via CRISPR-Cas9 mediated cellular reprogramming in rod photoreceptors by Jie Zhu, Chang Ming, Xin Fu, Yaou Duan, Duc Anh Hoang, Jeffrey Rutgard, Runze Zhang, Wenqiu Wang, Rui Hou, Daniel Zhang, Edward Zhang, Charlotte Zhang, Xiaoke Hao, Wenjun Xiong, and Kang Zhang. Cell Research advance online publication 21 April 2017; doi: 10.1038/cr.2017.57

This paper (it’s in the form of a letter to the editor) is open access.

Largest database of elemental crystal surfaces and shapes in the world

A Sept. 13, 2016 news item on Nanowerk describes the database,

Nanoengineers at the University of California San Diego [UCSD], in collaboration with the Materials Project at Lawrence Berkeley National Laboratory (Berkeley Lab), have created the world’s largest database of elemental crystal surfaces and shapes to date. Dubbed Crystalium, this new open-source database can help researchers design new materials for technologies in which surfaces and interfaces play an important role, such as fuel cells, catalytic converters in cars, computer microchips, nanomaterials and solid-state batteries.

rystalium is a new open-source database with the largest collection of elemental crystal surfaces and shapes to date. Image courtesy of the Materials Virtual Lab at UC San Diego

Crystalium is a new open-source database with the largest collection of elemental crystal surfaces and shapes to date. Image courtesy of the Materials Virtual Lab at UC San Diego

A Sept. 13, 2016 UCSD news release reveals more about the goals for the database and the database itself (Note: Links have been removed),

“This work is an important starting point for studying the material surfaces and interfaces, where many novel properties can be found. We’ve developed a new resource that can be used to better understand surface science and find better materials for surface-driven technologies,” said Shyue Ping Ong, a nanoengineering professor at UC San Diego and senior author of the study.

For example, fuel cell performance is partly influenced by the reaction of molecules such as hydrogen and oxygen on the surfaces of metal catalysts. Also, interfaces between the electrodes and electrolyte in a rechargeable lithium-ion battery host a variety of chemical reactions that can limit the battery’s performance. The work in this study is useful for these applications, said Ong, who is also part of a larger effort by the UC San Diego Sustainable Power and Energy Center to design better battery materials.

“Researchers can use this database to figure out which elements or materials are more likely to be viable catalysts for processes like ammonia production or making hydrogen gas from water,” said Richard Tran, a nanoengineering PhD student in Ong’s Materials Virtual Lab and the study’s first author. Tran did this work while he was an undergraduate at UC San Diego.

The work, published Sept. 13 [2016] in the journal Scientific Data, provides the surface energies and equilibrium crystal shapes of more than 100 polymorphs of 72 elements in the periodic table. Surface energy describes the stability of a surface; it is a measure of the excess energy of atoms on the surface relative to those in the bulk material. Knowing surface energies is useful for designing materials that perform their functions primarily on their surfaces, like catalysts and nanoparticles.

The surface energies of some elements in their crystal form have been measured experimentally, but this is not a trivial task. It involves melting the crystal, measuring the resulting liquid’s surface tension at the melting temperature, then extrapolating that value back to room temperature. This process also requires that the sample have a clean surface, which is challenging because other atoms and molecules (like oxygen and water) can easily adsorb to the surface and modify the surface energy.

Surface energies obtained by this method are averaged values that lack the facet-specific resolution that is necessary for design, Ong said. “This is one of the areas where the ’virtual laboratory’ can create the most value—by allowing us to precisely control the models and conditions in a way that is extremely difficult to do in experiments.”

Also, the surface energy is not just a single number for each crystal because it depends on the crystal’s orientation. “A crystal is a regular arrangement of atoms. When you cut a crystal in different places and at different angles, you expose different facets with unique arrangements of atoms,” explained Ong, who teaches the course NANO106 – Crystallography of Materials at UC San Diego.

To carry out this ambitious project, Ong and his team developed highly sophisticated automated workflows to calculate surface energies from first principles. These workflows are built on the popular open-source Python Materials Genomics library and FireWorks workflow codes of the Materials Project, which were co-authored by Ong.

“The techniques for calculating surface energies have been known for decades. The major accomplishment is the codification of how to generate surface models and run these complex calculations in a robust and efficient manner,” Tran said. The surface model generation software code developed by the team has already been extended by others to study substrates and interfaces. Powerful supercomputers at the San Diego Supercomputer Center and the National Energy Research Scientific Computing Center at the Lawrence Berkeley National Lab were used for the calculations.

Ong’s team worked with researchers from the Berkeley Lab’s Materials Project to develop and construct Crystalium’s website. Co-founded and directed by Berkeley Lab scientist Kristin Persson, the Materials Project is a Google-like database of material properties calculated by supercomputers.

“The Materials Project was designed to be an open and accessible tool for scientists and engineers to accelerate materials innovation,” Persson said. “In five years, it has attracted more than 20,000 users working on everything from batteries to photovoltaics to thermoelectrics, and it’s extremely gratifying to see scientists like Ong providing lots of high quality computed data of high interest and making it freely available and easily accessible to the public.”

The researchers pointed out that their database is the most extensive collection of calculated surface energies for elemental crystalline solids to date. Compared to previous compilations, Crystalium contains surface energies for far more elements, including both metals and non-metals, and for more facets in each crystal. The elements that have been excluded from their calculations are gases and radioactive elements. Notably, Ong and his team have validated their calculated surface energies with those from experiments, and the values are in excellent agreement.

Moving forward, the team will work on expanding the scope of the database beyond single elements to multi-element compounds like alloys, which are made of two or more different metals, and binary oxides, which are made of oxygen and one other element. Efforts are also underway to study the effect of common adsorbates, such as hydrogen, on surface energies, which is key to understanding the stability of surfaces in aqueous media.

“As we continue to build this database, we hope that the research community will see it as a useful resource for the rational design of target surface or interfacial properties,” said Ong,

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

Surface energies of elemental crystals by Richard Tran, Zihan Xu, Balachandran Radhakrishnan, Donald Winston, Wenhao Sun, Kristin A. Persson, & Shyue Ping Ong.  Scientific Data 3, Article number: 160080 (2016)  doi:10.1038/sdata.2016.80 Published online: 13 September 2016

This paper is open access.

Here, too, is a link to Crystalium.

A tattoo that’s a biobattery and a sensor?

It’s going to be an American Chemical Society (ACS) 248th meeting kind of week as yet another interesting piece of scientific research is bruited (spread) about the internet. This time it’s all about sweat, exercise, and biobatteries. From an Aug. 13, 2014 news item on Nanowerk,

In the future, working up a sweat by exercising may not only be good for your health, but it could also power your small electronic devices. Researchers will report today that they have designed a sensor in the form of a temporary tattoo that can both monitor a person’s progress during exercise and produce power from their perspiration.

An Aug. 13, 2014 ACS news release on EurekAlert, which originated the news item, describes the inspiration (as opposed to perspiration) for this technology,

The device works by detecting and responding to lactate, which is naturally present in sweat. “Lactate is a very important indicator of how you are doing during exercise,” says Wenzhao Jia, Ph.D.

In general, the more intense the exercise, the more lactate the body produces. During strenuous physical activity, the body needs to generate more energy, so it activates a process called glycolysis. Glycolysis produces energy and lactate, the latter of which scientists can detect in the blood.

Professional athletes monitor their lactate levels during performance testing as a way to evaluate their fitness and training program. In addition, doctors measure lactate during exercise testing of patients for conditions marked by abnormally high lactate levels, such as heart or lung disease. Currently, lactate testing is inconvenient and intrusive because blood samples must be collected from the person at different times during the exercise regime and then analyzed.

The news release goes on to describe the research process which resulted in a temporary tattoo that could be used to power small scale electronics,

Jia, a postdoctoral student in the lab of Joseph Wang, D.Sc., at the University of California San Diego, and her colleagues developed a faster, easier and more comfortable way to measure lactate during exercise. They imprinted a flexible lactate sensor onto temporary tattoo paper. The sensor contained an enzyme that strips electrons from lactate, generating a weak electrical current. The researchers applied the tattoo to the upper arms of 10 healthy volunteers. Then the team measured the electrical current produced as the volunteers exercised at increasing resistance levels on a stationary bicycle for 30 minutes. In this way, they could continuously monitor sweat lactate levels over time and with changes in exercise intensity.

The team then went a step further, building on these findings to make a sweat-powered biobattery. Batteries produce energy by passing current, in the form of electrons, from an anode to a cathode. In this case, the anode contained the enzyme that removes electrons from lactate, and the cathode contained a molecule that accepts the electrons.

When 15 volunteers wore the tattoo biobatteries while exercising on a stationary bike, they produced different amounts of power. Interestingly, people who were less fit (exercising fewer than once a week) produced more power than those who were moderately fit (exercising one to three times per week). Enthusiasts who worked out more than three times per week produced the least amount of power. The researchers say that this is probably because the less-fit people became fatigued sooner, causing glycolysis to kick in earlier, forming more lactate. The maximum amount of energy produced by a person in the low-fitness group was 70 microWatts per cm2 of skin.

“The current produced is not that high, but we are working on enhancing it so that eventually we could power some small electronic devices,” Jia says. “Right now, we can get a maximum of 70 microWatts per cm2, but our electrodes are only 2 by 3 millimeters in size and generate about 4 microWatts — a bit small to generate enough power to run a watch, for example, which requires at least 10 microWatts. So besides working to get higher power, we also need to leverage electronics to store the generated current and make it sufficient for these requirements.”

Biobatteries offer certain advantages over conventional batteries: They recharge more quickly, use renewable energy sources (in this case, sweat), and are safer because they do not explode or leak toxic chemicals.

“These represent the first examples of epidermal electrochemical biosensing and biofuel cells that could potentially be used for a wide range of future applications,” Wang says.

The ACS has made a video about this work available,

It seems to me this tattoo battery could be used as a self-powered monitoring device in a medical application for heart or lung disease.

Memristors, memcapacitors, and meminductors for faster computers

While some call memristors a fourth fundamental component alongside resistors, capacitors, and inductors (as mentioned in my June 26, 2014 posting which featured an update of sorts on memristors [scroll down about 80% of the way]), others view memristors as members of an emerging periodic table of circuit elements (as per my April 7, 2010 posting).

It seems scientists, Fabio Traversa, and his colleagues fall into the ‘periodic table of circuit elements’ camp. From Traversa’s  June 27, 2014 posting on nanotechweb.org,

Memristors, memcapacitors and meminductors may retain information even without a power source. Several applications of these devices have already been proposed, yet arguably one of the most appealing is ‘memcomputing’ – a brain-inspired computing paradigm utilizing the ability of emergent nanoscale devices to store and process information on the same physical platform.

A multidisciplinary team of researchers from the Autonomous University of Barcelona in Spain, the University of California San Diego and the University of South Carolina in the US, and the Polytechnic of Turin in Italy, suggest a realization of “memcomputing” based on nanoscale memcapacitors. They propose and analyse a major advancement in using memcapacitive systems (capacitors with memory), as central elements for Very Large Scale Integration (VLSI) circuits capable of storing and processing information on the same physical platform. They name this architecture Dynamic Computing Random Access Memory (DCRAM).

Using the standard configuration of a Dynamic Random Access Memory (DRAM) where the capacitors have been substituted with solid-state based memcapacitive systems, they show the possibility of performing WRITE, READ and polymorphic logic operations by only applying modulated voltage pulses to the memory cells. Being based on memcapacitors, the DCRAM expands very little energy per operation. It is a realistic memcomputing machine that overcomes the von Neumann bottleneck and clearly exhibits intrinsic parallelism and functional polymorphism.

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

Dynamic computing random access memory by F L Traversa, F Bonani, Y V Pershin, and M Di Ventra. Nanotechnology Volume 25 Number 28  doi:10.1088/0957-4484/25/28/285201 Published 27 June 2014

This paper is behind a paywall.

DARPA (US Defense Advanced Research Projects Agency), nanoparticles, and your traumatized brain

According to the May 10, 2013 news item on Nanowerk,

DARPA, the U.S. Defense Advanced Research Projects Agency, has awarded $6 million to a team of researchers to develop nanotechnology therapies for the treatment of traumatic brain injury and associated infections.

Led by Professor Michael J. Sailor, Ph.D., from the University of California San Diego [UC San Diego], the award brings together a multi-disciplinary team of renowned experts in laboratory research, translational investigation and clinical medicine, including Erkki Ruoslahti, M.D., Ph.D. of Sanford-Burnham Medical Research Institute, Sangeeta N. Bhatia, M.D., Ph.D. of Massachusetts Institute of Technology and Clark C. Chen, M.D., Ph.D. of UC San Diego School of Medicine.

Ballistics injuries that penetrate the skull have amounted to 18 percent of battlefield wounds sustained by men and women who served in the campaigns in Iraq and Afghanistan, according to the most recent estimate from the Joint Theater Trauma Registry, a compilation of data collected during Operation Iraqi Freedom and Operation Enduring Freedom.

“A major contributor to the mortality associated with a penetrating brain injury is the elevated risk of intracranial infection,” said Chen, a neurosurgeon with UC San Diego Health System, noting that projectiles drive contaminated foreign materials into neural tissue.

The May 9, 2013 UC San Diego news release by Susan Brown, which originated the news item, describes the reasons why DARPA wants to use nanoparticles in therapies for people suffering from traumatic brain injury,

Under normal conditions, the brain is protected from infection by a physiological system called the blood-brain barrier. “Unfortunately, those same natural defense mechanisms make it difficult to get antibiotics to the brain once an infection has taken hold,” said Chen, associate professor and vice-chair of research in the Division of Neurosurgery at UC San Diego School of Medicine.

DARPA hopes to meet these challenges with nanotechnology. The agency awarded this grant under its In Vivo Nanoplatforms for Therapeutics program to construct nanoparticles that can find and treat infections and other damage associated with traumatic brain injuries.

“Our approach is focused on porous nanoparticles that contain highly effective therapeutics on the inside and targeting molecules on the outside,” said Sailor, the UC San Diego materials chemist who leads the team. “When injected into the blood stream, we have found that these silicon-based particles can target certain tissues very effectively.”

Several types of nanoparticles have already been approved for clinical use in patients, but none for treatment of trauma or diseases in the brain. This is due in part to the inability of nanoparticle formulations to cross the blood-brain barrier and reach their intended targets.

“Poor penetration into tissues limits the application of nanoparticles to the treatment of many types of diseases,” said Ruoslahti, distinguished professor at Sanford-Burnham and partner in the research. “We are trying to overcome this limitation using targeting molecules that activate tissue-specific transport pathways to deliver nanoparticles.”

There is another major hurdle for treating brain injuries (from the news release),

Treating brain infections is becoming more difficult as drug-resistant strains of viruses and bacteria have emerged. Because drug-resistant strains mutate and evolve rapidly, researchers must constantly adjust their approach to treatment.

In an attempt to hit this moving target, the team is making their systems modular, so they can be reconfigured “on-the-fly” with the latest therapeutic advances.

Nanocomplexes that contain genetic material known as short interfering RNA, or siRNA, developed by Bhatia’s research group at MIT, will be key to this aspect of the team’s approach.

“The function of this type of RNA is that it specifically intereferes with processes in a diseased cell. The advantage of RNA therapies are that they can be quickly and easily modified when a new disease target emerges,” said Bhatia, a bioengineering professor at MIT and partner in the research.

But effective delivery of siRNA-based therapeutics in the body has proven to be a challenge because the negative charge and chemical structure of naked siRNA makes it very unstable in the body and it has difficulty crossing into diseased cells. To solve these problems, Bhatia has developed nanoparticles that form a protective coating around siRNA.

“The nanocomplexes we are developing shield the negative charge of RNA and protect it from nucleases that would normally destroy it. Adding Erkki’s tissue homing and cell-penetrating peptides allows the nanocomplex to transport deep into tissue and enter the diseased cells,” she said.

Bhatia has previously used the cell-penetrating nanocomplex to deliver siRNA to a tumor cell and shut down its protein production machinery. Although her group’s effort has focused on cancer, the team is now going after two other hard-to-treat cell types: drug-resistant bacteria and inflammatory cells in the brain.

“The work proposed by this multi-disciplinary team should provide new tools to mitigate the debilitating effects of penetrating brain injuries and offer our warfighters the best chance of meaningful recovery,” Chen said. [emphasis mine]

BTW, the term ‘warfighters’ is new to me; are we replacing the word ‘soldier’?

Returning to the matter at hand, I found DARPA’s In Vivo Nanoplatforms for Therapeutics program which is described this way on its home page,

Disease limits soldier readiness and creates healthcare costs and logistics burdens. Diagnosing and treating disease faster can help limit its impact. [emphasis mine] Current technologies and products for diagnosing disease are principally relegated to in vitro (in the lab) medical devices, which are often expensive, bulky and fragile.

DARPA’s In Vivo Nanoplatforms (IVN) program seeks to develop new classes of adaptable nanoparticles for persistent, distributed, unobtrusive physiologic and environmental sensing as well as the treatment of physiologic abnormalities, illness and infectious disease.

The IVN Diagnostics (IVN:Dx) program effort aims to develop a generalized in vivo platform that provides continuous physiological monitoring for the warfighter. [emphasis mine] Specifically, IVN:Dx will investigate technologies that may provide:

  • Implantable nanoplatforms using bio-compatible and nontoxic materials
  • In vivo sensing of small and large molecules of biological interest
  • Multiplexed detection of analytes at clinically relevant concentrations
  • External interrogation of the nanoplatform free from any implanted communications electronics
  • Complete system demonstration in a large animal

The IVN Therapeutics (IVN:Tx) program effort will seek unobtrusive nanoplatforms for rapidly treating disease in warfighters.

(I see DARPA is using both soldier and warfighter’.)

This team is not the only one wishing to deliver drug therapies in a targeted fashion to the brain. My Feb. 19, 2013 posting mentioned Chad Mirkin (Northwestern University) and his team’s efforts with spherical nucleic acids (SNAs), from the posting,

Potential applications include using SNAs to carry nucleic acid-based therapeutics to the brain for the treatment of glioblastoma, the most aggressive form of brain cancer, as well as other neurological disorders such as Alzheimer’s and Parkinson’s diseases. Mirkin is aggressively pursuing treatments for such diseases with Alexander H. Stegh, an assistant professor of neurology at Northwestern’s Feinberg School of Medicine. (originally excerpted from this the Feb. 15, 2013 news release on EurekAlert)

Coincidentally, Mirkin has just been named ‘Chemistry World Entrepreneur of the Year’ by the UK’s Royal Society of Chemistry, from the May 10, 2013 news item on Nanowerk,

Northwestern University scientist Chad A. Mirkin, a world-renowned leader in nanotechnology research and its application, has been named 2013 Chemistry World Entrepreneur of the Year by the Royal Society of Chemistry (RSC). The award recognizes an individual’s contribution to the commercialization of research.

The RSC is honoring Mirkin for his invention of spherical nucleic acids (SNAs), new globular forms of DNA and RNA. These structures form the basis for more than 300 products commercialized by licensees of the technology.

I’m never quite sure what to make of researchers who receive public funding then patent and license the results of that research.

Getting back to soldiers/warfighters, I’m glad to see this research being pursued. Years ago, a physician mentioned to me that soldiers in Iraq were surviving injuries that would have killed them in previous conflicts. The problem is that the same protective gear which insulates soldiers against many injuries makes them vulnerable to abusive head trauma (same principle as ‘shaken baby syndrome’). For example, imagine having a high velocity bullet hit your helmet. You’re protected from the bullet but the impact shakes your head so violently, your brain is injured.

Surveillance by design and by accident

In general, one thinks of surveillance as an activity undertaken by the military or the police or some other arm of the state (a spy agency of some kind). The  Nano Hummingbird, a drone from AeroVironment designed for the US Pentagon, would fit into any or all of those categories.

AeroVironment's hummingbird drone // Source: suasnews.com (downloaded from Homeland Security Newswire)

You can see the device in action here,

The inset screen shows you what is being seen via the hummingbird’s camera, while the larger screen image allows you to observe the Nano Hummingbird in action. I don’t know why they’ve used the word nano as part of the product unless it is for marketing purposes. The company’s description of the product is at a fairly high level and makes no mention of the technology, nano or otherwise, that makes the hummingbird drone’s capabilities possible (from the company’s Nano Hummingbird webpage),

AV [AeroVironment] is developing the Nano Air Vehicle (NAV) under a DARPA sponsored research contract to develop a new class of air vehicle systems capable of indoor and outdoor operation. Employing biological mimicry at an extremely small scale, this unconventional aircraft could someday provide new reconnaissance and surveillance capabilities in urban environments.

The Nano Hummingbird could be described as a traditional form surveillance as could the EyeSwipe iris scanners (mentioned in my Dec. 10, 2010 posting). The EyeSwipe allows the police, military, or other state agencies to track you with cameras that scan your retinas (they’ve had trials of this technology in Mexico).

A provocative piece by Nic Fleming for the journal, New Scientist, takes this a step further. Smartphone surveillance: The cop in your pocket can be found in the July 30, 2011 issue of New Scientist (preview here; the whole article is behind a paywall),

While many of us use smartphones to keep our social lives in order, they are also turning out to be valuable tools for gathering otherwise hard-to-get data. The latest smartphones bristle with sensors …

Apparently the police are wanting to crowdsource surveillance by having members of the public use their smartphones to track licence plate numbers, etc. and notify the authorities. Concerns about these activities are noted both in Fleming article and in the August 10, 2011 posting on the Foresight Institute blog,

“Christine Peterson, president of the Foresight Institute based in Palo Alto, California, warns that without safeguards, the data we gather about each other might one day be used to undermine rather than to protect our freedom. ‘We are moving to a new level of data collection that our society is not accustomed to,’ she says.”

Peterson’s comments about data collection struck me most particularly as I’ve noticed over the last several months a number of applications designed to make life ‘easier’ that also feature data collection (i. e., collection of one’s personal data). For example, there’s Percolate. From the July 7, 2011 article by Austin Carr for Fast Company,

Percolate, currently in its “double secret alpha” version, is a blogging platform that provides curated content for you to write about. The service taps into your RSS and Twitter feeds, culls content based on your interests–the stuff that “percolates up”–and then offers you the ability to share your thoughts on the subject with friends. “We’re trying to make it easy for anyone to create content,” Brier says, “to take away from the frustration of staring at that blank box and trying to figure out what to say.”

It not only removes the frustration, it removes at least some of the impetus for creativity. The service is being framed as a convenience. Coincidentally, it makes much easier for marketers or any one or any agency to track your activities.

This data collection can get a little more intimate than just your Twitter and RSS feeds. Your underwear can monitor your bodily functions (from the June 11, 2010 news item on Nanowerk),

A team of U.S. scientists has designed some new men’s briefs that may be comfortable, durable and even stylish but, unlike most underpants, may be able to save lives.

Printed on the waistband and in constant contact with the skin is an electronic biosensor, designed to measure blood pressure, heart rate and other vital signs.

The technology, developed by nano-engineering professor Joseph Wang of University of California San Diego and his team, breaks new ground in the field of intelligent textiles and is part of shift in focus in healthcare from hospital-based treatment to home-based management.

The method is similar to conventional screen-printing although the ink contains carbon electrodes.

The project is being funded by the U.S. military with American troops likely to be the first recipients.

“This specific project involves monitoring the injury of soldiers during battlefield surgery and the goal is to develop minimally invasive sensors that can locate, in the field, and identify the type of injury,” Wang told Reuters Television.

I realize that efforts such as the ‘smart underpants’ are developed with good intentions but if the data can be used to monitor your health status, it can be used to monitor you for other reasons.

While the military can insist its soldiers be monitored, civilian efforts are based on incentives. For example, Foodzy is an application that makes dieting fun. From the July 7, 2011 article by Morgan Clendaniel on Fast Company,

As more and more people join (Foodzy is aiming for 30,000 users by the end of the year and 250,000 by the end of 2012), you’ll also start being able to see what your friends are eating. This could be a good way to keep your intake of bits down, not wanting to embarrass yourself in front of your friends as you binge on some cookies, but Kamphuis [Marjolijn Kamphuis is one of the founders] sees a more social aspect to it: “On my dashboard I am able to see what the ‘food match’ between me and my friends is, the same way Last.FM has been comparing me and my friend’s music taste for ages! I am now able to share recipes with my friends or hook up with them in real life for dinner because I notice we have similar taste.”

That sure takes the discovery/excitement aspect out of getting to know someone. As I noted with my comments about Percolate, with more of our lives being mediated by applications of this nature, the easier we are to track.

Along a parallel track, there’s a campaign to remove anonymity and/or pseudonymity from the Internet. As David Sirota notes in his August 12, 2011 Salon essay about this trend, the expressed intention is to ensure civility and minimize bullying but there is at least one other consequence,

The big potential benefit of users having to attach real identities to their Internet personas is more constructive dialogue.

As Zuckerberg [Randi Zuckerberg, Facebook executive] and Schmidt [Eric Schmidt, former Google CEO]  correctly suggest, online anonymity is primarily used by hate-mongers to turn constructive public discourse into epithet-filled diatribes. Knowing they are shielded from consequences, trolls feel empowered to spew racist, sexist and other socially unacceptable rhetoric that they’d never use offline. …

The downside, though, is that true whistle-blowers will lose one of their most essential tools.

Though today’s journalists often grant establishment sources anonymity to attack weaker critics, anonymity’s real social value is rooted in helping the powerless challenge the powerful. Think WikiLeaks, which exemplifies how online anonymity provides insiders the cover they need to publish critical information without fear of retribution. Eliminating such cover will almost certainly reduce the kind of leaks that let the public occasionally see inconvenient truths.

It’s not always about whistleblowing, some people prefer pseudonyms.  Science writer and blogger, GrrlScientist, recently suffered a blow to her pseudonymity which was administered by Google (from her July 16, 2011 posting on the Guardian science blogs),

One week ago, my entire Google account was deactivated suddenly and without warning. I was not allowed to access gmail nor any other Google service until I surrendered my personal telephone number in exchange for reinstating access to my gmail account. I still cannot access many of my other accounts, such as Google+, Reader and Buzz. My YouTube account remains locked, too.

I was never notified as to what specifically had warranted this unexpected deactivation of my account. I only learned a few hours later that my account was shut down due to the name I use on my profile page, which you claim is a violation of your “community standards”. However, as stated on your own “display name” pages, I have not violated your community standards. I complied with your stated request: my profile name is “the name that [I] commonly go by in daily life.”

My name is a pseudonym, as I openly state on my profile. I have used GrrlScientist as my pseudonym since 2000 and it has a long track record. I have given public lectures in several countries, received mail in two countries, signed contracts, received monetary payments, published in a number of venues and been interviewed for news stories – all using my pseudonym. A recent Google search shows that GrrlScientist, as spelled, is unique in the world. This meets at least two of your stated requirements; (1) I am not impersonating anyone and (2) my name represents just one person.

GrrlScientist is not the only writer who prefers a pseudonym. Mark Twain did too. His real name was Samuel J. Clemens but widely known as Mark Twain, he was the author of The Adventures of Tom Sawyer, Adventures of Huckleberry Finn, and many more books, short stories, and essays.

Minimzing bullying, ensuring civility, monitoring vital signs in battle situations, encouraging people to write, helping a friend stay on diet are laudable intentions but all of this leads to more data being collected about us and the potential for abusive use of this data.