Simon Fraser University’s (Vancouver region, Canada) Cafe Scientifique

I am adding a new Café Scientifique series to my roster of occasional announcements. This one is sponsored by Simon Fraser University (SFU) and regularly held at a Boston Pizza restaurant in New Westminster (located in metro Vancouver Canada). The next session will take place Friday, Jan. 23, 2015.

From SFU’s Café Scientifique webpage,

In our series, speakers will discuss their health or popular-science related topic, without the use of audio visual materials or handouts, for approximately 30 minutes.  A discussion with the audience will ensue for about 45 minutes while participants enjoy appetizers and beverages.

Friday, January 23, 2015

Speaker: Dr. Tim Swartz, Professor, Dept of Statistics & Actuarial Science, SFU

Research interest: My general interest is statistical computing. Most of my work attempts to take advantage of the power of modern computing machinery to solve real statistical problems. The area where I have devoted a lot of attention is the integration problem arising in Bayesian applications. Lately, my interest in statistics in sport has grown to consume a fair bit of my time, perhaps too much of my time.

Topic: Sports Analytics

Sports analytics has become an important area of emphasis for professional sports teams in their attempt to obtain a competitive edge. The discussion will revolve around recent work that Dr. Swartz has conducted in sports analytics such as the optimal time to pull a goalie in hockey, insights into home team advantage and the value of draft positions in major league soccer.

Location: Boston Pizza (private room) 1045 Columbia St., New Westminster
(2 blks from the New West Skytrain station).

Refreshments are available for purchase. Everyone is welcome to attend.

Reserve your free seat by emailing: [email protected]
**Note that there is no accent above the “e” in this address.

Enjoy!

Part-time job at the Society for Canadian Women in Science and Technology (SCWIST)

The Vancouver-based Society for Canadian Women in Science and Technology (SCWIST) has a part-time, contract position available. From the SCWIST Coordinator – MS Infinity Program job page,

The Society for Canadian Women in Science and Technology (SCWIST) is a non-profit association that promotes, encourages and empowers women and girls in science, engineering and technology. Ms Infinity programs introduce girls to exciting career options and female role models in science and technology. Conferences and workshops with fun filled activities bring science alive. Girls are introduced to jobs from all areas of science and get the support they need when deciding how to take their interest in science further with e-mentor and role model programs.

POSITION OVERVIEW & KEY RESPONSIBILITIES

Title: Coordinator – MS Infinity Program
Type: Part-time contract (12 – 18 hours per week)
Start: ASAP
Application deadline: January 20, 2015
Reports to: Director of Outreach
Time Commitment:  This is a 6-month contract, to be renewed based on grant funding

Coordination and promotion of ms infinity programming:

  • Volunteer recruitment and management
  • Volunteer training, development and communication (quarterly e-newsletter)
  • Preparation of promotional material and marketing of the program
  • Organization of and communication with the ms infinity committee
  • Communication with workshop/ event/ conference organizers
  • Promotion of ms infinity offerings to SCWIST members
  • Assistance in workshop, event and conference organization
  • Research of new workshop and event possibilities to extend the reach of ms infinity
  • Development of new educational workshops
  • Grant application, reporting and budget management

Coordination of the e-mentoring program:

  • Program administration
  • Recruitment of mentors and mentees
  • Organization of discussion topics

Qualifications:

  • A degree in science or education
  • Experience in informal science education and program coordination
  • Positive, enthusiastic attitude
  • Ability to present the Society well in the science learning and promotion community
  • Strong organizational and communication skills
  • Self-motivated with attention to detail
  • Experience in event organization and management, as well as experience managing budgets
  • Excellent knowledge in MS Office and social media tools

Additional application information is on the job page.

PlasCarb: producing graphene and renewable hydrogen from food waster

I have two tidbits about PlasCarb the first being an announcement of its existence and the second an announcement of its recently published research. A Jan. 13, 2015 news item on Nanowerk describes the PlasCarb project (Note: A link has been removed),

The Centre for Process Innovation (CPI) is leading a European collaborative project that aims to transform food waste into a sustainable source of significant economic added value, namely graphene and renewable hydrogen.

The project titled PlasCarb will transform biogas generated by the anaerobic digestion of food waste using an innovative low energy microwave plasma process to split biogas (methane and carbon dioxide) into high value graphitic carbon and renewable hydrogen.

A Jan. 13, 2015 CPI press release, which originated the news item, describes the project and its organization in greater detail,

CPI  as the coordinator of the project is responsible for the technical aspects in the separation of biogas into methane and carbon dioxide, and separating of the graphitic carbon produced from the renewable hydrogen. The infrastructure at CPI allows for the microwave plasma process to be trialled and optimised at pilot production scale, with a future technology roadmap devised for commercial scale manufacturing.

Graphene is one of the most interesting inventions of modern times. Stronger than steel, yet light, the material conducts electricity and heat. It has been used for a wide variety of applications, from strengthening tennis rackets, spray on radiators, to building semiconductors, electric circuits and solar cells.

The sustainable creation of graphene and renewable hydrogen from food waste in provides a sustainable method towards dealing with food waste problem that the European Union faces. It is estimated that 90 million tonnes of food is wasted each year, a figure which could rise to approximately 126 million tonnes by 2020. In the UK alone, food waste equates to a financial loss to business of at least £5 billion per year.

Dr Keith Robson, Director of Formulation and Flexible Manufacturing at CPI said, “PlasCarb will provide an innovative solution to the problems associated with food waste, which is one of the biggest challenges that the European Union faces in the strive towards a low carbon economy.  The project will not only seek to reduce food waste but also use new technological methods to turn it into renewable energy resources which themselves are of economic value, and all within a sustainable manner.”

PlasCarb will utilise quality research and specialist industrial process engineering to optimise the quality and economic value of the Graphene and hydrogen, further enhancing the sustainability of the process life cycle.

Graphitic carbon has been identified as one of Europe’s economically critical raw materials and of strategic performance in the development of future emerging technologies. The global market for graphite, either mined or synthetic is worth over €10 billion per annum. Hydrogen is already used in significant quantities by industry and recognised with great potential as a future transport fuel for a low carbon economy. The ability to produce renewable hydrogen also has added benefits as currently 95% of hydrogen is produced from fossil fuels. Moreover, it is currently projected that increasing demand of raw materials from fossil sources will lead to price volatility, accelerated environmental degradation and rising political tensions over resource access.

Therefore, the latter stages of the project will be dedicated to the market uptake of the PlasCarb process and the output products, through the development of an economically sustainable business strategy, a financial risk assessment of the project results and a flexible financial model that is able to act as a primary screen of economic viability. Based on this, an economic analysis of the process will be determined. Through the development of a decentralised business model for widespread trans-European implementation, the valorisation of food waste will have the potential to be undertaken for the benefit of local economies and employment. More specifically, three interrelated post project exploitation markets have been defined: food waste management, high value graphite and RH2 sales.

PlasCarb is a 3-year collaborative project, co-funded under the European Union’s Seventh Framework Programme (FP7) and will further reinforce Europe’s leading position in environmental technologies and innovation in high value Carbon. The consortium is composed of eight partners led by CPI from five European countries, whose complimentary research and industrial expertise will enable the required results to be successfully delivered. The project partners are; The Centre for Process Innovation (UK), GasPlas AS (NO), CNRS (FR), Fraunhofer IBP (DE), Uvasol Ltd (UK), GAP Waste Management (UK), Geonardo Ltd. (HU), Abalonyx AS (NO).

You can find PlasCarb here.

The second announcement can be found in a PlasCarb Jan. 14, 2015 press release announcing the publication of research on heterostructures of graphene ribbons,

Few materials have received as much attention from the scientific world or have raised so many hopes with a view to their potential deployment in new applications as graphene has. This is largely due to its superlative properties: it is the thinnest material in existence, almost transparent, the strongest, the stiffest and at the same time the most strechable, the best thermal conductor, the one with the highest intrinsic charge carrier mobility, plus many more fascinating features. Specifically, its electronic properties can vary enormously through its confinement inside nanostructured systems, for example. That is why ribbons or rows of graphene with nanometric widths are emerging as tremendously interesting electronic components. On the other hand, due to the great variability of electronic properties upon minimal changes in the structure of these nanoribbons, exact control on an atomic level is an indispensable requirement to make the most of all their potential.

The lithographic techniques used in conventional nanotechnology do not yet have such resolution and precision. In the year 2010, however, a way was found to synthesise nanoribbons with atomic precision by means of the so-called molecular self-assembly. Molecules designed for this purpose are deposited onto a surface in such a way that they react with each other and give rise to perfectly specified graphene nanoribbons by means of a highly reproducible process and without any other external mediation than heating to the required temperature. In 2013 a team of scientists from the University of Berkeley and the Centre for Materials Physics (CFM), a mixed CSIC (Spanish National Research Council) and UPV/EHU (University of the Basque Country) centre, extended this very concept to new molecules that were forming wider graphene nanoribbons and therefore with new electronic properties. This same group has now managed to go a step further by creating, through this self-assembly, heterostructures that blend segments of graphene nanoribbons of two different widths.

The forming of heterostructures with different materials has been a concept widely used in electronic engineering and has enabled huge advances to be made in conventional electronics. “We have now managed for the first time to form heterostructures of graphene nanoribbons modulating their width on a molecular level with atomic precision. What is more, their subsequent characterisation by means of scanning tunnelling microscopy and spectroscopy, complemented with first principles theoretical calculations, has shown that it gives rise to a system with very interesting electronic properties which include, for example, the creation of what are known as quantum wells,” pointed out the scientist Dimas de Oteyza, who has participated in this project. This work, the results of which are being published this very week in the journal Nature Nanotechnology, therefore constitutes a significant success towards the desired deployment of graphene in commercial electronic applications.

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

Molecular bandgap engineering of bottom-up synthesized graphene nanoribbon heterojunctions by Yen-Chia Chen, Ting Cao, Chen Chen, Zahra Pedramrazi, Danny Haberer, Dimas G. de Oteyza, Felix R. Fischer, Steven G. Louie, & Michael F. Crommie. Nature Nanotechnology (2015) doi:10.1038/nnano.2014.307 Published online 12 January 2015

This article is behind a paywall but there is a free preview available via ReadCube access.

Of airborne nanomaterials, bacterial microbiomes, viral microbiomes, and paper sensors

There’s a Jan. 14, 2015 news item on Nanowerk from the Virginia Polytechnic Institute (Virginia Tech) which is largely a personal profile featuring some basic information (useful for those new to the topic) about airborne nanoparticles (Note: A link has been removed),

The Harvard educated undergraduate [Linsey Marr,  professor of civil and environmental engineering, Virginia Tech] who obtained her Ph.D. from University of California at Berkeley and trained as a postdoctoral researcher with a Nobel laureate of chemistry at MIT is now among a handful of researchers in the world who are addressing concerns about engineered nanomaterials in the atmosphere.

Marr is part of the National Science Foundation’s Center for the Environmental Implications of Nanotechnology and her research group has characterized airborne nanoparticles at every point of their life cycle. This cycle includes production at a commercial manufacturing facility, use by consumers in the home, and disposal via incineration.

A Jan. 14, 2015 Virginia Tech news release, which originated the news item, quotes Marr on the current thinking about airborne nanoparticles,

“Results have shown that engineered nanomaterials released into the air are often aggregated with other particulate matter, such as combustion soot or ingredients in consumer spray products, and that the size of such aggregates may range from smaller than 10 nanometers to larger than 10 microns,” Marr revealed. She was referring to studies completed by research group members Marina Quadros Vance of Florianopolis, Brazil, a research scientist with the Virginia Tech Institute of Critical Technology and Applied Science, and Eric Vejerano, of Ligao, Philippines, a post-doctoral associate in civil and environmental engineering.

Size matters if these aggregates are inhaled.

Another concern is the reaction of a nanomaterial such as a fullerene with ozone at environmentally relevant concentration levels. Marr’s graduate student, Andrea Tiwari, of Mankato, Minnesota, said the resulting changes in fullerene could lead to enhanced toxicity.

The story then segues into airborne pathogens and viruses eventually honing in on virus microbiomes and bacterial microbiomes (from the news release),

Marr is a former Ironman triathlete who obviously has strong interests in what she is breathing into her own body. So it would be natural for her to expand her study of engineered nanoparticles traveling in the atmosphere to focus on airborne pathogens.

She did so by starting to consider the influenza virus as an airborne pollutant. She applied the same concepts and tools used for studying environmental contaminants and ambient aerosols to the examination of the virus.

She looked at viruses as “essentially self-assembled nanoparticles that are capable of self-replication.”

Her research team became the first to measure influenza virus concentrations in ambient air in a children’s day care center and on airplanes. When they conducted their studies, the Virginia Tech researchers collected samples from a waiting room of a health care center, two toddlers’ rooms and one babies’ area of a childcare center, as well as three cross-country flights between Roanoke, Virginia., and San Francisco. They collected 16 samples between Dec. 10, 2009 and Apr. 22, 2010.

“Half of the samples were confirmed to contain aerosolized influenza A viruses,” Marr said. The childcare samples were the most infected at 75 percent. Next, airplane samples reached 67 percent contamination, and health center numbers came in at 33 percent.

This study serves as a foundation for new work started about a year ago in her lab.

Marr collaborated with Aaron J. Prussin II, of Blacksburg, Virginia, and they successfully secured for him a postdoctoral fellowship from the Alfred P. Sloan Foundation to characterize the bacterial and viral microbiome — the ecological community of microorganisms — of the air in a daycare center.

They are now attempting to determine seasonal changes of both the viral microbiome and the bacterial microbiome in a daycare setting, and examine how changes in the microbiome are related to naturally occurring changes in the indoor environment.

“Little is known about the viral component of the microbiome and it is important because viruses are approximately 10 times more abundant than bacteria, and they help shape the bacterial community. Research suggests that viruses do have both beneficial and harmful interactions with bacteria,” Prussin said.

With Prussin and Marr working together they hope to verify their hypothesis that daycare centers harbor unique, dynamic microbiomes with plentiful bacteria and viruses. They are also looking at what seasonal changes might bring to a daycare setting.

They pointed to the effect of seasonal changes because in previous work, Marr, her former graduate student Wan Yang, of Shantou, China, and Elankumaran Subbiah, a virologist in the biomedical sciences and pathobiology department of the Virginia-Maryland College of Veterinary Medicine, measured the influenza A virus survival rate at various levels of humidity.

Their 2012 study presented for the first time the relationship between the influenza A virus viability in human mucus and humidity over a large range of relative humidities, from 17 percent to 100 percent. They found the viability of the virus was highest when the relative humidity was either close to 100 percent or below 50 percent. The results in human mucus may help explain influenza’s seasonality in different regions.

According to the news release Marr and her colleagues have developed a fast and cheap technology for detection of airborne pathogens (Note: A link has been removed),

With the urgent need to understand the dynamics of airborne pathogens, especially as one considers the threats of bioterrorism, pandemic influenza, and other emerging infectious diseases, Marr said “a breakthrough technology is required to enable rapid, low-cost detection of pathogens in air.”

Along with Subbiah and Peter Vikesland,  professor of civil and environmental engineering, they want to develop readily deployable, inexpensive, paper-based sensors for airborne pathogen detection.

In 2013 they received funding of almost $250,000 from Virginia Tech’s Institute for Critical Technology and Applied Science, a supporter of the clustering of research groups, to support their idea of creating paper-based sensors based on their various successes to date.

Marr explained the sensors “would use a sandwich approach. The bottom layer is paper containing specialized DNA that will immobilize the virus. The middle layer is the virus, which sticks to the specialized DNA on the bottom layer. The top layer is additional specialized DNA that sticks to the virus. This DNA is attached to gold nanoparticles that are easily detectable using a technique known as Raman microscopy.”

They key to their approach is that it combines high-tech with low-tech in the hopes of keeping the assay costs low. Their sampling method will use a bicycle pump, and low cost paper substrates. They hope that they will be able to incorporate smart-phone based signal transduction for the detection. Using this approach, they believe “even remote corners of the world” would be able to use the technique.

Vikesland previously received funding from the Gates Foundation to detect the polio virus via paper-based diagnostics. Polio is still found in countries on the continents of Asia and Africa.

I have previously mentioned Linsey Marr in an Oct. 18, 2013 post about the revival of the Nanotechnology Consumer Products Inventory (originally developed by the Project for Emerging Nanotechnologies) by academics at Virginia Tech and first mentioned CEINT in an Aug. 15, 2011 post about a special project featuring a mesocosm at Duke University (North Carolina).

Tattoos that detect glucose levels

Temporary tattoos with a biomedical function are a popular topic and one of the latest detects glucose levels without subjecting a person with diabetes to pin pricks. From a Jan. 14, 2015 news item on ScienceDaily,

Scientists have developed the first ultra-thin, flexible device that sticks to skin like a rub-on tattoo and can detect a person’s glucose levels. The sensor, reported in a proof-of-concept study in the ACS [American Chemical Society] journal Analytical Chemistry, has the potential to eliminate finger-pricking for many people with diabetes.

A Jan. 14, 2015 ACS news release on EurekAlert, which originated the news item, describes the current approaches to testing glucose and the new painless technique,

Joseph Wang and colleagues in San Diego note that diabetes affects hundreds of millions of people worldwide. Many of these patients are instructed to monitor closely their blood glucose levels to manage the disease. But the standard way of checking glucose requires a prick to the finger to draw blood for testing. The pain associated with this technique can discourage people from keeping tabs on their glucose regularly. A glucose sensing wristband had been introduced to patients, but it caused skin irritation and was discontinued. Wang’s team wanted to find a better approach.

The researchers made a wearable, non-irritating platform that can detect glucose in the fluid just under the skin based on integrating glucose extraction and electrochemical biosensing. Preliminary testing on seven healthy volunteers showed it was able to accurately determine glucose levels. The researchers conclude that the device could potentially be used for diabetes management and for other conditions such as kidney disease.

There is a Jan. 14, 2015 University of California at San Diego news release (also on EurekAlert) describing the work in more detail,

Nanoengineers at the University of California, San Diego have tested a temporary tattoo that both extracts and measures the level of glucose in the fluid in between skin cells. …

The sensor was developed and tested by graduate student Amay Bandodkar and colleagues in Professor Joseph Wang’s laboratory at the NanoEngineering Department and the Center for Wearable Sensors at the Jacobs School of Engineering at UC San Diego. Bandodkar said this “proof-of-concept” tattoo could pave the way for the Center to explore other uses of the device, such as detecting other important metabolites in the body or delivering medicines through the skin.

At the moment, the tattoo doesn’t provide the kind of numerical readout that a patient would need to monitor his or her own glucose. But this type of readout is being developed by electrical and computer engineering researchers in the Center for Wearable Sensors. “The readout instrument will also eventually have Bluetooth capabilities to send this information directly to the patient’s doctor in real-time or store data in the cloud,” said Bandodkar.

The research team is also working on ways to make the tattoo last longer while keeping its overall cost down, he noted. “Presently the tattoo sensor can easily survive for a day. These are extremely inexpensive—a few cents—and hence can be replaced without much financial burden on the patient.”

The Center “envisions using these glucose tattoo sensors to continuously monitor glucose levels of large populations as a function of their dietary habits,” Bandodkar said. Data from this wider population could help researchers learn more about the causes and potential prevention of diabetes, which affects hundreds of millions of people and is one of the leading causes of death and disability worldwide.

People with diabetes often must test their glucose levels multiple times per day, using devices that use a tiny needle to extract a small blood sample from a fingertip. Patients who avoid this testing because they find it unpleasant or difficult to perform are at a higher risk for poor health, so researchers have been searching for less invasive ways to monitor glucose.

In their report in the journal Analytical Chemistry, Wang and his co-workers describe their flexible device, which consists of carefully patterned electrodes printed on temporary tattoo paper. A very mild electrical current applied to the skin for 10 minutes forces sodium ions in the fluid between skin cells to migrate toward the tattoo’s electrodes. These ions carry glucose molecules that are also found in the fluid. A sensor built into the tattoo then measures the strength of the electrical charge produced by the glucose to determine a person’s overall glucose levels.

“The concentration of glucose extracted by the non-invasive tattoo device is almost hundred times lower than the corresponding level in the human blood,” Bandodkar explained. “Thus we had to develop a highly sensitive glucose sensor that could detect such low levels of glucose with high selectivity.”

A similar device called GlucoWatch from Cygnus Inc. was marketed in 2002, but the device was discontinued because it caused skin irritation, the UC San Diego researchers note. Their proof-of-concept tattoo sensor avoids this irritation by using a lower electrical current to extract the glucose.

Wang and colleagues applied the tattoo to seven men and women between the ages of 20 and 40 with no history of diabetes. None of the volunteers reported feeling discomfort during the tattoo test, and only a few people reported feeling a mild tingling in the first 10 seconds of the test.

To test how well the tattoo picked up the spike in glucose levels after a meal, the volunteers ate a carb-rich meal of a sandwich and soda in the lab. The device performed just as well at detecting this glucose spike as a traditional finger-stick monitor.

The researchers say the device could be used to measure other important chemicals such as lactate, a metabolite analyzed in athletes to monitor their fitness. The tattoo might also someday be used to test how well a medication is working by monitoring certain protein products in the intercellular fluid, or to detect alcohol or illegal drug consumption.

This reminds me a little of the Google moonshot project concerning health diagnostics. Announced in Oct. 2014, that project involved swallowing a pill containing nanoparticles that would circulate through your body monitoring your health and recongregating at your wrist so a band worn there could display your health status (Oct. 30, 2014 article by Signe Brewster for GigaOm). Experts welcomed the funding while warning the expectations seemed unrealistic given the current state of research and technology. This temporary tattoo seems much better grounded in terms of the technology used and achievable results.

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

Tattoo-Based Noninvasive Glucose Monitoring: A Proof-of-Concept Study by Amay J. Bandodkar, Wenzhao Jia, Ceren Yardımcı, Xuan Wang, Julian Ramirez, and Joseph Wang. Anal. Chem., 2015, 87 (1), pp 394–398 DOI: 10.1021/ac504300n Publication Date (Web): December 12, 2014

Copyright © 2014 American Chemical Society

This appears to be an open access paper.

My latest posting posting on medical tattoos (prior to this) is an Aug. 13, 2014 post about a wearable biobattery.

Bacteria is shocked, I tell you, shocked

Casablanca (1942, black and white, Hollywood movie) lovers may recognize the paraphrase of just one of the many famous lines in the movie. However, this ‘shocking’ news has more to do with preventing bacteria from congregating on surfaces according to a Jan. 12, 2014 news item by Alexander Chilton on Azonano (Note: Links have been removed),

Researchers at Rensselaer Polytechnic Institute and Cornell University have devised a new nanoscale surface which uses an electrochemical anodization process in order to prevent the surface attachment of bacteria.

The research published in the Biofouling journal focuses on the formation of nanoscale pores which alter the surface energy and electrical charge of a metal surface. A repulsive force is exerted on the bacterial cells, which prevents the attachment of bacteria and the formation of a biofilm. The size of the nanoscale pores formed can be as small as 15 nanometers.

The application of the anodization process to aluminum created a nanoporous surface, known as alumina. This surface proved effective in preventing the attachment of two popular bacterial species: Listeria monocytogenes and Escherichia coli O157:H7.

Krishna Ramanujan’s Jan. 9, 2015 article for Cornell University’s Chronicle explains why the scientists are excited about the anodization technique,

“It’s probably one of the lowest-cost possibilities to manufacture a nanostructure on a metallic surface,” said Carmen Moraru, associate professor of food science and the paper’s senior author. …

Finding low-cost solutions to limiting bacterial attachments is key, especially in biomedical and food processing applications.  …

Anodized metals could be used to prevent buildups of biofilms – slick communities of bacteria that adhere to surfaces and are tricky to remove – in biomedical clean rooms and in equipment parts that are hard to reach or clean, Moraru said.

There are other strategies for limiting bacterial attachment to surfaces, including chemicals and bactericides, but these have limited applications, especially when it comes to food processing, Moraru said. With food processing, surfaces must meet food safety guidelines and be inert to food that they may contact.

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

Alumina surfaces with nanoscale topography reduce attachment and biofilm formation by Escherichia coli and Listeria spp. by Guoping Feng, Yifan Cheng, Shu-Yi Wang, Lillian C. Hsu, Yazmin Feliz, Diana A. Borca-Tasciuc, Randy W. Worobo, & Carmen I. Moraru. Biofouling: The Journal of Bioadhesion and Biofilm Research Volume 30, Issue 10, 2014 pages 1253-1268 DOI: 10.1080/08927014.2014.976561 Published online: 27 Nov 2014

This article is open access.

Maybe nano drug delivery not so magical after all?

There’s a lot of talk about the potential for a better way to treat disease with more accurate delivery of nanoparticle-based medicines to specific areas that need the treatment. For example, current treatments which shrink and eliminate cancer tumours also destroy healthy tissue and often have deleterious side effects while a nanoparticle-based treatment could seek out and eliminate the tumour only with few or no side effects. However, new research suggests that tumours may be more complex than previously understood.

From a Jan. 14, 2015 news item on Azonano,

Nanoparticle drugs–tiny containers packed with medicine and with the potential to be shipped straight to tumors–were thought to be a possible silver bullet against cancer. However new cancer drugs based on nanoparticles have not improved overall survival rates for cancer patients very much. Scientists at the University of North Carolina at Chapel Hill now think that failure may have less to do with the drugs and tumors than it does the tumor’s immediate surroundings.

The work, published in Clinical Cancer Research, merges relatively old and new ideas in cancer treatment, on one hand underscoring the importance of personalized medicine and on the other, reinforcing a relatively new idea that the tumor microenvironment might affect the delivery of drugs to tumors – a factor that may alter drug delivery from person to person, from cancer to cancer and even from tumor to tumor.

A Jan. 13, 2015 University of North Carolina news release (also on EurekAlert), which originated the news item, provides more details about the research,

“Tumors create bad neighborhoods,” said William Zamboni, the study’s senior author and an associate professor at the UNC Eshelman School of Pharmacy. “They spawn leaky, jumbled blood vessels that are like broken streets, blind alleys and busted sewers. There are vacant lots densely overgrown with collagen fibers. Immune-system cells patrolling the streets might be good guys turned bad, actually working for the tumor. And we’re trying to get a large truckload of medicine through all of that.”

In their work, Zamboni and colleagues from the UNC Lineberger Comprehensive Cancer Center and the UNC School of Medicine joined forces to see how much of the standard small-molecule cancer drug doxorubicin and its nanoparticle version, Doxil, actually made it into two varieties of triple-negative breast-cancer tumor models created by UNC’s Chuck Perou, the May Goldman Shaw Distinguished Professor of Molecular Oncology at the UNC School of Medicine and a professor at UNC Lineberger. Triple-negative breast cancer accounts for 10 to 17 percent of cases and has a poorer prognosis than other types of breast cancer.

At first, what they saw was no surprise: significantly more of the nanodrug Doxil made it into both triple-negative breast-cancer tumors compared with the standard small-molecule doxorubicin. “That’s nothing new,” Zamboni said. “We’ve seen that for twenty years.” They also saw the same amount of doxorubin in both tumors.

What did surprise them was that significantly more of the nanodrug Doxil – twice as much – was delivered to the C3-TAg triple-negative breast cancer tumor than to the T11 triple-negative breast cancer tumor.

“These tumors are subtypes of a subtype of one kind of cancer and are relatively closely related,” said Zamboni. “If the differences in delivering nanoagents to these two tumors are so significant, we can only imagine what the differences might be between breast cancer and lung cancer.”

Zamboni and his team suggest that better profiling of tumors and their microenvironments would allow doctors not only to better identify patients who would most benefit from nanoparticle-based cancer therapy, but also that clinicians may need to learn more about a patient’s tumor before prescribing treatment with one of the newer nanoparticle drugs.

This work gives the Israeli project I wrote about in my Jan. 7, 2015 post regarding a human clinical trial of nanobot delivery of a drug treatment (the world’s first) a new perspective. As a medical writer friend of mine (Susan Baxter) notes, these things are always more complicated than we think they’ll be and she adds tumours change over time.

Given how often we’ve discovered the human body is a complex, interwoven set of ecosystems, it’s perplexing that so much of the discussion around treatment is still  reductionist, i.e., drug kill tumour.

Getting back to this current research, here’s a link to and a citation for the paper,

Effects of Tumor Microenvironment Heterogeneity on Nanoparticle Disposition and Efficacy in Breast Cancer Tumor Models by Gina Song, David B. Darr, Charlene M. Santos, Mark Ross, Alain Valdivia, Jamie L. Jordan, Bentley R. Midkiff, Stephanie Cohen, Nana Nikolaishvili-Feinberg, C. Ryan Miller, Teresa K. Tarrant, Arlin B. Rogers, Andrew C. Dudley, Charles M. Perou, and William C. Zamboni. CCR-14-0493 Clin Cancer Res December 1, 2014 20 6083 doi: 10.1158/1078-0432 Published Online First September 17, 2014

This paper is behind a paywall of sorts. I haven’t seen this particular designation before but in addition to purchasing a subscription or short term access, there’s an option called: “patientACCESS – Patients/Caregivers desiring access to articles.” I’m not sure if that’s fee-based or not.

A newish Tekmira results from a merger with OnCore Biopharma

A Jan. 12, 2015 news item on Azonano announces a new business entity, a combined Tekmira Pharmaceuticals (located in North Vancouver, Canada) and OnCore Biopharma (located in Pennsylvania, US),

Tekmira Pharmaceuticals Corporation, a leading developer of RNA interference (RNAi) therapeutics, and OnCore Biopharma, Inc., a biopharmaceutical company dedicated to discovering, developing and commercializing an all-oral cure for patients suffering from chronic hepatitis B virus (HBV) infection, announced today that they have agreed to merge to create a new leading global HBV company focused on developing a curative regimen for hepatitis B patients by combining multiple therapeutic approaches.

A Jan. 11, 2015 Tekmira news release, which originated the news item, provides details including how this merger will affect the work on the Tekmira ebola treatment,

This transaction is expected to bring together the companies’ broad expertise in antiviral drug development, Tekmira’s Phase 1-ready HBV RNAi therapeutic and OnCore’s multiple HBV programs, to build a robust portfolio of compounds aimed at eradicating HBV. The combined company’s most advanced products are expected to be TKM-HBV, an RNAi therapeutic designed to eliminate HBV surface antigen (HBsAg) expression, a key component of host immune suppression, which is on track to begin human clinical trials in the first quarter of 2015; and OCB-030, a second-generation cyclophilin inhibitor focused on the suppression of viral replication, as well as stimulation and reactivation of the body’s immune response, which is anticipated to enter human clinical trials in the second half of 2015. The combined company anticipates progressing additional programs toward the clinic to achieve the goal of expeditiously evaluating combination regimens.

The combined pipeline is expected to target the three pillars necessary to develop a curative regimen for HBV, including assets focused on suppressing HBV replication, reactivating and stimulating the host immune response directed at HBV and eliminating covalently closed circular DNA (cccDNA). The parties believe that, together, these three pillars are the foundation for achieving a curative regimen.

Dr. Mark J. Murray, Chief Executive Officer of Tekmira, said, “We believe that the merger between Tekmira and OnCore has the potential to transform the HBV treatment landscape by bringing together the technologies and science needed to eradicate the virus and develop a cure for this debilitating and deadly disease. Our new company has the potential to advance multiple, highly active, complementary agents into the clinic in rapid succession, and create an HBV therapeutics powerhouse, thereby potentially offering significant benefits to the global medical community working to improve the lives of HBV patients. Importantly, we also believe this transaction has the potential to create significant value for our shareholders.”

Patrick Higgins, Chief Executive Officer of OnCore, said, “Tekmira and OnCore share a vision that effective combination regimens will ultimately cure HBV, a goal now being realized for hepatitis C virus. This merger is expected to bring together the promise of TKM-HBV with our existing HBV portfolio and accelerate our timeline for combination clinical trials. It is expected to deliver both near-term catalysts and long-term value creation. We believe that the ability to rapidly and sequentially combine novel HBV therapeutics is extremely valuable. We intend to utilize our collective expertise in liver disease and a focused development program, as we did at Pharmasset, to expeditiously and efficiently meet our shared goals.”

An Industry-Leading, Multi-Functional HBV Portfolio

Through the combined portfolio, OnCore and Tekmira intend to advance a robust pipeline of assets that uniquely targets the three pillars for delivering a curative regimen for HBV, including suppressing HBV replication, reactivating and stimulating the host immune response directed at HBV and eliminating cccDNA, the stable source of HBV viral genomic material. Post-closing, the combined company’s HBV portfolio is expected to include  product assets, which can be viewed in a chart by clicking on the following  link: http://media.globenewswire.com/cache/14025/file/31117.pdf

“We intend to take a focused, iterative approach to identifying the most effective combination regimens, while applying what we learn at each stage to optimize future compounds and combinations,” said Dr. Michael Sofia, the combined company’s Chief Scientific Officer and an inventor of sofosbuvir (Sovaldi) for the treatment of hepatitis C. “We believe that the ability to combine multiple unique programs housed in the same company is a significant competitive advantage, and should provide considerable efficiency in terms of speed and ease of decision-making. Combining the OnCore and Tekmira HBV portfolios underpins our vision to accelerate the delivery of a curative HBV regimen.”

Non-HBV Programs Continuing to Move Forward

Tekmira is a global leader in the RNAi field, and has created a diverse pipeline of products in development to treat serious human diseases, such as cancer and viral infections, including Ebola. The company has also licensed its leading lipid nanoparticle (LNP) delivery technology to partners around the world.

The management teams and Boards of Directors of Tekmira and OnCore believe that there is significant value in Tekmira’s non-HBV assets and collaborations. TKM-PLK1 is currently in Phase 2 in multiple indications and TKM-Ebola is expected to enter Phase 2 in West Africa in early 2015. Tekmira also maintains an active RNAi research and development effort. The combined management team and Board of Directors plans to continue to move forward with these programs with the goal of maximizing their value.

The news release goes on to describe the deal,

Under the terms of the agreement, the transaction will be carried out by way of a merger pursuant to which OnCore will merge with a wholly-owned subsidiary of Tekmira and thereby become a wholly-owned subsidiary of Tekmira. Upon closing of the transaction the stockholders of OnCore will hold approximately fifty percent (50%) of the total number of outstanding shares of capital stock of Tekmira, calculated on a fully-diluted and as-converted basis using the treasury stock method. The terms and conditions of the transaction are more fully set forth in the Merger Agreement. The implied market value of the combined company, based on the closing price of Tekmira common shares on the NASDAQ Global Market on January 9, 2015, is approximately USD$750 million.

The merger is subject to approval of a majority of the shareholders of Tekmira present, in person or by proxy, at a special meeting of Tekmira shareholders. Completion of the transaction is also subject to customary closing conditions, including regulatory approvals.  The transaction is expected to close in the first half of 2015, shortly after completion of the Securities and Exchange Commission (SEC) review process and receipt of Tekmira shareholder approval. The Tekmira Board of Directors unanimously approved and recommends that Tekmira shareholders vote FOR the proposed transaction at a special meeting of shareholders.

Details regarding these and other terms of the transaction are set out in the Merger Agreement, which will be filed by Tekmira on the SEC website at www.sec.gov and on the Canadian securities administrator’s website at www.sedar.com.

The combined company plans to retain top executives and board members from Tekmira and OnCore. The new company’s management team will include Mark J. Murray, PhD, Chief Executive Officer; Patrick T. Higgins, President and Chief Operating Officer; Bruce Cousins, Chief Financial Officer; Michael J. Sofia, PhD, Chief Scientific Officer; Mark Kowalski, MD, PhD, Chief Medical Officer; Bryce Roberts, Chief Legal Officer; Michael J. McElhaugh, Chief Business Officer; and Michael J. Abrams, PhD, Chief Discovery Officer. William T. Symonds, PharmD, who led the clinical development of sofosbuvir for the treatment of HCV infection at Pharmasset and later Gilead Sciences, Inc., will be Chief Development Officer and lead the clinical development of the portfolio.

Vivek Ramaswamy will serve as Chairman of the combined company; Dr. Daniel Kisner MD will serve as its Vice-Chairman. The combined company will be headquartered in Vancouver, BC.

I don’t understand how a company, OnCore, which is becoming a subsidiary qualifies as an equal partner in a merger but I gather this is business speak. In any event, the truly curious can find the webcast for a conference call about the deal held on Jan. 12, 2015 at 5 am PT (8 am ET)  along with an accompanying presentation here. The webcast will be available only from January 12, 2015 at 9:00 am PT  / 12 noon ET to January 17, 2015 at 9:00 am PT  / 12 noon ET and, for access, you must register on the site.

I have written previously about Tekmira, in a Nov. 19, 2014 post regarding another of its business deals and in a Sept. 23, 2014 post about its ebola treatment.

Silicon dioxide nanoparticles may affect the heart

This is an interesting piece of research although it’s difficult to draw conclusions since the testing was ‘in vitro’, which literally means ‘in glass’ and in practice means testing cells in a test tube, a petri dish or, possibly, on a slide. That said, this work centering on silicon dioxide nanoparticles, which are increasingly used in biomedical applications, suggests further investigation is warranted. From a Jan. 9, 2015 news item on Azonano,

Nanoparticles, extremely tiny particles measured in billionths of a meter, are increasingly everywhere, and especially in biomedical products. Their toxicity has been researched in general terms, but now a team of Israeli scientists has for the first time found that exposure nanoparticles (NPs) of silicon dioxide (SiO2) can play a major role in the development of cardiovascular diseases when the NP cross tissue and cellular barriers and also find their way into the circulatory system.

A Jan. 8, 2015American Technion Society news release by Kevin Hattori, which originated the news item, describes the research in more detail,

“Environmental exposure to nanoparticles is becoming unavoidable due to the rapid expansion of nanotechnology,” says the study’s lead author, Prof. Michael Aviram, of the Technion Faculty of Medicine, “This exposure may be especially chronic for those employed in research laboratories and in high tech industry where workers handle, manufacture, use and dispose of nanoparticles. Products that use silica-based nanoparticles for biomedical uses, such as various chips, drug or gene delivery and tracking, imaging, ultrasound therapy, and diagnostics, may also pose an increased cardiovascular risk for consumers as well.” [emphasis mine]

In this study, researchers exposed cultured laboratory mouse cells resembling the arterial wall cells to NPs of silicon dioxide and investigated the effects. SiO2 NPs are toxic to and have significant adverse effects on macrophages. a type of white blood cell that take up lipids, leading to atherosclerotic lesion development and its consequent cardiovascular events, such as heart attack or stroke. Macrophages accumulation in the arterial wall under atherogenic conditions such as high cholesterol, triglycerides, oxidative stress – are converted into lipids, or laden “foam cells” which, in turn, accelerate atherosclerosis development.

“Macrophage foam cells accumulation in the arterial wall are a key cell type in the development of atherosclerosis, which is an inflammatory disease” says co-author Dr. Lauren Petrick. “The aims of our study were to gain additional insight into the cardiovascular risk associated with silicon dioxide nanoparticle exposure and discover the mechanisms behind Si02’s induced atherogenic effects on macrophages. We also wanted to use nanoparticles as a model for ultrafine particle (UFP) exposure as cardiovascular disease risk factors.”

Both NPs and UFPs can be inhaled and induce negative biological effects. [emphasis mine] However, until this study, their effect on the development of atherosclerosis has been largely unknown. Here, researchers have discovered for the first time that the toxicity of silicon dioxide nanoparticles has a “significant and substantial effect on the accumulation of triglycerides in the macrophages,” at all exposure concentrations analyzed, and that they also “increase oxidative stress and toxicity.”

A recent update from the American Heart Association also suggested that “fine particles” in air pollution leads to elevated risk for cardiovascular diseases. However, more research was needed to examine the role of “ultrafine particles” (which are much smaller than “fine particles”) on atherosclerosis development and cardiovascular risk.

“The number of nano-based consumer products has risen a thousand fold in recent years, with an estimated world market of $3 trillion by the year 2020,” conclude the researchers. “This reality leads to increased human exposure and interaction of silica-based nanoparticles with biological systems. Because our research demonstrates a clear cardiovascular health risk associated with this trend, steps need to be taken to help ensure that potential health and environmental hazards are being addressed at the same time as the nanotechnology is being developed.

Unfortunately, there seems to be a little exaggeration at work in this news release. For example, I’m not sure how a consumer would go about inhaling a computer chip or more specifically the silicon dioxide nanoparticles embedded in the chip although I can see how someone involved in the manufacture of the chip might be exposed and inhale silicon dioxide nanoparticles. I’m not trying to negate the research but do want to point out that it has limitations.

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

Silicon dioxide nanoparticles increase macrophage atherogenicity: Stimulation of cellular cytotoxicity, oxidative stress, and triglycerides accumulation by Lauren Petrick, Mira Rosenblat, Nicole Paland, and Michael Aviram. Article first published online: 28 NOV 2014 DOI: 10.1002/tox.22084

Copyright © 2014 Wiley Periodicals, Inc.

This article is behind a paywall.

Engineering a small intestine

Researchers at the Children’s Hospital Los Angeles (CHLA) have successfully engineered small intestines that appear to be functional when transplanted into mice according to a Jan. 8, 2015 news item on ScienceDaily,

A new study by researchers at Children’s Hospital Los Angeles has shown that tissue-engineered small intestine grown from human cells replicates key aspects of a functioning human intestine. The tissue-engineered small intestine they developed contains important elements of the mucosal lining and support structures, including the ability to absorb sugars, and even tiny or ultra-structural components like cellular connections.

A Jan. 8, 2015 Children’s Hospital Los Angeles news release (also on EurekAlert), which originated the news item, describes the problems the researchers were addressing,

Tissue-engineered small intestine (TESI) grows from stem cells contained in the intestine and offers a promising treatment for short bowel syndrome (SBS), a major cause of intestinal failure, particularly in premature babies and newborns with congenital intestinal anomalies.  TESI may one day offer a therapeutic alternative to the current standard treatment, which is intestinal transplantation, and could potentially solve its largest challenges – donor shortage and the need for lifelong immunosuppression.

Grikscheit [Tracy C. Grikscheit, MD, a principal investigator in The Saban Research Institute of CHLA and its Developmental Biology and Regenerative Medicine program]  aims to help her most vulnerable young patients, including babies who are born prematurely and develop a devastating disease called necrotizing enterocolitis (NEC), where life-threatening intestinal damage requires removal of large portions of the small intestine. Without enough intestinal length, the babies are dependent on intravenous feeding, which is costly and may cause liver damage.  NEC and other contributors to intestinal failure occur in 24.5 out of 100,000 live births, and the incidence of SBS is increasing.  Nearly a third of patients die within five years.

The news release goes on to describe precursor work from 2011 before describing the latest research,

CHLA scientists had previously shown that TESI could be generated from human small intestine donor tissue implanted into immunocompromised mice. However, in those initial studies – published in July 2011 in the biomedical journal Tissue Engineering, Part A – only basic components of the intestine were identified. For clinical relevance, it remained necessary to more fully investigate intact components of function such as the ability to form a healthy barrier while still absorbing nutrition or specific mechanisms of electrolyte exchange.

The new study determined that mouse TESI is highly similar to the TESI derived from human cells, and that both contain important building blocks such as the stem and progenitor cells that will continue to regenerate the intestine as a living tissue replacement. And these cells are found within the engineered tissue in specific locations and in close proximity to other specialized cells that are known to be necessary in healthy human intestine for a fully functioning organ.

“We have shown that we can grow tissue-engineered small intestine that is more complex than other stem cell or progenitor cell models that are currently used to study intestinal regeneration and disease, and proven it to be fully functional as it develops from human cells,” said Grikscheit. “Demonstrating the functional capacity of this tissue-engineered intestine is a necessary milestone on our path toward one day helping patients with intestinal failure.”

If I read this rightly, the researchers engineered more complex intestinal tissues, than those in the 2011 study, in two separate processes where they grew mouse and human small intestinal tissue and successfully implanted both types of tissue into mice. The results showed that these more complex tissue-engineered small intestines (TESIs), human or mouse, resembled each other functionally within the mice tested.

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

Human and Mouse Tissue-Engineered Small Intestine Both Demonstrate Digestive And Absorptive Function by Christa Nicole Grant, Garcia Mojica Salvador, Frederic G Sala, Jeffrey Ryan Hill, Daniel E Levin, Allison L Speer, Erik R Barthel, Hiroyuki Shimada, Nicholas C. Zachos, and Tracy C. Grikscheit. American Journal of Physiology – Gastrointestinal and Liver Physiology Published 8 January 2015Vol. no. , DOI: 10.1152/ajpgi.00111.2014

This paper is behind a paywall.