Researchers at the University of Bath suggest developments in 3D printing techniques could open the door to the advancement of membrane capabilities.
This work is part of the University’s Centre for Advanced Separations Engineering (CASE) and is the first time the properties of different 3D printing techniques available to membrane fabrication have been assessed.
Wide ranging applications
Membranes are a semi-permeable selective barrier that separate the molecules in a mixture within a gas or liquid into two streams, a key example of this being the separation of salt from water for desalination using reverse osmosis membranes.
3D printing, otherwise known as Additive Manufacturing, has the ability to create almost any geometrically complex shape or feature in a range of materials across different scales. It has applications in various areas including medicine, art, manufacturing and engineering. However, its use in separation membrane engineering is relatively new.
Membranes are currently restricted mainly to tubular/hollow fibre and flat surface configurations due to the limitations of current manufacturing processes. As a result, the precision of present membranes are limited in successfully separating certain properties.
Innovative, more accurate membranes
The use of 3D printing techniques offers novel membrane preparation techniques that are able to produce membranes of different shapes, types and designs, which can be more precisely designed, fabricated and controlled than any other membrane fabrication method currently available.
The paper, which evaluates existing knowledge of the advantages and drawbacks of different 3D printing methods as well as the potential developments of membrane fabrication, identifies a bright future in which 3D printing will enable innovative and far more accurate membranes.
These potential increased capabilities could have significant implications for a number of key industries, including the water industry. New membranes with designer pores and surface shapes that enhance micro-mixing and shear flow across the membrane surface could be used to reduce the energy and down-time associated with cleaning blockages and fouling of the membranes.
Director of the Centre for Advanced Separations Engineering at the University of Bath, Dr Darrell Patterson, commented: “This review is the first to explore the possibility and challenges of using 3D printing for producing separation membranes.
“Although 3D printing technology is not quite well enough developed to yet produce large scale membranes that will be cost competitive with existing products, this work does signal what the future possibilities are with 3D printing, to produce membranes beyond that which are currently available, including controlled complex pore structures, integrated surface patterns and membranes based on nature.”
Lower energy, more sustainable molecular separations
Up to 15 per cent of energy used globally is from the separation and purification of industrial products such as gases, fine chemicals and fresh water. Separation processes also account for 40 to 70 per cent of industry capital and operating costs. Membrane technology potentially offers lower energy, more sustainable molecular separations that can be applied to a wide range of gas and liquid separations. It is therefore a key technology that could be used to help decrease the carbon footprint and costs within industry.
Journal of Neuroscience study examines medicinal properties of cannabis
OHSU research suggests an avenue for developing treatments for chronic pain that harness the medicinal properties of cannabis while minimizing the threat of addiction.
The study, conducted in a rodent model, provides additional rationale for the development of therapeutics using cannabinoid receptors to treat chronic pain, which afflicts about 30 percent of the U.S. population. OHSU investigators studied the function of two forms of cell membrane receptors that bind cannabinoids that occur naturally within the body, called endocannabinoids.
“It may be an avenue where we can get better pain medications that are not addictive,” said senior author Susan Ingram, Ph.D., an associate professor of neurosurgery in the OHSU School of Medicine.
Ingram and colleagues report the treatment of chronic pain has challenged the medical system, with medications that are ineffective or create serious side effects: “However, emerging data indicate that drugs that target the endocannabinoid system might produce analgesia with fewer side effects compared with opioids.”
The body’s endocannabinoid system comprises receptors, endocannabinoid molecules and enzymes that make and degrade the endocannabinoids located in the brain and throughout the central and peripheral nervous system. The research team focused on two cannabinoid receptors, known as CB1 and CB2, in the rostral ventromedial medulla – a group of neurons located in the brainstem known to modulate pain. The study is the first to examine CB1 and CB2 receptor function at the membrane level in late adolescent and adult neurons.
The researchers observed that chronic inflammatory pain increased activity of CB2 receptors and decreased CB1 activity. Cannabis activates both CB1 and CB2 receptors equally. The study suggests that selective activation of CB2 receptors contributes to the medicinal benefit of cannabis while minimizing the propensity of the other cannabinoid receptor, CB1, to induce tolerance and withdrawal. Ingram said the next phase of the research will further explore this area of brain circuitry, which ultimately could lead to the development of a new class of pain medications.
Drug shown to reduce new attacks/symptom progression in some patients
In separate clinical trials, a drug called ocrelizumab has been shown to reduce new attacks in patients with relapsing remitting multiple sclerosis (MS), and new symptom progression in primary progressive MS.
Three studies conducted by an international team of researchers, which included Amit Bar-Or and Douglas Arnold from the Montreal Neurological Institute and Hospital of McGill University, have discovered that ocrelizumab can significantly reduce new attacks in patients with relapsing MS, as well as slow the progression of symptoms caused by primary progressive MS.
In one study, 732 patients with primary progressive MS were randomized on a 2:1 ratio to receive either ocrelizumab, a humanized monoclonal antibody that depletes CD20+ B cells, or a placebo.
The proportion of patients with 12-week confirmed disability progression was 39.3 per cent with the placebo versus 32.9 per cent with ocrelizumab. After 24 weeks, the proportion with confirmed disability progression was 35.7 per cent with placebo versus 29.6 per cent with ocrelizumab. By week 120, timed 25-foot walk worsened by 55.1 per cent for placebo versus 38.9 per cent for ocrelizumab. Patients given ocrelizumab were also found to have fewer new brain lesions and less brain volume loss than those given the placebo.
Researchers also tested ocrelizumab in two separate studies of patients with relapsing remitting MS, one a group of 821 and the other 835. In both studies, patients were randomized on a 1:1 ratio to receive either ocrelizumab or an already established treatment for relapsing MS: subcutaneous interferon-beta, injected three times weekly. Compared to the placebo, relapse rates in patients given ocrelizumab were 46-per-cent lower in one study and 47-per-cent lower in the other. Ocrelizumab was found to reduce the risk of disability progression after 12 weeks and 24 weeks, and reduced the number of new brain lesions.
The study noted that infusion-related reactions occurred in 34.3 per cent of ocrelizumab-treated patients. Serious infections were not more frequent with ocrelizumab compared to the interferon (1.3 versus 2.9 per cent respectively). Malignancies occurred in four ocrelizumab-treated patients and in two interferon-treated patients. Further observation is required to determine the long-term safety of ocrelizumab.
“The results in patients with relapsing remitting MS not only demonstrate very high efficacy against relapses, but also underscore the important emerging role of B cells of the immune system in the development of relapses,” says Bar-Or. “While the results in patients with primary progressive MS are more modest, they nonetheless represent the very first successful trial in such patients, a breakthrough as primary progressive MS now transitions from a previously untreatable condition to one that can be impacted by therapy. It is an important step forward in the field.”
These studies, funded by Roche, were published in the New England Journal of Medicine on Dec. 21, 2016.
MS in Canada
Canada has one of the world’s highest rates of MS – about 1,100 new cases each year. Some 50,000 Canadians have MS, and more than one-in-five patients are in Quebec. MS is one of the most common neurological diseases among young Canadians. Children as young as two can develop the disease. It typically strikes people in their prime years, between 15 and 40. Women are twice as likely as men to contract MS.
Learn more: Breakthrough in MS treatment
Novel Drug May Help Repair Failing Hearts
Cimaglermin, a new experimental drug, may help restore cardiac function after heart failure, according to a first-in-man study published today in JACC: Basic to Translational Science.
Heart failure, characterized by a loss of cardiac function, is among the leading causes of death worldwide. A significant portion of heart failure patients, particularly those with severe left ventricular systolic dysfunction, do not sufficiently respond to current medical therapy.
Researchers examined the safety and efficacy of a single infusion of cimaglermin, which acts as a growth factor for the heart, helping the structural, metabolic and contractile elements of the heart to repair itself following injury. The study enrolled 40 heart failure patients who were taking optimal medical therapy for at least three months prior to the trial. Compared to patients who received a placebo, patients who received a high dose of cimaglermin had a sustained increase in left ventricular ejection fraction, or pumping capacity, through 90 days after dosing, with the maximum increase reached at day 28.
“These findings support continued clinical development of the investigational drug cimaglermin, including further safety evaluations and detailing the potential improvement on clinical heart failure outcome measures,” said Daniel J. Lenihan MD, from the division of cardiovascular medicine at Vanderbilt University and the lead author of the study. “As with all experimental therapeutics, additional studies will be required and subject to regulatory review to determine if the relative risks and benefits of cimaglermin warrant approval.”
The most common side effects were headache and nausea, which were temporarily associated with exposure to the drug. One patient receiving the highest planned dose of cimaglermin experienced an adverse reaction that met the stopping criteria of Federal Drug Administration guidance for drug induced liver injury.
Limitations of this study include the small sample size and the fact that patients only received a single infusion rather than multiple doses.
“Although the results of the study must be regarded as provisional because of the small numbers of patients, the results of this study are nonetheless very exciting,” said Douglas L. Mann, MD, FACC, editor-in-chief of JACC: Basic to Translational Science. “Instead of blocking the fundamental mechanisms that lead to cardiac injury, the early results with cimaglermin suggest that it may also be possible to administer therapeutics that allow the failing heart to repair itself using its own repair mechanisms. If the results of this study can be replicated and translated into improvements in clinical outcomes in larger numbers of patients in phase II and III clinical trials, it will represent a paradigm shift in the way in which clinicians treat patients with heart failure.”
Learn more: Novel Drug May Help Repair Failing Hearts
Using a mouse model, scientists from the RIKEN-Max Planck Joint Research Center for Systems Chemical Biology and a number of other institutes have identified a sugar molecule that reduced the inflammatory response and progress of emphysema, a common component of chronic obstructive pulmonary disease (COPD). According to Naoyuki Taniguchi, the leader of the group, this discovery could lead to the development of drugs based on glycans—biological sugar molecules—for the treatment of diseases such as COPD, which is the fourth leading cause of death worldwide.
As part of the research group’s work to explore the roles of sugar molecules in health and disease, they found that keratan sulfate, a large negatively charged saccharide found in the small airway of the lung, is decreased in mice that have been exposed to cigarette smoke. They wondered if this decrease might be associated with the damage that smoking causes to the lung. Taniguchi says, “We are not absolutely sure of the mechanism through which smoking leads to a reduction in keratan sulfate, but felt that clearly the reduction is important in thinking about glycan-based strategies for combating emphysema and COPD.”
They wondered whether the keratan sulfate might be playing a protective role in COPD. To test the hypothesis, they prepared a repeating disaccharide element of keratan sulfate, named L4, and administered it into two mouse models of emphysema—one a model of emphysema triggered by the enzyme elastase, and the other an exacerbation of smoking-induced emphysema triggered by LPS, a toxin found in bacterial cell walls.
In the first model, they found that that treatment with L4 prevented destruction of the alveoli—the small air sacs in lungs that are used to exchange gases, and in addition that it reduced the infiltration of a type of white blood cell called neutrophils, which is symptomatic of an inflammatory response, as well as levels of inflammatory cytokines and tissue-degrading enzymes. Although L4 was shown to inhibit these enzymes, they did not find any ability of L4 to directly reduce the production of cytokines or reactive oxygen species, so concluded that the action was also being done indirectly, through mechanisms involving the neutrophils.
In the exacerbation model, they found that the L4 administration prevented the influx of neutrophils. According to Taniguchi, “We found that L4 was as effective as dexamethasone in reducing neutrophil infiltration. This is very exciting, because dexamethasone, the treatment currently used for COPD, is a steroid medication that can have serious side effects and can in some cases make the outcome worse. It will be exciting if we can show that L4—a sugar molecule which we found had no adverse effects in the mice even at high doses—can be used as a treatment for this condition, which exerts a tremendous health burden.”
According to Taniguchi, there is still work to be done in the area. “We plan now to try to determine exactly how L4 blocks neutrophil migration, by finding a target receptor protein, and how L4 can suppress inflammation in vivo, as this could give us important insights into the mechanism of COPD progression and how it can be halted.”
A centuries-old herbal medicine, discovered by Chinese scientists and used to effectively treat malaria, has been found to potentially aid in the treatment of tuberculosis and may slow the evolution of drug resistance.
In a promising study led by Robert Abramovitch, a Michigan State University microbiologist and TB expert, the ancient remedy artemisinin stopped the ability of TB-causing bacteria, known as Mycobacterium tuberculosis, to become dormant. This stage of the disease often makes the use of antibiotics ineffective.
The study is published in the journal Nature Chemical Biology.
“When TB bacteria are dormant, they become highly tolerant to antibiotics,” Abramovitch said, an assistant professor in the College of Veterinary Medicine. “Blocking dormancy makes the TB bacteria more sensitive to these drugs and could shorten treatment times.”
One-third of the world’s population is infected with TB and the disease killed 1.8 million people in 2015, according to the Centers for Disease Control and Prevention.
Mycobacterium tuberculosis, or Mtb, needs oxygen to thrive in the body. The immune system starves this bacterium of oxygen to control the infection. Abramovitch and his team found that artemisinin attacks a molecule called heme, which is found in the Mtb oxygen sensor. By disrupting this sensor and essentially turning it off, the artemisinin stopped the disease’s ability to sense how much oxygen it was getting.
“When the Mtb is starved of oxygen, it goes into a dormant state, which protects it from the stress of low-oxygen environments,” Abramovitch said. “If Mtb can’t sense low oxygen, then it can’t become dormant and will die.”
Abramovitch indicated that dormant TB can remain inactive for decades in the body. But if the immune system weakens at some point, it can wake back up and spread. Whether it wakes up or stays ‘asleep’ though, he said TB can take up to six months to treat and is one of the main reasons the disease is so difficult to control.
“Patients often don’t stick to the treatment regimen because of the length of time it takes to cure the disease,” he said. “Incomplete therapy plays an important role in the evolution and spread of multi-drug resistant TB strains.”
He said the research could be key to shortening the course of therapy because it can clear out the dormant, hard-to-kill bacteria. This could lead to improving patient outcomes and slowing the evolution of drug-resistant TB.
After screening 540,000 different compounds, Abramovitch also found five other possible chemical inhibitors that target the Mtb oxygen sensor in various ways and could be effective in treatment as well.
“Two billion people worldwide are infected with Mtb,” Abramovitch said. “TB is a global problem that requires new tools to slow its spread and overcome drug resistance. This new method of targeting dormant bacteria is exciting because it shows us a new way to kill it. ”
Learn more: ANCIENT CHINESE MALARIA REMEDY FIGHTS TB
A team of scientists at the Children’s Medical Center Research Institute at UT Southwestern (CRI) discovered a new bone-forming growth factor, Osteolectin (Clec11a), which reverses osteoporosis in mice and has implications for regenerative medicine.
Although Osteolectin is known to be made by certain bone marrow and bone cells, CRI researchers are the first to show Osteolectin promotes the formation of new bone from skeletal stem cells in the bone marrow. The study, published in eLife, also found that deletion of Osteolectin in mice causes accelerated bone loss during adulthood and symptoms of osteoporosis, such as reduced bone strength and delayed fracture healing.
“These results demonstrate the important role Osteolectin plays in new bone formation and maintaining adult bone mass. This study opens up the possibility of using this growth factor to treat diseases like osteoporosis,” said Dr. Sean Morrison, who led the team that made the discovery. Dr. Morrison, CRI Director, holds the Mary McDermott Cook Chair in Pediatric Genetics at UT Southwestern Medical Center, and the Kathryne and Gene Bishop Distinguished Chair in Pediatric Research at Children’s Research Institute at UT Southwestern.
Osteoporosis, a progressive bone disease characterized by decreased bone mass and an increase in fractures, affects over 200 million people worldwide. Most existing therapies such as bisphosphonate drugs reduce the rate of bone loss, but they do not promote new bone growth. Teriparatide (PTH) is the only agent currently approved for the formation of new bone, but its use is limited to two years due to a potential risk of osteosarcoma.
To determine whether treatment with Osteolectin could reverse bone loss after the onset of osteoporosis, the CRI research team used mice that had their ovaries removed to model the type of osteoporosis that develops in postmenopausal women. Mice were given daily injections of PTH or recombinant Osteolectin. The study found that both recombinant Osteolectin- and PTH-treated mice had significantly increased bone volume compared to untreated mice. Both treatments effectively reversed the bone loss that occurred after the removal of the ovaries.
“These early results are encouraging, suggesting Osteolectin might one day be a useful therapeutic option for osteoporosis and in regenerative medicine,” said Dr. Morrison, also a Professor of Pediatrics at UT Southwestern, a CPRIT Scholar in Cancer Research, and a Howard Hughes Medical Institute Investigator.
Researchers in the Hamon Laboratory for Stem Cell and Cancer Biology, of which Dr. Morrison is the principal investigator, plan to further test Osteolectin’s therapeutic potential and to identify the receptor for Osteolectin, which is key to understanding the signaling mechanisms the protein uses to promote osteogenesis.
Technique enables development of viable diagnostic tests and instruments in fight against cancer
Cancer is the second leading cause of death in the U.S., making early, reliable diagnosis and treatment a priority for researchers. Genomic biomarkers offer great potential for diagnostics and new forms of treatment, such as immunotherapy. Miniaturized lab-on-chip approaches are prime candidates for developing viable diagnostic tests and instruments because they are small, need only limited test volumes, and can be cost-effective.
A team of scientists and engineers from the University of California, Santa Cruz and Brigham Young University have developed just such an approach capable of processing biomolecular samples from blood. Their method can analyze and identify multiple targets on a silicon-based molecular detection platform and is described this week in Biomicrofluidics, from AIP Publishing.
Laboratory–on-a-chip describes the miniaturization of laboratory functions such as blood testing on a chip. Instead of transferring relatively large (micro- to milliliters) samples between test tubes or using bulky analytical equipment, samples and reagents are handled on chip-scale devices with fluidic microchannels. This requires much smaller test volumes, and multiple functions can be integrated on a single device, improving speed, reliability and portability of these lab processes.
“Our approach uses optofluidic chips where both fluid processing and optical sensing are done on a chip, allowing for further miniaturization and performance enhancements of the chip system,” said Holger Schmidt, a Narinder Kapany professor of electrical engineering at the University of California, Santa Cruz.
The entire process of testing was a challenge for the team, led by Schmidt and Aaron Hawkins, a physics professor at Brigham Young University. Each of the chips had to be developed and tested for multiple functions, from filtering of blood cells without clogging the filter to reliably analyzing optical data to create the right excitation patterns on the silicon chip. However, the process worked as envisioned, and the team was pleasantly surprised to see just how powerful the multi-spot optical excitation method actually was.
The next step to realizing the potential of this research is to move toward real clinical samples and to detect individual DNA biomarkers.
“We have shown single nucleic acid analysis in the context of on-chip Ebola detection and would like to transfer that to this application,” said Schmidt.
Other goals for the team include increasing the speed of the analysis process, and integrating more optical elements on the chip. They also want to expand their capabilities to analyzing protein biomarkers in addition to nucleic acids and whole virus particles already demonstrated.
This research is expected to have a wide range of applications because the underlying principle of this kind of on-chip optical analysis and manipulation is very general.
“In the near term, we hope to build new diagnostic instruments for molecular diagnostics with applications in oncology and infectious disease detection, both viruses and (drug-resistant) bacteria,” Schmidt said. “In addition, these chips could be very useful for fundamental research in molecular biology and other life sciences since they can provide analysis of single nano- and microparticles without the need for expensive equipment. And they require a relatively low amount of experimental skills.”
Graphene quantum dots may offer a simple way to recycle waste carbon dioxide into valuable fuel rather than release it into the atmosphere or bury it underground, according to Rice University scientists.
Nitrogen-doped graphene quantum dots (NGQDs) are an efficient electrocatalyst to make complex hydrocarbons from carbon dioxide, according to the research team led by Rice materials scientist Pulickel Ajayan. Using electrocatalysis, his lab has demonstrated the conversion of the greenhouse gas into small batches of ethylene and ethanol.
The research is detailed this week in Nature Communications.
Though they don’t entirely understand the mechanism, the researchers found NGQDs worked nearly as efficiently as copper, which is also being tested as a catalyst to reduce carbon dioxide into liquid fuels and chemicals. And NGQDs keep their catalytic activity for a long time, they reported.
“It is surprising because people have tried all different kinds of catalysts. And there are only a few real choices such as copper,” Ajayan said. “I think what we found is fundamentally interesting, because it provides an efficient pathway to screen new types of catalysts to convert carbon dioxide to higher-value products.”
Those problems are hardly a secret. Atmospheric carbon dioxide rose above 400 parts per million earlier this year, the highest it’s been in at least 800,000 years, as measured through ice-core analysis.
“If we can convert a sizable fraction of the carbon dioxide that is emitted, we could curb the rising levels of atmospheric carbon dioxide levels, which have been linked to climate change,” said co-author Paul Kenis of the University of Illinois.
In lab tests, NGQDs proved able to reduce carbon dioxide by up to 90 percent and convert 45 percent into either ethylene or alcohol, comparable to copper electrocatalysts.
Graphene quantum dots are atom-thick sheets of carbon atoms that have been split into particles about a nanometer thick and just a few nanometers wide. The addition of nitrogen atoms to the dots enables varying chemical reactions when an electric current is applied and a feedstock like carbon dioxide is introduced.
“Carbon is typically not a catalyst,” Ajayan said. “One of our questions is why this doping is so effective. When nitrogen is inserted into the hexagonal graphitic lattice, there are multiple positions it can take. Each of these positions, depending on where nitrogen sits, should have different catalytic activity. So it’s been a puzzle, and though people have written a lot of papers in the last five to 10 years on doped and defective carbon being catalytic, the puzzle is not really solved.”
“Our findings suggest that the pyridinic nitrogen (a basic organic compound) sitting at the edge of graphene quantum dots leads the catalytic conversion of carbon dioxide to hydrocarbons,” said Rice postdoctoral researcher Jingjie Wu, co-lead author of the paper. “The next task is further increasing nitrogen concentration to help increase the yield of hydrocarbons.”
Ajayan noted that while electrocatalysis is effective at lab scales for now, industry relies on scalable thermal catalysis to produce fuels and chemicals. “For that reason, companies probably won’t use it any time soon for large-scale production. But electrocatalysis can be easily done in the lab, and we showed it will be useful in the development of new catalysts.”
Learn more: Carbon dots dash toward ‘green’ recycling role
Generation, storage, and time-delayed release of electrons in graphitic carbon nitride material for artificial photosynthesis
The storage of photogenerated electric energy and its release on demand are still among the main obstacles in artificial photosynthesis.
Scientists have now explored a modified form that can produce light-generated electrons and store them for catalytic hydrogen production even after the light has been switched off.
They present this biomimetic photosynthesis approach in the journal Angewandte Chemie.
A new technique that will allow scientists to determine the effects of turning on and off a set of molecules involved in almost every cellular pathway, determine their downstream effects, and uncover new drug targets has been developed by researchers at the University of Illinois at Chicago.
Protein kinases are enzymes involved in almost every biological process. Several hundred different kinases work to phosphorylate various proteins and drive the entire range of cellular activities.
The experiment demonstrated that even short-term activation of a kinase can have a long-lasting effect on cell behavior, and allowed researchers to identify the molecular mechanism driving these events.