#Nanoparticles used to breach mucus barrier in lungs Proof-of-concept study conducted in mice a key step toward better treatments for lung diseases Nanotechnology could one day provide an inhaled vehicle to deliver targeted therapeutic genes
Researchers at the Johns hopkins university School of medicine, Johns hopkins university Department of Chemical and Biomolecular engineering, and Federal University of Rio de janeiro in Brazil have designed a DNA-loaded nanoparticle that can pass through the mucus barrier covering conducting airways of lung tissue proving the concept,
they say, that therapeutic genes may one day be delivered directly to the lungs to the levels sufficient to treat cystic fibrosis (CF), chronic obstructive pulmonary disease,
asthma and other life-threatening lung diseases. o our knowledge, this is the first biodegradable gene delivery system that efficiently penetrates the human airway mucus barrier of lung tissue,
says study author Jung Soo Suk, Ph d, . a biomedical engineer and faculty member at the Center for Nanomedicine at the Wilmer Eye Institute at Johns Hopkins. A report on the work appeared in the Proceedings of the National Academy of Sciences on June 29.
The mucus barrier protects foreign materials and bacteria from entering and/or infecting lungs. In healthy lungs
Unfortunately, Suk notes, this essential protective mechanism also prevents many inhaled therapeutics, including gene-based medicine,
from reaching their target. His team experiments with human airway mucus and small animals, Suk adds,
or replacement genes or drugs inside a man-made biodegradable nanoparticle rapperthat patients inhale could penetrate the mucus barrier
Suk says their work with nanoparticles grew out of failed efforts to deliver treatments to people with lung diseases.
In patients with CF, for instance, they experience a buildup of excess mucus caused by impaired ciliary beating, resulting in an ideal breeding ground for chronic bacterial infection and inflammation.
but it also makes the airway mucus harder to overcome by inhaled therapeutic nanoparticles. Most of the existing drugs for CF help clear infections but do not solve the disease underlying problems.
A couple of recently approved drugs designed to target the underlying cause of CF require daily treatment for the entire lifetime
and can benefit only a subpopulation of patients with specific types of mutations. Yet this study, Suk notes, has demonstrated that delivering normal copies of CF-related genes
or corrective genes via the mucus-penetrating DNA-loaded nanoparticles could mediate production of normal, unctionalproteins long term.
This could eventually become an effective therapy for the lungs of patients, regardless of the mutation type.
DNA-loaded nanoparticles possess positive charge that caused them to adhere to negatively charged biological environments, in this case the mucus covering the lung airways.
In other words, conventional nanoparticles are too sticky to avoid unwanted off-target interactions during their journey toward the target cells.
the team developed a simple method to densely coat the nanoparticles with a nonsticky polymer called PEG,
They showed that these nanoparticles retained their sizes at a physiological environment and are capable of rapidly penetrating human airway mucus freshly collected from patients visiting the Johns Hopkins Adult Cystic fibrosis Program directed by Michael Boyle,
a co-author of the paper. The team also made the whole delivery system biodegradable so that it would not build up inside the body.
They demonstrated that inhaled delivery of the genes via the mucus-penetrating nanoparticles resulted in widespread production of the protein to levels superior to gold-standard,
you can get gene expression i e.,, production of therapeutic proteins for several months, Suk says, adding that the nanoparticles did not appear to show any adverse effects,
such as increased lung inflammation. Suk and his team caution that more animal studies are needed to confirm
and refine their proof-of-concept study, and that treatment of human disorders with nanowrapped therapies is years away a
#Small tilt in magnets makes them viable memory chips UC Berkeley researchers have discovered a new way to switch the polarization of nanomagnets,
paving the way for high-density storage to move from hard disks onto integrated circuits. This image taken from a computer simulation shows nanomagnets tilted at various angles,
with the white regions indicating greater angles of tilt. Researchers have found that even a small tilt of 2 degrees will facilitate magnetic switching.
Image credit: Samuel Smith, UC Berkeleythe advance, was reported on Monday, Aug 3, in the Proceedings of the National Academy of Sciences, will lead to computers that turn on in an instant,
operate with far greater speed and use significantly less power. A research team led by Sayeef Salahuddin,
an associate professor of electrical engineering and computer sciences, has found that tilting magnets slightly makes them easy to switch without an external magnetic field.
This opens the door to a memory system that can be packed onto a microprocessor, a major step toward the goal of reducing energy dissipation in modern electronics. o reduce the power draw
and increase the speed, we want to be able to manufacture a computer chip that includes memory
so that it is close to the computational action, said Salahuddin. owever, the physics needed to create long-term storage are not compatible with integrated circuits. reating
and switching polarity in magnets without an external magnetic field has been a key focus in the field of spintronics.
Generating a magnetic field takes power and space, which is why magnets have not yet been integrated onto computer chips.
Instead, there are separate systems for long-term magnetic memory. These include a computer hard disk drive where data are stored
and the various kinds of random-access memory, or RAM, on the integrated circuits of the central processing unit, or CPU, where calculations and logic operations are performed.
A large portion of the energy used in computing is spent on transferring data from one type of memory to another.
Doing that quickly takes more energy and generates more heat. In past research, Salahuddin and his colleagues found that directing electrical current through the rare metal tantalum creates polarity in magnets without an external magnetic field.
But the battle wasn over. Packing a sufficient number of nanomagnets onto a chip meant aligning them perpendicularly
but that vertical orientation negated the switching effects of tantalum. e found that by tilting the magnet just 2 degrees was enough you get all the benefits of a high-density magnetic switch without the need for an external magnetic field,
said Salahuddin f
#Power grid forecasting tool reduces costly errors Accurately forecasting future electricity needs is tricky, with sudden weather changes and other variables impacting projections minute by minute.
Errors can have grave repercussions, from blackouts to high market costs. Now, a new forecasting tool that delivers up to a 50 percent increase in accuracy
and the potential to save millions in wasted energy costs has been developed by researchers at the U s. Department of energy Pacific Northwest National Laboratory.
PNNL's Power grid Integrator has demonstrated up to a 50 percent improvement in forecasting future electricity needs over several commonly used tools.
Project lead Luke Gosink right, consults on the use of the new tool, which could save millions in wasted electricity costs.
PNNL Power grid Integrator has demonstrated up to a 50 percent improvement in forecasting future electricity needs over several commonly used tools.
Project lead Luke Gosink, right, consults on the use of the new tool, which could save millions in wasted electricity costs.
Performance of the tool, called the Power Model Integrator, was tested against five commonly used forecasting models processing a year worth of historical power system data. or forecasts one-to-four hours out,
we saw a 30-55 percent reduction in errors, said Luke Gosink, a staff scientist and project lead at PNNL. t was with longer-term forecasts the most difficult to accurately make where we found the tool actually performed best.
The advancement is featured this week as a best conference paper in the power system modeling and simulation session at the IEEE Power & Energy Society general meeting in Denver.
A delicate balancing act Fluctuations in energy demand throughout the day, season and year along with weather events and increased use of intermittent renewable energy from the sun
and wind all contribute to forecasting errors. Miscalculations can be costly put stress on power generators and lead to instabilities in the power system.
Grid coordinators have the daily challenge of forecasting the need for and scheduling exchanges of power to and from a number of neighboring entities.
The sum of these future transactions, called the net interchange schedule, is submitted and committed to in advance.
Accurate forecasting of the schedule is critical not only to grid stability, but a power purchaser bottom line. magine the complexity for coordinators at regional transmission organizations who must accurately predict electricity needs for multiple entities across several states,
Gosink noted. ur aim was to put better tools in their hands. Five heads better than one Currently
forecasters rely on a combination of personal experience, historical data and often a preferred forecasting model.
Each model tends to excel at capturing certain grid behavior characteristics, but not necessarily the whole picture.
To address this gap, PNNL researchers theorized that they could develop a method to guide the selection of an ensemble of models with the ideal, collective set of attributes in response to
what was occurring on the grid at any given moment. First, the team developed a statistical framework capable of guiding an iterative process to assemble,
design, evaluate and optimize a collection of forecasting models. Researchers then used this patent-pending framework to evaluate
and fine tune a set of five forecasting methods that together delivered optimal results. The resulting Power Model Integrator tool has the ability to adaptively combine the strengths of different forecasting models continuously
and in real time to address a variety scenarios that impact electricity use, from peak periods during the day to seasonal swings.
To do this, the tool accesses short-and long-term trends on the grid as well as the historical forecasting performance of the individual and combined models.
Minute by minute, the system adapts to and accounts for this information to form the best aggregated forecast possible at any given time. uring these forecasting tasks,
we noted that an ensemble of models, even those considered moderate performers, would routinely outperform individual, high-performing models,
Researchers used PNNL Institutional Computing resources to develop and validate the tool, making it possible to process a year worth of historical grid data within a few days.
High-performance computing also made it possible to evaluate the tool performance across multiple forecasting periods,
ranging from 15,30 and 60 minutes up to four hours. However, the tool also runs on standard computer workstations commonly used by the electric industry.
Flexibility in application he underlying framework is very adaptable, so we envision using it to create other forecasting tools for electric industry use,
and Color, to Microparticles A team of New york University scientists has developed a technique that prompts microparticles to form ordered structures in a variety of materials.
and color of optical materials used in computer screens along with other consumer products. The work is centered on enhancing the arrangement of colloidsmall particles suspended within a fluid medium.
Colloidal dispersions are composed of such everyday items such as paint, milk gelatin, glass, and porcelain, but their potential to create new materials remains largely untapped.
Notably, DNA-coated colloids offer particular promise because they can be linked together, with DNA serving as the glue to form a range of new colloidal structures.
However, previous attempts have produced uneven results, with these particles attaching to each other in ways that produce chaotic or inflexible configurations.
is akin to a builder having the capacity to construct a house using glass, metal, brick,
a professor of physics at NYU and chair of the Chemical and Bioengineering Department at NYU Polytechnic School of engineering. ur research shows that this be done
and trapping molecules in recent years has opened up an entirely new energy regime for studying chemical reactivity at temperatures below one micro-Kelvin,
or magnetic fields to control whether the interference is constructive or destructive. This new mechanism is a general property of ultracold chemical reactions
and Jisha Hazra and Naduvalath Balakrishnan of the University of Nevada-Las vegas a
#Words That Work Together Stay together How language gives your brain a break. Here a quick task:
Take a look at the sentences below and decide which is the most effective. 1) ohn threw out the old trash sitting in the kitchen.
2) ohn threw the old trash sitting in the kitchen out. ither sentence is grammatically acceptable,
but you probably found the first one to be more natural. Why? Perhaps because of the placement of the word ut,
That means language users have a global preference for more locally grouped dependent words, whenever possible. eople want words that are related to each other in a sentence to be close together,
says Richard Futrell, a Phd student in the Department of Brain and Cognitive sciences at MIT,
a professor of cognitive science and co-author of the paper. e though it was probably true more widely,
the researchers used four large databases of sentences that have been parsed grammatically: one from Charles University in Prague, one from Google, one from the Universal Dependencies Consortium (a new group of computational linguists),
and a Chinese-language database from the Linguistic Dependencies Consortium at the University of Pennsylvania.
The sentences are taken from published texts, and thus represent everyday language use. To quantify the effect of placing related words closer to each other,
Other scholars who have done research on this topic say the study provides valuable new information. t interesting and exciting work,
says David Temperley, a professor at the University of Rochester, who along with his Rochester colleague Daniel Gildea has authored co a study comparing dependency length in English
Gibson, and Mahowald readily note that the study leaves larger questions open: Does the DLM tendency occur primarily to help the production of language, its reception, a more strictly cognitive function,
and ommunicate withengineered bacteria Super productive factories of the future could employ fleets of genetically engineered bacterial cells,
such as common E coli, to produce valuable chemical commodities in an environmentally friendly way. By leveraging their natural metabolic processes,
bacteria could be reprogrammed to convert readily available sources of natural energy into pharmaceuticals, plastics and fuel products. he basic idea is that we want to accelerate evolution to make awesome amounts of valuable chemicals,
said Wyss Core Faculty member George Church, Ph d, . who is a pioneer in the converging fields of synthetic biology, metabolic engineering, and genetics.
Church is the Robert Winthrop Professor of Genetics at Harvard Medical school and Professor of Health Sciences and Technology at Harvard and MIT.
Critical to this process of metabolically engineering microbes is the use of biosensors. Made of a biological component such as a fluorescent protein
and a etectorthat responds to the presence of a specific chemical, biosensors act as the switches
and levers that turn programmed functions on and off inside the engineered cells. They also can be used to detect which microbial orkersare producing the most voluminous amounts of a desired chemical.
But so far, scientists have had only access to a limited variety of biosensors that have little relevance to the biomanufacturing of valuable chemicals.
Now, Wyss Institute researchers led by Church have developed a new suite of such sensors, reported in Nucleic acids Researchjournal,
but also respond to valuable products such as renewable plastics or costly pharmaceuticals and give microbes a voice to report on their own efficiency in making these products. e can communicate with cells much more effectively,
a graduate researcher at the Wyss Institute who is pursuing his Ph d. in Engineering sciences from Harvard university. f we compared this to controlling a computer,
the biosensors can be used to trigger individual cells to give off visible fluorescence in a rate directly proportional to how well they are able to produce a desired chemical commodity.
the most efficient microbial workers are identified easily so that they can serve as the predecessors for colonies of engineered bacteria that evolve to become more efficient at producing renewable chemicals with each subsequent generation.
The findings could also lead to new applications in environmental monitoring using genetically engineered microbes to issue warning signals in the presence of pollutants
and we still have many interesting new approaches. ith this work, George and his team are bringing us closer to a sustainable future in
which we would rely on biomanufacturing for the clean production of chemical and pharmaceutical commodities, said Wyss Institute Founding Director Donald E. Ingber,
M d.,Ph d.,who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical school and Boston Children Hospital,
and Professor of Bioengineering at the Harvard John A. Paulson School of engineering and Applied sciences o
#Bend me, shape me, any way you want me: Scientists curve nanoparticle sheets into complex forms Scientists have been making nanoparticles for more than two decades in two-dimensional sheets, three-dimensional crystals and random clusters.
But they have never been able to get a sheet of nanoparticles to curve or fold into a complex three-dimensional structure.
Now researchers from the University of Chicago, the University of Missouri and the U s. Department of energy Argonne National Laboratory have found a simple way to do exactly that.
This highly magnified image of a folded gold nanoparticle scroll shows that even though researchers can fold the membrane,
the internal structure remains intact. The findings open the way for scientists to design membranes with tunable electrical,
magnetic and mechanical properties that could be used in electronics and may even have implications for understanding biological systems.
Working at the Center for Nanoscale Materials (CNM) and the Advanced Photon Source (APS), two DOE Office of Science User Facilities located at Argonne,
the team got membranes of gold nanoparticles coated with organic molecules to curl into tubes when hit with an electron beam.
Equally importantly, they have discovered how and why it happens. The scientists coat gold nanoparticles of a few thousand atoms each with an oil-like organic molecule that holds the gold particles together.
When floated on water the particles form a sheet; when the water evaporates, it leaves the sheet suspended over a hole. t almost like a drumhead,
says Xiao-Min Lin, the staff scientist at the Center for Nanoscale Materials who led the project. ut it a very thin membrane made of a single layer of nanoparticles. rgonne researchers are able to fold gold nanoparticle membranes in a specific
direction using an electron beam because two sides of the membrane are different. Image credit:
Xiao-Min Lin et al, taken at Argonne Electron microscopy Center. To their surprise, when the scientists put the membrane into the beam of a scanning electron microscope,
it folded. It folded every time, and always in the same direction. hat got our curiosity up,
so they end up distributing themselves in a nonuniform way across the top and bottom layers of the nanoparticle sheet.
When the electron beam hits the molecules on the surface it causes them to form an additional bond with their neighbors,
creating an asymmetrical stress that makes the membranes fold. Zhang Jiang and Jin Wang, X-ray staff at the APS,
Subramanian Sankaranarayanan and Sanket Deshmukh at CNM used the high-performance computing resources at DOE National Energy Research Scientific Computing Center and the Argonne Leadership Computing Facility (ALCF
), both DOE Office of Science User Facilities, to analyze the surface of the nanoparticles. They discovered that the amount of surface covered by the organic molecules
and the moleculesmobility on the surface both have an important influence on the degree of asymmetry in the membrane. hese are said fascinating results
professor of chemical physics at the Imperial College in London and a leading theorist on soft matter physics. hey advance significantly our ability to make new nanostructures with controlled shapes. n principle,
scientists could use this method to induce folding in any nanoparticle membrane that has an asymmetrical distribution of surface molecules.
yet too small to trigger the thermonuclear reactions at their cores that power stars. The astronomers said their observations of LSR J1835+3259 indicate that the coolest stars
The aurora the scientists observed from LSR J1835+3259 appears powered by a little-understood dynamo process similar to that seen on larger planets in our Solar system.
which causes the Earth auroral displays the planet magnetic field interacting with the solar wind. hat we see on this object appears to be the same phenomenon wee seen on Jupiter, for example,
#Real-time data for cancer therapy In the battle against cancer, which kills nearly 8 million people worldwide each year,
doctors have in their arsenal many powerful weapons, including various forms of chemotherapy and radiation.
however, is good reconnaissance a reliable way to obtain real-time data about how well a particular therapy is working for any given patient.
Magnetic resonance imaging and other scanning technologies can indicate the size of a tumor, while the most detailed information about how well a treatment is working comes from pathologistsexaminations of tissue taken in biopsies.
Yet these methods offer only snapshots of tumor response and the invasive nature of biopsies makes them a risky procedure that clinicians try to minimize.
Now, researchers at MIT Koch Institute for Integrative Cancer Research are closing that information gap by developing a tiny biochemical sensor that can be implanted in cancerous tissue during the initial biopsy.
The sensor then wirelessly sends data about telltale biomarkers to an external eaderdevice, allowing doctors to better monitor a patient progress
and adjust dosages or switch therapies accordingly. Making cancer treatments more targeted and precise would boost their efficacy
while reducing patientsexposure to serious side effects. e wanted to make a device that would give us a chemical signal about what happening in the tumor,
says Michael Cima, the David H. Koch (1962) Professor in Engineering in the Department of Materials science and engineering and a Koch Institute investigator who oversaw the sensor development. ather than waiting months to see
if the tumor is shrinking, you could get an early read to see if youe moving in the right direction.
Two MIT doctoral students in Cima lab worked with him on the sensor project: Vincent Liu, now a postdoc at MIT,
and Christophoros Vassiliou, now a postdoc at the University of California at Berkeley. Their research is featured in a paper in the journal Lab on a Chip that has been published online.
Once implanted, the sensor wirelessly sends data about biomarkers to an external eaderdevice, allowing doctors to better monitor a patient progress
and adjust or switch therapies. Photo courtesy of the researchers. Measurements without MRI The sensors developed by Cima team provide real-time,
on-demand data concerning two biomarkers linked to a tumor response to treatment: ph and dissolved oxygen.
As Cima explains, when cancerous tissue is under assault from chemotherapy agents, it becomes more acidic. any times,
you can see the response chemically before you see a tumor actually shrink, Cima says.
In fact, some therapies will trigger an immune system reaction, and the inflammation will make the tumor appear to be growing,
even while the therapy is effective. Oxygen levels, meanwhile, can help doctors gauge the proper dose of a therapy such as radiation,
since tumors thrive in low-oxygen (hypoxic) conditions. t turns out that the more hypoxic the tumor is,
the more radiation you need, Cima says. o, these sensors, read over time, could let you see how hypoxia was changing in the tumor,
so you could adjust the radiation accordingly. The sensor housing, made of a biocompatible plastic,
is small enough to fit into the tip of a biopsy needle. It contains 10 microliters of chemical contrast agents typically used for magnetic resonance imaging (MRI)
and an onboard circuit to communicate with the external reader device. Devising a power source for these sensors was critical,
Cima explains. Four years ago, his team built a similar implantable sensor that could be read by an MRI SCANNER.
RI scans are expensive and not easy to make part of routine care, he says. e wanted to take the next step
and put some electronics on the device so we could take these measurements without an MRI.
For power, these new sensors rely on the reader. Specifically, there a metal coil inside the reader and a much smaller coil in the sensor itself.
An electric current magnetizes the coil inside the reader, and that magnetic field creates a voltage in the sensor coil
when the two coils are close together a process called mutual inductance. The reader sends out a series of pulses,
and the sensor ings back, as Cima puts it. The variation in this return signal over time is interpreted by a computer to
which the reader is wired, revealing changes in the targeted biomarkers. ith these devices, it like taking blood pressure.
It a simple measurement. You get the readout and move on, says Ralph Weissleder, a radiologist and director of the Center for Systems Biology lab at Massachusetts General Hospital who is familiar with the research. hatever you can do right then and there without any complicated testing,
the better it is. Additional applications Cima team successfully tested the sensors in lab experiments
including implanting them in rodents. While the sensors were implanted only for a few weeks, Cima believes they could be used to monitor a person health over many years. here are thousands of people alive today,
because they have implantable electronics, like pacemakers and defibrillators, he says. ee making these sensors out of materials that are in these kinds of long-term implants,
and given that theye so small, I don think there will be a problem. These initial experiments showed that the sensors could quickly, reliably,
and accurately detect ph and oxygen concentration in tissue. The researchers next want to see how well the sensors do measuring changes in ph over an extended period of time. want to push these probes
so we can use them to monitor tumor response, Cima says. e did a little bit of that in these experiments,
but we need to make that really robust. While the primary application of these sensors would be cancer care,
Cima is also eager to collaborate with researchers in other fields, such as environmental science. or example,
you could use these to measure dissolved oxygen or ph from a lot of different sites all over a pond or a lake,
Cima says. excited about using these sensors to bring big data to environmental monitoring
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