New Century Global Centre is a multipurpose building in the Tianfu New Area of Chengdu, China. The 100 m (330 ft) structure is 500 by 400 m  with 1,700,000 square metres of floor space, making it the world's biggest building measured by floor space.The Boeing Everett Factory in Everett, Washington has the largest volume, and the Aalsmeer Flower Auction Building in Aalsmeer, Netherlands, has the largest footprint
New Century Global Centre.jpg
Nearly 4,300,000 sq ft of the building will be devoted to shopping. It will also house offices, conference rooms, a university complex, two commercial centres, hotels, an IMAXcinema, a "Mediterranean village", a pirate ship and skating rink. The centrepiece of the building will be a 5,000 m2 (54,000 sq ft) artificial beach, a giant 150 by 40 m (490 by 130 ft) screen will form the horizon and offer sunrises and sunsets. The building will face the Chengdu Contemporary Arts Centre, designed by award-winning British-Iraqi architect Zaha Hadid.



The main pool will have a stage that extends out over the pool each night for concerts. A stand has been built overlooking the pool with a food court and entrance underneath at the floor level.The new Intercontinental Hotel will feature 1,009 rooms that are spread over 6 x 8 story blocks around the edge of the complex.While parts of the shopping area are open, the main opening is planned for 22 August 2013.                   
In 1935, the United States Congress announced the first Sunday of August as the National Friendship Day and declared it to be a holiday in honor of friends.

Women's Friendship Day is celebrated on the third Sunday of September.

Best Friends Weekend is an occasion established by the Best Friends Animal Society. It is celebrated every year from June 23 - June 25 to honor and protect the rights of animals. The first day of the weekend is called Best Friends' Day.

'D del Amigo' (The Spanish Friend's Day) is a celebration of friendship, held annually on July 20, mainly in Argentina and Uruguay.

Old Friends, New Friends Week is the third week of May.

The whole of February is designated as the International Friendship Month.

In 1997, the United Nations named Winnie - the Pooh, the famous cartoon character as the world's Ambassador of Friendship.

The immortal song "With a Little Help from My Friends" by Beatles, that deals with the theme of friendship, was released in 1967.
Monash University researchers have brought next generation energy storage closer with an engineering first -- a graphene-based device that is compact, yet lasts as long as a conventional battery.Published today in Science, a research team led by Professor Dan Li of the Department of Materials Engineering has developed a completely new strategy to engineer graphene-based supercapacitors (SC), making them viable for widespread use in renewable energy storage, portable electronics and electric vehicles.

SCs are generally made of highly porous carbon impregnated with a liquid electrolyte to transport the electrical charge. Known for their almost indefinite lifespan and the ability to re-charge in seconds, the drawback of existing SCs is their low energy-storage-to-volume ratio -- known as energy density. Low energy density of five to eight Watt-hours per litre, means SCs are unfeasibly large or must be re-charged frequently.Professor Li's team has created an SC with energy density of 60 Watt-hours per litre -- comparable to lead-acid batteries and around 12 times higher than commercially available SCs.

"It has long been a challenge to make SCs smaller, lighter and compact to meet the increasingly demanding needs of many commercial uses," Professor Li said.

Graphene, which is formed when graphite is broken down into layers one atom thick, is very strong, chemically stable and an excellent conductor of electricity.To make their uniquely compact electrode, Professor Li's team exploited an adaptive graphene gel film they had developed previously. They used liquid electrolytes -- generally the conductor in traditional SCs -- to control the spacing between graphene sheets on the sub-nanometre scale. In this way the liquid electrolyte played a dual role: maintaining the minute space between the graphene sheets and conducting electricity.

Unlike in traditional 'hard' porous carbon, where space is wasted with unnecessarily large 'pores', density is maximised without compromising porosity in Professor Li's electrode.To create their material, the research team used a method similar to that used in traditional paper making, meaning the process could be easily and cost-effectively scaled up for industrial use. These macroscopic graphene material that is a step beyond what has been achieved previously. It is almost at the stage of moving from the lab to commercial development.
The phenomenon of false memory has been well-documented: In many court cases, defendants have been found guilty based on testimony from witnesses and victims who were sure of their recollections, but DNA evidence later overturned the conviction.

The cells where memory traces are stored
in the mouse hippocampus.
In a step toward understanding how these faulty memories arise, MIT neuroscientists have shown that they can plant false memories in the brains of mice. They also found that many of the neurological traces of these memories are identical in nature to those of authentic memories.

"Whether it's a false or genuine memory, the brain's neural mechanism underlying the recall of the memory is the same," says Susumu Tonegawa, the Picower Professor of Biology and Neuroscience and senior author of a paper describing the findings in the July 25 edition of Science.

The study also provides further evidence that memories are stored in networks of neurons that form memory traces for each experience we have -- a phenomenon that Tonegawa's lab first demonstrated last year.

Neuroscientists have long sought the location of these memory traces, also called engrams. In the pair of studies, Tonegawa and colleagues at MIT's Picower Institute for Learning and Memory showed that they could identify the cells that make up part of an engram for a specific memory and reactivate it using a technology called optogenetics.

Lead authors of the paper are graduate student Steve Ramirez and research scientist Xu Liu. Other authors are technical assistant Pei-Ann Lin, research scientist Junghyup Suh, and postdocs Michele Pignatelli, Roger Redondo and Tomas Ryan.

Seeking the engram

Episodic memories -- memories of experiences -- are made of associations of several elements, including objects, space and time. These associations are encoded by chemical and physical changes in neurons, as well as by modifications to the connections between the neurons.

Where these engrams reside in the brain has been a longstanding question in neuroscience. "Is the information spread out in various parts of the brain, or is there a particular area of the brain in which this type of memory is stored? This has been a very fundamental question," Tonegawa says.

In the 1940s, Canadian neurosurgeon Wilder Penfield suggested that episodic memories are located in the brain's temporal lobe. When Penfield electrically stimulated cells in the temporal lobes of patients who were about to undergo surgery to treat epileptic seizures, the patients reported that specific memories popped into mind. Later studies of the amnesiac patient known as "H.M." confirmed that the temporal lobe, including the area known as the hippocampus, is critical for forming episodic memories.

However, these studies did not prove that engrams are actually stored in the hippocampus, Tonegawa says. To make that case, scientists needed to show that activating specific groups of hippocampal cells is sufficient to produce and recall memories.

To achieve that, Tonegawa's lab turned to optogenetics, a new technology that allows cells to be selectively turned on or off using light.

For this pair of studies, the researchers engineered mouse hippocampal cells to express the gene for channelrhodopsin, a protein that activates neurons when stimulated by light. They also modified the gene so that channelrhodopsin would be produced whenever the c-fos gene, necessary for memory formation, was turned on.

In last year's study, the researchers conditioned these mice to fear a particular chamber by delivering a mild electric shock. As this memory was formed, the c-fos gene was turned on, along with the engineered channelrhodopsin gene. This way, cells encoding the memory trace were "labeled" with light-sensitive proteins.

The next day, when the mice were put in a different chamber they had never seen before, they behaved normally. However, when the researchers delivered a pulse of light to the hippocampus, stimulating the memory cells labeled with channelrhodopsin, the mice froze in fear as the previous day's memory was reactivated.

"Compared to most studies that treat the brain as a black box while trying to access it from the outside in, this is like we are trying to study the brain from the inside out," Liu says. "The technology we developed for this study allows us to fine-dissect and even potentially tinker with the memory process by directly controlling the brain cells."

Incepting false memories

That is exactly what the researchers did in the new study -- exploring whether they could use these reactivated engrams to plant false memories in the mice's brains.

First, the researchers placed the mice in a novel chamber, A, but did not deliver any shocks. As the mice explored this chamber, their memory cells were labeled with channelrhodopsin. The next day, the mice were placed in a second, very different chamber, B. After a while, the mice were given a mild foot shock. At the same instant, the researchers used light to activate the cells encoding the memory of chamber A.

On the third day, the mice were placed back into chamber A, where they now froze in fear, even though they had never been shocked there. A false memory had been incepted: The mice feared the memory of chamber A because when the shock was given in chamber B, they were reliving the memory of being in chamber A.

Moreover, that false memory appeared to compete with a genuine memory of chamber B, the researchers found. These mice also froze when placed in chamber B, but not as much as mice that had received a shock in chamber B without having the chamber A memory activated.

The researchers then showed that immediately after recall of the false memory, levels of neural activity were also elevated in the amygdala, a fear center in the brain that receives memory information from the hippocampus, just as they are when the mice recall a genuine memory.

The MIT team is now planning further studies of how memories can be distorted in the brain.

"Now that we can reactivate and change the contents of memories in the brain, we can begin asking questions that were once the realm of philosophy," Ramirez says. "Are there multiple conditions that lead to the formation of false memories? Can false memories for both pleasurable and aversive events be artificially created? What about false memories for more than just contexts -- false memories for objects, food or other mice? These are the once seemingly sci-fi questions that can now be experimentally tackled in the lab.
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Quasars are among the brightest, oldest, most distant, and most powerful objects in the universe. Powered by massive black holes at the center of most known galaxies, quasars can emit enormous amounts of energy, up to a thousand times the total output of the hundreds of billions of stars in our entire Milky Way.

Dartmouth astrophysicists Ryan Hickox and Kevin Hainline and colleagues have a paper scheduled for publication in The Astrophysical Journal, detailing
 discoveries based upon observations of 10 quasars. They documented the immense power of quasar radiation, which reaches out for many thousands of light years to the limits of the quasar's galaxy. 

"For the first time, we are able to see the actual extent to which these quasars and their black holes can affect their galaxies, and we see that it is limited only by the amount of gas in the galaxy," says Hainline, a Dartmouth postdoctoral research associate. "The radiation excites gas all the way to the margins of the galaxy and stops only when it runs out of gas."

The radiation released by a quasar covers the entire electromagnetic spectrum, from radio waves and microwaves at the low-frequency end through infrared, ultraviolet, and X-rays, to high-frequency gamma rays. A central black hole, also called an active galactic nucleus, may grow by swallowing material from the surrounding interstellar gas, releasing energy in the process. This leads to the creation of a quasar, emitting radiation that illuminates the gas present throughout the galaxy.

"If you take this powerful, bright radiation source in the center of the galaxy and blast the gas with its radiation, it will get excited in just the same way the neon gets excited in neon lamps, producing light," says Hickox, an assistant professor in the Department of Physics and Astronomy at Dartmouth. "The gas will produce very specific frequencies of light that only a quasar can produce. This light functioned as a tracer that we were able to use to follow the gas excited by the black hole out to large distances."

Quasars are small compared to a galaxy, like a grain of sand on a beach, but the power of their radiation can extend to the galactic boundaries and beyond.

The illumination of gas can have a profound effect, since gas that is lit up and heated by the quasar is less able to collapse under its own gravity and form new stars. Thus, the tiny central black hole and its quasar can slow down star formation in the entire galaxy and influence how the galaxy grows and changes over time.

"This is exciting because we know from a number of different independent arguments that these quasars have a profound effect on the galaxies in which they live," Hickox says. "There is a lot of controversy about how they actually influence the galaxy, but now we have one aspect of the interaction that can extend on the scale of the entire galaxy. Nobody had seen this before."

Hickox, Hainline, and their co-authors based their conclusions on observations made with the Southern African Large Telescope (SALT), the largest optical telescope in the southern hemisphere. Dartmouth is a partner in SALT, giving faculty and students access to the instrument. The observations were performed using spectroscopy, in which light is broken down into its component wavelengths. "For this particular kind of experiment, it is among the best telescopes in the world," says Hickox.

They also used data from NASA's Wide-field Infrared Survey Explorer (WISE) -- a space telescope that imaged the whole sky in the infrared. The scientists used observations in infrared light because they give a particularly reliable measure of the total energy output by the quasar.


Their work helps to explain how insects control their movements using a close interplay of neuronal control and ‘clever biomechanical tricks,’ says lead researcher Dr Tom Matheson, a Reader in Neurobiology at the University of Leicester.

In a study published today in the journalCurrent Biology, the researchers show that the structure of some insect leg joints causes the legs to move even in the absence of muscles. So-called ‘passive joint forces’ serve to return the limb back towards a preferred resting position.

The passive movements differ in limbs that have different behavioural roles and different musculature, suggesting that the joint structures are specifically adapted to complement muscle forces. The researchers propose a motor control scheme for insect limb joints in which not all movements are driven by muscles.

The study was funded by the Biotechnology and Biological Sciences Research Council (BBSRC), The Royal Society, and the Heinrich Hertz-Foundation of the German State of North Rhine-Westphalia.

Dr Matheson, of the Department of Biology, said: “It is well known that some animals store energy in elastic muscle tendons and other structures. Such energy storage permits forces to be applied explosively to generate movements that are much more rapid than those which may be generated by muscle contractions alone. This is, for example, crucial when grasshoppers or fleas jump.

“This University of Leicester study provides a new insight into the ways that energy storage mechanisms can operate in a much wider range of movements.

“Our work set out to identify how the biomechanical properties of the limbs of a range of insects influence relatively slow movements such as those that occur during walking, scratching or climbing. The surprising result was that although some movements are influenced by properties of the muscles and tendons, other movements are generated by forces that arise from within the joints themselves.

“Even when we removed all of the muscles and associated tissues from a particular joint at the ‘knee’ of a locust, the lower part of the limb (the tibia) still moved back towards a midpoint from extended angles.”

Dr Matheson said that it was known from previous studies that some movements can be generated by spring-like properties of limbs, but the team was surprised to find passive forces that contribute to almost all movements made by the limbs that were studied - not just the highly specialised rapid movements needed to propel powerful jumps and kicks.

“We expected the forces to be generated within the muscles of the leg, but found that some continued to occur even when we detached both muscles – the extensor and the flexor tibiae – from the tibia.

“In the locust hind leg, which is specialised for jumping and kicking, the extensor muscle is much larger and stronger than the antagonist flexor muscle. This enables the animal to generate powerful kicks and jumps propelled by extensions of the tibia that are driven by contractions of the extensor muscle. When locusts prepare to jump, large amounts of energy generated by the extensor muscle are stored in the muscle’s tendon and in the hard exoskeleton of the leg.

“Surprisingly, we noticed that when the muscles were removed, the tibia naturally flexed back towards a midpoint, and we hypothesised that these passive return movements might be counterbalancing the strong extensor muscle.”

Jan M. Ache, a Masters student from the Department of Animal Physiology at the University of Cologne who worked in Matheson’s lab and is the first author on the paper, continues: “To test this idea we looked at the literature and examined other legs where the extensor and flexor muscles are more closely balanced in size or strength, or where the flexor is stronger than the extensor.

“We found that the passive joint forces really do counterbalance the stronger of the flexor or extensor muscle in the animals and legs we looked at. In the horsehead grasshopper, for example, passive joint forces even differ between the middle legs (which are primarily used for walking) and the hind legs (which are adapted for jumping), even in the same individual animal. In both pairs of legs, the passive joint forces support the weaker muscle.

“This could be very important for the generation of movements in insects because the passive forces enable a transfer of energy from the stronger to the weaker muscle.”

This work helps to explain how insects control their movements using a close interplay of neuronal control and clever biomechanical tricks. Using balanced passive forces may provide engineers with new ways to improve the control of robotic and prosthetic limbs, say the researchers.

Dr Matheson concluded: “We hope that our work on locusts and grasshoppers will spur a new understanding of how limbs work and can be controlled, by not just insects, but by other animals, people, and even by robots.”
Curiosity's Sample Analysis at Mars (SAM) suite of laboratory instruments inside the rover has measured the abundances of different gases and different isotopes in several samples of Martian atmosphere. Isotopes are variants of the same chemical element with different atomic weights due to having different numbers of neutrons, such as the most common carbon isotope, carbon-12, and a heavier stable isotope, carbon-13.

SAM checked ratios of heavier to lighter isotopes of carbon and oxygen in the carbon dioxide that makes up most of the planet's atmosphere. Heavy isotopes of carbon and oxygen are both enriched in today's thin Martian atmosphere compared with the proportions in the raw material that formed Mars, as deduced from proportions in the sun and other parts of the solar system. This provides not only supportive evidence for the loss of much of the planet's original atmosphere, but also a clue to how the loss occurred.

"As atmosphere was lost, the signature of the process was embedded in the isotopic ratio," said Paul Mahaffy of NASA Goddard Space Flight Center, Greenbelt, Md. He is the principal investigator for SAM and lead author of one of the two papers about Curiosity results in the July 19 issue of the journal Science.

Other factors also suggest Mars once had a much thicker atmosphere, such as evidence of persistent presence of liquid water on the planet's surface long ago even though the atmosphere is too scant for liquid water to persist on the surface now. The enrichment of heavier isotopes measured in the dominant carbon-dioxide gas points to a process of loss from the top of the atmosphere -- favoring loss of lighter isotopes -- rather than a process of the lower atmosphere interacting with the ground.

Curiosity measured the same pattern in isotopes of hydrogen, as well as carbon and oxygen, consistent with a loss of a substantial fraction of Mars' original atmosphere. Enrichment in heavier isotopes in the Martian atmosphere has previously been measured on Mars and in gas bubbles inside meteorites from Mars. Meteorite measurements indicate much of the atmospheric loss may have occurred during the first billion years of the planet's 4.6-billion-year history. The Curiosity measurements reported this week provide more precise measurements to compare with meteorite studies and with models of atmospheric loss.

The Curiosity measurements do not directly measure the current rate of atmospheric escape, but NASA's next mission to Mars, the Mars Atmosphere and Volatile Evolution Mission (MAVEN), will do so. "The current pace of the loss is exactly what the MAVEN mission now scheduled to launch in November of this year is designed to determine," Mahaffy said.

The new reports describe analysis of Martian atmosphere samples with two different SAM instruments during the initial 16 weeks of the rover's mission on Mars, which is now in its 50th week. SAM's mass spectrometer and tunable laser spectrometer independently measured virtually identical ratios of carbon-13 to carbon-12. SAM also includes a gas chromatograph and uses all three instruments to analyze rocks and soil, as well as atmosphere.

"Getting the same result with two very different techniques increased our confidence that there's no unknown systematic error underlying the measurements," said Chris Webster of NASA's Jet Propulsion Laboratory, Pasadena, Calif. He is the lead scientist for the tunable laser spectrometer and the lead author for one of the two papers. "The accuracy in these new measurements improves the basis for understanding the atmosphere's history."

Curiosity landed inside Mars' Gale Crater on Aug. 6, 2012 Universal Time (on Aug. 5 PDT). The rover this month began a drive of many months from an area where it found evidence for a past environment favorable for microbial life, toward a layered mound, Mount Sharp, where researchers will seek evidence about how the environment changed.
It had always been assumed that manure wasn't used as a fertiliser until Iron Age and Roman times. However, this new research shows that enriched levels of nitrogen-15, a stable isotope abundant in manure, have been found in the charred cereal grains and pulse seeds taken from 13 Neolithic sites around Europe.

Fossil Sample
The findings are published in the early edition of the journal Proceedings of the National Academy of Sciences. The study suggests that Neolithic farmers used the dung from their herds of cattle, sheep, goats and pigs as a slow release fertiliser for crops.Manuring involves a long-term investment in arable land because dung breaks down slowly and crops benefit from its nutrients over many years. This new theory indicates a long-term approach to farming.

The authors conclude that early farmers recognised the inherent value of intensively managed land and sought to maintain it for their descendants. This new perspective overturns the traditional view held by scholars that Neolithic farmers were nomadic people who used slash and burn to create temporary farmland for agricultural crops.

It is undisputed that the adoption of farming had a long-term impact on society. However, what has been unclear is the nature of early European farming and the role it has played in shaping social and economic change.

Lead author Dr Amy Bogaard from the School of Archaeology at the University of Oxford said: 'The fact that farmers made long-term investments such as manuring in their land sheds new light on the nature of early farming landscapes in Neolithic times. The idea that farmland could be cared for by the same family for generations seems quite an advanced notion, but rich fertile land would have been viewed as extremely valuable for the growing of crops. We believe that as land was viewed as a commodity to be inherited, social differences in early European farming communities started to emerge between the haves and the have-nots.'

The territoriality of early farming groups may help to explain documented events of the period involving extreme violence. The study cites the example of a Neolithic mass burial of the late sixth millennium BC at Talheim, Germany, which preserves the remains of a community killed by assailants wielding stone axes like those used to clear the land.

The research is based on stable carbon and nitrogen isotope analysis of 124 crop samples of barley, wheat, lentil and peas, totalling around 2,500 grains or seeds. The charred remains represent harvested crops preserved in Neolithic houses destroyed by fire. The samples were from archaeological excavations of Neolithic sites across Europe, dating from nearly 6,000 to 2,400 BC.

The study also has important implications for research into the diet of early farmers. Archaeologists rely on the stable isotope analysis of the skeletal remains to establish a signature, which provides information about what people once ate. The heavier stable isotope of nitrogen-15 found in manure mimics the isotopic effect of a diet rich in meat and milk.

It had been assumed that early farmers in northwest Europe had a diet full of animal protein. However, these results suggest that the protein from cereal and pulse crops is much higher than previously thought, and that Neolithic crops were a staple part of their diet.

The crop nitrogen isotope analysis suggests that early farmers in Europe used their manure strategically as a resource that was limited by the number of animals they owned and by the physical effort of hauling manure around. The study points out that there is evidence that the farmers carefully selected crops that would most benefit from fertiliser, leaving hardier crops to grow with little or no manure. This demonstrates a knowledge of growing crops that has been little acknowledged until now.

The cereal and pulse samples were taken from sites spread across Europe: in the UK, they included Hambledon Hill in Dorset and Lismore Fields near Buxton in Derbyshire. Other Neolithic sites included in the research were in Greece, Bulgaria, Germany and Denmark.
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The initial discovery, made June 20 by middle-school student Noah Traylor during a UA-hosted expedition, was later identified as part of a large neck vertebra of an elasmosaur, which is a subgroup of the late Cretaceous plesiosaurs.Elasmosaurid plesiosaurs are easily recognized by their large body size -- some species reach up to 45 feet in length.

"Think Loch Ness monster," said Dr. Dana Ehret, UA Museum paleontologist. "They have very large flippers for swimming and extremely long necks, consisting of up to about 70 neck vertebrae."


Artist Sketch

Plesiosaurs became extinct by the end of Cretaceous, or about 65.5 million years ago, and they are generally rare in the fossil record for Alabama. This is only the second elasmosaurid specimen containing more than one or two bones found in the state, Ehret said. The first, which consists of 22 vertebrae, was found in the late 1960s and is now part of UA Collections.This discovery appears to be on par with the first one. To date, about 15 large vertebrae, a few paddle bones and many bone fragments have been collected, but an extensive excavation is still in progress, so Ehret is uncertain how complete this skeleton is.

"We find a lot of the more common fossils here, but this is a macropredator that is not normally found in Alabama," Ehret said. "It's really interesting because it gives us a bigger picture of what was happening in Alabama at that time."

The skeleton was also not found near water. Ehret said during the late Cretaceous period, temperatures were much warmer than they are today, resulting in higher sea levels. The specimen was found in a small quarry in rural Greene County, a region commonly called the "Black Belt."The "Black Belt" represents the late Cretaceous shoreline in the Gulf Coast. The sediments found in this region are classified as chalk, are composed of extinct microscopic organisms and are extremely nutrient rich, making them the perfect place for farming.The discovery was made during the Museum's Expedition 35, which was hosted by UA's Alabama Museum of Natural History and led by Randy Mecredy, director of the Museum. The expedition is an annual summer program that is open to middle and high-school students.

In addition to Ehret, others involved in the excavation include students from the expedition, Dr. Takehito "Ike" Ikejiri with UA's department of geological sciences, museum staff, Dr. Prescott Atkinson of the University of Alabama at Birmingham, the UA Museum's Board of Regents and a few UA geology students.The bones were initially excavated in place from the chalk in the quarry. Once they were able to determine the size and extent of the individual bones, those working the excavation could take them out of the ground and transport them back to the museum. Some pieces came back loose, while others were wrapped to prevent them from falling apart.

In the paleontology lab, the bones are now being unwrapped and prepared. Specimens are washed and scrubbed to remove loose sediments, and, for those that are still embedded in the chalk sediment, Ehret said they will use different tools to remove the sediment.It will take several weeks to prepare the bones properly and then harden them to ensure they will not later fall apart. Once finished, the specimen will be displayed in UA's Smith Hall.

"From a research standpoint, this is an important find. To have this many pieces, you can do an extensive comparative analysis," Mecredy said. "But, it's also having the ability to take high-school and middle-school students in the field where they find these things. It inspires them to pursue science-related fields."
Researchers have developed a drug delivery technique for diabetes treatment in which a sponge-like material surrounds an insulin core. The sponge expands and contracts in response to blood sugar levels to release insulin as needed. The technique could also be used for targeted drug delivery to cancer cells.

"We wanted to mimic the function of health beta-cells, which produce insulin and control its release in a healthy body," says Dr. Zhen Gu, lead author of a paper describing the work and an assistant professor in the joint biomedical engineering program at North Carolina State University and the University of North Carolina at Chapel Hill. "But what we've found also holds promise for smart drug delivery targeting cancer or other diseases." The research team includes Daniel Anderson, the senior author and an associate professor of chemical engineering and member of the Koch Institute for Integrative Cancer Research at MIT, and researchers from the Department of Anesthesiology at Boston Children's Hospital.

The researchers created a spherical, sponge-like matrix out of chitosan, a material found in shrimp and crab shells. Scattered throughout this matrix are smaller nanocapsules made of a porous polymer that contain glucose oxidase or catalase enzymes. The sponge-like matrix surrounds a reservoir that contains insulin. The entire matrix sphere is approximately 250 micrometers in diameter and can be injected into a patient.

When a diabetic patient's blood sugar rises, the glucose triggers a reaction that causes the nanocapsules' enzymes to release hydrogen ions. Those ions bind to the molecular strands of the chitosan sponge, giving them a positive charge. The positively charged chitosan strands then push away from each other, creating larger gaps in the sponge's pores that allow the insulin to escape into the bloodstream. In type 1 and advanced type 2 diabetes, the body needs injections of insulin, a hormone that transports glucose -- or blood sugar -- from the bloodstream into the body's cells.

As the insulin is released, the body's glucose levels begin to drop. This causes the chitosan to lose its positive charge, and the strands begin to come back together. This shrinks the size of the pores in the sponge, trapping the remaining insulin.While this work created hydrogen ions by using enzymes that are responsive to glucose, the technique could be simplified to target cancers by eliminating the enzymes altogether. Tumors are acidic environments that have high concentrations of hydrogen ions. If the sponge reservoir were filled with anticancer drugs, the drugs would be released when the chitosan came into contact with the hydrogen ions in tumor tissues or cancer cells.

"We can also adjust the size of the overall 'sponge' matrix as needed, as small as 100 nanometers," Gu says. "And the chitosan itself can be absorbed by the body, so there are no long term health effects."
In tests using diabetic laboratory mice, the researchers found the sponge matrix was effective at reducing blood sugar for up to 48 hours. However, the researchers published a separate "smart system" for insulin delivery in May that maintained normal blood sugar levels for 10 days.

"But we learned a lot from the promising 'sponge' research and will further optimize it. Meanwhile, we are already exploring applications to combat cancer," Gu says
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