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Blocking cell division with two synergistic chemical inhibitors

Blocking cell division with two synergistic chemical inhibitors | Amazing Science | Scoop.it

The cycle of cell division—one cell splitting itself into two—is a crucial and complex process managed by finely tuned molecular machines. When working properly, cell division assures healthy growth. When running out of control, it can usher in cancer.


Blocking cell division in disease has been the target of researchers hoping to induce the death of abnormal cells before they become cancerous tumors. Finding the right chemical compound to inhibit cell division gone awry has proved difficult: Target the cell cycle too broadly and healthy cells will also suffer, as when chemotherapy hits all cells that divide rapidly, not just cancerous ones. Narrow the sights too tightly and the misbehaving machine churns on.


Now a team led by Randall King of Harvard Medical School has shown how two chemical inhibitors working together act better than either one alone, shutting down the dividing cell by stalling mitosis, one step in the cycle during which the cell copies and then lines up chromosomes properly so each daughter cell has a complete set.


"Simultaneous disruption of multiple interactions in a protein machine may be an interesting way to go in terms of trying to design future therapeutic strategies," said King, HMS professor of cell biology. "You're basically targeting one step in the pathway, but there's a lot of complexity in that one step. The idea is to disable the biochemical or enzymatic function by simultaneously targeting multiple sites."


King discovered the two inhibitors 10 years ago, in the very first screen conducted at the Institute of Chemistry and Cell Biology-Longwood Screening Facility at HMS. It was an unbiased chemical screen, set up with no assumptions about what they might find. Especially in the era before the discovery of RNA interference and its usefulness in silencing genes, scientists needed chemical tools that would perturb biological processes in other ways, so they could understand in detail how the mechanisms they were examining worked.


King's goal in 2004 was to fish through all the identified candidates from these early screens for chemical compounds that would somehow illuminate the cell cycle pathway and perhaps stymie one of its protein machines: the anaphase-promoting complex/cyclosome (APC/C). This protein complex marks certain proteins for degradation by the proteasome, the cell's waste-disposal site, before it can progress through mitosis.


If the APC/C doesn't tag these proteins with a protein called ubiquitin, the proteasome doesn't recognize them, they don't get discarded and mitosis cannot proceed, stalling the cell cycle before it can properly segregate its chromosomes for faithful division.


In 2010 King and his colleagues published a paper in Cancer Cell that described in detail how one of the inhibitors, called tosyl-L-arginine methyl ester (TAME), weakens the interaction between the APC/C and its critical activating protein, Cdc20. Degradation is blocked, but only partially. That means the cell cycle is delayed briefly, but still continues toward mitotic exit.


Now the scientists have shown how another compound, also discovered in the original 2004 chemical screen, binds in a pocket on Cdc20 that normally recruits the targets of APC/C. Called apcin (for APC inhibitor), it also delays mitosis, but only by a little bit.

Together, TAME and apcin slow mitosis to a crawl. The cell dies before it can leave mitosis.

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WIRED: Radical New Theory Could Kill the Multiverse Hypothesis and Gets Rid of Concepts Like "Length" and "Mass"

WIRED: Radical New Theory Could Kill the Multiverse Hypothesis and Gets Rid of Concepts Like "Length" and "Mass" | Amazing Science | Scoop.it
Mass and length may not be fundamental properties of nature, according to new ideas bubbling out of the multiverse.


Though galaxies look larger than atoms and elephants appear to outweigh ants, some physicists have begun to suspect that size differences are illusory. Perhaps the fundamental description of the universe does not include the concepts of “mass” and “length,” implying that at its core, nature lacks a sense of scale.


This little-explored idea, known as scale symmetry, constitutes a radical departure from long-standing assumptions about how elementary particles acquire their properties. But it has recently emerged as a common theme of numerous talks and papers by respected particle physicists. With their field stuck at a nasty impasse, the researchers have returned to the master equations that describe the known particles and their interactions, and are asking: What happens when you erase the terms in the equations having to do with mass and length?


Nature, at the deepest level, may not differentiate between scales. With scale symmetry, physicists start with a basic equation that sets forth a massless collection of particles, each a unique confluence of characteristics such as whether it is matter or antimatter and has positive or negative electric charge. As these particles attract and repel one another and the effects of their interactions cascade like dominoes through the calculations, scale symmetry “breaks,” and masses and lengths spontaneously arise.


Similar dynamical effects generate 99 percent of the mass in the visible universe. Protons and neutrons are amalgams — each one a trio of lightweight elementary particles called quarks. The energy used to hold these quarks together gives them a combined mass that is around 100 times more than the sum of the parts. “Most of the mass that we see is generated in this way, so we are interested in seeing if it’s possible to generate all mass in this way,” said Alberto Salvio, a particle physicist at the Autonomous University of Madrid and the co-author of a recent paper on a scale-symmetric theory of nature.


In the equations of the “Standard Model” of particle physics, only a particle discovered in 2012, called the Higgs boson, comes equipped with mass from the get-go. According to a theory developed 50 years ago by the British physicist Peter Higgs and associates, it doles out mass to other elementary particles through its interactions with them. Electrons, W and Z bosons, individual quarks and so on: All their masses are believed to derive from the Higgs boson — and, in a feedback effect, they simultaneously dial the Higgs mass up or down, too.


The new scale symmetry approach rewrites the beginning of that story. “The idea is that maybe even the Higgs mass is not really there,” said Alessandro Strumia, a particle physicist at the University of Pisa in Italy. “It can be understood with some dynamics.”


The concept seems far-fetched, but it is garnering interest at a time of widespread soul-searching in the field. When the Large Hadron Collider at CERN Laboratory in Geneva closed down for upgrades in early 2013, its collisions had failed to yield any of dozens of particles that many theorists had included in their equations for more than 30 years. The grand flop suggests that researchers may have taken a wrong turn decades ago in their understanding of how to calculate the masses of particles.


“We’re not in a position where we can afford to be particularly arrogant about our understanding of what the laws of nature must look like,” said Michael Dine, a professor of physics at the University of California, Santa Cruz, who has been following the new work on scale symmetry. “Things that I might have been skeptical about before, I’m willing to entertain.”

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Core root growth mechanism identified: PLETHORA proteins and plant hormone auxin orchestrate root growth together

Core root growth mechanism identified: PLETHORA proteins and plant hormone auxin orchestrate root growth together | Amazing Science | Scoop.it

During plant growth, dividing cells in meristems must coordinate transitions from division to expansion and differentiation. Three distinct developmental zones are generated: the meristem, where the cell division takes place, and elongation and differentiation zones. At the same time, plants can rapidly adjust their direction of growth to adapt to environmental conditions.


In Arabidopsis thaliana roots, many aspects of zonation are controlled by the plant hormone auxin and auxin-induced PLETHORA transcription factors. Both show a graded distribution with a maximum near the root tip. In addition, auxin is also pivotal for tropic responses of the roots.


Ari Pekka Mähönen from the University of Helsinki, Finland, with his group and Dutch colleagues has found out with the help of experimentation and mathematical modelling how the two factors together regulate root growth.


"Cell division in the meristem is maintained by PLETHORA transcription factors. These proteins are solely transcribed in the stem cells, in a narrow region within the meristematic cells located in the tip of the root. So PLETHORA proteins are most abundant in the stem cells," Ari Pekka Mähönen, Research Fellow financed by the Academy of Finland says.


Outside the stem cells the amount of PLETHORA protein in the cells halves each time the cells divide. In the end there is so little PLETHORA left in the cells that they cannot stay in the dividing mode. This is when the cells start to elongate and differentiate.


Auxin is the factor taking care of many aspects of root growth. If there is enough PLETHORA in the root cells, auxin affects the rate of root cell division. If there is little or no PLETHORA in the cells, auxin regulates cell differentiation and elongation. In addition to this direct, rapid regulation, auxin also regulates cell division, expansion and differentiation indirectly and slowly by promoting PLETHORA transcription. This dual action of auxin keeps the structure and growth of the root very stable.


When PLETHORA levels gradually diminish starting from the root tip upwards, the cell division, elongation and differentiation zones are created. And this inner organisation stays even if the growth direction of the root changes.


"The gravity and other environmental factors can change the auxin content of the cells, and quite rapidly. This all affects the growth direction of the root. And of course it is important for the plant to maintain the organization while directing their roots there where water and nutrients most likely are to be found."

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UAlberta engineers design nano-optical cables that could replace copper wiring on computer chips

UAlberta engineers design nano-optical cables that could replace copper wiring on computer chips | Amazing Science | Scoop.it

Cables designed by graduate student Saman Jahani (left) and electrical engineering professor Zubin Jacob are 10 times smaller than existing fiber optic cables—small enough to replace copper wiring still used on computer chips. “We’re already transmitting data from continent to continent using fiber optics, but the killer application is using this inside chips for interconnects—that is the Holy Grail,” says Zubin Jacob, an electrical engineering professor leading the research. “What we’ve done is come up with a fundamentally new way of confining light to the nano scale.”


Jahani and Jacob have used metamaterials to redefine the textbook phenomenon of total internal reflection, discovered 400 years ago by German scientist Johannes Kepler while working on telescopes.

Researchers around the world have been stymied in their efforts to develop effective fibre optics at smaller sizes. One popular solution has been reflective metallic claddings that keep light waves inside the cables. But the biggest hurdle is increased temperatures: metal causes problems after a certain point.


“If you use metal, a lot of light gets converted to heat. That has been the major stumbling block. Light gets converted to heat and the information literally burns up—it’s lost.”


Jacob and Jahani have designed a new, non-metallic metamaterial that enables them to “compress” and contain light waves in the smaller cables without creating heat, slowing the signal or losing data. Their findings will be published Aug. 20 in Optica, The Optical Society’s new high-impact photonics journal. The article is available online.

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21 Species of Metabolically Active Microbes In Hydrocarbon Lakes On Earth Boost Chances For Extraterrestrial Life

21 Species of Metabolically Active Microbes In Hydrocarbon Lakes On Earth Boost Chances For Extraterrestrial Life | Amazing Science | Scoop.it

In a ground-breaking discovery released by the journal Science, researchers have revealed microhabitats of metabolically active, thriving microbes living in the world’s largest asphalt lake, Pitch Lake, on the island of Trinidad in the Caribbean.  Asphalt lakes are large reservoirs of a sticky, black, viscous hydrocarbons (known as asphalt, bitumen or pitch) where no life was expected to be found.


The international team discovered the microbes in tiny water droplets recovered from the lake in 2011.  Each sample, measuring only one to three microliters, has the equivalent volume of approximately 1/50 of a conventional “drop” of water.


The team’s only United States-based researcher, Dirk Schulze-Makuch, is a professor at Washington University School of the Environment.  Using advanced sequencing technologies, the team extracted all the DNA of all organisms in each droplet simultaneously.  Reading through 12 microdroplets, they found 21 species of bacteria and archaebacteria.


Professor Schulze-Makuch explained that each water droplet seems representative of an entire ecosystem because of the observed diversity in bacteria and archaea.  Moreover, remarkably there was very little measurable ammonia or phosphates, both ingredients thought to be essential for life.


These microbes, the researchers report, are actively degrading oils in the lake, most likely to exploit it as a source of bioenergy.  One bioengineering implication of this discovery is to use these active microbes to clean up oil spills with as little impact to the environment as possible.


The water droplets also had an unusually high salt content.  By studying the isotope composition of droplets from Pitch Lake, the team was able to say that the microbes did not originate from surface waters that are part of the hydrologic cycle, but rather from much deeper, for example ancient underground seawater or another deep source of brine.


Professor Schulze-Makuch went on to explain that these microbes could mean life on other planets as well.  One well-known example is Saturn’s moon, Titan.  Its surface is characterized as being saturated with hydrocarbons, in liquid lakes on the ground and also in vapor form and liquid rain in the atmosphere.  Schulze-Makuch explains that this discovery has implications for astrobiology, the study of life on other planets.


Reference: Science 8 August 2014: Vol. 345 no. 6197 pp. 673-676

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Solar power with a view: Transparent luminescent solar concentrators

Solar power with a view: Transparent luminescent solar concentrators | Amazing Science | Scoop.it
Researchers have developed a new type of solar concentrator that when placed over a window creates solar energy while allowing people to actually see through the window. It is called a transparent luminescent solar concentrator and can be used on buildings, cell phones and any other device that has a flat, clear surface.


Research in the production of energy from solar cells placed around luminescent plastic-like materials is not new. These past efforts, however, have yielded poor results -- the energy production was inefficient and the materials were highly colored.


"No one wants to sit behind colored glass," said Lunt, an assistant professor of chemical engineering and materials science. "It makes for a very colorful environment, like working in a disco. We take an approach where we actually make the luminescent active layer itself transparent."


The solar harvesting system uses small organic molecules developed by Lunt and his team to absorb specific nonvisible wavelengths of sunlight. "We can tune these materials to pick up just the ultraviolet and the near infrared wavelengths that then 'glow' at another wavelength in the infrared," he said.


The "glowing" infrared light is guided to the edge of the plastic where it is converted to electricity by thin strips of photovoltaic solar cells. "Because the materials do not absorb or emit light in the visible spectrum, they look exceptionally transparent to the human eye," Lunt said.

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‘Shape-memory polymer’ material could help reconstruct faces

‘Shape-memory polymer’ material could help reconstruct faces | Amazing Science | Scoop.it

Injuries, birth defects (such as cleft palates) or surgery to remove a tumor can create gaps in bone that are too large to heal naturally. And when they occur in the head, face or jaw, these bone defects can dramatically alter a person's appearance. Researchers will report today that they have developed a "self-fitting" material that expands with warm salt water to precisely fill bone defects, and also acts as a scaffold for new bone growth.


Currently, the most common method for filling bone defects in the head, face or jaw (known as the cranio-maxillofacial area) is autografting. That is a process in which surgeons harvest bone from elsewhere in the body, such as the hip bone, and then try to shape it to fit the bone defect.


"The problem is that the autograft is a rigid material that is very difficult to shape into these irregular defects," says Melissa Grunlan, Ph.D., leader of the study. Also, harvesting bone for the autograft can itself create complications at the place where the bone was taken. Another approach is to use bone putty or cement to plug gaps. However, these materials aren't ideal. They become very brittle when they harden, and they lack pores, or small holes, that would allow new bone cells to move in and rebuild the damaged tissue.


To develop a better material, Grunlan and her colleagues at Texas A&M University made a shape-memory polymer (SMP) that molds itself precisely to the shape of the bone defect without being brittle. It also supports the growth of new bone tissue.


SMPs are materials whose geometry changes in response to heat. The team made a porous SMP foam by linking together molecules of poly(ε-caprolactone), an elastic, biodegradable substance that is already used in some medical implants. The resulting material resembled a stiff sponge, with many interconnected pores to allow bone cells to migrate in and grow. Upon heating to 140 degrees Fahrenheit, the SMP becomes very soft and malleable. So, during surgery to repair a bone defect, a surgeon could warm the SMP to that temperature and fill in the defect with the softened material. Then, as the SMP is cooled to body temperature (98.6 degrees Fahrenheit), it would resume its former stiff texture and "lock" into place.


The researchers also coated the SMPs with polydopamine, a sticky substance that helps lock the polymer into place by inducing formation of a mineral that is found in bone. It may also help osteoblasts, the cells that produce bone, to adhere and spread throughout the polymer. The SMP is biodegradable, so that eventually the scaffold will disappear, leaving only new bone tissue behind. To test whether the SMP scaffold could support bone cell growth, the researchers seeded the polymer with human osteoblasts. After three days, the polydopamine-coated SMPs had grown about five times more osteoblasts than those without a coating. Furthermore, the osteoblasts produced more of the two proteins, runX2 and osteopontin, that are critical for new bone formation.


Grunlan says that the next step will be to test the SMP's ability to heal cranio-maxillofacial bone defects in animals. "The work we've done in vitro is very encouraging," she says. "Now we'd like to move this into preclinical and, hopefully, clinical studies."

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More than just X and Y: miRNAs are responsible for sexual differences in fruit flies

More than just X and Y: miRNAs are responsible for sexual differences in fruit flies | Amazing Science | Scoop.it

Men and women differ in plenty of obvious ways, and scientists have long known that genetic differences buried deep within our DNA underlie these distinctions. In the past, most research has focused on understanding how the genes that encode proteins act as sex determinants. But Cold Spring Harbor Laboratory (CSHL) scientists have found that a subset of very small genes encoding short RNA molecules, called microRNAs (miRNAs), also play a key role in differentiating male and female tissues in the fruit fly.


A miRNA is a short segment of RNA that fine-tunes the activation of one or several protein-coding genes. miRNAs are able to silence the genes they target and, in doing so, orchestrate complex genetic programs that are the basis of development.


In work published in Genetics, a team of CSHL researchers and colleagues describe how miRNAs contribute to sexual differences in fruit flies. You've probably never noticed, but male and female flies differ visibly, just like other animals. For example, females are 25% larger than males with lighter pigmentation and more abdominal segments.


The team of researchers, including Delphine Fagegaltier, PhD, lead author on the study, and CSHL Professor and Howard Hughes Medical Institute Investigator Greg Hannon, identified distinct miRNA populations in male and female flies. "We found that the differences in miRNAs are important in shaping the structures that distinguish the two sexes," says Fagegaltier. "In fact, miRNAs regulate the very proteins that act as sex determinants during development."


The team found that miRNAs are essential for sex determination even after an animal has grown to adulthood. "They send signals that allow germ cells, i.e., eggs and sperm, to develop, ensuring fertility," Fagegaltier explains. "Removing one miRNA from mature, adult flies causes infertility." More than that, these flies begin to produce both male and female sex-determinants. "In a sense, once they have lost this miRNA, the flies become male and female at the same time," according to Fagegaltier. "It is amazing that the very smallest genes can have such a big effect on sexual identity."


Some miRNAs examined in the study, such as let-7, have been preserved by evolution because of their utility; humans and many other animals carry versions of them. "This is probably just the tip of the iceberg," says Fagegaltier. "There are likely many more miRNAs regulating sexual identity at the cellular and tissue level, but we still have a lot to learn about these differences in humans, and how they could contribute to developmental defects and disease."

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Scientists bypass spinal cord non-invasively to trigger walking

Scientists bypass spinal cord non-invasively to trigger walking | Amazing Science | Scoop.it

Japanese researchers have created an “artificial neural connection” (ANC) from the brain directly to the spinal locomotion center in the lower thoracic and lumbar regions of the spine, potentially one day allowing patients with spinal-cord damage, such as paraplegics, to walk.


The study led by Shusaku Sasada, research fellow, and Yukio Nishimura, associate professor, both of the National Institutes of Natural Sciences (NINS), was published online in The Journal of Neuroscience on August 13, 2014.


Neural networks called “central pattern generators” (see Ref. 2 and 3 below) in the locomotion center (lower than the lesion site) are capable of producing rhythmic movements, such as walking, even when isolated from the brain, the researchers suggest.


The researchers worked with neurologically intact subjects who are were asked to allow the computer to passively control their leg movements.


As a surrogate, the researchers used muscle signals normally generated by the arm movements associated with leg movements. These signals were used to control a computer-driven magnetic device that non-invasively (externally) stimulated neurons in the spinal locomotion center.


Additional simultaneous peripheral electrical stimulation to the foot via the ANC enhanced this walking-like behavior. Kinematics of the induced behaviors were identical to those observed in normal voluntary walking. The researchers said they are planning clinical studies in the near future.

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Plants may use RNA language to communicate with each other, Virginia Tech researcher finds

Plants may use RNA language to communicate with each other, Virginia Tech researcher finds | Amazing Science | Scoop.it

A Virginia Tech scientist has discovered a potentially new form of plant communication, one that allows them to share an extraordinary amount of genetic information with one another. 


The finding by Jim Westwood, a professor of plant pathology, physiology, and weed science in the College of Agriculture and Life Sciences, throws open the door to a new arena of science that explores how plants communicate with each other on a molecular level. It also gives scientists new insight into ways to fight parasitic weeds that wreak havoc on food crops in some of the poorest parts of the world. His findings were published on Aug. 15 in the journal Science.


“The discovery of this novel form of inter-organism communication shows that this is happening a lot more than any one has previously realized,” said Westwood, who is an affiliated researcher with the Fralin Life Science Institute. “Now that we have found that they are sharing all this information, the next question is, ‘What exactly are they telling each other?’.” 


Westwood examined the relationship between a parasitic plant, dodder, and two host plants, Arabidopsis and tomatoes. In order to suck the moisture and nutrients out the host plants, dodder uses an appendage called a haustorium to penetrate the plant. Westwood previously broke new ground when he found that during this parasitic interaction, there is a transport of RNA between the two species. RNA translates information passed down from DNA, which is an organism’s blueprint. 


His new work expands this scope of this exchange and examines the mRNA, or messenger RNA, which sends messages within cells telling them which actions to take, such as which proteins to code. It was thought that mRNA was very fragile and short-lived, so transferring it between species was unimaginable. 


But Westwood found that during this parasitic relationship, thousands upon thousands of mRNA molecules were being exchanged between both plants, creating this open dialogue between the species that allows them to freely communicate. Through this exchange, the parasitic plants may be dictating what the host plant should do, such as lowering its defenses so that the parasitic plant can more easily attack it. Westwood’s next project is aimed at finding out exactly what the mRNA are saying.


“Parasitic plants such as witchweed and broomrape are serious problems for legumes and other crops that help feed some of the poorest regions in Africa and elsewhere,” said Julie Scholes, a professor at the University of Sheffield, U.K., who is familiar with Westwood’s work but was not part of this project. “In addition to shedding new light on host-parasite communication, Westwood’s findings have exciting implications for the design of novel control strategies based on disrupting the mRNA information that the parasite uses to reprogram the host." 

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Parenting from before conception: Babies' health doesn't 'start from scratch'

Parenting from before conception: Babies' health doesn't 'start from scratch' | Amazing Science | Scoop.it
There's now overwhelming evidence that a child's future health is influenced by more than just their parents' genetic material, and that children born of unhealthy parents will already be pre-programmed for greater risk of poor health, according to researchers. "The reality is, the child doesn't quite start from scratch -- they already carry over a legacy of factors from their parents' experiences that can shape development in the fetus and after birth. Depending on the situation, we can give our children a burden before they've even started life," experts say.


At fertilization, the gametes endow the embryo with a genomic blueprint, the integrity of which is affected by the age and environmental exposures of both parents. Recent studies reveal that parental history and experiences also exert effects through epigenomic information not contained in the DNA sequence, including variations in sperm and oocyte cytosine methylation and chromatin patterning, noncoding RNAs, and mitochondria. Transgenerational epigenetic effects interact with conditions at conception to program the developmental trajectory of the embryo and fetus, ultimately affecting the lifetime health of the child. These insights compel us to revise generally held notions to accommodate the prospect that biological parenting commences well before birth, even prior to conception.

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Siri’s Inventors Are Building a Radical New AI That Does Anything You Ask

Siri’s Inventors Are Building a Radical New AI That Does Anything You Ask | Amazing Science | Scoop.it

When Apple announced the iPhone 4S on October 4, 2011, the headlines were not about its speedy A5 chip or improved camera. Instead they focused on an unusual new feature: an intelligent assistant, dubbed Siri. At first Siri, endowed with a female voice, seemed almost human in the way she understood what you said to her and responded, an advance in artificial intelligence that seemed to place us on a fast track to the Singularity. She was brilliant at fulfilling certain requests, like “Can you set the alarm for 6:30?” or “Call Diane’s mobile phone.” And she had a personality: If you asked her if there was a God, she would demur with deft wisdom. “My policy is the separation of spirit and silicon,” she’d say.


Over the next few months, however, Siri’s limitations became apparent. Ask her to book a plane trip and she would point to travel websites—but she wouldn’t give flight options, let alone secure you a seat. Ask her to buy a copy of Lee Child’s new book and she would draw a blank, despite the fact that Apple sells it. Though Apple has since extended Siri’s powers—to make an OpenTable restaurant reservation, for example—she still can’t do something as simple as booking a table on the next available night in your schedule. She knows how to check your calendar and she knows how to use Open­Table. But putting those things together is, at the moment, beyond her.


Now a small team of engineers at a stealth startup called Viv Labs claims to be on the verge of realizing an advanced form of AI that removes those limitations. Whereas Siri can only perform tasks that Apple engineers explicitly implement, this new program, they say, will be able to teach itself, giving it almost limitless capabilities. In time, they assert, their creation will be able to use your personal preferences and a near-infinite web of connections to answer almost any query and perform almost any function.


“Siri is chapter one of a much longer, bigger story,” says Dag Kittlaus, one of Viv’s cofounders. He should know. Before working on Viv, he helped create Siri. So did his fellow cofounders, Adam Cheyer and Chris Brigham.


For the past two years, the team has been working on Viv Labs’ product—also named Viv, after the Latin root meaning live. Their project has been draped in secrecy, but the few outsiders who have gotten a look speak about it in rapturous terms. “The vision is very significant,” says Oren Etzioni, a renowned AI expert who heads the Allen Institute for Artificial Intelligence. “If this team is successful, we are looking at the future of intelligent agents and a multibillion-dollar industry.”

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The Singularity approaches... :-)
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Case of a missing gene may help future Alzheimer's treatment

Case of a missing gene may help future Alzheimer's treatment | Amazing Science | Scoop.it
Research suggests that reducing or neutralizing one variety of the APOE gene would not harm the brain, while making Alzheimer’s less likely.


The 40-year-old man showed up in Dr. Mary Malloy’s clinic with sadly disfiguring symptoms. His hands, elbows, ears and feet were blemished with protruding pustules and tuber-like welts, some so painful it was hard for him to walk. He suffered from a rare genetic condition called dysbetalipoproteinemia, which caused his cholesterol levels to soar so high that pools of fatty tissue seemed to bubble up under his skin.


But there was something else about this patient. He was missing a gene that, when present in one form, greatly increases the risk of developing Alzheimer’s disease. Dr. Malloy, who co-directs the Adult Lipid Clinic at the University of California, San Francisco, and her colleagues saw an opportunity to answer an important neurological riddle: Does the absence of the gene — named apolipoprotein E, or APOE, after the protein it encodes — hurt the brain?


If a person with this rare condition were found to be functioning normally, that would suggest support for a new direction in Alzheimer’s treatment. It would mean that efforts — already being explored by dementia experts — to prevent Alzheimer’s by reducing, eliminating or neutralizing the effects of the most dangerous version of APOE might succeed without causing other problems in the brain.


The researchers, who reported their findings on Monday in the journal JAMA Neurology, discovered exactly that. They ran a battery of tests, including cognitive assessments, brain imaging and cerebrospinal fluid analyses. The man’s levels of beta-amyloid and tau proteins, which are markers of Alzheimer’s, gave no indication of neurological disease. His brain size was unaffected, and the white matter was healthy. His thinking and memory skills were generally normal.


“This particular case tells us you can actually live without any APOE in the brain,” said Dr. Joachim Herz, a neuroscientist and molecular geneticist at University of Texas Southwestern Medical Center, who was not involved in the research. “So if they were to develop anti-APOE therapies for Alzheimer’s, we would not have to worry about serious neurological side effects.”

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Do we live in a 2D hologram? New Fermilab experiment will test the nature of the universe

Do we live in a 2D hologram? New Fermilab experiment will test the nature of the universe | Amazing Science | Scoop.it
A unique experiment at the U.S. Department of Energy's Fermi National Accelerator Laboratory called the Holometer has started collecting data that will answer some mind-bending questions about our universe – including whether we live in a hologram.


Much like characters on a television show would not know that their seemingly 3D world exists only on a 2D screen, we could be clueless that our 3D space is just an illusion. The information about everything in our universe could actually be encoded in tiny packets in two dimensions. Get close enough to your TV screen and you'll see pixels, small points of data that make a seamless image if you stand back. Scientists think that the universe's information may be contained in the same way, and that the natural "pixel size" of space is roughly 10 trillion trillion times smaller than an atom, a distance that physicists refer to as the Planck scale.


"We want to find out whether space-time is a quantum system just like matter is," said Craig Hogan, director of Fermilab's Center for Particle Astrophysics and the developer of the holographic noise theory. "If we see something, it will completely change ideas about space we've used for thousands of years."


Quantum theory suggests that it is impossible to know both the exact location and the exact speed of subatomic particles. If space comes in 2D bits with limited information about the precise location of objects, then space itself would fall under the same theory of uncertainty . The same way that matter continues to jiggle (as quantum waves) even when cooled to absolute zero, this digitized space should have built-in vibrations even in its lowest energy state.


Essentially, the experiment probes the limits of the universe's ability to store information. If there are a set number of bits that tell you where something is, it eventually becomes impossible to find more specific information about the location – even in principle. The instrument testing these limits is Fermilab's Holometer, or holographic interferometer, the most sensitive device ever created to measure the quantum jitter of space itself.


Now operating at full power, the Holometer uses a pair of interferometers placed close to one another. Each one sends a one-kilowatt laser beam (the equivalent of 200,000 laser pointers) at a beam splitter and down two perpendicular 40-meter arms. The light is then reflected back to the beam splitter where the two beams recombine, creating fluctuations in brightness if there is motion. Researchers analyze these fluctuations in the returning light to see if the beam splitter is moving in a certain way – being carried along on a jitter of space itself.


"Holographic noise" is expected to be present at all frequencies, but the scientists' challenge is not to be fooled by other sources of vibrations. The Holometer is testing a frequency so high – millions of cycles per second – that motions of normal matter are not likely to cause problems. Rather, the dominant background noise is more often due to radio waves emitted by nearby electronics. The Holometer experiment is designed to identify and eliminate noise from such conventional sources.


"If we find a noise we can't get rid of, we might be detecting something fundamental about nature–a noise that is intrinsic to spacetime," said Fermilab physicist Aaron Chou, lead scientist and project manager for the Holometer. "It's an exciting moment for physics. A positive result will open a whole new avenue of questioning about how space works."

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Whole functional organ has been grown from scratch inside an animal for the first time

Whole functional organ has been grown from scratch inside an animal for the first time | Amazing Science | Scoop.it

A group of cells developed into a thymus - a critical part of the immune system - when transplanted into mice. The findings, published in Nature Cell Biology, could pave the way to alternatives to organ transplantation.

Experts said the research was promising, but still years away from human therapies.


The thymus is found near the heart and produces a component of the immune system, called T-cells, which fight infection. Scientists at the Medical Research Council centre for regenerative medicine at the University of Edinburgh started with cells from a mouse embryo.


These cells were genetically "reprogrammed" and started to transform into a type of cell found in the thymus. These were mixed with other support-role cells and placed inside mice.


Once inside, the bunch of cells developed into a functional thymus.

It is similar to a feat last year, when lab-grown human brains reached the same level of development as a nine-week-old fetus.


The thymus is a much simpler organ and in these experiments became fully functional. Structurally it contained the two main regions - the cortex and medulla - and it also produced T-cells.


Prof. Clare Blackburn, part of the research team, said it was "tremendously exciting" when the team realized what they had achieved. "This was a complete surprise to us, that we were really being able to generate a fully functional and fully organized organ starting with reprogrammed cells in really a very straightforward way. This is a very exciting advance and it's also very tantalising in terms of the wider field of regenerative medicine."


Patients who need a bone marrow transplant and children who are born without a functioning thymus could all benefit. Ways of boosting the thymus could also help elderly people. The organ shrinks with age and leads to a weaker immune system. However, there are a number of obstacles to overcome before this research moves from animal studies to hospital therapies. The current technique uses embryos. This means the developing thymus would not be a tissue match for the patient.

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Evolutionary history of honeybees revealed by genomics

Evolutionary history of honeybees revealed by genomics | Amazing Science | Scoop.it

In a study published in Nature Genetics, researchers from Uppsala University present the first global analysis of genome variation in honeybees. The findings show a surprisingly high level of genetic diversity in honeybees, and indicate that the species most probably originates from Asia, and not from Africa as previously thought.


The honeybee (Apis mellifera) is of crucial importance for humanity. One third of our food is dependent on the pollination of fruits, nuts and vegetables by bees and other insects. Extensive losses of honeybee colonies in recent years are a major cause for concern. Honeybees face threats from disease, climate change, and management practices. To combat these threats it is important to understand the evolutionary history of honeybees and how they are adapted to different environments across the world.


"We have used state-of-the-art high-throughput genomics to address these questions, and have identified high levels of genetic diversity in honeybees. In contrast to other domestic species, management of honeybees seems to have increased levels of genetic variation by mixing bees from different parts of the world. The findings may also indicate that high levels of inbreeding are not a major cause of global colony losses", says Matthew Webster, researcher at the department of Medical Biochemistry and Microbiology, Uppsala University.


Another unexpected result was that honeybees seem to be derived from an ancient lineage of cavity-nesting bees that arrived from Asia around 300,000 years ago and rapidly spread across Europe and Africa. This stands in contrast to previous research that suggests that honeybees originate from Africa.


Reference: A worldwide survey of genome sequence variation provides insight into the evolutionary history of the honeybee Apis mellifera, Nature Genetics, 2014. dx.doi.org/10.1038/ng.3077

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Widespread methane leakage from ocean floor off the US coast

Widespread methane leakage from ocean floor off the US coast | Amazing Science | Scoop.it

Researchers say they have found more than 500 bubbling methane vents on the seafloor off the US east coast. The unexpected discovery indicates there are large volumes of the gas contained in a type of sludgy ice called methane hydrate. There are concerns that these new seeps could be making a hitherto unnoticed contribution to global warming.

The scientists say there could be about 30,000 of these hidden methane vents worldwide.


Previous surveys along the Atlantic seaboard have shown only three seep areas beyond the edge of the US continental shelf. The findings came as a bit of a surprise.  "It is the first time we have seen this level of seepage outside the Arctic that is not associated with features like oil or gas reservoirs or active tectonic margins," said Prof Adam Skarke from Mississippi State University, who led the study.


The scientists have observed streams of bubbles but they have not yet sampled the gas within them. However, they believe there is an abundance of circumstantial evidence pointing to methane.


Most of the seeping vents were located around 500m down, which is just the right temperature and pressure to create a sludgy confection of ice and gas called methane hydrate, or clathrate.


The scientists say that the warming of ocean temperatures might be causing these hydrates to send bubbles of gas drifting through the water column. 


Prof. Skarke and his colleagues estimate that worldwide, there may be around 30,000 of the type of seeps they have discovered.

They acknowledge that this is a rough calculation but they believe that it could be significant.


While the vents may not be posing an immediate global warming threat, the sheer number means that our calculations on the potential sources of greenhouse gases may need revising. The scientists also found abundant life around many of these seeps, but not perhaps as we know it.


The creatures they describe are termed chemosynthetic, meaning they derive energy from chemical reactions and not from the Sun as do photosynthetic organisms.

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Genetically engineered pig hearts survived more than a year in baboon abdomens

Genetically engineered pig hearts survived more than a year in baboon abdomens | Amazing Science | Scoop.it

The heart didn't beat for the baboon, but it did overcome the risk of organ rejection.


By breeding piglets with a few choice human genes, scientists were able to create sort-of-pig hearts that seem to be compatible with primate hosts. The organ wasn't used as a heart, but was instead grafted into the abdomen of an otherwise healthy baboon. After over a year, the best of the hearts are still living, viable organs. Next stop, the chest cavity!


Researchers at the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health will publish their results in the September issue of The Journal of Thoracic and Cardiovascular Surgery, though their findings were discussed several months ago at a conference. According to the study, the researchers experimented with different degrees of genetic modification in the pigs. They prevented all of the piglets from producing certain enzymes known to cause organ rejection in baboons (and, by extension, humans) but were given different gene alterations to keep blood from clotting, which is another common issue.


The most successful group had the human thrombomodulin gene added to their genomes. The expression of this gene prevented clotting, lead investigator Muhammad M. Mohiuddin said in a statement. While the average survival of the other groups were 70 days, 21 days and 80 days, the thrombomodulin group survived an average of 200 days in the baboon abdomen. And three of the five grafts in the group were still alive at 200 to 500 days since their grafting, when the study was submitted for review.

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How lizards regenerate their tails: researchers discover genetic 'recipe'

How lizards regenerate their tails: researchers discover genetic 'recipe' | Amazing Science | Scoop.it

By understanding the secret of how lizards regenerate their tails, researchers may be able to develop ways to stimulate the regeneration of limbs in humans. Now, a team of researchers from Arizona State University is one step closer to solving that mystery. The scientists have discovered the genetic “recipe” for lizard tail regeneration, which may come down to using genetic ingredients in just the right mixture and amounts.


Other animals, such as salamanders, frog tadpoles and fish, can also regenerate their tails, with growth mostly at the tip. During tail regeneration, they all turn on genes in what is called the 'Wnt pathway’ – a process that is required to control stem cells in many organs, such as the brain, hair follicles and blood vessels. However, lizards have a unique pattern of tissue growth that is distributed throughout the tail.


"Regeneration is not an instant process," said Elizabeth Hutchins, a graduate student in ASU's molecular and cellular biology program and co-author of the paper. "In fact, it takes lizards more than 60 days to regenerate a functional tail. Lizards form a complex regenerating structure with cells growing into tissues at a number of sites along the tail.”


"We have identified one type of cell that is important for tissue regeneration," said Jeanne Wilson-Rawls, co-author and associate professor with ASU’s School of Life Sciences. "Just like in mice and humans, lizards have satellite cells that can grow and develop into skeletal muscle and other tissues."


"Using next-generation technologies to sequence all the genes expressed during regeneration, we have unlocked the mystery of what genes are needed to regrow the lizard tail," said Kusumi. "By following the genetic recipe for regeneration that is found in lizards, and then harnessing those same genes in human cells, it may be possible to regrow new cartilage, muscle or even spinal cord in the future."


The findings are published today in the journal PLOS ONE.

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An MRI-guided brain surgery technology goes global

An MRI-guided brain surgery technology goes global | Amazing Science | Scoop.it

An MRI-guided laser system that allows surgeons to perform brain surgery on tumors and epileptic lesions in the brain is expected to become widely available to patients in need now that the technology has been acquired from Visualase Inc. by the global medical device company Medtronic, Inc., says a biomedical engineering professor from Texas A&M University who co-founded the company responsible for the technology.


The technology, says Gerard Coté, professor in the university’s Department of Biomedical Engineering and director of the Center for Remote Healthcare Technology, enables surgeons to pinpoint and destroy brain tumors and lesions with extreme precision and is a much less-invasive alternative to conventional surgery.


The advantage of this approach over other approaches for brain surgery, Coté explains, is that it can be performed while the patient is awake, requires no radiation and no skull flap (the large opening in traditional craniotomies), and is often performed in otherwise inoperable areas of the brain.


Traditional brain surgery, he explains, is usually a daylong operation that involves removing part of the skull, cutting through healthy brain matter and physically removing the problematic tissue. That procedure, he adds, can be followed by a weeklong hospital stay and prolonged recovery period. 


The technology developed by former Texas A&M students Ashok Gowda and the late Roger McNichols, conversely, can be completed in about four hours, and most patients can return home the following day, Coté says. 


Known as “Visualase,” the technology is already used in more than 45 hospitals, nationwide, including 15 pediatric hospitals. Before the surgical procedure, computer software first helps identify the targeted tissue so that it may be treated and the surrounding healthy tissue can be avoided, Coté explains. During the procedure, a small entry is made in the skull that allows a laser applicator (about the size of a pencil lead) to be inserted into the tissue. The patient is placed in the MRI, and a physician receives and reviews images to verify proper positioning of the laser applicator in the skull. The clinician then uses a laser to heat and destroy the problematic tissue while imaging the tissue being damaged in real time to ensure destruction of the problematic tissue and to avoid damaging healthy tissue. The laser applicator is then removed, and the scalp is closed with one stitch, Coté notes.


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Recycling old car batteries into solar cells could convert dangerous waste into photovoltaics

Recycling old car batteries into solar cells could convert dangerous waste into photovoltaics | Amazing Science | Scoop.it

This could be a classic win-win solution: A system proposed by researchers at MIT recycles materials from discarded car batteries — a potential source of lead pollution — into new, long-lasting solar panels that provide emissions-free power. The system is described in a paper in the journal Energy and Environmental Science,co-authored by professors Angela M. Belcher and Paula T. Hammond, graduate student Po-Yen Chen, and three others. It is based on a recent development in solar cells that makes use of a compound called perovskite — specifically, organolead halide perovskite — a technology that has rapidly progressed from initial experiments to a point where its efficiency is nearly competitive with that of other types of solar cells.


“It went from initial demonstrations to good efficiency in less than two years,” says Belcher, the W.M. Keck Professor of Energy at MIT. Already, perovskite-based photovoltaic cells have achieved power-conversion efficiency of more than 19 percent, which is close to that of many commercial silicon-based solar cells. Initial descriptions of the perovskite technology identified its use of lead, whose production from raw ores can produce toxic residues, as a drawback. But by using recycled lead from old car batteries, the manufacturing process can instead be used to divert toxic material from landfills and reuse it in photovoltaic panels that could go on producing power for decades.


Amazingly, because the perovskite photovoltaic material takes the form of a thin film just half a micrometer thick, the team’s analysis shows that the lead from a single car battery could produce enough solar panels to provide power for 30 households.

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Scientists were able to zoom in and out in real time as the brain processed sound

Scientists were able to zoom in and out in real time as the brain processed sound | Amazing Science | Scoop.it

Researchers at Johns Hopkins have mapped a new technique for watching auditory processing in the brains of mice as brain cells lit up when the mice listened to tones and one another’s calls. The results, which represent a step toward better understanding how our own brains process language, appear online July 31 in the journal Neuron.


In the past, researchers often studied sound processing in various animal brains by poking tiny electrodes into the auditory cortex, the part of the brain that processes sound. They then played tones and observed the response of nearby neurons, laboriously repeating the process over a grid-like pattern to figure out where the active neurons were.


More recently, a technique called two-photon microscopy has allowed researchers to focus in on minute slices of the live mouse brain, observing activity in unprecedented detail. This newer approach has suggested that the precise arrangement of bands might be an illusion.


However, “you could lose your way within the zoomed-in views afforded by two-photon microscopy and not know exactly where you are in the brain,” says David Yue, M.D., Ph.D., a professor of biomedical engineering andneuroscience at the Johns Hopkins University School of Medicine. Yue led the study along with Eric Young, Ph.D., also a professor of biomedical engineering and a researcher in Johns Hopkins’ Institute for Basic Biomedical Sciences.


To get the bigger picture, John Issa, a graduate student in Yue’s lab, used a mouse genetically engineered to produce a molecule that glows green in the presence of calcium. Since calcium levels rise in neurons when they become active, neurons in the mouse’s auditory cortex glow green when activated by various sounds.


Issa used a two-photon microscope to peer into the brains of live mice as they listened to sounds and saw which neurons lit up in response, piecing together a global map of a given mouse’s auditory cortex.


“With these mice, we were able to both monitor the activity of individual populations of neurons and zoom out to see how those populations fit into a larger organizational picture,” he says.


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Fascinating rhythm: Light pulses illuminate a rare black hole

Fascinating rhythm: Light pulses illuminate a rare black hole | Amazing Science | Scoop.it

The universe has so many black holes that it's impossible to count them all. There may be 100 million of these intriguing astral objects in our galaxy alone. Nearly all black holes fall into one of two classes: big, and colossal. Astronomers know that black holes ranging from about 10 times to 100 times the mass of our sun are the remnants of dying stars, and that supermassive black holes, more than a million times the mass of the sun, inhabit the centers of most galaxies.


But scattered across the universe like oases in a desert are a few apparent black holes of a more mysterious type. Ranging from a hundred times to a few hundred thousand times the sun's mass, these intermediate-mass black holes are so hard to measure that even their existence is sometimes disputed. Little is known about how they form. And some astronomers question whether they behave like other black holes.


Now a team of astronomers has accurately measured—and thus confirmed the existence of—a black hole about 400 times the mass of our sun in a galaxy 12 million light years from Earth. The finding, by University of Maryland astronomy graduate student Dheeraj Pasham and two colleagues, was published online August 17 in the journal Nature.


Pasham focused on one object in Messier 82, a galaxy in the constellation Ursa Major. Messier 82 is our closest "starburst galaxy," where young stars are forming. Beginning in 1999 a NASA satellite telescope, the Chandra X-ray Observatory, detected X-rays in Messier 82 from a bright object prosaically dubbed M82 X-1. Astronomers, including Mushotzky and co-author Tod Strohmayer of NASA's Goddard Space Flight Center, suspected for about a decade that the object was an intermediate-mass black hole, but estimates of its mass were not definitive enough to confirm that.


Between 2004 and 2010 NASA's Rossi X-Ray Timing Explorer (RXTE) satellite telescope observed M82 X-1 about 800 times, recording individual x-ray particles emitted by the object. Pasham mapped the intensity and wavelength of x-rays in each sequence, then stitched the sequences together and analyzed the result

.

Among the material circling the suspected black hole, he spotted two repeating flares of light. The flares showed a rhythmic pattern of light pulses, one occurring 5.1 times per second and the other 3.3 times per second – or a ratio of 3:2.

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Scripps Research Institute Chemists Uncover Powerful New Click Chemistry Reactivity

Scripps Research Institute Chemists Uncover Powerful New Click Chemistry Reactivity | Amazing Science | Scoop.it

Chemists led by Nobel laureate K. Barry Sharpless at The Scripps Research Institute (TSRI) have used his click chemistry to uncover unprecedented, powerful reactivity for making new drugs, diagnostics, plastics, smart materials and many other products.


The new SuFEx—Sulfur Fluoride Exchange—reactions enable chemists to link molecules of their choice together using derivatives of a common commercial chemical considered essentially inert. The Sharpless team made this chemical reliably and predictably reactive. Astonishingly, acid-base constraints are rarely a concern, though they are central to nature's chemistry and an enormous hurdle for chemists. The stabile linkers are also non-polar and can enter cells, so have potential for crossing the blood-brain barrier.


Consequently, SuFEx gives easy access to an entire, unexplored galaxy within the chemical universe.  “This is a new, emergent phenomenon,” said Sharpless, the W.M. Keck Professor of Chemistry and member of the Skaggs Institute for Chemical Biology at TSRI.


Click chemistry, conceived in the mid-90s as a method for discovering new and improving existing chemical reactivity, became universally used in the chemical sciences after the 2002 discovery of copper-catalyzed azide-alkyne cycloaddition (CuAAC). Now SuFEx is the second “perfect” click reaction to be discovered at TSRI.


Sharpless shared the 2001 Nobel Prize in Chemistry for his discovery and development during the 80s of asymmetric catalytic reactions. Nature routinely makes “handed” molecules like DNA, which is like a spiral staircase you enter on the left, but chemists could not reliably make left- or right-handed molecules. The Sharpless asymmetric reactions gave chemists that gift with general reactions that made either left- or right-handed products at will.

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Tvashtar Catena, an active volcanic region on Jupiter’s moon Io

Tvashtar Catena, an active volcanic region on Jupiter’s moon Io | Amazing Science | Scoop.it

Tvashtar Catena is one of the most interesting features on Jupiter’s moon Io. It is an active volcanic region located near the moon’s north pole. This ever-changing, extremely active volcanic field consists of a chain of giant volcanic paterae, caldera-like depressions.


This chain has exhibited highly variable volcanic activity in a series of observations. Tvashtar was studied by the Galileo spacecraft over several years, from late 1999 until early 2002. In December 2000, the Cassini spacecraft had a distant and brief encounter with the Jupiter system en route to Saturn, allowing for joint observations with Galileo.


During this time, a 25 kilometres (16 mi) long, 1 to 2 kilometres (0.62 to 1.2 mi) high curtain of lava was seen to erupt from one crater, a lake of superheated silicate lava erupted in the largest crater, and finally a plume of gas burst out, rising 385 kilometres (239 mi) above the moon and blanketing areas as far away as 700 kilometres (430 mi).


Therefore scientists expected that the lava flow margins or patera boundaries within Tvashtar would have changed drastically. However, the series of observations revealed little modification of this sort suggesting that the intense eruptions at Tvashtar are topographically confined.


Another eruption on Tvashtar on February 26 2007 was photographed by the New Horizons probe as it went past Jupiter en route to Pluto. The probe observed an enormous 330 kilometres (210 mi) high plume from the volcano, with an as-yet unexplained filamentary structure, made clearly visible by the background light from the sun.


In these images, taken by NASA’s Galileo spacecraft, we can see Tvashtar Catena just after an active volcanic eruption. The left one is taken on 26 Nov 1999 and the right one on 22 Feb 2000. The red and yellow lava flows we see are illustrations based upon imaging data.


The two small bright spots are sites where molten rock is exposed to the surface at the toes of lava flows. The larger orange and yellow ribbon is a cooling lava flow that is more than 60 kilometers (37 mi) long. Dark, diffuse deposits surrounding the active lava flow were not there during the November 1999 flyby of Io.

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