#Researchers Reveal How Chronic Inflammation Can Lead to Cancer Chronic inflammation caused by disease or exposure to dangerous chemicals has long been linked to cancer,
but exactly how this process takes place has remained unclear. Now, a precise mechanism by which chronic inflammation can lead to cancer has been uncovered by researchers at MIT a development that could lead to improved targets for preventing future tumors.
In a paper published this week in the Proceedings of the National Academy of Sciences,
the researchers unveil how one of a battery of chemical warfare agents used by the immune system to fight off infection can itself create DNA mutations that lead to cancer.
As many as one in five cancers are believed to be caused or promoted by inflammation. These include mesothelioma,
a type of lung cancer caused by inflammation following chronic exposure to asbestos, and colon cancer in people with a history of inflammatory bowel disease, says Bogdan Fedeles,
a research associate in the Department of Biological engineering at MIT, and the paper lead author.
Innate immune response Inflammation is part of the body innate response to invading pathogens or potentially harmful irritants.
The immune system attacks the invader with a number of reactive molecules designed to neutralize it,
including hydrogen peroxide, nitric oxide and hypochlorous acid. However, these molecules can also cause collateral damage to healthy tissue around the infection site:
he presence of a foreign pathogen activates the immune response, which tries to fight off the bacteria,
but in this process it also damages some of the normal cells, Fedeles explains. Previous work by Peter Dedon, Steven Tannenbaum, Gerald Wogan,
and James Fox all professors of biological engineering at MIT had identified the presence of a lesion,
or site of damage in the structure of DNA, called 5-chlorocytosine (5clc) in the inflamed tissues of mice infected with the pathogen Helicobacter hepaticus.
This lesion, a damaged form of the normal DNA base cytosine, is caused by the reactive molecule hypochlorous acid the main ingredient in household bleach
which is generated by the immune system. The lesion 5clc, was present in remarkably high levels within the tissue,
says John Essigmann, the William R. 1956) and Betsy P. Leitch Professor in Residence Professor of Chemistry, Toxicology and Biological engineering at MIT,
who led the current research. hey found the lesions were very persistent in DNA, meaning we don have a repair system to take them out,
Essigmann says. n our field lesions that are persistent, if they are also mutagenic, are the kind of lesions that would initiate cancer,
he adds. DNA sequencing of a developing gastrointestinal tumor revealed two types of mutation: cytosine (C) bases changing to thymine (T) bases,
and adenine (A) bases changing to guanine (G) bases. Since 5clc had not yet been studied as a potentially carcinogenic mutagen,
the researchers decided to investigate the lesion further, in a bid to uncover if it is indeed mutagenic.
Using a technique previously developed in Essigmann laboratory, the researchers first placed the 5clc lesion at a specific site within the genome of a bacterial virus. They then replicated the virus within the cell.
The researchers found that, rather than always pairing with a guanine base as a cytosine would,
the 5clc instead paired with an adenine base around 5 percent of the time a medically relevant mutation frequency, according to Essigmann.
Damaged DNA The findings suggest that the immune system, when triggered by infection, fires hypochlorous acid at the site, damaging cytosines in the DNA of the surrounding healthy tissue.
This damage causes some of the cytosines to become 5clc. In addition, the researchers hypothesize that the hypochlorous acid also damages cytosines in the nucleotide pool,
he explains. his scenario would best explain the work of James Fox and his MIT colleagues on gastrointestinal cancer.
the researchers replicated the genome containing the lesion with a variety of different types of polymerase,
and causes the same kind of mutations seen within cells, Fedeles says. hat gave us confidence that this phenomenon would in fact happen in human cells containing high levels of 5clc.
the C-to-T mutation characteristic of 5clc is extremely common, and is present in more than 50 percent of mutagenic ignatures,
or patterns of DNA mutations, associated with cancerous tumors. e believe that in the context of inflammation-induced damage of DNA,
many of these C-to-T mutations may be caused by 5clc, possibly in correlation with other types of mutations as part of these mutational signatures,
Yinsheng Wang, a principal investigator in the Department of chemistry at the University of California at Riverside who was involved not in the research,
says the paper provides a novel mechanistic link between chronic inflammation and cancer development. ith a combination of biochemical,
genetic, and structural biology approaches, the researchers have found that 5-chlorocytosine is intrinsically miscoding during DNA replication
and it could give rise to significant frequencies of C-to-T mutation, a type of mutation that is frequently observed in human cancers,
Wang says. Studies of tissue samples of patients suffering from inflammatory bowel disease have found significant levels of 5clc,
Fedeles adds. By comparing these levels with his team findings on how mutagenic 5clc is,
the researchers predict that accumulation of the lesions would increase the mutation rate of a cell up to 30-fold,
who was honored with the prestigious Benjamin F. Trump award at the 2015 Aspen Cancer Conference for the research.
#Aluminum olk-and-Shellnanoparticle Boosts Capacity and Power of Lithium-ion Batteries One big problem faced by electrodes in rechargeable batteries,
degrading the battery performance over time. Now a team of researchers at MIT and Tsinghua University in China has found a novel way around that problem:
creating an electrode made of nanoparticles with a solid shell, and a olkinside that can change size again and again without affecting the shell.
The innovation could drastically improve cycle life, the team says, and provide a dramatic boost in the battery capacity and power.
The new findings, which use aluminum as the key material for the lithium-ion battery negative electrode,
or anode, are reported in the journal Nature Communications, in a paper by MIT professor Ju Li and six others.
The use of nanoparticles with an aluminum yolk and a titanium dioxide shell has proven to be he high-rate champion among high-capacity anodes
the team reports. Most present lithium-ion batteries the most widely used form of rechargeable batteries use anodes made of graphite, a form of carbon.
Graphite has a charge storage capacity of 0. 35 ampere-hours per gram (Ah/g; for many years, researchers have explored other options that would provide greater energy storage for a given weight.
Lithium metal, for example, can store about 10 times as much energy per gram, but is extremely dangerous,
capable of short-circuiting or even catching fire. Silicon and tin have very high capacity,
This expansion and contraction of aluminum particles generates great mechanical stress, which can cause electrical contacts to disconnect.
Also, the liquid electrolyte in contact with aluminum will always decompose at the required charge/discharge voltages,
forming a skin called solid electrolyte interphase (SEI) layer, which would be ok if not for the repeated large volume expansion and shrinkage that cause SEI particles to shed.
As a result, previous attempts to develop an aluminum electrode for lithium-ion batteries had failed.
That where the idea of using confined aluminum in the form of a yolk-shell nanoparticle came in.
In the nanotechnology business there is a big difference between what are called ore-shelland olk-shellnanoparticles.
The former have a shell that is bonded directly to the core, but yolk-shell particles feature a void between the two equivalent to where the white of an egg would be.
As a result, the olkmaterial can expand and contract freely, with little effect on the dimensions
hat separates the aluminum from the liquid electrolytebetween the battery two electrodes. The shell does not expand
and the aluminum inside is protected from direct contact with the electrolyte. The team didn originally plan it that way,
says Li, the Battelle Energy Alliance Professor in Nuclear Science and Engineering, who has a joint appointment in MIT Department of Materials science and engineering. e came up with the method serendipitously,
it was a chance discovery, he says. The aluminum particles they used, which are about 50 nanometers in diameter,
naturally have oxidized an layer of alumina (Al2o3). e needed to get rid of it, because it not good for electrical conductivity, Li says.
They ended up converting the alumina layer to titania (Tio2), a better conductor of electrons and lithium ions when it is very thin.
which reacts with titanium oxysulfate to form a solid shell of titanium hydroxide with a thickness of 3 to 4 nanometers.
the aluminum core continuously shrinks to become a 30-nm-across olk, which shows that small ions can get through the shell.
but the inside of the electrode remains clean with no buildup of the SEIS, proving the shell fully encloses the aluminum
The result is an electrode that gives more than three times the capacity of graphite (1. 2 Ah/g) at a normal charging rate
For applications that require a high power-and energy density battery, he says, t probably the best anode material available.
Full cell tests using lithium iron phosphate as cathode have been successful, indicating ATO is quite close to being ready for real applications. hese yolk-shell particles show very impressive performance in lab-scale testing,
says David Lou, an associate professor of chemical and biomolecular engineering at Nanyang Technological University in Singapore, who was involved not in this work. o me,
the most attractive point of this work is that the process appears simple and scalable.
There is much work in the battery field that uses omplicated synthesis with sophisticated facilities, Lou adds,
but such systems re unlikely to have impact for real batteries. Simple things make real impact in the battery field.
The research team included Sa Li, Yu Cheng Zhao, and Chang An Wang of Tsinghua University in Beijing and Junjie Niu,
Kangpyo So, and Chao Wang of MIT. The work was supported by the National Science Foundation and the National Natural science Foundation of China d
#Researchers Reveal Why Black Phosphorus May Surpass Graphene In a newly published study, researchers from the Pohang University of Science and Technology detail how they were able to turn black phosphorus into a superior conductor that can be mass produced for electronic and optoelectronics devices.
The research team operating out of Pohang University of Science and Technology (POSTECH), affiliated with the Institute for Basic Science (IBS) Center for Artificial Low Dimensional Electronic systems (CALDES), reported a tunable band gap in BP,
effectively modifying the semiconducting material into a unique state of matter with anisotropic dispersion. This research outcome potentially allows for great flexibility in the design and optimization of electronic and optoelectronic devices like solar panels and telecommunication lasers.
To truly understand the significance of the team findings, it instrumental to understand the nature of two-dimensional (2-D) materials,
and for that one must go back to 2010 when the world of 2-D materials was dominated by a simple thin sheet of carbon,
a layered form of carbon atoms constructed to resemble honeycomb, called graphene. Graphene was heralded globally as a wonder-material thanks to the work of two British scientists who won the Nobel prize for Physics for their research on it.
Graphene is extremely thin and has remarkable attributes. It is stronger than steel yet many times lighter
more conductive than copper and more flexible than rubber. All these properties combined make it a tremendous conductor of heat and electricity.
A defectree layer is also impermeable to all atoms and molecules. This amalgamation makes it a terrifically attractive material to apply to scientific developments in a wide variety of fields, such as electronics, aerospace and sports.
For all its dazzling promise there is however a disadvantage; graphene has no band gap. Stepping stones to a Unique Statea material band gap is fundamental to determining its electrical conductivity.
Imagine two river crossings, one with tightly-packed stepping-stones, and the other with large gaps between stones.
The former is far easier to traverse because a jump between two tightly-packed stones requires less energy.
A band gap is much the same; the smaller the gap the more efficiently the current can move across the material and the stronger the current.
Graphene has a band gap of zero in its natural state, however, and so acts like a conductor;
the semiconductor potential can be realized because the conductivity can be shut off, even at low temperatures. This obviously dilutes its appeal as a semiconductor,
as shutting off conductivity is a vital part of a semiconductor function. Birth of a Revolutionphosphorus is the fifteenth element in the periodic table
and lends its name to an entire class of compounds. Indeed it could be considered an archetype of chemistry itself.
Black phosphorus is the stable form of white phosphorus and gets its name from its distinctive color.
Like graphene, BP is a semiconductor and also cheap to mass produce. The one big difference between the two is BP natural band gap
allowing the material to switch its electrical current on and off. The research team tested on few layers of BP called phosphorene
which is an allotrope of phosphorus. Keun Su Kim, an amiable professor stationed at POSTECH speaks in rapid bursts when detailing the experiment,
e transferred electrons from the dopant potassium to the surface of the black phosphorus, which confined the electrons
which is required what we to tune the size of the band gap. his process of transferring electrons is known as doping
which tuned the band gap allowing the valence and conductive bands to move closer together, effectively lowering the band gap
and drastically altering it to a value between 0. 0 0. 6 Electron volt (ev) from its original intrinsic value of 0. 35 ev.
Professor Kim explained, raphene is a Dirac semimetal. It more efficient in its natural state than black phosphorus but it difficult to open its band gap;
therefore we tuned BP band gap to resemble the natural state of graphene, a unique state of matter that is different from conventional semiconductors. he potential for this new improved form of black phosphorus is beyond anything the Korean team hoped for,
and very soon it could potentially be applied to several sectors including engineering where electrical engineers can adjust the band gap
and create devises with the exact behavior desired. The 2-D revolution, it seems, has arrived and is here for the long run.
Publication: Jimin Kim, et al. bservation of tunable bandgap and anisotropic Dirac semimetal state in black phosphorus, Science 14 august 2015:
Vol. 349 no. 6249 pp. 723-726; DOI: 10.1126/science. aaa6486source: Institute for Basic Scienc t
#Unexpected Discovery Offers Insight into Mechanisms of Asthma, Other Diseases A new study from the Harvard T. H. Chan School of Public health reveals an unexpected discovery In people with asthma,
The findings could also have important ramifications for research in other areas, notably cancer, where the same kinds of cells play a major role.
or cars jammed in traffic, said Jeffrey Fredberg, professor of bioengineering and physiology at the Harvard Chan School and one of the senior authors of the study,
which was published online August 3 in Nature Materials. But the study showed that, in asthma, the opposite is true.
The physics of biologythe researchers decided to look at the detailed shape and movement of cells from the asthmatic airway because, according to Fredberg,
and the fact that no one knows what causes asthma, which afflicts more than 300 million people worldwide it made sense to look at the shape and movement of epithelial cells,
which many scientists think play a key role in the disease. The study included lead authors Jin-Ah Park and Jae Hun Kim, research scientists in the Department of Environmental Health who study asthma,
and Jeffrey M. Drazen, a pulmonologist and professor in the department, who studies echanotransductionin asthma how the bronchial constriction of asthma might trigger cell changes in the epithelium.
The study also included mathematical physicists James Butler, senior lecturer on physiology in the Department of Environmental Health
and M. Lisa Manning and Max Bi at Syracuse University, as well as colleagues from the Harvard Chan School and other Harvard institutions.
To analyze cell movement, the researchers took time-lapse images of epithelial cells. They also produced videos that show quite vividly the differences between normal cells and asthmatic cells.
whether asthma causes the cells to unjam, or the unjamming of the cells causes asthma. t a very big question to figure out why this particular cell shape
and movement is said happening Park. e know that asthma is related to genes, environment, and the interaction between the two,
but asthma remains poorly understood. hatever the reason, knowing more about how these cells jam
and unjam is said important Fredberg, because epithelial cells play a prominent role not just in asthma,
but in all processes involving cell growth and movement, including organ development, wound healing, and, importantly, cancer.
The findings open the door to new possibilities for developing drugs to fight asthma as well as other diseases
and to new research questions. rying to define how cells behave, how they exert forces on each other,
#Solid electrolyte Paves the Way for Rechargeable batteries with Almost Indefinite Lifetimes Engineers from MIT and Samsung have developed an approach for a solid electrolyte that could greatly improve both battery lifetime and safety,
while providing a significant boost in the amount of power stored in a given space.
If you pry open one of today ubiquitous high-tech devices whether a cellphone, a laptop,
or an electric car youl find that batteries take up most of the space inside. Indeed, the recent evolution of batteries has made it possible to pack ample power in small places.
But people still always want their devices to last even longer or go further on a charge,
so researchers work night and day to boost the power a given size battery can hold. Rare, but widely publicized, incidents of overheating or combustion in lithium-ion batteries have highlighted also the importance of safety in battery technology.
Now researchers at MIT and Samsung, and in California and Maryland, have developed a new approach to one of the three basic components of batteries, the electrolyte.
The new findings are based on the idea that a solid electrolyte, rather than the liquid used in today most common rechargeables,
could greatly improve both device lifetime and safety while providing a significant boost in the amount of power stored in a given space.
The results are reported in the journal Nature Materials in a paper by MIT postdoc Yan Wang, visiting professor of materials science and engineering Gerbrand Ceder,
and five others. They describe a new approach to the development of solid-state electrolytes that could simultaneously address the greatest challenges associated with improving lithium-ion batteries,
the technology now used in everything from cellphones to electric cars. The electrolyte in such batteries typically a liquid organic solvent whose function is to transport charged particles from one of a battery two electrodes to the other during charging
and discharging has been responsible for the overheating and fires that, for example, resulted in a temporary grounding of all of Boeing 787 Dreamliner jets,
Ceder explains. Others have attempted to find a solid replacement for the liquid electrolyte, but this group is the first to show that this can be done in a formulation that fully meets the needs of battery applications.
Solid-state electrolytes could be real game-changer, Ceder says, creating lmost a perfect battery, solving most of the remaining issuesin battery lifetime, safety, and cost.
Costs have already been coming down steadily, he says. But as for safety, replacing the electrolyte would be the key
Ceder adds: ll of the fires youe seen, with Boeing, Tesla, and others, they are all electrolyte fires.
The lithium itself is not flammable in the state it in in these batteries. With a solid electrolyte there no safety problem you could throw it against the wall,
drive a nail through it there nothing there to burn. he proposed solid electrolyte also holds other advantages,
he says: ith a solid-state electrolyte, there virtually no degradation reactions leftmeaning such batteries could last through undreds of thousands of cycles. he key to making this feasible,
Ceder says, was finding solid materials that could conduct ions fast enough to be useful in a battery. here was a view that solids cannot conduct fast enough,
he says. hat paradigm has been overthrown. he research team was able to analyze the factors that make for efficient ion conduction in solids,
and home in on compounds that showed the right characteristics. The initial findings focused on a class of materials known as superionic lithium-ion conductors
which are compounds of lithium, germanium, phosphorus, and sulfur, but the principles derived from this research could lead to even more effective materials,
the team says. The research that led to a workable solid-state electrolyte was part of an ongoing partnership with the Korean electronics company Samsung, through the Samsung Advanced Institute of technology in Cambridge, Massachusetts,
Ceder says. That alliance also has led to important advances in the use of quantum dot materials to create highly efficient solar cells and sodium batteries,
he adds. This solid-state electrolyte has unexpected other side benefits: While conventional lithium-ion batteries do not perform well in extreme cold,
and need to be preheated at temperatures below roughly minus 20 degrees Fahrenheit, the solid electrolyte versions can still function at those frigid temperatures,
Ceder says. The solid-state electrolyte also allows for greater power density the amount of power that can be stored in a given amount of space.
Such batteries provide a 20 to 30 percent improvement in power density with a corresponding increase in how long a battery of a given size could power a phone, a computer,
or a car. The team also included MIT graduate student William Richards and postdoc Jae Chul Kim;
Shyue Ping Ong at the University of California at San diego; Yifei Mo at the University of Maryland;
and Lincoln Miara at Samsung. The work is part of an alliance between MIT and the Samsung Advanced Institute of technology focusing on the development of materials for clean energy.
Publication: Yan Wang, et al. esign principles for solid-state lithium superionic conductors, i
#Hubble Reveals That Markarian 231 Is powered by a Double Black hole Using NASA Hubble space telescope, a team of astronomers discovered that Markarian 231 is powered by two central black holes furiously whirling about each other.
Markarian 231 is the nearest galaxy to Earth that hosts a quasar, located 581 million light-years away.
The finding suggests that quasarshe brilliant cores of active galaxies may commonly host two central supermassive black holes,
which fall into orbit about one another as a result of the merger between two galaxies. Like a pair of whirling skaters, the black-hole duo generates tremendous amounts of energy that makes the core of the host galaxy outshine the glow of its population of billions of stars
which scientists then identify as quasars. Scientists looked at Hubble archival observations of ultraviolet radiation emitted from the center of Markarian 231 (Mrk 231) to discover what they describe as xtreme and surprising properties.
If only one black hole were present in the center of the quasar, the whole accretion disk made of surrounding hot gas would glow in ultraviolet rays.
Instead, the ultraviolet glow of the dusty disk abruptly drops off toward the center. This provides observational evidence that the disk has a big donut hole encircling the central black hole.
The best explanation for the donut hole in the disk based on dynamical models, is that the center of the disk is carved out by the action of two black holes orbiting each other.
The second, smaller black hole orbits in the inner edge of the accretion disk, and has its own mini-disk with an ultraviolet glow. e are excited extremely about this finding
because it not only shows the existence of a close binary black hole in Mrk 231, but also paves a new way to systematically search binary black holes via the nature of their ultraviolet light emission,
said Youjun Lu of the National Astronomical observatories of China, Chinese Academy of Sciences. he structure of our universe,
and binary black holes are natural consequences of these mergers of galaxies, added co-investigator Xinyu Dai of the University of Oklahoma.
The results were published in the August 14, 2015 edition of The Astrophysical Journal. PDF Copy of the Study:
says Keith Schwab, a Caltech professor of applied physics, who led the study. ut we know that even at the quantum ground state, at zero-temperature, very small amplitude fluctuationsr noiseemain.
The plate is coupled to a superconducting electrical circuit as the plate vibrates at a rate of 3. 5 million times per second.
the residual energyuantum noiseemained. his energy is part of the quantum description of natureou just can get it out,
Coauthors Aashish Clerk from Mcgill University and Florian Marquardt from the Max Planck Institute for the Science of Light proposed a novel method to control the quantum noise,
Schwab explains. e showed that we can actually make the fluctuations of one of the variables smallert the expense of making the quantum fluctuations of the other variable larger.
Schwab says. n the 1970s, Kip Thorne Caltech Richard P. Feynman Professor of Theoretical physics, Emeritus and others wrote papers saying that these pulsars should be emitting gravity waves that are nearly perfectly periodic,
use these techniques on a gram-scale object to reduce quantum noise in detectors, thus increasing the sensitivity to pick up on those gravity waves,
In order to do that, the current device would have to be scaled up. ur work aims to detect quantum mechanics at bigger and bigger scales
uantum squeezing of motion in a mechanical resonator. In addition to Schwab, Clerk, and Marquardt, other coauthors include former graduate student Emma E. Wollman (Phd 5);
graduate students Chan U. Lei and Ari J. Weinstein; former postdoctoral scholar Junho Suh; and Andreas Kronwald of Friedrich-Alexander-Universität in Erlangen, Germany.
The work was funded by the National Science Foundation (NSF), the Defense Advanced Research Projects Agency,
and the Institute for Quantum Information and Matter, an NSF Physics Frontiers Center that also has support from the Gordon and Betty Moore Foundation r
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