Wednesday, May 23, 2018

Emerging Molecular Order

Research Reveals How Order
First Appears in Liquid Crystals
Brown University chemists have shown a technique that can identify regions in a liquid crystal system where molecular order begins to emerge just before the system fully transitions from disordered to ordered states

PROVIDENCE, R.I. [Brown University] — May 22, 2018 -- Liquid crystals undergo a peculiar type of phase change. At a certain temperature, their cigar-shaped molecules go from a disordered jumble to a more orderly arrangement in which they all point more or less in the same direction. LCD televisions take advantage of that phase change to project different colors in moving images.

For years, however, experiments have hinted at another liquid crystal state — an intermediate state between the disordered and ordered states in which order begins to emerge in discrete patches as a system approaches its transition temperature. Now, chemists at Brown University have demonstrated a theoretical framework for detecting that intermediate state and for better understanding how it works.

“People understand the ordered and disordered behaviors very well, but the state where this transition is just about to happen isn’t well understood,” said Richard Stratt, a professor of chemistry at Brown and coauthor of a paper describing the research. “What we’ve come up with is a sort of yardstick to measure whether a system is in this state. It gives us an idea of what to look for in molecular terms to see if the state is present.”

The research, published in the Journal of Chemical Physics, could shed new light not only on liquid crystals, but also molecular motion elsewhere in nature — phenomena such as the protein tangles involved in Alzheimer’s disease, for example. The work was led by Yan Zhao, a Ph.D. student in Stratt’s lab who expects to graduate from Brown this spring.

For the study, the researchers used computer simulations of phase changes in a simplified liquid crystal system that included a few hundred molecules. They used random matrix theory, a statistical framework often used to describe complex or chaotic systems, to study their simulation results. They showed that the theory does a good job of describing the system in both the ordered and disordered states, but fails to describe the transition state. That deviation from the theory can be used as a probe to identify the regions of the material where order is beginning to emerge.

“Once you realize that you have this state where the theory doesn’t work, you can dig in and ask what went wrong,” Stratt said. “That gives us a better idea of what these molecules are doing.”

Random matrix theory predicts that the sums of uncorrelated variables — in this case, the directions in which molecules are pointing — should form a bell curve distribution when plotted on a graph. Stratt and Zhao showed that that’s true of the molecules in liquid crystals when they’re in disordered and ordered states. In the disordered state, the bell curve distribution is generated by the entirely random orientations of the molecules. In the ordered state, the molecules are aligned along a common axis, but they each deviate from it a bit — some pointing a little to the left of the axis and some a little to right. Those random deviations, like the random molecule positions in the disordered state, could be fit to a bell curve.

But that bell curve distribution fell apart just before the phase change took place, as the temperature of the system was dropping down to its transition temperature. That suggests that molecules in discrete patches in the system were becoming correlated with each other.

“You now have several sets of molecules starting to cooperate with each other, and that causes the deviations from the bell curve,” Stratt said. “It’s as if these molecules are anticipating that this fully ordered state is going to take place, but they haven’t all decided which direction they’re going to face yet. It’s a little like politics, where everybody agrees that something needs to change, but they haven’t figured out exactly what to do.”

Stratt says the work could be helpful in providing insight into what governs the effectiveness of molecular motion. In both ordered and disordered liquid crystals, molecules are free to move relatively freely. But in the intermediate state, that movement is inhibited. This state then represents a situation in which the molecular progress is starting to slow down.

“There are a lot of problems in natural science where movement of molecules is slow,” Stratt said. “The molecules in molten glass, for example, progressively slow down as the liquid cools. The protein tangles involved in Alzheimer’s disease are another example where the molecular arrangement causes the motion to be slow. But what rules are governing those molecules as they slow down? We don’t fully understand it.”

Stratt hopes that a better understanding of slow molecular movement in liquid crystals could provide a blueprint for understanding slow movement elsewhere in nature.

Link (with a diagram showing the semi-ordered state as an example):  http://news.brown.edu/articles/2018/05/order

Tuesday, May 22, 2018

Millions of Synthetic Proteins

Chemists Synthesize Millions of .
Proteins not Found in Nature
New technology could lead to development of novel
“xenoprotein” drugs against infectious diseases
By Anne Trafton | MIT News Office

May 21, 2018 -- MIT chemists have devised a way to rapidly synthesize and screen millions of novel proteins that could be used as drugs against Ebola and other viruses.

All proteins produced by living cells are made from the 20 amino acids that are programmed by the genetic code. The MIT team came up with a way to assemble proteins from amino acids not used in nature, including many that are mirror images of natural amino acids.

These proteins, which the researchers call “xenoproteins,” offer many advantages over naturally occurring proteins. They are more stable, meaning that unlike most protein drugs, they don’t require refrigeration, and may not provoke an immune response.

“There is no other technological platform that can be used to create these xenoproteins because people haven’t worked through the ability to use completely nonnatural sets of amino acids throughout the entire shape of the molecule,” says Brad Pentelute, an MIT associate professor of chemistry and the senior author of the paper, which appears in the Proceedings of the National Academy of Sciences the week of May 21.

Zachary Gates, an MIT postdoc, is the lead author of the paper. Timothy Jamison, head of MIT’s Department of Chemistry, and members of his lab also contributed to the paper.

Nonnatural proteins

Pentelute and Jamison launched this project four years ago, working with the Defense Advanced Research Projects Agency (DARPA), which asked them to come up with a way to create molecules that mimic naturally occurring proteins but are made from nonnatural amino acids.

“The mission was to generate discovery platforms that allow you to chemically manufacture large libraries of molecules that don’t exist in nature, and then sift through those libraries for the particular function that you desired,” Pentelute says.

For this project, the research team built on technology that Pentelute’s lab had previously developed for rapidly synthesizing protein chains. His tabletop machine can perform all of the chemical reactions needed to string together amino acids, synthesizing the desired proteins within minutes.

As building blocks for their xenoproteins, the researchers used 16 “mirror-image” amino acids. Amino acids can exist in two different configurations, known as L and D. The L and D versions of a particular amino acid have the same chemical composition but are mirror images of each other. Cells use only L amino acids.

The researchers then used synthetic chemistry to assemble tens of millions of proteins, each about 30 amino acids in length, all of the D configuration. These proteins all had a similar folded structure that is based on the shape of a naturally occurring protein known as a trypsin inhibitor.

Before this study, no research group had been able to create so many proteins made purely of nonnatural amino acids.

“Significant effort has been devoted to development of methods for the incorporation of nonnatural amino acids into protein molecules, but these are generally limited with regard to the number of nonnatural amino acids that can simultaneously be incorporated into a protein molecule,” Gates says.

After synthesizing the xenoproteins, the researchers screened them to identify proteins that would bind to an IgG antibody against an influenza virus surface protein. The antibodies were tagged with a fluorescent molecule and then mixed with the xenoproteins. Using a system called fluorescence-activated cell sorting, the researchers were able to isolate xenoproteins that bind to the fluorescent IgG molecule.

This screen, which can be done in only a few hours, revealed several xenoproteins that bind to the target. In other experiments, not published in the PNAS paper, the researchers have also identified xenoproteins that bind to anthrax toxin and to a glycoprotein produced by the Ebola virus. This work is in collaboration with John Dye, Spencer Stonier, and Christopher Cote at the U.S. Army Medical Research Institute of Infectious Diseases.

“This is an extremely important first step in finding a good way of rapidly screening complex mirror image proteins,” says Stephen Kent, a professor of chemistry at the University of Chicago, who was not involved in the research. “Being able to use chemistry to make a library of mirror image proteins, with their high stability and specificity for a given target, is obviously of potential therapeutic interest.”

Built on demand

The researchers are now working on synthesizing proteins modeled on different scaffold shapes, and they are searching for xenoproteins that bind to other potential drug targets. Their long-term goal is to use this system to rapidly synthesize and identify proteins that could be used to neutralize any type of emerging infectious disease.

“The hope is that we can discover molecules in a rapid manner using this platform, and we can chemically manufacture them on demand. And after we make them, they can be shipped all over the place without refrigeration, for use in the field,” Pentelute says.

In addition to potential drugs, the researchers also hope to develop “xenozymes” — xenoproteins that can act as enzymes to catalyze novel types of chemical reactions.


 

Monday, May 21, 2018

The Warsaw Radio Mast

The Warsaw Radio Mast was the world's tallest structure from 1974 until its collapse on 8 August 1991. It is the second tallest structure ever built, being surpassed as tallest by the Burj Khalifa, completed in 2010.

The mast, which was designed by Jan Polak, was 646.38 metres (2,120.7 ft) tall. Its construction, started in July 1970, was completed on 18 May 1974, and its transmitter entered regular service on 22 July of that year. It was located in Konstantynów, Gąbin, Poland, and was used by Warsaw Radio-Television (Centrum Radiowo-Telewizyjne) for longwave radio broadcasting on a frequency of AM-LW (long wave) 227 kHz before 1 February 1988 and AM-LW (long wave) 225 kHz afterwards. Its base was 115.2 metres (378 ft) above sea level. Because a voltage potential of 120 kV existed between the mast and ground, it stood on a 2-metre (6.6 ft)-high insulator. It operated as a mast radiator (half-wave radiator), so its height was chosen in order to function as a half-wavelength antenna at its broadcasting frequency. The signals from its 2 megawatt transmitters could be received across essentially the entire globe. Its weight was debated: Polish sources claimed 420 tonnes (930,000 lb).

Collapse

At 16:00 UTC on 8 August 1991 a catastrophic failure led to the collapse of the mast. The mast first bent and then snapped at roughly half its height. The helix building and the transmitter building (including the transmitter devices in it) were not damaged. The construction coordinator and the division chief of the company which built and maintained the mast were found liable for the collapse, and both were sentenced to two years in prison.

Since the collapse of the Warsaw radio mast, the tallest structure in Poland has been the FM radio and TV transmission mast at Olsztyn-Pieczewo, measuring 360 metres.

Current State of the Facility

Except for the mast and the radio frequency transmission line that led to it, nearly all components of the facility remain in place, unused and slowly deteriorating.

Replica Erected in Brazil

Eldorado do Sul RBS Radio Mast, a mast radiator in Eldorado do Sul, Brazil, is a nearly perfect replica of Warsaw Radio Mast with 35.5% of its height


An American Rival

The KVLY-TV mast (formerly the KTHI-TV mast) is a 2,063-foot-tall (629 m) television-transmitting mast in Blanchard, Traill County, North Dakota, United States, used by Fargo station KVLY-TV channel 11. Completed during 1963, it was the tallest structure in the world until succeeded by the Warsaw radio mast during 1974, which collapsed in 1991, again making the KVLY-TV mast the tallest structure in the world until the Burj Khalifa exceeded it in 2008. It remains the fourth-tallest structure in the world (since the construction of the Tokyo Skytree and the Shanghai Tower), the tallest structure in the Western Hemisphere, and the tallest radio mast in the world.

Sunday, May 20, 2018

Writer Tom Wolfe Dies

Thomas Kennerly Wolfe Jr. (March 2, 1930 – May 14, 2018) was an American author and journalist widely known for his association with New Journalism, a style of news writing and journalism developed in the 1960s and 1970s that incorporated literary techniques.

Wolfe began his career as a regional newspaper reporter in the 1950s, achieving national prominence in the 1960s following the publication of such best-selling books as The Electric Kool-Aid Acid Test (a highly experimental account of Ken Kesey and the Merry Pranksters) and two collections of articles and essays, Radical Chic & Mau-Mauing the Flak Catchers and The Kandy-Kolored Tangerine-Flake Streamline Baby. In 1979, he published the influential book The Right Stuff about the Mercury Seven astronauts, which was made into a 1983 film of the same name directed by Philip Kaufman.

His first novel, The Bonfire of the Vanities, published in 1987, was met with critical acclaim and also became a commercial success. It was adapted as a major motion picture of the same name directed by Brian De Palma.

Journalism and New Journalism

Though Wolfe was offered teaching jobs in academia, he opted to work as a reporter. In 1956, while still preparing his [doctoral] thesis, Wolfe became a reporter for the Springfield Union in Springfield, Massachusetts. Wolfe finished his thesis in 1957.

In 1959, he was hired by The Washington Post. Wolfe has said that part of the reason he was hired by the Post was his lack of interest in politics. The Post's city editor was "amazed that Wolfe preferred cityside to Capitol Hill, the beat every reporter wanted." He won an award from The Newspaper Guild for foreign reporting in Cuba in 1961 and also won the Guild's award for humor. While there, Wolfe experimented with fiction-writing techniques in feature stories.

In 1962, Wolfe left Washington D.C. for New York City, taking a position with the New York Herald Tribune as a general assignment reporter and feature writer. The editors of the Herald Tribune, including Clay Felker of the Sunday section supplement New York magazine, encouraged their writers to break the conventions of newspaper writing. During the 1962 New York City newspaper strike, Wolfe approached Esquire magazine about an article on the hot rod and custom car culture of Southern California. He struggled with the article until his editor, Byron Dobell, suggested that Wolfe send him his notes so they could piece the story together.

Wolfe procrastinated. The evening before the deadline, he typed a letter to Dobell explaining what he wanted to say on the subject, ignoring all journalistic conventions. Dobell's response was to remove the salutation "Dear Byron" from the top of the letter and publish it intact as reportage. The result, published in 1963, was "There Goes (Varoom! Varoom!) That Kandy-Kolored Tangerine-Flake Streamline Baby." The article was widely discussed—loved by some, hated by others. Its notoriety helped Wolfe gain publication of his first book, The Kandy-Kolored Tangerine-Flake Streamline Baby, a collection of his writings from the Herald-Tribune, Esquire, and other publications.

This was what Wolfe called New Journalism, in which some journalists and essayists experimented with a variety of literary techniques, mixing them with the traditional ideal of dispassionate, even-handed reporting. Wolfe experimented with four literary devices not normally associated with feature writing: scene-by-scene construction, extensive dialogue, multiple points of view, and detailed description of individuals' status-life symbols (the material choices people make) in writing this stylized form of journalism. He later referred to this style as literary journalism. Of the use of status symbols, Wolfe has said, "I think every living moment of a human being’s life, unless the person is starving or in immediate danger of death in some other way, is controlled by a concern for status."

Wolfe also championed what he called “saturation reporting,” a reportorial approach in which the journalist “shadows” and observes the subject over an extended period of time. “To pull it off,” says Wolfe, “you casually have to stay with the people you are writing about for long stretches . . . long enough so that you are actually there when revealing scenes take place in their lives.” Saturation reporting differs from “in-depth” and “investigative” reporting, which involve the direct interviewing of numerous sources and/or the extensive analyzing of external documents relating to the story. Saturation reporting, according to communication professor Richard Kallan, “entails a more complex set of relationships wherein the journalist becomes an involved, more fully reactive witness, no longer distanced and detached from the people and events reported.”

Wolfe's The Electric Kool-Aid Acid Test is considered a striking example of New Journalism. This account of the Merry Pranksters, a famous sixties counter-culture group, was highly experimental in Wolfe's use of onomatopoeia, free association, and eccentric punctuation—such as multiple exclamation marks and italics—to convey the manic ideas and personalities of Ken Kesey and his followers.

In addition to his own work, Wolfe edited a collection of New Journalism with E.W. Johnson, published in 1973 and titled The New Journalism. This book published pieces by Truman Capote, Hunter S. Thompson, Norman Mailer, Gay Talese, Joan Didion, and several other well-known writers, with the common theme of journalism that incorporated literary techniques and which could be considered literature.

The Right Stuff

In 1979, Wolfe published The Right Stuff, an account of the pilots who became America's first astronauts. Following their training and unofficial, even foolhardy, exploits, he likened these heroes to "single combat champions" of a bygone era, going forth to battle in the space race on behalf of their country. In 1983, the book was adapted as a successful feature film.

Death

Wolfe died from an infection in Manhattan on May 14, 2018, at the age of 88.

Saturday, May 19, 2018

Pluto Probe Almost Failed

Here is an article about the New Horizons spacecraft approaching Pluto three years ago.  Communication with the craft ceased three days before the flyby with Pluto!  Pffft!  They hit the panic button at mission control and called in the engineers to try to straighten this out with no time to spare.

Friday, May 18, 2018

Life in Boiling Water

MSU Scientists’ Discovery in Yellowstone ‘Extremely Relevant’ to Origin of Life


BOZEMAN — May 14, 2018 -- Montana State University scientists have found a new lineage of microbes living in Yellowstone National Park’s thermal features that sheds light on the origin of life, the evolution of archaeal life and the importance of iron in early life.

Professor William Inskeep and his team of researchers published their findings May 14 in the scientific journal Nature Microbiology.

"The discovery of archaeal lineages is critical to our understanding of the universal tree of life and evolutionary history of the Earth," the group wrote. "Geochemically diverse thermal environments in Yellowstone National Park provide unprecedented opportunities for studying archaea in habitats that may represent analogues of early Earth."

Archaea is one of the three domains of life, the others being bacteria and eukaryotes. Like bacteria, archaea are single-cell organisms. The eukaryote domain contains more cellularly complex organisms, such as humans, other animals, plants and fungi.

The scientists called the new archaeal lineage Marsarchaeota after Mars, the red planet, because these organisms thrive in habitats containing iron oxides. Within Marsarchaeota, they discovered two main subgroups that live throughout Yellowstone and thrive in hot, acidic water where iron oxide is the main mineral. One subgroup lives in water above 122 degrees Fahrenheit, and the other lives in water above 140 to 176 degrees. The water is about as acidic as grapefruit juice. Their microbial mats are red because of the iron oxide.

"It's interesting that the habitat of these organisms contains (iron) minerals similar to those found on the surface of Mars," Inskeep said.

He added that microbes produce iron oxide, but the Marsarchaeota do not. They might be involved in reducing iron into a simpler form, "which is important from an early Earth standpoint. Iron cycling has been implicated as being extremely important in early Earth conditions."

The Marsarchaeota live fairly deep in microbial mats, but they still require low levels of oxygen, Inskeep said. The subgroups are so abundant that, together, they can account for as much as half of the organisms living within a single microbial mat.

The scientists studied microbial mats throughout Yellowstone. Microorganisms in these “microbial beaver dams” produce iron oxide that creates terraces, which, in turn, block streams. As water (only a couple of millimeters deep) runs over the terraces, oxygen is captured from the atmosphere and supplied to the Marsarchaeota.

"Physics comes together with chemistry and microbiology," Inskeep said. "It's like a sweet spot of conditions that this group of organisms likes."

In addition to learning more about life on early Earth and the potential for life on Mars, Inskeep said the research can help scientists understand more about high-temperature biology.

"Knowing about this new group of archaea provides additional pieces of the puzzle for understanding high-temperature biology," he said. "That could be important in industry and molecular biology."

The work that resulted in the Nature Microbiology paper was the culmination of research that took place over the past decade, said Inskeep, who has studied the geochemistry and microbiology of Yellowstone's high-temperature environments for the last 20 years. Inskeep is a professor of geomicrobiology in MSU's Department of Land Resources and Environmental Sciences in the College of Agriculture and co-founder of MSU's Thermal Biology Institute.

The lead authors of the Nature Microbiology paper earned their doctorates at MSU and were part of NSF's Integrative Graduate Education and Research Traineeship (IGERT) program while at MSU. Zackary Jay is now a postdoctoral researcher in the Department of Chemical and Biological Engineering in the Norm Asbjornson College of Engineering and the Center for Biofilm Engineering at MSU. Jacob Beam is now a postdoctoral researcher at Bigelow Laboratory for Ocean Sciences at East Boothbay, Maine.

“In the end, after many years of work, it’s exciting, and a relief, to have our team’s work recognized and published, particularly in a high impact journal,” Jay said.

Other co-authors were Mensur Dlakic from MSU's Department of Microbiology and Immunology in the College of Letters and Science and College of Agriculture; Douglas Rusch from the Center for Bioinformatics at Indiana University; and Mark Kozubal from the Thermal Biology Institute, MSU's Department of Land Resources and Environmental Sciences, and Sustainable Bioproducts in Bozeman.

Thursday, May 17, 2018

Boeing 7J7 Design

The Boeing 7J7 was a short- to medium-range airliner proposed by American aircraft manufacturer Boeing in the 1980s. It would have carried 150 passengers and was touted as the successor to the successful Boeing 727. It was initially planned to enter service in 1992. This was intended as a highly fuel-efficient aircraft employing new technologies, but it was cancelled when the price of oil dropped during the 1980s.

                                                                 Boeing 7J7 Design
 
Design and Development

The 7J7 was planned to include advanced technology and electronics, such as:

  • fly-by-wire flight control system by Bendix
  • glass cockpit by Honeywell utilizing LCDs
  • advanced integrated avionics suite
  • widespread use of high-strength composites such as carbon-fiber
  • two General Electric GE36 UDF rear-mounted advanced technology contra-rotating unducted fan (propfan) engines.

The sum of all these features promised better fuel consumption by more than 60% compared to any existing large passenger aircraft technology at the time. "Efficiency" was the key theme. The 7J7 was to have a twin-aisle (2+2+2) seating configuration, giving an unprecedented wide and spacious cabin for its class, with no passenger more than one seat from an aisle.

Foreign Partnership

It was also unprecedented in its foreign content with Japan having 25% industrial workshare. Potential customers were concerned about the economics and noise of the unproven propfan engines. Boeing cancelled the 7J7 in 1987 and instead concentrated its resources on further developments of the Boeing 737 and the Boeing 757.

The project's cancellation (as disappointing as it was to the Japanese aviation industry) signaled a new era of cooperation between Boeing and Japanese suppliers. Japanese companies contributed significantly larger percentages of subsequent Boeing projects (about 15% of the Boeing 767 and 25% of the Boeing 777).

Japanese industry continues to be a primary foreign partner on the Boeing 787 Dreamliner.

Competition

Competing with the 7J7 for airline interest was the McDonnell Douglas MD-94X, also powered by propfans, and the Airbus A320. The A320 featured a lot of similar advanced technology and electronics but was powered by conventional turbofan engines. The Boeing 737 Next Generation and the 777 incorporate many of the proposed 7J7 improvements.