Researchers strike gold with nanotech vaccine

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Researchers increase the success rate of tooth implants

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Researchers try to understand naked mole rats' resistance to cancer

With their pinkish, translucent and wrinkly skin, double-saber buck teeth and black-bead eyes, naked mole rats look like characters in a nightmare from hell. In fact, they do live underground in pitch-dark burrows where their air, from a human point of view, can contain chokingly little oxygen, toxic carbon dioxide levels and a perpetual stench of ammonia. What's more, even though they are mammals, these sausage-size rodents live more like ants and bees, with a queen, a few mating males and lots of workers.

But one other thing: They apparently never ever get cancer, which has made naked mole rats particularly beautiful to scientists.

In the past few years, researchers have been teasing out the biological bases for this cancer resistance, which they say may help explain how naked mole rats manage to live almost 10 times longer than their house mouse and street rat cousins. When Old Man, the oldest known naked mole rat on the planet, died at the University of Texas Health Science Center in San Antonio in November, he was 32 years old.

"These animals beat the odds and defy the aging process," says Rochelle Buffenstein, a physiologist at the center who had her scientific eye on Old Man since 1980, when she and colleagues captured him in a Kenyan sweet potato field. Now she maintains colonies with about 2,000 naked mole rats in her lab.

"A key finding of our work is that every physiological and biochemical system within the naked mole rat shows extended maintenance, leading to good health." Only in Old Man's final few years did he begin to appear sort of old. For most of his senior citizenhood, Buffenstein and her colleagues observed, his bones, muscles, heart and libido seemed like those of a teenager.

Getting old without the usual diseases and diminishments of the aging process has always been an intriguing idea. Vera Gorbunova, a biologist and cancer researcher at the University of Rochester in New York, is among those scientists trying to find out how naked mole rats do it. Most tantalizing to Gorbunova is that naked mole rats never get cancer even though 70 percent or more of mice that live even a few years die of cancer.

For many of the experiments her team wanted to do, they needed to grow naked mole rat cells in laboratory dishes, but this proved to be difficult. Whenever the cells touched one another, they stopped replicating. This was frustrating, but it also presented Gorbunova with a clue. She knew that normal mouse and human cells exhibit a less pronounced type of "contact inhibition" and that cancer cells grow into masses because they lack this inhibition.

"In naked mole rat cells," Gorbunova surmised, "we are seeing super contact inhibition." She wondered if there might be a linkage with the mole rats' immunity to cancer.

When the researchers dug deeper, they made a remarkable discovery that went all of the way down to the animals' genes and the biochemistry of their cells. "Naked mole rat cells possess two levels of contact inhibition, in contrast to the single level found in humans and mice," she and her colleagues wrote in late 2009 in the journal Proceedings of the National Academy of Sciences.

As Gorbunova sees it, living a long time and disease-thwarting mechanisms such as super contact inhibition go hand in hand. Mice are valuable animal models for studying cancer precisely because they get the disease so easily, she notes, and naked mole rats should become just as important for cancer research precisely because they never get the disease.

Her team is looking into potential therapeutic openings by which they might instigate super contact inhibition in other settings - say, in precancerous tissue of humans to stop the disease process in its tracks.

There's more to naked mole rats, though, than longevity and cancer resistance.

"Their pain biology is unique among animals," notes neuroscientist Thomas J. Park of the University of Illinois at Chicago. He and his colleauges have observed that the skin cells of naked mole rats lack certain pain-related signaling molecules. The animals appear undisturbed by acid and a hot-pepper irritant that bother other animals, including people. From this, the scientists hope to develop new means of pain management for humans.

Then there's the animals' ability to live without much oxygen. On that front, molecular evolutionary biologist Aaron Avivi of the University of Haifa in Israel and his colleagues have focused on the Spalax genus of mole rat, which he describes as a "hairy sausage whose ends are hard to tell apart."

Unlike the naked mole rat, Spalax individuals live solitary lives, are aggressive and cannot be bred in captivity. "Living underground has led to a lot of adaptations," Avivi says, including the ability to thrive in atmospheres that would quickly kill a human.

Especially during the winter in their northern Israeli habitats, there are days of intense rain that flood the mole rats' sealed tunnel systems. Oxygen concentrations dive to one-seventh that of normal above-ground levels, while carbon dioxide levels spike by a factor of 200, conditions that would permanently off most other air-breathing animals. Avivi says that developing a full understanding how the animals can shrug off such conditions holds great biomedical promise because of "its connection to ailments that practically kill the Western world," among them cancer, vascular and heart disease, heart attacks and strokes.

If for the past 24 million years you and your ancestors have lived in dark, dank subterranean niches, as have naked mole rats, you will have evolved plenty of adaptations in response to your habitat. And understanding those adaptations might well help us above-ground naked.

Amato is a writer and editor based in Silver Spring.

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Quantum probe technique resonates with Caltech/JPL researchers

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$(document).ready(function(){$('.star-rating').rating({callback: function(value, link){ $.post("../../", {fuseaction: 'starrating.submitrating', starratingid:$("#starratingid").val(), objecttype:$("#objecttype").val(), objectid:$("#objectid").val(),starrating:value}, function(obj) { $('.star-rating').rating('readOnly',true); var newobj = eval('(' + obj + ')'); $('#starratingleftcontainer').html('Average Rating: ' + newobj.ratio + ' / 5 ('+ newobj.ratinghits +' ratings)'); $('#starratingid').val(newobj.starratingid); });}});$("#starratinghelpicon").hover(function() {$("#starratinghelptextcontainer").animate({opacity: "show"}, "slow");}, function() {$("#starratinghelptextcontainer").animate({opacity: "hide"}, "fast");});});Average Rating: 5 / 5 (1 ratings) Quantum probe technique resonates with Caltech/JPL researchers

A team from the California Institute of Technology (Caltech) and the Jet Propulsion Laboratory (JPL) has successfully demonstrated a system that will serve as a test-bed for exploring quantum mechanics in new limits and could shed light on fundamental issues such as the division between the classical and quantum worlds.

One of the fundamental issues with making measurements in the quantum regime is that the act of measuring can actually destroy the fragile quantum state of such a system. This occurs despite one’s best attempts to be discreet in the characterization process. Basically, measuring messes things up.

Such sensitive measurements are especially difficult for macroscopic scale objects, and even on micrometer scales the quantum nature of objects is generally lost in the noise of the larger world.

In atomic physics and, more recently, in solid-state physics, researchers have gotten around this conundrum by using other quantum systems as probes. For example, the quantum signature of an oscillating system, like an electromagnetic cavity, can be imprinted on a probe and then inferred through an independent measurement of the probe – without destroying the quantum state of the original system. Such probes include individual atoms and nano-scale electronic quantum bits or "qubits."

A qubit is the quantum computing equivalent of the binary digital bit in classical computing. Like the “1” or “0” of its digital counterpart, the qubit has a state that can be controlled and measured.

In the new technique demonstrated by the Caltech and JPL team, the qubit is a tiny electrode in which electrons can be made to take on a single energy state, i.e., charged or uncharged. The qubit is placed in close proximity to a nanoresonator, which is a tiny beam of stiff material that vibrates at high frequency. In this configuration, the vibration frequency of the resonator is sensitive to the energy state of the quantum bit, and vice versa. The Caltech and JPL scientists used the sensitive dependence of the resonator frequency to probe the state of the qubit. In principle, though, either component can be used as a probe to determine quantum information about the other.

“We’ve demonstrated that we can use the nanomechanical resonator to probe quantum effects in the qubit. Based on these measurements, it looks we should be able to turn the experiment around and start looking for quantum effects in the mechanical system,” said Caltech’s Matt LaHaye. LaHaye is lead author of a paper describing the team’s work, published in the June 18 issue of the journal Nature.

According to quantum mechanics, the energy stored in any vibrating system – including macroscopic scale systems – should take discrete, or quantized, values. This discreteness of energy has been verified beautifully in other vibrating systems, such as atomic and electromagnetic systems. However, observation of this subtle quantum effect in ordinary mechanical structures, like the nanoresonator described above, remains a hotly pursued challenge in quantum measurement. The new nanoscale system demonstrated by the Caltech and JPL team is a very promising approach that could ultimately meet this challenge.

“What’s really exciting is that a lot of people have been thinking about how to use this coupled system for manipulating and measuring quantum states of mechanical objects. There are many possible experiments and directions in which we could head, all with the potential for very rich physics,” said LaHaye.

A tantalizing possibility for the team’s measurement technique is to observe the resonator in a quantum superposition of states, where it is simultaneously oscillating at two distinct frequencies. It may also be possible to examine the quantum imprint of the resonator on the energy state of the qubit to look for “quantum jumps” in the resonator’s energy.

The JPL team members had been developing the qubits for quantum computing applications and contributed to the research with fabrication of the structures and expertise in their measurement.

The work resulted from a collaboration between Profs. Michael Roukes and Keith Schwab at Caltech and Dr. Pierre Echternach at JPL. Measurements at milli-Kelvin temperatures were performed by Dr. Matt LaHaye and graduate student Junho Suh at Caltech. Electron beam lithography was performed by Richard Muller at JPL.

Reference: M.D. LaHaye, J. Suh, P.M. Echternach, K.C. Schwab, M.L. Roukes. (2009). “Nanomechanical measurements of a superconducting qubit.” Nature 459, 960-964.

Caltech press release: http://media.caltech.edu/press_releases/13271

JPL Microdevices Laboratory Website: http://microdevices.jpl.nasa.gov

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Super-CDMS researchers report possible evidence of WIMPs

(Phys.org) —Researchers working at the Super Cryogenic Dark Matter Search (CDMS) facility, located underground in Minnesota's Soudan Mine, are reporting in a paper uploaded to the preprint server arXiv that they've found three events that lie in the signal range of Weakly Interacting Massive Particles (WIMPs). The group also gave a talk detailing their results to an audience at this year's American Physical Society meeting—as part of that discussion, they made it clear the noted events do not rise to the level of discovery, nor do they imply the team has found evidence of the existence of dark matter.

Researchers in several facilities around the world (and aboard the International Space Station) are looking for evidence of WIMPs, because theory suggests that they constitute dark matter, the invisible material believed to make up approximately 85 percent of all matter that exists in the universe. Because WIMPs can't be seen directly, researchers look to events that might prove they exist, such as collisions between WIMPs and atomic nuclei. In order to find such evidence, researchers set up detectors they hope will catch such collisions that occur due to gravitational pull on WIMPs—they are believed to interact only rarely with normal matter through other means.

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The Cryogenic Dark Matter Search experiment uses five towers of dark matter detectors like the ones shown here. Credit: Fermilab

Researchers at the Super-CDMS facility have set up eight silicon detectors (cooled to -459.67 degrees Fahrenheit) in the hope of detecting the slight amount of heat given off by a collision between a WIMP and an atom's nucleus. The researchers report detection of three events that might have been the result of such collisions, though they are quick to add that the events might also have been due to something else, such as statistical errors. However, calculations indicate the events are 99.81 percent more likely to be WIMPs than background fluctuations, which translates to approximately a three-sigma level of confidence.

Interestingly, if the detected events do turn out to be the result of WIMP/nucleus collisions, it will mean that WIMPs are much lighter than scientists have been expecting—the detected collisions detected to just 8.6 giga-electronvolts. The researchers note this finding is in line with results from other research efforts, though they also acknowledge that it contradicts the findings of other researchers. Regardless, research at the Super-CDMS facility and elsewhere will continue until WIMP collisions are proven to exist, or not.

More information: Dark Matter Search Results Using the Silicon Detectors of CDMS II. arXiv astro-ph.CO, (2013)
Silicon Detector Results from the First Five-Tower Run of CDMS II. arXiv astro-ph.CO, (2013), arXiv:1304.3706
E. Figueroa-Feliciano's presentation at Light Dark Matter 2013.

cdms.berkeley.edu/

Journal reference: arXiv

© 2013 Phys.org

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Researchers open door to advanced molecular electronic metrology

Christina Hacker characterizes the individual monolayers prior to flip-chip lamination using a Fourier transform infrared spectrometer.

(Phys.org) —Continued advancements using a NIST-developed molecular-level fabrication technique are leading to new discoveries in the metrology for molecular electronics by advancing large-area (µm to mm range) connections to molecules (nm range). Researchers in the PML's Semiconductor and Dimensional Metrology Division have been able to build a simple bilayer molecular circuit, combining separately formed monolayers of organic materials on silicon and gold surfaces respectively to create a fully characterized molecular level device. Further, they were able to place copper atoms at specific locations within the bilayer device to test their influence on its electronic properties.

Incorporating molecular-based materials and elements into electronics has been of great interest because of the potential applications such as memory-based devices, organic thin-film transistors, and spintronic devices. The incorporation of organic monolayers with silicon is advantageous from a technological manufacturing point of view because of the extensive manufacturing infrastructure that would allow for rapid integration with Si-based CMOS technologies. Moreover, the molecular layer can be used to engineer and alter the surface energetics of the semiconductor.

"We're trying to miniaturize electronics," explains Christina Hacker, leader of the Nanoelectronic Device Metrology Project. "We can't really shrink existing transistors too much more. So, we're reaching the scale where we're looking for different ways of doing computing. With molecular electronics, you're looking at either a single monolayer or a single molecule and trying to understand how that molecule behaves in an electronic fashion."

"Organic molecules can actually serve different functions that a metal can't," Hacker continues. "A metal is going to be a conductor. A metal-oxide is going to be an insulator. A molecule could be something different. It could act as a switch. It could also change the work function of the system as a whole. You could have different properties when you put that molecule in there that couldn't have with just a metal or just an oxide."

Creating a test structure to enable measurements of organic molecular-level devices, however, has been a challenge. Previously, PML researchers solved the metrology bottleneck of how to put electrodes onto molecular layers without damage with a technique they invented and termed flip-chip lamination (FCL).1

"One of the challenges with molecular electronics is actually making the contact to the molecules," Hacker explains. "Molecules are very sensitive. You can think of molecules as kind of like lettuce—if you put hot metal on lettuce, bad things happen."

Bilayer molecular circuit formed with (right) and without (left) copper atoms.

Using FCL, the ultrasmooth, large area electrodes and optimized molecular monolayers are formed separately and fully characterized prior to the fabrication of the solid-state molecular electronic test structure. This provides stable devices of known nm scale structure necessary for proper metrology of the electronic function. After each layer has been characterized, they are brought together like the world's smallest sandwich.

Recently, PML researchers have succeeded in taking this FCL technique a critical step forward by making large area solid-state molecular electronic test structures from molecular bilayers and incorporating electrochemically active metal ions.2

Enlarge

Sujitra Pookpanratana applies the organic monolayers onto the gold and silicon surfaces using thiol chemistry and photochemical grafting.

"Before, we'd been able to do it with one layer, but we hadn't been able to do it with two molecules," Hacker explains. The new work provides a first-of-its-kind holistic snapshot of the electronic properties of molecular monolayers, bilayers, and atomic scale metal-molecule hybrids.

Hacker and her staff created the bilayers by self-assembing organic monolayers onto ultrasmooth layers of gold by using thiol chemistry and then bonded them to molecular layers that were reacted onto n-type silicon. This process created a silicon/molecular bilayer/metal junction, chemically sandwiching a molecular bilayer between silicon and gold electrodes. Prior to junction formation, the monolayers were physically characterized by using polarized infrared absorption spectroscopy, X-ray photoelectron spectroscopy, and near-edge X-ray absorption fine structure spectroscopy, confirming the molecular quality and functional group termination.

"We started from two pristine surfaces, one being gold and one being silicon, and then made monolayers on them," Hacker describes. "Bringing them together, we made a very high quality bilayer junction. Then, we were able to make bilayer junctions with copper in the middle and look at the function of how that copper, which is an electrically active ion, affects the electronic properties of the molecular junction as a whole. It turns out that it didn't, which was a bit of a surprise. We expected that it would."

"We saw an electrochemical connection," Sujitra Pookpanratana, Hacker's colleague, elaborates, "but those effects didn't propagate into a difference in electronic measurements of the completed bilayer device." This uncovers the unique challenge in the field of molecular electronics: Materials don't necessarily behave as previous research would indicate once they are scaled down to the molecular level. "It does change the way of thinking for molecular electronics," Pookpanratana states. "Based on previous research we think it should go in one direction, but in the end it might not propagate into the electronic properties that we'd hoped for."

Surprises were also found in the devices' current, which remained at the same level after a certain length despite increased distance from the charge source. This, Hacker and Pookpanratana believe, is due to the current transitioning to a different electron transport regime. So, despite huge advancements in the field, there is still much to learn about predicting the electrical properties.

"One of the fundamental metrology questions we have is, if we know this structure exists – that is, we know we have a bilayer and we know it's attached to electrodes in this fashion – if we were to try to predict what the electronic function would be, could we do it?" Hacker states. "Still, we are a long way away from doing that, because there are so many different things that really affect the electronic function."

Having expanded the utility of FCL to develop more complex molecular-level devices than ever before available, PML is paving the way for the future design and engineering of complex molecular electronic devices that will incorporate different molecules or materials for added device functionality and capabilities. These devices will help answer important metrology questions about electronic properties and continue to help advance the field.

More information: Coll, M. et al. Formation of Silicon-Based Molecular Electronic Structures Using Flip-Chip Lamination, Journal of the American Chemical Society, Vol. 131, pp. 12451-12457 (11-Aug- 2009).

Pookpanratana, S. et al. Electrical and Physical Characterization of Bilayer Carboxylic Acid Functionalized Molecular Layers, The Journal of Physical Chemistry C, Vol. 29, No. 6, pp. 2083-2091 (30-Jan-2013).

Journal reference: Journal of the American Chemical Society Journal of Physical Chemistry C

Provided by National Institute of Standards and Technology

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Researchers show stem cell fate depends on 'grip'

3D Traction Force Microscopy shows where and how hard this bone-like cell is pulling on the surrounding gel. Credit: Sudhir Khetan

The field of regenerative medicine holds great promise, propelled by greater understanding of how stem cells differentiate themselves into many of the body's different cell types. But clinical applications in the field have been slow to materialize, partially owing to difficulties in replicating the conditions these cells naturally experience.

A team of researchers from the University of Pennsylvania has generated new insight on how a stem cell's environment influences what type of cell a stem cell will become. They have shown that whether human mesenchymal stem cells turn into fat or bone cells depends partially on how well they can "grip" the material they are growing in.

The research was conducted by graduate student Sudhir Khetan and associate professor Jason Burdick, along with professor Christopher Chen, all of the School of Engineering and Applied Science's Department of Bioengineering. Others involved in the study include Murat Guvendiren, Wesley Legant and Daniel Cohen.

Their study was published in the journal Nature Materials.

Much research has been done on how stem cells grow on two-dimensional substrates, but comparatively little work has been done in three dimensions. Three-dimensional environments, or matrices, for stems cells have mostly been treated as simple scaffolding, rather than as a signal that influences the cells' development.

Burdick and his colleagues were interested in how these three-dimensional matrices impact mechanotransduction, which is how the cell takes information about its physical environment and translates that to chemical signaling.

"We're trying to understand how material signals can dictate stem cell response," Burdick said. "Rather than considering the material as an inert structure, it's really guiding stem cell fate and differentiation—what kind of cells they will turn into."

The mesenchymal stem cells the researchers studied are found in bone marrow and can develop into several cell types: osteoblasts, which are found in bone; chondrocytes, which are found in cartilage; and adipocytes, which are found in fat.

The researchers cultured them in water-swollen polymer networks known as hydrogels, which share some similarities with the environments stem cells naturally grow in. These materials are generally soft and flexible—contact lenses, for example, are a type of hydrogel—but can vary in density and stiffness depending on the type and quantity of the bonds between the polymers. In this case, the researchers used covalently cross-linked gels, which contain irreversible chemical bonds.

When seeded on top of two-dimensional covalently cross-linked gels, mesenchymal stem cells spread and pulled on the material differently depending on how stiff it was. Critically, the mechanics guide cell fate, or the type of cells they differentiate it into. A softer environment would produce more fat-like cells and a stiffer environment, where the cells can pull on the gel harder, would produce more bone-like cells.

However, when the researchers put mesenchymal stem cells inside three-dimensional hydrogels of varying stiffness, they didn't see these kinds of changes.

"In most covalently cross-linked gels, the cells can't spread into the matrix because they can't degrade the bonds—they all become fat cells," Burdick said. "That tells us that in 3D covalent gels the cells don't translate the mechanical information the same way they do in a 2D system."

To test this, the researchers changed the chemistry of their hydrogels so that the polymer chains were connected by a peptide that the cells could naturally degrade. They hypothesized that, as the cells spread, they would be able to get a better grip on their surrounding environment and thus be more likely to turn into bone-like cells.

In order to determine how well the cells were pulling on their environment, the researchers used a technique developed by Chen's lab called 3D traction force microscopy. This technique involves seeding the gel with microscopic beads, then tracking their location before and after a cell is removed.

"Because the gel is elastic and will relax back into its original position when you remove the cells," Chen said, "you can quantify how much the cells are pulling on the gel based on how much and which way it springs back after the cell is removed."

The results showed that the stem cells' differentiation into bone-like cells was aided by their ability to better anchor themselves into the growth environment.

"With our original experiment, we observed that the cells essentially didn't pull on the gel. They adhered to it and were viable, but we did not see bead displacement. They couldn't get a grip," Burdick said. "When we put the cells into a gel where they could degrade the bonds, we saw them spread into the matrix and deform it, displacing the beads."

As an additional test, the researchers synthesized another hydrogel. This one had the same covalent bonds that the stem cells could naturally degrade and spread through but also another type of bond that could form when exposed to light. They let the stem cells spread as before, but at the point the cells would begin to differentiate—about a week after they were first encapsulated—the researchers further "set" the gel by exposing it to light, forming new bonds the cells couldn't degrade.

"When we introduced these cross-links so they could no longer degrade the matrix, we saw an increase toward fat-like cells, even after letting them spread," Burdick said. "This further supports the idea that continuous degradation is needed for the cells to sense the material properties of their environment and transduce that into differentiation signals."

Burdick and his colleagues see these results as helping develop a better fundamental understanding of how to engineer tissues using stem cells.

"This is a model system for showing how the microenvironment can influence the fate of the cells," Burdick said.

More information: www.nature.com/nmat/journal/vaop/ncurrent/full/nmat3586.html

Journal reference: Nature Materials

Provided by University of Pennsylvania

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