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  • richardmitnick 7:07 am on September 23, 2014 Permalink | Reply
    Tags: , , Cornell University   

    From Cornell: “Gene linked to development of skin cancer in mice” 

    Cornell Bloc

    Cornell University

    Sept. 22, 2014
    Merry R. Buckley

    New research on an enzyme linked to cancer development shows that 37 percent of mice that produce excessive quantities of the enzyme developed skin tumors within four to 12 months of birth, and many of these growths progressed to highly invasive squamous cell carcinoma, a common form of skin cancer.

    This finding, published online Sept. 11 in the journal Cancer Research, provides the first genetic link between the activity of the enzyme, called PAD2, and cancer progression, and provides important supporting evidence for further studies aimed at using PAD2 inhibitors to block carcinoma progression in humans.

    Lead author Scott Coonrod, the Judy Wilpon Associate Professor of Cancer Biology at the Baker Institute for Animal Health in Cornell’s College of Veterinary Medicine, has studied links between PAD2 and other PAD (peptidylarginine deiminase) enzymes and cancer for some time. Those prior studies suggested that PAD2 plays an important role in regulating genes during cancer progression; however, a direct link between PADs and tumor progression had not yet been proven. Other work from the lab suggested that PAD2 is found at high concentrations in several tumor types, but it was not known whether these elevated levels of the enzyme were causing cancer or merely a consequence of tumor progression.

    two
    Ph.D. student and study co-author Sachi Horibata and Scott Coonrod, associate professor at the Baker Institute for Animal Health, work on research that linked an enzyme to cancer development.

    To directly test for links between PAD2 and cancer, the researchers engineered mice to overexpress PAD2 and then looked to see whether these mice developed cancer.

    Coonrod thinks that the reason PAD2 overproduction in the skin may cause cancer is likely due to its ability to promote inflammation.

    “Inflammation has long been known to play an important role in the development of many types of cancer,” he says. “Recent studies provide strong evidence that inflammation represents one of the 10 hallmarks of cancer.“It’s becoming clear that the activity of PAD enzymes seems to be low in most normal tissues, but becomes elevated in a whole range of inflammatory diseases – like rheumatoid arthritis, colitis and lupus. PAD activity is very high in the affected tissues and seems to be driving a lot of the inflammatory conditions that cause these diseases.”

    To test whether PAD2 might be promoting inflammation, Coonrod and his colleagues looked for classical markers of inflammation in the growths and found that a number of these markers were significantly elevated in the mouse tumors. To further test their hypothesis, they overexpressed PAD2 in human cell lines to better understand how the enzyme might behave in human tissue. They found that, similar to the mouse studies, PAD2 overproduction made these human cells more invasive and also enhanced inflammatory marker expression.

    Together, these studies suggest that increased PAD activity in human skin, and potentially other tissues, promotes an inflammatory environment that is favorable for cancer development, says Coonrod. His longtime collaborator, Paul Thompson at the University of Massachusetts Memorial Medical Center, has developed a range of new PAD inhibitors, and the team is now testing whether these compounds might suppress carcinoma progression in mouse models of both skin and mammary glands.

    Two of Coonrod’s co-authors on the paper, PAD2 Overexpression in Transgenic Mice Promotes Spontaneous Skin Neoplasia, are postdoctoral associate John McElwee, Ph.D. ’13, and graduate student Sunish Mohanan, DVM, who carried out some of the research for their thesis projects in Coonrod’s lab.

    See the full article here.

    Once called “the first American university” by educational historian Frederick Rudolph, Cornell University represents a distinctive mix of eminent scholarship and democratic ideals. Adding practical subjects to the classics and admitting qualified students regardless of nationality, race, social circumstance, gender, or religion was quite a departure when Cornell was founded in 1865.

    Today’s Cornell reflects this heritage of egalitarian excellence. It is home to the nation’s first colleges devoted to hotel administration, industrial and labor relations, and veterinary medicine. Both a private university and the land-grant institution of New York State, Cornell University is the most educationally diverse member of the Ivy League.

    On the Ithaca campus alone nearly 20,000 students representing every state and 120 countries choose from among 4,000 courses in 11 undergraduate, graduate, and professional schools. Many undergraduates participate in a wide range of interdisciplinary programs, play meaningful roles in original research, and study in Cornell programs in Washington, New York City, and the world over.

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  • richardmitnick 11:58 am on April 22, 2014 Permalink | Reply
    Tags: , CHESS Imaging, Cornell University   

    From Cornell: “Extraordinary Maia detector rocks x-ray imaging at CHESS” 

    Cornell Bloc

    Cornell University

    04/04/2014
    Arthur Woll, CHESS, Cornell University

    Over the course of two weeks this past March, scientists from three laboratories commissioned CHESS’s most recent purchase, a 384-sensor, energy-dispersive detector known as “Maia“. The large number of individual sensors enables much higher count-rates than prior generations of detectors with the same functionality. One use of this combination of energy resolution and high count rate is to map the elemental composition of objects with breathtaking resolution in a much shorter time than was previously possible. Figure 1 represents what the combination of a synchrotron source and this new detector can do. The image is a false-color representation of potassium, calcium, and zinc concentrations in a dried, pressed iris flower. It is striking for both its beauty and the precise information it contains.

    maia
    Brookhaven Maia Development Team

    fig 1
    Figure 1: False color representation of elemental distributions of potassium (red), calcium (green) and zinc (blue) in a pressed, dried iris flower, obtained with scanning x-ray fluorescence microscopy. The image has 1920×1320, 0.05 × 0.05 mm2 pixels, with a dwell time of 5 milliseconds/pixel and total scan time of 3.5 hours. (Sample prepared by Lucy E. Woll.)

    The Maia detector is an extremely new, award-winning technology developed by a collaboration between Australia’s national science agency, CSIRO, and Brookhaven National Laboratory (BNL) in Upton, NY . Two of the leaders of this collaboration, Robin Kirkham of CSIRO and Pete Siddons of BNL, along with BNL engineer Anthony Kuczewski, traveled to CHESS to join the commissioning run in March, which took place at the G3 station at CHESS. CHESS Staff scientist Arthur Woll led the project, with critical local assistance from a small army of staff and students.

    An important application of the Maia detector is scanning x-ray fluorescence microscopy, a well-established technique for obtaining the elemental composition of virtually any material. It works by scanning a sample across a small incident x-ray beam, and detecting secondary x-rays that are re-emitted by atoms at each position that the x-ray beam strikes. The resolution of the scan is determined by the size of the incident beam. For the short term, CHESS will target spatial resolutions ranging from 0.01 to 0.2 mm. For this run, the beam size was 0.05 × 0.05 mm2, with an incident energy of 10.1 keV. Future source and optics upgrades will allow CHESS to employ this technique well below 0.001 mm. The wavelength and intensity distribution of the photons re-emitted from the sample identify which elements are present at each position, but only if there are enough photons – typically thousands – to create a statistically meaningful measurement. The Maia detector allows these thousands of photons to be collected in a short time – about 1 millisecond – enabling faster scan speed.

    The image in Figure 1 was collected using this technique. After several days of set up, testing, training, and characterization, the Australian and BNL teams packed up early on March 6th, leaving the CHESS team some time to put the detector through its paces. Among the first samples to be scanned was a pressed iris flower provided by Lucy Woll (Arthur’s six-year old daughter). The scan started on March 5th at 11:45 PM, and after a brief analysis the next morning, images like Figure 1 began to appear.

    With this image in hand, Arthur and several CHESS staff members sought out other interesting objects to scan. The second week of commissioning, from March 12th-17th, was devoted to performing scans on the wide variety of samples that resulted from this very brief search. Below are some of the images resulting from these scans.

    Zak Brown, a CHESS operator and detector expert, contacted friend and entomologist Tarryn Goble, who brought several Asian longhorned beetles. This beetle species is invasive to North America and highly destructive. Tarryn, along with other members of Ann Hajek’s laboratory at Cornell, is working to develop a fungus, Metarhizium brunneum F52, as a biological control agent against this species. The results of scans of two pairs of beetle wings as well as the legs and antennae of beetles at differing stages of infection are shown in Figures 2 and 3. The presence of extra, concentrated forms of calcium in the left-most antennae and legs most likely result from the fungus. But both the presence of zinc in the uninfected beetle legs and the distribution of potassium in the wings were a surprise, and stimulate new questions about insect physiology.

    fig 2
    Figure 2: False color representation of the concentrations of elemental distributions within wings from two Asian longhorned beetles. Potassium and zinc concentrations are represented by red and blue, while green represents Compton scattering, which is particularly sensitive to low Z elements, such as carbon. (Sample prepared by Tarryn Goble, Ph.D., post-doctoral associate in the laboratory of Prof. Ann Hajek, in the Cornell Department of Entomology.)

    fig 3
    Figure 3: False color representation of concentrations of potassium (red), calcium (green) and zinc (blue) within legs and antennae of three Asian longhorned beetles. (Sample prepared by Tarryn Goble, Ph.D., post-doctoral associate in the laboratory of Prof. Ann Hajek, in the Cornell Department of Entomology.)

    CHESS outreach coordinator Lora Hine contacted her colleague Anne Rosenberg at the Lab of Ornithology, who provided a loose breast feather of a Great Blue Heron from the Cornell University Museum of Vertebrates’ teaching collection. Such scans show distribution patterns of elements in birds’ feathers, (e.g. Figure 4), that may reveal aspects of the birds’ chemical environments, such as exposure to pesticides.

    fig 4
    Figure 4: False color representation of concentrations of sulfur (red), calcium (green) and zinc (blue) within a breast feather of a Great Blue Heron. (Sample prepared by Anne Rosenberg, Cornell Lab of Ornithology.)

    The explicit scientific objective of this effort was to test the instrument, demonstrate its capability, and communicate that capability to potential user-communities. In essence, the goal was to produce eye-catching images to share right away, rather than new science. The surprise was how novel these images appeared to experts in the relevant fields of study.

    Arthur sent the iris image from Figure 1 to Karl Niklas, the Liberty Hyde Bailey Professor of Botany in the Cornell Department of Plant Biology, who responded enthusiastically and provided a variety of samples to measure. Two unassuming fern leaflets from the Department’s large collection yielded some of the most interesting data of the run, represented in Figure 5. Niklas comments that elemental compositions of plants are traditionally visualized at the scale of individual tissues or even cells. Being able to visualize this composition quantitatively and at “the whole organ level and even the level of an entire plant” is extremely useful, and may provide new understanding of “where and to what extent elements occur in leaves, stems, roots, and reproductive organs.”

    fig 5

    fig 5a
    Figure 5: The upper image is a false color representation of concentrations of potassium (red), calcium (green) and manganese (blue) within younger (top) and older (bottom) leaflets taken from a single fern leaf of the cinnamon fern (Osmunda cinnamomea). Both samples exhibit concentrated regions of calcium that are well correlated with leaflet veins. They also exhibit manganese-rich regions located preferentially near the leaflets’ outer borders, especially in the right-hand region of the younger leaflet. An enlarged view of this region is shown in the lower image, in which Compton scattering is exchanged for calcium for the green channel. A high degree of correlation between the Compton scattering and potassium distribution leads to an overall yellow hue. But Compton scattering also emphasizes the leaflet structure, from which it can be seen that the manganese regions coincide with the leaflet veins. (Sample supplied by Karl Niklas, professor of botany, Cornell Department of Plant Biology.)

    Based upon the capabilities of the Maia and interest of scientists across many disciplines, CHESS anticipates a substantial demand for this instrument. The next commissioning phase will occur in June, and general user access is planned for the Fall of 2014. To facilitate the process, CHESS plans to organize a tutorial workshop to introduce users to both the equipment and to the analysis software. Although users can certainly take their data home with them, the shear data volume – a single scan can easily exceed 100 GB – may present practical difficulties for many users. As a result, CHESS expects many users to perform data analyses remotely using the CLASSE compute cluster. This cluster is a multi-node compute farm maintained by the IT group with a very large, expandable storage array. Off-site access to the software has already been tested successfully.

    Further details about scheduling and availability of the Maia, and the tutorial workshop planned for this Fall, will be announced early this summer via the CHESS electronic newsletter and web site.

    See the full article here.

    Once called “the first American university” by educational historian Frederick Rudolph, Cornell University represents a distinctive mix of eminent scholarship and democratic ideals. Adding practical subjects to the classics and admitting qualified students regardless of nationality, race, social circumstance, gender, or religion was quite a departure when Cornell was founded in 1865.

    Today’s Cornell reflects this heritage of egalitarian excellence. It is home to the nation’s first colleges devoted to hotel administration, industrial and labor relations, and veterinary medicine. Both a private university and the land-grant institution of New York State, Cornell University is the most educationally diverse member of the Ivy League.

    On the Ithaca campus alone nearly 20,000 students representing every state and 120 countries choose from among 4,000 courses in 11 undergraduate, graduate, and professional schools. Many undergraduates participate in a wide range of interdisciplinary programs, play meaningful roles in original research, and study in Cornell programs in Washington, New York City, and the world over.


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  • richardmitnick 2:35 pm on April 17, 2014 Permalink | Reply
    Tags: , Cornell University, ,   

    From Cornell: “Tiny tool measures heat at the nanoscale” 

    Cornell Bloc

    Cornell University

    Feb. 26, 2014
    Story Contacts
    Cornell Chronicle

    Anne Ju

    607- 255-9735

    amj8@cornell.edu
    Media Contact

    Syl Kacapyr

    607-255-7701

    vpk6@cornell.edu

    How heat flows at the nanoscale can be very different than at larger scales. Understanding how surfaces affect the transport of the fundamental units of heat, called phonons, could impact everything from thermoelectric materials to microelectronic cooling devices.

    heat
    Design of the spectrometer to probe phonon transmission through silicon nanosheet arrays.

    Cornell researchers have developed a new way to precisely measure the extremely subtle movement of heat in nanostructures. Recently published online in Nano Letters and highlighted in Physics Today, the study features the researchers’ phonon spectrometer, whose measurements are 10 times sharper than standard methods. This boosted sensitivity has uncovered never-before-seen effects of phonon transport.

    The scientists used the new instrument to directly measure the surface scattering of phonons in silicon nanosheets. They made nanosheets only 100 nanometers wide, which is 1,000 times thinner than a human hair, using special tools at the Cornell NanoScale Science and Technology Facility (CNF) – a key component in the success of their project, said senior author Richard Robinson, assistant professor of materials science and engineering.

    The scattering of phonons on surfaces influences how well heat can flow through a structure. Similar to how light bounces off a lake, if a surface is smooth, phonons reflect off it, but when surfaces are rough phonons scatter in random directions, called diffuse scattering.

    “If waters are calm you see a reflection, but in choppy waters you see diffuse scattering,” said Jared Hertzberg, the paper’s first author, a former postdoctoral associate. “This diffuse scattering slows down the transmission of phonons. This decrease in phonon transport becomes particularly important in nanoscale materials where surfaces play a larger role in the heat flow.”

    Precise experimental techniques for probing phonon surface interactions – which depend on surface roughness and phonon wavelength – are lacking, Robinson said.

    “The fundamental science of heat flow is not as well understood in nanostructures as it is in bulk materials,” Robinson said. “If we can precisely understand how this process works, then we can begin to engineer heat flow at the nanoscale, which can lead to more efficient alternate energy applications, such as thermoelectrics, or advanced phononic heat-logic circuits. We’ve just scratched the surface, so to speak, of how heat behaves at the nanoscale. There’s so much more to learn, and so much more that can be done with these phonons now that we know how to spectroscopically measure them.”

    The researchers fabricated silicon nanosheets and measured phonon transmission rates with their spectrometer, and gauged the nanosheets’ surface roughness using atomic force microscopy. By comparing transmission rates with those predicted by theory, they could assess the validity of a 50-year-old theory called the Casimir-Ziman theory, which determines the probability of phonon scattering based on surface roughness and the phonon’s wavelength. While a perfectly smooth surface will reflect phonons perfectly, and a perfectly rough surface randomly scatters phonons in all directions, real surfaces fall somewhere in between.

    Yet the scientists found, in fact, that the total diffusive scattering occurred at much lower frequencies than had been previously predicted by the Casmimir-Ziman theory.

    Since diffusive scattering effectively lowers phonon transmission, high phonon scattering rates have implications for thermal conductivity in nanostructures: The actual thermal conductance will be much lower than predicted using the standard Casimir-Ziman theory.

    The paper, Direct Measurements of Surface Scattering in Si Nanosheets using a Microscale Phonon Spectrometer: Implications for Casimir-Limit Predicted by Ziman Theory, also co-authored by graduate students Mahmut Aksit and Obafemi Otelaja and Derek Stewart, a CNF senior research associate, was supported by the National Science Foundation and the Department of Energy, Office of Basic Energy Science.

    See the full article here.

    Once called “the first American university” by educational historian Frederick Rudolph, Cornell University represents a distinctive mix of eminent scholarship and democratic ideals. Adding practical subjects to the classics and admitting qualified students regardless of nationality, race, social circumstance, gender, or religion was quite a departure when Cornell was founded in 1865.

    Today’s Cornell reflects this heritage of egalitarian excellence. It is home to the nation’s first colleges devoted to hotel administration, industrial and labor relations, and veterinary medicine. Both a private university and the land-grant institution of New York State, Cornell University is the most educationally diverse member of the Ivy League.

    On the Ithaca campus alone nearly 20,000 students representing every state and 120 countries choose from among 4,000 courses in 11 undergraduate, graduate, and professional schools. Many undergraduates participate in a wide range of interdisciplinary programs, play meaningful roles in original research, and study in Cornell programs in Washington, New York City, and the world over.


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