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News Article | April 28, 2017
Site: www.eurekalert.org

BAR HARBOR, MAINE -- The MDI Biological Laboratory has announced that Sandra Rieger, Ph.D., has been awarded a highly competitive grant from the National Cancer Institute, an institute of the National Institutes of Health (NIH), to study the molecular mechanisms underlying chemotherapy-induced peripheral neuropathy, a side effect of cancer chemotherapy causing symptoms such as pain, tingling, temperature sensitivity and numbness in the extremities. The grant will allow Rieger to continue her research on peripheral neuropathy caused by Taxol (paclitaxel), a chemotherapy agent used in the treatment of ovarian, breast, lung, pancreatic and other cancers. About 60 to 70 percent of patients receiving Taxol experience peripheral neuropathy. In severe cases, patients may be forced to reduce or curtail treatment, which deprives them of cancer treatment and may decrease chances of survival. Rieger's research also has potential applications in the treatment of peripheral neuropathies caused by other conditions, including diabetes, aging and antibiotic treatment. Neuropathy is a general term for peripheral nerve degeneration, which is believed to affect at least 20 million Americans, with some estimates as high as 40 million. No treatments are currently available, other than for symptoms such as pain. "This grant is an acknowledgement of the importance of Dr. Rieger's research," said Kevin Strange, Ph.D. president of the MDI Biological Laboratory. "Peripheral neuropathy is much more common than generally believed. Her research on the underlying molecular mechanisms of nerve regeneration opens the door to the development of new drug therapies to help the millions who suffer from this potentially debilitating condition." The five-year grant, which takes effect July 1, totals approximately $1.8 million over five years, with additional funding for facilities and administrative costs. The grant will fund Rieger's continuing research in the zebrafish and research with neurologist Nathan P. Staff, M.D., Ph.D. on skin samples from breast cancer patients undergoing Taxol treatment at the Mayo Clinic in Rochester, Minn. The research at the Mayo Clinic, which will take place over the first two years of the grant, will seek to determine if the same mechanisms that underlie Taxol-induced peripheral neuropathy in zebrafish are also linked to the condition in humans. "The research with Dr. Staff at the Mayo Clinic is the first step to developing a drug therapy to treat peripheral neuropathy in humans," Rieger said. "That's my major interest -- finding a therapy to cure this condition." The grant will allow Rieger to build on earlier research showing that Taxol-induced peripheral neuropathy is linked to the increased activity of a matrix-degrading enzyme, matrix metalloproteinase-13, or MMP-13, in the skin. The increase in MMP-13 activity leads to decreased skin resistance and the degeneration of sensory nerve endings, which in turn causes the symptoms of peripheral neuropathy. Rieger has also discovered two compounds that prevent or reverse chemotherapy-induced peripheral neuropathy in zebrafish by inhibiting the activity of MMP-13. The compounds are the subject of a provisional patent filed last year by the MDI Biological Laboratory for their use in the treatment of chemotherapy- and diabetes-induced peripheral neuropathy. The compounds have yet to be tested in humans. The ability offered by the grant to gain a deeper understanding of the mechanisms underlying peripheral neuropathy raises the prospect that other MMP-inhibiting drugs can be developed to treat peripheral neuropathy. Our scientists are pioneering new approaches to regenerative medicine focused on drugs that activate our natural ability to heal, and that slow age-related degenerative changes. Our unique approach has identified new drugs with the potential to treat major diseases, demonstrating that regeneration could be as simple as taking a pill. As innovators and entrepreneurs, we also teach what we know. Our Center for Science Entrepreneurship prepares students for 21st century careers and equips entrepreneurs with the skills and resources to turn great ideas into successful products. For more information, please visit mdibl.org.


Schafer M.,University of Lapland | Zwinger T.,Center for Science Ltd. | Zwinger T.,Beijing Normal University | Christoffersen P.,University of Cambridge | And 9 more authors.
Cryosphere | Year: 2012

The dynamics of Vestfonna ice cap (Svalbard) are dominated by fast-flowing outlet glaciers. Its mass balance is poorly known and affected dynamically by these fast-flowing outlet glaciers. Hence, it is a challenging target for ice flow modeling. Precise knowledge of the basal conditions and implementation of a good sliding law are crucial for the modeling of this ice cap. Here we use the full-Stokes finite element code Elmer/Ice to model the 3-D flow over the whole ice cap. We use a Robin inverse method to infer the basal friction from the surface velocities observed in 1995. Our results illustrate the importance of the basal friction parameter in reproducing observed velocity fields. We also show the importance of having variable basal friction as given by the inverse method to reproduce the velocity fields of each outlet glacier-a simple parametrization of basal friction cannot give realistic velocities in a forward model. We study the robustness and sensitivity of this method with respect to different parameters (mesh characteristics, ice temperature, errors in topographic and velocity data). The uncertainty in the observational parameters and input data proved to be sufficiently small as not to adversely affect the fidelity of the model. ©2012 Author(s).


Schafer M.,University of Lapland | Schafer M.,Finnish Meteorological Institute | Moller M.,RWTH Aachen | Zwinger T.,Center for Science Ltd | And 2 more authors.
Journal of Glaciology | Year: 2015

Future projections of the evolution of ice caps as well as ice sheets and consequent sealevel rise face several methodological challenges, one being the two-way coupling between ice flow and mass-balance models. Full two-way coupling between mass-balance models - or, in a wider scope, climate models - and ice flow models has rarely been implemented due to substantial technical challenges. Here we examine some coupling effects for the Vestfonna ice cap, Nordaustlandet, Svalbard, by analysing the impacts of different coupling intervals on mass-balance and sea-level rise projections. By comparing coupled to traditionally deployed uncoupled strategies, we prove that neglecting the topographic feedbacks in the coupling leads to underestimations of 10-20% in sea-level rise projections on century timescales in our model. As imposed climate scenarios increasingly change mass balance, uncertainties in the unknown evolution of the fast-flowing outlet glaciers decrease in importance due to their deceleration and reduced mass flux as they thin and retreat from the coast. Parameterizing mass-balance adjustment for changes in topography using lapse rates as a cost-effective alternative to full coupling produces satisfactory results for modest climate change scenarios. We introduce a method to estimate the error of the presented partially coupled model with respect to as yet unperformed two-way fully coupled results.


Cook S.,University of Swansea | Zwinger T.,Center for Science Ltd | Rutt I.C.,University of Swansea | O'Neel S.,U.S. Geological Survey | Murray T.,University of Swansea
Annals of Glaciology | Year: 2012

A new implementation of a calving model, using the finite-element code Elmer, is presented and used to investigate the effects of surface water within crevasses on calving rate. For this work, we use a two-dimensional flowline model of Columbia Glacier, Alaska. Using the glacier's 1993 geometry as a starting point, we apply a crevasse-depth calving criterion, which predicts calving at the location where surface crevasses cross the waterline. Crevasse depth is calculated using the Nye formulation.We find that calving rate in such a regime is highly dependent on the depth of water in surface crevasses, with a change of just a few metres in water depth causing the glacier to change from advancing at a rate of 3.5kma-1 to retreating at a rate of 1.9km a-1. These results highlight the potential for atmospheric warming and surface meltwater to trigger glacier retreat, but also the difficulty of modelling calving rates, as crevasse water depth is difficult to determine either by measurement in situ or surface massbalance modelling. © 2012 Publishing Technology.


Corpas M.,Genome Analysis Center | Jimenez R.C.,ELIXIR | Bongcam-Rudloff E.,Swedish University of Agricultural Sciences | Budd A.,European Molecular Biology Laboratory | And 16 more authors.
Bioinformatics | Year: 2015

Summary: Rapid technological advances have led to an explosion of biomedical data in recent years. The pace of change has inspired new collaborative approaches for sharing materials and resources to help train life scientists both in the use of cutting-edge bioinformatics tools and databases and in how to analyse and interpret large datasets. A prototype platform for sharing such training resources was recently created by the Bioinformatics Training Network (BTN). Building on this work, we have created a centralized portal for sharing training materials and courses, including a catalogue of trainers and course organizers, and an announcement service for training events. For course organizers, the portal provides opportunities to promote their training events; for trainers, the portal offers an environment for sharing materials, for gaining visibility for their work and promoting their skills; for trainees, it offers a convenient one-stop shop for finding suitable training resources and identifying relevant training events and activities locally and worldwide. Availability and implementation: http://mygoblet.org/training-portal Contact: © 2014 The Author. Published by Oxford University Press.


De Fleurian B.,French National Center for Scientific Research | De Fleurian B.,University Grenoble Alpes | Gagliardini O.,French National Center for Scientific Research | Gagliardini O.,University Grenoble Alpes | And 8 more authors.
Cryosphere | Year: 2014

The flow of glaciers and ice streams is strongly influenced by the presence of water at the interface between ice and bed. In this paper, a hydrological model evaluating the subglacial water pressure is developed with the final aim of estimating the sliding velocities of glaciers. The global model fully couples the subglacial hydrology and the ice dynamics through a water-dependent friction law. The hydrological part of the model follows a double continuum approach which relies on the use of porous layers to compute water heads in inefficient and efficient drainage systems. This method has the advantage of a relatively low computational cost that would allow its application to large ice bodies such as Greenland or Antarctica ice streams. The hydrological model has been implemented in the finite element code Elmer/Ice, which simultaneously computes the ice flow. Herein, we present an application to the Haut Glacier d'Arolla for which we have a large number of observations, making it well suited to the purpose of validating both the hydrology and ice flow model components. The selection of hydrological, under-determined parameters from a wide range of values is guided by comparison of the model results with available glacier observations. Once this selection has been performed, the coupling between subglacial hydrology and ice dynamics is undertaken throughout a melt season. Results indicate that this new modelling approach for subglacial hydrology is able to reproduce the broad temporal and spatial patterns of the observed subglacial hydrological system. Furthermore, the coupling with the ice dynamics shows good agreement with the observed spring speed-up. © Author(s) 2014.


Lehtola J.,University of Helsinki | Manninen P.,Center for Science Ltd. | Hakala M.,University of Helsinki | Hamalainen K.,University of Helsinki
Journal of Chemical Physics | Year: 2012

In the current work we apply the completeness-optimization paradigm [P. Manninen and J. Vaara, J. Comput. Chem. 27, 434 (2006)] to investigate the basis set convergence of the moments of the ground-state electron momentum density at the self-consistent field level of theory. We present a black-box completeness-optimization algorithm that can be used to generate computationally efficient basis sets for computing any property at any level of theory. We show that the complete basis set (CBS) limit of the moments of the electron momentum density can be reached more cost effectively using completeness-optimized basis sets than using conventional, energy-optimized Gaussian basis sets. By using the established CBS limits, we generate a series of smaller basis sets which can be used to systematically approach the CBS and to perform calculations on larger, experimentally interesting systems. © 2012 American Institute of Physics.


Gagliardini O.,Joseph Fourier University | Durand G.,Joseph Fourier University | Zwinger T.,Center for Science Ltd. | Hindmarsh R.C.A.,Natural Environment Research Council | Le Meur E.,Joseph Fourier University
Geophysical Research Letters | Year: 2010

Increase in ice-shelf melting is generally presumed to have triggered recent coastal ice-sheet thinning. Using a full-Stokes finite element model which includes a proper description of the grounding line dynamics, we investigate the impact of melting below ice shelves. We argue that the influence of ice-shelf melting on the ice-sheet dynamics induces a complex response, and the first naive view that melting inevitably leads to loss of grounded ice is erroneous. We demonstrate that melting acts directly on the magnitude of the buttressing force by modifying both the area experiencing lateral resistance and the ice-shelf velocity, indicating that the decrease of back stress imposed by the ice-shelf is the prevailing cause of inland dynamical thinning. We further show that feedback from melting and buttressing forces can lead to nontrivial results, as an increase in the average melt rate may lead to inland ice thickening and grounding line advance. © 2010 by the American Geophysical Union.


Durand G.,CNRS Laboratory for Glaciology and Environmental Geophysics | Gagliardini O.,CNRS Laboratory for Glaciology and Environmental Geophysics | Gagliardini O.,Institut Universitaire de France | Favier L.,CNRS Laboratory for Glaciology and Environmental Geophysics | And 2 more authors.
Geophysical Research Letters | Year: 2011

Recent glaciological surveys have revealed a significant increase of ice discharge from polar ice caps into the ocean. In parallel, ice flow models have been greatly improved to better reproduce current changes and forecast the future behavior of ice sheets. For these models, surface topography and bedrock elevation are crucial input parameters that largely control the dynamics and the ensuing overall mass balance of the ice sheet. For obvious reasons of inaccessibility, only sparse and uneven bedrock elevation data is available. This raw data is processed to produce Digital Elevation Models (DEMs) on a regular 5 km grid. These DEMs are used to constrain the basal boundary conditions of all ice sheet models. Here, by using a full-Stokes finite element code, we examine the sensitivity of an ice flow model to the accuracy of the bedrock description. In the context of short-term ice sheet forecast, we show that in coastal regions, the bedrock elevation should be known at a resolution of the order of one kilometer. Conversely, a crude description of the bedrock in the interior of the continent does not affect modeling of the ice outflow into the ocean. These findings clearly indicate that coastal regions should be prioritized during future geophysical surveys. They also indicate that a paradigm shift is required to change the current design of DEMs describing the bedrock below the ice sheets: they must give users the opportunity to incorporate high-resolution bedrock elevation data in regions of interest. Copyright 2011 by the American Geophysical Union.


Malinen M.,Center for Science Ltd.
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2012

Computational methods for solving coupled systems of partial differential equations can generally be divided into segregated and monolithic solvers. Monolithic solvers are often considered to be computationally expensive, and it is believed that their rewards are realized only in situations where segregated solvers have convergence problems due to the strong coupling. We give opposite empirical evidence by demonstrating that cost-effective monolithic solvers may be derived from using segregated solvers as preconditioners in the iterative solution of monolithic systems. © 2012 Springer-Verlag.

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