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Recent studies carried out on Gallo-Roman site of Grand (France) illustrate the interest of using integrated methods in characterization of past occupation. Combination of excavations and surface surveying based on non-invasive techniques (such as geophysical surveys, LiDAR, aerial photography) allows a better identification of features. The cross-analysis of all data in GIS improves the global comprehension of the city framework and of its hydrogeological environment. Two case studies are presented: first we compare geophysical maps to speological observations for the detection of drainage galleries; then we show results of excavation and geophysical data in southern district of the agglomeration.


News Article | December 20, 2016
Site: www.eurekalert.org

The first mapping of carbon recovery in Amazonian forests following emissions released by commercial logging activities has been published in the journal eLife. The findings suggest that, in some of the forests disturbed by logging, surviving trees may be more reliable for storing carbon emissions than newly 'recruited' trees (juveniles that naturally regenerate in the logged forests). Amazonia, the largest tropical forest globally, holds 30% of the carbon stored in the earth's forests. Logging releases a significant amount of this carbon -- a key component of climate change - into the atmosphere, which is then recovered by surviving trees and new recruits. No investigations of post-logging carbon dynamics have previously been carried out Amazon-wide. Now, researchers from the Tropical managed Forest Observatory have created a unique modelling approach to estimate accurately how the different forest environments impact carbon changes in surviving and newly recruited trees during post-logging carbon recovery. "We studied long-term data from 133 permanent forest plots from 13 experimentally disturbed sites across Amazonia to model the changes in the aboveground carbon stocks in the first decades after logging," says first author and PhD student Camille Piponiot from UMR Écologie des Forêts de Guyane in Kourou, French Guiana. "We looked at regional differences in climate, soils, and initial aboveground biomass within the forests and linked these with the changes in carbon stocks caused by both newly recruited and surviving trees to predict the carbon recovery potential Amazon-wide." Their model reveals that carbon recovery is highest in the Guiana Shield in northeastern South America, and also in the western regions of the Amazonian forests, due mainly to the high carbon gain of trees that survived logging activity. In contrast, recovery is lower in the south. Piponiot explains: "Forests of the Guiana Shield are generally dense and grow on nutrient-poor soils, where wood productivity is constrained by competition for key nutrients. Short pulses of nutrients released from readily decomposed stems, twigs, and leaves of trees damaged and killed by logging explain the substantial but limited-duration increase in the growth of surviving trees. "In the southern Amazon, on the other hand, high seasonal water stress is the main constraint on carbon recovery. Stress-tolerant trees are generally poor competitors and this may explain the slower carbon accumulation in survivors in this region." Principal Investigator and senior author of the study, Bruno Hérault, from Cirad, adds: "As climate change continues, we can also expect to see increases in droughts and fires that will further disturb the Amazonian forests. Betting on newly recruited trees to store carbon in some of the forests disturbed by logging might be a risky gamble, as most of them are pioneer trees highly vulnerable to water stress. Trees that survive logging activities may therefore be more reliable in accumulating carbon in these disturbed forests." Hérault concludes: "While our study focuses mainly on carbon recovery after logging, our findings may also give useful clues to predict the forests' responses to carbon loss from fires and other events brought on by climate change, which is ironically caused in part by mass disturbance and deforestation." The paper 'Carbon recovery dynamics following disturbance by selective logging in Amazonian forests' can be freely accessed online at http://dx. . Contents, including text, figures, and data, are free to reuse under a CC BY 4.0 license. eLife is a unique collaboration between the funders and practitioners of research to improve the way important research is selected, presented, and shared. eLife publishes outstanding works across the life sciences and biomedicine -- from basic biological research to applied, translational, and clinical studies. All papers are selected by active scientists in the research community. Decisions and responses are agreed by the reviewers and consolidated by the Reviewing Editor into a single, clear set of instructions for authors, removing the need for laborious cycles of revision and allowing authors to publish their findings quickly. eLife is supported by the Howard Hughes Medical Institute, the Max Planck Society, and the Wellcome Trust. Learn more at elifesciences.org.


News Article | November 7, 2016
Site: www.sciencedaily.com

What would happen if a lengthy disruption befell the major mode of transportation of U.S. corn and soybeans? What ramifications would that have on U.S. producers and the national economy? How would that affect U.S. competitiveness in world grain markets? While hypothetical, these concerns are very real as the barge corridor in question contains a total of 36 locks and dams that have long since surpassed their designed lifespan. This corridor is the Upper Mississippi River and Illinois Waterway (UMR-IWW) that serves as the primary corridor for the movement of bulk commodities in the U.S. Corn and soybeans comprise nearly 90 percent of food and farm products on these waterways. Barge transportation is of great importance to U.S. agriculture because of its comparatively low transport costs as compared to overland modes. However, the inefficiencies of the locks are currently creating additional fuel and labor costs to barge operators, ultimately increasing transportation costs of grain and oilseeds, which means less profit for producers, higher costs for consumers and a handicap when competing in the world market. U.S. grain and oilseed producers have frequently expressed concerns about navigational inefficiencies of these aging and constrained waterways. Congress authorized the Navigation and Ecosystem Sustainability Program (NESP) in 2007 to address the capacity constraints on the most congested segments on these waterways; however, implementation of NESP has been delayed due to a lack of appropriations from Congress. USDA's Agricultural Marketing Service asked Edward Yu, associate professor at the University of Tennessee Institute of Agriculture Department of Agricultural and Resource Economics (AREC), to lead an economic analysis of the navigability on the UMR-IWW, which is crucial and timely to the U.S. agricultural sector and could help evaluate the need for NESP appropriations. Yu was selected due to his considerable experience and expertise in agricultural transportation economics. Professor Burton C. English and Jamey Menard, research leader, assisted Yu by estimating the economic impacts that would occur as a result of lock closures. "Resulting study recommendations stress how crucial it is to maintain the navigability of the UMR-IWW system for U.S. food and farm products and the risk of delaying infrastructure improvements," said Yu. The full report of this study can be found at http://tiny.utk.edu/9nhrs


News Article | November 2, 2016
Site: www.eurekalert.org

KNOXVILLE, Tenn. -- What would happen if a lengthy disruption befell the major mode of transportation of U.S. corn and soybeans? What ramifications would that have on U.S. producers and the national economy? How would that affect U.S. competitiveness in world grain markets? While hypothetical, these concerns are very real as the barge corridor in question contains a total of 36 locks and dams that have long since surpassed their designed lifespan. This corridor is the Upper Mississippi River and Illinois Waterway (UMR-IWW) that serves as the primary corridor for the movement of bulk commodities in the U.S. Corn and soybeans comprise nearly 90 percent of food and farm products on these waterways. Barge transportation is of great importance to U.S. agriculture because of its comparatively low transport costs as compared to overland modes. However, the inefficiencies of the locks are currently creating additional fuel and labor costs to barge operators, ultimately increasing transportation costs of grain and oilseeds, which means less profit for producers, higher costs for consumers and a handicap when competing in the world market. U.S. grain and oilseed producers have frequently expressed concerns about navigational inefficiencies of these aging and constrained waterways. Congress authorized the Navigation and Ecosystem Sustainability Program (NESP) in 2007 to address the capacity constraints on the most congested segments on these waterways; however, implementation of NESP has been delayed due to a lack of appropriations from Congress. USDA's Agricultural Marketing Service asked Edward Yu, associate professor at the University of Tennessee Institute of Agriculture Department of Agricultural and Resource Economics (AREC), to lead an economic analysis of the navigability on the UMR-IWW, which is crucial and timely to the U.S. agricultural sector and could help evaluate the need for NESP appropriations. Yu was selected due to his considerable experience and expertise in agricultural transportation economics. Professor Burton C. English and Jamey Menard, research leader, assisted Yu by estimating the economic impacts that would occur as a result of lock closures. "Resulting study recommendations stress how crucial it is to maintain the navigability of the UMR-IWW system for U.S. food and farm products and the risk of delaying infrastructure improvements," said Yu. The full report of this study can be found at http://tiny. Through its mission of research, teaching and extension, the University of Tennessee Institute of Agriculture touches lives and provides Real. Life. Solutions. ag.tennessee.edu


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Site: www.asminternational.org

After 12 years of serving as editor-in-chief of the Journal of Thermal Spray Technology (JTST), Dr. Christian Moreau, FASM, TS HoF, has transferred his responsibilities to Dr. Armelle Vardelle, FASM, announced Dr. Robert C. Tucker, Jr., FASM, TS HoF, chair of the Journal of Thermal Spray Technology Committee. Dr. Vardelle has been Lead Editor of JTST since 2013, and prior to that was an associate editor of the journal from 2006 through 2012. She will be succeeded as Lead Editor by Dr. André McDonald. Dr. Moreau became JTST editor in 2004, and led the journal through a period of extraordinary growth, in which the journal increased from a quarterly to six issues a year in 2007, then to eight issues in 2013. Building on the strong foundation laid by JTST Founding Editor Chris Berndt, FASM, TS HoF, Dr. Moreau enlarged the editorial staff to its current complement of five associate editors by identifying individuals who were both well-qualified technically and representative of the international readership of the journal. Furthermore, he created the position of "Lead Editor" to focus on special topical and event-related issues of the journal. Throughout Dr. Moreau's term as editor, the journal has continued to grow in number of submissions, quality, and articles published. Working closely with former JTST Committee chair Jockel Heberlein and Chris Berndt, Dr. Moreau brought into reality an annual special double issue containing invited and expanded papers originating from the International Thermal Spray Conference. He also led the journal through its transition into the publishing partnership with Springer, which has greatly increased the visibility and accessibility of the journal throughout the world. A professor at Concordia University (Canada Research Chair, Thermal Spray and Surface Engineering), Dr. Moreau will continue to offer the journal the benefit of his experience by remaining involved as a member of the JTST Committee. "On behalf of the ASM staff who have worked with Christian on JTST, I thank him for his unceasing insight and dedication," said Mary Anne Fleming, senior content developer of Journals at ASM International. "He has skillfully led the journal for the past 12 years, and now has ensured its future success by identifying a capable and qualified successor. We are delighted that Armelle has agreed to step into the editor position." Armelle Vardelle (D.Sc. 1987; Ph.D. 1979, M.Sc. 1975, B.Sc. 1973) is professor, University of Limoges, France. She is Co-Chair of the Department of Materials (Surface Treatments and Environment) at the Engineering School of the University of Limoges (Ecole Nationale Supérieure d'Ingénieurs de Limoges, ENSIL). She holds the title of Distinguished Professor and is involved in research in the laboratory of Sciences of Ceramics and Surface Treatment Processes, UMR-CNRS in the European Ceramic Center. Dr. Vardelle's current research interests are thermal spray and thermal plasma processes, modeling of plasma processes and torch operation, transport and chemical rate phenomena at high-temperature, thermal-sprayed coatings, and green manufacturing. Her teaching interests include thermal spraying, surface engineering, thermal sciences, transport phenomena in surface engineering processes, materials properties, industrial ecology, and lif cycle analysis. She has authored or coauthored more than 111 peer-reviewed scientific journal publications, 141 publications in International and National Conference Proceedings, and seven book chapters. She has presented 42 invited lectures at international conferences and 11 invited seminars at foreign universities. She has been a member of the Editorial Board of Plasma Chemistry and Plasma Processing since 2009. She became a Fellow of the International Plasma Chemistry Society in 2015 and a Fellow of ASM International in 2012. As newly-appointed editor-in-chief of JTST, Dr. Vardelle joins Dr. Tucker is announcing that Dr. André McDonald, University of Alberta, has been named Lead Editor of the journal. Dr. McDonald is chair of the ASM Thermal Spray Society Training Committee, Lead Editor of the 2015 International Thermal Spray Conference Proceedings, and has served as a guest co-editor of the journal. Currently an Associate Professor in the Department of Mechanical Engineering at the University of Alberta, Dr. McDonald received his BSME from the City College of New York (CCNY) in 2001, where he was the DuPont Mechanical Engineering Distinguished Graduate and won the Peggy Benline, Eliza Ford, and ALCOA awards. He was granted his MSME from that same institution in 2002. He received his Ph.D. from the University of Toronto in 2007, followed by a short post-doctoral fellowship at the Industrial Materials Institute - National Research Council Canada (IMI-NRC) in Boucherville, Québec. Dr. McDonald's current research includes the development of flame-sprayed coatings to provide wear and erosion resistance and to provide heating and structural health monitoring to polymer-based airfoil structures. In the area of cold-spraying, he has been working to develop a variety of metal matrix composite coatings with alumina or tungsten carbide as the reinforcing particle material. Since 2006, his work has resulted in 33 peer-reviewed journal articles, 39 conference articles, a textbook on the practical design of thermo-fluids systems, an industrial manual for thermal spraying for the oil and gas industry, 26 industrial reports, and several awards including the International Thermal Spray Conference and Exposition Best Paper Award, the Harold C. Simmons Best Paper Award from ILASS-Americas, the Composites Conference Best in Track Technical Paper Award for Manufacturing, and the Association of Professional Engineers and Geoscientists of Alberta's Early Accomplishment Award. Since becoming a professor, Dr. McDonald has trained 50 students, at both the graduate and undergraduate levels, in the areas of thermal spraying and/or heat transfer.


News Article | November 18, 2016
Site: www.prweb.com

Stop loss coverage is a key element to self-funded benefits plans, offering important protection against high-dollar claims. These policies contain complex and binding language, making it essential that you choose the right stop loss partner and understand the parameters of the agreement you are entering. To help HR professionals and business owners better understand stop loss solutions, United Benefit Advisors (UBA), in conjunction with UMR, will host a webinar — “The Right Stop Loss Solution = Savings & Security” — on Tuesday, December 6, at 3:00 p.m. ET. To receive complimentary access to the webinar, enter code UMRCmp122016 at registration. “Stop loss has become a popular solution to the problem of rising insurance premiums, but there are certain things to watch out for when controlling costs that will help reduce confusion regarding coverage and risk,” says Steven W. Goethel, CEBS, Vice President Customer Solutions – Stop Loss & Reporting at UMR. “Benefit administrators and HR professionals will benefit from learning how the differences in plan design and underwriting practices can impact a plan and its coverage.” ABOUT the Presenter Steven (Steve) Goethel is vice president customer solutions – stop loss and reporting for UMR, the third-party administrator (TPA) unit of UnitedHealthcare. He is responsible for the company's stop loss marketing, stop loss recovery activities and relationships. In addition, he also is responsible for the Information and Analytic Services (IAS) function, which is responsible for customer plan performance reporting. Mr. Goethel brings more than 25 years of marketing, business development, technology and customer solutions experience to his role. He joined the organization as a pension analyst and soon transferred to pension marketing and later employee benefits marketing. Mr. Goethel then joined the business development unit, helping to develop the request for proposal and renewal process. His technology management positions within UMR include work on Intranet and Internet initiatives and later technology management and business development. In 2003, he joined the customer solutions team as director product management -- middle market and stop loss. Mr. Goethel is a native of Grafton, Wis. He received a bachelor's degree in business administration from the University of Wisconsin-Eau Claire. He earned the designation of Certified Employee Benefits Specialist (CEBS) in 1995. ABOUT UMR UMR is a UBA Strategic Partner for third-party administration (TPA) services. UMR, the TPA solution from UnitedHealthcare, has more than 65 years of experience listening to and answering the needs of self-funded employers. We work closely with clients to build strategies that lower costs, improve employee health, and help them achieve their health plan goals. UMR is strategically built for solutions. We work closely with our self-funded clients to lower their medical costs, improve the health of their employee populations, and help them achieve their benefits goals. We achieve this by employing a comprehensive selection of in-house products and services and external vendor relationships. For more information, visit http://www.umr.com. ABOUT United Benefit Advisors® United Benefit Advisors® (UBA) is the nation’s leading independent employee benefits advisory organization with more than 200 offices throughout the United States, Canada and the United Kingdom. UBA empowers more than 2,000 Partners to both maintain their individuality and pool their expertise, insight, and market presence to provide best-in-class services and solutions. Employers, advisors and industry-related organizations interested in obtaining powerful results from the shared wisdom of our Partners should visit http://www.UBAbenefits.com.


News Article | December 9, 2016
Site: www.eurekalert.org

It has been 20 years since Dolly the sheep was successfully cloned in Scotland, but cloning mammals remains a challenge. A new study by researchers from the U.S. and France of gene expression in developing clones now shows why most cloned embryos likely fail. Dolly was cloned using the technique of "somatic cell nuclear transfer," when a nucleus from an adult cell is transferred into unfertilized egg that has had its nucleus removed, and is then shocked with electricity to start cell growth. Embryos are then transferred to recipient mothers who carry the clones to birth. Cloning cattle is an agriculturally important technology and can be used to study mammalian development, but the success rate remains low, with typically fewer than 10 percent of the cloned animals surviving to birth. The majority of losses are due to embryonic death, a failure during the implantation process, or the development of a defective placenta. In a study published Dec. 8 in the journal Proceedings of the National Academy of Sciences, Harris Lewin, professor in the UC Davis Department of Evolution and Ecology, and colleagues in France and the U.S. used RNA sequencing to look at gene expression in cloned cows during implantation in order to get a better understanding of the molecular mechanisms that lead to a high rate of pregnancy failure for clones. The study is the culmination of 12 years of collaboration and combines the French team's expertise in cloning and reproductive biology with the U.S. team's expertise in functional genomics. "Our work tackled fundamental questions relating to the cloning process," said Lewin. "The study has resulted in the redefinition of our understanding of how nuclear reprogramming affects gene expression in extraembryonic tissues of cloned cattle embryos, and the exquisite communication between clones and their recipient mothers." "The large amount of data our collaboration has generated sheds light on mechanisms that account for embryonic losses at implantation," said Olivier Sandra, team leader for the study at the Institut National de la Recherche Agronomique in France. "They also provide new insights on how events taking place at implantation drive the progression of pregnancy and shape the post-natal phenotype of the progeny, in cattle as well as in other mammalian species." The researchers studied tissue from cloned cow embryos--all derived from the same cell line--at 18 and 34 days of development, as well as the corresponding endometrial lining of the pregnant cows. They also looked at non-cloned cows conceived using artificial insemination. Using RNA sequencing, the researchers found multiple genes whose abnormal expression could lead to the high rate of death for cloned embryos, including failure to implant in the uterus and failure to develop a normal placenta. Looking at the extraembryonic tissue of the cloned cows at day 18, the researchers found anomalies in expression of more than 5,000 genes. When they compared the results to the Mouse Genomic Informatics Knockout database they found 123 genes that corresponded with functional annotation of abnormal extra-embryonic tissue morphology, 121 associated with embryonic lethality, and 14 with abnormal embryo implantation. By day 34 of development, however, the pattern of gene expression was much more similar to control cows derived from artificial insemination, suggesting that these surviving clones were able to implant in the uterus and begin to form a placenta. These results indicate that the large losses of cloned cows before implantation probably result from problems with critical developmental genes in the extraembryonic tissue. The study also revealed other points of potential failure for the clones, including problems with hormonal signaling between the developing cloned embryo and the pregnant cow. For example, the study found down-regulation of genes involved in interferon tau, the major signal of pregnancy recognition. The clones also appeared to have an effect on the gene expression of the pregnant cows themselves; on day 34, some uterus tissue showed grossly different gene expression, which could affect the placenta. "Our data confirm that the interactions between the uterus and the extra-embryonic tissues is critical during implantation, making this step a major hurdle for the progression of pregnancy," said Sandra. "We now understand why clones fail, which can lead to improvements in the process of cloning of animals," said Lewin. But, he cautioned, "Our discoveries also reinforce the need for a strict ban on human cloning for any purposes." "It's amazing that the process works at all, demonstrating the great plasticity that developing animals have to adapt to extreme conditions," Lewin said. The research was supported by a U.S. Department of Agriculture-Agricultural Research Service Grant, a European Program SABRE Grant, and French National Research Agency Grants. The pregnancies were initiated at the experimental farm of the Institut National de la Recherche Agronomique in France and at the University of Illinois at Urbana-Champaign. The experiment was conducted in accordance with the rules and regulations of the European Convention on Animal Experimentation. Additional authors include: Fernando H. Biase from the Institute for Genomic Biology, University of Illinois at Urbana-Champaign; Chanaka Rabel, Kalista Andropolis, Colleen A. Olmstead, Rosane Oliveira, and Richard Wallace from the Department of Animal Sciences, University of Illinois at Urbana-Champaign; Michel Guillomot, Isabelle Hue, Daniel Le Bourhis, Evelyne Campion, Aurélie Chaulot-Talmon, Corinne Giraud-Delville, Géraldine Taghouti, Hélène Jammes, and Jean-Paul Renard from UMR Biologie du Développement et Reproduction, Institut National de la Recherche Agronomique, École Nationale Vétérinaire d'Alford, Université Paris Saclay, Jouy en Josas, France; and Christophe Richard, Unité Commune d'Expérimentation Animale de Bressonvilliers, Leudeville, France.


TxCell SA (FR0010127662 – TXCL), a biotechnology company developing innovative, personalized cellular immunotherapies using regulatory T cells (Treg) to treat severe chronic inflammatory and autoimmune diseases, and Inserm Transfert, on behalf of Inserm, the Nantes University (Nantes, France) and the Nantes CHU, today announce the signature of an exclusive worldwide licensing agreement. As per the terms of this agreement, TxCell has been granted an exclusive worldwide license to two patent families filed by the Center for Research in Transplantation and Immunology (CRTI), a center of excellence in the field of transplantation and immunology. The CRTI is a research unit (UMR 1064) affiliated to both Inserm, a French public organization dedicated to human health, and to the Nantes University (Nantes, France). These patents cover a new type of regulatory T cells (Tregs) that express the CD8 marker. This is opposed to traditionally known Tregs that express CD4 such as the Type 1 Tregs and FoxP3+ Tregs. Specifically, these CD8+ Tregs are non-cytotoxic and display a unique and highly immunosuppressive mechanism of action. This mechanism is mediated through the release of cytokines with anti-inflammatory and tolerogenic (inducing immune tolerance) properties1,2,3,4. As a result, CD8+ Tregs could offer a different and complementary approach to treat inflammatory disorders, including autoimmunity and transplant rejection. In addition, these patents also cover CAR-Treg cells made from these CD8+ Tregs. The CRTI team, which is led by Ignacio Anegon and Carole Guillonneau, has already demonstrated the efficacy of these CD8+ Treg cell population in several preclinical models of inflammation including heart allograft, human skin transplant rejection and graft-versus-host disease (GvHD) in mice with humanized immune systems. In these models, the administration of CD8+ Treg cells has been shown to prevent the occurrence of skin graft rejection and GvHD, respectively. As per the terms of the agreement announced today, TxCell now has exclusive worldwide rights to both these patent families for all autoimmune diseases and transplantation-related disorders. "Regulatory T cells are composed of several subpopulations that act through complementary modes of action to prevent or treat inflammatory disorders. TxCell’s unparalleled patent estate is focused on therapeutic Treg cells and already covers type 1 Treg cells and CAR-Treg cells. TxCell, by obtaining an exclusive license on patents covering a new CD8+ Treg cell subpopulation, adds a new pillar to its patent portfolio and further strengthens TxCell’s position as the international Treg leading expert," said Arnaud Foussat, Senior Vice President, Corporate Development and Head of External Collaborations & Alliance Management of TxCell. "This is the fifth academic agreement signed in 2016. Specifically, this license enables TxCell to develop new types of cell therapy products, composed of CD8+ Treg cells, including CAR-CD8+ Tregs, for the treatment of autoimmune diseases as well as transplant-related disorders with high unmet medical need." "It is a great satisfaction for Inserm Transfert to be involved in such a major technology transfer and to complete it successfully. This license agreement is the first step towards future collaborations with TxCell," said Pascale Augé, President of Board of Inserm Transfert. Financial terms of the agreement have not been disclosed. Founded in 2000, Inserm Transfert SA is the private subsidiary of the French National Institute of Health and Medical Research (Inserm). Inserm Transfert is dedicated to technology and knowledge transfer of Inserm’s laboratories innovations, from scouting of invention disclosure to industrial partnership. Founded in 1964, the French National Institute of Health and Medical research (Inserm) is a public science and technology institute that supports more than 300 laboratories across France and include nearly 15,000 researchers, engineers, technicians, post-doctoral fellow, students... Inserm is the only French public research institute to focus entirely on human health and that positions itself on the pathway from research laboratory to the bed of the patient in a multidisciplinary approach. Inserm is a core member of the National Alliance for Life and Health Sciences (Aviesan), founded in April 2009. The Center for Research in Transplantation and Immunology (CRTI) is a research unit (UMR 1064) affiliated to INSERM and Nantes University. The CRTI research programs and organization rely on the definition of common scientific objectives, the development of translational research, sharing of resource, technical platforms development and research development towards clinical and industrial applications. Main research areas are immunology, transplantation, autoimmune diseases, regenerative medicine and genetics with the aim in the long term of: (i) improving graft survival in transplanted patients thanks to novel biomarkers and immuno-intervention strategies, (ii) implementing these new tools in other clinical conditions such as IMIDs and (iii) developing alternative solutions for replacement of organs and tissues. The CRTI UMR1064 and the clinical departments of Clinical Immunology, Nephrology and Urology at CHU Nantes together form the Institute of Transplantation-Urology-Nephrology (ITUN). The kidney and pancreas transplantation program of the ITUN ranks among the best in France and Europe. TxCell is a biotechnology company that develops platforms for innovative, personalized T cell immunotherapies for the treatment of severe chronic inflammatory and autoimmune diseases with high unmet medical need. TxCell is targeting a range of autoimmune diseases (both T-cell and B-cell-mediated) including Crohn’s disease, lupus nephritis, bullous pemphigoid and multiple sclerosis, as well as transplantation-related inflammatory disorders. TxCell is the only clinical-stage cellular therapy company fully dedicated to the science of regulatory T lymphocytes (Tregs). Tregs are a recently discovered T cell population for which anti-inflammatory properties have been demonstrated. Contrary to conventional approaches based on non-specific polyclonal Tregs, TxCell is exclusively developing antigen-specific Tregs. This antigen specificity may either come from pre-existing Treg cell T-Cell Receptor (TCR) or from genetic modifications with Chimeric Antigen Receptor (CAR). TxCell is developing two proprietary technology platforms, ASTrIA, which is composed of non-modified naturally antigen-specific Tregs, and ENTrIA, which is composed of genetically-engineered Tregs. Based in Sophia-Antipolis, France, TxCell is listed on Euronext Paris and currently has 45 employees. This press release contains certain forward-looking statements relating to the business of TxCell, which shall not be considered per se as historical facts, including TxCell’s ability to develop, market, commercialize and achieve market acceptance for specific products, estimates for future performance and estimates regarding anticipated operating losses, future revenues, capital requirements, needs for additional financing. In addition, even if the actual results or development of TxCell are consistent with the forward-looking statements contained in this press release, those results or developments of TxCell may not be indicative of their in the future. In some cases, you can identify forward-looking statements by words such as "could," "should," "may," "expects," "anticipates," "believes," "intends," "estimates," "aims," "targets," or similar words. Although the management of TxCell believes that these forward-looking statements are reasonably made, they are based largely on the current expectations of TxCell as of the date of this press release and are subject to a number of known and unknown risks and uncertainties and other factors that may cause actual results, performance or achievements to be materially different from any future results, performance or achievement expressed or implied by these forward-looking statements. In particular, the expectations of TxCell could be affected by, among other things, uncertainties involved in the development of the Company’s products, which may not succeed, or in the delivery of TxCell’s products marketing authorizations by the relevant regulatory authorities and, in general, any factor that could affects TxCell capacity to commercialize the products it develops, as well as, any other risk and uncertainties developed or identified in any public documents filed by TxCell with the AMF, included those listed in chapter 4 “Risk factors” of the 2015 document de référence approved by the AMF on May 24, 2016 under number R.16-048. In light of these risks and uncertainties, there can be no assurance that the forward-looking statements made in this press release will in fact be realized. Notwithstanding the compliance with article 223-1 of the General Regulation of the AMF (the information disclosed must be “accurate, precise and fairly presented“), TxCell is providing the information in these materials as of this press release, and disclaims any intention or obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise. 1 Picarda E, Bézie S, Venturi V, et al, J Clin Invest. 2014 Jun;124(6):2497-512. 2 Guillonneau C, Hill M, Hubert FX, et al J Clin Invest. 2007 Apr;117(4):1096-106. 3 Bézie S, Picarda E, Ossart J, Tesson L, Usal C, Renaudin K, Anegon I, Guillonneau C. J. Clin. Invest. 2015 Oct 1;125(10):3952-64. 4 Bézie S, Picarda E, Tesson L, Renaudin K, Durand J, Ménoret S, Mérieau E, Chiffoleau E, Guillonneau C, Caron L, Anegon I. PLoS One 2015 Mar 12;10(3):e0119686.


TxCell SA (FR0010127662 – TXCL), société de biotechnologies qui développe des immunothérapies cellulaires personnalisées innovantes à partir de cellules T régulatrices (Treg) pour le traitement de maladies inflammatoires et auto-immunes chroniques, et Inserm Transfert, pour le compte de l’Inserm, de l’Université de Nantes et du CHU de Nantes, annoncent aujourd'hui la signature d'un accord de licence mondiale exclusive. Selon les termes de l’accord, TxCell a obtenu une licence mondiale exclusive portant sur deux familles de brevets déposées par le Centre pour la Recherche en Transplantation et en Immunologie (CRTI). Le CRTI est un centre d'excellence dans le domaine de la transplantation et de l'immunologie. Il s’agit d’une unité de recherche (UMR 1064) affiliée à l’Institut National de la Santé et de la Recherche Médicale (Inserm) et à l'Université de Nantes. Ces brevets couvrent un nouveau type de lymphocytes T régulateurs (Treg) porteurs du marqueur CD8, par opposition aux Tregs traditionnels porteurs du marqueur CD4 tels que les Tregs de Type 1 et les Tregs FoxP3+. En particulier, ces Tregs CD8+ sont non-cytotoxiques et possèdent un mécanisme d'action unique et hautement immunosuppresseur. Ce mécanisme est médié par la libération de cytokines anti-inflammatoires et tolérogènes (qui induisent une tolérance immunitaire)1,2,3,4. Ces Tregs CD8+ pourraient ainsi offrir une approche différente et complémentaire pour traiter les troubles inflammatoires, y compris dans l'auto-immunité et le rejet de greffe. De plus, ces brevets couvrent également l’utilisation de cellules CAR-Treg fabriquées à partir de ces Tregs CD8+. L'équipe dirigée par Ignacio Anegon et Carole Guillonneau du CRTI a déjà démontré l'efficacité de cette population de cellules Treg CD8+ dans plusieurs modèles précliniques, dont l’allogreffe cardiaque, le rejet de peau humaine et la maladie du greffon contre hôte (GvHD) chez des souris humanisées pour leur système immunitaire. Dans ces modèles, l'administration de cellules Treg CD8+ a permis d’éviter, respectivement, le rejet de peau et la GvHD. Conformément aux termes de l’accord annoncé ce jour, TxCell dispose désormais des droits mondiaux exclusifs sur ces deux familles de brevets pour l’ensemble des maladies auto-immunes et des troubles liés à la transplantation. « Les cellules T régulatrices sont composées de plusieurs sous-populations agissant via des modes d'action complémentaires pour prévenir ou traiter les troubles inflammatoires. TxCell bénéficiant déjà d’un portefeuille de brevets inégalé axé sur les cellules Treg a visée thérapeutique, qui couvre les cellules Treg de type 1 et les cellules CAR-Treg, cette licence exclusive sur une nouvelle sous-population de cellules Treg CD8+ ajoute un nouveau pilier à notre portefeuille de brevets et renforce à nouveau le positionnement de TxCell en tant qu'expert mondial des Tregs, » commente Arnaud Foussat, Vice-président Senior, Corporate Development, Responsable des Collaborations Scientifiques et des Alliances chez TxCell. « Il s’agit déjà du cinquième accord académique signé depuis le début de l’année 2016. Cette licence permettra notamment à TxCell de développer de nouveaux types de thérapie cellulaire composés de cellules Treg CD8+, y compris des CAR-Tregs CD8+, pour le traitement de maladies auto-immunes et de troubles liés à la transplantation présentant un fort besoin médical non-satisfait. » L’Inserm, Institut National de la Santé et de la Recherche Médicale, est, depuis 1964, le seul organisme public français dédié à la recherche biologique, médicale et à la santé humaine avec près de 15 000 chercheurs, ingénieurs et techniciens et quelque 300 laboratoires de recherche. L’Institut se positionne sur l’ensemble du parcours allant du laboratoire de recherche au lit du patient et mène une recherche multithématique qui permet l’étude de toutes les maladies, des plus fréquentes aux plus rares. L’Inserm est membre fondateur d’Aviesan, l’Alliance nationale pour les sciences de la vie et de la santé créée en 2009. Le Centre pour la Recherche en Transplantation et en Immunologie (CRTI) est un centre de recherche (UMR 1064) affilié à l'INSERM et à l'Université de Nantes. Les programmes de recherche du CRTI reposent sur la définition d'objectifs scientifiques communs, le développement de la recherche translationnelle, le partage des ressources, le développement de plateformes techniques et la recherche tournée vers des applications cliniques et industrielles. Les principaux domaines de recherche du CRTI sont l'immunologie, la transplantation, les maladies auto-immunes, la médecine régénérative et la génétique fonctionnelle. Ses objectifs à long terme sont les suivants : (i) améliorer la survie du greffon chez les patients transplantés grâce à de nouveaux biomarqueurs et à des stratégies d'immunothérapie ; (ii) mettre en œuvre ces nouveaux outils dans d'autres conditions cliniques telles que les maladies inflammatoires d’origine immunologique ; et, (iii) développer des solutions alternatives pour le remplacement des organes et des tissus. Le CRTI UMR1064 et les départements cliniques d'Immunologie Clinique, de Néphrologie et d'Urologie du CHU de Nantes forment ensemble l'Institut de Transplantation-Urologie-Néphrologie (ITUN). Le programme de transplantation rénale et pancréatique de l'ITUN se classe parmi les meilleurs en France et en Europe. TxCell est une société de biotechnologies qui développe des plateformes d‘immunothérapies cellulaires T personnalisées innovantes pour le traitement de maladies inflammatoires et auto-immunes chroniques sévères présentant un fort besoin médical non satisfait. TxCell cible différentes maladies auto-immunes (liées aux cellules T ou aux cellules B), dont la maladie de Crohn, le lupus rénal, la pemphigoïde bulleuse et la sclérose en plaques, ainsi que les troubles inflammatoires liés à la transplantation. Ce communiqué contient des déclarations prospectives. Ces déclarations ne constituent pas des faits historiques. Ces déclarations comprennent des projections et des estimations ainsi que les hypothèses sur lesquelles celles-ci reposent, des déclarations portant sur des projets, des objectifs, des intentions et des attentes concernant des résultats financiers, des événements, des opérations, des services futurs, le développement de produits et leur potentiel ou les performances futures. Ces déclarations prospectives peuvent souvent être identifiées par les mots « s'attendre à » « anticiper », « croire », « avoir l'intention de », « estimer » ou « planifier », ainsi que par d'autres termes similaires. Bien que la direction de TxCell estime que ces déclarations prospectives sont raisonnables, les investisseurs sont alertés sur le fait que ces déclarations prospectives sont soumises à de nombreux risques et incertitudes, difficilement prévisibles et généralement en dehors du contrôle de TxCell qui peuvent impliquer que les résultats et événements effectifs réalisés diffèrent significativement de ceux qui sont exprimés, induits ou prévus dans les informations et déclarations prospectives. Ces risques et incertitudes comprennent notamment les incertitudes inhérentes aux développements des produits de la Société, qui pourraient ne pas aboutir, ou à la délivrance par les autorités compétentes des autorisations de mise sur le marché ou plus généralement tous facteurs qui peuvent affecter la capacité de commercialisation des produits développés par TxCell ainsi que ceux qui sont développés ou identifiés dans les documents publics déposés par TxCell auprès de l'Autorité des marchés financiers y compris ceux énumérés dans le chapitre 4 « Facteurs de risque » du document de référence 2015 de TxCell qui a été enregistré auprès de l'Autorité des marchés financiers le 24 mai 2016 sous le numéro R.16-048. TxCell ne prend aucun engagement de mettre à jour les informations et déclarations prospectives sous réserve de la réglementation applicable notamment les articles 223-1 et suivants du règlement général de l'Autorité des marchés financiers. 1 Picarda E, Bézie S, Venturi V, et al, J Clin Invest. 2014 Jun;124(6):2497-512. 2 Guillonneau C, Hill M, Hubert FX, et al J Clin Invest. 2007 Apr;117(4):1096-106. 3 Bézie S, Picarda E, Ossart J, Tesson L, Usal C, Renaudin K, Anegon I, Guillonneau C. J. Clin. Invest. 2015 Oct 1;125(10):3952-64. 4 Bézie S, Picarda E, Tesson L, Renaudin K, Durand J, Ménoret S, Mérieau E, Chiffoleau E, Guillonneau C, Caron L, Anegon I. PLoS One 2015 Mar 12;10(3):e0119686.


Scientists at the Earth-Life Science Institute at the Tokyo Institute of Technology report in Nature (22 February 2017) unexpected discoveries about the Earth’s core. The findings include insights into the source of energy driving the Earth’s magnetic field, factors governing the cooling of the core and its chemical composition, and conditions that existed during the formation of the Earth. The Earth’s core consists mostly of a huge ball of liquid metal lying at 3000 km beneath its surface, surrounded by a mantle of hot rock. Notably, at such great depths, both the core and mantle are subject to extremely high pressures and temperatures. Furthermore, research indicates that the slow creeping flow of hot buoyant rocks—moving several centimeters per year—carries heat away from the core to the surface, resulting in a very gradual cooling of the core over geological time. However, the degree to which the Earth’s core has cooled since its formation is an area of intense debate amongst Earth scientists. In 2013 Kei Hirose, now Director of the Earth-Life Science Institute (ELSI) at the Tokyo Institute of Technology (Tokyo Tech), reported that the Earth’s core may have cooled by as much as 1000˚C since its formation 4.5 billion years ago. This large amount of cooling would be necessary to sustain the geomagnetic field, unless there was another as yet undiscovered source of energy. These results were a major surprise to the deep Earth community, and created what Peter Olson of Johns Hopkins University referred to as, “the New Core Heat Paradox”, in an article published in Science. Core cooling and energy sources for the geomagnetic field were not the only difficult issues faced by the team. Another unresolved matter was uncertainty about the chemical composition of the core. “The core is mostly iron and some nickel, but also contains about 10% of light alloys such as silicon, oxygen, sulfur, carbon, hydrogen, and other compounds,” Hirose, lead author of the new study to be published in the journal Nature [1]. “We think that many alloys are simultaneously present, but we don’t know the proportion of each candidate element.” Now, in this latest research carried out in Hirose’s lab at ELSI, the scientists used precision cut diamonds to squeeze tiny dust-sized samples to the same pressures that exist at the Earth’s core. The high temperatures at the interior of the Earth were created by heating samples with a laser beam. By performing experiments with a range of probable alloy compositions under a variety of conditions, Hirose’s and colleagues are trying to identify the unique behavior of different alloy combinations that match the distinct environment that exists at the Earth’s core. The search of alloys began to yield useful results when Hirose and his collaborators began mixing more than one alloy. “In the past, most research on iron alloys in the core has focused only on the iron and a single alloy,” says Hirose. “But in these experiments we decided to combine two different alloys containing silicon and oxygen, which we strongly believe exist in the core.” The researchers were surprised to find that when they examined the samples in an electron microscope, the small amounts of silicon and oxygen in the starting sample had combined together to form silicon dioxide crystals—the same composition as the mineral quartz found at the surface of the Earth. "This result proved important for understanding the energetics and evolution of the core," says John Hernlund of ELSI, a co-author of the study. “We were excited because our calculations showed that crystallization of silicon dioxide crystals from the core could provide an immense new energy source for powering the Earth’s magnetic field.” The additional boost it provides is plenty enough to solve Olson’s paradox. The team has also explored the implications of these results for the formation of the Earth and conditions in the early Solar System. Crystallization changes the composition of the core by removing dissolved silicon and oxygen gradually over time. Eventually the process of crystallization will stop when then core runs out of its ancient inventory of either silicon or oxygen. "Even if you have silicon present, you can’t make silicon dioxide crystals without also having some oxygen available,” says ELSI scientist George Helffrich, who modeled the crystallization process for this study. “But this gives us clues about the original concentration of oxygen and silicon in the core, because only some silicon:oxygen ratios are compatible with this model.” Kei Hirose1, Guillaume Morard2, Ryosuke Sinmyo1, Koichio Umemoto1, John Hernlund1, George Helffrich1 & Stéphane Labrosse3. Crystallization of silicon dioxide and compositional evolution of the Earth’s core. Nature, published on-line 22 February, 2017 1. Earth-Life Science Institute, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro, Tokyo 152-8550, Japan. 2. Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie, UMR CNRS 7590, Sorbonne Universités—Université Pierre et Marie Curie, CNRS, Muséum National d’Histoire Naturelle, IRD, 4 Place Jussieu, 75005 Paris, France. 3. Université de Lyon, École normale supérieure de Lyon, Université Lyon-1, CNRS, UMR 5276 LGL-TPE, F-69364 Lyon, France. About Tokyo Institute of Technology Tokyo Institute of Technology stands at the forefront of research and higher education as the leading university for science and technology in Japan. Tokyo Tech researchers excel in a variety of fields, such as material science, biology, computer science and physics. Founded in 1881, Tokyo Tech has grown to host 10,000 undergraduate and graduate students who become principled leaders of their fields and some of the most sought-after scientists and engineers at top companies. Embodying the Japanese philosophy of “monotsukuri,” meaning technical ingenuity and innovation, the Tokyo Tech community strives to make significant contributions to society through high-impact research. Website: http://www.titech.ac.jp/english/ About ELSI Launched 4 years ago, ELSI is one of Japan’s ambitious World Premiere International research centers, whose aim is to achieve progress in broadly inter-disciplinary scientific areas by inspiring the world’s greatest minds to come to Japan and work on the most challenging as a collaborative effort. ELSI’s primary aim is to address the co-origin and co-evolution of the Earth and life. Hirose’s team also included ELSI researchers Ryosuke Simyo and Koichiro Umemoto, in addition to French colleagues Professor Stéphane Labrosse (Ecole Normale Superieure de Lyon) and Dr. Guillaume Morard (Institut de minéralogie, de physique des matériaux et de cosmochimie). Both Labrosse and Morard are frequent visitors to ELSI, including their collaboration on this project

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