238 resultados para Jeanette Winterson


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Through the use of Transient Diode Laser Absorption Spectroscopy (TDLAS), the rate coefficient for the vibrational relaxation of N2O (ν2) by O(3P) at room temperature (32 ºC)) was determined to be (1.51 ± 0.11)x10-12 cm3molecule-1sec-1. A Q-switched, frequency quadrupled (266 nm) Nd:YAG laser pulse was used as the pump for this experiment. This pulse caused the photodissociation of O3 into O2 and O atoms.Excited oxygen (O(1D)) was collisionally quenched to ground state (O(3P)) by Ar and/or Xe. Photodissociation also caused a temperature jump within the system, exciting the ν2 state of N2O molecules. Population in the ν2 state was monitored through a TDLASobservation of a ν3 transition. Data were fit using a Visual Fortran 6.0 Global Fitting program. Analysis of room temperature data taken using only Ar to quench O atoms to the ground state gave the same rate coefficient as analysis of data taken using an Ar/Xe mixture, suggesting Ar alone is a sufficient bath gas. Experimentation was alsoperformed at -27 ºC and -82 ºC for a temperature dependence analysis. A linear regression analysis gave a rate coefficient dependence on temperature of ... for the rate coefficient of the vibrational relaxation of N2O (ν2) by atomic oxygen.

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The article summarizes the collective views expressed at the fourth session of the workshop Tissue Engineering-the Next Generation, which was devoted to the translation of results of tissue engineering research into applications. Ernst Hunziker described the paradigm of a dual translational approach, and argued that tissue engineering should be guided by the dimensions and physiological setting of the bodily compartment to be repaired. Myron Spector discussed collagen-glycosaminoglycan (GAG) scaffolds for musculoskeletal tissue engineering. Jeanette Libera focused on the biological and clinical aspects of cartilage tissue engineering, and described a completely autologous procedure for engineering cartilage using the patient's own chondrocytes and blood serum. Arthur Gertzman reviewed the applications of allograft tissues in orthopedic surgery, and outlined the potential of allograft tissues as models for biological and medical studies. Savio Woo discussed a list of functional tissue engineering approaches designed to restore the biochemical and biomechanical properties of injured ligaments and tendons to be closer to that of the normal tissues. Specific examples of using biological scaffolds that have chemoattractants as well as growth factors with unique contact guidance properties to improve their healing process were shown. Anthony Ratcliffe discussed the translation of the results of research into products that are profitable and meet regulatory requirements. Michael Lysaght challenged the proposition that commercial and clinical failures of early tissue engineering products demonstrate a need for more focus on basic research. Arthur Coury described the evolution of tissue engineering products based on the example of Genzyme, and how various definitions of success and failure can affect perceptions and policies relative to the status and advancement of the field of tissue engineering.

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OBJECTIVE: To investigate the effects of tyrosine-kinase inhibitors of vascular endothelial growth factor (VECF) and platelet-derived growth factor (PDCF)-receptors on non-malignant tissue and whether they depend upon the stage of vascular maturation. MATERIALS AND METHODS: PTK787/ZK222584 and CGP53716 (VEGF- and PDGF-receptor inhibitor respectively), both alone and combined, were applied on chicken chorioallantoic membrane (CAM). RESULTS: On embryonic day of CAM development (E)8, only immature microvessels, which lack coverage of pericytes, are present: whereas the microvessels on E12 have pericytic coverage. This development was reflected in the expression levels of pericytic markers (alpha-smooth muscle actin, PDGF-receptor beta and desmin), which were found by immunoblotting to progressively increase between E8 and E12. Monotherapy with 2 microg of PTK787/ZK222584 induced significant vasodegeneration on E8, but not on E12. Monotherapy with CGP53716 affected only pericytes. When CGP53716 was applied prior to treatment with 2 microg of PTK787/ZK222584, vasodegeneration occurred also on E12. The combined treatment increased the apoptotic rate. as evidenced by the cDNA levels of caspase-9 and the TUNEL-assay. CONCLUSION: Anti-angiogenic treatment strategies for non-neoplastic disorders should aim to interfere with the maturation stage of the target vessels: monotherapy with VEGF-receptor inhibitor for immature vessels, and combined anti-angiogenic treatment for well developed mature vasculature.

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Inhibitors of angiogenesis and radiation induce compensatory changes in the tumor vasculature both during and after treatment cessation. To assess the responses to irradiation and vascular endothelial growth factor-receptor tyrosine kinase inhibition (by the vascular endothelial growth factor tyrosine kinase inhibitor PTK787/ZK222854), mammary carcinoma allografts were investigated by vascular casting; electron, light, and confocal microscopy; and immunoblotting. Irradiation and anti-angiogenic therapy had similar effects on the tumor vasculature. Both treatments reduced tumor vascularization, particularly in the tumor medulla. After cessation of therapy, the tumor vasculature expanded predominantly by intussusception with a plexus composed of enlarged sinusoidal-like vessels containing multiple transluminal tissue pillars. Tumor revascularization originated from preserved alpha-smooth muscle actin-positive vessels in the tumor cortex. Quantification revealed that recovery was characterized by an angiogenic switch from sprouting to intussusception. Up-regulated alpha-smooth muscle actin-expression during recovery reflected the recruitment of alpha-smooth muscle actin-positive cells for intussusception as part of the angio-adaptive mechanism. Tumor recovery was associated with a dramatic decrease (by 30% to 40%) in the intratumoral microvascular density, probably as a result of intussusceptive pruning and, surprisingly, with only a minimal reduction of the total microvascular (exchange) area. Therefore, the vascular supply to the tumor was not severely compromised, as demonstrated by hypoxia-inducible factor-1alpha expression. Both irradiation and anti-angiogenic therapy cause a switch from sprouting to intussusceptive angiogenesis, representing an escape mechanism and accounting for the development of resistance, as well as rapid recovery, after cessation of therapy.

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One-hundred years ago, in 1914, male voters in Montana (MT) extended suffrage (voting rights) to women six years before the 19th Amendment to the US Constitution was ratified and provided that right to women in all states. The long struggle for women’s suffrage was energized in the progressive era and Jeanette Rankin of Missoula emerged as a leader of the campaign; in 1912 both major MT political party platforms supported women suffrage. In the 1914 election, 41,000 male voters supported woman suffrage while nearly 38,000 opposed it. MT was not only ahead of the curve on women suffrage, but just two years later in 1916 elected Jeanette Rankin as the first woman ever elected to the United States Congress. Rankin became a national leader for women's equality. In her commitment to equality, she opposed US entry into World War I, partially because she said she could not support men being made to go to war if women were not allowed to serve alongside them. During MT’s initial progressive era, women in MT not only pursued equality for themselves (the MT Legislature passed an equal pay act in 1919), but pursued other social improvements, such as temperance/prohibition. Well-known national women leaders such as Carrie Nation and others found a welcome in MT during the period. Women's role in the trade union movement was evidenced in MT by the creation of the Women's Protective Union in Butte, the first union in America dedicated solely to women workers. But Rankin’s defeat following her vote against World War I was used as a way for opponents to advocate a conservative, traditionalist perspective on women's rights in MT. Just as we then entered a period in MT where the “copper collar” was tightened around MT economically and politically by the Anaconda Company and its allies, we also found a different kind of conservative, traditionalist collar tightened around the necks of MT women. The recognition of women's role during World War II, represented by “Rosie the Riveter,” made it more difficult for that conservative, traditionalist approach to be forever maintained. In addition, women's role in MT agriculture – family farms and ranches -- spoke strongly to the concept of equality, as farm wives were clearly active partners in the agricultural enterprises. But rural MT was, by and large, the bastion of conservative values relative to the position of women in society. As the period of “In the Crucible of Change” began, the 1965 MT Legislature included only three women. In 1967 and 1969 only one woman legislator served. In 1971 the number went up to two, including one of our guests, Dorothy Bradley. It was only after the Constitutional Convention, which featured 19 women delegates, that the barrier was broken. The 1973 Legislature saw 9 women elected. The 1975 and 1977 sessions had 14 women legislators; 15 were elected for the 1979 session. At that time progressive women and men in the Legislature helped implement the equality provisions of the new MT Constitution, ratified the federal Equal Rights Amendment in 1974, and held back national and local conservatives forces which sought in later Legislatures to repeal that ratification. As with the national movement at the time, MT women sought and often succeeded in adopting legal mechanisms that protected women’s equality, while full equality in the external world remained (and remains) a treasured objective. The story of the re-emergence of Montana’s women’s movement in the 1970s is discussed in this chapter by three very successful and prominent women who were directly involved in the effort: Dorothy Bradley, Marilyn Wessel, and Jane Jelinski. Their recollections of the political, sociological and cultural path Montana women pursued in the 1970s and the challenges and opposition they faced provide an insider’s perspective of the battle for equality for women under the Big Sky “In the Crucible of Change.” Dorothy Bradley grew up in Bozeman, Montana; received her Bachelor of Arts Phi Beta Kappa from Colorado College, Colorado Springs, in 1969 with a Distinction in Anthropology; and her Juris Doctor from American University in Washington, D.C., in 1983. In 1970, at the age of 22, following the first Earth Day and running on an environmental platform, Ms. Bradley won a seat in the 1971 Montana House of Representatives where she served as the youngest member and only woman. Bradley established a record of achievement on environmental & progressive legislation for four terms, before giving up the seat to run a strong second to Pat Williams for the Democratic nomination for an open seat in Montana’s Western Congressional District. After becoming an attorney and an expert on water law, she returned to the Legislature for 4 more terms in the mid-to-late 1980s. Serving a total of eight terms, Dorothy was known for her leadership on natural resources, tax reform, economic development, and other difficult issues during which time she gained recognition for her consensus-building approach. Campaigning by riding her horse across the state, Dorothy was the Democratic nominee for Governor in 1992, losing the race by less than a percentage point. In 1993 she briefly taught at a small rural school next to the Northern Cheyenne Indian Reservation. She was then hired as the Director of the Montana University System Water Center, an education and research arm of Montana State University. From 2000 - 2008 she served as the first Gallatin County Court Administrator with the task of collaboratively redesigning the criminal justice system. She currently serves on One Montana’s Board, is a National Advisor for the American Prairie Foundation, and is on NorthWestern Energy’s Board of Directors. Dorothy was recognized with an Honorary Doctorate from her alma mater, Colorado College, was named Business Woman of the Year by the Bozeman Chamber of Commerce and MSU Alumni Association, and was Montana Business and Professional Women’s Montana Woman of Achievement. Marilyn Wessel was born in Iowa, lived and worked in Los Angeles, California, and Washington, D.C. before moving to Bozeman in 1972. She has an undergraduate degree in journalism from Iowa State University, graduate degree in public administration from Montana State University, certification from the Harvard University Institute for Education Management, and served a senior internship with the U.S. Congress, Montana delegation. In Montana Marilyn has served in a number of professional positions, including part-time editor for the Montana Cooperative Extension Service, News Director for KBMN Radio, Special Assistant to the President and Director of Communications at Montana State University, Director of University Relations at Montana State University and Dean and Director of the Museum of the Rockies at MSU. Marilyn retired from MSU as Dean Emeritus in 2003. Her past Board Service includes Montana State Merit System Council, Montana Ambassadors, Vigilante Theater Company, Montana State Commission on Practice, Museum of the Rockies, Helena Branch of the Ninth District Federal Reserve Bank, Burton K. Wheeler Center for Public Policy, Bozeman Chamber of Commerce, and Friends of KUSM Public Television. Marilyn’s past publications and productions include several articles on communications and public administration issues as well as research, script preparation and presentation of several radio documentaries and several public television programs. She is co-author of one book, 4-H An American Idea: A History of 4-H. Marilyn’s other past volunteer activities and organizations include Business and Professional Women, Women's Political Caucus, League of Women Voters, and numerous political campaigns. She is currently engaged professionally in museum-related consulting and part-time teaching at Montana State University as well as serving on the Editorial Board of the Bozeman Daily Chronicle and a member of Pilgrim Congregational Church and Family Promise. Marilyn and her husband Tom, a retired MSU professor, live in Bozeman. She enjoys time with her children and grandchildren, hiking, golf, Italian studies, cooking, gardening and travel. Jane Jelinski is a Wisconsin native, with a BA from Fontbonne College in St. Louis, MO who taught fifth and seventh grades prior to moving to Bozeman in 1973. A stay-at-home mom with a five year old daughter and an infant son, she was promptly recruited by the Gallatin Women’s Political Caucus to conduct a study of Sex-Role Stereotyping in K Through 6 Reading Text Books in the Bozeman School District. Sociologist Dr. Louise Hale designed the study and did the statistical analysis and Jane read all the texts, entered the data and wrote the report. It was widely disseminated across Montana and received attention of the press. Her next venture into community activism was to lead the successful effort to downzone her neighborhood which was under threat of encroaching business development. Today the neighborhood enjoys the protections of a Historic Preservation District. During this time she earned her MPA from Montana State University. Subsequently Jane founded the Gallatin Advocacy Program for Developmentally Disabled Adults in 1978 and served as its Executive Director until her appointment to the Gallatin County Commission in 1984, a controversial appointment which she chronicled in the Fall issue of the Gallatin History Museum Quarterly. Copies of the issue can be ordered through: http://gallatinhistorymuseum.org/the-museum-bookstore/shop/. Jane was re-elected three times as County Commissioner, serving fourteen years. She was active in the Montana Association of Counties (MACO) and was elected its President in 1994. She was also active in the National Association of Counties, serving on numerous policy committees. In 1998 Jane resigned from the County Commission 6 months before the end of her final term to accept the position of Assistant Director of MACO, from where she lobbied for counties, provided training and research for county officials, and published a monthly newsletter. In 2001 she became Director of the MSU Local Government Center where she continued to provide training and research for county and municipal officials across MT. There she initiated the Montana Mayors Academy in partnership with MMIA. She taught State and Local Government, Montana Politics and Public Administration in the MSU Political Science Department before retiring in 2008. Jane has been married to Jack for 46 years, has two grown children and three grandchildren.

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The dog is the natural host of Staphylococcus pseudintermedius. Many research efforts are currently being undertaken to expand our knowledge and understanding of this important canine commensal and opportunistic pathogen. The objective of this review is to summarize the current knowledge of the species, including the latest research outcomes, with emphasis on taxonomy, diagnostics, ecology, epidemiology and pathogenicity. Despite the important taxonomic changes that have occurred over the past few years, the risk of misidentification in canine specimens is low and does not have serious consequences for clinical practice. Staphylococcus pseudintermedius carriage in the dog is more frequent and genetically heterogeneous compared with that of Staphylococcus aureus in man. It appears that these staphylococcal species have evolved separately through adaptation to their respective natural hosts and differ with regard to various aspects concerning ecology, population structure and evolution of antibiotic resistance. Further understanding of the ecology and epidemiology of S. pseudintermedius is hampered by the lack of a standard method for rapid and discriminatory typing and by the limited data available on longitudinal carriage and population structure of meticillin-susceptible strains. With regard to pathogenicity, it is only now that we are starting to explore the virulence potential of S. pseudintermedius based on genomic and proteomic approaches, and more research is needed to assess the importance of individual virulence factors and the possible existence of hypervirulent strains.

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Although vascular endothelial growth factor (VEGF) has been described as a potent angiogenic stimulus, its application in therapy remains difficult: blood vessels formed by exposure to VEGF tend to be malformed and leaky. In nature, the principal form of VEGF possesses a binding site for ECM components that maintain it in the immobilized state until released by local cellular enzymatic activity. In this study, we present an engineered variant form of VEGF, alpha2PI1-8-VEGF121, that mimics this concept of matrix-binding and cell-mediated release by local cell-associated enzymatic activity, working in the surgically-relevant biological matrix fibrin. We show that matrix-conjugated alpha2PI1-8-VEGF121 is protected from clearance, contrary to native VEGF121 mixed into fibrin, which was completely released as a passive diffusive burst. Grafting studies on the embryonic chicken chorioallantoic membrane (CAM) and in adult mice were performed to assess and compare the quantity and quality of neovasculature induced in response to fibrin implants formulated with matrix-bound alpha2PI1-8-VEGF121 or native diffusible VEGF121. Our CAM measurements demonstrated that cell-demanded release of alpha2PI1-8-VEGF121 increases the formation of new arterial and venous branches, whereas exposure to passively released wild-type VEGF121 primarily induced chaotic changes within the capillary plexus. Specifically, our analyses at several levels, from endothelial cell morphology and endothelial interactions with periendothelial cells, to vessel branching and network organization, revealed that alpha2PI1-8-VEGF121 induces vessel formation more potently than native VEGF121 and that those vessels possess more normal morphologies at the light microscopic and ultrastructural level. Permeability studies in mice validated that vessels induced by alpha2PI1-8-VEGF121 do not leak. In conclusion, cell-demanded release of engineered VEGF121 from fibrin implants may present a therapeutically safe and practical modality to induce local angiogenesis.

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Hereditary nasal parakeratosis (HNPK), an inherited monogenic autosomal recessive skin disorder, leads to crusts and fissures on the nasal planum of Labrador Retrievers. We performed a genome-wide association study (GWAS) using 13 HNPK cases and 23 controls. We obtained a single strong association signal on chromosome 2 (p(raw) = 4.4×10⁻¹⁴). The analysis of shared haplotypes among the 13 cases defined a critical interval of 1.6 Mb with 25 predicted genes. We re-sequenced the genome of one case at 38× coverage and detected 3 non-synonymous variants in the critical interval with respect to the reference genome assembly. We genotyped these variants in larger cohorts of dogs and only one was perfectly associated with the HNPK phenotype in a cohort of more than 500 dogs. This candidate causative variant is a missense variant in the SUV39H2 gene encoding a histone 3 lysine 9 (H3K9) methyltransferase, which mediates chromatin silencing. The variant c.972T>G is predicted to change an evolutionary conserved asparagine into a lysine in the catalytically active domain of the enzyme (p.N324K). We further studied the histopathological alterations in the epidermis in vivo. Our data suggest that the HNPK phenotype is not caused by hyperproliferation, but rather delayed terminal differentiation of keratinocytes. Thus, our data provide evidence that SUV39H2 is involved in the epigenetic regulation of keratinocyte differentiation ensuring proper stratification and tight sealing of the mammalian epidermis.

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Horses were domesticated from the Eurasian steppes 5,000-6,000 years ago. Since then, the use of horses for transportation, warfare, and agriculture, as well as selection for desired traits and fitness, has resulted in diverse populations distributed across the world, many of which have become or are in the process of becoming formally organized into closed, breeding populations (breeds). This report describes the use of a genome-wide set of autosomal SNPs and 814 horses from 36 breeds to provide the first detailed description of equine breed diversity. F(ST) calculations, parsimony, and distance analysis demonstrated relationships among the breeds that largely reflect geographic origins and known breed histories. Low levels of population divergence were observed between breeds that are relatively early on in the process of breed development, and between those with high levels of within-breed diversity, whether due to large population size, ongoing outcrossing, or large within-breed phenotypic diversity. Populations with low within-breed diversity included those which have experienced population bottlenecks, have been under intense selective pressure, or are closed populations with long breed histories. These results provide new insights into the relationships among and the diversity within breeds of horses. In addition these results will facilitate future genome-wide association studies and investigations into genomic targets of selection.

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Intense selective pressures applied over short evolutionary time have resulted in homogeneity within, but substantial variation among, horse breeds. Utilizing this population structure, 744 individuals from 33 breeds, and a 54,000 SNP genotyping array, breed-specific targets of selection were identified using an F(ST)-based statistic calculated in 500-kb windows across the genome. A 5.5-Mb region of ECA18, in which the myostatin (MSTN) gene was centered, contained the highest signature of selection in both the Paint and Quarter Horse. Gene sequencing and histological analysis of gluteal muscle biopsies showed a promoter variant and intronic SNP of MSTN were each significantly associated with higher Type 2B and lower Type 1 muscle fiber proportions in the Quarter Horse, demonstrating a functional consequence of selection at this locus. Signatures of selection on ECA23 in all gaited breeds in the sample led to the identification of a shared, 186-kb haplotype including two doublesex related mab transcription factor genes (DMRT2 and 3). The recent identification of a DMRT3 mutation within this haplotype, which appears necessary for the ability to perform alternative gaits, provides further evidence for selection at this locus. Finally, putative loci for the determination of size were identified in the draft breeds and the Miniature horse on ECA11, as well as when signatures of selection surrounding candidate genes at other loci were examined. This work provides further evidence of the importance of MSTN in racing breeds, provides strong evidence for selection upon gait and size, and illustrates the potential for population-based techniques to find genomic regions driving important phenotypes in the modern horse.

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With the advent of multimodality therapy, the overall five-year survival rate from childhood cancer has improved considerably now exceeding 80% in developed European countries. This growing cohort of survivors, with many years of life ahead of them, has raised the necessity for knowledge concerning the risks of adverse long-term sequelae of the life-saving treatments in order to provide optimal screening and care and to identify and provide adequate interventions. Childhood cancer survivor cohorts in Europe. Considerable advantages exist to study late effects in individuals treated for childhood cancer in a European context, including the complementary advantages of large population-based cancer registries and the unrivalled opportunities to study lifetime risks, together with rich and detailed hospital-based cohorts which fill many of the gaps left by the large-scale population-based studies, such as sparse treatment information. Several large national cohorts have been established within Europe to study late effects in individuals treated for childhood cancer including the Nordic Adult Life after Childhood Cancer in Scandinavia study (ALiCCS), the British Childhood Cancer Survivor Study (BCCSS), the Dutch Childhood Oncology Group (DCOG) LATER study, and the Swiss Childhood Cancer Survivor Study (SCCSS). Furthermore, there are other large cohorts, which may eventually become national in scope including the French Childhood Cancer Survivor Study (FCCSS), the French Childhood Cancer Survivor Study for Leukaemia (LEA), and the Italian Study on off-therapy Childhood Cancer Survivors (OTR). In recent years significant steps have been taken to extend these national studies into a larger pan-European context through the establishment of two large consortia - PanCareSurFup and PanCareLIFE. The purpose of this paper is to present an overview of the current large, national and pan-European studies of late effects after childhood cancer. This overview will highlight the strong cooperation across Europe, in particular the EU-funded collaborative research projects PanCareSurFup and PanCareLIFE. Overall goal. The overall goal of these large cohort studies is to provide every European childhood cancer survivor with better care and better long-term health so that they reach their full potential, and to the degree possible, enjoy the same quality of life and opportunities as their peers.

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There is growing clinical evidence that even young children experience pain and accompanying anxiety. Few instruments have been validated to assess pain characteristics in children. The study of related demographic, illness, psychologic and parental factors in children has also been limited. This study examines the reliability and validity of pain assessment tools in an outpatient pediatric cancer population. A total of 78 children from three to fifteen years of age were observed and interviewed about the pain of invasive procedures. The effect of cultural factors and the stress of acculturation were examined by comparing data from two cultural groups, Anglo and Hispanic.^ Spielberger State-Trait Anxiety Scales were administered to children and parents prior to an invasive procedure. The Procedure Behavioral Checklist (PBCL) was used for observation of the child's response during the procedure. The Children's Procedural Interview (CPI) which contains items on the PBCL and visual analogues (scales of faces indicating varying degrees of pain and anxiety) was administered following the procedure.^ Reliability coefficients for Anglos were.78 on the PBCL,.79 on the CPI and.85 on the visual analogue scales. For Hispanics, the reliability for the PBCL was.54, while the CPI had a reliability of.72 and the visual analogue scales,.87. Construct validity was demonstrated by high correlations between the PBCL and CPI scores for both ethnic groups (.66 for Anglos and.64 for Hispanics) and by the significant correlation of State anxiety scores with both PBCL and CPI scores. Age was inversely correlated with PBCL and CPI scores for both ethnic groups. Hispanic parents' anxiety scores were higher than Anglo parents, but were not highly correlated with their child's PBCL, CPI or State-Trait anxiety scores. Caregivers' ratings were correlated with the PBCL scores for Anglos but not for Hispanics.^ The findings of this study indicate that pain responses may be reliably assessed using both observational and self-report methods in children, though differences in Anglo and Hispanic cultures exist. Differences in pain symptomatology and assessment in the two cultural groups warrant further study. ^