979 resultados para Franklin, A.C. John, 1914-1972
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The fulcrum upon which were leveraged many of the dramatic progressive changes in Montana that are documented "In the Crucible of Change" series was the lead up to, preparation, writing and adoption of the 1972 Montana Constitution. As Montana citizens exhibited their concern over the dysfunctional state government in MT under its 1889 Constitution, one of the areas that stood out as needing serious change was the Montana Legislature. Meeting for only sixty calendar days every two years, the Legislature regularly tried to carry off the subterfuge of stopping the wall clock at 11:59 PM on the sixtieth day and placing a shroud over it so they could continue to conduct business as if it were still the 60th day. Lawyers hired by the Anaconda Company drafted most bills that legislators wanted to have introduced. Malapportionment, especially in the State Senate where each county had one Senator regardless of their population, created a situation where Petroleum County with 800 residents had one senator while neighboring Yellowstone County with 80,000 people also had one senator -- a 100-1 differential in representation. Reapportionment imposed by rulings of the US Supreme Court in the mid-1960s created great furor in rural Montana to go along with the previous dissatisfaction of the urban centers. Stories of Anaconda Company “thumbs up – thumbs down” control of the votes were prevalent. Committee meeting and votes were done behind closed doors and recorded votes were non-existent except for the nearly meaningless final tally. People were in the dark about the creation of laws that affected their daily lives. It was clear that change in the Legislature had to take the form of change in the Constitution and, because it was not likely that the Legislature would advance Constitutional amendments on the subject, a convention seemed the only remedy. Once that Convention was called and went to work, it became apparent that the Legislative Article provided both opportunity for change and danger that too dramatic a change might sink the whole new document. The activities of the Legislative Committee and the whole Convention when acting upon Legislative issues provides one of the more compelling stories of change. The story of the Legislative Article of the Montana Constitution is discussed in this episode by three major players who were directly involved in the effort: Jerry Loendorf, Arlyne Reichert and Rich Bechtel. Their recollections of the activities surrounding the entire Constitutional Convention and specifically the Legislative Article provide an insider’s perspective of the development of the entire Constitution and the Legislative portion which was of such a high degree of interest to the people of Montana during the important period of progressive change documented “In the Crucible of Change.” Jerry Loendorf, who served as Chair of the Legislative Committee at the 1972 Montana Constitutional Convention, received a BA from Carroll College in 1961 and a JD from the University of Montana Law School in 1964. Upon graduation he served two years as a law clerk for the Montana Supreme Court after which he was for 34 years a partner in the law firm of Harrison, Loendorf & Posten, Duncan. In addition to being a delegate to the Constitutional Convention, Jerry served on the Board of Labor Appeals from 2000 to 2004. He was designated a Montana Special Assistant Attorney General to represent the state in federal court on the challenge to the results of the ratification election of Montana's Constitution in 1972. Jerry served on the Carroll College Board of Directors in the late 1960s and then again as a member of the Board of Trustees of Carroll College from 2001 to 2009. He has served on the Board of Directors of the Rocky Mountain Development Council since 1970 and was on the board of the Helena YMCA from 1981 to 1987. He also served on the board of the Good Samaritan Ministries from 2009 to 2014. On the business side, Jerry was on the Board of Directors of Valley Bank to Helena from 1980 to 2005. He is a member of the American Bar Association, State Bar of Montana, the First Judicial District Bar Association, and the Montana Trial Lawyers Association. Carroll College awarded Jerry the Warren Nelson Award 1994 and the Insignias Award in 2007. At Carroll College, Jerry has funded the following three scholarship endowments: George C and Helen T Loendorf, Gary Turcott, and Fr. William Greytek. Arlyne Reichert, Great Falls Delegate to the Constitutional Convention and former State Legislator, was born in Buffalo, NY in 1926 and attended University of Buffalo in conjunction with Cadet Nurses Training during WWII. She married a Montanan in Great Falls in 1945 and was widowed in 1968. She is mother of five, grandmother of seven, great-grandmother of four. Arlyne was employed by McLaughlin Research Institute in Great Falls for 23 years, serving as Technical Editor of Transplantation Journal in 1967, retiring as Assistant Director in 1989. In addition to being a state legislator (1979 Session) and a delegate to the 1972 Montana Constitutional Convention, she has filled many public roles, including Cascade County Study Commissioner (1974), MT Comprehensive Health Council, US Civil Rights Commission MT Advisory Committee, MT Capitol Restoration Committee, and Great Falls Public Library Trustee. Arlyne has engaged in many non-profit activities including League of Women Voters (State & Local Board Officer – from where her interest in the MT Constitutional change developed), Great Falls Public Radio Association (President & Founder), American Cancer Society (President Great Falls Chapter), Chair of MT Rhodes Scholarship Committee, and Council Member of the National Civic League. She also served a while as a Television Legislative Reporter. Arlyne has been recipient of numerous awards, the National Distinguished Citizens Award from the National Municipal League, two Women of Achievement Awards from Business & Professional Women, the Salute to Women Award by YWCA, Heritage Preservation Award from Cascade County Historical Society and the State of Montana, and the Heroes Award from Humanities Montana. She remains active, serving as Secretary-Treasurer of Preservation Cascade, Inc., and as Board Member of the McLaughlin Research Institute. Her current passion is applied to the preservation/saving of the historic 10th Street Bridge that crosses the Missouri River in Great Falls. Rich Bechtel of Helena was born in Napa, California in 1945 and grew up as an Air Force brat living in such places as Bitberg, Germany, Tripoli, Libya, and Sevilla, Spain. He graduated from Glasgow High School and the University of Montana. Rich was a graduate assistant for noted Montana History professor Professor K. Ross Toole, but dropped out of graduate school to pursue a real life in Montana politics and government. Rich has had a long, varied and colorful career in the public arena. He currently is the Director of the Office of Taxpayer Assistance & Public Outreach for MT’s Department of Revenue. He previously held two positions with the National Wildlife Federation in Washington, DC (Sr. Legislative Representative [1989-91] and Sr. Legislative Representative for Wildlife Policy [2004-2006]). While in Washington DC, he also was Assistant for Senator Lee Metcalf (D-MT), 1974-1976; Federal-State Coordinator for State of Montana, 1976-1989; Director of the Western Governors’ Association Washington Office, 1991-2000; and Director of Federal Affairs for Governor Kitzhaber of Oregon, 2001- 2003. Earlier in Montana Government, between 1971 and 1974, Rich was Research Analyst for MT Blue Ribbon Commission on Postsecondary Education, Legislative Consultant and Bill Drafter for MT Legislative Council, Research Analyst for the MT Constitutional Convention Commission where he provided original research on legislatures, as well as Researcher/Staff for the MT Constitutional Convention Legislative Committee, from where he drafted the various provisions of the Legislative Article and the majority and minority reports on behalf of the Committee members. Rich has represented Montana’s Governor on a trade and cultural mission to Republic of China and participated in US-German Acid Rain Committee sessions in Germany and with European Economic Community environmental officials in Belgium. He is married to Yvonne Seng (Ph.D.) - T’ai Chi apprentice; author and birder.
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Many hepatitis C virus (HCV) infections worldwide are with the genotype 1 and 3 strains of the virus. Cellular immune responses are known to be important in the containment of HCV genotype 1 infection, and many genotype 1 T cell targets (epitopes) that are presented by host human leukocyte antigens (HLAs) have been identified. In contrast, there is almost no information known about the equivalent responses to genotype 3. Immune escape mechanisms used by HCV include the evolution of viral polymorphisms (adaptations) that abrogate this host-viral interaction. Evidence of HCV adaptation to HLA-restricted immune pressure on HCV can be observed at the population level as viral polymorphisms associated with specific HLA types. To evaluate the escape patterns of HCV genotypes 1 and 3, we assessed the associations between viral polymorphisms and specific HLA types from 187 individuals with genotype 1a and 136 individuals with genotype 3a infection. We identified 51 HLA-associated viral polymorphisms (32 for genotype 1a and 19 for genotype 3a). Of these putative viral adaptation sites, six fell within previously published epitopes. Only two HLA-associated viral polymorphisms were common to both genotypes. In the remaining sites with HLA-associated polymorphisms, there was either complete conservation or no significant HLA association with viral polymorphism in the alternative genotype. This study also highlights the diverse mechanisms by which viral evasion of immune responses may be achieved and the role of genotype variation in these processes. CONCLUSION: There is little overlap in HLA-associated polymorphisms in the nonstructural proteins of HCV for the two genotypes, implying differences in the cellular immune pressures acting on these viruses and different escape profiles. These findings have implications for future therapeutic strategies to combat HCV infection, including vaccine design.
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This booklet contains abstracts of papers presented at a biochemical engineering symposium conducted at the University of Nebraska-Lincoln on April 29, 1972. This was the second annual symposium on this subject, the first having been held at Kansas State University on June 4, 1971. It is expected that future symposia will alternate between the two campuses. ContentsS.H. Lin, Kansas State University, "Enzyme Reaction in a Tubular Reactor with Laminar Flow" Gregory C. Martin, University of Nebraska, "Estimation of Parameters in Population Models for Schizosaccharomyces pombe from Chemostat Data" Jaiprakash S. Shastry and Prakash N. Mishra, Kansas State University, "Immobilized Enzymes: Analysis of Ultrafiltration Reactors" Mark D. Young, University of Nebraska, "Modelling Unsteady-State Two-Species Data Using Ramkrishna's Staling Model" G.C.Y. Chu, Kansas State University, "Optimization of Step Aeration Waste Treatment Systems Using EVOP" Shinji Goto, University of Nebraska, "Growth of the Blue-Green Alga Microcytis aeruginosa under Defined Conditions" Prakash N. Mishra and Thomas M.C. Kuo, Kansas State University, "Digital Computer Simulation of the Activated Sludge System: Effect of Primary Clarifier on System Performance" Mark D. Young, University of Nebraska, "Aerobic Fermentation of Paunch Liquor"
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Background & Aims: HLA-B⁄27 is associated with spontaneous HCV genotype 1 clearance. HLA-B⁄27-restricted CD8+ T cells target three NS5B epitopes. Two of these epitopes are dominantly targeted in the majority of HLA-B⁄27+ patients. In chronic infection, viral escape occurs consistently in these two epitopes. The third epitope (NS5B2820) was dominantly targeted in an acutely infected patient. This was in contrast, however, to the lack of recognition and viral escape in the large majority of HLA-B⁄27+ patients. Here, we set out to determine the host factors contributing to selective targeting of this epitope. Methods: Four-digit HLA class I typing and viral sequence analyses were performed in 78 HLA-B⁄27+ patients with chronic HCV genotype 1 infection. CD8+ T cell analyses were performed in a subset of patients. In addition, HLA/peptide affinity was compared for HLA-B⁄27:02 and 05. Results: The NS5B2820 epitope is only restricted by the HLA-B⁄27 subtype HLA-B⁄27:02 (that is frequent in Mediterranean populations), but not by the prototype HLA-B⁄27 subtype B⁄27:05. Indeed, the epitope is very dominant in HLA-B⁄27:02+ patients and is associated with viral escape mutations at the anchor position for HLA-binding in 12 out of 13 HLA-B⁄27:02+ chronically infected patients. Conclusions: The NS5B2820 epitope is immunodominant in the context of HLA-B⁄27:02, but is not restricted by other HLA-B⁄27 subtypes. This finding suggests an important role of HLA subtypes in the restriction of HCV-specific CD8+ responses. With minor HLA subtypes covering up to 39% of specific populations, these findings may have important implications for the selection of epitopes for global vaccines.
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Activation of protein kinase C (PKC) causes multiple effects on adenylyl cyclase (AC), (i) an inhibition of (hormone) receptor/G$\sb{\rm s}$ coupling, consistent with PKC modification of the receptor and (ii) a postreceptor sensitization consistent with a PKC-mediated modification of the stimulatory (G$\sb{\rm s}$) or inhibitory (G$\sb{\rm i}$) G-proteins or the catalyst (C) of AC. In L cells expressing the wild-type beta-adrenergic receptor ($\beta$AR) 4-$\beta$ phorbol 12-myristate-13-acetate (PMA) caused 2-3-fold increases in the K$\sb{\rm act}$ and V$\sb{\rm max}$ for epinephrine-stimulated AC activity and an attenuation of GTP-mediated inhibition of AC. Deletion of a concensus site for PKC phosphorylation (amino acids 259-262) from the $\beta$AR eliminated the PMA-induced increase in the K$\sb{\rm act}$, but had no effect on the other actions of PMA. PMA also increased the K$\sb{\rm act}$ and V$\sb{\rm max}$ for prostaglandin E$\sb1$ (PGE$\sb1$)-stimulated AC and the V$\sb{\rm max}$ for forskolin-stimulated AC. Maximal PMA-induced sensitizations were observed when AC was assayed in the presence of 10 $\mu$M GTP and 0.3 mM (Mg$\sp{++}$).^ Liao et al. (J. Biol. Chem. 265:11273-11284 (1990)) have shown that the P$\sb2$ purinergic receptor agonist ATP stimulates hydrolysis of 4,5 inositol bisphosphate (PIP$\sb2$) by phospholipase C (PLC) in L cells. To determine if agonists that stimulate PLC and PMA had similar effects on AC function we compared the effects of ATP and PMA. ATP caused a rapid 50-150% sensitization of PGE$\sb1$-, epinephrine-, and forskolin-stimulated AC activity with an EC$\sb{50}$ of 3 $\mu$M ATP. The sensitization was similar (i.e. Mg$\sp{++}$ and GTP sensitivity) to that caused by 10 nM PMA. However, unlike PMA ATP did not affect the K$\sb{\rm act}$ for hormone-stimulated AC and its effects were unaltered by down-regulation of PKCs following long term PMA treatment. Our results demonstrate that a PKC concensus site in the $\beta$AR, is required for the PMA-induced decrease in receptor/G$\sb{\rm s}$ coupling. Our data also indicate that activation of P$\sb2$ purinergic receptors by ATP may be important in the sensitization of AC in L cells. The mechanism behind this effect remains to be determined. ^
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Bd 9 u. 10 sind nicht im Freimann-Kat. aufgeführt
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von S. M. Dubnow
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von Abraham Glaßberg
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von Emanuel Kirschner
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BACKGROUND & AIMS The safety and efficacy of the interferon-free combination of faldaprevir (NS3/A4 protease inhibitor), deleobuvir (BI 207127, non-nucleoside polymerase inhibitor), and ribavirin in treatment-naïve patients chronically infected with HCV genotype-1 was explored. METHODS SOUND-C3 was a multicenter, open-label Phase 2b study. Treatment-naïve patients chronically infected with HCV genotype-1a (IL28B CC genotype only; n = 12) and genotype-1b (n = 20) were assigned to 16 weeks of treatment with faldaprevir 120 mg once daily, deleobuvir 600 mg twice daily, and weight-based ribavirin. Patients with compensated liver disease, including cirrhosis, were eligible for inclusion in this study. The primary endpoint was sustained virological response 12 weeks after completion of therapy. RESULTS Sustained virological response rates 12 weeks after completion of therapy were 17% and 95% in patients infected with HCV genotype-1a and genotype-1b respectively. All four patients with cirrhosis achieved sustained virological response 12 weeks after completion of therapy. The most frequently reported adverse events of at least moderate intensity were anaemia (16%), nausea, vomiting and fatigue (9% each). Three (9%) patients discontinued because of adverse events. CONCLUSIONS The interferon-free regimen of faldaprevir, deleobuvir and ribavirin was efficacious in patients infected with genotype-1b and generally well tolerated.
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von Jacob Segall. Mit e. Vorw. von Heinrich Silbergleit