The Other Side of the Doors: Butte & Beyond -- Congressman Pat Williams “In the Crucible of Change”

Pat Williams emerged from the Mining City of Butte, Montana with a sense of grassroots, people-oriented politics. His inherent belief in the power of ordinary citizens carried him through the Montana Legislature and into Congress for a record-setting period. The accomplishments of his long career partially obscured his innate progressive and populist instinct that is reflective of the period of “in the Crucible of Change.” This film addresses Pat’s early years when his progressive instincts and activities resulted in pushback from the giant Anaconda Company which had held Montana hostage for 75 years. Pat is joined for part of the film by former campaign staffer, and now prominent media consultant, Michael Fenenbock for reflections on Pat’s 1978 “Door-to-Door to Congress” campaign, which demonstrated the power of his belief in the people on the other side of the doors. Pat Williams (b. 1937) rose from teaching grade school in his hometown of Butte, MT, to serving for the longest number of consecutive terms (9 terms, 18 years) in the US House of Representatives of anyone in Montana history. Pat was a member of the National Guard and attended UM in Missoula and William Jewel College, graduating from the University of Denver. Pat also served in the Montana legislature for 2 terms (1966 & 1968 elections). In 1969. Pat helped his legislative seat-mate John Melcher get elected as Montana’s Eastern District Congressman in the Special Election that June. Pat went to Washington DC as Melcher’s Executive Assistant. Upon returning to Montana, Pat headed up the Montana offices of the innovative Mountain Plains Family Education Program. In 1974, Pat ran unsuccessfully for Montana’s Western District Congressional seat in a three-way race with former Congressman Arnold Olsen and state Legislator Max Baucus. After the drafting and passage of the 1972 Montana Constitution, Pat was named a member of Montana’s first-ever Reapportionment Commission. In 1978 he successfully ran for Congress, conducting a massive grass-roots door-to-door campaign of 1½ years, reaching 50,000 doors. In a hotly contested 6-way Democratic primary, Pat won going away and also handily won the general election. Pat served in Congress from January, 1979 until January of 1997, 14 years representing the Western District and 4 years representing the entire state. Upon his retirement from Congress, in 1997 Williams returned to Montana where has been an instructor at the University of Montana and Senior Fellow and Regional Policy Associate at the Center for the Rocky Mountain West. He is a former member of the Montana Board of Regents and serves on a number of national education-related boards. In Congress Pat was a Deputy Whip of the U.S. House of Representatives and sat on committees on: Budget, Natural Resources, Education and Labor, and Agriculture. Pat’s leadership helped pass trailblazing legislation to assist hard-working middle-class families and ensure opportunities for every child. Pat’s fingerprints are on many pieces of important legislation, including the College Middle Income Assistance Act, the Family and Medical Leave Act, the Toddlers and Childhood Disability Act, the Library Services and Construction Act, and the Museum Services Act. Pat successfully sponsored the Lee Metcalf Wilderness Area and the Rattlesnake Wilderness area, helped save the Bob Marshall Wilderness from oil and gas exploration, and helped ban geothermal energy drilling near the borders of Yellowstone National Park. As Chairman of The Post-Secondary Education Committee, he protected the National Endowment for the Arts from elimination, a remarkable undertaking during a very trying time for the Agency. Pat worked tirelessly with Tribal College Leaders to build Montana’s seven Tribal Colleges. He was also responsible for the legislation that created The American Conservation Corps, which became the Corporation for National Service, giving thousands of America’s young people a chance to serve their country and pursue higher education. Pat lives in Missoula with his wife Carol Griffith Williams, former Montana Senate Majority Leader. They have three children and five grandchildren.

The Src inhibitor AZD0530 blocks invasion and may act as a radiosensitizer in lung cancer cells

BACKGROUND: With the emergence of Src inhibitors in clinical trials, improved knowledge of the molecular responses of cancer cells to these agents is warranted. This will facilitate the development of tests to identify patients who may benefit from these agents, allow drug activity to be monitored and rationalize the combination of these agents with other treatment modalities. METHODS: This study evaluated the molecular and functional effects of Src inhibitor AZD0530 in human lung cancer cells, by Western blotting and reverse transcription-polymerase chain reaction, and by assays for cell viability, migration, and invasion. RESULTS: Src was activated in four of five cell lines tested and the level corresponded with the invasive potential and the histologic subtype. Clinically relevant, submicromolar concentrations of AZD0530 blocked Src and focal adhesion kinase, resulting in significant inhibition of cell migration and Matrigel invasion. Reactivation of STAT3 and up-regulation of JAK indicated a potential mechanism of resistance. AZD0530 gave a potent and sustained blockage of AKT and enhanced the sensitivity to irradiation. CONCLUSIONS: The results indicated that AZD0530, aside from being a potent inhibitor of tumor cell invasion which could translate to inhibition of disease progression in the clinic, may also lower resistance of lung cancer cells to pro-apoptotic signals.

The Impact of the Sarbanes-Oxley Act on the Cost of Going Public

This paper examines the impact of the Sarbanes-Oxley Act (SOX), a legal framework intended to increase transparency and accountability of listed companies, on the cost of going public in the US. We expect SOX to increase the direct cost of going public, but decrease the underpricing because of reduced asymmetric information. Our main results corroborate these hypotheses. First, we find an increase in the cost of going public of 90 bp of gross proceeds. Second, we record a reduction in underpricing of 6 pp, which is related to a reduced offer price adjustment. This supports our hypothesis that SOX represents a mechanism to reduce asymmetric information.

Topo IIIalpha and BLM act within the Fanconi anemia pathway in response to DNA-crosslinking agents

The Bloom protein (BLM) and Topoisomerase IIIalpha are found in association with proteins of the Fanconi anemia (FA) pathway, a disorder manifesting increased cellular sensitivity to DNA crosslinking agents. In order to determine if the association reflects a functional interaction for the maintenance of genome stability, we have analyzed the effects of siRNA-mediated depletion of the proteins in human cells. Depletion of Topoisomerase IIIalpha or BLM leads to increased radial formation, as is seen in FA. BLM and Topoisomerase IIIalpha are epistatic to the FA pathway for suppression of radial formation in response to DNA interstrand crosslinks since depletion of either of them in FA cells does not increase radial formation. Depletion of Topoisomerase IIIalpha or BLM also causes an increase in sister chromatid exchanges, as is seen in Bloom syndrome cells. Human Fanconi anemia cells, however, do not demonstrate increased sister chromatid exchanges, separating this response from radial formation. Primary cell lines from mice defective in both Blm and Fancd2 have the same interstrand crosslink-induced genome instability as cells from mice deficient in the Fancd2 protein alone. These observations demonstrate that the association of BLM and Topoisomerase IIIalpha with Fanconi proteins is a functional one, delineating a BLM-Topoisomerase IIIalpha-Fanconi pathway that is critical for suppression of chromosome radial formation.

The Digital Economy Act in the dock: a proportionate ruling

The UK’s Digital Economy Act 2010 contains measures to enforce copyright on the Internet, specifically a two-tiered form of a graduated response.The Act was challenged in the High Court by two of the UK’s biggest Internet Service Providers (ISP), who obtained a Judicial Review of the copyright enforce- ment provisions. This paper is an overview of the case, based on the hearing of March 2011 and the ensuing judgement. It focuses on the two most hotly contested grounds for the challenge, namely an al- leged failure to notify the European Commission under the Technical Standards Directive, and the pro- portionality or otherwise of the contested provisions. It observes how the judgement accepted the defence argumentation of the government and the copyright owners as interested parties, and how the ISPs appeared to be put on the back foot.

Pelagic molybdenum concentration anomalies and the impact of sediment resuspension on the molybdenum budget in two tidal systems of the North Sea

The seasonal dynamics of molybdenum (Mo) were studied in the water column of two tidal basins of the German Wadden Sea (Sylt-Rømø and Spiekeroog) between 2007 and 2011. In contrast to its conservative behaviour in the open ocean, both, losses of more than 50% of the usual concentration level of Mo in seawater and enrichments up to 20% were observed repeatedly in the water column of the study areas. During early summer, Mo removal by adsorption on algae-derived organic matter (e.g. after Phaeocystis blooms) is postulated to be a possible mechanism. Mo bound to organic aggregates is likely transferred to the surface sediment where microbial decomposition enriches Mo in the pore water. First δ98/95Mo data of the study area disclose residual Mo in the open water column being isotopically heavier than MOMo (Mean Ocean Molybdenum) during a negative Mo concentration anomaly, whereas suspended particulate matter shows distinctly lighter values. Based on field observations a Mo isotope enrichment factor of ε = −0.3‰ has been determined which was used to argue against sorption on metal oxide surfaces. It is suggested here that isotope fractionation is caused by biological activity and association to organic matter. Pelagic Mo concentration anomalies exceeding the theoretical salinity-based concentration level, on the other hand, cannot be explained by replenishment via North Sea waters alone and require a supply of excess Mo. Laboratory experiments with natural anoxic tidal flat sediments and modelled sediment displacement during storm events suggest fast and effective Mo release during the resuspension of anoxic sediments in oxic seawater as an important process for a recycling of sedimentary sulphide bound Mo into the water column.

AN IMPLANTABLE MOSFET DOSIMETER MODIFIED TO ACT AS A FIDUCIAL MARKER

In external beam radiation therapy, it is imperative that the prescribed dose is administered to the correct location and in the correct amount. Though several ex vivo methods of quality assurance are currently employed to achieve this goal, verifying that the correct dose is received within the patient in situ is impossible without the capability of measuring dose inside the patient. Recently, a method of measuring dose delivered within the patient has been developed, an implantable MOSFET dosimeter. This dosimeter is implanted within the patient and records the dose received. Since the dosimeter is implanted in the patient, it could serve a dual function as a fiducial marker for image guided radiation therapy (IGRT) treatment if it could be modified to be visible on x-rays. In this study, modifications to the MOSFET dosimeter were made to increase its visibility for IGRT treatment. To test whether the modifications hindered the dosimeter’s ability to accurately measure and transmit dose information, the energy dependence, angular dependence and wireless read range of the modified dosimeter were measured and compared to unmodified dosimeters. It was found that the modified dosimeter performed as well as the unmodified dosimeter while also being suitable for use as a fiducial marker for IGRT treatment.

Clinical and radiographic outcomes at 2 years and the effect of tocilizumab discontinuation following sustained remission in the second and third year of the ACT-RAY study

OBJECTIVE To assess the efficacy and safety of tocilizumab (TCZ) plus methotrexate/placebo (MTX/PBO) over 2 years and the course of disease activity in patients who discontinued TCZ due to sustained remission. METHODS ACT-RAY was a double-blind 3-year trial. Patients with active rheumatoid arthritis despite MTX were randomised to add TCZ to ongoing MTX (add-on strategy) or switch to TCZ plus PBO (switch strategy). Using a treat-to-target approach, open-label conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), other than MTX, were added from week 24 if Disease Activity Score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) >3.2. Between weeks 52 and 104, patients in sustained clinical remission (DAS28-ESR <2.6 at two consecutive visits 12 weeks apart) discontinued TCZ and were assessed every 4 weeks for 1 year. If sustained remission was maintained, added csDMARDs, then MTX/PBO, were discontinued. RESULTS Of the 556 randomised patients, 76% completed year 2. Of patients entering year 2, 50.4% discontinued TCZ after achieving sustained remission and 5.9% achieved drug-free remission. Most patients who discontinued TCZ (84.0%) had a subsequent flare, but responded well to TCZ reintroduction. Despite many patients temporarily stopping TCZ, radiographic progression was minimal, with differences favouring add-on treatment. Rates of serious adverse events and serious infections per 100 patient-years were 12.2 and 4.4 in add-on and 15.0 and 3.7 in switch patients. In patients with normal baseline values, alanine aminotransferase elevations >3×upper limit of normal were more frequent in add-on (14.3%) versus switch patients (5.4%). CONCLUSIONS Treat-to-target strategies could be successfully implemented with TCZ to achieve sustained remission, after which TCZ was stopped. Biologic-free remission was maintained for about 3 months, but most patients eventually flared. TCZ restart led to rapid improvement. TRIAL REGISTRATION NUMBER NCT00810199.

The global carbon budget 1959–2011

Accurate assessments of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere is important to better understand the global carbon cycle, support the climate policy process, and project future climate change. Present-day analysis requires the combination of a range of data, algorithms, statistics and model estimates and their interpretation by a broad scientific community. Here we describe datasets and a methodology developed by the global carbon cycle science community to quantify all major components of the global carbon budget, including their uncertainties. We discuss changes compared to previous estimates, consistency within and among components, and methodology and data limitations. CO2 emissions from fossil fuel combustion and cement production (EFF) are based on energy statistics, while emissions from Land-Use Change (ELUC), including deforestation, are based on combined evidence from land cover change data, fire activity in regions undergoing deforestation, and models. The global atmospheric CO2 concentration is measured directly and its rate of growth (GATM) is computed from the concentration. The mean ocean CO2 sink (SOCEAN) is based on observations from the 1990s, while the annual anomalies and trends are estimated with ocean models. Finally, the global residual terrestrial CO2 sink (SLAND) is estimated by the difference of the other terms. For the last decade available (2002–2011), EFF was 8.3 ± 0.4 PgC yr−1, ELUC 1.0 ± 0.5 PgC yr−1, GATM 4.3 ± 0.1 PgC yr−1, SOCEAN 2.5 ± 0.5 PgC yr−1, and SLAND 2.6 ± 0.8 PgC yr−1. For year 2011 alone, EFF was 9.5 ± 0.5 PgC yr−1, 3.0 percent above 2010, reflecting a continued trend in these emissions; ELUC was 0.9 ± 0.5 PgC yr−1, approximately constant throughout the decade; GATM was 3.6 ± 0.2 PgC yr−1, SOCEAN was 2.7 ± 0.5 PgC yr−1, and SLAND was 4.1 ± 0.9 PgC yr−1. GATM was low in 2011 compared to the 2002–2011 average because of a high uptake by the land probably in response to natural climate variability associated to La Niña conditions in the Pacific Ocean. The global atmospheric CO2 concentration reached 391.31 ± 0.13 ppm at the end of year 2011. We estimate that EFF will have increased by 2.6% (1.9–3.5%) in 2012 based on projections of gross world product and recent changes in the carbon intensity of the economy. All uncertainties are reported as ±1 sigma (68% confidence assuming Gaussian error distributions that the real value lies within the given interval), reflecting the current capacity to characterise the annual estimates of each component of the global carbon budget. This paper is intended to provide a baseline to keep track of annual carbon budgets in the future.

Feierlicher Act der Religionsprüfung der zu entlassenden Schulkinder : entworfen und abgehalten in der Synagoge zu Carlsruhe am Sabbath den 23. April 1836 (6. Jjar 5596)

von M. Rosenfeld

The global carbon budget 1959–2011

Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere is important to better understand the global carbon cycle, support the climate policy process, and project future climate change. Present-day analysis requires the combination of a range of data, algorithms, statistics and model estimates and their interpretation by a broad scientific community. Here we describe datasets and a methodology developed by the global carbon cycle science community to quantify all major components of the global carbon budget, including their uncertainties. We discuss changes compared to previous estimates, consistency within and among components, and methodology and data limitations. Based on energy statistics, we estimate that the global emissions of CO2 from fossil fuel combustion and cement production were 9.5 ± 0.5 PgC yr−1 in 2011, 3.0 percent above 2010 levels. We project these emissions will increase by 2.6% (1.9–3.5%) in 2012 based on projections of Gross World Product and recent changes in the carbon intensity of the economy. Global net CO2 emissions from Land-Use Change, including deforestation, are more difficult to update annually because of data availability, but combined evidence from land cover change data, fire activity in regions undergoing deforestation and models suggests those net emissions were 0.9 ± 0.5 PgC yr−1 in 2011. The global atmospheric CO2 concentration is measured directly and reached 391.38 ± 0.13 ppm at the end of year 2011, increasing 1.70 ± 0.09 ppm yr−1 or 3.6 ± 0.2 PgC yr−1 in 2011. Estimates from four ocean models suggest that the ocean CO2 sink was 2.6 ± 0.5 PgC yr−1 in 2011, implying a global residual terrestrial CO2 sink of 4.1 ± 0.9 PgC yr−1. All uncertainties are reported as ±1 sigma (68% confidence assuming Gaussian error distributions that the real value lies within the given interval), reflecting the current capacity to characterise the annual estimates of each component of the global carbon budget. This paper is intended to provide a baseline to keep track of annual carbon budgets in the future.