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.

Analysis of non-porcine isolates of Actinobacillus suis

Twenty-four Actinobacillus suis isolates obtained from several species of non-porcine mammals were compared to the representative porcine strains, ATCC 15557 (serotype O1) and H89-1173 (serotype O2), by O serotyping, DNA fingerprinting, PCR amplification of apxICA, apxIICA and apxIIICA toxin genes and by rrs (16S rRNA) gene sequencing. Only two strains, both equine, reacted with O1 antiserum while two others, one canine and the other feline, reacted with O2 antiserum. One equine strain reacted weakly with both antisera. No amplification of apx genes was found with the non-porcine O1 or the "not O1/O2" strains but amplification of the apxICA and apxIICA genes was observed with the two O2 strains. In addition, these two O2 strains had both BamHI and BglII fingerprints that were very similar to the porcine O2 reference strain, H89-1173 and rrs gene sequences that were identical to the A. suis reference strain ATCC 15557. Taken together, these data suggest that although many non-porcine A. suis isolates are not A. suis (sensu stricto), some isolates are genotypically as well as phenotypically similar to A. suis.

Clustering subspecies of Aeromonas salmonicida using IS630 typing.

BACKGROUND The insertion element IS630 found in Aeromonas salmonicida belongs to the IS630-Tc1-mariner superfamily of transposons. It is present in multiple copies and represents approximately half of the IS present in the genome of A. salmonicida subsp. salmonicida A449. RESULTS By using High Copy Number IS630 Restriction Fragment Length Polymorphism (HCN-IS630-RFLP), strains of various subspecies of Aeromonas salmonicida showed conserved or clustering patterns, thus allowing their differentiation from each other. Fingerprints of A. salmonicida subsp. salmonicida showed the highest homogeneity while 'atypical' A. salmonicida strains were more heterogeneous. IS630 typing also differentiated A. salmonicida from other Aeromonas species. The copy number of IS630 in Aeromonas salmonicida ranges from 8 to 35 and is much lower in other Aeromonas species. CONCLUSIONS HCN-IS630-RFLP is a powerful tool for subtyping of A. salmonicida. The high stability of IS630 insertions in A. salmonicida subsp. salmonicida indicates that it might have played a role in pathoadaptation of A. salmonicida which has reached an optimal configuration in the highly virulent and specific fish pathogen A. salmonicida subsp. salmonicida.

Lake sediments as natural seismographs: A compiled record of Late Quaternary earthquakes in Central Switzerland and its implication for Alpine deformation

Central Switzerland lies tectonically in an intraplate area and recurrence rates of strong earthquakes exceed the time span covered by historic chronicles. However, many lakes are present in the area that act as natural seismographs: their continuous, datable and high-resolution sediment succession allows extension of the earthquake catalogue to pre-historic times. This study reviews and compiles available data sets and results from more than 10 years of lacustrine palaeoseismological research in lakes of northern and Central Switzerland. The concept of using lacustrine mass-movement event stratigraphy to identify palaeo-earthquakes is showcased by presenting new data and results from Lake Zurich. The Late Glacial to Holocene mass-movement units in this lake document a complex history of varying tectonic and environmental impacts. Results include sedimentary evidence of three major and three minor, simultaneously triggered basin-wide lateral slope failure events interpreted as the fingerprints of palaeoseismic activity. A refined earthquake catalogue, which includes results from previous lake studies, reveals a non-uniform temporal distribution of earthquakes in northern and Central Switzerland. A higher frequency of earthquakes in the Late Glacial and Late Holocene period documents two different phases of neotectonic activity; they are interpreted to be related to isostatic post-glacial rebound and relatively recent (re-)activation of seismogenic zones, respectively. Magnitudes and epicentre reconstructions for the largest identified earthquakes provide evidence for two possible earthquake sources: (i) a source area in the region of the Alpine or Sub-Alpine Front due to release of accumulated north-west/south-east compressional stress related to an active basal thrust beneath the Aar massif; and (ii) a source area beneath the Alpine foreland due to reactivation of deep-seated strike-slip faults. Such activity has been repeatedly observed instrumentally, for example, during the most recent magnitude 4.2 and 3.5 earthquakes of February 2012, near Zug. The combined lacustrine record from northern and Central Switzerland indicates that at least one of these potential sources has been capable of producing magnitude 6.2 to 6.7 events in the past.

Population genetics of VNTR loci and their applications in evolutionary studies

Variable number of tandem repeats (VNTR) are genetic loci at which short sequence motifs are found repeated different numbers of times among chromosomes. To explore the potential utility of VNTR loci in evolutionary studies, I have conducted a series of studies to address the following questions: (1) What are the population genetic properties of these loci? (2) What are the mutational mechanisms of repeat number change at these loci? (3) Can DNA profiles be used to measure the relatedness between a pair of individuals? (4) Can DNA fingerprint be used to measure the relatedness between populations in evolutionary studies? (5) Can microsatellite and short tandem repeat (STR) loci which mutate stepwisely be used in evolutionary analyses?^ A large number of VNTR loci typed in many populations were studied by means of statistical methods developed recently. The results of this work indicate that there is no significant departure from Hardy-Weinberg expectation (HWE) at VNTR loci in most of the human populations examined, and the departure from HWE in some VNTR loci are not solely caused by the presence of population sub-structure.^ A statistical procedure is developed to investigate the mutational mechanisms of VNTR loci by studying the allele frequency distributions of these loci. Comparisons of frequency distribution data on several hundreds VNTR loci with the predictions of two mutation models demonstrated that there are differences among VNTR loci grouped by repeat unit sizes.^ By extending the ITO method, I derived the distribution of the number of shared bands between individuals with any kinship relationship. A maximum likelihood estimation procedure is proposed to estimate the relatedness between individuals from the observed number of shared bands between them.^ It was believed that classical measures of genetic distance are not applicable to analysis of DNA fingerprints which reveal many minisatellite loci simultaneously in the genome, because the information regarding underlying alleles and loci is not available. I proposed a new measure of genetic distance based on band sharing between individuals that is applicable to DNA fingerprint data.^ To address the concern that microsatellite and STR loci may not be useful for evolutionary studies because of the convergent nature of their mutation mechanisms, by a theoretical study as well as by computer simulation, I conclude that the possible bias caused by the convergent mutations can be corrected, and a novel measure of genetic distance that makes the correction is suggested. In summary, I conclude that hypervariable VNTR loci are useful in evolutionary studies of closely related populations or species, especially in the study of human evolution and the history of geographic dispersal of Homo sapiens. (Abstract shortened by UMI.) ^

Provenance versus weathering control on the composition of tropical river mud (southern Africa)

This study presents an integrated mineralogical-geochemical data base on fine-grained sediments transported by all major rivers of southern Africa, including the Zambezi, Okavango, Limpopo, Olifants, Orange and Kunene. Clay mineralogy, bulk geochemistry, Sr and Nd isotopic signatures of river mud, considered as proxy of suspended load, are used to investigate the influence of source-rock lithology and weathering intensity on the composition of clay and silt produced in subequatorial to subtropical latitudes. Depletion in mobile alkali and alkaline-earth metals, minor in arid Namibia, is strong in the Okavango, Kwando and Upper Zambezi catchments, where recycling is also extensive. Element removal is most significant for Na, and to a lesser extent for Sr. Depletion in K, Ca and other elements, negligible in Namibia, is moderate elsewhere. The most widespread clay minerals are smectite, dominant in muds derived from Karoo or Etendeka flood basalts, or illite and chlorite, dominant in muds derived from metasedimentary rocks of the Damara Orogen or Zimbabwe Craton. Kaolinite represents 30-40% of clay minerals only in Okavango and Upper Zambezi sediments sourced in humid subequatorial Angola and Zambia. After subtracting the effects of recycling and of local accumulation of authigenic carbonates in soils, the regional distribution of clay minerals and chemical indices consistently reflect weathering intensity primarily controlled by climate. Bulk geochemistry identifies most clearly volcaniclastic sediments and mafic sources in general, but cannot discriminate the other sources of detritus in detail. Instead, Sr and Nd isotopic fingerprints are insensitive to weathering, and thus mirror faithfully the tectonic structure of the southern African continent. Isotopic tools thus represent a much firmer basis than bulk geochemistry or clay mineralogy in the provenance study of mudrocks.

The Chemical Space of Flavours

The flavour of foods is determined by the interaction of taste molecules with receptors in the mouth, and fragrances or aroma with receptors in the upper part of the nose. Here, we discuss the properties of taste and fragrance molecules, from the public databases Superscent, Flavornet, SuperSweet and BitterDB, taken collectively as flavours, in the perspective of the chemical space. We survey simple descriptor profiles in comparison with the public collections ChEMBL (bioactive small molecules), ZINC (commercial drug-like molecules) and GDB-13 (all possible organic molecules up to 13 atoms of C, N, O, S, Cl). A global analysis of the chemical space of flavours is also presented based on molecular quantum numbers (MQN) and SMILES fingerprints (SMIfp). While taste molecules span a very broad property range, fragrances occupy a narrow area of the chemical space consisting of generally very small and relatively nonpolar molecules distinct of standard drug molecules. Proximity searching in the chemical space is exemplified as a simple method to facilitate the search for new fragrances.

A Time-based Passive Source Localization System for Narrow-band Signal

Time-based indoor localization has been investigated for several years but the accuracy of existing solutions is limited by several factors, e.g., imperfect synchronization, signal bandwidth and indoor environment. In this paper, we compare two time-based localization algorithms for narrow-band signals, i.e., multilateration and fingerprinting. First, we develop a new Linear Least Square (LLS) algorithm for Differential Time Difference Of Arrival (DTDOA). Second, fingerprinting is among the most successful approaches used for indoor localization and typically relies on the collection of measurements on signal strength over the area of interest. We propose an alternative by constructing fingerprints of fine-grained time information of the radio signal. We offer comprehensive analytical discussions on the feasibility of the approaches, which are backed up by evaluations in a software defined radio based IEEE 802.15.4 testbed. Our work contributes to research on localization with narrow-band signals. The results show that our proposed DTDOA-based LLS algorithm obviously improves the localization accuracy compared to traditional TDOA-based LLS algorithm but the accuracy is still limited because of the complex indoor environment. Furthermore, we show that time-based fingerprinting is a promising alternative to power-based fingerprinting.

Melanotic tumors of the nervous system are characterized by distinct mutational, chromosomal and epigenomic profiles.

Melanotic tumors of the nervous system show overlapping histological characteristics but differ substantially in their biological behavior. In order to achieve a better delineation of such tumors, we performed an in-depth molecular characterization. Eighteen melanocytomas, 12 melanomas, and 14 melanotic and 14 conventional schwannomas (control group) were investigated for methylome patterns (450k array), gene mutations associated with melanotic tumors and copy number variants (CNVs). The methylome fingerprints assigned tumors to entity-specific groups. Methylation groups also showed a substantial overlap with histology-based diagnosis suggesting that they represent true biological entities. On the molecular level, melanotic schwannomas were characterized by a complex karyotype with recurrent monosomy of chromosome 22q and variable whole chromosomal gains and recurrent losses commonly involving chromosomes 1, 17p and 21. Melanocytomas carried GNAQ/11 mutations and presented with CNV involving chromosomes 3 and 6. Melanomas were frequently mutated in the TERT promoter, harbored additional oncogene mutations and showed recurrent chromosomal losses involving chromosomes 9, 10 and 6q, as well as gains of 22q. Together, melanotic nervous system tumors have several distinct mutational and chromosomal alterations and can reliably be distinguished by methylome profiling.

Use of pulsed-field gel electrophoresis in surveillance of Salmonella in Houston, Texas

Background. Pulsed-field gel electrophoresis (PFGE) is a laboratory technique in which Salmonella DNA banding patterns are used as molecular fingerprints for epidemiologic study for "PFGE clusters". State and national health departments (CDC) use PFGE to detect clusters of related cases and to discover common sources of bacteria in outbreaks. ^ Objectives. Using Houston Department of Health and Human Services (HDHHS) data, the study sought: (1) to describe the epidemiology of Salmonella in Houston, with PFGE subtype as a variable; and (2) to determine whether PFGE patterns and clusters detected in Houston were local appearances of PFGE patterns or clusters that occurred statewide. ^ Methods. During the years 2002 to 2005, the HDHHS collected and analyzed data from routine surveillance of Salmonella. We implemented a protocol, between May 1, 2007 and December 31, 2007, in which PFGE patterns from local cases were sent via e-mail to the Texas Department of State Health Services, to verify whether the local PFGE patterns were also part of statewide clusters. PFGE was performed from 106 patients providing a sample from which Salmonella was isolated in that time period. Local PFGE clusters were investigated, with the enhanced picture obtained by linking local PFGE patterns to PFGE patterns at the state and national level. ^ Results. We found that, during the years 2002 to 2005, there were 66 PFGE clusters, ranging in size from 2 to 22 patients within each cluster. Between different serotypes, there were marked differences in the sizes of PFGE clusters. A common source or risk factor was found in fewer than 5 of the 66 PFGE clusters. With the revised protocol, we found that 19 of 66 local PFGE patterns were indistinguishable from PFGE patterns at Texas DSHS. During the eight months, we identified ten local PFGE clusters with a total of 42 patients. The PFGE pattern for eight of the ten clusters matched the PFGE patterns for cases reported to Texas DSHS from other geographic areas. Five of the ten PFGE patterns matched PFGE patterns for clusters under investigation at PulseNet at the national level. HDHHS epidemiologists identified a mode of transmission in two of the ten local clusters and a common risk factor in a third local cluster. ^ Conclusion. In the extended-study protocol, Houston PFGE patterns were linked to patterns seen at the state and national level. The investigation of PFGE clusters was more efficacious in detecting a common transmission when local data were linked to state and national data. ^

INTEGRATIVE BIOMARKER IDENTIFICATION AND CLASSIFICATION USING HIGH THROUGHPUT ASSAYS

It is well accepted that tumorigenesis is a multi-step procedure involving aberrant functioning of genes regulating cell proliferation, differentiation, apoptosis, genome stability, angiogenesis and motility. To obtain a full understanding of tumorigenesis, it is necessary to collect information on all aspects of cell activity. Recent advances in high throughput technologies allow biologists to generate massive amounts of data, more than might have been imagined decades ago. These advances have made it possible to launch comprehensive projects such as (TCGA) and (ICGC) which systematically characterize the molecular fingerprints of cancer cells using gene expression, methylation, copy number, microRNA and SNP microarrays as well as next generation sequencing assays interrogating somatic mutation, insertion, deletion, translocation and structural rearrangements. Given the massive amount of data, a major challenge is to integrate information from multiple sources and formulate testable hypotheses. This thesis focuses on developing methodologies for integrative analyses of genomic assays profiled on the same set of samples. We have developed several novel methods for integrative biomarker identification and cancer classification. We introduce a regression-based approach to identify biomarkers predictive to therapy response or survival by integrating multiple assays including gene expression, methylation and copy number data through penalized regression. To identify key cancer-specific genes accounting for multiple mechanisms of regulation, we have developed the integIRTy software that provides robust and reliable inferences about gene alteration by automatically adjusting for sample heterogeneity as well as technical artifacts using Item Response Theory. To cope with the increasing need for accurate cancer diagnosis and individualized therapy, we have developed a robust and powerful algorithm called SIBER to systematically identify bimodally expressed genes using next generation RNAseq data. We have shown that prediction models built from these bimodal genes have the same accuracy as models built from all genes. Further, prediction models with dichotomized gene expression measurements based on their bimodal shapes still perform well. The effectiveness of outcome prediction using discretized signals paves the road for more accurate and interpretable cancer classification by integrating signals from multiple sources.

Sedimentology, magnetics and chemistry on palaeolake core D100 from the Gobi Desert

The Gaxun Nur Basin in arid China is tectonically influenced by the left-lateral displacements along the Gobi-Altay and Qilian Shan shear zones, resulting in a large pull-apart basin with strong subsidence in the interior. The up to 300 m thick basin fills consist of fluvio-lacustrine fine-grained deposits mainly transported by river discharges from the Tibetan Plateau. They led to a large depositional area of more than 28,000 qkm in size with presently dry terminal lakes at the outer edges. This vast area serves as a main source for loess transport to south-eastern regions of China (Loess Plateau) caused by the variable winter monsoon. Based on geochemical and sedimentological analyses of the sediment core D100 retrieved from a deep drilling in the centre of the Gaxun Nur Basin following questions have to be answered: 1. Reconstruction of the water balance and determination of hydrological cycles during interglacial and glacial periods. 2. Reconstructing variations in lacustrine environment and aeolian activities with respect to transitional phases fro, warm to cold stages (MIS 4 to 5 and older stages). 3. Establishing a sustainable chronology for the last 250 ka.

(Appendix A) Geochemical composition of snow and eolian mineral dust from Berkner Island ice sheet, Antarctica

The Sr and Nd isotopic composition of dust extracted from recent snow layers at the top of Berkner Island ice sheet (located within the Filchner-Ronne Ice Shelf at the southern end of the Weddell Sea) enables us, for the first time, to document dust provenance in Antarctica outside the East Antarctic Plateau (EAP) where all previous studies based on isotopic fingerprinting were carried out. Berkner dust displays an overall crust-like isotopic signature, characterized by more radiogenic 87Sr/86Sr and much less radiogenic 143Nd/144Nd compared to dust deposited on the EAP during glacial periods. Differences with EAP interglacial dust are not as marked but still significant, indicating that present-day Berkner dust provenance is distinct, at least to some extent, from that of the dust reaching the EAP. The fourteen snow-pit sub-seasonal samples that were obtained span a two-year period (2002-2003) and their dust Sr and Nd isotopic composition reveals that multiple sources are at play over a yearly time period. Southern South America, Patagonia in particular, likely accounts for part of the observed spring/summer dust deposition maxima, when isotopic composition is shifted towards 'younger' isotopic signatures. In the spring, possible additional inputs from Australian sources would also be supported by the data. Most of the year, however, the measured isotopic signatures would be best explained by a sustained background supply from putative local sources in East Antarctica, which carry old-crust-like isotopic fingerprints. Whether the restricted East Antarctic ice-free areas produce sufficient eolian material has yet to be substantiated however. The fact that large (> 5 µm) particles represent a significant fraction of the samples throughout the entire time-series supports scenarios that involve contributions from proximal sources, either in Patagonia and/or Antarctica (possibly including snow-free areas in the Antarctic Peninsula and other areas as well). This also indicates that additional dust transport, which does not reach the EAP, must occur at low-tropospheric levels to this coastal sector of Antarctica.