Regulation der Stress-aktivierten Proteinkinasen durch den gentoxischen Benzo[a]pyren-Metaboliten BPDE

Polyzyklische aromatische Kohlenwasserstoffe (PAK) sind ubiquitäre Verschmutzungen der Umwelt und entstehen während der unvollständigen Verbrennung organischen Materials wie Holz, Kohle und Erdöl. Werden diese chemisch nicht reaktiven PAK in den Körper aufgenommen, durchlaufen sie eine Reihe von enzymatischen Umsetzungen, die unter der Bezeichnung Fremdstoffmetabolismus zusammengefasst werden. Die chemische Umsetzung des PAK und Prokarzinogens Benzo[a]pyren (B[a]P) führt u.a. zur Bildung des reaktiven Metaboliten B[a]P-7,8-dihydrodiol-9,10-epoxid (BPDE). BPDE ist stark elektrophil und kann auf Grund dieser Eigenschaft an nukleophile Makromoleküle wie Proteine und DNA binden. Die Bildung von BPDE-DNA-Addukten resultiert in der Entstehung von Mutationen und kann zur Tumorbildung führen. Im Rahmen der vorliegenden Arbeit sollte die Wirkung von BPDE als Modellsubstanz für gentoxische Agenzien auf intrazelluläre Signalkaskaden und die Konsequenzen der BPDE-Exposition bezüglich der Zellaktivität untersucht werden. Es konnte gezeigt werden, dass BPDE-Behandlung von Mausfibroblasten eine intrazelluläre Signalkaskade induziert, welche zur Aktivierung der Stressaktivierten Proteinkinasen (SAPK) JNK und p38 führt. An dieser Signalkaskade sind Src-ähnliche Kinasen beteiligt. BPDE-Behandlung führt in den untersuchten Mausfibroblasten zur Induktion von DNA-Einzelstrangbrüchen, deren Auftreten zeitlich mit der SAPK-Aktivierung korreliert. Die BPDEinduzierten DNA-Strangbrüche sind die Folge der Entfernung dieser Läsionen aus dem Genom durch die Nukleotidexzisionsreparatur (NER). Erkannt werden BPDE-DNA-Addukte durch die NERProteine XPA und XPC (Xeroderma Pigmentosum Komplementationsgruppe A und C). Nach der Erkennung von BPDE-DNA-Addukten kommt es zur Rekrutierung von Nukleasen, welche die vorliegende Läsion und umliegende Nukleotide aus dem Genom entfernen. In XPA- und XPCdefizienten Mausfibroblasten induziert BPDE daher keine DNA-Strangbrüche. Jedoch ist nur in XPCdefizienten Zellen, aber nicht in XPA-defizienten Zellen, die SAPK-Aktivierung drastisch reduziert. Behandlung von Mausfibroblasten mit Benzo[c]phenanthren-3,4-Diol-1,2-Epoxid, einem PAK, dessen DNA-Addukte schlecht durch NER-Faktoren erkannt und repariert werden, führt zu keiner SAPKAktivierung. Die Aktivierung von p38 und JNK scheint demnach abhängig zu sein von der Erkennung des primären DNA-Schadens. Die XPC-abhängige SAPK-Aktivierung schützt die Zellen vor BPDEabhängiger Toxizität, da sowohl XPC- als auch p38-defiziente Mausfibroblasten eine höhere Sensitivität gegenüber BPDE zeigen als korrespondierende Wildtypzellen. Zusamenfassend konnte in dieser Arbeit ein neuer Signalweg beschrieben werden, in dem DNASchäden, verursacht durch BPDE, über die XPC-abhängige DNA-Schadenserkennung, die Aktivierung der SAPK induziert. Diese Aktivierung der SAPK schützt vor BPDE-induzierter Toxizität.

Studio di Flow-Assurance e sensitivity analysis in sistemi di distribuzione di petrolio e gas naturale

Argomento del lavoro è stato lo studio di problemi legati alla Flow-Asurance. In particolare, si focalizza su due aspetti: i) una valutazione comparativa delle diverse equazioni di stato implementate nel simulatore multifase OLGA, per valutare quella che porta a risultati più conservativi; ii) l’analisi della formazione di idrati, all’interno di sistemi caratterizzati dalla presenza di gas ed acqua. Il primo argomento di studio nasce dal fatto che per garantire continuità del flusso è necessario conoscere il comportamento volumetrico del fluido all’interno delle pipelines. Per effettuare tali studi, la Flow-Assurance si basa sulle Equazioni di Stato cubiche. In particolare, sono state confrontate: -L’equazione di Soave-Redlich-Kwong; -L’equazione di Peng-Robinson; -L’equazione di Peng-Robinson modificata da Peneloux. Sono stati analizzati 4 fluidi idrocarburici (2 multifase, un olio e un gas) con diverse composizioni e diverse condizioni di fase. Le variabili considerate sono state pressione, temperatura, densità e viscosità; sono state poi valutate le perdite di carico, parametro fondamentale nello studio del trasporto di un fluido, valutando che l'equazione di Peng-Robinson è quella più adatta per caratterizzare termodinamicamente il fluido durante una fase di design, in quanto fornisce l'andamento più conservativo. Dopo aver accertato la presenza di idrati nei fluidi multifase, l’obiettivo del lavoro è stato analizzare come il sistema rispondesse all’aggiunta di inibitori chimici per uscire dalla regione termodinamica di stabilità dell’idrato. Gli inibitori utilizzati sono stati metanolo e mono-etilen-glicole in soluzione acquosa. L’analisi è stata effettuata confrontando due metodi: -Metodo analitico di Hammerschmidt; -Metodo iterativo con PVTSim. I risultati ottenuti hanno dimostrato che entrambi gli inibitori utilizzati risolvono il problema della formazione di idrato spostando la curva di stabilità al di fuori delle pressioni e temperature che si incontrano nella pipeline. Valutando le quantità da iniettare, il metodo di Hammerschmidt risulta quello più conservativo, indicando portate maggiori rispetto al PVTsim, soprattutto aggiungendo metanolo.

Investigation of using waste engine oil blended with reclaimed asphalt materials to improve pavement recyclability

With the increasing importance of conserving natural resources and moving toward sustainable practices, the aging transportation infrastructure can benefit from these ideas by improving their existing recycling practices. When an asphalt pavement needs to be replaced, the existing pavement is removed and ground up. This ground material, known as reclaimed asphalt pavement (RAP), is then added into new asphalt roads. However, since RAP was exposed to years of ultraviolet degradation and environmental weathering, the material has aged and cannot be used as a direct substitute for aggregate and binder in new asphalt pavements. One material that holds potential for restoring the aged asphalt binder to a usable state is waste engine oil. This research aims to study the feasibility of using waste engine oil as a recycling agent to improve the recyclability of pavements containing RAP. Testing was conducted in three phases, asphalt binder testing, advanced asphalt binder testing, and laboratory mixture testing. Asphalt binder testing consisted of dynamic shear rheometer and rotational viscometer testing on both unaged and aged binders containing waste engine oil and reclaimed asphalt binder (RAB). Fourier Transform Infrared Spectroscopy (FTIR) testing was carried out to on the asphalt binders blended with RAB and waste engine oil compare the structural indices indicative of aging. Lastly, sample asphalt samples containing waste engine oil and RAP were subjected to rutting testing and tensile strength ratio testing. These tests lend evidence to support the claim that waste engine oil can be used as a rejuvenating agent to chemically restore asphalt pavements containing RAP. Waste engine oil can reduce the stiffness and improve the low temperature properties of asphalt binders blended with RAB. Waste engine oil can also soften asphalt pavements without having a detrimental effect on the moisture susceptibility.

Development of an optimization model for biofuel facility size and location and a simulation model for design of a biofuel supply chain

To mitigate greenhouse gas (GHG) emissions and reduce U.S. dependence on imported oil, the United States (U.S.) is pursuing several options to create biofuels from renewable woody biomass (hereafter referred to as “biomass”). Because of the distributed nature of biomass feedstock, the cost and complexity of biomass recovery operations has significant challenges that hinder increased biomass utilization for energy production. To facilitate the exploration of a wide variety of conditions that promise profitable biomass utilization and tapping unused forest residues, it is proposed to develop biofuel supply chain models based on optimization and simulation approaches. The biofuel supply chain is structured around four components: biofuel facility locations and sizes, biomass harvesting/forwarding, transportation, and storage. A Geographic Information System (GIS) based approach is proposed as a first step for selecting potential facility locations for biofuel production from forest biomass based on a set of evaluation criteria, such as accessibility to biomass, railway/road transportation network, water body and workforce. The development of optimization and simulation models is also proposed. The results of the models will be used to determine (1) the number, location, and size of the biofuel facilities, and (2) the amounts of biomass to be transported between the harvesting areas and the biofuel facilities over a 20-year timeframe. The multi-criteria objective is to minimize the weighted sum of the delivered feedstock cost, energy consumption, and GHG emissions simultaneously. Finally, a series of sensitivity analyses will be conducted to identify the sensitivity of the decisions, such as the optimal site selected for the biofuel facility, to changes in influential parameters, such as biomass availability and transportation fuel price. Intellectual Merit The proposed research will facilitate the exploration of a wide variety of conditions that promise profitable biomass utilization in the renewable biofuel industry. The GIS-based facility location analysis considers a series of factors which have not been considered simultaneously in previous research. Location analysis is critical to the financial success of producing biofuel. The modeling of woody biomass supply chains using both optimization and simulation, combing with the GIS-based approach as a precursor, have not been done to date. The optimization and simulation models can help to ensure the economic and environmental viability and sustainability of the entire biofuel supply chain at both the strategic design level and the operational planning level. Broader Impacts The proposed models for biorefineries can be applied to other types of manufacturing or processing operations using biomass. This is because the biomass feedstock supply chain is similar, if not the same, for biorefineries, biomass fired or co-fired power plants, or torrefaction/pelletization operations. Additionally, the research results of this research will continue to be disseminated internationally through publications in journals, such as Biomass and Bioenergy, and Renewable Energy, and presentations at conferences, such as the 2011 Industrial Engineering Research Conference. For example, part of the research work related to biofuel facility identification has been published: Zhang, Johnson and Sutherland [2011] (see Appendix A). There will also be opportunities for the Michigan Tech campus community to learn about the research through the Sustainable Future Institute.

DESIGN AND FABRICATION OF RESONANT GAS SENSOR FOR HIGH SENSITIVITY IN THE PRESENCE OF AIR DAMPING

Gas sensors have been used widely in different important area including industrial control, environmental monitoring, counter-terrorism and chemical production. Micro-fabrication offers a promising way to achieve sensitive and inexpensive gas sensors. Over the years, various MEMS gas sensors have been investigated and fabricated. One significant type of MEMS gas sensors is based on mass change detection and the integration with specific polymer. This dissertation aims to make contributions to the design and fabrication of MEMS resonant mass sensors with capacitance actuation and sensing that lead to improved sensitivity. To accomplish this goal, the research has several objectives: (1) Define an effective measure for evaluating the sensitivity of resonant mass devices; (2) Model the effects of air damping on microcantilevers and validate models using laser measurement system (3) Develop design guidelines for improving sensitivity in the presence of air damping; (4) Characterize the degree of uncertainty in performance arising from fabrication variation for one or more process sequences, and establish design guidelines for improved robustness. Work has been completed toward these objectives. An evaluation measure has been developed and compared to an RMS based measure. Analytic models of air damping for parallel plate that include holes are compared with a COMSOL model. The models have been used to identify cantilever design parameters that maximize sensitivity. Additional designs have been modeled with COMSOL and the development of an analytical model for Fixed-free cantilever geometries with holes has been developed. Two process flows have been implemented and compared. A number of cantilever designs have been fabricated and the uncertainty in process has been investigated. Variability from processing have been evaluated and characterized.

TIME LAPSE SEISMIC OBSERVATIONS AND EFFECTS OF RESERVOIR COMPRESSIBILITY AT TEAL SOUTH OIL FIELD

One of the original ocean-bottom time-lapse seismic studies was performed at the Teal South oil field in the Gulf of Mexico during the late 1990’s. This work reexamines some aspects of previous work using modern analysis techniques to provide improved quantitative interpretations. Using three-dimensional volume visualization of legacy data and the two phases of post-production time-lapse data, I provide additional insight into the fluid migration pathways and the pressure communication between different reservoirs, separated by faults. This work supports a conclusion from previous studies that production from one reservoir caused regional pressure decline that in turn resulted in liberation of gas from multiple surrounding unproduced reservoirs. I also provide an explanation for unusual time-lapse changes in amplitude-versus-offset (AVO) data related to the compaction of the producing reservoir which, in turn, changed an isotropic medium to an anisotropic medium. In the first part of this work, I examine regional changes in seismic response due to the production of oil and gas from one reservoir. The previous studies primarily used two post-production ocean-bottom surveys (Phase I and Phase II), and not the legacy streamer data, due to the unavailability of legacy prestack data and very different acquisition parameters. In order to incorporate the legacy data in the present study, all three poststack data sets were cross-equalized and examined using instantaneous amplitude and energy volumes. This approach appears quite effective and helps to suppress changes unrelated to production while emphasizing those large-amplitude changes that are related to production in this noisy (by current standards) suite of data. I examine the multiple data sets first by using the instantaneous amplitude and energy attributes, and then also examine specific apparent time-lapse changes through direct comparisons of seismic traces. In so doing, I identify time-delays that, when corrected for, indicate water encroachment at the base of the producing reservoir. I also identify specific sites of leakage from various unproduced reservoirs, the result of regional pressure blowdown as explained in previous studies; those earlier studies, however, were unable to identify direct evidence of fluid movement. Of particular interest is the identification of one site where oil apparently leaked from one reservoir into a “new” reservoir that did not originally contain oil, but was ideally suited as a trap for fluids leaking from the neighboring spill-point. With continued pressure drop, oil in the new reservoir increased as more oil entered into the reservoir and expanded, liberating gas from solution. Because of the limited volume available for oil and gas in that temporary trap, oil and gas also escaped from it into the surrounding formation. I also note that some of the reservoirs demonstrate time-lapse changes only in the “gas cap” and not in the oil zone, even though gas must be coming out of solution everywhere in the reservoir. This is explained by interplay between pore-fluid modulus reduction by gas saturation decrease and dry-frame modulus increase by frame stiffening. In the second part of this work, I examine various rock-physics models in an attempt to quantitatively account for frame-stiffening that results from reduced pore-fluid pressure in the producing reservoir, searching for a model that would predict the unusual AVO features observed in the time-lapse prestack and stacked data at Teal South. While several rock-physics models are successful at predicting the time-lapse response for initial production, most fail to match the observations for continued production between Phase I and Phase II. Because the reservoir was initially overpressured and unconsolidated, reservoir compaction was likely significant, and is probably accomplished largely by uniaxial strain in the vertical direction; this implies that an anisotropic model may be required. Using Walton’s model for anisotropic unconsolidated sand, I successfully model the time-lapse changes for all phases of production. This observation may be of interest for application to other unconsolidated overpressured reservoirs under production.

Insulin signaling and action in cultured skeletal muscle cells from lean healthy humans with high and low insulin sensitivity

The aim of these studies was to investigate whether insulin resistance is primary to skeletal muscle. Myoblasts were isolated from muscle biopsies of 8 lean insulin-resistant and 8 carefully matched insulin-sensitive subjects (metabolic clearance rates as determined by euglycemic-hyperinsulinemic clamp: 5.8 +/- 0.5 vs. 12.3 +/- 1.7 ml x kg(-1) x min(-1), respectively; P < or = 0.05) and differentiated to myotubes. In these cells, insulin stimulation of glucose uptake, glycogen synthesis, insulin receptor (IR) kinase activity, and insulin receptor substrate 1-associated phosphatidylinositol 3-kinase (PI 3-kinase) activity were measured. Furthermore, insulin activation of protein kinase B (PKB) was compared with immunoblotting of serine residues at position 473. Basal glucose uptake (1.05 +/- 0.07 vs. 0.95 +/- 0.07 relative units, respectively; P = 0.49) and basal glycogen synthesis (1.02 +/- 0.11 vs. 0.98 +/- 0.11 relative units, respectively; P = 0.89) were not different in myotubes from insulin-resistant and insulin-sensitive subjects. Maximal insulin responsiveness of glucose uptake (1.35 +/- 0.03-fold vs. 1.41 +/- 0.05-fold over basal for insulin-resistant and insulin-sensitive subjects, respectively; P = 0.43) and glycogen synthesis (2.00 +/- 0.13-fold vs. 2.10 +/- 0.16-fold over basal for insulin-resistant and insulin-sensitive subjects, respectively; P = 0.66) were also not different. Insulin stimulation (1 nmol/l) of IR kinase and PI 3-kinase were maximal within 5 min (approximately 8- and 5-fold over basal, respectively), and insulin activation of PKB was maximal within 15 min (approximately 3.5-fold over basal). These time kinetics were not significantly different between groups. In summary, our data show that insulin action and signaling in cultured skeletal muscle cells from normoglycemic lean insulin-resistant subjects is not different from that in cells from insulin-sensitive subjects. This suggests an important role of environmental factors in the development of insulin resistance in skeletal muscle.

Montana Oil Fields

Since the discovery of oil in Montana in1916, the petroleum industry has advanced to a point where over 5,000,000 barrels of oil worthover $6,500,000 has been produced in each of the three past years (1936, 1937, and 1938).

Oil and Gas Production Methods in Montana

Montana's oil and gas industries aggregate a gross income of over 12,000,000 annually to the state. Oil and gas fields have been thoroughly discussed in liter­ature as to geology, location, production and future possibilities. The specific object of this report has been to compile a comprehensive study of the production methods as they occur.

Report of Investigation on the Physical Characteristics of the Oil Sands from the Cut Bank Field, Montana

The purpose of this research was to study the physical characteristics, mainly, porosity and permeability of the oil sands from the Cut Bank field, Glacier County, Montana. In so doing, a better understanding of the relation­ship of these physical characteristics to one another and to the pool itself could be obtained.

Porosity and Oil Absorption Properties of Metal Compacts of Copper - Tin - Graphite

Powder metallurgy, the most recent innovation in met­allurgical process, is not a new art; although not until recently did it become a matter of general interest, this being due not only to the products formed but also to the possibilities of future developments. The manufacture and application of metal powders is now beginning to take a position as a recognized part of the science of metallurgy.

Permeability and Porosity Studies of the Cut Bank Oil Sand

In studying the Cut Bank field and its numerous wells, it is found that dry holes are surrounded by producing wells, and also that the field as a whole is very irregular; water, oil, and gas zones in many cases following no definite pattern. In some instances, this phenomenon may be due to the lensing and thinning of the producing sands, but it is evident that this is not the only factor. There­fore, the controlling factors must be porosity and permeability.

An Attempt to Increase the Permeability and Porosity of the Cut Bank Oil Sand By Treatment with Various Reagents

The purpose of this investigation was to attempt to find some means of increasing the effective porosity and permeabil­ity of the producing sands of the Cut Bank Oil Field, with the hope that thereby the ultimate recovery of petroleum from this field may be increased. Although the percentage increase in production thus effected would undoubtedly be small, it would represent a substantial volume of petroleum in view of the great quantity of oil and gas present in this field.

Isopach Maps and Discussion of the Ordovician and Devonian of Montana and Adjacent Areas

The intensive postwar search for new petroleum horizons has resulted in widespread prospecting in the northern Great Plains. No commercial production has as yet been derived from Ordovician or Devonian rocks in Montana, but the relat­ively few tests that have penetrated to critical depths have disclosed encouraging conditions which merit further consider­ation, especially in Devonian strata.