Modeling the relationships between urinary F2-isoprostanes, BMI, and risk of type 2 diabetes

Type 2 diabetes (T2DM) is a chronic condition affecting 1 in every 10 adults in the United States. There is evidence that individuals with greater levels of F2-isoprostanes at similar levels of adiposity have reduced risk of T2DM. F2-isprostanes have been validated as markers of oxidative status in animal and human studies. Many cross-sectional studies found correlations between F2-isprostanes and adiposity measured as body mass index (BMI). The connection of F2-isprostanes to the lower risk of diabetes and BMI suggests that these markers can be interpreted as a part of some compensatory mechanisms involved in metabolic adaptation to body fat accumulation. The purpose of this study was to compare the additive relationship between BMI, as a measure of adiposity, and 2,3-dinor-iPF2α-III (F2-isoP), as a measure of adaptation to increased BMI, to a model that proposes multiplicative relationships between F2-isoP to BMI expressed by the ratio of F2-isoP to BMI. The present analysis utilizes data from the Insulin Resistance Atherosclerosis Study (IRAS), a multicenter prospective cohort designed to study the relationships between insulin resistance, type 2 diabetes, cardiovascular disease risk factors and behaviors in a diverse population including non-Hispanic whites, African Americans, and Hispanics. Between October 1992 and April 1994 approximately 1625 participants, between 40-69 years of age at baseline, were recruited from four U.S. clinical centers located in San Antonio, TX; San Luis Valley, CO; Oakland, CA; Los Angeles, CA. Wilcoxon-rank sum/ Kruskal-Wallis tests and Wald-chi-square test were used to describe the study population. Logistic regression models were used assess the relationships between the exposures of interest as well as age, gender, race/ethnicity, glucose tolerance status. The additive model estimated the association between F2-isoP and the risk of T2DM with BMI being a covariate. The multiplicative model estimated the association between F2-isoP/BMI ratio, F2-isoP and the risk of T2DM. Percent differences of odds ratios were calculated between the two models, with \u3e10% difference indicating meaningful change. The results from the analysis show that the new variable F2-isoP/BMI ratio does not clearly indicate whether the multiplicative model represents a better way to evaluate the relationships between F2-isoP, BMI and risk for T2DM. Evaluation of the additive and multiplicative models for outcomes—such as weight change, decrease in insulin resistance, blood pressure and others—might clarify whether the additive or multiplicative relationships, between F2-isoP and BMI, better predict these outcomes

Optimization of the anaerobic digestion process by substrate pretreatment and the application of NIRS

Biogas production is a complex process depending on many factors and is an area that is being researched intensively. This thesis is based on studies that were aimed at optimizing the biogas production process by:• Reducing the time taken to assess the biochemical methane potentials (BMP) of substrates (specifically meadow grasses) by rapid analytical methods such as near infra-red spectroscopy (NIRS), in-vitro organic matter digestibility assay and the neutral detergent fibre assay• Applying NIRS as a monitoring tool to assess the concentrations of ammonia (which is inhibitory to the process) in the contents of anaerobic digesters.• Improving the BMP of materials such as cattle manure and dewatered pig manure and chicken manure by thermal pre-treatment at various temperatures between 100°C and 225°CResults show that the NIRS method can be used to discriminate between meadow grasses with high or low BMP. In detecting the ammonia content, NIRS was shown to have the potential to be a process monitoring tool. Thermal pre-treatment proved to be most effective on dewatered pig manure which showed improvements at lower pretreatment temperatures. Cattle manure required pre-treatment temperatures higher than 175°C to show improvement. Chicken manure did not show any improvements but instead showed a decrease in BMP at 225°C

Mass Spectrometry Based Quantification of 1, 3-Butadiene Induced DNA Adducts: Potential Biomarkers of Cancer Risk

University of Minnesota Ph.D. dissertation. November 2014. Major: Medicinal Chemistry. Advisor: Natalia Tretyakova. 1 computer file (PDF); xxiii, 300 pages.Chemical carcinogenesis involves metabolic activation of carcinogens to electrophilic species which can react with important cellular biomolecules including DNA to form covalent adducts. Covalent carcinogen-DNA adducts which are not removed by DNA repair mechanisms can induce transforming mutations, ultimately leading to cancer. Hence, carcinogen-DNA adducts are deemed the ultimate biomarkers of carcinogen exposure, metabolic activation, and possibly of cancer risk. 1,3-Butadiene (BD) is a recognized human and animal carcinogen present in cigarette smoke, automobile exhaust, wood fires, and also in some occupational settings such as BD monomer and polymer plants. BD is metabolically activated by CYP2E1 to form three electrophilic epoxides: 3,4-epoxy-1-butene (EB), 3,4-epoxy-1,2-butanediol (EBD), and 1,2,3,4-diepoxybutane (DEB). EB, EBD, and DEB can modify DNA bases to form covalent DNA adducts such as N-7-(1-hydroxy-3-buten-2-yl) guanine (EB-GII), N7-(2, 3, 4-trihydroxybut-1-yl)-guanine (N7-THBG) and 1,4-bis-(guan-7-yl)-2,3-butanediol (bis-N7G-BD). Although BD-DNA adducts had been successfully detected and quantified in tissues of laboratory animals exposed to relatively high concentrations of BD ( ≥ 6.25 ppm), they had not been previously quantified in humans, preventing their use as biomarkers of BD exposure, metabolic activation, and cancer risk. The main purpose of this research was to develop ultra-sensitive bioanalytical methodologies based on mass spectrometry to enable the detection and quantitation of BD-DNA adducts in animals treated with sup-ppm levels of BD and in exposed human populations. In Chapter 2 of the thesis, a novel nanoHPLC-nanoESI+-MS/MS method was developed for sensitive, accurate, and precise quantitation of BD-induced guanine-guanine cross-links (1,4-bis-(guan-7-yl)-2,3,-butanediol, bis-N7G-BD) in tissues of laboratory mice treated with low - sub-ppm concentrations of BD (0.5-1.5 ppm) which approximate human occupational exposure to BD (1 ppm). Bis-N7G-BD concentrations increased in a concentration-dependent manner in mouse liver DNA as a function of BD exposure. In Chapter 3 of this Thesis, we investigated DNA repair mechanisms responsible for bis-N7G-BD repair using isogenic Chinese hamster lung fibroblasts proficient or deficient in nucleotide excision repair (NER) and Fanconi Anemia (FA) repair pathways. We found that while both pathways contributed to bis-N7G-BD removal, FA pathway was most effective at alleviating the toxicity and replication blockage imposed by bis-N7G-BD cross-links. To enable BD-DNA adduct detection in humans, we developed an isotope dilution capillary HPLC-ESI+-HRMS/MS methodology for the most abundant BD-DNA adducts identified in vivo: N7-(2,3,4-trihydroxybut-1-yl)-guanine (N7-THBG) (Chapter 4). This method was successfully applied to quantify N7-THBG adducts in blood leukocyte DNA of smokers, nonsmokers, and occupationally exposed workers. In addition, we have developed an isotope dilution nanoLC/ESI+-HRMS3 methodology for the quantitation of BD-induced N-7-(1-hydroxy-3-buten-2-yl) guanine (EB-GII) adducts in human blood leukocyte DNA and human urine (Chapters 5 and 6). This method was applied to quantify EB-GII adducts in blood and urine of BD-exposed populations such as smokers, nonsmokers, and occupationally exposed workers. Overall, during the course of the studies described in this Thesis, we have developed a range of novel mass spectrometry-based quantitative methods which have excellent sensitivity, accuracy, and precision, and can be used for future human BD exposure biomonitoring studies. Furthermore, these methodologies are now being employed in epidemiological studies to identify any ethnic/racial differences in BD bioactivation and to help understand the origins of ethnic/racial differences in lung cancer risk in smokers

High pressure pyrolyzed non-precious metal oxygen reduction catalysts for alkaline polymer electrolyte membrane fuel cells

Non-precious metal catalysts, such as metal-coordinated to nitrogen doped-carbon, have shown reasonable oxygen reduction reaction (ORR) performances in alkaline fuel cells. In this report, we present the development of a highly active, stable and low-cost non-precious metal ORR catalyst by direct synthesis under autogenic-pressure conditions. Transmission electron microscopy studies show highly porous Fe-N-C and Co-N-C structures, which were further confirmed by Brunauer-Emmett-Teller surface area measurements. The surface areas of the Fe-N-C and Co-N-C catalysts were found to be 377.5 and 369.3 m2 g-1, respectively. XPS results show the possible existence of N-C and M-Nx structures, which are generally proposed to be the active sites in non-precious metal catalysts. The Fe-N-C electrocatalyst exhibits an ORR half-wave potential 20 mV higher than the reference Pt/C catalyst. The cycling durability test for Fe-N-C over 5000 cycles shows that the half-wave potential lost only 4 mV, whereas the half-wave potential of the Pt/C catalyst lost about 50 mV. The Fe-N-C catalyst exhibited an improved activity and stability compared to the reference Pt/C catalyst and it possesses a direct 4-electron transfer pathway for the ORR process. Further, the Fe-N-C catalyst produces extremely low HO2- content, as confirmed by the rotating ring-disk electrode measurements. In the alkaline fuel single cell tests, maximum power densities of 75 and 80 mW cm-2 were observed for the Fe-N-C and Pt/C cathodes, respectively. Durability studies (100 h) showed that decay of the fuel cell current was more prominent for the Pt/C cathode catalyst compared to the Fe-N-C cathode catalyst. Therefore, the Fe-N-C catalyst appears to be a promising new class of non-precious metal catalysts prepared by an autogenic synthetic method. © The Royal Society of Chemistry 2015.

Effects of high-temperature isochoric pre-treatment on the methane yields of cattle, pig and chicken manure

Cattle manure, dewatered pig manure and chicken manure were pre-treated in a high-temperature reactor under isochoric conditions for 15 min at temperatures between 100 and 225 ◦ C with 25 ◦ C intervals to study the effect on their methane yield. After 27 days of batch incubation, cattle manure showed a significant improvement in its biochemical methane potential (BMP) of 13% at 175 ◦ C and 21% at 200 ◦ C. Pig manure showed improvements at temperatures of 125 C and above, with a maximum 29% increase in yield at 200 ◦ C. The BMP of chicken manure was reduced by 18% at 225 C, but at lower temperatures there were no significant changes. It was found that this method of pre-treatment could be feasible if sufficient surplus energy was available or if the energy used in the pre-treatment could be recovered. Keywords: BMP; manure; biogas; thermal; pre-treatment; energy requirement

Metal induced crystallization of silicon thin films

Low temperature crystallization of thin film silicon is important for many industrial applications including flat panel displays and silicon thin film solar cells. Unfortunately this remains a major challenge since crystallization temperature of silicon is above 1,000 degrees Celsius, thus limiting to substrates that can tolerate high temperatures. The inability to deposit crystalline thin films on glass substrates is the reason why flat panel display industry uses amorphous silicon for LCD active matrix displays. Thus the ability to deposit crystallized thin film silicon at low temperatures will have significant impact on thin film silicon applications. It has been observed that certain metals can lower the crystallization temperature of silicon; however, investigation in this area has been rather limited. This thesis investigates the effect of two different metals, aluminum and silver, on the dependence of crystallization temperature of silicon thin films and investigates the properties of such materials

NanoHPLC-nanoESI + -MS/MS Quantitation of Bis -N7-Guanine DNA–DNA Cross-Links in Tissues of B6C3F1 Mice Exposed to subppm Levels of 1,3-Butadiene

1,3-butadiene (BD) is an important industrial chemical and a common environmental pollutant present in urban air. BD is classified as a human carcinogen based on epidemiological evidence for an increased incidence of leukemia in workers occupationally exposed to BD and its potent carcinogenicity in laboratory mice. A diepoxide metabolite of BD, 1,2,3,4-diepoxybutane (DEB), is considered the ultimate carcinogenic species of BD due to its ability to form genotoxic DNA-DNA cross-links. We have previously employed capillary HPLC-ESI+-MS/MS methods to quantify DEB-induced DNA-DNA conjugates, e.g. 1,4-bis-(guan-7-yl)-2,3-butanediol (bis-N7G-BD), 1-(guan-7-yl)-4-(aden-1-yl)-2,3-butanediol (N7G-N1A-BD), and 1,N6-(1-hydroxymethyl-2-hydroxypropan-1,3-diyl)-2′-deoxyadenosine (1,N6-HMHP-dA), in tissues of laboratory mice exposed to 6.25 – 625 ppm BD (Goggin et al. Cancer Research 69(6), 2479–2486, 2009). However, typical BD human exposure levels are 0.01 to 3.2 ppb in urban air and 1– 2.0 ppm in an occupational setting, requiring greater detection sensitivity for these critical lesions. In the present study, a nanoHPLC-nanoESI+-MS/MS method was developed for ultra-sensitive, accurate, and precise quantitation of bis-N7G-BD in tissues of laboratory mice treated with low ppm and sub-ppm concentrations of BD. The LOD value of the new method is 0.5 fmol/100 μg DNA, and the LOQ is 1.0 fmol/100 μg DNA, making it possible to quantify bis-N7G-BD adducts present at concentrations of 3 per 109 nucleotides. Bis-N7G-BD adduct amounts in liver tissues of mice exposed to 0.5, 1.0, 1.5 ppm BD for 2 weeks were 5.7 ± 3.3, 9.2 ± 1.5, and 18.6 ± 6.9 adducts per 109 nucleotides, respectively, suggesting that N7G-BD adduct formation is more efficient under low exposure conditions. To our knowledge, this is the first quantitative analysis of DEB specific DNA adducts following low ppm and sub-ppm exposure to BD

Can NLP Models 'Identify', 'Distinguish', and 'Justify' Questions that Don't have a Definitive Answer?

Though state-of-the-art (SOTA) NLP systems have achieved remarkable performance on a variety of language understanding tasks, they primarily focus on questions that have a correct and a definitive answer. However, in real-world applications, users often ask questions that don't have a definitive answer. Incorrectly answering such questions certainly hampers a system's reliability and trustworthiness. Can SOTA models accurately identify such questions and provide a reasonable response? To investigate the above question, we introduce QnotA, a dataset consisting of five different categories of questions that don't have definitive answers. Furthermore, for each QnotA instance, we also provide a corresponding QA instance i.e. an alternate question that ''can be'' answered. With this data, we formulate three evaluation tasks that test a system's ability to 'identify', 'distinguish', and 'justify' QnotA questions. Through comprehensive experiments, we show that even SOTA models including GPT-3 and Flan T5 do not fare well on these tasks and lack considerably behind the human performance baseline. We conduct a thorough analysis which further leads to several interesting findings. Overall, we believe our work and findings will encourage and facilitate further research in this important area and help develop more robust models.Comment: TrustNLP Workshop at ACL 202