Ethylene is an endogenously synthesized plant hormone that dissipates quickly in field conditions and seldom exceeds five nmol mol-1. Ethylene can accumulate to 1000 times this level in closed environments. The best-known effects of ethylene are its impacts on fruit ripening and senescence, yet ethylene influences growth and development throughout the plant life cycle. At low, continuous concentrations (20 to 50 nmol mol-1), ethylene reduces yield of many plants. Clean-air treatment during critical stages of floral development, silver thiosulfate (STS), and 1-methylcyclopropene (1- MCP) may delay flower senescence and reduce the detrimental effects of ethylene on peas and tomatoes grown in continuous ethylene. There is evidence of species differences in ethylene sensitivity, but limited information on cultivar differences. To address these issues, ethylene sensitivity of two dwarf tomato cultivars, Micro-Tom and Micro-Tina, and one dwarf pea cultivar, Earligreen, was examined. Ethylene by temperature interactions were examined in tomatoes at 0, 20, and 40 nmol mol-1 ethylene and 22 and 28°C. Three-day-long clean-air treatments were applied to tomatoes from germination through fruit set to identify the most ethylene-sensitive stage of floral development. The actions and toxicities of STS and 1-MCP were compared. Ethylene sensitivities of the two closely related dwarf tomato cultivars were examined. At 22°C, the 20 and 40 nmol mol-1 red fruit yields were 51 and 11 % of control. At 28°C, yields were 37 and 4% of control. Vegetative growth at 20 and 40 nmol mol-1 was 96 and 91 % of control, at both temperatures. Three-day-long clean-air treatments from days 22 to 33 (axillary flower opening) improved fruit set and final yield. Floral bud abortion in elevated ethylene occurred primarily at or before microsporogenesis. Floral bud initiation and vegetative development were not significantly affected. Tomato plants grown in continuous 70 nmol mol-1 ethylene conditions retained only 3% of the total number of floral buds initiated. STS-treated plants retained 50 to 54% of their floral buds. Leaf area of plants subjected to 100 nmol mol-1 ethylene was 26% of control, and plants subjected to 200 nmol mol-1 ethylene were 21 % of control. When plants were treated daily for 10 hours with 35 nmol mol-1 l-MCP, leaf area improved to 81 and 64% of control. Manipulating temperature had neither a statistically nor a biologically significant effect on ethylene sensitivity. Ethylene reduced yield primarily by arresting floral bud development and causing early floral bud senescence. Both STS and 1-MCP looked promising for improving yield in high ethylene environments, but concentrations and durations of application need to be further refined. Yield of Micro-Tom was significantly less sensitive to ethylene than Micro-Tina. These results indicate that solving ethylene sensitivity issues in controlled environments may be accommodated by cultivar choice as well as timely control of environmental ethylene, chemical inhibitors, and genetic manipulation.

Memory-trace theories of remembering suggest that performance in delayed matching-to-sample (DMTS) procedures depends on a memory trace that degrades with time. By contrast, the theory of direct remembering suggests that increasing the delay between sample and comparison stimuli in DMTS procedures is functionally equivalent to decreasing the disparity between sample stimuli. The present dissertation tested this assumption by assessing the degree to which changes in the frequency of reinforcement for correct choices biased the distribution of choice responses in a conditional-discrimination procedure. Seven pigeons responded under a temporal-discrimination procedure in which temporal sample-stimuli were categorized as being of either short or long duration by a response to a corresponding comparison key. In the sample-stimulus disparity condition, the disparity between the sample stimuli (difference between the short and long samples) was manipulated. In the retention-interval condition, the delay between sample offset and presentation of the comparison stimuli was manipulated. Importantly, the same general procedure was used across conditions, facilitating conclusions regarding functional equivalence of the two manipulations. The theory of direct remembering suggests that the relation between sensitivity of behavior to changes in reinforcer frequency and discriminability (accuracy) should be similar in the sample-stimulus disparity and retention-interval condition. The results showed that discriminability decreased with both the sample-stimulus disparity and retention-interval manipulations. Overall estimates of sensitivity were similar to those obtained previously. There was, however, no difference in the estimates of sensitivity as a function of discriminability during either the sample-stimulus disparity or retention-interval conditions; sensitivity was independent of discriminability. These results are in contrast to most previous reports, and are interpreted in terms of the use of temporal-sample stimuli in the current experiment. Further analyses of the choice-response data showed that the effects of variation in reinforcer ratios differed across conditions as a function of trial type and trial difficulty. These results suggest the need for careful consideration of behavioral outcomes at several levels of analysis when assessing functional equivalence of experimental manipulations. The potential benefits and hindrances of characterization of behavioral outcomes in terms of functional equivalence are discussed.

The pathogenesis of hepatotoxic and hepatocarcinogenic actions of the mycotoxin aflatoxin B1 (AFB1) involves initial bioactivation by microsomal cytochrome P450s (P450) to a reactive and electrophilic intermediate, exo-aflatoxin B1-8,9-epoxide (exo-AFBO). Poultry, especially turkeys, are extremely sensitive to AFB1, a condition associated with efficient epoxidation by P450s. The purpose of this research was to 1) discover and characterize the P450s in turkey liver responsible for AFB1 bioactivation, and 2) determine the relative importance of these P450s in turkey liver. Initial investigations led to the discovery of CYP1A5. We then identified CYP3A37, a human CYP3A4 homologue from turkey liver, which along with CYP1A5 plays an important role in the bioactivation of AFB1 to exo-AFBO. The E. coli-expressed CYP3A37 possessed striking similarities to human CYP3A4, in terms of its catalytic activities and the kinetics of AFB1 oxidation. After the discovery of CYP3A37, further research evaluated its relative importance to CYP1A5, with respect to the epoxidation of AFB1, to determine which of the homologues bioactivated relatively low "real world" AFB1 concentrations, reflective of the potential dietary exposure. Using antibodies directed to both the enzymes as tools in immuno-inhibition experiments, we determined that CYP1A5 contributes to about 98% of the exo-AFBO formation at the low AFB1 concentrations (0.1 µM), which led us to conclude that CYP1A5 is likely the dominant homologue involved in the extreme sensitivity of the turkeys to AFB1. CYP3A37 also efficiently epoxidated AFB1, but only at high concentrations of this mycotoxin, not likely to be achievable in turkey liver in vivo. Our research has helped shed light on the relative importance of CYP1A5 and CYP3A37 in the bioactivation of AFB1 to the toxic exo-AFBO, and thus on the mechanisms of the extreme sensitivity of turkeys to AFB1. Given that AFB1 is a ubiquitous component of corn-based poultry feed and contamination is practically unavoidable, we conducted further studies evaluating the chemopreventive action of probiotic bacteria, Lactobacillus, on AFB1 toxicity in turkeys. Probiotic bacteria are known to bind AFB1, thus reducing its bioavailability. A mix of probiotic bacteria provided protection against key endpoints of aflatoxicosis, like AFB1-induced reduction in body and liver weights. Our data demonstrate that Lactobacillus was protective against aflatoxicosis in turkeys, thus validating its use as a possible chemopreventive, thereby helping alleviate the significant annual losses to the poultry industry due to feed contamination by AFB1.

Alkali land occurs adjacent to nearly every extensively irrigated area. Much of this land is too alkaline to produce profitable crops. Each year thousands of acres or land are going out of production because or increasing alkalinity. This presents one or the most acute problem which confronts irrigation agriculture today.

The most common design among U.S. nuclear power plants is the pressurized water reactor (PWR). The three primary design disciplines of these plants are system analysis (which includes thermal hydraulics), neutronics, and fuel performance. The nuclear industry has developed a variety of codes over the course of forty years, each with an emphasis within a specific discipline. Perhaps the greatest difficulty in mathematically modeling a nuclear reactor, is choosing which specific phenomena need to be modeled, and to what detail. A multiphysics computational environment provides a means of advancing simulations of nuclear plants. Put simply, users are able to combine various physical models which have commonly been treated as separate in the past. The focus of this work is a specific multiphysics environment currently under development at Idaho National Labs known as the LOCA Toolkit for US light water reactors (LOTUS). The ability of LOTUS to use uncertainty quantification (UQ) and sensitivity analysis (SA) tools within a multihphysics environment allow for a number of unique analyses which to the best of our knowledge, have yet to be performed. These include the first known integration of the neutronics and thermal hydraulic code VERA-CS currently under development by CASL, with the well-established fuel performance code FRAPCON by PNWL. The integration was used to model a fuel depletion case. The outputs of interest for this integration were the minimum departure from nucleate boiling ratio (MDNBR) (a thermal hydraulic parameter indicating how close a heat flux is to causing a dangerous form of boiling in which an insulating layer of coolant vapour is formed), the maximum fuel centerline temperature (MFCT) of the uranium rod, and the gap conductance at peak power (GCPP). GCPP refers to the thermal conductance of the gas filled gap between fuel and cladding at the axial location with the highest local power generation. UQ and SA were performed on MDNBR, MFCT, and GCPP at a variety of times throughout the fuel depletion. Results showed the MDNBR to behave linearly and consistently throughout the depletion, with the most impactful input uncertainties being coolant outlet pressure and inlet temperature as well as core power. MFCT also behaves linearly, but with a shift in SA measures. Initially MFCT is sensitive to fuel thermal conductivity and gap dimensions. However, later in the fuel cycle, nearly all uncertainty stems from fuel thermal conductivity, with minor contributions coming from core power and initial fuel density. GCPP uncertainty exhibits nonlinear, time-dependent behaviour which requires higher order SA measures to properly analyze. GCPP begins with a dependence on gap dimensions, but in later states, shifts to a dependence on the biases of a variety of specific calculation such as fuel swelling and cladding creep and oxidation. LOTUS was also used to perform the first higher order SA of an integration of VERA-CS and the BISON fuel performance code currently under development at INL. The same problem and outputs were studied as the VERA-CS and FRAPCON integration. Results for MDNBR and MFCT were relatively consistent. GCPP results contained notable differences, specifically a large dependence on fuel and clad surface roughness in later states. However, this difference is due to the surface roughness not being perturbed in the first integration. SA of later states also showed an increased sensitivity to fission gas release coefficients. Lastly a Loss of Coolant Accident was investigated with an integration of FRAPCON with the INL neutronics code PHISICS and system analysis code RELAP5-3D. The outputs of interest were ratios of the peak cladding temperatures (highest temperature encountered by cladding during LOCA) and equivalent cladding reacted (the percentage of cladding oxidized) to their cladding hydrogen content-based limits. This work contains the first known UQ of these ratios within the aforementioned integration. Results showed the PCT ratio to be relatively well behaved. The ECR ratio behaves as a threshold variable, which is to say it abruptly shifts to radically higher values under specific conditions. This threshold behaviour establishes the importance of performing UQ so as to see the full spectrum of possible values for an output of interest. The SA capabilities of LOTUS provide a path forward for developers to increase code fidelity for specific outputs. Performing UQ within a multiphysics environment may provide improved estimates of safety metrics in nuclear reactors. These improved estimates may allow plants to operate at higher power, thereby increasing profits. Lastly, LOTUS will be of particular use in the development of newly proposed nuclear fuel designs.

The need for a self-report instrument that assesses internalizing problems in children ages 8 through 12 is evidenced in the lack of such an instrument, and in the prevalence of internalizing problems in children. A new self-report instrument, the Internalizing Symptoms Scale for Children (ISSC), has been proposed and developed to fit this need. The present study evaluated the criterion-related validity, clinical cutoff points, and discriminating power of the ISSC. Two groups of child subjects, clinic-referred and general-school-population, were recruited and administered the ISSC, and a parent of each subject completed the Child Behavior Checklist (CBCL). Each case within the clinic-referred group was then classified as an Internalizer or non-Internalizer based on the CBCL Internalizing T-score. The CBCL was identified as the criterion because of empirical methods used in creating the factor structure, extensive clinical use, psychometric properties, cross-informant design, and large research representation. Results of the evaluations indicated the ISSC to have moderate, yet adequate evidence of criterion-related validity, an optimum clinical cutoff point of 70 (raw score), and strong discriminating power. These results give support for the clinical use of the ISSC as a screening instrument, and for potential use in diagnosis and treatment planning.

This paper investigated the sensitivity, specificity, accuracy, and precision of laser fluorescence and tactile probing for the detection of subgingival calculus. The gold standard for subgingival calculus detection has always been tactile probing. In this study 27 teeth were collected and 108 surfaces investigated, one tooth was excluded (group #13) where no calculus was observed on any surface, and three surfaces because of subgingival root caries to avoid confounding data, which left a total of 101 surfaces of 26 extracted teeth that meet the investigation criteria. The presence of subgingival calculus was observed on 75 tooth surfaces (74.25%). There was a correlation between tooth surface and the presence of calculus. Subgingival calculus was from most to least frequently observed on the Distal surface (92.0%), Lingual surface (76.9%), Mesial surface (70.8%) and Facial surface (57.7%). The amount of laser fluoresce increased according to the amount of subgingival calculus. There was a correlation between the amount of subgingival calculus and the amount of laser fluorescence. The tactile probing had a similar sensitivity compared to laser fluorescence for the detection of subgingival calculus. The laser fluorescence was more specific compared to tactile probing for the detection of subgingival calculus. The tactile probing had a similar accuracy compared to laser fluorescence for the detection of subgingival calculus. The laser fluorescence had more precision compared to tactile probing for the detection of subgingival calculus. These results show that by using both tactile probing and laser fluorescence the sensitivity, specificity, accuracy, and precision of detecting subgingival calculus can be increased. An increase in the sensitivity, specificity, accuracy, and precision of detecting subgingival calculus could help in the diagnosis and treatment of patients suffering from gingival recession and periodontal disease.

Indiana University-Purdue University Indianapolis (IUPUI) / Insulin-stimulated glucose uptake into skeletal muscle cells requires translocation of the glucose transporter-4 (GLUT4) from the cell interior to the plasma membrane. Insulin-stimulated GLUT4 vesicle translocation is dysregulated in Type 2 diabetes (T2D). The Group I p21–activated kinase (PAK1) is a required element in insulin-stimulated GLUT4 vesicle translocation in mouse skeletal muscle in vivo, although its placement and function(s) in the canonical insulin signaling cascade in skeletal muscle cells, remain undetermined. Therefore, the objective of my project is to determine the molecular mechanism(s) underlying the requirement for PAK1 in the process of insulin-stimulated GLUT4 vesicle translocation and subsequent glucose uptake by skeletal muscle cells. Toward this, my studies demonstrate that the pharmacological inhibition of PAK1 activation blunts insulin-stimulated GLUT4 translocation and subsequent glucose uptake into L6-GLUT4myc skeletal myotubes. Inhibition of PAK1 activation also ablates insulin-stimulated F-actin cytoskeletal remodeling, a process known to be required for mobilizing GLUT4 vesicles to the plasma membrane. Consistent with this mechanism, PAK1 activation was also required for the activation of cofilin, another protein implicated in F-actin remodeling. Interestingly, my studies reveal a novel molecular mechanism involving PAK1 signaling to p41-ARC, a regulatory subunit of the cytoskeletal Arp2/3 complex, and its interactions with another cytoskeletal factor, N-WASP, to elicit the insulin-stimulated F-actin remodeling in skeletal muscle cells. Pharmacological inactivation of N-WASP fully abrogated insulin-stimulated GLUT4 vesicle translocation to the cell surface, coordinate with blunted F-actin remodeling. Furthermore, my studies revealed new insulin-induced interactions amongst N WASP, actin, p41-ARC and PAK1; inactivation of PAK1 signaling blocked these dynamic interactions. Taken together, the above studies demonstrate the significance of PAK1 and its downstream signaling to F-actin remodeling in insulin-stimulated GLUT4 vesicle translocation and glucose uptake, revealing new signaling elements that may prove to be promising targets for future therapeutic design.

Reprinted from Cancer Biomarkers, 15(4), Nakashima et al., Urine CXCL1 as a biomarker for tumor detection and outcome prediction in bladder cancer, 357-364, Copyright (2015), with permission from IOS Press. / 京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19596号 / 医博第4103号 / 新制||医||1014(附属図書館) / 32632 / 京都大学大学院医学研究科医学専攻 / (主査)教授 椛島 健治, 教授 武田 俊一, 教授 川村 孝 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・論文博士 / 博士(人間健康科学) / 乙第13064号 / 論人健博第3号 / 新制||人健||3(附属図書館) / (主査)教授 高桑 徹也, 教授 三谷 章, 教授 横出 正之 / 学位規則第4条第2項該当 / Doctor of Human Health Sciences / Kyoto University / DFAM