In vitro transformation of lymphoid cells by Abelson murine leukemia virus

Cell cultures prepared from fetal murine liver were infected by Abelson murine leukemia virus. After about 2 weeks, proliferating cells of lymphoid morphology appeared in some of the cultures. Addition of 2-mercaptoethanol to the initial culture medium greatly enhanced the appearance of the lymphoid cells. Immunoglobulin determinants were evident on the cells in some cultures. Continuous passage of the cells in certain cultures was possible and the passaged cells could form tumors after animal inoculation. Because Abelson murine leukemia virus is able to induce in vitro malignant transformation of lymphoid cells, it probably causes leukemia by directly affecting cellular growth control

Microstrip post production tuning bar error and compact resonators using negative refractive index metamaterials

In this thesis, two separate research topics are undertaken both in the general area of compact RF/microwave circuit design. The first topic involves characterizing the parasitic effects and error due to unused post-production tuning bars. Such tuning bars are used in microwave circuit designs to allow the impedance or length of a microstrip line to be adjusted after fabrication. In general, the tuning bars are simply patterns of small, isolated sections of conductor adjacent to the thru line. Changing the impedance or length of the thru line involves bonding the appropriate tuning bars to the line. Unneeded tuning bars are simply not removed and left isolated. Ideally, there should be no coupling between these unused tuning bars and the thru line. Therefore, the unused tuning bars should have a negligible effect on the circuit??s overall performance. To nullify the parasitic effects of the tuning bars, conventional wisdom suggests placing the bars 1.0 to 1.5 substrate heights away from the main line. While successful in the past, this practice may not result in the most efficient and cost-effective placement of tuning bars in today??s compact microwave circuits. This thesis facilitates the design of compact tuning bar configurations with minimum parasitic effects by analyzing the error attributable to various common tuning bar configurations with a range of parameters and offset distances. The error is primarily determined through electromagnetic simulations, and the accuracy of these simulations is verified by experimental results. The second topic in this thesis involves the design of compact microwave resonators using the transmission line approach to create negative refractive index metamaterials. A survey of the major developments and fundamental concepts related to negative refractive index technology (with focus on the transmission line approach) is given. Following is the design and measurement of the compact resonators. The resonators are also compared to their conventional counterparts to demonstrate both compactness and harmonic suppression

Affect and the perception of injustice

Traditional approaches to distributive justice have seen the determination of whether or not a distribution of rewards is fair as a cognitive process, with emotion entering the process only as an outcome of a decision that the distribution was unjust. In this paper, we propose a modification of this view. Namely, we propose that justice is not calculated unless the actor feels a justice-related emotion (anger or guilt). These emotions, which arise in the course of social interaction, lead to the instigation of justice deliberations. Using Affect Control Theory, we explain how the justice-related emotions could arise in situations that traditional models of justice would characterise as unjust. Thus, our theory is able to account for the existing literature on justice. We then show how our theory suggests several novel implications about situations that would be seen as unjust. Comparisons of our model to related models of justice are also discussed

An Investigation into the Advantages of In-Space Propellant Re-supply

In-space propellant re-supply has been proposed to extend space vehicle lifetimes, but only qualitative arguments supporting development have been made; this study focuses on quantitative support. Two basic concepts for propellant re-supply are propellant transfer and tank replacement. A quantitative assessment and comparison to no re-supply alternatives is necessary to choose the most cost-effective architecture. The analysis is primarily accomplished through the use of a new tool that facilitates propulsion system sizing and broad trade studies. The program was co-created by the author under a grant from NASA Langley Research Center and has been used at NASA Langley for lunar architecture studies to support the Vision for Space Exploration. For less than 100 missions, the preferred scenario is without re-supply, using direct Earth reentry. For more than 100 missions, tank replacement requires 38% fewer missions than propellant transfer to become more cost effective than no re-supply

Application of a single-objective, hybrid genetic algorithm approach to pharmacokinetic model building.

A limitation in traditional stepwise population pharmacokinetic model building is the difficulty in handling interactions between model components. To address this issue, a method was previously introduced which couples NONMEM parameter estimation and model fitness evaluation to a single-objective, hybrid genetic algorithm for global optimization of the model structure. In this study, the generalizability of this approach for pharmacokinetic model building is evaluated by comparing (1) correct and spurious covariate relationships in a simulated dataset resulting from automated stepwise covariate modeling, Lasso methods, and single-objective hybrid genetic algorithm approaches to covariate identification and (2) information criteria values, model structures, convergence, and model parameter values resulting from manual stepwise versus single-objective, hybrid genetic algorithm approaches to model building for seven compounds. Both manual stepwise and single-objective, hybrid genetic algorithm approaches to model building were applied, blinded to the results of the other approach, for selection of the compartment structure as well as inclusion and model form of inter-individual and inter-occasion variability, residual error, and covariates from a common set of model options. For the simulated dataset, stepwise covariate modeling identified three of four true covariates and two spurious covariates; Lasso identified two of four true and 0 spurious covariates; and the single-objective, hybrid genetic algorithm identified three of four true covariates and one spurious covariate. For the clinical datasets, the Akaike information criterion was a median of 22.3 points lower (range of 470.5 point decrease to 0.1 point decrease) for the best single-objective hybrid genetic-algorithm candidate model versus the final manual stepwise model: the Akaike information criterion was lower by greater than 10 points for four compounds and differed by less than 10 points for three compounds. The root mean squared error and absolute mean prediction error of the best single-objective hybrid genetic algorithm candidates were a median of 0.2 points higher (range of 38.9 point decrease to 27.3 point increase) and 0.02 points lower (range of 0.98 point decrease to 0.74 point increase), respectively, than that of the final stepwise models. In addition, the best single-objective, hybrid genetic algorithm candidate models had successful convergence and covariance steps for each compound, used the same compartment structure as the manual stepwise approach for 6 of 7 (86 %) compounds, and identified 54 % (7 of 13) of covariates included by the manual stepwise approach and 16 covariate relationships not included by manual stepwise models. The model parameter values between the final manual stepwise and best single-objective, hybrid genetic algorithm models differed by a median of 26.7 % (q₁ = 4.9 % and q₃ = 57.1 %). Finally, the single-objective, hybrid genetic algorithm approach was able to identify models capable of estimating absorption rate parameters for four compounds that the manual stepwise approach did not identify. The single-objective, hybrid genetic algorithm represents a general pharmacokinetic model building methodology whose ability to rapidly search the feasible solution space leads to nearly equivalent or superior model fits to pharmacokinetic data

Plantar fasciopathy: revisiting the risk factors

Background Plantar fasciopathy is the most common cause of acquired sub-calcaneal heel pain in adults. To-date, research of this condition has mainly focused on management rather than causal mechanisms. The aetiology of plantar fasciopathy is likely to be multifactorial, as both intrinsic and extrinsic risk factors have been reported. The purpose of this review is to critically reevaluate risk factors for plantar fasciopathy. Methods A detailed literature review was undertaken using English language medical databases. Results No clear consensus exists as to the relative strength of the risk factors reported. Conclusions To-date numerous studies have examined various intrinsic and extrinsic risk factors implicated in the aetiology of plantar fasciopathy. How these factors interact may provide useful data to establish an individuals’ risk profile for plantar fasciopathy and their potential for response to treatment. Further research is indicated to rank the relative significance of these risk factors

Vorinostat in advanced prostate cancer patients progressing on prior chemotherapy (National Cancer Institute Trial 6862)

BACKGROUND: This phase 2 trial was designed to evaluate the efficacy of vorinostat in chemotherapy-pretreated patients with metastatic castration-resistant prostate cancer. METHODS: Patients with disease progression on 1 prior chemotherapy, a prostate-specific antigen (PSA) ≥5 ng/mL, and adequate organ function were treated with 400 mg vorinostat orally daily. The primary endpoint was the 6-month progression rate. Secondary endpoints included safety, rate of PSA decline, objective response, overall survival, and effects of vorinostat on serum interleukin-6 (IL-6) levels. RESULTS: Twenty-seven eligible patients were accrued. The median number of cycles delivered was 2 (range, 1-7). All patients were taken off therapy before 6 months. The best objective response in the eligible patient was stable disease in 2 (7%) patients. No PSA decline of ≥50% was observed. There was 1 grade 4 adverse event (AE), and 44% of patients experienced grade 3 adverse events. The most common adverse events were fatigue (81%), nausea (74%), anorexia (59%), vomiting (33%), diarrhea (33%), and weight loss (26%). Median time to progression and overall survival were 2.8 and 11.7 months, respectively. Median IL-6 levels (pg/mL) were higher in patients removed from the protocol for toxicity compared with progression at all time points, including baseline (5.2 vs 2.1, P = .02), Day 15 Cycle 1 (9.5 vs 2.2, P = .01), Day 1 Cycle 2 (9.8 vs 2.2, P = .01), and end of study (11.0 vs 2.9, P = .09). CONCLUSIONS: Vorinostat at this dose was associated with significant toxicities limiting efficacy assessment in this patient population. The significant association between IL-6 levels and removal from the study for toxicities warrants further investigation. Cancer 2009. © 2009 American Cancer Society.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64445/1/24597_ftp.pd

The Apollo Lunar Orbit Rendezvous Architecture Decision Revisited

This conference features the work of authors from: Georgia Tech’s Space Systems Design Lab, Aerospace Systems Design Lab, School of Aerospace Engineering, Georgia Tech Research Institute; NASA’s Jet Propulsion Laboratory, Marshall Space Flight Center, Goddard Space Flight Center, Langley Research Center; and other aerospace industry and academic institutionsThe 1962 Apollo architecture mode decision process was revisited with modern analysis and systems engineer tools to determine driving selection criteria and technology/operational mode design decisions that may be used for NASA’s current Space Exploration program. Results of the study agreed with the Apollo selection of the Lunar Orbit Rendezvous mode based on the technology maturity and politics in 1962. Using today’s greater emphasis on human safety and improvements in technology and design maturity, a slight edge may be given to the direct lunar mode over lunar orbit rendezvous. Also, the NOVA direct mode and Earth orbit rendezvous mode are not competitive based any selection criteria. Finally, reliability and development, operations, and production costs are major drivers in today’s decision process.AIAA Space Systems Technical Committee ; AIAA Space Transportation Systems Technical Committee ; Space Technology Advanced Research Cente

Paleogene deepwater mass composition of the tropical Pacific and implications for thermohaline circulation in a greenhouse world

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94621/1/ggge1162.pd