Liver carcinogenesis associated with feeding of ethionine in a choline-free diet: evidence against a role of oval cells in the emergence of hepatocellular carcinoma

In an attempt to clarify the role of oval cells in the emergence of hepatocellular carcinoma, we fed rats a choline-free diet containing 0%, 0.05% or 0.1% ethionine. The incidence and nature of premalignant and malignant hepatic lesions were then related to the degree of oval cell proliferation. Intake of choline-free diet alone for up to 12 mo was associated with minimal oval cell proliferation; cholangiofibrosis, hepatocellular nodules and hepatocellular carcinoma were observed in 55%, 23% and 14% of the animals, respectively. When rats were given the choline-free diet with 0.05% ethionine, proliferation of oval cells was more pronounced; after a 6- to 12 mo feeding period, cholangiofibrosis (57%) was again observed. However, hepatocellular nodules (91%) and hepatocellular carcinoma (74%) were the most common lesions seen with this feeding regimen. Finally, rats fed the choline-free diet with 0.1% ethionine had massive oval cell proliferation and progressive loss of parenchymal liver tissue. Most of these animals died before they had consumed the choline-free diet with 0.1% ethionine for 12 mo. Rats in this group (96%) exhibited large and numerous cholangiofibrotic lesions, but hepatocellular nodules and carcinoma were not detected. In all animals of each experimental group, hyperplastic bile duct cells in areas of cholangiofibrosis and oval cells were positive for cytokeratin 19, an intermediate filament protein present only in bile duct cells in normal liver. Hepatocellular nodules and hepatocellular carcinoma were invariably negative for cytokeratin 19. We interpret these findings to suggest that oval cells are not involved in the histogenesis of hepatocellular carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)     

Omental transfer for salvage of the moribund lower extremity

Use of omental flaps is well documented in soft tissue reconstruction of the head and neck, chest wall, and abdomen. Three cases of omental transfer for soft tissue reconstruction of the lower extremities are presented. In two patients, free vascularized omental flaps were used to cover deep soft tissue defects over the lower leg and in one patient, a pedicle flap was used to cover a deep groin defect extending into the hip joint. In all patients, use of an omental graft allowed revascularization and subsequent wound healing with good cosmetic results.     

Ile115Leu mutation in the SRS1 region of an insect cytochrome P450 (CYP6B1) compromises substrate turnover via changes in a predicted product release channel

CYP6B1 represents the principal cytochrome P450 monooxygenase responsible for metabolizing furanocoumarins in Papilio polyxenes, an insect that specializes on host plants containing these toxins. Investigations of the amino acids responsible for the efficient metabolism of these plant toxins has identified Ile115 as one that modulates the rate of furanocoumarin metabolism even though it is predicted to be positioned at the edge of the heme plane and outside substrate contact regions. In contrast to previous expression studies conducted under conditions of limiting P450 reductase showing that the Ile115-to-Leu replacement enhances turnover of xanthotoxin and other furanocoumarins, studies conducted at high P450 reductase indicate that the Ile115-to-Leu replacement reduces turnover of these substrates. Further analysis of substrate binding affinities, heme spin state and NADPH consumption rates indicate that, whereas the I115L replacement mutant displays higher substrate affinity and heme spin state than the wild-type CYP6B1 protein, it utilizes NADPH more slowly than the wild-type CYP6B1 protein at high P450 reductase levels. Molecular models developed for the wild-type CYP6B1 and mutant protein suggest that more constricted channels extending from the catalytic site in the I115L mutant to the P450 surface limit the rate of product release from this mutant catalytic site under conditions not limited by the rate of electron transfer from NADPH.     

CuGaSe2 solar cells prepared by MOVPE

Metal organic vapor-phase epitaxy (MOVPE) is used to prepare epitaxial reference films and solar cells based on CuGaSe₂. Room temperature Hall measurements are performed on epitaxial CuGaSe₂. Conductivities up to 0.7 (Ω cm)⁻¹ were obtained. Highest mobilities of 270 cm²/Vs are observed for near stoichiometric slightly Ga-rich films. Net charge carrier concentration is higher in the Cu-rich grown films than in the Ga-rich films. Solar cells with epitaxial absorber are prepared that reach efficiencies of 3.3%. First polycrystalline solar cells are grown on Mo/glass at reduced substrate temperatures. Under AM1.5 illumination open-circuit voltages up to 740 mV and efficiencies of 2.0% are obtained.     

“At Your Own Risk”: Narratives of Migrant Sex Workers in Johannesburg

Existing evidence indicates that cross-border migrant women sex workers in South Africa are often marginalized by state and non-state actors professing to assist them. Trafficking discourses frequently conflate migrant sex workers with trafficking victims, denying them agency and silencing the women under discussion. This paper emphasizes the voices of the women themselves, drawing from the first academic research employing creative writing workshops as a methodology with migrant women sex workers in Johannesburg, South Africa. This work responds to calls for more innovative methodologies to reach marginalized or “invisible” groups and adds to the “voices” of urban poor migrants to provide more information about the lived experiences of migrant sex workers in Johannesburg. Narratives from five Zimbabwean sex workers in Johannesburg reveal representations of sex work that are paradoxically both “good” and “bad”—ambiguous in a way the polarized discussions around sex work rarely reflect and in a way that might be best expressed through creative writing. In a country increasingly concerned with issues of (anti-)immigration and (anti-)trafficking, these women are often positioned as vulnerable and misidentified as trafficked; however, their self-representations portrayed complex women calculating and making decisions, especially related to their health and safely. This paper concentrates on letters the participants wrote to young sex workers, which highlight the participatory aspect of this method and show the complexities an arts-based method can reveal.     

Rational Three-Step Method for Optimizing Value of Civil Engineering Research

State DOTs and other agencies and organizations desire to solve difficult practical problems in design, construction, and maintenance of infrastructure. To help accomplish this they request and receive proposals from researchers to solve such problems. An obstacle the agencies face in both writing the research request and in reviewing the proposals is to rationally determine how to obtain the best value for the research funding. This paper proposes a rational means to qualitatively and quantitatively determine relative values using a simple record-keeping matrix and basic tenets of error analysis. Using inferential or other means to estimate uncertainty, and using basic error propagation techniques, research value can be rationally optimized in a three-step method of (1) assembling or requiring an objective-variable matrix; (2) inferring assumptions of variable error based on practical observation; and (3) calculating error propagation through the proposed parametric functions. This methodology will also help with scope management of proposed research and organizing research results.     

Uncertainty analysis of the weighted equivalent lung dose per unit exposure to radon progeny in the home

A parameter uncertainty analysis has been performed to derive the probability distribution of the weighted equivalent dose to lung for an adult (w(lung) H(lung)) per unit exposure to radon progeny in the home. The analysis was performed using the ICRP Publication 66 human respiratory tract model (HRTM) with tissue weighting factor for the lung, w(lung) = 0.12 and the radiation weighting factor for alpha particles, wR = 20. It is assumed that the HRTM is a realistic representation of the physical and biological processes, and that the parameter values are uncertain. The parameter probability distributions used in the analysis were based on a combination of experimental results and expert judgement from several prominent European scientists. The assignment of the probability distributions describing the uncertainty in the values of the assigned fractions (ABB, Abb, AAI) of the tissue weighting factor proved difficult in practice due to lack of quantitative data. Because of this several distributions were considered. The results of the analysis give a mean value of w(lung) H(lung) per unit exposure to radon progeny in the home of 15 mSv per working level month (WLM) for a population. For a given radon gas concentration, the mean value of w(lung) H(lung) per unit exposure is 13 mSv per 200 Bq.m(-3).y of 222Rn. Parameters characterising the distributions of w(lung) H(lung) per unit exposure are given. If the ICRP weighting factors are fixed at their default values (ABB, Abb, AAI = 0.333, 0.333, 0.333; w(lung) = 0.12; and wr = 20) then on the basis of this uncertainty analysis it is extremely unlikely (P approximately 0.0007) that a value of Hw/Pp for exposure in the home is as low as 4 mSv per WLM, the value determined with the epidemiological approach. Even when the uncertainties in the ABB, Abb, AAI, values are included then this probability is predicted to be between 0.01 to 0.08 depending upon the distribution assumed for describing the uncertainties in the ABB, Abb, AAI, values. Thus, it is concluded that the uncertainties in the HRTM parameters considered in this study cannot totally account for the discrepancy between the dosimetric and epidemiological approaches.     

The Difference between Polynomial-Time Many-One and Truth-Table Reducibilities on Distributional Problems

In this paper we separate many-one reducibility from truth-table reducibility for distributional problems in DistNP under the hypothesis that P ≠ NP . As a first example we consider the 3-Satisfiability problem (3SAT) with two different distributions on 3CNF formulas. We show that 3SAT with a version of the standard distribution is truth-table reducible but not many-one reducible to 3SAT with a less redundant distribution unless P = NP . We extend this separation result and define a distributional complexity class C with the following properties: (1) C is a subclass of DistNP, this relation is proper unless P = NP. (2) C contains DistP, but it is not contained in AveP unless DistNP \subseteq AveZPP. (3) C has a ≤ ^p _m -complete set. (4) C has a ≤ ^p _tt -complete set that is not ≤ ^p _m -complete unless P = NP. This shows that under the assumption that P ≠ NP, the two completeness notions differ on some nontrivial subclass of DistNP.