Sustaining the Commons: The Coercive to Cooperative,Resilient, and Adaptive Nature of State Comprehensive Water Planning Legislation

Problem, research strategy, and findings: States need guidance to adopt comprehensive water planning legislation that can affect urban planning and built form. Current state legislation, however, may not yet incorporate emerging water resource paradigms that promote sustainable water management at the state and substate levels. Planners can improve existing state legislation, but need guidance on incorporating the latest thinking on resilience, adaptive capacity, and sustainable commons management. I identify the 26 states with comprehensive water planning legislation, and analyze that legislation using a new assessment tool that builds on the coercive versus cooperative metric (CvCA). I determine where each state's water planning legislation falls on a coercive versus cooperative spectrum, and the extent to which each state's legislation incorporates sustainable commons management (SCM) and social–ecological resilience (SER) mechanisms and attributes. Most of the 26 states with comprehensive water planning legislation balance coercive and cooperative approaches to achieve state and substate water plans, although research suggests that planning is most effective when legislation is more cooperative. Moreover, most have not codified SCM and SER mechanisms into state water planning legislation, suggesting that the plans that follow may lack the adaptive capacity to increase the resilience of the water system. Research limitations include the single data source and potential interpretive coding bias.

Takeaway for practice: Planners can advocate for new or improved state water legislation that incorporates integral adaptive and resiliency concepts, encouraging states to include the fundamental features of the social–ecological system that lead to better water management.     

Perfluorocyclobutane aromatic ether polymers. III. Synthesis and thermal stability of a thermoset polymer containing triphenylphosphine oxide

The preparation of a novel triaryl phosphine oxide thermoset polymer containing the perfluorocyclobutane linkage is described. The synthetic methodology involves the formation of a Grignard reagent from 4-bromotrifluorovinyloxybenzene and reaction with phosphorous trichloride to form the triaryl phosphine trifluorovinyl ether monomer. Oxidation of the phosphine monomer with hydrogen peroxide in ethanol provides quantitative conversion of the phosphine to the phosphine oxide. Analysis of the thermal decomposition of the resulting polymer in both nitrogen and air indicates improvement in thermal and thermal/oxidative stability with respect to the previously reported polymer prepared from 1,1,1-tris(4-trifluorovinyloxy)phenyl ethane. Differences in thermal and thermal/oxidative performance still exist, indicating that oxidative processes contribute to the polymer decomposition in air. © 1998 John Wiley & Sons, Inc. J Appl Polym Sci 69: 2005–2012, 1998     

Recombination signal sequence binding protein Jkappa is constitutively bound to the NF-kappaB site of the interleukin-6 promoter and acts as a negative regulatory factor

Analysis by electrophoretic mobility shift assays (EMSA) of the different proteins associated with the kappaB sequence of the interleukin-6 (IL-6) promoter (IL6-kappaB) allowed us to detect a specific complex formed with the recombination signal sequence binding protein Jkappa (RBP-Jkappa). Single-base exchanges within the oligonucleotide sequence defined the critical base pairs involved in the interaction between RBP-Jkappa and the IL6-kappaB motif. Binding analysis suggests that the amount of RBP-Jkappa protein present in the nucleus is severalfold higher than the total amount of inducible NF-kappaB complexes but that the latter bind DNA with a 10-fold-higher affinity. A reporter gene study was performed to determine the functional implication of this binding; we found that the constitutive occupancy of the IL6-kappaB site by the RBP-Jkappa protein was responsible for the low basal levels of IL-6 promoter activity in L929sA fibrosarcoma cells and that RBP-Jkappa partially blocked access of NF-kappaB complexes to the IL-6 promoter. We propose that such a mechanism could be involved in the constitutive repression of the IL-6 gene under normal physiological conditions.     

Development of new cancer chemoprevention agents: role of pharmacokinetic/pharmacodynamic and intermediate endpoint biomarker monitoring

Dimerization is a prerequisite for many growth factors in their receptor activation leading to cellular response. FGF-1 and FGF-2, members of the Fibroblast Growth Factor (FGF) family, were shown to form non-covalent dimers and oligomers in vitro. Using the two-hybrid system as an in vivo binding assay we show here that of three representative members of the FGF family, only FGF-2 is able to homodimerize. Moreover the FGF-2 isoforms could heterodimerize. Two single-point mutants (T121F and W123R), defective in their dimerization capability, were isolated through random mutagenesis and were used to study the role of FGF-2 dimerization with regard to its biological activity. Remarkably, these mutant proteins were still able to induce cell differentiation, but were strongly affected in their capacity to promote cell proliferation. This study thus highlights the uncoupling between proliferation and differentiation FGF-2 signaling pathways and the crucial role of FGF-2 dimerization in the mitogenic activity of this factor.     

An efficient strategy for detection of known and new mutations of the CYP2D6 gene using single strand conformation polymorphism analysis

To detect mutations in the cytochrome P450 CYP2D6 gene (CYP2D6), we developed a strategy based on single-strand conformation polymorphism (SSCP) analysis of the gene amplified by polymerase chain reaction (PCR). The efficiency of the method was evaluated by analysing DNA samples from extensive metabolizers (EM) and poor metabolizers (PM) of debrisoquine. Haplotypes, alleles and mutations of CYP2D6 had previously been characterized in each individual using PCR assays, Xba I restriction fragment length polymorphism (RFLP) and sequencing. PCR-SSCP results were in complete agreement with those obtained using established methods. All previously characterized mutations were associated with particular shifts in the electrophoretic mobility of DNA fragments allowing their identification. We further tested the efficiency of PCR-SSCP for detecting new CYP2D6 mutations. DNA from a PM subject presumed to carry an unknown non-functional mutant allele of CYP2D6 was amplified and bands with aberrant migration patterns were observed on SSCP gels. Sequence analysis of the corresponding DNA fragments revealed the causative mutations. In this way, a novel non-functional allele of the gene, carrying three previously reported mutations and a new mutation in the third exon which results in a premature termination codon, was characterized. Finally, CYP2D6 SSCP analysis was performed on DNA amplified with fluorescent primers and an automated DNA sequencer was used for SSCP analysis of products. We conclude that the PCR-SSCP approach is a powerful method of identifying simultaneously known and new mutations of the CYP2D6 gene.     

Maximum-likelihood x-ray computed-tomography finite-beamwidth considerations

The underlying model and iterative image-reconstruction algorithm, based on maximum-likelihood estimation, is extended to consider finite x-ray beam width. Simulations are presented by maximum-likelihood images compared with filtered-backprojection images. The main conclusion of this study is that it is feasible to obtain a marked improvement in image clarity and reduction of artifacts: (1) There is an improvement in delineation of the boundaries of low-contrast soft-tissue substructures. There is an improvement in the capability of identifying at least one of the low-contrast soft-tissue substructures. (2) The algorithm is capable of reconstructing onto a discrete array of finer resolution, again with better delineation of substructures than the filtered-backprojection algorithm. (3) Maximum-likelihood images at an atypically low photon flux level are, at the very least, comparable in image quality to filtered-backprojection images at a much higher and more typical photon flux level. These observations imply that the diagnostic capability of x-ray computed tomography may be improved to a broader range of otherwise adverse conditions. It may be capable of much better visualization of soft-tissue regions that reside near dense regions (such as bone or metal prostheses), of visualizing finer spatial detail, and of use with much lower x-ray dosages.     

N-acetyltransferase 2 acetylation polymorphism: prevalence of slow acetylators does not differ between atopic dermatitis patients and healthy subjects

The genetic polymorphism of human N-acetyltransferase 2 (NAT2) divides the human population into groups with rapid, intermediate and slow acetylator status. Slow acetylator status has been considered a predisposing factor for allergic diseases, lupus erythematosus, toxic epidermal necrolysis or Stevens-Johnson syndrome. The aim of this study was to investigate whether Caucasian patients suffering from atopic dermatitis differed from healthy individuals with regard to the genotype and phenotype of NAT2. Twenty unrelated healthy Caucasian volunteers (9 females and 11 males, aged from 22 to 59 years) and twenty unrelated Caucasian patients suffering from atopic dermatitis (9 females and 11 males, aged between 20 and 54 years) participated in this study. For each one, the NAT2 genotype was determined by polymerase chain reaction with DNA extracted from peripheral blood, using specific primers for the wild-type allele (wt) and the 3 most frequent mutated alleles of NAT2 (C481-->T, G590-->A and G857-->A). The NAT2 phenotype was evaluated with dapsone as a test substrate using high-pressure liquid chromatography. Statistical analysis was performed using the chi(2) test. Phenotype and genotype were distributed as follows: (1) of the healthy subjects, 60% were rapid acetylators (RA) and 40% were slow acetylators (SA); 10% of the RA and 15% of the SA were homozygous, 50% of the RA and 25% of the SA were heterozygous; (2) of the patients, 55% were RA, 40% were SA and 5% were intermediate acetylators (IA); 10% of the RA and 10% of the SA were homozygous, 45% of the RA and 35% of the SA were heterozygous. No significant statistical difference was found between the two groups for genotypes (p = 0.75) or phenotypes (p = 0.60). The phenotyping and genotyping results of healthy subjects were comparable to those found in previous studies. The absence of a significant statistical difference between healthy subjects and atopic dermatitis patients is in contrast to the results of previous studies. Some authors considered that allergic patients are mostly SAs. This could be explained by the fact that we only considered patients suffering from atopic dermatitis whereas, in other studies, patients suffered from different (one or several associated) allergic diseases. NAT2 polymorphism does not differ between patients suffering from atopic dermatitis and healthy subjects. The importance attributed to the SA status, which was previously considered a predisposing factor for allergic diseases such as atopic dermatitis, should be reviewed.     

Tonic and phasic activation and arousal effects as a function of feedback in repetitive-choice reaction time tasks.

This study examines the effects of positive and negative feedback on performance during choice reaction time tasks to assess whether they differentially affect phasic arousal and tonic activation. Participants (N=96) received either no feedback or signals of reward, punishment, or both during a semantic and a visuospatial repetitive-choice reaction time task. The number of errors made was analyzed both on a trial-by-trial basis and over a continuous series of 80 trials (assessing phasic and tonic feedback effects, respectively). The results show that punishment and reward have different phasic and tonic effects on performance. The data further show that feedback effects interact with the task characteristics: semantic versus visuospatial, and reaction stimulus preceded by a warning signal versus an irrelevant signal. The interaction effects appear to be consistent with the proposed neurological model. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Preclinical drug development paradigms for chemopreventives

Preclinical screening studies and animal efficacy testing models currently are used by the National Cancer Institute's chemoprevention drug discovery program to assess and identify chemical agents and natural products that may have the potential to prevent human cancer. Identification of potential cancer preventing agents begins by subjecting each compound to a sequential series of short-term, in vitro prescreens of mechanistic, biochemical assays to provide quantitative data to help establish an early indication of chemopreventive efficacy and to assist in prioritizing agents for further evaluation in longer-term, in vitro transformation bioassays and whole animal models. Promising chemical agents or combinations of agents that work through different inhibitory mechanisms subsequently are tested in well-established, chemically induced, animal tumor models, which include models of the lung, bladder, mammaries, prostate, and skin. These preclinical bioassays afford a strategic framework for evaluating agents according to defined criteria, and not only provide evidence of agent efficacy, but also serve to generate valuable dose-response, toxicity, and pharmacokinetic data required prior to phase I clinical safety testing. Based on preclinical efficacy and toxicity screening studies, only the most successful agents considered to have potential as human chemopreventives progress into clinical chemoprevention trials.