Synthesis and evaluation of a thiourea-modified chitosan derivative applied for adsorption of Hg(II) from synthetic wastewater

In this work, a thiourea-modified chitosan derivative (TMCD) was synthesized through two steps, O-carboxymethylated first and then modified by a polymeric Schiff's base of thiourea/glutaraldehyde. The adsorption behavior of mercury (II) ions onto TMCD was investigated through batch method. The maximum adsorption capacity for Hg(II) was found to be 6.29 mmol/g at pH 5.0 and both kinetic and thermodynamic parameters of the adsorption process were obtained. The results indicated that adsorption process was spontaneous exothermic reaction and kinetically followed pseudo-second-order model. The adsorption experiments also demonstrated TMCD had high adsorption selectivity towards Hg(II) ions when coexisted with Cu(II), Zn(II), Cd(II) and Ca(II) in solution and it could be easily regenerated and efficiently reused. (C) 2010 Elsevier B.V. All rights reserved.

EVALUATION OF HARMONIC MOTION ELASTOGRAPHY AND ACOUSTO-­OPTIC IMAGING FOR MONITORING LESION FORMATION BY HIGH INTENSITY FOCUSED ULTRASOUND

Malignant or benign tumors may be ablated with high‐intensity focused ultrasound (HIFU). This technique, known as focused ultrasound surgery (FUS), has been actively investigated for decades, but slow to be implemented and difficult to control due to lack of real‐time feedback during ablation. Two methods of imaging and monitoring HIFU lesions during formation were implemented simultaneously, in order to investigate the efficacy of each and to increase confidence in the detection of the lesion. The first, Acousto‐Optic Imaging (AOI) detects the increasing optical absorption and scattering in the lesion. The intensity of a diffuse optical field in illuminated tissue is mapped at the spatial resolution of an ultrasound focal spot, using the acousto‐optic effect. The second, Harmonic Motion Imaging (HMI), detects the changing stiffness in the lesion. The HIFU beam is modulated to force oscillatory motion in the tissue, and the amplitude of this motion, measured by ultrasound pulse‐echo techniques, is influenced by the stiffness. Experiments were performed on store‐bought chicken breast and freshly slaughtered bovine liver. The AOI results correlated with the onset and relative size of forming lesions much better than prior knowledge of the HIFU power and duration. For HMI, a significant artifact was discovered due to acoustic nonlinearity. The artifact was mitigated by adjusting the phase of the HIFU and imaging pulses. A more detailed model of the HMI process than previously published was made using finite element analysis. The model showed that the amplitude of harmonic motion was primarily affected by increases in acoustic attenuation and stiffness as the lesion formed and the interaction of these effects was complex and often counteracted each other. Further biological variability in tissue properties meant that changes in motion were masked by sample‐to‐sample variation. The HMI experiments predicted lesion formation in only about a quarter of the lesions made. In simultaneous AOI/HMI experiments it appeared that AOI was a more robust method for lesion detection.

Biological wastes as plant growth substrate amendments

Globally, agriculture is being intensified with mechanization and increased use of synthetic fertilizers and pesticides. There has been a scaling up of production to satisfy the demands of supermarket distribution. Problems associated with intensification of production, trade globalisation and a larger market demand for greater volumes of fresh produce, include consumers' concern about pesticide residues and leaching of nutrients and pesticides into the environment, as well as increases in the transmission of human food-poisoning pathogens on raw vegetables and in fruit juices. The first part of this research was concerned with the evaluation of a biological control strategy for soil-borne pathogens, these are difficult to eliminate and the chemicals of which the most effective fumigants e.g. methyl bromide, are being withdrawn form use. Chitin-containing crustaceans shellfish waste was investigated as a selective growth substrate amendment in the field, in glasshouse and in storage trials against Sclerotinia disease of Helianthus tuberosus, Phytophthora fragariae disease of Fragaria vesca and Fusarium disease of Dianthus. Results showed that addition to shellfish waste stimulated substrate microbial populations and lytic activity and induced plant defense proteins, namely chitinases and cellulases. Protective effects were seen in all crop models but the results indicate that further trials are required to confirm long-term efficacy. The second part of the research investigated the persistence of enteric bacteria in raw salad vegetables using model food poisoning isolates. In clinical investigations plants are sampled for bacterial contamination but no attempt is made to differentiate between epiphytes and endophytes. Results here indicate that the mode isolates persist endophytically thereby escaping conventional chlorine washes and they may also induce host defenses, which results in their suppression and in negative results in conventional plate count screening. Finally a discussion of criteria that should be considered for a HACCP plan for safe raw salad vegetable production is presented.

Synthesis and evaluation of novel quinolines and quinazolinediones as potential anti-cancer agents

This thesis outlines the design and effectuation of novel chemical routes towards a nascent class of functionalised quinoline-5,8-diones and the expansion of a series of contemporary quinazolinediones towards an innovative family of pyridinoquinazolinetetrone derivatives. This fragment based approach is envisaged to lead to advancements in the three scaffolds, expanding the SAR pool of both quinolines and quinazolinediones with subsequent evaluation of chemotherapeutic potential as well as furnishing a new class of tricycle for biological investigation. Development of novel quinoline-5,8-diones is provided for by expanding on existing methodology. Using a variety of nucleophiles on a critical intermediate, a broad range of novel compounds was afforded allowing chemotherapeutic potential to be assessed, while also serving as intermediates for accomplishing novel pyridinoquinazolinetetrone congeners. In order to incorporate functionality into our quinazolinedione template, an efficient synthetic strategy was constructed which provided a robust route to effectuate a highly derivatised pyrimidinedione ring. As derivatisation of this template is unreported our chief priority was to synthesise a range of diverse quinazolinediones. The application of annulation methodology using functionalised precursors provided a library of N-3 derivatised quinazolinedione analogues. These, along with their N-1 functionalised derivatives provide a wide scope from which to construct a series of pyridinoquinazolinetetrone derivatives while also serving as a unique class of molecules whose biological potential is uncharted. Although the actualisation of the pyridinoquinazolinetetrone was ultimately unsuccessful, our work has led to the development of novel quinoline-5,8-diones which were found to possess excellent anti-cancer activity when assessed by the NCI screen. Of the quinazolinediones synthesised eight compounds were accepted for screening by the NCI. Results from the single-dose tests however indicated that these compounds possessed little cytotoxic activity at 10 μM. The development of this novel template in conjunction with the highly active quinolinediones serves as an excellent rostrum for future synthetic endeavours.

Evaluation of HER2, p53, bcl-2, topoisomerase II-alpha, heat shock proteins 27 and 70 in primary breast cancer and metastatic ipsilateral axillary lymph nodes.

BACKGROUND: Breast cancer is a heterogeneous disease. Predictive biological markers (BM) of responsiveness to therapy need to be identified. Evaluation of BM is mainly done at the primary site. However, in the adjuvant therapy of breast cancer, the main goal is control of micrometastases. It is still unknown whether heterogeneity in the expression of BM between the primary site and its micrometastases exists. OBJECTIVE: To evaluate the expression of some BM with potential predictive value from the primary breast cancer site and metastatic ipsilateral axillary lymph nodes. PATIENTS AND METHODS: Focality (percentage of positive cells) and intensity staining scores were evaluated for each marker. Freshly cut sections (4 microm) from embedded blocks of breast cancer fixed in formalin or bouin were put onto superfrost slides (Menzel-Gläser). Protein expression was evaluated immunohistochemically (IHC) using monoclonal antibodies against: topo II-alpha (clone KiS1, 1 microg/ml, Roche) with a trypsine pre-treatment (P); HSP27 (clone G3.1, 1/60, Biogenex), HSP70 (clone BRM.22, 1/80, Biogenex) and HER2 (clone CB11, 1/40, Novocastra; without P); p53 (clone D07, 1/750, Dako) and bcl-2 (clone 124, 1/60, Dako) with citrate buffer as P. RESULTS: Overall, the percentage of discordant marker status in the primary tumour and its metastatic lymph nodes was 2% for HER2, 6% for p53, 15% for bcl-2, 19% for topoisomerase II-alpha, 24% for HSP27 and 30% for HSP70. For the subgroup of patients with positive BM in the primary tumour, the percentage of discordance was 6% for HER2, 7% for p53, 14% for bcl-2, 19% for HSP70, 21% for topoisomerase II-alpha and 36% for HSP27. For the subgroup of patients with positive BM in the lymph nodes, the percentage of discordance was 9% for bcl-2, 15% for HER2 and p53, 21% for topoisomerase II-alpha, 22% for HSP27 and 25% for HSP70. CONCLUSIONS: 1) No biological marker had 100% concordant results. 2) Although some discordant cases might be explained by the limitations of the IHC technique, future studies aiming to evaluate the predictive value of BM in the adjuvant therapy of breast cancer should take into account a possible difference in BM expression between the primary and the metastatic sites.

Evaluation of tumor response, disease control, progression-free survival, and time to progression as potential surrogate end points in metastatic breast cancer.

PURPOSE: Overall survival (OS) can be observed only after prolonged follow-up, and any potential effect of first-line therapies on OS may be confounded by the effects of subsequent therapy. We investigated whether tumor response, disease control, progression-free survival (PFS), or time to progression (TTP) could be considered a valid surrogate for OS to assess the benefits of first-line therapies for patients with metastatic breast cancer. PATIENTS AND METHODS: Individual patient data were collected on 3,953 patients in 11 randomized trials that compared an anthracycline (alone or in combination) with a taxane (alone or in combination with an anthracycline). Surrogacy was assessed through the correlation between the end points as well as through the correlation between the treatment effects on the end points. RESULTS: Tumor response (survival odds ratio [OR], 6.2; 95% CI, 5.3 to 7.0) and disease control (survival OR, 5.5; 95% CI, 4.8 to 6.3) were strongly associated with OS. PFS (rank correlation coefficient, 0.688; 95% CI, 0.686 to 0.690) and TTP (rank correlation coefficient, 0.682; 95% CI, 0.680 to 0.684) were moderately associated with OS. Response log ORs were strongly correlated with PFS log hazard ratios (linear coefficient [rho], 0.96; 95% CI, 0.73 to 1.19). Response and disease control log ORs and PFS and TTP log hazard ratios were poorly correlated with log hazard ratios for OS, but the confidence limits of rho were too wide to be informative. CONCLUSION: No end point could be demonstrated as a good surrogate for OS in these trials. Tumor response may be an acceptable surrogate for PFS.

Experimental evaluation of evolution and coevolution as agents of ecosystem change in Trinidadian streams.

Evolution has been shown to be a critical determinant of ecological processes in some systems, but its importance relative to traditional ecological effects is not well known. In addition, almost nothing is known about the role of coevolution in shaping ecosystem function. Here, we experimentally evaluated the relative effects of species invasion (a traditional ecological effect), evolution and coevolution on ecosystem processes in Trinidadian streams. We manipulated the presence and population-of-origin of two common fish species, the guppy (Poecilia reticulata) and the killifish (Rivulus hartii). We measured epilithic algal biomass and accrual, aquatic invertebrate biomass, and detrital decomposition. Our results show that, for some ecosystem responses, the effects of evolution and coevolution were larger than the effects of species invasion. Guppy evolution in response to alternative predation regimes significantly influenced algal biomass and accrual rates. Guppies from a high-predation site caused an increase in algae relative to guppies from a low-predation site; algae effects were probably shaped by observed divergence in rates of nutrient excretion and algae consumption. Rivulus-guppy coevolution significantly influenced the biomass of aquatic invertebrates. Locally coevolved populations reduced invertebrate biomass relative to non-coevolved populations. These results challenge the general assumption that intraspecific diversity is a less critical determinant of ecosystem function than is interspecific diversity. Given existing evidence for contemporary evolution in these fish species, our findings suggest considerable potential for eco-evolutionary feedbacks to operate as populations adapt to natural or anthropogenic perturbations.

An evaluation of remifentanil-sevoflurane response surface models in patients emerging from anesthesia: model improvement using effect-site sevoflurane concentrations.

INTRODUCTION: We previously reported models that characterized the synergistic interaction between remifentanil and sevoflurane in blunting responses to verbal and painful stimuli. This preliminary study evaluated the ability of these models to predict a return of responsiveness during emergence from anesthesia and a response to tibial pressure when patients required analgesics in the recovery room. We hypothesized that model predictions would be consistent with observed responses. We also hypothesized that under non-steady-state conditions, accounting for the lag time between sevoflurane effect-site concentration (Ce) and end-tidal (ET) concentration would improve predictions. METHODS: Twenty patients received a sevoflurane, remifentanil, and fentanyl anesthetic. Two model predictions of responsiveness were recorded at emergence: an ET-based and a Ce-based prediction. Similarly, 2 predictions of a response to noxious stimuli were recorded when patients first required analgesics in the recovery room. Model predictions were compared with observations with graphical and temporal analyses. RESULTS: While patients were anesthetized, model predictions indicated a high likelihood that patients would be unresponsive (> or = 99%). However, after termination of the anesthetic, models exhibited a wide range of predictions at emergence (1%-97%). Although wide, the Ce-based predictions of responsiveness were better distributed over a percentage ranking of observations than the ET-based predictions. For the ET-based model, 45% of the patients awoke within 2 min of the 50% model predicted probability of unresponsiveness and 65% awoke within 4 min. For the Ce-based model, 45% of the patients awoke within 1 min of the 50% model predicted probability of unresponsiveness and 85% awoke within 3.2 min. Predictions of a response to a painful stimulus in the recovery room were similar for the Ce- and ET-based models. DISCUSSION: Results confirmed, in part, our study hypothesis; accounting for the lag time between Ce and ET sevoflurane concentrations improved model predictions of responsiveness but had no effect on predicting a response to a noxious stimulus in the recovery room. These models may be useful in predicting events of clinical interest but large-scale evaluations with numerous patients are needed to better characterize model performance.

Characterisation of the South West European Marine Sites: Summary Report. Occasional Publication of the Marine Biological Association 14

The UK and EU have recently committed to an ecosystem-based approach to the management of our marine environment. In line with the requirements of the Habitats regulations, all consents likely to significantly affect Special Areas of Conservation (SACs) and Special Protection Areas (SPAs) are to be reviewed. As part of this process, 'site characterisation' is seen as an important first step towards the improved management of designated sites. This characterisation series, undertaken by the Marine Biological Association of the United Kingdom and funded by the Environment Agency and English Nature, sets out to determine the current status of designated marine sites in South West England, and how vulnerable (or robust) they are to contaminants (metals, organics, nutrients) and other anthropogenic pressures. Using published information and unpublished data-sets from regulatory agencies, conservation bodies and research institutes (particularly those of the PMPS*), evidence is compiled on the links between potentially harmful 'activities', environmental quality, and resultant biological consequences. This includes an evaluation of long-term change. The focus is the effect of water and sediment quality on the key interest features of European Marine sites in the South West of England, namely: - Fal and Helford cSAC (MBA Occasional Publication 8) - Plymouth Sound and Estuaries cSAC/ SPA (MBA Occasional Publication 9) - Exe Estuary SPA (MBA Occasional Publication 10) - Chesil and the Fleet cSAC/ SPA (MBA Occasional Publication 11) - Poole Harbour SPA (MBA Occasional Publication 12) - Severn Estuary pSAC/SPA (MBA Occasional Publication 13) Detailed analysis for each of these sites is provided individually. The summary report contains an overview of physical properties, uses and vulnerability for each of these sites, together with brief comparisons of pollution sources, chemical exposure (via sediment and water) and evidence of biological impact (from bioaccumulation to community-level response). Limitations of the data, and gaps in our understanding of these systems are highlighted and suggestions are put forward as to where future research and surveillance is most needed. Hopefully this may assist the statutory authorities in targeting future monitoring and remedial activities. * PMSP: Plymouth Marine Sciences Partnership, comprising the Marine Biological Association (MBA), University of Plymouth (UoP), the Sir Alister Hardy Foundation for Ocean Science, and Plymouth Marine Laboratories (PML)

Re-evaluation of Graneledone setebos (Cephalopoda : Octopodidae) and allocation to the genus Megaleledone

The holotype of the Antarctic octopodid Graneledone setebos was re-examined and found to lack the epidermal warts characteristic of the genus Graneledone. It is similar in its large size to another Southern Ocean species, Megaleledone senoi. A comparative study of G. setebos and specimens attributed to M. senoi led us to conclude that M. senoi is a junior synonym of G. setebos. Although M. senoi is not valid, the genus Megaleledone can be separated from other genera by the structure of the radula (which lacks marginal plates) and we therefore consider the genus to be valid. We propose the new combination of Megaleledone setebos and have refigured the beaks and radula of the holotype herein and expanded the description. A search of museum specimens and the literature shows that Megaleledone setebos is more common in Antarctic waters than previously supposed.

Evaluation of glycated insulin in diabetic animals using immunocytochemistry and radioimmunoassay

Glycated insulin was evaluated in plasma and biological tissues of diabetic animal models by immuno. cytochemistry (ICC) and a novel radioimmunoassay. Glycated insulin circulated at 0.10 +/-0.04 ng/ml and 2.20 +/-0.14 ng/ml in lean and diabetic obese (ob/ob) mice, corresponding to 12.5 and 9.8% total plasma insulin, respectively. The concentration of glycated insulin was elevated 22-fold in obese mice compared to controls (P10 and 83 +/-4 ng/g wt (P0.17 mug/g wt). ICC revealed fluorescent positively stained cells in pancreatic islets from hydrocortisone (HC)treated diabetic rats. Fasting of HC-treated rats, resulted in 3-fold and 15-fold reductions in plasma glycated insulin (P

Thermogravimetric evaluation of perennial ryegrass (Lolium perenne) for the prediction of in vitro dry matter digestibility

Thermogravimetry (TG) can be used for assessing the compositional differences in grasses that relate to dry matter digestibility (DMD) determined by pepsin-cellulase assay. This investigation developed regression models for predicting DMD of herbage grass during one growing season using TG results. The calibration samples were obtained from a field trial of eight cultivars and two breeding lines. The harvested materials from five cuts were analysed by TG to identify differences in the combustion patterns within the range of 30-600 degrees C. The discrete results including weight loss, peak height, area, temperature, widths and residue of three decomposition peaks were regressed against the measured DMD values of the calibration samples. Similarly, continuous weight loss results of the same samples were also utilised to generate DMD models. The r(2) for validation of the discrete and the best continuous models were 0.90 and 0.95, respectively, and the two calibrations were validated using independent samples from 24 plots from a trial carried out in 2004. The standard error for prediction of the 24 samples by the discrete model (4.14%) was higher than that by the continuous model (2.98%). This study has shown that DMD of grass could be predicted from the TG results. The benefit of thermal analysis is the ability to detect and show changes in composition of cell wall fractions of grasses during different cuts in a year.

Microscopical evaluation of neural connectivity between paired stages of Eudiplozoon nipponicum (Monogenea : Diplozoidae)

Diplozoidae monogeneans are fish-gill ectoparasites comprising 2 individuals fused in so-called permanent copula. This unique situation occurs when 2 larvae (diporpae) make contact on the host gill, such that their union triggers maturation into an individual adult worm. The present study examined paired stages of Eudiplozoon nipponicum microscopically to ascertain whether somatic fusion involves neural connectivity between these 2 heterogenic larvae. Neuronal pathways were demonstrated in whole-mount preparations of the worm, using indirect immunocytochemical techniques interfaced with confocal scanning laser microscopy for peptidergic and serotoninergic innervations and enzyme cytochemical methodology and light microscopy for cholinergic components. Elements of the central nervous systems of paired worms are connected by commissures the region of fusion so that the 2 systems are in structural continuity. Interindividual connections were most apparent between corresponding ventral nerve cords. All 3 classes of neuronal mediators were identified throughout both central and peripheral connections of the 2 nervous systems. The anatomical complexity and apparent plasticity of the diplozoon nervous system suggest that it has a pivotal role not only in motility, feeding, and reproductive behaviors but also in the events of larval pairing and somatic fusion.