A demonstration of an affinity between pyrite and organic matter in a hydrothermal setting

One of the key-principles of the iron-sulphur world theory is to bring organic molecules close enough to interact with each other, using the surface of pyrite as a substrate in a hydrothermal setting. The present paper explores the relationship of pyrite and organic matter in a hydrothermal setting from the geological record; in hydrothermal calcite veins from Carboniferous limestones in central Ireland. Here, the organic matter is accumulated as coatings around, and through, pyrite grains. Most of the pyrite grains are euhedral-subhedral crystals, ranging in size from ca 0.1-0.5 mm in diameter, and they are scattered throughout the matrix of the vein calcite. The organic matter was deposited from a hydrothermal fluid at a temperature of at least 200°C, and gives a Raman signature of disordered carbon. This study points to an example from a hydrothermal setting in the geological record, demonstrating that pyrite can have a high potential for the concentration and accumulation of organic materials

Using self-organizing maps to investigate environmental factors regulating colony size and breeding success of the White Stork (Ciconia ciconia)

We studied variations in the size of breeding colonies and in breeding performance of White Storks Ciconia ciconia in 2006–2008 in north-east Algeria. Each colony site was characterized using 12 environmental variables describing the physical environment, land-cover categories, and human activities, and by three demographic parameters: the number of breeding pairs, the number of pairs with chicks, and the number of fledged chicks per pair. Generalized linear mixed models and the self-organizing map algorithm (SOM, neural network) were used to investigate effects of biotic, abiotic, and anthropogenic factors on demographic parameters and on their relationships. Numbers of breeding pairs and of pairs with chicks were affected by the same environmental factors, mainly anthropogenic, which differed from those affecting the number of fledged chicks per pair. Numbers of fledged chicks per pair was not affected by colony size or by the number of nests with chicks. The categorization of the environmental variables into natural and anthropogenic, in connection with demographic parameters, was relevant to detect factors explaining variation in colony size and breeding parameters. The SOM proved a relevant tool to help determine actual dynamics in White Stork colonies, and thus to support effective conservation decisions at a regional scale

Influence of monolayer, spheroid, and tumor growth conditions on chromosome 3 gene expression in tumorigenic epithelial ovarian cancer cell lines

<p>Abstract</p> <p>Background</p> <p>Expression microarray analyses of epithelial ovarian cancer (EOC) cell lines may be exploited to elucidate genetic and epigenetic events important in this disease. A possible variable is the influence of growth conditions on discerning candidates. The present study examined the influence of growth conditions on the expression of chromosome 3 genes in the tumorigenic EOC cell lines, OV-90, TOV-21G and TOV-112D using Affymetrix GeneChip^®HG-U133A expression microarray analysis.</p> <p>Methods</p> <p>Chromosome 3 gene expression profiles (n = 1147 probe sets, representing 735 genes) were extracted from U133A expression microarray analyses of the EOC cell lines OV-90, TOV-21G and TOV-112D that were grown as monolayers, spheroids or nude mouse xenografts and monolayers derived from these tumors. Hierarchical cluster analysis was performed to compare chromosome 3 transcriptome patterns of each growth condition. Differentially expressed genes were identified and characterized by two-way comparative analyses of fold-differences in gene expression between monolayer cultures and each of the other growth conditions, and between the maximum and minimum values of expression of all growth conditions for each EOC cell line.</p> <p>Results</p> <p>An overall high degree of similarity (> 90%) in gene expression was observed when expression values of alternative growth conditions were compared within each EOC cell line group. Two-way comparative analysis of each EOC cell line grown in an alternative condition relative to the monolayer culture showed that overall less than 15% of probe sets exhibited at least a 3-fold difference in expression profile. Less than 23% of probe sets exhibited greater than 3-fold differences in gene expression in comparisons of the maximum and minimum value of expression of all growth conditions within each EOC cell line group. The majority of these differences were less than 5-fold. There were 17 genes in common which were differentially expressed in all EOC cell lines. However, the patterns of expression of these genes were not necessarily the same for each growth condition when one cell line was compared with another.</p> <p>Conclusion</p> <p>The various alternative <it>in vivo </it>and <it>in vitro </it>growth conditions of tumorigenic EOC cell lines appeared to modestly influence the global chromosome 3 transcriptome supporting the notion that the <it>in vitro </it>cell line models are a viable option for testing gene candidates.</p

Clinical aspects of sentinel node biopsy

Sentinel lymph node (SLN) biopsy requires validation by a backup axillary dissection in a defined series of cases before becoming standard practice, to establish individual and institutional success rates and the frequency of false negative results. At least 90% success in finding the SLN with no more than 5-10% false negative results is a reasonable goal for surgeons and institutions learning the technique. A combination of isotope and dye to map the SLN is probably superior to either method used alone, yet a wide variety of technical variations in the procedure have produced a striking similarity of results. Most breast cancer patients are suitable for SLN biopsy, and the large majority reported to date has had clinical stage T1-2N0 invasive breast cancers. SLN biopsy will play a growing role in patients having prophylactic mastectomy, and in those with 'high-risk' duct carcinoma in situ, microinvasive cancers, T3 disease, and neoadjuvant chemotherapy. SLN biopsy for the first time makes enhanced pathologic analysis of lymph nodes logistically feasible, at once allowing greater staging accuracy and less morbidity than standard methods. Retrospective data suggest that micrometastases identified in this way are prognostically significant, and prospective clinical trials now accruing promise a definitive answer to this issue

Data management for prospective research studies using SAS® software

<p>Abstract</p> <p>Background</p> <p>Maintaining data quality and integrity is important for research studies involving prospective data collection. Data must be entered, erroneous or missing data must be identified and corrected if possible, and an audit trail created.</p> <p>Methods</p> <p>Using as an example a large prospective study, the Missouri Lower Respiratory Infection (LRI) Project, we present an approach to data management predominantly using SAS software. The Missouri LRI Project was a prospective cohort study of nursing home residents who developed an LRI. Subjects were enrolled, data collected, and follow-ups occurred for over three years. Data were collected on twenty different forms. Forms were inspected visually and sent off-site for data entry. SAS software was used to read the entered data files, check for potential errors, apply corrections to data sets, and combine batches into analytic data sets. The data management procedures are described.</p> <p>Results</p> <p>Study data collection resulted in over 20,000 completed forms. Data management was successful, resulting in clean, internally consistent data sets for analysis. The amount of time required for data management was substantially underestimated.</p> <p>Conclusion</p> <p>Data management for prospective studies should be planned well in advance of data collection. An ongoing process with data entered and checked as they become available allows timely recovery of errors and missing data.</p

Self-reported competence, attitude and approach of physicians towards patients with dementia in ambulatory care: Results of a postal survey

<p>Abstract</p> <p>Background</p> <p>Caring for patients with dementia is a demanding task. Little is known as to whether physicians feel competent enough to perform this task or whether a lack of self-perceived competence influences attitudes and professional approach. Even less is known with respect to potential differences between general practitioners (GPs) and specialists. The purpose of this study was to investigate the interrelationship between the self-perceived competence, attitude and professional approach of physicians in ambulatory care in Germany. A further aim was to compare GPs and specialists with regard to differences in these areas.</p> <p>Methods</p> <p>A standardised postal survey was sent to 389 GPs and 239 neurologists and psychiatrists in six metropolitan areas in Germany. The 49-item questionnaire consisted of attitudinal statements to be rated on a Likert-type scale. Return rates were 54 percent for GPs and 40 percent for specialists. Statistical methods used to analyze data included correlation analysis, cluster analysis and ordinal regression analysis.</p> <p>Results</p> <p>No differences were found between GPs and specialists with regard to their general attitude towards caring for patients with dementia. Approximately 15 percent of both disciplines showed a clearly negative attitude. Self-reported competence was strongly associated with general attitude. In particular among GPs, and less so among specialists, a strong positive association was found between self-reported competence, general attitude and professional approach (e.g. early detection, active case finding and cooperation with caregivers). Differences between GPs and specialists were smaller than expected and appear to predominantly reflect task differences within the German health care system.</p> <p>Conclusion</p> <p>Training opportunities which enable in particular GPs to enhance not only their competence but also their general attitude towards dementia care would appear to be beneficial and might carry positive consequences for patients and their caregivers.</p

Surface Aggregation of Urinary Proteins and Aspartic Acid-Rich Peptides on the Faces of Calcium Oxalate Monohydrate Investigated by In Situ Force Microscopy

The growth of calcium oxalate monohydrate in the presence of Tamm-Horsfall protein (THP), osteopontin, and the 27-residue synthetic peptides (DDDS)6DDD and (DDDG)6DDD (D = aspartic acid, S = serine, and G = glycine) was investigated via in situ atomic force microscopy. The results show that these four growth modulators create extensive deposits on the crystal faces. Depending on the modulator and crystal face, these deposits can occur as discrete aggregates, filamentary structures, or uniform coatings. These proteinaceous films can lead to either the inhibition of or an increase in the step speeds (with respect to the impurity-free system), depending on a range of factors that include peptide or protein concentration, supersaturation, and ionic strength. While THP and the linear peptides act, respectively, to exclusively increase and inhibit growth on the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\left( {\bar{1}01} \right)$$\end{document} face, both exhibit dual functionality on the (010) face, inhibiting growth at low supersaturation or high modulator concentration and accelerating growth at high supersaturation or low modulator concentration. Based on analyses of growth morphologies and dependencies of step speeds on supersaturation and protein or peptide concentration, we propose a picture of growth modulation that accounts for the observations in terms of the strength of binding to the surfaces and steps and the interplay of electrostatic and solvent-induced forces at the crystal surface

Potentiating antibacterial activity by predictably enhancing endogenous microbial ROS production

The ever-increasing incidence of antibiotic-resistant infections combined with a weak pipeline of new antibiotics has created a global public health crisis1. Accordingly, novel strategies for enhancing our antibiotic arsenal are needed. As antibiotics kill bacteria in part by inducing reactive oxygen species (ROS)2–4, we reasoned that targeting microbial ROS production might potentiate antibiotic activity. Here we show that ROS production can be predictably enhanced in Escherichia coli, increasing the bacteria’s susceptibility to oxidative attack. We developed an ensemble, genome-scale metabolic modeling approach capable of predicting ROS production in E. coli. The metabolic network was systematically perturbed and its flux distribution analyzed to identify targets predicted to increase ROS production. In silico–predicted targets were experimentally validated and shown to confer increased susceptibility to oxidants. Validated targets also increased susceptibility to killing by antibiotics. This work establishes a systems-based method to tune ROS production in bacteria and demonstrates that increased microbial ROS production can potentiate killing by oxidants and antibiotics

A Dynamical Systems Model for Combinatorial Cancer Therapy Enhances Oncolytic Adenovirus Efficacy by MEK-Inhibition

Oncolytic adenoviruses, such as ONYX-015, have been tested in clinical trials for currently untreatable tumors, but have yet to demonstrate adequate therapeutic efficacy. The extent to which viruses infect targeted cells determines the efficacy of this approach but many tumors down-regulate the Coxsackievirus and Adenovirus Receptor (CAR), rendering them less susceptible to infection. Disrupting MAPK pathway signaling by pharmacological inhibition of MEK up-regulates CAR expression, offering possible enhanced adenovirus infection. MEK inhibition, however, interferes with adenovirus replication due to resulting G1-phase cell cycle arrest. Therefore, enhanced efficacy will depend on treatment protocols that productively balance these competing effects. Predictive understanding of how to attain and enhance therapeutic efficacy of combinatorial treatment is difficult since the effects of MEK inhibitors, in conjunction with adenovirus/cell interactions, are complex nonlinear dynamic processes. We investigated combinatorial treatment strategies using a mathematical model that predicts the impact of MEK inhibition on tumor cell proliferation, ONYX-015 infection, and oncolysis. Specifically, we fit a nonlinear differential equation system to dedicated experimental data and analyzed the resulting simulations for favorable treatment strategies. Simulations predicted enhanced combinatorial therapy when both treatments were applied simultaneously; we successfully validated these predictions in an ensuing explicit test study. Further analysis revealed that a CAR-independent mechanism may be responsible for amplified virus production and cell death. We conclude that integrated computational and experimental analysis of combinatorial therapy provides a useful means to identify treatment/infection protocols that yield clinically significant oncolysis. Enhanced oncolytic therapy has the potential to dramatically improve non-surgical cancer treatment, especially in locally advanced or metastatic cases where treatment options remain limited.National Institutes of Health (U.S.) (Grant R01 CA118545)National Institutes of Health (U.S.) (Grant R01 CA095701)National Institutes of Health (U.S.) (Grant U54 CA11297)National Institutes of Health (U.S.) (Grant U54-CA112967