Taenia taeniaeformis: Increased cell growth and neutral mucus production in the gastric mucosa of the rat with a larval infection

Gross hyperplasia of the gastric mucosa and excessive mucus production in the stomach occur in rats heavily parasitized with larvae of Taenia taeniaeformis. In this study, a positive correlation between the number of larvae recovered from hepatic cysts and the weight of the stomachs of infected rats was found. By light microscopy, the hyperplasia was restricted to the glandular mucosa. Parietal and chief cells were very rare, and densely PAS-positive mucous cells were the major cell types in the hyperplastic stomach while, in comparison, alcian blue-positive cells were much fewer in number. The isolated gastric mucosa in organ culture had an increased [³H]thymidine incorporation rate in rats infected with T. taeniaeformis. The hexosamine concentration per milligram protein in the hyperplastic stomach mucosa was twice that in the control rat stomach mucosa. By electron microscopy, the apical cytoplasm of the mucous cells was found to be filled with small dark granules. These results indicate that the gastric hyperplasia is caused by stimulation of growth and major differentiation of stem cells to neutral mucus-producing cells.     

Evaluating the Impact of Flexible Alcohol Trading Hours on Violence: An Interrupted Time Series Analysis

Background

On November 24^th 2005, the Government of England and Wales removed regulatory restrictions on the times at which licensed premises could sell alcohol. This study tests availability theory by treating the implementation of Licensing Act (2003) as a natural experiment in alcohol policy.

Methods

An interrupted time series design was employed to estimate the Act’s immediate and delayed impact on violence in the City of Manchester (Population 464,200). We collected police recorded rates of violence, robbery, and total crime between the 1st of February 2004 and the 31st of December 2007. Events were aggregated by week, yielding a total of 204 observations (95 pre-, and 109 post-intervention). Secondary analysis examined changes in daily patterns of violence. Pre- and post-intervention events were separated into four three-hour segments 18∶00–20∶59, 21∶00–23.59, 00∶00–02∶59, 03∶00–05∶59.

Results

Analysis found no evidence that the Licensing Act (2003) affected the overall volume of violence. However, analyses of night-time violence found a gradual and permanent shift of weekend violence into later parts of the night. The results estimated an initial increase of 27.5% between 03∶00 to 06∶00 (ω = 0.2433, 95% CI = 0.06, 0.42), which increased to 36% by the end of the study period (δ = −0.897, 95% CI = −1.02, −0.77).

Conclusions

This study found no evidence that a national policy increasing the physical availability of alcohol affected the overall volume of violence. There was, however, evidence suggesting that the policy may be associated with changes to patterns of violence in the early morning (3 a.m. to 6 a.m.).     

HPOSim: An R Package for Phenotypic Similarity Measure and Enrichment Analysis Based on the Human Phenotype Ontology

BackgroundPhenotypic features associated with genes and diseases play an important role in disease-related studies and most of the available methods focus solely on the Online Mendelian Inheritance in Man (OMIM) database without considering the controlled vocabulary. The Human Phenotype Ontology (HPO) provides a standardized and controlled vocabulary covering phenotypic abnormalities in human diseases, and becomes a comprehensive resource for computational analysis of human disease phenotypes. Most of the existing HPO-based software tools cannot be used offline and provide only few similarity measures. Therefore, there is a critical need for developing a comprehensive and offline software for phenotypic features similarity based on HPO.ResultsHPOSim is an R package for analyzing phenotypic similarity for genes and diseases based on HPO data. Seven commonly used semantic similarity measures are implemented in HPOSim. Enrichment analysis of gene sets and disease sets are also implemented, including hypergeometric enrichment analysis and network ontology analysis (NOA).ConclusionsHPOSim can be used to predict disease genes and explore disease-related function of gene modules. HPOSim is open source and freely available at SourceForge (https://sourceforge.net/p/hposim/).     

Marathon: An Open Source Software Library for the Analysis of Markov-Chain Monte Carlo Algorithms

We present the software library marathon, which is designed to support the analysis of sampling algorithms that are based on the Markov-Chain Monte Carlo principle. The main application of this library is the computation of properties of so-called state graphs, which represent the structure of Markov chains. We demonstrate applications and the usefulness of marathon by investigating the quality of several bounding methods on four well-known Markov chains for sampling perfect matchings and bipartite graphs. In a set of experiments, we compute the total mixing time and several of its bounds for a large number of input instances. We find that the upper bound gained by the famous canonical path method is often several magnitudes larger than the total mixing time and deteriorates with growing input size. In contrast, the spectral bound is found to be a precise approximation of the total mixing time.     

ALLocator: An Interactive Web Platform for the Analysis of Metabolomic LC-ESI-MS Datasets,Enabling Semi-Automated,User-Revised Compound Annotation and Mass Isotopomer Ratio Analysis

Adduct formation, fragmentation events and matrix effects impose special challenges to the identification and quantitation of metabolites in LC-ESI-MS datasets. An important step in compound identification is the deconvolution of mass signals. During this processing step, peaks representing adducts, fragments, and isotopologues of the same analyte are allocated to a distinct group, in order to separate peaks from coeluting compounds. From these peak groups, neutral masses and pseudo spectra are derived and used for metabolite identification via mass decomposition and database matching. Quantitation of metabolites is hampered by matrix effects and nonlinear responses in LC-ESI-MS measurements. A common approach to correct for these effects is the addition of a U-¹³C-labeled internal standard and the calculation of mass isotopomer ratios for each metabolite. Here we present a new web-platform for the analysis of LC-ESI-MS experiments. ALLocator covers the workflow from raw data processing to metabolite identification and mass isotopomer ratio analysis. The integrated processing pipeline for spectra deconvolution “ALLocatorSD” generates pseudo spectra and automatically identifies peaks emerging from the U-¹³C-labeled internal standard. Information from the latter improves mass decomposition and annotation of neutral losses. ALLocator provides an interactive and dynamic interface to explore and enhance the results in depth. Pseudo spectra of identified metabolites can be stored in user- and method-specific reference lists that can be applied on succeeding datasets. The potential of the software is exemplified in an experiment, in which abundance fold-changes of metabolites of the l-arginine biosynthesis in C. glutamicum type strain ATCC 13032 and l-arginine producing strain ATCC 21831 are compared. Furthermore, the capability for detection and annotation of uncommon large neutral losses is shown by the identification of (γ-)glutamyl dipeptides in the same strains. ALLocator is available online at: https://allocator.cebitec.uni-bielefeld.de. A login is required, but freely available.     

Regulating Shipping in the Arctic Ocean: An Analysis of State Practice

The United Nations Convention on the Law of the Sea (LOSC) permits state parties to establish an Exclusive Economic Zone (EEZ) 200 nautical miles from their coast. Coastal states have exclusive jurisdiction over resources within the EEZ, but navigational and other high seas freedoms continue to exist. A significant number of states have, however, enacted legislation that departs from the LOSC, interfering with the navigational rights and freedoms of other states. This article analzses this development with a specific focus on the Arctic. It investigates the powers of Arctic coastal states to regulate shipping in the EEZ and thereby navigation in the Arctic Ocean. It adds to the existing literature by providing an analysis of state practice, suggesting that despite uncertainty concerning the interpretation of the LOSC Article 234 and the right to exercise legislative jurisdiction over ice-covered waters, a not insignificant number of states have claimed jurisdiction in their own EEZ beyond the rights granted in the LOSC, and are therefore not in a position to object to extensive jurisdictional claims in the Arctic.     

LVTree Viewer:An Interactive Display for the All-Species Living Tree Incorporating Automatic Comparison with Prokaryotic Systematics

We describe an interactive viewer for the All-Species Living Tree (LVTree). The viewer incorporates treeing and lineage information from the ARB-SILVA website. It allows collapsing the tree branches at different taxonomic ranks and expanding the collapsed branches as well, keeping the overall topology of the tree unchanged. It also enables the user to observe the consequence of trial lineage modifications by re-collapsing the tree. The system reports taxon statistics at all ranks automatically after each collapsing and re-collapsing. These features greatly facilitate the compar-ison of the 16S rRNA sequence phylogeny with prokaryotic taxonomy in a taxon by taxon manner. In view of the fact that the present prokaryotic systematics is largely based on 16S rRNA sequence analysis, the current viewer may help reveal discrepancies between phylogeny and taxonomy. As an application, we show that in the latest release of LVTree, based on 11,939 rRNA sequences, as few as 24 lineage modifications are enough to bring all but two phyla (Proteobacteria and Firmicutes) to monophyletic clusters.     

生态网络分析与模拟的软件系统ASSEN及其应用

生态网络分析是研究生态网络的理论和方法,ＡＳＳＥＮ（ｔｈｅＡｎａｌｙｓｉｓａｎｄｓｉｍｕｌａｔｉｏｎＳｙｓｔｅｍｆｏＥｃｏｎｅｔｗｏｒｋｓ）是生态网络分析和模拟的软件系统,本文在简述生态网络分析基本方法的基础上,介绍了ＡＳＳＥＮ的结构和功能,并利用ＡＳＳＥＮ对一个简单水流生态网络进行了分析和模拟。     

Ascertainment: An Overwiew of the Classical Segregation Analysis Model for Independent Sibships

Several different methodologies for parameter estimation under various ascertainment sampling schemes have been proposed in the past. In this article, some of the methodologies that have been proposed for independent sibships under the classical segregation analysis model are synthesized, and the general likelihoods derived for single, multiple and complete ascertainment. The issue of incorporating the sibship size distribution into the analysis is addressed, and the effect of conditioning the likelihood on the observed sibship sizes is discussed. It is shown that when the number of probands in a sibship is not specified, the corresponding likelihood can be used for a broader class of ascertainment schemes than is subsumed by the classical model.     

Time intervals from first symptom to diagnosis for head and neck cancers: An analysis of linked patient reports and medical records from the UK

BackgroundEngland has significantly higher mortality risks due to Head and Neck Cancer (HNC) compared with other European countries. Early diagnosis is important as it is likely to increase early-stage diagnosis and improve survival and better quality of life. This study sought to improve understanding of the intervals from first symptom recognition to diagnosis for HNC and investigate associations between patient-reported symptoms and socio-demographic factors.MethodsPeople within 3 months of diagnosis, completed a researcher-administered questionnaire and data were extracted from primary and secondary care clinical records.ResultsEighty (mean age 62.9 [SD 11.7] years; 66% men) were interviewed. The appraisal interval was longer than a month for 39% of participants and the help-seeking interval was longer than a week for 44%. The median diagnostic interval was 92 (IQR; 34-172) days. Appraisal intervals of > 1 month were associated with male gender, ulceration and persistent throat pain. The only symptom that associated with a help-seeking interval of > 1 week was ulceration. Participants who reported red/white patches in the mouth and ulceration were associated with a reduced likelihood of a diagnostic interval of > 3 months. A higher proportion of participants with a diagnostic interval of > 3 months were diagnosed with advanced disease (78%) than those with an interval < 3 months (68%).ConclusionThese data improve understanding of the intervals from first symptom recognition to HNC diagnosis and provide preliminary evidence to identify targets to reduce overall time to diagnosis.     

Basic Analysis of the Cerebrospinal Fluid: An Important Framework for Laboratory Diagnostics of the Impairment of the Central Nervous System

Laboratory analysis of basic cerebrospinal fluid (CSF) parameters is considered as essential for any CSF evaluation. It can provide rapidly very valuable information about the status of the central nervous system (CNS). Our retrospective study evaluated parameters of basic CSF analysis in cases of either infectious or non-infectious CNS involvement. Neutrophils are effector cells of innate immunity. Predominance of neutrophils was found in 98.2% of patients with purulent inflammation in CNS. Lymphocytes are cellular substrate of adaptive immunity. We found their predominance in 94.8% of patients with multiple sclerosis (MS), 66.7% of patients with tick-borne encephalitis (TBE), 92.2% of patients with neuroborreliosis, 83.3% of patients with inflammatory response with oxidative burst of macrophages in CNS and 75.0% of patients with malignant infiltration of meninges (MIM). The simultaneous assessment of aerobic and anaerobic metabolism in CSF using the coefficient of energy balance (KEB) allows us to specify the type of inflammation in CNS. We found predominantly aerobic metabolism (KEB > 28.0) in 100.0% CSF of patients with normal CSF findings and in 92.8% CSF of patients with MS. Predominant faintly anaerobic metabolism (28.0 > KEB > 20.0) in CSF was found in 71.8% patients with TBE and in 64.7% patients with neuroborreliosis. Strong anaerobic metabolism (KEB < 10.0) was found in the CSF of 99.1% patients with purulent inflammation, 100.0% patients with inflammatory response with oxidative burst of macrophages and in 80.6% patients with MIM. Joint evaluation of basic CSF parameters provides sufficient information about the immune response in the CSF compartment for rapid and reliable diagnosis of CNS involvement.     

Integrating Comparative Risk Assessment with Multi-Criteria Decision Analysis to Manage Contaminated Sediments: An Example for the New York/New Jersey Harbor

Current environmental challenges involve complex assessment and analysis of tradeoffs among differing criteria, expectations, and levels of certainty. Using multi-criteria decision analysis in combination with comparative risk assessment, a systematic and transparent framework can be created to integrate different types and sources of decision-relevant information. Although examples of decision analysis abound in the literature and academic efforts, its use within the practice of risk assessment and environmental management is still being established. This article provides an example of the use of decision analysis study that builds on a previous screening-level, comparative risk assessment of contaminated sediment from the New York/New Jersey harbor area. Using multi-criteria decision analysis, we explored the effect of different criteria weights, utility functions, and cost estimates on the ranking of seven contaminated sediment management alternatives. Values used in weighting decision criteria were surveyed from two interaction sessions with sediment management professionals.     

An Integrated Case Study for Evaluating the Impacts of an Oil Refinery Effluent on Aquatic Biota in the Delaware River: Integration and Analysis of Study Components

A series of statistical and graphical techniques incorporating a “weight of evidence” approach were used to interpret results from an integrated Triad case study designed to determine potential environmental impacts to aquatic biota in the Delaware River that may be linked to PAHs found in Motiva's oil refinery effluent. Sediment concentrations of various metals, PCBs and LMW PAHs exceeding both ERL and ERM sediment quality guidelines (SQGs) were reported in the study area. However, most chemical contaminants did not exceed their respective SQGs. Results from a long-term sediment coring study indicated that there was no evidence of significant historical PAH contamination of sediments related to Motiva's exceedences. PAHs comprising the Motiva “fingerprint” were found in the surficial sediments at four near-field sites but non-Motiva PAH concentrations (background) were shown to be significantly higher at other far-field sites (non-Motiva influence). Chronic sediment toxicity appears to have significant relationships to the patterns of most PAH isomers, certain PCB isomers, and certain metals. However, sediment toxicity does not appear to be related to the PAH isomers that are characteristic of Motiva's effluent nor to the near-field sites. Impacted benthic communities were reported in the study area, primarily at one near-field and two far-field sites. However, there were no apparent relationships between benthic community health and sediment contaminants. The status of benthic communities does not appear to be related to PAHs derived from the Motiva effluent. The “weight of evidence” analysis developed from a systematic and comprehensive series of statistical and graphical assessments indicates that, although the study area displayed some degree of sediment contamination, chronic sediment toxicity, and benthic health impacts, these environmental effects generally could not be related to Motiva's exceedences.     

An Integrated Approach for Analysis of the DNA Damage Response in Mammalian Cells: NUCLEOTIDE EXCISION REPAIR,DNA DAMAGE CHECKPOINT,AND APOPTOSIS*

DNA damage by UV and UV-mimetic agents elicits a set of inter-related responses in mammalian cells, including DNA repair, DNA damage checkpoints, and apoptosis. Conventionally, these responses are analyzed separately using different methodologies. Here we describe a unified approach that is capable of quantifying all three responses in parallel using lysates from the same population of cells. We show that a highly sensitive in vivo excision repair assay is capable of detecting nucleotide excision repair of a wide spectrum of DNA lesions (UV damage, chemical carcinogens, and chemotherapeutic drugs) within minutes of damage induction. This method therefore allows for a real-time measure of nucleotide excision repair activity that can be monitored in conjunction with other components of the DNA damage response, including DNA damage checkpoint and apoptotic signaling. This approach therefore provides a convenient and reliable platform for simultaneously examining multiple aspects of the DNA damage response in a single population of cells that can be applied for a diverse array of carcinogenic and chemotherapeutic agents.     

Evidence for the Induction of Repetitive Action Potentials in Synaptosomes by K+-Channel Inhibitors: An Analysis of Plasma Membrane Ion Fluxes

Abstract: The effects of four K⁺-channel inhibitors on synaptosomal free Ca²⁺ concentrations and ⁸⁶Rb⁺ fluxes are analysed. 4-Aminopyridine, α-dendrotoxin, charybdotoxin, and tetraethylammonium all increase the free Ca²⁺ concentration, although their potencies differ widely. In each case, the elevation in free Ca²⁺ concentration is reversed by the subsequent addition of tetrodotoxin. The transient ⁸⁶Rb⁺ efflux from preequilibrated synaptosomes induced with high concentrations of veratridine is partially inhibited by 4-aminopyridine and α-dendrotoxin. In contrast, when 4-aminopyridine or α-dendrotoxin is added to polarized synaptosomes, an enhanced⁸⁶Rb⁺ flux is seen, both for uptake and for efflux with no change in the total ⁸⁶Rb⁺/K⁺ content of the synaptosomes and with only a slight time-averaged plasma membrane depolarization (6.4 and 3.3 mV, respectively). The enhancements of flux by 4-aminopyridine or α-dendrotoxin are sensitive to ouabain and/or to tetrodotoxin. Furthermore, these flux changes show the same concentration dependencies as the blocked component of veratridine-stimulated ⁸⁶Rb⁺ efflux, the elevation of free Ca²⁺ concentration, and the facilitation of glutamate exocytosis that are elicited by 4-aminopyridine or α-dendrotoxin. It is concluded that these findings support the proposal of spontaneous, repetitive firing of synaptosomes evoked by K⁺-channel inhibitors and that the enhanced ⁸⁶Rb⁺ flux is a consequence of the activity of 4-aminopyridine- and α-dendrotoxin-insensitive K⁺ channels during these action potentials.     

A Semiautomated Analysis Method for Catecholamines, Indoleamines, and Some Prominent Metabolites in Microdissected Regions of the Nervous System: An Isocratic HPLC Technique Employing Coulometric Detection and Minimal Sample Preparation

The application of a commercially available coulometric electrochemical detector to the automated HPLC analysis of some monoamines and their metabolites in microdissected areas of the rat nervous system is described. Apart from the stability and high sensitivity of the system, other appealing features of the technique are the facile sample preparation and long-term sample storage characteristics which show minimal analyte degradation. Basal values of some regional monoamine and metabolite concentration are listed together with a brief appendix that serves as a user's guide to the operation and maintenance of the detection system.