Expression of αvβ6integrin in oral leukoplakia

The distribution of αvβ6integrin was examined in oral leukoplakia, lichen planus and squamous cell carcinomas using immunohistochemistry. Controls included oral mucosal wounds, chronically inflamed and normal oral mucosa. Integrins β1, β3, β4, β5, fibronectin and tenascin were also studied. The integrin αvβ6was highly expressed throughout the whole lesion of 90% of the squamous cell carcinomas but was not present in any of the normal specimens. αvβ6integrin was also expressed in 41% of the leukoplakia specimens, and 85% of the lichen planus samples, but in none of the tissues with inflammatory hyperplasia or chronic inflammation. The expression of β1 integrins was localized in the basal layer, and that of the β4at the cell surface facing the basement membrane of all specimens. The integrins β3and β5were absent from all normal and leukoplakia specimens. Fibronectin and tenascin were present in the connective tissue underneath the epithelium of all the sections, and their expression was similar in both αvβ6-positive and αvβ6-negative tissues. A group of 28 leukoplakia patients were followed 1–4 years after first diagnosis. In this group, initially αvβ6integrin-positive leukoplakia specimens had high tendency for disease progression while αvβ6-negative specimens did not progress. These results suggest that the expression of αvβ6integrin could be associated in the malignant transformation of oral leukoplakias. © 2000 Cancer Research Campaig

The desmosome and pemphigus

Desmosomes are patch-like intercellular adhering junctions (“maculae adherentes”), which, in concert with the related adherens junctions, provide the mechanical strength to intercellular adhesion. Therefore, it is not surprising that desmosomes are abundant in tissues subjected to significant mechanical stress such as stratified epithelia and myocardium. Desmosomal adhesion is based on the Ca2+-dependent, homo- and heterophilic transinteraction of cadherin-type adhesion molecules. Desmosomal cadherins are anchored to the intermediate filament cytoskeleton by adaptor proteins of the armadillo and plakin families. Desmosomes are dynamic structures subjected to regulation and are therefore targets of signalling pathways, which control their molecular composition and adhesive properties. Moreover, evidence is emerging that desmosomal components themselves take part in outside-in signalling under physiologic and pathologic conditions. Disturbed desmosomal adhesion contributes to the pathogenesis of a number of diseases such as pemphigus, which is caused by autoantibodies against desmosomal cadherins. Beside pemphigus, desmosome-associated diseases are caused by other mechanisms such as genetic defects or bacterial toxins. Because most of these diseases affect the skin, desmosomes are interesting not only for cell biologists who are inspired by their complex structure and molecular composition, but also for clinical physicians who are confronted with patients suffering from severe blistering skin diseases such as pemphigus. To develop disease-specific therapeutic approaches, more insights into the molecular composition and regulation of desmosomes are required

A scoping review of simulation models of peer review

Peer review is a process used in the selection of manuscripts for journal publication and proposals for research grant funding. Though widely used, peer review is not without flaws and critics. Performing large-scale experiments to evaluate and test correctives and alternatives is difficult, if not impossible. Thus, many researchers have turned to simulation studies to overcome these difficulties. In the last ten years this field of research has grown significantly but with only limited attempts to integrate disparate models or build on previous work. Thus, the resulting body of literature consists of a large variety of models, hinging on incompatible assumptions, which have not been compared, and whose predictions have rarely been empirically tested. This scoping review is an attempt to understand the current state of simulation studies of peer review. Based on 46 articles identified through literature searching, we develop a proposed taxonomy of model features that include model type (e.g. formal models vs. ABMs or other) and the type of modeled peer review system (e.g. peer review in grants vs. in journals or other). We classify the models by their features (including some core assumptions) to help distinguish between the modeling approaches. Finally, we summarize the models’ findings around six general themes: decision-making, matching submissions/reviewers, editorial strategies; reviewer behaviors, comparisons of alternative peer review systems, and the identification and addressing of biases. We conclude with some open challenges and promising avenues for future modeling work.Science Foundation Irelan

Calibration and validation of a simulation model for predicting pedestrian fatalities at unsignalized crosswalks by means of statistical traffic data

This work presents a simulation model for unsignalized crosswalks which takes into account collisions between vehicles and pedestrians, thus allowing to assess the estimated yearly pedestrian fatality. In particular, we focus on a method to calibrate such a model combining measurable crosswalk characteristics, such as maximum speed limit or drivers' compliance, with statistical data for past accidents obtained from local municipality. In order to perform simulations under realistic conditions, we constructed a one-week scenario where pedestrian and vehicle traffic vary using specific patterns each hour of the week. The constructed traffic profile is based on openly available data and the suitability for the scenario considered (a crosswalk in Milan, Italy) is investigated showing that cultural/lifestyle elements determine the variation of weekly traffic. Simulations using the constructed one-week scenario were used to obtain the only non-measurable parameter which account for pedestrians' and drivers' distraction. In addition, we also focused on the presence of elderly pedestrians which have different physiological characteristics compared to adults or children and are becoming an important part of the population in several countries around the globe. The simulation model presented here and the method suggested for calibration may be employed in different contexts, thus allowing to build an important tool to be used not only for transportation efficiency/optimization but also for safety analysis. Keywords: Traffic simulation, Accident prevention, Unsignalized crosswalk, Vehicle-pedestrian interaction, Weekly traffic variatio