Waves Generated by Recreational Traffic on the Upper Mississippi River System

Movement of recreational boats in a waterway such as the Upper Mississippi River System (UMRS) generates waves that can impact the river biota and the stability of the shorelines. This report presents the results of a research project undertaken to determine the characteristics of waves generated by recreational craft within the UMRS. To meet the goals of the project, 246 controlled runs were made with 12 different boats at two sites, one on the Illinois River and the other on the Mississippi River. Data from the controlled runs indicated that recreational boats can generate from 4 to 40 waves per event, with a mean of about 10 to 20 waves. These waves can last from 6 to 40 seconds or more. Average wave heights for these controlled events varied from 0.01 to 0.25 meter, with a median of about 0.06 to 0.12 meter. The maximum wave height was as much as 0.6 meter. The wave data from the controlled runs were used to develop a regression equation for estimating maximum wave heights on the basis of the speed, draft, and length of the boats, and their distance from the measuring point. This relationship is now recommended for use in determining wave heights generated by recreational boats. Data from uncontrolled boating events on the Mississippi River indicated that as many as 704 boats passed a highly used area of the UMRS in a single day on a busy weekend. Up to 120 boats passed the site in a single hour. Sustained movement of recreational boats can generate essentially continuous waves, giving the appearance of random waves at or near the shoreline. During the day of heaviest boating activity at the Mississippi River site, the maximum wave height measured was 0.52 meter, and the average for the whole day was 0.065 meter. Analyses were also performed by partitioning the wave heights on an hourly basis. These analyses indicated that significant wave height can reach a magnitude of 0.4 meter or higher, and maximum wave height can reach 0.5 meter or higher. Calculations were also performed to show that for waves of 0.4 meter in height to develop at the Mississippi River site from wind alone, the wind would have to be blowing at a speed of about 26 meters per second (58 mph) across the measuring point. Wave energies were computed by partitioning the waves into five-minute intervals. These analyses showed that the shorelines are subjected to wave activity of fairly high intensity. No analyses were performed to determine the bank erosion potential or sediment resuspension characteristics of the waves generated by recreational boats. However, existing mathematical formulations can be used to analyze the stability of banks composed of noncohesive bank materials. Additional research should be initiated to determine the effects of recreational boats on the stability of cohesive and noncohesive banks, and the way in which wave activity resuspends bed materials.Ope

An extracellular steric seeding mechanism for Eph-ephrin signaling platform assembly

Erythropoetin-producing hepatoma (Eph) receptors are cell-surface protein tyrosine kinases mediating cell-cell communication. Upon activation, they form signaling clusters. We report crystal structures of the full ectodomain of human EphA2 (eEphA2) both alone and in complex with the receptor-binding domain of the ligand ephrinA5 (ephrinA5 RBD). Unliganded eEphA2 forms linear arrays of staggered parallel receptors involving two patches of residues conserved across A-class Ephs. eEphA2-ephrinA5 RBD forms a more elaborate assembly, whose interfaces include the same conserved regions on eEphA2, but rearranged to accommodate ephrinA5 RBD. Cell-surface expression of mutant EphA2s showed that these interfaces are critical for localization at cell-cell contacts and activation-dependent degradation. Our results suggest a 'nucleation' mechanism whereby a limited number of ligand-receptor interactions 'seed' an arrangement of receptors which can propagate into extended signaling arrays

New generalized fuzzy metrics and fixed point theorem in fuzzy metric space

In this paper, in fuzzy metric spaces (in the sense of Kramosil and Michalek (Kibernetika 11:336-344, 1957)) we introduce the concept of a generalized fuzzy metric which is the extension of a fuzzy metric. First, inspired by the ideas of Grabiec (Fuzzy Sets Syst. 125:385-389, 1989), we define a new G-contraction of Banach type with respect to this generalized fuzzy metric, which is a generalization of the contraction of Banach type (introduced by M Grabiec). Next, inspired by the ideas of Gregori and Sapena (Fuzzy Sets Syst. 125:245-252, 2002), we define a new GV-contraction of Banach type with respect to this generalized fuzzy metric, which is a generalization of the contraction of Banach type (introduced by V Gregori and A Sapena). Moreover, we provide the condition guaranteeing the existence of a fixed point for these single-valued contractions. Next, we show that the generalized pseudodistance J:X×X→[0,∞) (introduced by Włodarczyk and Plebaniak (Appl. Math. Lett. 24:325-328, 2011)) may generate some generalized fuzzy metric NJ on X. The paper includes also the comparison of our results with those existing in the literature

Genetic and biochemical analyses of chromosome and plasmid gene homologues encoding ICL and ArCP domains in Vibrioanguillarum strain 775

Anguibactin, the siderophore produced by Vibrio anguillarum 775 is synthesized from 2,3-dihydroxybenzoic acid (DHBA), cysteine and hydroxyhistamine via a nonribosomal peptide synthetase (NRPS) mechanism. Most of the genes encoding anguibactin biosynthetic proteins are harbored by the pJM1 plasmid. In this work we report the identification of a homologue of the plasmid-encoded angB on the chromosome of strain 775. The product of both genes harbor an isochorismate lyase (ICL) domain that converts isochorismic acid to 2,3-dihydro-2,3-dihydroxybenzoic acid, one of the steps of DHBA synthesis. We show in this work that both ICL domains are functional in the production of DHBA in V. anguillarum as well as in E. coli. Substitution by alanine of the aspartic acid residue in the active site of both ICL domains completely abolishes their isochorismate lyase activity in vivo. The two proteins also carry an aryl carrier protein (ArCP) domain. In contrast with the ICL domains only the plasmid encoded ArCP can participate in anguibactin production as determined by complementation analyses and site-directed mutagenesis in the active site of the plasmid encoded protein, S248A. The site-directed mutants, D37A in the ICL domain and S248A in the ArCP domain of the plasmid encoded AngB were also tested in vitro and clearly show the importance of each residue for the domain function and that each domain operates independently.

c-erbB2 and topoisomerase IIα protein expression independently predict poor survival in primary human breast cancer: a retrospective study

INTRODUCTION: c-erbB2 (also known as HER-2/neu) and topoisomerase IIα are frequently overexpressed in breast cancer. The aim of the study was to analyze retrospectively whether the expression of c-erbB2 and topoisomerase IIα protein influences the long-term outcome of patients with primary breast cancer. METHODS: In this study c-erbB2 and topoisomerase IIα protein were evaluated by immunohistochemistry in formalin-fixed paraffin-embedded tissue from 225 samples of primary breast cancer, obtained between 1986 and 1998. The prognostic value of these markers was analyzed. RESULTS: Of 225 primary breast tumor samples, 78 (34.7%) showed overexpression of either c-erbB2 (9.8%) or topoisomerase IIα protein (24.9%), whereas in 21 tumors (9.3%) both proteins were found to be overexpressed. Patients lacking both c-erbB2 and topoisomerase IIα overexpression had the best long-term survival. Overexpression of either c-erbB2 or topoisomerase IIα was associated with shortened survival, whereas patients overexpressing both c-erbB2 and topoisomerase IIα showed the worst disease outcome (P < 0.0001). Treatment with anthracyclines was not capable of reversing the negative prognostic impact of topoisomerase IIα or c-erbB2 overexpression. CONCLUSION: The results of this exploratory study suggest that protein expression of c-erbB2 and topoisomerase IIα in primary breast cancer tissues are independent prognostic factors and are not exclusively predictive factors for anthracycline response in patients with primary breast cancer

Critical roles for EGFR and EGFR–HER2 clusters in EGF binding of SW620 human carcinoma cells

Epidermal growth factor (EGF) signalling regulates normal epithelial and other cell growth, with EGF receptor (EGFR) overexpression reported in many cancers. However, the role of EGFR clusters in cancer and their dependence on EGF binding is unclear. We present novel single-molecule total internal reflection fluorescence microscopy of (i) EGF and EGFR in living cancer cells, (ii) the action of anti-cancer drugs that separately target EGFR and human EGFR2 (HER2) on these cells and (iii) EGFR–HER2 interactions. We selected human epithelial SW620 carcinoma cells for their low level of native EGFR expression, for stable transfection with fluorescent protein labelled EGFR, and imaged these using single-molecule localization microscopy to quantify receptor architectures and dynamics upon EGF binding. Prior to EGF binding, we observe pre-formed EGFR clusters. Unexpectedly, clusters likely contain both EGFR and HER2, consistent with co-diffusion of EGFR and HER2 observed in a different model CHO-K1 cell line, whose stoichiometry increases following EGF binding. We observe a mean EGFR : EGF stoichiometry of approximately 4 : 1 for plasma membrane-colocalized EGFR–EGF that we can explain using novel time-dependent kinetics modelling, indicating preferential ligand binding to monomers. Our results may inform future cancer drug developments.journal articl

Computational modelling of cancerous mutations in the EGFR/ERK signalling pathway

This article has been made available through the Brunel Open Access Publishing Fund - Copyright @ 2009 Orton et al.BACKGROUND: The Epidermal Growth Factor Receptor (EGFR) activated Extracellular-signal Regulated Kinase (ERK) pathway is a critical cell signalling pathway that relays the signal for a cell to proliferate from the plasma membrane to the nucleus. Deregulation of the EGFR/ERK pathway due to alterations affecting the expression or function of a number of pathway components has long been associated with numerous forms of cancer. Under normal conditions, Epidermal Growth Factor (EGF) stimulates a rapid but transient activation of ERK as the signal is rapidly shutdown. Whereas, under cancerous mutation conditions the ERK signal cannot be shutdown and is sustained resulting in the constitutive activation of ERK and continual cell proliferation. In this study, we have used computational modelling techniques to investigate what effects various cancerous alterations have on the signalling flow through the ERK pathway. RESULTS: We have generated a new model of the EGFR activated ERK pathway, which was verified by our own experimental data. We then altered our model to represent various cancerous situations such as Ras, B-Raf and EGFR mutations, as well as EGFR overexpression. Analysis of the models showed that different cancerous situations resulted in different signalling patterns through the ERK pathway, especially when compared to the normal EGF signal pattern. Our model predicts that cancerous EGFR mutation and overexpression signals almost exclusively via the Rap1 pathway, predicting that this pathway is the best target for drugs. Furthermore, our model also highlights the importance of receptor degradation in normal and cancerous EGFR signalling, and suggests that receptor degradation is a key difference between the signalling from the EGF and Nerve Growth Factor (NGF) receptors. CONCLUSION: Our results suggest that different routes to ERK activation are being utilised in different cancerous situations which therefore has interesting implications for drug selection strategies. We also conducted a comparison of the critical differences between signalling from different growth factor receptors (namely EGFR, mutated EGFR, NGF, and Insulin) with our results suggesting the difference between the systems are large scale and can be attributed to the presence/absence of entire pathways rather than subtle difference in individual rate constants between the systems.This work was funded by the Department of Trade and Industry (DTI), under their Bioscience Beacon project programme. AG was funded by an industrial PhD studentship from Scottish Enterprise and Cyclacel

Prospective monitoring improves outcomes of primary total hip replacement: a cohort study

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

A Systematic Review Identifying Adverse Health Outcomes and Mortality Rates Associated with Telehealth

Background: The literature supporting telehealth management is growing accelerated by the COVID-pandemic. We hypothesize that there are risks of adverse events associated with telehealth interventions. Methods: A review of PubMed (including MEDLINE), Embase, ISI (Web of Science), VHL/GHL, Scopus, Science Direct, and PsycINFO was conducted for all adverse events associated with telehealth from January 1, 1960 to March 1, 2021. This systematic review and meta-analyses were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Of 5,144 citations 78 published studies met criteria for quality evaluation and underwent full text abstraction including the qualitative synthesis. Of the 78 included studies 8 were included in the quantitative synthesis resulting in 2 meta-analyses. The results of the meta-analysis suggest that monitoring patients using telehealth techniques is associated with 40% lower mortality risks among patients suffering from heart failure, compared to those who received traditional care. The results of the random-effects meta-analysis showed the pooled relative risk of mortality to be 0.60, indicating that patients that underwent telemonitoring had a lower mortality risk compared with the patients that underwent usual care. Among patients with heart implants, patients who received telemonitoring had a 35% lower mortality risk compared to patients receiving traditional care. Conclusions: While RCTs of telehealth interventions demonstrate enhanced patient outcomes in a number of studies and pave the way to evidence-based practice, the heterogeneity of the research questions suggest an important need for more complementary studies with consistent outcome assessments

Membranes by the Numbers

Many of the most important processes in cells take place on and across membranes. With the rise of an impressive array of powerful quantitative methods for characterizing these membranes, it is an opportune time to reflect on the structure and function of membranes from the point of view of biological numeracy. To that end, in this article, I review the quantitative parameters that characterize the mechanical, electrical and transport properties of membranes and carry out a number of corresponding order of magnitude estimates that help us understand the values of those parameters.Comment: 27 pages, 12 figure