The Compelling Case for Indentation as a Functional Exploratory and Characterization Tool

The utility of indentation testing for characterizing a wide range of mechanical properties of brittle materials is highlighted in light of recent articles questioning its validity, specifically in relation to the measurement of toughness. Contrary to assertion by some critics, indentation fracture theory is fundamentally founded in Griffith–Irwin fracture mechanics, based on model crack systems evolving within inhomogeneous but well-documented elastic and elastic–plastic contact stress fields. Notwithstanding some numerical uncertainty in associated stress intensity factor relations, the technique remains an unrivalled quick, convenient and economical means for comparative, site-specific toughness evaluation. Most importantly, indentation patterns are unique fingerprints of mechanical behavior and thereby afford a powerful functional tool for exploring the richness of material diversity. At the same time, it is cautioned that unconditional usage without due attention to the conformation of the indentation patterns can lead to overstated toughness values. Limitations of an alternative, more engineering approach to fracture evaluation, that of propagating a pre-crack through a 'standard' machined specimen, are also outlined. Misconceptions in the critical literature concerning the fundamental nature of crack equilibrium and stability within contact and other inhomogeneous stress fields are discussed.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1111/jace.1372

Extracting scientific articles from a large digital archive: BioStor and the Biodiversity Heritage Library

Background: The Biodiversity Heritage Library (BHL) is a large digital archive of legacy biological literature, comprising over 31 million pages scanned from books, monographs, and journals. During the digitisation process basic metadata about the scanned items is recorded, but not article-level metadata. Given that the article is the standard unit of citation, this makes it difficult to locate cited literature in BHL. Adding the ability to easily find articles in BHL would greatly enhance the value of the archive. Description: A service was developed to locate articles in BHL based on matching article metadata to BHL metadata using approximate string matching, regular expressions, and string alignment. This article locating service is exposed as a standard OpenURL resolver on the BioStor web site http://biostor.org/openurl/. This resolver can be used on the web, or called by bibliographic tools that support OpenURL. Conclusions: BioStor provides tools for extracting, annotating, and visualising articles from the Biodiversity Heritage Library. BioStor is available from http://biostor.org

Activation of Epidermal Growth Factor Receptor Is Required for NTHi-Induced NF-κB-Dependent Inflammation

Inflammation is a hallmark of many serious human diseases. Nontypeable Haemophilus influenzae (NTHi) is an important human pathogen causing respiratory tract infections in both adults and children. NTHi infections are characterized by inflammation, which is mainly mediated by nuclear transcription factor-kappa B (NF-κB)-dependent production of proinflammatory mediators. Epidermal growth factor receptor (EGFR) has been shown to play important roles in regulating diverse biological processes, including cell growth, differentiation, apoptosis, adhesion, and migration. Its role in regulating NF-κB activation and inflammation, however, remains largely unknown.In the present study, we demonstrate that EGFR plays a vital role in NTHi-induced NF-κB activation and the subsequent induction of proinflammatory mediators in human middle ear epithelial cells and other cell types. Importantly, we found that AG1478, a specific tyrosine kinase inhibitor of EGFR potently inhibited NTHi-induced inflammatory responses in the middle ears and lungs of mice in vivo. Moreover, we found that MKK3/6-p38 and PI3K/Akt signaling pathways are required for mediating EGFR-dependent NF-κB activation and inflammatory responses by NTHi.Here, we provide direct evidence that EGFR plays a critical role in mediating NTHi-induced NF-κB activation and inflammation in vitro and in vivo. Given that EGFR inhibitors have been approved in clinical use for the treatment of cancers, current studies will not only provide novel insights into the molecular mechanisms underlying the regulation of inflammation, but may also lead to the development of novel therapeutic strategies for the treatment of respiratory inflammatory diseases and other inflammatory diseases

Assessment of alcohol problems using AUDIT in a prison setting: more than an 'aye or no' question

<br>Background: Alcohol problems are a major UK and international public health issue. The prevalence of alcohol problems is markedly higher among prisoners than the general population. However, studies suggest alcohol problems among prisoners are under-detected, under-recorded and under-treated. Identifying offenders with alcohol problems is fundamental to providing high quality healthcare. This paper reports use of the AUDIT screening tool to assess alcohol problems among prisoners.</br> <br>Methods: Universal screening was undertaken over ten weeks with all entrants to one male Scottish prison using the AUDIT standardised screening tool and supplementary contextual questions. The questionnaire was administered by trained prison officers during routine admission procedures. Overall 259 anonymised completed questionnaires were analysed.</br> <br>Results: AUDIT scores showed a high prevalence of alcohol problems with 73% of prisoner scores indicating an alcohol use disorder (8+), including 36% having scores indicating ‘possible dependence’ (20-40). AUDIT scores indicating ‘possible dependence’ were most apparent among 18-24 and 40-64 year-olds (40% and 56% respectively). However, individual questions showed important differences, with younger drinkers less likely to demonstrate habitual and addictive behaviours than the older age group. Disparity between high levels of harmful/hazardous/dependent drinking and low levels of ‘treatment’ emerged (only 27% of prisoners with scores indicating ‘possible dependence’ reported being ‘in treatment’). Self-reported associations between drinking alcohol and the index crime were identified among two-fifths of respondents, rising to half of those reporting violent crimes.</br> <br>Conclusions: To our knowledge, this is the first study to identify differing behaviours and needs among prisoners with high AUDIT score ranges, through additional analysis of individual questions. The study has identified high prevalence of alcohol use, varied problem behaviours, and links across drinking, crime and recidivism, supporting the argument for more extensive provision of alcohol-focused interventions in prisons. These should be carefully targeted based on initial screening and assessment, responsive, and include care pathways linking prisoners to community services. Finally, findings confirm the value and feasibility of routine use of the AUDIT screening tool in prison settings, to considerably enhance practice in the detection and understanding of alcohol problems, improving on current more limited questioning (e.g. ‘yes or no’ questions).</br&gt

Assessing weight perception accuracy to promote weight loss among U.S. female adolescents: A secondary analysis

<p>Abstract</p> <p>Background</p> <p>Overweight and obesity have become a global epidemic. The prevalence of overweight and obesity among U.S. adolescents has almost tripled in the last 30 years. Results from recent systematic reviews demonstrate that no single, particular intervention or strategy successfully assists overweight or obese adolescents in losing weight. An understanding of factors that influence healthy weight-loss behaviors among overweight and obese female adolescents promotes effective, multi-component weight-loss interventions. There is limited evidence demonstrating associations between demographic variables, body-mass index, and weight perception among female adolescents trying to lose weight. There is also a lack of previous studies examining the association of the accuracy of female adolescents' weight perception with their efforts to lose weight. This study, therefore, examined the associations of body-mass index, weight perception, and weight-perception accuracy with trying to lose weight and engaging in exercise as a weight-loss method among a representative sample of U.S. female adolescents.</p> <p>Methods</p> <p>A nonexperimental, descriptive, comparative secondary analysis design was conducted using data from Wave II (1996) of the National Longitudinal Study of Adolescent Health (Add Health). Data representative of U.S. female adolescents (N = 2216) were analyzed using STATA statistical software. Descriptive statistics and survey weight logistic regression were performed to determine if demographic and independent (body-mass index, weight perception, and weight perception accuracy) variables were associated with trying to lose weight and engaging in exercise as a weight-loss method.</p> <p>Results</p> <p>Age, Black or African American race, body-mass index, weight perception, and weight perceptions accuracy were consistently associated with the likeliness of trying to lose weight among U.S. female adolescents. Age, body-mass index, weight perception, and weight-perception accuracy were positively associated (<it>p </it>< 0.05) with trying to lose weight. Black/African American subjects were significantly less likely than their White counterparts to be trying to lose weight. There was no association between demographic or independent variables and engaging in exercise as a weight-loss method.</p> <p>Conclusions</p> <p>Findings suggest that factors influencing weight-loss efforts, including age, race, body-mass index, weight perception, and weight-perception accuracy, should be incorporated into existing or new multi-component weight-loss interventions for U.S. adolescent females in order to help reduce the national epidemic of overweight and obesity among U.S. female adolescents.</p

The Cortisol Response to Anticipated Intergroup Interactions Predicts Self-Reported Prejudice

Objectives: While prejudice has often been shown to be rooted in experiences of threat, the biological underpinnings of this threat–prejudice association have received less research attention. The present experiment aims to test whether activations of the hypothalamus-pituitary-adrenal (HPA) axis, due to anticipated interactions with out-group members, predict self-reported prejudice. Moreover, we explore potential moderators of this relationship (i.e., interpersonal similarity; subtle vs. blatant prejudice). Methodology/Principal findings: Participants anticipated an interaction with an out-group member who was similar or dissimilar to the self. To index HPA activation, cortisol responses to this event were measured. Then, subtle and blatant prejudices were measured via questionnaires. Findings indicated that only when people anticipated an interaction with an out-group member who was dissimilar to the self, their cortisol response to this event significantly predicted subtle (r =.50) and blatant (r =.53) prejudice. Conclusions: These findings indicate that prejudicial attitudes are linked to HPA-axis activity. Furthermore, when intergroup interactions are interpreted to be about individuals (and not so much about groups), experienced threat (or its biological substrate) is less likely to relate to prejudice. This conclusion is discussed in terms of recent insights from social neuroscience

Holding it together: rapid evolution and positive selection in the synaptonemal complex of Drosophila

Background The synaptonemal complex (SC) is a highly conserved meiotic structure that functions to pair homologs and facilitate meiotic recombination in most eukaryotes. Five Drosophila SC proteins have been identified and localized within the complex: C(3)G, C(2)M, CONA, ORD, and the newly identified Corolla. The SC is required for meiotic recombination in Drosophila and absence of these proteins leads to reduced crossing over and chromosomal nondisjunction. Despite the conserved nature of the SC and the key role that these five proteins have in meiosis in D. melanogaster, they display little apparent sequence conservation outside the genus. To identify factors that explain this lack of apparent conservation, we performed a molecular evolutionary analysis of these genes across the Drosophila genus. Results For the five SC components, gene sequence similarity declines rapidly with increasing phylogenetic distance and only ORD and C(2)M are identifiable outside of the Drosophila genus. SC gene sequences have a higher dN/dS (ω) rate ratio than the genome wide average and this can in part be explained by the action of positive selection in almost every SC component. Across the genus, there is significant variation in ω for each protein. It further appears that ω estimates for the five SC components are in accordance with their physical position within the SC. Components interacting with chromatin evolve slowest and components comprising the central elements evolve the most rapidly. Finally, using population genetic approaches, we demonstrate that positive selection on SC components is ongoing. Conclusions SC components within Drosophila show little apparent sequence homology to those identified in other model organisms due to their rapid evolution. We propose that the Drosophila SC is evolving rapidly due to two combined effects. First, we propose that a high rate of evolution can be partly explained by low purifying selection on protein components whose function is to simply hold chromosomes together. We also propose that positive selection in the SC is driven by its sex-specificity combined with its role in facilitating both recombination and centromere clustering in the face of recurrent bouts of drive in female meiosis

Google Goes Cancer: Improving Outcome Prediction for Cancer Patients by Network-Based Ranking of Marker Genes

Predicting the clinical outcome of cancer patients based on the expression of marker genes in their tumors has received increasing interest in the past decade. Accurate predictors of outcome and response to therapy could be used to personalize and thereby improve therapy. However, state of the art methods used so far often found marker genes with limited prediction accuracy, limited reproducibility, and unclear biological relevance. To address this problem, we developed a novel computational approach to identify genes prognostic for outcome that couples gene expression measurements from primary tumor samples with a network of known relationships between the genes. Our approach ranks genes according to their prognostic relevance using both expression and network information in a manner similar to Google's PageRank. We applied this method to gene expression profiles which we obtained from 30 patients with pancreatic cancer, and identified seven candidate marker genes prognostic for outcome. Compared to genes found with state of the art methods, such as Pearson correlation of gene expression with survival time, we improve the prediction accuracy by up to 7%. Accuracies were assessed using support vector machine classifiers and Monte Carlo cross-validation. We then validated the prognostic value of our seven candidate markers using immunohistochemistry on an independent set of 412 pancreatic cancer samples. Notably, signatures derived from our candidate markers were independently predictive of outcome and superior to established clinical prognostic factors such as grade, tumor size, and nodal status. As the amount of genomic data of individual tumors grows rapidly, our algorithm meets the need for powerful computational approaches that are key to exploit these data for personalized cancer therapies in clinical practice

Efflux pump inhibitors (EPIs) as new antimicrobial agents against Pseudomonas aeruginosa

Pseudomonas aeruginosa is an opportunistic human pathogen and one of the leading causes of nosocomial infections worldwide. The difficulty in treatment of pseudomonas infections arises from being multidrug resistant (MDR) and exhibits resistance to most antimicrobial agents due to the expression of different mechanisms overcoming their effects. Of these resistance mechanisms, the active efflux pumps in Pseudomonas aeruginosa that belong to the resistance nodulation division (RND) plays a very important role in extruding the antibiotics outside the bacterial cells providing a protective means against their antibacterial activity. Beside its role against the antimicrobial agents, these pumps can extrude biocides, detergents, and other metabolic inhibitors. It is clear that efflux pumps can be targets for new antimicrobial agents. Peptidomimetic compounds such as phenylalanine arginyl β-naphthylamide (PAβN) have been introduced as efflux pump inhibitors (EPIs); their mechanism of action is through competitive inhibition with antibiotics on the efflux pump resulting in increased intracellular concentration of antibiotic, hence, restoring its antibacterial activity. The advantage of EPIs is the difficulty to develop bacterial resistance against them, but the disadvantage is their toxic property hindering their clinical application. The structure activity relationship of these compounds showed other derivatives from PAβN that are higher in their activity with higher solubility in biological fluids and decreased toxicity level. This raises further questions on how can we compact Pseudomonas infections. Of particular importance, the recent resurgence in the use of older antibiotics such as polymyxins and probably applying stricter control measures in order to prevent their spread in clinical sittings