Analysis of the capability of cork and cork agglomerates to absorb multiple compressive quasi-static loading cycles

Despite the higher specific mechanical properties and the lower density of polymeric foams, these materials present cumulative damage behaviour that implies in the second and successive impacts, their mechanical properties decrease drastically. However, cork and cork agglomerates have the ability to absorb multiple impacts so they could be a more suitable material in some products, such as bumpers and helmets. This article is focused on the study of five different cork agglomerates and a natural cork under four different maximum deformations subjected to four consecutive compression loading cycles. Main diagrams, such as the stress–strain, energy density and efficiency, and the variation in diverse parameters, such as the absorbed energy density and maximum efficiency, were investigated and compared with an expanded polystyrene foam

Characterization of cork and cork agglomerates under compressive loads by means of energy absorption diagrams

Cork and cork agglomerates could be suitable replacements for petroleum-based polymeric foams due to their similar internal structure of cells and grains. Additionally, cork products have a renewable origin and are recyclable. Despite these notable properties, few studies have analysed the mechanical properties, especially the specific properties, of these materials under compressive loads. Moreover, although efficiency, ideality, and energy-normalized stress diagrams are commonly used for polymeric foams and 3D-printed lattice structures, these types of diagrams are not yet applied to cork products. It must be highlighted that efficiency diagrams are plotted only against nonspecific properties so, this article proposes additionally the use of nonspecific properties to compare materials not only in terms of properties per unit volume instead but also in terms of properties per unit mass that is more suitable for certain applications in which the weight is crucial. The materials studied herein include three different white cork agglomerates, a brown cork agglomerate, a black cork agglomerate, natural cork, and expanded polystyrene foam, which are subjected to quasi-static compressive loads

Terror from the Sky: Unconventional Linguistic Clues to the Negrito Past

Within recorded history. most Southeast Asian peoples have been of southern Mongoloid physical type, whether they speak Austroasiatic, Tibeto-Burman, Austronesian, Tai-Kadai, or Hmong-Mien languages. However, population distributions suggest that this is a post-Pleistocene phenomenon and that for tens of millennia before the last glaciation ended Greater Mainland Southeast Asia, which included the currently insular world that rests on the Sunda Shelf, was peopled by short, dark-skinned, frizzy-haired foragers whose descendants in the Philippines came to be labeled by the sixteenth-century Spanish colonizers as negritos, a term that has since been extended to similar groups throughout the region. There are three areas in which these populations survived into the present so as to become part of written history: the Philippines, the Malay Peninsula, and the Andaman Islands. All Philippine negritos speak Austronesian languages, and all Malayan negritos speak languages in the nuclear Mon-Khmer branch of Austroasiatic, but the linguistic situation in the Andamans is a world apart. Given prehistoric language shifts among both Philippine and Malayan negritos, the prospects of determining whether disparate negrito populations were once a linguistically or culturally unified community would appear hopeless. Surprisingly, however, some clues to a common negrito past do survive in a most unexpected way

Intracellular redox potential is correlated with miRNA expression in MCF7 cells under hypoxic conditions

Hypoxia is a ubiquitous feature of cancers, encouraging glycolytic metabolism, proliferation, and resistance to therapy. Nonetheless, hypoxia is a poorly defined term with confounding features described in the literature. Redox biology provides an important link between the external cellular microenvironment and the cell's response to changing oxygen pressures. In this paper, we demonstrate a correlation between intracellular redox potential (measured using optical nanosensors) and the concentrations of microRNAs (miRNAs) involved in the cell's response to changes in oxygen pressure. The correlations were established using surprisal analysis (an approach derived from thermodynamics and information theory). We found that measured redox potential changes reflect changes in the free energy computed by surprisal analysis of miRNAs. Furthermore, surprisal analysis identified groups of miRNAs, functionally related to changes in proliferation and metastatic potential that played the most significant role in the cell's response to changing oxygen pressure. © 2019 National Academy of Sciences. All rights reserved

SrfB, a member of the Serum Response factor family of transcription factors, regulates starvation response and early development in Dictyostelium

The Serum Response Factor (SRF) is an important regulator of cell proliferation and differentiation. Dictyostelium discoideum srfB gene codes for an SRF homologue and is expressed in vegetative cells and during development under the control of three alternative promoters, which show different cell-type specific patterns of expression. The two more proximal promoters directed gene transcription in prestalk AB, stalk and lower-cup cells. The generation of a strain where the srfB gene has been interrupted (srfB(−)) has shown that this gene is required for regulation of actin–cytoskeleton-related functions, such as cytokinesis and macropinocytosis. The mutant failed to develop well in suspension, but could be rescued by cAMP pulsing, suggesting a defect in cAMP signaling. srfB(−) cells showed impaired chemotaxis to cAMP and defective lateral pseudopodium inhibition. Nevertheless, srfB(−) cells aggregated on agar plates and nitrocellulose filters 2 h earlier than wild type cells, and completed development, showing an increased tendency to form slug structures. Analysis of wild type and srfB(−) strains detected significant differences in the regulation of gene expression upon starvation. Genes coding for lysosomal and ribosomal proteins, developmentally-regulated genes, and some genes coding for proteins involved in cytoskeleton regulation were deregulated during the first stages of development

Respiratory health status is impaired in UK HIV-positive adults with virologically suppressed HIV infection

OBJECTIVES: We sought to evaluate whether people living with HIV (PLWH) using effective antiretroviral therapy (ART) have worse respiratory health status than similar HIV-negative individuals. METHODS: We recruited 197 HIV-positive and 93 HIV-negative adults from HIV and sexual health clinics. They completed a questionnaire regarding risk factors for respiratory illness. Respiratory health status was assessed using the St George's Respiratory Questionnaire (SGRQ) and the Medical Research Council (MRC) breathlessness scale. Subjects underwent spirometry without bronchodilation. RESULTS: PLWH had worse respiratory health status: the median SGRQ Total score was 12 [interquartile range (IQR) 6-25] in HIV-positive subjects vs. 6 (IQR 2-14) in HIV-negative subjects (P < 0.001); breathlessness was common in the HIV-positive group, where 47% compared with 24% had an MRC breathlessness score ≥ 2 (P = 0.001). Eighteen (11%) HIV-positive and seven (9%) HIV-negative participants had airflow obstruction. In multivariable analyses (adjusted for age, gender, smoking, body mass index and depression), HIV infection remained associated with higher SGRQ and MRC scores, with an adjusted fold-change in SGRQ Total score of 1.54 [95% confidence interval (CI) 1.14-2.09; P = 0.005] and adjusted odds ratio of having an MRC score of ≥ 2 of 2.45 (95% CI 1.15-5.20; P = 0.02). Similar findings were obtained when analyses were repeated including only HIV-positive participants with a viral load < 40 HIV-1 RNA copies/mL. CONCLUSIONS: Despite effective ART, impaired respiratory health appears more common in HIV-positive adults, and has a significant impact on health-related quality of life

Supported discharge service versus Inpatient care Evaluation (SITE): a randomised controlled trial comparing effectiveness of an intensive community care service versus inpatient treatment as usual for adolescents with severe psychiatric disorders: self-harm, functional impairment, and educational and clinical outcomes.

Background: Clinical guidelines recommend intensive community care service treatment (ICCS) to reduce adolescent psychiatric inpatient care. We have previously reported that the addition of ICCS led to a substantial decrease in hospital use and improved school re-integration. Aim: To undertake a randomised controlled trial (RCT) comparing an inpatient admission followed by an early discharge supported by ICCS with usual inpatient admission (treatment as usual; TAU). In this paper, we report the impact of ICCS on self-harm and other clinical and educational outcomes. Method: 106 patients aged 12-18 admitted for psychiatric inpatient care were randomised (1:1) to either ICCS or TAU. Six months after randomization, we compared the two treatment arms on the number and severity of self-harm episodes, the functional impairment, severity of psychiatric symptoms, clinical improvement, reading and mathematical ability, weight, height and the use of psychological therapy and medication. Results: At six-month follow-up, there were no differences between the two groups on most measures. Patients receiving ICCS were significantly less likely to report multiple episodes (5 or more) of self-harm (OR=0·18, 95% CI: 0·05 to 0·64). Patients admitted to private inpatient units spent on average 118.4 (95% CI: 28·2 to 208.6) fewer days in hospitals if they were in the ICCS group compared to TAU. Conclusion: The addition of ICCS to TAU may lower the risk of multiple self-harm and may reduce the duration of inpatient stay, especially in those patients admitted for private care. Early discharge with ICCS appears to be a viable alternative to standard inpatient treatment

Chlorpromazine and amitriptyline are substrates and inhibitors of the acrb multidrug efflux pump

Efflux is an important mechanism in Gram-negative bacteria conferring multidrug resistance. Inhibition of efflux is an encouraging strategy to restore the antibacterial activity of antibiotics. Chlorpromazine and amitriptyline have been shown to behave as efflux inhibitors. However, their mode of action is poorly under-stood. Exposure of Salmonella enterica serovar Typhimurium and Escherichia coli to chlorpromazine selected for mutations within genes encoding RamR and MarR, regu-lators of the multidrug tripartite efflux pump AcrAB-TolC. Further experiments with S. Typhimurium containing AcrB D408A (a nonfunctional efflux pump) and chlor-promazine or amitriptyline resulted in the reversion of the mutant acrB allele to the wild type. Together, this suggests these drugs are AcrB efflux substrates. Subsequent docking studies with AcrB from S. Typhimurium and E. coli, followed by molecular dynamics simulations and free energy calculations showed that chlorpromazine and amitriptyline bind at the hydrophobic trap, a preferred binding site for substrates and inhibitors within the distal binding pocket of AcrB. Based on these simulations, we suggest that chlorpromazine and amitriptyline inhibit AcrB-mediated efflux by in-terfering with substrate binding. Our findings provide evidence that these drugs are substrates and inhibitors of AcrB, yielding molecular details of their mechanism of action and informing drug discovery of new efflux inhibitors. IMPORTANCE Efflux pumps of the resistance nodulation-cell division (RND) super-family are major contributors to multidrug resistance for most of the Gram-negative ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acineto-bacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens. The development of inhibitors of these pumps would be highly desirable; how-ever, several issues have thus far hindered all efforts at designing new efflux in-hibitory compounds devoid of adverse effects. An alternative route to de novo design relies on the use of marketed drugs, for which side effects on human health have been already assessed. In this work, we provide experimental evidence that the antipsychotic drugs chlorpromazine and amitriptyline are inhibi-tors of the AcrB transporter, the engine of the major RND efflux pumps in Escherichia coli and Salmonella enterica serovar Typhimurium. Furthermore, in silico calculations have provided a molecular-level picture of the inhibition mechanism, allowing rationalization of experimental data and paving the way for similar studies with other classes of marketed compounds

Whole blood gene expression profiling of neonates with confirmed bacterial sepsis

peer-reviewedNeonatal infection remains a primary cause of infant morbidity and mortality worldwide and yet our understanding of how human neonates respond to infection remains incomplete. Changes in host gene expression in response to infection may occur in any part of the body, with the continuous interaction between blood and tissues allowing blood cells to act as biosensors for the changes. In this study we have used whole blood transcriptome profiling to systematically identify signatures and the pathway biology underlying the pathogenesis of neonatal infection. Blood samples were collected from neonates at the first clinical signs of suspected sepsis alongside age matched healthy control subjects. Here we report a detailed description of the study design, including clinical data collected, experimental methods used and data analysis workflows and which correspond with data in Gene Expression Omnibus (GEO) data sets (GSE25504). Our data set has allowed identification of a patient invariant 52-gene classifier that predicts bacterial infection with high accuracy and lays the foundation for advancing diagnostic, prognostic and therapeutic strategies for neonatal sepsis