Static Friction between Elastic Solids due to Random Asperities

Several workers have established that the Larkin domains for two three dimensional nonmetallic elastic solids in contact with each other at a disordered interface are enormously large. This implies that there should be negligible static friction per unit area in the macroscopic solid limit. The present work argues that the fluctuations in the heights of the random asperities at the interface that occur in the Greenwood-Williamson model can account for static friction.Comment: Contains some improvements in the treatment of the subjec

The antimicrobial polymer PHMB enters cells and selectively condenses bacterial chromosomes

To combat infection and antimicrobial resistance, it is helpful to elucidate drug mechanism(s) of action. Here we examined how the widely used antimicrobial polyhexamethylene biguanide (PHMB) kills bacteria selectively over host cells. Contrary to the accepted model of microbial membrane disruption by PHMB, we observed cell entry into a range of bacterial species, and treated bacteria displayed cell division arrest and chromosome condensation, suggesting DNA binding as an alternative antimicrobial mechanism. A DNA-level mechanism was confirmed by observations that PHMB formed nanoparticles when mixed with isolated bacterial chromosomal DNA and its effects on growth were suppressed by pairwise combination with the DNA binding ligand Hoechst 33258. PHMB also entered mammalian cells, but was trapped within endosomes and excluded from nuclei. Therefore, PHMB displays differential access to bacterial and mammalian cellular DNA and selectively binds and condenses bacterial chromosomes. Because acquired resistance to PHMB has not been reported, selective chromosome condensation provides an unanticipated paradigm for antimicrobial action that may not succumb to resistance

Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism.

Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation. Loss of the MPC in Lgr5-EGFP-positive stem cells, or treatment of intestinal organoids with an MPC inhibitor, increases proliferation and expands the stem cell compartment. Similarly, genetic deletion of the MPC in Drosophila intestinal stem cells also increases proliferation, whereas MPC overexpression suppresses stem cell proliferation. These data demonstrate that limiting mitochondrial pyruvate metabolism is necessary and sufficient to maintain the proliferation of intestinal stem cells

Surface specific asperity model for prediction of friction in boundary and mixed regimes of lubrication

Machine downsizing, increased loading and better sealing performance have progressively led to thinner lubricant films and an increased chance of direct surface interaction. Consequently, mixed and boundary regimes of lubrication are prevalent with ubiquitous asperity interactions, leading to increased parasitic losses and poor energy inefficiency. Surface topography has become an important consideration as it influences the prevailing regime of lubrication. As a result a plethora of machining processes and surface finishing techniques have emerged. The stochastic nature of the resulting topography determines the separation at which asperity interactions are initiated and ultimately affect the conjunctional load carrying capacity and operational efficiency. The paper presents a procedure for modelling of asperity interactions of real rough surfaces, from measured data, which do not conform to the usually assumed Gaussian distributions. The model is validated experimentally using a bench top reciprocating sliding test rig. The method demonstrates accurate determination of the onset of mixed regime of lubrication. In this manner, realistic predictions are made for load carrying and frictional performance in real applications where commonly used Gaussian distributions can lead to anomalous predictions

Development of a multiplexed bead-based immunoassay for the simultaneous detection of antibodies to 17 pneumococcal proteins

Presently, several pneumococcal proteins are being evaluated as potential vaccine candidates. Here, we gather novel insights in the immunogenicity of PLY, PsaA, PspA, PspC, NanA, Hyl, PpmA, SlrA, Eno, IgA1-protease, PdBD, BVH-3, SP1003, SP1633, SP1651, SP0189 and SP0376. We developed a multiplex bead-based immunoassay (xMAP® Technology, Luminex Corporation) to simultaneously quantify antibodies against these 17 pneumococcal proteins in serum. The median fluorescence intensity (MFI) values obtained for human pooled serum with the multiplex assay were between 82% and 111% (median 94%) of those obtained with the singleplex assays. For IgG, the coefficient of variation (CV) in serum ranged from 2% to 9%, for IgA, the CV ranged from 3% to 14% and for IgM, the CV ranged from 11% to 15%. Using this immunoassay, we showed that anti-pneumococcal antibody levels exhibited extensive inter-individual variability in young children suffering from invasive pneumococcal disease. All proteins, including the proteins with, as yet, unknown function, were immunogenic. In conclusion, the multiplex Streptococcus pneumoniae immunoassay based on proteins is reproducible. This assay can be used to monitor anti-S. pneumoniae antibody responses in a material- and time-saving manner

Reconsidering the Tribal-State Compact Process

This essay evaluates the tribal‐state compact process, as one of several alternative, nonadversarial processes, warranting attention. It argues that, because of its binding character and relatively low cost (in contrast to litigation), and because it is based in the idea of tribes and states exhibiting mutual respect, the compact process is an advanced version of negotiation and bargaining that tribes and states should consider where appropriate

Larger and More Prominent Graphic Health Warnings on Plain-Packaged Tobacco Products and Avoidant Responses in Current Smokers: a Qualitative Study

Background: The introduction of tobacco plain packaging legislation in Australia meant that all tobacco products were to be sold in plain dark-brown packaging with 75 % front-of-pack graphic health warnings and standardised font type and size for brand name and product variant. The change in the size and prominence of the warnings has been proposed as a reason for behaviour change in smokers in terms of increased intentions to quit and quit attempts. Purpose: The current research examined attitudes and beliefs of cigarette smokers toward the increased size and prominence of the warnings and effects on their behaviour. Method: Participants (N = 160) completed open-ended responses to questions on beliefs, attitudes and responses to plain packaging. Responses were subjected to inductive thematic content analysis for key themes. Results: Four themes emerged from the analysis: emotional response to packaging, scepticism of health warnings, warnings and cessation behaviour, and avoidant coping behaviours. Participants reported increased negative emotional responses to the packaging and made specific reference to the graphic health warnings. Some participants attempted to discredit the messages. Others reported increased intentions to quit or quitting attempts. There were pervasive reports of avoidant responses including covering or hiding the warnings. Conclusion: Consistent with theories of illness perceptions and coping, current findings indicate that the larger, prominent graphic health warnings on plain-packaged tobacco products had pervasive effects on threat perceptions and subsequent behavioural responses. While some of the reported responses were adaptive (e.g. attempts to quit), others were maladaptive (e.g. avoiding the warnings)

Genetic Evidence for Inhibition of Bacterial Division Protein FtsZ by Berberine

Background: Berberine is a plant alkaloid that is widely used as an anti-infective in traditional medicine. Escherichia coli exposed to berberine form filaments, suggesting an antibacterial mechanism that involves inhibition of cell division. Berberine is a DNA ligand and may induce filamentation through induction of the SOS response. Also, there is biochemical evidence for berberine inhibition of the cell division protein FtsZ. Here we aimed to assess possible berberine mechanism(s) of action in growing bacteria using genetics tools. Methodology/Principal Findings: First, we tested whether berberine inhibits bacterial growth through DNA damage and induction of the SOS response. The SOS response induced by berberine was much lower compared to that induced by mitomycin C in an SOS response reporter strain. Also, cell filamentation was observed in an SOS-negative E. coli strain. To test whether berberine inhibits FtsZ, we assessed its effects on formation of the cell division Z-rings, and observed a dramatic reduction in Z-rings in the presence of berberine. We next used two different strategies for RNA silencing of ftsZ and both resulted in sensitisation of bacteria to berberine, visible as a drop in the Minimum Inhibitory Concentration (MIC). Furthermore, Fractional Inhibitory Concentration Indices (FICIs) showed a high level of synergy between ftsZ silencing and berberine treatment (FICI values of 0.23 and 0.25 for peptide nucleic acid- and expressed antisense RNA-based silencing of ftsZ, respectively). Finally, over-expression of ftsZ led to a mild rescue effect in berberine-treated cells

Detecting unilateral phrenic paralysis by acoustic respiratory analysis

The consequences of phrenic nerve paralysis vary from a considerable reduction in respiratory function to an apparently normal state. Acoustic analysis of lung sound intensity (LSI) could be an indirect non-invasive measurement of respiratory muscle function, comparing activity on the two sides of the thoracic cage. Lung sounds and airflow were recorded in ten males with unilateral phrenic paralysis and ten healthy subjects (5 men/5 women), during progressive increasing airflow maneuvers. Subjects were in sitting position and two acoustic sensors were placed on their back, on the left and right sides. LSI was determined from 1.2 to 2.4 L/s between 70 and 2000 Hz. LSI was significantly greater on the normal (19.3±4.0 dB) than the affected (5.7±3.5 dB) side in all patients (p = 0.0002), differences ranging from 9.9 to 21.3 dB (13.5±3.5 dB). In the healthy subjects, the LSI was similar on both left (15.1±6.3 dB) and right (17.4±5.7 dB) sides (p = 0.2730), differences ranging from 0.4 to 4.6 dB (2.3±1.6 dB). There was a positive linear relationship between the LSI and the airflow, with clear differences between the slope of patients (about 5 dB/L/s) and healthy subjects (about 10 dB/L/s). Furthermore, the LSI from the affected side of patients was close to the background noise level, at low airflows. As the airflow increases, the LSI from the affected side did also increase, but never reached the levels seen in healthy subjects. Moreover, the difference in LSI between healthy and paralyzed sides was higher in patients with lower FEV1 (%). The acoustic analysis of LSI is a relevant non-invasive technique to assess respiratory function. This method could reinforce the reliability of the diagnosis of unilateral phrenic paralysis, as well as the monitoring of these patients.Peer ReviewedPostprint (published version