Lipid membrane instability and poration driven by capacitive charging

A new model for the interaction of an electric pulse with a lipid membrane is proposed. Using this model we show that when a DC electric pulse is applied to an insulating lipid membrane separating fluids with different conductivities, the capacitive charging current through the membrane drives electrohydrodynamic flow that destabilizes the membrane. The instability is transient and decays as the membrane charges. The bulk conductivity mismatch plays an essential role in this instability because it results in a different rate of charge accumulation on the membrane's physical surfaces. Shearing stresses created by the electric field acting on its own induced free charge are non-zero as long as the charge imbalance exists. Accordingly, the most unstable mode is related to the ratio of membrane charging time and the electrohydrodynamic time.Comment: 4 pages, 4 figure

Analysis and modelling of the dislocation response during non-isothermal creep in Ni-SX superalloys

Nickel-based single-crystal superalloys are commonly used as the material of choice for turbine blades in modern aircrafts. The temperatures and stresses in the turbine are subject to continuous change during in-flight operation. The deformation rates of the turbine blades during operation are currently approximated based on isothermal creep tests. This dissertation seeks to understand how the high temperature creep response of the single-crystal nickel-based superalloys CMSX-4 and CMSX-10 changes when subjected to a non-isothermal test cycle varying between the tertiary and rafting creep regimes. For this purpose, creep tests cycling between a base temperature of 900 ◦C and a peak temperature of 1050 ◦C under a constant load (σ = 200 MPa) were carried out and the samples were subse- quently analyzed using TEM dislocation analysis. The creep results displayed significantly faster non-isothermal strain rates than would be expected when adding up the isothermal strain rates at each temperature. By studying tests interrupted at different stages of creep, it is argued that the faster strain accumulation results from a higher dislocation activity compared to isothermal studies which are driven by the non-isothermal evolution of the interfacial lattice misfit. Furthermore, the thermal cycling creep rate under these conditions depends on the creation of interfacial dislocation networks that can take two shapes (a classical edge-type network, or one in which the dislocations are paired) and their disintegration by the γ′-shear of dissimilar Burgers vector pairs. The experimental findings were used to create a non-isothermal creep model to better understand the dislocation-based creep response. In particular, the role of γ′-shear and dislocation glide and climb in the γ-phase on the overall creep resistance of the alloys were examined with the model. Furthermore, the rate of non-isothermal micro-structural transfor- mation (via rafting and coarsening) and its impact on the creep response was examined. The non-isothermal creep model is based on the evolution of key creep parameters during thermal cycling. These parameters include the effective γ-interdiffusivity, the γ-Orowan resistance, the interfacial lattice misfit, the anti-phase boundary energy, the γ′-critical resolved shear stress and the solid solution hardening in both phases. The computation of the key creep parameters was based on an in situ measured phase fraction evolution of the alloy CMSX-4.EPSRC and Rolls-Royce plc

Exploring the Full Potential of Photocatalytic Carbon Dioxide Reduction Using a Dinuclear Re2Cl2 Complex Assisted by Various Photosensitizers

Photosensitizing units have already been applied to enable light-driven catalytic reduction of CO2 with mononuclear rhenium complexes. However, dinuclear catalytic systems that are able to activate CO2 in a cooperative bimetallic fashion have only rarely been combined with photosensitizers. We here present detailed studies on the influence of additional photosensitizers on the catalytic performance of a dirhenium complex (Re2Cl2) and present correlations with spectroscopic measurements, which shed light on the reaction mechanism. The use of [Ir(dFppy)3] (Ir, dFppy=2-(4,6-difluorophenyl)pyridine)) resulted in considerably faster CO2 to CO transformation than [Cu(xant)(bcp)]PF6 (Cu, xant=xantphos, bcp=bathocuproine). Emission quenching studies, transient absorption as well as IR spectroscopy provide information about the electron transfer paths of the intermolecular systems. It turned out that formation of double reduced species [Re2Cl2]2− along with an intermediate with a Re−Re bond ([ReRe]) can be taken as an indication of multi-electron storage capacity. Furthermore, under catalytic conditions a CO2-bridged intermediate was identified.German Research FoundationDFG http://dx.doi.org/10.13039/501100001659Peer Reviewe

Neutralization of X4- and R5-tropic HIV-1 NL4-3 variants by HOCl-modified serum albumins

<p>Abstract</p> <p>Background</p> <p>Myeloperoxidase (MPO), an important element of the microbicidal activity of neutrophils, generates hypochlorous acid (HOCl) from H₂O₂and chloride, which is released into body fluids. Besides its direct microbicidal activity, HOCl can react with amino acid residues and HOCl-modified proteins can be detected <it>in vivo</it>.</p> <p>Findings</p> <p>This report is based on binding studies of HOCl-modified serum albumins to HIV-1 gp120 and three different neutralization assays using infectious virus. The binding studies were carried out by surface plasmon resonance spectroscopy and by standard ELISA techniques. Virus neutralization assays were carried out using HIV-1 NL4-3 virus and recombinant strains with CXCR4 and CCR5 coreceptor usage. Viral infection was monitored by a standard p24 or X-gal staining assay. Our data demonstrate that HOCl-modified mouse-, bovine- and human serum albumins all bind to the HIV-1 NL4-3 gp120 (LAV) glycoprotein in contrast to non-modified albumin. Binding of HOCl-modified albumin to gp120 correlated to the blockade of CD4 as well as that of V3 loop specific monoclonal antibody binding. In neutralization experiments, HOCl-modified serum albumins inhibited replication and syncytium formation of the X4- and R5-tropic NL4-3 isolates in a dose dependent manner.</p> <p>Conclusions</p> <p>Our data indicate that HOCl-modified serum albumin veils the binding site for CD4 and the V3 loop on gp120. Such masking of the viral gp120/gp41 envelope complex might be a simple but promising strategy to inactivate HIV-1 and therefore prevent infection when HOCl-modified serum albumin is applied, for example, as a topical microbicide.</p

Next-generation systematics: An innovative approach to resolve the structure of complex prokaryotic taxa

Prokaryotic systematics provides the fundamental framework for microbiological research but remains a discipline that relies on a labour- and time-intensive polyphasic taxonomic approach, including DNA-DNA hybridization, variation in 16S rRNA gene sequence and phenotypic characteristics. These techniques suffer from poor resolution in distinguishing between closely related species and often result in misclassification and misidentification of strains. Moreover, guidelines are unclear for the delineation of bacterial genera. Here, we have applied an innovative phylogenetic and taxogenomic approach to a heterogeneous actinobacterial taxon, Rhodococcus, to identify boundaries for intrageneric and supraspecific classification. Seven species-groups were identified within the genus Rhodococcus that are as distantly related to one another as they are to representatives of other mycolic acid containing actinobacteria and can thus be equated with the rank of genus. It was also evident that strains assigned to rhodococcal species-groups are underspeciated with many misclassified using conventional taxonomic criteria. The phylogenetic and taxogenomic methods used in this study provide data of theoretical value for the circumscription of generic and species boundaries and are also of practical significance as they provide a robust basis for the classification and identification of rhodococci of agricultural, industrial and medical/veterinary significance

Child mental health in Jordanian orphanages: effect of placement change on behavior and caregiving

Background: To assess the mental health and behavioral problems of children in institutional placements in Jordan to inform understanding of current needs, and to explore the effects of placement change on functioning and staff perceptions of goodness-of-fit. Methods: An assessment was completed of 134 children between 1.5? 12 years-of-age residing in Jordanian orphanages. The Child Behavior Checklist was used to assess prevalence rates of problems across externalizing and internalizing behavior and DSM-IV oriented subscales. Also included was caregiver perceived goodness-of-fit with each child, caregiving behavior, and two placement change-clock variables; an adjustment clock measuring time since last move, and an anticipation clock measuring time to next move. Results: 28% were in the clinical range for the internalizing domain on the CBCL, and 22% for the externalizing domain. The children also exhibited high levels of clinical range social problems, affective disorder, pervasive developmental disorder, and conduct problems. Internalizing problems were found to decrease with time in placement as children adjust to a prior move, whereas externalizing problems increased as the time to their next age-triggered move drew closer, highlighting the anticipatory effects of change. Both behavioral problems and the change clocks were predictive of staff perceptions of goodness-of-fit with the children under their care. Conclusions: These findings add to the evidence demonstrating the negative effects of orphanage rearing, and highlight the importance of the association between behavioral problems and child-caregiver relationship pathways including the timing of placement disruptions and staff perceptions of goodness-of-fit

Demonstration of visualization techniques for the control room engineer in 2030.:ELECTRA Deliverable D8.1. WP8: Future Control Room Functionality

Deliverable 8.1 reports results on analytics and visualizations of real time flexibility in support of voltage and frequency control in 2030+ power system. The investigation is carried out by means of relevant control room scenarios in order to derive the appropriate analytics needed for each specific network event

Conformational changes in the expression domain of the Escherichia coli thiM riboswitch

The thiM riboswitch contains an aptamer domain that adaptively binds the coenzyme thiamine pyrophosphate (TPP). The binding of TPP to the aptamer domain induces structural rearrangements that are relayed to a second domain, the so-called expression domain, thereby interfering with gene expression. The recently solved crystal structures of the aptamer domains of the thiM riboswitches in complex with TPP revealed how TPP stabilizes secondary and tertiary structures in the RNA ligand complex. To understand the global modes of reorganization between the two domains upon metabolite binding the structure of the entire riboswitch in presence and absence of TPP needs to be determined. Here we report the secondary structure of the entire thiM riboswitch from Escherichia coli in its TPP-free form and its transition into the TPP-bound variant, thereby depicting domains of the riboswitch that serve as communication links between the aptamer and the expression domain. Furthermore, structural probing provides an explanation for the lack of genetic control exerted by a riboswitch variant with mutations in the expression domain that still binds TPP

Minimal methylation classifier (MIMIC): A novel method for derivation and rapid diagnostic detection of disease-associated DNA methylation signatures

Rapid and reliable detection of disease-associated DNA methylation patterns has major potential to advance molecular diagnostics and underpin research investigations. We describe the development and validation of minimal methylation classifier (MIMIC), combining CpG signature design from genome-wide datasets, multiplex-PCR and detection by single-base extension and MALDI-TOF mass spectrometry, in a novel method to assess multi-locus DNA methylation profiles within routine clinically-applicable assays. We illustrate the application of MIMIC to successfully identify the methylation-dependent diagnostic molecular subgroups of medulloblastoma (the most common malignant childhood brain tumour), using scant/low-quality samples remaining from the most recently completed pan-European medulloblastoma clinical trial, refractory to analysis by conventional genome-wide DNA methylation analysis. Using this approach, we identify critical DNA methylation patterns from previously inaccessible cohorts, and reveal novel survival differences between the medulloblastoma disease subgroups with significant potential for clinical exploitation