Molecular dynamics simulation of a bilayer membrane

We have applied the computer simulation method of molecular dynamics (MD) to a realistic representation of a lipid bilayer, which serves as a model for a biological membrane. The bilayer consists of 2×16 decanoate molecules and is periodic in two dimensions. Interactions include Lennard‐Jones, dihedral, and bond angle potentials while bond lengths are constrained. Head groups are confined near the bilayer surfaces by harmonic forces representing their interaction with the water layer. After equilibration, a simulation extending over 80 ps at 300 K was carried out for a head group surface area of 25 Å2. Experimental order parameters are perfectly reproduced. A highly interesting cooperative tilt of the molecules, persisting over several tens of picoseconds, is observed. The molecular plane is strongly correlated with the plane of tilt. The popular kink model for the hydrocarbon chain order and dynamics is not supported. In view of the observed extended spatial correlation, a simulation was also carried out for a bilayer consisting of 2×64 decanoate molecules

Минералогические исследования в пещерной системе Снежная-Меженного-Иллюзия (Западный Кавказ, Бзыбский хребет): предварительные результаты и направления дальнейших работ

В статье приводятся сведения о минеральном составе водных хемогенных и водных механических отложений в пещерной системе Снежная-Меженного-Иллюзия. В состав водных хемогенных отложений входят Mg- и Sr-содержащий кальцит, арагонит, гипс, гидромагнезит, целестин, стронцианит, доломит, гетит, рутил и циркон. Водные механические отложения сложены преимущественно доломитом, кварцем и кальцитом. В схожих по морфологии и микроклимату частях пещерной системы наблюдаются одинаковые вторичные минералы.У статті наводяться відомості про мінеральний склад водних хемогенних і водних механічних відкладень в печерній системі Сніжна-Меженого-Ілюзія. До складу водних хемогенних відкладень входять кальцит, який містить Mg і Sr, арагоніт, гіпс, гідромагнезіт, целестин, стронціаніт, доломіт, гетит, рутил і циркон. Водні механічні відкладення складені переважно доломітом, кварцом і кальцитом. У схожих за морфологєю та мікрокліматом частинах печерної системи спостерігаються однакові вторинні мінерали.The article presents the preliminary characteristic of the mineral composition of chemogenic formations and clastic deposits of Snezhnaya-Mezhennogo-Illusia cave system. Chemogenic formations are composed by Mg- and Sr-calcite, aragonite, gypsum and hydromagnesite, celestite, strontianite, dolomite, goethite, rutile and zircon. Clastic sediments are composed mainly by dolomite, quartz and calcite. Same secondary minerals are observed in those parts of the cave system that have similar morphology and microclimate

A Search Strategy for Detecting Duodenoscope-Associated Infections:A Retrospective Observational Study

Background: Duodenoscope-associated infections (DAIs) are exogenous infections resulting from the use of contaminated duodenoscopes. Though numerous outbreaks of DAI have involved multidrug-resistant micro-organisms (MDROs), outbreaks involving non-MDROs are also likely to occur. Detection challenges arise as these infections often resolve before culture or because causative strains are not retained for comparison with duodenoscope strains. Aim: To identify and analyse DAIs spanning a seven-year period in a tertiary care medical centre. Methods: This was a retrospective observational study. Duodenoscope cultures positive for gastrointestinal flora between March 2015 and September 2022 were paired with duodenoscope usage data to identify patients exposed to contaminated duodenoscopes. Analysis encompassed patients treated after a positive duodenoscope culture and those treated within the interval from a negative to a positive culture. Patient identification numbers were cross-referenced with a clinical culture database to identify patients developing infections with matching micro-organisms within one year of their procedure. A ‘pair’ was established upon a species-level match between duodenoscope and patient cultures. Pairs were further analysed via antibiogram comparison, and by whole-genome sequencing (WGS) to determine genetic relatedness. Findings: Sixty-eight pairs were identified; of these, 21 exhibited matching antibiograms which underwent WGS, uncovering two genetically closely related pairs categorized as DAIs. Infection onset occurred up to two months post procedure. Both causative agents were non-MDROs. Conclusion: This study provides crucial insights into DAIs caused by non-MDROs and it highlights the challenge of DAI recognition in daily practice. Importantly, the delayed manifestation of the described DAIs suggests a current underestimation of DAI risk.</p

Polymer tensiometers with ceramic cones: direct observations of matric pressures in drying soils

Measuring soil water potentials is crucial to characterize vadose zone processes. Conventional tensiometers only measure until approximately −0.09 MPa, and indirect methods may suffer from the non-uniqueness in the relationship between matric potential and measured properties. Recently developed polymer tensiometers (POTs) are able to directly measure soil matric potentials until the theoretical wilting point (−1.6 MPa). By minimizing the volume of polymer solution inside the POT while maximizing the ceramic area in contact with that polymer solution, response times drop to acceptable ranges for laboratory and field conditions. Contact with the soil is drastically improved with the use of cone-shaped solid ceramics instead of flat ceramics. The comparison between measured potentials by polymer tensiometers and indirectly obtained potentials with time domain reflectometry highlights the risk of using the latter method at low water contents. By combining POT and time domain reflectometry readings in situ moisture retention curves can be measured over the range permitted by the measurement range of both POT and time domain reflectometry

Somatostatin analogues for receptor targeted photodynamic therapy

Photodynamic therapy (PDT) is an established treatment modality, used mainly for anticancer therapy that relies on the interaction of photosensitizer, light and oxygen. For the treatment of pathologies in certain anatomical sites, improved targeting of the photosensitizer is necessary to prevent damage to healthy tissue. We report on a novel dual approach of targeted PDT (vascular and cellular targeting) utilizing the expression of neuropeptide somatostatin receptor (sst2) on tumor and neovascular-endothelial cells. We synthesized two conjugates containing the somatostatin analogue [Tyr3]-octreotate and Chlorin e6 (Ce6): Ce6-K3-[Tyr3]-octreotate (1) and Ce6-[Tyr3]-octreotate-K3-[Tyr3]-octreotate (2). Investigation of the uptake and photodynamic activity of conjugates in-vitro in human erythroleukemic K562 cells showed that conjugation of [Tyr3]-octreotate with Ce6 in conjugate 1 enhances uptake (by a factor 2) in cells over-expressing sst2 compared to wild-type cells. Co-treatment with excess free Octreotide abrogated the phototoxicity of conjugate 1 indicative of a specific sst2-mediated effect. In contrast conjugate 2 showed no receptor-mediated effect due to its high hydrophobicity. When compared with un-conjugated Ce6, the PDT activity of conjugate 1 was lower. However, it showed higher photostability which may compensate for its lower phototoxicity. Intra-vital fluorescence pharmacokinetic studies of conjugate 1 in rat skin-fold observation chambers transplanted with sst2+ AR42J acinar pancreas tumors showed significantly different uptake profiles compared to free Ce6. Co-treatment with free Octreotide significantly reduced conjugate uptake in tumor tissue (by a factor 4) as well as in the chamber neo-vasculature. These results show that conjugate 1 might have potential as an in-vivo sst2 targeting photosensitizer conjugate

Frontiers of Climate Change Economics

The economics of climate change is an active field of research. The contributions to a Special Issue are put in context of the literature, and it is suggested that second-best issues such as carbon leakage and the Green Paradox need to be complemented with a political economy analysis of why certain instruments are politically infeasible and with intra- and intergenerational analyses of the impact of climate policy. A case is also made for more empirical work on the gradual and catastrophic damages of global warming

Measurement of the ground-state flux diagram of three coupled qubits as a first step towards the demonstration of adiabatic quantum computation

The ground state susceptibility of a system consisting of three flux-qubits was measured in the complete three dimensional flux space around the common degeneracy point of the qubits. The system's Hamiltonian could be completely reconstructed from measurements made far away from the common degeneracy point. The subsequent measurements made around this point show complete agreement with the theoretical predictions which follow from this Hamiltonian. The ground state anti-crossings of the system could be read-out directly from these measurements. This allows one to determine the ground-state flux diagram, which provides the solution for the non-polynomial optimization problem MAXCUT encoded in the Hamiltonian of the three-flux-qubit system. Our results show that adiabatic quantum computation can be demonstrated with this system provided that the energy gap and/or the speed of the read-out is increased.Comment: accepted for publication by Europhysics Letter

Social-cognitive functioning and social skills in patients with early treated phenylketonuria:a PKU-COBESO study

OBJECTIVE: Early treatment of phenylketonuria (ET-PKU) prevents mental retardation, but many patients still show cognitive and mood problems. In this study, it was investigated whether ET-PKU-patients have specific phenylalanine (Phe-)related problems with respect to social-cognitive functioning and social skills. METHODS: Ninety five PKU-patients (mean age 21.6 ± 10.2 years) and 95 healthy controls (mean age 19.6 ± 8.7 years) were compared on performance of computerized and paper-and-pencil tasks measuring social-cognitive abilities and on parent- and self-reported social skills, using multivariate analyses of variance, and controlling for general cognitive ability (IQ-estimate). Further comparisons were made between patients using tetrahydrobiopterin (BH4, N = 30) and patients not using BH4. Associations with Phe-levels on the day of testing, during childhood, during adolescence and throughout life were examined. RESULTS: PKU-patients showed poorer social-cognitive functioning and reportedly had poorer social skills than controls (regardless of general cognitive abilities). Quality of social-cognitive functioning was negatively related to recent Phe-levels and Phe-levels between 8 and 12 years for adolescents with PKU. Quality of social skills was negatively related to lifetime phenylalanine levels in adult patients, and specifically to Phe-levels between 0 and 7, and between 8 and 12 years. There were no differences with respect to social outcome measures between the BH4 and non-BH4 groups. CONCLUSION: PKU-patients have Phe-related difficulties with social-cognitive functioning and social skills. Problems seem to be more evident among adolescents and adults with PKU. High Phe-levels during childhood and early adolescence seem to be of greater influence than current and recent Phe-levels for these patients