A systematic molecular simulation study of ionic liquid surfaces using intrinsic analysis methods

In this paper, we apply novel intrinsic analysis methods, coupled with bivariate orientation analysis, to obtain a detailed picture of the molecular-level structure of ionic liquid surfaces. We observe pronounced layering at the interface, alternating non-polar with ionic regions. The outermost regions of the surface are populated by alkyl chains, which are followed by a dense and tightly packed layer formed of oppositely charged ionic moieties. We then systematically change the cation chain length, the anion size, the temperature and the molecular model, to examine the effect of each of these parameters on the interfacial structure. Increasing the cation chain length promotes orientations in which the chain is pointing into the vapor, thus increasing the coverage of the surface with alkyl groups. Larger anions promote a disruption of the dense ionic layer, increasing the orientational freedom of cations and increasing the amount of free space. The temperature had a relatively small effect on the surface structure, while the effect of the choice of molecular model was clearly significant, particularly on the orientational preferences at the interface. Our study demonstrates the usefulness of molecular simulation methods in the design of ionic liquids to suit particular applications

Telemedicine Pre and Post Covid-19: Lessons for Commercialisation Based on Previous Use Cases

Telemedicine used to be slow, difficult, expensive and widely neglected by doctors and patients. COVID-19 changed everything; telemedicine is entering a period of rapid economic and business growth. This paper discusses the reasons for change in telemedicine over the last 20 years, through real-life medical technology projects, telemetry, ehealth and health IT. Our methods are based on the analysis of telemedicine projects we have implemented and characteristic historical data.  The results of our investigation demonstrate a clear increase of significance in telemedicine in the present and near future. We envision the evolution of mobile phones to personal telehealth monitors.  Prior to COVID-19, market penetration and economic factors of telemedicine evolved slowly and in an uneven manner on a global scale. Many of the projects remained active only as long as the grant or corporate or national support was provided. The age of novel globally spreading infectious diseases, exemplified by COVID-19, has created an unusual, different setting. Recent pandemics and epidemics have changed global economics significantly and generated a new motivation and a new market with a projected trillion-dollar market value. Post COVID-19, regular and periodic epidemics and pandemics are expected to continue to occur. This will generate an enormous global market for isolated high-tech services, including telemedicine and telemetry

What does an ionic liquid surface really look like? Unprecedented details from molecular simulations

We present the first intrinsic analysis of the surface of the [bmim][PF6] room-temperature ionic liquid. Our detailed analysis reveals unprecedented details about the structure of the interface by providing the relative prevalence of different molecular orientations. These results suggest that experimental data should be reinterpreted considering a distribution of molecular arrangements

Selected Aspects in the Pathogenesis of Autoimmune Diseases

Autoimmune processes can be found in physiological circumstances. However, they are quenched with properly functioning regulatory mechanisms and do not evolve into full-blown autoimmune diseases. Once developed, autoimmune diseases are characterized by signature clinical features, accompanied by sustained cellular and/or humoral immunological abnormalities. Genetic, environmental, and hormonal defects, as well as a quantitative and qualitative impairment of immunoregulatory functions, have been shown in parallel to the relative dominance of proinflammatory Th17 cells in many of these diseases. In this review we focus on the derailed balance between regulatory and Th17 cells in the pathogenesis of autoimmune diseases. Additionally, we depict a cytokine imbalance, which gives rise to a biased T-cell homeostasis. The assessment of Th17/Treg-cell ratio and the simultaneous quantitation of cytokines, may give a useful diagnostic tool in autoimmune diseases. We also depict the multifaceted role of dendritic cells, serving as antigen presenting cells, contributing to the development of the pathognomonic cytokine signature and promote cellular and humoral autoimmune responses. Finally we describe the function and role of extracellular vesicles in particular autoimmune diseases. Targeting these key players of disease progression in patients with autoimmune diseases by immunomodulating therapy may be beneficial in future therapeutic strategies.Peer reviewe

The intrinsic structure of the interface of partially miscible fluids : an application to ionic liquids

We investigate by means of Molecular Dynamics simulations how the intrinsic sur- face structure of liquid/liquid interfaces involving ionic liquids depends on the opposite phase of varying polarity. We study 1-n-butyl-3-methylimidazolium hexa uorophos- phate (BMIM PF 6 ) and 1-n-butyl-3-methylimidazolium bis(tri uoromethylsulfonyl)imid (BMIM NTf 2 ). The opposite phase is either cyclohexane or water, but as a reference, IL { vacuum interfaces are also studied. We combine a distance-based cluster search algorithm with the ITIM intrinsic analyzing method to separate liquid phases showing non-negligible mutual miscibility and to identify atoms residing at the instantaneous surface. In contrast to the well structured surface of IL { vacuum systems, at liq- uid/liquid interfaces of ILs density correlations, ionic associations and orientational preferences are all weakened, this eect being much more pronounced when the other species is water. In such systems we observe a drastic reduction in the presence of the cation at the surface and an increase of appearance of polar moieties (of both the cations and anions) leading to decreased apolar character of the interface. Furthermore, cations are mostly found to turn with their butyl chains toward the bulk while having their methyl groups sticking towards water. Anion-cation associations are reduced and partially replaced by water-anion and rarely also water-cation associations

NAADP receptors are present and functional in the heart

AbstractAlongside the well-studied inositol 1,4,5 trisphosphate and ryanodine receptors, evidence is gathering that a new intracellular release mechanism, gated by the pyridine nucleotide nicotinic acid adenine dinucleotide phosphate (NAADP), is present in numerous organisms, ranging from plant to mammalian cells (reviewed in [1]). Most cells have been shown to express at least two Ca2+-release mechanisms controlled by different messengers, and this can lead to redundancy, convergence, or divergence of responses. One exception appears to be muscle and heart contractile tissues. Here, it is thought that the dominant intracellular channel is the ryanodine receptor, while IP3 receptors are poorly expressed and their role appears to be negligible. We now report that NAADP receptors are functional and abundant in cardiac microsomes. NAADP binds specifically and with high affinity (130 pM and 4 nM) to two sites on cardiac microsomes and releases Ca2+ with an apparent EC50 of 323 ± 14 nM. Furthermore, binding experiments show that this receptor displays both positive and negative cooperativity, a peculiarity unique among intracellular Ca2+ channels. Therefore, we show that the heart possesses multiple mechanisms to increase the complexity of Ca2+ signaling and that NAADP may be integral in the functioning of this organ

Charge storage at the Pt/YSZ interface

The electrochemical behavior of Pt/YSZ electrodes in oxygen containing atmosphere at 450 A degrees C has been investigated by double-step chronoamperometry and programmed linear sweep cyclic voltammetry. The response of the O-2(g),Pt/YSZ system in these experiments could be separated into a time dependent and a steady state contribution, the former being dominated by pseudocapacitive processes. It is proposed that Pt-O type species were stored via different processes at three different locations in the O-2(g),Pt/YSZ system: (1) Build-up of a platinum oxide monolayer at the Pt/YSZ binary interface. (2) Formation of Pt-O species at the triple phase boundary and their spreading-out along the Pt/gas interface. (3) Growth of the platinum oxide layer from the binary Pt/YSZ interface toward the bulk of the platinum electrode

Isocost Lines Describe the Cellular Economy of Genetic Circuits

Genetic circuits in living cells share transcriptional and translational resources that are available in limited amounts. This leads to unexpected couplings among seemingly unconnected modules, which result in poorly predictable circuit behavior. In this study, we determine these interdependencies between products of different genes by characterizing the economy of how transcriptional and translational resources are allocated to the production of proteins in genetic circuits. We discover that, when expressed from the same plasmid, the combinations of attainable protein concentrations are constrained by a linear relationship, which can be interpreted as an isocost line, a concept used in microeconomics. We created a library of circuits with two reporter genes, one constitutive and the other inducible in the same plasmid, without a regulatory path between them. In agreement with the model predictions, experiments reveal that the isocost line rotates when changing the ribosome binding site strength of the inducible gene and shifts when modifying the plasmid copy number. These results demonstrate that isocost lines can be employed to predict how genetic circuits become coupled when sharing resources and provide design guidelines for minimizing the effects of such couplings.United States. Air Force Office of Scientific Research (Grant FA9550-14-1-0060)United States. Defense Advanced Research Projects Agency (Contract W911NF-12-1-0540)National Institutes of Health (U.S.) (Grant P50 GM098792

Breast Conserving Surgery in Combination With Targeted Intraoperative Radiotherapy Compared to Mastectomy for In-breast-tumor-recurrence

BACKGROUND/AIM: Mastectomy is the standard treatment of in-breast-recurrence of breast cancer after breast conserving surgery (BCS) and external beam radiation therapy (EBRT). In selected cases, it is possible to preserve the breast if targeted intraoperative radiotherapy (TARGIT-IORT) can be given during the second lumpectomy. This is a comparative analysis of overall survival and quality of life (QoL). PATIENTS AND METHODS: Patients in our database with in-breast-recurrence and either mastectomy or BCS and TARGIT-IORT were included. Identified patients were offered participation in a prospective QoL-analysis using the BREAST-Q questionnaire. The cohorts were compared for confounding parameters, overall survival, and QoL. RESULTS: Thirty-six patients treated for in-breast-recurrence were included, 21 had received a mastectomy and 16 patients had received BCS with TARGIT-IORT. Mean follow-up was 12.8 years since primary diagnosis and 4.2 years since recurrence. Both groups were balanced regarding prognostic parameters. Overall survival was numerically longer for BCS and TARGIT-IORT, but the numbers were too small for formal statistical analysis. No patient had further in-breast-recurrence. Psychosocial and sexual wellbeing did not differ between both groups. Physical wellbeing was significantly superior for those whose breast could be preserved (p-value=0.021). Patient-reported incidence and severity of lymphedema of the arm was significantly worse in the mastectomy group (p=0.007). CONCLUSION: Preserving the breast by use of TARGIT-IORT was safe with no re-recurrence and no detriment to overall survival in our analysis and led to a statistically significant improvement in physical wellbeing and incidence of lymphedema. These data should increase the confidence in offering breast preservation after in-breast-recurrence of breast cancer