Multiporphyrin coordination arrays based on complexation of magnesium(II) porphyrins with porphyrinylphosphine oxides

Di- and triporphyrin arrays consisting of 5,15-diphenylporphyrinatomagnesium(II) (MgDPP) coordinated to free- base and Ni( II) porphyrinyl mono- and bis-phosphine oxides, as well as the self-coordinating diphenyl[10,20-diphenylporphyrinatomagnesium(II)-5-yl]phosphine oxide [MgDPP(Ph2PO)], were synthesised in excellent yields and characterised by various spectroscopic techniques. Phosphine oxides stabilise Mg(II) coordination to porphyrins and the resulting complexes have convenient solubilities, while the Ni(II) complexes exhibit interesting intramolecular fluorescence quenching behaviour. The binding constant of MgDPP to triphenylphosphine oxide (5.3 +/- 0.1 x 10(5) M-1) and the very high self- association constant of [MgDPP(Ph2PO)] (5.5 +/- 0.5 x 10(8) M-1) demonstrate the strong affinity of phosphine oxides towards Mg(II) porphyrins. These complexes are the first strongly bound synthetic Mg(II) multiporphyrin complexes and could potentially mimic the "special pair" in the photosynthetic reaction centre

Association Rule Learning Is an Easy and Efficient Method for Identifying Profiles of Traumas and Stressors that Predict Psychopathology in Disaster Survivors: The Example of Sri Lanka.

Research indicates that psychopathology in disaster survivors is a function of both experienced trauma and stressful life events. However, such studies are of limited utility to practitioners who are about to go into a new post-disaster setting as (1) most of them do not indicate which specific traumas and stressors are especially likely to lead to psychopathology; and (2) each disaster is characterized by its own unique traumas and stressors, which means that practitioners have to first collect their own data on common traumas, stressors and symptoms of psychopathology prior to planning any interventions. An easy-to-use and easy-to-interpret data analytical method that allows one to identify profiles of trauma and stressors that predict psychopathology would be of great utility to practitioners working in post-disaster contexts. We propose that association rule learning (ARL), a big data mining technique, is such a method. We demonstrate the technique by applying it to data from 337 survivors of the Sri Lankan civil war who completed the Penn/RESIST/Peradeniya War Problems Questionnaire (PRPWPQ), a comprehensive, culturally-valid measure of experienced trauma, stressful life events, anxiety and depression. ARL analysis revealed five profiles of traumas and stressors that predicted the presence of some anxiety, three profiles that predicted the presence of severe anxiety, four profiles that predicted the presence of some depression and five profiles that predicted the presence of severe depression. ARL allows one to identify context-specific associations between specific traumas, stressors and psychological distress, and can be of great utility to practitioners who wish to efficiently analyze data that they have collected, understand the output of that analysis, and use it to provide psychosocial aid to those who most need it in post-disaster settings

Distribution of ELF magnetic fields in Swedish dwellings

The purpose of this study is to assess the distribution of magnetic fields in the frequency range 10 Hz - 2000 Hz in randomly selected Swedish dwellings. The fields were measured in up to 3 rooms in each residence. In the master bedroom a 24 h logging of the fields was performed. The results show that 89 % of the measured houses have average magnetic fields below 0.2 μT with mean value of 0.11 μT and median value 0.05 μT. The comparison of magnetic fields in urban and rural area show that the lowest fields were found in rural areas with 97% of the residences have average magnetic fields below 0.2 μT with median value 0.04 μT. Comparing villas and apartments show that the median magnetic fields value for apartments is 0.07 μT compared to 0.04 μT for villas. The dominating frequency of the magnetic field was 50 Hz. The total harmonic distortion (THD) of the magnetic field was measured; the median value of THD was 10.3 %

Serration pattern analysis for differentiating epidermolysis bullosa acquisita from other pemphigoid diseases

Background: Direct immunofluorescence (DIF) microscopy of a skin biopsy specimen is the reference standard for the diagnosis of pemphigoid diseases (PDs). Serration pattern analysis enables the differentiation of epidermolysis bullosa acquisita (EBA) from other PDs using DIF microscopy alone. However, practice gaps need to be addressed in order to implement this technique in the routine diagnostic procedure. Objective: We sought to determine and optimize the technical requirements for serration pattern analysis of DIF microscopy and determine interrater conformity of serration pattern analysis. Methods: We compared serration pattern analysis of routine DIF microscopy from laboratories in Groningen, The Netherlands and Lubeck, Germany with 4 blinded observers. Skin biopsy specimens from 20 patients with EBA and other PDs were exchanged and analyzed. Various factors were evaluated, including section thickness, transport medium, and biopsy specimen processing. Results: The interrater conformity of our 4 observers was 95.7%. Recognition of serration patterns was comparable in samples transported in saline and in Michel's medium and with section thicknesses of 4, 6, and 8 mu m. Limitations: Limitations include our small sample size and the availability of 20 samples that were compared retrospectively. Conclusion: DIF serration pattern analysis is not restricted by variation in laboratory procedures, transport medium, or experience of observers. This learnable technique can be implemented as a routine diagnostic method as an extension of DIF microscopy for subtyping PD. (J Am Acad Dermatol 2018;78:754-9.

Variation in morpho‑physiological and metabolic responses to low nitrogen stress across the sorghum association panel

Background: Access to biologically available nitrogen is a key constraint on plant growth in both natural and agricultural settings. Variation in tolerance to nitrogen deficit stress and productivity in nitrogen limited conditions exists both within and between plant species. However, our understanding of changes in different phenotypes under long term low nitrogen stress and their impact on important agronomic traits, such as yield, is still limited. Results: Here we quantified variation in the metabolic, physiological, and morphological responses of a sorghum association panel assembled to represent global genetic diversity to long term, nitrogen deficit stress and the relationship of these responses to grain yield under both conditions. Grain yield exhibits substantial genotype by environment interaction while many other morphological and physiological traits exhibited consistent responses to nitrogen stress across the population. Large scale nontargeted metabolic profiling for a subset of lines in both conditions identified a range of metabolic responses to long term nitrogen deficit stress. Several metabolites were associated with yield under high and low nitrogen conditions. Conclusion: Our results highlight that grain yield in sorghum, unlike many morpho-physiological traits, exhibits substantial variability of genotype specific responses to long term low severity nitrogen deficit stress. Metabolic response to long term nitrogen stress shown higher proportion of variability explained by genotype specific responses than did morpho-pysiological traits and several metabolites were correlated with yield. This suggest, that it might be possible to build predictive models using metabolite abundance to estimate which sorghum genotypes will exhibit greater or lesser decreases in yield in response to nitrogen deficit, however further research needs to be done to evaluate such model

On the early and developed stages of surface condensation: competition mechanism between interfacial and condensate bulk thermal resistances

Financial supports from the National Natural Science Foundation of China (51406205), the Beijing Natural Science Foundation (3142021) and the Engineering and Physics Science Research Council (EPSRC) of the UK (EP/L001233/1) are acknowledged.Financial supports from the National Natural Science Foundation of China (51406205), the Beijing Natural Science Foundation (3142021) and the Engineering and Physics Science Research Council (EPSRC) of the UK (EP/L001233/1) are acknowledged.Financial supports from the National Natural Science Foundation of China (51406205), the Beijing Natural Science Foundation (3142021) and the Engineering and Physics Science Research Council (EPSRC) of the UK (EP/L001233/1) are acknowledged.We use molecular dynamics simulation to investigate the early and developed stages of surface condensation. We find that the liquid-vapor and solid-liquid interfacial thermal resistances depend on the properties of solid and fluid, which are time-independent, while the condensate bulk thermal resistance depends on the condensate thickness, which is time-dependent. There exists intrinsic competition between the interfacial and condensate bulk thermal resistances in timeline and the resultant total thermal resistance determines the condensation intensity for a given vapor-solid temperature difference. We reveal the competition mechanism that the interfacial thermal resistance dominates at the onset of condensation and holds afterwards while the condensate bulk thermal resistance gradually takes over with condensate thickness growing. The weaker the solid-liquid bonding, the later the takeover occurs. This competition mechanism suggests that only when the condensate bulk thermal resistance is reduced after it takes over the domination can the condensation be effectively intensified. We propose a unified theoretical model for the thermal resistance analysis by making dropwise condensation equivalent to filmwise condensation. We further find that near a critical point (contact angle being ca. 153°) the bulk thermal resistance has the least opportunity to take over the domination while away from it the probability increases.Financial supports from the National Natural Science Foundation of China (51406205), the Beijing Natural Science Foundation (3142021) and the Engineering and Physics Science Research Council (EPSRC) of the UK (EP/L001233/1) are acknowledged

On the analysis of the contact angle for impacting droplets using a polynomial fitting approach

ractical considerations on the measurement of the dynamic contact angle and the spreading diameter of impacting droplets are discussed in this paper. The contact angle of a liquid is commonly obtained either by a polynomial or a linear fitting to the droplet profile around the triple phase point. Previous works have focused on quasi-static or sessile droplets, or in cases where inertia does not play a major role on the contact angle dynamics. Here, we study the effect of droplet shape, the order of the fitting polynomial, and the fitting domain, on the measurement of the contact angle on various stages following droplet impact where the contact line is moving. Our results, presented in terms of the optical resolution and the droplet size, show that a quadratic fitting provides the most consistent results for a range of various droplet shapes. As expected, our results show that contact angle values are less sensitive to the fitting conditions for the cases where the droplet can be approximated to a spherical cap. Our experimental conditions include impact events with liquid droplets of different sizes and viscosities on various substrates. In addition, validating past works, our results show that the maximum spreading diameter can be parameterised by the Weber number and the rapidly advancing contact angle

PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro

Abstract Introduction Alterations in cell cycle regulators have been implicated in human malignancies including breast cancer. PD 0332991 is an orally active, highly selective inhibitor of the cyclin D kinases (CDK)4 and CDK6 with ability to block retinoblastoma (Rb) phosphorylation in the low nanomolar range. To identify predictors of response, we determined the in vitro sensitivity to PD 0332991 across a panel of molecularly characterized human breast cancer cell lines. Methods Forty-seven human breast cancer and immortalized cell lines representing the known molecular subgroups of breast cancer were treated with PD 0332991 to determine IC50 values. These data were analyzed against baseline gene expression data to identify genes associated with PD 0332991 response. Results Cell lines representing luminal estrogen receptor-positive (ER+) subtype (including those that are HER2 amplified) were most sensitive to growth inhibition by PD 0332991 while nonluminal/basal subtypes were most resistant. Analysis of variance identified 450 differentially expressed genes between sensitive and resistant cells. pRb and cyclin D1 were elevated and CDKN2A (p16) was decreased in the most sensitive lines. Cell cycle analysis showed G0/G1 arrest in sensitive cell lines and Western blot analysis demonstrated that Rb phosphorylation is blocked in sensitive lines but not resistant lines. PD 0332991 was synergistic with tamoxifen and trastuzumab in ER+ and HER2-amplified cell lines, respectively. PD 0332991 enhanced sensitivity to tamoxifen in cell lines with conditioned resistance to ER blockade. Conclusions These studies suggest a role for CDK4/6 inhibition in some breast cancers and identify criteria for patient selection in clinical studies of PD 0332991

Reversing Melanoma Cross-Resistance to BRAF and MEK Inhibitors by Co-Targeting the AKT/mTOR Pathway

The sustained clinical activity of the BRAF inhibitor vemurafenib (PLX4032/RG7204) in patients with BRAF(V600) mutant melanoma is limited primarily by the development of acquired resistance leading to tumor progression. Clinical trials are in progress using MEK inhibitors following disease progression in patients receiving BRAF inhibitors. However, the PI3K/AKT pathway can also induce resistance to the inhibitors of MAPK pathway.The sensitivity to vemurafenib or the MEK inhibitor AZD6244 was tested in sensitive and resistant human melanoma cell lines exploring differences in activation-associated phosphorylation levels of major signaling molecules, leading to the testing of co-inhibition of the AKT/mTOR pathway genetically and pharmacologically. There was a high degree of cross-resistance to vemurafenib and AZD6244, except in two vemurafenib-resistant cell lines that acquired a secondary mutation in NRAS. In other cell lines, acquired resistance to both drugs was associated with persistence or increase in activity of AKT pathway. siRNA-mediated gene silencing and combination therapy with an AKT inhibitor or rapamycin partially or completely reversed the resistance.Primary and acquired resistance to vemurafenib in these in vitro models results in frequent cross resistance to MEK inhibitors, except when the resistance is the result of a secondary NRAS mutation. Resistance to BRAF or MEK inhibitors is associated with the induction or persistence of activity within the AKT pathway in the presence of these drugs. This resistance can be potentially reversed by the combination of a RAF or MEK inhibitor with an AKT or mTOR inhibitor. These combinations should be available for clinical testing in patients progressing on BRAF inhibitors