Inhibition by recurrent excitation: a mechanism for spike synchronization in a network of coupled neuronal oscillators

Egelhaaf M, Benjamin PR. Inhibition by recurrent excitation: a mechanism for spike synchronization in a network of coupled neuronal oscillators. Journal of Experimental Biology. 1982;96:447-451

Regulatory impact of the C-terminal tail on charge transfer pathways in drosophila cryptochrome

Interconnected transcriptional and translational feedback loops are at the core of the molecular mechanism of the circadian clock. Such feedback loops are synchronized to external light entrainment by the blue light photoreceptor cryptochrome (CRY) that undergoes conformational changes upon light absorption by an unknown photoexcitation mechanism. Light-induced charge transfer (CT) reactions in Drosophila CRY (dCRY) are investigated by state-of-the-art simulations that reveal a complex, multi-redox site nature of CT dynamics on the microscopic level. The simulations consider redox-active chromophores of the tryptophan triad (Trp triad) and further account for pathways mediated by W314 and W422 residues proximate to the C-terminal tail (CTT), thus avoiding a pre-bias to specific W-mediated CT pathways. The conducted dissipative quantum dynamics simulations employ microscopically derived model Hamiltonians and display complex and ultrafast CT dynamics on the picosecond timescale, subtly balanced by the electrostatic environment of dCRY. In silicio point mutations provide a microscopic basis for rationalizing particular CT directionality and demonstrate the degree of electrostatic control realized by a discrete set of charged amino acid residues. The predicted participation of CT states in proximity to the CTT relates the directionality of CT reactions to the spatial vicinity of a linear interaction motif. The results stress the importance of CTT directional charge transfer in addition to charge transfer via the Trp triad and call for the use of full-length CRY models including the interactions of photolyase homology region (PHR) and CTT domains. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Positive noise cross-correlations in superconducting hybrids: Roles of interfaces and interactions

Shot noise cross-correlations in normal metal-superconductor-normal metal structures are discussed at arbitrary interface transparencies using both the scattering approach of Blonder, Tinkham and Klapwik and a microscopic Green's function approach. Surprisingly, negative crossed conductance in such set-ups [R. Melin and D. Feinberg, Phys. Rev. B 70, 174509 (2004)] does not preclude the possibility of positive noise cross-correlations for almost transparent contacts. We conclude with a phenomenological discussion of interactions in the one dimensional leads connected to the superconductor, which induce sign changes in the noise cross-correlations.Comment: 15 pages, 9 figure

Association of PET-measured myocardial flow reserve with echocardiography-estimated pulmonary artery systolic pressure in patients with hypertrophic cardiomyopathy

BackgroundPulmonary hypertension (PH) is a known complication of HCM and is a strong predictor of mortality. We aim to investigate the relationship between microvascular dysfunction measured by quantitative PET and PH in HCM patients.MethodsEighty-nine symptomatic HCM patients were included in the study. Each patient underwent two 20-min 13N-NH3 dynamic PET scans for rest and stress conditions, respectively. A 2-tissue irreversible compartmental model was used to fit the segments time activity curves for estimating segmental and global myocardial blood flow (MBF) and myocardial flow reserve (MFR). Echocardiographic derived PASP was utilized to estimate PH.ResultsPatients were categorized into two groups across PASP: PH (PASP > 36 mmHg) and no-PH (PASP ≤ 36 mmHg). patients with PH had larger left atrium, ratio of higher inflow early diastole (E) and atrial contraction (A) waves, E/A, and ratio of inflow and peak early diastolic waves, E/e', significantly reduced global stress MBF (1.85 ± 0.52 vs. 2.13 ± 0.56 ml/min/g; p = 0.024) and MFR (2.21 ± 0.57 vs. 2.62 ± 0.75; p = 0.005), while the MBFs at rest between the two groups were similar. There were significant negative correlations between global stress MBF/MFR and PASP (stress MBF: r = -0.23, p = 0.03; MFR: r = -0.32, p = 0.002); for regional MBF and MFR measurements, the highest linear correlation coefficients were observed in the septal wall (stress MBF: r = -0.27, p = 0.01; MFR: r = -0.31, p = 0.003). Global MFR was identified to be independent predictor for PH in multivariate regression analysis.ConclusionEchocardiography-derived PASP is negatively correlated with global MFR measured by 13N-NH3 dynamic PET. Global MFR is suggested to be an index of PH in HCM patients.</div

Quadrilateral-octagon coordinates for almost normal surfaces

Normal and almost normal surfaces are essential tools for algorithmic 3-manifold topology, but to use them requires exponentially slow enumeration algorithms in a high-dimensional vector space. The quadrilateral coordinates of Tollefson alleviate this problem considerably for normal surfaces, by reducing the dimension of this vector space from 7n to 3n (where n is the complexity of the underlying triangulation). Here we develop an analogous theory for octagonal almost normal surfaces, using quadrilateral and octagon coordinates to reduce this dimension from 10n to 6n. As an application, we show that quadrilateral-octagon coordinates can be used exclusively in the streamlined 3-sphere recognition algorithm of Jaco, Rubinstein and Thompson, reducing experimental running times by factors of thousands. We also introduce joint coordinates, a system with only 3n dimensions for octagonal almost normal surfaces that has appealing geometric properties.Comment: 34 pages, 20 figures; v2: Simplified the proof of Theorem 4.5 using cohomology, plus other minor changes; v3: Minor housekeepin

Homogenized lattice Boltzmann model for simulating multi-phase flows in heterogeneous porous media

A homogenization approach for the simulation of multi-phase flows in heterogeneous porous media is presented. It is based on the lattice Boltzmann method and combines the grayscale with the multi-component Shan–Chen method. Thus, it mimics fluid–fluid and solid–fluid interactions also within pores that are smaller than the numerical discretization. The model is successfully tested for a broad variety of single- and two-phase flow problems. Additionally, its application to multi-scale and multi-phase flow problems in porous media is demonstrated using the electrolyte filling process of realistic 3D lithium-ion battery electrode microstructures as an example. The approach presented here shows advantages over comparable methods from literature. The interfacial tension and wetting conditions are independent and not affected by the homogenization. Moreover, all physical properties studied here are continuous even across interfaces of porous media. The method is consistent with the original multi-component Shan–Chen method (MCSC). It is as stable as the MCSC, easy to implement, and can be applied to many research fields, especially where multi-phase fluid flow occurs in heterogeneous and multi-scale porous media

Electronic properties of molecular solids: the peculiar case of solid Picene

Recently, a new organic superconductor, K-intercalated Picene with high transition temperatures $T_c$ (up to 18\,K) has been discovered. We have investigated the electronic properties of the undoped relative, solid picene, using a combination of experimental and theoretical methods. Our results provide detailed insight into the occuopied and unoccupied electronic states

The influence of pregnancy on the pharmacokinetic properties of artemisinin combination therapy (ACT): a systematic review

Pregnancy has been reported to alter the pharmacokinetic properties of anti-malarial drugs, including the different components of artemisinin-based combination therapy (ACT). However, small sample sizes make it difficult to draw strong conclusions based on individual pharmacokinetic studies. The aim of this review is to summarize the evidence of the influence of pregnancy on the pharmacokinetic properties of different artemisinin-based combinations. A PROSPERO-registered systematic review to identify clinical trials that investigated the influence of pregnancy on the pharmacokinetic properties of different forms of ACT was conducted, following PRISMA guidelines. Without language restrictions, Medline/PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, LILACS, Biosis Previews and the African Index Medicus were searched for studies published up to November 2015. The following components of ACT that are currently recommend by the World Health Organization as first-line treatment of malaria in pregnancy were reviewed: artemisinin, artesunate, dihydroartemisinin, lumefantrine, amodiaquine, mefloquine, sulfadoxine, pyrimethamine, piperaquine, atovaquone and proguanil. The literature search identified 121 reports, 27 original studies were included. 829 pregnant women were included in the analysis. Comparison of the available studies showed lower maximum concentrations (Cmax) and exposure (AUC) of dihydroartemisinin, the active metabolite of all artemisinin derivatives, after oral administration of artemether, artesunate and dihydroartemisinin in pregnant women. Low day 7 concentrations were commonly seen in lumefantrine studies, indicating a low exposure and possibly reduced efficacy. The influence of pregnancy on amodiaquine and piperaquine seemed not to be clinically relevant. Sulfadoxine plasma concentration was significantly reduced and clearance rates were higher in pregnancy, while pyrimethamine and mefloquine need more research as no general conclusion can be drawn based on the available evidence. For atovaquone, the available data showed a lower maximum concentration and exposure. Finally, the maximum concentration of cycloguanil, the active metabolite of proguanil, was significantly lower, possibly compromising the efficacy. These findings suggest that reassessment of the dose of the artemisinin derivate and some components of ACT are necessary to ensure the highest possible efficacy of malaria treatment in pregnant women. However, for most components of ACT, data were insufficient and extensive research with larger sample sizes will be necessary to identify the exact influences of pregnancy on the pharmacokinetic properties of different artemisinin-based combinations. In addition, different clinical studies used diverse study designs with various reported relevant outcomes. Future pharmacokinetic studies could benefit from more uniform designs, in order to increase quality, robustness and effectiveness. CRD42015023756 (PROSPERO

Molecular and fossil evidence place the origin of cichlid fishes long after Gondwanan rifting.

Cichlid fishes are a key model system in the study of adaptive radiation, speciation and evolutionary developmental biology. More than 1600 cichlid species inhabit freshwater and marginal marine environments across several southern landmasses. This distributional pattern, combined with parallels between cichlid phylogeny and sequences of Mesozoic continental rifting, has led to the widely accepted hypothesis that cichlids are an ancient group whose major biogeographic patterns arose from Gondwanan vicariance. Although the Early Cretaceous (ca 135 Ma) divergence of living cichlids demanded by the vicariance model now represents a key calibration for teleost molecular clocks, this putative split pre-dates the oldest cichlid fossils by nearly 90 Myr. Here, we provide independent palaeontological and relaxed-molecular-clock estimates for the time of cichlid origin that collectively reject the antiquity of the group required by the Gondwanan vicariance scenario. The distribution of cichlid fossil horizons, the age of stratigraphically consistent outgroup lineages to cichlids and relaxed-clock analysis of a DNA sequence dataset consisting of 10 nuclear genes all deliver overlapping estimates for crown cichlid origin centred on the Palaeocene (ca 65-57 Ma), substantially post-dating the tectonic fragmentation of Gondwana. Our results provide a revised macroevolutionary time scale for cichlids, imply a role for dispersal in generating the observed geographical distribution of this important model clade and add to a growing debate that questions the dominance of the vicariance paradigm of historical biogeography