Time-dependent bond-current functional theory for lattice Hamiltonians: fundamental theorem and application to electron transport

The cornerstone of time-dependent (TD) density functional theory (DFT), the Runge-Gross theorem, proves a one-to-one correspondence between TD potentials and TD densities of continuum Hamiltonians. In all practical implementations, however, the basis set is discrete and the system is effectively described by a lattice Hamiltonian. We point out the difficulties of generalizing the Runge-Groos proof to the discrete case and thereby endorse the recently proposed TD bond-current functional theory (BCFT) as a viable alternative. TDBCFT is based on a one-to-one correspondence between TD Peierl's phases and TD bond-currents of lattice systems. We apply the TDBCFT formalism to electronic transport through a simple interacting device weakly coupled to two biased non-interacting leads. We employ Kohn-Sham Peierl's phases which are discontinuous functions of the density, a crucial property to describe Coulomb blockade. As shown by explicit time propagations, the discontinuity may prevent the biased system from ever reaching a steady state.Comment: 11 pages, 7 figure

Many-body current formula and current conservation for non-equilibrium fully interacting nanojunctions

We consider the electron transport properties through fully interacting nanoscale junctions beyond the linear-response regime. We calculate the current flowing through an interacting region connected to two interacting leads, with interaction crossing at the left and right contacts, by using a non-equilibrium Green's functions (NEGF) technique. The total current at one interface (the left one for example) is made of several terms which can be regrouped into two sets. The first set corresponds to a very generalised Landauer-like current formula with physical quantities defined only in the interacting central region and with renormalised lead self-energies. The second set characterises inelastic scattering events occurring in the left lead. We show how this term can be negligible or even vanish due to the pseudo-equilibrium statistical properties of the lead in the thermodynamic limit. The expressions for the different Green's functions needed for practical calculations of the current are also provided. We determine the constraints imposed by the physical condition of current conservation. The corresponding equation imposed on the different self-energy quantities arising from the current conservation is derived. We discuss in detail its physical interpretation and its relation with previously derived expressions. Finally several important key features are discussed in relation to the implementation of our formalism for calculations of quantum transport in realistic systems

Tetrazole as a Replacement of the Electrophilic Group in Characteristic Prolyl Oligopeptidase Inhibitors

4-Phenylbutanoyl-aminoacyl-2(S)-tetrazolylpyrrolidines were studied as prolyl oligopeptidase inhibitors. The compounds were more potent than expected from the assumption that the tetrazole would also here be a bioisostere of the carboxylic acid group and the corresponding carboxylic acids are at their best only weak inhibitors. The aminoacyl groups L-prolyl and L-alanyl gave potent inhibitors with IC50 values of 12 and 129 nM, respectively. This was in line with typical prolyl oligopeptidase inhibitors; however, we did observe a difference with N-methyl-L-alanyl, which gave potent inhibitors in typical prolyl oligopeptidase inhibitors but not in our novel compound series. Furthermore, all studied 4-phenylbutanoyl-aminoacyl-2(S)-tetrazolylpyrrolidines decreased alpha-synuclein dimerization at the concentration of 10 mu M, also when they were only weak inhibitors of the proteolytic activity of the enzyme with an IC50 value of 205 mu M. Molecular docking studies revealed that the compounds are likely to bind differently to the enzyme compared to typical prolyl oligopeptidase inhibitors represented in this study by 4-phenylbutanoyl-aminoacyl-2(S)-cyanopyrrolidines.Peer reviewe

Removal of proteinase K resistant alpha Syn species does not correlate with cell survival in a virus vector-based Parkinson's disease mouse model

Parkinson's disease (PD) is characterized by degeneration of nigrostriatal dopaminergic neurons and accumu-lation of alpha-synuclein (alpha Syn) as Lewy bodies. Currently, there is no disease-modifying therapy available for PD. We have shown that a small molecular inhibitor for prolyl oligopeptidase (PREP), KYP-2047, relieves alpha Syn-induced toxicity in various PD models by inducing autophagy and preventing alpha Syn aggregation. In this study, we wanted to study the effects of PREP inhibition on different alpha Syn species by using cell culture and in vivo models.We used Neuro2A cells with transient alpha Syn overexpression and oxidative stress or proteasomal inhibition -induced alpha Syn aggregation to assess the effect of KYP-2047 on soluble alpha Syn oligomers and on cell viability. Here, the levels of soluble alpha Syn were measured by using ELISA, and the impact of KYP-2047 was compared to anle138b, nilotinib and deferiprone. To evaluate the effect of KYP-2047 on alpha Syn fibrillization in vivo, we used unilateral nigral AAV1/2-A53T-alpha Syn mouse model, where the KYP-2047 treatment was initiated two-or four -weeks post injection.KYP-2047 and anle138b protected cells from alpha Syn toxicity but interestingly, KYP-2047 did not reduce soluble alpha Syn oligomers. In AAV-A53T-alpha Syn mouse model, KYP-2047 reduced significantly proteinase K-resistant alpha Syn oligomers and oxidative damage related to alpha Syn aggregation. However, the KYP-2047 treatment that was initiated at the time of symptom onset, failed to protect the nigrostriatal dopaminergic neurons. Our results emphasize the importance of whole alpha Syn aggregation process in the pathology of PD and raise an important question about the forms of alpha Syn that are reasonable targets for PD drug therapy.Peer reviewe

Nonequilibrium Green function approach to photoionization processes in atoms

We present a quantum kinetic approach for the time-resolved description of many-body effects in photoionization processes in atoms. The method is based on the non-equilibrium Green functions formalism and solves the Keldysh/Kadanoff-Baym equations in second Born approximation. An approximation scheme is introduced and discussed, which provides a complete single-particle description of the continuum, while the atom is treated fully correlated.Comment: 11 pages, 6 figure

Integration of 150 Gbps/fiber optical engines based on multicore fibers and 6-channel VCSELs and PDs

Multicore fiber enables a parallel optic data link with a single optical fiber, thus providing an attractive way to increase the total throughput and the integration density of the interconnections. We study and present photonics integration technologies and optical coupling approaches for multicore transmitter and receiver subassemblies. Such optical engines are implemented and characterized using multimode 6-core fibers and multicore-optimized active devices: 850-nm VCSEL and PD arrays with circular layout and multi-channel driver and receiver ICs. They are developed for bit-rates of 25 Gbps/channel and beyond, i.e. <150 Gbps per fiber, and also optimized for ruggedized transceivers with extended operation temperature range, for harsh environment applications, including space

Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk