Analytical Rebridging Monte Carlo: Application to cis/trans Isomerization in Proline-Containing, Cyclic Peptides

We present a new method, the analytical rebridging scheme, for Monte Carlo simulation of proline-containing, cyclic peptides. The cis/trans isomerization is accommodated by allowing for two states of the amide bond. We apply our method to five peptides that have been previously characterized by NMR methods. Our simulations achieve effective equilibration and agree well with experimental data in all cases. We discuss the importance of effective equilibration and the role of bond flexibility and solvent effects on the predicted equilibrium properties.Comment: 29 pages, 8 PostScript figures, LaTeX source. to appear in J. Chem. Phys., 199

VAChT knock-down mice show normal prepulse inhibition but disrupted long-term habituation

The neurotransmitter acetylcholine (ACh) plays a crucial role in both the central and peripheral nervous system. Central cholinergic transmission is important for cognitive functions and cholinergic disruptions have been associated with different neural disorders. We here tested the role of cholinergic transmission in basic cognitive functions, i.e. in prepulse inhibition (PPI) and short-term habituation (STH) as well as long-term habituation (LTH) of startle using mice with a 65% knockdown (KD) of the vesicular ACh transporter (VAChT). These mice are slow in refilling cholinergic synaptic transmitter vesicles, leading to a reduced cholinergic tone. Prepulse inhibition has been assumed to be mediated by cholinergic projections from the midbrain to the reticular formation. Surprisingly, PPI and STH were normal in these mice, whereas LTH was disrupted. This disruption could be rescued by pre-testing injections of the ACh esterase inhibitor galantamine, but not by post-testing injections. The lack of a PPI deficit might be because of the fact that VAChT KD mice show disruptions mainly in prolonged cholinergic activity, therefore the transient activation by prepulse processing might not be sufficient to deplete synaptic vesicles. The disruption of LTH indicates that the latter depends on a tonic cholinergic inhibition. Future experiments will address which cholinergic cell group is responsible for this effect

Integrating process design and control: An application of optimal control to chemical processes

In this paper, the optimal design of process systems generically used in chemical industries is studied. The closely coupled nature of optimal design specification of the equipment, the determination of the optimal process parameters in steady-state, moreover, some issues of the application of optimal control is shown. The solution of the overall optimization problem including (i) optimal design of the equipment and (ii) specification of its optimal control strategy can be found relying on two different design concepts, namely, on the conventionally used sequential or, on the newly emerged simultaneous design approaches. This paper gives the theoretical background of the ideas and presents a comparative summary of the approaches. The two approaches are contrasted to each other in which the effects of the interaction of optimal process design and optimal control is highlighted. A new simultaneous optimization procedure providing economic and operability benefits over the traditional stand-alone approach is proposed. The applicability of the idea is demonstrated by means of a design study carried out for optimal design of a coaxial heat exchanger and a reactive distillation column for the synthesis of ethyl tert butyl ether (ETBE), relying on the benefits of the utilization of optimal control

Atmospheric characterization of Proxima b by coupling the Sphere high-contrast imager to the Espresso spectrograph

Context. The temperate Earth-mass planet Proxima b is the closest exoplanet to Earth and represents what may be our best ever opportunity to search for life outside the Solar System. Aims. We aim at directly detecting Proxima b and characterizing its atmosphere by spatially resolving the planet and obtaining high-resolution reflected-light spectra. Methods. We propose to develop a coupling interface between the SPHERE high-contrast imager and the new ESPRESSO spectrograph, both installed at ESO VLT. The angular separation of 37 mas between Proxima b and its host star requires the use of visible wavelengths to spatially resolve the planet on a 8.2-m telescope. At an estimated planet-to-star contrast of ~10^-7 in reflected light, Proxima b is extremely challenging to detect with SPHERE alone. However, the combination of a ~10^3-10^4 contrast enhancement from SPHERE to the high spectral resolution of ESPRESSO can reveal the planetary spectral features and disentangle them from the stellar ones. Results. We find that significant but realistic upgrades to SPHERE and ESPRESSO would enable a 5-sigma detection of the planet and yield a measurement of its true mass and albedo in 20-40 nights of telescope time, assuming an Earth-like atmospheric composition. Moreover, it will be possible to probe the O2 bands at 627, 686 and 760 nm, the water vapour band at 717 nm, and the methane band at 715 nm. In particular, a 3.6-sigma detection of O2 could be made in about 60 nights of telescope time. Those would need to be spread over 3 years considering optimal observability conditions for the planet. Conclusions. The very existence of Proxima b and the SPHERE-ESPRESSO synergy represent a unique opportunity to detect biosignatures on an exoplanet in the near future. It is also a crucial pathfinder experiment for the development of Extremely Large Telescopes and their instruments (abridged).Comment: 16 pages, 7 figures, revised version accepted to A&

Integrative analysis of key candidate genes and signaling pathways in autoimmune thyroid dysfunction related to anti-CTLA-4 therapy by bioinformatics

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), the first immune checkpoint to be targeted clinically, has provided an effective treatment option for various malignancies. However, the clinical advantages associated with CTLA-4 inhibitors can be offset by the potentially severe immune-related adverse events (IRAEs), including autoimmune thyroid dysfunction. To investigate the candidate genes and signaling pathways involving in autoimmune thyroid dysfunction related to anti-CTLA-4 therapy, integrated differentially expressed genes (DEGs) were extracted from the intersection of genes from Gene Expression Omnibus (GEO) datasets and text mining. The functional enrichment was performed by gene ontology (GO) annotation and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis. Protein-protein interaction (PPI) network, module enrichment, and hub gene identification were constructed and visualized by the online Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape software. A total of 22 and 17 integrated human DEGs in hypothyroidism and hyperthyroidism group related to anti-CTLA-4 therapy were identified, respectively. Functional enrichment analysis revealed 24 GO terms and 1 KEGG pathways in the hypothyroid group and 21 GO terms and 2 KEGG pathways in the hyperthyroid group. After PPI network construction, the top five hub genes associated with hypothyroidism were extracted, including ALB, MAPK1, SPP1, PPARG, and MIF, whereas those associated with hyperthyroidism were ALB, FCGR2B, CD44, LCN2, and CD74. The identification of the candidate key genes and enriched signaling pathways provides potential biomarkers for autoimmune thyroid dysfunction related to anti-CTLA-4 therapy and might contribute to the future diagnosis and management of IRAEs for cancer patients

Anomalous tunneling conductances of a spin singlet \nu=2/3 edge states: Interplay of Zeeman splitting and Long Range Coulomb Interaction

The point contact tunneling conductance between edges of the spin singlet $\nu=2/3,\hat{K}=(3/3/0)$ quantum Hall states is studied both in the quasiparticle tunneling picture and in the electron tunneling picture. Due to the interplay of Zeeman splitting and the long range Coulomb interaction between edges of opposite chirality novel spin excitations emerge, and their effect is characterized by anomalous exponents of the charge and spin tunneling conductances in various temperature ranges. Depending on the kinds of scatterings at the point contact and the tunneling mechanism the anomalous interaction in spin sector may enhance or suppress the tunneling conductances. The effects of novel spin excitation are also relevant to the recent NMR experiments on quantum Hall edges.Comment: Revtex File, 7 pages: To be published in Physical Reviews

Open Luttinger liquids

We study the problem of Luttinger liquids interacting with an active environment. We are particularly interested in how dissipation affects the response and correlation functions of non-isolated Luttinger liquids. We show that the exchange of particles, energy, and momentum lead to changes in the exponents characterizing the various correlations functions. We discuss the importance of the zero mode physics in this context.Comment: Revtex, 4 pages. Final version published in PR

Critical points in edge tunneling between generic FQH states

A general description of weak and strong tunneling fixed points is developed in the chiral-Luttinger-liquid model of quantum Hall edge states. Tunneling fixed points are a subset of `termination' fixed points, which describe boundary conditions on a multicomponent edge. The requirement of unitary time evolution at the boundary gives a nontrivial consistency condition for possible low-energy boundary conditions. The effect of interactions and random hopping on fixed points is studied through a perturbative RG approach which generalizes the Giamarchi-Schulz RG for disordered Luttinger liquids to broken left-right symmetry and multiple modes. The allowed termination points of a multicomponent edge are classified by a B-matrix with rational matrix elements. We apply our approach to a number of examples, such as tunneling between a quantum Hall edge and a superconductor and tunneling between two quantum Hall edges in the presence of interactions. Interactions are shown to induce a continuous renormalization of effective tunneling charge for the integrable case of tunneling between two Laughlin states. The correlation functions of electronlike operators across a junction are found from the B matrix using a simple image-charge description, along with the induced lattice of boundary operators. Many of the results obtained are also relevant to ordinary Luttinger liquids.Comment: 23 pages, 6 figures. Xiao-Gang Wen: http://dao.mit.edu/~we

The edge state network model and the global phase diagram

The effects of randomness are investigated in the fractional quantum Hall systems. Based on the Chern-Simons Ginzburg-Landou theory and considering relevant quasi-particle tunneling, the edge state network model for the hierarchical state is introduced and the plateau-plateau transition and liquid-insulator transition are discussed. This model has duality which corresponds to the relation of the quantum Hall liquid phase and the Hall insulating phase and reveals a mechanism in the weak coupling regime.Comment: 5 page RevTe