Perfect quantum transport in arbitrary spin networks

Spin chains have been proposed as wires to transport information between distributed registers in a quantum information processor. Unfortunately, the challenges in manufacturing linear chains with engineered couplings has hindered experimental implementations. Here we present strategies to achieve perfect quantum information transport in arbitrary spin networks. Our proposal is based on the weak coupling limit for pure state transport, where information is transferred between two end-spins that are only weakly coupled to the rest of the network. This regime allows disregarding the complex, internal dynamics of the bulk network and relying on virtual transitions or on the coupling to a single bulk eigenmode. We further introduce control methods capable of tuning the transport process and achieve perfect fidelity with limited resources, involving only manipulation of the end-qubits. These strategies could be thus applied not only to engineered systems with relaxed fabrication precision, but also to naturally occurring networks; specifically, we discuss the practical implementation of quantum state transfer between two separated nitrogen vacancy (NV) centers through a network of nitrogen substitutional impurities.Comment: 5+7 page

Speaker and Expression Factorization for Audiobook Data: Expressiveness and Transplantation

Expressive synthesis from text is a challenging problem. There are two issues. First, read text is often highly expressive to convey the emotion and scenario in the text. Second, since the expressive training speech is not always available for different speakers, it is necessary to develop methods to share the expressive information over speakers. This paper investigates the approach of using very expressive, highly diverse audiobook data from multiple speakers to build an expressive speech synthesis system. Both of two problems are addressed by considering a factorized framework where speaker and emotion are modelled in separate sub-spaces of a cluster adaptive training (CAT) parametric speech synthesis system. The sub-spaces for the expressive state of a speaker and the characteristics of the speaker are jointly trained using a set of audiobooks. In this work, the expressive speech synthesis system works in two distinct modes. In the first mode, the expressive information is given by audio data and the adaptation method is used to extract the expressive information in the audio data. In the second mode, the input of the synthesis system is plain text and a full expressive synthesis system is examined where the expressive state is predicted from the text. In both modes, the expressive information is shared and transplanted over different speakers. Experimental results show that in both modes, the expressive speech synthesis method proposed in this work significantly improves the expressiveness of the synthetic speech for different speakers. Finally, this paper also examines whether it is possible to predict the expressive states from text for multiple speakers using a single model, or whether the prediction process needs to be speaker specific.This is the accepted manuscript. The final version is available from IEEE at http://ieeexplore.ieee.org/xpl/articleDetails.jsp?arnumber=6995936&filter%3DAND%28p_IS_Number%3A7055953%29

High-Resolution 3D Structure Determination of Kaliotoxin by Solid-State NMR Spectroscopy

High-resolution solid-state NMR spectroscopy can provide structural information of proteins that cannot be studied by X-ray crystallography or solution NMR spectroscopy. Here we demonstrate that it is possible to determine a protein structure by solid-state NMR to a resolution comparable to that by solution NMR. Using an iterative assignment and structure calculation protocol, a large number of distance restraints was extracted from 1H/1H mixing experiments recorded on a single uniformly labeled sample under magic angle spinning conditions. The calculated structure has a coordinate precision of 0.6 Å and 1.3 Å for the backbone and side chain heavy atoms, respectively, and deviates from the structure observed in solution. The approach is expected to be applicable to larger systems enabling the determination of high-resolution structures of amyloid or membrane proteins

Histamine Derived from Probiotic Lactobacillus reuteri Suppresses TNF via Modulation of PKA and ERK Signaling

Beneficial microbes and probiotic species, such as Lactobacillus reuteri, produce biologically active compounds that can modulate host mucosal immunity. Previously, immunomodulatory factors secreted by L. reuteri ATCC PTA 6475 were unknown. A combined metabolomics and bacterial genetics strategy was utilized to identify small compound(s) produced by L. reuteri that were TNF-inhibitory. Hydrophilic interaction liquid chromatography-high performance liquid chromatography (HILIC-HPLC) separation isolated TNF-inhibitory compounds, and HILIC-HPLC fraction composition was determined by NMR and mass spectrometry analyses. Histamine was identified and quantified in TNF-inhibitory HILIC-HPLC fractions. Histamine is produced from L-histidine via histidine decarboxylase by some fermentative bacteria including lactobacilli. Targeted mutagenesis of each gene present in the histidine decarboxylase gene cluster in L. reuteri 6475 demonstrated the involvement of histidine decarboxylase pyruvoyl type A (hdcA), histidine/histamine antiporter (hdcP), and hdcB in production of the TNF-inhibitory factor. The mechanism of TNF inhibition by L. reuteri-derived histamine was investigated using Toll-like receptor 2 (TLR2)-activated human monocytoid cells. Bacterial histamine suppressed TNF production via activation of the H2 receptor. Histamine from L. reuteri 6475 stimulated increased levels of cAMP, which inhibited downstream MEK/ERK MAPK signaling via protein kinase A (PKA) and resulted in suppression of TNF production by transcriptional regulation. In summary, a component of the gut microbiome, L. reuteri, is able to convert a dietary component, L-histidine, into an immunoregulatory signal, histamine, which suppresses pro-inflammatory TNF production. The identification of bacterial bioactive metabolites and their corresponding mechanisms of action with respect to immunomodulation may lead to improved anti-inflammatory strategies for chronic immune-mediated diseases

Altered Metabolism of Growth Hormone Receptor Mutant Mice: A Combined NMR Metabonomics and Microarray Study

Growth hormone is an important regulator of post-natal growth and metabolism. We have investigated the metabolic consequences of altered growth hormone signaling in mutant mice that have truncations at position 569 and 391 of the intracellular domain of the growth hormone receptor, and thus exhibit either low (around 30% maximum) or no growth hormone-dependent STATS signaling respectively. These mutants result in altered liver metabolism, obesity and insulin resistance

Brucellosis Vaccines: Assessment of Brucella melitensis Lipopolysaccharide Rough Mutants Defective in Core and O-Polysaccharide Synthesis and Export

Background: The brucellae are facultative intracellular bacteria that cause brucellosis, one of the major neglected zoonoses. In endemic areas, vaccination is the only effective way to control this disease. Brucella melitensis Rev 1 is a vaccine effective against the brucellosis of sheep and goat caused by B. melitensis, the commonest source of human infection. However, Rev 1 carries a smooth lipopolysaccharide with an O-polysaccharide that elicits antibodies interfering in serodiagnosis, a major problem in eradication campaigns. Because of this, rough Brucella mutants lacking the O-polysaccharide have been proposed as vaccines. Methodology/Principal Findings: To examine the possibilities of rough vaccines, we screened B. melitensis for lipopolysaccharide genes and obtained mutants representing all main rough phenotypes with regard to core oligosaccharide and O-polysaccharide synthesis and export. Using the mouse model, mutants were classified into four attenuation patterns according to their multiplication and persistence in spleens at different doses. In macrophages, mutants belonging to three of these attenuation patterns reached the Brucella characteristic intracellular niche and multiplied intracellularly, suggesting that they could be suitable vaccine candidates. Virulence patterns, intracellular behavior and lipopolysaccharide defects roughly correlated with the degree of protection afforded by the mutants upon intraperitoneal vaccination of mice. However, when vaccination was applied by the subcutaneous route, only two mutants matched the protection obtained with Rev 1 albeit at doses one thousand fold higher than this reference vaccine. These mutants, which were blocked in O-polysaccharide export and accumulated internal O-polysaccharides, stimulated weak anti-smooth lipopolysaccharide antibodies. Conclusions/Significance: The results demonstrate that no rough mutant is equal to Rev 1 in laboratory models and question the notion that rough vaccines are suitable for the control of brucellosis in endemic areas.This work was funded by the European Commission (Research Contract QLK2-CT-2002-00918) and the Ministerio de Ciencia y Tecnología of Spain (Proyecto AGL2004-01162/GAN)

Isolation, structure, and activity of GID, a novel alpha 4/7-conotoxin with an extended N-terminal sequence

Using assay-directed fractionation of Conus geographus crude venom, we isolated a-conotoxin GID, which acts selectively at neuronal nicotinic acetylcholine receptors (nAChRs). Unlike other neuronally selective alpha-conotoxins, alpha-GID has a four amino acid N-terminal tail, gamma-carboxyglutamate (Gla), and hydroxyproline (0) residues, and lacks an amidated C terminus. GID inhibits alpha7 and alpha3beta2 nAChRs with IC50 values of 5 and 3 nm, respectively and is at least 1000-fold less potent at the alpha1beta1gammadelta, alpha3beta4, and alpha4beta4 combinations. GID also potently inhibits the alpha4beta2 subtype (IC50 of 150 nm). Deletion of the N-terminal sequence (GIDDelta1-4) significantly decreased activity at the alpha4beta2 nAChR but hardly affected potency at alpha3beta2 and alpha7 nAChRs, despite enhancing the off-rates at these receptors. In contrast, Arg(12) contributed to alpha4beta2 and alpha7 activity but not to alpha3beta2 activity. The three-dimensional structure of GID is well defined over residues 4-19 with a similar motif to other a-conotoxins. However, despite its influence on activity, the tail appears to be disordered in solution. Comparison of GID with other alpha4/7-conotoxins which possess an NN(P/O) motif in loop II, revealed a correlation between increasing length of the aliphatic side-chain in position 10 (equivalent to 13 in GID) and greater alpha7 versus alpha3beta2 selectivity

Disulfide folding pathways of cystine knot proteins: Tying the knot within the circular backbone of the cyclotides

The plant cyclotides are a fascinating family of circular proteins that contain a cyclic cystine knot motif. The knotted topology and cyclic nature of the cyclotides pose interesting questions about folding mechanisms and how the knotted arrangement of disulfide bonds is formed. In the current study we have examined the oxidative refolding and reductive unfolding of the prototypic cyclotide, kalata B1. A stable two-disulfide intermediate accumulated during oxidative refolding but not in reductive unfolding. Mass spectrometry and NMR spectroscopy were used to show that the intermediate contained a native-like structure with two native disulfide bonds topologically similar to the intermediate isolated for the related cystine knot protein EETI-II (LeNguyen, D., Heitz, A., Chiche, L., El Hajji, M., and Castro B. (1993) Protein Sci. 2, 165-174). However, the folding intermediate observed for kalata B1 is not the immediate precursor of the three-disulfide native peptide and does not accumulate in the reductive unfolding process, in contrast to the intermediate observed for EETI-II. These alternative pathways of linear and cyclic cystine knot proteins appear to be related to the constraints imposed by the cyclic backbone of kalata B1 and the different ring size of the cystine knot. The three-dimensional structure of a synthetic version of the two-disulfide intermediate of kalata B1 in which Ala residues replace the reduced Cys residues provides a structural insight into why the two-disulfide intermediate is a kinetic trap on the folding pathway