An Analysis of Resting-State Functional Transcranial Doppler Recordings from Middle Cerebral Arteries

Functional transcrannial Doppler (fTCD) is used for monitoring the hemodynamics characteristics of major cerebral arteries. Its resting-state characteristics are known only when considering the maximal velocity corresponding to the highest Doppler shift (so called the envelope signals). Significantly more information about the resting-state fTCD can be gained when considering the raw cerebral blood flow velocity (CBFV) recordings. In this paper, we considered simultaneously acquired envelope and raw CBFV signals. Specifically, we collected bilateral CBFV recordings from left and right middle cerebral arteries using 20 healthy subjects (10 females). The data collection lasted for 15 minutes. The subjects were asked to remain awake, stay silent, and try to remain thought-free during the data collection. Time, frequency and time-frequency features were extracted from both the raw and the envelope CBFV signals. The effects of age, sex and body-mass index were examined on the extracted features. The results showed that the raw CBFV signals had a higher frequency content, and its temporal structures were almost uncorrelated. The information-theoretic features showed that the raw recordings from left and right middle cerebral arteries had higher content of mutual information than the envelope signals. Age and body-mass index did not have statistically significant effects on the extracted features. Sex-based differences were observed in all three domains and for both, the envelope signals and the raw CBFV signals. These findings indicate that the raw CBFV signals provide valuable information about the cerebral blood flow which can be utilized in further validation of fTCD as a clinical tool. © 2013 Sejdić et al

Two-orbital SU(N) magnetism with ultracold alkaline-earth atoms

Fermionic alkaline-earth atoms have unique properties that make them attractive candidates for the realization of novel atomic clocks and degenerate quantum gases. At the same time, they are attracting considerable theoretical attention in the context of quantum information processing. Here we demonstrate that when such atoms are loaded in optical lattices, they can be used as quantum simulators of unique many-body phenomena. In particular, we show that the decoupling of the nuclear spin from the electronic angular momentum can be used to implement many-body systems with an unprecedented degree of symmetry, characterized by the SU(N) group with N as large as 10. Moreover, the interplay of the nuclear spin with the electronic degree of freedom provided by a stable optically excited state allows for the study of spin-orbital physics. Such systems may provide valuable insights into strongly correlated physics of transition metal oxides, heavy fermion materials, and spin liquid phases.Comment: 15 pages, 10 figures. V2: extended experimental accessibility and Kondo sections in the main text (including new Fig. 5b) and in the Methods; reorganized other parts; added reference

Generalized quark-antiquark potential at weak and strong coupling

We study a two-parameter family of Wilson loop operators in N=4 supersymmetric Yang-Mills theory which interpolates smoothly between the 1/2 BPS line or circle and a pair of antiparallel lines. These observables capture a natural generalization of the quark-antiquark potential. We calculate these loops on the gauge theory side to second order in perturbation theory and in a semiclassical expansion in string theory to one-loop order. The resulting determinants are given in integral form and can be evaluated numerically for general values of the parameters or analytically in a systematic expansion around the 1/2 BPS configuration. We comment about the feasibility of deriving all-loop results for these Wilson loops.Comment: 43 pages: 15 comprising the main text and 25 for detailed appendice

Light-like polygonal Wilson loops in 3d Chern-Simons and ABJM theory

We study light-like polygonal Wilson loops in three-dimensional Chern-Simons and ABJM theory to two-loop order. For both theories we demonstrate that the one-loop contribution to these correlators cancels. For pure Chern-Simons, we find that specific UV divergences arise from diagrams involving two cusps, implying the loss of finiteness and topological invariance at two-loop order. Studying those UV divergences we derive anomalous conformal Ward identities for n-cusped Wilson loops which restrict the finite part of the latter to conformally invariant functions. We also compute the four-cusp Wilson loop in ABJM theory to two-loop order and find that the result is remarkably similar to that of the corresponding Wilson loop in N=4 SYM. Finally, we speculate about the existence of a Wilson loop/scattering amplitude relation in ABJM theory.Comment: 37 pages, many figures; v2: references added, minor changes; v3: references added, sign error fixed and note adde

Towards multi-scale dynamics on the baryonic branch of Klebanov-Strassler

We construct explicitly a new class of backgrounds in type-IIB supergravity which generalize the baryonic branch of Klebanov-Strassler. We apply a solution-generating technique that, starting from a large class of solutions of the wrapped-D5 system, yields the new solutions, and then proceed to study in detail their properties, both in the IR and in the UV. We propose a simple intuitive field theory interpretation of the rotation procedure and of the meaning of our new solutions within the Papadopoulos-Tseytlin ansatz, in particular in relation to the duality cascade in the Klebanov-Strassler solution. The presence in the field theory of different VEVs for operators of dimensions 2, 3 and 6 suggests that this is an important step towards the construction of the string dual of a genuinely multi-scale (strongly coupled) dynamical model.Comment: 37 pages, 7 figures. References added, version to appear in JHE

Strong interface-induced spin-orbit coupling in graphene on WS2

Interfacial interactions allow the electronic properties of graphene to be modified, as recently demonstrated by the appearance of satellite Dirac cones in the band structure of graphene on hexagonal boron nitride (hBN) substrates. Ongoing research strives to explore interfacial interactions in a broader class of materials in order to engineer targeted electronic properties. Here we show that at an interface with a tungsten disulfide (WS2) substrate, the strength of the spin-orbit interaction (SOI) in graphene is very strongly enhanced. The induced SOI leads to a pronounced low-temperature weak anti-localization (WAL) effect, from which we determine the spin-relaxation time. We find that spin-relaxation time in graphene is two-to-three orders of magnitude smaller on WS2 than on SiO2 or hBN, and that it is comparable to the intervalley scattering time. To interpret our findings we have performed first-principle electronic structure calculations, which both confirm that carriers in graphene-on-WS2 experience a strong SOI and allow us to extract a spin-dependent low-energy effective Hamiltonian. Our analysis further shows that the use of WS2 substrates opens a possible new route to access topological states of matter in graphene-based systems.Comment: Originally submitted version in compliance with editorial guidelines. Final version with expanded discussion of the relation between theory and experiments to be published in Nature Communication

Neutralizing and non-neutralizing monoclonal antibodies against dengue virus E protein derived from a naturally infected patient

<p>Abstract</p> <p>Background</p> <p>Antibodies produced in response to infection with any of the four serotypes of dengue virus generally provide homotypic immunity. However, prior infection or circulating maternal antibodies can also mediate a non-protective antibody response that can enhance the course of disease in a subsequent heterotypic infection. Naturally occurring human monoclonal antibodies can help us understand the protective and pathogenic roles of the humoral immune system in dengue virus infection.</p> <p>Results</p> <p>Epstein-Barr Virus (EBV) transformation of B cells isolated from the peripheral blood of a human subject with previous dengue infection was performed. B cell cultures were screened by ELISA for antibodies to dengue (DENV) envelope (E) protein. ELISA positive cultures were cloned by limiting dilution. Three IgG1 human monoclonal antibodies (HMAbs) were purified and their binding specificity to E protein was verified by ELISA and biolayer interferometry. Neutralization and enhancement assays were conducted in epithelial and macrophage-like cell lines, respectively. All three HMAbs bound to E from at least two of the four DENV serotypes, one of the HMAbs was neutralizing, and all were able to enhance DENV infection.</p> <p>Conclusions</p> <p>HMAbs against DENV can be successfully generated by EBV transformation of B cells from patients at least two years after naturally acquired DENV infections. These antibodies show different patterns of cross-reactivity, neutralizing, and enhancement activity.</p

Structure of the Vesicular Stomatitis Virus N0-P Complex

Replication of non-segmented negative-strand RNA viruses requires the continuous supply of the nucleoprotein (N) in the form of a complex with the phosphoprotein (P). Here, we present the structural characterization of a soluble, heterodimeric complex between a variant of vesicular stomatitis virus N lacking its 21 N-terminal residues (NΔ21) and a peptide of 60 amino acids (P60) encompassing the molecular recognition element (MoRE) of P that binds RNA-free N (N0). The complex crystallized in a decameric circular form, which was solved at 3.0 Å resolution, reveals how the MoRE folds upon binding to N and competes with RNA binding and N polymerization. Small-angle X-ray scattering experiment and NMR spectroscopy on the soluble complex confirms the binding of the MoRE and indicates that its flanking regions remain flexible in the complex. The structure of this complex also suggests a mechanism for the initiation of viral RNA synthesis

Structural Basis for GTP-Dependent Dimerization of Hydrogenase Maturation Factor HypB

Maturation of [NiFe]-hydrogenase requires the insertion of iron, cyanide and carbon monoxide, followed by nickel, to the catalytic core of the enzyme. Hydrogenase maturation factor HypB is a metal-binding GTPase that is essential for the nickel delivery to the hydrogenase. Here we report the crystal structure of Archeoglobus fulgidus HypB (AfHypB) in apo-form. We showed that AfHypB recognizes guanine nucleotide using Asp-194 on the G5 loop despite having a non-canonical NKxA G4-motif. Structural comparison with the GTPγS-bound Methanocaldococcus jannaschii HypB identifies conformational changes in the switch I region, which bring an invariant Asp-72 to form an intermolecular salt-bridge with another invariant residue Lys-148 upon GTP binding. Substitution of K148A abolished GTP-dependent dimerization of AfHypB, but had no significant effect on the guanine nucleotide binding and on the intrinsic GTPase activity. In vivo complementation study in Escherichia coli showed that the invariant lysine residue is required for in vivo maturation of hydrogenase. Taken together, our results suggest that GTP-dependent dimerization of HypB is essential for hydrogenase maturation. It is likely that a nickel ion is loaded to an extra metal binding site at the dimeric interface of GTP-bound HypB and transferred to the hydrogenase upon GTP hydrolysis

Integrative modeling of transcriptional regulation in response to antirheumatic therapy

<p>Abstract</p> <p>Background</p> <p>The investigation of gene regulatory networks is an important issue in molecular systems biology and significant progress has been made by combining different types of biological data. The purpose of this study was to characterize the transcriptional program induced by etanercept therapy in patients with rheumatoid arthritis (RA). Etanercept is known to reduce disease symptoms and progression in RA, but the underlying molecular mechanisms have not been fully elucidated.</p> <p>Results</p> <p>Using a DNA microarray dataset providing genome-wide expression profiles of 19 RA patients within the first week of therapy we identified significant transcriptional changes in 83 genes. Most of these genes are known to control the human body's immune response. A novel algorithm called TILAR was then applied to construct a linear network model of the genes' regulatory interactions. The inference method derives a model from the data based on the Least Angle Regression while incorporating DNA-binding site information. As a result we obtained a scale-free network that exhibits a self-regulating and highly parallel architecture, and reflects the pleiotropic immunological role of the therapeutic target TNF-alpha. Moreover, we could show that our integrative modeling strategy performs much better than algorithms using gene expression data alone.</p> <p>Conclusion</p> <p>We present TILAR, a method to deduce gene regulatory interactions from gene expression data by integrating information on transcription factor binding sites. The inferred network uncovers gene regulatory effects in response to etanercept and thus provides useful hypotheses about the drug's mechanisms of action.</p