Magnetotelluric data processing: a case study

Magnetotelluric (MT) data collected simultaneously at one or more sites may be processed by a number of different methods. Such methods attempt to remove or suppress the effect of noise on the data channels. The desired results are accurate, unbiased and repeatable estimates of the impedance tensor as a function of frequency and location. In this study we perform an investigation of the analysis of an MT data set sampled at 5 s. Both single-site (SS) and remote-reference (RR) techniques are employed to estimate the impedance tensor Z. Two biased SS estimates of Z are used to compare the performance of five coherence­ based acceptance criteria. It is demonstrated that the RR predicted coherence between local fields can be used for selecting data windows, and provides a necessary assessment of the reliability of a given RR estimate. It is demonstrated that the variance of an RR estimate depends strongly on the local signal-to-noise ratios (as monitored by the local predicted coherence) and depends weakly on the number of data windows, as long as coherences are above a moderate threshold. Although, for our data, an estimate of Z obtained using a remote electric field is grossly inaccurate, its associated predicted coherence is as efficient in selecting low-noise-level data windows as its counterpart obtained using a remote magnetic field. The relation between SS and RR predicted coherences, the latter estimated using both electric and magnetic fields, is investigated. A hybrid selection technique that uses a remote electric field is suggested

Experimental simulation of quantum graphs by microwave networks

We present the results of experimental and theoretical study of irregular, tetrahedral microwave networks consisting of coaxial cables (annular waveguides) connected by T-joints. The spectra of the networks were measured in the frequency range 0.0001-16 GHz in order to obtain their statistical properties such as the integrated nearest neighbor spacing distribution and the spectral rigidity. The comparison of our experimental and theoretical results shows that microwave networks can simulate quantum graphs with time reversal symmetry. In particular, we use the spectra of the microwave networks to study the periodic orbits of the simulated quantum graphs. We also present experimental study of directional microwave networks consisting of coaxial cables and Faraday isolators for which the time reversal symmetry is broken. In this case our experimental results indicate that spectral statistics of directional microwave networks deviate from predictions of Gaussian orthogonal ensembles (GOE) in random matrix theory approaching, especially for small eigenfrequency spacing s, results for Gaussian unitary ensembles (GUE). Experimental results are supported by the theoretical analysis of directional graphs.Comment: 16 pages, 7 figures, to be published in Phys. Rev.

Experimental and numerical investigation of the reflection coefficient and the distributions of Wigner's reaction matrix for irregular graphs with absorption

We present the results of experimental and numerical study of the distribution of the reflection coefficient P(R) and the distributions of the imaginary P(v) and the real P(u) parts of the Wigner's reaction K matrix for irregular fully connected hexagon networks (graphs) in the presence of strong absorption. In the experiment we used microwave networks, which were built of coaxial cables and attenuators connected by joints. In the numerical calculations experimental networks were described by quantum fully connected hexagon graphs. The presence of absorption introduced by attenuators was modelled by optical potentials. The distribution of the reflection coefficient P(R) and the distributions of the reaction K matrix were obtained from the measurements and numerical calculations of the scattering matrix S of the networks and graphs, respectively. We show that the experimental and numerical results are in good agreement with the exact analytic ones obtained within the framework of random matrix theory (RMT).Comment: 15 pages, 8 figure

Clinical profile of patients with ATP1A3 mutations in Alternating Hemiplegia of Childhood\u2014a study of 155 patients

Background: Mutations in the gene ATP1A3 have recently been identified to be prevalent in patients with alternating hemiplegia of childhood (AHC2). Based on a large series of patients with AHC, we set out to identify the spectrum of different mutations within the ATP1A3 gene and further establish any correlation with phenotype. Methods: Clinical data from an international cohort of 155 AHC patients (84 females, 71 males; between 3 months and 52 years) were gathered using a specifically formulated questionnaire and analysed relative to the mutational ATP1A3 gene data for each patient. Results: In total, 34 different ATP1A3 mutations were detected in 85 % (132/155) patients, seven of which were novel. In general, mutations were found to cluster into five different regions. The most frequent mutations included: p.Asp801Asn (43 %; 57/132), p.Glu815Lys (16 %; 22/132), and p.Gly947Arg (11 %; 15/132). Of these, p.Glu815Lys was associated with a severe phenotype, with more severe intellectual and motor disability. p.Asp801Asn appeared to confer a milder phenotypic expression, and p.Gly947Arg appeared to correlate with the most favourable prognosis, compared to the other two frequent mutations. Overall, the comparison of the clinical profiles suggested a gradient of severity between the three major mutations with differences in intellectual (p = 0.029) and motor (p = 0.039) disabilities being statistically significant. For patients with epilepsy, age at onset of seizures was earlier for patients with either p.Glu815Lys or p.Gly947Arg mutation, compared to those with p.Asp801Asn mutation (p < 0.001). With regards to the five mutation clusters, some clusters appeared to correlate with certain clinical phenotypes. No statistically significant clinical correlations were found between patients with and without ATP1A3 mutations. Conclusions: Our results, demonstrate a highly variable clinical phenotype in patients with AHC2 that correlates with certain mutations and possibly clusters within the ATP1A3 gene. Our description of the clinical profile of patients with the most frequent mutations and the clinical picture of those with less common mutations confirms the results from previous studies, and further expands the spectrum of genotype-phenotype correlations. Our results may be useful to confirm diagnosis and may influence decisions to ensure appropriate early medical intervention in patients with AHC. They provide a stronger basis for the constitution of more homogeneous groups to be included in clinical trial

Transmitted drug resistance, selection of resistance mutations and moderate antiretroviral efficacy in HIV-2: Analysis of the HIV-2 Belgium and Luxembourg database

BACKGROUND: Guidelines established for the treatment of HIV-1 infection and genotype interpretation do not apply for HIV-2. Data about antiretroviral (ARV) drug efficacy and resistance mutations is scarce. METHODS: Clinical data about HIV-2 infected patients in Belgium and Luxembourg were collected and the effect of ARV therapy on plasma viral load and CD4 counts were analysed. Viral RNA encoding for protease (PR) and reverse transcriptase (RT) from ARV-naive and treated patients were sequenced. RESULTS: Sixty-five HIV-2 infected patients were included in this cohort. Twenty patients were treated with 25 different ARV combinations in a total of 34 regimens and six months after the start of ARV therapy, only one third achieved viral load suppression. All of these successful regimens bar one contained protease inhibitors (PIs). Mean CD4 gains in the group of viral load suppressors and the group of patients treated with PI-containing regimens were respectively significantly higher than in the group of non-suppressors and the group of PI-sparing regimens. The most frequent mutations selected under therapy (compared to HIV-2 ROD) were V71I, L90M and I89V within PR. Within RT, they were M184V, Q151M, V111I and K65R. All of these mutations, except K65R and M184V, were also found in variable proportions in ARV-naive patients. CONCLUSION: Despite a high rate of ARV treatment failure, better virological and immunological results were achieved with PI-containing regimens. The analysis of polymorphic positions and HIV-2 specific mutations selected during therapy showed for the first time that transmission of drug resistant viruses has occurred in Belgium and Luxembourg. The high heterogeneity in ARV combinations reflects a lack of guidelines for the treatment of HIV-2 infection

Innate Killing of Leishmania donovani by Macrophages of the Splenic Marginal Zone Requires IRF-7

Highly phagocytic macrophages line the marginal zone (MZ) of the spleen and the lymph node subcapsular sinus. Although these macrophages have been attributed with a variety of functions, including the uptake and clearance of blood and lymph-borne pathogens, little is known about the effector mechanisms they employ after pathogen uptake. Here, we have combined gene expression profiling and RNAi using a stromal macrophage cell line with in situ analysis of the leishmanicidal activity of marginal zone macrophages (MZM) and marginal metallophilic macrophages (MMM) in wild type and gene targeted mice. Our data demonstrate a critical role for interferon regulatory factor-7 (IRF-7) in regulating the killing of intracellular Leishmania donovani by these specialised splenic macrophage sub-populations. This study, therefore, identifies a new role for IRF-7 as a regulator of innate microbicidal activity against this, and perhaps other, non-viral intracellular pathogens. This study also highlights the importance of selecting appropriate macrophage populations when studying pathogen interactions with this functionally diverse lineage of cells

The Intracellular DNA Sensor IFI16 Gene Acts as Restriction Factor for Human Cytomegalovirus Replication

Human interferon (IFN)-inducible IFI16 protein, an innate immune sensor of intracellular DNA, modulates various cell functions, however, its role in regulating virus growth remains unresolved. Here, we adopt two approaches to investigate whether IFI16 exerts pro- and/or anti-viral actions. First, the IFI16 gene was silenced using specific small interfering RNAs (siRNA) in human embryo lung fibroblasts (HELF) and replication of DNA and RNA viruses evaluated. IFI16-knockdown resulted in enhanced replication of Herpesviruses, in particular, Human Cytomegalovirus (HCMV). Consistent with this, HELF transduction with a dominant negative form of IFI16 lacking the PYRIN domain (PYD) enhanced the replication of HCMV. Second, HCMV replication was compared between HELFs overexpressing either the IFI16 gene or the LacZ gene. IFI16 overexpression decreased both virus yield and viral DNA copy number. Early and late, but not immediate-early, mRNAs and proteins were strongly down-regulated, thus IFI16 may exert its antiviral effect by impairing viral DNA synthesis. Constructs with the luciferase reporter gene driven by deleted or site-specific mutated forms of the HCMV DNA polymerase (UL54) promoter demonstrated that the inverted repeat element 1 (IR-1), located between −54 and −43 relative to the transcription start site, is the target of IFI16 suppression. Indeed, electrophoretic mobility shift assays and chromatin immunoprecipitation demonstrated that suppression of the UL54 promoter is mediated by IFI16-induced blocking of Sp1-like factors. Consistent with these results, deletion of the putative Sp1 responsive element from the HCMV UL44 promoter also relieved IFI16 suppression. Together, these data implicate IFI16 as a novel restriction factor against HCMV replication and provide new insight into the physiological functions of the IFN-inducible gene IFI16 as a viral restriction factor

Aquaporins: important but elusive drug targets.

The aquaporins (AQPs) are a family of small, integral membrane proteins that facilitate water transport across the plasma membranes of cells in response to osmotic gradients. Data from knockout mice support the involvement of AQPs in epithelial fluid secretion, cell migration, brain oedema and adipocyte metabolism, which suggests that modulation of AQP function or expression could have therapeutic potential in oedema, cancer, obesity, brain injury, glaucoma and several other conditions. Moreover, loss-of-function mutations in human AQPs cause congenital cataracts (AQP0) and nephrogenic diabetes insipidus (AQP2), and autoantibodies against AQP4 cause the autoimmune demyelinating disease neuromyelitis optica. Although some potential AQP modulators have been identified, challenges associated with the development of better modulators include the druggability of the target and the suitability of the assay methods used to identify modulators