Mitochondrial encephalocardio-myopathy with early neonatal onset due to TMEM70 mutation

Objective Mitochondrial disturbances of energy-generating systems in childhood are a heterogeneous group of disorders. The aim of this multi-site survey was to characterise the natural course of a novel mitochondrial disease with ATP synthase deficiency and mutation in the TMEM70 gene. Methods Retrospective clinical data and metabolic profiles were collected and evaluated in 25 patients (14 boys, 11 girls) from seven European countries with a c. 317-2A -> G mutation in the TMEM70 gene. Results Severe muscular hypotonia (in 92% of newborns), apnoic spells (92%), hypertrophic cardiomyopathy (HCMP; 76%) and profound lactic acidosis (lactate 5-36 mmol/l; 92%) with hyperammonaemia (100-520 mu mol/l; 86%) were present from birth. Ten patients died within the first 6 weeks of life. Most patients surviving the neonatal period had persisting muscular hypotonia and developed psychomotor delay. HCMP was non-progressive and even disappeared in some children. Hypospadia was present in 54% of the boys and cryptorchidism in 67%. Increased excretion of lactate and 3-methylglutaconic acid (3-MGC) was observed in all patients. In four surviving patients, life-threatening hyperammonaemia occurred during childhood, triggered by acute gastroenteritis and prolonged fasting. Conclusions ATP synthase deficiency with mutation in TMEM70 should be considered in the diagnosis and management of critically ill neonates with early neonatal onset of muscular hypotonia, HCMP and hypospadias in boys accompanied by lactic acidosis, hyperammonaemia and 3-MGC-uria. However, phenotype severity may vary significantly. The disease occurs frequently in the Roma population and molecular-genetic analysis of the TMEM70 gene is sufficient for diagnosis without need of muscle biopsy in affected children

ABJM Dibaryon Spectroscopy

We extend the proposal for a detailed map between wrapped D-branes in Anti-de Sitter space and baryon-like operators in the associated dual conformal field theory provided in hep-th/0202150 to the recently formulated AdS_4 \times CP^3/ABJM correspondence. In this example, the role of the dibaryon operator of the 3-dimensional CFT is played by a D4-brane wrapping a CP^2 \subset CP^3. This topologically stable D-brane in the AdS_4 \times CP^3 is nothing but one-half of the maximal giant graviton on CP^3.Comment: 26 page

Expression of microRNAs and target proteins in skeletal muscle of rats selectively bred for high and low running capacity

Impairments in mitochondrial function and substrate metabolism are implicated in the etiology of obesity and Type 2 diabetes. MicroRNAs (miRNAs) can degrade mRNA or repress protein translation and have been implicated in the development of such disorders. We used a contrasting rat model system of selectively bred high- (HCR) or low- (LCR) intrinsic running capacity with established differences in metabolic health to investigate the molecular mechanisms through which miRNAs regulate target proteins mediating mitochondrial function and substrate oxidation processes. Quantification of select miRNAs using the rat miFinder miRNA PCR array revealed differential expression of 15 skeletal muscles (musculus tibialis anterior) miRNAs between HCR and LCR rats (14 with higher expression in LCR; P < 0.05). Ingenuity Pathway Analysis predicted these altered miRNAs to collectively target multiple proteins implicated in mitochondrial dysfunction and energy substrate metabolism. Total protein abundance of citrate synthase (CS; miR-19 target) and voltage-dependent anion channel 1 (miR-7a target) were higher in HCR compared with LCR cohorts (~57 and ~26%, respectively; P < 0.05). A negative correlation was observed for miR-19a-3p and CS (r = 0.32, P = 0.015) protein expression. To determine whether miR-19a-3p can regulate CS in vitro, we performed luciferase reporter and transfection assays in C2C12 myotubes. MiR-19a-3p binding to the CS untranslated region did not change luciferase reporter activity; however, miR-19a-3p transfection decreased CS protein expression (∼70%; P < 0.05). The differential miRNA expression targeting proteins implicated in mitochondrial dysfunction and energy substrate metabolism may contribute to the molecular basis, mediating the divergent metabolic health profiles of LCR and HCR rat

Nonlinear response of the vacuum Rabi resonance

On the level of single atoms and photons, the coupling between atoms and the electromagnetic field is typically very weak. By employing a cavity to confine the field, the strength of this interaction can be increased many orders of magnitude to a point where it dominates over any dissipative process. This strong-coupling regime of cavity quantum electrodynamics has been reached for real atoms in optical cavities, and for artificial atoms in circuit QED and quantum-dot systems. A signature of strong coupling is the splitting of the cavity transmission peak into a pair of resolvable peaks when a single resonant atom is placed inside the cavity - an effect known as vacuum Rabi splitting. The circuit QED architecture is ideally suited for going beyond this linear response effect. Here, we show that increasing the drive power results in two unique nonlinear features in the transmitted heterodyne signal: the supersplitting of each vacuum Rabi peak into a doublet, and the appearance of additional peaks with the characteristic sqrt(n) spacing of the Jaynes-Cummings ladder. These constitute direct evidence for the coupling between the quantized microwave field and the anharmonic spectrum of a superconducting qubit acting as an artificial atom.Comment: 6 pages, 4 figures. Supplementary Material and Supplementary Movies are available at http://www.eng.yale.edu/rslab/publications.htm

Infrared behavior of interacting bosons at zero temperature

We review the infrared behavior of interacting bosons at zero temperature. After a brief discussion of the Bogoliubov approximation and the breakdown of perturbation theory due to infrared divergences, we present two approaches that are free of infrared divergences -- Popov's hydrodynamic theory and the non-perturbative renormalization group -- and allow us to obtain the exact infrared behavior of the correlation functions. We also point out the connection between the infrared behavior in the superfluid phase and the critical behavior at the superfluid--Mott-insulator transition in the Bose-Hubbard model.Comment: 8 pages, 4 figures. Proceedings of the 19th International Laser Physics Workshop, LPHYS'10 (Foz do Iguacu, Brazil, July 5-9, 2010

Fuzzy Fibers: Uncertainty in dMRI Tractography

Fiber tracking based on diffusion weighted Magnetic Resonance Imaging (dMRI) allows for noninvasive reconstruction of fiber bundles in the human brain. In this chapter, we discuss sources of error and uncertainty in this technique, and review strategies that afford a more reliable interpretation of the results. This includes methods for computing and rendering probabilistic tractograms, which estimate precision in the face of measurement noise and artifacts. However, we also address aspects that have received less attention so far, such as model selection, partial voluming, and the impact of parameters, both in preprocessing and in fiber tracking itself. We conclude by giving impulses for future research

Consequences of converting graded to action potentials upon neural information coding and energy efficiency

Information is encoded in neural circuits using both graded and action potentials, converting between them within single neurons and successive processing layers. This conversion is accompanied by information loss and a drop in energy efficiency. We investigate the biophysical causes of this loss of information and efficiency by comparing spiking neuron models, containing stochastic voltage-gated Na+ and K+ channels, with generator potential and graded potential models lacking voltage-gated Na+ channels. We identify three causes of information loss in the generator potential that are the by-product of action potential generation: (1) the voltage-gated Na+ channels necessary for action potential generation increase intrinsic noise and (2) introduce non-linearities, and (3) the finite duration of the action potential creates a ‘footprint’ in the generator potential that obscures incoming signals. These three processes reduce information rates by ~50% in generator potentials, to ~3 times that of spike trains. Both generator potentials and graded potentials consume almost an order of magnitude less energy per second than spike trains. Because of the lower information rates of generator potentials they are substantially less energy efficient than graded potentials. However, both are an order of magnitude more efficient than spike trains due to the higher energy costs and low information content of spikes, emphasizing that there is a two-fold cost of converting analogue to digital; information loss and cost inflation

The Calcitonin and Glucocorticoids Combination: Mechanistic Insights into Their Class-Effect Synergy in Experimental Arthritis

PMCID: PMC3564948This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Single-shot qubit readout in circuit Quantum Electrodynamics

The future development of quantum information using superconducting circuits requires Josephson qubits [1] with long coherence times combined to a high-fidelity readout. Major progress in the control of coherence has recently been achieved using circuit quantum electrodynamics (cQED) architectures [2, 3], where the qubit is embedded in a coplanar waveguide resonator (CPWR) which both provides a well controlled electromagnetic environment and serves as qubit readout. In particular a new qubit design, the transmon, yields reproducibly long coherence times [4, 5]. However, a high-fidelity single-shot readout of the transmon, highly desirable for running simple quantum algorithms or measur- ing quantum correlations in multi-qubit experiments, is still lacking. In this work, we demonstrate a new transmon circuit where the CPWR is turned into a sample-and-hold detector, namely a Josephson Bifurcation Amplifer (JBA) [6, 7], which allows both fast measurement and single-shot discrimination of the qubit states. We report Rabi oscillations with a high visibility of 94% together with dephasing and relaxation times longer than 0:5 \mu\s. By performing two subsequent measurements, we also demonstrate that this new readout does not induce extra qubit relaxation.Comment: 14 pages including 4 figures, preprint forma

Quantum Non-demolition Detection of Single Microwave Photons in a Circuit

Thorough control of quantum measurement is key to the development of quantum information technologies. Many measurements are destructive, removing more information from the system than they obtain. Quantum non-demolition (QND) measurements allow repeated measurements that give the same eigenvalue. They could be used for several quantum information processing tasks such as error correction, preparation by measurement, and one-way quantum computing. Achieving QND measurements of photons is especially challenging because the detector must be completely transparent to the photons while still acquiring information about them. Recent progress in manipulating microwave photons in superconducting circuits has increased demand for a QND detector which operates in the gigahertz frequency range. Here we demonstrate a QND detection scheme which measures the number of photons inside a high quality-factor microwave cavity on a chip. This scheme maps a photon number onto a qubit state in a single-shot via qubit-photon logic gates. We verify the operation of the device by analyzing the average correlations of repeated measurements, and show that it is 90% QND. It differs from previously reported detectors because its sensitivity is strongly selective to chosen photon number states. This scheme could be used to monitor the state of a photon-based memory in a quantum computer.Comment: 5 pages, 4 figures, includes supplementary materia