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At least 397 records · Page 22

Clock Synchronization

Experimental goals are: (1) synchronize 1 pulse per second outputs derived from two different crystal oscillator sources, (2) generate near atomic clock accuracy for other experimental needs.

atomic clock↗

Clocks and oscillators in space

In this paper a short review of the role of clocks and oscillators in space is presented, together with some future projections for laser based systems.

clocks↗

Identification of a Glycogen Synthase Kinase-3[beta] Inhibitor that Attenuates Hyperactivity in CLOCK Mutant Mice

Bipolar disorder is characterized by a cycle of mania and depression, which affects approximately 5 million people in the United States. Current treatment regimes include the so-called 'mood-stabilizing drugs', such as lithium and valproate that are relatively dated drugs with various known side effects. Glycogen synthase kinase-3{beta} (GSK-3{beta}) plays a central role in regulating circadian rhythms, and lithium is known to be a direct inhibitor of GSK-3{beta}. We designed a series of second generation benzofuran-3-yl-(indol-3-yl)maleimides containing a piperidine ring that possess IC{sub 50} values in the range of 4 to 680 nM against human GSK-3{beta}. One of these compounds exhibits reasonable kinase selectivity and promising preliminary absorption, distribution, metabolism, and excretion (ADME) data. The administration of this compound at doses of 10 to 25 mg kg{sup -1} resulted in the attenuation of hyperactivity in amphetamine/chlordiazepoxide-induced manic-like mice together with enhancement of prepulse inhibition, similar to the effects found for valproate (400 mg kg{sup -1}) and the antipsychotic haloperidol (1 mg kg{sup -1}). We also tested this compound in mice carrying a mutation in the central transcriptional activator of molecular rhythms, the CLOCK gene, and found that the same compound attenuates locomotor hyperactivity in response to novelty. This study further demonstrates the use of inhibitors of GSK-3{beta} in the treatment of manic episodes of bipolar/mood disorders, thus further validating GSK-3{beta} as a relevant therapeutic target in the identification of new therapies for bipolar patients.

59 BASIC BIOLOGICAL SCIENCES↗

Angiographic Anatomy and Relevance of 3 and 9 O’clock Arteries During Radioembolization

Purpose3 and 9 o’clock arteries (3&9As) which supply the common hepatic duct connect hepatic with duodenal/pancreatic territories. The study purpose is to describe the angiographic anatomy of 3&9As and discuss their relevance when performing radioembolization (RE) of liver malignancies.Materials and MethodsThe anatomy of the 3&9As was systematically investigated by a retrospective analysis of angiograms, technetium Tc-99 m-macroaggregated albumin (MAA) scintigrams, yttrium-90 (Y90) Bremsstrahlung-SPECT/CT datasets, and clinical data of 153 patients who underwent RE between 2010 and 2013.ResultsAnalysis of preprocedural angiograms identified 3&9As in 36 (24%) of the 153 patients. Following embolization of the gastroduodenal artery, 3&9As were seen in 53 cases (35%). The three most common origins of the 3&9As were the right hepatic artery (n = 14), the cystic artery (n = 11), and S5 and S6 segmental arteries (n = 5 each). Extrahepatic Tc-99 m-MAA deposition in the territory of the 3&9As was significantly more frequent when 3&9As were detectable on preprocedural angiograms (28%{sub visible} vs. 11%{sub not} {sub visible}; p = 0.001) and especially when the 3&9As were not embolized or bridged prior to RE (50%{sub not} {sub occluded/bridged} vs. 19%{sub occupied/bridged}; p = 0.043). The presence of extrahepatic Y90 Bremsstrahlung after RE (n = 17) was attributable to microsphere diversion via the 3&9A territory in four patients and possible diversion via this territory in nine patients. Five of these 13 patients presented with epigastric pain, nausea, or vomiting (CTCAE severity grade ≤ 3) (p = 0.014).Conclusion3&9As are commonly detectable during evaluation angiography prior to RE, have a variable angioanatomic origin, and should be prophylactically occluded to prevent complications.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

TNF-α induces expression of the circadian clock gene Bmal1 via dual calcium-dependent pathways in rheumatoid synovial cells

Highlights: • TNF-α induces over-expression of Bmal1 in rheumatoid synovial cells. • This over-expression was induced through dual calcium dependent pathways. • These dual pathways were regulated by p300/CBP histone acetyltransferases. • Ca{sup 2+} influx-p300/CBP pathway may provide a novel therapeutic strategy for RA. Tumor necrosis factor (TNF)-α is responsible for expressions of several clock genes and affects joint symptoms of rheumatoid arthritis (RA) with diurnal fluctuation. We tried to determine the mechanism involved in over-expression of Bmal1, induced by TNF-α, in primary cultured rheumatoid synovial cells. Cells were incubated with intra-cellular Ca{sup 2+} chelator BAPTA-AM, calcineurin inhibitor FK506 and p300/CBP (CREB binding protein) inhibitor C646, respectively, or transfected with p300 and CBP small interfering RNA (siRNA) before stimulation with TNF-α. Oscillation phase and amplitude of Bmal1, transcriptional activator Rorα, transcriptional repressor Rev-erbα, and histone acetyltransferases (p300 and Cbp) were evaluated by quantitative real-time PCR. As results, TNF-α did not influence the oscillation phase of Rev-erbα, while enhanced those of Rorα, resulting in over-expression of Bmal1. When Ca{sup 2+} influx was inhibited by BAPTA-AM, TNF-α-mediated up-regulation of Rorα was cancelled, however, that of Bmal1 was still apparent. When we further explored another pathway between TNF-α and Bmal1, TNF-α suppressed the expression of Rev-erbα in the absence of Ca{sup 2+} influx, as well as those of p300 and Cbp genes. Finally, actions of TNF-α, in increasing Bmal1/Rorα and decreasing Rev-erbα, were cancelled by C646 treatment or silencing of both p300 and Cbp. In conclusion, we determined a novel role of TNF-α in inducing Bmal1 via dual calcium dependent pathways; Rorα was up-regulated in the presence of Ca{sup 2+} influx and Rev-erbα was down-regulated in the absence of that. Results proposed that inhibition of p300/CBP could be new therapeutic targets for RA.

60 APPLIED LIFE SCIENCES↗

Knocking down clock control gene CRY1 decreases adipogenesis via canonical Wnt/β-catenin signaling pathway

Highlights: • Adipogenic differentiation induces CRY1 expression. . • Knockdown of CRY1 inhibits adipogenic differentiation and adipogenesis-specific gene expression. • Knockdown of CRY1 activates canonical Wnt/β-catenin signaling pathway. Cryptochrome gene 1(CRY1) is a member of circadian clock genes, which play an important role in adipocyte biology. CRY1 was reported to be related with the lipid metabolism, but the molecule mechanism of CRY1 in regulating the adipogenesis remains unclear. Here we report that CRY1 is a key regulator in adipogenic differentiation. We found that the expression levels of CRY1 in 3T3-L1 cells and C3H10T1/2 cells gradually increased during the process of adipogenic differentiation. Knockdown of endogenous CRY1 significantly inhibited the expression of adipogenic markers and lipid droplet formation in cells under adipogenic induction. In addition, knockdown of endogenous CRY1 promoted the expression and nuclear accumulation of β-catenin, the critical signal molecular in the canonical canonical Wnt signaling pathway, suggesting the regulation effect of CRY1 in adipogenesis was mediated by canonical Wnt/β-catenin signaling. Taken together, our study suggests that CRY1 regulates adipogenic differentiation through modulating the canonical Wnt/β-catenin signaling pathway.

60 APPLIED LIFE SCIENCES↗

Characterization and calibration of a viscoelastic simplified potential energy clock model for inorganic glasses

In this study, to analyze the stresses and strains generated during the solidification of glass-forming materials, stress and volume relaxation must be predicted accurately. Although the modeling attributes required to depict physical aging in organic glassy thermosets strongly resemble the structural relaxation in inorganic glasses, the historical modeling approaches have been distinctly different. To determine whether a common constitutive framework can be applied to both classes of materials, the nonlinear viscoelastic simplified potential energy clock (SPEC) model, developed originally for glassy thermosets, was calibrated for the Schott 8061 inorganic glass and used to analyze a number of tests. A practical methodology for material characterization and model calibration is discussed, and the structural relaxation mechanism is interpreted in the context of SPEC model constitutive equations. SPEC predictions compared to inorganic glass data collected from thermal strain measurements and creep tests demonstrate the ability to achieve engineering accuracy and make the SPEC model feasible for engineering applications involving a much broader class of glassy materials.

36 MATERIALS SCIENCE↗

Structures of the intermediates of Kok’s photosynthetic water oxidation clock

Inspired by the period-four oscillation in flash-induced oxygen evolution of photosystem II discovered by Joliot in 1969, Kok performed additional experiments and proposed a five-state kinetic model for photosynthetic oxygen evolution, known as Kok’s S-state clock or cycle. The model comprises four (meta)stable intermediates (S 0 , S 1 , S 2 and S 3 ) and one transient S 4 state, which precedes dioxygen formation occurring in a concerted reaction from two water-derived oxygens bound at an oxo-bridged tetra manganese calcium (Mn 4 CaO 5 ) cluster in the oxygen-evolving complex. This reaction is coupled to the two-step reduction and protonation of the mobile plastoquinone QB at the acceptor side of PSII. Here in this paper, using serial femtosecond X-ray crystallography and simultaneous X-ray emission spectroscopy with multi-flash visible laser excitation at room temperature, we visualize all (meta)stable states of Kok’s cycle as high-resolution structures (2.04–2.08 Å). In addition, we report structures of two transient states at 150 and 400 µs, revealing notable structural changes including the binding of one additional ‘water’, Ox, during the S 2 →S 3 state transition. Our results suggest that one water ligand to calcium (W3) is directly involved in substrate delivery. The binding of the additional oxygen Ox in the S 3 state between Ca and Mn1 supports O–O bond formation mechanisms involving O5 as one substrate, where Ox is either the other substrate oxygen or is perfectly positioned to refill the O5 position during O 2 release. Thus, our results exclude peroxo-bond formation in the S 3 state, and the nucleophilic attack of W3 onto W2 is unlikely.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Mapping the magnetic field vector in a fountain clock

We show how the mapping of the magnetic field vector components can be achieved in a fountain clock by measuring the Larmor transition frequency in atoms that are used as a spatial probe. We control two vector components of the magnetic field and apply audio frequency magnetic pulses to localize and measure the field vector through Zeeman spectroscopy.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Critical analysis and remedy of switching failures in straintronic logic using Bennett clocking in the presence of thermal fluctuations

Straintronic logic is a promising platform for beyond Moore's law computing. Using Bennett clocking mechanism, information can propagate through an array of strain-mediated multiferroic nanomagnets, exploiting the dipolar coupling between the magnets without having to physically interconnect them. Here, we perform a critical analysis of switching failures, i.e., error in information propagation due to thermal fluctuations through a chain of such straintronic devices. We solved stochastic Landau-Lifshitz-Gilbert equation considering room-temperature thermal perturbations and show that magnetization switching may fail due to inherent magnetization dynamics accompanied by thermally broadened switching delay distribution. Avenues available to circumvent such issue are proposed.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Selection and amplification of a single optical frequency comb mode for laser cooling of the strontium atoms in an optical clock

In this paper, we report on the active filtering and amplification of a single mode from an optical femtosecond laser comb with mode spacing of 250 MHz by optical injection of two external-cavity diode lasers operating in cascade to build a narrow linewidth laser for laser cooling of the strontium atoms in an optical lattice clock. Despite the low injection of individual comb mode of approximately 50 nW, a single comb line at 689 nm could be filtered and amplified to reach as high as 10 mW with 37 dB side mode suppression and a linewidth of 240 Hz. This method could be applied over a broad spectral band to build narrow linewidth lasers for various applications.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Clock transitions guard against spin decoherence in singlet fission

Short coherence times present a primary obstacle in quantum computing and sensing applications. In atomic systems, clock transitions (CTs), formed from avoided crossings in an applied Zeeman field, can substantially increase coherence times. We show how CTs can dampen intrinsic and extrinsic sources of quantum noise in molecules. Conical intersections between two periodic potentials form CTs in electron paramagnetic resonance experiments of the spin-polarized singlet fission photoproduct. We report on a pair of CTs for a two-chromophore molecule in terms of the Zeeman field strength, molecular orientation relative to the field, and molecular geometry.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Development of a prototype compact fibre frequency synthesiser for mobile femtosecond optical clocks

A prototype compact fibre frequency synthesiser based on a femtosecond erbium fibre laser and an original hybrid highly nonlinear fibre is developed and preliminarily studied. This synthesiser will ensure an extremely low relative instability of synthesised frequencies (down to 10{sup -17}) with the use of a corresponding optical standard and will be used in mobile optical clocks. The realised frequency stabilisation principle makes the synthesiser universal and allows it to transfer the frequency stability of various types of optical standards to the synthesised radio- and optical frequencies. (extreme light fields and their applications)

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Detection of the clock transition (1.14 μm) in ultra-cold thulium atoms

The magnetic dipole transition between fine structure sublevels of the ground state of thulium atom 4f{sup 13}({sup 2}F{sup o})6s{sup 2} has been directly excited in a cloud of ultra-cold atoms by a frequency-stabilised laser. This transition at the wavelength λ = 1.14 μm is planned to be used as the clock one in an optical frequency reference on laser-cooled thulium atoms. (extreme light fields and their applications)

74 ATOMIC AND MOLECULAR PHYSICS↗