Ultrafast Coherent Control of Condensed Matter with Attosecond Precision.

Coherent control is a technique to manipulate wave functions of matter with light. Coherent control of isolated atoms and molecules in the gas phase is well-understood and developed since the 1990s, whereas its application to condensed matter is more difficult because its coherence lifetime is shorter. We have recently applied this technique to condensed matter samples, one of which is solid para-hydrogen ( p-H2). Intramolecular vibrational excitation of solid p-H2 gives an excited vibrational wave function called a "vibron", which is delocalized over many hydrogen molecules in a manner similar to a Frenkel exciton. It has a long coherence lifetime, so we have chosen solid p-H2 as our first target in the condensed phase. We shine a time-delayed pair of femtosecond laser pulses on p-H2 to generate vibrons. Their interference results in modulation of the amplitude of their superposition. Scanning the interpulse delay on the attosecond time scale gives a high interferometric contrast, which demonstrates the possibility of using solid p-H2 as a carrier of information encoded in the vibrons. In the second example, we have controlled the terahertz collective phonon motion, called a "coherent phonon", of a single crystal of bismuth. We employ an intensity-modulated laser pulse, whose temporal envelope is modulated with terahertz frequency by overlap of two positively chirped laser pulses with their adjustable time delay. This modulated laser pulse is shined on the bismuth crystal to excite its two orthogonal phonon modes. Their relative amplitudes are controlled by tuning the delay between the two chirped pulses on the attosecond time scale. Two-dimensional atomic motion in the crystal is thus controlled arbitrarily. The method is based on the simple, robust, and universal concept that in any physical system, two-dimensional particle motion is decomposed into two orthogonal one-dimensional motions, and thus, it is applicable to a variety of condensed matter systems. In the third example, the double-pulse interferometry used for solid p-H2 has been applied to many-body electronic wave functions of an ensemble of ultracold rubidium Rydberg atoms, hereafter called a "strongly correlated ultracold Rydberg gas". This has allowed the observation and control of many-body electron dynamics of more than 40 Rydberg atoms interacting with each other. This new combination of ultrafast coherent control and ultracold atoms offers a versatile platform to precisely observe and manipulate nonequilibrium dynamics of quantum many-body systems on the ultrashort time scale. These three examples are digested in this Account.

Attosecond Control of Restoration of Electronic Structure Symmetry.

Laser pulses can break the electronic structure symmetry of atoms and molecules by preparing a superposition of states with different irreducible representations. Here, we discover the reverse process, symmetry restoration, by means of two circularly polarized laser pulses. The laser pulse for symmetry restoration is designed as a copy of the pulse for symmetry breaking. Symmetry restoration is achieved if the time delay is chosen such that the superposed states have the same phases at the temporal center. This condition must be satisfied with a precision of a few attoseconds. Numerical simulations are presented for the C_{6}H_{6} molecule and ^{87}Rb atom. The experimental feasibility of symmetry restoration is demonstrated by means of high-contrast time-dependent Ramsey interferometry of the ^{87}Rb atom.

Simultaneous manipulation and observation of multiple ro-vibrational eigenstates in solid para-hydrogen.

We have experimentally performed the coherent control of delocalized ro-vibrational wave packets (RVWs) of solid para-hydrogen (p-H2) by the wave packet interferometry (WPI) combined with coherent anti-Stokes Raman scattering (CARS). RVWs of solid p-H2 are delocalized in the crystal, and the wave function with wave vector k ∼ 0 is selectively excited via the stimulated Raman process. We have excited the RVW twice by a pair of femtosecond laser pulses with delay controlled by a stabilized Michelson interferometer. Using a broad-band laser pulse, multiple ro-vibrational states can be excited simultaneously. We have observed the time-dependent Ramsey fringe spectra as a function of the inter-pulse delay by a spectrally resolved CARS technique using a narrow-band probe pulse, resolving the different intermediate states. Due to the different fringe oscillation periods among those intermediate states, we can manipulate their amplitude ratio by tuning the inter-pulse delay on the sub-femtosecond time scale. The state-selective manipulation and detection of the CARS signal combined with the WPI is a general and efficient protocol for the control of the interference of multiple quantum states in various quantum systems.

Photoluminescence characterization in silicon nanowire fabricated by thermal oxidation of nano-scale Si fin structure.

Low-temperature photoluminescence (PL) spectra of electron-hole systems in Si nanowires (NWs) prepared by thermal oxidization of Si fin structures were studied. Mapping of PL reveals that NWs with uniform width are formed over a large area. Annealing temperature dependence of PL peak intensities was maximized at 400 °C for each NW type, which are consistent with previous reports. Our results confirmed that the micro-PL demonstrated here is one of the important methods for characterizations of the interface defects in Si NWs.

Theoretical/numerical study on strong-laser-induced interference in the B state of I2.

In the B state of I2, strong-laser-induced interference (SLI) was recently observed in the population of each vibrational eigenstate within a wave packet, which was initially prepared by a pump pulse and then strongly modulated by an intense femtosecond near-infrared (NIR) laser pulse. It was suggested that the interference as a function of the time delay occurs between the eigenstate reached by Rayleigh scattering and that by Raman scattering. To verify this mechanism and further discuss its characteristics, we theoretically/numerically study the SLI by adopting a two-electronic-state model of I2. Numerical simulation reasonably reproduces the experimental signals and confirms the theoretical consequences, which include the π-phase shifts between Stokes and anti-Stokes transitions and (practically) no contribution from the energy shifts induced by the NIR pulse.

Similar phenotypes of Girdin germ-line and conditional knockout mice indicate a crucial role for Girdin in the nestin lineage.

Girdin is an Akt substrate and actin-binding protein. Mice with germ-line deletions of Girdin (a non-conditional knockout, (ncKO)) exhibit complete postnatal lethality accompanied by growth retardation and neuronal cell migration defects, which results in hypoplasia of the olfactory bulb and granule cell dispersion in the dentate gyrus. However, the physiological and molecular abnormalities in Girdin ncKO mice are not fully understood. In this study, we first defined the distribution of Girdin in neonates (P1) and adults (6months or older) using ß-galactosidase activity in tissues from ncKO mice. The results indicate that Girdin is expressed throughout the nervous system (brain, spinal cord, enteric and autonomic nervous systems). In addition, ß-galactosidase activity was detected in non-neural tissues, particularly in tissues with high tensile force, such as tendons, heart valves, and skeletal muscle. In order to identify the cellular population where the Girdin ncKO phenotype originates, newly generated Girdin flox mice were crossed with nestin promoter-driven Cre transgenic mice to obtain Girdin conditional knockout (cKO) mice. The phenotype of Girdin cKO mice was almost identical to ncKO mice, including postnatal lethality, growth retardation and decreased neuronal migration. Our findings indicate that loss of Girdin in the nestin cell lineage underlies the phenotype of Girdin ncKO mice.

Ultrafast Fourier transform with a femtosecond-laser-driven molecule.

Wave functions of electrically neutral systems can be used as information carriers to replace real charges in the present Si-based circuit, whose further integration will result in a possible disaster where current leakage is unavoidable with insulators thinned to atomic levels. We have experimentally demonstrated a new logic gate based on the temporal evolution of a wave function. An optically tailored vibrational wave packet in the iodine molecule implements four- and eight-element discrete Fourier transform with arbitrary real and imaginary inputs. The evolution time is 145 fs, which is shorter than the typical clock period of the current fastest Si-based computers by 3 orders of magnitudes.

Wave packet interferometry with attosecond precision and picometric structure.

Wave packet (WP) interferometry is applied to the vibrational WPs of the iodine molecule. Interference fringes of quantum waves weave highly regular space-time images called "quantum carpets." The structure of the carpet has picometre and femtosecond resolutions, and changes drastically depending on the amplitudes and phases of the vibrational eigenstates composing the WP. In this review, we focus on the situation where quantum carpets are created by two counter-propagating nuclear vibrational WPs. Such WPs can be prepared with either a single or double femtosecond (fs) laser pulse. In the single pulse scheme, the relevant situation appears around the half revival time. Similar situations can be generated with a pair of fs laser pulses whose relative phase is stabilized on the attosecond time scale. In the latter case we can design the quantum carpet by controlling the timing between the phase-locked pulses. We demonstrate this carpet design and visualize the designed carpets by the fs pump-probe measurements, tuning the probe wavelength to resolve the WP density-distribution along the internuclear axis with ~3 pm spatial resolution and ~100 fs temporal resolution.

Development of ultrahigh-precision coherent control and its applications.

Coherent control is based on optical manipulation of the amplitudes and phases of wave functions. It is expected to be a key technique to develop novel quantum technologies such as bond-selective chemistry and quantum computing, and to better understand the quantum worldview founded on wave-particle duality. We have developed high-precision coherent control by imprinting optical amplitudes and phases of ultrashort laser pulses on the quantum amplitudes and phases of molecular wave functions. The history and perspective of coherent control and our recent achievements are described.

Investigation of switching mechanism in HfOx-ReRAM under low power and conventional operation modes.

Low-power resistive random access memory (LP-ReRAM) devices have attracted increasing attention owing to their advantages of low operation power. In this study, a vertical-type LP-ReRAM consisting of TiN/Ti/HfO2/TiN structure was fabricated. The switching mechanism for LP-ReRAM was elucidated as the conductive filament mechanism for conventional mode, and an interface-type switching mechanism for low power mode was proposed. The analysis of low frequency noise shows that power spectral density (PSD) is approximately proportional to 1/f for conventional operation mode. Nevertheless, for low power mode, the PSD of low resistance state (LRS) is proportional to 1/f, while that of high resistance state (HRS) is clear proportional to 1/f2. The envelope of multiple Lorentzian spectra of 1/f2 characteristics due to different traps reveals the characteristics of 1/f. For HRS of low power mode, a limited number of traps results in a characteristic of 1/f2. During the set process, the number of oxygen vacancies increases for LRS. Therefore, the PSD value is proportional to 1/f. Owing to the increase in the number of traps when the operation mode changes to conventional mode, the PSD value is proportional to 1/f. To the best of our knowledge, this is the first study that reveals the different noise characteristics in the low power operation mode from that in the conventional operation mode.

Direct observation of ultrafast many-body electron dynamics in an ultracold Rydberg gas.

Many-body correlations govern a variety of important quantum phenomena such as the emergence of superconductivity and magnetism. Understanding quantum many-body systems is thus one of the central goals of modern sciences. Here we demonstrate an experimental approach towards this goal by utilizing an ultracold Rydberg gas generated with a broadband picosecond laser pulse. We follow the ultrafast evolution of its electronic coherence by time-domain Ramsey interferometry with attosecond precision. The observed electronic coherence shows an ultrafast oscillation with a period of 1 femtosecond, whose phase shift on the attosecond timescale is consistent with many-body correlations among Rydberg atoms beyond mean-field approximations. This coherent and ultrafast many-body dynamics is actively controlled by tuning the orbital size and population of the Rydberg state, as well as the mean atomic distance. Our approach will offer a versatile platform to observe and manipulate non-equilibrium dynamics of quantum many-body systems on the ultrafast timescale.

Histamine H1 receptor antagonist blocks histamine-induced proinflammatory cytokine production through inhibition of Ca2+-dependent protein kinase C, Raf/MEK/ERK and IKK/I kappa B/NF-kappa B signal cascades.

Histamine H1 receptor (H1R), a therapeutic target for alleviation of acute allergic reaction, may be also involved in mediating inflammatory responses via effects on cytokine production. However, the mechanisms whereby histamine induces cytokine production are poorly defined. In this study, we comprehensively investigated the signaling pathway involved in cytokine expression caused by histamine, using native human epidermal keratinocytes. We confirmed the expression of functional H1R by reverse transcription-polymerase chain reaction (RT-PCR), Western blotting and histamine-induced Ca(2+) elevation. Histamine induced concentration- and time-dependent production of granulocyte-macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-8 and IL-6, which was completely blocked by olopatadine, an H1 antagonist. Histamine activated the phosphorylation of protein kinase C (PKC), c-Raf, mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK), extracellular signal-regulated kinase (ERK), I kappa B kinase (IKK), inhibitory kappa B (I kappa B)-alpha and nuclear factor-KB (NF-kappa B) p65, which was inhibited by Ro-31-8220, a PKC inhibitor. Also, Ro-31-8220 significantly suppressed the expression of these cytokines. BAPTA-AM, an intracellular Ca(2+) chelator, also reduced PKC phosphorylation and cytokine expression. PD98059, a MEK inhibitor, and BAY 11-8702, an I kappa B-alpha inhibitor, reduced ERK and NF-kappa B cascade activation, respectively, with little effect on PKC phosphorylation. PD98059 preferentially inhibited GM-CSF production whereas BAY 11-8702 prevented IL-8 and IL-6 production. Furthermore, in addition to the above cytokines, histamine stimulated the biosynthesis and/or release of numerous keratinocyte-derived mediators, which are probably regulated by the ERK or NF-kappa B cascades. Our study suggests that histamine activates Ca(2+)-dependent PKC isoforms that play crucial roles in the activation of Raf/MEK/ERK and IKK/I kappa B/NF-kappa B cascades, leading to up-regulation of cytokine expression. Thus, the anti-inflammatory benefit of H1 antagonists may be in part due to prevention of cytokine production.

The effects of olopatadine hydrochloride on the number of scratching induced by repeated application of oxazolone in mice.

It is suggested that atopic dermatitis is a skin disease associated with itching as subjective symptoms, and histamine H(1) receptor antagonists are used in order to prevent the itching, and the deterioration for scratch by itching. Histamine H(1) receptor selective anti-histamine olopatadine hydrochloride (olopatadine; Allelock shows consistent efficacy and safety in the treatment of allergic disorders. We investigated the possible efficacy of olopatadine on the number of scratching induced by repeated application of oxazolone in BALB/c mice. The repeated treatment of olopatadine significantly inhibited the ear swelling and the increased number of scratching. It significantly inhibited the increased production of interleukin (IL)-4, IL-1beta and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the lesioned ear. Moreover, it significantly inhibited the increased production of nerve growth factor (NGF) and substance P. On the other hand, loratadine, bepotastine and chlorpheniramine did not inhibit the ear swelling and the increased number of scratching. These results indicate that olopatadine inhibited not only the increased production of cytokines but also NGF and substance P unlike other histamine H(1) receptor antagonists. It was suggested that olopatadine suppressed the increased number of scratching by the anti-inflammatory effects. Therefore, olopatadine appears to exert additional biological effects besides its blockade of a histamine H(1) receptor.

Differential regulation of IL-4 expression and degranulation by anti-allergic olopatadine in rat basophilic leukemia (RBL-2H3) cells.

Olopatadine hydrochloride (olopatadine) is an anti-allergic drug that functions as a histamine H(1) antagonist and inhibits both mast cell degranulation and the release of arachidonic acid metabolites in various types of cells. In this study, we examined the ability of olopatadine to inhibit the expression of cytokine genes in vitro via high-affinity receptors for immunoglobulin E in mast cells, using a rat basophilic leukemia (RBL-2H3) cell line and an in vivo mouse model. Levels of gene expression in RBL-2H3 cells were determined by semi-quantitative RT-PCR, and serum interleukin-4 (IL-4) level in mice was quantified by ELISA. Olopatadine inhibited significantly the induction of IL-4 expression by mast cells both in vivo and in vitro. Olopatadine inhibited Ca(2+) influx through receptor-operated channels (ROC) without affecting Ca(2+) release from intracellular stores. Comparative analysis of olopatadine with other anti-allergic drugs and the ROC blocker SKF-96365 demonstrated that the potency of inhibition of Ca(2+) influx correlated with the degree of suppression of degranulation and arachidonic acid release. Inhibition of Ca(2+) influx decreased phosphorylation of p38 mitogen-activated protein kinase and c-Jun NH(2)-terminal kinase, which participate in regulation of cytokine (e.g. IL-4) gene expression. However, the rank order of inhibition of Ca(2+) influx did not correspond to reduction of IL-4 expression, suggesting that an unknown mechanism(s) of action, in addition to inhibition of Ca(2+) influx, is involved in the expression of cytokines in mast cells.

Pharmacological studies of diacerein in animal models of inflammation, arthritis and bone resorption.

Diacerein has proved to be effective in the treatment of osteoarthritis. We investigated the effects of diacerein in animal models of carrageenin-, zymosan-, or dextran-induced paw edema and adjuvant-induced arthritis and in ovariectomized rats. In acute inflammatory models, unlike classical nonsteroidal anti-inflammatory drugs such as naproxen and ibuprofen, diacerein inhibited the rat paw edema induced by various agents. In the adjuvant-induced arthritic rats, diacerein at 100 mg/kg/day significantly suppressed the paw edema and the increase in serum mucoprotein. Addition of 3 mg/kg/day naproxen to each diacerein (3, 10, 30 mg/kg/day) dose resulted in significantly greater anti-inflammatory activity than with naproxen alone. In the ovariectomized rats, diacerein (10, 100 mg/kg/day) also significantly prevented bone loss and reduced the serum alkaline phosphatase and decreased the excretion of urinary hydroxyproline. In addition, rhein (10, 30 microM) inhibited calcium release from mouse calvaria induced by interleukin-1 beta, prostaglandin E(2) and parathyroid hormone 1-34 human fragment. These findings indicate that diacerein is a novel anti-inflammatory drug with pharmacological properties different from those of classical nonsteroidal anti-inflammatory drugs and support the clinical investigation of the use of combination therapy with diacerein and nonsteroidal anti-inflammatory drugs in patients with not only osteoarthritis but also rheumatoid arthritis.

Protective effects of benidipine on hydrogen peroxide-induced injury in rat isolated hearts.

We investigated the effects of benidipine (hydrochloride), a calcium antagonist, on hydrogen peroxide (H(2)O(2))-induced injury in Langendorff-perfused rat hearts. The hearts were aerobically perfused at a constant flow and exposed to H(2)O(2) (600 micromol L(-1)) for 4 min, resulting in the oxidative stress-induced myocardial dysfunction (e.g., decrease in the left ventricular developed pressure) and myocardial cell injury (e.g., increase in the release of lactate dehydrogenase). Pretreatment of the hearts with benidipine or nifedipine was performed for 20 min until the start of H(2)O(2) exposure. Benidipine at 1 nmol L(-1) and nifedipine at 10 nmol L(-1) decreased the myocardial contractility and perfusion pressure to a similar degree in the hearts under normal conditions. Benidipine (1 nmol L(-1)) significantly reduced the H(2)O(2)-induced myocardial damage. Nifedipine (10 nmol L(-1)) also tended to exhibit similar effects. Benidipine inhibited the increase in tissue lipid peroxidation induced by H(2)O(2). The results suggest that, in addition to the calcium antagonism, benidipine possesses other actions responsible for the cardioprotective effects, to which the antioxidant activity of benidipine may partly contribute.

[Expectations for the education of graduate school of pharmaceutical sciences from the viewpoint of discovery and development of new drugs].

For the purpose of the development of new drugs for incurable diseases, many students enter graduate school of pharmaceutical sciences every year. At first, I expect education to let it develop more and spread without forgetting this will. Recently, withdrawals from Japan of the research institutes of the foreign-affiliated pharmaceutical companies have occurred successively. It is pointed out that there is it for the study about the biomedical research that is the next step of fundamental researches having been weak. I expect the immediate construction of the cluster, which consists of pharmaceutical companies and graduate schools of pharmaceutical sciences. Time of ten several years and a cost of one hundred billion yen are necessary for the research and development of new drug. The success probability is low, besides. Many trials are accomplished to raise the success probability. The one is introduction of the project system. The best members are gathered from the fields such as medicinal chemistry, molecular biology, biochemistry, pharmacology, pharmacokinetics, pharmaceutics and toxicological sciences, etc. The project system is a system enforcing go or stop by own judgment, an authority and the responsibility of the purpose are given. It is necessary for the project leader to have great knowledge and the abilities to hold lively discussion. It is a researcher from graduate school of pharmaceutical sciences that is the most suited to be as a project leader. I expect to upbring education from the time when a leader is young.

Optical manipulation of coherent phonons in superconducting YBa2Cu3O7-delta thin films.

The coherent phonons of YBa2Cu3O7-delta are believed to be strongly coupled to its superconductivity. Controlling the phonons below its transition temperature, therefore, may serve as a promising scheme of the control of superconductivity. Here we demonstrate optical manipulation of the Ba-O and Cu-O vibrations in a thin-film YBa2Cu3O7-delta below its transition temperature using a pair of femtosecond laser pulses. The interpulse delay is tuned to integral and half-integral multiples of the oscillation period of a specific phonon mode (Ba-O or Cu-O vibration) to enhance and suppress its amplitude, respectively.

Wave-packet and coherent control dynamics.

This review summarizes progress in coherent control as well as relevant recent achievements, highlighting, among several different schemes of coherent control, wave-packet interferometry (WPI). WPI is a fundamental and versatile scenario used to control a variety of quantum systems with a sequence of short laser pulses whose relative phase is finely adjusted to control the interference of electronic or nuclear wave packets (WPs). It is also useful in retrieving quantum information such as the amplitudes and phases of eigenfunctions superposed to generate a WP. Experimental and theoretical efforts to retrieve both the amplitude and phase information are recounted. This review also discusses information processing based on the eigenfunctions of atoms and molecules as one of the modern and future applications of coherent control. The ultrafast coherent control of ultracold atoms and molecules and the coherent control of complex systems are briefly discussed as future perspectives.

Actively tailored spatiotemporal images of quantum interference on the picometer and femtosecond scales.

Interference fringes of quantum waves weave highly regular space-time images, which could be seen in various wave systems such as wave packets in atoms and molecules, Bose-Einstein condensates, and fermions in a box potential. We have experimentally designed and visualized spatiotemporal images of dynamical quantum interferences of two counterpropagating nuclear wave packets in the iodine molecule; the wave packets are generated with a pair of femtosecond laser pulses whose relative phase is locked within the attosecond time scale. The design of the image has picometer and femtosecond resolutions, and changes drastically as we change the relative phase of the laser pulses, providing a direct spatiotemporal control of quantum interferences.