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Contains fulltext : 238693.pdf (Publisher’s version ) (Open Access) Objectives: More than 40 drugs are available to treat affective disorders. Individual selection of the optimal drug and dose is required to attain the highest possible efficacy and acceptable tolerability for every patient.Methods: This review, which includes more than 500 articles selected by 30 experts, combines relevant knowledge on studies investigating the pharmacokinetics, pharmacodynamics and pharmacogenetics of 33 antidepressant drugs and of 4 drugs approved for augmentation in cases of insufficient response to antidepressant monotherapy. Such studies typically measure drug concentrations in blood (i.e. therapeutic drug monitoring) and genotype relevant genetic polymorphisms of enzymes, transporters or receptors involved in drug metabolism or mechanism of action. Imaging studies, primarily positron emission tomography that relates drug concentrations in blood and radioligand binding, are considered to quantify target structure occupancy by the antidepressant drugs in vivo. Results: Evidence is given that in vivo imaging, therapeutic drug monitoring and genotyping and/or phenotyping of drug metabolising enzymes should be an integral part in the development of any new antidepressant drug.Conclusions: To guide antidepressant drug therapy in everyday practice, there are multiple indications such as uncertain adherence, polypharmacy, nonresponse and/or adverse reactions under therapeutically recommended doses, where therapeutic drug monitoring and cytochrome P450 genotyping and/or phenotyping should be applied as valid tools of precision medicine.

Ultrafast modulation of optical response is realized in a multi-resonant magnetoplasmonic metasurface under resonant femtosecond pump. A saturation of resonant probe transient transmission is shown at dielectric quazi-waveguide mode.

The coherent elastic neutrino-nucleus scattering (CEvNS) plays a crucial role at the final evolution of stars. The detection of it would be of importance in astroparticle physics. Among all available neutrino sources, galactic supernovae give the highest neutrino flux in the MeV range. Among all liquid xenon dark matter experiments, XMASS has the largest sensitive volume and light yield. The possibility to detect galactic supernova via the CEvNS-process on xenon nuclei in the current XMASS detector was investigated. The total number of events integrated in about 18 seconds after the explosion of a supernova 10~kpc away from the Earth was expected to be from 3.5 to 21.1, depending on the supernova model used to predict the neutrino flux, while the number of background events in the same time window was measured to be negligible. All lead to very high possibility to detect CEvNS experimentally for the first time utilizing the combination of galactic supernovae and the XMASS detector. In case of a supernova explosion as close as Betelgeuse, the total observable events can be more than ten thousand, making it possible to distinguish different supernova models by examining the evolution of neutrino event rate in XMASS., Comment: 6 pages, 5 figures

The onset and growth of subependymal giant cell astrocytoma (SEGA) in tuberous sclerosis complex (TSC) typically occurs in childhood. There is minimal information on SEGA evolution in adults with TSC. Of 2,211 patients enrolled in TOSCA, 220 of the 803 adults (27.4%) ever had a SEGA. Of 186 patients with SEGA still ongoing in adulthood, 153 (82.3%) remained asymptomatic, and 33 (17.7%) were reported to ever have developed symptoms related to SEGA growth. SEGA growth since the previous scan was reported in 39 of the 186 adults (21%) with ongoing SEGA. All but one patient with growing SEGA had mutations in TSC2. Fourteen adults (2.4%) were newly diagnosed with SEGA during follow-up, and majority had mutations in TSC2. Our findings suggest that surveillance for new or growing SEGA is warranted also in adulthood, particularly in patients with mutations in TSC2. © 2019 Jansen, Belousova, Benedik, Carter, Cottin, Curatolo, D'Amato, Beaure d'Augères, de Vries, Ferreira, Feucht, Fladrowski, Hertzberg, Jozwiak, Lawson, Macaya, Marques, Nabbout, O'Callaghan, Qin, Sander, Sauter, Shah, Takahashi, Touraine, Youroukos, Zonnenberg and Kingswood.

Double electron capture is a rare nuclear decay process in which two orbital electrons are captured simultaneously in the same nucleus. Measurement of its two-neutrino mode would provide a new reference for the calculation of nuclear matrix elements whereas observation of its neutrinoless mode would demonstrate lepton number violation. A search for two-neutrino double electron capture on $^{124}$Xe is performed using 165.9 days of data collected with the XMASS-I liquid xenon detector. No significant excess above background was observed and we set a lower limit on the half-life as $4.7 \times 10^{21}$ years at 90% confidence level. The obtained limit has ruled out parts of some theoretical expectations. We obtain a lower limit on the $^{126}$Xe two-neutrino double electron capture half-life of $4.3 \times 10^{21}$ years at 90% confidence level as well., 6 pages, 3 figures, accepted for publication in Physics Letters B

In September 2013, we observed an expanse of surface water with low CO2 partial pressure (pCO2sea) (2 in this region was the result of massive primary production after the sea-ice retreat in June and July. In the surface of the Canada Basin, salinity was low (pCO2sea was closer to the air–sea CO2 equilibrium (∼ 360 µatm). From the relationships between salinity and total alkalinity, we confirmed that the low salinity in the Canada Basin was due to the larger fraction of meltwater input (∼ 0.16) rather than the riverine discharge (∼ 0.1). Such an increase in pCO2sea was not so clear in the coastal region near Point Barrow, where the fraction of riverine discharge was larger than that of sea-ice melt. We also identified low pCO2sea (pCO2sea was attributed to the advection of Pacific-origin water, in which dissolved inorganic carbon is relatively low, through the Chukchi Sea where net primary production is high. Oxygen supersaturation (> 20 µmol kg−1) in the subsurface low pCO2sea layer in the Canada Basin indicated significant net primary production undersea and/or in preformed condition. If these low pCO2sea layers surface by wind mixing, they will act as additional CO2 sinks; however, this is unlikely because intensification of stratification by sea-ice melt inhibits mixing across the halocline.

We propose and demonstrate a new measurement technique for the radiation pattern inspection of the Frequency Modulated Continuous Wave (FMCW) signal. The proposed measurement system makes it possible to measure FMCW signal based on a photonic frequency tracking in asynchronous electro-optic measurement system. The radiation pattern of the FMCW signal measured by our new system is the average value of the radiation patterns of all the CW signals in the signal bandwidth. We measured a radiation pattern of a FMCW signal at quasi-millimeter wave band $(24\ \text{GHz} \pm 80\ \text{MHz})$ and compared it with the radiation pattern of a monotonous signal at 24 GHz. We confirmed deviation between the radiation pattern of the FMCW signal and that of the CW signal when we place a vehicle emblem in front of the horn antenna. The proposed technique is considered to be useful when measuring the signal with the larger frequency deviation width at the millimeter-wave band such as an FMCW radar of 79 GHz with a fractional bandwidth of 5%.

We demonstrate the visualization of the spatial distribution of electric field vector components using an electro-optic (EO) sensor in millimeter (mm) wave band. The result of the proof-of-concept experiment shows the relative angle between the measured polarization direction and the propagation direction, which was determined from the phase front distribution, was 90.6 ± 0.8°. The vector components of the mm wave (77GHz) reflected by a metal plate were also measured to check the feasibility of the proposed measurement technique.

XMASS is a multipurpose liquid-xenon detector that currently aims to directly detect dark matter. In this paper, we describe the fabrication and characterization of reference sources used for the energy calibration and position reconstruction of the present XMASS detector. Several gamma-ray sources were produced in the form of a sealed needle-source. A thin-wall tube with a diameter of approximately 0.2 mm was sealed at both ends, with the 241 Am or 57 Co source material contained inside. The active region of the source was observed to be 1–2 mm long, close to the tip of the needle. These sources were tested in the XMASS detector, and the results were compared with Monte-Carlo simulations.

The purpose of this paper is to explore the theoretical structure of what we call multicultural apprenticeships in teacher education. This structure is drawn from decades of scholarship and research in teacher education, in general, and in preparing teachers for diversity, in particular. It is further situated within our own work in an Early Childhood Education Masters in Education program and our commitments to preparing teachers to support diverse populations of children. Three different multicultural apprenticeships are used to provide concrete examples of the characteristics of this approach to preparing teachers for diverse classrooms.

Introduction The demand to reduce the power consumption of electronic devices continues to increase. To meet the need for reduced supply power to the transistor, the operating voltage of the transistor has been reduced by further miniaturization of the transistor; however, this has presented some problems e.g. the inability to obtain the necessary electrical current for transistor operation and the increase in leakage current from the shrinkage of the transistor. Ge devices, which have higher mobility than Si, are being investigated and developed. In this study, NiGe, which was made by reaction of Ni and Ge as source-drain electrode, was used in order to achieve low contact resistance between Ni and Ge. The choice of the appropriate chemistry for selective removal of excess Ni to NiGe after annealing is required.

On April 11, 2014, the Government of Japan made the decision to approve the Strategic Energy Plan. Then, on June 23, 2014, the Council for a Strategy for Hydrogen and Fuel Cells established by the Ministry of Economy, Trade and Industry compiled a Strategic Road Map for Hydrogen and Fuel Cells, containing all the measures to be taken by those involved in realizing a hydrogen society. In December 2015, fuel cell vehicles will begin to be sold commercially and hydrogen refueling stations are supposed to be constructed in about 100 places, mainly in the four major metropolitan areas in Japan.

Many low background experiments using xenon need to remove radioactive radon to improve their sensitivities. However, no method of continually removing radon from xenon has been described in the literature. We studied a method to remove radon from xenon gas through an activated charcoal trap. From our measurements we infer a linear relationship between the mean propagation velocity vRn of radon and vXe of xenon in the trap with vRn=vXe ¼ð 0:967 0:10 Þ� 10

The visual simulation of natural phenomena has been widely s tudied. Although several methods have been proposed to simulate melting, the flows of meltwater drops on thesurfaces of objects are not taken into account. In this paper, we propose a particle-based method for the simul ation of the melting and freezing of ice objects and the interactions between ice and fluids. To simulate the flow of meltwater on ice and the formation of water droplets, a simple interfacial tension is proposed, which can be easil y incorporated into common particle-based simulation methods such as Smoothed Particle Hydrodynamics. The compu tations of heat transfer, the phase transition between ice and water, the interactions between ice and fluids,and the separation of ice due to melting are further accelerated by implementing our method using CUDA. We demon strate our simulation and rendering method for depicting melting ice at interactive frame-rates.

Peripheral leucocytes from 10 patients with chronic myelogenous leukaemia (CML) were cultured in liquid medium and observed morphologically for 6 to 10 weeks. All cultures showed in increased proportion of mature basophilis at about 3 weeks and most cultures consisted predominantly of mature basophilis at about 5 weeks. The results indicate preferential basophilic differentiation of CML leucocytes in vitro and are consistent with basophilia frequently observed in CML patients.

40-Gb/s clock and data recovery (CDR) circuit with an integrated high-precision eye-opening monitor (EOM) circuit and an adaptive control scheme for optimizing the data decision point are presented. An adaptive decision-point control (ADPC) scheme using the EOM feedback overcomes the time-varying waveform distortion due to transmission impairment, which causes severe degradation of bit-error-rate (BER) performance in high-speed (>40 Gb/s) data link systems. A 2.5 times 2.0-mm prototype chip is implemented in 0.18 -mum SiGe BiCMOS technology. The power consumption is 1.6 W with a +3.3-V supply voltage. Stable CDR operation with low-jitter performance (189 fs-rms) and the ADPC scheme using EOM feedback are demonstrated at 40 Gb/s. For a 30% duty-distorted 53 -mV signal, the proposed ADPC scheme drastically reduces the BER to le-12 compared to that (2e-7) without adaptive control. The experimental results demonstrate that the proposed CDR circuit greatly improves BER performance and provides robust CDR operation in high-speed data link systems.

Brugada Syndrome (BrS) is a low-prevalent entity (with the exception of certain endemic areas from Southeastern Asia, such as Thailand, the Philippines, and Japan) that affects the sarcolemmal channels of cardiomyocytes (channelopathy), characterized by a typical clinical-electrocardiographic pattern, occurring with great predominance in the male gender (male/female ratio—8:1 in nonAsian and 10:1 in Asian people1). The average age of the initial diagnosis is 41 ± 15 years; it is either sporadic (≈63% of the cases) or caused by a genetic mutation2 (≈37%) with dominant autosomal transmission and variable degrees of penetrance. The affected gene in ≈20% of the cases is SCN5A, located in the short arm of chromosome 3p21–23, which encodes the α subunit of the Na+ channel, a protein complex of the sarcolemma present in the contractile muscle of the atria, ventricles, and the excitoconductor system, being fundamental in the onset, conduction, excitability, excitation-contraction, and maintenance of cardiac rhythm.3 There are four genetic subtypes described as responsible for BrS1, BrS2, BrS3, and BrS4 variants4 that affect different locus, channels, and genes, and with particular clinical-electrocardiographic manifestations. BrS1: With mutation in the sodium channel: locus 3p21–23, INa+ channel, and SCN5A.Nav1.5 gene. This is the classical and predominant variety.5 BrS2:6 locus 3p24, INa+ channel, and GPD1L gene:7 more benign clinical course, with progressive conduction disease, minimal tendency to sudden cardiac death, and pharmacological test with procainamide, which does not identify the affected individuals. BrS3: With mutation in the slow calcium channel: associated to discretely short QT interval corrected by heart rate (QTc) (≤360 ms), locus 12p13.3, ICaL+2 channel, and CACNA1C.Cav1.2 gene. BrS4: locus 10p12.33, ICaL+2 channel, CACNB2b.CAvβ2b gene.8 There is a wide spectrum of mutations in the SCN5A gene with allelic phenotypes to BrS1, which led to consider the group as Na+ channel syndrome9 with overlay of clinical presentations. Mutations in the Na+ channel are responsible for variant 3 in congenital long QT syndrome, BrS, progressive conduction defect, and several mixed phenotypes.10 BrS1 necessarily occurs in the absence of any apparent demonstrable structural heart disease, even with invasive methods (except for biopsy), and not related to ischemia, electrolytic imbalances, and action of drugs. It is considered a “primary electrical heart disease.” The following factors stand out: possible positive family background for sudden cardiac death (SCD) or syncope in first-degree family members ≤40 years, a high tendency of the appearance during night sleep (rest) (>85% of the cases) of very fast malignant runs of polymorphic ventricular tachycardia (PVT) that may be aborted or degenerate into ventricular fibrillation (VF) and lead, respectively, to syncope or SCD. The annual mortality rate in Thailand has been estimated in 26 to 38 deaths per 100,000 inhabitants/year.1 Since the first consensus, three ECG patterns are acknowledged, called types 1, 2, and 3.11,12 Only type 1—much rarer—is diagnostic and characterized by presenting in the right precordial leads (V1 and V2 or V3)13 of ECG, ST-segment elevation ≥2 mm with superior convexity followed by T wave of negative polarity. Type 2 pattern displays in the right precordial leads, elevation of the J point, and the initial portion of ST segment of ≥ 2 mm and in the terminal portion ≥ 1 mm with saddleback appearance, followed by positive or biphasic T wave. In type 3, the ST segment also has saddleback configuration with elevation in J point and the onset of ST segment ≥ 2 mm and terminal portion ≤ 1 mm followed by positive T wave. Types 2 and 3 are found as normal variants, being included within the group of right end conduction delays by the fascicles of the right bundle branch of the His bundle.14 In many patients, type 1 ECG pattern is not observed, and the ECG could be transitorily normal making diagnosis difficult. The administration of certain class IA and class IC sodium channel blockers can unmask type 1 ECG pattern.15 There are different drugs and clinical circumstances that may trigger both type 1 ECG pattern and runs of PVT/VF: tricyclic antidepressants,16 vagotonic agents,17 α-agonists,18 antihistamines,19 cocaine,20 prajmalium bitartrate,21 antimalarial agents, some anesthetic agents,22 nocturnal vagotonia, and febrile states.23 In symptomatic patients, the treatment of choice is the implantable cardioverter defibrillator (ICD).24 In newborn babies and small infants, where ICD is not technically feasible, or in poor countries, where its high cost is unaffordable, oral quinidine is used with encouraging results.25 Quinidine is indicated in patients that already have an ICD implanted, to decrease the number of shocks. With very severe symptoms known as electrical storm, the therapy of choice consists of the association of isoproterenol infusion, general anesthesia, and bypass.26

In this study, we present evidence that gene transfer of the CD40-ligand (CD154) into human immature dendritic cells (DC) imparts direct antitumor effects on tumor cells. DC infected with adenovirus directed to express human CD154 on the cell surface (CD154-DC) elicited significantly higher levels of immune accessory molecules commonly found on mature DC. We found that co-cultivation with a human squamous cell carcinoma cell line (OSC-70) with CD154-DC significantly inhibited cell growth. We further demonstrate that OSC-70 cells stimulated with CD154-DC were more susceptible to apoptosis via TNF-related apoptosis inducing ligand (TRAIL). Importantly, tumor cells co-cultured with CD154-DC in transwell plates expressed upregulated cell surface TRAIL-R2. CD154-DC produced higher levels of interferon (IFN)-gamma, IL-12p70 and soluble CD154, but the ability of CD154-DC to inhibit tumor cell growth was significantly abrogated by a neutralizing antibody to IFN-gamma, indicating that this was mainly mediated by IFN-gamma. Furthermore, intratumoral injection of CD154-DC significantly suppressed OSC-70 tumor growth in a xenograft model. Overall, these results reveal that CD154-DC have potential as an anti-cancer therapy by producing IFN-gamma to arrest adjacent tumor cell growth and increase the susceptibility of apoptosis via TRAIL.

This study investigated the baseline level of faecal corticosterone in dogs relinquished to a shelter and compared changes in it caused by social events that dogs experienced. Faecal corticosterone was measured to assess the average stress levels of dogs that depend on the actual conditions of the shelter. One category of subject animals was dogs relinquished by their owner or stray dogs who were penned in a group (group RG) or caged individually due to their incompatibility (group RI), and the other category was demonstration dogs kept for dog training classes (group DT) and petting activities held in welfare facilities for the elderly and in elementary schools (group DP). While the number of dogs that were included in groups RG and RI fluctuated almost daily, the demonstration dogs were kept together for three months. The average level of faecal corticosterone was significantly higher in group RG than in groups DT and DP. The level of group RI was also relatively high, but the difference from the other three groups was not statistically significant. Faecal corticosterone concentrations of groups DT and DP rose somewhat from the baseline levels on the day after social service activities. The results of this study reaffirm that temporarily relinquished and socially unstable dogs especially suffer a certain level of stress in a shelter.

We have demonstrated sulfur monolayer doping (MLD) of In(53%)GaAs on III–V buffer/Si substrate at 300mm wafer scale and obtained sheet resistance of 303 ohms/sq with 8% uniformity. Mono-layer doping was achieved via molecular doping of sulfur and conventional annealing for dopant drive-in. Chemical reactivity, cost, environmental, safety and health aspects (all of which are crucial for high volume manufacturing) were considered in the chemical down-selection. MLD demonstrates molecular-scale control with conformal, nondestructive introduction of dopants to III–V materials

We attempted to fabricate a new type of magneto optic spatial light modulator (MO-SLM) for multiple-tone modulation by using in-plane magnetization. In the MO-SLM, magnetic property of magneto-optical layer was modified to be suitable for multiple-tone expression by substituting Al in Bi:YIG film. At a driving current to 28 mA in an electrode of the fabricated MO-SLM, changes in brightness of pixels were observed using a polarization microscope.

Genetic parameters for performance traits on 409 bulls and growth and carcass traits on 591 of their steer progeny were estimated in Japanese Black cattle with Gibbs sampling. Traits of bulls included body weight at the start (BWS) and finish (BWF) of test, daily gain (DG), concentrate, roughage and TDN intake, and TDN conversion ratio. Progeny traits were BWS, BWF, DG, rib eye area, marbling score (MSR), dressing percentage and subcutaneous fat thickness (SFT). In bulls, heritabilities were high for BWS (0.50) and BWF (0.63) and moderate for concentrate (0.48) and TDN intake (0.45), while in progeny, the heritability for all the studied traits was moderate to high (ranging from 0.30 to 0.73), highlighting the potential for genetic improvement of these traits. Genetic correlations between TDN intake and growth traits (BWS, BWF and DG) in bulls were highly positive (ranging from 0.77 to 0.94). The weak but negative genetic correlation (-0.20) between MSR and SFT in progeny indicated that improvement of beef marbling without increasing subcutaneous fat deposition could be possible. The estimated genetic correlations of roughage intake of bulls with body weights (BWS and BWF) and MSR of their progeny were moderate (ranging from 0.35 to 0.52). On the basis of the selection for bulls, growth traits and TDN intake correlated positively with SFT (ranging from 0.43 to 0.53) of their progeny, suggesting the necessity of controlling the increase of SFT in selection programs.