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Autorzy: Abe K., Adrich P., Aihara H., Akutsu, R., Alekseev I., Ali A. , Ameli F., Anghel I., Anthony L. H. V., Antonova M. , Araya A., Asaoka Y., Ashida Y., Aushev V., Ballester F., Bandac I., Barbi M., Barker G. J., Barr G., Batkiewicz-Kwasniak M., Bellato M., Berardi V., Bergevin M., Bernard L., Bernardini E., Berns L., Bhadra S., Bian J., Blanchet A., Blaszczyk F. d. M., Blonde A., Boiano A., Bolognesi S., Bonavera L., Booth N., Borjabad S., Boschi, T., Bose D., Boyd S . B., Bozza C., Bravar A., Bravo-Berguño D., Bronner C., Brown L., Bubak Arkadiusz, Buchowicz A., Buizza Avanzini M., Cafagna F. S., Calabria N. F., Calvo-Mozota J. M., Cao S., Cartwright S.L., Carroll A., Catanesi M. G., Cebriàn, S., Chabera M., Chakraborty, S., Checchia C., Choi J.H., Choubey S., Cicerchia M., Coleman J., Collazuol G., Cook L., Cowan G., Cuen-Rochin, S., Danilov M., Díaz López G., De la Fuente E., de Perio P., De Rosa G., Dealtry T., Densham C. J., Dergacheva A., Deshmukh N., Devi M. M., Di Lodovico F., Di Meo, P., Di Palma I., Doyle T. A., Drakopoulou E., Drapier O., Dumarchez J., Dunne P., Dziewiecki M., Eklund L., El Hedri S., Ellis J., Emery S., Esmaili A., Esteve R., Evangelisti A., Feely M., Fedotov S., Feng J., Fernandez P., Fernández-Martinez E., Ferrario P., Ferrazzi,B., Feusels T., Finch A., Finley C., Fiorentini A., Fiorillo G., Fitton M., Frankiewicz K., Friend M., Fujii Y., Fukuda Y., Galinski G., Gao J., Garde C., Garfagnini A., Garode S., Gialanella L., Giganti C., Gomez-Cadenas J.J., Gonin M., González-Nuevo J., Gorin A., Gornea R., Gousy-Leblanc V. Gramegna F. Grassi M. Grella G. Guigue M. Gumplinger P. Hadley D.R. Harada M., Hartfiel B., Hartz M., Hassani S., Hastings N.C., Hayato Y., Hernando-Morata J.A., Herrero V., Hill J., Hiraide K., Hirota S., Holin A., Horiuchi S., Hoshina K., Hultqvist K., Iacob F., Ichikawa A.K., Idrissi Ibnsalih W., Iijima T., Ikeda M., Inomoto M., Inoue K., Insler J., Ioannisian A., Ishida T., Ishidoshiro K., Ishino H., Ishitsuka M., Ito H., Ito S., Itow Y., Iwamoto K., Izmaylov A., Izumi N., Izumiyama S., Jakkapu M., Jamieson B., Jang H.I., Jang J.S., Jenkins S.J., Jeon S.H., Jiang M., Jo H.S., Jonsson P., Joo K.K., Kajita T., Kakuno H., Kameda J., Kano Y., Kalaczynski P., Karlen D., Kasperek J., Kataoka Y., Kato A., Katori T., Kazarian N., Kearns E., Khabibullin M., Khotjantsev A., Kikawa T., Kekic M., Kim J.H., Kim J.Y., Kim S.B., Kim S.Y., King S., Kinoshita T., Kisiel Jan, Klekotko A., Kobayashi T., Koch L., Koga M., Koerich L., Kolev N., Konaka A., Kormos L.L., Koshio Y., Korzenev A., Kotsar Y., Kouzakov K.A., Kowalik K.L., Kravchuk L., Kryukov A.P., Kudenko Y., Kumita T., Kurjata R., Kutter T., Kuze M., Kwak K., La Commara M., Labarga L., Lagoda J., Lamers James J., Lamoureux M., Laveder M., Lavitola L., Lawe M., Learned J.G., Lee J., Leitner R., Lezaun V., Lim I.T., Lindner T., Litchfield R.P., Long K.R., Longhin A., Loverre P., Lu X., Ludovici L., Maekawa Y., Magaletti L., Magar K., Mahn K., Makida Y., Malek M., Malinský M., Marchi T., Maret L., Mariani C., Marinelli A., Martens K., Marti L., Martin J.F. Martin D., Marzec J., Matsubara T., Matsumoto R., Matsuno S., Matusiak M., Mazzucato E., McCarthy M., McCauley N., McElwee J., McGrew C., Mefodiev A., Medhi A., Mehta P., Mellet L., Menjo H., Mermod P., Metelko C., Mezzetto M., Migenda J., Migliozzi P., Mijakowski P., Miki S., Miller E.W., Minakata H., Minamino A., Mine S., Mineev O., Mitra A., Miura M., Moharana R., Mollo C.M., Mondal T., Mongelli M., Monrabal F., Moon D.H., Moon C.S., Mora F.J., Moriyama S., Mueller Th.A., Munteanu L., Murase K., Nagao Y., Nakadaira T., Nakagiri K., Nakahata M., Nakai S., Nakajima Y., Nakamura K., Nakamura KI., Nakamura H., Nakano Y., Nakaya T., Nakayama S., Nakayoshi K., Nascimento Machado L., Naseby C.E.R., Navarro-Garcia B., Needham M., Nicholls T., Niewczas K., Nishimura Y., Noah E., Nova F., Nugent J.C., Nunokawa H., Obrebski W., Ochoa-Ricoux J.P., O’Connor E., Ogawa N., Ogitsu T., Ohta K., Okamoto K., O’Keeffe H.M., Okumura K., Onishchuk Y., Orozco-Luna F., Oshlianskyi A., Ospina N., Ostrowski M., O’Sullivan E., O’Sullivan L., Ovsiannikova T., Oyama Y., Ozaki H., Pac M.Y., Paganini P., Palladino V., Paolone V., Pari M., Parsa S., Pasternak J., Pastore C., Pastuszak G., Patel D.A., Pavin M., Payne D., Peña-Garay C., Pidcott C., Pinzon Guerra E., Playfer S., Pointon B.W., Popov A., Popov B., Porwit Kamil, Posiadala-Zezula M., Poutissou J.M., Pozimski J., Pronost G., Prouse N.W., Przewlocki P., Quilain B., Quiroga A.A., Radicioni E., Radics B., Rajda P.J., Renner J., Rescigno M., Retiere F., Ricciardi G., Riccio C., Richards B., Rondio E., Rose H.J., Roskovec B., Roth S., Rott C., Rountree S.D., Rubbia A., Ruggeri A.C., Ruggles C., Russo S., Rychter A., Ryu D., Sakashita K., Samani S., Sánchez F., Sánchez M.L., Sanchez M.C., Sano S., Santos J.D., Santucci G., Sarmah P., Sashima I., Sato K., Scott M., Seiya Y., Sekiguchi T., Sekiya H., Seo J.W., Seo S.H., Sgalaberna D., Shaikhiev A., Shan Z., Shaykina A., Shimizu I., Shin C.D., Shinoki M., Shiozawa M., Sinnis G., Skrobova N., Skwarczynski K., Smy M.B., Sobczyk J., Sobel H.W., Soler F. J. P., Sonoda Y., Spina R., Spisso B., Spradlin B., Stankevich K.L., Stawarz L., Stellacci S.M., Stopa K., Studenikin A.I., Suárez Gómez S.L., Suganuma T., Suvorov S., Suwa Y., Suzuki A.T., Suzuki S.Y., Suzuki Y., Svirida D., Svoboda R., Taani M., Tada M., Takeda A., Takemoto Y., Takenaka A., Taketa A., Takeuchi Y., Takhistov V., Tanaka H., Tanaka H.A., Tanaka H.I., Tanaka M., Tashiro T., Thiesse M., Thompson L.F., Toledo J., Tomatani-Sánchez A.K., Tortone G., Tsui K.M., Tsukamoto T., Tzanov M., Uchida Y., Vagins M.R., Valder S., Valentino V., Vasseur G., Vijayvargi A., Vilela C., Vinning W. G. S., Vivolo D., Vladisavljevic T., Vogelaar R.B., Vyalkov M.M., Wachala T., Walker J., Wark D., Wascko M.O., Wendell R.A., Wilkes R.J., Wilking M.J., Wilson M.R., Wronka S., Xia J., Xie Z., Xin T., Yamaguchi Y., Yamamoto K., Yanagisawa C., Yano T., Yen S., Yershov N., Yeum D.N., Yokoyama M., Yonenaga M., Yoo J., Yu I., Yu M., Zakrzewski T., Zaldivar B., Zalipska J., Zaremba K., Zarnecki G., Ziembicki M., Zietara K., Zito M., Zsoldos S., Core-collapse supernovae are among the most magnificent events in the observable universe. They produce many of the chemical elements necessary for life to exist and their remnants-neutron stars and black holes-are interesting astrophysical objects in their own right. However, despite millennia of observations and almost a century of astrophysical study, the explosion mechanism of core-collapse supernovae is not yet well understood. Hyper-Kamiokande is a next-generation neutrino detector that will be able to observe the neutrino flux from the next galactic core-collapse supernova in unprecedented detail. We focus on the first 500 ms of the neutrino burst, corresponding to the accretion phase, and use a newly-developed, high-precision supernova event generator to simulate Hyper-Kamiokandeʼs response to five different supernova models. We show that Hyper-Kamiokande will be able to distinguish between these models with high accuracy for a supernova at a distance of up to 100 kpc. Once the next galactic supernova happens, this ability will be a powerful tool for guiding simulations toward a precise reproduction of the explosion mechanism observed in nature.

We present the results of a time-coincident event search for low-energy electron antineutrinos in the KamLAND detector with gamma-ray bursts from the Gamma-ray Coordinates Network and Fermi Gamma-ray Burst Monitor. Using a variable coincidence time window of $\pm$500s plus the duration of each gamma-ray burst, no statistically significant excess above background is observed. We place the world's most stringent 90% confidence level upper limit on the electron antineutrino fluence below 17.5 MeV. Assuming a Fermi-Dirac neutrino energy spectrum from the gamma-ray burst source, we use the available redshift data to constrain the electron antineutrino luminosity and effective temperature., 9 pages, 3 figures

Rare event searches allow us to search for new physics at energy scales inaccessible with other means by leveraging specialized large-mass detectors. Machine learning provides a new tool to maximize the information provided by these detectors. The information is sparse, which forces these algorithms to start from the lowest level data and exploit all symmetries in the detector to produce results. In this work we present KamNet which harnesses breakthroughs in geometric deep learning and spatiotemporal data analysis to maximize the physics reach of KamLAND-Zen, a kiloton scale spherical liquid scintillator detector searching for neutrinoless double beta decay ($0\nu\beta\beta$). Using a simplified background model for KamLAND we show that KamNet outperforms a conventional CNN on benchmarking MC simulations with an increasing level of robustness. Using simulated data, we then demonstrate KamNet's ability to increase KamLAND-Zen's sensitivity to $0\nu\beta\beta$ and $0\nu\beta\beta$ to excited states. A key component of this work is the addition of an attention mechanism to elucidate the underlying physics KamNet is using for the background rejection., Comment: 12 pages, dual submission with upcoming KamLAND-Zen 800 main result

We report on a search for electron antineutrinos ($\bar{\nu}_e$) from astrophysical sources in the neutrino energy range 8.3 to 30.8 MeV with the KamLAND detector. In an exposure of 6.72 kton-year of the liquid scintillator, we observe 18 candidate events via the inverse beta decay reaction. Although there is a large background uncertainty from neutral current atmospheric neutrino interactions, we find no significant excess over background model predictions. Assuming several supernova relic neutrino spectra, we give upper flux limits of 60--110 cm$^{-2}$ s$^{-1}$ (90% CL) in the analysis range and present a model-independent flux. We also set limits on the annihilation rates for light dark matter pairs to neutrino pairs. These data improves on the upper probability limit of $^{8}$B solar neutrinos converting into $\bar{\nu}_e$'s, $P_{\nu_e \rightarrow \bar{\nu}_e} < 3.5\times10^{-5}$ (90% CL) assuming an undistorted $\bar{\nu}_e$ shape. This corresponds to a solar $\bar{\nu}_e$ flux of 60 cm$^{-2}$ s$^{-1}$ (90% CL) in the analysis energy range., Comment: 21 pages, 9 figures, 4 tables, accepted for publication in Astrophysical Journal

We present the results of a search for core-collapse supernova neutrinos, using long-term KamLAND data from 2002 March 9 to 2020 April 25. We focus on the electron antineutrinos emitted from supernovae in the energy range of 1.8--111 MeV. Supernovae will make a neutrino event cluster with the duration of $\sim$10 s in the KamLAND data. We find no neutrino clusters and give the upper limit on the supernova rate as to be 0.15 yr$^{-1}$ with a 90% confidence level. The detectable range, which corresponds to a >95% detection probability, is 40--59 kpc and 65--81 kpc for core-collapse supernovae and failed core-collapse supernovae, respectively. This paper proposes to convert the supernova rate obtained by the neutrino observation to the Galactic star formation rate. Assuming a modified Salpeter-type initial mass function, the upper limit on the Galactic star formation rate is, 10 pages, 4 figures, accepted for publication in Astrophysical Journal

We report the result of a search for neutrinos in coincidence with solar flares from the GOES flare database. The search was performed on a 10.8 kton-year exposure of KamLAND collected from 2002 to 2019. This large exposure allows us to explore previously unconstrained parameter space for solar flare neutrinos. We found no statistical excess of neutrinos and established 90% confidence level upper limits of $8.4 \times 10^7$ cm$^{-2}$ ($3.0 \times 10^{9}$ cm$^{-2}$) on electron anti-neutrino (electron neutrino) fluence at 20 MeV normalized to the X12 flare, assuming that the neutrino fluence is proportional to the X-ray intensity., 13 pages, 9 figures, accepted October 27, 2021

The KamLAND-Zen 800 experiment is searching for the neutrinoless double-beta decay of $^{136}$Xe by using $^{136}$Xe-loaded liquid scintillator. The liquid scintillator is enclosed inside a balloon made of thin, transparent, low-radioactivity film that we call Inner Balloon (IB). The IB, apart from guaranteeing the liquid containment, also allows to minimize the background from cosmogenic muon-spallation products and $^{8}$B solar neutrinos. Indeed these events could contribute to the total counts in the region of interest around the Q-value of the double-beta decay of $^{136}$Xe. In this paper, we present an overview of the IB and describe the various steps of its commissioning minimizing the radioactive contaminations, from the material selection, to the fabrication of the balloon and its installation inside the KamLAND detector. Finally, we show the impact of the IB on the KamLAND background as measured by the KamLAND detector itself., 23 pages, 16 figures, to be submitted to JINST

Hyper-Kamiokande is the next generation underground water Cherenkov detector that builds on the highly successful Super-Kamiokande experiment. The detector which has an 8.4~times larger effective volume than its predecessor will be located along the T2K neutrino beamline and utilize an upgraded J-PARC beam with 2.6~times beam power. Hyper-K's low energy threshold combined with the very large fiducial volume make the detector unique, that is expected to acquire an unprecedented exposure of 3.8~Mton$\cdot$year over a period of 20~years of operation. Hyper-Kamiokande combines an extremely diverse science program including nucleon decays, long-baseline neutrino oscillations, atmospheric neutrinos, and neutrinos from astrophysical origins. The scientific scope of this program is highly complementary to liquid-argon detectors for example in sensitivity to nucleon decay channels or supernova detection modes. Hyper-Kamiokande construction has started in early 2020 and the experiment is expected to start operations in 2027. The Hyper-Kamiokande collaboration is presently being formed amongst groups from 19 countries including the United States, whose community has a long history of making significant contributions to the neutrino physics program in Japan. US physicists have played leading roles in the Kamiokande, Super-Kamiokande, EGADS, K2K, and T2K programs., 6 pages, prepared as Snowmass2021 LOI

We present a precision analysis of the ^{136}Xe two-neutrino ββ electron spectrum above 0.8 MeV, based on high-statistics data obtained with the KamLAND-Zen experiment. An improved formalism for the two-neutrino ββ rate allows us to measure the ratio of the leading and subleading 2νββ nuclear matrix elements (NMEs), ξ_{31}^{2ν}=-0.26_{-0.25}^{+0.31}. Theoretical predictions from the nuclear shell model and the majority of the quasiparticle random-phase approximation (QRPA) calculations are consistent with the experimental limit. However, part of the ξ_{31}^{2ν} range allowed by the QRPA is excluded by the present measurement at the 90% confidence level. Our analysis reveals that predicted ξ_{31}^{2ν} values are sensitive to the quenching of NMEs and the competing contributions from low- and high-energy states in the intermediate nucleus. Because these aspects are also at play in neutrinoless ββ decay, ξ_{31}^{2ν} provides new insights toward reliable neutrinoless ββ NMEs.

Liquid scintillator detectors have many properties which are highly advantageous for neutrino research at the MeV energy scale. There are various choices of additives to an organic liquid scintillator which typically function as the nuclear targets in a neutrino interaction. More recently, new techniques for loading a large amount of nuclei into liquid scintillator enable sensitive searches for double beta decay with various nuclei. KamLAND was an existing detector constructed for neutrino physics at the MeV scale, later upgraded to a sensitive detector for double beta decay (KamLAND-Zen). In this experiment, isotopically enriched xenon gas was loaded into the highly radiopure liquid scintillator. As xenon is a stable noble gas, the scintillation performance changes little, and it is safe for long-term use. To mitigate backgrounds, xenon was loaded only into the liquid scintillator in the central part of the detector, contained in a spherical nylon balloon. Owing to the large amount of xenon and low background level, the KamLAND-Zen experiment achieved the most sensitive search to date for neutrinoless double beta decay in the standard mechanism. The next phase of the experiment plans to increase the amount of xenon by almost double. In the future, sensitivity can be further enhanced by detector upgrades. SNO+ (successor to the Sudbury Neutrino Observatory) is a liquid scintillator detector that is currently being commissioned and will soon be taking data. Originally, SNO+ developed a technique to load neodymium into the liquid scintillator in order to conduct a double beta decay search with the isotope 150Nd. Later, SNO+ developed two new techniques that enable loading tellurium into liquid scintillator. The large natural abundance of 130Te and the ability to load tellurium at a significant concentration in the SNO+ liquid scintillator, while maintaining excellent scintillation optical properties, offer the prospect of a very sensitive search for neutrinoless double beta decay. This article will discuss both experiments, KamLAND-Zen and SNO+, highlighting the results achieved, the techniques involved in loading the liquid scintillator, and describing the purification of components of the loaded liquid scintillator to very low background levels.

Appropriate animal models are necessary to determine the molecular and cellular mechanisms underlying attention-deficit/hyperactivity disorder (ADHD). This study used a battery of behavioral tests to compare Lister hooded rats (LHRs), an old outbred strain frequently used for autistic epilepsy research, with Wistar rats and spontaneously hypertensive rats (SHRs), a commonly used ADHD model. The open field, elevated plus maze, light/dark box, and drop tests demonstrated that LHRs were the most hyperactive animals and displayed the most inattentive- and impulsive-like behaviors, which are characteristics of ADHD. The radial arm maze, social interaction, and Morris water maze tests showed that LHRs did not display deficits characteristic of autism or intellectual disability. Although LHRs did not show different monoamine contents, the mRNA expression levels of various genes linked to ADHD (Cdh13, Drd5, Foxp2, Maoa, Sema6d, Slc9a9, and St3gal3) and tyrosine hydroxylase protein expression levels were lower in the prefrontal cortex of LHRs compared with that of Wistar rats or SHRs. c-Fos, synapsin I, and tau protein expression levels in the prelimbic region of the medial prefrontal cortex were also increased in LHRs compared with Wistar rats. Atomoxetine and guanfacine, commonly used non-stimulant treatments for ADHD, ameliorated ADHD-like behaviors in LHRs. These results suggest that LHRs can serve as a better ADHD model to develop novel pharmacological interventions.

Pancreatic ductal adenocarcinoma (PDAC) is a very aggressive tumor with a five-year survival of less than 6%. Chronic pancreatitis (CP), an inflammatory process in of the pancreas, is a strong risk factor for PDAC. Several genetic polymorphisms have been discovered as susceptibility loci for both CP and PDAC. Since CP and PDAC share a consistent number of epidemiologic risk factors, the aim of this study was to investigate whether specific CP risk loci also contribute to PDAC susceptibility. We selected five common SNPs (rs11988997, rs379742, rs10273639, rs2995271 and rs12688220) that were identified as susceptibility markers for CP and analyzed them in 2,914 PDAC cases, 356 CP cases and 5,596 controls retrospectively collected in the context of the international PANDoRA consortium. We found a weak association between the minor allele of the PRSS1-PRSS2-rs10273639 and an increased risk of developing PDAC (ORhomozygous = 1.19, 95% CI 1.02–1.38, p = 0.023). Additionally all the SNPs confirmed statistically significant associations with risk of developing CP, the strongest being PRSS1-PRSS2-rs10273639 (ORheterozygous = 0.51, 95% CI 0.39–0.67, p = 1.10 × 10−6) and MORC4-rs 12837024 (ORhomozygous = 2.07 (1.55–2.77, ptrend = 0.7 × 10−11). Taken together, the results from our study do not support variants rs11988997, rs379742, rs10273639, rs2995271 and rs12688220 as strong predictors of PDAC risk, but further support the role of these SNPs in CP susceptibility. Our study suggests that CP and PDAC probably do not share genetic susceptibility, at least in terms of high frequency variants. © 2017 UICC

We describe a compact, ultra-clean device used to deploy radioactive sources along the vertical axis of the KamLAND liquid-scintillator neutrino detector for purposes of calibration. The device worked by paying out and reeling in precise lengths of a hanging, small-gauge wire rope (cable); an assortment of interchangeable radioactive sources could be attached to a weight at the end of the cable. All components exposed to the radiopure liquid scintillator were made of chemically compatible UHV-cleaned materials, primarily stainless steel, in order to avoid contaminating or degrading the scintillator. To prevent radon intrusion, the apparatus was enclosed in a hermetically sealed housing inside a glove box, and both volumes were regularly flushed with purified nitrogen gas. An infrared camera attached to the side of the housing permitted real-time visual monitoring of the cable's motion, and the system was controlled via a graphical user interface., Revised author affiliations, corrected typos, made minor improvements to text, and revised references

The removal of radioactivity from liquid scintillator has been studied in preparation of a low background phase of KamLAND. This paper describes the methods and techniques developed to measure and efficiently extract radon decay products from liquid scintillator. We report the radio-isotope reduction factors obtained when applying various extraction methods. During this study, distillation was identified as the most efficient method for removing radon-born lead from liquid scintillator.

Geoneutrinos are antineutrinos produced in radioactive decays within Earth's interior. Those antineutrinos can be detected by inverse β-decays of protons, however, due to extremely small cross section, there were no feasible experiments for a long time. Owing to the development of large-size antineutrino detectors, the observation of geoneutrinos has been finally made, and then composition models of the Earth are constrained from the radiogenic heat estimate. In this article, the latest results from ongoing experiments, KamLAND and Borexino, are reviewed.

Author(s): Gando, A; Gando, Y; Hachiya, T; Hayashi, A; Hayashida, S; Ikeda, H; Inoue, K; Ishidoshiro, K; Karino, Y; Koga, M; Matsuda, S; Mitsui, T; Nakamura, K; Obara, S; Oura, T; Ozaki, H; Shimizu, I; Shirahata, Y; Shirai, J; Suzuki, A; Takai, T; Tamae, K; Teraoka, Y; Ueshima, K; Watanabe, H; Kozlov, A; Takemoto, Y; Yoshida, S; Fushimi, K; Piepke, A; Banks, TI; Berger, BE; Fujikawa, BK; O'Donnell, T; Learned, JG; Maricic, J; Sakai, M; Winslow, LA; Krupczak, E; Ouellet, J; Efremenko, Y; Karwowski, HJ; Markoff, DM; Tornow, W; Detwiler, JA; Enomoto, S; Decowski, MP; Collaboration, KamLAND

Geoneutrinos are antineutrinos produced in radioactive isotope decays inside the Earth. Those antineutrinos are neutral particle and can be detected by weak interaction, however, due to extremely small cross section, there were no feasible experiments for a long time. The observation of geoneutrinos has been finally made using large-size liquid scintillator detectors, KamLAND and Borexino. In this article, the latest result of KamLAND and future prospects of geo ν e measurements are reviewed.

Levels of high mobility group box 1 (HMGB1), an important inflammatory mediator, are high in the serum of febrile seizure (FS) patients. However, its roles in FS and secondary epilepsy after prolonged FS are poorly understood. We demonstrate HMGB1’s role in the pathogenesis of hyperthermia-induced seizures (HS) and secondary epilepsy after prolonged hyperthermia-induced seizures (pHS). In the first experiment, 14–15-day-old male rats were divided into four groups: high-dose HMGB1 (100 μg), moderate-dose (10 μg), low-dose (1 μg), and control. Each rat was administered HMGB1 intranasally 1 h before inducing HS. Temperature was measured at seizure onset with electroencephalography (EEG). In the second experiment, 10–11-day-old rats were divided into four groups: pHS + HMGB1 (10 μg), pHS, HMGB1, and control. HMGB1 was administered 24 h after pHS. Video-EEGs were recorded for 24 h at 90 and 120 days old; histological analysis was performed at 150 days old. In the first experiment, the temperature at seizure onset was significantly lower in the high- and moderate-dose HMGB1 groups than in the control group. In the second experiment, the incidence of spontaneous epileptic seizure was significantly higher in the pHS + HMGB1 group than in the other groups. Comparison between pHS + HMGB1 groups with and without epilepsy revealed that epileptic rats had significantly enhanced astrocytosis in the hippocampus and corpus callosum. In developing rats, HMGB1 enhanced HS and secondary epilepsy after pHS. Our findings suggest that HMGB1 contributes to FS pathogenesis and plays an important role in the acquired epileptogenesis of secondary epilepsy associated with prolonged FS.

We present a search for low energy antineutrino events coincident with the gravitational wave events GW150914 and GW151226, and the candidate event LVT151012 using KamLAND, a kiloton-scale antineutrino detector. We find no inverse beta-decay neutrino events within $\pm 500$ seconds of either gravitational wave signal. This non-detection is used to constrain the electron antineutrino fluence and the luminosity of the astrophysical sources., 11 pages, 4 figures, as published in ApJL. Updated to replace power law spectrum with Fermi Dirac spectrum

Author(s): Gando, A; Gando, Y; Hachiya, T; Hayashi, A; Hayashida, S; Ikeda, H; Inoue, K; Ishidoshiro, K; Karino, Y; Koga, M; Matsuda, S; Mitsui, T; Nakamura, K; Obara, S; Oura, T; Ozaki, H; Shimizu, I; Shirahata, Y; Shirai, J; Suzuki, A; Takai, T; Tamae, K; Teraoka, Y; Ueshima, K; Watanabe, H; Kozlov, A; Takemoto, Y; Yoshida, S; Fushimi, K; Banks, TI; Berger, BE; Fujikawa, BK; O'Donnell, T; Winslow, LA; Efremenko, Y; Karwowski, HJ; Markoff, DM; Tornow, W; Detwiler, JA; Enomoto, S; Decowski, MP; KamLAND-Zen Collaboration | Abstract: This corrects the article DOI: 10.1103/PhysRevLett.117.082503.

We present an improved search for neutrinoless double-beta ($0\nu\beta\beta$) decay of $^{136}$Xe in the KamLAND-Zen experiment. Owing to purification of the xenon-loaded liquid scintillator, we achieved a significant reduction of the $^{110m}$Ag contaminant identified in previous searches. Combining the results from the first and second phase, we obtain a lower limit for the $0\nu\beta\beta$ decay half-life of $T_{1/2}^{0\nu} > 1.07 \times 10^{26}$ yr at 90% C.L., an almost sixfold improvement over previous limits. Using commonly adopted nuclear matrix element calculations, the corresponding upper limits on the effective Majorana neutrino mass are in the range 61-165 meV. For the most optimistic nuclear matrix elements, this limit reaches the bottom of the quasi-degenerate neutrino mass region., Comment: 6 pages, 3 figures, the results were updated based on the revised estimation of the 137Xe background

In the late stages of nuclear burning for massive stars ($M>8~M_{\sun}$), the production of neutrino-antineutrino pairs through various processes becomes the dominant stellar cooling mechanism. As the star evolves, the energy of these neutrinos increases and in the days preceding the supernova a significant fraction of emitted electron anti-neutrinos exceeds the energy threshold for inverse beta decay on free hydrogen. This is the golden channel for liquid scintillator detectors because the coincidence signature allows for significant reductions in background signals. We find that the kiloton-scale liquid scintillator detector KamLAND can detect these pre-supernova neutrinos from a star with a mass of $25~M_{\sun}$ at a distance less than 690~pc with 3$\sigma$ significance before the supernova. This limit is dependent on the neutrino mass ordering and background levels. KamLAND takes data continuously and can provide a supernova alert to the community., Comment: 19 pages, 6 figures, 1 table

This paper discusses a feasibility of magnetic flux leakage (MFL) method for estimation of wall thinning on pipes under reinforcing plates in nuclear power plants. The layered steel plates having a slit on its underlayer were prepared and the estimation of slit size by MFL method was examined. A single magnetic yoke is fixed on a layered specimen, and then a magnetic field sensor scans the leakage flux between the yoke legs for condition monitoring. The single magnetic yoke with a field sensor fixed at the center of the yoke is also scanned over layered specimens. It is clarified that estimation of the size of slit fabricated on underlayer of the layered specimen using profile of leakage field is possible: this indicates monitoring conditions of wall thinning to be occurred under reinforcing plates will be possible by MFL methods. Additionally, the effect of an air gap between yoke and first layer and a gap between first and under layer were also investigated experimentally.

The analytical form for the reconstructed field of a hologram illuminated by a reference beam coded with a multicolored aperture array filter is derived. Experiments showed that the colored aperture array filter improved the quality of the reconstructed image by reducing the intensity of crosstalk images. Some parameters of the aperture array configuration that influence image quality were investigated. This technique presented here can be applied to full-color holographic displays and dot matrix holographic printers, etc.

We reported that invariant NKT-cell knockout (iNKT KO) mice are resistant to the induction of intrathymic chimerism and clonal deletion in the cyclophosphamide (CP)-induced tolerance system (CPS). However, another report shows that clonal deletion with chimerism may be intact in iNKT KO recipients in a bone marrow transplantation model. We also reported that pretreatment with anti-Thy1.2 mAb, which reduces the number of T cells and iNKT cells, promotes allograft tolerance across H-2 barriers in the CPS. In this study, we evaluated the efficacy of T-cell depletion in the CPS, and the relationship between the role played by iNKT cells in central tolerance and mixed chimerism. BALB/c (H-2(d)) wild-type, or iNKT KO (Jalpha18(-/-)) mice were pretreated with 20-100 microg of anti-Thy1.2 mAb and given 10(8) donor DBA/2 (H-2(d)) spleen cells on Day 0, and 200 mg/kg CP on Day 2. Pretreatment with T-cell depletion resulted in higher levels of mixed chimerism, increased intrathymic clonal deletion of donor-reactive cells, and the induction of skin graft tolerance in iNKT KO recipients in CPS. This suggests that the high levels of mixed chimerism overcame the resistance to CP-induced tolerance in iNKT KO mice. Consistently, the enhancement of mixed chimerism by injection of tolerant donor spleen cells (SC) rendered iNKT KO recipients susceptible to CP-induced tolerance. These results suggest that iNKT-cell-mediated immunoregulation of central tolerance is evident at low levels of peripheral mixed chimerism in the CPS.

Aims Food deprivation (fasting) is commonly encountered in the lives of animals and humans. In mammals, adaptive responses predominantly include the induction of hepatic gluconeogenesis, but the regulatory mechanisms remain unclear. Atf5 (activating transcription factor 5) is a transcription factor of the ATF/cAMP response element-binding protein family and is expressed abundantly in human liver. Atf5 has been associated with stress responses, cell differentiation, proliferation, and survival. However, its role in the liver response to in vivo food deprivation has not yet been investigated. Main methods Adult mice were food-deprived for 48 h and the expression of two Atf5 mRNA subtypes (Atf5-R1 and Atf-R2) and gluconeogenic factors was investigated. Using in vitro cell culture, Pgc-1α (peroxisome proliferator-activated receptor-gamma coactivator-1alpha) promoter activities after ectopic expression of Atf5 and Cebpg (CCAAT/enhancer-binding protein gamma) proteins were measured. Key findings The Atf5-R1 transcript was found to be abundant in liver and other energy metabolism-related organs; Atf5-R2 was prominent in the testis. Fasting resulted in elevation of the expression of both Atf5-R1 and R2 in the liver. Interestingly, up-regulation of Atf5 was accompanied by increased expression of Cebpg and Pgc-1α. In human hepatoma cells (HepG2), but not in human cervical carcinoma cells (HeLa), forced expression of Atf5 and Cebpg cooperatively stimulated Pgc-1α promoter activity, suggesting that hepatic Pgc-1α could be induced by Atf5 and Cebpg in cooperation with other hepatic factors. Significance Hepatic Atf5 might be potentially involved in the induction of gluconeogenetic factors during in vivo fasting stress.

Background Cyclophosphamide (CP)-induced tolerance is a mixed chimerism-based tolerance induction protocol. Recently, we reported that invariant natural killer T (iNKT) cells were essential for the tolerance induction in this system. In this study, we evaluated the roles of the cytokines produced by iNKT cells. Methods DBA/2 (H-2d) mice and BALB/c (H-2d) wild-type (WT) or iNKT knock out (KO) mice were used as donors and recipients. WT recipients received three doses (days -7, -4, -1 or 35, 38, 41) or a single dose (day -1 or 0) of alpha-galactosylceramide (GC) in conjunction with our conditioning regimen that consisted of 10(8) donor spleen cells on day 0 and 200 mg/kg CP on day 2. To investigate the iNKT cell function, iNKT KO recipients were reconstituted with cytokine (interferon-gamma, interleukin [IL]-4, or IL-10) KO iNKT cells and received donor spleen cells and CP. Results Mixed chimerism was observed in WT recipients, but was reduced in iNKT KO recipients. However, mixed chimerism was absent in WT recipients given GC on days -7, -4, -1, but not in WT recipients given GC on day 35, 38, 41. Donor skin grafts were chronically rejected when mixed chimerism was diminished. Skin grafts were accepted in iNKT KO recipients reconstituted with iNKT cells from interferon-gamma, IL-4, or IL-10 KO mice and receiving our conditioning regimen. Conclusions Invariant NKT cells were required in the initial phase of the induction of chimerism. Our results indicated that known major cytokines produced by iNKT cells were dispensable for the regulatory function of iNKT cells.

Hyperacute rejection (HAR) mediated by the natural antibody (nAb) against Gal alpha 1-3Gal beta-4-GlcNAc (alpha Gal) is the major obstacle in xenogeneic organ transplantation. Previously, we reported the acceptance of donor heart grafts in anti-alpha Gal nAb-producing galactosyltransferase knockout (GalT KO) mice after cyclophosphamide (CP)-induced tolerance conditioning. In the present study, we applied our tolerance induction conditioning in presensitized recipient mice.GalT KO (alpha Gal(-/-), H-2(b/d)) recipient mice were presensitized with alpha Gal(+) rabbit red blood cells (RRBCs). Presensitized or nonsensitized recipient mice were treated with CP-induced tolerance conditioning, consisting of AKR (alpha Gal(+/+), H-2(k)) spleen cells (SC), CP, busulfan (BU), and AKR bone marrow cells (BMC). We assessed the survival of donor hearts and skin grafts and analyzed the production of anti-alpha Gal Abs by flow cytometry.Donor mixed chimerism was achieved in the presensitized GalT KO mice treated with CP-induced tolerance conditioning. In parallel with the disappearance of anti-alpha Gal Abs, permanent acceptance of donor heart grafts and skin grafts was observed in presensitized and GalT KO mice treated with CP-induced tolerance conditioning.Both B-cell and T-cell tolerance was achieved in the presence of a higher titer of anti-alpha Gal Abs after treatment with CP-induced tolerance conditioning.

The European bumblebee B. terrestris was recently introduced in Japan for agricultural purposes and has now become naturalized. The naturalization of this exotic species may have great detrimental effects on closely related native Japanese bumblebees. The Japanese bumblebee Bombus florilegus is a rare and locally distributed species found in the Nemuro Peninsula of Hokkaido, Japan. In order to assess its population genetics, we estimated the genetic structure of B. florilegus in 16 breeding colonies (queen, workers, and males) and 20 foraging queens by analyzing microsatellite DNA markers. Of the 36 queens analyzed by genotyping and dissection, 32 had been inseminated by a male. The remaining 4 had not been inseminated at all. Of the 4 nonmated queens, one was triploid. Diploid males were found in 4 breeding colonies. Based on the microsatellite data, it appears that B. florilegus has low reproductive success. Since matched mating and nonmating within local populations are high, the extinction risk is correspondingly higher. Our results suggest that conservation of the Japanese B. florilegus is required in order to protect it from both habitat destruction and the naturalization of alien species.

Background. Recent studies have indicated that natural killer T (NKT) cells are essential for the establishment of transplantation tolerance. In the present study, we have elucidated the role of recipient and donor NKT cells in cyclophosphamide (CP)-induced tolerance. Method. DBA/2 (DBA; H-2 d ) mice were used as donors and BALB/c (BALB; H-2 d ) wild-type (WT) or Vaα14 NKT-knockout (KO, BALB/c background) mice were used as recipients. Recipients were treated with CP-induced tolerance regimen, which consists of donor spleen cells (SC) on day 0 and CP on day 2. In some experiments, NKT KO mice, which received NKT cells from either WT, inferon- y KO, or interleukin-4 KO mice, were treated with tolerant regimen. To deplete Ly49 inhibitory receptors on NKT cells in the recipient mice, anti-Ly49 monoclonal antibody cocktails were injected on day - 1 when indicated. Results. Donor skin graft was permanently accepted in recipient BALB WT mice with induction of donor mixed chimerism. On the contrary, donor DBA skin allografts were chronically rejected in NKT KO recipient. Lower levels of mixed chimerism were observed in NKT KO recipients comparing to the WT recipients. The production of interferon-γ or interleukin-4 from NKT cells did not affect the induction of tolerance. Depletion of Ly49 positive NKT cells abrogated the induction of skin graft tolerance. Conclusion. Recipient NKT cells, but not donor NKT cells, were dominantly required for the induction of allograft tolerance. Our results indicated that the single cytokine produced by NKT cells did not mediate the regulatory function in the induction of allograft tolerance.

ATF5 is a transcription factor in the cAMP response element (CRE)-binding protein/activating transcription factor (CREB/ATF) family. We studied the effect of amino acid limitation on ATF5 mRNA levels in a mammalian cell line. Northern-blot analysis demonstrated that limitation of a single amino acid, glutamine, methionine, or leucine, resulted in increased ATF5 mRNA levels in HeLaS3 cells. This resulted, at least in part, from increased half-life of the ATF5 mRNA transcript. Cycloheximide inhibited the increase in ATF5 mRNA expression induced by glutamine limitation, indicating that it was dependent on de novo protein synthesis. Moreover, rapamycin had no effect on basal ATF5 mRNA expression or on increased expression induced by glutamine limitation. These results indicate that amino acid limitation regulates ATF5 mRNA expression during post-transcription in a rapamycin-independent manner. The potential role for ATF5 in protecting cells from amino acid-limitation is of considerable interest.

We present a search for the proton decay mode p→ν¯K+ based on an exposure of 8.97 kton-years in the KamLAND experiment. The liquid scintillator detector is sensitive to successive signals from p→ν¯K+ with unique kinematics, which allow us to achieve a detection efficiency of 44%, higher than previous searches in water Cherenkov detectors. We find no evidence of proton decays for this mode. The expected background, which is dominated by atmospheric neutrinos, is 0.9±0.2 events. The nonbackground-subtracted limit on the partial proton lifetime is τ/B(p→ν¯K+)>5.4×1032 years at 90% C.L.

Artículo escrito por muchos autores, sólo se referencian el primero, los autores que firman como Universidad Autónoma de Madrid y el grupo de colaboración en el caso de que aparezca en el artículo, Hyper-Kamiokande will be a next-generation underground water Cherenkov detector with a total (fiducial) mass of 0.99 (0.56) million metric tons, approximately 20 (25) times larger than that of Super-Kamiokande. One of the main goals of Hyper-Kamiokande is the study of CP asymmetry in the lepton sector using accelerator neutrino and anti-neutrino beams. In this paper, the physics potential of a long-baseline neutrino experiment using the Hyper- Kamiokande detector and a neutrino beam from the J-PARC proton synchrotron is presented. The analysis uses the framework and systematic uncertainties derived from the ongoing T2K experiment. With a total exposure of 7.5 MW ×107 s integrated proton beam power (corresponding to 1.56 × 1022 protons on target with a 30 GeV proton beam) to a 2.5° off-axis neutrino beam, it is expected that the leptonic CP phase δCP can be determined to better than 19 degrees for all possible values of δCP, and CP violation can be established with a statistical significance of more than 3 σ (5 σ) for 76% (58%) of the δCP parameter space. Using both νeappearance and νμ disappearance data, the expected 1 σ uncertainty of sin2 Θ23 is 0.015(0.006) for sin2 Θ23= 0.5(0.45), This work was supported by a MEXT Grant-in-Aid for Scientific Research on Innovative Areas Number 25105004, titled “Unification and Development of the Neutrino Science Frontier.” In addition, the participation of individual researchers has been further supported by funds from JSPS, Japan; the European Union ERC-207282, H2020 RISE-GA644294-JENNIFER, and H2020 RISE-GA641540-SKPLUS; RSF, RFBR, and MES, Russia; and JSPS and RFBR under the Japan–Russia Research Cooperative Program

Activating transcription factor 5 (ATF5) is a stress response transcription factor of the cAMP-responsive element-binding/ATF family. Earlier, we reported that ATF5 expression is up-regulated in response to stress, such as amino acid limitation or arsenite exposure. Although ATF5 is widely expressed in the brain and the olfactory epithelium, the role of ATF5 is not fully understood. Here, the olfactory bulbs (OBs) of ATF5-deficient mice are smaller than those of wild-type mice. Histological analysis reveals the disturbed laminar structure of the OB, showing the thinner olfactory nerve layer, and a reduced number of interneurons. This is mainly due to the reduced number of bromodeoxyuridine-positive proliferating cells in the subventricular zone, where the interneuron progenitors are formed and migrate to the OBs. Moreover, the olfaction-related aggressive behavior of ATF5-deficient mice is reduced compared to wild-type mice. Our data suggest that ATF5 plays a crucial role in mouse OB development via interneuron.

We report a measurement of the neutrino-electron elastic scattering rate of 862 keV 7Be solar neutrinos based on a 165.4 kton-day exposure of KamLAND. The observed rate is 582 +/- 90 (kton-day)^-1, which corresponds to a 862 keV 7Be solar neutrino flux of (3.26 +/- 0.50) x 10^9 cm^-2s^-1, assuming a pure electron flavor flux. Comparing this flux with the standard solar model prediction and further assuming three flavor mixing, a nu_e survival probability of 0.66 +/- 0.14 is determined from the KamLAND data. Utilizing a global three flavor oscillation analysis, we obtain a total 7Be solar neutrino flux of (5.82 +/- 0.98) x 10^9 cm^-2s^-1, which is consistent with the standard solar model predictions., 8 pages, 6 figures, submitted to Phys. Rev. C

KamLAND-Zen reports on a preliminary search for neutrinoless double-beta decay with 136Xe based on 114.8 live-days after the purification of the xenon loaded liquid scintillator. In this data, the problematic 110mAg background peak identified in previous searches is reduced by more than a factor of 10. By combining the KamLAND-Zen pre- and post-purification data, we obtain a preliminary lower limit on the 0νββ decay half-life of T 0ν 1/2 > 2.6 × 1025 yr at 90% C.L. The search sensitivity will be enhanced with additional low background data after the purification. Prospects for further improvements with future KamLAND-Zen upgrades are also presented.

A search for double-beta decays of 136Xe to excited states of 136Ba has been performed with the first phase data set of the KamLAND-Zen experiment. The 0+1, 2+1 and 2+2 transitions of 0{\nu}\{beta}\{beta} decay were evaluated in an exposure of 89.5kg-yr of 136Xe, while the same transitions of 2{\nu}\{beta}\{beta} decay were evaluated in an exposure of 61.8kg-yr. No excess over background was found for all decay modes. The lower half-life limits of the 2+1 state transitions of 0{\nu}\{beta}\{beta} and 2{\nu}\{beta}\{beta} decay were improved to T(0{\nu}, 0+ \rightarrow 2+) > 2.6\times10^25 yr and T(2{\nu}, 0+ \rightarrow 2+) > 4.6\times10^23 yr (90% C.L.), respectively. We report on the first experimental lower half-life limits for the transitions to the 0+1 state of 136Xe for 0{\nu}\{beta}\{beta} and 2{\nu}\{beta}\{beta} decay. They are T (0{\nu}, 0+ \rightarrow 0+) > 2.4\times10^25 yr and T(2{\nu}, 0+ \rightarrow 0+) > 8.3\times10^23 yr (90% C.L.). The transitions to the 2+2 states are also evaluated for the first time to be T(0{\nu}, 0+ \rightarrow 2+) > 2.6\times10^25 yr and T(2{\nu}, 0+ \rightarrow 2+) > 9.0\times10^23 yr (90% C.L.). These results are compared to recent theoretical predictions., Comment: 16 pages, 4 figures. Published in Nuclear Physics A

We search for electron anti-neutrinos ($\overline{\nu}_e$) from long and short-duration gamma-ray bursts~(GRBs) using data taken by the KamLAND detector from August 2002 to June 2013. No statistically significant excess over the background level is found. We place the tightest upper limits on $\overline{\nu}_e$ fluence from GRBs below 7 MeV and place first constraints on the relation between $\overline{\nu}_e$ luminosity and effective temperature., Comment: 16 pages and 5 figures

We previously developed a cyclophosphamide (CP)-induced tolerance protocol, consisting of an intravenous injection of 1 x 10(8) donor spleen cells (SC) given on day 0 and an intraperitoneal injection of 200 mg/kg CP given on day 2. In the present study, we modified this protocol with natural killer cell (NK) depletion in recipient mice, and evaluated the efficacy of tolerance induction.We used B10.D2 (H-2d; IE+) and B10 (H-2b; IE-) mice as both donors and recipients. The recipient mice were treated with donor SC, CP, and donor bone marrow cells (BMCs) with or without NK depletion.A higher level of mixed chimerism was achieved in the NK-depleted recipients. Survival of both the skin and heart donor grafts was significantly prolonged in the NK-depleted recipients. Donor reactive Vbeta11+ T cells were found at the same level as in untreated control mice. Pretreatment with recipient NK cell depletion was effective in inducing higher levels of donor mixed chimerism; however, permanent engraftment of donor bone marrow was not achieved.Survival of donor grafts was remarkably prolonged in the NK cell-depleted group, but transplantation tolerance could not be induced. Our results suggest that NK cell depletion in CP-induced tolerance conditioning has some effect on the induction of donor-specific tolerance.

The current critical shortage of human donor organs has stimulated the feasibility of the xenogenic transplantation, such as swine to primate. We have previously reported the induction of donor-specific tolerance in MHC-disparated recipient mice by using our cyclophosphamide (CP)-induced tolerance conditioning. In this study, we examined the efficacy of our CP-induced tolerance conditioning in xenogenic transplantation model. F344 rats and B10 mice were used as donors and recipients. Recipient mice were treated with donor spleen cells, CP, Busulfan and bone marrow cells, with or without prior NK-cell depletion. Donor mixed chimerism, and the presence of donor reactive T-cell population were analysed by flow cytometry. The survival of the donor skin grafts were observed after the conditioning. Donor mixed chimerism was temporary induced but terminated at 10 weeks after treatments. Donor-specific prolongation of the skin graft survival was observed after the treatments, however, grafts were rejected in the long term. NK-cell depletion, prior to the treatments, did not affect the levels of the mixed chimerism or graft prolongation. The donor-reactive recipient T-cell population was remained the same level as the untreated mice, suggesting the failure of the induction of the central T-cell tolerance. Thus, partial efficacy of our CP-induced tolerance treatments in the rat to mice xenotransplantation was observed. Our results suggested that the additional treatments were required to establish the stable xenogenic tolerance.

In the present study, we have elucidated the efficacy of two cyclophosphamide (CP)-induced tolerance protocols for the induction of B-cell tolerance against Galalpha1-3Galbeta1-4GlcNAc (alphaGal) antigens. alpha1,3-galactosyltransferase-deficient (GalT-/-; H-2(b/d)) mice received with 1 x 10(8) AKR (alphaGal+/+ H-2k) spleen cells (SC) followed by 200 mg/kg CP, or alternatively followed by 200 mg/kg CP, 30 mg/kg Busulfan (BU) and 1 x 10(8) T-cell-depleted AKR bone marrow cells (BMC). The generation of both anti-alphaGal and anti-donor antibodies were completely suppressed, but normal antibody production against third party antigens was observed after BALB/c skin grafting in both groups of GalT-/- mice. In GalT-/- mice, treated with SC and CP, mixed chimerism was not observed. Cellular rejection was observed in grafted donor AKR hearts with an absence of humoral rejection, whereas humoral rejection was observed in untreated GalT-/- mice. On the other hand, long-term mixed chimerism and permanent acceptance of donor AKR skin graft and heart graft were achieved in GalT-/- mice treated with SC, CP, BU and BMC. These results demonstrate the efficacy of classical drug-induced tolerance in the induction of B-cell tolerance against alphaGal antigens. However, induction of stable mixed chimerism was required for the suppression of cellular rejection.

We recently described using cyclophosphamide (CP) plus busulfan (BU) to create drug-induced skin and heart allograft tolerance capable of regularly overcoming fully H-2 mismatched barriers in mice. The present study investigates the intragraft mRNA expressions of Th1 and Th2 cytokines.This method consists of the intravenous (i.v.) injection of 1 x 10(8) allogeneic spleen cells on day 0, the intraperitoneal injection of 200 mg/kg CP and 30 mg/kg BU on day 2, and the i.v. injection of 1 x 10(7) T cell-depleted allogeneic bone marrow cells from the same strain of mice on day 3. Heart grafting (HG) was performed on day 28. Chimerism in the peripheral blood was monitored by flow cytometric (FCM) analysis. The frequency of certain V(beta) families was determined by FCM to assess deletion of donor-reactive T cells. Th1 (interleukin [IL]-2, interferon [IFN]-gamma) and Th2 (IL-4, IL-10) cytokine expression in the heart grafts was analyzed with reverse transcription-polymerase chain reaction.In a fully MHC mismatched combination of B10.D2 (H-2d, IE+) --B10 (H-2b, IE-), B10.D2 heart grafts were accepted permanently in a donor-specific manner, mixed chimerism was observed, and IE-reactive V(beta)11+ T cells were specifically reduced in the periphery from the recipient B10 mice. In the donor B10.D2 heart grafts, there was no accumulation of Th1 (IL-2, IFN-gamma) or Th2 (IL-4, IL-10) cytokines.These results show that the drug-induced tolerance we established can regularly induce long-lasting heart allograft tolerance without intragraft mRNA accumulation of Th1 or Th2.

By using a cyclophosphamide (CP)-induced tolerance system, we previously raised the possibility that the degree of chimerism might determine the induction of heart and skin allograft tolerance. When C3H (H-2k; Thy1.2, Mls-1b) mice were intravenously primed with 1 x 10(8) spleen cells (SCs) from H-2 matched AKR (H-2k; Thy1.1, Mls-1a) mice and then treated intraperitoneally with 200 mg/kg CP, the survival of AKR skin grafts was permanently prolonged in a tolerogen-specific fashion. After this treatment, a minimal degree of mixed chimerism and the clonal destruction of Mls-1a-reactive CD4+Vbeta6+ T cells in the periphery were observed. When AKR SCs and 100 mg/kg CP were used for conditioning, the survival of the AKR skin grafts was mildly prolonged. The clonal destruction of CD4+Vbeta6+ T cells in the periphery was induced and a minimal degree of mixed chimerism was detectable. The degree of mixed chimerism induced with AKR SCs and 200 mg/kg CP was significantly higher than that with AKR SCs and 100 mg/kg CP during the observation. On the other hand, neither skin allograft prolongation nor permanent mixed chimerism could be induced when C3H mice were treated with AKR SCs and 50 mg/kg CP. In order to increase the degree of mixed chimerism, we injected 1 x 10(8) tolerant AKR SCs on day 3 into the recipient C3H mice that had been treated with AKR SCs on day 0 and with 100 mg/kg CP on day 2. The reason that we used tolerant SCs was that untreated AKR SCs caused graft-versus-host disease in most of the recipients. Tolerant AKR SCs were harvested from AKR mice that had been treated with C3H SCs and 200 mg/kg CP 2 weeks earlier, and did not contain regulatory cells. By adoptive transfer, the degree of chimerism was stably and significantly increased in all recipients, and AKR skin graft tolerance was induced in half of the recipients. T-cell-depleted bone marrow cells (BMCs) from untreated AKR mice induced skin allograft tolerance in 83% of recipients. Thus, the present study strongly confirmed the hypothesis that a higher degree of chimerism is required for the induction of skin allograft tolerance in CP-induced tolerance.

A nickel−magnesia solid solution Ni−Mg−O was examined as a catalyst for solar CO2 reforming of methane. The activity was tested in a laboratory-scale transparent (quartz) reactor under direct irradiation of the catalyst by high-flux visible light from a sun-simulator. The 8−11 wt % Ni−Mg−O catalyst gave the high reforming activity or about 100% of chemical conversion, with little coking, under a high-flux irradiation of 890 kW m-2 and at a short residence time of about 0.15 s while passing a 1:1 CH4−CO2 gas mixture at 1 atm. The comparison of the activity data with those obtained in a light-irradiated, nontransparent (steel) reactor showed that the intensification of heat supply by the direct light irradiation of the Ni−Mg−O catalyst leads to considerable reaction rate enhancement. Applying this Ni−Mg−O catalyst, a new type of “catalytically activated” ceramic (alumina) foam absorber was prepared and tested on activity in a laboratory-scale volumetric receiver-reactor using the sun-simulator. This new abs...

For the improvement of the phase-mode parallel multiplier, we propose to use a Booth encoder as a substitute of an AND array. Booth's algorithm is often used for the generation of partial products. The scale of the encoder does not matter for defining its operation frequency because the phase-mode Booth encoder is a pipelined structure. We suggest that the encoder is used as a serial encoder to reduce the number of Josephson junctions (JJ). There are two methods for applying the Booth encoder to the current structure. The first method is shifting multiplicands. The second method is shifting partial products and complementary signals. The total JJ's in both methods are less than the AND array in large scale. The phase-mode Booth encoder with 2.5 kA/cm/sup 2/ Nb/AlO/sub x//Nb junctions can operate over 30 GHz according to the numerical simulations.