Open String on Symmetric Product

We develop some basic properties of the open string on the symmetric product which is supposed to describe the open string field theory in discrete lightcone quantization (DLCQ). After preparing the consistency conditions of the twisted boundary conditions for Annulus/M\"obius/Klein Bottle amplitudes in generic non-abelian orbifold, we classify the most general solutions of the constraints when the discrete group is $S_N$. We calculate the corresponding orbifold amplitudes from two viewpoints -- from the boundary state formalism and from the trace over the open string Hilbert space. It is shown that the topology of the world sheet for the short string and that of the long string in general do not coincide. For example the annulus sector for the short string contains all the sectors (torus, annulus, Klein bottle, M\"obius strip) of the long strings. The boundary/cross-cap states of the short strings are classified into three categories in terms of the long string, the ordinary boundary and the cross-cap states, and the ``joint'' state which describes the connection of two short strings. We show that the sum of the all possible boundary conditions is equal to the exponential of the sum of the irreducible amplitude -- one body amplitude of long open (closed) strings. This is typical structure of DLCQ partition function. We examined that the tadpole cancellation condition in our language and derived the well-known gauge group $SO(2^{13})$.Comment: 56 pages, 11 figures, Late

Adsorption of Saliva Related Protein on Denture Materials: An X-Ray Photoelectron Spectroscopy and Quartz Crystal Microbalance Study

The aim of this study was to evaluate the difference in the adsorption behavior of different types of bovine salivary proteins on the PMMA and Ti QCM sensors are fabricated by spin-coating and sputtering onto bare QCM sensors by using QCM and X-ray photoelectron spectroscopy (XPS). SPM, XPS, and contact angle investigations were carried out to determine the chemical composition and surface wettability of the QCM surface. We discuss the quality of each sensor and evaluate the potential of the high-frequency QCM sensors by investigating the binding between the QCM sensor and the proteins albumin and mucin (a salivary-related protein). The SPM image showed a relatively homogeneous surface with nano-order roughness. The XPS survey spectra of the thin films coated on the sensors were similar to the binding energy of the characteristic spectra of PMMA and Ti. Additionally, the amount of salivary-related protein on the PMMA QCM sensor was higher than those on the Ti and Au QCM sensors. The difference of protein adsorption is proposed to be related to the wettability of each material. The PMMA and Ti QCM sensors are useful tools to study the adsorption and desorption of albumin and mucin on denture surfaces

N-methyl-N-nitrosourea(MNU)により実験的に誘発したラット小頭症児の行動奇形学的研究

近年，アルコール，向精神薬，放射線などが，ヒトで行動奇形を誘発する外因となることが明らかになったことから，動物実験においても出生後の行動・機能を検索することが重要視されるようになった。　しかし，実験動物では，化学物質の暴露により神経系の形態学的発生異常が成立した時に，行動にはどのような異常が起こるかという知見に乏しく，実験的な行動奇形学の方法論は，いまだに確立されていないのが現状である。このことから実験行動奇形学の課題の一つとして中枢神経系の巨視的ないし微視的異常と機能障害との関連を調べることが挙げられている。　本研究は，中枢神経系に選択的な催奇形作用を示すことで知られるN-methyl-N-nitrosourea(MNU)を妊娠中の母ラットに投与して誘発した小頭症(小脳症)児の行動を検索し，中枢神経系の巨視的な障害とその障害によって発現する行動異常との関連性を明らかにすることを目的とした。　第1章　ラット胎児に及ぼすMNUの影響　胎児の器官形成期にあたる妊娠時期(妊娠7～17日)の母ラットに3用量(2.5，5，10mg/kg)のMNUを連日，腹腔内投与し，胎児の発生，出生児の発育に及ぼす影響を検討した。その結果，10mg/kgの投与では全着床胚が死亡すること，5mg/kg以下の投与では胎児体重が減少し，ほぼ全例に外表異常として偏平な頭頂部がみられること，この外表異常は終脳の形成不全(小頭症)に基づくこと，5mg/kgの投与では出生児が，生後に生存しないことが判った。また，2.5mg/kgの投与では出生した児はほぼ全例が生育し，用量を選択すれば小頭症の出生児でも生後の長期生存が可能なことが判った。この小頭症児では行動検査の結果，顕著な迷路学習能力の障害および情動性の変化を示唆する寡動傾向がみられた。　第2章　ラット胎児の脳に及ぼすMNUの影響　詳細な行動・機能検査を行うための前段実験として器官形成期にあたる妊娠時期(妊娠7～17日)のいずれか1日に1用量(5mg/kg)のMNUを投与し，胎児とその脳の発生に対する発生時期依存的な影響の有無を検討した。その結果，胎児脳の障害感受期は，妊娠10日以降にあり，感受部位は，中脳-終脳-嗅葉-後脳の順に互いに交錯しながら移行すること，最も強く障害を受ける部位は終脳であることおよび終脳の障害感受期は妊娠12～15日にあり，最障害感受期は妊娠13日にあることが判った。また，妊娠13日に2mg/kgを単回処理した結果，胎児には他の奇形を伴わずに用量依存的な終脳の形成不全が生じることも明らかとなった。　第3章　MNUによって誘発された小頭症ラットの行動異常　そこで新生児の脳，特に終脳が最も障害を受ける時期(最障害感受期：妊娠13日)を選び，MNUの5mg/kgおよび2mg/kgを単回投与して誘発した小頭症児について生後1日から22日(離乳日)に神経行動学的発達検査(初期行動発達検査)を行い，生後4週齢から10週齢に情動性，迷路学習および回避学習能力の検査を行った。その結果，初期行動発達検査では5mg/kg処理の小頭症児に脊髄反射・姿勢反応の発達遅延，生後早期の異常な反射亢進ならびに運動遂行中の四肢の位置きめ能力について測定障害を疑わせる異常がみられた。また，歩行および遊泳行動においては肢の運動に通常ではみられない左右両側肢の同期運動が発現し，この異常は2mg/kg処理の小頭症児においても低率ながら認められた。この他に2mg/kg処理の小頭症児にみられた変化は発達の遅延のみであった。離乳後の情動性の検査では，2mg/kg処理の小頭症児で寡動傾向，5mg/kg処理の小頭症児で新奇刺激に対する過敏反応がみられた。迷路学習能力は，5mg/kg処理において高度に，2mg/kg処理では軽度に障害された。回避学習能力の検査では，5mg/kg処理の小頭症児は全試行において，2mg/kg処理の小頭症児は初期の試行において異常に高い回避反応率を示した。これらの結果から，脳の最障害感受期にMNU5mg/kgを投与しても誘発された小頭症ラットは充分に長期生存が可能なこと，および特定の行動については用量依存的な反応が行動異常として成立することが明らかとなった。　第4章　各投与時期に誘発された小頭症ラットの初期行動発達の異常　上の実験において初期行動発達にみられた小頭症児の行動異常が，MNUによって特異的に，あるいは妊娠13日の処理に限って誘発される異常であるかを調べる目的で，終脳の障害感受期間である妊娠12日～15日のいずれか1日にMNUの5mg/kg，あるいは小頭症を誘発することで知られるmethylazoxymethanol(MAM)の40mg/kgを単回投与し，得られた出生児の初期行動発達を比較した。その結果，MNU，MAM処理の間で生起した行動異常に差は認められなかった。一方，処理時期が異なると，特に随意的要素の高い行動に生じた異常には著しい差が認められた。すなわち，妊娠12，13および14日処理の小頭症児では，歩行あるいは遊泳行動時に異常な左右両側肢の同期運動が生起し，この異常は妊娠12日処理の小頭症児で前肢に，妊娠13日および14日処理の小頭症児で後肢に支配的に発現する新知見が得られた。また，この異常は，妊娠14日処理の小頭症児では生後早期に回復したが，妊娠12および13日処理の小頭症児では離乳時に至っても消失しなかった。上位中枢からの投射により抑制的制御を受けるといわれる脊髄反射および姿勢反応の一部は，処理時期と無関係に生後早期に亢進していた。また，その多くは，発達が遅延する傾向にあったが，いずれも最終的には正常に生起した。これらの結果から終脳の形成が障害されると処理時期とは無関係に，出生児の感覚-運動統御機構の機能構築は遅延すること，随意運動中に発現する肢の異常運動の責任障害部位は上位中枢にあることおよびその責任障害部位は処理日に対応して異なる可能性が示唆された。　第5章　小頭症の程度と小頭症ラットの高次行動の異常　妊娠13日に5段階濃度(1，2，3，4および5mg/kg)のMNUを処理して得た出生児について，離乳後に情動性，自発運動量(走行運動量)，迷路学習能力および回避学習能力の検査を行い，成立した小頭症の程度と高次行動異常との関連性を検討した。対照群に対する各処理群の脳重量の比は，95～55%の範囲で用量依存的に減少した。情動性の検査では，全処理群の小頭症児で紛移動距離および立ち上がり回数の増加が，また4および5mg/kg処理の小頭症児で反応潜時の減少が，5mg/kg処理の小頭症児で排尿数の増加および後肢の歩行運動異常がみられた。自発運動量は全処理群の小頭症児で明瞭に増加し，とくに5mg/kgの処理で顕著であった。迷路学習および回避学習能力の異常は，5mg/kg処理の小頭症児においてのみみられた。これらの結果から，終脳の最障害感受期に誘発された小頭症ラットの基本的な行動の変化は，活動性の増大であり，加えて終脳形成障害の程度に応じた用量依存的な情動性の変化が重複していることが判った。また軽度の小頭症では明らかな学習能力の障害は成立しないことが示唆された。　第6章　各投与時期に誘発された小頭症ラットの高次行動の異常　妊娠12，13，14および15日の各日にMNUを処理し，得られた小頭症児について情動性，自発運動量(走行運動量)，迷路学習能力および回避学習能力を検査した。その結果，出生児の終脳の障害程度には，12日14日>15日の関係がみられ，15日の処理による終脳形成不全が，他の処理日群と比較して最も軽度であった。情動性の検査においては，13日処理の行動特性が多動であるのに対し，12日および15日処理の特性はともに寡動であった。しかし，15日処理ではこの反応が動物の積極的な対応行動と推察されたのに対し，12日処理の小頭症児では生理的反応亢進が随伴しており，寡動傾向は情動性の変化を示唆していた。自発活動性についても処理日の差は明らかで，12日処理で寡動傾向，15日処理で無変化であった。迷路学習は，12日，13日および15日処理において障害されていたが，脳重量の低下の程度からみて15日処理が相対的に最も高度に障害されているものと考えられた。したがって妊娠12日～15日に限れば，迷路学習の最障害感受期は，妊娠15日にあると結論される。一方，回避学習能力の異常がみられたのは，妊娠13日処理の小頭症児のみであり，この課題の遂行に係わる中枢神経系の責任部位が，迷路学習のそれとはかなり異なることが示唆された。14日処理の小頭症児ではいずれの行動検査においても顕著な変化はみられず，14日処理の小頭症児における行動の変容は，不明であった。　以上，本研究の結果からMNUの胎生期投与に起因する中枢神経系の巨視的な発生障害は，妊娠12日～15日の短期間においてもその処理強度および処理時期の差異により，異なる行動異常を誘発することが明らかとなった。また，動物の活動性は中枢神経系の障害を敏感に反映すること，学習能力の障害には終脳の障害量より障害を受ける時期が重要に関与していること，ならびに神経行動学的発達検査は，生後，早期の段階で敏感に行動異常を捉え，神経系に生じた障害の性質を推定しえる点で有用性が高いことが示唆された。従って生後の行動検索においては，動物の活動性，学習能力および神経行動学的発達の検索が重要と判断される。Recently, documented evidence of behavioral disorder in humans who prenatally exposed to a variety of agents, including alcohol, psychotropic drugs and x-irradiation, strongly indicates the need for behavioral evaluation in the animal experiments, e.g. the safety assessment of new drugs or chemicals. However, in experimental animals, reproducible and available testing method to evaluate behavioral teratogenicity has not been established, since a few evidences have so far specified relationships between developmental anomalies in the nervous system and behavioral responses in the postnatal period. Therefore, it has been pointed out that to characterize the behavioral disorders resulting from macroscopic or microscopic brain disorders makes an advantage to animal experiments on behavioral teratology. In the present study, micrencephalic rats were obtained from dams treated prenatally with N-methyl-N-nitrosourea (MNU), one of the known agents having a teratogenic action selectively on the central nervous system, and neurobehavioral functions in the micrencephalic rats were examined in order to characterize the behavioral disorders in relation to the gross brain disorders. 1. The effect of MNU on the development of rat fetuses. The effect of MNU was assessed on the fetal and postnatal development of rat offspring by giving the drug (2.5, 5 and 10 mg/kg/day) intraperitoneally to pregnant rats during the period of embryonic organogenesis (day 7 to day 17 of gestation). The results were as follows; 10 mg/kg of MNU caused total implantation losses in all dams. No significant increase in the intrauterine mortality was observed up to 5 mg/kg. Fetuses exposed to 2.5 and 5 mg/kg showed a decrease in body weight. Most of these fetuses revealed flat head as external abnormality that resulted from the small cerebrum involving sever telencephalic hypoplasia (micrencephaly). As for the neonates, none of neonates exposed to 5 mg/kg survived after birth. However, the postnatal viability was not altered by the exposure to 2.5 mg/kg. This indicates that when appropriate doses are chosen, neonates can survive over a long period though they have sever micrencephaly. By the behavioral tests conducted during postweaning period, the pups exposed to 2.5 mg/kg revealed remarkable maze learning deficit and hypoactivity that possibly reflected an alteration in emotionality. 2. The effect of MNU on the brain development of rat fetuses. As a preliminary study on behavioral teratogenic action of MNU, pregnant rats were once treated with 5 mg/kg of MNU on one of gestational days (GD) from 7 to 17, and stage-specific teratogenicity on the developing brain was evaluated in the fetuses. The vulnerability of the developing fetal brain was confirmed from GD10 to GD17. The sensitive part showing hypoplastic change in the brain was transferred, and overlapped each other, from mesencephalon, telencephalon, olfactory lobe and metencephalon in that order, with the advance of the day of treatment. Among these brain areas, the telencephalon was the most sensitive area and its vulnerability occured from GD12 to GD15. GD13 was the period of maximum vulnerability of the telencephalon. Furthermore, additional examination where the rats were given 2 mg/kg of MNU on GD13 indicated that the micrencephaly was dose-dependently induced in the fetuses without other malformations. 3. Behavioral disorders in the micrencephalic rat induced by the MNU-treatment. On GD13, the maximum vulnerable stage of telencephalon, micrencephalic rats were induced by the treatment with 2 or 5 mg/kg of MNU and they were subjected to a variety of tests for neurobehavioral ontogeny (behavioral development tests) during the suckling period, and for emotionality, maze and active avoidance learning in the postweaning period, from 4 to 10 weeks of age. By the tests for neurobehavioral ontogeny, micrencephalic pups exposed to 5 mg/kg showed retardation in ontogeny of spinal reflexes and postural reactions, early hyperreflexia, and dysmetric abnormality in the limbs. Furthermore, as an distinctively impaired behavior, paired pelvic limbmovement was observed in the pups while walking or swimming. A few pups exposed to 2 mg/kg showed similar impairement. However, most of 2 mg/kg pups did not show other behavioral abnormalities except for slight retardation in the neurobehavioral ontogeny. As for the tests conducted after weaning, neophilic hyperreactivity of the 5 mg/kg pups and slight hypoactivity of the 2 mg/kg were observed by the test for emotionality. Maze learning ability was impaired remarkably in the 5 mg/kg pups and slightly in the 2 mg/kg. By the active avoidance tasks, abnormal high response was occured in the 5 mg/kg pups at all through sessions and at early in the 2 mg/kg. These results indicate that the MNU-treatment could induce specific type of behavioral disorders in the rat offspring but the type and magnitude of the behavioral teratogenic effect probably depend on the dose of MNU. 4. Early neurobehavioral disorders in the micrencephalic rats. Micrencephalic neonatal pups were obtained from pregnant rats once treated with 5 mg/kg of MNU or 40 mg/kg of methylazoxymethanol (MAM), as a reference compound, on GD12, 13, 14 or 15. They were reared by their own mothers and were subjected to various neurobehavioral tests during the suckling period, days 0 to 22 after birth. The brain weights in the MNU- and MAM-treated pups on postnatal day 22 were significantly less than those in the control pups. These mi0rencephalic pups were retarded in neurobehavioral ontogeny. By several tests, each of them showed an impaired performance such as paired limb movement, clumsy locomotion or hyperreflexive reaction. These behavioral disorders appeared different according to the day of treatment, without any substantial difference between the test compounds, MNU and MAM. The findings suggest that the different neurobehavioral characteristics in the micrencephalic pups may reflect their different brain disorders induced by the test compounds given on the different period of the treatment. 5. Degree of micrencephaly and disorders of the integrated behavior. Microcephalic offspring were obtained from rats treated with MNU at a dose of 1, 2, 3, 4 or 5 mg/kg on GD13. Brain weights of weanlings in the MNU treated groups were significantly reduced to approximately 95%, 85%, 80%, 70% and 55% of the controls, respectively, in the 1 to 5 mg/kg groups. Open-field test (for emotionality), wheel cage activity test (for spontaneous activity levels), Biel type water T-maze test (for maze learning ability) and shuttle-box avoidance test (for avoidance learning ability) were subsequently performed to determine the behavioral alterations in these offspring at 4, 5-6, 6-7 and 7-8 weeks of age, respectively. In the open-field test, the scores of ambulation and rearing significantly increased in all treated groups and the latent period significantly decreased in the groups treated with 3 mg/kg or more. Moreover, a significant increase of urination and a significant decrease of grooming and uncoordinated movement of the pelvic limbs were observed in the 5 mg/kg group. Spontaneous motor activity in the wheel cage also increased in all treated groups. In the water T-maze test and shuttle-box avoidance test, however, alteration in learning ability was detected only in the 5 mg/kg group. These findings suggest that hyperactivity is the fundamental disorder in these microcephalic rats and alteration of emotionality occurs dose-dependently. Threshold level on the learning deficit is higher than that on any other disorders. 6. Disorders of the integrated behavior in the micrencephalic rats. To determine the stage specific effect of MNU on the integrated behavior, micrencephalic rats were obtained from dams once treated with 1, 3 or 5 mg/kg of MNU on GD12, 13, 14 or 15 and their emotionality, maze and active avoidance learning, and spontaneous locomotor activity levels were examined during the postweaning period, from 4 to 10 weeks of age. The brain disorders appeared different according to the day of treatment, and GD15-treatment caused the least effect. As for the behavioral disorders, by the test for emotionality, a hyperreactive response was noticed in the GD13-treated pups and, in contrast, both GD12- and GD15-treated pups showed marked hyporeactivity. However, spontaneous locomotor activity in the GD15-treated pups was equivalent to the control levels, though other GD12- and GD13-treated pups revealed corresponding response to their emotionality. The period of maximum susceptibility of maze learning was GD15 and that of avoidance learning was GD13. This result seems that localization of lesions in the central nervous system corresponding to the maze learning deficit differs from that to the active avoidance learning. No dose-related change was examined in any behavioral test in the GD14-treated pups. Generally, the above findings suggest that the type and magnitude of behavioral teratogenic effect of MNU depend on the stage and dose of the treatment, even in the sort period of organogenesis, from GD12 to GD15. Furthermore, the tests for neurobehavioral ontogeny, learning and activity would be useful to evaluate behavioral teratogenicity.博士(獣医学)麻布大

Meta-Stable Supersymmetry Breaking Vacua on Intersecting Branes

We identify configurations of intersecting branes that correspond to the meta-stable supersymmetry breaking vacua in the four-dimensional N=1 supersymmetric Yang-Mills theory coupled to massive flavors. We show how their energies, the stability properties, and the decay processes are described geometrically in terms of the brane configurations.Comment: 15 pages, 4 figure

Influence of exposure to new circumstances on pharmacokinetics of plasma drugs concentrations in rats.

The influences of emotional changes induced by being exposed to a new environment on the pharmacokinetics of plasma drug concentration were studied in male Wistar rats. Transfer from a familiar home cage to a new home cage was considered to induce psychological (non-physical) emotional changes. First, nicorandil and zonisamide, drugs that act on the peripheral system and central nervous systems, were used, respectively. Immediately after oral administration of nicorandil (10 mg/kg) or zonisamide (50 mg/kg), the animals were transferred to new home cages. Plasma nicorandil and zonisamide concentrations were determined by high-performance liquid chromatography at 1 and 4 h after administration. Plasma nicorandil concentration in the group transferred to new home cages was significantly decreased relative to levels in the non-transferred control group. However, zonisamide concentrations were unchanged. These findings suggest that the pharmacokinetics of nicorandil, but not those of zonisamide, tend to be influenced by non-physically induced emotional changes.</p

A pilot trial of an online guided self-help cognitive behavioral therapy program for bulimia nervosa and binge eating disorder in Japanese patients

BackgroundThe purpose of this study was to develop an internet-based Guided Self-Help CBT (iGSH-CBT) for Bulimia Nervosa (BN) / Binge Eating Disorder (BED) for Japanese patients and to test its feasibility.MethodsA single-arm feasibility study. After baseline assessment, patients underwent a 16-week iGSH-CBT program, our Japanese adaption of the European-based Salut BN program. During the treatment period, weekly email support from trained counselors was provided. Evaluations were performed at baseline, after 8 weeks, at the end of the 16-week intervention, and at 2 months after treatment had ended. The primary outcome measure was the change in the weekly frequency of objective binging. Secondary outcomes were the change in the weekly frequency of objective purge episodes, responses on self-report questionnaires of the frequencies of binging and purging, psychopathological characteristics of eating disorders found on BITE, EDE-Q, EDI-2, HADS and EQ-5D, measurements of motivation, and completion of intervention (vs. dropout).ResultsParticipants were 9 female outpatients with BN (n = 5) or BED (n = 4), of whom 8 (88.9%) attended the assessment at the end of the 16-week intervention. Mean age was 28 years (SD = 7.9). Percent change of the weekly frequency of objective binging was -4.40%, and at the end of the 16-week intervention 25% of the participants had achieved symptom abstinence.ConclusionsNo adverse events were observed during the treatment period and follow-up, and the implementation and operation of the program could be performed without any major problems, confirming the feasibility of iGSH-CBT for BN and BED for Japanese patients. Although no significant change was observed in the weekly frequency of objective binging, the abstinence rate from bulimic behaviors of those who completed the assessments was 25.0% at the end of treatment, and the drop-out rate was 11.1%. iGSH-CBT may be an acceptable and possibly even a preferred method of CBT delivery for Japanese patients with BN or BED, and our Japanese adaptation of Salut BN seems feasible.Trial registrationUMIN, UMIN000031962. Registered 1 April 2018 - Retrospectively registered, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R00003633

Mechanisms Underlying the Comorbidity of Schizophrenia and Type 2 Diabetes Mellitus

The mortality rate of patients with schizophrenia is high, and life expectancy is shorter by 10 to 20 years. Metabolic abnormalities including type 2 diabetes mellitus (T2DM) are among the main reasons. The prevalence of T2DM in patients with schizophrenia may be epidemiologically frequent because antipsychotics induce weight gain as a side effect and the cognitive dysfunction of patients with schizophrenia relates to a disordered lifestyle, poor diet, and low socioeconomic status. Apart from these common risk factors and risk factors unique to schizophrenia, accumulating evidence suggests the existence of common susceptibility genes between schizophrenia and T2DM. Functional proteins translated from common genetic susceptibility genes are known to regulate neuronal development in the brain and insulin in the pancreas through several common cascades. In this review, we discuss common susceptibility genes, functional cascades, and the relationship between schizophrenia and T2DM. Many genetic and epidemiological studies have reliably associated the comorbidity of schizophrenia and T2DM, and it is probably safe to think that common cascades and mechanisms suspected from common genes' functions are related to the onset of both schizophrenia and T2DM. On the other hand, even when genetic analyses are performed on a relatively large number of comorbid patients, the results are sometimes inconsistent, and susceptibility genes may carry only a low or moderate risk. We anticipate future directions in this field