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Background The neuronal ceroid lipofuscinosis (NCL) are a group of autosomal recessive neurodegenerative disorders that are characterized by the accumulation of ceroid lipofuscins. The NCLs are categorized into four classes based on the age of onset. Kufs disease is a rare adult-onset NCL caused by mutations in the CLN6 gene, which is rarely observed in the Japanese population. Case We previously reported a case study on a patient with Kufs disease, whose parents had a consanguineous marriage. Later, we observed another unrelated patient with Kufs. Here we present the case and mutational gene report in patients with Kufs disease. Conclusions Gene analysis results of the first patient revealed a homozygous mutation c231C > G, p.Asn77Lys in exon 3 and a homozygous c.297 + 48 A > T mutation in intron 3 in the CLN6 gene. The Asn amino acid is perfectly conserved among species. In silico analysis showed that the mutation is predicted to be probably damaging. Moreover, the second patient with Kufs disease also had the same homozygous mutations. These data suggest that the missense mutation must be pathogenic. Furthermore, the patients had lived in the same district; therefore, they both potentially inherited the founder effect mutations.

CLN6 (Ceroid Lipofuscinosis, Neuronal, 6) is a 311-amino acid protein spanning the endoplasmic reticulum membrane. Mutations in CLN6 are linked to CLN6 disease, a hereditary neurodegenerative disorder categorized into the neuronal ceroid lipofuscinoses. CLN6 disease is an autosomal recessive disorder and individuals affected with this disease have two identical (homozygous) or two distinct (compound heterozygous) CLN6 mutant alleles. Little has been known about CLN6's physiological roles and the disease mechanism. We recently found that CLN6 prevents protein aggregate formation, pointing to impaired CLN6's anti-aggregate activity as a cause for the disease. To comprehensively understand the pathomechanism, overall anti-aggregate activity derived from two different CLN6 mutants needs to be investigated, considering patients compound heterozygous for CLN6 alleles. We focused on mutant combinations involving the S132CfsX18 (132fsX) prematurely terminated protein, produced from the most frequent mutation in CLN6. The 132fsX mutant nullified anti-aggregate activity of the P299L CLN6 missense mutant but not of wild-type CLN6. Wild-type CLN6's resistance to the 132fsX mutant was abolished by replacement of amino acids 297-301, including Pro297 and Pro299, with five alanine residues. Given that removal of CLN6's C-terminal fifteen amino acids 297-311 (luminal tail) did not affect the resistance, we suggested that CLN6's luminal tail, when unleashed from Pro297/299-mediated conformational constraints, is improperly positioned by the 132fsX mutant, thereby blocking the induction of anti- aggregate activity. We here reveal a novel mechanism for dissipating CLN6 mutants' residual functions, providing an explanation for the compound heterozygosity-driven pathogenesis.

CLN6, spanning the endoplasmic reticulum transmembrane, is a protein of unknown function. Mutations in the CLN6 gene are linked to an autosomal recessively inherited disorder termed CLN6 disease, classified as a form of the neuronal ceroid lipofuscinoses (NCL). The pathogenesis of CLN6 disease remains poorly understood due to a lack of information about physiological roles CLN6 plays. We previously demonstrated that CLN6 has the ability to prevent protein aggregate formation, and thus hypothesized that the abrogation of CLN6’s anti-aggregate activity underlies the development of CLN6 disease. To test this hypothesis, we narrowed down the region vital for CLN6’s anti-aggregate activity, and subsequently investigated if pathogenic mutations within the region attenuate CLN6’s anti-aggregate activity toward four aggregation-prone αB-crystallin (αBC) mutants. None of the four αBC mutants was prevented from aggregating by the Arg106ProfsX truncated CLN6 mutant, the human counterpart of the nclf mutant identified in a naturally occurring mouse model of late infantile-onset CLN6 disease. In contrast, the Arg149Cys and the Arg149His CLN6 mutants, both associated with adult-onset CLN6 disease, blocked aggregation of two out of and all of the four αBC mutants, respectively, indicating that CLN6’s anti-aggregate activity is differentially modulated according to the substitution pattern at the same amino acid position. Collectively, we here propose that the graded reduction in CLN6’s anti-aggregate activity governs the clinical course of late infantile- and adult- onset NCL.

An examination of the technical and economic feasibility of the combined mining of the rare-earth element-rich mud (REE-rich mud) and ferromanganese nodules (FN) around Minamitorishima (Marcus) Island in Northwest Pacific is introduced. A previous study showed that the mining of REE-rich mud around Minamitorishima Island was not economically feasible. Therefore, in this study, three changes from the previous mining model to improve its economy are proposed. The first one is combined mining with FN in the area. The second one is introducing a pulp-lifting system that can lift both REE-rich mud and FN at high concentrations through a riser pipe. The third one is the reuse of waste mud and processed slag for construction materials. The economic evaluation results show a change from a slightly negative to quite positive economy depending on the mixing ratio of REE-rich mud and FN in the pulp-lifting. In addition, some technical approaches necessary to realize the combined mining method are introduced.

αB-crystallin (αBC) is a small heat shock protein. Mutations in the αBC gene are linked to α-crystallinopathy, a hereditary myopathy histologically characterized by intracellular accumulation of protein aggregates. The disease-causing R120G αBC mutant, harboring an arginine-to-glycine replacement at position 120, is an aggregate-prone protein. We previously showed that the R120G mutant’s aggregation in HeLa cells was prevented by enforced expression of αBC on the endoplasmic reticulum (ER). To elucidate the molecular nature of the preventive effect on the R120G mutant, we isolated proteins binding to ER-anchored αBC (TMαBC). The ER transmembrane CLN6 protein was identified as a TMαBC's binder. CLN6 knockdown in HeLa cells attenuated TMαBC's anti-aggregate activity against the R120G mutant. Conversely, CLN6 overexpression enhanced the activity, indicating that CLN6 operates as a downstream effector of TMαBC. CLN6 physically interacted with the R120G mutant, and repressed its aggregation in HeLa cells even when TMαBC was not co-expressed. Furthermore, CLN6’s antagonizing effect on the R120G mutant was compromised upon treatment with a lysosomal inhibitor, suggesting CLN6 requires the intact autophagy-lysosome system to prevent the R120G mutant from aggregating. We hence conclude that CLN6 is not only a molecular entity of the anti-aggregate activity conferred by the ER manipulation using TMαBC, but also serves as a potential target of therapeutic interventions.

The importance of manganese nodules, seafloor massive sulfides, and cobalt-rich manganese crusts as future metal sources has been well recognized. However, less geotechnical information of the resources is available to aid the design of mining system. The results of fundamental studies for geotechnical characteristics of the resources and sediments associated with the resources are presented in this chapter. Effects of the characteristics on the design of mining system are examined. Some additional engineering and economic considerations for the design are also discussed.

Calumin is an endoplasmic reticulum (ER)-transmembrane protein, and little is known about its physiological roles. Here we showed that calumin homozygous mutant embryos die at embryonic days (E) 10.5−11.5. At mid-gestation, calumin was expressed predominantly in the yolk sac. Apoptosis was enhanced in calumin homozygous mutant yolk sacs at E9.5, pointing to a possible link to the embryonic lethality. Calumin co-immunoprecipitated with ERAD components such as p97, BIP, derlin-1, derlin-2 and VIMP, suggesting its involvement in ERAD. Indeed, calumin knockdown in HEK 293 cells resulted in ERAD being less efficient, as demonstrated by attenuation in both degradations of a misfolded α1-antitrypsin variant and the ER-to-cytosol dislocation of cholera toxin A1 subunit. In calumin homozygous mutant yolk sac endoderm cells, ER stress-associated alterations were observed, including lipid droplet accumulation, fragmentation of the ER and dissociation of ribosomes from the ER. In this context, the ER-overload response, assumed to be cytoprotective, was also triggered in the mutant endoderm cells, but seemed to fully counteract the excessive ER stress generated due to defective ERAD. Taken together, our findings suggested that calumin serves to maintain the yolk sac integrity through participation in the ERAD activity, contributing to embryonic development.

Bone remodeling is regulated by local factors that regulate bone-forming osteoblasts and bone-resorbing osteoclasts, in addition to hormonal activity. Recent studies have shown that reactive oxygen species (ROS) act as an intracellular signal mediator for osteoclast differentiation. However the role of ROS on osteoblast differentiation is poorly understood. Here, we investigated the impact of ROS on osteoblastic differentiation of MC3T3-E1 cells. Osteogenic induction resulted in notable enhancement of mineralization and expression of osteogenic marker gene alkaline phosphatase, which were accompanied by an increase in ROS production. Additionally, we found that mitochondrial morphology dynamically changed from tubular reticulum to fragmented structures during the differentiation, suggesting that mitochondrial morphological transition is a novel osteoblast differentiation index. The antioxidant N-acetyl cysteine prevented not only ROS production but also mineralization and mitochondrial fragmentation. It is therefore suggested that the ROS-dependent signaling pathways play a role in osteoblast differentiation accompanied by mitochondrial morphological transition.

Many seafloor massive sulfide (SMS) deposits have been discovered in Japan’s exclusive economic zones (EEZ). They have some useful metals and are expected to become future metal resources. In Japan, because of an expensive waste disposal cost, it seems to be difficult to realize the SMS mining. Adding a function of primary waste separation from metal-rich parts of SMS ore on seafloor by a hyrocyclone is proposed to overcome the problem. The water flow structure in a model hydrocyclone is observed in the study at first. Secondly, the performance of separation using differences in specific gravities of particles by the hydrocyclone is experimentally examined. Finally, the application of hydrocyclone in the actual sea area is examined. The result shows that 67% of larger specific gravity are collected and 67% of smaller one are rejected. From the separation efficiency, the hydrocyclone method is recognized to have a high possibility of application in the actual sea area.Copyright © 2016 by ASME

Because of the higher Au, Ag, and Cu contents, seafloor massive sulfides (SMS) have received much attention as future commercial mining targets by private companies and nations. One of them, Solwara 1 Project in Papua New Guinea (PNG), is scheduled to start the commercial mining operation from 2018. Because the mining site is inter-island area and almost no cost is necessary for the waste disposal in PNG, the economy of the mining is expected very well. In contrast with this, because all the SMS distribution sites in Japan locate outer ocean areas and the waste disposal cost on land in Japan is very expensive, the economy of SMS mining in Japan is quite negative. In order to overcome the problems, a self-standing riser with flexible link to the sea surface platform and a primary ore separation on the seafloor prior to the ore lift-up are proposed. The improved SMS mining concept named Japan’s model is examined.Copyright © 2016 by ASME

Although great advancements have been witnessed in treatment results for hematopoietic tumors in recent years, development of secondary malignant tumors induced by anti-cancer drugs still remains a serious issue. We experienced a case of secondary myelodysplastic syndrome (MDS), possibly induced by cyclophosphamide (CY), which was spontaneously resolved by discontinuance of CY. A 24-year-old woman was diagnosed with follicular lymphoma in January 1998: she had developed bulky intra-abdominal lymphadenopathy, with repeated relapse and remission by several chemotherapy treatments. Remission was induced by rituximab, administered at the time of relapse in 2001, followed by administration of 50 mg/day of CY since December 2001 for the prevention of relapse. Anemia and thrombocytopenia developed around January 2003. Bone marrow aspiration revealed abnormality in two lineages and a complicated chromosomal anomaly, and the patient was diagnosed with MDS. Discontinuance of CY and administration of an anabolic steroid improved anemia and thrombocytopenia within 2 years. Bone marrow aspiration in 2006 showed improvement in morphological abnormality and disappearance of chromosomal abnormality.

TRIC channels function as monovalent cation-specific channels that mediate counter ion movements coupled with ryanodine receptor-mediated Ca2+ release from intracellular stores in muscle cells. Mammalian tissues differentially contain two TRIC channel subtypes: TRIC-A is abundantly expressed in excitable cells, whereas TRIC-B is ubiquitously expressed throughout tissues. Here, we report the physiological role of TRIC-B channels in mouse perinatal development. TRIC-B-knockout neonates were cyanotic owing to respiratory failure and died shortly after birth. In the mutant neonates, the deflated lungs exhibited severe histological defects, and alveolar type II epithelial cells displayed ultrastructural abnormalities. The metabolic conversion of glycogen into phospholipids was severely interrupted in the mutant type II cells, and surfactant phospholipids secreted into the alveolar space were insufficient in the mutant neonates. Moreover, the mutant type II cells were compromised for Ca2+ release mediated by inositol-trisphosphate receptors, despite Ca2+ overloading in intracellular stores. Our results indicate that TRIC-B channels take an active part in Ca2+ signalling to establish specialised functions in type II cells and are thus essential for perinatal lung maturation.

Ca(2+) mobilization from intracellular stores is mediated by Ca(2+) release channels, designated ryanodine and IP(3) receptors, and directly regulates important cellular reactions including muscle contraction, endo/exocrine secretion, and neural excitability. In order to function as an intracellular store, the endo/sarcoplasmic reticulum is equipped with cooperative Ca(2+) uptake, storage and release machineries, comprising synergic collaborations among integral-membrane, cytoplasmic and luminal proteins. Our recent studies have demonstrated that junctophilins form junctional membrane complexes between the plasma membrane and the endo/sarcoplasmic reticulum in excitable cells, and that TRIC (trimeric intracellular cation) channels act as novel monovalent cation-specific channels on intracellular membrane systems. Knockout mice have provided evidence that both junctophilins and TRIC channels support efficient ryanodine receptor-mediated Ca(2+) release in muscle cells. This review focuses on cardiac Ca(2+) release by discussing pathological defects of mutant cardiomyocytes lacking ryanodine receptors, junctophilins, or TRIC channels.

Laser amplification using a 12 µm mid-infrared free-electron laser (MIR-FEL) was observed at the Institute of Advanced Energy (IAE), Kyoto University. A 25 MeV electron beam of 17 A peak current was used for the lasing experiment. A beam loading compensation method with an RF amplitude control in the thermionic RF gun was used to extend the macropulse duration against the backbombardment effect in the thermionic RF gun. As a result, an electron beam with a 4 µs duration was generated. A laser output with an intensity 50 times as high as the spontaneous emission intensity was observed. FEL gain was estimated to be 16% from the exponential growth of the laser output signal, and a cavity loss of 2.8% was estimated from the decay of the laser output signal. Three-dimensional (3D) FEL simulation was also performed to achieve the gain saturation in our FEL device.

In B lymphocytes, the B-cell adaptor for phosphatidylinositol 3-kinase (BCAP) facilitates signaling from the antigen receptor. Mice lacking BCAP have a predominantly immature pool of B cells with impaired immune function and increased susceptibility to apoptosis. Unexpectedly, we have found that natural killer (NK) cells from BCAP-deficient mice are more mature, more long-lived, more resistant to apoptosis, and exhibit enhanced functional activity compared with NK cells from wild-type mice. Surprisingly, these effects are evident despite a severe impairment of the immunoreceptor tyrosine-based activation motif-mediated Akt signaling pathway. The seemingly paradoxical phenotype reveals inherent differences in the signals controlling the final maturation of B cells and NK cells, which depend on positive and negative signals, respectively. Both enhanced interferon-γ responses and augmented maturation of NK cells in BCAP-deficient mice are independent of available MHC class I ligands. Our data support a model in which blunting of BCAP-mediated activation signaling in developing NK cells promotes functionality, terminal maturation, and long-term survival.

A mid-infrared free electron laser (FEL) has been constructed for energy science in the Institute of Advanced Energy, Kyoto University. The FEL system consists of a compact S-band Linac and an undulator to generate 4–13 μm coherent mid-infrared radiations. The Linac consists of a 4.5 cell rf gun with a thermionic cathode and a 3-m traveling-wave-type accelerator tube fed by 10 MW and 20 MW rf power, respectively. We have succeeded to produce 40 MeV, 40 mA and 3 μs electron beams. Last December, the 9.2 μm spontaneous emission from the undulator generated by 29.5 MeV electron beams was observed for the first time. Further optimization parameters of both the electron beam and the optical cavity are being pursued for an FEL lasing in the near future.

Despite the importance of phosphoinositide 3-kinase (PI3K) in B-cell development, its activation mechanism still remains elusive. In this study, we show that deletion of both BCAP and CD19 leads to an almost complete block of BCR-mediated Akt activation and to severe defects in generation of immature and mature B cells. The YXXM motifs in BCAP and CD19 are crucial for regulating B-cell development in that mutation of these motifs abrogated their ability to induce BCR-mediated Akt activation as well as to promote B-cell development. Furthermore, the developmental defect in CD19−/−BCAP−/− B cells was partly relieved by introducing a constitutively active form of PI3K or PDK1. Together, our data suggest that BCAP and CD19 have complementary roles in BCR-mediated PI3K activation, thereby, at least in part, contributing to B-cell development.

Japan has a manganese nodule mining claim in the Clarion Clipperton Fracture Zones, the Kuroko-type massive seafloor sulfide deposits (SMS) and cobalt-rich manganese crusts (CMC) in Japan's exclusive economic zone (EEZ) and the continental shelves. Japan needs to use these deep-sea mineral resources as future strategic metal and rare earth element supply sources. Furthermore, the development technologies have wide variations in applying for the other food and energy supply targets in EEZ and continental shelves and the same-type resources of Pacific island nations'.Some current topics in deep-sea mineral resources development and the development technologies are introduced. Possibility and necessity of deep-sea mineral resources development for Japan are discussed.

To determine the contribution of the endoplasmic reticulum (ER) to cell fate decision, we focused on BRI3-binding protein (BRI3BP) residing in this organelle. BRI3BP, when overexpressed, augmented the apoptosis of human embryonic kidney 293T cells challenged with drugs including the anti-cancer agent etoposide. In contrast, the knockdown of BRI3BP reduced the drug-triggered apoptosis. BRI3BP overexpression enhanced both mitochondrial cytochrome c release and caspase-3 activity in etoposide-treated cells. In response to etoposide, the ER reorganized into irregularly shaped lamellae in mock-transfected cells, whereas in BRI3BP-overexpressing cells, such reorganization was not observed. These observations suggest that BRI3BP is involved in the structural dynamics of the ER and affects mitochondrial viability. Taken together, BRI3BP, widely expressed in animal cell types, seems to possess a pro-apoptotic property and can potentiate drug-induced apoptosis.

Junctional membrane complexes (JMCs) generated by junctophilins are required for Ca(2+)-mediated communication between cell-surface and intracellular channels in excitable cells. Knockout mice lacking neural junctophilins (JP-DKO) show severe motor defects and irregular cerebellar plasticity due to abolished channel crosstalk in Purkinje cells (PCs). To precisely understand aberrations in JP-DKO mice, we further analyzed the mutant PCs. During the induction of cerebellar plasticity via electrical stimuli, JP-DKO PCs showed insufficient depolarizing responses. Immunochemistry detected mild impairment in synaptic maturation and hyperphosphorylation of protein kinase Cgamma in JP-DKO PCs. Moreover, gene expression was slightly altered in the JP-DKO cerebellum. Therefore, the mutant PCs bear marginal but widespread abnormalities, all of which likely cause cerebellar motor defects in JP-DKO mice.

We have identified a novel endoplasmic reticulum (ER)-resident protein, named "calumin", which is expressed in various tissues. This protein has a molecular mass of approximately 60 kDa and is composed of an ER-luminal domain rich in acidic residues, a single transmembrane segment, and a large cytoplasmic domain. Biochemical experiments demonstrated that the amino-terminal luminal domain is capable of binding Ca2+ with a high capacity and moderate affinity. In embryonic fibroblasts derived from calumin-knockout mice exhibiting embryonic and neonatal lethality, fluorometric Ca2+ imaging detected insufficient Ca2+ contents in intracellular stores and attenuated store-operated Ca2+ entry. Moreover, the mutant fibroblasts were highly sensitive to cell death induced by ER stress. These observations suggest that calumin plays an essential role in ER Ca2+ handling and is also implicated in signaling from the ER, which is closely associated with cell-fate decision.

This case report describes a patient with a biventricular pacing system in whom right ventricular anodal capture had no hemodynamic benefit. While controlling the ventricular output, three morphologies of the paced QRS complex were obtained: right ventricular stimulation, biventricular stimulation, and biventricular pacing with additional stimulation from the anodal electrode in the right ventricle. While the QRS duration was 5 ms longer, the left ventricular systolic pressure and dP/dtmax during biventricular pacing without anodal capture of the right ventricle were greater than that during biventricular pacing with anodal capture. To avoid useless high output settings, the hemodynamic and clinical data should be compared with and without right ventricular anodal capture in each individual patient.

A preliminary tank experiment for clarifying the effect of micro-bubbles on settling behavior of fine particles was conducted. The behavior of the particles was continuously photographed by a still camera and the images were analyzed by the gray scale intensity. From the results the authors found a suspension effect of micro-bubbles for the settling of fine particles. The effect should be studied in detail for preventing some serious environmental impacts during deep-sea mining.Copyright © 2015 by ASME

We investigated the efficacy of a dose-intensified double-CHOP regimen followed by high-dose chemotherapy with or without peripheral blood stem cell transplantation (PBSCT) in 11 patients with four types of peripheral T-cell lymphoma (PTCL). Three of the 4 patients with unspecified PTCL (PTCLu) achieved complete response (CR); 1 patient relapsed and 1 died of secondary leukemia after consolidation therapy. All angioimmunoblastic T-cell lymphoma (AILT) and subcutaneous panniculitis-like T-cell lymphoma (SPTCL) patients achieved CR; 5 of 6 have remained disease free for more than 3 years. The patient with hepatosplenic lymphoma did not achieve CR even after PBSCT and underwent allogenic bone marrow transplantation (allo-BMT). Thus, our regimen appears to be effective for high-risk AILT and SPTCL. However, allo-BMT should be considered for high-risk of PTCLu and hepatosplenic T-cell lymphoma.

A 65-year-old Japanese woman was diagnosed in 1996 with a pathological fracture of the left femur caused by immunoglobulin D-type myeloma (IgD myeloma). She responded well to combination chemotherapy followed by irradiation. The patient experienced renal failure and became dependent on haemodialysis. In 1999, large plasmacytomas developed in the abdomen and left humerus. The abdominal tumour appeared to induce gastroduodenal ulcers and jejunal obstruction. We initiated irradiation therapy without chemotherapy to prevent further growth of the plasmacytoma, although treatment-resistant gastroduodenal ulcers developed. Continued blood loss from the gastroduodenal ulcers resulted in a deterioration in the patient's health, which prevented successful haemodialysis. An autopsy showed that the plasmacytoma had undergone coagulation necrosis. We conclude that the use of combination chemotherapy with topical irradiation was an acceptable treatment measure against IgD plasmacytoma; irradiation without chemotherapy was the most likely cause of the coagulation necrosis seen in the plasmacytoma at autopsy.

An infrared FEL facility for advanced energy research is under construction at the Institute of Advanced Energy, Kyoto University. An S-band linac with a thermionic RF gun have been installed and measurement of beam quality has been performed until the entrance of the accelerator tube. The energy spread of below 5% and above 100 mA beam current was measured. The emittance of 8 πmm mrad in horizontal and 15 πmm mrad in vertical at the gun section was obtained by the tomographic method. PARMELA calculation well reproduced both in the energy spectrum and in the emittance.

A long beam macropulse is strongly required for free-electron lasers. RF guns can potentially produce high brightness electron beam using a simple and compact system. However, due to a back-bombardment, a cathode surface is overheated. Thus, it is difficult to maintain a constant beam current and beam energy during a macropulse. The use of a photo cathode with a short-pulsed laser is one of the solutions, but it affects the simplicity and the compactness of the RF guns. We studied a mechanism of back-bombardment and experimentally and numerically found that a low energy component of the back-streaming electrons plays an important role in cathode surface heating.

Interactions between accelerated beams and reinjected spent beams in an energy recovery linac (ERL) were studied numerically aiming at an enhanced efficiency and a reduced shielding load. With low injector energy, 1 MeV, the orthodox scheme for reinjecting spent beams, on one hand, is found to result in undesirable beam-loading deviations in an ERL owing to velocity variations of the beams. On the other hand, a counter reinjection scheme is found to be effective for suppressing the deviations, but it is also found to result in an appreciable degradation in a fresh beam's properties due to enhanced beam–beam interactions. To realize the advantages of both of these two schemes, a new combined scheme for an ERL-based FEL is proposed. Also the effects of spent beams’ properties on fresh beams’ emittances are discussed.

Thirty patients with lymphoma of the tonsils were treated in the Nihon University Itabashi Hospital between January 1991 and December 2001. Good prognosis was obtained in stage I tonsillar lymphoma with either radiation or chemotherapy. The 5-year survival rate in stage II disease was 76% with either full cycle chemotherapy or induction chemotherapy followed by radiation. In the latter instances, locoregional recurrences increased but did not impair survival. Otolaryngologists should play an important role in improving survival by diagnosing primary tonsillar lymphoma and by detecting early local recurrences.

In the Free Electron Laser (FEL) experiment, where a long beam macro-pulse is required, energy shift caused by an increase of current density at the cathode surface due to heating by back-streaming electrons is quite serious. It was numerically found that the low-energy component of the back-streaming electrons causes a serious effect. It was also found that the effect can be decreased by applying a transverse magnetic field by calculating time evolution of the cathode surface temperature with a one-dimensional thermal conduction model.

The feasibility of energy recovery with an S-band linac was studied based on two-dimensional particle-in-cell simulations. A 1-m standing-wave accelerating tube with 20 cells was chosen for the numerical model, with a 4.5-cell RF gun as the injector which is to be used for our IR FEL project. For ample reduction of beam energy to the dump with a typical beam energy from the gun of 5.49 MeV, the phase acceptance of the re-injection of the spent beam is found to be ±0.16π rad which corresponds to a feasible longitudinal deviation of ±27 ps. Furthermore, for a lower beam energy to the dump and a higher wall plug efficiency, simulations with a lower beam energy of 2.42 MeV from the gun were carried out. Counter re-injection of the spent beam is found to be effective for compensating longitudinal velocity variations of low-energy beams along the tube, while degradation in the transverse emittance due to enhanced space–charge effect was found.

An infrared FEL facility for bio/chemical energy research is under construction at the Institute of Advanced Energy, Kyoto University. The electron beam of 25–40 MeV with macropulse duration up to 3 μs will be generated by an S-band linac with a thermionic RF gun. Numerical studies to estimate the electron beam parameters and expected FEL gain of the present system have been performed to settle the goal for the system commissioning and the first operational condition. The results show that the present system can provide lasing in the wavelength from 4 to 13 μm by using a 180° arc. However, the macropulse duration is too short to deliver stable FEL for a practical usage.

Mice deficient in the B cell adaptor for phosphoinositide 3-kinase (BCAP) have reduced numbers of mature B lymphocytes, which show defects in cell survival and proliferation. We found here that the NF-kappa B (Rel) pathway was impaired in BCAP-deficient mature B cells and that NF-kappa B target genes, indispensable for cell survival and division, were not induced in response to B cell receptor (BCR) stimulation. Among the NF-kappa B (Rel) family, expression of c-Rel was specifically reduced in BCAP-deficient B cells. Retrovirus-mediated reintroduction of c-Rel restored the pool size of immunoglobulin (Ig)M(lo)IgD(hi) mature B cells in the spleen as well as proliferative responses to BCR stimulation. These results indicate BCAP is essential in the maintenance of mature B cells through functional coupling with c-Rel.

A review is made of the principle and recent development of free-electron lasers (FELs) with emphasis on applications in the infrared wavelength region. Technologies of FEL generation have become mature, and now, it is time to expand the application areas.