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AbstractJapan-US cooperation program TITAN (Tritium, Irradiation and Thermofluid for America and Nippon) started in April 2007 as 6-year project. This is the summary report at the midterm of the project. Historical overview of the Japan-US cooperation programs and direction of the TITAN project in its second half are presented in addition to the technical highlights.

Favorable outcomes after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) are well described for patients who fall within defined tumor criteria. The effectiveness of tumor therapies to maintain tumor characteristics within these criteria or to downstage more advanced tumors to fall within these criteria is not well understood. The aim of this study was to examine the response to transcatheter arterial chemoinfusion (TACI) in HCC patients awaiting LT and its efficacy for downstaging or bridging to transplantation. We performed a retrospective study of 248 consecutive TACI cases in 122 HCC patients at a single U.S. medical center. Patients were divided into two groups: those who met the Milan criteria on initial HCC diagnosis (n 95) and those with more advanced disease (n 27). With TACI treatment, 87 of the Milan criteria group remained within the Milan criteria and 63 of patients with more advanced disease were successfully downstaged to fall within the Milan criteria. In conclusion, TACI appears to be an effective treatment as a bridge to LT for nearly 90 patients presenting within the Milan criteria and an effective downstaging modality for over half of those whose tumor burden was initially beyond the Milan criteria.

Oral anticancer drug treatment represents a significant change to current oncology practice. Support for oral anticancer treatment is driven by issues of pharmacoeconomics, accommodating the need for protracted drug administration for many emerging cytostatic therapies, response to patient preference and in improving patient quality of life. Much focus has concentrated on defining the cellular mechanisms underlying the pharmacokinetic limitations associated with the oral route of administration. However, the potential effects of oral anticancer drugs on gut associated host mediated immunity have been overlooked. Given that the immune system is central for tumour rejection, an assessment of the potential effects oral anticancer drugs may have at this level, and the impact of this on the treatment of gastrointestinal malignancy is of significant clinical importance. P-glycoprotein is a multidrug transporter that contributes to the reduced bioavailability of many orally administered medications. Pglycoprotein achieves this by virtue of its drug efflux capacity at the level of the gut epithelia. P-glycoprotein is also notorious for contributing to the multidrug resistance phenotype observed in many drug refractory human cancers. Likewise, this drug transporter serves a role in the cells of the immune system; particularly in dendritic cell maturation and function. This multifaceted involvement in drug disposition, cancer drug resistance and regulation of the immune response makes P-glycoprotein an attractive target for the optimization of oral anticancer drug treatment strategies. This review introduces and discusses for the first time the potential impact that oral anticancer drugs may have on P-glycoprotein expression and function and the potential consequences of this on dendritic cell function in relation to human cancer. This review also aims to foster a better understanding of the host mediated immunological mechanisms which may be potentially manipulated in cancer patients undergoing oral chemotherapy.

Current cancer chemotherapeutic drugs have limited efficacy due to the fact that tumour cells are a rapidly changing target characterised by genomic instability. Unlike tumour cells, activated endothelial cells (ECs) required for angiogenesis, a process indisputably crucial to tumour growth and metastasis, were originally considered to be ideal therapeutic targets free of drug resistance. Additionally, unlike preclinical studies in mice using inhibitors targeting the powerful EC mitogen- vascular endothelial growth factor (VEGF)- overall survival benefit with anti-VEGF therapy used as monotherapy has yet to be demonstrated in phase III clinical trials. In contrast, VEGF-specific antibodies combined with current chemotherapy have resulted in improved outcomes in certain previously untreated cancers. This has led some researchers to hypothesize that combined treatments targeting other angiogenic molecules besides VEGF, and/or targeting not only ECs but other angiogenic non-EC types, may offer alternative but effective therapeutic options for eradicating malignant tumours. A rational approach to effective anti-angiogenic combination therapy will, however, require further understanding of the molecular and cellular mechanisms which undergird tumour vascularisation. Recent studies involving judicious use of powerful new genetic approaches have provided unprecedented insights into how different molecular and cellular mechanisms cooperate to build, branch and mature the growing vessel network so pivotal to tumour growth and survival. This review covers our current understanding of how the various key players - the tumour cells, stromal cells, endothelial cells and pericytes, and bone-marrowderived haematopoietic and putative endothelial progenitors interact via their cell-derived pro- or anti-angiogenic factors to regulate tumour angiogenesis.

AbstractAs candidate blanket concepts for a U.S. advanced reactor power plant design, with consideration of the time frame for ITER development, we assessed first wall and blanket design concepts based on the use of reduced activation ferritic steel as structural material and liquid breeder as the coolant and tritium breeder. The liquid breeder choice includes the conventional molten salt Li2BeF4and the low melting point molten salts such as LiBeF3and LiNaBeF4(FLiNaBe). Both self-cooled and dual coolant molten salt options were evaluated. We have also included the dual coolant leadeutectic Pb-17Li design in our assessment. We take advantage of the molten salt low electrical and thermal conductivity to minimize impacts from the MHD effect and the heat losses from the breeder to the actively cooled steel structure. For the Pb-17Li breeder we employ flow channel inserts of SiCf/SiC composite with low electrical and thermal conductivity to perform respective insulation functions. We performed preliminary assessments of these design options in the areas of neutronics, thermal-hydraulics, safety, and power conversion system. Status of the R&D items of selected high performance blanket concepts is reported. Results from this study will form the technical basis for the formulation of the U.S. ITER test module program and corresponding test plan.

AbstractTesting blanket concepts in the integrated fusion environment is one of the principal objectives of ITER. Blanket test modules will be inserted in ITER from Day 1 of its operation and will provide the first experimental data on the feasibility of the D-T cycle for fusion. With the US rejoining ITER, the US community has decided to have strong participation in the ITER Test Blanket Module (TBM) Program. A US strategy for ITER-TBM has evolved that emphasizes international collaboration. A study was initiated to select the two blanket options for the US ITER-TBM in light of new R&D results from the US and world programs over the past decade. The study is led by the Plasma Chamber community in partnership with the Materials, PFC, Safety, and physics communities. The study focuses on assessment of the critical feasibility issues for candidate blanket concepts and it is strongly coupled to R&D of modeling and experiments. Examples of issues are MHD insulators, SiC insert viability and compatibility with PbLi, tritium permeation, MHD effects on heat transfer, solid breeder “temperature window” and thermomechanics, and chemistry control of molten salts. A dual coolant liquid breeder and a helium-cooled solid breeder blanket concept have been selected for the US ITER-TBM.

AbstractExperiment of D2permeation through Ni facing with purified Flibe is being carried out under the Japan-US joint research project (JUPITER-II). The experiment is proceeding in the following phases; (i) fabrication and assembly of a dual-probe permeation apparatus, (ii) a single-probe Ni/D2permeation experiment without Flibe, (iii) a dual-probe Ni/D2permeation experiment without Flibe, (iv) Flibe chemical purification by HF/H2gas bubbling, (v) physical purification by Flibe transport through a porous Ni filter, (vi) Ni/Flibe/D2permeation experiment, and (vii) Ni/Flibe/HT permeation experiment. The present paper describes results of the single and dual Ni/D2permeation experiments in detail.

ABSTRACTThe second Japan/US Program on Irradiation Tests for Fusion Research (JUPITER-II) began on April 1, 2001. Part of the collaborative research centers on studies of the molten salt 2LiF-BeF2(also known as Flibe) for fusion applications. Flibe has been proposed as a self-cooled breeder in both magnetic and inertial fusion power plant designs over the last twenty years. The key feasibility issues associated with the use of Flibe are the corrosion of structural material by the molten salt, tritium control in the molten salt blanket system, and safe handling practices and releases from Flibe during an accidental spill. An overview of the experimental program to address the key feasibility issues is presented.

A thick flowing layer of liquid (e.g., flibe–a molten salt, Sn80Li20or Li –liquid metals) protects the structural walls of the field-reversed configuration (FRC) so that they can last the life of the plant even with intense 14 MeV neutron bombardment from the D-T fusion reaction. The surface temperature of the liquid rises as it passes from the inlet nozzles to the exit nozzles due to absorption of line and bremsstrahlung radiation, and neutrons. The surface temperature can be reduced by enhancement of convection near the surface to transport hot surface liquid into the cooler interior. The resulting temperature for evaporation estimates called, Teff, is 660, 714 and 460°C for flibe, SnLi and Li, where thermal conductivity was assumed enhanced by a factor of ten for flibe. The corresponding evaporative flux from the wall must result in an acceptable impurity level in the core plasma. The shielding of the core by the edge plasma is modeled with a 2D transport code for the resulting impurity ions; these ions are either swept out to the distant end tanks, or diffuse to the hot plasma core. The calculations show core impurity levels adequately low for Li and Sn80Li20but is about ten times too large for flibe. An auxiliary plasma between the edge plasma and the liquid wall can further attenuate evaporating flux of atoms and molecules by ionization. The current in this auxiliary plasma might serve as the antenna for the current drive method, which produces a rotating magnetic field.

The purpose of the ALPS program is to identify and evaluate advanced limiter/divertor systems that will enhance the attractiveness of fusion power. The highest priority goals at present are achieving high power density, up to 50 MW/m2, and showing compatibility of plasma-facing surfaces with plasma operation. Personnel representing a wide range of disciplines from a number of institutions are engaged in the program, where an evaluation phase of the program is planned for three years. Successful identification of promising concepts in the evaluation phase should lead to an R&D phase that includes proof-of-principle experiments.

The PULSAR pulsed tokamak power plant design utilizes the outboard shield for thermal energy storage to maintain full 1000 MW(e) output during the dwell period of 200 s. Thermal energy resulting from direct nuclear heating is accumulated in the shield during the 7200 s fusion power production phase. The maximum shield temperature may be much higher than that for the blanket because radiation damage is significantly reduced. During the dwell period, thermal power discharged from the shield and coolant temperature are simultaneously regulated by controlling the coolant mass flow rate at the shield inlet. This is facilitated by throttled coolant bypass. Design concepts using helium and lithium coolant have been developed. Two-dimensional time-dependent thermal hydraulic calculations were performed to confirm performance capabilities required of the design concepts. The results indicate that the system design and performance can accommodate uncertainties in material limits or the length of the dwell period.

The value of T2-weighted fast spin-echo imaging of the musculoskeletal system was assessed in 22 patients with various neoplastic, inflammatory, and traumatic disorders. Images were acquired with high echo number (i.e., echo train length) fast spin-echo (FSE; TR 2000 ms, effective TE 100 ms, echo number 13, lineark-space ordering), conventional spin-echo (SE; TR 2000 ms, TE 100 ms) and gradient-echo (GRE) sequences (TR 600 ms, TE 34 ms, flip angle 25°). Signal intensities, signal-to-noise ratios, contrast, contrast-to-noise ratios, lesion conspicuousness, detail perceptibility, and sensitivity towards image artifacts were compared. The high signal intensity of fat on FSE images resulted in a slightly inferior lesion-to-fat contrast on FSE images. However, on the basis of lesion conspicuity, FSE is able to replace time-consuming conventional T2-weighted SE imaging in musculoskeletal MRI. In contrast, GRE images frequently showed superior lesion conspicuity. One minor disadvantage of FSE in our study was the frequent deterioration of image quality by blurring, black band, and rippling artifacts. Some of these artifacts, however, can be prevented using short echo trains and/or short echo spacings.

As a candidate plasma-facing material for ITER, beryllium has been evaluated with respect to deuterium plasma erosion characteristics using the PISCES-B Mod facility at ion fluxes around 5 X 1021ions s−1m−2in the ion bombarding energy range from 100 to 300 eV. It is found that at elevated temperatures beryllium tends to be contaminated with trace amounts of plasma impurities such as carbon, hydrocarbon, oxygen and nitrogen even under the energetic deuterium plasma bombardment. Among these plasma impurities, carbon and hydrocarbon are observed to form thin films. This carbon deposition effect has made it difficult to interpret the weight loss data in evaluating the erosion yield. A first-order model has been developed to account for the dynamics of this carbon deposition process and has suggested that some surface chemistry effect plays an important role. This surface chemistry effect has been experimentally proved from the observation that carbon deposition can be avoided only at room temperature. Without impurity deposition, the beryllium surface after plasma bombardment is found to be cleaner in oxygen content and smoother in surface topography than the as-received material. Interestingly, however, even without impurity effects, the erosion yield data still tend to agree with beryllium oxide data.

Immunoglobulin (Ig) class switch recombination is associated with the production and splicing of germline IgCH messenger RNA transcripts. Levels of gamma 1 transcripts in mouse spleen sections were assessed by semiquantitative analysis of reverse transcriptase polymerase chain reaction (PCR) products during primary and secondary antibody responses to chicken gamma globulin (CGG). This was correlated with the appearance of CGG-specific B cells and their growth and differentiation to plasma cells. After primary immunization with CGG, gamma 1 switch transcripts appeared after 4 d, peaked at a median of six times starting levels between 10 and 18 d after immunization, and returned to background levels before secondary immunization at 5 wk. By contrast, after secondary challenge with CGG, a sevenfold increase in transcripts occurs during the first d. The level again doubles by day 3, when it is six times that which is seen at the peak of the primary response. After day 4, there was a gradual decline over the next 2-3 wk. Within 12 h of secondary immunization, antigen-specific memory B cells appeared in the outer I zone and by 24 h entered S phase, presumably as a result of cognate interaction with primed T cells. Over the next few hours, they migrated to the edge of the red pulp, where they grew exponentially until the fourth day, when they synchronously differentiated to become plasma cells. The same pattern was seen for the migration, growth, and differentiation of virgin hapten-specific B cells when CGG-primed mice were challenged with hapten protein. The continued production of transcripts after day 3 indicates that switching also occurs in germinal centers, but in a relatively small proportion of their B cells. The impressive early production of switch transcripts during T cell-dependent antibody responses occurs in cells that are about to undergo massive clonal expansion. It is argued that Ig class switching at this time, which is associated with cognate T cell-B cell interaction in the T zone, has a major impact on the class and subclasses of Ig produced during the response.