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Methodological constraints have limited our ability to study protein corona formation, slowing nanomedicine development and their successful translation into the clinic. We determined hard and soft corona structural properties along with the corresponding proteomic compositions on liposomes in a label-free workflow: surface plasmon resonance and a custom biosensor for in situ structure determination on liposomes and corona separation, and proteomics using sensitive nanoliquid chromatography tandem mass spectrometry with open-source bioinformatics platforms. Undiluted human plasma under dynamic flow conditions was used for in vivo relevance. Proof-of-concept is presented with a regular liposome formulation and two light-triggered indocyanine green (ICG) liposome formulations in preclinical development. We observed formulation-dependent differences in corona structure (thickness, protein-to-lipid ratio, and surface mass density) and protein enrichment. Liposomal lipids induced the enrichment of stealth-mediating apolipoproteins in the hard coronas regardless of pegylation, and their preferential enrichment in the soft corona of the pegylated liposome formulation with ICG was observed. This suggests that the soft corona of loosely interacting proteins contributes to the stealth properties as a component of the biological identity modulated by nanomaterial surface properties. The workflow addresses significant methodological gaps in biocorona research by providing truly complementary hard and soft corona compositions with corresponding in situ structural parameters for the first time. It has been designed into a convenient and easily reproducible single-experiment format suited for preclinical development of lipid nanomedicines.

Otto K. Deutelmoser: Die Ehrbarkeit und andere württembergische Eliten. Hohenheim Verlag Stuttgart 2010. 248 Seiten mit zahlreichen Abbildungen. Pappband € 24,80. ISBN 978-3-89850-201-6

Light-activated liposomes permit site and time-specific drug delivery to ocular and systemic targets. We combined a light activation technology based on indocyanine green with a hyaluronic acid (HA) coating by synthesizing HA&ndash, lipid conjugates. HA is an endogenous vitreal polysaccharide and a potential targeting moiety to cluster of differentiation 44 (CD44)-expressing cells. Light-activated drug release from 100 nm HA-coated liposomes was functional in buffer, plasma, and vitreous samples. The HA-coating improved stability in plasma compared to polyethylene glycol (PEG)-coated liposomes. Liposomal protein coronas on HA- and PEG-coated liposomes after dynamic exposure to undiluted human plasma and porcine vitreous samples were hydrophilic and negatively charged, thicker in plasma (~5 nm hard, ~10 nm soft coronas) than in vitreous (~2 nm hard, ~3 nm soft coronas) samples. Their compositions were dependent on liposome formulation and surface charge in plasma but not in vitreous samples. Compared to the PEG coating, the HA-coated liposomes bound more proteins in vitreous samples and enriched proteins related to collagen interactions, possibly explaining their slightly reduced vitreal mobility. The properties of the most abundant proteins did not correlate with liposome size or charge, but included proteins with surfactant and immune system functions in plasma and vitreous samples. The HA-coated light-activated liposomes are a functional and promising alternative for intravenous and ocular drug delivery.

Despite the success of immune checkpoint inhibitors in the clinic, they only benefit a fraction of patients. A theoretical strategy to increase efficacy would be to enhance such antibodies with Fc-mediated effector mechanisms. Current IgG1 antibodies are excellent activators of natural killer cells yet neglect a crucial effector population, neutrophils. Hence, we designed a cross-hybrid Fc-fusion peptide against PD-L1 able to elicit simultaneously effector mechanisms of an IgG1 but also IgA1, consequently activating neutrophils, in order to combine multiple effector mechanisms. Moreover, to prevent toxicities, these Fc-fusion peptides were cloned in oncolytic adenoviruses whose replication is restricted to the tumor. Our oncolytic adenoviruses were able to selectively infect tumor cells, secrete the cross-hybrid Fc-fusion peptides able to bind to PD-L1 and activate multiple immune components enhancing tumor cytotoxicity compared to FDA-approved immune checkpoint inhibitors. We validated this in various human and murine cancer cell lines and also renal cell carcinoma patient derived organoids from four patients. In conclusion, our cross-hybrid Fc-fusion peptides demonstrate that activating multiple immune effector populations increases tumor cytotoxicity potentially leading to improved clinical outcomes. Citation Format: Firas Hamdan, Erkko Ylösmäki, Jacopo Chiaro, Yvonne Giannoula, Maeve Long, Manlio Fusciello, Sara Feola, Beatriz Martins, Michaela Feodoroff, Gabriella Antignani, Otto Kari, Moon Hee Lee, Petrus Järvinen, Harry Nisen, Anna Kreutzman, Satu Mustjoki, Thomas G McWilliams, Mikaela Grönholm, Vincenzo Cerullo. Characterization in patient derived tumor organoids of novel oncolytic adenoviruses expressing enhanced cross-hybrid IgGA Fc PD-L1 inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1867.

This paper presents a performance study of deep borehole heat exchangers. The coaxial borehole heat exchanger (BHE) has been selected because for the present conditions it has a better performance ...

In this paper a simplified and not fully discretized numerical model is used to simulate the performance of a non-grouted (water filled) borehole heat exchanger (BHE). The model enables simulation ...

Biohybrid nanosystems represent the cutting‐edge research in biofunctionalization of micro‐ and nano‐systems. Their physicochemical properties bring along advantages in the circulation time, camouflaging from the phagocytes, and novel antigens. This is partially a result of the qualitative differences in the protein corona, and the preferential targeting and uptake in homologous cells. However, the effect of the cell membrane on the cellular endocytosis mechanisms and time has not been fully evaluated yet. Here, the effect is assessed by quantitative flow cytometry analysis on the endocytosis of hydrophilic, negatively charged porous silicon nanoparticles and on their membrane‐coated counterparts, in the presence of chemical inhibitors of different uptake pathways. Principal component analysis is used to analyze all the data and extrapolate patterns to highlight the cell‐specific differences in the endocytosis mechanisms. Furthermore, the differences in the composition of static protein corona between naked and coated particles are investigated together with how these differences affect the interaction with human macrophages. Overall, the presence of the cell membrane only influences the speed and the entity of nanoparticles association with the cells, while there is no direct effect on the endocytosis pathways, composition of protein corona, or any reduction in macrophage‐mediated uptake.

Biohybrid nanosystems represent the cutting‐edge research in biofunctionalization of micro‐ and nano‐systems. Their physicochemical properties bring along advantages in the circulation time, camouflaging from the phagocytes, and novel antigens. This is partially a result of the qualitative differences in the protein corona, and the preferential targeting and uptake in homologous cells. However, the effect of the cell membrane on the cellular endocytosis mechanisms and time has not been fully evaluated yet. Here, the effect is assessed by quantitative flow cytometry analysis on the endocytosis of hydrophilic, negatively charged porous silicon nanoparticles and on their membrane‐coated counterparts, in the presence of chemical inhibitors of different uptake pathways. Principal component analysis is used to analyze all the data and extrapolate patterns to highlight the cell‐specific differences in the endocytosis mechanisms. Furthermore, the differences in the composition of static protein corona between naked and coated particles are investigated together with how these differences affect the interaction with human macrophages. Overall, the presence of the cell membrane only influences the speed and the entity of nanoparticles association with the cells, while there is no direct effect on the endocytosis pathways, composition of protein corona, or any reduction in macrophage‐mediated uptake.

We report on the feasibility of preparing nickel and niobium nitride coated cellulose acetate (CA) topographical features through a combination of template-synthesis and sputter deposition. Using femtosecond laser micromachining, a template was produced by patterning a fused silica substrate with a square array of holes of estimated depth $> 10\ \mu \mathbf{m}$ . The template was subjected to CA polymer thin-film replication to create freestanding CA topographical features (i.e., the negative replica of the pattern on the template). The CA replicas were coated with thin layers of nickel and niobium nitride by magnetron sputtering to investigate the feasibility of functionalizing these soft topographical features. Preliminary results show that CA based soft topographical features obtained by thin-film replication can be successfully coated by magnetron sputtering without disintegrating and bending.

Artificial nanoparticles accumulate a protein corona layer in biological fluids, which significantly influences their bioactivity. As nanosized obligate intracellular parasites, viruses share many biophysical properties with artificial nanoparticles in extracellular environments and here we show that respiratory syncytial virus (RSV) and herpes simplex virus type 1 (HSV-1) accumulate a rich and distinctive protein corona in different biological fluids. Moreover, we show that corona pre-coating differentially affects viral infectivity and immune cell activation. In addition, we demonstrate that viruses bind amyloidogenic peptides in their corona and catalyze amyloid formation via surface-assisted heterogeneous nucleation. Importantly, we show that HSV-1 catalyzes the aggregation of the amyloid β-peptide (Aβ42), a major constituent of amyloid plaques in Alzheimer’s disease, in vitro and in animal models. Our results highlight the viral protein corona as an acquired structural layer that is critical for viral–host interactions and illustrate a mechanistic convergence between viral and amyloid pathologies., The protein corona around artificial nanoparticles is known to influence activity and biological fate, the formation around viruses is less well understood. Here, the authors observe the formation of protein corona on viruses and study the effects this corona has on viral infectivity and on amyloid protein assembly.

Informationssysteme in der Logistik sind spezielle betriebliche Informationssysteme. Ihr Aufbau und ihre Gestaltung folgen dem Grundkonzept fur betriebliche Informationssysteme. Logistische Systeme beinhalten Leistungssysteme fur die Durchfuhrung von Guterflussen in und zwischen Unternehmen sowie Informationssysteme fur die Lenkung der Leistungssysteme. Der Beitrag zeigt Konzepte fur die Modellierung betrieblicher Informationssysteme und geht auf die speziellen Eigenschaften logistischer Systeme ein.

The endemic fish fauna of the Southern Ocean are cold-adapted stenotherms and are acutely sensitive to elevated temperature. Many of these species lack a heat shock response and cannot increase the production of heat shock proteins in their tissues. However, some species retain the ability to induce other stress-responsive genes, some of which are involved in cell cycle arrest and apoptosis. Here, the effect of heat on cell cycle stage and its ability to induce apoptosis were tested in thermally stressed hepatocytes from a common Antarctic fish species from McMurdo Sound in the Ross Sea. Levels of proliferating cell nuclear antigen were also measured as a marker of progression through the cell cycle. The results of these studies demonstrate that even sub-lethal heat stress can have deleterious impacts at the cellular level on these environmentally sensitive species.

Herr Prof. Dimitris Karagiannis hat zum Buch "Geschaftsprozessorientierte Systementwicklung: Von der Unternehmensarchitektur zum IT-System", herausgegeben von Thomas Benker, Carsten Jurck und Matthias Wolf ein Geleitwort verfasst

Die Modellierungsmethodik Semantisches Objektmodell (SOM) entstand ab Ende der 1980er-Jahre mit dem Ziel, bestehende Modellierungsdefizite zu schliesen und eine umfassende Modellierung betrieblicher Systeme zu ermoglichen. SOM hat sich seitdem in verschiedene Richtungen weiter entwickelt, die in diesem Buch dargestellt werden. Ausgangspunkt und Motivation fur die Entwicklung der Methodik werden in diesem Kapitel vorgestellt.

This chapter introduces tool support for the semantic object model (SOM). The conceptual design of a multi-view modeling tool is presented after describing the core concepts of the SOM method and laying the corresponding methodological foundation. The chapter foremost addresses the modeling enthusiast, interested in how to utilize the SOM method with the ADOxx modeling tool.

The meaningful sharing and combining of clinical results from different centers in the world performing boronneutron capture therapy (BNCT) requires improved precision in dose specification between programs. To this end absorbed dose normalizations were performed for the European clinical centers at the Joint Research Centre of the European Commission, Petten (The Netherlands), Nuclear Research Institute, Rez (Czech Republic), VTT, Espoo (Finland), and Studsvik, Nykoping (Sweden). Each European group prepared a treatment plan calculation that was benchmarked against Massachusetts Institute of Technology (MIT) dosimetry performed in a large, water-filled phantom to uniformly evaluate dose specifications with an estimated precision of ± 2 % – 3 % . These normalizations were compared with those derived from an earlier exchange between Brookhaven National Laboratory (BNL) and MIT in the USA. Neglecting the uncertainties related to biological weighting factors, large variations between calculated and measured dose are apparent that depend upon the B 10 uptake in tissue. Assuming a boron concentration of 15 μ g g − 1 in normal tissue, differences in the evaluated maximum dose to brain for the same nominal specification of 10 Gy ( w ) at the different facilities range between 7.6 and 13.2 Gy ( w ) in the trials using boronophenylalanine (BPA) as the boron delivery compound and between 8.9 and 11.1 Gy ( w ) in the two boron sulfhydryl (BSH) studies. Most notably, the value for the same specified dose of 10 Gy ( w ) determined at the different participating centers using BPA is significantly higher than at BNL by 32% (MIT), 43% (VTT), 49% (JRC), and 74% (Studsvik). Conversion of dose specification is now possible between all active participants and should be incorporated into future multi-center patient analyses.

A dosimetry intercomparison between the boron neutron capture therapy groups of the Massachusetts Institute of Technology (MIT) and the Comisión Nacional de Energía Atómica (CNEA), Argentina was performed to enable combined analyses of NCT patient data between the different centers. In-air and dose versus depth measurements in a rectangular water phantom were performed at the hyperthermal neutron beam facility of the RA-6 reactor, Bariloche. Calculated dose profiles from the CNEA treatment planning system NCTPlan that were calibrated against in-house measurements required normalizations of 1.0 (thermal neutrons), 1.13 (photons), and 0.74 (fast neutrons) to match the dosimetry of MIT.

High temperature cleaning of producer gas from biomass gasification has been investigated with a granular filter. Field tests were performed for several hours on a single filter element at about 550 °C. The results show cake filtration on the granular material and indicate good filtration of the biomass gasification producer gas. The relatively low pressure drop over the filter during filtration is comparable to those of bag filters. The granular filter can operate with high filtration velocities compared to bag filters and maintain high efficiency and a low residual pressure. This work is a part of the BioSOFC-up project that has a goal of utilizing the producer gas from the gasification plant in a solid oxide fuel cell (SOFC). The BioSOFC-up project will continue to the end of 2007.

Normalisation of prescribed dose in boron neutron capture therapy (BNCT) is needed to facilitate combining clinical data from different centres in the world to help expedite development of the modality. The approach being pursued within the BNCT community is based upon improving precision in the measurement and specification of absorbed dose. Beam characterisations using a common method are complete as are comparative dosimetry measurements between clinical centres in Europe and the USA. Results from treatment planning systems at these centres have been compared with measurements performed by MIT, and the scale factors determined are being confirmed with independent tests using measurements in an ellipsoidal water phantom. Dose normalisations have successfully been completed and applied to retrospectively analyse treatment plans from Brookhaven National Laboratory (1994-99) so that reported doses are consistently expressed with the trials performed during 1994-2003 at Harvard-MIT. Dose response relationships for adverse events and other endpoints can now be more accurately established.

Purpose: The aim of this study was to construct a 6 Li filter and to improve penetration of thermal neutrons produced by the fission converter–based epithermal neutron beam (FCB) for brain irradiation during boron neutron capture therapy (BNCT). Methods and Materials: Design of the 6 Li filter was evaluated using Monte Carlo simulations of the existing beam line and radiation transport through an ellipsoidal water phantom. Changes in beam performance were determined using three figures of merit: ( 1 ) advantage depth (AD), the depth at which the total biologically weighted dose to tumor equals the maximum weighted dose to normal tissue; ( 2 ) advantage ratio (AR), the ratio of the integral tumor dose to that of normal tissue averaged from the surface to the AD; and ( 3 ) advantage depth dose rate (ADDR), the therapeutic dose rate at the AD. Dosimetry performed with the new filter installed provided calibration data for treatment planning. Past treatment plans were recalculated to illustrate the clinical potential of the filter. Results: The 8-mm-thick Li filter is more effective for smaller field sizes, increasing the AD from 9.3 to 9.9 cm, leaving the AR unchanged at 5.7 but decreasing the ADDR from 114 to 55 cGy min −1 for the 12 cm diameter aperture. Using the filter increases the minimum deliverable dose to deep seated tumors by up to 9% for the same maximum dose to normal tissue. Conclusions: Optional 6 Li filtration provides an incremental improvement in clinical beam performance of the FCB that could help to establish a therapeutic window in the future treatment of deep-seated tumors.

Die Nutzung von Wind- und Solarenergie, Gezeitenkraft und Biomasse stellt neue Herausforderungen an die Stabilitat von Leitungsnetzen. Elektrochemische Speicher konnen ein Baustein einer intelligenten und dezentralen Energieversorgung sein. Das erste Kapitel stellt die masgeblichen Typen von Energiespeichern vergleichend dar.

Laboratory studies, confirmed by field studies at both large and small scales, elucidated behavior of a granular panel bed for gas filtration with accumulation of filter cakes on gas-entry surfaces (filtering occurring by a sieving mechanism). Filtration is cyclic: intermittently, flow of dusty gas is interrupted, and the panel is subjected to a sharp “reverse” puff of gas (a “puffback”), producing a body movement of sand toward gas-entry faces, dumping both dust cake and a relatively small quantity of sand from each face.

A Phase I/II clinical trial of neutron capture therapy (NCT) was conducted at Harvard–MIT using a fission converter epithermal neutron beam. This epithermal neutron beam has nearly ideal performance characteristics (high intensity and purity) and is well-suited for clinical use. Six glioblastoma multiforme (GBM) patients were treated with NCT by infusion of the tumor-selective amino acid boronophenylalanine-fructose (BPA-F) at a dose of 14.0 g/m 2 body surface area over 90 min followed by irradiation with epithermal neutrons. Treatments were planned using NCTPlan and an accelerated version of the Monte Carlo radiation transport code MCNP 4B. Treatments were delivered in two fractions with two or three fields. Field order was reversed between fractions to equalize the average blood boron concentration between fields. The initial dose in the dose escalation study was 7.0 RBE Gy, prescribed as the mean dose to the whole brain volume. This prescription dose was increased by 10% to 7.7 RBE Gy in the second cohort of patients. A pharmacokinetic model was used to predict the blood boron concentration for determination of the required beam monitor units with good accuracy; differences between prescribed and delivered doses were 1.5% or less. Estimates of average tumor doses ranged from 33.7 to 83.4 RBE Gy (median 57.8 RBE Gy), a substantial improvement over our previous trial where the median value of the average tumor dose was 25.8 RBE Gy.

An immunologic tool based on manipulation of the boron neutron capture reaction was previously proposed in the context of heart transplantation research to examine the temporal relationship between parenchymal rejection (representing immune cell infiltration) and transplantation-associated arteriosclerosis (characterized by progressive vascular occlusion). Critical to the development of this method is the uptake of boron by specific cells of the immune system, namely T cells, without adverse effects on cell function, which may be assessed by the ability of boron-loaded cells to produce IFN γ , a protein with substantial impact on rejection. This work presents the evaluation of two carboranyl thymidine analogs. Advantages of this type of boron compound are reduced risk of leakage and effective dose delivery based on their incorporation into cellular nuclear material. Results indicate that uptake of these boronated nucleosides is high with no adverse effects on cell function, thereby warranting the continued development of this technique that has potentially wide applicability in immunological models.

The tissue substitute A-181 plastic, which has an elemental composition matching both the constituent hydrogen and nitrogen of brain tissue, was assessed for dosimetry in boron neutron capture therapy (BNCT). The sensitivity of an A-181 walled ionization chamber relative to photons for all neutrons in a clinical epithermal beam was calculated to vary between 0.79 +/- 0.04 in-air and 0.95 +/- 0.01 at depths of 4 cm and greater in-phantom. Differences in the total neutron doses measured with A-150 and A-181 plastic-walled chambers were attributed, within experimental error, to the dose produced by thermal neutron capture reactions from the different concentrations of nitrogen in the two tissue substitutes. The response of the A-181 chamber was converted to total neutron dose with an uncertainty increasing with depth in-phantom from 13 to 23% the magnitude of which is determined by the subtraction of a relatively large photon dose. The use of A-181 in place of A-150 plastic will no longer require partitioning the measured neutron dose by energy and should simplify dose reporting in BNCT.

A patient collimator for the fission converter based epithermal neutron beam (FCB) at the Massachusetts Institute of Technology Research Reactor (MITR-II) was built for clinical trials of boron neutron capture therapy (BNCT). A design was optimized by Monte Carlo simulations of the entire beam line and incorporates a modular construction for easy modifications in the future. The device was formed in-house by casting a mixture of lead spheres (7.6 mm diameter) in epoxy resin loaded with either 140 mg cm(-3) of boron carbide or 210 mg cm(-3) of lithium fluoride (95% enriched in 6Li). The cone shaped collimator allows easy field placement anywhere on the patient and is equipped with a laser indicator of central axis, beam's eye view optics and circular apertures of 80, 100, 120 and 160 mm diameter. Beam profiles and the collateral dose in a half-body phantom were measured for the 160 mm field using fission counters, activation foils as well as tissue equivalent (A-150) and graphite walled ionization chambers. Leakage radiation through the collimator contributes less than 10% to the total collateral dose up to 0.15 m beyond the edge of the aperture and becomes relatively more prominent with lateral displacement. The measured whole body dose equivalent of 24 +/- 2 mSv per Gy of therapeutic dose is comparable to doses received during conventional therapy and is due principally (60-80%) to thermal neutron capture reactions with boron. These findings, together with the dose distributions for the primary beam, demonstrate the suitability of this patient collimator for BNCT.

Microdosimetric measurements have been performed at the clinical beam intensities in two epithermal neutron beams, the Brookhaven Medical Research Reactor and the M67 beam at the Massachusetts Institute of Technology Research Reactor, which have been used to treat patients with Boron Neutron Capture Therapy (BNCT). These measurements offer an independent assessment of the dosimetry used at these two facilities, as well as provide information about the radiation quality not obtainable from conventional macrodosimetric techniques. Moreover, they provide a direct measurement of the absorbed dose resulting from the BNC reaction. BNC absorbed doses measured within this study are approximately 15% lower than those estimated using foil activation at both MIT and BNL. Finally, an intercomparison of the characteristics and radiation quality of these two clinical beams is presented. The techniques described here allow an accurate quantitative comparison of the physical absorbed dose as well as a measure of the biological effectiveness of the absorbed dose delivered by different epithermal beams. No statistically significant differences were observed in the predicted RBEs of these two beams. The methodology presented here can help to facilitate the effective sharing of clinical results in an effort to demonstrate the clinical utility of BNCT.

A pre-clinical characterization of the first fission converter based epithermal neutron beam (FCB) designed for boron neutron capture therapy (BNCT) has been performed. Calculated design parameters describing the physical performance of the aluminium and Teflon filtered beam were confirmed from neutron fluence and absorbed dose rate measurements performed with activation foils and paired ionization chambers. The facility currently provides an epithermal neutron flux of 4.6 x 10(9) n cm(-2) s(-1) in-air at the patient position that makes it the most intense BNCT source in the world. This epithermal neutron flux is accompanied by very low specific photon and fast neutron absorbed doses of 3.5 +/- 0.5 and 1.4 +/- 0.2 x 10(-13) Gy cm2, respectively. A therapeutic dose rate of 1.7 RBE Gy min(-1) is achievable at the advantage depth of 97 mm when boronated phenylalanine (BPA) is used as the delivery agent, giving an average therapeutic ratio of 5.7. In clinical trials of normal tissue tolerance when using the FCB, the effective prescribed dose is due principally to neutron interactions with the nonselectively absorbed BPA present in brain. If an advanced compound is considered, the dose to brain would instead be predominately from the photon kerma induced by thermal neutron capture in hydrogen and advantage parameters of 0.88 Gy min(-1), 121 mm and 10.8 would be realized for the therapeutic dose rate, advantage depth and therapeutic ratio, respectively. This study confirms the success of a new approach to producing a high intensity, high purity epithermal neutron source that attains near optimal physical performance and which is well suited to exploit the next generation of boron delivery agents.

The status of fission reactor-based neutron beams for neutron capture therapy (NCT) is reviewed critically. Epithermal neutron beams, which are favored for treatment of deep-seated tumors, have been constructed or are under construction at a number of reactors worldwide. Some of the most recently constructed epithermal neutron beams approach the theoretical optimum for beam purity. Of these higher quality beams, at least one is suitable for use in high through-put routine therapy. It is concluded that reactor-based epithermal neutron beams with near optimum characteristics are currently available and more can be constructed at existing reactors. Suitable reactors include relatively low power reactors using the core directly as a source of neutrons or a fission converter if core neutrons are difficult to access. Thermal neutron beams for NCT studies with small animals or for shallow tumor treatments, with near optimum properties have been available at reactors for many years. Additional high quality thermal beams can also be constructed at existing reactors or at new, small reactors. Furthermore, it should be possible to design and construct new low power reactors specifically for NCT, which meet all requirements for routine therapy and which are based on proven and highly safe reactor technology.

This paper presents results from an experimental study of transmission of gaseous detonation waves through various granular filters. Spherical glass beads of 4 and 8 mm diameter and crushed rock of 7.5 mm volume averaged diameter were used as filter material. Varying the initial pressure of the detonating gas mixture controlled the detonation cell size. Dilution with argon was used to vary the detonation cell regularity. The complete range from almost no detonation velocity deficit to complete extinction of the combustion wave was observed. The existing correlation for gaseous detonation velocity deficit \(V/V_{CJ} = [1-0.35\log(d_ c/d_{ps})] \pm 0.1\) where \(d_c\) is the critical diameter for the gaseous detonation and \(d_{ps}\) is the pore size, is found to be applicable for both smooth spherical particles and irregular crushed rock when considering irregular detonation structures. Soot films and pressure measurements show that as the detonation cell size is increased, reinitiation of a reanular filter until it finally no longer occurs at \(V/V_{CJ} \approx 0.4--0.45\). Complete extinction of the combustion wave occurs at \(V/V_{CJ} \approx 0.25--0.3\). These two limits appear to be about the same for irregular and regular detonation cell structures. For irregular structures without argon dilution, \(d_c/d_{ps} \approx 50\) can be found for detonation wave failure, and \(d_c/d_{ps} \approx 100\) can be found for complete extinction of the combustion wave. For argon dilution these limits are changed to \(d_c/d_{ps} \approx 10\) and \(d_c/d_{ps} \approx 40\), respectively. The data are a bit scarce as a basis for proposing a new correlation for regular structures, but as a first approximation \(V/V_{CJ} =[0.8--0.35\)log\((d_c/d_{ps})] \pm 0.1\) is suggested for regular structures. The detonation or combustion wave is found to approach a constant velocity in the granular filter if not extinguished.

Business-to-business processes require an inter-company integration of the application systems supporting these business processes. Integration is based on inter-company couplings of application systems, which are specified in coupling architectures. The necessity of coupling of application systems arises from relationships between business tasks which are to be supported by these application systems. Starting with relevant relationships between business tasks, three classes of coupling architectures are identified and illustrated by concrete instances. It is investigated to which extent coupling mechanisms as provided by SAP R/3 are suitable for an implementation of these coupling architectures.

A new epithermal neutron irradiation facility, based on a fission converter assembly placed in the thermal column outside the reactor core, has been put into operation at the Massachusetts Institute of Technology Research Reactor (MITR). This facility was constructed to provide a high-intensity, forward-directed beam for use in neutron capture therapy with an epithermal flux of [approximately equal to]10{sup 10} n/cm{sup 2}.s at the medical room entrance with negligible fast neutron and gamma-ray contamination. The fission converter assembly consists of 10 or 11 MITR fuel elements placed in an aluminum tank and cooled with D{sub 2}O. Thermal-hydraulic criteria were established based on heat deposition calculations. Various startup tests were performed to verify expected neutronic and thermal-hydraulic behavior. Flow testing showed an almost flat flow distribution across the fuel elements with

Purpose : A Phase I trial of cranial neutron capture therapy (NCT) was conducted at Harvard-MIT. The trial was designed to determine maximum tolerated NCT radiation dose to normal brain. Methods and Materials : Twenty-two patients with brain tumors were treated by infusion of boronophenylalanine-fructose (BPA-f) followed by exposure to epithermal neutrons. The study began with a prescribed biologically weighted dose of 8.8 RBE (relative biologic effectiveness) Gy, escalated in compounding 10% increments, and ended at 14.2 RBE Gy. BPA-f was infused at a dose 250–350 mg/kg body weight. Treatments were planned using MacNCTPlan and MCNP 4B. Irradiations were delivered as one, two, or three fields in one or two fractions. Results : Peak biologically weighted normal tissue dose ranged from 8.7 to 16.4 RBE Gy. The average dose to brain ranged from 2.7 to 7.4 RBE Gy. Average tumor dose was estimated to range from 14.5 to 43.9 RBE Gy, with a mean of 25.7 RBE Gy. Conclusions : We have demonstrated that BPA-f-mediated NCT can be precisely planned and delivered in a carefully controlled manner. Subsequent clinical trials of boron neutron capture therapy at Harvard and MIT will be initiated with a new high-intensity, high-quality epithermal neutron beam.

A new type of epithermal neutron irradiation facility for use in neutron capture therapy has been designed, constructed, and put into operation at the Massachusetts Institute of Technology Research...

Learning environments offer high potential to improve learning processes. Starting with an analysis of the effectiveness and efficiency of learning processes when using different methods and instruments to teach and learn, the paper identifies demands for highly effective learning environments. They have to integrate several subsystems to adapt to different situations and of course must be available on the Internet. The second part of the paper describes the architecture of a learning environment which is adjusted to these demands.