A Scalable Runtime Platform for Multiagent-Based Simulation

Abstract. Using purely agent-based platforms for any kind of simulation requires to address the following challenges: (1) scalability (efficient scheduling of agent cycles is difficult), (2) efficient memory management (when and which data should be fetched, cached, or written to/from disk), and (3) modelling (no generally accepted meta-models exist: what are essential concepts, what just implementation details?). While dedicated professional simulation tools usually provide rich domain libraries and advanced visualisation techniques, and support the simulation of large scenarios, they do not allow for "agentization" of single components. We are trying to bridge this gap by developing a distributed, scalable runtime platform for multiagent simulation, MASeRaTi, addressing the three problems mentioned above. It allows to plug-in both dedicated simulation tools (for the macro view ) as well as the agentization of certain components of the system (to allow a micro view ). If no agent-related features are used, its performance should be as close as possible to the legacy system used

Mode competition in broad-ridge-waveguide lasers

The lateral brightness achievable with high-power GaAs-based laser diodes having long and broad waveguides is commonly regarded to be limited by the onset of higher-order lateral modes. For the study of the lateral-mode competition two complementary simulation tools are applied, representing different classes of approximations. The first tool bases on a completely incoherent superposition of mode intensities and disregards longitudinal effects like spatial hole burning, whereas the second tool relies on a simplified carrier transport and current flow. Both tools yield agreeing power-current characteristics that fit the data measured for 5 to 23 µm wide ridges. Also, a similarly good qualitative conformance of the near and far fields is found. However, the threshold of individual modes, the partition of power between them at a given current, and details of the near and far fields show differences. These differences are the consequence of a high sensitivity of the mode competition to details of the models and of the device structure. Nevertheless, it can be concluded concordantly that the brightness rises with increasing ridge width irrespective of the onset of more and more lateral modes. The lateral brightness 2W · mm¯¹ 1mrad¯¹ at 10MW · cm¯²2 power density on the front facet of the investigated laser with widest ridge (23 µm) is comparable with best values known from much wider broad-area lasers. In addition, we show that one of the simulation tools is able to predict beam steering and coherent beam

Mode competition in broad-ridge-waveguide lasers

The lateral brightness achievable with high-power GaAs-based laser diodes having long and broad waveguides is commonly regarded to be limited by the onset of higher-order lateral modes. For the study of the lateral-mode competition two complementary simulation tools are applied, representing different classes of approximations. The first tool bases on a completely incoherent superposition of mode intensities and disregards longitudinal effects like spatial hole burning, whereas the second tool relies on a simplified carrier transport and current flow. Both tools yield agreeing power-current characteristics that fit the data measured for 5 to 23 µm wide ridges. Also, a similarly good qualitative conformance of the near and far fields is found. However, the threshold of individual modes, the partition of power between them at a given current, and details of the near and far fields show differences. These differences are the consequence of a high sensitivity of the mode competition to details of the models and of the device structure. Nevertheless, it can be concluded concordantly that the brightness rises with increasing ridge width irrespective of the onset of more and more lateral modes. The lateral brightness 2W · mm¯¹ 1mrad¯¹ at 10MW · cm¯²2 power density on the front facet of the investigated laser with widest ridge (23 µm) is comparable with best values known from much wider broad-area lasers. In addition, we show that one of the simulation tools is able to predict beam steering and coherent bea

Phase II Trial with Carboplatin and Bendamustine in Patients with Extensive Stage Small-Cell Lung Cancer

Background:Bendamustine is an alkylating agent with hybrid activity and proven efficacy in small-cell lung cancer associated with a favorable toxicity rate. This phase II study of carboplatin/bendamustine was conducted to evaluate the efficacy of this combination in patients with extensive disease small-cell lung cancer (ED-SCLC).Methods:Fifty-six untreated patients with ED-SCLC were enrolled. Their median age was 63 years. Sixty-seven percent of patients were male and 18% had a World Health Organization performance status of 2. Bendamustine was administered as a 30- to 60-minute infusion at a dose of 80 mg/m2 on days 1 and 2, and carboplatin was given at an area under the curve of 5 on day 1 of a 21-day cycle.Results:Fifty-five patients were assessable for response and toxicity. The overall response rate was 72.7% (95% confidence interval: 59%–84%), with one complete remission (1.8%). The median time to progression was 5.2 months (95% confidence interval: 4.2–5.6). At the time of evaluation, 71% of the patients had died. The median survival time reached 8.3 months (95% confidence interval: 6.6–9.9). The major toxicity of this regimen was myelosuppression, including grade 3 or 4 neutropenia (46%), thrombopenia (26%), anemia (15%), and infections (11%). Toxic death was recorded in two patients (3.6%).Conclusions:The carboplatin/bendamustine regimen is a well-tolerated cytostatic combination in ED-SCLC with activity comparable with that of other platinum-based regimens. Further investigations, such as a phase III trial, are currently planned

Anti-L1CAM radioimmunotherapy is more effective with the radiolanthanide terbium-161 compared to lutetium-177 in an ovarian cancer model

Purpose: The L1 cell adhesion molecule (L1CAM) is considered a valuable target for therapeutic intervention in different types of cancer. Recent studies have shown that anti-L1CAM radioimmunotherapy (RIT) with 67Cu- and 177Lu-labelled internalising monoclonal antibody (mAb) chCE7 was effective in the treatment of human ovarian cancer xenografts. In this study, we directly compared the therapeutic efficacy of anti-L1CAM RIT against human ovarian cancer under equitoxic conditions with the radiolanthanide 177Lu and the potential alternative 161Tb in an ovarian cancer therapy model. Methods: Tb was produced by neutron bombardment of enriched 160Gd targets. 161Tb and 177Lu were used for radiolabelling of DOTA-conjugated antibodies. The in vivo behaviour of the radioimmunoconjugates (RICs) was assessed in IGROV1 tumour-bearing nude mice using biodistribution experiments and SPECT/CT imaging. After ascertaining the maximal tolerated doses (MTD) the therapeutic impact of 50% MTD of 177Lu- and 161Tb-DOTA-chCE7 was evaluated in groups of ten mice by monitoring the tumour size of subcutaneous IGROV1 tumours. Results: The average number of DOTA ligands per antibody was 2.5 and maximum specific activities of 600MBq/mg were achieved under identical radiolabelling conditions. RICs were stable in human plasma for at least 48h. 177Lu- and 161Tb-DOTA-chCE7 showed high tumour uptake (37.8-39.0 %IA/g, 144h p.i.) with low levels in off-target organs. SPECT/CT images confirmed the biodistribution data. 161Tb-labelled chCE7 revealed a higher radiotoxicity in nude mice (MTD: 10MBq) than the 177Lu-labelled counterpart (MTD: 12MBq). In a comparative therapy study with equitoxic doses, tumour growth inhibition was better by 82.6% for the 161Tb-DOTA-chCE7 than the 177Lu-DOTA-chCE7 RIT. Conclusions: Our study is the first to show that anti-L1CAM 161Tb RIT is more effective compared to 177Lu RIT in ovarian cancer xenografts. These results suggest that 161Tb is a promising candidate for future clinical applications in combination with internalising antibodies

The drivers of biogeochemistry in beach ecosystems: A cross-shore transect from the dunes to the low water line

This study addresses key processes in high-energy beach systems using an interdisciplinary approach. We assess spatial variations in subsurface pore water residence times, salinity, organic matter (OM) availability, and redox conditions and their effects on nutrient cycles as well as on microbial community patterns and microphytobenthos growth. At the study site on Spiekeroog Island, southern North Sea, beach hydrology is characterized by the classical zonation with an upper saline plume (USP), a saltwater wedge, and a freshwater discharge tube in between. Sediment and pore water samples were taken along a cross-shore transect from the dunes to the low water line reaching sediment depths down to 5 m below sediment surface. Spatial variations in pore water residence time, salinity, and organic matter availability lead to steep redox and nutrient gradients. Vertical and horizontal differences in the microbial community indicate the influence of these gradients and salinity on the community structure. Modeled seawater flux through the USP and freshwater flux through the tube are on average 2.8 and 0.75 m3 per day and meter of shoreline, respectively. Furthermore, ridge sediments at the lower beach discharge seawater at rates of 0.5 and 1.0 m3 per day and meter of shoreline towards the runnel and seaside, respectively. Applying seawater and freshwater fluxes and representative nutrient concentrations for the discharge zones, nutrient fluxes to adjacent nearshore waters are 117 mmol NH4+, 55 mmol PO43 − and 575 mmol Si(OH)4 per day and meter of shoreline. We propose that this nutrient efflux triggers growth of microphytobenthos on sediment surfaces of the discharge zone. A first comparison of nutrient discharge rates of the beach site with a nearby sandy backbarrier tidal flat margin indicates that the beach system might be of less importance in supplying recycled nutrients to nearshore waters than the backbarrier tidal flat area