Radiobiology of normal rat lung in Boron Neutron Capture Therapy

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Nuclear Science and Engineering, 2006.Includes bibliographical references.Boron Neutron Capture Therapy (BNCT) is a binary cancer radiation therapy that utilizes biochemical tumor cell targeting and provides a mixed field of high and low Linear Energy Transfer (LET) radiation with differing biological effectiveness. This project investigated the radiobiology of normal rat lung in BNCT and measured the relative biological effectiveness factors for the lung. Rat thorax irradiations were carried out with x-rays and neutrons with or without the boron compound boronophenylalanine-fructose (BPA-F). Monte Carlo radiation transport simulations were used to design the rat lung neutron irradiations. Among the neutron beam facilities available for BNCT at the MIT Research Reactor, the thermal neutron beam facility was found to provide a suitable dose distribution for this project. A delimiter was designed and constructed for the rat lung irradiations as a lithiated-polyethylene plate of 1.5 cm thickness with an aperture tapered from 4 to 3 cm in width to expose the lung to the beam and shield adjacent radiosensitive organs. The simulation design was validated with in-phantom measurements using gold foil activation and the dual ion chamber technique. By using a two-field irradiation, a relatively uniform dose distribution could be delivered to the rat lung. The mean lung dose rate was 18.7 cGy/min for neutron beam only irradiation and 37.5 cGy/min with neutrons plus BPA and a blood boron concentration of 18 gg/g.(cont.) The delimiter designed for rat lung irradiation, and another similar delimiter, along with the animal holding box, all designed in this project, also serve as the apparatus for other small animal irradiations and cell irradiations at the thermal neutron facility at the MIT Research Reactor. An open-flow whole-body plethysmography system with fully automated signal processing programs was developed to non-invasively measure rat breathing rates and lung functional damage after lung irradiation. Noise reduction was carried out against high frequencies beyond the range of rat breathing frequency and large amplitude spikes due to abnormal animal movement. The denoised breathing signals were analyzed using the Fast Fourier Transform with a circular moving block in combination with the bootstrap for noise suppression and to allow estimation of the statistical uncertainty (standard deviation) of frequency measurements. The major frequency of the mean frequency spectrum was determined as the breathing frequency. The mean control breathing rate was 176 ± 13 (7.4%) min' (mean ± SD), and breathing rates 20% (- 3 SD) above the control average were considered to be abnormally elevated. The mean standard deviation of all measurements (n = 4269) was 2.4%. The dose responses of different irradiation groups with breathing rate elevation as the biological endpoint were evaluated with probit analysis. Two response phases of breathing rate elevation were observed as the early response phase (100 days). The ED50 values for x-rays, neutrons only, and neutrons plus BPA during the early response phase, and neutrons plus BPA during the late response phase, were 11.5 ± 0.4 Gy, 9.2 + 0.5 Gy, 8.7 ± 0.6 Gy and 6.7 ± 0.4 Gy, respectively.(cont.) The radiobiological weighting factors for the neutron beam (neutrons and photons), thermal neutrons only, %°B dose component during the early response phase, and 10B dose component during the late response phase were 1.24 ± 0.08, 2.2 ± 0.4, 1.4 ± 0.2, and 2.3 + 0.3, respectively. The histological damage to the lung during the late phase was also quantified with a histological scoring system. A set of linear dose response curves with histological damage as the endpoint was constructed. The radiobiological weighting factors for the different dose components were also determined at a degree of lung histological damage corresponding to a median histological score between the baseline (similar to the control) and the maximum. The weighting factors measured, 1.22 ± 0.09 for the thermal neutron beam and 1.9 + 0.2 for the o1B dose component, are consistent with the corresponding weighting factors measured using functional damage. The knowledge gained in these radiobiological studies of the normal rat lung indicates that the lung complications experienced by two patients in the Harvard-MIT clinical trial of BNCT for brain tumors do not appear to be related to the BNCT irradiations. This project is also helpful for evaluating the feasibility of BNCT for lung cancer.by Jingli Liu Kiger.Ph.D

Novel insights into bacterial dimethylsulfoniopropionate catabolism in the East China Sea

The compatible solute Dimethylsulfoniopropionate (DMSP), made by many marine organisms, is one of Earth’s most abundant organosulfur molecules. Many marine bacteria import DMSP and can degrade it as a source of carbon and/or sulfur via DMSP cleavage or DMSP demethylation pathways, which can generate the climate active gases dimethyl sulfide (DMS) or methanthiol (MeSH), respectively. Here we used culture-dependent and -independent methods to study bacteria catabolising DMSP in East China Sea (ECS). Of bacterial isolates, 42.11% showed DMSP-dependent DMS (Ddd+) activity, and 12.28% produced detectable levels of MeSH. Interestingly, although most Ddd+ isolates were Alphaproteobacteria (mainly Roseobacters), many gram-positive Actinobacteria were also shown to cleave DMSP producing DMS. The mechanism by which these Actinobacteria cleave DMSP is unknown, since no known functional ddd genes have been identified in genome sequences of Ddd+ Microbacterium and Agrococcus isolates or in any other sequenced Actinobacteria genomes. Gene probes to the DMSP demethylation gene dmdA and the DMSP lyase gene dddP demonstrated that these DMSP-degrading genes are abundant and widely distributed in ECS seawaters. dmdA was present in relatively high proportions in both surface (19.53% ± 6.70%) and bottom seawater bacteria (16.00% ± 8.73%). In contrast, dddP abundance positively correlated with chlorophyll a, and gradually decreased with the distance from land, which implies that the bacterial DMSP lyase gene dddP might be from bacterial groups that closely associate with phytoplankton. Bacterial community analysis showed positive correlations between Rhodobacteraceae abundance and concentrations of DMS and DMSP, further confirming the link between this abundant bacterial class and the environmental DMSP cycling

7-Chloro-5-(chloro­meth­yl)pyrazolo­[1,5-a]pyrimidine-3-carbonitrile

All non-H atoms of the title compound, C8H4Cl2N4, are essentially coplanar, with an r.m.s. deviation of 0.011 Å. In the crystal, weak C—H⋯N hydrogen bonds link the mol­ecules into infinite sheets parallel to the bc plane

Biogenic production of DMSP and its degradation to DMS-their roles in the global sulfur cycle

Dimethyl sulfide (DMS) is the most abundant form of volatile sulfur in Earth's oceans, and is mainly produced by the enzymatic clevage of dimethylsulfoniopropionate (DMSP). DMS and DMSP play important roles in driving the global sulfur cycle and may affect climate. DMSP is proposed to serve as an osmolyte, a grazing deterrent, a signaling molecule, an antioxidant, a cryoprotectant and/or as a sink for excess sulfur. It was long believed that only marine eukaryotes such as phytoplankton produce DMSP. However, we recently discovered that marine heterotrophic bacteria can also produce DMSP, making them a potentially important source of DMSP. At present, one prokaryotic and two eukaryotic DMSP synthesis enzymes have been identified. Marine heterotrophic bacteria are likely the major degraders of DMSP, using two known pathways: demethylation and cleavage. Many phytoplankton and some fungi can also cleave DMSP. So far seven different prokaryotic and one eukaryotic DMSP lyases have been identified. This review describes the global distribution pattern of DMSP and DMS, the known genes for biosynthesis and cleavage of DMSP, and the physiological and ecological functions of these important organosulfur molecules, which will improve understanding of the mechanisms of DMSP and DMS production and their roles in the environment

Climatic Control on Plant and Soil d13C along an Altitudinal Transect of Lushan Mountain in Subtropical China: Characteristics and Interpretation of Soil Carbon Dynamics

<div><p>Decreasing temperature and increasing precipitation along altitude gradients are typical mountain climate in subtropical China. In such a climate regime, identifying the patterns of the C stable isotope composition (δ¹³C) in plants and soils and their relations to the context of climate change is essential. In this study, the patterns of δ¹³C variation were investigated for tree leaves, litters, and soils in the natural secondary forests at four altitudes (219, 405, 780, and 1268 m a.s.l.) in Lushan Mountain, central subtropical China. For the dominant trees, both leaf and leaf-litter δ¹³C decreased as altitude increased from low to high altitude, whereas surface soil δ¹³C increased. The lower leaf δ¹³C at high altitudes was associated with the high moisture-related discrimination, while the high soil δ¹³C is attributed to the low temperature-induced decay. At each altitude, soil δ¹³C became enriched with soil depth. Soil δ¹³C increased with soil C concentrations and altitude, but decreased with soil depth. A negative relationship was also found between O-alkyl C and δ¹³C in litter and soil, whereas a positive relationship was observed between aromatic C and δ¹³C. Lower temperature and higher moisture at high altitudes are the predominant control factors of δ¹³C variation in plants and soils. These results help understand C dynamics in the context of global warming.</p></div

SurrealDriver: Designing Generative Driver Agent Simulation Framework in Urban Contexts based on Large Language Model

Simulation plays a critical role in the research and development of autonomous driving and intelligent transportation systems. However, the current simulation platforms exhibit limitations in the realism and diversity of agent behaviors, which impede the transfer of simulation outcomes to the real world. In this paper, we propose a generative driver agent simulation framework based on large language models (LLMs), capable of perceiving complex traffic scenarios and providing realistic driving maneuvers. Notably, we conducted interviews with 24 drivers and used their detailed descriptions of driving behavior as chain-of-thought prompts to develop a `coach agent' module, which can evaluate and assist driver agents in accumulating driving experience and developing human-like driving styles. Through practical simulation experiments and user experiments, we validate the feasibility of this framework in generating reliable driver agents and analyze the roles of each module. The results show that the framework with full architect decreased the collision rate by 81.04% and increased the human-likeness by 50%. Our research proposes the first urban context driver agent simulation framework based on LLMs and provides valuable insights into the future of agent simulation for complex tasks.Comment: 12 pages, 8 figure

Effect of Microstructure on the Compressive Mechanical Properties of Ti-20Zr-6.5Al-4V Alloy

The effect of microstructure on the mechanical properties of Ti-20Zr-6.5Al-4V alloy after solution and aging treatment was investigated by compression tests. The results showed that the microstructure was consisted of a duplex phase αʺ + β structure after solution treatment. With increasing solution treatment temperature, the size of β phase grain increased and the amount of αʺ phase decreased. The ultimate compressive strength and elongation decreased with increasing solution treatment temperature, while the yield strength increased. After aging-treatment at 700 ºC for 1.5 h, the microstructure consisted of a large amount of globular α phase, a little amount of fine acicular α phase and bulk β phase for the samples solution-treated at 850 ºC for 0.5 h. With increasing initial solution treatment temperature, the amount of globular α phase and bulk β phase decreased, however, the amount and size of acicular α phase increased after aging treatment. The ultimate compressive strength and elongation decreased with increasing initial solution treatment temperature, whereas the yield strength firstly increased, and then slightly decreased.</p