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The lipids of mouse peritoneal macrophages contain high levels (25 mole percent) of esterified arachidonic acid (20:4). Following in vitro exposure to unopsonized zymosan, these cells synthesize and release oxygenated products of 20:4. Maximal levels of zymosan ingestion promote the release of 40-50% of the 20:4 content of cultures without loss of viabilitiy. Release of radiolabel from macrophages prelabeled with [3H]20:4 provides a quantitative measure for the synthesis of 20:4-derived products. Approximately 67% of the released 20:4 is recovered as prostaglandins (PG) (51% PGE and 16% 6-oxo-PGF1 alpha) and the remainder as apolar products tentatively identified as hydroxy-eicosatetraenoic acids. The kinetics of synthesis are comparable for both sets of products. A detailed examination of PGE synthesis indicated the PGE levels rise in parallel with phagocytosis during a continuous exposure of macrophages to zymosan. The concentration of particles determines the initial rate of PGE release, but the time-course of synthesis is finite (approximately 60 min), regardless of the zymosan dose. These observations are compatible with the notion that phagocytosis results in a burst of PG synthesis, the size of which is determined by the phagocytic stimulus. This is supported by the finding that secondary challenges of zymosan promote new rounds of PG synthesis by macrophages.
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Ácidos Araquidónicos/metabolismo , Macrófagos/metabolismo , Animales , Fenómenos Fisiológicos Sanguíneos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Ácidos Grasos/metabolismo , Femenino , Ratones , Fagocitosis , Prostaglandinas E/biosíntesis , Tritio , Zimosan/farmacologíaRESUMEN
Clinical application of light ion beams requires correct understanding of the complex processes of ion interaction with matter and the development of accurate transport methods. Knowledge of the fluence differential in energy of primary and secondary particles is important since it allows evaluation of different linear energy transfer (LET) dose components in the patient. The low LET and high LET particle distributions and the corresponding absorbed doses due to primary and secondary particles were evaluated for different depths in a water phantom using the Monte Carlo code SHIELD-HIT. SHIELD-HIT calculations are compared with the experimental LET distributions for a carbon beam of energy 278 MeV u(-1) from the HIMAC facility in Japan. The capability of the code for the evaluation of particle transport in thin layers of a few micrometres is demonstrated.
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Radioisótopos de Carbono/uso terapéutico , Radioterapia de Iones Pesados , Transferencia Lineal de Energía , Modelos Biológicos , Radiometría/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Animales , Carga Corporal (Radioterapia) , Simulación por Computador , Humanos , Dosificación Radioterapéutica , Efectividad Biológica Relativa , Dispersión de RadiaciónRESUMEN
Exposure of cultured rat epididymal preadipocytes to human very low density lipoproteins (VLDL) resulted in the rapid accumulation of large amounts of cellular triglyceride which was accompanied by the appearance of numerous large cellular lipid inclusions. Addition of heparin produced a two-fold stimulation of lipoprotein induced triglyceride accumulation. Supplementation of the growth medium with either low density lipoprotein, oleic acid or artificial triglyceride emulsion did not produce cellular triglyceride levels equivalent to that obtained with VLDL. Fibroblastic cells from rat skin and lung did not accumulate triglycerides when exposed to VLDL and heparin.
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Tejido Adiposo/efectos de los fármacos , Lipoproteínas VLDL/farmacología , Triglicéridos/metabolismo , Tejido Adiposo/citología , Tejido Adiposo/metabolismo , Animales , Células Cultivadas , Fibroblastos/efectos de los fármacos , Heparina/farmacología , Pulmón/efectos de los fármacos , Ratas , Piel/efectos de los fármacosRESUMEN
Tetrahymena pyriformis W cells were grown with short- and long-chain, odd and even normal fatty acid supplements. Tris acetate addition had no effect on the fatty acyl composition of the glycerophospholipids or sphingolipids, while Tris propionate supplementation led to a marked increase in odd normal fatty acids at the expense of even normal acids in both classes of complex lipids. This enhancement of odd normal acids permitted the identification of 17:1 delta 9(n), 17:2 delta 6,9(n), 17:2 delta 9,12(n), 17:3 delta 6,9,12(n), 19:1 delta 9(n), 19:2 delta 9,12(n) and 19:3 delta 6,9,12(n) by oxidation with periodate-permanganate and examination of the short-chain fragments. Supplementation with pentadecanoic acid (15:0(n)) led to an increase in the proportions of normal C15, C17 and C19 acids. The increase in C15 acids primarily reflected a rise in 15:0(n), whereas the rise in the levels of C17 and C19 acids was accounted for by an elevation of unsaturated acids. Growth with heptadecanoic acid (17:0(n)) resulted in substantial increases in unsaturated normal C17 and C19 fatty acids, while nonadecanoic acid (19:0(n)) addition led only to an increase in the proportion of unsaturated C19 acids. Retroconversion of these saturated, odd normal long chain fatty acid supplements was limited. Supplementation with arachidic acid (20:0(n)) resulted in only a marginal increase (1.4%) in normal C20 fatty acids of both the glycerophospholipids and the mild alkali labile neutral lipids and provided no evidence that desaturation occurred. The release of 14CO2 from [1-14C]arachidic acid when incubated with the ciliates indicated that this long-chain saturate is accumulated, activated and degraded. Normal C16-C19 saturated fatty acids are substrates for the delta 9 desaturase. The delta 11 isomers arise by chain elongation. Normal C16-C19 delta 9 monoenoic acids are substrates for the delta 12 desaturase. Normal C16-C18 delta 9 monoenes, normal C16-C19 delta 9,12 dienes and 18:1 delta 11(n) are desaturated at the C-6,7 position.
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Ácidos Grasos no Esterificados/metabolismo , Tetrahymena pyriformis/metabolismo , Animales , Dióxido de Carbono/metabolismo , Ácido Graso Desaturasas/metabolismo , Cromatografía de Gases y Espectrometría de Masas , Cinética , Oxidación-Reducción , Relación Estructura-Actividad , Especificidad por SustratoRESUMEN
A general scheme to perform universal, fault-tolerant quantum computation within decoherence-free subspaces (DFSs) is presented. At most two-qubit interactions are required, and the system remains within the DFS throughout the entire implementation of a quantum gate. We show explicitly how to perform universal computation on clusters of the four-qubit DFS encoding one logical qubit each under spatially symmetric (collective) decoherence. Our results have immediate relevance to quantum computer implementations in which quantum logic is implemented through exchange interactions, such as the recently proposed spin-spin coupled quantum dot arrays and donor-atom arrays.
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The goal of this research is to calculate the daily and cumulative dose distribution received by the radiotherapy patient while accounting for variable anatomy, by tracking the dose distribution delivered to tissue elements (voxels) that move within the patient. Non-linear image registration techniques (i.e., thin-plate splines) are used along with a conventional treatment planning system to combine the dose distributions computed for each 3D computed tomography (CT) study taken during treatment. For a clinical prostate case, we demonstrate that there are significant localized dose differences due to systematic voxel motion in a single fraction as well as in 15 cumulative fractions. The largest positive dose differences in rectum, bladder and seminal vesicles were 29%, 2% and 24%, respectively, after the first fraction of radiation treatment compared to the planned dose. After 15 cumulative fractions, the largest positive dose differences in rectum, bladder and seminal vesicles were 23%, 32% and 18%, respectively, compared to the planned dose. A sensitivity analysis of control point placement is also presented. This method provides an important understanding of actual delivered doses and has the potential to provide quantitative information to use as a guide for adaptive radiation treatments.
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Radiometría/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Tomografía Computarizada por Rayos X/métodos , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Modelos Estadísticos , Fantasmas de Imagen , Próstata/efectos de la radiación , Neoplasias de la Próstata/radioterapia , Dosificación Radioterapéutica , Radioterapia Conformacional , Sensibilidad y Especificidad , Distribución TisularRESUMEN
PURPOSE: To use Control Point Analysis (Sun Nuclear Corporation, Melbourne, Florida, USA) to analyze and compare delivered VMAT plans for three different treatment planning complexity levels. METHODS: Nineteen patients were chosen and fully anonymized for the purpose of this study. Ten SBRT, six H&N, one breast and two prostate VMAT plans were generated on Pinnacle3 and delivered on a Varian LINAC. The delivered dose was measured using ArcCHECK™. Each plan was analyzed using SNC Patient 6 and Control Point Analysis. Gamma passing percentage was used to assess the differences between the measured and planned dose distributions and to assess the role of various control point binning scenarios. RESULTS: The prostate cases reported the highest gamma passing percentages for SNC Patient 6 (99.3%-99.5%,3%/3mm) and Control Point Analysis (99.1--99.3%,3%/3mm). The mean percentage of passing control point sectors for the prostate cases increased from 48.9±3.1% for individual control points to 69.5 ± 3.9% for 5 control points binned together to 100±0% for 10 control points binned together. Over all, there was a trend in the percentage of sectors passing gamma analysis increasing with the increase of the number of control points binned together in one sector for both passing criteria considered (48.9±3.1% for individual control points to 69.5±3.9% for 5 control points binned together in one sector to 100±0% for 10 control points binned together in one sector for the prostate). CONCLUSION: The delivery accuracy per control point depends on the MU/control point (SBRT) and the plan degree of modulation (H&N).
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On-line CT imaging in the radiotherapy room has become the norm for targeted intensity-modulated radiotherapy (IMRT), enabling precise adjustments of the daily patient setup based on soft tissue visualization. Corrections for plasticity of the anatomy and dose deformation are within technological reach but will require more on-line resources. We have developed a computer model that allows exploration of "what if" scenarios for assessing the benefits of Image Guidance strategies in terms of the multi-fraction dose distribution and DVH metrics (Target D95 and rectum V70). In this work we report on changes in anatomy and resultant dose distribution as observed in 35 daily megavoltage CT (MVCT) scans of the pelvis during prostate therapy for 13 patients. Our goal is to assess the effectiveness and efficiency of various adaptive strategies involving imaging schedule with and without dose re-planning of 5-field IMRT with 18 MV x-rays. Our research questions are: To what extent do radiation dose distributions delivered to individual patients (in vivo) diverge from the planned dose distributions (in silico)? Is there a robust schedule of CT image guidance, with or without dose re-planning that will mitigate discrepancies? For prostate IMRT, we conclude that image guidance schedule can be relaxed when generous GTV margins (10/7mm) are used. Tighter margins (isotropic 5 mm) reduce the dose to the rectum as expected. However, daily re-planning may be required to maintain adequate target coverage as planned when tighter margins are used.
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The purpose of the present work is to develop analytical expressions for the depth variation of the fluence, planar fluence, the energy fluence, planar energy fluence, the mean energy and absorbed dose of primary ions and their associated fragments in tissue-like media with ranges of clinical interest. The analytical expressions of the primary ions and associated fragments take into account nuclear interactions, energy losses, range straggling and multiple scattering. The analytical models of the radiation field quantities were compared with the results of the modified Monte Carlo (MC) code SHIELD-HIT(+). The results show that the shape of the depth absorbed dose distribution of the primary particles is characterized by an increasingly steep exponential fluence decrease with depth as the charge and atomic weight increase. This is accompanied by a compensating increased energy loss towards the Bragg peak as the charge of the ion increases. These largely compensating mechanisms are the main reason that the depth absorbed dose curve of all light ions is surprisingly similar. In addition, a rather uniform dose in the plateau region is obtained since the increasing fragment production almost precisely compensates the loss of primaries. The dominating light fragments such as protons and alpha particles are characterized by longer ranges than the primaries and their depth dose curves to some extent coincide well with the depth fluence curves due to a rather slow variation of mean stopping powers. In contrast, the heavier fragments are characterized by the build up of a slowing down spectrum similar to that of the primaries but with initially slightly shorter or longer ranges depending on their mass to atomic number ratio. The presented analytical theory for the light ion penetration in matter agree quite well with the MC and experimental data and may be very useful for fast analytical calculations of quantities like mean energy, fluence, energy fluence, absorbed dose, and LET.
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Iones , Algoritmos , Simulación por Computador , Humanos , Transferencia Lineal de Energía , Litio , Método de Montecarlo , Dosis de Radiación , Dispersión de Radiación , AguaRESUMEN
To characterize petroleum products, a method based on the combination of IR-spectrometric structural group analysis, GC-simulated boiling analysis and multivariate regression techniques (PLS, PCR) has been developed. The best performance was achieved by a PLS regression model with six aliphatic and aromatic structural groups. Thereby, structural group distribution related to the boiling temperature could be obtained in order to quantify product-specific distribution parameters and to control material-conversion processes caused by biodegradation.
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A remarkable feature of quantum entanglement is that an entangled state of two parties, Alice ( A) and Bob ( B), may be more disordered locally than globally. That is, S(A)>S(A,B), where S(*) is the von Neumann entropy. It is known that satisfaction of this inequality implies that a state is nonseparable. In this paper we prove the stronger result that for separable states the vector of eigenvalues of the density matrix of system AB is majorized by the vector of eigenvalues of the density matrix of system A alone. This gives a strong sense in which a separable state is more disordered globally than locally and a new necessary condition for separability of bipartite states in arbitrary dimensions.
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The ingestion of particles by macrophages leads to the prompt induction of prostaglandin (PG) synthesis. We have now dissected the endocytic process and examined the requirements of prostaglandin E (PGE) synthesis for particle attachment, membrane interiorization, and phagosome-lysosome fusion. Macrophages that were loaded with the polyanion dextran sulfate and exhibited a greater than 99% inhibition of phagosome-lysosome fusion produced normal amounts of PGE upon challenge with zymosan. Inhibition of membrane interiorization with cytochalasin D was similarly ineffective in blocking PGE synthesis. The addition of large numbers of unmodified polystyrene latex beads, which were readily ingested by macrophages, failed to stimulate PGE synthesis. However, when macrophages were challenged with latex beads coated with immune complexes, an increased synthesis of PGE resulted. No response occurred if the complex was prepared with the F(ab')2 fragment of IgG. Similar results occurred when nonphagocytizable Sephadex beads coated with immune complexes were employed. We conclude that particle binding to the Fc receptor of the macrophage plasma membrane is a sufficient stimulus for PGE synthesis.
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Macrófagos/metabolismo , Prostaglandinas/biosíntesis , Receptores de Droga/metabolismo , Animales , Complejo Antígeno-Anticuerpo , Células Cultivadas , Endocitosis , Femenino , Lisosomas/fisiología , Ratones , Fagocitosis , Prostaglandinas E/biosíntesis , Receptores Fc/metabolismoRESUMEN
Various physical implementations of quantum computers are being investigated, although the requirements that must be met to make such devices a reality in the laboratory at present involve capabilities well beyond the state of the art. Recent solid-state approaches have used quantum dots, donor-atom nuclear spins or electron spins; in these architectures, the basic two-qubit quantum gate is generated by a tunable exchange interaction between spins (a Heisenberg interaction), whereas the one-qubit gates require control over a local magnetic field. Compared to the Heisenberg operation, the one-qubit operations are significantly slower, requiring substantially greater materials and device complexity--potentially contributing to a detrimental increase in the decoherence rate. Here we introduced an explicit scheme in which the Heisenberg interaction alone suffices to implement exactly any quantum computer circuit. This capability comes at a price of a factor of three in additional qubits, and about a factor of ten in additional two-qubit operations. Even at this cost, the ability to eliminate the complexity of one-qubit operations should accelerate progress towards solid-state implementations of quantum computation.