Semi-empirical formulation of multiple scattering for Gaussian beam model of heavy charged particles stopping in tissue-like matter

Dose calculation for radiotherapy with protons and heavier ions deals with a large volume of path integrals involving a scattering power of body tissue. This work provides a simple model for such demanding applications. There is an approximate linearity between RMS end-point displacement and range of incident particles in water, empirically found in measurements and detailed calculations. This fact was translated into a simple linear formula, from which the scattering power that is only inversely proportional to residual range was derived. The simplicity enabled analytical formulation for ions stopping in water, which was designed to be equivalent with the extended Highland model and agreed with measurements within 2% or 0.02 cm in RMS displacement. The simplicity will also improve the efficiency of numerical path integrals in the presence of heterogeneity.Comment: 6 pages, 3 figures, submitted to Physics in Medicine and Biolog

Computational modeling of beam-customization devices for heavy-charged-particle radiotherapy

A model for beam customization with collimators and a range-compensating filter based on the phase-space theory for beam transport is presented for dose distribution calculation in treatment planning of radiotherapy with protons and heavier ions. Independent handling of pencil beams in conventional pencil-beam algorithms causes unphysical collimator-height dependence in the middle of large fields, which is resolved by the framework comprised of generation, transport, collimation, regeneration, range-compensation, and edge-sharpening processes with a matrix of pencil beams. The model was verified to be consistent with measurement and analytic estimation at a submillimeter level in penumbra of individual collimators with a combinational-collimated carbon-ion beam. The model computation is fast, accurate, and readily applicable to pencil-beam algorithms in treatment planning with capability of combinational collimation to make best use of the beam-customization devices.Comment: 16 pages, 5 figure

GABA(A) receptor phospho-dependent modulation is regulated by phospholipase C-related inactive protein type 1, a novel protein phosphatase 1 anchoring protein

GABA(A) receptors are critical in controlling neuronal activity. Here, we examined the role for phospholipase C-related inactive protein type 1 (PRIP-1), which binds and inactivates protein phosphatase 1alpha (PP1alpha) in facilitating GABA(A) receptor phospho-dependent regulation using PRIP-1(-/-) mice. In wild-type animals, robust phosphorylation and functional modulation of GABA(A) receptors containing beta3 subunits by cAMP-dependent protein kinase was evident, which was diminished in PRIP-1(-/-) mice. PRIP-1(-/-) mice exhibited enhanced PP1alpha activity compared with controls. Furthermore, PRIP-1 was able to interact directly with GABA(A) receptor beta subunits, and moreover, these proteins were found to be PP1alpha substrates. Finally, phosphorylation of PRIP-1 on threonine 94 facilitated the dissociation of PP1alpha-PRIP-1 complexes, providing a local mechanism for the activation of PP1alpha. Together, these results suggest an essential role for PRIP-1 in controlling GABA(A) receptor activity via regulating subunit phosphorylation and thereby the efficacy of neuronal inhibition mediated by these receptors

Regeneration of Graft Livers and Limited Contribution of Extrahepatic Cells After Partial Liver Transplantation in Humans

Background Liver regeneration is still not fully understood. Partial liver transplantation (LT) can provide the opportunity to investigate the mechanisms of liver regeneration, including the contribution of extrahepatic cells to liver regeneration. Methods Of 61 patients transplanted with partial liver graft between August 1997 and October 2006, 56 patients were studied, including 49 adults and 7 children. Sequential computed tomography volumetric analysis was performed for volume measurement, while proliferating cell nuclear antigen (PCNA) labeling index was investigated for liver cell proliferation in nonprotocol liver biopsy specimens. In addition, 15 male recipients who had female liver grafts were investigated in order to detect Y chromosomes as extrahepatic cells in nonprotocol liver biopsy specimens. Results Graft volume per standard liver volume was markedly increased after adult-to-adult living-donor (LD) LT. In pediatric transplants, there was no volume increase over time. PCNA labeling index was vigorous in adult-to-adult LDLT in the early period after LDLT. No Y chromosome was evident in hepatocytes from female-donor male-recipient grafts during or after liver regeneration. However, in the cases of failing grafts of this type, many Y-chromosome-positive cells were observed in the graft liver. The character of those cells was CD34(−), CK9(−), hepatocyte-specific antigen(−), and CD68(+/−). Conclusion In adult-to-adult LDLT, vigorous liver regeneration occurs in the graft liver, demonstrated by not only volumetric but cell kinetic analysis. Involvement of extrahepatic cells in normal liver regeneration seems limited

Critical Roles of Macrophages in the Formation of Intracranial Aneurysm

Background and Purpose-Abnormal vascular remodeling triggered by hemodynamic stresses and inflammation is believed to be a key process in the pathophysiology of intracranial aneurysms. Numerous studies have shown infiltration of inflammatory cells, especially macrophages, into intracranial aneurysmal walls in humans. Using a mouse model of intracranial aneurysms, we tested whether macrophages play critical roles in the formation of intracranial aneurysms. Methods-Intracranial aneurysms were induced in adult male mice using a combination of a single injection of elastase into the cerebrospinal fluid and angiotensin II-induced hypertension. Aneurysm formation was assessed 3 weeks later. Roles of macrophages were assessed using clodronate liposome-induced macrophage depletion. In addition, the incidence of aneurysms was assessed in mice lacking monocyte chemotactic protein-1 (CCL2) and mice lacking matrix metalloproteinase-12 (macrophage elastase). Results-Intracranial aneurysms in this model showed leukocyte infiltration into the aneurysmal wall, the majority of the leukocytes being macrophages. Mice with macrophage depletion had a significantly reduced incidence of aneurysms compared with control mice (1 of 10 versus 6 of 10; P\u3c0.05). Similarly, there was a reduced incidence of aneurysms in mice lacking monocyte chemotactic protein-1 compared with the incidence of aneurysms in wild-type mice (2 of 10 versus 14 of 20, P\u3c0.05). There was no difference in the incidence of aneurysms between mice lacking matrix metalloproteinase-12 and wild-type mice. Conclusions-These data suggest critical roles of macrophages and proper macrophage functions in the formation of intracranial aneurysms in this model. © 2010 American Heart Association, Inc

A straw drift chamber spectrometer for studies of rare kaon decays

We describe the design, construction, readout, tests, and performance of planar drift chambers, based on 5 mm diameter copperized Mylar and Kapton straws, used in an experimental search for rare kaon decays. The experiment took place in the high-intensity neutral beam at the Alternating Gradient Synchrotron of Brookhaven National Laboratory, using a neutral beam stop, two analyzing dipoles, and redundant particle identification to remove backgrounds

First Observation of the Rare Decay Mode K-long -> e+ e-

In an experiment designed to search for and study very rare two-body decay modes of the K-long, we have observed four examples of the decay K-long -> e+ e-, where the expected background is 0.17+-0.10 events. This observation translates into a branching fraction of 8.7^{+5.7}_{-4.1} X 10^{-12}, consistent with recent theoretical predictions. This result represents by far the smallest branching fraction yet measured in particle physics.Comment: 9 pages, 3 figure

Measurements of total and partial charge-changing cross sections for 200-400 MeV/nucleon 12C in water and polycarbonate

We have studied charged nuclear fragments produced by 200 - 400 MeV/nucleon carbon ions, interacting with water and polycarbonate, using a newly developed emulsion detector. Total and partial charge-changing cross sections for the production of B, Be, and Li fragments were measured and compared with both previously published measurements, and model predictions. This study is of importance for validating and improving carbon ion therapy treatment planning systems, and for estimating the radiological risks for personnel on space missions, since carbon is a significant component of the Galactic Cosmic Rays

Transmission of Fusarium boothii Mycovirus via Protoplast Fusion Causes Hypovirulence in Other Phytopathogenic Fungi

There is increasing concern regarding the use of fungicides to control plant diseases, whereby interest has increased in the biological control of phytopathogenic fungi by the application of hypovirulent mycoviruses as a possible alternative to fungicides. Transmission of hypovirulence-associated double-stranded RNA (dsRNA) viruses between mycelia, however, is prevented by the vegetative incompatibility barrier that often exists between different species or strains of filamentous fungi. We determined whether protoplast fusion could be used to transmit FgV1-DK21 virus, which is associated with hypovirulence on F. boothii (formerly F. graminearum strain DK21), to F. graminearum, F. asiaticum, F. oxysporum f. sp. lycopersici, and Cryphonectria parasitica. Relative to virus-free strains, the FgV1-DK21 recipient strains had reduced growth rates, altered pigmentation, and reduced virulence. These results indicate that protoplast fusion can be used to introduce FgV1-DK21 dsRNA into other Fusarium species and into C. parasitica and that FgV1-DK21 can be used as a hypovirulence factor and thus as a biological control agent

Characterization of Transcription Start Sites of Putative Non-coding RNAs by Multifaceted Use of Massively Paralleled Sequencer

On the basis of integrated transcriptome analysis, we show that not all transcriptional start site clusters (TSCs) in the intergenic regions (iTSCs) have the same properties; thus, it is possible to discriminate the iTSCs that are likely to have biological relevance from the other noise-level iTSCs. We used a total of 251 933 381 short-read sequence tags generated from various types of transcriptome analyses in order to characterize 6039 iTSCs, which have significant expression levels. We analyzed and found that 23% of these iTSCs were located in the proximal regions of the RefSeq genes. These RefSeq-linked iTSCs showed similar expression patterns with the neighboring RefSeq genes, had widely fluctuating transcription start sites and lacked ordered nucleosome positioning. These iTSCs seemed not to form independent transcriptional units, simply representing the by-products of the neighboring RefSeq genes, in spite of their significant expression levels. Similar features were also observed for the TSCs located in the antisense regions of the RefSeq genes. Furthermore, for the remaining iTSCs that were not associated with any RefSeq genes, we demonstrate that integrative interpretation of the transcriptome data provides essential information to specify their biological functions in the hypoxic responses of the cells