11. The analysis of doses in the tumour and in critical tissues in the brachytherapy of malignant melanoma localised in eyes

Brachytherapy is known and used procedure in the treatment of tumours localised in eyes, especially recommended when avoiding of enucleation accompany the long term cure.AimThe aim of this paper was to compare the doses delivered to the tumour and critical tissues during the treatment of the group of patients treated with Ru-106 applicator.PatientsBetween 1994 and 2000, 67 patients (dgn. melanoma malignum in eye) underwent brachytherapy. At 51 patients the tumour was localized in the back of eye, at 15 equatorially and at one in the front section of the eyeball. The median of the patients’ age was 56.3 years. The CCB type applicator was applied for 56 patients, the COB for 7 and the ROA for 4 patients.MethodIrradiation – Prescribed dose of 60 Gy was normalized to the top of the tumour, it decreased by 50%—10% per millimetre with the distance from applicator. The isotope producer determined the dose-rate accuracy for +/−30%. This caused that therapeutic dose had to be calculated taking account for the minimal dose-rate, while the doses in critical organs for maximal dose-rate possible.AnalysisAll patients were divided into three subgroups: 8 patients into 1st, 19 into 2nd and 40 into 3rd. The inclusion criterion was size of tumour: up to 3 mm of height (1st group), 3–5 mm (2nd), and larger than 5 mm (3rd) respectively.ResultsTable presents mean doses in the tumour, sclera and lens (calculated at it's middle) for each group of patients.[[tgroup cols="4"]][[colspec colname="col1"/]][[colspec colname="col2"/]][[colspec colname="col3"/]][[colspec colname="col4"/]][[tbody]][[row]][[entry morerows="1" rowsep="1" align="center"]]Tumour size [mm][[/entry]][[entry namest="col2" nameend="col4" rowsep="1" align="center"]]Doses [Gy][[/entry]][[/row]][[row]][[entry rowsep="1" align="center"]]Tumour[[/entry]][[entry rowsep="1" align="center"]]Sclera[[/entry]][[entry rowsep="1" align="center"]]lens[[/entry]][[/row]][[row]][[entry rowsep="1" align="center"]]5[[/entry]][[entry align="center"]]268.2[[/entry]][[entry align="center"]]974.9[[/entry]][[entry align="center"]]840.6[[/entry]][[/row]][[/tbody]][[/tgroup]]ConclusionsMean doses in tumour varied from 102.9 Gy to 268.2 Gy depending on the tumour size. Doses in sclera and lens did not exceed the tolerance levels in all three groups of patients

Effect of irradiation on interleukin 6 and soluble interleukin 6 receptor modified melanoma genetic vaccine

We have designed phase I/II human melanoma gene therapy clinical protocol. The aim of the study was to actively immunize HLA-A1 and/or HLA-A2-positive patients with melanoma with an admixture of irradiated autologous tumor cells and allogeneic melanoma cells genetically engineered to secrete IL-6 and sIL-6R in order to elicit or enhance specific and nonspecific anti-melanoma immune responses to autologous tumor cells to eradicate distant melanoma lesions. Irradiation of autologous and allogeneic tumor cells is a key step in preparation of cellular vaccine because of two major reasons, (i) it inhibits cell proliferation which is crucial in the case of autologous cells which may form a tumor; (ii) it increases melanoma vaccine immunogenicity. The aim of the study was to estimate the optimal dose of ionizing radiation which will provide sterilization of both autologous and allogeneic melanoma cells and will ensure cytokine secretion.Human melanoma cells (Mich-1) were transduced with IL-6 and sIL-6R cDNA using double copy bicistronic retroviral vector. Parental and transduced cells were seeded at in six-well tissue culture plates and were irradiated with 10, 50, 100 and 200 Gy. Secretion of both recombinant proteins into culture was analyzed before and 24, 48, 72, 96 h and 6, 7, 10 and 12 days following irradiation. At the same time adherent cells were enumerated, evaluated for viability and proliferation. At 24, 48, 72 and 96 h postirradiation specific IL-6 and sIL-6R mRNA levels were analyzed.Irradiation of gene modified cells inhibited their proliferation in the dose dependant manner. Dose of 50 Gy sufficiently affected cell proliferation, however, for safety reasons we decided to use the dose of 100 Gy for vaccine preparation. Irradiation did not inhibit secretion of IL-6 and sIL-6R. In contrary, on a per cell basis it significantly increased their secretion which lasted 12 days postirradiation. Interestingly, we did not observe dose or time dependent differences in specific mRNA cellular levels suggesting that increased secretion of both proteins is regulated not on the transcriptional but rather on the posttranscriptional level. Taking all these facts into account we concluded that irradiation of tumor cells may provide an effective and safe approach for gene-modified vaccine preparation

Effect of irradiation on interleukin 6 and soluble interleukin 6 receptor modified melanoma genetic vaccine

We have designed phase I/II human melanoma gene therapy clinical protocol. The aim of the study was to actively immunize HLA-A1 and/or HLA-A2-positive patients with melanoma with an admixture of irradiated autologous tumor cells and allogeneic melanoma cells genetically engineered to secrete IL-6 and sIL-6R in order to elicit or enhance specific and nonspecific antimelanoma immune responses to autologous tumor cells to eradicate distant melanoma lesions. Irradiation of autologous and allogeneic tumor cells is a key step in preparation of cellular vaccine because of two major reasons, (i) it inhibits cell proliferation which is crucial in the case of autologous cells which may form a tumor; (ii) it increases melanoma vaccine immunogenicity. The aim of the study was to estimate the optimal dose of ionizing radiation which will provide sterilization of both autologous and allogeneic melanoma cells and will ensure cytokine secretion.Human melanoma cells (Mich-1) were transduced with IL-6 and sIL-6R cDNA using double copy bicistronic retroviral vector. Parental and transduced cells were seeded at in six-well tissue culture plates and were irradiated with 10, 50, 100 and 200 Gy. Secretion of both recombinant proteins into culture was analyzed before and 24, 48,72,96 h and 6, 7, 10 and 12 days following irradiation. At the same time adherent cells were enumerated, evaluated’ for viability and proliferation. At 24, 48, 72 and 96 h postirradiation specific IL-6 and sIL-6R mRNA levels were analyzed.Irradiation of gene modified cells inhibited their proliferation in the dose dependant manner. Dose of 50 Gy sufficiently affected cell proliferation, however, for safety reasons we decided to use the dose of 100 Gy for vaccine preparation. Irradiation did not inhibit secretion of IL-6 and sIL-6R. In contrary, on a per cell basis it significantly increased their secretion which lasted 12 days postirradiation. Interestingly, we did not observe dose or time dependent differences in specific mRNA cellular levels suggesting that increased secretion of both proteins is regulated not on the transcriptional but rather on the posttranscriptional level. Taking all these facts into account we concluded that irradiation of tumor cells may provide an effective and safe approach for gene-modified vaccine preparation

Low-Rank Subspace Override for Unsupervised Domain Adaptation

Current supervised learning models cannot generalize well across domain boundaries, which is a known problem in many applications, such as robotics or visual classification. Domain adaptation methods are used to improve these generalization properties. However, these techniques suffer either from being restricted to a particular task, such as visual adaptation, require a lot of computational time and data, which is not always guaranteed, have complex parameterization, or expensive optimization procedures. In this work, we present an approach that requires only a well-chosen snapshot of data to find a single domain invariant subspace. The subspace is calculated in closed form and overrides domain structures, which makes it fast and stable in parameterization. By employing low-rank techniques, we emphasize on descriptive characteristics of data. The presented idea is evaluated on various domain adaptation tasks such as text and image classification against state of the art domain adaptation approaches and achieves remarkable performance across all tasks

3D time series analysis of cell shape using Laplacian approaches

Background: Fundamental cellular processes such as cell movement, division or food uptake critically depend on cells being able to change shape. Fast acquisition of three-dimensional image time series has now become possible, but we lack efficient tools for analysing shape deformations in order to understand the real three-dimensional nature of shape changes. Results: We present a framework for 3D+time cell shape analysis. The main contribution is three-fold: First, we develop a fast, automatic random walker method for cell segmentation. Second, a novel topology fixing method is proposed to fix segmented binary volumes without spherical topology. Third, we show that algorithms used for each individual step of the analysis pipeline (cell segmentation, topology fixing, spherical parameterization, and shape representation) are closely related to the Laplacian operator. The framework is applied to the shape analysis of neutrophil cells. Conclusions: The method we propose for cell segmentation is faster than the traditional random walker method or the level set method, and performs better on 3D time-series of neutrophil cells, which are comparatively noisy as stacks have to be acquired fast enough to account for cell motion. Our method for topology fixing outperforms the tools provided by SPHARM-MAT and SPHARM-PDM in terms of their successful fixing rates. The different tasks in the presented pipeline for 3D+time shape analysis of cells can be solved using Laplacian approaches, opening the possibility of eventually combining individual steps in order to speed up computations

Active target TPC for study of photonuclear reactions at astrophysical energies

A setup designed to study photonuclear reactions at astrophysical energies - an active target Time Projection Chamber was developed and constructed at the Faculty of Physics, University of Warsaw. The device was successfully employed in two experiments at the Institute of Nuclear Physics Polish Academy of Sciences in Cracow, in which {\gamma}- and neutron-induced reactions with CO2 gas target were measured. The reaction products were detected and their momenta reconstructed. Preliminary results are shown.Comment: Presented at Zakopane Conference on Nuclear Physics 202

"Pi of the Sky" - all-sky, real-time search for fast optical transients

An apparatus to search for optical flashes in the sky is described. It has been optimized for gamma ray bursts (GRB) optical counterparts. It consists of 2x16 cameras covering all the sky. The sky is monitored continuously and the data are analysed on-line. It has self-triggering capability and can react to external triggers with negative delay. The prototype with two cameras has been installed at Las Campanas (Chile) and is operational from July 2004. The paper presents general idea and describes the apparatus in detail. Performance of the prototype is briefly reviewed and perspectives for the future are outlined

The SERRATE protein is involved in alternative splicing in <em>Arabidopsis thaliana</em>

Howalternative splicing (AS) is regulated in plants has not yet been elucidated. Previously, we have shown that the nuclear cap-binding protein complex (AtCBC) is involved in AS in Arabidopsis thaliana. Here we show that both subunits of AtCBC (AtCBP20 and AtCBP80) interact with SERRATE (AtSE), a protein involved in the microRNA biogenesis pathway. Moreover, using a high-resolution reverse transcript-ase-polymerase chain reaction AS system we have found that AtSE influences AS in a similar way to the cap-binding complex (CBC), preferentially affecting selection of 50 splice site of first introns. The AtSE protein acts in cooperation with AtCBC: many changes observed in the mutant lacking the correct SERRATE activity were common to those observed in the cbp mutants. Interestingly, significant changes in AS of some genes were also observed in other mutants of plant microRNA biogenesis pathway, hyl1-2 and dcl1-7, but a majority of them did not cor-respond to the changes observed in the se-1mutant. Thus, the role of SERRATE in AS regulation is distinct from that of HYL1andDCL1, and is similar to the regu-lation of AS in which CBC is involved

An RPC-based Technical Trigger for the CMS Experiment

In the CMS experiment, sub-detectors may send special trigger signals, called "Technical Triggers", for special purposes like test and calibration. The Resistive Plate Chambers are part of the Muon Trigger System of the experiment, but might also produce a cosmic muon trigger as Technical Trigger to be used during the commissioning to the detectors, the CMS magnet Test Cosmic Challenge and the later running of CMS. The proposed implementation is based on the development of a new board, the RBC Balcony Collector (RBC); the test results on prototypes and their performance during the recent CMS Cosmic Challenge are presented