Towards a Role-Based Contextual Database

Traditional modeling approaches and information systems assume static entities that represent all information and attributes at once. However, due to the evolution of information systems to increasingly context-aware and self-adaptive systems, this assumption no longer holds. To cope with the required flexibility, the role concept was introduced. Although researchers have proposed several role modeling approaches, they usually neglect the contextual characteristics of roles and their representation in database management systems. Unfortunately, these systems do not rely on a conceptual model of an information system, rather they model this information by their own means leading to transformation and maintenance overhead. So far, the challenges posed by dynamic complex entities, their first class implementation, and their contextual characteristics lack detailed investigations in the area of database management systems. Hence, this paper, presents an approach that ties a conceptual role-based data model and its database implementation together, to directly represent the information modeled conceptually inside a database management system. In particular, we propose a formal database model to describe roles and their contextual information in compartments. Moreover, to provide a context-dependent role-based database interface, we extend RSQL by compartments. Finally, we introduce RSQL Result Net to preserve the contextual role semantics as well as enable users and applications to both iterate and navigate over results produced by RSQL. In sum, these means allow for a coherent design of more dynamic, complex software systems

RSQL - a query language for dynamic data types

Database Management Systems (DBMS) are used by software applications, to store, manipulate, and retrieve large sets of data. However, the requirements of current software systems pose various challenges to established DBMS. First, most software systems organize their data by means of objects rather than relations leading to increased maintenance, redundancy, and transformation overhead when persisting objects to relational databases. Second, complex objects are separated into several objects resulting in Object Schizophrenia and hard to persist Distributed State. Last but not least, current software systems have to cope with increased complexity and changes. These challenges have lead to a general paradigm shift in the development of software systems. Unfortunately, classical DBMS will become intractable, if they are not adapted to the new requirements imposed by these software systems. As a result, we propose an extension of DBMS with roles to represent complex objects within a relational database and support the exibility required by current software systems. To achieve this goal, we introduces RSQL, an extension to SQL with the concept of objects playing roles when interacting with other objects. Additionally, we present a formal model for the logical representation of roles in the extended DBMS

Ion therapy of prostate cancer: daily rectal dose reduction by application of spacer gel

Background: Ion beam therapy represents a promising approach to treat prostate cancer, mainly due to its high conformity and radiobiological effectiveness. However, the presence of prostate motion, patient positioning and range uncertainties may deteriorate target dose and increase exposure of organs at risk. Spacer gel injected between prostate and rectum may increase the safety of prostate cancer (PC) radiation therapy by separating the rectum from the target dose field. The dosimetric impact of the application of spacer gel for scanned carbon ion therapy of PC has been analyzed at Heidelberg Ion-Beam Therapy Center (HIT). Materials and methods: The robustness of ion therapy treatment plans was investigated by comparison of two data sets of patients treated with and without spacer gel. A research treatment planning system for ion therapy was used for treatment plan optimization and calculation of daily dose distributions on 2 to 9 Computed Tomography (CT) studies available for each of the 19 patients. Planning and daily dose distributions were analyzed with respect to target coverage, maximal dose to the rectum (excluding 1 ml of the greatest dose; Dmax-1 ml) and the rectal volume receiving dose greater than 90% of prescribed target dose (V90Rectum), respectively. Results: The application of spacer gel did substantially diminish rectum dose. Dmax-1 ml on the treatment planning CT was on average reduced from 100.0 ± 1.0% to 90.2 ± 4.8%, when spacer gel was applied. The robustness analysis performed with daily CT studies demonstrated for all analyzed patient cases that application of spacer gel results in a decrease of the daily V90Rectum index, which calculated over all patient cases and CT studies was 10.2 ± 10.4 [ml] and 1.1 ± 2.1 [ml] for patients without and with spacer gel, respectively. Conclusions: The dosimetric benefit of increasing the distance between prostate and rectum using spacer gel for PC treatment with carbon ion beams has been quantified. Application of spacer gel substantially reduced rectal exposure to high treatment dose and, therefore, can reduce the hazard of rectal toxicity in ion beam therapy of PC. The results of this study enable modifications of the PC ion therapy protocol such as dose escalation or hypofractionation

Randomized phase II study evaluating a carbon ion boost applied after combined radiochemotherapy with temozolomide versus a proton boost after radiochemotherapy with temozolomide in patients with primary glioblastoma: The CLEOPATRA Trial

<p>Abstract</p> <p>Background</p> <p>Treatment standard for patients with primary glioblastoma (GBM) is combined radiochemotherapy with temozolomide (TMZ). Radiation is delivered up to a total dose of 60 Gy using photons. Using this treatment regimen, overall survival could be extended significantly however, median overall survival is still only about 15 months.</p> <p>Carbon ions offer physical and biological advantages. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increase relative biological effectiveness (RBE), which can be calculated between 2 and 5 depending on the GBM cell line as well as the endpoint analyzed. Protons, however, offer an RBE which is comparable to photons.</p> <p>First Japanese Data on the evaluation of carbon ion radiation therapy showed promising results in a small and heterogeneous patient collective.</p> <p>Methods/Design</p> <p>In the current Phase II-CLEOPATRA-Study a carbon ion boost will be compared to a proton boost applied to the macroscopic tumor after surgery at primary diagnosis in patients with GBM applied after standard radiochemotherapy with TMZ up to 50 Gy. In the experimental arm, a carbon ion boost will be applied to the macroscopic tumor up to a total dose of 18 Gy E in 6 fractions at a single dose of 3 Gy E. In the standard arm, a proton boost will be applied up to a total dose 10 Gy E in 5 single fractions of 2 Gy E.</p> <p>Primary endpoint is overall survival, secondary objectives are progression-free survival, toxicity and safety.</p> <p>Discussion</p> <p>The Cleopatra Trial is the first study to evaluate the effect of carbon ion radiotherapy within multimodality treatment of primary glioblastoma in a randomized trial comparing this innovative treatment of the treatment standard, consisitng of photon radiotherapy in combination with temozolomide.</p> <p>Trial Registration</p> <p>ISRCTN37428883 and NCT01165671</p

Overcoming hypoxia-induced tumor radioresistance in non-small cell lung cancer by targeting DNA-dependent protein kinase in combination with carbon ion irradiation

Background: Hypoxia-induced radioresistance constitutes a major obstacle for a curative treatment of cancer. The aim of this study was to investigate effects of photon and carbon ion irradiation in combination with inhibitors of DNA-Damage Response (DDR) on tumor cell radiosensitivity under hypoxic conditions. Methods: Human non-small cell lung cancer (NSCLC) models, A549 and H1437, were irradiated with dose series of photon and carbon ions under hypoxia (1% O2) vs. normoxic conditions (21% O2). Clonogenic survival was studied after dual combinations of radiotherapy with inhibitors of DNA-dependent Protein Kinase (DNAPKi, M3814) and ATM serine/threonine kinase (ATMi). Results: The OER at 30% survival for photon irradiation of A549 cells was 1.4. The maximal oxygen effect measured as survival ratio was 2.34 at 8 Gy photon irradiation of A549 cells. In contrast, no significant oxygen effect was found after carbon ion irradiation. Accordingly, the relative effect of 6 Gy carbon ions was determined as 3.8 under normoxia and. 4.11 under hypoxia. ATM and DNA-PK inhibitors dose dependently sensitized tumor cells for both radiation qualities. For 100 nM DNAPKi the survival ratio at 4 Gy more than doubled from 1.59 under normoxia to 3.3 under hypoxia revealing a strong radiosensitizing effect under hypoxic conditions. In contrast, this ratio only moderately increased after photon irradiation and ATMi under hypoxia. The most effective treatment was combined carbon ion irradiation and DNA damage repair inhibition. Conclusions: Carbon ions efficiently eradicate hypoxic tumor cells. Both, ATMi and DNAPKi elicit radiosensitizing effects. DNAPKi preferentially sensitizes hypoxic cells to radiotherapy

Exportin 4 mediates a novel nuclear import pathway for Sox family transcription factors

SRY and other Sox-type transcription factors are important developmental regulators with various implications in human disease. In this study, we identified Exp4 (exportin 4) as an interaction partner of Sox2 in mouse embryonic stem cells and neural progenitors. We show that, besides its established function in nuclear export, Exp4 acts as a bona fide nuclear import receptor for Sox2 and SRY. Thus, Exp4 is an example of a nuclear transport receptor carrying distinct cargoes into different directions. In contrast to a published study, we observed that the import activity of Imp-α (importin-a) isoforms toward Sox2 is negligible. Instead, we found that Imp9 and the Imp-β/7 heterodimer mediate nuclear import of Sox2 in parallel to Exp4. Import signals for the three pathways overlap and include conserved residues in the Sox2 high-mobility group (HMG) box domain that are also critical for DNA binding. This suggests that nuclear import of Sox proteins is facilitated by several parallel import pathways

Single \pi^- production in np collisions for excess energies up to 90 MeV

The quasifree reaction np\to pp\pim was studied in a kinematically complete experiment by bombarding a liquid hydrogen target with a deuteron beam of momentum 1.85 GeV/c and analyzing the data along the lines of the spectator model. In addition to the three charged ejectiles the spectator proton was also detected in the large-acceptance time-of-flight spectrometer COSY-TOF. It was identified by its momentum and flight direction thus yielding access to the Fermi motion of the bound neutron and to the effective neutron 4-momentum vector $\mathbb{P}_n$ which differed from event to event. A range of almost 90 MeV excess energy above threshold was covered. Energy dependent angular distributions, invariant mass spectra as well as fully covered Dalitz plots were deduced. Sizeable $pp$ FSI effects were found as were contributions of $p$ and $d$ partial waves. The behavior of the elementary cross section $\sigma_{01}$ close to threshold is discussed in view of new cross section data. In comparison with existing literature data the results provide a sensitive test of the spectator model.Comment: 21 pages, 9 figures, 4 tables, submitted to EPJ