Mutation Analysis of Radioresistant Early-Stage Cervical Cancer

Radiotherapy is a definitive treatment for early-stage cervical cancer; however, a subset of this disease recurs locally, necessitating establishment of predictive biomarkers and treatment strategies. To address this issue, we performed gene panel-based sequencing of 18 stage IB cervical cancers treated with definitive radiotherapy, including two cases of local recurrence, followed by in vitro and in silico analyses. Simultaneous mutations in KRAS and SMAD4 (KRAS^mt/SMAD4^mt) were detected only in a local recurrence case, indicating potential association of this mutation signature with radioresistance. In isogenic cell-based experiments, a combination of activating KRAS mutation and SMAD4 deficiency led to X-ray resistance, whereas either of these factors alone did not. Analysis of genomic data from 55,308 cancers showed a significant trend toward co-occurrence of mutations in KRAS and SMAD4. Gene Set Enrichment Analysis of the Cancer Cell Line Encyclopedia dataset suggested upregulation of the pathways involved in epithelial mesenchymal transition and inflammatory responses in KRAS^mt/SMAD4^mt cancer cells. Notably, irradiation with therapeutic carbon ions led to robust killing of X-ray-resistant KRAS^mt/SMAD4^mt cancer cells. These data indicate that the KRAS^mt/SMAD4^mt signature is a potential predictor of radioresistance, and that carbon ion radiotherapy is a potential option to treat early-stage cervical cancers with the KRAS^mt/SMAD4^mt signature.     

欧盟之外的绿色法规美国和世界其他许多国家都在制定环境法规

欧盟的《禁止使用有害物质指令》（RoHS）和《报废电子电气设备指令》（WEEE）有力地推动了将已颁布的环保法律付诸实施．其影响已经扩展到欧盟以外的地区。下面是其他国家和地区的有关概况。     

Glucose Production from Maltohexaose as a Substrate by the Bacterial Alpha-amylase-catalyzed Reaction. Its Time Courses Obtained by a Theoretical and an Experimental Approaches

Based on the subsite structure of an α-amylase from Bacillus subtilis, production of glucose from a substrate maltohexaose in the amylase-catalyzed reaction was theoretically predicted as a function of time. The theoretical time course was found consistent with the experimental results, which were obtained by the determination of a product glucose with a commercial assay-kit. Hence, glucose, product from a substrate maltohexaose, will be a useful probe for the amylase-catalyzed reaction.     

Solubility of NiO in Al2O3

Solubility of NiO in Al₂O₃ was determined by electron probe microanalysisy A diffusion couple method was used by coupling an NiO-doped Al₂O₃ polycrystal to a pure single crystal of Al₂O₃. The solubility of NiO in Al₂O₃ in air was 230 wt ppm (157 at. ppm of cations) and 170 wt ppm (116 at. ppm) at 2073 and 1973 K, respectively. The solubility of NiO in Al₂O₃ obtained in this work was compared with our previous work of the solubility of MgO in Al₂o₃.     

OWL‐based acquisition and editing of computer‐interpretable guidelines with the CompGuide editor

Computer‐Interpretable Guidelines (CIGs) are the dominant medium for the delivery of clinical decision support, given the evidence‐based nature of their source material. Therefore, these machine‐readable versions have the ability to improve practitioner performance and conformance to standards, with availability at the point and time of care. The formalisation of Clinical Practice Guideline knowledge in a machine‐readable format is a crucial task to make it suitable for the integration in Clinical Decision Support Systems. However, the current tools for this purpose reveal shortcomings with respect to their ease of use and the support offered during CIG acquisition and editing. In this work, we characterise the current landscape of CIG acquisition tools based on the properties of guideline visualisation, organisation, simplicity, automation, manipulation of knowledge elements, and guideline storage and dissemination. Additionally, we describe the CompGuide Editor, a tool for the acquisition of CIGs in the CompGuide model for Clinical Practice Guidelines that also allows the editing of previously encoded guidelines. The Editor guides the users throughout the process of guideline encoding and does not require proficiency in any programming language. The features of the CIG encoding process are revealed through a comparison with already established tools for CIG acquisition.     

Robustness of linearly solvable Markov games employing inaccurate dynamics model

As a model-based reinforcement learning technique, linearly solvable Markov decision process (LMDP) gives an efficient way to find an optimal policy by making the Bellman equation linear under some assumptions. Since LMDP is regarded as model-based reinforcement learning, the performance of LMDP is sensitive to the accuracy of the environmental model. To overcome the problem of the sensitivity, linearly solvable Markov game (LMG) has been proposed, which is an extension of LMDP based on the game theory. This paper investigates the robustness of LMDP- and LMG-based controllers against modeling errors in both discrete and continuous state-action problems. When there is a discrepancy between the model used for building the control policy and dynamics of the tested environment, the LMG-based control policy maintained good performance while that of the LMDP-based control policy deteriorated drastically. Experimental results support the usefulness of LMG framework when acquiring an accurate model of the environment is difficult.     

From Pencils to Partners: The Next Role of Computation in Building Design

As building information modelling (BIM) software becomes ever more powerful, how will the architect's role be affected? Ian Keough and Anthony Hauck of the AEC Generative Design group at leading software corporation Autodesk present their vision. They argue that the value of building professionals' expertise in advising clients on priorities and choices has never been higher. BIM offers greater guarantees of structural integrity and constructional feasibility, and scalable cloud computing allows numerous factors to be explored simultaneously; but success is only assured if the right parameters are set.