104 research outputs found
Co-using Infrastructure for Sustainability in Maritime Transports
Sustainable transportation systems require optimal co-use of infrastructure. Different means of transportation use infrastructure for its operations. At certain points these means of transportation utilizes the same infrastructure, such as e.g. passages on or under bridges, which require co-modal coordination. To create means for such coordination, situational awareness needs to be established among involved actors by digitalization and principles for information sharing. In this short paper, a co-modal transport system, GOTRIS (Göta Älv River Information Services), is used as a basis for a deeper understanding of the challenges for reaching an optimal co-use of infrastructure. By integrating information from maritime transports as one source in this coordination effort, sustainable transportation systems can be reached. This challenge is formulated in a research question and a preferred approach is stated
Exploring the potential of ancestral phenylalanine/tyrosine ammonia-lyases for therapeutic applications
Phenylalanine/tyrosine ammonia-lyases (PAL/TAL) have been approved by the FDA for treatment of phenylketonuria and may also harbor potential for complimentary treatment of hereditary tyrosinemia type II. Herein, we explore ancestral sequence reconstruction as an enzyme engineering tool to increase stability and alter substrate specificity, which could enhance the therapeutic potential of these enzymes. We used MEGA and PAML to reconstruct putative ancestors of PAL/TAL from fungi and compared them to two modern enzymes that have a relatively low PAL/TAL activity ratio. The majority of ancestors could be functionally expressed in E. coli and showed activity towards both phenylalanine and tyrosine. All ancestral enzymes displayed increased thermostability compared to both modern enzymes, however, the increase in thermostability was accompanied by a loss in activity when going back in the phylogenetic tree. One reconstructed ancestral enzyme could be interesting for further development, as its catalytic turnover of tyrosine is slightly higher than one of the modern enzymes and it is significantly more thermostable than both modern enzymes. More detailed characterization of the ancestral variants with a focus on stability is currently ongoing. Our results indicate that ancestral sequence reconstruction programs are robust in terms of stability, whereas activity of ancestral variants seems to vary depending on the reconstruction method. We believe that this approach has great potential for enhancing the properties of therapeutic enzymes and biocatalysts for various applications
Prognostic and predictive impact of stroma cells defned by PDGFRb expression in early breast cancer: results from the randomized SweBCG91RT trial
Purpose
Predictive biomarkers are needed to aid the individualization of radiotherapy (RT) in breast cancer. Cancer-associated fibroblasts have been implicated in tumor radioresistance and can be identified by platelet-derived growth factor receptor-beta (PDGFRb). This study aims to analyze how PDGFRb expression affects RT benefit in a large randomized RT trial.
Methods
PDGFRb was assessed by immunohistochemistry on tissue microarrays from 989 tumors of the SweBCG91RT trial, which enrolled lymph node-negative, stage I/IIA breast cancer patients randomized to RT after breast-conserving surgery. Outcomes were analyzed at 10 years for ipsilateral breast tumor recurrence (IBTR) and any recurrence and 15 years for breast cancer specific death (BCSD).
Results
PDGFRb expression correlated with estrogen receptor negativity and younger age. An increased risk for any recurrence was noted in univariable analysis for the medium (HR 1.58, CI 95% 1.11–2.23, p = 0.011) or PDGFRb high group (1.49, 1.06–2.10, p = 0.021) compared to the low group. No differences in IBTR or BCSD risk were detected. RT benefit regarding IBTR risk was significant in the PDGFRb low (0.29, 0.12–0.67, p = 0.004) and medium (0.31, 0.16–0.59, p < 0.001) groups but not the PDGFRb high group (0.64, 0.36–1.11, p = 0.110) in multivariable analysis. Likewise, risk reduction for any recurrence was less pronounced in the PDGFRb high group. No significant interaction between RT and PDGFRb-score could be detected.
Conclusion
A higher PDGFRb-score conferred an increased risk of any recurrence, which partly can be explained by its association with estrogen receptor negativity and young age. Reduced RT benefit was noted among patients with high PDGFRb, however without significant interaction.publishedVersio
Validation of a breast cancer assay for radiotherapy omission: an individual participant data meta-analysis
Background: There are currently no molecular tests to identify individual breast cancers where radiotherapy (RT) offers no benefit. Profile for the Omission of Local Adjuvant Radiotherapy (POLAR) is a 16-gene molecular signature developed to identify low risk cancers where RT will not further reduce recurrence rates. Methods: An individual participant data meta-analysis was performed in 623 cases of node-negative ER+/HER2-negative early breast cancer enrolled in three RT randomized trials for whom primary tumor material was available for analysis. A Cox proportional hazards model on time to locoregional recurrence (LRR) was used to test the interaction between POLAR score and RT.Results: 429 (69%) patients’ tumors had a high POLAR score and 194 (31%) had a low score. Patients with high POLAR score had, in the absence of RT, a 10-year cumulative incidence of LRR: 20% (15%-26%) vs 5% (2%-11%) for those with a low score. Patients with a high POLAR score had a large benefit from RT (hazard ratio [HR] for RT vs no RT: 0.37 [0.23-0.60], p<0.001). In contrast, there was no evidence of benefit from RT for patients with a low POLAR score (HR: 0.92 [0.42-2.02], p = 0.832). The test for interaction between RT and POLAR was statistically significant (p = 0.022).Conclusions: POLAR is not only prognostic for locoregional recurrence but also predictive of benefit from radiotherapy in selected patients. Patients ≥ 50 years with ER+/HER2-negative disease and a low POLAR score could consider omitting adjuvant RT. Further validation in contemporary clinical cohorts is required.<br/
Integrerade mobilitetstjänster – Plattformar, roller och industriarkitekturer – en svensk utblick
Chalmers, i samverkan med RISE Viktoria, har inom ramen för K2 omvärldsbevakat området integrerade mobilitetstjänster utifrån ett brett kollektivtrafikrelaterat perspektiv. Målet är ökad förståelse för hur området utvecklasIntegrerade mobilitetstjänster – systematisk omvärldsbevaknin
Decision Support System for Fault Isolation of JAS 39 Gripen : Development and Implementation
This thesis is a result of the increased requirements on availability and costs of the aircraft Jas 39 Gripen. The work has been to specify demands and to find methods suitable for development of a decision support system for the fault isolation of the aircraft. The work has also been to implement the chosen method. Two different methods are presented and a detailed comparison is performed with the demands as a starting point. The chosen method handle multiple faults in O(N2)-time where N is the number of components. The implementation shows how all demands are fulfilled and how new tests can be added during execution. Since the thesis covers the development of a prototype no practical evaluation with compare of manually isolation is done
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