| 1. |
- Mainwaring, Oliver, et al.
(författare)
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ARF suppression by MYC but not MYCN confers increased malignancy of aggressive pediatric brain tumors
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Medulloblastoma, the most common malignant pediatric brain tumor, often harbors MYC amplifications. Compared to high-grade gliomas, MYC-amplified medulloblastomas often show increased photoreceptor activity and arise in the presence of a functional ARF/p53 suppressor pathway. Here, we generate an immunocompetent transgenic mouse model with regulatable MYC that develop clonal tumors that molecularly resemble photoreceptor-positive Group 3 medulloblastoma. Compared to MYCN-expressing brain tumors driven from the same promoter, pronounced ARF silencing is present in our MYC-expressing model and in human medulloblastoma. While partial Arf suppression causes increased malignancy in MYCN-expressing tumors, complete Arf depletion promotes photoreceptor-negative high-grade glioma formation. Computational models and clinical data further identify drugs targeting MYC-driven tumors with a suppressed but functional ARF pathway. We show that the HSP90 inhibitor, Onalespib, significantly targets MYC-driven but not MYCN-driven tumors in an ARF-dependent manner. The treatment increases cell death in synergy with cisplatin and demonstrates potential for targeting MYC-driven medulloblastoma.
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| 2. |
- Zamora, Juan Carlos, et al.
(författare)
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Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
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Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
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Tidskriftsartikel (refereegranskat)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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| 3. |
- Afifi, Haitham, et al.
(författare)
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Reinforcement learning for autonomous vehicle movements in wireless multimedia applications
- 2023
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Ingår i: Pervasive and Mobile Computing. - : Elsevier. - 1574-1192 .- 1873-1589. ; 92
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Tidskriftsartikel (refereegranskat)abstract
- We develop a Deep Reinforcement Learning (DeepRL)-based, multi-agent algorithm to efficiently control autonomous vehicles that are typically used within the context of Wireless Sensor Networks (WSNs), in order to boost application performance. As an application example, we consider wireless acoustic sensor networks where a group of speakers move inside a room. In a traditional setup, microphones cannot move autonomously and are, e.g., located at fixed positions. We claim that autonomously moving microphones improve the application performance. To control these movements, we compare simple greedy heuristics against a DeepRL solution and show that the latter achieves best application performance. As the range of audio applications is broad and each has its own (subjective) per-formance metric, we replace those application metrics by two immediately observable ones: First, quality of information (QoI), which is used to measure the quality of sensed data (e.g., audio signal strength). Second, quality of service (QoS), which is used to measure the network's performance when forwarding data (e.g., delay). In this context, we propose two multi-agent solutions (where one agent controls one microphone) and show that they perform similarly to a single-agent solution (where one agent controls all microphones and has a global knowledge). Moreover, we show via simulations and theoretical analysis how other parameters such as the number of microphones and their speed impacts performance.
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| 4. |
- Ahlgren, Bengt, et al.
(författare)
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Content, Connectivity and Cloud: Ingredients for the Network of the Future
- 2011. - 9
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Ingår i: IEEE Communications Magazine. - : IEEE Communications Society. - 0163-6804 .- 1558-1896. ; 49, s. 62-70
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Tidskriftsartikel (refereegranskat)abstract
- A new network architecture for the Internet needs ingredients from three approaches: information-centric networking, cloud computing integrated with networking, and open connectivity. Information-centric networking considers pieces of information as first-class entities of a networking architecture, rather than only indirectly identifying and manipulating them via a node hosting that information; this way, information becomes independent from the devices they are stored in, enabling efficient and application-independent information caching in the network. Cloud networking offers a combination and integration of cloud computing and virtual networking. It is a solution that distributes the benefits of cloud computing more deeply into the network, and provides a tighter integration of virtualisation features at computing and networking levels. To support these concepts, open connectivity services need to provide advanced transport and networking mechanisms, making use of network and path diversity (even leveraging direct optical paths) and encoding techniques, and dealing with ubiquitous mobility of user, content and information objects in a unified way.
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| 5. |
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| 6. |
- Bolin, Sara, 1988-, et al.
(författare)
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Dormant SOX9-positive cells behind MYC-driven medulloblastoma recurrence
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Tidskriftsartikel (refereegranskat)abstract
- Tumor recurrence is a slow biological process involving therapy resistance, immune escape, and metastasis and is the leading cause of death in medulloblastoma, the most frequent malignant pediatric brain tumor. By studying paired primary-recurrent patient samples and patient-derived xenografts we identified a significant accumulation of SOX9-positive cells in relapses and metastases. They exist as rare, quiescent cells in Group 3 and Group 4 patients that constitute two-thirds of medulloblastoma. To follow relapse at the single-cell level we developed an inducible dual Tet model of MYC-driven MB, where MYC can be directed from treatment-sensitive bulk cells to resistant, dormant SOX9-positive cells by doxycycline. SOX9 promoted immune es-cape, DNA repair suppression and was essential for recurrence. Tumor cell dormancy was non-hierarchical, migratory, and depended on MYC suppression by SOX9 to promote relapse. By using computational modeling and treatment we further showed how doxorubicin and MGMT inhibitors are specifically targeting relapsing cells.
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| 7. |
- Borgenvik, Anna, et al.
(författare)
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CDK2 as a therapeutic target in MYC-driven medulloblastoma
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Group 3 medulloblastoma (MB) is a malignant pediatric brain tumor that shows aberrant cell cycle activation, therapy resistance, and poor prognosis. Here, we identified that MYC expression and poor prognosis in Group 3 MB correlates with elevated levels of core cell cycle members CDK2 and cyclin A2, suggesting they would be promising targets for direct inhibition. Tumor cells in a novel transgenic MYC-driven MB mouse model further displayed increased p27 levels, decreased viability, and cell growth in vitro upon conditional CDK2 depletion using tamoxifen-induced recombination. Human Group 3 MB cells transduced with dominant-negative CDK2 mutants similarly exhibited decreased viability and increased p27 activation. As compared to controls, CDK2-depleted cells responded less to CDK2-specific inhibitors but were not more sensitive to BET inhibition or CDK4/6 inhibition as previously proposed. We finally used global transcriptional profiling and found that mTOR and B-Myb/ZMYM2 signaling pathways are compensating for CDK2 loss in Group 3MB cells. Our analysis suggests that specific inhibitors of these pathways could in combination with approved cell cycle inhibitors provide more efficient treatments for this severe childhood brain cancer.
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| 8. |
- Borgenvik, Anna, 1987-, et al.
(författare)
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Dormant SOX9-Positive Cells Facilitate MYC-Driven Recurrence of Medulloblastoma
- 2022
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Ingår i: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 82:24, s. 4586-4603
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Tidskriftsartikel (refereegranskat)abstract
- Relapse is the leading cause of death in patients with medulloblas-toma, the most common malignant pediatric brain tumor. A better understanding of the mechanisms underlying recurrence could lead to more effective therapies for targeting tumor relapses. Here, we observed that SOX9, a transcription factor and stem cell/glial fate marker, is limited to rare, quiescent cells in high-risk medulloblastoma with MYC amplification. In paired primary-recurrent patient samples, SOX9-positive cells accumulated in medulloblastoma relapses. SOX9 expression anti-correlated with MYC expression in murine and human medulloblastoma cells. However, SOX9-positive cells were plastic and could give rise to a MYC high state. To follow relapse at the single-cell level, an inducible dual Tet model of medulloblastoma was developed, in which MYC expression was redirected in vivo from treatment-sensitive bulk cells to dormant SOX9-positive cells using doxycycline treatment. SOX9 was essential for relapse initiation and depended on suppression of MYC activity to promote therapy resistance, epithelial-mesenchymal transition, and immune escape. p53 and DNA repair pathways were downregulated in recurrent tumors, whereas MGMT was upregulated. Recurrent tumor cells were found to be sensitive to treatment with an MGMT inhibitor and doxorubicin. These findings suggest that recurrence-specific targeting coupled with DNA repair inhibition comprises a potential therapeutic strategy in patients affected by medulloblastoma relapse.Significance: SOX9 facilitates therapy escape and recurrence in medulloblastoma via temporal inhibition of MYC/MYCN genes, revealing a strategy to specifically target SOX9-positive cells to prevent tumor relapse.
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| 9. |
- Bousquet, Jean, et al.
(författare)
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ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice
- 2021
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 76:1, s. 168-190
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Forskningsöversikt (refereegranskat)abstract
- Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
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| 10. |
- Bousquet, J. Jean, et al.
(författare)
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Next-generation ARIA care pathways for rhinitis and asthma : a model for multimorbid chronic diseases
- 2019
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Ingår i: Clinical and Translational Allergy. - : BMC. - 2045-7022. ; 9
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Forskningsöversikt (refereegranskat)abstract
- Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy.Main body: As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Sante as a Good Practice in the field of digitally-enabled, integrated, person-centred care.Conclusion: In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.
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