| 1. |
- Olmeda, David, et al.
(författare)
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Whole-body imaging of lymphovascular niches identifies pre-metastatic roles of midkine
- 2017
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Ingår i: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 546:7660, s. 676-680
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Tidskriftsartikel (refereegranskat)abstract
- Cutaneous melanoma is a type of cancer with an inherent potential for lymph node colonization, which is generally preceded by neolymphangiogenesis(1-3). However, sentinel lymph node removal does not necessarily extend the overall survival of patients with melanoma(4,5). Moreover, lymphatic vessels collapse and become dysfunctional as melanomas progress(6,7). Therefore, it is unclear whether (and how) lymphangiogenesis contributes to visceral metastasis. Soluble and vesicle-associated proteins secreted by tumours and/or their stroma have been proposed to condition pre-metastatic sites in patients with melanoma(8-14). Still, the identities and prognostic value of lymphangiogenic mediators remain unclear(2,14). Moreover, our understanding of lymphangiogenesis (in melanomas and other tumour types) is limited by the paucity of mouse models for live imaging of distal pre-metastatic niches(15). Injectable lymphatic tracers have been developed(7), but their limited diffusion precludes whole-body imaging at visceral sites(16). Vascular endothelial growth factor receptor 3 (VEGFR3) is an attractive 'lymphoreporter' 17 because its expression is strongly downregulated in normal adult lymphatic endothelial cells, but is activated in pathological situations such as inflammation and cancer(17,18). Here, we exploit this inducibility of VEGFR3 to engineer mouse melanoma models for whole-body imaging of metastasis generated by human cells, clinical biopsies or endogenously deregulated oncogenic pathways. This strategy revealed early induction of distal pre-metastatic niches uncoupled from lymphangiogenesis at primary lesions. Analyses of the melanoma secretome and validation in clinical specimens showed that the heparin-binding factor midkine is a systemic inducer of neo-lymphangiogenesis that defines patient prognosis. This role of midkine was linked to a paracrine activation of the mTOR pathway in lymphatic endothelial cells. These data support the use of VEGFR3 reporter mice as a 'MetAlert' discovery platform for drivers and inhibitors of metastasis.
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| 2. |
- Labit, B., et al.
(författare)
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Dependence on plasma shape and plasma fueling for small edge-localized mode regimes in TCV and ASDEX Upgrade
- 2019
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:8
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Tidskriftsartikel (refereegranskat)abstract
- © 2019 Institute of Physics Publishing. All rights reserved. Within the EUROfusion MST1 work package, a series of experiments has been conducted on AUG and TCV devices to disentangle the role of plasma fueling and plasma shape for the onset of small ELM regimes. On both devices, small ELM regimes with high confinement are achieved if and only if two conditions are fulfilled at the same time. Firstly, the plasma density at the separatrix must be large enough (ne,sep/nG ∼ 0.3), leading to a pressure profile flattening at the separatrix, which stabilizes type-I ELMs. Secondly, the magnetic configuration has to be close to a double null (DN), leading to a reduction of the magnetic shear in the extreme vicinity of the separatrix. As a consequence, its stabilizing effect on ballooning modes is weakened.
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| 3. |
- Morales, Carmen, et al.
(författare)
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PDS5 proteins are required for proper cohesin dynamics and participate in replication fork protection
- 2020
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Ingår i: Journal of Biological Chemistry. - : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 295:1, s. 146-157
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Tidskriftsartikel (refereegranskat)abstract
- Cohesin is a chromatin-bound complex that mediates sister chromatid cohesion and facilitates long-range interactions through DNA looping. How the transcription and replication machineries deal with the presence of cohesin on chromatin remains unclear. The dynamic association of cohesin with chromatin depends on WAPL cohesin release factor (WAPL) and on PDS5 cohesin-associated factor (PDS5), which exists in two versions in vertebrate cells, PDS5A and PDS5B. Using genetic deletion in mouse embryo fibroblasts and a combination of CRISPR-mediated gene editing and RNAi-mediated gene silencing in human cells, here we analyzed the consequences of PDS5 depletion for DNA replication. We found that either PDS5A or PDS5B is sufficient for proper cohesin dynamics and that their simultaneous removal increases cohesin's residence time on chromatin and slows down DNA replication. A similar phenotype was observed in WAPL-depleted cells. Cohesin down-regulation restored normal replication fork rates in PDS5-deficient cells, suggesting that chromatin-bound cohesin hinders the advance of the replisome. We further show that PDS5 proteins are required to recruit WRN helicase-interacting protein 1 (WRNIP1), RAD51 recombinase (RAD51), and BRCA2 DNA repair associated (BRCA2) to stalled forks and that in their absence, nascent DNA strands at unprotected forks are degraded by MRE11 homolog double-strand break repair nuclease (MRE11). These findings indicate that PDS5 proteins participate in replication fork protection and also provide insights into how cohesin and its regulators contribute to the response to replication stress, a common feature of cancer cells.
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| 4. |
- Nanni, Mirco, et al.
(författare)
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Give more data, awareness and control to individual citizens, and they will help COVID-19 containment
- 2020
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Ingår i: Transactions on Data Privacy. - : Institut d'Investigació en Intel·ligència Artificial. - 1888-5063 .- 2013-1631. ; 23, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- The rapid dynamics of COVID-19 calls for quick and effective tracking of virus transmission chains and early detection of outbreaks, especially in the "phase 2" of the pandemic, when lockdown and other restriction measures are progressively withdrawn, in order to avoid or minimize contagion resurgence. For this purpose, contact-tracing apps are being proposed for large scale adoption by many countries. A centralized approach, where data sensed by the app are all sent to a nation-wide server, raises concerns about citizens' privacy and needlessly strong digital surveillance, thus alerting us to the need to minimize personal data collection and avoiding location tracking. We advocate the conceptual advantage of a decentralized approach, where both contact and location data are collected exclusively in individual citizens' "personal data stores", to be shared separately and selectively (e.g., with a backend system, but possibly also with other citizens), voluntarily, only when the citizen has tested positive for COVID-19, and with a privacy preserving level of granularity. This approach better protects the personal sphere of citizens and affords multiple benefits: it allows for detailed information gathering for infected people in a privacy-preserving fashion; and, in turn this enables both contact tracing, and, the early detection of outbreak hotspots on more finely-granulated geographic scale. The decentralized approach is also scalable to large populations, in that only the data of positive patients need be handled at a central level. Our recommendation is two-fold. First to extend existing decentralized architectures with a light touch, in order to manage the collection of location data locally on the device, and allowthe user to share spatio-temporal aggregates - if and when they want and for specific aims - with health authorities, for instance. Second, we favour a longerterm pursuit of realizing a Personal Data Store vision, giving users the opportunity to contribute to collective good in the measure they want, enhancing self-awareness, and cultivating collective efforts for rebuilding society.
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| 5. |
- Salas, Julián, et al.
(författare)
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Differentially private graph publishing through noise-graph addition
- 2023
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Ingår i: Modeling decisions for artificial intelligence. - : Springer Science+Business Media B.V.. - 9783031334979 - 9783031334986 ; , s. 253-264
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Konferensbidrag (refereegranskat)abstract
- Differential privacy is commonly used for graph analysis in the interactive setting, were a query of some graph statistic is answered with additional noise to avoid leaking private information. In such setting, only a statistic can be studied. However, in the non-interactive setting, the data may be protected with differential privacy and then published, allowing for all kinds of privacy preserving analyses. We present a noise-graph addition method to publish graphs with differential privacy guarantees. We show its relation to the probabilities in the randomized response matrix and prove that such probabilities can be chosen in such a way to preserve the sparseness of the original graph in the protected graph. Thus, better preserving the utility for different tasks, such as link prediction. Additionally, we show that the previous models of random perturbation and random sparsification are differentially private, and calculate the ϵ guarantees that they provide depending on their specifications.
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| 6. |
- Salas, Julián, et al.
(författare)
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SwapMob : Swapping trajectories for mobility anonymization
- 2018
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Ingår i: Privacy in Statistical Databases. - Cham : Springer. - 9783319997704 - 9783319997711 ; , s. 331-346
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Konferensbidrag (refereegranskat)abstract
- Mobility data mining can improve decision making, from planning transports in metropolitan areas to localizing services in towns. However, unrestricted access to such data may reveal sensible locations and pose safety risks if the data is associated to a specific moving individual. This is one of the many reasons to consider trajectory anonymization. Some anonymization methods rely on grouping individual registers on a database and publishing summaries in such a way that individual information is protected inside the group. Other approaches consist of adding noise, such as differential privacy, in a way that the presence of an individual cannot be inferred from the data. In this paper, we present a perturbative anonymization method based on swapping segments for trajectory data (SwapMob). It preserves the aggregate information of the spatial database and at the same time, provides anonymity to the individuals. We have performed tests on a set of GPS trajectories of 10,357 taxis during the period of Feb. 2 to Feb. 8, 2008, within Beijing. We show that home addresses and POIs of specific individuals cannot be inferred after anonymizing them with SwapMob, and remark that the aggregate mobility data is preserved without changes, such as the average length of trajectories or the number of cars and their directions on any given zone at a specific time.
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| 7. |
- Salas, Julián, et al.
(författare)
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Swapping trajectories with a sufficient sanitizer
- 2020
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Ingår i: Pattern Recognition Letters. - : Elsevier. - 0167-8655 .- 1872-7344. ; 131, s. 474-480
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Tidskriftsartikel (refereegranskat)abstract
- Real-time mobility data is useful for several applications such as planning transports in metropolitan areas or localizing services in towns. However, if such data is collected without any privacy protection it may reveal sensible locations and pose safety risks to an individual associated to it. Thus, mobility data must be anonymized preferably at the time of collection. In this paper, we consider the SwapMob algorithm that mitigates privacy risks by swapping partial trajectories. We formalize the concept of sufficient sanitizer and show that the SwapMob algorithm is a sufficient sanitizer for various statistical decision problems. That is, it preserves the aggregate information of the spatial database in the form of sufficient statistics and also provides privacy to the individuals. This may be used for personalized assistants taking advantage of users’ locations, so they can ensure user privacy while providing accurate response to the user requirements. We measure the privacy provided by SwapMob as the Adversary Information Gain, which measures the capability of an adversary to leverage his knowledge of exact data points to infer a larger segment of the sanitized trajectory. We test the utility of the data obtained after applying SwapMob sanitization in terms of Origin-Destination matrices, a fundamental tool in transportation modelling.
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| 8. |
- Salas, Julián, et al.
(författare)
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Towards measuring fairness for local differential privacy
- 2023
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Ingår i: Data privacy management, cryptocurrencies and blockchain technology. - Cham : Springer. - 9783031257339 - 9783031257346 ; , s. 19-34
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Konferensbidrag (refereegranskat)abstract
- Local differential privacy (LDP) approaches provide data subjects with the strong privacy guarantees of Differential Privacy under the scenario of untrusted data curators. They are used by companies (e.g., Google’s RAPPOR) to collect potentially sensitive data from clients through randomized response. Randomized response was proposed as a method to allow respondents to surveys to answer questions about sensitive issues such as illegal behavior or private preferences. By randomizing their answers, the respondents are provided by plausible deniability, their answers about a sensitive issue may be “yes” either because it is true or by chance.We study how randomized response mechanisms that provide LDP for a fixed ε, may provide different privacy guarantees to respondents depending on their sensitive attribute value, i.e., they have disparate impact regarding the privacy protection. We propose measures for fair privacy when applying LDP and show that the parameters on the randomized response matrix can be tuned to generate fairer-LDP mechanisms with the same global privacy guarantee ε. We show the effectiveness of our approach through an experimental evaluation in Machine Learning Classification tasks on three commonly used benchmark datasets: Adult Income, COMPAS and German Credit.
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