11,443 research outputs found
KYT2022 Finnish Research Programme on Nuclear Waste Management 2019–2022 : Final Report
KYT2022 (Finnish Research Programme on Nuclear Waste Management 2019–2022), organised by the Ministry of Economic Affairs and Employment, was a national research programme with the objective to ensure that the authorities have sufficient levels of nuclear expertise and preparedness that are needed for safety of nuclear waste management.
The starting point for public research programs on nuclear safety is that they create the conditions for maintaining the knowledge required for the continued safe and economic use of nuclear energy, developing new know-how and participating in international collaboration.
The content of the KYT2022 research programme was composed of nationally important research topics, which are the safety, feasibility and acceptability of nuclear waste management.
KYT2022 research programme also functioned as a discussion and information-sharing forum for the authorities, those responsible for nuclear waste management and the research organizations, which helped to make use of the limited research resources. The programme aimed to develop national research infrastructure, ensure the continuing availability of expertise, produce high-level scientific research and increase general knowledge of nuclear waste management
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Ensuring Access to Safe and Nutritious Food for All Through the Transformation of Food Systems
Passive Radio Frequency-based 3D Indoor Positioning System via Ensemble Learning
Passive radio frequency (PRF)-based indoor positioning systems (IPS) have
attracted researchers' attention due to their low price, easy and customizable
configuration, and non-invasive design. This paper proposes a PRF-based
three-dimensional (3D) indoor positioning system (PIPS), which is able to use
signals of opportunity (SoOP) for positioning and also capture a scenario
signature. PIPS passively monitors SoOPs containing scenario signatures through
a single receiver. Moreover, PIPS leverages the Dynamic Data Driven
Applications System (DDDAS) framework to devise and customize the sampling
frequency, enabling the system to use the most impacted frequency band as the
rated frequency band. Various regression methods within three ensemble learning
strategies are used to train and predict the receiver position. The PRF
spectrum of 60 positions is collected in the experimental scenario, and three
criteria are applied to evaluate the performance of PIPS. Experimental results
show that the proposed PIPS possesses the advantages of high accuracy,
configurability, and robustness.Comment: DDDAS 202
High-Dimensional Private Empirical Risk Minimization by Greedy Coordinate Descent
In this paper, we study differentially private empirical risk minimization
(DP-ERM). It has been shown that the worst-case utility of DP-ERM reduces
polynomially as the dimension increases. This is a major obstacle to privately
learning large machine learning models. In high dimension, it is common for
some model's parameters to carry more information than others. To exploit this,
we propose a differentially private greedy coordinate descent (DP-GCD)
algorithm. At each iteration, DP-GCD privately performs a coordinate-wise
gradient step along the gradients' (approximately) greatest entry. We show
theoretically that DP-GCD can achieve a logarithmic dependence on the dimension
for a wide range of problems by naturally exploiting their structural
properties (such as quasi-sparse solutions). We illustrate this behavior
numerically, both on synthetic and real datasets
Learning disentangled speech representations
A variety of informational factors are contained within the speech signal and a single short recording of speech reveals much more than the spoken words. The best method to extract and represent informational factors from the speech signal ultimately depends on which informational factors are desired and how they will be used. In addition, sometimes methods will capture more than one informational factor at the same time such as speaker identity, spoken content, and speaker prosody.
The goal of this dissertation is to explore different ways to deconstruct the speech signal into abstract representations that can be learned and later reused in various speech technology tasks. This task of deconstructing, also known as disentanglement, is a form of distributed representation learning. As a general approach to disentanglement, there are some guiding principles that elaborate what a learned representation should contain as well as how it should function. In particular, learned representations should contain all of the requisite information in a more compact manner, be interpretable, remove nuisance factors of irrelevant information, be useful in downstream tasks, and independent of the task at hand. The learned representations should also be able to answer counter-factual questions.
In some cases, learned speech representations can be re-assembled in different ways according to the requirements of downstream applications. For example, in a voice conversion task, the speech content is retained while the speaker identity is changed. And in a content-privacy task, some targeted content may be concealed without affecting how surrounding words sound. While there is no single-best method to disentangle all types of factors, some end-to-end approaches demonstrate a promising degree of generalization to diverse speech tasks.
This thesis explores a variety of use-cases for disentangled representations including phone recognition, speaker diarization, linguistic code-switching, voice conversion, and content-based privacy masking. Speech representations can also be utilised for automatically assessing the quality and authenticity of speech, such as automatic MOS ratings or detecting deep fakes. The meaning of the term "disentanglement" is not well defined in previous work, and it has acquired several meanings depending on the domain (e.g. image vs. speech). Sometimes the term "disentanglement" is used interchangeably with the term "factorization". This thesis proposes that disentanglement of speech is distinct, and offers a viewpoint of disentanglement that can be considered both theoretically and practically
Estudo da remodelagem reversa miocárdica através da análise proteómica do miocárdio e do líquido pericárdico
Valve replacement remains as the standard therapeutic option for aortic
stenosis patients, aiming at abolishing pressure overload and triggering
myocardial reverse remodeling. However, despite the instant hemodynamic
benefit, not all patients show complete regression of myocardial hypertrophy,
being at higher risk for adverse outcomes, such as heart failure. The current
comprehension of the biological mechanisms underlying an incomplete reverse
remodeling is far from complete. Furthermore, definitive prognostic tools and
ancillary therapies to improve the outcome of the patients undergoing valve
replacement are missing. To help abridge these gaps, a combined myocardial
(phospho)proteomics and pericardial fluid proteomics approach was followed,
taking advantage of human biopsies and pericardial fluid collected during
surgery and whose origin anticipated a wealth of molecular information
contained therein.
From over 1800 and 750 proteins identified, respectively, in the myocardium
and in the pericardial fluid of aortic stenosis patients, a total of 90 dysregulated
proteins were detected. Gene annotation and pathway enrichment analyses,
together with discriminant analysis, are compatible with a scenario of increased
pro-hypertrophic gene expression and protein synthesis, defective ubiquitinproteasome system activity, proclivity to cell death (potentially fed by
complement activity and other extrinsic factors, such as death receptor
activators), acute-phase response, immune system activation and fibrosis.
Specific validation of some targets through immunoblot techniques and
correlation with clinical data pointed to complement C3 β chain, Muscle Ring
Finger protein 1 (MuRF1) and the dual-specificity Tyr-phosphorylation
regulated kinase 1A (DYRK1A) as potential markers of an incomplete
response. In addition, kinase prediction from phosphoproteome data suggests
that the modulation of casein kinase 2, the family of IκB kinases, glycogen
synthase kinase 3 and DYRK1A may help improve the outcome of patients
undergoing valve replacement. Particularly, functional studies with DYRK1A+/-
cardiomyocytes show that this kinase may be an important target to treat
cardiac dysfunction, provided that mutant cells presented a different response
to stretch and reduced ability to develop force (active tension).
This study opens many avenues in post-aortic valve replacement reverse
remodeling research. In the future, gain-of-function and/or loss-of-function
studies with isolated cardiomyocytes or with animal models of aortic bandingdebanding will help disclose the efficacy of targeting the surrogate therapeutic
targets. Besides, clinical studies in larger cohorts will bring definitive proof of
complement C3, MuRF1 and DYRK1A prognostic value.A substituição da válvula aórtica continua a ser a opção terapêutica de
referência para doentes com estenose aórtica e visa a eliminação da
sobrecarga de pressão, desencadeando a remodelagem reversa miocárdica.
Contudo, apesar do benefício hemodinâmico imediato, nem todos os pacientes
apresentam regressão completa da hipertrofia do miocárdio, ficando com maior
risco de eventos adversos, como a insuficiência cardíaca. Atualmente, os
mecanismos biológicos subjacentes a uma remodelagem reversa incompleta
ainda não são claros. Além disso, não dispomos de ferramentas de
prognóstico definitivos nem de terapias auxiliares para melhorar a condição
dos pacientes indicados para substituição da válvula. Para ajudar a resolver
estas lacunas, uma abordagem combinada de (fosfo)proteómica e proteómica
para a caracterização, respetivamente, do miocárdio e do líquido pericárdico
foi seguida, tomando partido de biópsias e líquidos pericárdicos recolhidos em
ambiente cirúrgico.
Das mais de 1800 e 750 proteínas identificadas, respetivamente, no miocárdio
e no líquido pericárdico dos pacientes com estenose aórtica, um total de 90
proteínas desreguladas foram detetadas. As análises de anotação de genes,
de enriquecimento de vias celulares e discriminativa corroboram um cenário de
aumento da expressão de genes pro-hipertróficos e de síntese proteica, um
sistema ubiquitina-proteassoma ineficiente, uma tendência para morte celular
(potencialmente acelerada pela atividade do complemento e por outros fatores
extrínsecos que ativam death receptors), com ativação da resposta de fase
aguda e do sistema imune, assim como da fibrose.
A validação de alguns alvos específicos através de immunoblot e correlação
com dados clínicos apontou para a cadeia β do complemento C3, a Muscle
Ring Finger protein 1 (MuRF1) e a dual-specificity Tyr-phosphoylation
regulated kinase 1A (DYRK1A) como potenciais marcadores de uma resposta
incompleta. Por outro lado, a predição de cinases a partir do fosfoproteoma,
sugere que a modulação da caseína cinase 2, a família de cinases do IκB, a
glicogénio sintase cinase 3 e da DYRK1A pode ajudar a melhorar a condição
dos pacientes indicados para intervenção. Em particular, a avaliação funcional
de cardiomiócitos DYRK1A+/- mostraram que esta cinase pode ser um alvo
importante para tratar a disfunção cardíaca, uma vez que os miócitos mutantes
responderam de forma diferente ao estiramento e mostraram uma menor
capacidade para desenvolver força (tensão ativa).
Este estudo levanta várias hipóteses na investigação da remodelagem reversa.
No futuro, estudos de ganho e/ou perda de função realizados em
cardiomiócitos isolados ou em modelos animais de banding-debanding da
aorta ajudarão a testar a eficácia de modular os potenciais alvos terapêuticos
encontrados. Além disso, estudos clínicos em coortes de maior dimensão
trarão conclusões definitivas quanto ao valor de prognóstico do complemento
C3, MuRF1 e DYRK1A.Programa Doutoral em Biomedicin
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Efficient Neural Network Verification Using Branch and Bound
Neural networks have demonstrated great success in modern machine learning systems. However, they remain susceptible to incorrect corner-case behaviors, often behaving unpredictably and producing surprisingly wrong results. Therefore, it is desirable to formally guarantee their trustworthiness for certain robustness properties when applied to safety-/security-sensitive systems like autonomous vehicles and aircraft. Unfortunately, the task is extremely challenging due to the complexity of neural networks, and traditional formal methods were not efficient enough to verify practical properties. Recently, a Branch and Bound (BaB) framework is generally extended for neural network verification and shows great success in accelerating the verification.
This dissertation focuses on state-of-the-art neural network verifiers using BaB. We will first introduce two efficient neural network verifiers ReluVal and Neurify using basic BaB approaches involving two main steps: (1) They will recursively split the original verification problem into easier independent subproblems by splitting input or hidden neurons; (2) For each split subproblem, we propose an efficient and tight bound propagation method called symbolic interval analysis, producing sound estimated bounds for outputs using convex linear relaxations. Both ReluVal and Neurify are three orders of magnitude faster than previously state-of-the-art formal analysis systems on standard verification benchmarks.
However, basic BaB approaches like Neurify have to construct each subproblem into a Linear Programming (LP) problem and solve it using expensive LP solvers, significantly limiting the overall efficiency. This is because each step of BaB will introduce neuron split constraints (e.g., a ReLU neuron larger or smaller than 0), which are hard to be handled by existing efficient bound propagation methods. We propose novel designs of bound propagation method -CROWN and its improved variance -CROWN, solving the verification problem by optimizing Lagrangian multipliers and with gradient ascent without requiring to call any expensive LP solvers. They were built based on previous work CROWN, a generalized efficient bound propagation method using linear relaxation. BaB verification using -CROWN and -CROWN cannot only provide tighter output estimations than most of the bound propagation methods but also can fully leverage the accelerations by GPUs with massive parallelization.
Combining our methods with BaB empowers the state-of-the-art verifier ,-CROWN (alpha-beta-CROWN), the winning tool in the second International Verification of Neural Networks Competition (VNN-COMP 2021) with the highest total score. Our $\alpha,-CROWN can be three orders of magnitude faster than LP solver based BaB verifiers and is notably faster than all existing approaches on GPUs. Recently, we further generalize -CROWN and propose an efficient iterative approach that can tighten all intermediate layer bounds under neuron split constraints and strengthen the bound tightness without LP solvers. This new approach in BaB can greatly improve the efficiency of ,-CROWN, especially on several challenging benchmarks.
Lastly, we study verifiable training that incorporates verification properties in training procedures to enhance the verifiable robustness of trained models and scale verification to larger models and datasets. We propose two general verifiable training frameworks: (1) MixTrain that can significantly improve verifiable training efficiency and scalability and (2) adaptive verifiable training that can improve trained verifiable robustness accounting for label similarity. The combination of verifiable training and BaB based verifiers opens promising directions for more efficient and scalable neural network verification
Monitoring genotypic and phenotypic progression of systemic melanoma by cell lineage tree analysis and for molecular disease staging
A recent study on metastatic seeding in melanomas showed that lymphatic dissemination occurs very early. Disseminated cancer cells (DCCs) of melanoma patients can leave the primary tumor (PT) in a genomically immature state, then evolve within the lymph nodes (LNs) and adapt to the ectopic site until they start to proliferate and form metastasis. Since the PT and the metastasis are often genetically disparate, the focus for treating metastases should be on the DCCs. The molecular characterization of the DCCs that left the PT at an early stage could reveal new therapeutic targets against metastasis. After routine LN removal in melanoma patients, staining of LNs against the tumour marker MCSP identified two different phenotypes: small MCSP-positive and large MCSP-positive DCCs. While the small phenotype appears mostly in LNs with a low DCCD (DCC-density; number of DCCs per million mononuclear cells), the large phenotype could be found in LNs with a higher DCCD. Furthermore, we also observed LNs with both small and large DCCs, that had a medium DCCD.
Based on these findings we hypothesized that small MCSP-DCCs are precursors of large MCSP-DCCs and represent very early DCCs. In addition, we wanted to have a closer look at the two most common BRAF mutations in malignant melanoma and its association with the DCCD of the LNs. We hypothesized that acquisition of BRAF mutations marks the transition from pre-colonizing DCCs to colonizing DCCs and hence a significant progression step in systemic cancer development.
The hypothesis if small MCSP-positive DCCs are the precursors of large MCSP-positive DCCs should be investigated with the help of a cell lineage tree reconstruction based on short tandem repeats (STRs). To study the incidence of the BRAF mutations we established an allele-specific PCR with a blocking reagent (ASB-PCR) for DCCs.
The cell lineage tree reconstruction of patient MM15-127 resulted in three distinct clusters of DCCs. Two of the clusters were found in close proximity to the PT, while one DCC cluster was closer to the metastatic tumour cells than the PT. Both small and large MCSP-positive DCCs were found in the two clusters close to the PT. The cluster closer to the metastatic tumour cells only contained large MCSP-positive DCCs.
Retrospective testing of 80 DCCs with the established ASB-PCR resulted in the correct identification of wild type and mutant DCCs in 98% and 96% of the samples, respectively. From patient MM16-423, DCCs were isolated from the sentinel lymph node (SLN) and the non-SLNs and tested for BRAF mutations by the ASB-PCR. While the PT and the DCCs isolated from the SLN at primary diagnosis were wild type, the DCCs isolated from non-SLNs after LN relapse harboured a BRAF mutation. Testing a cohort of 150 malignant melanoma patients for BRAF mutations in DCCs, showed that 19.8% patients with a pathologically negative LN and 59.4% with a pathologically positive LN harboured a mutation. However, studying the incidence of the BRAF mutation depending on the DCCD, we found out that there is a large increase of the BRAF mutation from 14.9% in LNs with a DCCD>1≤10 to 62.5% in LNs with a DCCD>10≤30. Based on the result of the cell lineage tree reconstruction of patient MM15-127 our hypothesis that small MCSP-positive DCCs are the precursors of large MCSP-positive DCCs could neither be confirmed nor rejected. The resolution of the cell lineage tree is no yet good enough
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to provide such accurate insights. However, three distinct clusters of DCCs were identified which could be an indication that DCCs disseminated at different time points. The ASB-PCR of DCCs from patient MM16-423 showed that BRAF mutations were acquired outside of the PT at a later time point of disease progression, when metastases were detected in the non-SLN. However, 62.5% of patients with a DCCD>10≤30 harboured a BRAF mutation, indicating that the BRAF mutation could be acquired early before colonisation of the DCCs
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