7,326 research outputs found
Evaluation Methodologies in Software Protection Research
Man-at-the-end (MATE) attackers have full control over the system on which
the attacked software runs, and try to break the confidentiality or integrity
of assets embedded in the software. Both companies and malware authors want to
prevent such attacks. This has driven an arms race between attackers and
defenders, resulting in a plethora of different protection and analysis
methods. However, it remains difficult to measure the strength of protections
because MATE attackers can reach their goals in many different ways and a
universally accepted evaluation methodology does not exist. This survey
systematically reviews the evaluation methodologies of papers on obfuscation, a
major class of protections against MATE attacks. For 572 papers, we collected
113 aspects of their evaluation methodologies, ranging from sample set types
and sizes, over sample treatment, to performed measurements. We provide
detailed insights into how the academic state of the art evaluates both the
protections and analyses thereon. In summary, there is a clear need for better
evaluation methodologies. We identify nine challenges for software protection
evaluations, which represent threats to the validity, reproducibility, and
interpretation of research results in the context of MATE attacks
Urbanised forested landscape: Urbanisation, timber extraction and forest care on the Vișeu Valley, northern Romania
By looking at urbanisation processes from the vantage point of the forest, and the ways in which it both constitutes our living space while having been separated from the bounded space of the urban in modern history, the thesis asks: How can we (re)imagine urbanisation beyond the limits of the urban? How can a feminine line of thinking engage with the forest beyond the capitalist-colonial paradigm and its extractive project? and How can we “think with care” (Puig de la Bellacasa 2017) towards the forest as an inhabitant of our common world, instead of perpetuating the image of the forest as a space outside the delimited boundaries of the city? Through a case study research, introducing the Vișeu Valley in northern Romania as both a site engaged in the circulation of the global timber flow, a part of what Brenner and Schmid (2014) name “planetary urbanisation”, where the extractive logging operations beginning in the late XVIIIth century have constructed it as an extractive landscape, and a more than human landscape inhabited by a multitude of beings (animal, plant, and human) the thesis argues towards the importance of forest care and indigenous knowledge in landscape management understood as a trans-generational transmission of knowledge, that is interdependent with the persistence of the landscape as such. Having a trans-scalar approach, the thesis investigates the ways in which the extractive projects of the capitalist-colonial paradigm have and still are shaping forested landscapes across the globe in order to situate the case as part of a planetary forest landscape and the contemporary debates it is engaged in. By engaging with emerging paradigms within the fields of plant communication, forestry, legal scholarship and landscape urbanism that present trees and forests as intelligent beings, and look at urbanisation as a way of inhabiting the landscape in both indigenous and modern cultures, the thesis argues towards viewing forested landscapes as more than human living spaces. Thinking urbanisation through the case of the Vișeu Valley’s urbanised forested landscape, the thesis aligns with alternate ways of viewing urbanisation as co-habitation with more than human beings, particularly those emerging from interdisciplinary research in the Amazon river basin (Tavares 2017, Heckenberger 2012) and, in light of emerging discourses on the rights of nature, proposes an expanded concept of planetary citizenship, to include non-human personhood
Studies on human cancer variant and mycobacterial isocitrate dehydrogenases
Mutations in human IDH genes occur in cancer and result in active site IDH variants with a gain-of-function ability to reduce the normal 2-oxoglutarate (2-OG) product of IDH catalysis to 2-hydroxyglutarate (2-HG). As reviewed in Chapter 1, elevated 2-HG levels are proposed to promote tumorigenesis via chromatin remodelling. Efficient IDH1 variant inhibitors bind in an allosteric manner at the dimer-interface and hinder binding of 2-OG and Mg2+. Ivosidenib is an IDH1 variant inhibitor that is approved for acute myeloid leukaemia (AML) treatment; however, acquired second-site S280F mutations to IDH1 render cancer cells resistant to ivosidenib treatment. The research described in this thesis investigated the mechanism of action of the second site IDH1 mutation and how to overcome resistance due to it.
Kinetic analyses show that the IDH1 S280F substitution not only leads to resistance against ivosidenib but results in a higher affinity for 2-OG and Mg2+, and consequently, more efficient turnover of 2-OG to 2-HG. 1H Nuclear magnetic resonance (NMR) studies reveal that IDH1 cancer variants can turn over D-isocitrate to 2-HG. The rate of conversion of D-isocitrate to 2-HG by S280F substituted variants is more efficient than for IDH1 wildtype or active site variants without the S280F substitution. Mechanistic studies on IDH1 variants provide insights into the influence of various R132 substitutions and the role of the dimer-interface in IDH1 catalysis.
In addition to resistance enabled by more efficient 2-HG production, ivosidenib binding is hindered by the loss of a hydrogen bond to S280, steric hindrance due to the S280F substitution, formation of a new hydrophobic pocket at the dimer-interface, and higher enzymatic affinity for 2-OG and Mg2+. Certain IDH1 variant inhibitors were shown to retain activity against isolated IDH1 R132C S280F and R132H S280F, some with high potency. Non-denaturing mass spectrometry (MS) reveals that inhibitors retaining activity bind with a stoichiometry of two inhibitors per IDH1 variant dimer, in contrast to ivosidenib, which binds with a stoichiometry of one inhibitor per dimer. Several inhibitors reduce 2-HG levels in cell lines overexpressing IDH1 R132C S280F or R132H S280F. Some of these inhibitors are in phase 2 clinical studies (FT-2102, DS-1001B) indicating that S280F-mediated ivosidenib resistance can be overcome by using alternative inhibitors.
Targeting metabolism has also been of long-standing interest in the antibacterial field, including for Mycobacterium tuberculosis (Mtb) and Mycobacterium smegmatis (Msm). After establishing production strategies and an activity assay for Mtb IDH1/IDH2 and Msm IDH, kinetic studies support the proposal that Mtb IDH2 is likely the essential IDH isoform for oxidative decarboxylation of isocitrate in Mtb metabolism. Mtb IDH2 activity is enhanced by several reactive carbonyl group containing metabolites. Most Hs IDH1 cancer variant inhibitors are not active against Mtb IDH1/IDH2 and Msm IDH but some exhibit weak activity.
The overall results provide mechanistic insights into resistance to Hs IDH1 variant inhibitors and show how this can be overcome. The studies suggest that targeting IDH may be a viable strategy for mycobacterial treatment
Using machine learning to predict pathogenicity of genomic variants throughout the human genome
Geschätzt mehr als 6.000 Erkrankungen werden durch Veränderungen im Genom verursacht. Ursachen gibt es viele: Eine genomische Variante kann die Translation eines Proteins stoppen, die Genregulation stören oder das Spleißen der mRNA in eine andere Isoform begünstigen. All diese Prozesse müssen überprüft werden, um die zum beschriebenen Phänotyp passende Variante zu ermitteln. Eine Automatisierung dieses Prozesses sind Varianteneffektmodelle. Mittels maschinellem Lernen und Annotationen aus verschiedenen Quellen bewerten diese Modelle genomische Varianten hinsichtlich ihrer Pathogenität.
Die Entwicklung eines Varianteneffektmodells erfordert eine Reihe von Schritten: Annotation der Trainingsdaten, Auswahl von Features, Training verschiedener Modelle und Selektion eines Modells. Hier präsentiere ich ein allgemeines Workflow dieses Prozesses. Dieses ermöglicht es den Prozess zu konfigurieren, Modellmerkmale zu bearbeiten, und verschiedene Annotationen zu testen. Der Workflow umfasst außerdem die Optimierung von Hyperparametern, Validierung und letztlich die Anwendung des Modells durch genomweites Berechnen von Varianten-Scores.
Der Workflow wird in der Entwicklung von Combined Annotation Dependent Depletion (CADD), einem Varianteneffektmodell zur genomweiten Bewertung von SNVs und InDels, verwendet. Durch Etablierung des ersten Varianteneffektmodells für das humane Referenzgenome GRCh38 demonstriere ich die gewonnenen Möglichkeiten Annotationen aufzugreifen und neue Modelle zu trainieren. Außerdem zeige ich, wie Deep-Learning-Scores als Feature in einem CADD-Modell die Vorhersage von RNA-Spleißing verbessern. Außerdem werden Varianteneffektmodelle aufgrund eines neuen, auf Allelhäufigkeit basierten, Trainingsdatensatz entwickelt.
Diese Ergebnisse zeigen, dass der entwickelte Workflow eine skalierbare und flexible Möglichkeit ist, um Varianteneffektmodelle zu entwickeln. Alle entstandenen Scores sind unter cadd.gs.washington.edu und cadd.bihealth.org frei verfügbar.More than 6,000 diseases are estimated to be caused by genomic variants. This can happen in many possible ways: a variant may stop the translation of a protein, interfere with gene regulation, or alter splicing of the transcribed mRNA into an unwanted isoform. It is necessary to investigate all of these processes in order to evaluate which variant may be causal for the deleterious phenotype. A great help in this regard are variant effect scores. Implemented as machine learning classifiers, they integrate annotations from different resources to rank genomic variants in terms of pathogenicity.
Developing a variant effect score requires multiple steps: annotation of the training data, feature selection, model training, benchmarking, and finally deployment for the model's application. Here, I present a generalized workflow of this process. It makes it simple to configure how information is converted into model features, enabling the rapid exploration of different annotations. The workflow further implements hyperparameter optimization, model validation and ultimately deployment of a selected model via genome-wide scoring of genomic variants.
The workflow is applied to train Combined Annotation Dependent Depletion (CADD), a variant effect model that is scoring SNVs and InDels genome-wide. I show that the workflow can be quickly adapted to novel annotations by porting CADD to the genome reference GRCh38. Further, I demonstrate the integration of deep-neural network scores as features into a new CADD model, improving the annotation of RNA splicing events. Finally, I apply the workflow to train multiple variant effect models from training data that is based on variants selected by allele frequency.
In conclusion, the developed workflow presents a flexible and scalable method to train variant effect scores. All software and developed scores are freely available from cadd.gs.washington.edu and cadd.bihealth.org
Knowledge-based Modelling of Additive Manufacturing for Sustainability Performance Analysis and Decision Making
Additiivista valmistusta on pidetty käyttökelpoisena monimutkaisissa geometrioissa, topologisesti optimoiduissa kappaleissa ja kappaleissa joita on muuten vaikea valmistaa perinteisillä valmistusprosesseilla. Eduista huolimatta, yksi additiivisen valmistuksen vallitsevista haasteista on ollut heikko kyky tuottaa toimivia osia kilpailukykyisillä tuotantomäärillä perinteisen valmistuksen kanssa. Mallintaminen ja simulointi ovat tehokkaita työkaluja, jotka voivat auttaa lyhentämään suunnittelun, rakentamisen ja testauksen sykliä mahdollistamalla erilaisten tuotesuunnitelmien ja prosessiskenaarioiden nopean analyysin. Perinteisten ja edistyneiden valmistusteknologioiden mahdollisuudet ja rajoitukset määrittelevät kuitenkin rajat uusille tuotekehityksille. Siksi on tärkeää, että suunnittelijoilla on käytettävissään menetelmät ja työkalut, joiden avulla he voivat mallintaa ja simuloida tuotteen suorituskykyä ja siihen liittyvän valmistusprosessin suorituskykyä, toimivien korkea arvoisten tuotteiden toteuttamiseksi. Motivaation tämän väitöstutkimuksen tekemiselle on, meneillään oleva kehitystyö uudenlaisen korkean lämpötilan suprajohtavan (high temperature superconducting (HTS)) magneettikokoonpanon kehittämisessä, joka toimii kryogeenisissä lämpötiloissa. Sen monimutkaisuus edellyttää monitieteisen asiantuntemuksen lähentymistä suunnittelun ja prototyyppien valmistuksen aikana. Tutkimus hyödyntää tietopohjaista mallinnusta valmistusprosessin analysoinnin ja päätöksenteon apuna HTS-magneettien mekaanisten komponenttien suunnittelussa. Tämän lisäksi, tutkimus etsii mahdollisuuksia additiivisen valmistuksen toteutettavuuteen HTS-magneettikokoonpanon tuotannossa. Kehitetty lähestymistapa käyttää fysikaalisiin kokeisiin perustuvaa tuote-prosessi-integroitua mallinnusta tuottamaan kvantitatiivista ja laadullista tietoa, joka määrittelee prosessi-rakenne-ominaisuus-suorituskyky-vuorovaikutuksia tietyille materiaali-prosessi-yhdistelmille. Tuloksina saadut vuorovaikutukset integroidaan kaaviopohjaiseen malliin, joka voi auttaa suunnittelutilan tutkimisessa ja täten auttaa varhaisessa suunnittelu- ja valmistuspäätöksenteossa. Tätä varten testikomponentit valmistetaan käyttämällä kahta metallin additiivista valmistus prosessia: lankakaarihitsaus additiivista valmistusta (wire arc additive manufacturing) ja selektiivistä lasersulatusta (selective laser melting). Rakenteellisissa sovelluksissa yleisesti käytetyistä metalliseoksista (ruostumaton teräs, pehmeä teräs, luja niukkaseosteinen teräs, alumiini ja kupariseokset) testataan niiden mekaaniset, lämpö- ja sähköiset ominaisuudet. Lisäksi tehdään metalliseosten mikrorakenteen karakterisointi, jotta voidaan ymmärtää paremmin valmistusprosessin parametrien vaikutusta materiaalin ominaisuuksiin. Integroitu mallinnustapa yhdistää kerätyn kokeellisen tiedon, olemassa olevat analyyttiset ja empiiriset vuorovaikutus suhteet, sekä muut tietopohjaiset mallit (esim. elementtimallit, koneoppimismallit) päätöksenteon tukijärjestelmän muodossa, joka mahdollistaa optimaalisen materiaalin, valmistustekniikan, prosessiparametrien ja muitten ohjausmuuttujien valinnan, lopullisen 3d-tulosteun komponentin halutun rakenteen, ominaisuuksien ja suorituskyvyn saavuttamiseksi. Valmistuspäätöksenteko tapahtuu todennäköisyysmallin, eli Bayesin verkkomallin toteuttamisen kautta, joka on vankka, modulaarinen ja sovellettavissa muihin valmistusjärjestelmiin ja tuotesuunnitelmiin. Väitöstyössä esitetyn mallin kyky parantaa additiivisien valmistusprosessien suorituskykyä ja laatua, täten edistää kestävän tuotannon tavoitteita.Additive manufacturing (AM) has been considered viable for complex geometries, topology optimized parts, and parts that are otherwise difficult to produce using conventional manufacturing processes. Despite the advantages, one of the prevalent challenges in AM has been the poor capability of producing functional parts at production volumes that are competitive with traditional manufacturing. Modelling and simulation are powerful tools that can help shorten the design-build-test cycle by enabling rapid analysis of various product designs and process scenarios. Nevertheless, the capabilities and limitations of traditional and advanced manufacturing technologies do define the bounds for new product development. Thus, it is important that the designers have access to methods and tools that enable them to model and simulate product performance and associated manufacturing process performance to realize functional high value products. The motivation for this dissertation research stems from ongoing development of a novel high temperature superconducting (HTS) magnet assembly, which operates in cryogenic environment. Its complexity requires the convergence of multidisciplinary expertise during design and prototyping. The research applies knowledge-based modelling to aid manufacturing process analysis and decision making in the design of mechanical components of the HTS magnet. Further, it explores the feasibility of using AM in the production of the HTS magnet assembly. The developed approach uses product-process integrated modelling based on physical experiments to generate quantitative and qualitative information that define process-structure-property-performance interactions for given material-process combinations. The resulting interactions are then integrated into a graph-based model that can aid in design space exploration to assist early design and manufacturing decision-making. To do so, test components are fabricated using two metal AM processes: wire and arc additive manufacturing and selective laser melting. Metal alloys (stainless steel, mild steel, high-strength low-alloyed steel, aluminium, and copper alloys) commonly used in structural applications are tested for their mechanical-, thermal-, and electrical properties. In addition, microstructural characterization of the alloys is performed to further understand the impact of manufacturing process parameters on material properties. The integrated modelling approach combines the collected experimental data, existing analytical and empirical relationships, and other data-driven models (e.g., finite element models, machine learning models) in the form of a decision support system that enables optimal selection of material, manufacturing technology, process parameters, and other control variables for attaining desired structure, property, and performance characteristics of the final printed component. The manufacturing decision making is performed through implementation of a probabilistic model i.e., a Bayesian network model, which is robust, modular, and can be adapted for other manufacturing systems and product designs. The ability of the model to improve throughput and quality of additive manufacturing processes will boost sustainable manufacturing goals
The Viability and Potential Consequences of IoT-Based Ransomware
With the increased threat of ransomware and the substantial growth of the Internet of Things (IoT) market, there is significant motivation for attackers to carry out IoT-based ransomware campaigns. In this thesis, the viability of such malware is tested.
As part of this work, various techniques that could be used by ransomware developers to attack commercial IoT devices were explored. First, methods that attackers could use to communicate with the victim were examined, such that a ransom note was able to be reliably sent to a victim. Next, the viability of using "bricking" as a method of ransom was evaluated, such that devices could be remotely disabled unless the victim makes a payment to the attacker. Research was then performed to ascertain whether it was possible to remotely gain persistence on IoT devices, which would improve the efficacy of existing ransomware methods, and provide opportunities for more advanced ransomware to be created. Finally, after successfully identifying a number of persistence techniques, the viability of privacy-invasion based ransomware was analysed.
For each assessed technique, proofs of concept were developed. A range of devices -- with various intended purposes, such as routers, cameras and phones -- were used to test the viability of these proofs of concept. To test communication hijacking, devices' "channels of communication" -- such as web services and embedded screens -- were identified, then hijacked to display custom ransom notes. During the analysis of bricking-based ransomware, a working proof of concept was created, which was then able to remotely brick five IoT devices. After analysing the storage design of an assortment of IoT devices, six different persistence techniques were identified, which were then successfully tested on four devices, such that malicious filesystem modifications would be retained after the device was rebooted. When researching privacy-invasion based ransomware, several methods were created to extract information from data sources that can be commonly found on IoT devices, such as nearby WiFi signals, images from cameras, or audio from microphones. These were successfully implemented in a test environment such that ransomable data could be extracted, processed, and stored for later use to blackmail the victim.
Overall, IoT-based ransomware has not only been shown to be viable but also highly damaging to both IoT devices and their users. While the use of IoT-ransomware is still very uncommon "in the wild", the techniques demonstrated within this work highlight an urgent need to improve the security of IoT devices to avoid the risk of IoT-based ransomware causing havoc in our society. Finally, during the development of these proofs of concept, a number of potential countermeasures were identified, which can be used to limit the effectiveness of the attacking techniques discovered in this PhD research
Deep Transfer Learning Applications in Intrusion Detection Systems: A Comprehensive Review
Globally, the external Internet is increasingly being connected to the
contemporary industrial control system. As a result, there is an immediate need
to protect the network from several threats. The key infrastructure of
industrial activity may be protected from harm by using an intrusion detection
system (IDS), a preventive measure mechanism, to recognize new kinds of
dangerous threats and hostile activities. The most recent artificial
intelligence (AI) techniques used to create IDS in many kinds of industrial
control networks are examined in this study, with a particular emphasis on
IDS-based deep transfer learning (DTL). This latter can be seen as a type of
information fusion that merge, and/or adapt knowledge from multiple domains to
enhance the performance of the target task, particularly when the labeled data
in the target domain is scarce. Publications issued after 2015 were taken into
account. These selected publications were divided into three categories:
DTL-only and IDS-only are involved in the introduction and background, and
DTL-based IDS papers are involved in the core papers of this review.
Researchers will be able to have a better grasp of the current state of DTL
approaches used in IDS in many different types of networks by reading this
review paper. Other useful information, such as the datasets used, the sort of
DTL employed, the pre-trained network, IDS techniques, the evaluation metrics
including accuracy/F-score and false alarm rate (FAR), and the improvement
gained, were also covered. The algorithms, and methods used in several studies,
or illustrate deeply and clearly the principle in any DTL-based IDS subcategory
are presented to the reader
On the Principles of Evaluation for Natural Language Generation
Natural language processing is concerned with the ability of computers to understand natural language texts, which is, arguably, one of the major bottlenecks in the course of chasing the holy grail of general Artificial Intelligence. Given the unprecedented success of deep learning technology, the natural language processing community has been almost entirely in favor of practical applications with state-of-the-art systems emerging and competing for human-parity performance at an ever-increasing pace. For that reason, fair and adequate evaluation and comparison, responsible for ensuring trustworthy, reproducible and unbiased results, have fascinated the scientific community for long, not only in natural language but also in other fields. A popular example is the ISO-9126 evaluation standard for software products, which outlines a wide range of evaluation concerns, such as cost, reliability, scalability, security, and so forth. The European project EAGLES-1996, being the acclaimed extension to ISO-9126, depicted the fundamental principles specifically for evaluating natural language technologies, which underpins succeeding methodologies in the evaluation of natural language.
Natural language processing encompasses an enormous range of applications, each with its own evaluation concerns, criteria and measures. This thesis cannot hope to be comprehensive but particularly addresses the evaluation in natural language generation (NLG), which touches on, arguably, one of the most human-like natural language applications. In this context, research on quantifying day-to-day progress with evaluation metrics lays the foundation of the fast-growing NLG community. However, previous works have failed to address high-quality metrics in multiple scenarios such as evaluating long texts and when human references are not available, and, more prominently, these studies are limited in scope, given the lack of a holistic view sketched for principled NLG evaluation.
In this thesis, we aim for a holistic view of NLG evaluation from three complementary perspectives, driven by the evaluation principles in EAGLES-1996: (i) high-quality evaluation metrics, (ii) rigorous comparison of NLG systems for properly tracking the progress, and (iii) understanding evaluation metrics. To this end, we identify the current state of challenges derived from the inherent characteristics of these perspectives, and then present novel metrics, rigorous comparison approaches, and explainability techniques for metrics to address the identified issues.
We hope that our work on evaluation metrics, system comparison and explainability for metrics inspires more research towards principled NLG evaluation, and contributes to the fair and adequate evaluation and comparison in natural language processing
Deep Learning Enabled Semantic Communication Systems
In the past decades, communications primarily focus on how to accurately and effectively transmit symbols (measured by bits) from the transmitter to the receiver. Recently, various new applications appear, such as autonomous transportation, consumer robotics, environmental monitoring, and tele-health. The interconnection of these applications will generate a staggering amount of data in the order of zetta-bytes and require massive connectivity over limited spectrum resources but with lower latency, which poses critical challenges to conventional communication systems. Semantic communication has been proposed to overcome the challenges by extracting the meanings of data and filtering out the useless, irrelevant, and unessential information, which is expected to be robust to terrible channel environments and reduce the size of transmitted data. While semantic communications have been proposed decades ago, their applications to the wireless communication scenario remain limited. Deep learning (DL) based neural networks can effectively extract semantic information and can be optimized in an end-to-end (E2E) manner. The inborn characteristics of DL are suitable for semantic communications, which motivates us to exploit DL-enabled semantic communication. Inspired by the above, this thesis focus on exploring the semantic communication theory and designing semantic communication systems. First, a basic DL based semantic communication system, named DeepSC, is proposed for text transmission. In addition, DL based multi-user semantic communication systems are investigated for transmitting single-modal data and multimodal data, respectively, in which intelligent tasks are performed at the receiver directly. Moreover, a semantic communication system with a memory module, named Mem-DeepSC, is designed to support both memoryless and memory intelligent tasks. Finally, a lite distributed semantic communication system based on DL, named L-DeepSC, is proposed with low complexity, where the data transmission from the Internet-of-Things (IoT) devices to the cloud/edge works at the semantic level to improve transmission efficiency. The proposed various DeepSC systems can achieve less data transmission to reduce the transmission latency, lower complexity to fit capacity-constrained devices, higher robustness to multi-user interference and channel noise, and better performance to perform various intelligent tasks compared to the conventional communication systems
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