5,959 research outputs found
UMSL Bulletin 2023-2024
The 2023-2024 Bulletin and Course Catalog for the University of Missouri St. Louis.https://irl.umsl.edu/bulletin/1088/thumbnail.jp
A systematic literature review on source code similarity measurement and clone detection: techniques, applications, and challenges
Measuring and evaluating source code similarity is a fundamental software
engineering activity that embraces a broad range of applications, including but
not limited to code recommendation, duplicate code, plagiarism, malware, and
smell detection. This paper proposes a systematic literature review and
meta-analysis on code similarity measurement and evaluation techniques to shed
light on the existing approaches and their characteristics in different
applications. We initially found over 10000 articles by querying four digital
libraries and ended up with 136 primary studies in the field. The studies were
classified according to their methodology, programming languages, datasets,
tools, and applications. A deep investigation reveals 80 software tools,
working with eight different techniques on five application domains. Nearly 49%
of the tools work on Java programs and 37% support C and C++, while there is no
support for many programming languages. A noteworthy point was the existence of
12 datasets related to source code similarity measurement and duplicate codes,
of which only eight datasets were publicly accessible. The lack of reliable
datasets, empirical evaluations, hybrid methods, and focuses on multi-paradigm
languages are the main challenges in the field. Emerging applications of code
similarity measurement concentrate on the development phase in addition to the
maintenance.Comment: 49 pages, 10 figures, 6 table
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
An empirical investigation of the relationship between integration, dynamic capabilities and performance in supply chains
This research aimed to develop an empirical understanding of the relationships between integration,
dynamic capabilities and performance in the supply chain domain, based on which, two conceptual
frameworks were constructed to advance the field. The core motivation for the research was that, at
the stage of writing the thesis, the combined relationship between the three concepts had not yet
been examined, although their interrelationships have been studied individually.
To achieve this aim, deductive and inductive reasoning logics were utilised to guide the qualitative
study, which was undertaken via multiple case studies to investigate lines of enquiry that would
address the research questions formulated. This is consistent with the authorâs philosophical
adoption of the ontology of relativism and the epistemology of constructionism, which was considered
appropriate to address the research questions. Empirical data and evidence were collected, and
various triangulation techniques were employed to ensure their credibility. Some key features of
grounded theory coding techniques were drawn upon for data coding and analysis, generating two
levels of findings. These revealed that whilst integration and dynamic capabilities were crucial in
improving performance, the performance also informed the former. This reflects a cyclical and
iterative approach rather than one purely based on linearity. Adopting a holistic approach towards
the relationship was key in producing complementary strategies that can deliver sustainable supply
chain performance.
The research makes theoretical, methodological and practical contributions to the field of supply
chain management. The theoretical contribution includes the development of two emerging
conceptual frameworks at the micro and macro levels. The former provides greater specificity, as it
allows meta-analytic evaluation of the three concepts and their dimensions, providing a detailed
insight into their correlations. The latter gives a holistic view of their relationships and how they are
connected, reflecting a middle-range theory that bridges theory and practice. The methodological
contribution lies in presenting models that address gaps associated with the inconsistent use of
terminologies in philosophical assumptions, and lack of rigor in deploying case study research
methods. In terms of its practical contribution, this research offers insights that practitioners could
adopt to enhance their performance. They can do so without necessarily having to forgo certain
desired outcomes using targeted integrative strategies and drawing on their dynamic capabilities
Resilience and food security in a food systems context
This open access book compiles a series of chapters written by internationally recognized experts known for their in-depth but critical views on questions of resilience and food security. The book assesses rigorously and critically the contribution of the concept of resilience in advancing our understanding and ability to design and implement development interventions in relation to food security and humanitarian crises. For this, the book departs from the narrow beaten tracks of agriculture and trade, which have influenced the mainstream debate on food security for nearly 60 years, and adopts instead a wider, more holistic perspective, framed around food systems. The foundation for this new approach is the recognition that in the current post-globalization era, the food and nutritional security of the worldâs population no longer depends just on the performance of agriculture and policies on trade, but rather on the capacity of the entire (food) system to produce, process, transport and distribute safe, affordable and nutritious food for all, in ways that remain environmentally sustainable. In that context, adopting a food system perspective provides a more appropriate frame as it incites to broaden the conventional thinking and to acknowledge the systemic nature of the different processes and actors involved. This book is written for a large audience, from academics to policymakers, students to practitioners
Rational development of stabilized cyclic disulfide redox probes and bioreductive prodrugs to target dithiol oxidoreductases
Countless biological processes allow cells to develop, survive, and proliferate. Among these, tightly balanced regulatory enzymatic pathways that can respond rapidly to external impacts maintain dynamic physiological homeostasis. More specifically, redox homeostasis broadly affects cellular metabolism and proliferation, with major contributions by thiol/disulfide oxidoreductase systems, in particular, the Thioredoxin Reductase Thioredoxin (TrxR/Trx) and the Glutathione Reductase-Glutathione-Glutaredoxin (GR/GSH/Grx) systems.
These cascades drive vital cellular functions in many ways through signaling, regulating other proteins' activity by redox switches, and by stoichiometric reductant transfers in metabolism and antioxidant systems. Increasing evidence argues that there is a persistent alteration of the redox environment in certain pathological states, such as cancer, that heavily involve the Trx system: upregulation and/or overactivity of the Trx system may support or drive cancer progression, making both TrxR and Trx promising targets for anti-cancer drug development.
Understanding the biochemical mechanisms and connections between certain redox cascades requires research tools that interact with them. The state-of-the-art genetic tools are mostly ratiometric reporters that measure reduced:oxidized ratios of selected redox pairs or the general thiol pool. However, the precise cellular roles of the central oxidoreductase systems, including TrxR and Trx, remain inaccessible due to the lack of probes to selectively measure turnover by either of these proteins. However, such probes would allow measuring their effective reductive activity apart from expression levels in native systems, including in cells, animals, or patient samples. They are also of high interest to identify chemical inhibitors for TrxR/Trx in cells and to validate their potential use as anti-cancer agents (to date, there is no selective cellular Trx inhibitor, and most known TrxR inhibitors were not comprehensively evaluated considering selectivity and potential off-targets). However, small molecule redox imaging tools are underdeveloped: their protein specificity, spectral properties, and applicability remain poorly precedented.
This work aimed to address this opportunity gap and develop novel, small molecule diagnostic and therapeutic tools to selectively target the Trx system based on a modular trigger cargo design: artificial cyclic disulfide substrates (trigger) for oxidoreductases are tethered to molecular agents (cargo) such that the cargoâs activity is masked and is re-established only through reduction by a target protein.
The rational design of these novel reduction sensors to target the cell's strongest disulfide-reducing enzymes was driven by the following principles: (i) cyclic disulfide triggers with stabilized ring systems were used to gain low reduction potentials that should resist reduction except by the strongest cellular reductases, such as Trx; and (ii) the cyclic topology also offers the potential for kinetic reversibility that should select for dithiol-type redox proteins over the cellular monothiol background. Creating imaging agents based on such two-component designs to selectively measure redox protein activity in native cells required to combine the correct trigger reducibility, probe activation kinetics, and imaging modalities and to consider the overall molecular architecture.
The major prior art in this field has applied cyclic 5-membered disulfides (1,2 dithiolanes) as substrates for TrxR in a similar way to create such tools. However, this motif was described elsewhere as thermodynamically instable and was due to widely used for dynamic covalent cascade reactions. By comparing a novel 1,2 dithiolane-based probe to the state-of-the-art probes, including commercial TrxR sensors, by screening a conclusive assay panel of cellular TrxR modulations, I clarified that 1,2 dithiolanes are not selective substrates for TrxR in biological settings (Nat Commun 2022).
Instead, aiming for more stable ring systems and thus more robust redox probes, during this work, I developed bicyclic 6 membered disulfides (piperidine fused 1,2 dithianes) with remarkably low reduction potentials. I showed that molecular probes using them as reduction sensors can be mostly processed by thioredoxins while being stable against reduction by GSH. The thermodynamically stabilized decalin like topology of the cis-annelated 1,2 dithianes requires particularly strong reductants to be cleaved. They also select for dithiol type redox proteins, like Trx, based on kinetic reversibility and offer fast cyclization due to the preorganization by annelation (JACS 2021).
This work further expanded the systemâs modularity with structural cores based on piperazine-fused 1,2 dithianes with the two amines allowing independent derivatization. Diagnostic tools using them as reduction sensors proved equally robust but with highly improved activation kinetics and were thus cellularly activated. Cellular studies evolved that they are substrates for both Trxs and their protein cousins Grxs, so measuring the cellular dithiol protein pool rather than solely Trx activity (preprint 2023).
Finally, a trigger based on a slightly adapted reduction sensor, a desymmetrized 1,2 thiaselenane, was designed for selective reduction by TrxRâs selenol/thiol active site, then combined with a precipitating large Stokesâ shift fluorophore and a solubilizing group, to evolve the first selective probe RX1 to measure cellular TrxR activity, which even allowed high throughput inhibitor screening (Chem 2022).
The central principle of this work was further advanced to therapeutic prodrugs based on the duocarmycin cargo (CBI) with tunable potency (JACS Au 2022) that can be used to create off-to-on therapeutic prodrugs. Such CBI prodrugs employing stabilized 1,2 dichalcogenide triggers proved to be cytotoxins that depend on Trx system activity in cells. They could further be exploited for cell-line dependent reductase activity profiling by screening their redox activation indices, the reduction-dependent part of total prodrug activation, in 177 cell lines. Beyond that, these prodrugs were well-tolerated in animals and showed anti-cancer efficacy in vivo in two distinct mouse tumor models (preprint 2022).
Taken together, I introduced unique monothiol-resistant reducible motifs to target the cellular Trx system with chemocompatible units for each for TrxR and Trx/Grx, where the cyclic nature of the dichalcogenides avoids activation by GSH. By using them with distinct molecular cargos, I developed novel selective fluorescent reporter probes; and introduced a new class of bioreductive therapeutic constructs based on a common modular design. These were either applied to selectively measure cellular reductase activity or to deliver cytotoxic anti cancer agents in vivo. Ongoing work aims to differentiate between the two major redox effector proteins Trx and Grx, requiring additional layers of selectivity that may be addressed by tuned molecular recognition. The flexible use of various molecular cargos allows harnessing the same cellular redox machinery by either probes or prodrugs. This allows predictive conclusions from diagnostics to be directly translated into therapy and offers great potential for future adaptation to other enzyme classes and therapeutic venues.Die zellulĂ€re Redox-Homöostase hĂ€ngt von Thiol/Disulfid-Oxidoreduktasen ab, die den Stoffwechsel, die Proliferation und die antioxidative Antwort von Zellen beeinflussen. Die wichtigsten Netzwerke sind die Thioredoxin Reduktase-Thioredoxin (TrxR/Trx) und Glutathion Reduktase-Glutathion-Glutaredoxin (GR/GSH/Grx) Systeme, die ĂŒber Redox-Schalter in Substratproteinen lebenswichtige zellulĂ€re Funktionen steuern und so an der Redox-Regulation und -SignalĂŒbertragung beteiligt sind. Persistente VerĂ€nderungen des Redoxmilieus in pathologischen ZustĂ€nden, wie z. B. bei Krebs, sind in hohem MaĂe mit dem Trx-System verbunden. Eine Hochregulierung und/oder ĂberaktivitĂ€t des Trx-Systems, die bei vielen Krebsarten auftreten, unterstĂŒtzt zudem das Fortschreiten des Krebswachstums, was TrxR/Trx zu vielversprechenden Zielproteinen fĂŒr die Entwicklung neuer Krebsmedikamente macht.
Um die biochemischen Prozesse dahinter zu erforschen, sind spezielle Techniken zur Visualisierung und Messung enzymatischer AktivitĂ€t nötig. Die hierzu geeigneten, meist genetischen Sensoren messen ratiometrisch das VerhĂ€ltnis reduzierter/oxidierter Spezies in zellulĂ€rem Umfeld oder spezifisch ausgewĂ€hlte Redoxpaare. Die weitere Erforschung der exakten Funktion von TrxR/Trx und deren Substrate ist jedoch durch mangelnde Nachweismethoden limitiert. Diese sind auĂerdem zur Validierung chemischer Hemmstoffe fĂŒr TrxR/Trx in Zellen und deren potenziellen Verwendung als Krebsmittel von groĂem Interesse. Bislang gibt es keinen selektiven zellulĂ€ren Trx-Inhibitor und potenzielle Off-Target-Effekte der bekannten TrxR-Inhibitoren wurden nicht abschlieĂend bewertet.
Ziel dieser Arbeit ist die Entwicklung niedermolekularer, diagnostischer und therapeutischer Werkzeuge, die selektiv auf das Trx-System abzielen und auf einem modularen Trigger-Cargo Design basieren. Hierzu werden zyklische Disulfid-Substrate (Trigger) fĂŒr Oxidoreduktasen so mit molekularen Wirkstoffen (Cargo) verknĂŒpft, dass dabei die WirkstoffaktivitĂ€t maskiert, und erst nach Reduktion durch ein Zielprotein wiederhergestellt wird. Diese neuartigen, synthetischen Reduktionssensoren basieren auf den folgenden Grundprinzipien: (i) Zyklische Disulfide sind thermodynamisch stabilisiert und können nur durch die stĂ€rksten Reduktasen gespalten werden; und (ii) die zyklische Topologie ermöglicht die kinetische ReversibilitĂ€t der zwei Thiol-Disulfid-Austauschreaktionen, die eine erste Reaktion mit Monothiolen, wie z. B. GSH, sofort umkehrt und so eine vollstĂ€ndige Reduktion verhindert.
Die meisten frĂŒheren Arbeiten auf diesem Gebiet verwendeten ein zyklisches, fĂŒnfgliedriges Disulfid (1,2 Dithiolan) als Substrat fĂŒr TrxR. Das gleiche Strukturmotiv wurde jedoch an anderer Stelle als thermodynamisch instabil beschrieben und aufgrund dieser Eigenschaft explizit fĂŒr dynamische Kaskadenreaktionen verwendet. Deshalb vergleicht diese Arbeit zu Beginn einen neuen 1,2 Dithiolan basierten fluorogenen Indikator mit bestehenden, z. T. kommerziellen, Redox Sonden fĂŒr TrxR in einer Reihe von Zellkultur-Experimenten unter Modulation der zellulĂ€ren TrxR AktivitĂ€t und stellt so einen Widerspruch in der Literatur klar: 1,2 Dithiolane eignen sich nicht als selektive Substrate fĂŒr TrxR, da sie labil sowohl gegen die Reduktion durch andere Redoxproteine, als auch gegen den Monothiol Hintergrund in Zellen sind (Nat. Commun. 2022).
Als alternatives Strukturmotiv wird in dieser Arbeit ein bizyklisches sechsgliedriges Disulfid (anneliertes 1,2 Dithian) etabliert. Durch sein niedriges Reduktionspotenzial, also seine hohe Resistenz gegen Reduktion, werden molekulare Sonden basierend auf diesem 1,2 Dithian als Reduktionssensor fast ausschlieĂlich von Trx aktiviert, nicht aber von TrxR oder GSH (JACS 2021). Dieses Kernmotiv bestimmt dabei die Reduzierbarkeit, und damit die EnzymspezifitĂ€t, durch seine zyklische Natur und die Annelierung, auch unter Verwendung unterschiedlicher Farb-/Wirkstoffe. Auf dieser Grundlage konnte die molekulare Struktur durch einen weiteren Modifikationspunkt fĂŒr die flexible Verwendung weiterer funktioneller Einheiten ergĂ€nzt werden. Obwohl zellulĂ€re Studien ergaben, dass diese neuartigen 1,2 Dithian Einheiten in Zellen sowohl Trx als auch das strukturell verwandte Grx adressieren, sind die daraus resultierenden diagnostischen MolekĂŒle wertvoll, um den katalytischen Umsatz zellulĂ€rer Dithiol-Reduktasen, der sogenannten Trx Superfamilie, selektiv anzuzeigen (Preprint 2023).
BegĂŒnstigt durch das modulare MolekĂŒldesign stellt diese Arbeit zudem das erste Reportersystem RX1 zum selektiven Nachweis der TrxR-AktivitĂ€t in Zellen vor. Es basiert auf der Verwendung eines zyklischen, unsymmetrischen Selenenylsulfid-Sensors (1,2 Thiaselenan), der selektiv von dem einzigartigen Selenolat der TrxR angegriffen wird, und dadurch letztlich nur von TrxR reduziert werden kann. RX1 eignete sich zudem fĂŒr eine Hochdurchsatz-Validierung bestehender TrxR Inhibitoren und unterstreicht dadurch den kommerziellen Nutzen derartiger Diagnostika (Chem 2022).
Das zentrale Trigger-Cargo Konzept dieser Arbeit wurde fĂŒr therapeutische Zwecke weiterentwickelt und nutzt dabei den einzigartigen Wirkmechanismus der Duocarmycin-Naturstoffklasse (CBI) (JACS Au 2022) zur Entwicklung reduktiv aktivierbarer Therapeutika. CBI Prodrugs basierend auf stabilisierten Redox-Schaltern (1,2 Dithiane fĂŒr Trx; 1,2 Thiaselenan fĂŒr TrxR) reagierten signifikant auf TrxR-Modulation in Zellen. Sie wurden darĂŒber hinaus durch das Referenzieren ihrer AktivitĂ€t gegenĂŒber nicht-reduzierbaren KontrollmolekĂŒle fĂŒr die Erstellung zelllinienabhĂ€ngiger Profile der ReduktaseaktivitĂ€t in 177 Zelllinien genutzt. SchlieĂlich waren diese neuen Krebsmittel im Tiermodell gut vertrĂ€glich und zeigten in zwei verschiedenen Mausmodellen eine krebshemmende Wirkung (Preprint 2022b).
Zusammenfassend prĂ€sentiert diese Dissertation monothiol-resistente reduzierbare Trigger-Einheiten fĂŒr das zellulĂ€re Trx-System zur Entwicklung neuartiger, selektiver Reporter-Sonden, sowie eine neue Klasse reduktiv aktivierbarer Krebsmittel auf Basis eines adaptierbaren Trigger-Cargo Designs. Diese fanden entweder zur selektiven Messung zellulĂ€rer ProteinaktivitĂ€t oder zum Einsatz als Antikrebsmittel Verwendung. Es wurden chemokompatible Motive sowohl fĂŒr TrxR als auch fĂŒr Trx/Grx identifiziert, wobei deren zyklische Natur eine Aktivierung durch GSH verhindert. Eine weitere Differenzierung zwischen den beiden Redox-Proteinen Trx und Grx und anderen Proteinen der Trx-Superfamilie erfordert eine zusĂ€tzliche Ebene der Selektierung, z. B. durch molekulare Erkennung, und ist Gegenstand laufender Arbeiten.
Die flexible Verwendung verschiedener molekularer Wirkstoffe ermöglicht dabei die âPipeline-Entwicklungâ von Diagnostika und Therapeutika, die von der zellulĂ€ren Redox-Maschinerie analog umgesetzt werden, und dadurch Schlussfolgerungen aus der Diagnostik direkt auf eine Therapie ĂŒbertragbar machen. Dies birgt groĂes Potenzial fĂŒr kĂŒnftige Entwicklungen bei einer potenziellen Ăbertragung des modularen Konzepts auf andere Enzymklassen und therapeutische Einsatzgebiete
Reframing museum epistemology for the information age: a discursive design approach to revealing complexity
This practice-based research inquiry examines the impact of an epistemic shift, brought about by the dawning of the information age and advances in networked communication technologies, on physical knowledge institutions - focusing on museums. The research charts adapting knowledge schemas used in museum knowledge organisation and discusses the potential for a new knowledge schema, the network, to establish a new epistemology for museums that reflects contemporary hyperlinked and networked knowledge. The research investigates the potential for networked and shared virtual reality spaces to reveal new âknowledge monumentsâ reflecting the epistemic values of the network society and the space of flows.
The central practice for this thesis focuses on two main elements. The first is applying networks and visual complexity to reveal multi-linearity and adapting perspectives in relational knowledge networks. This concept was explored through two discursive design projects, the Museum Collection Engine, which uses data visualisation, cloud data, and image recognition within an immersive projection dome to create a dynamic and searchable museum collection that returns new and interlinking constellations of museum objects and knowledge. The second discursive design project was Shared Pasts: Decoding Complexity, an AR app with a unique âanti-personalisationâ recommendation system designed to reveal complex narratives around historic objects and places. The second element is folksonomy and co-design in developing new community-focused archives using the community's language to build the dataset and socially tagged metadata. This was tested by developing two discursive prototypes, Women Reclaiming AI and Sanctuary Stories
A Closer Look into Recent Video-based Learning Research: A Comprehensive Review of Video Characteristics, Tools, Technologies, and Learning Effectiveness
People increasingly use videos on the Web as a source for learning. To
support this way of learning, researchers and developers are continuously
developing tools, proposing guidelines, analyzing data, and conducting
experiments. However, it is still not clear what characteristics a video should
have to be an effective learning medium. In this paper, we present a
comprehensive review of 257 articles on video-based learning for the period
from 2016 to 2021. One of the aims of the review is to identify the video
characteristics that have been explored by previous work. Based on our
analysis, we suggest a taxonomy which organizes the video characteristics and
contextual aspects into eight categories: (1) audio features, (2) visual
features, (3) textual features, (4) instructor behavior, (5) learners
activities, (6) interactive features (quizzes, etc.), (7) production style, and
(8) instructional design. Also, we identify four representative research
directions: (1) proposals of tools to support video-based learning, (2) studies
with controlled experiments, (3) data analysis studies, and (4) proposals of
design guidelines for learning videos. We find that the most explored
characteristics are textual features followed by visual features, learner
activities, and interactive features. Text of transcripts, video frames, and
images (figures and illustrations) are most frequently used by tools that
support learning through videos. The learner activity is heavily explored
through log files in data analysis studies, and interactive features have been
frequently scrutinized in controlled experiments. We complement our review by
contrasting research findings that investigate the impact of video
characteristics on the learning effectiveness, report on tasks and technologies
used to develop tools that support learning, and summarize trends of design
guidelines to produce learning video
Making Connections: A Handbook for Effective Formal Mentoring Programs in Academia
This book, Making Connections: A Handbook for Effective Formal Mentoring Programs in Academia, makes a unique and needed contribution to the mentoring field as it focuses solely on mentoring in academia. This handbook is a collaborative institutional effort between Utah State Universityâs (USU) Empowering Teaching Open Access Book Series and the Mentoring Institute at the University of New Mexico (UNM). This book is available through (a) an e-book through Pressbooks, (b) a downloadable PDF version on USUâs Open Access Book Series website), and (c) a print version available for purchase on the USU Empower Teaching Open Access page, and on Amazon
A Novel Paradigm for Sentiment Analysis on COVID-19 Tweets with Transfer Learning Based Fine-Tuned BERT
The rapid escalation in global COVID-19 cases has engendered profound emotions of fear, agitation, and despondency within society. It is evident from COVID-19-related tweets that spark panic and elevate stress among individuals. Analyzing the sentiment expressed in online comments aids various stakeholders in monitoring the situation. This research aims to improve the performance of pre-trained bidirectional encoder representations from transformers (BERT) by employing transfer learning (TL) and fine hyper-parameter tuning (FT). The model is applied to three distinct COVID-19-related datasets, and each of the datasets belongs to a different class. The evaluation of the modelâs performance involves six different machine learning (ML) classification models. This model is trained and evaluated using metrics such as accuracy, precision, recall, and F1-score. Heat maps are generated for each model to visualize the results. The performance of the model demonstrates accuracies of 83%, 97%, and 98% for Class-5, Class-3, and binary classifications, respectively
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