6,875 research outputs found

    Graduate Catalog of Studies, 2023-2024

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    Beam scanning by liquid-crystal biasing in a modified SIW structure

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    A fixed-frequency beam-scanning 1D antenna based on Liquid Crystals (LCs) is designed for application in 2D scanning with lateral alignment. The 2D array environment imposes full decoupling of adjacent 1D antennas, which often conflicts with the LC requirement of DC biasing: the proposed design accommodates both. The LC medium is placed inside a Substrate Integrated Waveguide (SIW) modified to work as a Groove Gap Waveguide, with radiating slots etched on the upper broad wall, that radiates as a Leaky-Wave Antenna (LWA). This allows effective application of the DC bias voltage needed for tuning the LCs. At the same time, the RF field remains laterally confined, enabling the possibility to lay several antennas in parallel and achieve 2D beam scanning. The design is validated by simulation employing the actual properties of a commercial LC medium

    Introduction to Facial Micro Expressions Analysis Using Color and Depth Images: A Matlab Coding Approach (Second Edition, 2023)

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    The book attempts to introduce a gentle introduction to the field of Facial Micro Expressions Recognition (FMER) using Color and Depth images, with the aid of MATLAB programming environment. FMER is a subset of image processing and it is a multidisciplinary topic to analysis. So, it requires familiarity with other topics of Artifactual Intelligence (AI) such as machine learning, digital image processing, psychology and more. So, it is a great opportunity to write a book which covers all of these topics for beginner to professional readers in the field of AI and even without having background of AI. Our goal is to provide a standalone introduction in the field of MFER analysis in the form of theorical descriptions for readers with no background in image processing with reproducible Matlab practical examples. Also, we describe any basic definitions for FMER analysis and MATLAB library which is used in the text, that helps final reader to apply the experiments in the real-world applications. We believe that this book is suitable for students, researchers, and professionals alike, who need to develop practical skills, along with a basic understanding of the field. We expect that, after reading this book, the reader feels comfortable with different key stages such as color and depth image processing, color and depth image representation, classification, machine learning, facial micro-expressions recognition, feature extraction and dimensionality reduction. The book attempts to introduce a gentle introduction to the field of Facial Micro Expressions Recognition (FMER) using Color and Depth images, with the aid of MATLAB programming environment.Comment: This is the second edition of the boo

    Facilitating prosociality through technology: Design to promote digital volunteerism

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    Volunteerism covers many activities involving no financial rewards for volunteers but which contribute to the common good. There is existing work in designing technology for volunteerism in HumanComputer Interaction (HCI) and related disciplines that focuses on motivation to improve performance, but it does not account for volunteer wellbeing. Here, I investigate digital volunteerism in three case studies with a focus on volunteer motivation, engagement, and wellbeing. My research involved volunteers and others in the volunteering context to generate recommendations for a volunteer-centric design for digital volunteerism. The thesis has three aims: 1. To investigate motivational aspects critical for enhancing digital volunteers’ experiences 2. To identify digital platform attributes linked to volunteer wellbeing 3. To create guidelines for effectively supporting volunteer engagement in digital volunteering platforms In the first case study I investigate the design of a chat widget for volunteers working in an organisation with a view to develop a design that improves their workflow and wellbeing. The second case study investigates the needs, motivations, and wellbeing of volunteers who help medical students improve their medical communication skills. An initial mixed-methods study was followed by an experiment comparing two design strategies to improve volunteer relatedness; an important indicator of wellbeing. The third case study looks into volunteer needs, experiences, motivations, and wellbeing with a focus on volunteer identity and meaning-making on a science-based research platform. I then analyse my findings from these case studies using the lens of care ethics to derive critical insights for design. The key contributions of this thesis are design strategies and critical insights, and a volunteer-centric design framework to enhance the motivation, wellbeing and engagement of digital volunteers

    Rational development of stabilized cyclic disulfide redox probes and bioreductive prodrugs to target dithiol oxidoreductases

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    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 cargo’s 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 system’s 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 TrxR’s selenol/thiol active site, then combined with a precipitating large Stokes’ 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 zelluläre Redox-Homöostase hängt 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 über Redox-Schalter in Substratproteinen lebenswichtige zelluläre Funktionen steuern und so an der Redox-Regulation und -Signalübertragung beteiligt sind. Persistente Veränderungen des Redoxmilieus in pathologischen Zuständen, wie z. B. bei Krebs, sind in hohem Maße mit dem Trx-System verbunden. Eine Hochregulierung und/oder Überaktivität des Trx-Systems, die bei vielen Krebsarten auftreten, unterstützt zudem das Fortschreiten des Krebswachstums, was TrxR/Trx zu vielversprechenden Zielproteinen für die Entwicklung neuer Krebsmedikamente macht. Um die biochemischen Prozesse dahinter zu erforschen, sind spezielle Techniken zur Visualisierung und Messung enzymatischer Aktivität nötig. Die hierzu geeigneten, meist genetischen Sensoren messen ratiometrisch das Verhältnis reduzierter/oxidierter Spezies in zellulärem Umfeld oder spezifisch ausgewählte Redoxpaare. Die weitere Erforschung der exakten Funktion von TrxR/Trx und deren Substrate ist jedoch durch mangelnde Nachweismethoden limitiert. Diese sind außerdem zur Validierung chemischer Hemmstoffe für TrxR/Trx in Zellen und deren potenziellen Verwendung als Krebsmittel von großem Interesse. Bislang gibt es keinen selektiven zellulären Trx-Inhibitor und potenzielle Off-Target-Effekte der bekannten TrxR-Inhibitoren wurden nicht abschließend 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) für Oxidoreduktasen so mit molekularen Wirkstoffen (Cargo) verknüpft, dass dabei die Wirkstoffaktivität 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 stärksten Reduktasen gespalten werden; und (ii) die zyklische Topologie ermöglicht die kinetische Reversibilität der zwei Thiol-Disulfid-Austauschreaktionen, die eine erste Reaktion mit Monothiolen, wie z. B. GSH, sofort umkehrt und so eine vollständige Reduktion verhindert. Die meisten früheren Arbeiten auf diesem Gebiet verwendeten ein zyklisches, fünfgliedriges Disulfid (1,2 Dithiolan) als Substrat für TrxR. Das gleiche Strukturmotiv wurde jedoch an anderer Stelle als thermodynamisch instabil beschrieben und aufgrund dieser Eigenschaft explizit für dynamische Kaskadenreaktionen verwendet. Deshalb vergleicht diese Arbeit zu Beginn einen neuen 1,2 Dithiolan basierten fluorogenen Indikator mit bestehenden, z. T. kommerziellen, Redox Sonden für TrxR in einer Reihe von Zellkultur-Experimenten unter Modulation der zellulären TrxR Aktivität und stellt so einen Widerspruch in der Literatur klar: 1,2 Dithiolane eignen sich nicht als selektive Substrate für 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 ausschließlich von Trx aktiviert, nicht aber von TrxR oder GSH (JACS 2021). Dieses Kernmotiv bestimmt dabei die Reduzierbarkeit, und damit die Enzymspezifität, durch seine zyklische Natur und die Annelierung, auch unter Verwendung unterschiedlicher Farb-/Wirkstoffe. Auf dieser Grundlage konnte die molekulare Struktur durch einen weiteren Modifikationspunkt für die flexible Verwendung weiterer funktioneller Einheiten ergänzt werden. Obwohl zelluläre 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 Moleküle wertvoll, um den katalytischen Umsatz zellulärer Dithiol-Reduktasen, der sogenannten Trx Superfamilie, selektiv anzuzeigen (Preprint 2023). Begünstigt durch das modulare Moleküldesign stellt diese Arbeit zudem das erste Reportersystem RX1 zum selektiven Nachweis der TrxR-Aktivität 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 für eine Hochdurchsatz-Validierung bestehender TrxR Inhibitoren und unterstreicht dadurch den kommerziellen Nutzen derartiger Diagnostika (Chem 2022). Das zentrale Trigger-Cargo Konzept dieser Arbeit wurde für 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 für Trx; 1,2 Thiaselenan für TrxR) reagierten signifikant auf TrxR-Modulation in Zellen. Sie wurden darüber hinaus durch das Referenzieren ihrer Aktivität gegenüber nicht-reduzierbaren Kontrollmoleküle für die Erstellung zelllinienabhängiger Profile der Reduktaseaktivität in 177 Zelllinien genutzt. Schließlich waren diese neuen Krebsmittel im Tiermodell gut verträglich und zeigten in zwei verschiedenen Mausmodellen eine krebshemmende Wirkung (Preprint 2022b). Zusammenfassend präsentiert diese Dissertation monothiol-resistente reduzierbare Trigger-Einheiten für das zelluläre 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 zellulärer Proteinaktivität oder zum Einsatz als Antikrebsmittel Verwendung. Es wurden chemokompatible Motive sowohl für TrxR als auch für 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 zusätzliche Ebene der Selektierung, z. B. durch molekulare Erkennung, und ist Gegenstand laufender Arbeiten. Die flexible Verwendung verschiedener molekularer Wirkstoffe ermöglicht dabei die „Pipeline-Entwicklung“ von Diagnostika und Therapeutika, die von der zellulären Redox-Maschinerie analog umgesetzt werden, und dadurch Schlussfolgerungen aus der Diagnostik direkt auf eine Therapie übertragbar machen. Dies birgt großes Potenzial für künftige Entwicklungen bei einer potenziellen Übertragung des modularen Konzepts auf andere Enzymklassen und therapeutische Einsatzgebiete

    Systemic Circular Economy Solutions for Fiber Reinforced Composites

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    This open access book provides an overview of the work undertaken within the FiberEUse project, which developed solutions enhancing the profitability of composite recycling and reuse in value-added products, with a cross-sectorial approach. Glass and carbon fiber reinforced polymers, or composites, are increasingly used as structural materials in many manufacturing sectors like transport, constructions and energy due to their better lightweight and corrosion resistance compared to metals. However, composite recycling is still a challenge since no significant added value in the recycling and reprocessing of composites is demonstrated. FiberEUse developed innovative solutions and business models towards sustainable Circular Economy solutions for post-use composite-made products. Three strategies are presented, namely mechanical recycling of short fibers, thermal recycling of long fibers and modular car parts design for sustainable disassembly and remanufacturing. The validation of the FiberEUse approach within eight industrial demonstrators shows the potentials towards new Circular Economy value-chains for composite materials

    Making Connections: A Handbook for Effective Formal Mentoring Programs in Academia

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    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 University’s (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 USU’s Open Access Book Series website), and (c) a print version available for purchase on the USU Empower Teaching Open Access page, and on Amazon

    Testing SOAR Tools in Use

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    Modern security operation centers (SOCs) rely on operators and a tapestry of logging and alerting tools with large scale collection and query abilities. SOC investigations are tedious as they rely on manual efforts to query diverse data sources, overlay related logs, and correlate the data into information and then document results in a ticketing system. Security orchestration, automation, and response (SOAR) tools are a new technology that promise to collect, filter, and display needed data; automate common tasks that require SOC analysts' time; facilitate SOC collaboration; and, improve both efficiency and consistency of SOCs. SOAR tools have never been tested in practice to evaluate their effect and understand them in use. In this paper, we design and administer the first hands-on user study of SOAR tools, involving 24 participants and 6 commercial SOAR tools. Our contributions include the experimental design, itemizing six characteristics of SOAR tools and a methodology for testing them. We describe configuration of the test environment in a cyber range, including network, user, and threat emulation; a full SOC tool suite; and creation of artifacts allowing multiple representative investigation scenarios to permit testing. We present the first research results on SOAR tools. We found that SOAR configuration is critical, as it involves creative design for data display and automation. We found that SOAR tools increased efficiency and reduced context switching during investigations, although ticket accuracy and completeness (indicating investigation quality) decreased with SOAR use. Our findings indicated that user preferences are slightly negatively correlated with their performance with the tool; overautomation was a concern of senior analysts, and SOAR tools that balanced automation with assisting a user to make decisions were preferred

    Using Crowd-Based Software Repositories to Better Understand Developer-User Interactions

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    Software development is a complex process. To serve the final software product to the end user, developers need to rely on a variety of software artifacts throughout the development process. The term software repository used to denote only containers of source code such as version control systems; more recent usage has generalized the concept to include a plethora of software development artifact kinds and their related meta-data. Broadly speaking, software repositories include version control systems, technical documentation, issue trackers, question and answer sites, distribution information, etc. The software repositories can be based on a specific project (e.g., bug tracker for Firefox), or be crowd-sourced (e.g., questions and answers on technical Q&A websites). Crowd-based software artifacts are created as by-products of developer-user interactions which are sometimes referred to as communication channels. In this thesis, we investigate three distinct crowd-based software repositories that follow different models of developer-user interactions. We believe through a better understanding of the crowd-based software repositories, we can identify challenges in software development and provide insights to improve the software development process. In our first study, we investigate Stack Overflow. It is the largest collection of programming related questions and answers. On Stack Overflow, developers interact with other developers to create crowd-sourced knowledge in the form of questions and answers. The results of the interactions (i.e., the question threads) become valuable information to the entire developer community. Prior research on Stack Overflow tacitly assume that questions receives answers directly on the platform and no need of interaction is required during the process. Meanwhile, the platform allows attaching comments to questions which forms discussions of the question. Our study found that question discussions occur for 59.2% of questions on Stack Overflow. For discussed and solved questions on Stack Overflow, 80.6% of the questions have the discussion begin before the accepted answer is submitted. The results of our study show the importance and nuances of interactions in technical Q&A. We then study dotfiles, a set of publicly shared user-specific configuration files for software tools. There is a culture of sharing dotfiles within the developer community, where the idea is to learn from other developers’ dotfiles and share your variants. The interaction of dotfiles sharing can be viewed as developers sources information from other developers, adapt the information to their own needs, and share their adaptations back to the community. Our study on dotfiles suggests that is a common practice among developers to share dotfiles where 25.8% of the most stared users on GitHub have a dotfiles repository. We provide a taxonomy of the commonly tracked dotfiles and a qualitative study on the commits in dotfiles repositories. We also leveraged the state-of-the-art time-series clustering technique (K-shape) to identify code churn pattern for dotfile edits. This study is the first step towards understanding the practices of maintaining and sharing dotfiles. Finally, we study app stores, the platforms that distribute software products and contain many non-technical attributes (e.g., ratings and reviews) of software products. Three major stakeholders interacts with each other in app stores: the app store owner who governs the operation of the app store; developers who publish applications on the app store; and users who browse and download applications in the app store. App stores often provide means of interaction between all three actors (e.g., app reviews, store policy) and sometimes interactions with in the same actor (e.g., developer forum). We surveyed existing app stores to extract key features from app store operation. We then labeled a representative set of app store collected by web queries. K-means is applied to the labeled app stores to detect natural groupings of app stores. We observed a diverse set of app stores through the process. Instead of a single model that describes all app stores, fundamentally, our observations show that app stores operates differently. This study provide insights in understanding how app stores can affect software development. In summary, we investigated software repositories containing software artifacts created from different developer-user interactions. These software repositories are essential for software development in providing referencing information (i.e., Stack Overflow), improving development productivity (i.e., dotfiles), and help distributing the software products to end users (i.e., app stores)
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